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ABSTRACTS PRESENTED AT CONCURRENT SESSIONS November 10-11, 2013 Baltimore Convention Center baltimore, maryland TABLE OF CONTENTS TOPIC ABSTRACT NUM...

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ABSTRACTS PRESENTED AT CONCURRENT SESSIONS November 10-11, 2013 Baltimore Convention Center baltimore, maryland




Adverse Food and Drug Reactions, Insect Reactions, Anaphylaxis



Asthma and Other Lower Airway Disorders



Aerobiology, Allergens, Allergen Extracts, Allergy Testing/Clinical Laboratory Immunology/ Immunotherapy and Immunizations



Basic Science Allergy & Immunology and Clinical Immunology, Immunodeficiency



Clinical Case Reports



Food Allergy



Other and Skin Disorders



Pharmacology & Pharmacotherapeutics and Rhinitis, Other Upper Airway Disorders, Ocular Disorders













Background: The diagnosis of perioperative anaphylaxis (PA) remains challenging to healthcare providers, given its clinical setting, exposure to multiple medications, and infrequency of occurrence. Previous reports have found PA is most frequently caused by neuromuscular blocking agents (Mertes, et al. Anesthesiology 2003). We sought to determine the pattern of PA at our center. Methods: We performed a retrospective medical record review from 2002-2012 to identify patients with anaphylaxis. The ICD-9 codes used included 995.0 (other anaphylactic shock), 989.82 (toxic effect of latex), 995.20 (adverse effect of medical/biological substance NOS), and 995.27 (other drug allergy). The diagnosis of anaphylaxis was made using WHO guidelines. Cases of PA were included in our series. Confirmed cases were further categorized by cause of and symptoms associated with the diagnosis, age, gender, atopic status and tryptase level. Cases with a causative agent identified by positive skin testing or serum specific IgE were classified as IgE mediated anaphylaxis. Results: Twenty-nine cases of PA were identified; 15 cases (51%) had an identifiable cause: antibiotics in 7 cases (47%)-6 due to β-lactams, 1 due to metronidazole, latex in 4 cases (27%), and neuromuscular blockers in 4 cases (27%). There was no identifiable cause in 14 cases. The most frequent presenting sign was hypotension (82%). Only 3 patients had a history of atopy. Elevated serum tryptase was found in 5/7 (71%) cases of IgE mediated anaphylaxis, compared to 5/12 (41%) cases without identifiable cause. Conclusion: We found antibiotics were the most common identifiable cause of PA; however, in many cases, a cause was not identified by skin or in vitro testing.

Introduction: Evidence-based guidelines regarding the optimal number of steps to use for drug challenges and data on the safety and outcomes of these challenges are lacking. Additionally, controversy exists over whether multi-step drug challenges induce tolerance. Therefore, for all hypersensitivity reactions (HSR) referred to our Allergy/Immunology service in patients felt unlikely to develop an allergic reaction with re-exposure to the culprit drug, we proposed a standardized one- or two-step test dose protocol. Methods: We performed a 5-year retrospective review of all patients who underwent a standardized oneor two-step test dose protocol at our institution. Patient demographics, symptoms of HSR, culprit drug and outcomes of standardized test doses were reviewed. All HSR were classified by reaction type and graded by severity. Institutional Review Board approval was obtained. Results: Between 2008 and 2013, we identified 456 patients who underwent 497 test doses. The majority of patients were female (68%) with a mean age of 51 years. Beta-lactams (62%), other antimicrobials (14%) and NSAIDs (12%) were the most common culprit drug HSR prompting test doses. Most of the initial reactions were classified as IgE-mediated (43%) or other immunologic (26%) with symptoms of rash or hives reported in 52%. Only 53 test doses (11%) were associated with adverse events, which occurred more frequently in females (85% vs. 65%, P=0.0009). Most of the adverse reactions were non-immune mediated (45%) or IgE-mediated (32%) with non-life-threatening symptoms (53%) or mild cutaneous symptoms (45%). The majority of adverse events (n=51, 96%) did not require any treatment or were adequately treated with antihistamines. Two women developed HSR to opiate test doses requiring epinephrine treatment. One patient reported subjective throat tightness and one patient developed dysphonia with diffuse erythema. Conclusion: Standardized one- or two-step test dose protocols are safe and allow patients to reach therapeutic doses of required medication more rapidly. Moreover, these protocols raise no concern for induction of tolerance, allowing patients to remove these medications from their drug allergy list. Female patients were referred more frequently for test doses and found to be at increased risk for developing adverse events during the standardized test dose protocol.

2 ANXIETY AND DEPRESSION IN HYMENOPTERA VENOM ALLERGY PATIENTS. S. Findeis*, A. Fouche, E. Saunders, T. Craig, Hershey, PA. Introduction: Allergies to Hymenoptera stings are very common, causing over one hundred deaths annually in the United States. Increased anxiety has been documented in this patient population in other countries, however there is variance in the reported percentage. Current therapies for hymenoptera venom allergies include venom immunotherapy (VIT) and/or epinephrine injections. While literature elsewhere has suggested that VIT decreases anxiety compared to only using epinephrine injections, there have been no published studies assessing the anxiety and depression of these patients in the United States. Our objective is to study the effect of venom immunotherapy and epinephrine injections on anxiety and depression in a United States cohort. Methods: An initial 437 adult patients with documented Hymenoptera sting allergies from our institution was used as a source for IRB approved phone interviews. Responses were collected regarding their sting allergies, current therapies (none, epinephrine injections, and/or VIT)) and anxiety and depression utilizing the Hamilton anxiety and depression indices (HAM-A, HAM-D). Additionally, a literature review using PubMed and OVID Medline was done using the terms ‘venom immunotherapy,’ ‘anxiety,’ ‘depression,’ ‘hymenoptera sting allergy,’ ‘bee sting allergy.’ Results: VIT group patients had overall decreased anxiety and depression, indicated by lower HAM-D and HAM-A scores. Furthermore, almost all patients reported to currently carrying an epinephrine pen in addition to undergoing VIT. The highest average HAM-A and HAM-D scores were of the epinephrine group whereas the non-treatment group had lower averages. However, the non-treatment group did not have as severe grades of anaphylaxis on average compared to the group only carrying injectable epinephrine. Conclusion: This study suggests that in comparison to other treatments, patients who are currently receiving or have received VIT have lessened anxiety and depression as compared to other treatment groups, despite having very severe grades of anaphylaxis among the surveyed patients. These findings are in agreement with those reported in other countries and indicate that VIT has utility for both the biologic modulation of allergies as well as a significant psychological impact in the areas of anxiety and depression.

4 EVALUATION OF AGALSIDASE BETA-SPECIFIC SERUM IGE IN PATIENTS WITH FABRY DISEASE. C.D. Clay*, R. Hopkin, C. Wehmeyer, J. Tan, P. Amin, J.A. Bernstein, Cincinnati, OH. Introduction: Fabry Disease (FD) is an X-linked recessive inherited disorder caused by the deficiency of alpha-galactosidase A (alpha-GAL) and intracellular deposition of its substrate, glycolipid globotriaosylceramide (GL3). Agalsidase beta (Fabrazyme®, GenzymeTherapeutics) infusions are approved as alpha-GAL enzyme replacement therapy in the US. Side effects including shortness of breath, nausea, chest pain, hives, hypotension, facial swelling occur in up to 5% of treated patients and up to 1% of patients can develop anaphylaxis. Alpha-GAL specific serum IgE levels are reported to correlate with systemic allergic reactions. Methods: Two patients with FD and a history of allergic reactions to agalsidase beta were referred for further assessment and management. Each was skin prick tested (SPT) followed by threshold intracutaneous (IC) testing to agalsidase beta to determine current levels of cutaneous sensitization. Serum samples from FD patients and 7 healthy non-atopic control subjects were analyzed using an optimized agalsidase beta-specific serum IgE ELISA. A result of greater than 3 standard deviations above the average control optical density (OD) was positive. FD patients were also tested for alpha-GAL specific serum IgE. Result: Patient-1 developed systemic reactions (hives, laryngeal edema) to agalsidase beta on 3 occasions despite desensitization, pretreatment with H1- and H2-antagonists, LTMA and corticosteroids or prior treatment with rituximab to suppress IgE production. SPT and serum specific IgE levels were positive before and after each infusion attempt. Patient-2 discontinued infusion therapy in 2009 after developing diffuse hives that coincided with agalsidase beta specific IgE. However, he needed to restart therapy secondary to worsening renal disease. Pre-infusion SPT and IC testing was negative.Agalsidase beta-specific serum IgE levels became positive after the second of 3 successive infusions without clinical symptoms. IC testing after the third infusion turned positive. Interestingly, specific IgE to anti-alpha-GAL was negative for both patients. Conclusion: FD patients with agalsidase beta systemic reactions represent a challenging management problem as treatment approaches to induce tolerance are not uniformly effective. Patient 1 will receive



ABSTRACTS: CONCURRENT SESSIONS omalizumab to determine tolerability to ongoing infusions; Patient 2 is being pretreated with H1-antagonists and currently tolerating infusions.

5 ANNUAL EPINEPHRINE AUTO-INJECTOR PRESCRIPTIONS IN OUTPATIENT CLINICS FOR CHILDREN WITH FOOD-INDUCED ANAPHYLAXIS. C. Couch*, S. McKnight, Las Vegas, NV. Background: The National Institute of Allergy and Infectious Diseases (NIAID) guidelines on the management of food allergies recommend patients who present with a history of food-induced anaphylaxis be prescribed selfinjectable epinephrine yearly. Appropriate administration instructions should be given, a plan for monitoring expiration dates outlined, and a written emergency action plan completed. Epinephrine auto-injector prescribing practices by pediatricians are poorly investigated. The primary objective of this study was to evaluate the frequency of annual self-injectable epinephrine prescriptions by pediatricians in outpatient clinics. Methods: A retrospective chart review was performed for patients seen between January 2010 and December 2012 at two outpatient pediatric clinics to determine compliance with NIAID guidelines. A sample of charts coded for food allergies (ICD-9 codes V15.01V15.05, 995.60-995.69, 995.70) was reviewed. Patients with milk protein intolerance were excluded. Results: Fifty-seven patients were included in the study. Mean age was 6 years, with 29 females and 28 males. The most frequent allergen was peanut (53%), followed by egg (30%), shellfish (26%), treenut (18%), milk (5%), and wheat (4%). Documentation of an epinephrine autoinjector prescription was present in 67% of charts (95% confidence interval [CI], 55-79%), while only 30% of charts (95% CI, 18-42%) had documentation of a current prescription (within one year of chart review). Epinephrine auto-injector administration instructions were given to 18% of patients (95% CI, 8-28%). A food allergy action plan was completed in 14% of patient visits (95% CI, 5-23%). Serum IgE testing was performed in 58% of patients (95% CI, 45-71%), and 58% (95% CI, 45-71%) were referred to an allergist for further testing and management. Conclusions: Although NIAID guidelines recommend all patients with food-induced anaphylaxis be prescribed selfinjectable epinephrine with annual renewal, the majority of children seen at outpatient pediatric clinics do not have a current prescription. Epinephrine auto-injector administration instructions and food allergy action plan documentation are rarely performed. Quality improvement measures, including physician education and chart reminders, would be of benefit to improve compliance with current management guidelines.

7 CHARACTERIZATION OF REACTIONS TO VANCOMYCIN IN THE PEDIATRIC POPULATION. S.K. Lin*, K.M. Mulieri, F.T. Ishmael, Hershey, PA. Background: Vancomycin has been used increasingly in pediatrics, yet there have been few studies of vancomycin-induced reactions in children. We sought to determine the prevalence of vancomycin reactions and to characterize the nature of these reactions in the pediatric population. Methods: After IRB approval, a search of electronic medical records through October 2011 was utilized to identify patients 16 and younger with vancomycin reactions documented at our academic medical center. Charts on these patients were reviewed to obtain patient demographics and information regarding the nature of the reactions. Results: There were 164 patients (ages 4 months – 16 years) with reactions to vancomycin documented from April 2004 to September 2011. There were 91 patients (55.5%) with documentation of red man syndrome, a vancomycin infusion-dependent mast cell activation typically characterized by erythema, flushing, and pruritis of the face and upper torso. Reaction types of rash or flushing were documented in an additional 11 patients (6.7%). While red man syndrome does not preclude future use of vancomycin, 45.2% of these reactions were entered as vancomycin allergies. For 42 patients (25%) there was no description of the nature of the reaction. Reactions consistent with true hypersensitivity (hives, isolated pruritis, systemic rash, swelling, fever, anaphylaxis, hemodynamic instability) were documented in 16 patients (9.8%, 2 with red man syndrome concurrently). Five reactions were considered nonimmunologic reactions consistent with side effects or intolerances. Out of 2,722 children who actively received vancomycin in our hospital, 104 had reactions documented (prevalence 3.8%). Of the 104 patients, 90 (86.5%) had documentation consistent with red man syndrome (prevalence of 3.3%) and 15 patients (14.4%) had documentation consistent with true hypersensitivity reactions (prevalence of 0.6%). Two patients were included in both of these categories and 1 had acute renal failure. Conclusions: Red man syndrome was the most common reaction type in our pediatric population, while reactions consistent with true hypersensitivity were rare. More complete and accurate documentation of drug reactions is needed in our medical record to prevent needless avoidance of vancomycin.


6 CURE OF PEANUT ALLERGY AFTER BONE MARROW TRANSPLANTATION FOR ACUTE LYMPHOCYTIC LEUKEMIA (ALL). Y. Luo*1, S.J. Weiss2, 1. Great Neck, NY; 2. Syosset, NY. Rationale: Peanut allergy is the most common cause of fatal food anaphylaxis. Its prevalence in general population is about 1% and there are 3 million school-age children being affected. Its incidence in pediatric population continues to increase. Peanut food allergy carries significant adverse effects on quality of life and currently there is no proactive therapy available as a standard of care. It has been reported that bone marrow transplantation (BMT) and liver transplantation could transfer peanut food allergy from donor to recipient. However, resolution of peanut allergy in a previously allergic recipient after BMT was rarely reported. Methods: We describe a 10-year-old male with peanut allergy, who successfully passed peanut oral challenge 2 years after BMT. In 2003 at age of 15 months, he presented initially with an immediate food allergic reaction including whole body urticaria and vomiting after ingestion of peanut product. His skin prick test and ImmunoCap test to peanut were positive. He was followed in the office annually thereafter without accidentally ingestion of peanut. In October 2006 at age of 4 years, he was diagnosed with pre-B cell ALL. He was treated with chemotherapy with multiple relapses. In September 2010, he received allogeneic unrelated BMT (10/10 HLA match) with myeloablative conditioning. The donor had no known allergy. One year after BMT, his immune system recovered and the immunosppressants were discontinued. His skin prick test and ImmunoCap test to peanut became negative. In July 2012, he successfully passed peanut oral challenge in the office, confirming the resolution of his peanut allergy. Results: Skin prick test to peanut was positive at age of 15 months in 2003. ImmunoCap to peanut was 0.87 kUA/L in 2007. His repeat skin prick test to peanut and ImmunoCap to peanut were both negative one year after BMT. Conclusions: We present a rare case with resolution of peanut allergy after BMT for ALL. Our case indicated that


the mechanism for abnormal IgE production associated with food allergy may be embedded in early stage of immune cell development in the bone marrow. Epigenetic modification may play a significant role in the process.

HAZELNUT REACTIVITY IS BETTER IDENTIFIED BY COMPONENT TESTING THAN TRADITIONAL TESTING METHODS. J. Kattan*, S.H. Sicherer, H.A. Sampson, New York, NY. Background: Skin prick testing (SPT) and serum food-specific IgE (sIgE) levels are sensitive testing options for identifying food allergy, but positive test results to tolerated foods are common. We reviewed our oral food challenges (OFCs) to hazelnut to establish if SPT and serum IgE results correlate with clinical reactivity, and performed hazelnut component testing to determine if this modality would improve predictability. Methods: We performed a retrospective chart review of all OFCs to hazelnut conducted at our outpatient pediatric allergy practice from January 1, 2010 to January 17, 2013. All patients were referred for unblinded OFC based on allergists’ clinical impression. We reviewed a number of patient factors, including age, hazelnut and birch sIgE levels, SPT results, and OFC outcomes. In patients who consented to component testing, we obtained sIgE levels to the hazelnut components Cor a 1, 8, 9, and 14. IRB approval was obtained for this study. Results: We performed 116 OFCs to hazelnut in patients aged 2 to 21 years. 107 patients passed OFC (92.2%), while 9 failed (7.8%). The median SPT wheal size in those who passed OFC (3 mm) was not significantly different from those who failed (5 mm). The median hazelnut-sIgE in the patients who passed OFC (5.96 kUA/L) was higher, but not significantly different from those who failed (3.74 kUA/L). Seven patients with hazelnut sIgE levels >100 kUA/L passed OFC. We obtained hazelnut component testing on 41 patients. The median Cor a 1 level was not significantly different between those with a negative OFC (3.88 kUA/L) and the hazelnut reactive patients (2.26 kUA/L). Only 3 patients had a Cor a 8 level >0.36 kUA/L. There were significant differences in both the median Cor a 9 levels (0.20 kUA/L, 2.51 kUA/L; P<.0001) and Cor a 14 levels (0.05, 2.18; P=.0001) between the patients who passed OFC and the reactive patients. When used together, a cutoff of 2.0 kUA/L for Cor a 9 or 1.0 kUA/L for Cor a 14 yields a sensitivity of 92% and specificity of 93% in predicting hazelnut reac-


ABSTRACTS: CONCURRENT SESSIONS tivity. Conclusion: Our results demonstrate that current testing for hazelnut allergy, including SPT and hazelnut-sIgE, is poor, and provides many false positive results. Hazelnut component testing using the components Cor a 9 and Cor a 14, greatly improves the specificity of hazelnut allergy testing, while maintaining strong sensitivity.

9 THE ASSESSMENT OF ASTHMA CONTROL IN THE DELIVERY OF ALLERGEN IMMUNOTHERAPY: A RETROSPECTIVE CHART REVIEW. A. Biggs*1, S. Shayegan2, S. Gada1, 1. Bethesda, MD; 2. Gaithersburg, MD. Introduction: Severe and poorly controlled asthma are two known risk factors for systemic reactions to allergen immunotherapy (AIT). The most recent AIT Practice Parameter recommends an assessment of asthma control prior to the administration of AIT using a subjective evaluation and the objective measurement of peak expiratory flow (PEF), both of which are performed in our clinic. However, no literature exists demonstrating the impact of subjective assessment of asthma control and measurement of PEF on the administration and safe delivery of AIT to asthmatics. Methods: A retrospective chart review was performed on asthmatic patients receiving AIT between January 2011 and July 2013. For each AIT visit, the prescreening health questionnaire was reviewed in addition to the documented PEF. A positive questionnaire was defined as an answer of “yes” to one of three questions addressing asthma symptoms while an abnormal peak flow was defined as PEF less than the physician established minimum at the time of the visit. All encounters with positive questionnaires and/or abnormal peak flows were then evaluated for whether these indicators led to change in the AIT treatment plan on that particular visit. Results: 50 patients with asthma received AIT between January 2011 and July 2013. A total of 1, 694 individual visits occurred during this period, with 67 (4%) of visits having a positive questionnaire and 7 (0.4%) of visits having an abnormal peak flow. 16/67 (23%) of positive questionnaires compared to 1/7 (14%) of abnormal peak flows led to a change in the AIT treatment plan for that visit. Of note, the patient with the abnormal peak flow leading to a change in management also had a positive questionnaire during that visit. Conclusions: Assessment of asthma control impacts the course of AIT in patients presenting with symptomatic or poorly controlled asthma. Subjective assessment of asthma control in the form of a screening questionnaire is not only a more sensitive tool, but leads to a greater number of changes in management compared with PEF measurements. In our cohort of asthmatics receiving AIT, PEF measurement did not offer any benefit over a screening questionnaire without PEF when determining the management of patients presenting with uncontrolled or symptomatic asthma.

10 TIME TO TREATMENT FOR PEDIATRIC ASTHMA EXACERBATIONS AT RISK OF HOSPITAL ADMISSION IS IMPROVED THROUGH UTILIZATION OF A STANDING ORDER SET. M.E. Breslin*1, A.G. Miller2, R. Vandrick2, L. Pineda2, J. Fox2, 1. Los Angeles, CA; 2. Durham, NC. Background: A triage nurse initiated standing order set (SOS) was implemented in our pediatric emergency department (PED) after data revealed inadequate compliance with evidence-based guidelines for initial treatment. We hypothesized the SOS would reduce time to initial treatment for pediatric asthma patients at risk of hospital admission (defined by patients who received both bronchodilators and systemic corticosteroids). Methods: Patients were identified from a search of electronic records for patients with known asthma aged 2 to 17 years, who were evaluated in our PED. The SOS was implemented on 2/23/2012. The pre-SOS group included patients treated from 4/01/2011 to 6/30/2011, and the post-SOS those treated from 4/1/2012 to 6/30/2012. Data tracked included: time to bronchodilator treatment, time to corticosteroid administration, number of ipratropium bromide treatments, and patient disposition. Time to treatment was measured from triage to medication administration. Statistical analysis was done via Fisher’s Exact Test for categorical variables and the unpaired t-test for continuous variables. Results: Overall, 258 patients were evaluated, with a total of 137 patients (mean age 8.0 years) meeting inclusion criteria. The pre-SOS group comprised 58 patients (mean age 7.3 years) while the post-SOS group comprised 79 patients (mean age 8.5 years). Compared with patients in the pre-SOS group, post-SOS patients were more likely to receive inhaled bronchodilators within 30 minutes (31% vs. 52%, p=0.02), receive corticosteroids within 60 minutes (50% vs. 83%, p≤0.01), and receive

the recommended 3 doses of ipratropium bromide (14% vs. 37%, p≤0.01). While improvement in the mean time to corticosteroid administration (92±71 vs. 53±47 minutes, p≤0.01) was demonstrated, the improvement in mean time to bronchodilator treatment (73±92 and 51±60 minutes, p=0.09) improved but was not statistically significant. Conclusion: Implementing a SOS for acute asthma exacerbations in our PED resulted in a decreased time to inhaled bronchodilator and systemic corticosteroid administration among pediatric asthma patients at risk of hospital admission. Adherence to evidence-based guidelines for ipratropium administration was also improved.

11 INTEGRATION OF DOSE-COUNTERS INTO METERED-DOSE RESCUE INHALERS MAY REDUCE INCIDENCE OF RESPIRATORY-RELATED EMERGENCY ROOM VISITS. A. Rigazio*1, P. Buck2, M. Lepore2, A. Burden1, A. Gilchrist1, J. von Ziegenweidt1, D.B. Price1, 1. Cambridge, United Kingdom; 2. Frazer, PA. Dose counters can effectively monitor rescue inhaler usage yet are not currently integrated as standard into all metered dose inhalers (MDIs). We conducted a retrospective, comparative analysis of US claims data to estimate the impact of integrated dose-counters for rescue inhalers on incidence of respiratory-related emergency room (ER) visits. The dataset was extracted from the Clinformatics™ Data Mart retrospective claims data from an employed, commercially insured population with dependents, and included patients aged 4-64 with a diagnosis of asthma, exercise induced bronchospasm (EIB) or chronic obstructive pulmonary disease (COPD) and a first prescription of albuterol MDI with dose counter (Ventolin®) or without dose counter (ProAir® /Proventil®) between Jan 2010 – Sep 2011 and two years continuous data (one year baseline, one year outcome). A zero-inflated Poisson model including identified baseline confounders (respiratory-related ER visits, diagnosis of gastroesophageal reflux disease, diagnosis of rhinitis, use of short acting muscarinic antagonists, use of beta blockers, inpatient admission and asthma consultations) was used to compare incidence of respiratory-related ER visits (ER visit plus any lower respiratory ICD-9 code) between the cohorts during outcome year. An unadjusted, zero-inflated Poisson regression model was also used to compare incidence of respiratory-related ER visits and asthma-related ER visits (ER visit plus ICD-9 code for asthma, EIB or COPD with asthma) made by patients diagnosed with asthma only. After adjusting for baseline confounders (as above) the incidence rate of respiratory-related ER visits in the total population was estimated to be 45% lower in the dose counter cohort compared with the non dose-counter cohort (Table 1).Likewise, in the asthmaonly sub-group, the unadjusted incidence rate of respiratory-related and asthmarelated ER visits during the outcome year were estimated to be 55% and 56% lower respectively in the dose-counter cohort (Table 1). Integrated MDI dose counters for rescue inhalers are associated with a reduced incidence of respiratory-related ER visits in the real world setting, most likely due to a reduced risk of sub-therapeutic dosing or entire therapy depletion. Table 1: Incidence rate of ER visits

12 A REVIEW OF PEDIATRIC ASTHMA DEATHS IN NORTH CAROLINA, 1999-2011. K.C. Gilbert*1, W.A. Gower1, K.L. Ragan2, M.C. Mirabelli3, E.W. Gower1, 1. Winston-Salem, NC; 2. Raleigh, NC; 3. Atlanta, GA. Introduction: Asthma is the most common chronic disease of childhood; however, it is rarely fatal. Asthma deaths are generally considered preventable, especially in children, who typically do not have comorbidities. Previous stud-



ABSTRACTS: CONCURRENT SESSIONS ies have evaluated potential risk factors such as demographics and time of year. The purpose of this study was to evaluate both previously described and new risk factors, such as obesity. Methods: We compiled a retrospective case series using information from the North Carolina Office of the Chief Medical Examiner. We reviewed cases of fatal asthma in children ages 1-18 from 1999-2011 to assess the current state of asthma fatalities. Results: Out of 24 pediatric asthma deaths across North Carolina, 22 were black (92%), and 13 were male (54%). Ages ranged from 15 months to 17 years with an average age of 9 years. Deaths were distributed evenly across the four seasons. Twenty-two of the deaths occurred at home, while one occurred at school and one at a hospital. Detailed autopsy findings were available for 20 cases. Only one of these 20 decedents had a BMI above the 95th percentile; one additional case had a BMI above the 85th percentile. The majority mentioned mucus plugging, hyperinflation of the lungs, eosinophils and thickening of the basement membrane. However, 4 reports specifically mentioned that mucus plugging was not observed. Approximate time from symptom onset to death was available for 12 cases. Four cases noted symptom onset within one hour of the death. Of these 4 cases, 3 mentioned the lack of mucus plugging. Conclusions: Black children were substantially overrepresented in this case series. Findings are consistent with data from the 2007 CDC North Carolina state profile, which reported asthma prevalence and ageadjusted death rates nearly twice as high for black individuals as for whites. Surprisingly, obesity was not common among the decedents.

13 FACTORS ASSOCIATED WITH INITIATION OF INHALED CORTICOSTEROIDS IN ASTHMATICS DISCHARGED HOME FROM A PEDIATRIC EMERGENCY DEPARTMENT. C. Word*1, C. Cochran2, S. Adams3, M.O. Titus3, J.R. Roberts3, A.L. Andrews3, 1. Charlottesville, VA; 2. Chicago, IL; 3. Charleston, SC. Introduction:Children with asthma seen in the emergency department (ED) have low rates of inhaled corticosteroid (ICS) use and outpatient follow-up. The ED is an optimal setting to initiate ICS and possibly reduce subsequent ED visits in children with asthma. Our objectives were to determine current rates of ICS prescribing at ED discharge and identify factors associated with higher rates of ICS prescribing. Methods:We conducted a retrospective chart review of a random sample of patients ages 2-18 yo with a primary diagnosis of asthma discharged home from our pediatric ED between 7/11 and 6/12. For patients who did not report ICS as a home medication, we determined whether or not ICS was prescribed at discharge. The primary outcome variable assessed was initiation of ICS at discharge. Additional variables assessed included age, race, insurance, initial asthma severity score and number of albuterol treatments given. Bivariate analyses utilized chi-square tests to determine association with current ICS use and ICS initiation. Logistic regression models identified patient and clinical variables associated with the initiation of ICS at discharge. Results:Of the 198 charts analyzed, 76% of patients were African American (AA), 14% Caucasian, 58% between 2-6 yo (mean 6.6 yo), and 66% insured with Medicaid. Forty-one percent of patients reported ICS as a home medication. Bivariate analysis showed patients ages 2-6 yo were less likely to be on ICS at presentation (31% v. 52% ages 7-12 yo v. 60% ages 13 and up, p<0.05). Race and insurance type were not significantly associated with being on ICS at time of presentation. ICS therapy was initiated on 17% of patients not on ICS at time of presentation. Bivariate analysis showed Caucasian patients were more likely to be initiated on ICS at time of discharge (40% v. 13% for AA v. 0% for Hispanic/Other, p<0.05). Age and insurance type were not significantly associated with initiation of ICS at time of discharge. When controlling for age and severity, Caucasian patients were significantly more likely to have ICS initiated at time of discharge (OR 4.4, 95% CI 1.3-15.1). Conclusions:A low percentage of children with persistent asthma were prescribed ICS at time of ED discharge. These results reveal significant room for improvement in the delivery of preventative asthma care in the acute setting.


14 INTERIM RESULTS FROM A RANDOMIZED, CONTROLLED TRIAL OF REMOTE MONITORING OF INHALED BRONCHODILATOR USE ON ASTHMA CONTROL AND MANAGEMENT. R. Merchant*1, R. Inamdar2, R. Quade3, D. Van Sickle4, J.E. Marcus4, M. Maenner4, M. Patmas1, 1. Woodland, CA; 2. Sacramento, CA; 3. San Francisco, CA; 4. Madison, WI. Background: Remote monitoring of the use of inhaled bronchodilators has the potential to improve self management of asthma and provide physicians with a new perspective on disease control. This report summarizes interim results, as measured by frequency of rescue inhaler use, from an ongoing clinical trial. Methods: Patients at two health care facilities in California are enrolled in a randomized, controlled trial, with allocation stratified by type of insurance, language (Spanish or English) and level of asthma control. Intervention group participants receive inhaler sensors and feedback through smartphone apps and online interfaces, while control group patients are outfitted with sensors but do not receive feedback. Physicians can monitor the status of their patients in the intervention group, but not those in the control group, and receive notifications if a patient is worsening. Results: At one year, a total of 382 patients had been enrolled and followed for 114 person-years altogether (median time in study = 110 days, IQR: 37-176 days). The age of participants ranged from 5-80 years old at enrollment with a mean of 35.33 years. Thirty two percent of participants were publically insured (155), while approximately 68 percent held some form of private insurance (237). At enrollment, the mean number of rescue medication events per week did not differ (p=0.70) between control (3.23 ±5.60) and intervention (3.09 ±6.07) groups. A mixed model regression reveals that the average person in the control group used their rescue inhaler 20 times more through week 30 than the average person in the treatment group (p = 0.036). Participating physicians report identification of patients requiring treatment adjustments and improved efficiencies in clinical care. Conclusions: Remote monitoring of rescue inhaler provides information valuable to guide and improve self-management, and help physicians identify patients who need more attention to get the disease under control. Subsequent analyses will investigate any effects on healthcare utilization.

15 SALIVARY MICRORNAS AS BIOMARKERS IN ASTHMA. F. Ishmael*, A. Roff, T. Craig, E. Rael, J. Howrylak, G. Ghaffari, Hershey, PA. Background: There is a crucial need for non-invasive biomarkers in the diagnosis and characterization of asthma. MicroRNAs (miRNAs) are small, non-coding RNAs that are found in many bodily fluids, and have been shown to be novel biomarkers in a variety of diseases. Our aim was to determine whether miRNAs in saliva could be used as biomarkers in asthma. Methods: After IRB approval, saliva was collected from non-allergic, non-asthmatic subjects (n=13), patients with allergic rhinitis (n=18) and patients with allergic rhinitis and asthma (n=22). MiRNAs were isolated by guanidium hydrochloride, phenol-chloroform extraction, reversed transcribed using a poly-A addition and 3’adaptor system, and analyzed by quantitative real-time PCR. Expression of 32 miRNAs was profiled and Wilcoxon Rank Sum testing was used to determine significance (p < 0.05). Results: Four miRNAs, Let-7A, miR-92b, 330-5p, and 200b were expressed at a higher level (>2.5 fold increase, p<0.05) in saliva of asthmatics as compared to patients with allergic rhinitis or nonallergic subjects. There was no difference in expression observed between patients with allergic rhinitis and non-allergic subjects. Expression of Let-7A was positively correlated with lung function (FEV1% predicted) in asthmatics, with a Person Coefficient of 0.4, p=0.038. Expression of miR-200c was increased in both asthma and allergic rhinitis as compared to non-allergic controls, indicating that it is a marker of allergic disease not asthma. An in silico analysis of the four miRNAs that were differentially expressed in asthma indicated a predilection for regulation of cytokine and other inflammatory mediator signaling. Let-7A was specifically predicted to regulate Th2 cytokines and TGF-b pathway regulation. Using novel binding assays and reporter assays, we demonstrated that Let-7A binds to- and regulates IL-13 and the TGF-b receptor 1. Conclusions: miRNAs are differentially expressed in saliva in asthmatics and have potential to be used as biomarkers in the diagnosis and characterize asthma. Differentially expressed miRNAs regulate inflammatory mediators and may have therapeutic potential.







Introduction: At least 70% of smokers visit a physician each year, providing key opportunities for intervention. Research suggests that physician intervention has the potential to increase long-term cessation rates to 30% from 7% in adult smokers attempting to quit on their own. 66% of primary care physicians and fewer specialists had tobacco related discussions with smokers. Despite this evidence, physicians often fail to ask about smoking status or advise smokers to quit. The aim of this study was to assess the effectiveness of adding a smoking status checklist to the physician chart in prompting physicians to increase the number of times they ask and advise patients about smoking related issues. Method: All asthmatic patients attending the asthma/allergy clinic at an inner city hospital based clinic were included. Exclusion criteria included the inability to answer the survey due to an emergent medical illness and active psychiatric illness. A 6 question checklist addressing smoking behavior and willingness to quit was distributed in the allergy/asthma clinic from Jan-March 2013 and reviewed for completion. Results: During the baseline monitoring period, 4% of patients had their smoking status assessed. 91 patients were seen, 35 checklists were completed. During week one there was a 41% completion rate, which decreased to 17% the following week. The drop in completion rate between the first and second week may have been due to an increase in patient volume. Simple reminders to complete the checklist did not improve completion rates. During the second week we asked the discharge nurse to review the chart prior to discharging patient and put the checklists aside. During the third week we noticed the triage nurse had forgotten to put the checklist in some of the charts. During the final week, the checklists were then placed near the nursing station the triage nurse remembered to put the checklist in the chart 53% of the time. Conclusion: Assessing an asthma patient’s smoking status is paramount to optimal care of this chronic disease. In general this project demonstrates the difficulties in implementing what should be a relatively simple measure- a smoking checklist. Possible solutions include putting a marker or reminder on each asthma patient’s chart or having regular meetings with the nursing staff and physicians and residents that are rotating in each clinic.

17 INCREASE IN THE DURATION AND INTENSITY OF COTTONWOOD SEASON OVER THE PAST 15 YEARS IN THE MIDWESTERN US. S. Anvari*, C. Barnes, P. Dowling, M. Dhar, J. Portnoy, Kansas City, MO. Rationale: Eastern Cottonwood (Populus deltoides) is the state tree of Kansas. Cottonwood trees prefer to grow along the banks of rivers, streams and lakes and are exceptionally tolerant of flooding, erosion and flood deposits filling around the trunk. Cottonwood trees are known to produce abundant pollen in the early spring and can be a sensitizing agent for many allergic persons. To evaluate the relationship of cottonwood pollen release, rainfall and the length of the cottonwood pollen season, we conducted the following. Methods: Between February and May of 1998 through 2013, cottonwood pollen was collected daily using a Burkard device mounted atop a 5 story building in Kansas City. Pollen grains were collected on glass slides coated with silicone grease and counted every 4 hours. The slides were stained with Calberlas stain and counted using the twelve vertical traverse method. Weather data was available from an Automated Weather Station mounted adjacent to the collector. Data was entered into an Access database and values were analyzed using Excel. Results: Total yearly cottonwood counts for the 15 year period ranged from 156 to 1488. The length of time cottonwood pollen was collected from the air ranged from a minimum of 11 days in 2002 to a maximum of 46 days in 2009. A positive correlation was observed between annual cottonwood totals and the length of cottonwood season (R = 0.41). The earliest first day of cottonwood season was observed on February 10, 2008 and the latest final day was on May 29, 2008. There has been a trend for cottonwood season to begin earlier in the past few years. When observing annual cottonwood totals, there was no significant correlation between rainfall either for the previous year or for the first part of the current year. Cottonwood pollen has increased during the last 5 years even though there was no significant association with rainfall patterns. Conclusion: Overall, cottonwood pollen release appears to be increasing in the Kansas City area. Our data demonstrates that this is correlated with the number of days cottonwood is seen in the air and a trend for earlier and longer yearly observations in the cottonwood season in recent years. Furthermore, our data shows that cottonwood pollen release does not appear to be influenced by rainfall patterns.

Introduction: Exposure to high concentrations of indoor airborne particles is known to affect several disease states, including asthma. Many indoor mold species are also linked to such conditions.To explore the relationship of total airborne particles and total airborne spores in indoor environments we conducted the following study. Methods: Data on indoor particle estimations and indoor spore counts was collected from basements in 53 homes in a major Midwestern city. Other rooms were excluded due to possible confounding effects of outdoor air. An ARTI particle counter produced estimates of airborne particles in 6 ranges from 0.3 mm-10 mm. For our study, we focused on particles sized 0.5, 5, and 10 mm.Airborne spores were collected for 10 minutes onto a silicon grease coated glass slide using a Buck Bioaire sampler operating at 15 liters a minute. Spore counts were log transformed to produce a more Normal distribution. Pearson’s correlation coefficients were computed in Microsoft Excel. Results: High particle counts ranged from 17,470 to 845 per cubic meter. High spore counts ranged from 72, 951 to 68 spores per cubic meter of air. As one would expect, Aspergillus/Penicillium spore counts strongly correlated with total spore counts (r=0.949). In addition, the best correlations were between total particle counts and total spore counts as well as total particle counts andAspergillus/Penicillium spore counts. Notable correlations were also seen between total spores and particle counts in the 5 mm range, Ascospores and particle counts in the 5 mm range, and Aspergillus/Penicillium spores and particles in the 0.5 mm range. Conclusion:Aspergillus/Penicillium spores can be prevalent enough to influence not only total spore levels but also total particle counts in indoor air.

19 FACTORS ASSOCIATED WITH NEGATIVE HISTAMINE RESPONSE FOR PENICILLIN ALLERGY SKIN TESTING IN THE INPATIENT SETTING. B. Geng*, A. Thakor, L. Finkas, E. Clayton, S. Vangala, M. Riedl, Los Angeles, CA. Identification of factors adversely affecting diagnostic utility of allergy skin testing is important in optimizing patient care. Our inpatient penicillin (PCN) skin test data from 1997-2007 demonstrates up to 20% of attempted PCN skin tests are indeterminate due to negative histamine control despite exclusion of H1-antagonists. Critical illness, pressors, steroids, and psychotropic medicines have been postulated to influence skin test outcomes but large studies are lacking. We conducted IRB approved retrospective case control study to evaluate factors potentially associated with negative histamine response. From our 20102012 inpatient PCN skin test records 52 cases were identified with negative histamine response despite exclusion of H1-antagonists up to 72 hours prior to testing. 125 controls with normal histamine response were randomly selected from same population of inpatient skin test records. Independent variables assessed in both groups included ICU status during/prior to skin test, use of pressors, H2-blocker, steroids, other immunosuppressives, thyroid replacement, proton-pump inhibitors, diuretics, psychotropic medicines and amiodarone. Bivariate analysis showed odds ratio (OR) for ICU status and unresponsive histamine skin test as 6.46 [3.13-13.3], but statistically insignificant OR for all other variables. OR for Amiodarone 2.47 [0.98-6.23] and H2-blocker 2.66 [0.947.52] trended towards significance. Logistic regression showed OR for ICU status 10.64 [4.24-26.0] and steroids 3.38 [1.24-9.19] as significantly associated with lack of histamine response. Counter-intuitively OR for immunosuppressives 0.165 [0.04-0.67] was negatively associated with lack of histamine response. Mean age for cases was 68 vs. 60 years for controls (p=0.002). Bivariate and logistic regression analyses support ICU admission during/prior to skin test as associated with high OR of negative histamine response rendering test invalid. Steroids are associated with significant OR of negative histamine response. Older age may play role in degree of histamine response. OR for H2-blockers and amiodarone trended towards significant association with negative histamine response. This is one of the largest studies on factors associated with negative histamine skin test in the inpatient setting and has significant implications for clinical practice.








The interaction of atopy and airway inflammation in asthma is multi-factorial. Many studies regarding this association have been done, but few have been able to pinpoint specific clinical relationships. We attempted to study a specific allergen common to our population and environment and its effect on specific markers of airway inflammation. A retrospective chart review of atopic asthmatic children who had a documented history of dust mite sensitivity by history and prick skin testing was performed. A total of 127 children (83 males, 44 females) with a mean age of 8 years had the following clinical indices analyzed: exhaled nitric oxide (FeNO), serum eosinophils, total IgE, wheal and flare sizes of prick skin test (PST) results for dust mites (Der p1 and Der f1), and indoor allergen dust sampling (MARIA) collection for Der p1 and Der f1. Results showed a positive correlation between Der p1 dust samples and FeNO was statistically significant (rho=0.4760, *p<0.0001). Moreover, positive correlations with both Der p1 and Der f1 wheal and flare sizes on PST and FeNO were statistically significant (rho=0.4080, *p<0.0004). Correlations were found between FeNO and serum eosinophils and total IgE, respectively (rho=0.3798, *p<0.001). No correlation was found between Der f1 dust samples and FeNO (rho=0.0881, p=0.4432 NS). The means of the following clinical indices were FeNO = 30 ppb, serum eosinophils = 6%, total IgE = 656 IU/ml, indoor allergen samples of Der p1 + Der f1 = 42.95 ng/ml. All of the clinical indices were elevated as expected since the children were all atopic asthmatics. These results show for the first time in the literature that there is a correlation between Der p1 and Der f1 wheal and flare sizes on PST and FeNO. Additionally, correlations found between indoor allergen dust samples of dust mite and FeNO support findings from previous studies, but the novelty was that it came entirely from Der p1 and not Der f1. This finding elucidates an allergen trigger (Der p1) that increases the airway inflammation measured by FeNO in atopic asthmatic children.

Introduction: Dust mite have a recognized role to induce or exacerbate the skin damage related with atopic dermatitis (AD). Sublingual allergen immunotherapy (SLIT) has proven to be clinically effective in children with selected allergic entities, but its effects in AD remain controversial. Our aim was to compare the clinical effect of SLIT vs. placebo in the severity of AD in children sensitized to D. pteronnyssinus (the dust mite species with the highest prevalence in our setting). Methods: We designed a double blind, placebocontrolled clinical trial in children (age range 4-10 year old) attending a tertiary referral hospital with moderate to severe AD and monosensitized to D. pteronnyssinus who were randomized to receive either a specific SLIT or sublingual placebo during a 12-month period. The main outcome variable was the change in SCORAD index score respect to baseline (Δ SCORAD). Statistics: Mann-Whitney U to continue variables, Wilcoxon to paired variables, chi-square to categorical variables. Results: 68 patients were recruited, (34 allocated to receive SLIT and 34 placebo). Sociodemographic and clinical characteristics were similar in both groups at baseline. The drop-out rate was (9%) in the SLIT group and (18%) in controls. Clinical variability of the severity of AD showed statistical differences both in inter-group (Δ SCORAD -18.4±6.5 in the SLIT group vs. -6.6±4.1 in the placebo group, p=0.008) and the paired intra-group comparisons (p=0.02 in SLIT group, p=0.1 in the placebo group). This clinical effect expressed in the SLIT treated group was greater in patients with former severe AD. Complementary analysis showed than ITSL group needed significatively less rescue medications than the controls. The calculation of the necessary number of patients to treat in order to gain benefit from the intervention was 1.7, CI 95% =1.2-2.6. Conclusions: Our results show significative improvement related to a 12-month SLIT program to D. pteronnyssinus in terms of severity of AD in mite-sensitized children.

21 SEASONAL ADMINISTRATION OF RUSH IMMUNOTHERAPY IS NOT A RISK FACTOR FOR SYSTEMIC REACTIONS. M.E. Kuruvilla*, M. Alvares, D.A. Khan, Dallas, TX. Background: Seasonal administration of pollen immunotherapy is thought to exacerbate systemic reaction (SR) rates, secondary to incremented allergen exposure. This phenomenon should then be more pronounced in patients undergoing rush immunotherapy (RIT), due to increased pollen exposure during the initial visit, and early rise in specific IgE during buildup. Objective: To determine SR incidence and severity with seasonal RIT administration of pollens. Methods: A case-control study based on retrospective review was conducted by analyzing charts of patients who underwent pollen containing RIT. Treatment was initiated with one day rush protocols, with buildup to maintenance over the next 8 weeks, and SR documented for this duration. Controls received similar RIT protocols without SR. The primary endpoint was SR incidence with pollen RIT during periods of elevated counts. Average pollen counts surrounding 8 week buildup were determined. For patients with SR, significant correlation was based on elevated pollen counts, if that pollen was contained in the RIT extract. Also, for those patients who developed SR on the day of RIT, pollen counts on that day were compared with those on the day of RIT in controls. Results: Data from 171 patients were collected, with SR noted in 71 (41.5%) patients. On day one of RIT, SR occurred in 17 (9.9%) patients. Over the subsequent 8 weeks of buildup, 54 (31.5%) patients experienced a total of 63 reactions. The majority of these reactions were mild, and there was no relationship between severity and elevated pollen counts. Seasonal administration of pollen containing RIT was not a risk factor for SR. There was no significant difference between reactors and controls when analyzed by high, moderate and undetectable pollen counts. Similarly, no correlation was detected between seasonality and SR rates during RIT and post-RIT, respectively. Neither was an increased frequency of SR observed during one particular season. Conclusion: SR during and after RIT do not appear to be associated with specific pollens or seasonal exposure. Periods of high pollen counts should therefore not preclude the initiation of respective immunotherapy.


23 PHASE I STUDY OF JRC-LAMP-VAX, A DNA IMMUNOTHERAPY VACCINE TO TREAT JAPANESE RED CEDAR ALLERGY. L. Weiner*1, T. Heiland2, B. Mackler3, D. Fitzpatrick4, B. Hearl2, A. Anagnostou2, 1. Isle of Palms, SC; 2. Rockville, MD; 3. Bethesda, MD; 4. Honolulu, HI. A Phase I study was conducted with a DNA vaccine, (JRC-LAMP-Vax), containing the sequence of CryJ2 allergen from (JRC), Japanese Red Cedar and (LAMP) Lysosomal Associated Membrane Protein. Subjects, including previously sensitized Japanese expatriates in Hawaii, were assessed for safety. IRB/HAC approval was obtained and all subjects were consented in English/Japanese. Group 1 contained non-sensitive and Groups 2 & 3 sensitive patients, defined by +/- skin test to JRC allergen. All subjects received 4 doses at 14 day intervals. Groups 1 and 3 received full doses (each 4mg/1ml) and Group 2 received a half dose (2 mg/0.5ml). Safety data through 132 days after the 1st vaccination showed 85% mild adverse events (AE’s), mainly injection site erythema, swelling and pain, the majority occurring in Group 3. The remaining 15% mild AE’s were mild fatigue events. No events required medication or medical attention. JRC-LAMP-Vax did not remarkably change the IgE/IgG levels relative to baseline. At all six time points, subjects tested negative for anti-LAMP antibodies. These data suggested the vaccine was safe. At 132 days, the skin prick tests (Greer Pik) indicated that JRC-LAMP-Vax converted 10 of 12 subjects’ JRC positive skin test reactions to negative. This pattern was also seen in 6/11 Mountain cedar skin test positive conversions to negative. These subjects presumptively were sensitive to the Jun a2 allergen, 91% homologous to CryJ2. The most striking observation at Day 132 was the skin test reactions to unrelated allergens-Southern Grass, Western Ragweed, Southern California Tree Mix and Dust Mite Mix. In Groups 2 & 3, 10/17 patients with positive skin tests to these unrelated allergens at Day 0 converted to negative. The nonJRC sensitive subjects had no skin test conversions. These skin test conversions from positive to negative at day 132 for allergens unrelated to JRC possibly represents a general T cell response due to the DNA vaccine. The Phase I clinical data and laboratory results support the conclusion that vaccination with JRC-LAMP-Vax is safe. The majority of AE’s were mild skin injection reactions, primarily in the high dose /Group 3. The conversion of 21 patient JRC/MC


ABSTRACTS: CONCURRENT SESSIONS skin tests to negative suggests that the DNA-LAMP vaccine modulated the immune system.

ylase message to 191.1±14.9% and 227.4±28.8%, respectively (P<0.05, n=3). High concentrations of IL-33 (20 and 50ng/ml) reduced efflux protein expression to that of untreated cells while doubling expression of scavenger receptors CD36, LOX-1 and CXCL16 versus control cells (P<0.05, n=3). These changes contributed to increased oxLDL accumulation and at 50ng/ml IL-33, ox LDL reached 155.7±8.8% above control (P<0.05, n=5). Blocking of the IL-33 receptor abrogated IL-33-induced alterations in gene expression, confirming an IL33 receptor-dependent mechanism for observed changes in cholesterol metabolism. Conclusions: We have demonstrated a dose-dependent effect of IL-33 on the expression of ABCA1, CXCL16, CD36 and LOX1. The effect is mediated through the IL-33 receptor. High concentrations of IL-33 relevant to those observed in AP plasma resulted in a switch from an anti-atherogenic to a proatherogenic state. Such changes could support the development of a pro-atherogenic profile in macrophages that may be improved with treatment.



THE EFFECT OF ALLERGY IMMUNOTHERAPY ON THE ATOPIC STATUS OF OFFSPRING - A SURVEY STUDY. B. Todd*, Q.T. Tran, P. Lieberman, J. Lieberman, Memphis, TN. Introduction: Recent studies have suggested that tolerance following allergy immunotherapy (IT) may be associated with epigenetic alterations. In addition, trans-generational epigenetic inheritance suggests that certain epigenetic alterations can cause persistent phenotypes across generations. Therefore, we performed a pilot study to determine if an association exists between IT in mothers and allergic disease status in offspring. Methods: We performed a survey study of women ages 18-48 with a physician diagnosis of allergic rhinitis who are followed in a single outpatient allergy clinic. Anonymous surveys assessing IT history and the presence of allergic disease in each biological child were randomly mailed to 800 women matching the above criteria. Data were analyzed using Chi-square, Wilcoxon, and multiple logistic regression analysis. Results: Of the 800 surveys sent out, 192 were returned. A total of 277 children (median age 11, 54.2% male) from 143 mothers were analyzed. In the univariate analysis, treatment with IT while pregnant was not associated with the prevalence of allergic disease in the offspring. When analysis was made using a logistic regression model, controlling for confounding variables (breastfeeding, gender, presence of older siblings, and father’s allergic status) there was a non-statistically significant trend suggesting decreased rates of any type of allergy in a child if the mother was receiving IT while pregnant (odds ratio 0.84, 95% CI 0.38-1.84) or had received IT before pregnancy (OR 0.83, 95% CI 0.49-1.43). These trends were supported by the expected, but non-statistically significant associations of decreased rates of any type of allergic disease in children who were breastfed (OR 0.70, 95% CI 0.40-1.22), decreased rates of any type of allergic disease in children with older siblings (OR 0.73, 95% CI 0.44-1.20), and increased rates of any type of allergic disease in children whose fathers have allergies or asthma (OR 1.38, 95% CI 0.81-2.36). Conclusion: When the data was controlled for a number of confounding variables, non-statistically significant trends suggested that IT in mothers could be associated with decreased rates of allergic disease in offspring.

PARENTAL DIETARY FAT INTAKE ALTERS OFFSPRING MICROBIOME AND IMMUNITY. I.A. Myles*, N.M. Fontecella, B.M. Janelsins, P.J. Vithayathil, J.A. Segre, S.K. Datta, Bethesda, MD. Mechanisms underlying modern increases in prevalence of human inflammatory diseases remain unclear. The hygiene hypothesis postulates that decreased microbial exposure has, in part, driven this immune dysregulation. However, dietary fatty acids also influence immunity, partially through modulation of responses to microbes. Prior reports have described the direct effects of high fat diets on the gut microbiome and inflammation, and some have additionally shown metabolic consequences for offspring. Our study sought to expand on these previous observations to identify the effects of parental diet on offspring immunity using mouse models to provide insights into challenging aspects of human health. To test the hypothesis that parental dietary fat consumption during gestation and lactation influences offspring immunity, we compared pups of mice fed either a Western diet fatty acid profile or a standard low fat diet. All pups were weaned onto the control diet to specifically test the effects of early developmental fat exposure on immune development. Pups from Western diet breeders were not obese or diabetic, but still had worse outcomes in models of infection, autoimmunity, and allergic sensitization. They had heightened colonic inflammatory responses, with increased circulating bacterial lipopolysaccharide (LPS) and muted systemic LPS responsiveness. These deleterious impacts of the Western diet were associated with alterations of the offspring gut microbiome. These results indicate that parental fat consumption can leave a “lard legacy” impacting offspring immunity and suggest inheritable microbiota may contribute to the modern patterns of human health and disease.

25 PARADOXICAL EFFECT OF IL-33 ON CHOLESTEROL HOMEOSTASIS IN THP-1 HUMAN MACROPHAGES. T. Mucci*, M. Littlefield, A. Reiss, S. Carsons, L. Fonacier, I. Voloshyna, Mineola, NY. Introduction: IL-33 in plasma of atopic patients (AP) is elevated to 10 times that seen in healthy control (HC). Our group has previously demonstrated that human recombinant IL-33 and AP plasma alters cholesterol homeostasis in human macrophages. However, the role of IL-33 in cholesterol transport and accumulation is unclear. The current study assesses the specific effects of human IL-33 on cholesterol transport proteins and oxidized low density lipoprotein uptake (oxLDL) in THP-1 human macrophages. Methods: THP-1 macrophages were incubated ± 1:500 dilution of human anti-IL-33 receptor-blocking antibody (3h), followed by 18h incubation ± 1, 10, 20, 50 ng/ml of human IL-33 (each condition in triplicate). Following incubation, total RNA was isolated. Expression level was determined by QRT-PCR for cholesterol efflux proteins ABCA1 and 27-hydroxylase, and for cholesterol uptake proteins CD36, LOX1, SRA1 and CXCL16. Expression was normalized to the housekeeper gene, GAPDH. (Dil)-oxLDL (Intracel, Frederick, MD) uptake was analyzed by fluorescence microscopy. Data were analyzed by one-way ANOVA with Bonferroni correction. Results: IL-33 at 10 ng/ml augmented ABCA1 and 27-hydrox-



ABSTRACTS: CONCURRENT SESSIONS Significant Laboratory Associations with CVID Lung Disease


27 ASSOCIATION OF LABORATORY TESTS WITH RADIOLOGIC FINDINGS IN CVID LUNG DISEASE. P.J. Maglione*, J. Overbey, C. Cunningham-Rundles, New York, NY. Introduction: Lung disease complicates CVID in 28.5 - 58% patients depending on the population studied. Once established, CVID lung disease does not appear to be improved by immunoglobulin (Ig) replacement therapy, imparts marked morbidity and mortality, and is difficult to treat. Radiologic changes can precede clinical symptoms, and earlier recognition may be beneficial. High resolution computed tomography (HRCT) of CVID lung disease demonstrates bronchiectasis, emphysema, hilar adenopathy, and/or nodular changes. We examined whether laboratory test values were associated with pulmonary radiologic findings in CVID. Methods: Retrospective chart review and statistical analysis was performed for 33 subjects with CVID who had HRCT of the chest as part of their medical care. All HRCT scans in the electronic medical record were included, not all were initial scans. Mean laboratory measurements of IgG, IgA, IgM, WBC, leukocyte and lymphocyte subjects calculated over 3 consecutive years were examined. Statistics were calculated using Chi-square analysis or Fisher’s exact test. All patients were on Ig replacement therapy for at least 3 years. RESULTS: Patients with T cells <800/ul were more likely to have radiologic evidence of bronchiectasis (72% vs 30%, p < 0.05) or >4 nodules (76.9% vs 40%, p < 0.05). Hilar lymphadenopathy was more common in patients with <1% switched memory B cells (57% vs 10%, p <0.05). B cells > 100/ul was associated with emphysematous changes (83% vs 36%, p = 0.06), as was IgA >6 mg/dl (p = 0.06). IgG, IgM, neutrophils, monocytes, eosinophils, and basophils did not have significant associations with radiologic findings. Conclusions: In CVID patients on Ig replacement who had HRCT as part of clinical care, selected laboratory tests are associated with pulmonary radiologic findings. Significantly lower T cell counts were associated with bronchiectasis and nodular disease. Hilar adenopathy was more common in those with fewer switched memory B cells. Interestingly, elevated B cell numbers and IgA levels trended with emphysematous changes. Evaluation of peripheral T cells, total and switched memory B cells, and IgA may be useful in identifying CVID patients who should have HRCT of the chest to evaluate for lung disease. Moreover, T cell and switched-memory B cell lymphopenia, as well as residual B cell activity, may contribute to the pathology of CVID lung disease.


Introduction: Several gene defects, including ICOS, BAFF-R, and TACI have been observed in patients with common variable immunodeficiency (CVID). Intracellular calcium plays a critical role in lymphocyte functions. The objective of the study is to report extensive immunological analysis of the first case of CVID associated with interstitial microdeletion of chromosome 1q42.142.3 and a novel deficiency of inositol tris-phosphate kinase β (ITPKβ), the later plays an important role in intracellular calcium homeostasis. Methods: Seven different subsets of B cells, expression of ICOS, BAFF-R and TACI, regulatory T cells, and naïve, central, and effector memory CD4 and CD8 were measured with specific antibodies and flow cytometry. T cell proliferative response to mitogens and antigens, cytogenetic and FISH analysis, PCR for ITPKβ, and oxidative burst by flow cytometry were analyzed. This study was approved by the Institution Review Board. Results: Diagnosis of CVID was confirmed by low serum IgG and IgA, and poor specific antibody response to pneumococci. B cell subset analysis revealed increased transitional B cells, marginal zone B cells, CD21low, and IgM memory B cells. Natural antibody producing B1 cells were normal. Naïve CD8+ T cells were decreased and CD45RA+ effector memory CD8+ T cells were markedly increased. ICOS expression on T cells and BAFF-R expression on naïve and memory B cells was normal; however, TACI expression on naïve and memory B cells was reduced. CD4+ (CD25+FoxP3+) and CD8+ T regulatory cells were normal. Number of NK cells reduced and PMN oxidative burst was impaired. Mitogen and antigen responses were low. ITPKβ expression was low, and cytogentic and FISH analysis revealed interstitial microdeletion of chromosome 1q42.1-42.3. Conclusion: Chromosome 1q42.1-42.3 region carries gene encoding for ITPKβ, Therefore, microdeletion of this region associated with deficiency of ITPKβ may be responsible for impaired intracellular signaling resulting in B and T cell defects in CVID.

29 TARGETED GENE THERAPY IN THE TREATMENT OF X-LINKED HYPER-IGM SYNDROME (XHIM). C.Y. Kuo*, A.V. Joglekar, D.B. Kohn, Los Angeles, CA. Background: X-linked hyper-IgM Syndrome is characterized by absent IgG, IgA, and IgE with normal/elevated IgM due to defects in the CD40 ligand (CD40L) gene. To date, hematopoietic stem cell transplantation is the only curative modality, but it carries significant risks and is often not considered until there is uncontrolled disease, suggesting that alternative methods of treatment should be addressed. Previous studies using gene therapy for XHIM with a constitutively expressed CD40L transgene in mouse models resulted in abnormal lymphoproliferation. Alternatively, targeted genome modification to repair defective CD40L genes may be a safe and effective method that provides definitive treatment. Hypothesis: An alternative approach to uncontrolled viral-mediated gene addition is the use of targeted gene repair. Our hypothesis is that TAL effector nucleases (TALENs), which can target specific DNA sequences and create double-strand breaks (DSBs), combined with the effective delivery of homologous donor sequences serving as repair templates can allow homology directed repair of DSBs with correction of the genetic mutation rather than error prone non-homologous end-joining. This will ultimately result in physiologic expression of the endogenous CD40L gene. Methodology/Results: Three custom TALEN pairs targeting the 5’ untranslated region (UTR) of the CD40L gene have been developed. Using a surveyor endonuclease assay (Cel-1), allelic disruption was demonstrated in a dose dependent fashion in up to 31% of K562 cells using TALEN pair 1, 9.2% using pair 2, and no activity with pair 3. K562 cells were then electroporated with the two functional TALEN pairs and a donor template homologous to the 5’UTR and Exon 1 of the CD40L gene but containing a single base pair change that introduces a unique EcoRV restriction


ABSTRACTS: CONCURRENT SESSIONS enzyme site. PCR amplification of genomic DNA from this region demonstrated the expected EcoRV bands at 212 and 239 base pairs representing gene modification with TALEN pair 1. Future experiments will evaluate long-term efficacy of TALENs in in vitro and in vivo models of XHIM using immortalized T cell lines and humanized murine models. Significance: This approach will allow site-specific correction and physiologic expression of the endogenous CD40L gene, rather than constitutive expression from ectopically inserted CD40L transgenes, to safely provide permanent immune reconstitution.

transitioning to 20% SCIG biweekly were to improve adherence (n=1), insurance purposes (n=1), and prior product discontinuation (n=2). Two patients originally treated weekly had switched to biweekly SCIG (both 16%) due to patient or parent preference. Conclusions: Biweekly Hizentra (20% SCIG) has been effective in 6 patients with PIDD. Two patients have received highconcentration SCIG biweekly for more than 5 years. Therapeutic serum IgG levels have been maintained on biweekly 20% SCIG. These data demonstrate flexibility in dosing and the ability to individualize SCIG therapy to maintain patients long-term using biweekly administration.

30 INITIAL DATA FROM A PROSPECTIVE STUDY OF HYPOGAMMAGLOBULINEMIA IN SUBJECTS UNDERGOING LUNG TRANSPLANTATION. R. Traister*, J. Gribowicz, M. Crespo, F.P. Silveira, J. Pilewski, A.A. Petrov, Pittsburgh, PA. Introduction: While immunosuppressive therapies have led to remarkable improvements in survival in lung transplantation (LT) recipients, one adverse effect of these therapies is hypogammaglobulinemia. Retrospective studies have found increased infections in LT recipients with hypogammaglobulinemia, but prospective data is lacking. We have recently initiated a prospective study of hypogammaglobulinemia in LT recipients. Here we report our initial findings on the study population to date. Methods: This is a single center study of all LT recipients at the University of Pittsburgh Medical Center. IgG levels were collected prospectively prior to lung transplantation and 6 months after transplantation. Data were analyzed using parametric tests if either raw data or natural log-transformed data were normally distributed, or non-parametric tests if non-normally distributed. Results: To date, 125 LT recipients have been evaluated. The most common indication for transplant was IPF (n=41), followed by COPD (n=39), cystic fibrosis (n=13), and scleroderma (n=12). There were overall differences in pre-transplant and 6 month post-transplant IgG levels (p=0.0002 and 0.04, respectively), with subjects with COPD having the lowest levels in both instances (838 mg/dl and 532 mg/dl, respectively). Overall, the IgG level post-transplant was an average of 500 mg/dl lower than pre-transplant levels (p<0.0001). Though each group had significant decreases in IgG levels post-transplant, the largest decrease was observed in subjects transplanted for cystic fibrosis (-936 mg/dl). Conclusions: There were significant differences in pre- and post-transplant IgG levels, regardless of indication. The lowest IgG levels were observed in subjects undergoing lung transplantation for COPD, while the largest decrease in IgG level post-transplant was seen in those undergoing transplantation for cystic fibrosis. Future studies will examine the incidence of infections in LT recipients with hypogammaglobulinemia.

31 CLINICAL UTILITY OF BIWEEKLY DOSING WITH HIGH-CONCENTRATION SUBCUTANEOUS IMMUNOGLOBULIN IN PATIENTS WITH PRIMARY IMMUNODEFICIENCY: RETROSPECTIVE CASE SERIES. R.L. Wasserman*, J. Zidik, Dallas, TX. Introduction: Currently, subcutaneous immunoglobulin (SCIG) treatment is approved by the US Food and Drug Administration only for weekly dosing. Hizentra® (20% SCIG; CSL Behring), however, by virtue of its high concentration and consequent low volume, may facilitate less frequent SCIG administration. We conducted a retrospective chart review to describe the clinical utility of biweekly (every 14 days) administration of 20% SCIG in 6 patients with humoral primary immunodeficiency diseases (PIDDs). Methods: This was a retrospective chart review of patients with PIDD receiving 20% SCIG every 14 days from a single center that was approved by the North Texas Institutional Review Board. Results: Six patients (5 F; 1 M) aged 10–46 years (3 patients <18 y) received 20% SCIG biweekly (Table). Prior immunoglobulin (Ig) therapy included 20% SCIG weekly (n=1), 16% SCIG weekly (n=3), or 16% SCIG biweekly (n=2). All patients have received 20% SCIG biweekly for ≥15 months (current maximum 35 mo); 2 patients have received high-concentration SCIG biweekly for >5 years, including the duration of prior biweekly 16% SCIG. Monthly 20% SCIG doses ranged from 343–744 mg/kg. In the 4 patients who switched from weekly SCIG, the most current IgG levels with biweekly 20% SCIG (range 1119–1828 mg/dL) were comparable to their IgG levels with weekly SCIG (range 1272–1841 mg/dL). Only 1 patient was hospitalized for pneumonia during her >28 months of biweekly treatment; 5 patients have experienced no acute serious bacterial infections or required hospitalization. Of the 4 patients who were receiving prior weekly SCIG, reasons for

CVID=common variable immune deficiency; n/a=not available; Pt=patient.

32 MEMORY B-CELL AS A MARKER FOR COMMON VARIABLE IMMUNODEFICIENCY AND SPECIFIC ANTIBODY DEFICIENCY. A. Khojah*1, O. Alpan2, A. Bukhari1, 1. Vienna, VA; 2. Fairfax, VA. Introduction: CVID is characterized by marked decrease of serum IgG and poor antibody response to polysaccharide vaccines, while SAD (specific antibody deficiency) is characterize by poor response to polysaccharide vaccination but normal immunoglobulin G level. For SAD, diagnosis relies on measuring antibody response after vaccination. This study was conducted to evaluate B-cell markers that correlate to the diagnosis of SAD in a more expedited way, before obtaining post-vaccine titers or in cases in which post vaccination antibody response is borderline. Methods: Total of 361 subjects, evaluated in allergy and immunology clinic between 2010 -2013, were included in this study (205 adults and 156 children). We excluded patients under 2 years of age or those with known immunodeficiency other than SAD and CVID. Subjects were divided based on their diagnosis into 3 groups: SAD, CVID and Control. Clinical and laboratory data including B-cell subset were obtained from patient’s records. Data was analyzed using SPSS, version 21. Results: Fifty seven patients with SAD were included in the study. Of those, thirty patients (53%) were males and thirty three (58%) were children. CVID category included 32 patients, 18 (56%) of them were male and only 7 (22%) were children. 120 males and 153 females with normal immune workup were selected for the control group. Mean age of the three groups: SAD, CVID and control were 26.2, 43.4, and 29.7 years respectively. More than 85% of the patients in each group were Caucasian. The mean of switched memory B-cell (CD20+CD27+IgM-) was significantly lower than control in SAD (6.6 vs. 11.9, p <0.00001) and CVID patients (4.49 vs. 11.9, p <0.00001). The percentage of switched memory B-cell increased with age in control group whereas in SAD and CVID the percentage remained stable over time. We used a cut-off value of 12% for switched memory B-cells (of total B cells) as a marker to diagnose SAD and CVID. This gave a sensitivity of 92.5% and 96% respectively. In conclusion, switched memory B-cell can be utilized as a screening tool to diagnose SAD and CVID with good sensitivity.



ABSTRACTS: CONCURRENT SESSIONS patient’s episodes began to improve gradually without the use of prednisone, and at 8-week follow-up, she had reported no further episodes of fever. The spontaneous resolution of her febrile episodes coincides with previously observed reports delineating the natural history of PFAPA in children. Discussion: 19q13.32 is the gene map locus for dystrophia myotonia-protein kinase (DMPK). DMPK has been shown to interact with heat shock protein B2 (HSPB2), which interacts with TRAF6, a member of the TNF receptor associated factor protein family. This may provide a link to a distinct pro-inflammatory signaling pathway as TRAF6 mediates signal transduction in the NF-kappaB pathway, which is activated in response to pro-inflammatory cytokines. The only episodic inflammatory disorder reported to be associated with a mutation in the long arm of chromosome 19 is in one patient with systemic-onset juvenile idiopathic arthritis. Two de novo micro-duplications were found at 19q13.42, which spans the NOD-like receptor (NLRP) family and heat shock protein B1 (HSPBP1), both of which function in pro-inflammatory pathways. Conclusion: A novel mutation has been described in a patient with PFAPA with atypical clinical components. Expanded investigations are necessary to determine the relevance of this novel mutation to PFAPA pathogenesis, and to evaluate its diagnostic efficacy in association with clinical and immunologic findings.

35 IL-12RB1 DEFICIENCY PRESENTING WITH SALMONELLA INFECTION. M. Girdhar*1, T. Federly2, P. Dowling1, 1. Kansas City, MO; 2. Des Moines, IA.

33 A CASE SERIES AND GENETIC ANALYSIS OF THE CO-OCCURRENCE OF EOSINOPHILIC ESOPHAGITIS AND HYPERTROPHIC CARDIOMYOPATHY. B.P. Davis*, T. Epstein, P. Amin, L. Kottyan, M. Collins, K. Von Tiehl, J. Sherrill, J. Francoisi, P. Abonia, M. Rothenberg, Cincinnati, OH. Background and Purpose:Eosinophilic esophagitis (EoE) is a recently recognized, polygenic, chronic inflammatory disorder of the esophagus triggered by immune sensitization to food. Chest pain can be the primary symptom of EoE. Hypertrophic cardiomyopathy (HCM) is an important consideration as a cause for chest pain in young adults. We initially identified a patient with both HCM and EoE who was found to have a known HCM causing mutation in Myosin Binding Protein C3 (MYBPC3). This prompted further investigation into an association between EoE and HCM. Methods: A retrospective chart review was conducted to determine if there might be an association between EoE and HCM. Additionally, the frequency of MYBPC3 genetic variants in 562 EoE patients was compared with 9294 controls. Results:W e identified 2100 cases of EoE and 241 cases of HCM based on ICD-9 codes, out of a total of 1,279,132 patients at Cincinnati Children’s Hospital Medical Center (CCHMC). Three of patients had both EoE and HCM. Based on these numbers the odds ratio for the co-occurrence of EoE and HCM is 7.58 (95% CI= 2.43-23.70, p<0.001). There was a significant association (OR: 0.82-2.33, p value: 0.0009-0.01) of EoE with twelve SNPs in the main linkage disequilibrium block surrounding MYBPC3. Conclusion: EoE and HCM have substantial co-risk and therefore clinical suspicion for HCM should be raised in patients with EoE with persistent, unexplained chest symptoms. Further, EoE is linked with genetic variants in the MYBPC3 locus substantiating a common pathogenic mechanism between these two diseases.

34 A NOVEL MUTATION OF 19Q13.32 IN A PATIENT WITH ATYPICAL PERIODIC FEVER, APHTHOUS STOMATITIS, PHARYNGITIS, AND ADENITIS (PFAPA) SYNDROME. S. Kim*, J. Chase, J. Sheikh, B. Goldberg, M. Kaplan, Los Angeles, CA. Background: Periodic fever, aphthous stomatitis, pharyngitis, and adenitis syndrome (PFAPA) is the most common episodic febrile disease in childhood. It is characterized by recurrent bouts of inflammation in those genetically susceptible, with episodes usually resolving by 10 years of age. A recent report identified NLRP3 variants in 20% of patients with PFAPA. Mutations in various complement, IL-1-related, and IFN-induced genes have been identified during flares, yet its etiology remains unknown. Case Presentation: A novel 19q13.32 mutation, the deletion of 204 kb (kilobases), was identified by comparative genomic hybridization array in a 7-year-old girl with a 3-year history of episodic fevers (101-104F). Each flare lasted 3-5 days, and occurred every 3-5 weeks. While she had no evidence of aphthous stomatitis, pharyngitis, or adenitis, her history strongly suggested an atypical presentation of PFAPA. The


Introduction: The interferon gamma pathway is an important host defense system against salmonellae species along with tuberculous and non-tuberculous mycobacteria. In patients with an IL-12RB1 deficiency, patients are more susceptible to disseminated nontuberculous mycobacterial and Salmonella infections, and therefore patients with these illnesses require a higher level of clinical suspicion. We describe a report of a patient with an unusual presentation of Salmonella infection who tested positive for the IL-12RB1 deletion. Case History: We managed a 14 year-old boy with persistent cervical lymphadenopathy after he and his family had an episode of what was thought to be viral gastroenteritis 5 months prior to presentation. He was initially seen in hematology/oncology clinic with a normal CBC and a CT scan of the neck positive for significant cervical lymphadenopathy. He did not have any other symptoms such as fever, weight change, night sweats, rash, bone pain, joint pain, or other recent illnesses. There was no family history of severe infections or immunodeficiency. Given his persistent symptoms, he was sent for lymph node biopsy. Diagnostic Results: Lymph node biopsy results revealed chronic lymphadenitis with reactive lymphoid hyperplasia, negative for malignancy. Cultures were growing gram negative organisms: Salmonella species, group D. Suspicion was then raised for potential MSMD (Mendalian Susceptibility for Mycobacterial Disease). Genetic testing revealed that patient is heterozygous in the IL-12RB1 gene for two disease causing variants: c.1791+2T>G and c.354G>A (p.Trp118X). Assuming these variants on opposite alleles his result is consistent with a diagnosis of IL-12RB1-related susceptibility to myocobacterial and salmonella infections. He had an elevated IgG level at 4930 mg/dL and a normal T and B cell flow cytometry. Conclusion: In patients with disseminated Salmonella or nontuberculous mycobacterial infections, mutations in the gene encoding for IL-12B1 receptor have been described. Therefore, we encourage clinicians to consider this possibility in patients who present with infections of unusual presentation with either organism. M Girdhar, T Federly, P Dowling

36 PREVALENCE OF ALLERGIC DISORDERS AND MAST CELL ACTIVATION SYNDROME IN PATIENTS WITH EHLERS DANLOS SYNDROME. M. Louisias1, S. Silverman*2, A. Maitland3, 1. Boston, MA; 2. Philadelphia, PA; 3. New York, NY. Background: Patients with Ehlers Danlos Syndrome appear to have a significant prevalence of allergic disease and mast cell activation syndrome, a recurrent non-IgE mediated allergic reaction. This study aims to determine the prevalence of allergic disease and mast cell activation syndrome in Ehlers Danlos Syndrome patients. Methods: Patients with confirmed genetic diagnosis of Ehlers Danlos Syndrome were identified at an allergist’s clinical practice. Information regarding patients’ allergic rhinitis, asthma, urticaria and anaphylaxis were obtained via validated questionnaires. Chart review was also conducted


ABSTRACTS: CONCURRENT SESSIONS for review of spirometry and laboratory results, symptoms and medications. Descriptive statistics was used for analysis. Results: 6 adults (5 female, 1 male, ages 31-53) and 3 children (1 female, 2 male, ages 5-9) were included. 7 patients (78%) reported symptoms highly likely to be anaphylaxis based on clinical diagnostic criteria: acute onset of illness, either spontaneous or after exposure to a likely allergen, involving skin, mucosal tissue, hypotension, and respiratory and gastrointestinal symptoms. 7 patients (78%) had a history of asthma. All patients with a history of asthma were treated with an inhaled beta-agonist, and 44% were on an inhaled corticosteroid. 7 patients (78%) had nasal congestion over the past month, the majority with symptoms severe enough to interfere with sleep. There were no objective signs of IgE-mediated allergy in the patients who had Immunocap and percutaneous skin testing. However, all patients reported rhinitis symptoms that were controlled on some form of antimediator therapy, such as an antihistamine, mast cell stabilizer or antileukotriene. 100% of patients reported pruritus over the past month, the majority (89%) with hives/itch. Children had hives/itch more frequently in an average week than adults. 7 patients (78%) used antihistamines to control their skin symptoms. 5 patients were tested for objective evidence of mast cell activation, and all tests were unremarkable. Conclusion: Ehlers Danlos Syndrome patients appear to display non-IgE mediated allergic disease controlled by anti-mediator therapy. Some of the patients met 2 to 3 of the proposed diagnostic criteria for mast cell activation syndrome. However, none of the patients met all of the proposed criteria for mast cell activation syndrome.

37 WAY OFF BASE: A CASE OF DELAYED ASPERGILLUS OSTEOMYELITIS DIAGNOSIS AFTER A PRESUMED BASEBALL INJURY. M. Morsheimer*, G. Ram, J. Garrett, K. Sullivan, J. Spergel, Philadelphia, PA. Introduction: Chronic granulomatous disease (CGD) is a primary immunodeficiency characterized by impaired phagocyte function with susceptibility to catalase-positive organisms such as Aspergillus. The lifetime risk of fungal infections among CGD patients is estimated at 25-40%; osteomyelitis is diagnosed in 13-25%. Aspergillus is the most common cause of mortality and osteomyelitis among CGD patients. Case Description: An 8 year old baseball player with a history of CGD consulted a local orthopedist after one week of right leg, ankle and foot pain refractory to over-the-counter analgesics. Pain was temporally attributed to sliding into home base at a recent baseball game. X-ray did not reveal fracture; the limb was immobilized and ultimately casted for symptom control. Over the course of the following week the right foot became progressively swollen and left ankle pain developed. The cast was removed, left ankle immobilized, crutches issued and he was referred to immunology for an atypical response to therapy for musculoskeletal strain. Upon contact with CHOP Immunology he was urgently referred to the ED for the evaluation and treatment of presumed osteomyelitis. In the ED he was febrile to 38.6 degrees Celcius, and labs were significant for elevated WBC with left shift, ESR 26, CRP 15.2. Imaging revealed multifocal osteomyelitis involving the right metatarsal, distal left tibia; and multiple pulmonary nodules with extension through the pleura and diaphragm to the peri-hepatic, subcapsular space. Surgical I&D of the right metatarsal revealed a large abscess and cultures grew Aspergillus fumigatus. Ambisome and voriconazole were initiated and broad-spectrum antibacterial coverage stopped. Clinical and laboratory improvement was observed on antifungal therapy and mobility was recovered. He remains on a year-long treatment course of voriconazole. Discussion: Although distal osteomyelitis is a relatively uncommon finding in invasive aspergillosis, the overall risk of osteomyelitis among CGD patients is high. According to PubMed, it has been more than 20 years since an English language orthopedic medical journal published a paper reviewing osteomyelitis among CGD patients. This case highlights an opportunity for immunologists to update the orthopedic community regarding skeletal complications among this vulnerable population.

38 EARLY DETECTION AND DEFINITIVE TREATMENT OF SEVERE COMBINED IMMUNE DEFICIENCY IN CONNECTICUT. T. Rubin*1, A. Manning2, D. Chirnomas1, N. Romberg1, 1. New Haven, CT; 2. Hartford, CT. Introduction: Clinical outcomes for patients with Severe Combined Immune Deficiency (SCID) are dependent upon early detection and timely initiation of hematopoetic stem cell transplantation. Case Description: The patient, a non-

syndromic African American male infant, is the only product of the union of an unrelated man and woman, identified on day 10 of life by newborn screening as having undetectable T cell receptor excision circles (TRECs). The diagnosis of T-B+NK+ SCID was confirmed on day 11 of life by flow cytometry. T cell lymphopenia was severe (51 CD3+ cells/ul). The few circulating T cells that were present did not proliferate to mitogen stimulation, and although they were primarily memory cells they were not maternal in origin. A molecular diagnosis was sought first through direct sequencing of the genes known to be associated with SCID by a commercial laboratory and then by whole exome sequencing. Neither approach identified a genetic lesion responsible for the patient’s disease. In the fourth month of life, after conditioning with fludarabine and busulfan, the patient received a matched unrelated stem cell transplant through Yale’s pediatric bone marrow transplant program. Engraftment occurred on day +20 and the patient was soon discharged to home. Reconstitution of the patients T cell compartment is followed by serial TREC enumeration in collaboration with the State of Connecticut’s Department of Public Health’s Newborn Screening Laboratory. Discussion: Our case demonstrates the importance of a regionally integrated system of universal newborn screening, appropriate pre-transplant management by a clinical immunologist and definitive treatment in a pediatric bone marrow transplant center. It also highlights the reality that 5-10% of SCID cases have no identifiable genetic cause despite recent advances in genetic analysis. Importantly, the lack of a molecular diagnosis in a patient with SCID does not preclude and should not significantly delay the initiation of life-saving hematopoetic stem cell transplantation.

39 A NOVEL MUTATION IN AN AFRICAN AMERICAN MALE WITH CHRONIC MUCOCUTANEOUS CANDIDIASIS. D.K. Jhaveri*1, J. Horbal2, J. Sterbank2, L. Chernin2, T.S. Platinga3, H. Tcheurekdjian2, R.W. Hostoffer2, 1. Cleveland Heights, OH; 2. Cleveland, OH; 3. Nijmegen, Netherlands. Background: Chronic mucocutaneous candidiasis (CMC) is a disorder that manifests with frequent episodes of candidiasis of the skin and mucous membranes. The cause of CMC is frequently unknown but STAT1 mutations have recently been identified. We introduce a novel mutation in exon 9 of STAT1 in a patient with CMC. Methods: A 19 year-old African American male with esophageal candidiasis, onycholysis, no endocrinopathy, and intact delayed type hypersensitivity responses was diagnosed with CMC in infancy. Two known generations of CMC suggested an autosomal dominant mode of inheritance of a monogenic defect. Genomic sequencing for known STAT1 mutations was normal. Whole exome sequencing was subsequently performed. Results: Whole exome sequencing identified a novel mutation consisting of an amino acid substitution from glutamine to glutamic acid at position 243 of exon 9 of the STAT1 gene. Conclusions: In past decades, patients with CMC were diagnosed on a clinical basis. Only recently have patients been able to be definitively identified with this disorder by genomic analysis. We report a novel STAT1 mutation presenting with a different CMC phenotype than previously reported with described STAT1 mutations.

40 THE SIX YEAR DERMATOSIS: CHRONIC URTICARIA DUE TO SCHNITZLER SYNDROME. A.K. Pinion*1, S. Gierer2, 1. Fairway, KS; 2. Kansas City, KS. Introduction: We describe a 48 year old male with a six year history of urticaria, polyarthralgia, fatigue, lymphadenopathy, fevers, neutrophilic urticarial dermatosis, and monoclonal gammopathy; diagnosed with Schnitzler’s syndrome, an extremely rare disorder. Case Presentation: Patient is a 48 year old caucasian male with a history of hypertension and allergic rhinitis who presented for evaluation of perennial chronic urticaria primarily involving the trunk and extremities since 2007. Lesions were warm, non-pruritic, painful, persisted for 2-3 days and resolved without sequelae. He had diffuse myalgias, arthralgias, night sweats, fever, lymphadenopathy and fatigue. He denied angioedema. No medication, environmental, food or contact triggers could be identified. Initial physical examination was normal aside from multiple urticarial lesions involving his torso and extremities. He had a history of negative aeroallergen skin testing. An SPEP with monoclonal gammopathy was noted. A skin biopsy showed significant superficial perivascular inflammation with few eosinophils. After evaluation in our clinic, he was started on and failed multiple antihistamine and immunomodulatory therapies. Due to the monoclonal gammopathy, the patient was sent to hematology and had a normal bone marrow biopsy and



ABSTRACTS: CONCURRENT SESSIONS skeletal survey. Complete chronic urticarial lab evaluation was negative, except an elevated ESR and CRP. Our dermatopathologist reviewed the outside skin biopsy, which showed perivascular mixed cellular dermatitis with frequent neutrophils with some leukocytoclasis. There was insufficient evidence of vascular injury to warrant the diagnosis of vasculitis and was suggestive of neutrophilic urticarial dermatosis. Subsequently, the patient was diagnosed with Schnitzler Syndrome. He received 4 weeks of Rituximab without improvement. Anakinra was initiated with improvement of the rash. He is transitioning to Canakinumab. Discussion: Schnitzler Syndrome is a rare disease characterized by neutrophilic urticarial dermatosis, monoclonal IgM gammopathy, arthralgia, bone pain, and elevated ESR. Patients may have palpable lymphadenopathy, fever, hepatosplenomegaly and leukocytosis. The pathogenesis is unclear, but given improvement using IL-1 receptor antagonists, an auto-inflammatory process is suspected. Patients can develop lymphoproliferative disorders, so long term monitoring is essential.


Urticarial lesions in patient with Schnitzler syndrome.


41 PARENT-REPORTED FOOD ALLERGY QUALITY OF CARE. R. Gupta*, J. Blumenstock, E. Oh, M. Sohn, Chicago, IL. Rationale: A strong relationship with care providers and high quality of care are essential to ensuring proper management of food allergy. The objective of this study was to evaluate the quality of care received by families of children with food allergy from both pediatricians and allergists. Methods: 940 families of food-allergic children were included in a family-based cohort. Food allergy was determined by objective symptoms developing within 2 hours of ingestion, corroborated by skin prick test/specific IgE. Parents were asked questions about satisfaction and quality of care. Bivariate analyses were used to describe parent reports of the quality of health services. A Mann-Whitney U test was used to compare perceived quality between mothers and fathers. Results: Satisfaction with care and trust in physicians was high. Nearly all parents reported that pediatricians and allergists treated them with courtesy and respect, listened carefully, and treated their views with respect. Most parents also reported that their child’s physicians explained food allergies in a way they could understand and reported that they showed concern for the impact of food allergy on the family. Management steps in the NIAID guidelines were also assessed. Parents reported that 36% of pediatricians and 71% of allergists explained when to use an epinephrine autoinjector. Fewer pediatricians (17%) and allergists (46%) demonstrated how to use the device. A written food allergy action plan was provided by 20% of pediatricians and 56% of allergists. 23% of parents reported that pediatricians explained their child’s long term prognosis and 61% reported the same of allergists. Mothers largely reported more pessimistic perceptions of the quality of care they received while fathers generally recalled slightly higher perceptions of physician concern for impact and explanation of food allergy (p<0.05). Overall, there was strong within family agreement on perception of healthcare quality. Conclusion: Parents of children with food allergies feel cared for and respected by their child’s doctors. Ensuring proper management of food allergy by both pediatricians and allergists is critical. Increased education in healthcare settings around recognizing symptoms of an anaphylactic reaction and how and when to use an epinephrine autoinjector are needed. A food allergy action plan and counseling of prognosis are also vital for all children with food allergy.


LOWER BASELINE COMPONENT ARA H 1/ARA H 2 RATIO PREDICTS FEWER ADVERSE EFFECTS IN SUBJECTS ON PEANUT OIT. J. Cronin*, J. Wisniewski, E. Berg, S. Commins, Charlottesville, VA. Introduction: Peanut oral immunotherapy (OIT) is an investigational yet promising approach to treating food allergies in children. However, side effects, particularly those involving the gastrointestinal system, are common. In prior peanut OIT studies, approximately 15% of subjects discontinue therapy due to persistent symptoms. Methods: Nineteen peanut-allergic subjects ages 4-19 were treated with peanut OIT. IRB approval and informed consent was obtained from all research subjects. Peanut component IgE analysis was performed on serum from each subject at the start of the study. Dosing side effects and adjunctive medications were recorded in daily symptom logs. Results: Daily symptom logs, length of the buildup phase, number of dose reductions and repetitions, and use of adjunctive medications were reviewed. Ten subjects were determined to have a low incidence of adverse effects (less than 2 days of doserelated symptoms or adjunctive medications per month; no dose reductions or repetitions). The Ara h 1 / Ara h 2 ratio for these subjects ranged from 0.02 to 0.76 with a mean of 0.31 ± 0.08. Nine subjects were determined to have a high incidence of adverse effects. The Ara h 1 / h 2 ratio for these subjects ranged from 0.02 to 2.57 with a mean of 1.02 ± 0.27. Four of the 9 subjects in the high side effects group dropped out of the study due to symptoms prior to the desensitization challenge. The average Ara h 1 / Ara h 2 ratio of those 4 subjects was 0.66. Among sibling and twin pairs, a higher ratio accurately predicts the development of adverse effects associated with OIT. Interestingly, the Ara h 1 / h 2 ratio does not appear to influence efficacy as all 15 subjects who reached maintenance dosing passed the desensitization challenge. Conclusions: In pediatric subjects treated with peanut OIT, a lower Ara h 1 / Ara h 2 ratio appears to predict fewer dose reductions, a shorter buildup phase, and fewer adjunctive medications. Using the Ara h 1 / h 2 ratio may allow for OIT escalation schedule and doses to be modified for individual participants in order to minimize symptoms.

DISSECTION OF THE IGE ANTIBODY RESPONSE TO FOODS AND INHALANTS IN ADULTS AND CHILDREN WITH EOSINOPHILIC ESOPHAGITIS. A. Tripathi*1, L.J. Workman1, P.U. Ogbogu2, H.R. James1, B.H. Barnes1, S.P. Commins1, T.A. Platts-Mills1, R.G. Hamilton3, E.A. Erwin2, 1. Charlottesville, VA; 2. Columbus, OH; 3. Baltimore, MD. Introduction: Understanding food and aeroallergen sensitivity in Eosinophilic Esophagitis (EoE) is critical for tailoring treatment. Elimination diets have been shown to improve clinicopathologic symptoms and signs, and although identification of inciting foods is difficult since skinprick testing (SPT) is often negative, re-introduction of certain foods, including milk and wheat, has been shown to cause recurrence. Presence of low IgE titers to milk, wheat, egg, soy, or peanut has been reported in these patients; however, significance of these antibodies remains unclear. Methods: Adults and children with biopsy-diagnosed EoE were evaluated with SPT and serum IgE testing to a panel of food and inhalant allergens using the ImmunoCAP (CAP) assay. To further investigate allergen component specificity, sera were evaluated with: ISAC (CAP biochip assay for 112 components), assays on dilutions of sera, and CAP assays for components of milk and wheat. Results: CAP assay analysis of sera from adults (n= 33) and children (n=46) yielded positive IgE titers to various aeroallergens and foods (with mostly negative SPT for foods) including: dust mite (24/79 patients), cat (30/79), wheat (37/79), milk (31/79), and peanut (29/79). Food allergen component testing using ISAC was generally negative whereas serial dilutions of sera (positive for foods and/or aeroallergens) analyzed by CAP gave calculated IgE titer values at up to six times the original (undiluted) value for foods tested (Fig 1). CAP assays for five milk components revealed a higher number of positive titers to minor components (> 50%); wheat component titers were positive for at least one of three components tested. For aeroallergens, ISAC component results correlated well with whole CAP assays, as did undiluted values with calculated values from serial dilution assays (Fig 1). Conclusions: Due to frequently negative skin test results, serum IgE measurements, although low for foods, may be preferential in guiding therapy in EoE. ISAC analysis suggests that the components of foods currently recognized as important allergens, may not be relevant in EoE. The dilution data provide evidence for IgE to a minor or undefined


ABSTRACTS: CONCURRENT SESSIONS component of these food allergens, which is further supported by predominance of positive titers to minor milk (and potentially wheat) allergens by component testing using CAP.

Figure 1. Calculated results on dilutions of sera from adults and children with Eosinophilic Esophagitis. As sera with specific IgE to dust mite (D. pteronyssinus) and cat dander are diluted, the value of the calculated titer of specific IgE does not change significantly from the value observed in undiluted sera. In contrast, as sera with specific IgE to milk, wheat, and peanut are diluted, the calculated values differ dramatically from the observed, undiluted values.

44 THE BALB/C MICE CAN BE USED TO EVALUATE ALLEGENICITY OF DIFFERENT FOOD PROTEIN. C. Zhou*, N. Sun, X. Zhou, L. Sun, H. Che, Beijing, China. Background: The viability of animal model to evaluate food allergenicity always in controversy and this study first verified the BALB/c oral allergy model and then investigated allergenicity of different food protein. Methods: Female BALB/c mice were i.g treated with glycinin (11S), OVA, OVM, Peanut protein extract (PPE), Cow milk protein extract (CME), potato protein extract (PAPE), saline respectively and then compared specific antibody, mMCP-1 and histamine in different groups. BALB/c mice were oral treated with OVA on day 0, 7, 14, 21, 28, 42 (challenge) and then detected above parameters. The same protocol was used to evaluate allegenicity of PPE, CME and PAPE. Beside above the intestinal lymph node (LN) and spleen cells were extracted to detect proportion of Th1, Th2 population and secretion level of cytokines. Results: When mice were treated using purify protein or food protein extract once, levels of specific IgE, IgG1, histamine and mMCP-1 were not increased comparing to saline group. Mice treated with OVA appeared higher levels of OVAIgE, OVA-IgG and histamine than saline group. The specific IgG1 and IgE of animals in different groups reached the highest level on day 35 when oral administrated with PPE, CME and PAPE. Specific IgG1 level in CME treatment group was significantly higher than the other groups and also the PPE-specific IgE. The cytokine levels secreted by LN cells were apparently higher than spleen cells. IL-4 level in CME treatment group was appeared higher than PPE treatment group, and conversely the INF-γ levels. The histamine concentration in plasma of CME treatment animals was significant higher than that in control group but PPE group. And in addition, the proportion of Th2 cells in CME group was obviously higher than the other groups. Mice in CME treated group produced the strongest humoral immunity reaction, cell-mediated immunity reaction and systematic manifestation. Conclusion: Daily diet does not prime immune reaction in BALB/c mice and OVA supporting the viability of BALB/c to assess food allergenicity. Gavage of CME caused evident Th2 type allergy while PPE Th1 and Th2. Allergy reaction maybe initiates in local intestinal and then develops to whole body. These provide reference for allergy animal model system and food allergy mechanism research.

Figure 1 The key findings of this research. In the establishment of animal model, levels of specific antibody were significantly higher than control group (A). The results of IgE and IgG1 in PPE, CME and PAPE treated groups were shown in B. The proportion of Th1 and Th2 cell population were appeared in the C (Th1 type) and D (Th2 Type).

45 THE CHARACTERISTICS OF CHILDREN REFERRED FOR FOOD ALLERGY: DIFFERENCES IN DIAGNOSIS, WORK-UP AND TREATMENT. B.J. Pelz*, K. Rychlik, R.G. Robison, Chicago, IL. Background: Food allergy is a growing public health concern. As no current therapy exists for food allergy, patients must practice allergen avoidance and promptly treat severe allergic reactions with epinephrine. Front line providers play an essential role in the prescription of auto-injectable epinephrine. Objectives: To determine whether patients referred to a tertiary care allergy clinic for evaluation of a food allergy were prescribed an epinephrine autoinjector at the time of the referral and what factors influence whether an epinephrine autoinjector was prescribed. Methods: A retrospective chart review of children who were referred for a new visit for evaluation of possible food allergy at a tertiary care center was performed. IRB approval was obtained. General demographic data, the implicated foods, symptoms at the time of the reaction, location of the initial evaluation, family history, previous work up, and provision of an Epipen were collected. Chi square tests and logistic regression analyses were performed. Results: Forty-two of 149 patients (28%) were prescribed an Epipen. 65% of referrals came from primary care offices and 27.5% from emergency departments (ED). Reactions to peanut, tree nut, and shellfish had a statistically significant higher likelihood of receiving an epinephrine auto-injector prescription (p values = 0.024, 0.021, and <0.001, respectively). Children who presented with vomiting or with shortness of breath were statistically more likely to receive an epinephrine auto-injector prescription (p=0.005 and 0.033, respectively). A logistic regression model demonstrated that reactions to tree nut, presentation with vomiting, or initial presentation to the ED all were statistically significant predictors of having an epinephrine auto-injector prescribed. Conclusions: Many children referred for



ABSTRACTS: CONCURRENT SESSIONS evaluation of food allergy have not been prescribed life-saving epinephrine auto-injectors. Children with reactions to tree nuts, vomiting, and initial presentations in the ED are more likely to receive epinephrine auto-injectors prior to evaluation by an allergy specialist.

46 POSITIVE ORAL FOOD CHALLENGES DESPITE NEGATIVE SERUM SPECIFIC IGE LEVELS AND SKIN PRICK TESTING. H. Mehta*1, J. Lieberman2, A. Nowak-Wegrzyn1, 1. New York, NY; 2. Memphis, TN. Background: Double-blind, placebo-controlled oral food challenges (OFC) remain the gold standard for diagnosis of food allergy, however open OFC are often offered instead in the outpatient setting due to factors such as cost and time. Negative skin prick testing in addition to serum specific IgE have a high negative predictive value. However despite these results, patients may react, rarely with severe systemic reactions. Objective: To present a case series of 8 children with allergic reactions after an open OFC with negative SPT and food serum specific testing. Cases: During a retrospective chart review of all open OFCs performed at our institute from August 2008 to May 2010 we identified 7/132 positive challenges with negative SPT of 0/0 and serum food specific IgE <0.35 kUA/L. The ages of these children ranged from 23 months to 7 years (median 4.58 years). Risk factors such as asthma and the presence of multiple food allergies were not identified. 2/8 of these patients had never ingested the challenged food, whereas the other 6 had prior reaction histories. The reactions have ranged from mild cutaneous symptoms to systemic reactions, however none required epinephrine. Since these findings we have recently identified a patient with walnut specific IgE <0.35 kUA/L and SPT 0/0 that developed a severe reaction requiring epinephrine. GM is a 2 year old female who had her initial reaction to walnut when she developed oral erythema after ingesting a walnut cookie at 20 months of age. During the OFC she vomited after her first dose of approximately 1/2 of a walnut. She subsequently developed repetitive vomiting and abdominal distention 1.5 hours into the observation period and received epinephrine. Though it is unclear if this episode was an IgE mediated systemic reaction verses a non IgE reaction such as food protein induced enterocolitis the patient required medical attention and treatment. Conclusions: We describe 8 cases of positive open OFC with negative SPT of 0/0 and serum food specific IgE <0.35 kUA/L. In the outpatient setting OFC can be effective in establishing tolerance and is often offered once the testing and clinical history suggests low risk. Though an open OFC is generally considered safe, it should be undertaken in the allergist’s office with trained medical professionals who can quickly identify reactions and treat if deemed necessary.


sensitization were frequently associated with shrimp allergy, and asthma may be a potential risk factor for anaphylactic reactions to shrimp in children. The rate of anaphylaxis to shrimp in our pediatric cohort was lower in children than a previously reported adult population. Prospective studies with doubleblind placebo-controlled food challenges are needed to further characterize the clinical characteristics in adults and children with shrimp allergy.

48 CELL MODELS IN VITRO FOR EVALUATING THE POTENTIAL ALLERGENICITY OF FOODS AND NOVEL PROTEINS. N. Sun*, C. Zhou, X. Zhou, L. Sun, H. Che, Beijing, China. Background: An in vitro functional test system, based on the activation and mediator release of effector cells, can detect the potential of allergens to elicit an IgE-mediated allergic reactions, on which the nonfunctional immunochemical methods cannot provide any information. Therefore, this study aimed to develop an in vitro cell model for the determination of the biological activity of food allergens. Methods: Female Balb/c mice (3-wk-old) were orally sensitized once or 5 times with Glycinin (Gly), ovalbumin (OVA), or potato acid phosphatase (PAP). Allergen-specific IgE and IgG1 antibodies, histamine and vascular permeability were determined. Rat basophilic leukaemia (RBL) cells passively sensitized with pooled mouse sera were triggered by exposure to ranging concentrations of proteins. Subsequently, the experimental parameters were optimized including the dilution ratio of sensitized serum, the allergen concentrations, time course of degranulation, and cell culture time. Results: Oral exposure of Balb/c mice to Gly, OVA or PAP once exhibited no significantly increased responses in allergen-specific IgE and IgG1 antibodies, plasma histamine levels and vascular permeability when compared to saline-sensitized mice, indicated that the Balb/c mice model was available for obtaining the sensitized serum pool and detecting the allergenicity of proteins. Our results with the RBL-2H3 release assay are in agreement with the observations of the Balb/c mice model, suggesting higher allergenic potential of Gly (57% degranulation of β-hexosaminidase, EC50=0.954nM) compared with OVA (38% degranulation, EC50=8.88nM) and almost no allergenic potential of PAP (8% degranulation, EC50=21.8nM). However, 10% or less β-hexosaminidase release occurred with RBL-1 cells. With all the allergens, RBL-2H3 cells sensitized with these sera that only contain 100-200ng/ml of total IgE, degranulated optimally upon exposure to a 10-100ng/ml of purified allergens. The 45-60 min time point was chosen as the optimal time course of degranulation and the prolongation of the culture time had no effect on the intensity of the degranulation. Conclusion: The RBL-2H3 cells, but not RBL-1 cells, form the basis of a useful model system for evaluating the potential allergenicity of foods and novel proteins and for the futher research on the signalling pathway of IgEmediated mast cell degranulation.

SHRIMP ALLERGY PRESENTATION AS ANAPHYLAXIS IS RARE IN CHILDREN. N. Chokshi*, Z. Maskatia, S. Miller, C. Davis, Houston, TX. Background: The prevalence of shellfish allergy is 1.3% in the United States with shrimp most commonly reported. Shellfish is the third most commonly implicated food in anaphylactic reactions. The rate of anaphylaxis in children with shellfish allergy is 21%. There are no reported rates of anaphylaxis specifically to shrimp in children. In our adult cohort with shrimp allergy, the incidence of anaphylaxis was 44%. Despite the high prevalence and rate of anaphylaxis to shrimp, there is limited literature regarding the demographics, clinical presentation, risk factors, and differences between children and adults in anaphylaxis risk. Methods: Retrospective chart review of children 0-18 years of age with shrimp allergy presenting to Texas Children’s Hospital Allergy and Immunology Clinic over 7 years (2002-2009). Results: Seventy-seven patients were identified with shrimp allergy (61% male, 39% female) with a median age of diagnosis at 56 months (range: 3 months to 16.7 years). Angioedema was the most common presenting symptom (22.1%), followed by eczematous reactions or hives (16.9%). The rate of anaphylaxis was 7.8%. Past medical history of asthma was identified as the clinical characteristic most likely to be associated with an anaphylactic reaction (p=0.052). In this group of pediatric shrimp-allergic patients, 44.2% had dust mite sensitization and 18.2% had cockroach sensitization. Twenty-two percent of patients had negative shrimp-specific IgE. Patients with positive shrimp sensitization (positive IHST and/or shrimp specific IgE) often had dust mite sensitization (65.4%) and cockroach sensitization (26.9%). Conclusions: In this large tertiary center, the majority of pediatric patients with shrimp allergy presented with mild to moderate reactions with angioedema and or cutaneous symptoms. Dust mite and cockroach


49 COMPARISON OF CHROMOGENIC AND ENZYME-LINKED IMMUNOSORBENT ASSAY (ELISA) TESTING METHODS OF FUNCTIONAL C1 ESTERASE INHIBITOR (C1 INH) IN DIAGNOSING HEREDITARY ANGIOEDEMA (HAE). H. Li*1, P. Busse2, W.R. Lumry3, T. Steele4, H. Levy4, J. Dayno4, M. Riedl5, 1. Chevy Chase, MD; 2. New York, NY; 3. Dallas, TX; 4. Exton, PA; 5. Pacific Palisades, CA. Introduction: Measuring functional C1 INH with chromogenic or ELISA assays can confirm a diagnosis of HAE. Previous studies have found differences in the sensitivity and specificity of these assays. The objective of this


ABSTRACTS: CONCURRENT SESSIONS analysis was to evaluate the concordance between these two assays in the context of an observational study. Methods: US subjects with confirmed diagnoses of HAE (index subjects) underwent functional C1 INH testing. These subjects contacted first-degree relatives (parents, siblings, or offspring) who had not been previously diagnosed with HAE (general subjects), and they underwent a panel of complement testing, including functional C1 INH activity. Functional C1 INH activity testing with the ELISA method (Quidel® Corporation, USA) was conducted at LabCorp (Burlington, NC); testing using the chromogenic method (DiaPharma®, USA) was conducted at National Jewish Medical and Research Center (Denver, CO). Protocol was IRB-approved; subjects provided written informed consent. Results: In total, 31 index subjects and 46 general subjects enrolled. Of 46 general subjects, 14 (30%) were newly diagnosed with HAE based on their lab test results. Overall, there was strong concordance between the results of the ELISA and chromogenic methods (Table). Among the 31 index subjects, 22 (71%) were categorized as having low functional C1 INH in both tests. However, 9 (29%) index subjects, all with confirmed HAE, had normal or equivocal functional C1 INH test results according to the ELISA method, while having low functional C1 INH levels according to the chromogenic assay. In the 14 newly diagnosed subjects, 11 (79%) were reported to have low functional C1 INH using both test methods; 3 (21%) had equivocal ELISA results and low chromogenic results. One general subject for whom HAE was ruled out had a low functional C1 INH level according to the chromogenic assay but a normal level according to the ELISA method (C1 INH antigen and C4 levels were normal). Conclusion: The chromogenic assay correctly identified subjects with confirmed diagnoses of HAE as having low C1 INH functional levels, but the ELISA method miscategorized some subjects. The rates of discordance between the two assays among the index subjects were similar to that of the newly diagnosed general subjects. Concordance of chromogenic and ELISA methods for functional C1 INH testing


ELISA Method results were categorized as follows: <41% of Normal or ‘None Detected’ as Low, 41-67% of Normal as Equivocal, and >67% of Normal as Normal. b Chromogenic Method results were categorized as follows: <74% of Normal as Low and ≥74% of Normal as Normal.

50 REDEFINING TOTAL AND PEAK RAGWEED POLLEN SEASON FOR THE PRACTICING ALLERGIST. K. Schmidlin*, K. McWhorter, A. Kelley, L. Levin, A. Smith, Cincinnati, OH. Rationale: Currently the peak and onset of a pollen season is identified retrospectively. The objective of this study is to develop a real-time method to define total and peak short ragweed (RW) pollen season to guide clinical practice. Methods: Ragweed pollen counts were collected over 27 years and used for analysis. Weekday morning pollen counts were collected using a Rotorod sampler during a 24-hour period, counted, and reported in grains/m3 air. The start of RW season was defined as the first occurrence of a 3-day mean count ≥10 grains/m3 and the end as the first occurrence of a 3-day mean count <10 grains/m3. This approach was compared to the retrospective approach of the first of 3 consecutive days with counts >10 grains/m3 and the last day of the last occurrence of 3 consecutive days >10 grains/m3. Peak day was defined as the highest raw value. A 5-day mean from Monday thru Friday was calculated, with the highest 5-day mean defined as the peak week of pollen season. Means and standard deviations were calculated and compared using t-tests. Results: Using the 3-day mean approach, the start and end dates were August 14±3 days and September 26±3 days. The total average RW season was 43±7 days and included 93.5±3.2% of the total RW pollen catch. These results were not significantly different from the 3 consecutive day method. The average peak day was September 1±6.4 days. Peak week occurred 3.1 weeks±1 day after the start date and captured the peak day for that year 63% of the time. Over the 27 years, once the peak week had been reached, RW levels tended to decline until the

end of the season without another substantial increase (>50% of the peak week value). Conclusions: The real-time method of using a 3-day rolling mean to define pollen season is comparable to the retrospective 3 consecutive day method and could be used for starting seasonal medication or adjusting immunotherapy dosing. Peak pollen interval can be defined using a 5-day mean. The week that yields a 5-day average below the preceding week’s average can be defined as the post-peak week. Peak week is defined as the week preceding this decline. Future directions of this study include applying this method to other regions and determining the clinical value of defining peak and total pollen season in real-time.

51 PREVALENCE OF DIAGNOSED AND UNDIAGNOSED HEREDITARY ANGIOEDEMA (HAE) IN FIRST-DEGREE BLOOD RELATIVES OF KNOWN SUBJECTS WITH HEREDITARY ANGIOEDEMA. M. Riedl*1, W.R. Lumry2, P. Busse3, T. Steele4, H. Levy4, J. Dayno4, H. Li5, 1. La Jolla, CA; 2. Dallas, TX; 3. New York, NY; 4. Exton, PA; 5. Chevy Chase, MD. Introduction: Hereditary angioedema (HAE) is a rare autosomal dominant disease characterized by recurring attacks of nonpruritic, nonpitting edema caused by an inherited deficiency or dysfunction of C1 esterase inhibitor (C1 INH). Symptoms can present years before an accurate diagnosis. The objective of this study was to determine the prevalence of diagnosed and undiagnosed HAE in first-degree blood relatives of known US subjects with HAE, as well as the clinical manifestations of HAE in these relatives. Methods: Subjects with confirmed diagnoses of HAE (index subjects) recruited first-degree relatives (parents, siblings, or offspring) who had not been evaluated for HAE (general subjects). General subjects were enrolled in the study, and blood samples were taken for complement testing (C4, C1 INH antigen, functional C1 INH). If the lab tests were consistent with a diagnosis of HAE, the general subjects returned to the site for a follow-up visit and questionnaire; if not, their study participation was complete. Protocol was IRB-approved; subjects provided written informed consent. Results: Overall, 31 index subjects enrolled in the study (mean (SD) age 35.8 (2.46) years); 24 (77%) were female, and 25 (81%) were Caucasian. Forty-six first-degree relatives of the index subjects enrolled in the study as general subjects. The mean (SD) age of general subjects was 25.9 (15.63) years; 25 (54%) of general subjects were female, and 42 (91%) were Caucasian. Of 46 general subjects, 30 (65%) had lab test results that ruled out a diagnosis of HAE, 2 (4%) were categorized as “HAE not ruled out,” and 14 (30%) were newly diagnosed with HAE. Among these 14 subjects, the mean (SD) age was 13.9 (4.18); 8 subjects (57%) were 11 years of age or less. Of 14 newly diagnosed subjects, 9 (64%) reported having experienced symptoms in the past that may have been related to HAE, such as swelling in the throat, face, or extremities or abdominal pain. These 14 subjects reported a historic mean (SD) rate of 2.51 (5.59) swelling episodes per month with a mean (SD) duration of 1.6 (0.74) days. Conclusion: In previously unevaluated, undiagnosed first-degree relatives of subjects with HAE, 30% were newly diagnosed with HAE. This finding reinforces the importance of testing families of subjects with HAE in order to detect this hereditary disease.

52 DAPSONE FOR THE TREATMENT OF CHRONIC URTICARIA: A REVIEW OF SAFETY, EFFICACY AND REMISSION RATES. J.M. Sher*, P. Naik, M.R. Aquino, M. Davis-Lorton, L.S. Fonacier, Mineola, NY. Rationale: Allergists are increasingly facing the difficult challenge of treating antihistamine-resistant chronic urticaria. There is limited data regarding alternative treatments such as dapsone for antihistamine-resistant chronic urticaria. This study aims to demonstrate the efficacy and adverse effect profile of dapsone for the treatment of patients with chronic urticaria resistant to conventional therapy. Methods: A retrospective chart review of 70 patients with chronic urticaria was performed. Of these patients, 21 were treated with dapsone. All patients treated with dapsone had previously failed high-dose antihistamine therapy. Clinical response (complete, partial and no response) to treatment was assessed at 1,2,4,6,8,12,16 and 20 weeks. When available, laboratory tests and skin biopsies were reviewed. The causes for discontinuation of therapy were evaluated. Results: Partial to complete response was seen in 20/21 (95%) patients. Ninety five % of patients were female and the mean age was 46.17 ± 19.52 years (mean ± SD). 19 of 21 patients had a skin biopsy which



ABSTRACTS: CONCURRENT SESSIONS showed neutrophilic infiltrates. Responses were typically seen in the first week [p=0.03]. Complete response was seen in 13/20 (65%) and partial response in 7/20 (35%) patients. Mean time to complete response was 7.10 weeks on 75100mg daily. By week 12, 9/21 (42.8%) patients had stopped secondary to side effects and 2/21 (9.5%) were lost to follow-up. In patients who discontinued therapy, 6/9 (66.7%) were partial responders, 2/9 (22.2%) were complete responders, and 1/9 (11.1%) had no response. The most common adverse effects noted were anemia (38%) and myalgias (9%). Interestingly, 33.3% (4/12) of patients maintained remission after discontinuing dapsone for an average of 9.33 ± 5.02 months (mean ± SD). Conclusion: A majority of this cohort demonstrated a robust response to treatment with dapsone, as early as one week. However, the use of dapsone was limited by its adverse effect profile, specifically anemia. Overall, adverse effects were mild and resolved with discontinuation of therapy. A subset of patients experienced prolonged maintenance of remission after discontinuation of dapsone.

to-treat (mITT) population. At baseline, the mean (SD) weekly ISS was 14.3 (3.5) and the UAS7 score was 31.1 (6.6). For all three omalizumab doses, a statistically significant difference from placebo in mean change from baseline in weekly ISS at week 12 was observed (all P<0.002; Table). All nine secondary endpoints were met for the 300-mg dose, P<0.0001. The incidence of adverse events (AEs) during the 24-week treatment period was between 57% and 69% in the omalizumab groups and 51% in the placebo group. Most AEs were considered mild or moderate in severity. Overall, the incidence of serious AEs in omalizumab groups was low (0-3%). Conclusions: Omalizumab treatment significantly improved symptoms in patients with refractory CIU/CSU when used as add-on therapy. A dose-response relationship with omalizumab was observed. For all the efficacy endpoints, the 300-mg omalizumab group demonstrated greatest efficacy relative to the placebo group at week 12. Compared with the known safety profile of omalizumab, no additional safety issues or concerns were identified.

53 CHRONIC URTICARIA – THE SASKATCHEWAN EXPERIENCE AND QUESTIONNAIRE SURVEY. N. Gattey*, B. Bahrani, P. Hull, Saskatoon, SK, Canada. Chronic spontaneous urticaria (CSU) is defined as urticaria persisting for more than 6 weeks with no inducible cause. An autoimmune basis is held responsible for more than half the cases. Many cases have no identifiable cause. 179 patients with CSU had been seen between 2003 and 2013. There were significantly more females than males (132:47). The age range was 1 year to 81. The mean age was 36 years. The average duration was 8.5 years. An autologous serum skin test (ASST) was performed on 138 patients and was positive in 57 (41.3%). A questionnaire and informed consent, approved by the Research Ethics Office, was sent to patients and replies were received from 105 participants. We were unable to contact 25 patients, and 2 patients had died. Of the respondents, 40 were ASST positive and 47 were ASST negative participants. 55.0% of ASST (+) participants and 46.8% of ASST (-) participants no longer had hives. 21 ASST positive patients who had significant quality of life issues were treated with intravenous immunoglobulin (IVIG), and 95.2% of these patients had improved quality of life with 13 of these patients now free of urticaria and no longer receiving IVIG. Patients were most bothered by pruritus, disturbed sleep, anxiety and their physical appearance including facial swelling. Many (70.4%) had missed work or school because the urticaria. The majority of patients felt that over the counter antihistamines were useful in disease control although prednisone as prescribed by emergency room physicians and family practitioners were added in about a fifth of the patients. In conclusion, about 40% of patients may have chronic spontaneous urticaria caused by autoimmunity as assessed by the ASST. IVIG was an effective treatment for this group of patients.

54 EFFICACY AND SAFETY OF OMALIZUMAB IN H1-ANTIHISTAMINE-REFRACTORY CHRONIC IDIOPATHIC/SPONTANEOUS URTICARIA: RESULTS OF A PHASE III RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED TRIAL. S.S. Saini*1, C. Bindslev-Jensen2, M. Maurer3, J.J. Grob4, E. Bulbul Baskan5, M.S. Bradley6, P. Georgiou7, O. Alpan8, S. Spector9, K. Rosen6, 1. Baltimore, MD; 2. Odense, Denmark; 3. Berlin, Germany; 4. Marseille, France; 5. Bursa, Turkey; 6. South San Francisco, CA; 7. Horsham, United Kingdom; 8. Fairfax, VA; 9. Los Angeles, CA. Background: Many patients with chronic idiopathic urticaria/chronic spontaneous urticaria (CIU/CSU) remain symptomatic despite H1-anthistamine treatment. This 40-week (24-week treatment, 16-week follow up), global, Phase III, double-blind, placebo-controlled study evaluated the safety and efficacy of add-on therapy with omalizumab, an anti-IgE antibody, in patients with H1antihistamine-refractory CIU/CSU. Methods: CIU/CSU patients aged 12–75 years who remained symptomatic (Urticaria Activity Score over 7 days [UAS7] ≥16 and itch component of UAS7 ≥8 during the week prior to randomization) despite standard-dose H1-antihistamines were randomized (1:1:1:1) to receive a total of 6 doses of omalizumab (75, 150 or 300mg) or placebo administered subcutaneously every 4 weeks. The primary efficacy endpoint was change from baseline in weekly itch severity score (ISS) at Week 12. Nine secondary efficacy endpoints and safety were also evaluated. IRB approval and informed consent was obtained from all research subjects. Results: A total of 318 patients with a mean (SD) age of 41.2 (14.5) years were included in the modified intent-


DLQI, Dermatology life quality index; ISS, itch severity score; MID, minimally important difference (MID=5 for ISS) Scores are mean (SD) unless otherwise stated. *P<0.05, **P<0.002, ***P<0.0001 vs. placebo

55 VIRTUAL PATCH TESTING: DATA DRIVEN EMPIRIC CONTACT ALLERGEN AVOIDANCE. J.A. Yiannias*1, R. el-Azhary2, 1. Scottsdale, AZ; 2. Rochester, MN. Introduction: Many patients cannot afford the time or money for patch testing. Moreover, as a nation, we are working to moderate health care costs. While patients with specialized jobs or hobbies may have specific allergen exposures that are difficult to empirically avoid, why hypothesize that a large portion of lay patients could successfully avoid the allergen triggering their eruption with patch test data driven avoidance education. Traditional patch testing may be able to be avoided with this “virtual patch testing.” Methods: After Institutional Review Board approval, we reviewed the results of the 8348 standard series patch tests that were performed at our institution from January 2000 to December 2011. We identified the twelve most commonly positive allergens overall, as well as the top eight allergens found in skin care products. Results: 4422 (53.0%) of patients were allergic to one of the twelve most commonly positive allergens including metals and skin care product allergens. 3110 (37.3%) had at least one positive to our eight most common skin care product allergens. Conclusion: Nearly 40% of patients with contact allergy skin care product allergy could successfully avoid their allergens with “virtual patch testing” based on our contact allergy data. We describe and share the straightforward written and on-line tools that we use to facilitate empiric and patch test driven allergen avoidance.

56 A RETROSPECTIVE REVIEW OF HYDROXYCHLOROQUINE USE IN PATIENTS WITH CHRONIC IDIOPATHIC URTICARIA (CIU). A. Hall*1, G.D. Marshall2, 1. Abilene, TX; 2. Jackson, TX. Introduction: The proposed autoimmune pathogenesis of chronic urticaria has prompted trials of immunomodulating medications for the condition. Hydroxychloroquine offers potential efficacy for CIU with fewer short and


ABSTRACTS: CONCURRENT SESSIONS long term side effects compared with other treatment modalities. The aim of this study is to evaluate the control of symptoms in CIU patients who are placed on hydroxychloroquine therapy. Methods: The charts of 36 patients with CIU that were treated with hydroxychloroquine from January 2007 to December 2011 were extensively evaluated retrospectively. The outcome was measured based on categories of percent improvement of urticaria (no response 0-25%, partial response 25-90%, and complete response 90-100%) based on patients symptoms and perception. Results: Of the 36 patients, the median age was 48.7 years and 69% were female. 13/36 (36%) patients were started on hydroxychloroquine 200 mg qday. Of those 13 patients, 7 were increased to BID therapy due to lack of a complete response after a median time of 4 months. 23% (3/13) had a complete response at the first follow up visit at an average of 4.7 months (range 3-8 months). 5/13 had a partial response and 5/13 had no response. Of the patients started on hydroxychloroquine 200mg BID, 43% (10/23) had a complete response at the first follow up visit at an average of 3.1 months (range 1-5 months). 7/23 had no response and 6/23 had a partial response. Overall 13/36 (36%) patients had a complete response at the first follow up visit which was at an average of 3.1 months (range 1-8 months). Eventually 26/36 (69%) patients achieved complete control at an average of 7 months (range 1-24 months). 9/36 (25%) had no response and 1/36 continued to have a partial response. The one patient with a partial response was only followed for 2 months after initiation of hydroxychloroquine 200mg BID and then lost to follow up. Of the 9 patients with no response, 5 were treated with another immunomodulating drug (cyclosporine, tacrolimus or methotrexate) after an average of 5.4 months. The other 4 were not followed for longer than 6 months after initiation thus their ultimate response was not determined. Conclusion: A longer course of hydroxychloroquine may be considered before it is deemed a treatment failure. Demographics

itive 27% of the time. Positive tests for ragweed peaked during weeks 32-35 but were also quite high in weeks 23-27. A specific IgE test for ragweed performed during ragweed season (weeks 31-40) was significantly more likely to yield a positive result than a test performed during the early part of the year (weeks 2-11). Conclusion: Although the test is performed throughout the year, the probability of having a positive result for ragweed is higher when aeroallergens are in the air and highest when airborne ragweed is present. Further investigation is needed to delineate the clinical significance of this finding.

58 ALCAFTADINE 0.25% VERSUS OLOPATADINE 0.2% IN THE PREVENTION OF OCULAR ITCHING IN ALLERGIC CONJUNCTIVITIS. E.B. McLaurin*1, N.P. Marsico2, J.B. Ciolino3, J.M. Williams4, D.A. Hollander4, 1. Memphis, TN; 2. Los Angeles, CA; 3. Boston, MA; 4. Irvine, CA. Purpose: To compare the efficacy, at 16 hours post dose, of the once daily anti-allergic, alcaftadine 0.25% with that of olopatadine 0.2% and both with placebo in preventing the ocular itching of allergic conjunctivitis. Methods: This double-masked, randomized, multicenter, 3-arm (alcaftadine 0.25%, olopatadine 0.2%, or placebo) study used the Conjunctival Allergen Challenge (CAC™) model. The primary efficacy measure was subject-evaluated ocular itching 16 hours post dose at 3 minutes post allergen challenge. Secondary measures included proportion of subjects with minimal itching (score<1) or zero itching (score=0) and percent distribution of itching scores. IRB approval and written informed consent from all research subjects were obtained. Results: A total of 156 subjects completed the study. At 16 hours post dose and 3 minutes post CAC™, subjects treated with alcaftadine had a significantly lower mean itching score than olopatadine (p=0.008). A significantly greater proportion of alcaftadine-treated subjects achieved minimal itch (itch score <1) as well as zero itch (itch score =0) vs olopatadine (Figure). At 3 minutes post CAC™, subjects receiving alcaftadine or olopatadine achieved significantly lower mean ocular itching scores vs placebo (p<0.0001). A significantly greater proportion of both alcaftadine and olopatadine-treated subjects achieved minimal itch and zero itch vs placebo (Figure). There were no treatment-related adverse events or serious adverse events during the course of the study. Conclusion: Alcaftadine 0.25% ophthalmic solution demonstrated greater efficacy with regard to ocular itching compared to olopatadine 0.2% in a CAC™ model at 16 hours post dose. Alcaftadine and olopatadine provided highly effective relief versus placebo. Both treatments were safe and well tolerated.

57 VARIATION IN THE FREQUENCY OF POSITIVE SPECIFIC IGE TEST RESULTS FOR RAGWEED IN RELATION TO AIRBORNE RAGWEED LEVELS. M. Reddy*, C. Dinakar, C. Barnes, Kansas City, MO. Rationale: Ragweed is a major sensitizing allergen in the Midwestern United States. Airborne ragweed typically appears in mid-August, achieves highest concentration in early September and has mostly disappeared by mid-October. Allergy testing may be performed using in-vitro techniques. We compared the relationship between frequency of positive ragweed specific IgE test results and the presence of airborne ragweed pollen. Methods: Pollen was collected daily from March to November atop a 5-story building in Kansas City, Missouri. Glass slides with collected pollen were stained with Calberlas stain and examined microscopically. Pollen grains were enumerated using the 12 vertical traverse method following guidelines established by the National Allergy Bureau. Data on specific IgE testing for ragweed performed on ImmunoCap 250 was retrieved for the years 2000 to 2012 (n = 8,128 tests). A test result >0.34 kIU/L was considered positive. IRB approval and an informed consent waiver were obtained for this retrospective review of laboratory data. Results: Ragweed pollen typically appeared in week 31 (August) and was mostly gone by week 45 (November). Ragweed specific IgE testing was performed every week of the year. The mean number of allergens tested along with ragweed was 18 and the mode was 15. Ragweed specific IgE testing was performed alone less than one percent of the time. The fewest number of tests were performed during week one and week 52 when clinics were closed for holidays; the most number of tests were performed in weeks 11-21 during the late winter and early spring aeroallergen season. Overall, tests for ragweed were pos-






THE ALLERGIC RHINITIS CLINICAL INVESTIGATOR COLLABORATIVE–CYTOKINE PROFILING OF SYNTHETIC ABSORPTIVE MATRIX ELUATES TO OPTIMIZE A STANDARD NASAL ALLERGEN CHALLENGE PROTOCOL. A.K. Ellis*1, J. Thiele1, L.P. Boulet2, H. Vlagoftis3, P. Keith4, S. Waserman4, L.M. Steacy1, M.E. Boulay2, H. Neighbour4, 1. Kingston, ON, Canada; 2. Quebec City, QC, Canada; 3. Edmonton, AB, Canada; 4. Hamilton, ON, Canada.


Introduction: The Allergic Rhinitis Clinical Investigator Collaborative (ARCIC) is a Canadian multi-center initiative with the primary goal of performing standardized nasal allergen challenge (NAC) to study the anti-allergic effects of novel therapeutic agents for allergic rhinitis (AR). The model further allows identification of potential mechanisms of allergic disease and biomarkers. For this study we examined a multiplexed panel of 17 cytokines in synthetic absorptive matrix (SAM) eluates from nasal samples before and after direct nasal allergen challenge. Methods: Seven participants were enrolled locally for an initial Pilot study, and 8 participants in a Follow-up study with a slightly revised protocol. All participants had AR symptoms following exposure to ragweed and a supportive skin test response. Using the Pfeiffer Bidose Nasal Delivery Device 100ml ragweed solution was delivered to each nostril. Pilot study participants were challenged with a threshold dose of allergen determined via titration 1 week prior to NAC. In the Follow-up study, participants were challenged with an accumulative threshold dose that included allergen amounts received during titration up to the threshold dose. At Baseline, 1 hour (1H) and 6 hours (6H) post NAC SAM samples were collected. Cytokine profiles in all SAM eluates were determined using a Bio-Plex ProTM17-plex assay (Bio-Rad). Results: Overall, cytokine profiles appeared less variable in the Followup group compared to the Pilot, and more significant changes were observed. In the Follow-up group, ragweed NAC resulted in a significant up-regulation of IL-1b, IL-4, IL-8, MIP-1b and TNF-a concentrations at 6H post dose (P < 0.05, compared to baseline). Furthermore, IL-13 and MIP-1b levels were significantly elevated at 1H. IL-5 exhibited a strong trend towards up-regulation at 6H. GM-CSF was significantly down-regulated at 6H. IL-2, IL-10 and GM-CSF concentration were not detectable in the Pilot samples, however were measurable in the Follow-up samples. Conclusions: Significant differences were noted in the TH2-specific set of cytokines between baseline, 1H & 6H post direct NAC in participants with AR. SAM collection for cytokine analysis is a robust assay that can be integrated into clinical trials conducted using the AR-CIC.

60 BRADYKININ MEDIATES TRANSIENT RECEPTOR POTENTIAL VANILLOID 1 CHANNEL ACTIVITY ON NEURONAL MEMBRANES. J.A. Bernstein*, U. Singh, K. Jones, Cincinnati, OH. Background: Bradykinin (BK) has been implicated in allergen induced nasal hyper-reactivity mediated through transient receptor potentials (TRP) ion channels localized on neuronal cell membranes. The mechanism for BK-induced neuronal hyper-responsiveness is still unclear. The objective of this study was to further investigate in vitro the mechanistic role of BK on TRPV1 (vanilloid) ion channel activation using Cath.a sensory neuronal cells. Methods: Confocal microscopic imaging was used to investigate cytosolic changes in Ca2+ concentration, [Ca2+]i, using Cath.a cells after repeated capsaicin application with or without BK pre-treatment. The BK2 receptor antagonist, Icatibant, was used to demonstrate whether BK observed effects were specific. To determine how BK pretreatment influenced capsaicin-induced TRPV1 turnover on neuronal membranes, immunofluorescence (IF) using TRPV1 (extracellular) antibodies was performed after capsaicin treatment in BK-pretreated and BKuntreated Cath.a cells that quantified surface expression of TRPV1 in these treatment groups. Results: Capsaicin induced TRPV1 specific increases in [Ca2+]i within Cath.a cells that was attenuated after TRPV1-desensitization by repeated capsaicin application. Pre-treatment with BK revealed increased [Ca2+]i resulting in activation of TRPV1 ion channels even in the continued presence of capsaicin that was inhibited by the B2R antagonist, Icatibant. Immunofluorescence assays demonstrated an increased expression of TRPV1 on the cell surface 15 minutes after being stimulated with capsaicin in BK pretreated Cath.a cells compared to BK untreated cells. Conclusions: This data suggest that BK potentiates agonist-induced TRPV1 channel expression on neuronal membranes either by their reduced internalization or increased trafficking to the cell membranes. These findings have important clinical implications for designing specific and effective therapies targeting neurogenic nasal mucosal hyperreactive conditions such as non-allergic rhinitis.


Rationale: Beclomethasone dipropionate (BDP) nasal aerosol, a nonaqueous formulation, is approved in the United States for the treatment of allergic rhinitis (AR) in adolescents and adults and has a well-established efficacy and safety profile. Previously published results (van Bavel Allergy and Asthma Proc 2012) demonstrated that BDP nasal aerosol significantly improves nasal and ocular symptoms compared to placebo and has a similar adverse event (AE) profile in patients with seasonal AR (SAR). The objective of this post hoc subgroup analysis was to evaluate the effectiveness of BDP nasal aerosol based on baseline symptom severity in SAR patients. Methods: In this 2-week, double-blind, placebo-controlled, parallel-group study, patients (≥12 years) with SAR were randomized (1:1 ratio) to treatment with BDP nasal aerosol 320 mg/d (n=169) or placebo (n=171). In this post hoc subgroup analysis, efficacy endpoints of change from baseline in average patient-reported AM and PM reflective and instantaneous total nasal symptom scores (rTNSS and iTNSS) were evaluated by patient nasal symptom severity at baseline: less severe (with baseline rTNSS < baseline median [9.7]) and more severe (rTNSS ≥ baseline median [9.7]). Results: At week 2, treatment with BDP nasal aerosol resulted in greater improvement in average AM and PM rTNSS compared to placebo in patients with more severe baseline symptoms (least squares [LS] mean [95% CI] difference: –1.12 [–1.8,–0.5]; P < 0.001) and in patients with less severe baseline symptoms (LS mean [95% CI] difference: –0.75 [–1.3,–0.2]; P = 0.011). Similarly, treatment with BDP nasal aerosol resulted in greater improvement in average AM and PM iTNSS compared to placebo in patients with more severe baseline symptoms (LS mean [95% CI] difference: –1.07 [–1.7,–0.5]; P < 0.001) and in patients with less severe baseline symptoms (LS mean [95% CI] difference: –0.79 [–1.4,–0.2]; P = 0.007). BDP nasal aerosol was well-tolerated and AE profiles were similar in patients compared with placebo. Conclusions: Results of this post hoc analysis showed that treatment with BDP nasal aerosol was effective in improving both reflective and instantaneous nasal symptoms compared to placebo in SAR patients regardless of their symptom severity at baseline.

62 IMPROVEMENT IN NASAL CONGESTION AND SLEEP WITH MP29-02 IN A RANDOMIZED CONTROLLED TRIAL IN SEASONAL ALLERGIC RHINITIS. D. Soteres*1, G. Olson2, S. Shah3, P. Ratner4, L. Gever5, 1. Colorado Springs, CO; 2. Denver, CO; 3. Collegeville, CO; 4. San Antonio, TX; 5. Somerset, NJ. Introduction. This analysis assessed the improvement in the nasal congestion component of the reflective total nasal symptom score (rTNSS) with MP2902 (Dymista) relative to improvement in the sleep domain of the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ). Methods. In a 2-week study in SAR, a total of 207 patients received MP29-02 (fluticasone propionate 50 mcg/spray and azelastine hydrochloride 137 mcg/spray) 1 spray/nostril bid and 210 received placebo spray 1 spray/nostril bid. The primary endpoint was the change from baseline in the rTNSS recorded twice daily (AM and PM). A key secondary endpoint was change from baseline to day 14 in the RQLQ score. Results. Treatment with MP29-02 produced a significant (P<.001) mean improvement in the rTNSS of 5.61 points (31.0%) from baseline compared to 2.92 points (15.6%) with placebo. The mean improvement from baseline in nasal congestion was 1.22 points (24.0%) with MP29-02 and 0.67 points (12.2%) with placebo (P<.001). The improvement from baseline in the mean overall RQLQ score was -1.64 points with MP 29-02 vs. -0.85 with placebo (P<.001), which meets the criteria of a minimum -0.5 unit difference as evidence of a clinically important effect. The improvement in the sleep domain of the RQLQ with MP29-02 was -1.62 points vs. -0.87 with placebo (P<.001). There was a significant (P<.01, r=0.48) positive correlation between change from baseline in nasal congestion and change from baseline in sleep with MP2902. Conclusion. The results suggest that improvement in nasal congestion with MP29-02 may be related to improved quality of sleep in patients with SAR.



63 CLIMATE INFLUENCES ON HAY FEVER IN CHILDREN: A US POPULATION-BASED STUDY. M.Z. Braunstein*1, J. Silverberg2, 1. New Rochelle, NY; 2. New York, NY. Introduction: Hay fever or allergic rhinitis is caused by a complex interaction between environmental factors and genetic predisposition. We sought to investigate the associations between climate factors and the US prevalence and statewide variation of hay fever in children. Methods: We used a merged analysis of the 2007 National Survey of Children’s Health from a representative sample of 91,642 children aged 0–17 years and the 2006–2007 National Climate Data Center and Weather Service measurements of mean annual and seasonal temperature (degrees Fahrenheit), relative humidity (%), indoor heating degree days (HDD), UV index, stratospheric ozone levels (parts per billion), precipitation and palmer hydrological drought index. Results: The US prevalence of hay fever in children and adolescents was 18.5% (95% confidence interval: 18.3–18.8). There was significant statewide variation, with highest hay fever prevalence in the Southeastern and Southern states (Rao-Scott chi square, P<0.0001). States with the lowest prevalence included Vermont, Montana and Alaska. In multivariate models controlling for sex, race/ethnicity, age, and household income, hay fever prevalence was significantly lower in geographical locations with the second (adjusted odds ratio [95% confidence interval]: 0.90 [0.82–0.98], P=0.02) and third-quartile (0.89 [0.81–0.98], P=0.02) mean annual relative humidity, highest quartile of drought index (i.e. wetter conditions) (0.86 [0.77–0.96], P=0.006) and second (0.86 [0.74–0.99], P=0.04), third (0.86 [0.77–0.96], P=0.006) and highest quartiles (0.70 [0.62–0.78], P<0.0001) of stratospheric ozone levels. In contrast, factors significantly associated with increased hay fever prevalence were the second (1.18 [1.06-1.30], P=0.002), third (1.45 [1.32-1.59], P<0.0001), and fourth quartiles (1.27 [1.11-1.44], P=0.0004) of UV index, second (1.14 [1.02-1.28], P=0.02), third (1.27 [1.11-1.45], P=0.0005), and fourth quartiles (1.41 [1.26-1.59], P<0.0001) of temperature, second (1.30 [1.09-1.56], P=0.004) and fourth quartiles (1.27 [1.07-1.51], P=0.008) of precipitation. Conclusions: This study provides evidence of climate influences on the US prevalence and statewide variation of childhood hay fever.

Figure 1: Papillary changes seen with slit lamp biomicroscope using fluorescein dye, cobalt blue light and yellow wratten filter

64 PREVALENCE OF OCULAR PAPILLARY CHANGES AND DRY EYE SUB-TYPES IN ALLERGIC CONJUNCTIVITIS. M.M. Hom*1, D. Opitz2, L. Bielory3, 1. Azusa, CA; 2. Chicago, IL; 3. Springfield, NJ. Purpose: Along with itch as a symptom, papillary changes in the conjunctiva are considered the hallmark sign of allergic conjunctivitis (AC). We looked at the prevalence of papillary conjunctivitis and crossover with dry eye subtypes in an optometric practice. Dry eye have been defined as two basic subtypes: aqueous tear deficient (ATD) and evaporative dry eye (EDE). There are no published reports regarding prevalence of dry eye sub-types and papillary changes. Methods: Prospective study performed on consecutive patients (n=204; age range 15-86; Mean: 45.6 years old, 77 M: 127 F) presenting for routine eye examination. Illinois College of Optometry Institutional Review Board approved the study. All of the patients consented for the study were seen in optometric practices and underwent three objective ocular surface tests: papillary changes, Schirmer tests and meibomian gland expression. Papillary changes were graded with slit lamp biomicroscope with fluorescein dye and viewed with cobalt blue light and a yellow wratten filter. (See Figure 1) The grading scale was 0 to 4, in 0.5 increments and Grade 1.0+ was considered clinically significant. EDE was determined by meibomian gland expression of Grade 1 or higher. ATD was determined with Schirmer I score (without anesthesia) of 5mm or lower. Results: Papillary changes were seen in 75% (153/204) while normal was 25% (51/204) of the patients. ATD was 14.2% (29/204) and EDE 36.8% (75/204) of the total patient sample. The crossovers between ATD and papillary changes were 51.7% (15/29) and EDE and papillary changes were 53.3% (40/75). For papillary changes, the crossovers between papillary and ATD were 9.8% (15/153) and papillary and EDE were 26.1% (40/153). 35.9% of those with papillary changes had dry eye (55/153). Conclusions: Conjunctival papillary changes were seen the vast majority of the patient sample (75%). Over one-third of these patients had dry eye. We previously reported that approximately 50% of patients with dry eye disease had AC symptoms and vice versa. This study reflects that objective signs are late seqeula and symptoms come first before papillary changes.






ABSTRACTS PRESENTED AT POSTER SESSIONS November 9-10, 2013 Baltimore convention center baltimore, maryland




Adverse Food and Drug Reactions Insect Reactions, Anaphylaxis



Aerobiology, Allergens, Allergen Extracts



Allergy Testing, Clinical Laboratory Immunology



Asthma & Other Lower Airway Disorders



Basic Science Allergy and Immunology



Clinical Case Reports



Clinical Immunology, Immunodeficiency



Food Allergy



Immunotherapy, Immunizations






Pharmacology and Pharmacotherapeutics



Rhinitis, Other Upper Airway and Ocular Disorders



Skin Disorders









P1 A CLASSICAL BUT NOT LESS IMPORTANT CASE OF DRESS SYNDROME SECONDARY TO AROMATIC ANTIEPILEPTIC DRUGS. C.T. Quezada-Chalita*, Mexico City, DF, Mexico. DRESS syndrome (Drug Rash with Eosinophilia and Systemic Symptoms in Relation to the Eliciting Drug) is a life-threatening adverse reaction characterized by skin rashes, fever, leukocytosis with eosinophilia or atypical lymphocytosis, lymph node enlargement, and liver or renal dysfunctions. The incidence is 1/10,000 and the mortality rate is between 10 to 30 %. The syndrome typically develops 2 to 6 weeks or longer after initiation of administration of a specific drug. We present the case of a 24-year-old, Mexican male patient diagnosed with epilepsy since three months ago, presenting absence seizures on carbamazepine medication (100 milligrams once daily). The patient denies previous adverse reactions to drugs as well any other allergic diseases. The patient began with intense pruritus on chest and upper limbs, three weeks after the neurologist decided to increase the dose of carbamazepine (200 milligrams). Several days after he began with an erythematous rash appeared on the same affected areas. His primary care physician decided to prescribe an intramuscular dexametasone injection (8 milligrams) and antihistamine medication during three days, presenting improvement in his symptoms. After that he complained about pruritus and generalized erythematous rash including face, palms, soles and genitals. Hospital admission was decided and he was treated with parenteral steroids (methylprednisolone) and antihistamines. He had high fever (40°C), prominent non-tender cervical lymphadenopaty, bilateral otorrhea, hyperpigmented papules and pustules and facial angioedema (Fig. 1). The CBC revealed eosinophilia of 1,600 and thrombocytopenia of 50,000. Hepatic function test: AST and ALT elevation as well increased alkaline phosfatase and GGT. CRP (c reactive protein) was increased in 108.0. Liver ultrasound images revealed no pathologic changes. He was on steroid therapy (Prednisone 50 milligrams) because the internal organ involvement with tapering schedule during six weeks presenting improvement in the symptoms and normalization in the complete blood count and hepatic function tests. The patient had criteria for the diagnosis of DRESS proposed by Bocquet and colleagues. Clinicians should be alert to the classical symptoms in patients who are taking aromatic antiepileptic drugs like carbamazepine.

Skin lesions on face

P2 THE ASSOCIATION BETWEEN SEVERE MANIFESTATIONS OF ORAL ALLERGY SYNDROME AND CONCURRENT ANGIOTENSIN-CONVERTING ENZYME INHIBITOR THERAPY. D. Ferastraoaru*, D. Rosenstreich, S. Jariwala, Bronx, NY. Introduction: Oral allergy syndrome (OAS) is caused by cross-reacting allergens found in pollen and raw fruits, vegetables and some tree nuts. It usually presents with mouth and throat itching; but, it can present with severe symptoms such as angioedema and anaphylaxis. It is also known that angioedema and anaphylaxis can be caused by angiotensin-converting enzyme inhibitor

(ACEI) therapy. However, it is not known if there is an association between severe manifestations of OAS and concurrent ACEI use. Methods: Case series and literature review Results: We present two cases of patients with OAS and concomitant ingestion of ACEI. Patient 1 presented with 2 episodes of tongue and lip angioedema and oral itching ten minutes after apple consumption. The second episode required hospital admission for facial angioedema and dyspnea. The patient had been taking lisinopril 10 mg daily for 10 years before the initial symptoms occurred. Specific IgE blood testing was positive for apple and birch. The patient was switched to angiotensin II receptor blocker (ARB) therapy (losartan 50 mg daily) and advised to avoid raw fruits. No further symptoms have occurred. Patient 2 presented with three episodes of tongue angioedema and mouth itching several minutes after jackfruit and cashew ingestion. The patient had been taking lisinopril 10 mg daily for 1 year before the symptoms occurred. Specific IgE blood testing was positive for birch allergen. The patient was switched to losartan 25 mg daily and was advised to avoid the culprit foods. No further oral symptoms have occurred. Of note, both patients had normal levels of complement, C1-esterase inhibitor, serum total IgE, and serum eosinophils. Conclusion: OAS usually manifests as mild symptoms, and rarely presents with severe manifestations such as angioedema. However, these cases suggest that concomitant use of ACEI in patients with OAS might represent a priming effect, thereby increasing the severity of OAS symptoms. This possible association has not been yet described in the literature and further studies are needed.

P3 SURVEY OF WINE INTOLERANCE SYMPTOMS AND PATIENT CHARACTERISTICS. S. Montoya*1, P.S. Creticos2, J. Santilli3, 1. Belmont, MA; 2. Annapolis, MD; 3. Bridgeport, CT. Introduction: Wine intolerance is not uncommon, being reported by 5-8% of patients in surveys. Its prevalence in the United States has not been looked at by a systematic epidemiological approach. We report here the demographic details, clinical manifestations, and consumption habits of subjects who have reported wine intolerance. Methods: A detailed wine intolerance questionnaire (WIQ) was distributed to 30 people who had reported wine intolerance to a west coast wine distributor. Our electronic WIQ had 12 domains [Demographics/Type Symptoms/Symptom Grading Chart/Onset Data/Extraneous Factors/Wine Characteristics/Food Allergy/Food Sensitivity/Other Reactions/Other Allergies/Family History/GI Conditions]. Results: Sixteen of 30 wine intolerant subjects (52%) completed the WIQ (62% female; mean age: 56). First wine ingestion occurred at age 20 (median 18.5 yrs); average age of onset of intolerance: 34 (median 34.5 yrs). Headache (69%) was the most commonly reported symptom, followed by flushing (38%), nasal congestion (38%) and nausea or vomiting (19%). No anaphylaxis reported. Most (75%) reported that their symptoms began within the first hour. Fifty-four percent (54%) reported symptoms with red wine, 23% reported symptoms with white wine and 31% reported symptoms with all types of wine; 75% reported food additive/preservative sensitivity. Allergic rhinitis was reported by 12% of respondents and drug allergy by 43%. Many reported experimenting with wines made from different grapes or from different countries to try to find a solution. Conclusion: This survey provided preliminary data on patient characteristics, clinical manifestations, and consumption habits of subjects who have reported wine intolerance. A better understanding of the epidemiology of the problem coupled with a tailored diagnostic workup should provide a better insight into both non-allergic intolerance (eg, susceptibility to biogenic amines; sensitivity to preservatives or wine metabolites; vascular reflexes) and true IgE-mediated immunologic mechanisms for wine sensitivity. Moreover, our interactions with wine producers and distributors has shown there is growing awareness of wine intolerance in the community of wine consumers, and those individuals who experience the problem are keenly motivated to find a solution. Our survey provides a template to expand our database to that of a systematic review of the condition.

P4 RADIOCONTRAST MEDIA REACTIONS: FACT VERSUS FICTION. A.N. Pepper, E. Westermann-Clark*, N. Talreja, R.F. Lockey, Tampa, FL. Introduction: Medical professionals misconceive that shellfish allergy and “iodine allergy” are risk factors for radiocontrast media (RCM) adverse events. This is incorrect. However, the myth persists, even in academic institutions.



ABSTRACTS: POSTER SESSIONS The objective of this study is to determine the effectiveness of an educational tool to rectify this misconception. Methods: A survey was administered before and after an educational lecture about anaphylaxis during internal medicine grand rounds at an academic institution. The pre-lecture survey assessed the perceptions of physicians and other healthcare professionals about RCM reactions, shellfish allergy, and “iodine allergy.” The lecture on anaphylaxis included information refuting the link between RCM reactions, shellfish allergy, and “iodine allergy.” The post-lecture survey assessed the impact of the educational program. The study was approved by the Institutional Review Board and informed consent was obtained. Results: Fifty physicians and other healthcare professionals attended the grand rounds. Thirty-two completed both the preand post-lecture surveys, seven completed only the pre-lecture survey, and eleven declined to participate. The mean pre- and post-lecture survey correct response scores were 31% and 94%, respectively (p <0.005). Pre-lecture survey correct response scores for shellfish and iodine questions were 42% and 21%, respectively, indicating a significantly higher baseline knowledge about shellfish than iodine (p <0.005). The educational program had a greater impact on participants’ perceptions about iodine than shellfish, most likely due to the difference in baseline knowledge. There was no statistically significant correlation with level of training (attending, trainee, and other) or specialty (internal medicine versus other). Conclusion: An educational program successfully rectifies misconceptions by medical professionals about RCM reactions, shellfish allergy, and “iodine allergy.”

P5 DESENSITIZATION TO OMALIZUMAB IN AN INNER CITY SEVERE PERSISTENT ASTHMATIC. A. Mathew*, P.R. Smith, M. Vastardi, F. Abi Fadel, R. Joks, Brooklyn, NY. Introduction: Inner city minority patients are at disproportionate risk for death from asthma. Therefore, utilization of all available therapies for optimal control of asthma is warranted. Immediate hypersensitivity reactions (HSR) are relatively uncommon to omalizumab, the only biologic treatment available for allergic disease, however they are a serious side effect that warranted a black box warning and requires discontinuation. In patients with allergic asthma that is inadequately controlled, omalizumab may be the only treatment that provides relief, making desensitization necessary. There is a paucity of reports of successful desensitization to omalizumab. We present our experience in desensitizing an inner city African-American woman with severe persistent asthma. Presentation: A 53 year-old woman with severe oral corticosteroid-dependent asthma, frequent hospital admissions including intubations for asthma, receiving omalizumab 375 mg SC every 2 weeks for 6 months without reactions, developed neck and arm urticaria 45 minutes after receiving her 12th dose of omalizumab. As she was poorly controlled on high-dose inhaled steroids and chronic oral corticosteroids, and improved after omalizumab was added, it was determined she would benefit from omalizumab desensitization. Results: Desensitization occurred in the ICU, with premedication 1 hour prior with oral fexofenadine 180 mg and famotidine 40 mg. Her vital signs and physical exam were normal, and her PEFR of 310 L/min was at her baseline. Omalizumab was administered SC using the protocol outlined in Table 1. The patient’s vital signs, physical exam, and PEFR remained stable for the duration of the protocol. She completed all 10 doses without events and was monitored for an additional 3 hours before discharge. Conclusion: Desensitization to omalizumab is important in cases where there is no treatment alternative, and leads to clinical improvement. Our patient was successfully desensitized to omalizumab and has been receiving omalizumab 187.5 mg SC on a weekly basis without any further reactions. Her asthma is under good control on inhaled corticosteroids and she has been weaned off of prednisone. While exact determination of the cause of this HSR to omalizumab remains unknown, hypotheses in the literature implicate antibodies to omalizumab as the cause versus an anaphylactoid reaction to polysorbate, an excipient in omalizumab.


Table 1: Omalizumab Desensitization Protocol

P6 STEVENS JOHNSON SYNDROME: TOXIC EPIDERMAL NECROLYSIS OVERLAP DEVELOPMENT DUE TO CITRIC ACID OF SCHOLL’S SOLUTION IN A PATIENT WITH CYSTINOSIS. Öner. Özdemir1, D. Kizmaz2, P. Ebru Aslan*2, 1. Adapazar, Turkey; 2. Istanbul, Turkey. Introduction: Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are two forms of a life-threatening skin condition, in which cell death causes the epidermis to separate from the dermis. The syndrome is thought to be an immune-complex–mediated hypersensitivity that affects the skin and the mucous membranes. Both SJS and TEN are most often adverse effects of medications (sulfa drugs), followed by infections. Scholl ‘s solution is a medication containing citric acid and salt of sodium citrate; or, without citric acid, salt of sodium and potassium citrate in distilled water used to correct electrolyte imbalance in the treatment of renal tubular acidosis. SJS has not been reported to be related to Scholl ‘s solution up to now. Goal: We present a rare patient with renal tubular acidosis due to cystinosis developing SJS-TEN overlap after using an alternative Scholl’s solution. Case: 3 year-old-female having cytinosis presented to us with complaints of maculo-papular rash on her face and over the trunk. She has been followed by nephrology and taking cysteamine bitartrate, carnitine, calcitriol, neutral phosphate and Scholl’s solution. After consanguineous marriage in the family, her two siblings have cytinosis as well and one of them was transplanted. Physical exam showed maculo-papular rash on her face and over the trunk and extremities, later skin lesions were resulted in exfoliation. Laboratory results revealed hemoglobin: 11.5 gr/dl; haematocrit: 33%; WBC: 6.700/mm3; with the differentials of neutrophil: 68%, lymphocyte: 30%, eosinophil: 0.1%; and PLT: 359.000/mm3. CRP: negative, biochemistry was normal. Blood gas analysis demonstrated pH: 7.32; pCO2: 25.1; HCO3: 13. The patient was diagnosed as SJS-TEN overlap after biopsy, but the patient was thought to be inclined to develop TEN. Methyl-prednisolone, pheniramine, desloratadin, and oral treatments were started. Intravenous immunoglobulin (1g/kg/day) was given to prevent developing TEN. Provocation trials were performed with regular medications of the patient using for cystinosis. These trials showed that citric acid in the Scholl’s solution causing patient’s skin symptoms. Conclusion: This patient shows us that physicians keep citric acid in mind as a cause for SJS-TEN overlap in cystinosis patients.

P7 VANCOMYCIN RESISTANT ENTEROCOCCUS INFECTIONS ARE ASSOCIATED WITH A HIGHER PREVALENCE OF REPORTED PENICILLIN ALLERGY. V. Reddy*, P. Jhaveri, F.T. Ishmael, Hershey, PA. Introduction: Penicillin allergy has a reported high prevalence and occurs in approximately 10% of the population. It is estimated that 90% of these patients are not truly allergic, but patients labeled as allergic are treated with alternative antibiotics, which may be less efficacious or have more side effects. Penicillin-allergic patients may be more likely to receive vancomycin as an alternative antibiotic. We hypothesized that patients with a reported penicillin allergy have an increased prevalence of resistant infections such as Vancomycin Resistant Enterococcus (VRE). Methods: After IRB approval, lists of hospitalized patients with VRE infections were compiled from our institution. Retrospective review of electronic records was performed from hospitalized patients of all ages from January 2009 to December 2011 to obtain antibiotic allergy information. Differences between rates of drug allergy were analyzed by chi-squared tested, with a significance set at p<0.05. Results: Over a 36 month period there was a statistically significant increase in prevalence of penicillin allergy in


ABSTRACTS: POSTER SESSIONS patients with VRE (24%; 100/426; p<0.001) compared to the general hospital population (6%; 20249/369721). The prevalence of other antibiotic drug allergies not including penicillin was also higher in the VRE group (33.6%; 143/426) compared to the general hospital population (7%; 25589/369721; p<0.001). Conclusion: There is an increased prevalence of penicillin and other antibiotic allergies in patients with VRE infections compared to the general hospitalized population. Future studies are needed to determine whether inpatient penicillin allergy testing can improve antibiotic utilization and prevent these resistant infections.


ng/ml), and a positive IgE to bovine protein (0.45 ng/ml). The patient was advised to avoid all gelatin containing medications, vaccines, and products. Conclusions: Anaphylaxis may occur because of animal gelatin components in topical hemostatic matrix, such as Floseal. Our findings suggest that before using products that contain animal-derived gelatin, a thorough history about previous reactions to beef or gelatin-containing vaccines or medications should be obtained. After obtaining a history and prior to surgical intervention, it is imperative to have a low threshold in testing patients to prevent future cases of intraoperative anaphylaxis. This case highlights the importance of using a broader differential when determining the cause for intraoperative anaphylaxis, and suggests that Floseal should only be given to patients with a negative history of allergies to gelatin or bovine protein.



Introduction: Cyclosporine (CsA) is an immunosuppressant commonly used to prevent graft-versus-host disease (GVHD). CsA rarely causes anaphylaxis, which when reported is typically while receiving the IV CsA formulation with subsequent oral formulation tolerance. Previous groups have demonstrated that the polyoxl-40 hydrogenated castor oil component of the IV medication formulation, not present in the oral formulation, is the common allergenic component. We report a patient with a similar clinical presentation and subsequent literature review. Case Description: A 4 year-old male underwent a 10/10 matched sibling donor bone marrow transplantation due to severe aplastic anemia. Oral CsA was tolerated starting on day -2 of transplantation. On day +7, a change from oral CsA to IV CsA was made due to severe mucositis. Initially, the IV CsA was tolerated with only mild, non-progressive facial flushing. On day +17, within 30 minutes of completing his daily CsA infusion, he developed throat pain, lip swelling, facial swelling, and diffuse erythema. On exam he had decreased lung aeration, hypoxemia (85-89% on room air), and hypotension (86/62). He was immediately given IM epinephrine, oxygen, and nebulized albuterol. He also received IV diphenhydramine, IV fluids, hydrocortisone and methylprednisolone with subsequent transfer to the ICU for further care. These interventions quickly improved his symptoms. A tryptase level drawn at the initiation of the reaction was elevated (42ng/ml). Discussion: A review of the allergy and transplantation literature revealed the castor oil component of the IV CsA to be the most likely allergenic component, as many reports detailed the empiric switch to oral CsA without any allergen testing or subsequent medication reactions. Due to the severity of the reaction and the continued need for immunosuppression to prevent GVHD, oral tacrolimus was started and has continued to be tolerated by the patient without any noted issues. Unfortunately due to other transplantation related complications, we have not been able to conduct any allergen skin testing or oral CsA challenge at this point in time. We believe this case illustrates the example of an IgE-related reaction to a drug diluent, not the commonly implicated active drug component.

Angioedema related to ACE-inhibitors occurs in 0.1-2.2% of patients, with higher incidences in women and African-Americans. Though rare, ACEinhibitor associated angioedema may represent a life-threatening condition requiring emergent management. A 58 year old female presented with acute tongue, orbital, and lip swelling with dyspnea. She has a history of hypertension, treated with daily lisinopril for the past 20 years. She denied any prior anaphylaxis, allergic rhinitis, asthma, or atopy. The patient is African-American. She was started on IV dexamethasone, famotidine, diphenhydramine, and subcutaneous epinephrine. Despite treatment, the patient quickly decompensated, developing respiratory failure requiring intubation and admission to the intensive care unit. An allergist was consulted, as the tongue swelling continued beyond her chin and progressed to occupy the whole oropharynx. Her angioedema was determined to be secondary to an acute process involving the renin-angiotensin-bradykinin systems, and her lisinopril was discontinued. The patient tested negative for complement deficiencies, C1 esterase deficiency, and lupus. She was successfully extubated after her angioedema resolved and was discharged 28 days after admission. ACE- inhibitors are frequently prescribed, and the most common cause of angioedema presenting to the hospital. Literature review indicates the majority of cases present within the first week or, at most, after a few months. In this setting, angioedema from an ACEinhibitor occurring after 20 years is very rare. Several studies indicate a strong ethnic predilection towards African-Americans, with an incidence of 1 in 50. Although unusual, this case demonstrates that the dreaded complication of angioedema can occur at any time.

P9 A CASE OF INTRAOPERATIVE ANAPHYLAXIS TO GELATIN IN A GELATIN-BASED HEMOSTATIC MATRIX DURING SPINAL SURGERY. N.S. Agarwal*, C. Spalding, M. Nassef, New York, NY. Introduction: We present a case of severe intraoperative anaphylaxis to the gelatin component in Floseal, a topical hemostatic agent used to reduce bleeding during surgical procedures, in a patient with unknown bovine allergy. Case Report: BP is a 9 year old boy with a past medical history significant for Marden-Walker Syndrome, asthma, fish, and dust mite allergies, who presented with severe intraoperative anaphylaxis during scoliosis surgery. The patient initially received Cefazolin and Tobramycin and sixty minutes later received Floseal to the pedicles, which immediately resulted in hypotension and respiratory compromise. No latex products were used during this procedure. The patient was initially given epinephrine, became pulseless, and required one minute of CPR before regaining a pulse. His condition finally improved after additional epinephrine, vasopressin, albuterol, terbutaline, and steroids. Upon further questioning, our patient had a history of a milder version of anaphylaxis during a procedure eight years prior when Floseal had been administered. He also had an episode of anaphylaxis after MMR, varicella, diphtheria, and polio vaccines were administered together, all of which contain gelatin except for the polio vaccine. Additionally, the patient’s mother stated he had a facial rash after eating beef years ago and has been avoiding it since. Results: Postoperative workup revealed an elevated tryptase of 72 ng/ml, a positive IgE to bovine gelatin (1.61


P11 ANAPHYLAXIS AND A SPLINTER HEMORRHAGE IN A PATIENT WITH CAT ALLERGY. K. Dass*1, C. Lauter2, O. Niculescu2, 1. Bloomfield Hills, MI; 2. Royal Oak, MI. A 47 year old man with HIV presented to the emergency room with swelling and rash. The morning of admission, the patient tried to flick off dried cat saliva from his couch, which led to a splinter hemorrhage in his right forefinger. His finger quickly became pale, swollen, and numb. The patient developed bilateral palmar pruritus that spread to his arms, a diffuse urticarial rash of the chest and trunk, and generalized edema. In the ER, the patient received IV diphenhydramine, 25 mg every four hours and IV methylprednisolone 125 mg once. After initial improvement, the patient developed wheezing, hypotension and increasing tachycardia four hours later. He denied prior anaphylactic reactions despite owning a cat; however, cat and dog exposures had caused mild skin reactions. After an allergy consultation, epinephrine and famotidine were given; the patient improved. He was diagnosed with biphasic anaphylaxis and discharged with a prednisone taper, famotidine, loratadine and diphenhydramine. Allergen specific IgE tests were positive for dog and cat dander. He was advised to avoid contact with these animals. Anaphylaxis is an acute multi-system reaction secondary to IgE mediated mediator release from mast cells and basophils. Many triggers cause anaphylaxis with variation in severity, onset and appearance. We report a case of severe anaphylaxis and splinter hemorrhage secondary to dry cat secretions in a patient who has not had prior severe reactions to his cat. A literature review revealed anaphylaxis to animal secretions is rare, and a splinter hemorrhage as the trigger has not been described






THE FORBIDDEN FRUIT. A. Fiocchi*, C. Dionisi-Vici, G. Cotugno, A. Boiani, P.L. Koch, L. Dahdah, Rome, Holy See (Vatican City State).


Background: Hereditary fructose intolerance (HFI) is a metabolic disease caused by mutation in the gene encoding aldolase B. Symptoms - including vomiting, pallor, sweating, lethargy, coma, and hypoglycaemic seizures - usually appear at weaning when fructose-containing foods are introduced. We report on a suspect HFI infant, presenting with repeated episodes of vomiting and hypotension following ingestion of fruit containing meals. Case History: The first episode occurred at four months: the boy was hospitalized because of repeated vomiting with irritability, pallor and shock. Lab findings showed increased WBC count (49,000/mm3) and mild hypertransaminasemia (ALT 85, AST 41 kUI/L). Two days after discharge, a similar episode led to admittance to our hospital. As both episodes happened after apple consumption, HFI was suspected. An oral fructose tolerance testing carried on with an apple mousse did not yield hypoglycaemia nor fructosuria, but the infant developed severe hypotension, treated as an anaphylactic reaction with epinephrine, chlorpheniramine and hydrocortisone. Symptomatic control was achieved within 60 minutes. Skin prick tests (SPT) were negative with foods. Specific IgE determinations (CAP-FEIA from Pharmacia, Sweden) returned negative with CM (0.12 kU/L), apple (0.10 kU/L) and banana (0.17 kU/L), total IgE levels were 5 kU/L. Despite negative genetic testing for HFI, based on the clinical history, strict avoidance of fruit ingestion resulted in lack of recurrence of symptoms. Before deciding to fully exclude HFI by enzymatic determination in liver biopsy, the allergist was consulted again. No further test was necessary to diagnose fruit-induced FPIES. Prick-by-prick tests with native allergens and SPT carried out with commercial extracts of allergens associated in the literature with fruit allergy were confirmed negative. The boy, now aged one year, is free from food-related symptoms. Comment: The reported case fits perfectly with the diagnostic criteria for FPIES, a non–IgE-mediated gastrointestinal food hypersensitivity that manifests as profuse, repetitive vomiting, often with diarrhoea, leading to acute dehydration and lethargy. FPIES is most frequently due to cow’s milk, egg and rice, but two cases of fruit-induced FPIES were described in Italy. In one of them, genetic tests for HFI had been performed. We advise to consider FPIES when a suspect of HFI comes out.

P13 LINEZOLID HYPERSENSITIVITY REACTIONS IN HOSPITALIZED PATIENTS. G.H. Bennett*, F.T. Ishmael, Hershey, PA. Objective: With the emergence of multi-drug resistant organisms, there is increasing use of oxazolidinones such as linezolid. Case reports of hypersensitivity to linezolid have been described, but reactions have not been well characterized. The goal of this study was to identify and characterize linezolid reactions, and elucidate trends associated with the reactions. Methods: A retrospective study was performed following IRB approval. A search of electronic medical records was performed for patients admitted to an academic institution from January 2009 to September 2011 to identify those with a recorded allergy to linezolid. Demographic patient information, nature of reaction, reasons for linezolid administration, subsequent antibiotic use, and other antibiotic allergy were analyzed. Results: Seventeen patients (9 male, 8 female) with documented linezolid hypersensitivity were identified. Patient mean age was 50 years, with a range from 12 to 90 years of age. All patients were hospitalized and treated for serious bacterial infections. Six reactions were consistent with immunologic reactions (five patients developed a rash and one developed thrombocytopenia). Six patients reported nausea/vomiting and 3 patients presented with lowered seizure threshold. Three patients had no documentation of the reaction. Sixteen of the patients had a history of other antibiotic allergy, and 10 of these had a history of allergy to more than 3 classes of other antibiotics. All patients that developed a rash with the medication had a history of allergy to multiple antibiotics. Conclusions: The number of reactions to linezolid were low, and most reactions were non-immunologic in nature. The rashes attributed to linezolid occurred in patients with a history of reactions to more than three classes of antibiotics, raising the question of whether these reactions were part of a multiple drug allergy syndrome that involves a nonspecific immune reaction to structurally unrelated compounds. There were no life threatening reactions documented. We conclude that linezolid has low allergenic potential.


Rationale: There have been multiple case reports of inadvertent transfer of food allergy from an allergic donor to an unsuspecting recipient by transfusion or organ donation. There have been 3 cases described in lung transplantation. Methods: A 71 year old male with history of interstitial pulmonary fibrosis underwent bilateral lung transplantation. He had no history of food allergy before transplantation. The donor received the transplant from a 15 year old peanut allergic asthmatic patient who died of anaphylaxis following ingestion of peanuts and an unknown history of allergy to treenut. Four days after transplant he developed acute emesis and malaise. He was taken to the ER and intubated for respiratory failure. He was extubated after 2 days, but reintubated 3 days later due to acute bronchospasm 15 mins after eating. Prior to both episodes he had eaten a dessert prepared by his wife, which contained walnuts, cashews and peanuts. The recipient’s post-transplant serum specific IgE levels was elevated to walnut, hazelnut, pistachio and cashews. Skin testing was not performed due to the severity of the previous reactions. Results: Possible mechanisms of transfer of food allergy include passive transfer of serum specific IgE to peanut and/or treenut the time of lung transplant. Alternately there may be transfer of specific B and Th2 CD4+ donor lymphocytes in the lung tissue or blood which sensitize the recipient. Conclusions: This case emphasizes the importance of the recipient being cautioned about food allergy status of the donor post transplantation. The allergic profile of the donor should be readily on the donor card.

P15 ASPIRATION OF SUNFLOWER SEED DISGUISED AS ANAPHYLAXIS. J.A. Sigua*1, M. Zacharisen2, 1. Milwaukee, WI; 2. Bozeman, MT. Introduction: Acute respiratory compromise such as wheezing is a common feature seen in anaphylaxis. Acute wheezing in children in particular can also be commonly seen with foreign body aspiration (FBA), which can make a distinction with anaphylaxis difficult. Without a detailed history, careful lung examination, or appropriate diagnostic studies, FBA can be overlooked and mimic other causes of acute wheezing such as infection or anaphylaxis. Case Description: A 5 year old girl presented with acute onset of vomiting and wheezing immediately after eating a few sunflower seeds. Ingestion of sunflower seeds had been previously tolerated, though without the outer shell in contrast to the current episode. Past medical history was notable for a prior history of uncomplicated RSV bronchiolitis. Exam was remarkable for stridor, diffuse expiratory wheezing, and generalized urticaria. Chest x-rays including an anterior-posterior film and bilateral decubitus radiographs were normal without evidence of a foreign body. Laboratory studies including a serum tryptase were not obtained. Immediate treatment with intramuscular epinephrine, nebulized albuterol and racemic epinephrine, and systemic corticosteroids significantly improved her symptoms. Anaphylaxis secondary to sunflower seed was suspected, triggering an allergy evaluation. Subsequent examination however revealed coarse breath sounds in her right lung associated with mild localized end-expiratory wheezing, therefore prompting an emergent bronchoscopy, which revealed an intact sunflower seed blocking the right mainstem bronchus. Removal of the sunflower seed normalized her auscultated lung findings. Concomitant anaphylaxis from sunflower seed however could not be excluded, since urticaria would be atypical for aspiration. Serum specific IgE and skin testing to sunflower seed were negative two months later. Subsequent sunflower seed challenge in a controlled setting was tolerated, excluding a sunflower seed allergy. Conclusion: This case illustrates how FBA can imitate anaphylaxis, contributing to its delay in diagnosis and intervention. An astute history and physical examination should prompt further investigation with appropriate confirmatory studies regardless of conflicting exam and radiographic findings.



P16 SUBLINGUAL IMMUNOTHERAPY (SLIT) AND HENOCHSCHOENLEIN PURPURA (HSP): ANOTHER CAUSE AND EFFECT? A. Gaye*1, A. Korenblit2, 1. Brussels, Belgium; 2. Chicago, IL. Rationale: HSP, an IgA1-mediated immune complex disease with post-capillary venule-deposition, the most common vasculitis of young children (incidence of 70/10 000), presents with palpable purpura, arthritis, abdominal pain and intestinal bleeding, orchitis and nephritis. With a higher incidence in boys from the Northern hemisphere, and in Fall, Winter and Spring, its etiology remains unclear. An infectious trigger is suspected as more than 50% of cases can be linked to a streptococcal infection, but many other common factors have also been put forward as potential contributing agents, such as environmental conditions (cold temperatures), various agents introduced by ingestion (foods, medications), or by injection (horse serum, vaccines, insect bites). The pathogenesis of an elevated serum IgA level in HSP remains unexplained. Genetic polymorphism is suspected in the severity of the immune response, as it especially leads to nephritis and intestinal manifestations. Methods: Report of a case and review of the literature Results: A 9 y old Caucasian boy presented with bilateral knee pain 29 days after initiating mold SLIT for allergic rhinitis and intermittent asthma - 6 days of 10 IR/ml, 5 days of 100 IR/ml in the usual build-up fashion, followed with daily maintenance of 300 IR/ml. On day 31 of the SLIT program, intense abdominal pain lead to appendectomy, as discreet skin lesions went almost unnoticed, to become obvious only 2 days later. Parents resumed SLIT as soon as oral feedings were allowed after surgery, until day 34 when HSP was diagnosed and SLIT interrupted. Per protocol, proteinuria was addressed first with NSAID, but systemic steroids (SCS) at high doses were soon needed. After 6 weeks of SCS weaning, remission was obtained, with residual proteinuria and microscopic hematuria. However, 48 hours after resuming strenuous physical activity, gross hematuria occurred, without skin lesions, abdominal discomfort, nor joint pain, and prompted a reinstatement of SCS. SLIT was not restarted. Conclusions: This is the first report of a case of HSP that would be related to SLIT. SLIT would act as an immune trigger of gastro-intestinal IgA formation, followed by a deposition of IgA1 subtype immune-complexes in the wall of small vessels, characteristic of HSP. SLIT could be another lead to elucidating the pathogenesis of this common systemic vasculitis.

ment. An educational intervention by allergists may successfully address these deficiencies in the short-term, although additional interventions may be needed to optimize long-term retention of this knowledge.

P18 ANAPHYLAXIS IN CHILDREN AND ADULTS REFERRED TO A TERTIARY ALLERGY CLINIC: A RETROSPECTIVE STUDY OF 1292 ANAPHYLACTIC REACTIONS. N.N. Jiang*, J. Yin, P.L. Wen, Beijing, China. Introduction: Anaphylaxis is a potentially life-threatening reaction and its incidence is increasing. Little is known about the characteristics of anaphylaxis in China.We aimed to describe the clinical manifestations, triggers and management of anaphylaxis in children and adults referred to a tertiary allergy clinic.Methods: We performed a retrospective review of clinical records of patients who admitted to our allergy clinic for anaphylactic reactions between January 1, 2000 and December 31, 2012. Results: We identified 1292 anaphylactic reactions in 569 patients (305 male patients). 385 patients had recurrent reactions. The median age at time of the first reaction was 30 years (age range, 10 months to 75 years). The skin (80.3%) was the most frequently affected organ followed by the respiratory system (71.2%) and cardiovascular system (56.5%). The triggers included food (78.6%), drugs (7.7%), insect (0.4%) and “unknown” (13.3%). Wheat (31.4%) was the culprit agent of food-induced anaphylactic reactions. Traditional Chinese medicine (35.0%) was the most common cause of drug-induced anaphylaxis. 777(60.1%) reactions were managed in emergency department, corticosteroid (71.9%) were more often administered than adrenaline (24.4%). When compared with adults, children were more often presented with respiratory symptoms (81.8% vs.68.8% P<0.001) and less often presented with cardiovascular symptoms(41.7% vs.60.0%,P<0.001).Food is the leading cause of anaphylaxis, especially in children. However, druginduced anaphylaxis were more common in adults than in children(8.8% vs.3.2%,p=0.003). Conclusions: The present study indicates that the most common symptoms of anaphylaxis were skin presentations. Respiratory presentations are more frequent in children. Food is the leading cause of anaphylaxis,but shows a different picture from the West, wheat is the main food trigger in children and adults. Chinese herb is the main cause of drug-induced anaphylax-is .Adrenaline, the first-line treatment of anaphylaxis, is used in a minority of anaphylactic reactions.

P17 KNOWLEDGE, ATTITUDES AND BEHAVIORS OF EMERGENCY MEDICINE RESIDENTS REGARDING ANAPHYLAXIS DIAGNOSIS AND MANAGEMENT. S. Bina*1, A.M. Jongco2, R.J. Sporter2, S.J. Schuval1, 1. Stony Brook, NY; 2. New Hyde Park, NY. Introduction: Despite the availability of anaphylaxis guidelines, many physicians are unable to recognize and manage this potentially life-threatening allergic reaction. We designed an educational intervention to improve this knowledge gap among residents in-training. Previously, we assessed the efficacy of this intervention on Internal Medicine and Pediatric residents. We have now expanded this study to include Emergency Medicine (EM) residents. IRB approval and informed consent was obtained from all research subjects. Methods: We administered an anonymous questionnaire to EM residents that included an assessment of baseline knowledge, attitudes, and behaviors (KAB) regarding anaphylaxis diagnosis and management, along with a 10-item quiz testing key concepts (pretest). An Allergy/Immunology physician then presented a short educational program, consisting of key evidence-based concepts regarding anaphylaxis. Residents then completed a 10-item quiz (post-test) to assess the efficacy of the educational intervention. Six weeks later, the same residents completed a 10-item quiz (follow up-test) to assess long-term retention. We hypothesized that KAB regarding anaphylaxis diagnosis and management would improve after the intervention. Results: Of 30 eligible EM residents, 15 (50%) participated in the pretest/post-test and 10 (33%) participated in the follow up-test. Prior to the study, 73% had diagnosed anaphylaxis, 73% had managed anaphylaxis, 20% had used an epinephrine autoinjector, 40% had demonstrated how to use an autoinjector, and 67% had referred a patient for outpatient allergy evaluation after anaphylaxis. In addition, 87% of residents felt confident in diagnosing anaphylaxis and 100% were confident in the management of anaphylaxis. Post-test quiz mean scores (8.60+1.18) were higher than pre-test quiz mean scores (8.0+1.07, p=0.0025). Six weeks later, follow-up-test mean scores (8.1+1.29) were higher than pre-test scores (p=0.83) but lower than post-test mean scores (p=0.33). Conclusions: Although EM residents feel confident in diagnosing and managing anaphylaxis, an objective evaluation of their knowledge shows need for improve-

P19 ASSESSMENT AND CHARACTERIZATION OF PATIENTS HOSPITALIZED FOR ANAPHYLAXIS IN VILNIUS, LITHUANIA, USING WAO CRITERIA. A. Blazine*1, N. Buterleviciute1, V. Paltarackiene1, L.M. DuBuske2, 1. Vilnius, Lithuania; 2. Gardner, MA. Background: Anaphylaxis is the most severe IgE-mediated hypersensitivity reaction. The incidence of anaphylaxis in Lithuania is unknown as are the factors inducing anaphylaxis along with patient demographics. This study analyses the incidence of anaphylaxis, assesses the cases based on WAO criteria for diagnosis, and describe the causes, symptoms and management of anaphylaxis at this Vilnius, Lithuania, academic hospital center. Methods:Patients with anaphylaxis hospitalized from 2009 to 2012 in Vilnius University Hospital Santariskiu Klinikos Pulmonology and Allergology Department were included in this study. 70 patients including 38 women (54.3%) and 32 men (45.7%), 47.31 ± 17.63 (range 20 to 83) years old, were assessed. Results:The main suspected causes were drugs in 26 patients (37.1%), mainly NSAIDS and antibiotics; insect stings in 18 patients (25.7%); and food in 4 patients (5.7%). The etiology was confirmed in 9 patients (12.9%): 3 patients had provocation tests performed; and 6 patients had allergen specific IgE positive for the allergen. Ony 22 cases fulfilled the first WAO criteria for anaphylaxis diagnosis; 38 met the second criteria; and 10 met the third criteria. Diagnosis of anaphylaxis was not confirmed in 2 patients after re-evaluation by WAO criteria. Symptoms most often seen were cardiovascular in 64 patients (91.4%); followed by dermatologic in 59 patients (84.3%); respiratory in 38 patients (54.3%) and gastrointestinal in 21 patients (30.0%). Most anaphylaxis, including 25 patients (35.7%), occurred in summer. Care was provided to 51 patients (72.8%) by emergency physicians and 24 patients (34.3%) were treated in the intensive care unit. Conclusions: The main causes of anaphylaxis in patients hospitalized at this academic center in Vilnius, Lithuania, were drugs. The cardiovascular system was the most frequently affected, followed by skin and respiratory systems. Most anaphylaxis occurred in summer. One third of patients with anaphylaxis required



ABSTRACTS: POSTER SESSIONS admission to the intensive care unit. Use of WAO criteria for anaphylaxis allowed for rigourous charterization of these patients.

P20 IDIOPATHIC ANAPHYLAXIS: A REVIEW OF 77 CASES. N.N. Jiang*, J. Yin, P.L. Wen, Beijing, China. Introduction: Idiopathic anaphylaxis is anaphylactic reactions with no definable external stimulus or potential allergens. Few Asian groups have published data on patients with this syndrome. Our aim was to describe clinical characteristics of idiopathic anaphylaxis in Chinese population. Method: We conducted a retrospective study of medical records of patients with idiopathic anaphylaxis referred to a tertiary allergy clinic from January 2000 to December 2012. Results: We identified 155 anaphylactic reactions in 77 patients with idiopathic anaphylaxis (45 female patients). 60 patients (78%) had recurrent anaphylaxis. 39 patients (51%) companied with atopic diseases. 17 patients (22%) suffered from idiopathic urticaria. The mean age at time of the first reaction was 33 years (age range: 8 years to 61 years). The duration of symptoms prior to presentation ranged from 4 days to 40 years (mean 2.4 years). 43 patients (56%) experienced with at least one severe life-threatening event. Skin (74%) was the most frequently affected organ followed by the respiratory system (69%), cardiovascular system (58%) and gastrointestinal system (46%). 14 (9%) reactions were self-relieve, 18 (12%) reactions were treated at home by patients themselves, 103 (66%) reactions were managed in the emergency department. The most frequently given drug was corticosteroid (65%), but not adrenaline (25%). Conclusion: The present study indicates that idiopathic anaphylaxis can occur at any age, skin and respiratory system are the most common affected organs. Adrenaline is underused in anaphylactic reactions by emergency physicians. It is important to recognize this syndrome and should take more attention by allergist.

P22 DRESS SYNDROME ASSOCIATED WITH LAMOTRIGINE EXPOSURE RESPONDED TO HIGH DOSE OF SYSTEMIC STEROIDS. N. Jinjolava*, G. De Vos, Bronx, NY. We present an interesting case of DRESS syndrome, most likely associated with Lamotrigine exposure, in a patient with diffuse rash, eosinophilia, fever and elevated liver function tests, which improved with increased systemic prednisone treatment. Case Presentation: 18 year old female with history of Schizoaffective Disorder, was send to emergency from Psychiatric Center due to worsening rash and fever despite treatment with short course of low dose 20mg prednisone with fast taper over 5 days. 2 weeks prior the patient received penicillin for possible streptococcal pharingitis in the emergency department. At that time she was noted to have a facial rash . According to available records patient was also started on Lamotrigine one week prior. Patient had no history of atopy and no known drug allergies, no asthma, no recent bacterial infection. On physical exam patient had cervical and axillary lymphadenopathy, diffuse erythematous, partially scaly rash on the face, chest and arms. Laboratory tests were significant for eosinophilia and elevated Liver function tests concerning for DRESS syndrome . Interestingly, the heterophile antibody test for infectious mononucleosis was positive, however Ig M for EBV was negative with positive Ig G. Antibodies for CMV, B19, ANA and anti-smooth were negative. Workup for hepatitis was also negative . Due to persistent fever and worsening liver function tests on low dose steroids, prednisone was increased to 80mg/day. Patient showed good response to treatment. Fast taper of prednisone after discharge from the hospital resulted in increase of eosinophilia and worsening of rash and required a prolonged taper. Discussion: The importance of this case is that early diagnosis and proper treatment of DRESS syndrome is crucial for patient, as this syndrome carries about 10% mortality. There are no controlled clinical trials to assess the efficacy or dosing of systemic steroid treatment. There are some case reports with shown benefit of pulse high dose steroids.

P21 SAFETY OF REPEATED IMPORTED FIRE ANT ULTRA-RUSH PROTOCOLS. K.E. Adams*1, K.S. Johnson2, 1. Lackland AFB, TX; 2. Abilene, TX. Background:Treatment of imported fire ant (IFA) hypersensitivity includes avoidance and venom immunotherapy (VIT). VIT reduces the risk of stinging insect reactions to less than 5%. Despite this, one year IFA VIT adherence rates are only 35%. Previous studies have shown that rush immunotherapy (RIT) is safe and efficacious. It is unknown if multiple RIT procedures on individuals with breaks in VIT are safe and effective. Methods:Retrospective chart review of three patients who have undergone six IFA VIT ultra-rush protocols from 1996-2013 at our institution. Results:Patients were all female with a median age of 27 years. All are active duty service members without medical problems who reside in an IFA endemic area. Initial IFA reactions were mild-moderate. All patients had positive IFA skin tests. The initial RIT protocol for patient 1 was unavailable for review. Reviewed protocols consisted of 10 injections with a final dose of 0.3 mL 1:1 v/v IFA whole body extract given in 1 day. Four of the protocols included premedication with loratadine, prednisone and ranitidine. Local reactions (LRs) of 1-2 cm were the only side effect and did not require dose adjustments. LRs occurred on initial protocols in 2 patients and in 1 patient during repeat RIT. All patients completed the protocols without further incident. Patients 2 and 3 successfully tolerated sting challenges on day 22. Following each protocol, median VIT adherence was 9 months (range 2-72 months). Reasons for stopping VIT were deployment and pregnancy. The decision to stop VIT prior to pregnancy was made by the patients. Two patients remain on VIT; the third patient plans to resume VIT after her most recent pregnancy. Conclusion:Non-adherence is common and leads to breaks in VIT. RIT provides immunologic protection within weeks as noted through in vitro and in vivo studies. The risk of VIT resumption in patients with previous RIT or VIT is unknown. This case series illustrates the safety and efficacy of repeated IFA VIT ultra-rush procedures in patients who for personal and work reasons had breaks in VIT. Successful repeat RIT provided an earlier state of protection as proved by lack of clinical reactivity to sting challenges done 3 weeks after ultra-rush procedures. Additional studies to consider include the safety of repeated RIT in patients with breaks in VIT to other Hymenoptera species as this may improve VIT adherence rates.


P23 PREHOSPITAL MANAGEMENT OF ACUTE ANGIOTENSIN CONVERTING ENZYME INHIBITOR-INDUCED ANGIOEDEMA: A CASE REPORT. N. El Sanadi*1, K. Raczek2, T. Heiser1, D. Oatmeyer1, M. Camp2, 1. Ft. Lauderdale, FL; 2. Miami, FL. Acute angioedema is a true medical emergency due to high mortality rate resulting from severely compromised airway. Angioedema can be either hereditary or acquired. The acquired form is a rare but well-recognized side effect of angiotensin-converting enzyme (ACE) inhibitors such as Lisinopril. ACE inhibitor-induced angioedema is more common in African Americans and is more severe in older African American females (1). Emergency medical services (EMS) personnel are often the first contact for patients with acute angioedema. Paramedics must act rapidly while using the correct management protocols for patients presenting with symptoms consistent with this possibly fatal condition. Case Report: In June 2013 a 66 year old African American female contacted 911 complaining of “swelling to tongue” which began 10 minutes prior to calling EMS. She complained only of shortness of breath and denied any other symptoms. She was observed to be seated upright, breathing in the tripod position. The patient was noted to have swelling to mouth, tongue, and lips. The patient had been taking Lisinopril for 2 days. The patient was treated by paramedics with 3.00 LPM oxygen via nasal cannula, and 0.3 mg epinephrine 1:1,000 SQ. A 4-lead EKG showed sinus tachycardia. The patient was also treated with 50 mg diphenhydramine IV, 125 mg methylprednisolone IV, and an additional 0.3 mg nebulized epinephrine 1:10,000. Upon arrival in the ED, the patient’s condition continued to deteriorate. In this case report a patient who recently began taking Lisinopril developed severe angioedema. Despite promptly calling 911 and the appropriate medical management by EMS personnel, the patient’s condition continued to worsen. More aggressive measures such as emergency tracheostomy may be the best and first lifesaving option by EMS personnel for patients with life-threatening airway compromise. We believe that ours is the first case report to review and assess management options for angioedema (and specifically ACE inhibitor-induced angioedema) in the prehospital setting by EMS personnel. References 1. Kupfer Y, Ramachandran K, Tessler S. ACE inhibitor-induced angioedema in elderly African American females requiring tracheostomy. J Natl Med Assoc. 2010 Jun;102(6):529-30.


ABSTRACTS: POSTER SESSIONS Patient Vital Signs Pre and Post Treatment (a 15 minute interval)

2011 to 99.8% in 2012 after this campaign. Initiatives like this should be embraced and implemented among other health care organizations.

P26 Patient continued to deteriorate on arrival to the Emergency Department.

P24 PROTRACTED ANAPHYLAXIS IN A 35 YEAR OLD FEMALE WITH NO PRIOR HISTORY OF FOOD ALLERGIES. A. Patel*1, E. Rael2, 1. Morgantown, WV; 2. Hershey, PA. Anaphylaxis is an acute and potentially lethal multi-system allergic reaction. The clinical picture most often reported is one of respiratory compromise or cardiovascular collapse. Many allergens have been identified that as cause for anaphylaxis including medications, insect stings, foods, and vaccinations. Here we present a case of a 35 year old woman with new onset anaphylaxis which later presented as protracted anaphylaxis. This is a 35 year old female with no prior history of food allergies who while on vacation in Fiji ingested a shrimp salad in the morning, lobster bisque in the afternoon and trace amounts of lobster later that night and developed an anaphylaxis immediately after the second lobster ingestion. Her episode resolved after receiving two EpiPen injections and a 100 mg of oral prednisone. Her skin prick test was positive to trees, weeds, cockroach, dust mite pteronyssinus and farinae, cat and dog hair, and crab. She was educated on avoidance of specific food allergens and instructed on epinephrine use. She remained asymptomatic until 6 months later after accidental ingestion of crab at a restaurant. She had dyspnea, the feeling of throat closing and was taken to the emergency room. She received racemic epinephrine and albuterol without any relief. Decadron was administered but she developed hives and pruritis and it was discontinued. She was noted to have stridor with respiratory saturation of 88%. She was monitored in the ICU for four days and required epinephrine every 4 hours with subjective improvement in symptoms and maintained stable vital signs avoiding the need for intubation. However, recurrent episodes of dyspnea ensued with wheezing noted on exam. ENT performed laryngoscopy with no findings of vocal cord dysfunction. She continued to be on oral corticosteroids for two months after discharge. She underwent further work up as she had several other bouts of anaphylaxis that were treated with epinephrine and corticosteroids. ImmunoCap levels were elevated to apple, crab, shrimp, and lobster. Total IgE levels were elevated at 628. Her tryptase levels to assess for mastocytosis on several occasions as well as a 24-hr urinary histamine collection have been within normal limits. To our knowledge, this case report represents a dramatic case of protracted anaphylaxis after sensitization within one day to a previously tolerated food.

P25 IMPACT OF MANDATORY INFLUENZA VACCINATION INITIATIVE ON A MAJOR TEACHING HOSPITAL. A. Chouksey*, Cleveland, OH. Background: Influenza is a communicable disease and a major cause of morbidity and mortality. In any community, patients evaluated in a hospital are more susceptible for contracting Influenza virus if the care provider is not immunized with the influenza vaccine. Objective: In 2012 MetroHealth Medical Center launched a policy of mandatory influenza vaccination for its employees. This was done to minimize the risk of transmission of influenza virus to patients seen within the health system. Methods: A Influenza Vaccine Committee was formed with representation from allergy/immunology, infectious diseases and hospital administration. An official policy was launched and all the employees were requested to be immunized with Influenza vaccine. Those who reported to be allergic to influenza vaccine were referred to Allergy division for evaluation. Results: Out of 6200 hospital employees, a total of 41 patients were referred to the allergy clinic. 29 patients underwent definitive workup and 22 patients were successfully immunized with the influenza vaccine. 7 patients were confirmed to be allergic to influenza vaccine and granted official exemption. 5 patients declined to undergo definitive workup. 4 patients did not come for evaluation. 1 patient’s workup was deferred due to pregnancy. 1 patient was granted exemption by the committee without undergoing definitive workup.1 employee retired. Conclusion: The mandatory influenza vaccination campaign was effective .The immunization rate increased from 64% in

A CASE REPORT OF AN IGE-MEDIATED ALLERGIC REACTION TO DIPHENHYDRAMINE. S.R. Hariri*, J.A. Kleinman, M.E. Gianos, J.S. Yusin, Los Angeles, CA. Introduction: Diphenhydramine is a widely used first generation H1-antihistamine,used to treat and prevent allergic reactions. It is generally safe and mainly used in treating IgE-mediated reactions (such as urticaria, pruritus, localized edema and erythema) to other allergens. To our knowledge, diphenhydramine is the only antihistamine that can be given intravenously, and therefore is often used in the inpatient setting for drug-induced/iatrogenic adverse reactions, as well as for premedication with blood transfusions and other IV infusions to prevent allergic reactions. Allergic reactions to diphenhydramine are rare, and have been sparsely reported. Study Design: We describe a case report of an 84 year-old female with multiple myeloma, who received IV diphenhydramine as part of her treatment for multiple myeloma. Within minutes, the patient experienced localized edema and erythema at the IV site in which she was receiving diphenhydramine. Though rare, there have been case reports of diphenhydramine allergies in the literature, and thus skin prick test protocols for diphenhydramine are available and were utilized. Skin prick testing with diphenhydramine at 50 mg/ml was performed, and was positive with a 7 mm wheal. This was subsequently confirmed with intradermal skin testing with increasing concentrations of diphenhydramine (.005 mg/mL, .5mg/mL, 5mg/mL). The ID tests were positive at each concentration, causing wheals of 7 mm, 12 mm, and 22 mm, respectively. Thus, skin testing suggested that the patient’s localized reaction to IV diphenhydramine was most likely an IgEmediated adverse reaction to diphenhydramine. Conclusion: Based on the skin testing results, we confirm that the patient’s localized reaction to IV diphenhydramine was likely secondary to an IgE-mediated adverse reaction to diphenhydramine. An allergy to diphenhydramine does not preclude use of other H1antihistamines due to the unique, distinct chemical structure of each antihistamine. However, to our knowledge, there is no alternative antihistamine that can be administered intravenously.

P27 SEVERE DELAYED SYSTEMIC REACTION FROM STREPTOCOCCUS PNEUMONIAE VACCINATION. K. Achar*, D. Ferastraoaru, D. Rosenstreich, New York, NY. Introduction: Pneumovax®23 is indicated for prevention of pneumococcal disease by the 23 serotypes contained in the vaccine. Despite its extensive use, relatively few cases of severe hypersensitivity reactions have been reported. We present a case of a severe delayed systemic reaction to Pneumovax associated with very high levels of anti-pneumococcal antibodies. Method: Case Report. Result: 24 year old female with a history of persistent asthma and allergic rhinitis was referred for a suspected allergic reaction to immunization. She had been immunized with both Pneumovax and Tdap (tetanus, diphtheria, pertussis) for school enrollment. One day after the immunizations she developed a 10 cm induration and erythema at the Pneumovax injection site and a fever (104.3 F), fatigue, dizziness, headache and nausea. She was admitted for presumed erysipelas vs. a vaccine allergic reaction. Relevant laboratory values on admission were a leukocytosis (19,100/uL with 86% granulocytes, no eosinophilia). She was treated with intravenous antibiotics for two days with improvement and was discharged on antibiotics. An allergy clinic follow-up visit (two months later) revealed very high titers against Streptococcus pneumoniae (serotype 14-223.0 mcg/ml; serotype 5 > 100 mcg/ml; and elevated, but normal range protective titers for all other serotypes). In contrast, antiTdap antigen titers were only moderately elevated (tetanus toxoid-5.34 IU/ml; diphtheria-2.67 IU/ml; and pertussis-12 IU/ml). Total serum IgE was elevated (317.6 IU/ml), but quantitative serum immunoglobulin levels were normal. She had a history of gelatin intolerance (nausea) and porcine gelatin-specific serum IgE levels were minimally elevated. However, none of the two vaccines she received contain gelatin. Conclusion: This severe delayed systemic reaction associated with very high anti-pneumococcal antibody levels, suggested a type III (immune complex-mediated) hypersensitivity. Although her previous medical records were not available, it is presumed that she had previously been immunized with pediatric pneumonia vaccine (Prevnar), and her highest antibody titers after the Pneumovax were against two serotypes (5 and 14 ) that are contained in the 13 serotype Prevnar. This case suggests that caution



ABSTRACTS: POSTER SESSIONS should be used when immunizing younger individuals with Pneumovax, especially if they have previously been immunized with Prevnar.

P28 EVIDENCE FOR ETHYLENE OXIDE AS A CAUSE OF ANAPHYLAXIS DURING HEMODIALYSIS. S. Vishwanath*, S.A. Schwartz, Buffalo, NY. Introduction: Hypersensitivity reactions associated with hemodialysis are well known. Reactions secondary to complement activation by the cellulose membranes and sensitization to ethylene oxide have been reported. Ethylene oxide is a sterilizing agent used to clean heat sensitive medical, surgical instruments and tubing. This report emphasizes the importance of considering ethylene oxide as a causative agent for allergic reactions during hemodialysis and surgical procedures. Methods: We describe a patient admitted with acute renal failure and tumor lysis syndrome who tolerated the first hemodialysis without any problems. However he had anaphylactic reactions within 15 minutes of initiating his second and third hemodialysis sessions. He required epinephrine, methylprednisolone, and diphenhydramine during both of these episodes and underwent emergent intubation during his second hemodialysis. He had no further anaphylactic reactions with triple rinsing of the tubing thus minimizing his exposure to ethylene oxide. Results: During both the second and third hemodialysis sessions, the blood was discarded and not returned to the patient, therefore minimizing exposure to dialyzer membrane material. The dialyzer membrane and the sterilizing agent for the dialyzer membrane were Baxter 210 Cellulose Triacetate and gamma irradiation respectively. They were the same agents used in his first hemodialysis. Hence to avoid any further exposure, the dialyzer membrane and the sterilizing agent of the dialyzer membrane were both changed to Revaclear synthetic polymer PAES/PVP and steam respectively in his third dialysis session. Heparin was not the etiologic agent as he was receiving heparin for deep venous thrombosis prophylaxis without any problems. Complement studies were done including C2, C3, C4, and complement activating enzyme all of which were within normal limits. The common agent that the patient was exposed to in both of these sessions was ethylene oxide used as the sterilizing agent for the dialysis tubing. Conclusions: Our patient’s presentation of anaphylaxis with two different exposures to ethylene oxide emphasizes that this is an important etiologic agent for hypersensitivity reactions during hemodialysis. As it is also used in sterilizing surgical instruments, perioperative anaphylaxis may be another presentation noted in ethylene oxide hypersensitivity.

P30 ASSOCIATION OF ANAPHYLAXIS, URTICARIA, AND ANGIOEDEMA WITH CD203C EXPRESSION ON HUMAN BASOPHILS. N. Paluvoi*1, S. Rajan2, M. Plassmeyer2, M. Brown2, B. Enav2, O. Alpan2, 1. Leesburg, VA; 2. Fairfax, VA. Introduction: The basophil surface protein CD203c, is a marker for basophil activation and is utilized as a component of basophil activation test in various anaphylactic and urticarial disorders. The goal of this study is to identify normal range values for CD203c and compare the expression of this surface molecule in resting peripheral blood basophils of patients with anaphylaxis, urticaria, and angioedema. Methods: All patients and their medical history were examined prior to sample collection. Venous blood was collected into BD Vacutainer tubes containing EDTA (purple top) and processed within 24 hours. Erythrocytes were lysed using FACSLysing solution (BD Biosciences) according to the manufacturer’s instructions, and then the remaining PBMCs were analyzed on an AccuriC6 Flow Cytometer (BD Biosciences). Peripheral blood granulocyte population was first identified by forward and side scatter and basophils were further identified as CD203c+CD123+HLA-DR- cells within this granulocyte population. Results: A total of 83 allergy patients were evaluated. Subjects were divided based on their diagnosis into 4 groups: Anaphylaxis (8), Urticaria (39), Angioedema (16), and Control (20). There was no significant overall variation of peripheral blood basophil numbers in the control group versus the anaphylaxis patients. The p value for anaphylaxis patients was over 0.05, which seemed to show no significant variance from the control group. Conversely CD203c was statistically significant in the urticaria with a mean value of 33% (p < 0.05) and angioedema 38% (p = 0.01) in comparison with the control group (26%). Conclusion: Basophil activation markers, especially CD63 and CD203c have been reported to correlate with various anaphylactic disorders, and have been mostly examined in the setting of an activating stimuli (e.g. bee venom and drug allergens). The increase in the percentage of resting basophils expressing CD203c in patients with urticaria and angioedema indicates the need for further correlation studies in establishing in vitro activation ranges for this surface marker in comparison to patients with anaphylaxis, which seem to behave similarly to healthy controls.




Introduction: Peanut allergy is one of the most severe and common among food allergies. Peanut molecular component testing for IgE to Ara h 1, 2, 3, 8, and 9 has been developed as an improved in vitro blood test to predict the likelihood of an allergic reaction. Methods:A retrospective review of national laboratory data was performed over the first eight months of the testing for IgE to Ara h 1, 2, 3, 8, and 9 (Phadia), utilizing data with de-identified patient health information. Data was compiled into risk groups based on current research utilizing a cutoff of 0.1 kU/L as a positive test. Results: Sixty one percent of samples were positive for Ara h 2, which carries the highest risk for anaphylaxis. Of these samples thirty percent were positive for only Ara h 2, and 44 percent were positive for Ara h 1, 2, and 3. Positivity for Ara h 9 with or without Ara h 8 positivity accounted for only 4 percent of samples.These patients have a moderate risk for a systemic reaction due to the cross reactivity ofAra h 9 with peach pollen. Only 7 percent of samples were positive for Ara h 8 alone, which represents the lowest risk of a systemic reaction due to the cross reactivity between Ara h 8 and birch pollen. Conclusions: Molecular component allergy testing represents a major step forward in diagnosing and assessing risk for peanut allergic individuals. A significant rate of high risk identification indicates the importance of this information for patients and their families. Additional studies and subsequent practice guidelines are likely to emerge in the near future now that component testing is available for clinical use.








Introduction: we report a case of a patient with achalasia and multiple anesthetic allergy. Case presentation: A 37 years old male with achalasia presentes intraoperatively an adverse drug reaction “anaphylaxis”, manifested by tachycardia, hypotension, and generalized urticaria suspending the procedure. Systemic steroid, antihistamine and norepinephrine were indicated requiring ICU monitoring. He was sent to our department for evaluation of adverse drug reaction because of the need for a new surgical procedure. The patient had no history of atopy or previous drug allergy. We performed an intradermal testing protocol for Rocuronium, Metoclopramide, Ondansetron, Omeprazole, Ceftriaxone, Fentanyl, Propofol, Rupivacaine, Vecuronium, Bupivacaine, Etomidate, Thiopental, Cisatracurium, with positive results for all of them. Only lidocaine and lidocaine with epinephrine were negative. Discussion: Anaphylaxis is a severe systemic hypersensitivity caused by the release of a large number of biologically active mediators acting on various target organs (cardiovascular, respiratory, cutaneous and gastrointestinal mucosa) giving rise to diverse clincal manifestations. Immediate hypersensitivity often (52-60%) is immunologically mediated by the interaction of specific IgE antibodies with the responsible agent, causing the activation of mast cells and basophils (anaphylaxis). However, non immunologic mechanisms can also activate mast cells (anaphylactoid reactions), resulting in similar clinical syndrome and indistinguishable by clinical manifestations. There are three mechanisms responsible for the allergic reactions to drugs: 1. IgE-mediated anaphylaxis (Type I immediate hypersensitivity). 2. Activation of the complement system. 3. Pharmacological release of mediators. Conclusion: In this case pharmacological activation and chemical mediators released by effector cells caused anaphylaxis. Given the need to solve the underlying disease, it is recommended not to use anesthetics and find another alternative for the treatment of achalasia, including pneumatic dilatation.

P32 RECURRENT FLUSHING AND ANGIOEDEMA WITH INHALED ALBUTEROL. L. Helfner*, D. Hirsch, B. Kaplan, Great Neck, NY. Introduction: Albuterol, a widely used selective beta2 agonist, is the most commonly used short acting bronchodilator. It is generally well tolerated, although significant adverse events include tremor, palpitations, and tachycardia. Less frequently encountered side effects include hyperglycemia, hypokalemia, nausea, and headache. We report a case of recurrent flushing and facial angioedema, with nebulized albuterol, in a patient who previously tolerated albuterol HFA. Methods: An 80-year-old woman with a history of COPD and seasonal allergic rhinitis on Advair, Flonase, and albuterol prn presented following a reaction to albuterol. After wheezing was heard by a visiting RN, the patient was instructed to use nebulized albuterol via mouthpiece three times a day for 2 days. After the first day, her face appeared mildly swollen. After the first dose of albuterol the following morning, she developed a persistant erythematous rash on her face, along with swelling of her cheeks and eyelids. On the eighth day of her facial rash, she developed a similar pruritic rash on her chest, which improved with hydrocortisone 2.5% cream BID and Aquaphor cream daily. She denied any fevers, urticaria or increase in respiratory distress during these events. She had not used any new soaps, lotions, detergents, or items of jewelry that could have caused a contact reaction. She had used albuterol, both via HFA and nebulized, in the recent past without any adverse reactions. Results: Skin prick testing was negative to albuterol 0.83% nebulizer solution. After a negative response was elicited, the patient was given an albuterol challenge via nebulizer. One hour after receiving the nebulized Albuterol, the patient developed facial erythema and pruritis of her hands. Her symptoms resolved within 40 minutes of receiving oral diphenhydramine. She returned for a challenge to Levalbuterol. She tolerated a total of 3 puffs of Levalbuterol delivered via HFA with no adverse reaction. Conclusion: We present an uncommon case of flushing and angioedema to nebulized albuterol with negative albuterol skin prick testing, in a patient who previously tolerated albuterol HFA. Etiology includes a hypersensitivity response to a preservative of nebulized albuterol. This case highlights that even such a commonly prescribed and seemingly benign drug such as Albuterol can cause significant adverse reactions, and clinicians must remain alert.

Background: Recent studies have demonstrated that Alternaria and German cockroach allergens can be degraded by proteases in certain insect and fungal extracts when combined for immunotherapy. Data supporting the compatibility of other fungal or insect products in comparable mixtures have not been reported. Objectives: To determine the stabilities and compatibilities of Aspergillus fumigatus and American cockroach allergens in mixtures containing other high-protease, whole-body fungal and insect (cockroach, imported fire ant) extracts at final product concentrations consistent with injection dose targets for maintenance immunotherapy. Methods: Mixtures containing Aspergillus fumigatus, American cockroach, and other fungal and insect extracts were analyzed by quantitative (IgE ELISA inhibition) and qualitative (IgE/IgG immunoblotting) methods. Mixtures and analogous single-extract controls containing 10-50% glycerin were evaluated after storage for up to 12 months at 2-8°C. Results: Aspergillus fumigatus extracts retained high levels of allergenic activity under all conditions examined, with control samples producing moderate to high recoveries relative to freshlyprepared references. American cockroach extract controls were partially degraded at 10-25% glycerin, and were further reduced to a significant degree in mixtures with several fungal extracts at 25% glycerin. Combination with other insect extracts did not compromise the stability of American cockroach allergens at 25-50% glycerin concentrations. Conclusions: The IgE-binding activities of American cockroach extracts were destabilized upon mixing with several fungal extracts, consistent with recent data on German cockroach allergen compatibilities. Separation of fungal and cockroach products into different treatment vials, or formulation of fungal-insect extract mixtures at elevated glycerin levels, may be required to produce stable patient vaccines for subcutaneous immunotherapy.

P34 COMPARISON OF SEASONAL VARIABILITY OF AIR POLLEN OBTAINED IN THE SAME THREE-YEAR PERIOD, BETWEEN THE CITY OF BUENOS AIRES AND BAHIA BLANCA, ARGENTINA. G.D. Ramon*, L. Barrionuevo, N. Arango, F.M. Ramon, Bahia Blanca, Buenos Aires, Argentina. The aim of this work was to follow up and comparison (between 20102012) for two cities of Argentina. To determine if the seasonality of pollinosis is still maintained or if the same during the year. This study was conducted for the city of Bahia Blanca and Buenos Aires, both from Argentina. For this analysis we used the data sheets on pollen rain aerobiological surveyed by stations in Bahia Blanca and Buenos Aires in the years mentioned. The presence of pollen in the air was discriminated into three categories (trees, grasses and herbs). Within this classification, we determined whether the pollen rain corresponded to some of the following ranges: none, mild, moderate, high, very high. Comparing the pollen rainy days in the two cities sampled, no differences were observed between pollen rain days and without it. However it is observed that the pollen rainless days have increased over the three years in both cities. When considering the Tree pollen there was a greater concentration of pollen grains /m3 in the air sampled in Bahia Blanca, despite observed the presence of a less definite seasonality than in previous years. A peculiarity observed in the city of Buenos Aires is the presence of pollen from trees throughout the calendar year, but always finding higher concentrations between the months of July-August and November-December. In the category Grasses there is a greater concentration of pollen grains /m3 sampled in Buenos Aires. While there are no differences at the time of onset of pollinosis, yes there is regarding the time of finalization, extending in a month and a half more in the city of Bahía Blanca. For the category of weeds, there was an increase in pollinosis season that extends throughout the calendar year, but always the highest concentrations were found in the months of January to March compared to the two cities. Based on the above, we conclude that the Grasses category is what keeps most marked seasonality in the two cities. In the Buenos Aires City the trees have extended their season, and we found tree pollen throughout the year, without changing the time of beginning of flowering. Meanwhile, the presence of Weeds remains during the whole year, having sometimes so highest records that are not normally observed in the two cities sampled.



ABSTRACTS: POSTER SESSIONS nae (52.4%) and Blattella germanica (25.7%). A mixed pattern was observed in 51.4% of patients. Conclusion. Most of the allergic adults attended in our service are poly-sensitized to aeroallergens. In-door allergens are the most frequently involved, the most common are house dust mites (Dermatophagoides pteronyssinus and Dermatophagoides farinae).


P36 SENSITIZATION TO AEROALLERGENS IN ADULT PATIENTS ATTENDED AT THE ALLERGY SERVICE OF THE UNIVERSITY HOSPITAL IN MONTERREY, MEXICO. H. Hernández Sánchez*1, S.N. Gonzalez-Diaz2, A. Arias Cruz2, C.I. Gallego-Corella2, A. Macias-Weinmann2, J.I. Canseco-Villarreal2, L.A. Dominguez-Sansores2, V.I. Yanez Perez2, L. Rangel-Garza2, 1. Escobedo, Nuevo Leon, Mexico; 2. Monterrey, Nuevo Leon, Mexico. Background. The aeroallergens are the most common cause of allergic sensitization in adults and have a preponderant role in the pathogenesis of allergic respiratory diseases. The biodiversity of airborne allergens varies by geographic area and climate of each region. The skin prick tests are the standard method for identifying sensitization IgE mediated. Objective. Identify the aeroallergens that most often cause allergic sensitization in patients treated in the allergy department at the University Hospital of Monterrey. Methods. We performed an observational and descriptive study, consisting of the review of medical records of patients who had undergone skin prick tests with extracts of aeroallergens, from 2009 to 2012. We obtained demographic and clinical data of patients, the results of skin tests. All skin testing included 36 different extracts of common aeroallergens in the northeastern region of Mexico. We evaluated the frequency of sensitization to allergens, as well as the pattern of that (outdoor, in-door or mixed allergen sensitization). Data were analyzed using descriptive statistics using the SPSS 20. Results. The records of 2,170 patients were reviewed. 1,777 patients were sensitized to at least one of the tested aeroallergens. The mean age of these patients was 35.1 years and 57.3% were female. In relation to age, 12.4% had <20 years; 56.2% 21 to 40 years; 26.4% 41 - 60 years; and 5% 61 to 80 years. Aeroallergen sensitization was more frequent in the group of 21 to 40 years. The diagnoses of patients included allergic rhinitis (82.7%), asthma (8%), atopic dermatitis (2.4%) and urticaria (6.9%). 92% of patients were poly-sensitized and only 8% mono-sensitized. Sensitization to out-door aeroallergens only occurred in 15%, and the most frequent were Prosopis spp (32%), Cynodon dactylon (31%) and Amaranthus palmeri (28.9%). Sensitization to in-door aeroallergens only occurred in 33.6% and the most frequent were Dermatophagoides pteronyssinus (57.9%), Dermatophagoides fari-


Introduction: The aim of this study was to determine differences in extractability of tree nuts using varied extraction conditions. Methods: Prior to extraction, walnut (W), pecan (PN), Brazil nut (BN), almond (A) and pistachios (P) were macerated, defatted with 100% acetone or a 50% acetone, petroleum ether mix, and extracted overnight in 50% glycerin or aqueous extraction buffer using multiple extraction techniques (i.e., blending, persistent stirring or rocking). Extractions were performed at 4°C for all tree nuts, with additional room temperature extractions for walnut. Following extraction, all samples were adjusted to contain 50% glycerin, centrifuged and sterile filtered. The extracts were then evaluated for differences in protein profiles and concentrations using SDS-PAGE and Coomassie Blue. Results: The solvent used to defat the various tree nuts did not significantly alter final protein concentrations or protein banding patterns. The average protein concentrations for A, BN, PN and P extracts were 12.2 mg/ml, 10.2 mg/ml, 1.1 mg/ml and 10.2 mg/ml, respectively. There were no significant differences in protein profiles or concentrations, within the same nut species, with glycerin or aqueous extraction, nor were there differences when various extraction conditions were utilized. Walnut extraction, however, produced contrasting results. The final protein concentrations of the walnut extracts varied significantly, according to the extraction method. Glycerin extraction resulted in an average final concentration of 1.9 mg/ml, versus 0.3 mg/ml for aqueous extraction. Furthermore, room temperature extraction resulted in higher protein yields (2.8 mg/ml), when compared to extraction at 4°C (1.7 mg/ml), and persistent stirring was the superior method of agitation. Overall, the protein band intensity correlated directly with the final protein concentrations, regardless of species. Conclusions: Optimal extraction conditions for tree nuts vary according to species. No significant protein differences were observed in almond, pistachio, Brazil nut and pecan extracts, however, significant alterations in protein concentrations were observed among walnut extracts. Ideal conditions for walnut extraction include room temperature, glycerin extraction with persistent stirring. Further work is needed to evaluate correlations between extraction conditions and overall extract potency and stability.

P38 IDENTIFICATION AND CHARACTERIZATION OF CYANOBACTERIAL ALLERGENIC PEPTIDES. E. Geh, D. Ghosh, J.A. Bernstein, Cincinnati, OH. Background: Health effects caused by cyanobacteria (blue green algae) remain poorly elucidated. The cyanobacteria specie, Microcystis aeruginosa (Ma), produces an array of diverse metabolites believed responsible for their toxicity and/or immunogenicity. Previously, chronic rhinitis patients were demonstrated to elicit a specific IgE response to non-toxic strains of Ma by skin-prick testing indicating that cyanobacteria allergenicity likely resides in the non-toxin producing component of the organism. This study’s objective was to identify and characterize Ma peptide(s) responsible for allergic sensitization in susceptible individuals. Methods: Sera collected from Ma sensitized rhinitis patients were used to identify sensitizing proteins by IgE-specific direct and indirect ELISAs in response to Ma. Gel filtration chromatography followed by specific IgE immunoblots and mass spectroscopy was performed to identify relevant protein bands. Results:Specific IgE was increased in sera of Ma sensitized patients which was inhibited by pre-incubation of serum with the Ma lysate in a dose-dependent manner. Gel filtration chromatography revealed the relevant sensitizing peptides were isolated to the high molecular weight fraction of the lysate. Specific IgE immunoblotting revealed three distinct bands with molecular weights 105 kD, 75 kD and 50 kD. Mass spectroscopy identified one of these proteins to be C-phycocyanin which exhibits 85% sequence homology with the C-phycocyanin found in the food supplement, Spirulina, previously reported to cause anaphylaxis. Conclusions:Specific peptides in non-toxic strains of Ma that elicit specific IgE responses in Ma sensitized individuals have been identified. Further investigation is ongoing to determine the functional significance of this finding.



P39 IMPACT OF PRE-POLLEN SEASON WEATHER PATTERNS ON THE ONSET AND PEAKS OF TREE POLLINATION IN VINNITSA, UKRAINE. V. Rodinkova1, O. Palamarchuk1, L. Slobodjnuk1, I. Motruk1, L.M. DuBuske*2, 1. Vinnitsa, Ukraine; 2. Gardner, MA. Background: Tree pollen seasons may be highly susceptible to weather conditions before pollination begins. This study analyzes the impact of weather on the onset, peak and end of tree pollination in Vinnitsa, Ukraine in 2013, a year in which tree pollen was more intense than in prior years. Method: Pollen counts were obtained at Vinnitsa National Pirogov Memorial Medical University (VNMU) in 2009 to 2012 on a daily basis employing volumetric methods using a Burkard trap placed on a roof at 25 meters above ground. Weather conditions for this analysis were obtained from TuTiempo.net. Results: Weather condition analysis before the pollen season showed March, 2013 was colder than the previous four years. The monthly mean temperature of March, 2013 was -2.1°C, but was above zero degrees C for each year from 2009 to 2011. Maximal temperature in March, 2013 was 0.8°C while from 2009 to 2011 the maximal temperature was 5 to 6°C. Early pollinating genera Alnus and Populus showed rapid and late pollination with shifted seasonal onset and peaks. While usually starting from March 10 to March 17 from 2009 to 2011, Alnus pollen season in 2013 started April 3 with peak pollination shifted 17 to 20 days later than seen in the previous seasons, going from March 24 to 26 to April 13 in 2013. Later pollination onset was observed for Populus beginning April 10, 10 to 29 days later than in the previous years although the peak on April 19, 2013 was similar to the peaks of April 24, 2009 and April 21, 2011. Corylus typically has early pollination beginning March 6 but was on April 20 in 2013, which is 28 to 33 days later than it was observed the prior years. While seasonal onset for Betula was normal, the second maximum of Betula pollen, usually seen no later than April 25 to 26 was noted on April 30. Onset for Carpinus pollination was normal, but the seasonal peak was shifted one week later from April 11 to April 19, while the season ended on time. Late pollination of Quercus and Juglans was not affected by weather. Conclusion: Various trees react differently to cold weather before the onset of pollen season with delayed onset and delayed seasonal pollen peaks. Early pollinating trees are most sensitive to weather parameters before the pollen season, whereas late pollinating trees are less impacted.

P40 KNOWLEDGE EVALUATION OF POLLINOSIS AND ALLERGENIC FLORA TO ALLERGISTS IN MEDICAL CENTERS OF MEXICO CITY. P. Cano*, G. Guidos, J.C. Sandino, Mexico City, DF, Mexico. Allergic diseases have become a significant issue. About 20% of the world’s population has an allergic disease; primarily by pollen sensitization. This implies an impact as it involves and requires economic and social costs. Treatment for this with leads integral handling between specified allergological immunotherapy, pharmacotherapy for symptoms and patient education measures. It also implies knowledge of pathogenetic diseases through specialist, knowledge of allergic flora of region and pollination of plant. Objective: Evaluate knowledge of allergenic flora of allergists. Hypothesis: Allergists in main medical centers have limited knowledge of pollinosis and allergenic flora identification. Methodology: An interview was conducted as an open questionnaire evaluating knowledge through allergenic flora photos of the Valley of Mexico; selected by their important concentration of pollen in atmosphere and allergenicity. Photos provided by the Center for Science of the Atmosphere of UNAM were reviewed by botanic experts and palynologists. Seven trees (Fraxinus, Cupressaceae, Salix, Eucalyptus, Pinus, Schinus, Populus) one grass (Lolium) and three weed photos (Amaranthus, Artemisia, Chenopodium) were used. Present allergists were interviewed. Descriptive methodology, averages and percentages were performed, using a spreadsheet in Excel ™ 2007 Results: Allergists’ answers about allergenic flora Understanding of pollinosis: 25% knew concept, 70% somewhat sense, 5% didn’t know Number of patients they considered attended for pollen regularly: 45% said between 50-99%, 30% said between 20-50%, 25% said less than 20% Knowledge about allergenic flora in metropolitan area: 30% said acceptable, 20% regular, 50% low Knowledge of allergenicity of pollen species: 100% didn’t identify all photos, 25% identified at least 5, 75% identified less than 4 Consideration for allergenic flora in region: 75% didn’t know allergenic flora found in region, 25% knew 5 or less Allergists presented with photos: Identified at least one: Tree 85%, Grass 25%, Weed 25% Did not identified at least one: Tree 15%, Grass 75%, Weed 75% Identifies incorrectly at

least one: Tree 75%, Grass 25%, Weed 85% Conclusion: Allergists show to have poor knowledge, and is suggested a continuous update of the knowledge using study programs for precise recognition of important allergenic flora in region.

P41 UTILITY OF SERUM IMMUNOASSAY SENDOUT TESTS AT A VA HOSPITAL. K.J. Garg*1, B. Bauer2, J. Fernandez2, 1. Cleveland Heights, OH; 2. Cleveland, OH. Background: Patients with symptoms of allergic rhinitis (AR) are frequently referred to an allergy/immunology specialist for allergy skin testing and consideration of allergy immunotherapy. Prior to referral, many patients undergo serum immunoassay tests (RAST) to test their individual IgE response to common allergens. Allergy skin testing has been consistently reported in previous literature as superior to RAST for diagnosis of allergen triggers for AR. At this Cleveland VA hospital, the RAST panel is a sendout lab with an estimated cost of $217.25 per sendout. We sought to determine the utility of this expensive sendout test by seeing how frequently and in what situations it is accurate, and whether or not it affects clinical management. Methods: Retrospective chart review. Results: 36 charts were reviewed of Cleveland VA patients who had undergone RAST testing prior to referral to an allergy/immunology specialist between January 2013 and June 2013. Skin test was considered the gold standard for diagnosing allergen triggers, as decisions for immunotherapy were made based on results of skin testing and correlation with patient symptoms. RAST testing was considered positive if the level was 3 or greater. Positive skin testing for the following allergens correlated with positive RAST testing in the following percentage of cases: 0% (weeds), 64% (ragweed), 25% (dustmite), 57% (grasses), 53% (cat), 25% (dog), 31% (molds). Positive RAST testing correlated with positive skin testing in the following percent of cases: N/A (weeds), 72% (ragweed), 75% (dustmite), 75% (grasses), 100% (cat), 100% (dog), 100% (molds). Negative RAST testing correlated with positive skin testing in the following percent of cases: 82% (weeds), 60% (ragweed), 100% (dustmite), 67% (grasses), 73% (cat), 86% (dog), 82% (molds). Conclusions: For most environmental allergens, RAST testing for AR triggers is accurately positive less than 50% of the time. Although positive RAST testing correlates fairly well with skin test positives, the RAST test result does not preclude patients from undergoing skin testing and does not independently allow an allergist to make decisions regarding immunotherapy in the absence of skin testing. Negative RAST testing to most environmental allergens is associated with positive skin testing in the vast majority of patients and represents false negatives.

P42 ASSOCIATIONS BETWEEN PERSISTENT VIRAL INFECTIONS AND ALLERGIC RHINITIS WITH ASSOCIATED CROSS-REACTIVE FOOD ALLERGY IN WESTERN UKRAINE. K. Lishchuk-Yakymovych*1, R. Pukalyak1, L.M. DuBuske2, 1. Lviv, Ukraine; 2. Gardner, MA. Background: Pollen allergy can lead to plant-derived food allergy based on cross-reactive allergens. Infectious viral illnesses may complicate treatment of allergic diseases leading to poor responses to therapy. Methods: 335 patients with allergic rhinitis (195 women and 140 men, mean age 29±5.6 years) were studied at the Lviv Regional Clinical Diagnostic Center, Ukraine from 2010 through June, 2013. Laboratory assessments included absolute eosinophil counts, total IgE levels, and allergen specific IgE levels (Polycheck-tests, Biocheck, Germany). Serum samples were assessed for presence of antibodies to Human Herpesvirus 6 (HHV6), Cytomegalovirus (CMV), and Epstein–Barr virus (EBV) by ELISA (Vector Best). Results: Allergic rhinitis patients may have cross-reacting sensitizations to two or more foods, especially in the presence of persistent EBV and HHV6 infections. Frequent symptoms are: oral tingling, 78 (23.3%) patients; oral swelling, 118 (35.2%) patients, mouth/lip itching, 205 (61.2%) patients; and gastrointestinal symptoms in 11%. A correlation was noted among clinical symptoms, eosinophilia severity and elevated titers of IgG anti-EBV viral capsid antigen, and IgG anti-HHV6 in patients with severe allergic rhinitis. Mild rhinitis and oral swelling were noted in 149 (44.5%) patients with mild eosinophilia (Eos 0.8±0.12 G/l), increased total IgE level (232±147 IU/ml) and IgG antibodies to EBV early antigen. Rhinitis, conjunctivitis and lymphadenopathy were noted in patients with moderate eosinophilia (EOS 1.9±0.29 G/l), increased total IgE level (290±18.3 IU/ml) and elevated IgG anti-EBV viral capsid antigen, and elevated IgG anti-HHV6. Allergen specific IgE to inhalant and food allergens revealed cross-reactions between: a) birch pollen/



ABSTRACTS: POSTER SESSIONS hazel pollen, and apple/ carrot in 116 (34.6%) patients; b) timothy grass pollen and peanut/ tomato in 52 (15.5%) patients; c) alder pollen/ birch pollen and celery/ tomato in 31 (9.3%) patients; and d) cheese and mold allergens in 16 (4.8%) patients. Conclusion: Management of patients with allergic rhinitis having symptomatic cross-reactive food allergen sensitization may be influenced by the presence of chronic persistent viral infections.

in sera from subjects in Canada and the West (Table). Conclusion: Most subjects were sensitized to Phl p 1 (73%) and Phl p 5 (50%). The highest mean IgE levels and proportion of Phl p 1- and Phl p 5-positive subjects were found in Canada and the western part of the USA, corresponding to regions where Timothy grass (Phleum pratense) is most prevalent. Average levels of specific IgE levels (kU/L) for each region and Timothy grass component (Phl p).

P43 AGE-DEPENDENT TRENDS IN IGE SENSITIZATION AT THE COMPONENT LEVEL. J.C. Thompson*1, R.D. Duquette2, 1. Augusta, GA; 2. La Crosse, WI. Introduction: During infancy and early childhood, allergen sensitization occurs via gut, skin and respiratory tract exposure. In later childhood through adulthood, sensitization is primarily via respiratory tract exposure. This trend is reflected in sensitization profiles to specific protein allergens or components which supports the “atopic march” hypothesis. While southern European investigators have described the IgE component repertoire in children and adolescents, little is known about corresponding North American subjects who are exposed to similar but not identical environments. The following IRB-approved cross-sectional study shows age-dependant trends in the prevalence of IgE sensitizations. Methods: Serum samples from 170 Midwest American patients with known allergic disease were assayed by the ISAC microarray (Thermo-Fisher Scientific) which quantifies IgE to112 allergenic components. Subjects were divided into three age groups, < 5 years (n=37), 5-12 years (n=69) and those >12 years (n=64). For each component, a least-squares regression slope reflects the age-dependant trend of decreasing, stable or increasing prevalence of sensitization. Results: Similar to European findings, the prevalence of sensitization to food components (egg, milk, wheat, peanut and tree nut sources) is greater in young children than in adolescents and adults. Sensitization to lipid transfer proteins (LTP) in foods (peach, wheat) is common in children. In adults, pollen LTP (mugwort) sensitization predominates food sources of LTP. In contrast to European findings, pollen (mugwort, grass, ragweed, cedar, birch) sensitization is common in early childhood but similarly the prevalence increases through adulthood. The most common sensitization in the entire group is to Fel d 1, cat uteroglobin, which predominates sensitization to foods, dust mite, pollens, and animal lipocalins. Sensitization to Alternaria Alt a 1 persists across the age groups. Conclusions: These findings support a decrease in the prevalence of sensitization to food allergens (egg, milk, peanut, tree nuts) beyond childhood. This may reflect maturation of the immune system and gastrointestinal tract as well as the natural resolution of some food sensitizations. Variation in the sensitization profiles to both food and environmental allergens by region invites geographic mapping of IgE component results.

P44 MOLECULAR PROFILES OF IGE TO TIMOTHY GRASS ALLERGENS IN PATIENTS SCREENED FOR GRASS TABLET IMMUNOTHERAPY. M. Nolte*1, J. Maloney2, H. Nolte2, 1. Bozeman, MT; 2. Whitehouse Station, NJ. Rationale: Serum specific IgE levels to individual allergen components may vary depending on pollen exposure and allergen cross-reactivity. Regional differences in allergen exposure may induce different sensitization patterns. The objective of this post hoc analysis was to describe the IgE sensitization pattern in a SPT-positive patient population reporting Timothy grass allergy screened in 6 regions of North America. Specific IgE levels to a panel of 113 different allergens were measured using a microarray specific IgE method. Methods: 1922 subject sera from the P08067 (NCT01385371) study were collected in Canada and 5 regions of the USA (Mid-Atlantic [MA], North Central [NC], Northeast [NE], South [S], West [W]). Serum specific IgE was measured using the Phadia ISAC microchip method in grass-pollen−allergic patients who consented to the analysis. Approval was obtained from appropriate IRBs. Results: Most subjects were multi-sensitized with detectable (≥0.35 kU/L) serum specific IgE to grass and other common allergens, including tree (56%), weed (44%), animal dander (43%), mites (26%), foods (23%), and mold (22%). Out of 1922 subjects with a positive skin test to Timothy grass and history of grass pollen allergy, 1584 (82%) had measurable specific IgE to at least one of several Timothy grass allergen components (Phl p). Most subjects were sensitized to Phl p 1 (73%) and Phl p 5 (50%). The highest proportions of Phl p 1- and Phl p 5-positive subjects were found in Canada and the western part of the USA. The highest mean IgE levels against Phl p 1 and Phl p 5 occurred


P45 UPDATE ON MANNITOL CHALLENGE EXPERIENCE FOR DIAGNOSIS OF EXERCISE INDUCED BRONCHOCONSTRICTION. C.C. Randolph*, Waterbury, CT. Introduction:Exercise induced bronchoconstriction(EIB) is the earliest sign of asthma and the last to resolve .Up to 90% of asthmatics have EIB.Diagnosis of EIB is accomplished by pulmonary function testing pre and post bronchodilator or by exercise challenge .Mannitol is a surrogate exercise challenge.We update our experience with mannitol challenge for EIB diagnosis in practice which is specific for EIB and easily performed in an office setting. Methods:Patients with a history of EIB and /or asthma with normal pulmonary function pre and post bronchodilator were consecutively evaluated by mannitol challenge and prick test for inhalant allergen. Results: There were 80 patients demographically mean age 19 years,median 16 year,range 8-68 years,36 male(45%),44female(55%),77 Caucasian(96%),3 AfroAmerican(4%)with history:31(39%) with EIB,35(44%)asthma,6(8%) both,10(13%) nonspecific,52(65%)with allergic rhinitis .Mannitol was positive in 33(41%)with mean 279mg,median 130mg,range 5-635mg with FEVI decline mean and median 17%,range 10-27%.Mannitol had 100% specificity,52%sensitivity,100%PPV,38%NPV using history as the standard. Conclusions.Mannitol challenge is highly specific though not as sensitive with high positive predictive value for diagnosis of EIB using history as a standard.Comparison with objective exercise challenge would be the preferred standard but is not easily available in all office settings.

P46 IMPROVING ASTHMA RISK STRATIFICATION AT AN ACADEMIC PEDIATRIC CLINIC. J.A. Grillo*, L.E. Robbins-Milne, L.A. Matiz, M.M. Lane, New York, NY. Background: Asthma is the leading chronic illness in children with a prevalence of 8% nationally, and 18-22% in Washington Heights, NY. A quality improvement (QI) project was initiated to explore the feasibility of obtaining Asthma Control Test (ACT) scores and assigning priority levels to asthmatics in order to implement risk stratification. Methods: Goal: to increase the percentage of asthmatics receiving priority levels. QI interventions included: educational sessions for support staff and physicians about ACT Score distribution and implementation for the purpose of identifying asthmatic patients and assigning priority levels, implementation of a novel automated task column in the electronic health record (EHR) to improve recognition of patients requiring an ACT score and priority assignment, and personal provider report cards of the percentage of asthmatic patients with a priority level in a provider’s practice. Providers were surveyed to obtain feedback about the impact of a report card on their practice. Results: Over a six-month period, priority level assignment increased from a baseline rate of 22% to 54%. Of asthmatic patients, 34% were assigned priority levels at walk-in visits and 54% at scheduled visits. When surveyed, 75% of providers found the report cards helpful, 68% felt report cards helped sustain change. Conclusion: Asthma risk stratification following a series of QI interventions was feasible through the use of ACT scores and priority levels. Staff education alone did not impact stratification rates. Implementation of an automated task column in an EHR and individual provider feedback improved stratification rates. The impact of the task


ABSTRACTS: POSTER SESSIONS column may have been diminished by its deployment in the middle of the improvement process, missing patients presenting in earlier stages. Fewer asthmatics were assigned priority levels during walk-in visits likely due to time constraints and the difficulty of assessing control during an acute exacerbation. The majority of providers found the report cards helpful and felt they sustained change. To sustain progress, provider report cards will expand to include the percentage of patients in each priority level. Prospectively, children with asthma will be targeted based on their priority level to assess for prescribing rates of controller medications, to schedule follow-up visits, and to provide reminders for influenza vaccines.

from January 1 to December 31, 2011 with a diagnosis of asthma exacerbation (code 493.xx). 343 admissions were reviewed for demographic data, diagnoses and interventions received in the Emergency Department and hospital ward. For patients with multiple admissions, only the first was used for the primary analysis. 319 charts were included. Results: The average LOS for an asthmatic patient was 1.7 days. Descriptive statistics were stratified by hospital LOS: < 2 days (the average) versus >= 2 days. The majority of patients were admitted to the hospitalist or private pediatricians’ services. A greater percentage of patients in the LOS >= 2 days group received antibiotics (P<0.0001), chest x-rays (P=0.0001), or supplemental oxygen (P<0.0001) compared to the LOS < 2 days group. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using a final best multiple logistic regression model for longer hospital LOS. Patients had increased odds of a longer LOS if they received antibiotics (OR 3.44; 95% CI 1.85-6.39) or were categorized as having severe persistent compared to intermittent asthma on admission (OR 4.46; 95% CI 1.36-14.58). Patients admitted on the Asthma Pathway were more likely to have a shorter LOS (OR 0.47; 95% CI 0.25-0.90). In addition, patients admitted to the hospitalists had shorter LOS compared to the private pediatricians’ services (OR 3.02, 95% CI 1.45-6.31). Finally, the impact of supplemental oxygen on LOS was dependent on the number of patient diagnoses and vice versa. Conclusion: Factors increasing the average LOS for pediatric patients with status asthmaticus include: 1) a need for antibiotic therapy or supplemental oxygen, 2) multiple diagnoses at the time of admission or 3) severe persistent asthma at baseline. These factors may be used to influence DRG reimbursement in the future.

P49 P47 THE RISK OF ASTHMA EXACERBATION AFTER REDUCING INHALED CORTICOSTEROIDS: A SYSTEMATIC REVIEW AND META-ANALYSIS OF RANDOMIZED CONTROLLED TRIALS. J.B. Hagan*1, S.A. Samant1, G.W. Volcheck1, J.T. Li1, C.R. Hagan2, P.J. Erwin1, M.A. Rank3, 1. Rochester, MN; 2. Waco, TX; 3. Scottsdale, AZ. Background Asthma guidelines suggest reducing controller medications when asthma is stable. Methods The purpose of the study is to estimate the risk of asthma exacerbation in stable asthmatics who reduce inhaled corticosteroids (ICS) compared to those who maintain a stable ICS dose. We identified articles from a systematic review of English and non-English articles using MEDLINE, EMBASE, Web of Science, and CENTRAL (inception to May 25, 2013). We included randomized controlled trials (RCTs) with a stable asthma run-in period of 4 weeks or more, an intervention to stop or reduce ICS, and a follow-up period of at least 3 months. Results The search strategy identified 2,179 potential articles, of which 192 were reviewed at the full text level and 5 met criteria for inclusion. The relative risk for an asthma exacerbation in individuals who reduced ICS compared to those who maintained the same ICS dose was 1.27 (95% CI 0.97,1.67 ; p=0.08; I2=0%) in studies with a mean followup of 21 weeks. Individuals who reduced ICS had a decreased % predicted FEV1 of 2.15% (95% CI 0.30%,4.00%; p=0.02, I2=0%) and a trend toward decreased mean morning peak expiratory flow of 14.90 L/min (95% CI 4.97,34.78; p=0.14; I2=89%) compared to those individuals who maintained a stable ICS dose. Conclusions A decrease in FEV1 and a trend towards a small increase in asthma exacerbation risk was seen in individuals who reduced ICS dose compared to those who maintained a stable ICS dose.

P48 FACTORS PREDICTING LONGER LENGTH OF STAY IN HOSPITALIZED PEDIATRIC ASTHMATIC PATIENTS. S. Hom*, A. Perkins, B. Fine, C. Kelly, Norfolk, VA. Objective: Insurance companies often use diagnosis-related groups (DRGs) to determine reimbursement for patients hospitalized with a particular diagnosis. However, patients with the same diagnosis may require different lengths of stay (LOS). This study’s objective was to determine which factors might predict a longer than average LOS for a child hospitalized with status asthmaticus. Methods: We conducted a retrospective chart review of patients discharged from Children’s Hospital of The King’s Daughters in Norfolk, VA

EFFECT OF BREASTFEEDING ON LUNG FUNCTION IN ASTHMATIC CHILDREN. H. Kim*, K.W. Kim, S.M. Sohn, K.E. Kim, J.S.Yoon, J.S. Lee, Seoul, Korea, Republic of. Introduction: Breastfeeding has shown to have protective effect on allergic disease. However studies regarding lung function have shown conflicting results. The aim of this study was to find the correlation between breastfeeding duration and lung function in asthmatic children. Methods: Feeding practices were evaluated based on questionnaires completed on visiting Severance Children’s Hospital Allergy Clinic. We categorized the duration of breast feeding as not breastfed (n = 141), 0-6 months (n = 175), and >6months (n = 239), in patients diagnosed with asthma(n = 555) and compared with control group(n = 178). Lung function test and laboratory tests were performed. Results: In total, forced expiratory volume in 1 second(FEV1)/forced vital capacity(FVC)(%) of asthma group was significantly larger according to breastfeeding duration: 86.6±8.7 for not breastfed group, 87.2±8.6 and 88.8±7.7 for 0-6 months group and >6months group respectively(p = 0.023). However, FEV1 (% predicted, p = 0.321), FVC (% predicted, p = 0.54), peak expiratory flow (PEF) (% predicted, p = 0.571) and maximal midexpiratory flow (FEF25-75) (% predicted, p = 0.2111) did not show any differences according to breastfeeding duration. Within asthma group, when compared with atopics, non-atopics showed increased FEV1/FVC (%) according to breastfeeding duration: 82.4±8.9 of not breastfed group, 89.3±8.0 for 0-6 months group, 92.1±7.0 for >6months group (p = 0.0006), and FEF25-75 (% predicted): 64.7±21.7 of not breastfed group, 90.5±33.2 for 0-6 months group and 95.9±22.9 for >6months group(p = 0.0008). Non-atopic group also showed decreased maximal response to bronchodilator(% change in FEV1 after bronchodilator) according to breastfeeding duration: 14.3±9.6 of not breastfed group, 8.3±7.9 for 0-6 months group, 7.4±6.5 for >6months group(p = 0.0131). Certain indices of lung function improved in relation to duration of breastfeeding but there was no difference in lung function depending on exclusivity of breastfeeding. Conclusions: Longer duration of breastfeeding seems to have favorable effect on lung function in asthmatic children, especially in non-atopic asthma. Longer duration rather than exclusivity of breastfeeding is important in improved lung function.

P50 INDOOR AIR POLLUTION AND ASTHMA IN CHILDREN AT DELHI, INDIA. R. Kumar*, J. Nagar, N. Goel, P. Kumar, A. Kushwah, S. Gaur, Delhi, India. Objectives: The aim of present study is to determine the relationship between indoor air pollutants and asthma in children. Methods: This study took place at Delhi, capital of India. Eight locations based on the source of pollution such as industrial, residential and villages were included in study. Recording of the demographic profile and clinical examination of each child was conducted at



ABSTRACTS: POSTER SESSIONS their residence. Indoor SO2, NO2 and SPM levels were measured by using Handy Air Sampler (Low Volume Sampler). Results: A total of 3104 children were examined of which 60.3% were male and 39.7% were female. 32.4% children were exposed to environmental tobacco smoke. 31.5 % children’s families were using biomass fuels for cooking. History of respiratory symptoms included cough (43.9%), phlegm production (21.9%), shortness of breath (19.3%) and wheezing (14.0%). 7.9% children were diagnosed as having asthma, which was highest in industrial areas (11.8%) followed by residential areas (7.5%) and village areas (3.9%). The mean indoor SO2, NO2 and SPM level were 4.28±4.61 mg/m3, 26.70±17.72 mg/m3 and 722.0±457.6 mg/m3 respectively. Indoor suspended particulate matter was significantly high in industrial area followed by residential area and urban village area. Indoor SPM level was significantly (p<0.001) high in the asthmatic children’s houses. Conclusion: This study suggests that industries play an important role to increase the concentration of indoor suspended particulate matter and occurrence of asthma in children in developing countries like India.

P52 THE EFFECT OF INFLUENZA VIRUS INFECTION ON AIRWAY INFLAMMATION IN A MURINE MODEL OF ASTHMA. K. Bang*, S. Won, E. Lee, Y. Chun, J. Yoon, H. Kim, J. Lee, Seoul, Korea, Republic of. Background and Objectives: Respiratory viral infection is a leading cause for asthma exacerbation. It is known that respiratory syncytial virus (RSV) infection induces IL-5 dependent eosinophilia and Th2-polarized immunity, which are typical phenotypes of virus-induced aggravation in allergic asthma. However, although influenza infection, accounts for a relatively high proportion of severe cases, pathogenic mechanism of asthma exacerbation is not well understood. The purpose of this study was to examine the mechanisms of airway inflammation after influenza virus infection in a murine model of asthma. Materials and Methods: House dust mite (HDM)-sensitized BALB/c mice were used as asthma mouse model. The airway hyperresponsiveness, pulmonary histopathological changes, and bronchoalveolar lavage fluid (BALF) analysis including cells and cytokines were studied 24 h after influenza virus infection. Results: Influenza virus infection increased the airway hyperresponsiveness to inhaled methacholine in asthma mice(P < 0.05). In the lung tissue pathology and BALF analysis, both neutrophils and eosinophils showed a statistically significant increase in the influenza virus infected asthma mice as compared to asthma mice, but neutrophils being more prominent. These changes correlated with the increase of CXCL1, RANTES, MIP-1α, INF-γ, IL-1β, TNF-α in the BALF (P < 0.05). The levels of IL-4, IL-5, IL-10 in the BALF also increased in the influenza virus infected asthma mice, although the change was less than the asthma mice. Conclusions: The pathogenic mechanism of the influenza virus infected asthma mice is associated with simultaneous activations of neutrophilic, eosinophilic, and Th2 inflammation.

P51 IMPACT OF FRACTIONAL EXHALED NITRIC OXIDE (FENO) TESTING ON ASTHMA TREATMENT DECISIONS AND COSTS. C. LaForce*1, N. Herje2, P. Dorinsky3, K. Rickard2, 1. Raleigh, NC; 2. Morrisville, NC; 3. Chapel Hill, NC. Introduction: The standard clinical approach for managing patients with asthma includes symptom assessment via history or questionnaire such as the Asthma Control Test (ACT), physical examination and spirometry. However, none of the standard clinical assessment tools provide information regarding underlying airway inflammation, the control of which is central to an effective asthma management strategy. Objectives: To evaluate the impact of FeNO assessments on asthma treatment decisions and costs. Methods: 50 subjects with asthma, age 7 to 60 years, were recruited from an allergy practice for this single-visit study. Demographic information and medical history were collected, an Asthma Control Test (ACT) questionnaire was administered, and spirometry was performed. Physicians used this information to assess airway inflammation as low, intermediate, high or unknown and determined a treatment plan. Subjects then underwent FeNO testing and the results were provided to the physician who had an opportunity to modify the treatment plan. The physicians assessment of airway inflammation before knowledge of FeNO results and the proportion of subjects correctly categorized once the FeNO results were revealed to the physician are presented in the table below. Results: Asthma medication reductions were made in 8 (16%) subjects with the average per month cost reduction estimated to be $221/subject. Knowledge of FeNO levels also resulted in added/increased medications in 10 sub-optimally managed subjects to prevent worsening asthma, likely resulting in significant long term cost savings. Conclusion: Knowledge of FeNO may augment routine clinical assessment of airway inflammation and affect medication treatment decisions; both have important cost effectiveness implications.


Estimated and True Levels of Airway Inflammation

P53 RAISED BLOOD EOSINOPHIL LEVELS AS AN INDICATOR OF PROSPECTIVE ASTHMA OUTCOMES. A. Rigazio*1, D.B. Price1, E.R. Bleecker2, J.D. Campbell3, C.J. Corrigan4, I.D. Pavord5, S. Wenzel6, F. Barion1, A. Burden1, A. Gilchrist1, S. Gould1, J. von Ziegenweidt1, P.O. Buck7, G. Gopalan7, M. Buatti Small7, 1. Cambridge, United Kingdom; 2. Winston-Salem, NC; 3. Denver, CO; 4. London, United Kingdom; 5. Leicester, United Kingdom; 6. Pittsburgh, PA; 7. Frazer, PA. Raised eosinophil counts in the airway mucosa are a characteristic feature of asthma, with blood eosinophilia also observed in a proportion of patients. We examined the relationship between elevated blood-eosinophil counts, exacerbations and asthma control. Data were obtained from Optimum Patient Care and Clinical Practice Research Databases, two representative UK primary care databases. Patients included were: 12–80 years with diagnostic code for asthma (severity not specified) and recorded blood eosinophil count with at least one year data before (baseline) and after (outcome) count date. Patients with any other chronic respiratory disease or eosinophil count >5000/ml were excluded. Blood eosinophil count was categorized as either ≤400 or >400/ml (400/ml - upper limit of normal range in the UK). Outcomes were ATS-defined exacerbations (asthma-related hospital admission or ER attendance or use of acute oral steroids), clinical exacerbations (ATS exacerbations or GP consultations for lower respiratory tract infections treated with antibiotics), risk domain asthma control (absence of clinical exacerbations and out-patient visits) and overall asthma control (risk domain asthma control and average daily dose ≤200mcg salbutamol). A Poisson regression model was used to compare outcome exacerbation rates and a logistic regression model to compare asthma control between patient groups. All results adjusted for age, BMI and gender. Of the total cohort (n=130,248) 16.1% had an eosinophil count >400/ml. 33% of the group with counts ≤400/ml and 41% of the group with counts >400/ml were male (p<0.001 χ^2-test). Median age was 50 and 45 and median BMI was


ABSTRACTS: POSTER SESSIONS 28 and 27 for patients with low and high counts respectively (both p<0.001 Mann-Whitney test). Comparing the low vs. the high, 17.4% vs. 21.9% of patients experienced ≥1 ATS exacerbation and 25.8% vs. 29.4% ≥1 clinical exacerbation. 28% of patients failed to achieve risk domain asthma control and 58.5% overall asthma control. Figure 1 shows patients with higher eosinophil counts exacerbated more frequently and achieved poorer asthma control (all significant at p<0.001). Data suggest patients with blood eosinophil counts >400/ml are more likely to experience increased future exacerbations and poorer asthma control. This supports the use of blood eosinophil counts as potential markers of prospective asthma outcomes.

P55 Figure 1: Adjusted results for study outcome

P54 DECREASED EXHALED NITRIC OXIDE LEVELS AFTER A TARGETED EDUCATIONAL INTERVENTION IN HISPANIC AND AFRICAN AMERICAN ADULT ASTHMATICS: A PRELIMINARY STUDY. R. Patel*, J. Fogel, M. Zitt, M. Frieri, East Meadow, NY. Objective: We studied whether a targeted educational intervention would have greater benefits for adult asthma patients than standard education for our primary outcome of exhaled nitric oxide (FeNO) and our secondary outcome of the Asthma Control Test (ACT) score. Methods: A randomized controlled trial over 8 weeks between a treatment group (n=7) receiving targeted education (evidence-based educational pamphlets and tailored learning style) and a control group (n=8) receiving standard education (medication review). Change scores of baseline minus follow-up measurement were calculated for the outcomes. Results: In both groups, the sample was middle aged, mostly women, and mostly of Hispanic race/ethnicity. Comparisons of baseline characteristics between the treatment and control groups with analysis of variance (ANOVA) for the continuous variables and the Fisher’s exact test for the categorical variables did not find any statistical significance (p>0.05) for demographics (age, sex, race/ethnicity), comorbidities (allergic rhinitis, atopic dermatitis, sleep apnea, gastroesophageal reflux), and medications (beta agonists, inhaled corticosteroids, leukotrienes). The Mann-Whitney test for the skewed distribution continuous outcome variables (Figure) found that FeNO mean change score significantly differed (p=0.049) between the treatment (M=9.4, SD=13.04) and control (M=-3.3, SD=7.38) groups with a larger mean change score for the treatment group. There was no significant difference for ACT mean change score (p=0.41) between the treatment (M=-2.0, SD=2.51) and control (M=-0.9, SD=5.87) groups. Conclusion: FeNO measurement is as an important biomarker and helps clinicians understand Th2-airway inflammation. FeNO measurements can alert providers to non-asthma conditions, address the need for an extended differential diagnosis, identify asthma phenotypes that respond to inhaled corticosteroids, and measure patient non-adherence to asthma treatment regimens. Clinicians should consider incorporating targeted education of evidence-based educational pamphlets and tailored learning style into their treatment of Hispanic and African American adult asthma patients.

BRONCHODILATOR EFFECTS OF FORMOTEROL SINGLE DOSES ADMINISTERED BY PRESSURIZED METERED-DOSE INHALER IN ASTHMATIC CHILDREN AGED 6 TO 11 YEARS. W.E. Berger*1, K. Lampl2, F. Trudo2, T. Uryniak2, M. Gillen2, 1. Mission Viejo, CA; 2. Wilmington, DE. Introduction: Formoterol (FM) plus budesonide (BUD) has greater clinical benefit vs BUD alone in children with persistent asthma (Allergy Asthma Proc. 2010;31:26-3). This phase 2, randomized, double-blind study (NCT01136655) examined dose response of single-dose FM in children aged 6-11 years with stable asthma on medium dose-range inhaled corticosteroids with no hospitalizations/ED visits or systemic corticosteroids in the prior 6 months or 12 weeks, respectively. Methods: Patients had to have an FEV1 of ≥60% and ≤85% of predicted normal and reversibility of FEV1 of ≥15% after standard-dose albuterol. A 5-way crossover study design compared single FM doses via pressurized metered-dose inhaler (pMDI) (2.25mg, 4.5mg, and 9mg; delivered dose) or dry powder inhaler (DPI) (12mg metered dose) and BUD alone via pMDI. Single doses administered as BUD 80mg pMDI+placebo, BUD/FM as 80/2.25mg or 80/4.5mg pMDI or FM DPI+BUD 80mg pMDI were separated by washout periods of 3-14 days. BUD pMDI 160mg bid was given throughout the study. Rescue medication (albuterol HFA pMDI 90mg) was taken as needed. Mean 12-hour FEV1 was the primary outcome with 12-hour FEV1, maximum FEV1, and FM AUC secondary outcomes. Results: 54 patients, 31 males and 23 females, with a mean asthma history of 73 months were randomized from 14 US sites. All FM doses had a significantly higher mean 12hour FEV1 compared with BUD alone (Figure). Differences between 4.5mg and 9mg FM doses were not statistically significant, numerically supporting doseresponse peaking at 9mg. FM 4.5mg and 9mg had a significantly greater change from baseline in average 12-hour FEV1 than FM 2.25mg (P=.0007 and P=.0001). Greater improvements in FEV1 at 12 hours after dosing and maximum FEV1 during the 12-hour study period were observed with 4.5mg, 9mg FM pMDI, and 12mg FM DPI doses vs BUD and 2.25mg FM. Bronchodilation was not maintained over the 12-hour dosing interval with 2.25mg FM. Mild headache was more common in patients receiving FM 9mg. No serious AEs were reported. FM pMDI demonstrated generally dose-proportional pharmacokinetics up to 9mg, as determined by urinary excretion. Conclusion: Single doses of FM demonstrated a dose-response with FM 9mg exhibiting a maximum response in children aged 6 to 11 years with persistent stable asthma maintained on BUD 160mg bid.



ABSTRACTS: POSTER SESSIONS states in the U.S. The date of first diagnosis was defined as the ‘index date’. Patients were required to have at least 1 peripheral EOS test (elevated and normal EOS defined as > 400 cells/mL and < 400 cells/mL, respectively) in the 12 month ‘assessment’ period following the index date. We classified patients as mild, moderate, and severe by their medication use in the assessment period, as recommended by the Expert Panel Report 3: Guidelines for the Diagnosis and Management of Asthma (EPR III). Descriptive statistics and Chi-square tests were utilized to compare the proportion of patients with elevated EOS across the severity groups. Logistic regression was performed to assess the probability that severity was associated with EOS elevation. Results: Forty percent of 1,144 patients meeting our eligibility criteria had mild asthma, 44% had moderate asthma and 16% had severe asthma. Twenty percent of severe, 25% of moderate, and 19% of patients with mild asthma had elevated EOS counts. Logistic regression controlling for patient factors showed that moderate-tosevere asthma was associated with 38% increased odds of abnormal EOS level compared to mild asthma (p=0.04). Conclusion: Moderate-to-severe asthma is significantly associated with increased odds of EOS elevation.




ECONOMIC AND CLINICAL BURDEN OF SEVERE ASTHMA WITH ELEVATED BLOOD EOSINOPHIL LEVEL. J. Casciano*1, J.A. Krishnan2, M. Buatti Small3, P.O. Buck3, G. Gopalan3, C. Li4, R. Kemp1, Z. Dotiwala1, 1. White Plains, NY; 2. Chicago, IL; 3. Frazer, PA; 4. Little Rock, AR.

Rationale: Quick-relief or “rescue” inhalers such as albuterol are critical for the relief of asthma symptoms. Although these medications are generally self-administered through metered-dose inhalers (MDIs), many available MDIs lack an integrated dose counter to track the number of doses remaining in a device. The Asthma Inhaler Design (ID)™ Survey was conducted to assess the behaviors, attitudes, and preferences of asthma patients with respect to rescue inhalers. Methods: Between December 7, 2012, and January 13, 2013, the Asthma and Allergy Foundation of America invited >19,000 adults with asthma and caregivers of children with asthma to take part in an online survey. The survey included 29 multiple-choice and open-ended questions that focused on asthma diagnosis, severity of symptoms, rescue and controller medication use, spacers, cost, dose counters, problems with inhalers, and overall inhaler design. Results: After screening, data from 590 respondents (366 adults, 224 children) were included in the final analysis. Most respondents (78.5%) have at least 2 rescue inhalers, and 38.8% have ≥3 devices. 50.6% of respondents stated that they previously allowed their rescue inhalers to expire. 48.2% of respondents previously found their rescue inhalers to be empty when needed; 10.4% had to go to the emergency room for treatment, and 20% had to go without treatment. At the time of the survey, 32% of respondents reported current use of a rescue inhaler with a dose counter. When asked what they would do to improve the device functionality of their quick-relief inhalers, 31% responded that they would add a dose counter. Other design improvements included builtin spacer, more secure mouthpiece, stronger propellant/plume, and voice/notice alarm alerting patients of the expiration date. Conclusions: This survey highlights that many patients do not have their quick-relief inhalers at hand and that, even when they do, the inhalers may be empty because the number of remaining doses is not indicated. Thus, inclusion of a dose counter should be considered a critical element in the development of quick-relief inhalers for asthma.

P57 THE ASSOCIATION OF BLOOD EOSINOPHIL LEVELS AND ASTHMA SEVERITY IN THE MIDWESTERN UNITED STATES. J. Casciano*1, J.A. Krishnan2, M. Buatti Small3, P.O. Buck3, G. Gopalan3, C. Li4, R. Kemp1, Z. Dotiwala1, 1. White Plains, NY; 2. Chicago, IL; 3. Frazer, PA; 4. Little Rock, AR. Background: Asthma represents a significant clinical and economic burden to the US healthcare system. There exists an information gap in literature regarding the association of eosinophil (EOS) level and severity of disease among asthmatics. Understanding this relationship may offer additional guidance to providers and payers in assessing patient-level and population disease risk among asthmatics. Objective: The objective of this study was to assess the association of asthma severity with blood EOS levels. Methods: Patients with a primary or secondary diagnosis of asthma defined by ICD-9-CM code 493.xx between January 2004 and July 2011, at least 12 years of age were extracted from the eMRClaims+ database (eMAX Health, White Plains NY) containing electronic medical records linked to insurance claims across 6 Midwestern


Background: Resource use correlates with asthma severity, and asthma severity correlates with elevated peripheral blood eosinophils (EOS). However, the economic burden associated with elevated EOS in asthma has not been widely reported in the literature. Objective: To assess the economic burden and healthcare utilization of asthma patients with elevated EOS defined at > 400 cells/mL overall and for those with severe disease. Methods: Patients with a primary or secondary diagnosis of asthma defined by ICD-9-CM code 493.xx between January 2004 and July 2011, at least 12 years of age were extracted from eMRClaims+ database (eMAX Health, White Plains NY) containing electronic medical records linked to insurance claims across 6 Midwestern states in the U.S. EOS level and disease severity was determined during a 12-month assessment period. Patients were followed for resource use and cost (study outcomes) for a minimum of 1 (maximum of 12) month(s) after the assessment period. We classified patients as mild, moderate, or severe by their medication use in the assessment period, using step treatments defined by the Expert Panel Report 3: Guidelines for the Diagnosis and Management of Asthma (EPR III). Non-parametric tests were used to compare resource use and associated billed claim amounts between elevated and normal EOS groups. Multivariate modeling was performed to assess influence of EOS level on study outcomes among the severe asthmatic patients. Results: Among the 2,164 patients meeting our inclusion/exclusion criteria, those with elevated EOS compared to normal EOS had significantly greater mean annual hospital admissions (0.513 vs. 0.207, p=0.006) and billed hospital claims ($7,686 vs. $3,306, p=0.011). Within the severe asthmatics cohort (n=179), the group with elevated EOS had 4.8 times more annual hospital admissions (p=0.001) and significantly greater billed amounts ($7,302 vs. $3,332, p=0.002). Controlling for patient demographics and comorbidities for severe asthmatics, elevated EOS was associated with 5.14 times increased odds of all cause admissions (p=0.003) and 4.07 times increased odds of asthma related admissions (p=0.002). Conclusion: Elevated EOS was independently associated with an increased economic burden among asthmatics overall as well as the severe asthmatic cohort.

P59 SEVERE ASTHMA WITH MULTIPLE ALLERGIC DISORDERS: FAVORABLE RESPONSE TO OMALIZUMAB. T. Bertozzi*1, P. Lang1, M. Frieri2, 1. New Hyde Park, NY; 2. East Meadow, NY. Introduction: Omalizumab is a monoclonal anti-IgE antibody approved for severe allergic asthma and an effective treatment for inducing and maintaining long-term remission for patients with severe chronic urticaria. There are also many reports of treatment of omalizumab for food hypersensitivity, angioedema and anaphylaxis. Case: We report a 19 year old male who presented at age 13 with severe asthma, allergic rhinitis oral allergy syndrome, idiopathic urticaria, angioedema and food allergy. He was evaluated by many specialists and on numerous medications including various antihistamines, asthma steroid inhalers, short acting bronchodilators, montelukast, nasal aze-


ABSTRACTS: POSTER SESSIONS lastine and nasal steroids, prilosec and had many episodes of these disorders requiring emergency room visits. Family history is significant for anaphylaxis, urticaria and angioedema in multiple family members to shellfish, other foods and drug allergy. Methods: Allergen skin testing and specific IgE tests over time were strongly positive peanuts, hazelnuts, tree nuts, carrots, apples, celery, various fruits including, peach and strawberry, melon, potato, trees, especially birch, oak, beech, and alder, june grass, molds, weeds, animal dander. Anti IgE receptor antibody was positive @ 66.6 sent to National Jewish Laboratory in 2008.Total IgE was 125.Anti-gliadin, tissue transaminase, endomysial antibodies were negative for celiac disease, HAE evaluation for all types and tryptase were negative. Conclusion: The patient was started on allergen immunotherapy and omalizumab in 2012.Since then he has had no asthma exacerbations or emergency department visits, fewer angioedema episodes, and medication dosages have been lowered or discontinued. Omalizumab reduces FcεR1 expression on dendritic cells and basophils, may produces a down regulation of IgE-mediated basophil activity and in FcεRI dependent-secretion of cytokines and chemokines. Clinical improvement is determined by an independent IgE mechanism due to a reduction in mast cells and basophils. Proposed mechanisms of action have been eosinophil apoptosis induction, down regulation of cytokines such as IL-2 and 13 which interfere with T lymphocyte proliferation, reduction in TNF-α, IL-4, in B cells activation, their homing, and increase in IFN-γ synthesis.

P60 MALADY OF THE MELODIES. M.R. Shams*, D. Berkowitz, F.E. Lee, J. Shih, Atlanta, GA. Rationale: Saxophone Lung is a rare entity of Hypersensitivity Pneumonitis (HP). Patients develop allergic pulmonary disease to specific fungal antigens that collect over time in their reed instruments if not thoroughly cleaned. While Saxophone Lung shares clinical similarities with ABPA, entities must be distinguished for proper management. Ultimate resolution of Saxophone Lung requires antigen identification and elimination. Methods: A patient with Saxophone Lung was identified at the Emory University Adult Asthma, Allergy and Immunology Clinic. He presented with cough and wheeze of one-year refractory to inhaled corticosteroids, bronchodilators and oral antibiotics. Chest imaging was obtained. Epicutaneous skin testing (SPT) and serum hypersensitivity precipitans for fungal antigens were performed. Fungal culture of patient’s clarinet was obtained. Results: Chest imaging revealed posterior right upper lobe bronchiectasis, tree-in-bud and consolidative opacities, high-attenuated mucus plugging and calcified mediastinal lymphadenopathy. Hypersensitivity precipitans were positive for Alternaria. SPT was positive to Alternaria and Curvularia. Fungal culture of his saxophone reed was positive for Exophiala. Alternaria, Curvularia and Exophiala are black molds in the same phylum Ascomycota and may be cross-reactive. The patient received oral steroids but did not improve until sterilization of his instrument. Serial CT scans and decreased serum IgE levels mirrored his clinical improvement. Conclusions: This patient with Saxophone Lung was initially diagnosed with ABPA until history revealed he was a Dixie band player who had not cleaned his clarinet in over 30 years. While both ABPA and Saxophone Lung present with persistent cough and wheeze due to localized mold allergy and are treated with systemic steroids, it is imperative for allergists to distinguish these clinical entities. Like other cases of HP, Saxophone Lung is improved by systemic steroids, but only remedied by complete removal of the offending antigen. While no known allergen extract is available for Exophiala, there may be cross-reactivity with Curvularia and Alternaria to which our patient has positive reactions making the addition of immunotherapy a potential option. He is currently doing well without any respiratory issues.

P61 A CASE OF CHURG STRAUSS SYNDROME (CSS) PRESENTING AS ASPIRIN EXACERBATED RESPIRATORY DISEASE (AERD). S. Mane*, A. Casillas, Shreveport, LA. Introduction: CSS is a rare multisystem disorder characterized by chronic rhinosinusitis (CRS), severe asthma, and blood eosinophilia. Typically, symptoms develop in sequential phases - allergic, eosinophilic, and vasculitic. Clinical features during the allergic state are similar to AERD, namely CRS, asthma and nasal polyps (NP), making the diagnosis of CSS difficult. We describe an interesting case of CSS, initially presenting with features of AERD. Case report: A 47 year old female with a history of hypertension, Raynaud’s phenomenon, and CRS with NP requiring multiple polypectomies was referred to our clinic for a 2 year history of uncontrolled asthma exacerbated by aspirin use. Expi-

ratory wheeze and bilateral polyps were noted on examination. Spirometry showed mixed obstruction and restriction. AERD was diagnosed and strict avoidance of all NSAIDS was recommended. After being lost to follow up for two years, she presented with worsening asthma despite maximum daily therapy with inhaled corticosteroids, a leukotriene antagonist, antihistamines, intranasal corticosteroids and strict NSAIDS avoidance. She presented with eosinophilia, right eye blindness and polyneuropathy. There was significant expiratory wheezing on exam. Spirometry showed a mixed pattern as before. Review of medical records was significant for absolute eosinophil count 3007800/mL (normal 0-600/mL), total IgE 210-345 IU/ml (normal 1.6-165 IU/ml), rheumatoid factor 20-60 lu/ml (normal 0-15 lu/ml), positive myeloperoxidase antibody. Sural nerve biopsy was suggestive of vasculopathy. CT chest showed granulomatous changes. ANA, p-ANCA, angiotensin converting enzyme, serum immunoglobulin electrophoresis, and fungal hypersensitivity panel were negative. She was started on 1 mg/kg/day of prednisone for CSS. After 3 weeks, she had marked improvement and reduced bronchodilator use from 3 times/day to once/month. Conclusion: Only a few cases of AERD associated with CSS have been reported. It is unclear whether AERD is a feature of CSS or progression into CSS. Regardless, diagnosis and treatment should be considered in patients with severe asthma, multisystem involvement, and NSAID sensitivity to help prevent progression and fatality.

P62 ALTERNARIA ALTERNATA INDUCED ASTHMA. K. Dass*1, O. Niculescu2, 1. Bloomfield Hills, MI; 2. Royal Oak, MI. Alternaria spores are a global indoor and outdoor risk factor for asthma that can be life threatening and, at times, fatal. Multiple studies have documented Alternaria alternata’s extensive association with asthma and its relation to patients who have either died or experienced near fatal asthmatic episodes. Further studies have even documented that asthma fatalities doubled during high mold spore counts of Alternaria species. A 56 year old female presented with respiratory distress and a new asthma exacerbation that started five days prior to admission. She has a past medical history of asthma that required multiple hospitalizations for asthma secondary to a suspected household antigen. On examination, the patient was tachycardic, tachypneic, in respiratory distress with audible wheezing, and hypoxia. Extensive studies determined that the patient was strongly allergic to Alternaria alternate, a fungal allergen known to cause severe, and sometimes fatal, asthma. The patient was treated aggressively with bronchodilators, steroids, scheduled ipratropium, oxygenation, and scheduled monteleukoast. The patient was continued on an anti-histamine and fluticasone nasal spray. Upon discharge, the patient had close follow up with her pulmonlogist and allergist. She is scheduled to start allergen immunotherapy and omalizumab. The patient was also advised to have all household plants removed, as well as professional carpet and ducts cleaning. Asturias et al. demonstrated that diagnosing an Alternaria alternata allergy may be made easier using only Alt a 1 from either a natural or recombinant source. If this is possible, more targeted immunotherapy may be available for patients. Further, with more awareness of Alternaria alternata as an indoor allergen, patients can take greater care to monitor for mold in their homes. Newer diagnostic approaches to fungal allergens can further assist with more accurate allergen desensitization therapy. Studies continue to focus on more standardized diagnostic and therapeutic agents. Increasing awareness of Alternaria alternata as an indoor allergen may help control respiratory symptoms in asthmatic patients.

P63 PREVALENCE OF ASTHMA IN ADOLESCENTS IN RURAL COUNTIES IN GEORGIA. P. Davoodi*1, D.R. Ownby1, S. Havstad2, J.L. Waller1, C.L. Joseph2, M.S. Tingen1, 1. Augusta, GA; 2. Detroit, MI. Introduction: While the prevalence of asthma in children in urban settings is as high as 18-20 percent, few studies have focused on the prevalence of asthma in adolescents from rural areas. Methods: The Lung Health survey was completed by students in grades 9-11 attending 4 rural public Georgia high schools as part of the Puff City clinical trial. IRB/HAC approval and informed consent was obtained from all research subjects. Current asthma diagnosis was identified as a report of a physician’s diagnosis accompanied by at least 1 of the following: daytime and/or nighttime symptoms in the past 30 days, use of asthma medication in the past 30 days, 1 or more emergency department (ED) visits or hospitalizations, or over 2 doctor’s visits in the past 12 months. An undiagnosed asthma category was defined as students who had multiple respiratory symptoms of asthma but who denied a physician diagnosis of asthma. Results:



ABSTRACTS: POSTER SESSIONS Of 2523 students surveyed in the rural counties in Georgia, 456 (18.1%) had a physician diagnosis of asthma and 185 (7.5%) had undiagnosed asthma. Out of the 456 students with asthma, 246 (54%) were male, 293 (64%) were AfricanAmerican (AA), and 143 (31%) were Caucasian (C), and 18 (4%) reported Other. AAs were more likely to have a physician diagnosis of asthma than Cs, 19.4% versus 16.2%. In the previous 12 months students reported an average of 0.69 (SD 1.59) ED visits and 0.24 (SD 1.08) hospitalizations for asthma. Those with undiagnosed asthma reported an average of 0.72 (SD 1.45) ED visits and 0.23 (SD 1.11) hospitalizations for asthma-like symptoms. In the physician diagnosed asthma group, frequency of symptoms in the past 30 days was reported as 1.86 (SD 2.70) days with nocturnal awakenings of 1.19 (SD 2.31) and school absences of 1.44 (SD 1.99) days. The students with undiagnosed asthma reported symptoms in the past 30 days as 3.53 (SD 3.17) days with nocturnal awakenings of 2.38 (SD 2.91) days and school absences of 1.77 (SD 1.77) days. Conclusion: The prevalence of asthma among adolescents in rural Georgia is similar to the prevalence of asthma in adolescents in urban populations. Adolescents with undiagnosed asthma have frequent respiratory symptoms and a similar frequency of ED visits and hospitalizations to those with a physician diagnosis.

P64 DEMOGRAPHIC IMPACT ON ASTHMA AND HEALTHRELATED QUALITY OF LIFE: A PILOT STUDY. C. Caruthers*, H. Shah, A. Agrawal, C. Desai, T. Solanky, S. Kamboj, P. Kumar, New Orleans, LA. Introduction: Asthma is a chronic inflammatory disorder with significant morbidity and mortality. It is a medically managed disease affected by proper medication reconciliation. Presumably, the higher the compliance, the better control of asthma and improved health-related quality of life (HRQOL). We analyzed the impact of demographic factors on a patient’s ability to access medications and disease comprehension. Methods: IRB approval was obtained. Adults with asthma were studied at Allergy-Immunology clinics. Informed consent was obtained from all research subjects. Asthma control test (ACT) and HRQOL, via SF-36 standard quality of life scores, were assessed and demographics collected. Compliance was determined by ascertaining proper medication usage. Results: 49 bronchial asthmatic patients were studied – 14 in charity clinics and 35 in private clinics. Insured patients had mean SF-36 of 42.40 compared to uninsured patients who had mean of 35.94 (p=0.04). Analysis of the different income levels with ANOVA model showed statistical significance (p=0.01) for SF-36. Upon further analysis between income levels of less than $25,000 and more than $50,000, the mean was 38.66 and 47.58 (p=0.01). Analysis of clinic location, age and education level were not statistically significant, although there was a trend in SF-36 and ACT scores. In private clinics, the mean SF-36 and ACT scores were 42.27 and 16.69, while in charity clinics, 39.02 and 14.64. Older age groups had a lower SF-36 when comparing younger age group. For patients aged 18-25, mean SF-36 was 45.33, 25-50 years old was 41.73, and older than 50 was 40.69. Higher education level demonstrated improved SF-36 and ACT scores. Patients who did not complete high school had mean SF-36 and ACT scores of 37.90 and 14.14, high school graduates were 39.94 and 15.43, and college graduates were 44.31 and 17.63. Conclusion: Patients with health insurance and higher income have an improved quality of life and better asthma control. Higher education was associated with better quality of life and asthma control, although the differences were not statistically significant.

P65 DEPRESSION AND ANXIETY IN PATIENTS WITH ALPHA-1ANTITRYPSIN DEFICIENCY. S.L. Buchman*, A.S. Fouche, E.F. Saunders, T.J. Craig, Hershey, PA. Background: Alpha-1-antitrypsin deficiency (AATD) is an inherited inflammatory disorder that may lead to severe lung and hepatic damage. Depression and anxiety have been associated with other chronic disorders. A number of factors may contribute to an increased risk of depression and/or anxiety in patients with AATD. Improper management of patients due to delayed diagnosis or misdiagnosis as well as lack of familiarity with AATD among clinicians can lead to a significant disease burden. Additionally, previous research related to psychoneuroimmunology has illustrated a potential relationship between activation of inflammatory cytokines and a change in mental status, which may provide a possible mechanistic explanation for the development of depression in patients with AATD. Our objective was to assess depression and


anxiety in our cohort of AATD. Methods: In this pilot retrospective cohort study, phone interview was used to survey 20 participants. IRB approval and informed consent was obtained from all research subjects. The Hamilton Depression Rating Scale (HAM-D) and the Hamilton Anxiety Rating Scale (HAM-A) were used as the survey questionnaires. Other relevant parameters were also examined including smoking habits, occupational exposure, and time period of AATD diagnosis. Respiratory and/or liver symptoms were not inclusive criteria. Participants had at least one identified A1AT deficient gene. The small sample size, reflecting rarity of diagnosed AATD, was the major limitation of the study. Results: 45% of participants were identified as experiencing depression of mild (44%), moderate (33%), severe (11%), or very severe (11%) levels. The mean score for the HAM-D was 8.4 +/-7.8, which can be compared to a reference value of 3.2 +/- 3.2 from the normal population. The HAM-A revealed 15% as having prominent, moderate anxiety. Conclusion: Our results and review of the literature indicate that patients with AATD are at significant risk for depression, and substantially less risk for anxiety. In summary, these findings suggest that depression is common and screening and treatment for depression in AATD is critical. The increased risk for depression may be secondary to the disease burden, the inflammatory cytokines involved in the pathophysiology of A1AT deficiency, or a combination of factors. Further research is needed to assess the etiology of the depression.

P66 RELATIONSHIP BETWEEN SUB-POPULATIONS OF LYMPHOCYTES AND SEVERITY OF PERSISTENT ALLERGIC ASTHMA. V. Tsybulkina*1, N. Kurmaeva1, Y. Skibo1, Z. Abramova1, N. Tsybulkin1, L.M. DuBuske2, 1. Kazan, Russian Federation; 2. Gardner, MA. Introduction. Chronic airway inflammation in allergic asthma (AA) may vary dependent on disease severity. This study assesses the relationships between absolute counts and ratios of lymphocyte sub-populations and the clinical course and severity of AA. Methods. Cohorts of 10 consecutive patients, 19 to 45 years of age, each with either mild (MA) or severe (SA) persistent atopic asthma, comprised the 20 subjects who were studied, excluding patients with moderate persistent AA. The control group (CG) included ten healthy non-atopic volunteers of comparable age and gender. AA patients were assessed in remission. Assessment included history, allergen skin prick tests, IgE level, bronchoprovocation tests, lung function assessment and leukocyte cell counts. Lymphocyte populations were measured in absolute numbers and ratios by flow cytometry (FASCalibur, Becton Dickinson), identifying CD3, CD4, CD8, CD16, CD19 and CD56 cell surface markers (MultiTEST IMK, Becton Dickinson). Results. MA patients had absolute T cell counts per ml similar to the CG (3478.88±1427.29 versus 3141.83±929.13), but SA patients had lower counts (2473.97±940.30). The percentage of T cells within the total lymphocyte count was similar in all groups (75.50±8.06% in SA; 73.13±5.54% in MA; 74.33±7.87% in CG). Absolute numbers of CD8+ T cells were significantly reduced in SA patients (755.38±241.44) compared to MA (1516.85±725.57) and CG (1302.83±479.94) groups and their percentage was also lowest in the SA group (23.50±1.73%) versus MA (31.38±3.74%) and CG (30.33±5.68) groups. NKT (CD3+/CD16+/CD56+) cells, however, were significantly elevated in SA patients (4.06±2,34%) compared with MA (1.48±1.01%) and CG (1.41±0.63%) groups. NK (CD16+/CD56+) cells were fewer in the SA group both in absolute counts(230.25±111.40) and percentage (7.75±4.92%) compared to absolute counts (603.50±302.40) and percentage (12.88±4.85%) in the MA group while intermediate absolute counts (463.00±142.56) and percentages (11.50±3.78%) occurred in the CG group. Conclusions. Severe AA patients have lower T cell counts, reduced number and percentage of CD8+ and CD16+/CD56+ cells but a significant increase in NKT cells. This suggests that the pathologic evolution when advancing from mild to severe allergic asthma may include a shift towards increased influence of NKT and NK cells on maintenance of inflammation.

P67 IMBALANCE IN HUMORAL AND MUCOSAL ANTI-ENDOTOXIN IMMUNE RESPONSES IN UNCONTROLLED MODERATE TO SEVERE PERSISTENT ASTHMA. V. Beloglazov*1, Y. Popenko1, A. Gordienko1, L.M. DuBuske2, 1. Simferopol, Ukraine; 2. Gardner, MA. Introduction: Endotoxin (ET) from gram-negative bacteria can induce intense inflammation potentially leading to asthma with direct exposure. Humoral and mucosal anti-endotoxin immune responses may have a role in the


ABSTRACTS: POSTER SESSIONS pathogenesis of asthma. The immune response to endotoxin could have a role in determination of controlled versus uncontrolled status of moderate to severe persistent asthma. Methods: 80 patients with asthma age 18 to 55 years old including 36 males (45%) and 44 females (55%) who received outpatient treatment with moderate to high doses of inhaled glucocorticosteroids (fluticasone propionate 500-1000 mcg/day) were studied. Asthma control was assessed using the Asthma Control Questionnaire (ACQ). Patients were divided into two groups. Group 1- patients with controlled moderate to severe asthma (14 subjects 17.5%), ACQ score 0.43±0.045; Group 2 - patients with uncontrolled moderate to severe asthma (66 subjects – 82.5%), ACQ score 3.62±0.12. Levels of serum and salivary anti-endotoxin antibodies (anti-ET IgA, anti-ET IgM and anti-ET IgG), secretory anti-endotoxin IgA (anti-LPS-sIgA) and total secretory IgA in saliva were determined by ELISA. Results: Levels of anti-ET IgG in Groups 1 and 2 were similar (P>0.1) being within the normal range. Levels of anti-ET IgM (0.2652 ± 0.029 O.D.) in Group 2 were 1.5 –fold greater than the normal value (0.171 ± 0.033 O.D.; p<0.05) indicative of translocation of ET from gut to portal blood, while in Group 1 these levels were normal (0.166 ± 0.048 O.D.; p>0.05). Levels of anti-ET IgA in Group 1 (0.200 ± 0.02 O.D.) were in the normal range (0.167 ± 0.023 O.D., p>0.05), while in Group 2 these levels (0.258 ± 0.021 O.D.) were 1.5- fold greater than normal (p<0.01) suggesting enhancement of the intestinal anti-ET barrier function. The levels of total secretory IgA in Groups 1 and 2 were 2.5 fold greater than normal (p<0.01). The level of secretory anti-ET IgA in Group 1 was 3.4-fold greater than normal (0.059 ± 0.073 O.D.; p<0.05) and in Group 2 was 4.7-fold greater than normal, being 1.3-fold greater than in Group 1 (p<0.05). Conclusions: An imbalance of anti-endotoxin immunity exists in uncontrolled moderate to severe asthma suggesting endotoxin immune responses may have a role determining asthma severity and subsequent control.

P68 ASSOCIATIONS BETWEEN ASTHMA RELATED HOSPITALIZATIONS AND USE OF BUDESONIDE OR FIXED DOSE COMBINATION BUDESONIDE AND FORMOTEROL IN THE ADOLESCENT ADULT POPULATION. X. Yang*, A. Parente, B. Jones, B. Zhang, J. Scoggins, P. Chen, R. Bhattacharjee, S. Mehta, Z. Pulungan, C. Teigland, Bowie, MD. Background: The safety of combination therapy of an inhaled corticosteroid and a long-acting β2-agonist is insufficiently studied. This study assessed the association between asthma-related hospitalizations and use of budesonide or combination of budesonide and formoterol (bud/form) in a single inhaler among an adolescent adult population. Methods: A retrospective matched cohort study was conducted using a large nationally representative administrative claims database from 2006 to 2011. Individuals aged 13 to 64 years with an asthma diagnosis and with one or more claims of budesonide or bud/form after asthma diagnosis were included. Individuals also had to be continuously enrolled in a health plan 12 months before and after index date. Individuals were excluded if they were not new users of budesonide or bud/form, had a diagnosis of COPD, or used another asthma controller medication after the index date. Associations between asthma-related hospitalization and use of budesonide or bud/form were assessed using a logistic regression model, controlling for other risk factors. Results: A total of 14,946 individuals (budesonide users, n=5,925[39.6%]; bud/form users, n=9,021[60.4%]) were identified after meeting inclusion criteria. A total of 5,392 budesonide users were matched with 5,392 bud/form users based on propensity scores. Age at index date was 13-17 years for 19.8% (n=2,139), 18-34 years for 28.5% (n=3,072), 35-49 years for 28.6% (n=3,079), and 50-64 years for 23.1% (n=2,494). The mean age of the sample was 35.5 years (standard deviation=15.5); 65.0% (n=7,012) were female; 63.9% (n=6,891) were enrolled in a commercial plan and 36.1% (n=3,893) in a Medicaid plan. Individuals with bud/form use were 25.0% less likely to have asthmarelated hospitalization in the 12 months after initiation as compared to individuals initiating treatment of budesonide (odds ratio [OR]=0.75; 95% CI, 0.61-0.93) after adjusting for demographic, baseline clinical and health care utilization risk factors. Conclusions: Individuals who initiated use of fixed dose combination bud/form were at lower risks of asthma-related hospitalization as compared to individuals with budesonide use alone.

P69 EXHALED BREATH TEMPERATURE ASSESSMENT IN LUNG DISEASES. T. Kralimarkova*1, T. Popov1, L.M. DuBuske2, 1. Sofia, Bulgaria; 2. Gardner, MA. Background. Exhaled breath temperature (EBT) assessment was first proposed as a surrogate marker of airway inflammation over 10 years ago. This literature search identifies published studies related to EBT assessment to outline possible applications of this method to management of respiratory disease including allergic asthma. Methods. A MEDLINE search with keywords “exhaled breath temperature”; or “temperature of exhaled air” and “asthma”; or “COPD”; or “chronic lung disease” was performed. An additional search was made of abstracts presented at international meetings of organizations representing allergy, asthma and respiratory disease physician specialists. Results: 32 studies were included in the analysis: 15 published in peer reviewed journals and 17 presented at international meetings in Europe and North America. While the number of studied subjects in the individual studies was small, the overall number of studied subjects was 2885 having diverse respiratory conditions. Associations of EBT with indices of respiratory diseases included: spirometry (32 studies), with respiratory symptom scores (6 studies), fractional exhaled nitric oxide (5 studies), quality of life (4 studies), induced sputum cells (4 studies), airway responsiveness (3 studies), daily peak expiratory flow (2 studies), airway remodeling (1 study) and bronchial blood flow (1 study). EBT seams to reflect a unique parameter which when combined with other parameters may create a vector which helps to shape individual disease state patterns related to both inflammation and airflow. Conclusions. EBT assessment may be useful in monitoring airway diseases either alone or in combination with other objective measurements in asthma and other respiratory diseases.

P70 RELATIONSHIP OF ADENOSINE 5’-MONOPHOSPHATE CHALLENGE TO METHACHOLINE CHALLENGE AND EXHALED NITRIC OXIDE IN MILD-MODERATE ASTHMATIC CHILDREN. Y. Yoo*1, S. Seo2, Y. Kim2, W. Yoon2, J. Choung2, M.S. Perzanowski1, 1. New York, NY; 2. Seoul, Korea, Republic of. Introduction: Airway hyperresponsiveness (AHR) and airway inflammation are two main hallmarks of asthma. AHR, an exaggerated bronchoconstrictive response of the airway to a variety of stimuli, can be measured by direct (methacholine) and indirect (adenosine 5’-monophosphate, AMP) challenges. Fractional exhaled nitric oxide (FeNO) was proposed as a biomarker of airway inflammation in asthmatics. Methods: Sixty-nine asthmatic children aged 618 years underwent FeNO measurements, spirometry, and blood tests for serum total IgE, blood eosinophil counts, and serum eosinophil cationic protein (ECP). All subjects were asked to perform methacholine and AMP challenge tests with an interval of three days. Results: The average age of studied subjects was 9.9 ± 2.7 years. The geometric means (range of 1 SD) of serum total IgE levels, blood eosinophils and serum ECP concentrations were 158.5 IU/mL (33.9 – 741.3), 275.4 /mL (117.5 – 645.7) and 17.8 mg/mL (6.8 – 46.8), respectively. The geometric mean (range of 1SD) of FeNO was 33.27 ppb (19.01 - 57.94). The mean (± SD) FEV1 and FEV1/FVC were 96.4 ± 14.9% predicted and 83.5 ± 7.6%, respectively. The geometric mean (range of 1 SD) of methacholine PC20 was 3.44 mg/mL (0.56 – 21.04) and that of AMP PC20 was 66.37 mg/mL (6.50 – 677.64). FeNO levels significantly correlated with serum IgE levels (r = 0.473, p = 0.001), blood eosinophil counts (r = 0.338, p = 0.009), and serum ECP concentrations (r = 0.289, p = 0.027) but neither FEV1 (r = - 0.227, p = 0.077) nor FEV1/FVC (r = - 0.111, p = 0.402). FeNO levels significantly correlated with AMP PC20 (R2 = 0.341, p = 0.001) but not with methacholine PC20 (R2 = 0.062, p = 0.058). Conclusions: FeNO levels in asthmatic children is elevated and positively related to serum IgE levels and blood eosinophil markers. FeNO levels were significantly correlated with AHR to AMP but not with AHR to methacholine in mild-moderate asthmatic children.




P71 RETROSPECTIVE ANALYSIS OF DOXYCYCLINE PROPHYLAXIS FOR PATIENTS WITH CHRONIC OBSTRUCTIVE PULMONARY DISEASE. E. Johnson1, A. Khan2, S. Sekhsaria*3, 1. Washington, DC; 2. Columbia, MD; 3. Baltimore, MD. Rationale: Exacerbations of Chronic Obstructive Pulmonary Disorder (COPD) lead to increased morbidities and mortality. A recent study demonstrated that prophylactic azithromycin decreased the frequency of exacerbations in a population of COPD patients. However, a significant percentage of these patients developed hearing deficits. There is a need to study other antibiotics as possible prophylaxis for patients with moderate/severe COPD. This retrospective study is a preliminary analysis evaluating the effectiveness of doxycycline prophylaxis in fall and winter months for patients with moderate/severe COPD. Methods: We studied patients with moderate/severe COPD who were treated with prophylactic doxycycline (50 mg, BID) for about six month periods in the fall/winter months. From the patients’ histories, we determined the number of exacerbations/year and hospitalizations/year prior to and after doxycycline treatments. Exacerbations were defined as any hospitalization for COPD or any acute bronchitis episode requiring a course of antibiotics and/or prednisone. Only patients with previous hospitalization records were considered for the respective analysis. Paired t-tests were used for analysis. Results: In our database, we identified fifteen COPD patients with an average age of 70.73 years (range: 58-80) and an average FEV1% predicted value of 36.3% (range: 16.3-60.9) who were treated with prophylactic doxycycline. Five of these patients had a history of hospitalizations. Patients were on prophylaxis during the fall/winter months for an average number of 2.78 years (range: 0.5-7.5). The number of average exacerbations/year decreased from 3.43 to 1.01 (n=15, p = 0.0034) and the number of hospitalizations/year decreased from 1.75 to 0.00 (n=5, p =0.0125). Furthermore, doxycycline was tolerated well except for a few cases of mild nausea in the first days of treatment. Conclusion: Based on the data, our retrospective study demonstrates a significant decrease in the number of exacerbations/year and in the number of hospitalizations/year for patients with moderate/severe COPD undergoing doxycycline prophylaxis. Furthermore, patients tolerated doxycycline well. This small study strongly suggests the need for a prospective randomized well-controlled study evaluating prophylactic treatments with doxycycline or other antibiotics.

Table 1. Summary of the average number of exacerbations/year and hospitalizations/year for patients with moderate to severe COPD on doxycycline prophylaxis.

cohort of patients with asthma who completed a questionnaire asking the number of times they had a burst of oral steroids with an asthma exacerbation from July 2006 thru July 2011. . During this 5 year time frame (July 2006-2011) 69.7% of patients had 3 or more bursts of oral steroids using pharmacy refill records for at least one of these years while only 29.4% gave a oral history of having 3 or more bursts of oral steroids during this 5 year time frame. Compared with patients recall of number of times oral steroids were used with a recent exacerbation, patients with a history of refills from pharmacy data base of 3 or more “bursts of oral steroids” with exacerbations were at increased risk of future exacerbation during the year or years they had 3 or more bursts of oral steroids (odds ratio=6.33; 95% CI 3.2 7, 8.33), even after adjustment for demographics and clinical factors (odds ratio=4.77; 95% CI 3.4 2,6.43), asthma severity (physician-assessed: odds ratio=4.44; 95% CI 4.03, 7.83). Conclusion: This analysis suggests that recent asthma exacerbations derived from pharmacy database predict future exacerbations and, as such, should be considered as part of the clinical assessment of patients with difficult-to-treat asthma.

P73 INCREASED ALLERGY SKIN TEST REACTIVITY IN ASTHMATICS: RESULTS FROM THE SECOND AND THIRD NATIONAL HEALTH AND NUTRITION EXAMINATION SURVEY (1976-1994). P. Koutsoupias1, Q. Meng1, L. Bielory*2, 1. Piscataway, NJ; 2. Springfield, NJ. Background: Allergy skin test results from the Second and Third National Health and Nutrition Examination Survey (NHANES) have been published. However, trends in allergen sensitivity in sensitized asthmatics have not been well studied. Methods: Allergy skin test data was collected from NHANES II (1976 to 1980; n = 11,044) and NHANES III (1988 to 1994; n = 10,833). Skin test results were assessed for the six allergens common to NHANES II and NHANES III: cat, ragweed, perennial rye, oak, Bermuda grass, and Alternaria alternata. An individual was considered sensitized, or Immediate Skin Test positive (IST+), if he or she tested positive for one or more of the six allergens. The IST+ populations were then assessed for asthma status. An individual was considered asthmatic if he or she had a past history of the disease and still had the disease. Results: Of 2,144 IST+ individuals in NHANES II, 109 (5.08%) were IST+ asthmatic. Of 4,538 IST+ individuals in NHANES III, 378 (8.33%) were IST+ asthmatic. From the Second to the Third Survey, the prevalence of positive skin tests in the IST+ asthmatic population increased for each of the six allergens common to NHANES II and NHANES III. From NHANES II to NHANES III in the IST+ asthmatic population, cat allergen sensitivity increased from 21.1% to 52.9%; ragweed sensitivity increased from 56.9% to 71.4%; ryegrass sensitivity increased from 55.1% to 69.3%; oak sensitivity increased from 26.6% to 40.2%; Bermuda grass sensitivity increased from 22.0% to 54.0%; and Alternaria alternata sensitivity increased from 33.9% to 52.7%. Conclusion: From 1976 to 1994, the prevalence of positive allergy skin tests in asthmatics has increased significantly. For cat allergen and Bermuda grass, the prevalence of IST+ has more than doubled. Moderate increases in reactivity were observed for ragweed, ryegrass, oak, and Alternaria alternata. Supported in part by US EPA STAR Grant #: RD834547; Observational, Laboratory, and Modeling Studies of the Impacts of Climate Change on Allergic Airway Disease; PI: Leonard Bielory, M.D.

P72 IS PHARMACY DATA BETTER AT PREDICTING ASTHMA EXACERBATIONS? D. Bukstein*, Fitchburg, WI. Background: The relationship between oral steroid use derived from patient history verses oral steroid use for 5-10 days for asthma exacerbations derived from pharmacy refill data (termed steroid bursts) is not currently known. Objective: To evaluate the relationship between the history of oral steroid bursts derived from patient history compared with oral steroid bursts derived from computerized pharmacy refill data and their relationship to asthma-related exacerbations and other outcomes. Methods: We evaluated oral steroid use for exacerbations among 1688 patients with asthma ages 5 to 65 years who were members of a large health maintenance organization. IRB/HAC approval and informed consent was obtained from all research subjects. Frequency of oral steroid bursts was estimated from the patient’s history at one year follow-up and pharmacy data assessing the timing and amount of oral steroid fills. Database indexes of asthma control were derived based on dispensed prescriptions and on medical services and testing recorded in a large administrative database 12 months and this pharmacy refill data was applied to data from to a



ABSTRACTS: POSTER SESSIONS albuterol pump for suspected diagnosis of asthma, especially with a history of atopy. His mother had used the albuterol pump on a few occasions and decided to discontinue due to minimal improvement. During his presentation in the emergency room, he was noted to have bilateral wheezing with noticeable respiratory distress. Again, he was assessed as having an asthma exacerbation and treated with nebulization without much improvement. Blood work was also done which was normal. A chest x-ray was performed and showed hyperlucency and hyperaeration on the left lung. There was a shift in the mediastinum with underlying chronic lung changes. The left hemidiaphragm was also depressed while the right lung was compressed. A preliminary diagnosis of congenital lobar emphysema was made. Subsequently the patient was diagnosed with pleuropulmonary blastoma (PPB), a rare childhood cancer. Conclusion: It is well known that all that wheezes is not asthma, but most of the time it is the correct diagnosis. We present a case of an infant with multiple episodes of wheezing that was due to Pleuropulmonary Blastoma Type 1. This type of “soft tissue sarcoma” has the best prognosis and is the most benign. It is quite rare and only 60 patients are currently in the data registry. Physicians should be vigilant in their search for the proper diagnosis of asthma, even though the patient might have a history of atopy. However minimal improvement with bronchodilators should be a clue that other diagnosis should be investigated.

P74 ALLERGEN SENSITIZATION PATTERNS IN ASTHMATIC CHILDREN ARE RELATED TO RACE AND GENDER. K. Robben*1, B.L. Jones2, 1. Olathe, KS; 2. Kansas City, MO. Rationale: Identification and classification of differing phenotypes are important in the therapeutic treatment of asthma. Asthma has been associated with perennial allergen sensitization among African Americans and Hispanics. We aim to evaluate rates of allergic sensitization among children in relation to demographic characteristics in further defining asthma phenotypes in children. Methods: A convenience sample of 140 children with asthma underwent skin prick testing for seasonal and perennial allergens, performed according to standard practice. IRB approval and informed consent was obtained from all research subjects. Chi square test or Fishers Exact test was used to compare rates of allergic sensitization and type of allergic sensitization (seasonal vs. perennial) among children by race and gender. Significance was determine at an α < 0.05. Results: Complete data were available for 137 children (mean age of 12, range 7-18 years). The cohort was (41%) Caucasian, (49%) African American, (2%) Asian, and (7%) more than one race. Of the entire cohort 53% were allergic and 47% were non-allergic. When compared to other racial groups, African American children were more often allergic (30% African American, 18% white, <1% Asian, 4% more than 1 race, p=0.23). Among those classified as African American race, 62% were allergic (38% non-allergic) (p=0.05). Seasonal allergies were significantly more prevalent in both the allergic African American children (53% seasonal, 17% perennial, 29% both, p<0.014) and allergic white children (61% seasonal, 26% perennial, 13% both, p<0.015) and African Americans tended to more often have both seasonal and perennial allergens. Males were more often allergic than females (35% of males vs. 18% of females) (p < 0.0031). Conclusions: In the pediatric asthmatic population, African Americans more often exhibit the allergic asthma phenotype, which is consistent with previous reports. We also observed that type of allergic sensitization may differ by race. Additionally, more males are classified as the allergic phenotype when compared to females. Gender and race appears to have a significant impact on asthma phenotype which is important to consider for the adequate treatment of the disease among the general population.

P75 A RARE CASE OF PLEUROPULMONARY BLASTOMA MASQUERADING AS ASTHMA IN AN INFANT. Y.K. Persaud*, T. Moulton, L. Kin, Bronx, NY. Background: Many conditions may mimic wheezing, which leads to a misdiagnosis and inappropriate treatment. Common differentials for wheezing in children include infantile wheezing, viral-associated wheeze, bronchiolitis, pneumonia, etc.; however rare diseases can masquerade as asthma. Case Report: An 8 month old infant with a history of neonatal jaundice and atopic dermatitis presented with a two month history of intermittent wheezing and coughing. Two months prior he was assessed for wheezing and was discharged with an

P76 LONGITUDINAL IMPACT OF OMALIZUMAB ON ASTHMA CONTROL: 5-YEAR DATA FROM THE EXCELS STUDY. K. Raimundo*, J. Zazzali, B. Trzaskoma, K. Rosen, South San Francisco, CA. Introduction: Omalizumab has been shown to be efficacious in the treatment of moderate-to-severe persistent allergic asthma in clinical trials. This analysis evaluates the long-term impact of omalizumab on asthma control. Methods: EXCELS was a 5-year prospective observational cohort study of approximately 5,000 omalizumab-treated and 2,500 non-omalizumab–treated moderate-to-severe persistent allergic asthma patients, aged ≥ 12 years. Since EXCELS was an observational study, no treatment was assigned to any patient. We assessed asthma control in omalizumab ‘new starts,’ ‘established users,’ and non-omalizumab treated patients. Asthma control was assessed using the Asthma Control Test every 6 months from baseline to month 24 and yearly thereafter, and was defined as ‘well controlled’ (>20) and ‘poorly controlled’ (<15). Results: In the omalizumab new starts cohort (n=576), the proportion of patients who were well controlled increased substantially from baseline to month 6 (25% to 51%); and was relatively stable after thereafter, with 60% being well controlled at year 5. Conversely, the proportion of new starts patients who were poorly controlled decreased substantially from baseline to month 6 (52% to 25%), and was relatively stable out to year 5 (20%). There was an improvement in asthma control in the established users group (n=4,354): the proportion of patients who were well controlled increased between baseline and year 5 (48% to 61%), while the proportion of poorly controlled patients decreased (29% to 19%). The proportion of non-omalizumab users (n=2,779) who were well controlled increased from baseline to year 5 (49% to 67%), while the proportion of poorly controlled patients decreased (27% to 15%). Conclusions: On average, patients in EXCELS who initiated omalizumab experienced



ABSTRACTS: POSTER SESSIONS clinically significant improvement in asthma control that was observed within 6 months and persisted for 5 years.

P77 EFFECT OF POSTURE ON SPIROMETRY IN CHILDREN. K. Swamy*, C. Isroff, A. Chouksey, Cleveland, OH. Background: Spirometry is essential for the evaluation and management of asthma. Traditionally, posture is not documented on the Spirometry report. With the increasing prevalence of obesity, a risk factor for asthma that also influences spirometry, a Quality Assurance project was done to evaluate the effect of posture on Spirometry. Objective: To evaluate the effect of posture on Spirometry in asthmatic patients. Methods: Spirometry was performed on 40 patients between the ages of 5 and 20 in Allergy clinic. The best of 3 tests were chosen according to ATS guidelines. In the first 27 patients, the test was performed initially in the sitting posture, then in the standing. In the next 13 patients, the order was reversed. Forced vital capacity (FVC), Forced expiratory volume in one second (FEV1), Forced expiratory flow during the middle 50% (FEF2575%) and Peak expiratory flow (PEF) measurements were recorded. These values were analyzed in relation to the patient’s body mass index (BMI), gender and posture. Results: No statistically significant difference was found between the tests performed in the sitting or standing postures. The patient’s BMI did not affect the spirometry results. 10% of patients demonstrated changes in 2 out of 3 parameters including FVC, FEV1, and FEF25-75%. The changes included an increment or reduction in the parameters and varied between 1052 %. Conclusions: Posture did not have a significant effect on Spirometry. Recording the posture on the Spirometry record may be helpful in clinical management of the patient.

P78 BRONCHIAL HYPERRESPONSIVENESS IN MEXICAN PATIENTS WITH ASTHMA AND ASPIRIN EXACERBATED RESPIRATORY DISEASE. G. Pavon-Romero, F. Ramirez-Jimenez*, M. Garcia-Cruz, H. CuevasCastillejos, N. Alvarado-Franco, L. Teran-Juarez, Mexico City, DF, Mexico. Background: Asthma is a chronic disorder of the airways characterized by bronchial hyperresponsiveness (BHR) which produces airflow obstruction secondary to bronchoconstriction and mucus hypersecretion. Aspirin Exacerbated Respiratory Disease (AERD) is a specific phenotype of severe asthma associated with nasal polyps, chronic rhinosinusitis and aspirin intolerance, which are factors contributing to the increase of the BHR. The most common method for measuring AERD and it’s grade of severity is the methacholine challenge test (MCT). The grade of severity of the BHR is important for the adjustment of treatment in order to achieve an adequate control of the disease. Objective: To identify the severity of BHR by MCT in patients with asthma and AERD. Method: A cross-sectional comparative study was performed, including 45 patients in each of the two groups -asthma and AERD-. IRB/HAC approval and informed consent was obtained from all research subjects. The diagnosis for Asthma and AERD was confirmed by reversibility and nasal provocation test (using lisyne aspirin) respectively. MCT was performed using Jaegger spirometer; the methacholine was nebulized into different concentrations with a starting dose of 0.03 mg/mL, which was doubled every 2 minutes until the concentration of 32mg/mL was obtained. A positive test was considered at the moment where a decrease of 20% FEV1 -compared with the baseline- was obtained, and when a PC20 (provocative concentration of methacholine that cause a 20% fall in FEV1) less than or equal to 16mg/dl was obtained. Statistical analysis was performed using χ2 test with SPSS v.20. Results: The grade of BHR severity in asthmatic and AERD patients was high in 59% vs 25% respectively, moderate in 31% vs 35% and mild in 10% vs 40%. When the mild and severe group of patients where compared, a statistical significance of p=0.002 was obtained. The proportion of patients that used more than three drugs for achieving asthma control was 31.8% vs 68.2% (p=0.002). Conclusions: The severity of BHR was lower in the AERD patients compared with the asthma group, although this may be attributed to the greater amount of drugs used for AERD patients in order to achieve control of their disease.


P79 DIET-INDUCED OBESITY ALTERS HOUSE DUST MITE-MEDIATED ASTHMA IN C57BL/6 MICE. J.M. Diaz*1, M. Solanki1, X. Xue1, P. Chatterjee1, M. Gupta1, V. Bonagura1, C.N. Metz2, 1. Great Neck, NY; 2. Manhasset, NY. Introduction: Worldwide obesity has become an epidemic. When associated with asthma, a subset of these obese patients are considerably less responsive to traditional glucocorticoid therapy. What makes these obese asthmatics different from their non-obese counterparts? We hypothesized that the differences in inflammation observed in obesity alters asthma complexity. We established a mouse model of asthma in the setting of obesity in C57BL/6 mice to investigate the pathogenesis of this steroid resistance. Methods: Mice (C57BL/6, males, 8-10/group) were randomized to be fed either a regular ‘lean’ chow or high fat chow (60% lard) for the entire study. After 6 months, mice were given intranasal saline (Sal) or house dust mite extract (HDM), 5 days/week for 4 weeks. Animals were euthanized with pentobarbital/phenytoin. Blood was obtained via cardiac puncture & bronchioalveolar lavage(BAL) was collected. BAL cell differentials were determined after modified Wright staining. Cytokine & total IgE levels were determined by ELISA. Results: The absolute cell count in the BAL was similar for in obese asthmatic mice and lean controls. Both HDM groups had a significant increase in eosinophils when compared to Salcontrol mice. The BAL of the lean asthmatics was comprised of mainly macrophages (40-60%) & eosinophils (30-60%), while the BAL of the obese asthmatics had more macrophages (60-75%) but fewer eosinophils (18-40%). The mean plasma IgE level in the lean–HDM mice was 124ng/mL (+9SD) while the obese–HDM mice had a level of 249ng/mL (+ 58SD). Evaluation of the BAL showed significantly elevated levels of IL-4 (lean-HDM 4,782pg/mL, obese-HDM 15,840pg/mL(P<0.05)) & IL-5 (lean-HDM 3,252pg/mL & obeseHDM 24,070pg/ml(P<0.05)). Conclusion: To our knowledge, this is the first diet-induced obesity with HDM asthma model in C57BL/6 mice. As opposed to the eosinophil-predominant inflammation seen in lean-HDM models, this obese-HDM model exhibits greater macrophage participation in conjunction with the expected eosinophil infiltration. Obese-asthmatic mice also showed a significant increase in cytokines & total IgE levels. There are two subsets of obese asthmatic phenotypes described in the literature. The increased levels of IgE & TH2 cytokines shown in this model closely emulate the early-onset obeseasthmatic phenotype. Understanding of this subset may lead to improved therapies.

P80 AN EVALUATION OF COMPLEMENTARY AND ALTERNATIVE MEDICINE (CAM) THERAPIES FOR ASTHMA ON THE INTERNET. C. Tharpe*, A. Patel, J. Glisson, G. Marshall, Jackson, MS. Purpose of Study: Studies have suggested that up to 70% of adult Americans have used CAM therapies for symptomatic management of asthma. The purpose of this study is to examine various characteristics of websites promoting CAM therapies for asthma, including the CAM therapies recommended, claims being made about these therapies, and if adverse effects, drug interactions or disease state interactions are mentioned. Methods Used: Search results were generated using asthma and common terms for CAM therapies. Five search terms were used on Google and a total of 200 sites were evaluated by the primary investigator using a datasheet that was created to assess the key areas of interest. A co-investigator evaluated these same sites independently. Results: Out of the 200 sites reviewed by the primary investigator, 12 sites were found to be no longer active when the co-investigator reviewed the sites. Thus, a total of 188 websites were analyzed. Our study demonstrated that garlic, ginger, licorice, honey, and mullein were the most frequent CAM therapies recommended for asthma. Over 94% of the sites made a therapeutic claim about the CAM therapies recommended and 24% made a claim that these therapies will cure or eliminate asthma. Over 80% of the sites did not mention any adverse effects, drug interactions, or disease state interactions. The vast majority of sites, approximately 70%, did not make a recommendation as to whether the therapy should be used as complementary or alternative to the patient’s prescribed asthma therapy. Also, 60% of the sites had a medical disclaimer yet only about 40% recommended consulting a health care provider prior to using the CAM therapy. Only 18% of sites were promoted by health care providers. Conclusions: The internet is not only a source for myriad amounts of medical information for asthma but also provides well documented CAM therapies for asthma. CAM therapy use is increasing and active inquiry by providers is a must. Knowledge about patient use of these therapies would help the health


ABSTRACTS: POSTER SESSIONS care provider monitor for potential adverse effects, drug interactions, and exacerbations of co-morbid conditions. Thus, it is prudent to be aware of these therapies as it can have a major impact on asthma treatment plans and the overall well-being of the patient.

gesting patients with higher IgE levels may have more improvement with treatment. There was also a negative insignificant trend towards FEV1 improvement and increased weight suggesting heavier patients may have a less robust response to treatment as measured by FEV1 improvement at 1 year.





Introduction: Extracorporeal membrane oxygenation (ECMO) can be life saving therapy in cases of severe respiratory acidosis and hypoxemic and hypercapnic respiratory failure. Status asthmaticus is a severe acute exacerbation of asthma which may be refractory to standard therapeutic modalities and may require ECMO as a life saving therapy. Case Description: A 4 year old Caucasian female born full term with severe persistent asthma, 5 previous pediatric intensive care unit (PICU) admissions, and 3 previous intubations, was admitted to the PICU with status asthmaticus and respiratory failure. Exam was notable for hypoxemia, hypercapnia, and respiratory failure. Initial imaging at the time with chest x-ray (CXR) revealed hyperinflated lungs with atelectasis and no focal consolidation. While intubated, despite extensive therapeutic modalities, the patient’s clinical status did not improve. She continued to demonstrate hypoxemia, and severe respiratory acidosis on repeated arterial blood gases. ECMO was initiated. Initially on veno-venous ECMO, her respiratory acidosis was corrected however adequate oxygen levels could not be maintained. The patient was then switched to a veno-arterial ECMO circuit for a total of 12 days. The patient had been followed closely and had an extensive work up completed by both pulmonary and allergy for her asthma. A high resolution CT demonstrated normal anatomy, Surfactant protein C and ABCA were negative, bronchoscopy demonstrated some mucosal thickening but otherwise normal anatomy and a completed modified barium swallow study was negative. No evidence of primary immunodeficiency was found. Allergic bronchopulmonary aspergillosis (ABPA) work up was negative. IgE levels were elevated with mild allergic sensitizations on skin testing. The patient had a normal nasal ciliary biopsy and normal sweat test. A pulmonary function test prior to this admission was negative for any signs of obstructive or restrictive pulmonary disease. Conclusion: This case illustrates the life saving therapeutic modality of ECMO. It can provide management and support during a severe asthma exacerbation. ECMO, despite many risks of its own, may need to be considered more often in cases of severe asthma and respiratory failure.

P82 OMALIZUMAB TREATMENT AND IMPROVEMENT IN FEV1 AT 1 YEAR IN YOUNGER PATIENTS. L. Finkas*, J. Rosenberg, R. Katial, Denver, CO. Rationale: Omalizumab has been approved for treatment of asthma since 2003. Analyze objective data to identify factors associated with improvement with the treatment with Omalizumab. Methods: Retrospective analysis on data obtained on 157 patients undergoing treatment with omalizumab at National Jewish Health. Data was collected on both pediatric and adult populations receiving treatment. Information obtained included age, baseline IgE level as well as FEV1 prior to treatment and at 3 month intervals up to 1 year. Data was then analyzed using Pearson analysis. Results: Of the 157 patients in whom data was collected, 69 had FEV1 measurements 1 year into treatment with omalizumab. Of these patients, average age observed was 42. Average baseline FEV1 prior to initiation treatment was 2.08L and with average FEV1 at 1 year of 2.26L. Average weight and IgE level prior to initiation of treatment was 74kg and 361kU/L respectively. Absolute FEV1 change was 0.19L improvement 1 year post initiation with treatment with omalizumab. Following analysis, there was significant negative correlation seen between patient age and improvement in FEV1 at 1 year with treatment with omalizumab. Pearson Correlation coefficient -0.53253 with a p value <0.001. Similar correlation was not observed between age and change in FEV1 at intervals observed prior to 1 year . Weak negative correlations were observed with BMI and FEV1 improvement at 1year, with higher BMI associated with less improvement in FEV1 from baseline, however findings were not significant. There was also weak trend toward increased improvement in FEV1 associated with increased IgE levels prior to treatment. Conclusion: Omalizumab has been shown to decrease frequency of asthma exacerbation and use of steroids in patients with severe persistent asthma. Our data shows that older patients have less improvement in FEV1 at 1year while on treatment with omalizumab. Also, there was an insignificant trend towards increased FEV1 improvement at 1 year and pretreatment IgE level sug-

Introduction: Hereditary angioedema (HAE) manifests as recurrent attacks of cutaneous/submucosal edema. We describe the efficacy and safety of icatibant for repeated HAE attacks in the For Angioedema Subcutaneous Treatment3 study (FAST-3;NCT00912093). Methods: FAST-3 was a Phase III study of icatibant in adults with HAE type I or II. In a controlled, doubleblind phase, patients were randomized to a single subcutaneous injection of icatibant 30 mg or placebo for a moderate to very severe abdominal or cutaneous attack or mild to moderate laryngeal attack; patients with severe laryngeal symptoms received open-label icatibant. After the controlled phase, patients could enter an openlabel phase in which they could receive up to 3 injections of open-label icatibant for each subsequent attack. Primary endpoint was time to onset of symptom relief (≥50% reduction from pretreatment in patient reported, 3 item composite visual analog scale [VAS] symptom score). Secondary endpoints included time to onset of symptom relief for a single primary symptom (assessed by VAS) and safety. IEC/IRB approval and informed consent were obtained. Results: Of 98 patients enrolled in FAST-3, 93 were randomized to icatibant (n=46) or placebo (n=47) in the controlled phase, 5 with severe laryngeal attacks received open-label icatibant in the controlled phase, and 82 received icatibant in the open-label phase. Across both phases, 88 patients had 1-5 icatibant treated attacks (total: 489 attacks). When groups of patients with at least 1, 2, 3, 4 or 5 icatibant treated attacks were analyzed, median time to onset of symptom relief (3 item composite VAS) was 1.9-2.1h and median time to onset of primary symptom relief (1 item VAS) 1.5-2.0h. Twenty seven patients had ≥1 icatibant treated laryngeal attack. In these patients, median time to onset of symptom relief (≥50% reduction from pretreatment) and median time to onset of primary symptom relief were 2.0h. Treatment-related adverse events (TRAEs) were reported in 13.6% patients with ≥1 icatibant treated attack. Two patients had serious TRAEs (after 4 and 5 icatibant treated attacks, respectively). Conclusions: Icatibant provided onset of symptom relief in a median of ≤2.1h in patients experiencing abdominal, cutaneous and/or laryngeal HAE attacks. Efficacy was sustained over repeated attacks.

P84 EARLY ICATIBANT TREATMENT IS ASSOCIATED WITH FASTER RESOLUTION OF HEREDITARY ANGIOEDEMA ATTACKS: REAL-WORLD DATA FROM THE ICATIBANT OUTCOME SURVEY. H. Longhurst*1, T. Caballero2, A. Zanichelli3, W. Aberer4, V. Fabien5, L. Bouillet6, M. Maurer7, 1. London, United Kingdom; 2. Madrid, Spain; 3. Milan, Italy; 4. Graz, Austria; 5. Eysins, Switzerland; 6. Grenoble, France; 7. Berlin, Germany. Introduction: The Hereditary Angioedema (HAE) International Working Group (HAWK) Consensus and World Allergy Organization (WAO) Guidelines recommend early treatment of HAE attacks. We used data from the prospective, international, multicenter, observational Shire-sponsored Icatibant Outcome Survey (IOS; NCT01034969) to explore the effects of early icatibant treatment on HAE acute attacks outcomes in a real-world setting. Methods: Adult patients received subcutaneous injections of icatibant 30 mg for the treatment of acute non-laryngeal HAE type I or type II attacks. Icatibant could be self-administered after training in subcutaneous injection technique by a healthcare professional (HCP), or administered by an HCP. Time to treatment (time from attack onset to icatibant injection), time to resolution (time from icatibant injection to complete resolution of symptoms), and attack duration (time from attack onset to complete resolution of symptoms) were assessed. IEC/IRB approval and informed consent were obtained. Results: Of 345 HAE attacks between July 2008 and December 2012, 251 were treated with selfadministered icatibant and 94 with HCP-administered icatibant. When compared with HCP-administration, self-administration was associated with a



ABSTRACTS: POSTER SESSIONS shorter median time to treatment (2.4 vs 1.5 hours; p=0.026) and a greater proportion of attacks treated in <1 hour (20.2% vs 37.9%; p=0.002); a similar, but non-significant trend was observed for the proportion of attacks treated in <2 hours (43.6% vs 54.6%; p=0.070) or <5 hours (63.8% vs 74.1%; p=0.060). Median attack duration was significantly shorter for attacks treated in <1 hour versus ≥1 hour, <2 hours versus ≥2 hours, and <5 hours versus ≥5 hours (Table). Similarly, median time to resolution was significantly shorter for attacks treated in <1 hour vs ≥1 hour (2.3 vs 4.4 hours; p=0.045), <2 hours vs ≥2 hours (2.5 vs 5.0 hours; p=0.032), and <5 hours vs ≥5 hours (2.7 vs 6.5 hours; p=0.022). Conclusions: HAE attacks were more likely to be treated earlier if icatibant was self-administered rather than HCP-administered. Earlier icatibant treatment was associated with improved outcomes in terms of shorter attack duration and time to resolution.

P86 P85 ICATIBANT FOR THE TREATMENT OF NON-LARYNGEAL HEREDITARY ANGIOEDEMA ATTACKS: COMPARISON OF OUTCOMES FROM A CONTROLLED PHASE III TRIAL AND A REAL-WORLD SETTING. M. Riedl*1, H. Longhurst2, V. Fabien3, W.R. Lumry4, M. Maurer5, 1. Los Angeles, CA; 2. London, United Kingdom; 3. Eysins, Switzerland; 4. Dallas, TX; 5. Berlin, Germany. Introduction: Icatibant demonstrated efficacy and was generally well tolerated for the treatment of hereditary angioedema (HAE) attacks in the double-blind, placebo-controlled, Phase III For Angioedema Subcutaneous Treatment (FAST)-3 study (NCT00912093). Using data from the prospective, international, observational Shire-sponsored Icatibant Outcome Survey (IOS; NCT01034969), we compared real-world outcomes with the results of FAST3. Methods: In FAST-3, adult patients with moderate-to-very-severe non-laryngeal HAE type I or II attacks were randomized to receive a single healthcare professional- (HCP-) administered subcutaneous (sc) injection of icatibant 30 mg. In IOS, adult patients with mild-to-very severe non-laryngeal HAE type I or II attacks self-administered icatibant 30 mg sc (after training by an HCP), or had icatibant administered by an HCP. Time to treatment, time to symptom resolution (almost complete resolution [FAST-3] or complete resolution [IOS]), and attack duration were compared. To aid comparison with FAST-3, attacks treated ≥12 h after onset in IOS were excluded. IEC/IRB approval and informed consent were obtained. Results: In FAST-3, data were collected for 43 patients (43 attacks) vs 104 patients in IOS (378 attacks; IOS data cut-off, 21 March 2013). In IOS, most attacks (80.2%) were treated with self-administered icatibant. Median time from attack onset to treatment was shorter in IOS (selfand HCP-administration, 1.6 h [n=104]; HCP-administration only, 2.0 h [n=50]) than in FAST-3 (6.5 h [n=43]; p<0.001 for both comparisons). Median time from treatment to symptom resolution was shorter in IOS (self- and HCP-administration, 4.1 h [n=92]; HCP-administration only, 3.5 h [n=45]) than in FAST3 (8.0 h [n=43]; p<0.0001 for both comparisons). Median attack duration was also shorter in IOS (self- and HCP-administration combined, 7.4 h [n=92]; HCP-administration only, 7.3 h [n=45]) than in FAST-3 (16.9 h [n=43]; p<0.0001 for both comparisons). Icatibant was generally well tolerated in both studies. Conclusions: In IOS, median attack duration, time to treatment and time to attack resolution were shorter vs FAST-3 (Fig). This suggests that the real-world setting enables earlier treatment, which may result in shorter time to attack resolution and attack duration.


M2 MUSCARINIC ACETYLCHOLINE RECEPTOR MODULATES RAT AIRWAY SMOOTH MUSCLE CELL PROLIFERATION. F.A. Placeres-Uray*, C. Febres-Aldana, R. Fernandez-Ruiz, R. Gonzalez de Alfonzo, I. Lippo de Becemberg, M.J. Alfonzo, Caracas, Distrito Capital, Venezuela, Bolivarian Republic of. Airways chronic inflammatory conditions in asthma and COPDare characterized by tissue remodeling, being smooth muscle hyperplasia, the most important feature. Non-neuronal and neuronal Acetylcholine acting on muscarinic receptors (MAchR) has been postulated as determinant of tissue remodeling in asthma and COPD by promoting proliferation and phenotypic changes of airway smooth muscle cells(ASMC). The objective of this work was to evaluate proliferative responses to muscarinic agonist as carbamylcholine (Cch) and to identify the MAchR subtype involved. ASMCwere isolated from trachealfragments of Sprague-Dawley ratsby enzymatic digestion. Proliferation assays were performed by MTS-PMS method. Viability was confirmed by trypan blue exclusion method.Mitogens as, epidermal growth factor (EGF), Tumor necrosis factor-alpha (TNF-α) and fetal bovine serum (FBS) increased ASMC proliferation (p<0.05, n=5).Cch alone increased ASMC proliferation at 24 and 48 hrs. However, combination of Cch with other mitogens exhibited a dual effect, inhibiting the proliferation induced by 10%FBS, EGF (10ng/mL) and TNF-α (10ng/mL), and synergistic proliferation effect in the presence of EGF (5ng/mL) and 5%FBS. To determine the MAChRsubtype involved in these biological responses, a titration curve doses of selective muscarinic antagonists were performed. The Cchstimulatory and inhibitory effects on ASCM proliferation was blocked by AFDX-116 (M2AChR selective antagonist), in greater proportion than 4-DAMP (M3AChR selective antagonist), suggesting that the modulation of Cchproliferation is M2AChR mediated responses.Thus, M2AChR can activate multiple signal transductionsystems and mediate both effectsonASMC proliferation depending on the plethora and variable airway microenvironments existing in asthma and COPD

P87 PURIFICATION, IDENTIFICATION AND CHARACTERIZATION OF A PLASMA MEMBRANE BOUND PHOSPHODIESTERASE1A FROM BOVINE TRACHEAL SMOOTH MUSCLE. P. Mastromatteo-Alberga*, F.A. Placeres-Uray, R. Gonzalez de Alfonzo, I. lippo de Becemberg, M.J. Alfonzo, Caracas, Distrito Capital, Venezuela, Bolivarian Republic of. Muscarinic antagonists increase cAMP/cGMP levels at Bovine Tracheal smooth muscle (BTSM) through the inhibition of phosphodiesterases (PDEs), being a similar behavior of IBMX (non- selective PDE inhibitor) and vinpocetine (a specific PDE-1 inhibitor). We purify and characterize a Calmodulin (CaM) dependent and vinpocetine sensitive PDE-1 from plasma membranes (PM) fractions from BTSM. PM fractions were prepared from BTSM and the PDE-1 activity was removed using a low ionic strength buffer and purify 38 fold using two columns, (Q-Sepharose y CaM-Agarose). The purified enzyme was stimulated by CaM and inhibited by vinpocetine showing two bands in PAGE-SDS (56,58 KDa) being identified the 58 kDa as PDE1A using


ABSTRACTS: POSTER SESSIONS Western blotting. PDE activity was assayed with [3H]cGMP and [3H]cAMP exhibiting the kinetic parameters: Km (uM) for cAMP (8.42 + 0.67) and cGMP (6.07 + 1.49); Vmax (pmol/min/mg of protein) for cAMP (99 + 3) and cGMP (66 + 5). Vinpocetine showed IC50 (uM) for cAMP (4.9 + 0.20) and cGMP (4.6 + 0.30). CaM increases twice PDE-1A activity with Ka (nM) for cAMP (2.03 + 0.5) and cGMP (1.65 + 0.3) and Vmax values for cAMP (130 + 12) and cGMP (110 + 10). The co-factor Mg2+ showed Ka (mM) for cAMP (0.27 + 0.02) and cGMP (0.15 + 0.01) exhibiting Vmax for cAMP (99 + 3) and cGMP (72 + 5). The original finding was purify and characterize a membrane-bound PDE-1A couples to M2AChR via Gi/o protein at sarcolema from BTSM. Supported by grants CDCH-UCV # PG -09-7401-2008/2 (RGA) and PG 09-77722009/1(MJA).

P88 INTERNATIONAL PRACTICE OF SELF-ADMINISTRATION IN THE MANAGEMENT OF HEREDITARY ANGIOEDEMA: SURVEY RESULTS AND DISCUSSION FROM AN INTERNATIONAL EXPERT PANEL. T. Craig*1, T. Caballero2, P.K. Keith3, I. Boccon-Gibod4, K. Bork5, H. Longhurst6, H.B. Boysen7, L. Bouillet4, S. Neri8, J. Hebert9, E. AygorenPursun10, I. Martinez-Saguer10, C. Bethune11, C. Symons11, K. Andritschke12, A. Sala-Cunill13, M. Cancian14, O. Rossi15, M. Magerl16, M. Cicardi17, 1. Hershey, PA; 2. Madrid, Spain; 3. Hamilton, ON, Canada; 4. Grenoble, France; 5. Mainz, Germany; 6. London, United Kingdom; 7. Aarhus, Denmark; 8. Catania, Italy; 9. Quebec, QC, Canada; 10. Frankfurt, Germany; 11. Plymouth, United Kingdom; 12. Morfelden, Germany; 13. Barcelona, Spain; 14. Padova, Italy; 15. Florence, Italy; 16. Berlin, Germany; 17. Milan, Italy. Background: Until recently, most patients were required to present to a clinic or emergency department for treatment of hereditary angioedema (HAE) attacks, however, pasteurized-nanofiltered (pnf) C1 inhibitor (C1-INH) [CSL Behring (CSLB) or ViroPharma (VP)] and icatibant (bradykinin receptor blocker) are now indicated for self-administration. Self-administration has the potential to minimize burden of disease through early intervention in an attack. Our objective was to assess physicians for their insight on instituting self-administration. Methods: A 16-question online survey about self-administration was sent to 21 centers in Europe (EU), Canada and the United States (US) to capture an international snapshot of current self-administration practice in HAE. Survey results were used to guide discussions at an international HAE expert meeting. Results: Ten HAE specialists completed the survey. All centers offer self-administration and reported an increasing number of patients taking up this treatment option. In the EU and Canada (n=9), HAE centers provide selfadministration training, while the US center provides training through a homenursing agency. The majority of centers (70%) reported that ≥50% of patients were receiving self-administration therapy; pnfC1-INH CSLB and icatibant were the most widely used treatments (pnfC1-INH VP was not available in some countries at the time of the survey). The three main requirements agreed upon for a patient to qualify for self-administration were: patient motivation, mental ability and clinical need; the experts felt that all patients should be considered for self-administration if these characteristics are met. Survey respondents agreed that self-administration improved patients’ quality of life and outlined the key benefits as: time saved, independence and convenience. Barriers to self-administration, such as difficulty in infusion skill set (mainly for intravenous treatment), were identified and solutions, including a 24-hour helpline, were proposed. Conclusion: Internationally, the number of patients being offered and opting for self-administration therapy is increasing. The outcome of selfadministration is to improve time to treatment, quality of life, self-confidence and independence of HAE patients.

P89 DEVELOPMENT AND VALIDATION OF A PATIENT-REPORTED OUTCOME QUESTIONNAIRE FOR THE ASSESSMENT OF HEREDITARY ANGIOEDEMA IN OBSERVATIONAL STUDIES. N. Bonner*1, L. Abetz-Webb1, L. Renault2, T. Caballero3, H. Longhurst4, M. Maurer5, S. Christiansen6, B. Zuraw6, 1. Bollington, Cheshire, United Kingdom; 2. Eysins, Switzerland; 3. Madrid, Spain; 4. London, United Kingdom; 5. Berlin, Germany; 6. San Diego, CA.

can mimic an allergic reaction, appendicitis and anaphylaxis. Qualitative research was conducted to select items for inclusion in a patient reported outcome (PRO) questionnaire that assesses acute HAE attacks and their impact on patients’ lives (HAE PRO). Methods: A first draft of the HAE PRO instrument was developed based on exploratory, semi-structured interviews with HAE patients in Argentina (n=10) and the US (n=33) on attack symptoms, triggers and the impact of attacks. Subsequently, cognitive debriefing of the HAE PRO was performed with HAE patients in the UK (n=10), Brazil (n=10), Germany (n=23), France (n=12) and US (n=12) to ensure patient understanding and the relevance of questionnaire items. The HAE PRO was reviewed by clinical experts. Results: A total of 110 patients with HAE who had experienced abdominal, cutaneous or laryngeal attacks of varying severity levels were interviewed. Patients reported that cutaneous attacks caused skin swelling, pain and redness. Abdominal attack symptoms experienced included pain, vomiting, stomach swelling, diarrhoea and nausea. Laryngeal attacks led to difficulty breathing, voice change and difficulty swallowing. Patients also discussed factors that could trigger an attack including emotional distress, physical trauma, hormonal changes and pressure on the skin. Attack warning signs included skin redness, irritability and nausea. HAE attacks affected patient’s ability to work, perform daily tasks and led them to curtail social plans. Patients also discussed their current treatment options and their resource use associated with HAE attacks. Based on these findings, 17 items were included in the HAE PRO, which assesses the domains symptoms, triggers, resource use and treatments taken for attacks. Cognitive debriefing interviews confirmed that the items and concepts were relevant to patients. Data elicited from the interviews was used to revise the questionnaire and make it culturally appropriate across countries. Conclusion: The HAE PRO can be considered a valid and appropriate tool for the long term assessment of HAE patients.

P90 CHARACTERIZING HEREDITARY ANGIOEDEMA ATTACKS REQUIRING RE-INJECTION OF ICATIBANT: A POOLED ANALYSIS OF THREE PHASE III OPEN-LABEL EXTENSION STUDIES. J. Bernstein*1, W. Lumry2, J. Baptista3, M. Riedl4, 1. Cincinnati, OH; 2. Dallas, TX; 3. Lexington, MA; 4. Los Angeles, CA. Introduction: The Phase 3, randomized, double-blind, controlled For Angioedema Subcutaneous Treatment (FAST)-1, -2, and -3 trials have demonstrated the efficacy and safety of subcutaneous icatibant in adult patients with hereditary angioedema (HAE) type I or II. Open-label extensions (OLEs) of these studies included patients previously treated in the controlled phase, or patients whose first eligible attack occurred after enrollment into the controlled phase was complete. A retrospective analysis of data pooled from the OLE phases of FAST-1, -2 and -3 has been conducted to characterize HAE attacks requiring >1 injection of icatibant. Methods: In the OLEs, a maximum of three subcutaneous injections of icatibant, administered at intervals of at least 6 hours, could be given per attack if the attack worsened (within 48 hours of initial treatment) or symptoms remained severe enough to warrant further treatment. If symptoms became worse >48 hours after initial treatment, the event was considered a new attack. OLE phase data were examined to identify predictors associated with reinjection of icatibant. IEC/IRB approval and informed consent were obtained. Results: A total of 208 patients were treated in the three FAST OLEs. Of 1149 attacks treated with icatibant in the OLE, 1051 (91.5%), 92 (8.0%), and six (0.5%) attacks were treated with one, two, and three injections, respectively. The proportions of attacks requiring >1 icatibant injection were similar for abdominal, cutaneous and laryngeal attacks (8.9%, 8.0% and 8.2%, respectively) with small differences observed for mild, moderate and severe attacks (4.8%, 7.6% and 9.3%, respectively). Patient sex, age group and HAE type also did not appear to influence the need for >1 injection of icatibant. With 1 injection, median time to onset of symptom relief (composite visual analog scale [VAS] score decreased by ≥50% from baseline) was 2.3 hours and median time to almost complete symptom relief (three VAS scores <10 mm) was 5.7 hours. Conclusions: In the FAST OLEs, over 90% of attacks were successfully treated with a single icatibant injection. The need for reinjection of icatibant for a single attack was infrequent and appears to be independent of patient age or sex, HAE type, and attack location.

Background: Hereditary Angioedema (HAE), a rare genetic disease, manifests as intermittent, painful attacks of angioedema. Attacks vary in frequency and severity and include cutaneous, abdominal and laryngeal swellings. Attacks



ABSTRACTS: POSTER SESSIONS oral mucosa is extremely rare. In review of the literature, there are several case reports of extranodal Hodgkin Lymphoma of the oral mucosa. However, to our knowledge, this is the first case of extranodal gingival Hodgkin Lymphoma leading to the diagnosis of Common Variable Immunodeficiency. The development of Hodgkin Lymphoma in a 72-year-old female was not unusual for her age. However, it was the extremely rare location of the patient’s disease that led to the concern for underlying immune defect and ultimately the diagnosis of Common Variable Immunodeficiency. Conclusion: This case illustrates the importance of a heightened index of clinical suspicion for underlying immune deficiency when a patient is diagnosed with an atypical presentation of lymphoma.


P91 BEDBUG BITES AS A RE-EMERGING RELEVANT DIFFERENTIAL DIAGNOSIS FOR UNEXPLAINED RASH. A. Kerr, L. Yao*, Phoenix, AZ. Rationale: The common human bedbug, Cimex lectularius, has long been considered a problem of the developing world. We discuss the case of a patient in Arizona who presented with an unexplained rash; two family members in the same household also developed rashes. The rashes were eventually determined to be caused by bedbug bites. Methods: A 38-year-old male presented with a pruritic rash; his exam was otherwise normal. He was referred to two dermatologists. Neither antihistamines nor oral or topical steroids resolved his rash. Meanwhile, his 37-year-old wife and son presented with unexplained maculopapular rashes. The family first reported that they did not know of anything in the home which could be causing their symptoms. Additionally, they performed extensive cleaning of the home and made changes to detergent, soap and other possible offending agents. Results: Clinical work-up revealed that the patient’s total IgE was elevated. Skin biopsy revealed superficial and deep, perivascular and interstitial, mixed-cell infiltrate with eosinophils beneath papillary dermal edema. These findings are suggestive of a hypersensitivity reaction compatible with arthropod assaults, drug and fungal hypersensitivity reactions or exposure to other exogenous allergens. The family later reported that a bedbug infestation had been discovered in the home. The bedbugs were eradicated with heat, and the family’s rashes subsequently resolved. Conclusion: Bedbug bites may cause cutaneous manifestations ranging from pruritic macules to papules, vesicles and bullae. Reports of bedbug infestations have increased recently throughout the developed world. We should be aware of bedbug bites as a differential diagnosis in the case of unexplained rash.

P92 RARE PRESENTATION OF HODGKIN LYMPHOMA LEADS TO DIAGNOSIS OF COMMON VARIABLE IMMUNODEFICIENCY IN 72-YEAR-OLD FEMALE. A.L. Jones*, R. Casper, Phoenix, AZ. Introduction: This case discusses a patient diagnosed with extranodal Hodgkin Lymphoma of the gingiva, who was subsequently found to have Common Variable Immunodeficiency (CVID). Clinical Case: A 72-year-old female was found to have a gingival irregularity in her right upper gum by her dentist. The gingiva was biopsied and sent for pathology. Atypical large cells resembling Hodgkin Reed-Sternberg cells were visualized, and in situ hybridization testing was EBV positive. The patient was diagnosed with Classical Hodgkin Lymphoma of the gingiva. She underwent staging and was diagnosed as stage 1E (involvement of a single extralymphatic organ or site) according to the Ann Arbor staging classification. Given the unusual location of the Hodgkin Lymphoma, immunologic evaluation was performed prior to the initiation of chemotherapy. The patient denied a history of recurrent infections aside from one episode of pneumonia and several sinus infections. HIV was negative and hepatic profile was normal. Low levels of serum IgG (<100), IgA (<8), and IgM (<25) were discovered. The patient was referred to immunology for further evaluation and was diagnosed with Common Variable Immunodeficiency. The patient was started on IgG immunoglobulin therapy and continues to receive chemotherapy and radiation therapy. Discussion: Hodgkin Lymphoma of the


Background: DRESS is a rare and severe adverse drug reaction with an associated mortality of 10-20%. Clinical worsening despite discontinuation of the culprit drug is a characteristic feature of DRESS. This syndrome is difficult to diagnose due to its clinical heterogeneity and long latency periods. AntiTB drugs are usually well tolerated but clinicians should be aware of its potential to cause DRESS. Case Summary: A case of a 24 year-old female treated with a four-drug fixed dose combination of anti TB medication for pulmonary TB, presented after 6 weeks of therapy with fever, jaundice and right upper quadrant pain consistent with acute cholecystitis. Whole abdomen ultrasound revealed acalculous cholecystitis thus surgical intervention was contemplated however liver function tests were deranged. Anti-TB medications were withheld and the patient was started on intravenous ampicillin-sulbactam and metronidazole as an empiric treatment. Despite antibiotic therapy, there was progression of jaundice, abdominal pain and persistence of fever. Hepatitis panel were all non-reactive and blood culture showed no growth of microorganism. On the 3rd hospital day, there was onset of generalized non-pruritic, exanthematous, maculo-papular rash associated with progressive derangement of liver function tests. Peripheral blood smear showed anemia, eosinophilia and atypical lymphocytosis. Due to the clinical presentation and temporal relation to antiTB therapy and recent use of antibiotics, the diagnosis of DRESS syndrome became more likely. All antibiotics were discontinued and intravenous hydrocortisone, diphenhydramine and oral N-acetyl cysteine was started resulting to significant clinical improvement. During a 2-month follow up period, liver function tests started to normalize and repeat chest X-ray showed resolution of Koch’s infiltrates after the initiation of alternative anti-TB regimen. Conclusion: The recent introduction of anti-TB drugs followed by acute liver injury, eosinophilia and late onset rash should raise suspicion for DRESS syndrome. Timely recognition is crucial and the mainstay of treatment is immediate withdrawal of the inciting drug. Even with much controversy, the use of both corticosteroids and N-acetylcysteine showed significant resolution of clinical signs and symptoms of DRESS.

P94 ALL SKIN AND HEART: A UNIQUE MYOCARDIAL MANIFESTATION OF NORMO-COMPLEMENTEMIC URTICARIAL VASCULITIS. L.U. Karkhanis*, Y.S. Kousari, P.K. Woodard, H.J. Wedner, St. Louis, MO. Introduction: Urticarial vasculitis is characterized by recurrent episodes of urticaria that have the histopathologic features of leukocytoclastic vasculitis. We describe a case of normo-complementemic urticarial vasculitis with a unique form of myocardial vasculitis. Case Report: A 56 year old Caucasian male presented with a sudden onset of hives on his trunk, arms and legs for the past 20 months, which would take 1-2 weeks to resolve, and leave a hyperpigmented area behind. The lesions were mildly itchy, not painful, and did not burn and the pattern was random and intermittent. They gradually spread to involve his scalp and face, and were associated with occasional heart palpitations. They did not respond to antihistamines, and required high dose cyclosporine and oral corticosteroids. On presentation, he had multiple brown circular lesions of various sizes all over trunk, arms, and legs, which were non-blanching, with no tenderness or warmth. Tryptase, sedimentation rate and C-reactive protein were elevated, while complement, autoimmune studies and viral serologies were nor-


ABSTRACTS: POSTER SESSIONS mal. Skin biopsy revealed superficial and deep small vessel vasculitis with eosinophils, with no evidence of mast cell neoplasm. Cardiac magnetic resonance imaging showed patchy, nodular mesocardial enhancement in the inferolateral wall at the base of the left ventricle without wall thinning or wall motion abnormality. The patient was started on mycophenolate mofetil, and oral corticosteroids were gradually tapered. Conclusion: Urticarial vasculitis can be idiopathic, or in association with autoimmune disorders, infections, drug reactions, or as a paraneoplastic syndrome, and tends to have a chronic course. Common laboratory findings are an elevated ESR with low serum complement. Myocardial involvement, seen more with hypocomplementemic urticarial vasculitis syndrome, is usually in the form of pericarditis, pericardial effusions, valvular dysfunction. Normo-complementemic patients usually have little to no systemic involvement, and better prognosis. Our case describes a unique presentation of myocardial vasculitis in the setting of urticarial vasculitis with a normal complement. It is imperative for clinicians to be aware of variant types of urticarial vasculitis and myocardial manifestations.

Delayed contrast-enhanced T1-weighted inversion recovery short axis, high resolution cardiac magnetic resonance images shows patchy, nodular mesocardial enhancement in the inferolateral wall at the base of the left ventricle (arrows) without wall thinning


responses to polysaccharide antigens should be evaluated in patients with MECP2 syndrome with recurrent infections, regardless of their immunoglobulin levels. The treatment response remains to be determined on our patient.

P96 JOB’S SYNDROME: UNUSUAL PRESENTATION IN A TEENAGER. K. Al Atassi*, S.R. Patel, Los Angeles, CA. Job’s Syndrome: Unusual presentation in a Teen Hyper IgE Syndrome is a rare PID characterized by recurrent skin abscesses, sino-pulmonary infections with formation of pneumotoceles, eczematous dermatitis, and elevated serum IgE levels. HIES was initially reported to have an AD inheritance pattern, but cases with AR inheritance and sporadic cases have been reported. Mutations of the STAT3 gene were shown in 70% of the patients with AD HIES. Patients with AD HIES have more connective tissue involvement. Patient with AR HIES are susceptible to severe viral infections. Some patients with AR HIES have mutations in DOCK 8. An 18 year old Armenian male presented with a history of recurrent abscesses and rashes since the age of 14 requiring multiple ED visits and hospital admissions. The lesions started as small pustules on the thigh that increased in size and number to form large abscesses. Over the next 4 years he had more than 20 abscesses involving the sacrum, perineum, buttocks, thighs, and axilla. Some abscesses remain with very poor healing, granulation tissue formation, recurrent drainage or deep scarring. Several consultations were obtained including Surgery, Plastic surgery, Derm, ID, and GI. He required multiple procedures such as I&D, unroofing, and colonoscopy to rule out Crohn Disease. Positive cultures from the drainage included Coag negative Staph., MRSA, and Proteus mirabilis. Treatment consisted of prolonged courses of antibiotics including Bactrim, Clindamycin, Doxycycline, Linezolid, Benzoyl Peroxide, in addition to IM & Oral steroids. Severe nodulo-cystic acne was also noted on the face, upper torso and arms. An eczematous rash also noted on wrists. The patient’s dental history was significant for four retained primary teeth. Immunology work up was negative for CGD, LAD, and Complement deficiencies. Normal antibody response to vaccines. Normal Ig levels except for IgE level of 2372. STAT 3 negative. Diagnosis of Atypical Job Syndrome was made and patient was started on Bactrim prophylactically. Although our patient lacks the typical history of recurrent sino-pulmonary infections, and had a negative STAT3, his history of retained primary teeth, recurrent abscesses, eczema, severe acne, elevated IgE levels, and negative immunologic work up otherwise are most suggestive of Atypical or AR Hyper IgE Syndrome. Currently we are looking at different mutations in STAT 3 and DOCK 8.

SPECIFIC ANTIBODY DEFICIENCY IN A PATIENT WITH MECP2 DUPLICATION SYNDROME. M. Kitcharoensakkul*, A. Beigelman, St. Louis, MO. Introduction: Clinical manifestations of MECP2 (methyl-CpG binding protein 2) duplication syndrome include: hypotonia, mental retardation, poor speech development, epilepsy, and progressive spasticity. Moreover, patient with MECP2 duplication syndrome are well known to have recurrent respiratory infections. The most common immune defect found in these patients seems to be IgA deficiency, and these patients might also have an impaired TH1 immunity. Here we describe a patient with MECP2 duplication syndrome who has had recurrent respiratory tract infections and was recently found to have specific antibody deficiency (SAD): an impaired IgG response to polysaccharide in the presence of normal immunoglobulin levels. Case Report: The patient is a 9-year-old Caucasian male with a significant history of MECP2 duplication syndrome (5p deletion with X duplication) manifesting with developmental delay, neuromuscular weakness, and seizures. He was also diagnosed with Crohn’s disease at 7 years old and has asthma. He was referred to the immunology clinic for evaluation of CD19 lymphopenia found during a workup for recurrent pneumonia and tracheitis. His last course of prednisolone was 6 months before the Immunology clinic visit. His immunizations were up-to-date. There was no family history of immunodeficiency or inflammatory diseases. The physical examination was significant for generalized hypotonia. The immunology workup showed normal CBC. The lymphocyte subpopulation studies were remarkable for B-cell lymphopenia (151 cells/mm3) with normal T-cell and NK-cell counts. His immunoglobulin levels were normal. The titers to tetanus toxoid and Haemophilus influenza B were normal. The titers to Streptococcus pneumoniae were protective to 3 out of 23 serotypes. He was given a Pneumovax booster but the repeat titers at 6 weeks remained suboptimal (4/23) and 10/23 serotype titers even went down post-vaccination. Additional evaluations revealed normal numbers of switched memory B cells, and normal lymphocyte proliferation to phytohemagglutinin. We initiated with IVIG replacement and continue to follow him in the immunology clinic. Conclusions: Antibody

P97 USE OF OMALIZUMAB (OMAL) IN TREATMENT OF CHILDREN WITH SEVERE ATOPIC DERMATITIS: CASE REPORT OF TWO PATIENTS. J.L. Hoang*1, S. Rosenberg2, 1. Baltimore, MD; 2. Orlando, FL. Introduction: Atopic patients with severe eczema are often refractory to conventional therapy. Eczema can lead to significant morbidity including skin disfigurement, secondary infections, and a decrease in quality of life. OMAL, a humanized monoclonal anti-IgE antibody, is FDA approved for patients 12



ABSTRACTS: POSTER SESSIONS years and older for treatment of moderate to severe allergic asthma. OMAL may also show promise in treating severe eczema. Case Report: 2 pediatric patients presented with a history of severe atopy characterized by symptom onset prior to age 1. In addition to severe eczema concurrent diagnoses also included allergic rhinoconjunctivitis, allergic asthma, and food allergy. The 2 patients’ eczema was characterized by total body involvement, severe pruritus, and recurrent bacterial skin infections. They had positive RAST and skin testing for multiple food and environmental allergens. Serum IgE was markedly elevated. Spirometry showed reversible obstructive airway disease. Conventional treatment included immunotherapy, SABAs, LABAs, inhaled corticosteroids, antihistamines, dietary manipulation, topical and oral corticosteroids, tacrolimus, and cyclosporine. Despite therapy, both patients were refractory to treatment. OMAL was started 375 mg IM bi-weekly. Results: After starting OMAL both patients experienced marked improvement in spirometry. There was reduction in skin involvement with eczema, skin infections, and symptoms of pruritus (especially at night). Oral corticosteroids, antibiotics, and hydroxyzine were discontinued without symptom relapse. Conclusion: OMAL is currently only approved for the treatment of moderate to severe allergic asthma. 2 pediatric patients with severe clinical atopy including eczema not controlled with conventional therapy, one of whom was also refractory to cyclosporine, showed significant improvement after starting OMAL. There was also reduction in both topical and systemic corticosteroid use. OMAL acts by binding to IgE and inhibiting it from binding to the FcεRI receptor on mast cells and basophils, decreasing release of inflammatory mediators. This mechanism likely makes OMAL effective in treating eczema. OMAL was tolerated without adverse effects making it an appealing alternative to prolonged oral and topical steroid use. OMAL may have a role in conventional treatment of eczema in select pediatric patients.

P98 A CASE OF HYPEREOSINOPHILIA ASSOCIATED WITH AN HERBAL SUPPLEMENT. J. Rajan*, A. White, San Diego, CA. Introduction: Eosinophilia is known to have a wide variety of etiologies including atopic diseases, connective tissue diseases, certain infections and malignancies. In addition, there have been prior reports of eosinophilia and even eosinophilic syndrome as a result of supplements or contaminants. Examples of these include L-tryptophan which led to eosinophilia-myalgia syndrome as well as Spanish toxic oil syndrome. Here we report a case of hypereosinophilia after use of the herbal supplement, Gentle Senna. Case Report: A 68 year old woman was seen evaluated for new-onset hypereosinophilia. Patient had history of anemia of chronic disease of unknown etiology, responsive to Aranesp, thought to be secondary to early myelodysplasia versus chronic renal failure. On a routine blood draw, 4 weeks prior to evaluation, she was noted to have marked eosinophilia. This steadily increased from 497 to 6,413. She denied any history of allergic rhinitis, asthma, food allergies, or eczema. In regards to gastrointestinal symptoms, she did report longstanding constipation for which she had recently started “Gentle Senna” by Health Concerns®. On review of systems she denied any joint pains, skin changes, fevers, night sweats, weight loss or lymphadenopathy. She also denied any shortness of breath, orthopnea, chest pain, edema of the extremities or neuropathy. Physical exam revealed a healthy-appearing woman with normal head and neck exam, clear lungs, and without lymphadenopathy. The patient was advised to stop using the supplement “Gentle Senna.” Serial blood counts demonstrated a prompt reduction in eosinophilia which ultimately returned to the normal range. Discussion: It is known that there instances of eosinophilic syndrome occurring with supplements or their contaminants. More recently, there has been report of eosinophilia (without evidence of end organ damage) with use of Echinacea. To our knowledge, this is the first reported case of eosinophilia occurring with the combined herbal supplement, sold under the name “Gentle Senna.” It is unknown which herbal component led to the eosinophilia or whether a contaminant in the product was the culprit. This case exemplifies the importance of taking a thorough history when evaluating cases of isolated eosinophilia and educating patients on potential adverse effects of non-regulated herbal supplementation.


P99 CYCLOSPORINE IN CHRONIC IDIOPATHIC URTICARIA WITH POSITIVE THYROID AUTOANTIBODIES. A. Nanda1, A.N. Wasan*2, 1. Lewisville, TX; 2. Lansdowne, VA. Introduction: A subset of patients with chronic idiopathic urticaria do not respond to anthistamines, the standard therapy. It has been estimated that approximately 10-35% of patients with chronic idiopathic urticaria have clinical or laboratory evidence of thyroid autoimmunity. There have been multiple studies and case reports detailing positive clinical responses to thyroid hormone therapies in these patients. However, some of these patients do not respond clinically to thyroid hormone therapy. Case Presentation: A 28 year old man presented with a two month history of new-onset daily urticaria. He had been initially treated by primary care physician with oral prednisone. Multiple antihistamines were not sufficient to wean the patient off of daily prednisone(2040mg daily needed to control symptoms). Complete blood count with differential and comprehensive metabolic profile(including liver function testing) were within normal limits. TSH level was 3.25 mIU/L(normal: 0-4.5) and Free T4 level was 1.2 ng/dL(normal: 0.8-1.8). Thyroglobulin antibody level was 86 IU/mL(normal: <20) and thyroid peroxidase level was 322 IU/mL (normal: <35). Based upon the elevated thyroid antibodies, treatment with levothyroxine was initiated at 25 mcg and increased by 25 mcg every 3 weeks due to failure of clinical improvement. Synthroid was eventually increased to a maximum dose of 150 mcg daily with no significant clinical improvement. Synthroid was weaned down and discontinued due to lack of clinical benefit. As patient still had significant symptoms requiring daily prednisone, cyclosporine was started at 25 mg daily and titrated upwards every 2 weeks based upon clinical response. As cyclosporine dose was increased, the patient was able to wean down the prednisone. At 150 mg cyclosporine daily (approximately 1.5 mg/kg), the patient was able to be completely discontinue prednisone and had no significant urticaria or angioedema symptoms. Appropriate laboratories and blood pressure were closely monitored while patient was on cyclosporine without any significant abnormalities. Discussion: Cyclosporine is an important steroid-sparing agent, and it has been used in the treatment of chronic idiopathic urticaria. This case illustrates the effectiveness of cyclosporine in a chronic idiopathic urticaria patient with thyroid autoantibodies.

P100 AN ATYPICAL PRESENTATION OF EOSINOPHILIC ANNULAR ERYTHEMA (EAE). N.N. Patel*1, Z. Jacobs2, 1. Overland Park, KS; 2. Kansas City, MO. Background: Eosinophilic Annular Erythema (EAE), first described in children in the 1980s, is characterized by recurrent appearances of persistent, urticarial annular lesions predominantly over the trunk and proximal extremities. There is debate regarding its association with Well’s Syndrome and whether it is a separate entity or a sub-type. Case Description: A 32 year old Caucasian male presented to Allergy/Immunology clinic at the consultative request of dermatology for evaluation of a pruritic, urticarial rash that had been present for 9 months. He had undergone multiple skin biopsies, which showed a dense infiltrate predominantly composed of lymphocytes, numerous eosinophils and absence of vasculitis. The lesions responded to high doses of steroids (prednisone 80mg daily) however he was unable to go below 50mg of prednisone without the lesions recurring. We ordered CBC with differential, CMP, CK, Anti-Jo antibody, Anti-CCP antibody, RF, ESR, CRP, C3, C4, CH50, IgG, IgA, IgM, Chronic Urticaria Index and ANA. CBC showed mild absolute leukocytosis and neutrophilia, both of which were attributed to chronic steroid use. IgG was mildly low at 464 mg/dl, most likely due to hypercatabolism of IgG while on a prolonged course of steroids. All other testing yielded no abnormalities. Interestingly, there was no peripheral eosinophilia prior to steroids being used. He was started on hydroxychloroquine 200mg BID and indomethacin 50mg TID with complete resolution of his lesions and is now on a prolonged prednisone taper without recurrence. Discussion: Here we present an unusual case of EAE with its chronicity, predominance of lymphocytes in the histopathology and absence of peripheral eosinophilia. Treatment of EAE with steroids has been shown to have suboptimal results - as in this case. EAE appears to be treated best with antimalarials plus or minus indomethacin. In suspected Well’s Syndrome unresponsive to steroids it is important to consider EAE. It is also essential to consider EAE if the histopathology has predominantly lymphocytes along with eosinophils in the absence of vasculitis. It is imperative to keep this diagnosis in mind when dealing with the differential diagnosis of annular rash and Well’s Syndrome, as the


ABSTRACTS: POSTER SESSIONS treatment is very different and may prevent exposing patients to the harmful effects of long-term steroids.


patients with ACE inhibitor-induced angioedema who were followed between 1 to 14 years, nearly half had recurrences, usually within one month of stopping the medication. Even after cessation, ACE inhibitors should always be considered in the differential of angioedema especially if recently stopped.

SUCCESSFUL TREATMENT OF CHURG-STRAUSS SYNDROME WITH RITUXIMAB. L.E. Howe*, J.R. Baker, Ann Arbor, MI. Introduction: Churg-Strauss is one of the more commonly encountered vasculidites in Allergy/Immunology Clinics. Unfortunately 26% of patients have relapses, despite aggressive initial therapy. Recent research supports consideration of rituximab in ANCA-associated vasculidities, and successful treatment of patients with Churg-Strauss. Methods: A patient with relapse of ChurgStrauss Syndrome was treated with rituximab. Data: A 36-year-old man presented with adult onset asthma, sinus disease, stroke, and mononeuritis multiplex. Laboratory testing showed an eosinophil count of 8,000. He was subsequently diagnosed with Churg-Strauss Syndrome. Initial treatment included cyclophosphamide, oral steroids, and azathioprine. He developed hematuria while on cyclophosphamide and a pelvic fracture that was attributed to long term steroid use. He initially achieved remission but despite aggressive initial treatment and continuation of maintenance azathioprine, at age 55 he had a relapse. This was manifested by increase in sinus symptoms, asthma flare, eosinophilia (absolute count 1.62) and elevated inflammatory markers (CRP 38, ESR 47). Given his history of prolonged treatment with cyclophosphamide, it was felt the risks outweighed the benefits of treatment with cyclophosphamide, so alternative therapies were considered. The patient was placed on rituximab and received induction with 800 mg (375 mg/m2) weekly for four doses, and then monthly for two doses. He was continued on azathioprine. After this initial therapy, he had notable clinical and laboratory response (eosinophil count improved to 0.98, CRP decreased to 6.99, ESR decreased to 16). Four months later, he had worsening of inflammatory markers, and decision was made to undergo a second induction with rituximab. He again responded to therapy with rituximab. Six months later, his eosinophil count was down to 0.66, CRP was 1.4, and ESR was 15. He has a planned maintenance regimen of 800 mg of rituximab every 3-6 months as needed. Conclusion: Rituximab is an effective therapy to treat Churg-Strauss. No side effects were observed in our patient, and a body of evidence is growing supporting the efficacy and safety of this treatment. Churg-Strauss may be encountered by allergists/immunologists, and knowledge of emerging therapies is important for the care of these patients.

P102 TIMING ISN’T EVERYTHING: A CASE OF RECURRENT ANGIOEDEMA. A. Pham*, S. Hariri, J. Yusin, Los Angeles, CA. Introduction: ACE inhibitor-induced angioedema, through rare, is easily diagnosed. This is a case in which the diagnosis was more challenging. Case Presentation: A 67-year old Caucasian male presented with recurrent episodes of angioedema. In February 2012, the patient received amoxicillin for endocarditis prophylaxis for a dental extraction. He developed moderate tongue angioedema after taking two tablets. A similar episode occurred the following month, attributed to lisinopril (taken for years), which was subsequently discontinued. Two months later in May 2012, the patient had a less severe recurrence of tongue swelling. Niacin, started two days prior, was stopped. None of the episodes were associated with urticaria or pruritus. Past medical history was significant for diabetes, hypertension, and hyperlipidemia. Medications included aspirin, amlodipine, metoprolol, metformin, glipizide, insulin, vitamins, and the previously discontinued lisinopril and niacin. He denied any prior urticaria, pruritus, allergic conditions, or adverse drug reaction. Family history was unremarkable. Laboratory data showed C1 inhibitor quantitative 36, C1 esterase inhibitor functional > 90%, C3 188, C4 30.7, and C1q complement 19 (all normal range). The diagnosis of ACE inhibitor-induced angioedema was confirmed with negative penicillin skin testing and graded challenge to niacin. The patient remains on niacin and has not had any further episodes of angioedema. Discussion: Angioedema evaluation includes a review of medications particularly any new ones. Here, two episodes occurred with starting new drugs, obscuring the diagnosis of ACE inhibitor-induced angioedema. Making the diagnosis required two forms of allergy testing: penicillin skin testing and graded oral challenge to niacin. Without the latter, the third episode may have been erroneously attributed to the newly begun medication. Our case suggests a graded challenge protocol, as a literature search yielded no previously published ones. Lastly, our case highlights that ACE inhibitor-induced angioedema can recur even months after discontinuation. In a study of 111

P103 MYCOPHENOLATE MOFETIL INDUCTION OF TOLERANCE (DESENSITIZATION) IN A PATIENT WITH SYSTEMIC LUPUS ERYTHEMATOSUS. J. Hochfelder*1, C. Aranow2, B. Kaplan1, 1. New Hyde Park, NY; 2. Manhasset, NY. Introduction: Mycophenolate mofetil (MMF) is routinely used for induction and/or maintenance therapy for lupus nephritis. Though hypersensitivity reactions to MMF are rare, they do occur. We present a case of MMF desensitization for a patient with SLE. Methods: A 27-year-old female with a history of SLE was referred for evaluation of an allergy to MMF. She had previously tolerated MMF without difficulty when it was given as maintenance therapy for lupus nephritis following induction with cyclophosphamide. The MMF was subsequently discontinued and her lupus activity was well controlled for more than 10 years on low dose prednisone, hydroxychloroquine and methotrexate. In late 2012, she developed active lupus nephritis. A repeat renal biopsy revealed Class III lupus nephritis and MMF was prescribed. On reintroduction of MMF, she developed generalized pruritus, flushing of the hands and face, and facial angioedema 20 minutes after the first dose. The reaction was treated with diphenhydramine and corticosteroids, and the patient was observed in the emergency room. Results: As MMF was the preferred treatment for this patient, an induction of tolerance (IOT) to MMF was planned. Over the first 7 days, the MMF dose was increased to 500 mg twice daily. Each day, 1 to 3 doses were given in increasing increments with a 2 to 3 hour interval between each dose. After dose 2 on day 1 (100 mg), she complained of facial flushing and tingling of the palms and soles that resolved after diphenhydramine. The dose was adjusted and desensitization continued. On day 7 after the first 500 mg dose, she developed mild urticaria on the posterior neck, which resolved after cetirizine 10 mg. Three hours later she was given a second 500 mg dose of MMF, which she tolerated. She continued taking MMF 500 mg twice daily for one week at home, and then it was increased to three times daily with at least a 4 hour interval between doses for one week. She then returned to the allergy office and over 3 days, the MMF was increased to 1000 mg twice daily uneventfully. She currently tolerates 2500 mg of MMF a day in divided doses. Conclusion: This case report demonstrates that tolerance to MMF can be induced in allergic individuals who require this medication. IOT procedure can be continued despite mild allergic reactions with proper observation until the optimal therapeutic dose is reached.

P104 A PATIENT WITH GELATIN ALLERGY AND ANAPHYLAXIS TO THE INFLUENZA VACCINE. S. Albin*, A. Nowak-Wegrzyn, New York, NY. Introduction: Gelatin is a mixture of peptides and proteins produced by partial hydrolysis of collagen extracted from cow, pig, and fish. It is found in various foods, beverages, medications, plasma expanders, and vaccines. We present a case report of a 4 year old patient with anaphylaxis to the influenza vaccine who was referred for evaluation of egg allergy, but was found to also have significant gelatin IgE-sensitization. Methods: The patient was evaluated with both skin prick testing and serum levels of gelatin-specific IgE. Results: The patient was avoiding unbaked egg secondary to a history of perioral rash with ingestion of meringue icing, but the parents were more acutely concerned about an egg allergy given a recent reaction to the influenza vaccine. He had received the influenza vaccine in the past without any issue, but that year he developed diffuse hives, watery eyes, sneezing, and vomiting within 15 minutes of receiving the immunization. Upon further food reaction history, the patient’s mother endorsed that in the past he developed a watery mouth, abdominal pain, and



ABSTRACTS: POSTER SESSIONS weakness with ingestion of gummy candies, gummy vitamins, and marshmallows. Skin prick testing showed a wheal of 4 mm and flare of 21 mm with commercial egg extract, and a wheal of 13 mm and flare of 33 mm with fresh gelatin [Knox, non-kosher]. Serum testing showed an IgE level of 4.76 kIU/L for egg white and 0.39 kIU/L for bovine gelatin [ImmunoCAP, ARUP Laboratories, Salt Lake City, UT]. We offered follow up skin prick testing with fish derived gelatin to determine if the patient could tolerate non-mammalian gelatin, but the family declined further testing. We recommended avoidance of all foods containing unbaked egg and gelatin, and the family opted to defer additional immunization with gelatin-containing vaccines. We prescribed an epinephrine auto-injector, provided an emergency action plan, and reviewed the management of food allergies. Conclusion: Gelatin allergy should be considered in any patient with a history of reaction to gelatin-containing foods or pharmaceutical products. Management of gelatin allergy includes provision of thorough avoidance measures, prescription of epinephrine, and periodic reevaluation to determine if oral food challenges should be considered with decreasing IgE levels and skin prick testing.

P105 A PERPLEXING CASE OF ANGIOEDEMA. G. Kubicz*, C. Mikita, Bethesda, MD. Introduction: Angioedema is a common symptom frequently referred to Allergy & Immunology for evaluation. There are many pathophysiologic causes of angioedema including but not limited to: IgE mediated allergy, direct mast cell mediator release or can be a result of dysfunctional arachadonic acid metabolism within mast cells as seen with NSAIDs. Rarely, the cause is acquired or hereditary angioedema secondary to C1 inhibitor deficiency. However, when the presentation is atypical or the standard treatments are ineffective, the differential diagnosis should remain broad. Case Report: We were consulted for recommendations on the management of recurrent angioedema in a 69-yearold African-American woman with end stage renal disease, admitted for symptomatic anemia. Shortly after admission she was noted to be unresponsive so ACLS was initiated and the patient was intubated. Immediately after this event, she was noted to have significant angioedema of her eyes, lips and tongue. Despite treatment with H1, H2 receptor antagonists as well as high-dose corticosteroids, the edema persisted. A thorough evaluation was done including a negative laboratory workup for acquired and hereditary angioedema. Imaging was notable only for multi-compartment edema of her neck, face, tongue and retropharyngeal tissues as well as diffuse chest wall anasarca yet on physical exam, she had no evidence of edema of her lower extremities or back. Doppler imaging showed normal blood flow in her upper extremities without evidence of central venous thrombosis. Her edema gradually improved and corresponded with net fluid removal with hemodialysis. Unfortunately, she suffered from respiratory arrest and ultimately passed away. Pathology findings on autopsy noted diffuse collateralization and dilation of her central venous system as a result of chronic increased venous pressure. Conclusion: To our knowledge, this is the first case report of angioedema caused by nonobstructive superior vena cava (SVC) syndrome. The majority of cases of SVC syndrome are caused by mass or mediastinal inflammation which result in obstruction of venous return to the heart. Autopsy findings confirmed she had evidence of upper extremity venous hypertension, a known complication of and consistent with her history of prior central vein thrombosis. This case highlights the importance of keeping a broad differential diagnosis when evaluating an atypical presentation of angioedema.

P106 SEVERE ATYPICAL MYCOBACTERIAL INFECTION IN A PATIENT WITH NOVEL MUTATION OF IFN-γ R1 RECEPTOR. N. Kalra*, A. Horwitz, Hershey, PA. Introduction: Mendelian susceptibility to mycobacterial diseases (MSMD) is a spectrum of inherited defects characterized by increased susceptibility to low virulence mycobacterial organisms. The IL-12/ IFN-γ pathway plays critical role in immunity against mycobacterial infection. A number of mutations in the genes encoding various components of IL-12/IFN-γ axis have been described to cause MSMD.We present a child with invasive pulmonary mycobacterial infection who was found to have a novel IFN-γ R1 receptor mutation. Methods: Case report and literature review through OVID, PubMed with the following terms: Mendelian susceptibility to mycobacterial diseases, IL12/IFN-γ receptor deficiency, atypical mycobacterial infection Case Report: A 2 ½ years old male with one year history of recurrent low grade fever, intermittent cough and


wheezing was transferred to our hospital for fever, leukocytosis and mediastinal widening on chest X ray. CT scan of the chest showed extensive mediastinal lymphadenopathy with compression of right bronchus and complete collapse of right upper lobe. Bronchoalveolar lavage and biopsy of the right bronchus showed acid fast bacilli. Culture of lavage fluid was positive for Mycobacterium avium complex. Patient was started on anti mycobacterial treatment. He underwent multiple bronchoscopies with debulking procedures. Subsequent genetic analysis revealed homozygous nonsense mutation, c.672G>A of IFNGR1 gene, resulting in IFN-γ R1 deficiency. Patient responded well to anti mycobacterial treatment. Genetic testing of the family is pending. Literature review: Based on literature review various mutations have been identified in the autosomal genes involved in IL-12/IFN-γ pathway. The variant c.672G>A, detected in this patient is novel and has not been previously described in the literature. Conclusion: This case highlights that a high index of suspicion for immunodeficiency should be maintained in patients with disseminated non-tubercular mycobacterial infection. MSMD should be considered early in the differential diagnosis in patients with severe infections with low virulence mycobacteria. Early diagnosis can decrease the morbidity and mortality for the patient and can be critical for other family members who may need genetic counseling.

P107 ALLERGIC REACTION TO LOCAL ANESTHETIC AGENT FROM THE AMIDE AND ESTER GROUPS IN A SINGLE PATIENT. L. Anderson*, M. Gianos, J. Yusin, Los Angeles, CA. Introduction: Type I hypersensitivity reactions to local anesthetics (LAs) are estimated to be less than 1% and not well documented in the literature (1-4) Rarer still are IgE mediated reactions to LAs from both the amide and ester groups in a single patient. We present the case of a patient with IgE mediated hypersensitivity reactions and LAs from both the amide and ester groups as the etiologic agent. Case: A 21 year-old female, current smoker with mild intermittent asthma, penicillin allergy with resultant urticaria, presented 2 years after an allergic reaction to LA mepivacaine. The reaction took place during a dental procedure minutes after 3% mepivacaine HCL without epinephrine was locally injected into the gums. Symptoms included eye and throat pruritus, nasal congestion, throat tightness, dyspnea and diffuse urticaria. The patient was treated with 20ml Benadryl and observed for 1hour with symptom resolution. Upon evaluation, physical exam, complete blood count, biochemical panel and chest x-ray were unremarkable. Aeroallergen panel, food commercial battery and latex were negative on skin prick testing. Percutaneous and graded intradermal skin tests were performed with culprit anesthetic mepivicane, 3 amide and 1 ester group anesthetics. Skin prick test results were negative for all reagents. Intradermal testing yielded positive results to full strength 1ml lidocaine 2% with epinephrine (1cm induration, 5cm erythema), mepivicane 3% (1cm induration, 3.5cm erythema), full strength 0.02ml articaine with epinephrine (12mm induration and erythema), prilocaine (10mm induration and erythema), and tetracaine 1% preservative free (1cm induration, 4cm erythema). Discussion: We report reactions caused by LAs from the ester and amide group highly suggestive of type I hypersensitivity reaction given the clinical sequelae of immediate urticarial reaction and subsequent positive intradermal tests. The reactions were not due to preservatives added during manufacturing, epinephrine, latex allergy nor dose related LA toxicity. This case highlights the implications of hypersensitivity to both ester and amide group LAs as these are commonly utilized medications in medicine. Additionally, this patient of child bearing age should avoid epidural LA from the amide group during childbirth given the demonstrable cross-sensitivity between amide anesthetics.

P108 A CASE OF EOSINOPHILIC PNEUMONIA ATTRIBUTED TO LEVOFLOXACIN. O. Fadugba*, K. Babe, Nashville, TN. Introduction: Eosinophilic Pneumonia(EP) is diagnosed by clinical symptoms, pulmonary imaging, and alveolar eosinophilia, with or without peripheral eosinophilia. Causes of pulmonary eosinophilia include parasitic or nonhelminthic infection, Churg-Strauss Syndrome, allergic bronchopulmonary aspergillosis, and medications/toxins. Cutaneous rash may be a clue to druginduced EP. Approximately 20 drugs have been confidently associated with EP; the most common culprits are antibiotics and NSAIDs. There have only been 2 reports of EP attributed to levofloxacin. We present the case of a patient who developed rash, dyspnea, peripheral and pulmonary eosinophilia after levofloxacin treatment. Case Description: A 58 year old female with a distant his-


ABSTRACTS: POSTER SESSIONS tory of breast cancer, mild asthma, and recent travel, presents with fever and dyspnea. Two days after returning from a cruise in Southeast Asia, the patient and her husband developed fever, cough and myalgia. The patient and her spouse were treated empirically with levofloxacin for 5 days. The husband’s symptoms resolved after 1 week, but the patient’s fever and dyspnea progressively worsened. She also developed a pruritic, erythematous rash on her back. A chest CT revealed extensive bilateral peripheral patchy and nodular infiltrates. Laboratory evaluation revealed WBC of 30,000 cells/mL with 9,400 eosinophils/mL. Infectious evaluation for legionella, tuberculosis, schistosoma, coccidioides, strongyloides, echinococcus were negative. IgE level was 195 IU/ml. Bronchoalveolar lavage showed 1700 nucleated cells, with 69% eosinophils. BAL studies were negative for infection and malignancy. Transbronchial biopsy showed organizing pneumonia with intra-alveolar fibrin and increased intraalveolar eosinophils. The patient was diagnosed with eosinophilic pneumonia caused by levofloxacin. One day after starting prednisone treatment, her peripheral eosinophilia improved dramatically to 1,500 cells/mL. Discussion: Patients who present with acute onset of eosinophilic pneumonia must undergo extensive evaluation to rule out reversible causes such as infection and medications. Treatment of drug-induced EP includes removal of the offending agent and corticosteroids. Given the timing of symptom progression, appearance of rash, and exclusion of other etiologies - we concluded that her presentation was likely due to levofloxacin treatment.

P109 CONTACT REACTION TO ULTRASOUND TRANSMISSION GEL. Y. Hui*1, J. Camacho2, E. Resnick2, 1. Great Neck, NY; 2. New York, NY. Ultrasound transmission gel (USTG) is widely applied in both diagnostic and interventional procedures to optimize contact between the ultrasound probe and skin. The major components of gels are polymers to provide thickening and viscosity and preservatives for infection control. Aquasonic 100 (Parker laboratories, Fairfield, New Jersey) is one of the most popular hypoallergenic USTG. Very few allergic reactions have been reported with this product. We report a case of immediate contact urticaria upon Aquasonic 100 application. A 75 yo Asian male developed prominent urticaria immediately after finishing an echocardiogram examination. The rash was localized at the area of gel contact, and resolved quickly after Diphenhydramine treatment. Similar symptoms with reduced severity were reproduced 3 times by gentle application of the gel from a different bottle without skin rubbing. The patient has a past medical history of asthma, hypercholesterolemia, and asymptomatic chronic lymphocytic leukemia; but no history of drug or chemical allergies. Physical examination revealed dermatographism. Skin prick test to the gel was negative. Product ingredients (color dye, fragrance, humectant, polymer, and 2 preservatives) were obtained from the manufacturer, and placed side by side with Aquasonic 100 gel. Polymer was the only ingredient to elicit a mild but reproducible urticarial reaction. The manufacturer released the identity of the polymer to the patient, but not the formulation or processing steps for proprietary protection. In conclusion, hypoallergenic ultrasound transmission gel, although rare, may cause an immediate urticarial reaction. The exact mechanism is yet to be identified.

P110 AN ICHTYOTIC PATIENT WITH IDIOPATHIC ACUTE TRANSVERSE MYELITIS (CASE REPORT). Öner. Özdemir1, K. Yilmaz2, D. Kizmaz*2, 1. Adapazar, Turkey; 2. Istanbul, Turkey. Introduction: Idiopathic acute transverse myelitis (ATM) is an immunemediated inflammatory demyelinating disorder of the spinal cord with motor, sensory and autonomic involvement. The spinal cord inflammation is focal and the signs/symptoms are usually bilateral and based on the extent and site of the lesion, with the thoracic spinal cord being the most common localization. Motor involvement is characterized by limb weakness, stiffness and muscle spasms. Annual incidence is estimated at between 1/250,000 and 1/1,000,000. Onset occurs at any age and both sexes may be affected. The etiology of ATM is various and includes post-infectious, post-vaccinal, collagenous, autoimmune, neoplastic causes and multiple sclerosis. There has been no report of ATM development in the course of X-linked ichtyosis. Purpose: A rare ichtyotic patient developing ATM, resistant to every known therapeutic approach, is being discussed. Case: 13-year-old male patient was admitted owing to complaints of inability of walk and numbness/weakness in the legs. His sensory and motor deficit increased up to umblicus in addition to sphincter defect in time. Physical exam revealed sensory and motor loss. Scaling on the skin was

consistent with ichtyosis. Although pulse steroid, intravenous immunoglobulin and plasmapheresis were performed, there was response to these therapies. He was put on physical therapy. Hemogram, CRP, routine biochemistry, and vitamin B12 values were normal. Viral serology (HAV, HBV, HCV, HIV, EBV, TORCH, VZV, HHV-6 ve influenza A-B-C) and bacterial (VDRL, Brucellosis, Borreliosis and Mycoplasma) as well as rheumatologic evaluations were all negative. Thyroid hormones were normal, anti-TPO and anti-thyroglobulin antibodies were negative. Lumbar puncture revealed normal CSF indices. Oligoclonal band and IgG index in CSF were normal. Spine MR demonstrated swelling and marked T2 signal prolongation of the spinal cord from approximately C7 to T7 suggestive of an active inflammatory process. Electromyography (EMG) could not record bilaterally motor responses of peroneal and tibial nerves. H reflex responses from Soleus muscles bilaterally were not recorded. EMG results were consistent with ATM. Conclusion: Although we consider ATM in this patient as idiopathic (immune-mediated), this case suggests that congenital X-linked ichtyosis should be considered in the differential diagnosis of ATM.

P112 SUCCESSFUL IMPORTED FIRE ANT RUSH DESENSITIZATION UTILIZING BOTH OMALIZUMAB AND A PREMEDICATION REGIMEN. K.S. Tille*1, A.L. Parker2, 1. RAF Lakenheath, United Kingdom; 2. Landstuhl, Germany. Rush immunotherapy (IT) for imported fire ant (IFA) whole body extract (WBE) has previously been shown to be safe and efficacious; the clinical utility of premedication for rush IT is debatable. Omalizumab, an anti-IgE monoclonal antibody targeting IgE, has been reported as a useful adjunct to ragweed and bee venom rush IT. We present the case of a 25-year old female with allergic asthma and a history of five systemic reactions (immediate onset urticaria, globus, rhinitis and bronchospasm) to IFA stings over a 1-year period. Although not currently residing in an endemic area, she anticipated returning to one in the near future, so both aeroallergen immunotherapy (AIT) and IFA WBE IT were begun. Her course was complicated by two systemic reactions at low doses of IT. In an attempt to continue with IT, the patient was subsequently started on omalizumab, and AIT and VIT injections were separated by 24 hours. She suffered a third systemic reaction after another low-dose IFA WBE injection. Since the third reaction involved IFA WBE alone, and the patient continued on AIT separately without reactions, it was assumed that IFA WBE was the etiology for her IT reactions. Due to the patient’s wish to become pregnant and relocate to an IFA endemic area, the decision was made to continue omalizumab and initiate IFA WBE rush IT with premedication (three days of cetirizine, ranitidine, and prednisone). Omalizumab was dosed the day prior to starting the rush protocol, which involved IFA WBE injections given hourly over a two-day period, progressing to a final rush dose of 0.3ml (1:200 wt/vol). The course was complicated only by mild ocular pruritus and conjunctival injection in the 1:200,000 wt/vol vial, which resolved with oral diphenhydramine. Full IFA WBE IT maintenance dosing (0.5ml (1:200 wt/vol)) was reached two weeks after the rush procedure concluded. Shortly after this, the patient became pregnant and now expects to relocate to North Carolina in one year. Her clinical course has been without further reactions, and she remains on monthly omalizumab and maintenance IFA WBE IT, with plans to continue this through her pregnancy. To our knowledge, this is the first reported case of successful rush IT for IFA-sensitivity utilizing omalizumab and premedication in a patient with previous systemic reactions to IFA WBE IT injections.

P113 A CASE OF MASTOCYTIC ENTEROCOLITIS AND CHRONIC ABDOMINAL PAIN. J. Toh*, S. Jariwala, K. Anastos, K. Tanaka, D. Rosenstreich, Bronx, NY. Introduction: Mastocytic enterocolitis is defined by the presence of increased mast cells (>20 cells/HPF) with immunohistochemical staining for mast cell tryptase or c-kit (CD 117) localized to the gastrointestinal tract. Clinical presentation includes diarrhea, abdominal pain, bloating, and dysmotility. It is rarely considered in the differential diagnosis of abdominal pain. Mast cell stabilizers and H1 and H2 receptor antagonists are considered therapeutic. We present an interesting case of mastocytic enterocolitis which was initially difficult to diagnose, and subsequently has responded suboptimally to treatment. Methods: Case description Results: A 30-year old male presented to the Allergy consult service with 3 years of chronic severe abdominal pain requiring high dose



ABSTRACTS: POSTER SESSIONS opiates following a renal infarct, hepatosplenomegaly and chronic eosinophilia. Other findings include hepatic steatosis, vitamin D deficiency, iron deficiency and myoclonic jerks with no epileptiform activity on EEG. Previous evaluation included negative testing for anti-phospholipid antibody syndrome, porphyria, Whipple’s disease, rheumatologic diseases, celiac disease, Lyme disease, syphilis, HIV, hereditary angioedema, and familial mediterranean fever. He had an unremarkable endoscopy with no significant findings on initial histopathology in 2009. On our evaluation, he was found with an elevated serum tryptase level of 23 ng/mL (nl < 1ng/mL). Skin biopsy was negative for amyloid. Bone marrow biopsy revealed normal trilineage hematopoiesis with eosinophilia. Given the chronic abdominal pain and elevated serum tryptase, we requested that the endoscopic biopsies from 2009 be re-stained for c-kit (CD117). Re-staining demonstrated 70-80 mast cells/HPF and 90-100 mast cells/HPF, which met the criteria for mastocytic enterocolitis. Liver biopsy restaining demonstrated 6-9 mast cells/HPF. The patient has thus far been treated with multiple H2 receptor antagonists including cetirizine, loratadine, fexofenadine, mast cell stabilizers (cromolyn), and leukotriene receptor antagonists (montelukast) with persistent abdominal symptoms. Conclusion: Mastocytic enterocolitis should be considered in chronic abdominal pain of unknown origin. Although considered standard treatment, mast cell stabilizers and H1 and H2 receptor antagonists may only produce suboptimal improvement. Further investigation is needed for better treatment.

using the terms ‘eosinophilic esophagitis complications’, ‘esophageal rupture’, ‘Boerhaave syndrome’ and ‘Mallory Weiss tear’. Results: We describe two patients with esophageal rupture as the presenting symptom of EoE. The first one is a 48 year old man who presented to the Emergency Department (ED) with progressive chest pain after ingestion of a pill. He had a history of dysphagia but did not seek medical care previously. CT scan of the chest revealed an esophageal perforation which was treated with a stent placement. Esophageal biopsy showed up to 30 eosinophils per high power field (hpf) and his symptoms resolved with swallowed topical steroids. The second patient is a 63 year old woman who presented to the ED with acute onset of chest pain after eating dinner. She developed coffee-ground emesis and an upper endoscopy revealed a linear esophageal tear and greater than 20 eosinophils/hpf. She was treated with a proton pump inhibitor and swallowed topical steroids. Literature review revealed 8 cases of esophageal perforation as the initial manifestation of EoE and 1 case where esophageal perforation was a complication of preexisting EoE. Conclusion: Esophageal rupture is not a common initial manifestation of EoE. The majority of the patients from the literature review and one of our patients had a previous history of dysphagia. EoE should be suspected in patients with dysphagia. Early diagnosis and treatment may prevent complications such as esophageal rupture.


THYMOMA PRESENTING AS CHRONIC MUCOCUTANEOUS CANDIDIASIS. N.D. Schroeder*1, J. Kennedy1, S. Browne2, L. Borish1, 1. Charlottesville, VA; 2. Bethesda, MD.

GRANULOMATOUS INTERSTITIAL LUNG DISEASE IN ASSOCIATION WITH SELECTIVE ANTIBODY DEFICIENCY. E.V. Randolph*, D.S. Hummell, Nashville, TN. Introduction: Granulomatous-lymphocytic interstitial lung disease (GLILD) is a known complication of common variable immunodeficiency (CVID), although the etiology and treatment are unknown. Selective antibody deficiency with normal immunoglobulins (SADNI) is not associated with granulomatous lung disease, although SADNI can evolve into CVID. Methods: We report a case of a 23 year old female who developed granulomatous lung disease in the setting of SADNI, with resolution of granulomata with IVIg. Our patient has tuberous sclerosis (TS), asthma, chronic sinusitis, and GERD, and presented at 18 with multiple admissions for respiratory distress. She was found on lung biopsy to have a non-necrotizing, pulmonary interstitial and granulomatous disease. TB, sarcoid, histoplasmosis and other infectious causes were investigated and ruled out. Steroids resulted in mild improvement, but her lung disease ultimately worsened. Methotrexate had a similar, short term effect. Due to the association of GLILD with CVID, immunologic evaluation was initiated, which demonstrated low IgM (41 mg/dL) but normal IgG (931 mg/dL) and IgA (175 mg/dL), with poor immune response to the 23-valent pneumococcal polysaccharide vaccine. A diagnosis of SADNI was made, and she started monthly IVIg at 400 mg/kg/dose. Her clinical status improved on IVIg, as did the nodular densities previously seen on high-resolution CT. At age 22, she developed thrombocytopenia that has been persistent. Biopsy of her gastric mucosa, completed for GERD and abdominal pain, showed non-necrotizing granulomatous change. Discussion: This unusual case suggests that granulomatous pulmonary, and perhaps gastroenteric, disease may be associated with not only CVID, but with SADNI in susceptible individuals. This patient’s granulomatous disease may also be the first manifestation of CVID, and the complete phenotype may evolve. Another explanation is that this patient’s underlying TS alters her response to infection, making her more susceptible to granulomatous disease, however, at this time, granulomatous disease is not described in TS. Questions that remain to be answered are whether her thrombocytopenia is related to SADNI, whether her immune dysfunction will remain persistent over time, and whether she will remain dependent upon IVIg to maintain her pulmonary function.

P115 ESOPHAGEAL RUPTURE AS A PRIMARY MANIFESTATION OF EOSINOPHILIC ESOPHAGITIS. N. Vernon*, D. Mohananey, G. Ghaffari, Hershey, PA. Introduction: Eosinophilic esophagitis (EoE) is a chronic inflammatory process characterized by esophageal dysfunction and eosinophilic infiltration. In adults, it mostly commonly manifests as dysphagia, food impaction, heartburn, chest or abdominal pain. Chronic inflammation can lead to narrowing of the esophageal lumen which may cause food impaction requiring surgical intervention. Although endoscopic procedures may lead to rupture of a friable esophagus, partial or complete tear of the esophagus as a primary manifestation of EoE is rare. Methods: Case series and literature review through PubMed



Introduction: Chronic mucocutaneous candidiasis (CMC) is associated with impaired T cell immunity, autoimmunity, or hyper-IgE syndrome. We present the case of a 55-year-old male with history of transverse myelitis who was referred to our clinic with chronic onychodystrophy and recurrent oropharyngeal candidiasis. Methods: Our initial evaluation included DTH skin testing and flow cytometry to enumerate lymphocyte subtypes, including Th17 cells. Results: DTH testing confirmed reduced controls and absent candida response. CBC profile was striking for the absence of eosinophils and basophils. Flow cytometry showed a reduced number of CD4 cells (540/mL), and, unexpectedly no CD19 B cells (confirmed as absence of CD20 cells). He displayed normal numbers of Th17-like cells (3.7%). His immunoglobulin levels were normal including specific antibodies. We therefore performed CT chest, which revealed thymoma and achalasia. Serological studies were performed at the NIAID using cytokine-conjugated microspheres in a particle-based multiplex assay for autoantibodies against IL-12p70, IFN-γ, IFNα, IL-17A, IL-22, and GM-CSF. Surprisingly, IL-17A and IL-22 autoantibodies were negative, however, he did demonstrate autoantibodies to anti-IFN-α and anti-IL-12p70. Conclusions: CMC presents secondary to numerous medical conditions, typically involving deficient expression of Th17 cells. The absence of B lymphocytes in our patient led us to evaluate him for a thymoma. While patients with thymoma often develop CMC secondary to the presence of anti-IL-17 antibodies, our patient’s disease appears to be related to his expression of anti-IFN-α and anti-IL-12 antibodies.

P117 THE VALUE OF BAL IN ACUTE EOSINOPHILIC PNEUMONIA OF ALLEN. B. Buelow*1, B.T. Kelly1, H. Zafra1, K.J. Kelly2, 1. Milwaukee, WI; 2. Chapel Hill, NC. Background: Acute Eosinophilic Pneumonia (AEP) first described by Allen is characterized by abrupt onset of tachypnea, dyspnea, and hypoxemia. The disease may rapidly progress to respiratory failure requiring therapy with mechanical ventilation, high PEEP, and delivery of a high percentage FiO2. Failure to recognize this disease may lead to death while corticosteroid administration causes rapid improvement in symptoms. Case: A 17 year old previously healthy Caucasian male presented with three days of fever, dry cough and progressive dyspnea. Family history was unremarkable. Social history included initiation of tobacco smoking 3 months ago, which he quit 1 week ago. He denied other recreational drug use. He recently traveled to Corpus Christi, TX, and had recent contact with his cousin’s pet rats and snakes. On physical exam he exhibited tachycardia, tachypnea, and hypoxia requiring supplemental oxygen. He had diffuse coarse breath sounds. His CBC showed a neutrophilic leukocytosis without peripheral eosinophilia. Chest x-ray (CXR) demonstrated diffuse bilateral interstitial pulmonary opacities with a right pleu-


ABSTRACTS: POSTER SESSIONS ral effusion without cardiomegaly. He clinically worsened requiring intubation with mechanical ventilation, chest tube placement and vasopressor support. Bronchoscopy revealed a prominent eosinophilia with a negative infectious work-up. AEP was diagnosed. He received high dose corticosteroids with extubation 4 days after diagnosis. One week after presentation, he developed a profound peripheral eosinophilia. After 8 days he returned to baseline and went home to complete a month long corticosteroid wean. He was lost to follow up. Conclusion: The abrupt onset of respiratory distress, especially in a male, with severe hypoxemia and a CXR with the mirror image of pulmonary edema, fluffy peripheral infiltrates, and pleural effusion should suggest AEP to the allergist. The lack of peripheral eosinophilia is common and diagnosis requires BAL. Few diseases with the presentation described above mimic AEP and include rare diagnoses such as eosinophilic leukemia. Without evidence of multiple cell lines being depressed (e.g. platelets, red cells), the acute deterioration with a high percentage of eosinophils warrants the life saving intervention of high dose corticosteroid. The allergist should be very familiar with and serve as a knowledgeable resource for diagnoses and recommendations in such cases.

P118 PRIMARY BILIARY CIRRHOSIS AND PERIPHERAL EOSINOPHILIA. E.M. Slaughter*1, K.K. McKinney2, 1. Tacoma, WA; 2. Gig Harbor, WA.

Liver biopsy - Portal tract inflammation of primarily lymphocytes, eosinophils, and few plasma cells with preserved hepatic inflammation

Introduction: Primary Biliary Cirrhosis (PBC) is a chronic cholestatic liver disease characterized by autoimmune mediated destruction of epithelial biliary cells. Lymphocytes play the pivotal role in biliary duct destruction; however intrahepatic eosinophilic infiltration is often documented on liver biopsy. Peripheral eosinophilia has rarely been reported to be a distinctive feature in PBC, compared to other chronic liver diseases. PBC is not often considered in the differential diagnosis (DDx) of eosinophilia. Here we report the first case documented of peripheral eosinophilia as the presenting symptom of anti-mitochondrial antibody (AMA) negative PBC. Methods: A 49-year old female presented to the Allergy clinic with a 25 year history of labile peripheral eosinophilia, and past medical history significant for unexplained transaminitis and thyroiditis. No symptoms of chronic fatigue, itching, skin hyperpigmentation or arthralgias reported. Her absolute eosinophil count (AEC) ranged from 0 to 1300 cells x(6)/uL. Eosinophilia was attributed to allergic disease. 15 years after the initial eosinophilia, her alkaline phosphatase (ALP) became elevated at 154 U/L. The ALP continued to rise, reaching 944 U/L with mild elevations of ALT (75 U/L) and AST 66 U/L. With the progressive transaminitis, she underwent further evaluation. Results: RUQ ultrasound showed cholelithiasis; ANA, Anti-Mitochondrial Antibody (AMA) and hepatitis panel negative; Anti-Smooth Muscle Antibody weakly positive. Liver biopsy showed portal tract inflammation of primarily lymphocytes, eosinophils and few plasma cells with preserved hepatic architecture. Based on biopsy and laboratory data, patient was diagnosed with AMA-negative PBC. Within one month of ursodial therapy, AEC decreased to 400 x(6)/uL with normalization of AST, ALP and reduction of ALP to 239 U/L. Conclusions: Peripheral eosinophilia may be a more common feature of PBC than previously believed and should always be considered in the DDx for peripheral eosinophilia. Early stage diagnosis can lead to normal life expectancy with treatment. Other important signs of PBC are ALP >1.5 times the upper limit of normal and AST not markedly elevated (<5 times the upper limit of normal). 95% of patients with PBC will have positive AMA. Resolution of peripheral eosinophilia with ursodial therapy is not well understood, but has a positive response to therapy.

P119 OMALIZUMAB THERAPY IN SEVERE ADOLESCENT ATOPIC DERMATITIS. S. Smith*1, A. Rooklin2, 1. Philadelphia, PA; 2. Upland, PA. Introduction: Atopic Dermatitis (AD), a common skin disease of childhood and adolescence, is often associated with high serum levels of IgE and may occur concomitantly with allergic asthma. Omalizumab is a humanized monoclonal antibody to human IgE. It is approved for treatment of refractory allergic asthma in individuals whose serum IgE levels range from 30-700 IU/ml. We describe 3 patients with serum IgE levels ranging from 9,000-15,000 IU/ml with severe refractory AD, severe allergic asthma and high SCORAD indices. Omalizumab therapy decreased SCORAD scores in all patients. Methods: Three patients, 1 male and 2 female, age 13-15 with average length of disease of 10.6 years and whose AD was unresponsive to topical treatments (triamcinolone and tacrolimus) were treated with 375 mg of omalizumab every 2 weeks for 6-12 months. SCORAD was used as a clinical tool to determine the patients’ disease burden pre and post omalizumab therapy. Results: At the start of therapy SCORAD indices ranged from 67.4-89.7. Patients received twice-monthly antiIgE therapy for 6-12 months with improvement after 2 months. None of the patients experienced adverse effects from medication. All three patients continued to use topical steroid and tacrolimus as needed. While on omalizumab therapy, SCORAD indices ranged from 16.9-27.4 with an average of 22.3. Subjective scores decreased by over 50% in 2 patients and by 75% in the third suggesting improvement in quality of life. The adolescents were perceived as shy and lacking self-confidence prior to therapy. Since treatment, patients, families and medical staff observe improved social interactions and self-confidence. Two of the patients suffered bullying in school and no longer are bullied regarding their AD. Conclusion: Omalizumab markedly decreased the SCORAD and subjective scores of each patient by over 50% demonstrating efficacy of this therapy for adolescent patients with markedly elevated IgE levels and severe AD refractory to standard topical therapy.

P120 A CASE OF DRESS WITH RENAL, PULMONARY AND NEUROLOGIC MANIFESTATIONS. G. Bhargave*, A. Peters, Chicago, IL. Drug rash (or reaction) eosinophilia and systemic symptoms (DRESS) syndrome is a potentially life-threatening syndrome characterized by severe skin eruption, fever, eosinophilia or atypical lymphocytes, and internal organ involvement. The onset of symptoms is typically delayed by 2 to 6 weeks after initiation of the drug. Symptoms may persist despite discontinuation of the offending agent and the treatment is corticosteroids. We describe a 67 year old woman with a history of atopic dermatitis and left hip replacement that was complicated by infection requiring debridement, a vancomycin spacer, and IV antibiotics with vancomycin and ceftriaxone. While on antibiotics, the patient presented with hip pain, a morbilliform rash, lymphadenopathy, and fever. Labs



ABSTRACTS: POSTER SESSIONS revealed an eosinophilia of 30% (peak absolute count of 8900) and acute kidney injury with a creatinine of 1.59 (baseline 0.6). Strongyloides antibody and ANCAs were negative. CT of her chest, abdomen, and pelvis revealed multiple bilateral pulmonary emboli, a lower lobe pulmonary infarct, bilateral patchy groundglass opacities, and extensive lymphadenopathy. She was thought to have DRESS and thus antibiotics were discontinued and treatment was started with methylprednisolone IV 60mg once a day. Skin biopsy results subsequently confirmed a diagnosis of DRESS with findings of lymphocytic infiltrate, spongiosis, and many eosinophils. On hospital day 10, she developed altered mental status and a MR brain revealed innumerable scattered acute infarcts with a distribution suggesting emboli from a central source. Other causes of embolic strokes were excluded and her encephalopathy was attributed to eosinophilia from DRESS. The steroid dose was increased to methylprednisolone 60mg IV every 6 hours. The patient subsequently had resolution of her eosinophilia and associated improvement in altered mental status, rash, pulmonary, and renal manifestations. The steroid dose was tapered slowly over 6 months as she had recurrence of rash and eosinophilia if the dose was tapered quickly. Overall, this case suggests that CNS complications may arise in the setting of DRESS, including encephalopathy and stroke, and may be related to hypereosinophilia. Given the potentially devastating nature of these complications, they are important to consider in the evaluation of patients with DRESS.

ral effusions, hepatosplenomegaly, ascites and para-aortic lymphadenopathy. Renal and hepatic function, immunoglobulin levels, T-cell subsets, and thyroid function tests were normal. Viral studies for EBV, cytomegalovirus, HIV, parvovirus, and HHV-8 were negative. Bone marrow biopsy was negative for lymphoma. Left axillary lymph node biopsy was consistent with CD with predominant hyaline-vascular architecture. Treatment with daily glucocorticoids and weekly rituximab was initiated with subsequent resolution of anemia and thrombocytopenia with improved anasarca, ascites, and pleural effusions. Conclusion: Consequent to its low incidence, CD is often misdiagnosed or diagnosed with delay. It is important to consider CD in the differential diagnosis of lymphadenopathy, hepatosplenomegaly, fevers, and night sweats. For some patients with multicentric, hyaline vascular CD, combination treatment with rituximab and glucocorticoids may be useful.


Background: EBV+ mucocutaneous ulcer is a rare presentation of EBV related lymphoproliferative disease in immunocompromised patients. We present a patient with no previous diagnosis of immunodeficiency who was diagnosed with an EBV+ lymphoproliferative lesion in her esophagus. Methods: A 61 year old female with a history of recurrent sinopulmonary and urinary tract infections presented with epigastric pain, dysphagia, odynophagia, and weight loss. Endoscopy showed a well circumscribed esophageal ulceration. Stains revealed lymphoid infiltrate as well as actinomyces and candida. Immunostains and EBV testing were subsequently performed and the patient was evaluated for immunodeficiency. Results: Immunostains were positive for CD20 and CD30. In situ hybridization for EBER revealed many positive cells. Serum EBV antibody testing was consistent with previous exposure. Serum immunoglobulin levels showed IgG of 351 mg/dL (700-1600), IgA of 9 mg/dL (70-400), and IgM of 26 mg/dL (40-230). The patient was diagnosed with EBV+ mucocutaneous ulcer secondary to hypogammaglobulinemia and initiated on rituximab and intravenous immunoglobulin therapy. Conclusion: Patients with EBV+ mucocutaneous ulcers without known underlying immunodeficiency should be evaluated for humoral immunodeficiencies.

Introduction: There is a very limited treatment options available for patient with hereditary angioedema (HAE) who also have polycystic ovary syndrome (PCOS). Case Description and Methods: An extensive literature review using Google, PubMed and Ovid was performed to assess appropriate therapy of PCOS in HAE. Our patient is a 24 year old female with HAE who began experiencing increasing facial hair, acne and weight gain (BMI 32.8). She was on Depo-Provera for birth control and had no menses even after discontinuing the progesterone. She was diagnosed by her rheumatologist with PCOS based on her clinical findings of elevated testosterone and ovarian ultrasound. Her past medical history includes HAE type 1, lupus, hypothyroidism, anxiety, depression and reflux. She takes hydroxychloroquine, levothyroxine, gabapentin, citalopram, rabeprazole and C1-inhibitor 1,000 units biweekly. Initially, she was prescribed metformin for her PCOS, but experienced gastrointestinal side effects. She was also prescribed spironolactone without benefit. She was then started on ethinylestradiol birth control pills (BCP) after consultation with her allergist, which helped her PCOS symptoms. However, despite prophylaxis with C1-inhibitor her HAE attacks became more frequent with several attacks a week. She also experienced systemic symptoms such as fatigue, depression, headaches and persistent erythema marginatum. Because of her severe symptoms C1-inhibitor was increased to 20,000 units twice a week, estrogen BCP was discontinued and her systemic symptoms resolved. Unfortunately, the hirsutism and acne returned. Results: An extensive literature review using Google, PubMed and Ovid failed to reveal alternative therapy for PCOS treatment in HAE. This is the first case in the literature to attempt the use of C1-inhibitor to suppress HAE while a patient is on estrogen for PCOS. Discussion: Estrogen can precipitate HAE attacks. Our case suggests that even high dose prophylaxis with C1-inhibitor is insufficient to control estrogen worsening of HAE. Unfortunately patients with PCOS and HAE have limited therapy options available and further research in this area is necessary.





Introduction: Castleman disease (CD) is a rare lymphoproliferative disorder with etiology and pathogenesis not thoroughly clarified. Present evidence supports defective immunoregulation, resulting in excessive proliferation of B lymphocytes and plasma cells in lymphoid organs. Theories include an abnormal response to viral infections such as Epstein-Barr virus (EBV), human herpes virus 8 (HHV-8), and human immunodeficiency virus (HIV). Other suspected etiologies include elevated production of interleukin 6 (IL-6) leading to lymphoproliferation and plasma cell differentiation. Three histologic variants (hyaline vascular, plasma cell, and mixed) and 2 clinical variants (unicentric and multicentric) have been described. There is no established treatment option for multicentric CD. Methods: Evaluation, diagnosis and successful treatment of a rare presentation of CD. Data: A previously healthy 31 year old woman presented with two weeks of fever, shortness of breath, extremity swelling, and axillary lymphadenopathy. Initial laboratories revealed profound hypoalbuminemia (2.0 G/DL), anemia (hemoglobin 9.3 g/dL), and leukocytosis (white blood cell count 15.6K/mm3). Urinalysis revealed non-nephrotic range proteinuria. CT of the chest, abdomen and pelvis showed bilateral pleu-

Background: Hypereosinophilic syndrome (HES) is a group of rare disorders defined by overproduction of eosinophils, with peripheral blood eosinophil counts >1,500/mL, resulting in infiltration and subsequent end organ damage. Most common clinical manifestations are dermatologic, pulmonary, and gastrointestinal. Life-threatening presentations include cardiac and neurologic manifestations. In one case series of 188 patients with HES in the United States and Europe only 5% had cardiac involvement on initial presentation. Case Summary: A 5-year-old female presented with one week of vomiting and a diagnosis of presumptive urinary tract infection (abnormal urinalysis and prior history of grade 2 vesicoureteral reflux). Urine culture was negative. Serum laboratory analyses incidentally found an eosinophil count of 12,500/mL. She developed transient altered mental status and extensive workup ensued. Brain MRI showed trace ischemic changes, and hypercoagulability workup demonstrated abnormal protein C and PAI gene (4G homozygous). Rheumatologic and infectious workups were negative. Bone marrow was negative for malignancy. Pleural effusion was noted on imaging studies. She developed cardiac tamponade and echocardiogram showed large pericardial effusion. Pericardio-

P121 A RARE PRESENTATION OF EBV RELATED LYMPHOMA LEADING TO A DIAGNOSIS OF HYPOGAMMAGLOBULINEMIA. S.H. Kleinman*, D.K. Jhaveri, J. Sterbank, J. Horbal, P. Caimi, R.B. Cameron, H. Meyerson, R.W. Hostoffer, H. Tcheurekdjian, Cleveland, OH.



ABSTRACTS: POSTER SESSIONS centesis was performed emergently, and effusion was composed of WBC 1,310/mL, with 80% eosinophils. She had impaired cardiac contractility with increased diastolic pressures, intracardiac thrombus, and BNP of 2,480 pg/mL. Abundant eosinophils, inflammatory changes, and early fibrosis were found on myocardial biopsy consistent with eosinophilic myocarditis. Enoxaparin was started for hypercoagulability, and enalapril for heart failure. She was given methylprednisolone and eosinophil counts decreased rapidly, undetectable on hospital discharge. She demonstrated marked clinical improvement, with no recurrence of pericardial effusion, and BNP trended down to 550 pg/mL at time of discharge. Conclusions: We report a rare pediatric case of idiopathic HES presenting with cardiac manifestations, as well as neurologic, pulmonary, and gastrointestinal symptoms. Patients presenting with markedly elevated eosinophils and cardiac manifestations require a complete evaluation for eosinophilic infiltration. Despite the lack of strong evidence, prompt treatment is required to prevent irreversible cardiac damage.

P125 HYPOGAMMAGLOBULINEMIA AND GRANULOMATOUS DISEASE IN AN ADULT CASE OF HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS. L.C. Tuong*, M.J. Gutierrez, F.T. Ishmael, Hershey, PA. Abstract: We present a case of hemophagocytic lymphohistiocytosis (HLH) in an adult patient with recent diagnosis of granulomatous lesions in the spleen who presented with abdominal pain and an unusual bacterial infection in setting of progressive hypogammaglobulinemia. Background: HLH is an unusual syndrome characterized by fever, hepatosplenomegaly, cytopenias, hypertriglyceridemia, hypofibrinogenemia, hyperferritinemia and pathologic findings of hemophagocytosis in the bone marrow and other tissues. In adults, lateonset familial HLH may occur, but more often are associated with infections, autoimmune disorders or malignancies. Case presentation: A 42-year old male with history of recurrent sinus infection, presented with five weeks of worsening abdominal pain. Imaging showed an enlarged spleen and lymph nodes. Splenic biopsy showed necrotizing granulomatous inflammation. He was treated with prednisone, but did not improve. He again presented with three weeks of fevers, chills, night sweats, shortness of breath, fatigue and ankle arthralgia. Physical examination was remarkable for fever, tachycardia and tachypnea. His lungs were clear; his abdomen was mildly tender, significant for splenomegaly, but no hepatomegaly. Skin exam revealed a nonpalpable petechial rash over both shins and ankles. Labs were remarkable for leukocytosis of 13.89 x 10(3)/mL, hemoglobin of 16.4g/dl and platelets of 110,000/mL, ESR of 18mm/hr and CRP of 21.44mg/L. Blood cultures were positive for Beta Streptococcus Group G. Blood counts later showed pancytopenia notable for absolute neutrophil count of 4.19k/ul and absolute lymphocyte count of 0.13k/ul. Immunoglobulin levels revealed progression of hypoglammaglobulinemia (IgG 253 mg/dL, IgM 43 mg/dL, and IgA 40 mg/dL), levels decreased compared to prior. Ferritin was elevated at 11,428ng/mL. Bone marrow biopsy showed hemophagocytic lymphohistiocytosis, confirming diagnosis. He was treated with HLH-94 protocol. Conclusion: HLH is an uncommon disease in adults. Features of HLH can overlap with sepsis syndromes, causing it to be under diagnosed. This case illustrates that in setting of fever, pancytopenia, hypogammaglobulinemia and granulomatous disease, clinical suspicion for HLH should be high and warrants further investigation to ensure prompt treatment.

P126 RESOLUTION OF URTICARIA AND ANGIOEDEMA ASSOCIATED WITH CARCINOID SYNDROME AFTER TRANSARTERIAL CHEMOEMBOLIZATION. T. Jacobs*, A. Petrov, Pittsburgh, PA. Introduction: Carcinoid tumors are well-differentiated neuroendocrine tumors originating most commonly from the gastrointestinal tract and lungs. Carcinoid tumors can produce a variety of vasoactive amines and polypeptides leading to carcinoid syndrome, manifested by a constellation of symptoms typically including flushing and diarrhea. We report a rare case of refractory urticaria and angioedema in a patient with carcinoid syndrome that only resolved after transarterial chemoembolization (TACE) treatment. Case Description: A 71 year old male with a history significant for neuroendocrine cancer of presumed ileal origin and liver metastases presented with chest pain, nausea, vomiting, bilateral hand swelling and systemic urticaria just prior to his scheduled TACE procedure. Physical exam was notable for low systolic blood pressure, severe angioedema of his upper and lower extremities, most notably over his hands, as well as a diffuse and pruritic urticarial eruption. Laboratory

findings demonstrated elevated BUN and serotonin levels. Further work up revealed normal EKG, chest X-ray, and chest CT with PE protocol. He was given IV fluids, high-dose IV corticosteroids, antihistamines, and admitted to the liver surgery service. Allergy/immunology was consulted for management of urticaria and angioedema. He was initially started on fexofenadine 180 mg twice daily and prednisone 60 mg daily. With no improvement, his therapy was increased to methylprednisolone 60 mg IV every 6 hours. His hand angioedema continued to worsen, and the morphology of his urticarial lesions became annular and targetoid. As it was suspected that the underlying carcinoid tumor metastases may be driving his symptoms, the patient was recommended to proceed with his planned TACE procedure. The patient then underwent his first intra-arterial streptozocin chemotherapy and biosphere embolization of the right hepatic artery, which led to complete resolution of urticaria and angioedema by the next day. Conclusion: This is the first reported case of urticaria and angioedema associated with metastatic carcinoid tumor that was refractory to high dose corticosteroid therapy and resolved only after TACE treatment of liver metastases.

P127 RESOLUTION OF CHRONIC URTICARIA IN TWO PEDIATRIC PATIENTS FOLLOWING TREATMENT OF GRAVES’ DISEASE. K.R. Brown*, S.N. Chadha, J.P. Ker, D.S. Hummell, Nashville, TN. Chronic urticaria (CU) is defined as the presence of hives on most days of the week, for a period of at least 6 weeks. In approximately 80-90% of cases, the underlying cause remains unknown. While most theories describing the pathogenesis of CU are not fully developed, evidence suggests involvement of histamine-releasing factors and abnormalities in basophil functioning. Studies indicate that 30-50% of cases may be due to an autoimmune process. CU is known to be associated with thyroid autoimmunity, determined by the presence of antibodies against thyroid peroxidase or thyroglobulin. Most patients are euthyroid, however, when thyroid dysfunction is present, hypothyroidism is more commonly diagnosed than hyperthyroidism (9.8% and 2.6%, respectively). Patients with both CU and autoimmune thyroiditis typically report a longer duration of disease and urticaria that is refractory to standard antihistamine regimens. We describe two unique pediatric cases of Graves’ Disease (GD) initially presenting as CU with resolution of hives following treatment of GD. The first patient was a 16-year female who reported 3 years of intermittent urticaria. The second patient was an 8 year-old female with 8 months of recurrent angioedema and urticaria. Evaluation revealed low TSH, high FT4, and elevated anti-thyroglobulin and anti-thyroperoxidase antibodies in both patients. Their symptoms were difficult to control on maximal dosages of twice daily antihistamines. Endocrinologists confirmed a diagnosis of GD in both patients. The first patient opted for total surgical thyroidectomy with expected reduction in FT4. Resolution of her recurrent urticaria off antihistamine treatment was observed at her follow-up visit 1 week later. The second patient received radioactive iodine ablation with significant improvement in CU symptoms 2 months post-procedure on minimal antihistamines. Despite dramatic improvement in her CU, her FT4 remained elevated 2 months post ablation. A second ablation was considered. However, 4 months post-ablation she was found to be biochemically hypothyroid. Resolution of hives and swelling off antihistamines was achieved following initiation of thyroid replacement therapy. These cases highlight the significant improvement in CU that can be observed following treatment of GD in pediatric patients.

P128 EOSINOPHILIC FASCIITIS ASSOCIATED WITH REFRACTORY APLASTIC ANEMIA. S. Patel*, J.L. Hill, Tucson, AZ. Introduction: Eosinophilic fasciitis (EF) is a rare sclerodermiform disorder characterized by inflammatory thickening of the skin and fascia and peripheral eosinophilia. It has been associated with hematological conditions including aplastic anemia. EF is generally treated with high dose corticosteroids; however, therapy for EF associated with aplastic anemia remains poorly understood and is not well described in the literature. We report a case of EF associated with refractory aplastic anemia treated with horse antithymocyte globulin (ATG), high dose prednisone, and granulocyte colony-stimulating factor (G-CSF). Case presentation: A 42 year-old male with recent diagnosis of EF on high dose prednisone therapy, presented for evaluation of worsening pancytopenia. Patient was dependent on weekly platelet and packed red blood cell transfusions despite treatment with cyclosporine and 4 weeks of Ritaximab. Physical examination revealed induration of the subcutaneous tissue of the



ABSTRACTS: POSTER SESSIONS limbs. Complete blood count demonstrated white blood cell count of 1.2 1000/uL, hemoglobin 10 g/dL, hematocrit 28.2 g/dL, and platelet count 58 1000/uL. IgG, IgA, IgM, and C-reactive protein were normal. HIV, EBV and CMV serologies were negative. ANA, Anti-SS-A, and Anti-SS-B were also negative. Bone marrow biopsy demonstrated hypocellularity (<30%) consistent with aplastic anemia. Fluorescence in situ hybridization and flow cytometry were normal. Therapy with cyclosporine was initiated; however, required discontinuation secondary to acute kidney injury. Finally, he had treatment response to horse ATG, high dose prednisone, and G-CSF with a reduction in transfusion requirements. The patient continues to do well on G-CSF and prednisone 20 mg daily and is being evaluated for hematopoietic stem cell transplantation. Conclusion: Aplastic anemia should be considered in any EF patient presenting with pancytopenia. In contrast to isolated EF, the associated aplastic anemia often fails to respond to corticosteroid therapy and is associated with a high mortality rate. Early treatment and diagnosis of aplastic anemia in these patients can prevent complete aplasia. Ideal treatment remains anecdotal, with current regimens including G-CSF, cyclosporine, rituximab, or ultimately hematopoietic stem cell transplantation for refractory cases.

P129 LATEX ALLERGY IN OBSTETRICS: A TARGET FOR PRIMARY PREVENTION. M. Shum*1, K. Achar2, N. Jinjolava2, Z. Ren2, E. Jerschow2, 1. New York, NY; 2. Bronx, NY. Introduction: Latex is the second most common cause of anaphylaxis in the intraoperative setting. This risk increases substantially during obstetric surgery due to latex contact with mucosal surfaces and may be enhanced by intrauterine oxytocin injection. Increased awareness of the risk in obstetric patients offers opportunities for primary prevention of latex induced anaphylaxis in obstetrics. Methods: Case Description. Results: A 40-year-old G4P3 with a history of uncomplicated cesarean section was admitted for cesarean section. She reported a history of allergies to tree, cat, and birch, but no prior drug or latex allergy. Spinal anesthesia with bupivacaine and morphine was administered and surgery was started at 1130. After delivery of neonate, intrauterine oxytocin infusion was initiated, followed by odansetron and cefazolin at 1200. Twenty minutes later, she started experiencing pruritus and numbness of fingers. She became combative due to extreme discomfort and her blood pressure decreased to 80/35 mmHg. Hives and erythema appeared on her arms, thighs and torso. She was treated with epinephrine, methylprednisolone and diphenhydramine and her symptoms resolved within 24 hours. Allergy testing was performed upon follow up. Skin tests were negative to general anesthesia, local anesthesia, beta-lactams and opiate panel. Oral challenge to amoxicillin was negative. She was found to have a serum IgE level of 1184 IU/ml and a positive immunoCAP assay for latex IgE level of 2.07 kU/L demonstrating sensitivity to latex antigens. Conclusion: Obstetric patients are at an increased risk for anaphylaxis. Sensitization to latex antigens may occur due to repeat clinic exposures during pregnancy and extensive contact with mucosal surfaces during obstetric procedure. In addition, oxytocin may facilitate allergic reaction to latex. Similar to previously reported cases, anaphylaxis in our patient occurred about 30 minutes after the start of oxytocin infusion. Oxytocin induces uterine contraction and may provoke the release of latex particles from the uterus into the blood stream. The cross-reactivity between synthetic oxytocin and latex may also play a role. Primary prevention would be an important intervention in obstetric patients given their increased risk of latex sensitization. Further studies should be focused on instituting primary latex allergy prevention in obstetric settings as an early intervention.

P130 NOVEL PRESENTATION FOR COMMON VARIABLE IMMUNODEFICIENCY: GROUP B STREPTOCOCCAL ENDOMETRITIS. C. Cruz*1, R.H. Kobayashi1, V. Mehta2, J.M. Tracy1, 1. Omaha, NE; 2. Lincoln, NE. Common variable immunodeficiency disorder (CVID) is an important primary immunodeficiency characterized by B cell dysfunction with impaired immunoglobulin secretion and associated T cell abnormalities. With a prevalence of 1 in 25 000 to 1 in 50 000 in the United States and variable manifestations with multisystem involvement, CVID can present to physicians in diverse specialties, including obstetrics and gynecology. The diagnosis is typically made at 20 to 40 years of age, but due to the vast heterogeneity in the clinical presentation of the disease, there is an average delay in making the diagnosis of 6 to 7 years. CVID in pregnancy is also an important concern as the risk of


infections during this period seems to be enhanced. We describe a 34 year old female with CVID in whom the correct diagnosis was not reached until she developed postpartum group B streptococcal (GBS) endometritis with abscess formation. GBS is common in the general population yet resultant endometritis is rare. She presented with persistent fever and abdominal pain 5 days after an emergent cesarean delivery at 40 weeks with her first child. CT scan of the abdomen and pelvis showed an abnormal appearing uterus with focal areas of air and fluid levels consistent with endometritis and bilateral rectus sheath hematomas. Treatment with intravenous ertapenem was administered following CT guided drainage of the abscess with eventual resolution of the infection. She was referred to allergy and immunology where work-up revealed profound hypogammaglobulinemia with immunoglobulin G (IgG) 41 mg/dl (normal 600-1400 mg/dl) and undetectable immunoglobulin A (IgA) (normal 60-380 mg/dl) and immunoglobulin M (IgM) (normal 40-345 mg/dl). She had no functional titers to polysaccharide or protein antigens. She was diagnosed with CVID and started on intravenous immunoglobulin with an initial loading dose of 800mg/kg. She remained asymptomatic and maintained with 400mg/kg on a four week regimen. To the best of our knowledge, no cases of GBS infection during pregnancy have been described in the context of CVID. This case demonstrates a possible presentation of CVID in obstetrics and emphasizes that maintaining a high index of suspicion is essential in making the diagnosis of rare immunodeficiency disorders.

P131 IMMUNE COMPLEX GLOMERULONEPHRITIS IN A PATIENT WITH X-LINKED AGAMMAGLOBULINEMIA. J.K. Patel*, S. Afshan, B.H. Ault, R.J. Wyatt, J. Lieberman, M.E. Conley, Memphis, TN. Introduction: X-linked agammaglobulinemia (XLA) is a primary immunodeficiency characterized by severe hypogammaglobulinemia, less than 2% B cells, and increased susceptibility to infection. The mainstay of treatment is gammaglobulin therapy. A review of literature revealed 2 cases of membranous glomerulonephritis in XLA patients. Both patients had severe mutations in the Bruton’s tyrosine kinase (BTK), a single base pair insertion in one and a duplication of exons 6-18 in the other, and both were receiving IV gammaglobulin. Here we report a case of immune complex glomerulonephritis in a child with XLA due to a mild BTK mutation, a single base pair substitution that impaired but did not ablate splicing of BTK message. He had a higher number of B cells (2-5%) than the typical XLA patient. Case: The patient was recognized to have XLA at 1 month of age because of a positive family history and was started on subQ gammaglobulin. At 5 years of age he presented with sore throat, periorbital edema, dark urine, and hypertension. Laboratory studies revealed BUN of 24 mg/dL, creatinine 0.98 mg/dL, albumin 2.4 g/L, and decreased C3 and C4. Serum IgG was 316 mg/dL and IgM was 28 mg/dL. Renal biopsy showed diffuse proliferative glomerulonephritis and electron microscopy revealed subendothelial immune complex type dense deposits. Immunofluorescence showed 3+ IgG, trace IgA, and 3+ C3. Immune globulin replacement was held and he was treated with 6 doses of 30mg/kg methylprednisolone and then oral prednisone 2mg/kg/day. Lab values improved slightly but repeat renal biopsy was unchanged. Because the source of the IgG in the kidney might have been endogenous, we treated the patient with 4 weekly doses of Rituximab. Renal function stabilized and he was discharged on oral prednisone. Immune globulin replacement was resumed with monthly IV infusions. Conclusion: Immune complex glomerulonephritis is an unusual complication in an XLA patient on replacement immune globulin. The source of the IgG in the renal deposits could be endogenous, exogenous or both. To decrease the endogenous source of IgG, we treated our patient with Rituximab. Although the use of Rituximab in a patient with XLA may seem paradoxical, it may be useful in patients with autoimmune complications

P132 CROHN’S DISEASE IN A CHILD ORIGINALLY DIAGNOSED WITH EOSINOPHILIC GASTROENTERITIS AND FOOD PROTEIN-INDUCED ENTEROCOLITIS SYNDROME. W.M. Rassbach*, J. Wang, New York, NY. Both Crohn’s disease and eosinophilic gastroenteritis with protein-losing enteropathy can result in failure to thrive, patchy mucosal inflammation, hypoalbuminemia, anemia, elevated erythrocyte sedimentation rate (ESR), and occult gastrointestinal bleeding. While eosinophils on biopsy (≥20 per high power field) are necessary for diagnosis of eosinophilic gastroenteritis, they do not exclude the possibility of Crohn’s disease or other inflammatory conditions.


ABSTRACTS: POSTER SESSIONS We report a case of a patient who, at one year of age, was initially diagnosed with eosinophilic gastroenteritis with protein-losing enteropathy as well as food-protein induced enterocolitis syndrome (FPIES) based on symptoms of recurrent abdominal pain, nausea, and delayed vomiting (after ingestion of suspected food triggers), failure to thrive, hypoalbuminemia, and an endogastric duodenoscopy (EGD) showing duodenitis and eosinophils in the gastric antrum. The improvement of her symptoms while on an elemental formula diet appeared to confirm an allergic cause. Despite avoidance of her suspected FPIES trigger foods (milk, soy, egg, beef, apple, pineapple, banana, squash, lettuce) and increasing doses of proton-pump inhibitors, however, she again began to experience poor growth, rising ESR, and worsening anemia and hypoalbuminemia in the absence of blood in her stools. She was subsequently diagnosed with Crohn’s disease at age 7 based on EGD and colonoscopy showing inflammation in her duodenum, stomach, and terminal ileum with no elevation in her eosinophil count. Her concomitant diagnosis of FPIES (eventually confirmed with oral food challenge to banana) and the earlier presence of eosinophils on mucosal biopsy likely contributed to the delay in her diagnosis of Crohn’s. Her case highlights the diagnostic dilemma inherent in finding eosinophils on mucosal biopsy: the eosinophils may be diagnostic of a primary allergy-driven process or they may be part of the body’s response to another inflammatory process. We suggest that her case underscores the need for avoiding premature closure and seeking periodic reevaluation of nonresponders to therapy in the case of eosinophilic gastrointestinal disease.

P133 EMPYEMA NECESSITANS: AN UNEXPECTED INFECTIOUS COMPLICATION OF MULTIPLE MYELOMA. A. Kapila*, J. Goldstein, J. Moorman, C. Forker, E. Velilla, K. Bajaj, G. Krishnaswamy, Johnson City, TN. Introduction: Empyema Necessitans (EN) results from the spread of empyema to the thoracic wall, culminating in draining sinuses. The most common organisms associated with it are Mycobacterium Tuberculosis and Actinomycosis Israelii. EN secondary to underlying multiple myeloma (MM) is rare. We describe a case of MM-associated EN with streptococcus pneumoniae secondary to underlying osteolytic rib lesions and associated immunological abnormalities. Case Report: A 41 yr old male presented with worsening right sided chest swelling, fever, chills, night sweats and weight loss over 8 months. Examination demonstrated erythema, tenderness and induration of the chest wall. Chest x ray and CT Chest showed destructive changes involving the right seventh rib laterally, and underlying evidence of a gas-containing infection of the contiguous lung and pleural space. Following placement of a drainage catheter, cream colored pus was noticed to exude from the site. Serum protein electrophoresis revealed an IgG lambda monoclonal band. Urine electrophoresis showed a monoclonal band identified in the beta-gamma region, composed of free lambda light chains. Immunoglobulin levels were determined to be IgG 3292 mg/dL(700–1600), IgA 30 mg/dL (70-400 and IgM 13mg/dL(40–230). The bone survey revealed lytic lesions in the frontal bone of the skull, mid to distal shaft of the left clavicle, iliac bone and left femur. Rib and bone marrow biopsy confirmed the diagnosis of MM. Culture of the pus showed streptococcus pneumoniae sensitive to levofloxacin. The EN was treated with drainage and rocephin for 4 weeks. The MM was treated with conventional chemotherapy, the patient is currently doing well. Discussion: EN complicating MM is rare, and a review of the literature has demonstrated no case of MM-related EN to the best of our knowledge. The reason for this aggressive infection might be related to underlying immunological abnormalities. Paraproteinemia may be associated with suppression of other immunoglobulin isotypes(such as IgA and IgM in our patient),other studies have shown complement and opsonophagocytic defects in MM - all of which contribute to complications. Our patient has responded so far to antimicrobials, drainage and chemotherapy. However, there is a role for IGIV therapy if the infection responds poorly to therapy and or is associated with severe complications or sepsis.

CT Chest shows cavitary consolidation in the lateral basal segment of the right lower lobe is noted with extensive soft tissue thickening, inflammation and gas in the right lateral chest wall contiguous with the right lower lobe pleuroparenchymal and rib abnormalities representing empyema necessitans (indicated by an arrow)

P134 A CASE OF CHRONIC MUCOCUTANEOUS CANDIDIASIS AND PROGRESSIVE IMMUNODEFICIENCY. N.S. Patel*, M. DeFelice, S. McGeady, Philadelphia, PA. Introduction: Chronic mucocutaneous candidiasis (CMC) presents as superficial candida infections. It is associated with autoimmunity and variable degrees of immune dysregulation. Autoimmune regulator (AIRE) mutations account for 20-40% of CMC cases. Two additional mutations have been identified in patients with an autosomal dominant form of CMC. The first is a monoallelic mutation in the cc domain of signal transducer and activator of transcription 1 (STAT1) and the second is a heterozygous mutation in the DNA binding domain of STAT 1. A recent study identified 14 CMC patients with toll like receptor 3(TLR3) L412F mutation all of whom suffered from chronic candidiasis and sinopulmonary infections. We report a patient with CMC associated with both TLR3 L412F and STAT1 mutations. Methods: A 13 year old Caucasian male with CMC and type I diabetes presented with recurrent sinusitis and mucocutaneous fungal infections. There was no history of pneumonia or serious bacterial infections. Daily diflucan was given with dramatic improvement in his skin and oral candidiasis. At age 15, he was admitted to the pediatric intensive care unit with respiratory insufficiency due to pneumonia complicated by pleural effusion requiring chest tube decompression. He was readmitted shortly after discharge for refractory pneumonia and positive enterovirus PCR. Results: AIRE gene was normal. Quantitative immunoglobulins were normal. Polysaccharide response was poor despite repeat boosting with Pneumovax. Tetanus and diphtheria titers were protective. Stool alpha anti-trypsin and neutrophil oxidative burst were normal. Lymphocyte enumeration was persistently abnormal (Table 1) and mitogen stimulation shows reduced T-cell proliferation. HIV PCR was negative. Adenosine deaminase and purine nucleoside phosphorylase were normal. TLR assay showed absent TLR3 function but normal TLR1-8 function. Further evaluation confirmed a heterozygous L412F mutation of TLR3 and a heterozygous mutation in the DNA-binding domain of STAT 1. Conclusion: The combination of TLR and STAT gene mutations may produce a severe form of CMC. The patient was clinically stable until age15 and both immunoglobulin replacement and bone marrow transplant (BMT) are treatment considerations. There is a paucity of data on BMT in CMC but there have been two successful cases reported. Additional studies are necessary to determine the role of BMT in CMC.



ABSTRACTS: POSTER SESSIONS Table 1. Lymphocyte Enumeration

be related to her occasional use of ibuprofen and her only regularly taken medications were H1 and H2 inhibitors, which had conferred no benefit. On review of systems, she complained dry mouth and eyes, fatigue, and occasional low grade fevers. Results: On exam, she had an enlarged upper lip that appeared less swollen than photographs of past episodes. Her submandibular glands were prominent. There was no rash or other physical findings. Serum tryptase, IgE, C4, and C1 esterase inhibitor levels were all within the normal range. She was noted to be leukopenic with WBC 3700. Prior to referral, she had been found to have a positive ANA with SSA >8 and SSB 4.8 (nl <1 IU/ML), and she had seen a rheumatologist prior to her referral visit. In the absence of more typical symptoms and findings, the only diagnosis was osteoarthritis of the knee. On follow-up in our clinic, the lip swelling appeared unchanged so a lip biopsy was preformed with the pathology report revealing minor salivary glands with features compatible with Sjögren’s syndrome. She had a histomorphometric focus score of 2, indicating preiductal and perivascular foci of 50 or more lymphocytes per 4 square millimeter of glandular tissue adjacent to intact normal appearing acini. Discussion: Persistent lip swelling, especially in the absence of urticaria should not be diagnosed as angioedema. This case of probable Sjogren’s syndrome was atypical in a number of respects including the age of onset and the absence of inflammatory arthritis. Her sense of throat tightness might be attributable to a dry mucosa.

P135 IMMUNOTHERAPY AS TREATMENT FOR AEROALLERGEN TRIGGERED EOSINOPHILIC ESOPHAGITIS. A. Castilano*1, D. Zacharias2, 1. Akron, OH; 2. Cleveland, OH. Introduction: Eosinophilic Esophagitis (EoE) is characterized by esophageal dysfunction and eosinophil-predominant inflammation on biopsy that is limited to the esophagus. Despite an increase in prevalence of EoE, the trigger factors for EoE are still poorly understood thus limiting treatment strategies. Food borne allergens have long been implicated in the pathogenesis of EoE and treatment has been focused upon off-label use of leukotriene inhibitors, steroidal preparations, proton pump inhibitors and mast cell stabilizers. However, emerging evidence is supporting a link between aeroallergens and EoE. This correlation between environmental airborne allergens and EoE has led to improve diagnostic recognition during seasonal susceptible months and treatment strategies. The following case highlights a patient with aeroallergen induced EoE. Recognizing that EoE can be triggered by factors other than food can prevent unnecessary esophageal dilation and food avoidances. Patients should be referred early in the initial work up for skin prick testing for aeroallergens. Case: A 30-year-old white male presented to his primary care physician with symptoms of dysphagia; he was diagnosed with GERD and placed on esomeprazole. One year later, he presented with food impaction and underwent esophageal dilation. Biopsy of the esophagus revealed predominance of eosinophils and EoE was diagnosed. Despite treatment with oral fluticasone for two years, the patient had persistent dysphagia requiring multiple esophageal dilations. The patient was referred to an allergist and underwent skin prick testing to foods and aeroallergens. A panel of 60 foods was uniformly negative. Skin testing did identify reactions to dust mites, cockroaches, common weeds and trees. The patient received immunotherapy to these aeroallergens over a course of three years without any relapse in dysphagia or food impaction. Esophageal biopsy performed three years into immunotherapy showed complete resolution of eosinophil infiltration. Conclusion: Both aeroallergens and food borne allergens must be considered in the evaluation of patients with suspected EoE. Seasonal triggers with supportive skin testing are valuable diagnostic indicators along with esophageal biopsy. Early referral to an allergist is vital in the management of EoE patients to direct treatment strategies.

P136 SJÖGREN’S SYNDROME MASKING AS RECURRENT ANGIOEDEMA. T. Hwangpo*1, P. DeVilliers2, J. Bonner2, 1. Helena, AL; 2. Birmingham, AL. Background: Angioedema causes self-limited, localized subcutaneous swelling especially likely to affect the periorbital and circumoral areas. Here, we report a case where lip swelling, at first mistaken for angioedema, was shown to be due to Sjögren’s syndrome. Case: A 30 year-old obese woman with a history of non-allergic asthma and osteoarthritis was referred for a second opinion in March 2013 for episodic angioedema and throat tightness without urticaria that started in July of 2012. There was no family history of angioedema and tests for food and inhallant allergy had been negative. The episodes could not


Left image: Patient with upper lip swelling. Right image: Minor salivary glands with features compatible with Sjogren’s syndrome.

P137 INTRAVENOUS IMMUNOGLOBULIN USE IN A CHILD WITH KIKUCHI DISEASE. T. Peng*1, D. Chefitz2, S. Gaur2, W. Pan2, L.N. Moorthy2, 1. Edison, NJ; 2. New Brunswick, NJ. Background: Kikuchi syndrome is a rare, generally self-limited condition characterized by necrotizing cervical lymphadenitis and fever. Treatment may be required with NSAIDS and/or corticosteroids. Intravenous immunoglobulin (IVIG) use has been reported in a few cases. Objective: To describe a case of a boy with Kikuchi syndrome who responded to IVIG. Case Description: A 9-year-old Asian male presented with 12 days of fever (Tmax 105F) and 2 days of painful right neck lymphadenopathy. He subsequently developed palatal ulcers and a macular rash over his legs, feet and back. The differential diagnosis included incomplete Kawasaki’s disease, Lemierre’s syndrome, systemic lupus erythematosus, systemic juvenile arthritis, and Kikuchi syndrome. Results: Patient had elevated liver function tests, inflammatory factors and ferritin, but decreased white blood cell count, as seen in the table below: Lymph node biopsy noted multifocal necrosis with many apoptotic bodies, virtually no neutrophils, and many histiocytes with crescentic nuclei within the necrosis and scattered immunoblasts. The majority of cells within the node were CD3+ T-cells with one area of CD20/PAX-5 positive cells that may represent a residual germinal center. These findings were highly suggestive of Kikuchi disease. Infectious and oncologic etiologies were ruled out with laboratory testing, bone marrow and lymph node biopsy. The patient was treated with IVIG with clinical improvement. The patient was readmitted two months later for recurrence of cervical lymphadenopathy and fever that resolved with a short course of corticosteroids. Discussion: Tissue diagnosis is critical for diagnosing Kikuchi disease. Our patient responded successfully to IVIG. Although there are limited reports of the use of IVIG in these patients, IVIG may be a therapeutic option in patients with Kikuchi disease. Kikuchi disease has been described as a T-cell mediated immune response to non-specific and unknown stimuli in a genetically predisposed patient. While the exact role of IVIG is unclear in Kikuchi disease, it may work by regulating T-cell-dependent inflammation with nonspecific antiinflammatory effects.




tively), undetectable C1q, and undetectable C2. C2 gene mutation testing was negative, and she had increased C1 inhibitor autoantibodies. Other laboratory testing demonstrated increased serum total IgE level of 371 kU/L, negative anti-nuclear antibody, and the absence of eosinophilia. Given the patient’s high IgE and frequent travel to Puerto Rico, Strongyloides serology was checked and was positive. She was treated with ivermectin for 2 days for presumed Strongyloides infection. Since the completion of therapy, the patient has not experienced further significant episodes of angioedema. Discussion: This patient experienced refractory angioedema in the setting of MGUS and untreated Strongyloides infection. Given the potential dangers associated with Strongyloides infection, clinicians must maintain a high index of suspicion in those being considered for steroid therapy. Strongyloides infection should be considered in any patient who presents with severe allergic manifestations, and who has a history of travel to endemic regions.



Laboratory Results

Introduction: Mast cell activation syndrome (MCAS) is a multi-system disorder of mast cell hyperreactivity, the criteria include: episodic symptoms of mast cell mediator release affecting ≥2 organ systems; decrease in the frequency/severity or symptom resolution with antimediator therapy and increased in urinary or serum markers of mast cell activation. We describe a case of MCAS who presented with recurrent angioedema. Methods: Case description Results: A 58-year old male with a history of hypertension and chronic rhinosinusitis presented with recurrent episodes of angioedema triggered by certain foods. The patient’s symptoms began two years prior with throat swelling after eating peanuts and facial swelling after eating sesame seeds. Medications included lisinopril 40 mg daily for the past 3 years. The patient’s laboratory evaluation revealed an elevated serum total IgE (401 IU/ml), elevated tryptase of 17 ng/ml (normal, 1-15 ng/ml), and an elevated ANA titer (1:160 speckled). Specific IgE testing was positive for hazelnut, peanut, wheat, and mugwort. Laboratory testing demonstrated the absence of eosinophilia, negative strongyloides serology, and normal levels of C1 esterase inhibitor, C2, C3, and C4. Repeat serum tryptase after 6 weeks was found to be 20 ng/mL. Our management included changing the lisinopril to losartan, starting daily loratadine 10 mg, prescribing an epi-pen, and counseling the patient to avoid the culprit foods. The patient was referred to Hematology and underwent a bone marrow biopsy, which was significant for mild mastocytosis (10%), and 2% CD2, CD25, and CD117 cells on flow cytometry. There were no granulomas, eosinophilic fibrous histiocytic lesions, or immunophenotypically abnormal mast cells seen. The patient has had no further angioedema, and is undergoing Rheumatologic evaluation for the positive ANA. Conclusion: MCAS represents a complex disease and may be difficult to diagnose. This patient’s recurrent angioedema in the setting of multiple possible triggers (ACE inhibitor, several foods) prompted us to investigate for underlying mast cell-related diseases. This patient met the clinical criteria for MCAS, and will need close monitoring for disease stability/progression. Mast cell disease may present through heterogeneous clinical manifestations, and clinicians must maintain a high index of suspicion for this under-recognized entity.

P139 ACQUIRED C1 INHIBITOR DEFICIENCY IN THE SETTING OF STRONGYLOIDES INFECTION AND MONOCLONAL GAMMOPATHY OF UNDETERMINED SIGNIFICANCE. L. Rampur*, G. Hudes, D.L. Rosenstreich, S. Jariwala, Bronx, NY. Introduction: Acquired angioedema (AAE) is characterized by episodic swelling, which typically affects the skin, or mucosal tissues of the gastrointestinal and/or respiratory tract. AAE cases often have an underlying disorder, medication or food hypersensitivity, infections, malignancies, autoimmune diseases, or lymphoproliferative disorders. We present an interesting case of AAE (C1 esterase inhibitor deficiency) associated with monoclonal gammopathy of undetermined significance (MGUS) and Strongyloides infection. Following ivermectin therapy, she had no further episodes of angioedema. Methods: Case description Results: A 62-year-old Puerto Rican (yearly travel to Puerto Rico) female with a history of recently diagnosed MGUS initially presented with recurrent episodes of facial, extremity, and oropharyngeal angioedema since 2008, without any clearly associated triggers. Following the onset of angioedema, she had been started on danazol and continued to experience symptoms. From 2009 to 2011, the patient also received intermittent prednisone courses and C1 esterase inhibitor (human) prophylaxis with continued symptoms. Our laboratory evaluation revealed persistently low C4 levels (2-3 mg/dL), decreased C1-esterase inhibitor level and function (1:2 to 1:4 and 12%, respec-

CUTANEOUS ABSORPTION OF GRASS POLLEN: AN UNDERRECOGNIZED CAUSE OF ANAPHYLAXIS. K. Lotvi, J.A. Saryan*, Burlington, MA. Introduction: Food, stinging insect, latex and drug allergies are readily recognized as causes of severe allergic reactions. Environmental allergens, however, are often ignored as a potential trigger. Grass pollen absorption through abrasions in the skin is often overlooked as a cause of life-threatening anaphylaxis and has rarely been reported in the past. We report 2 cases of anaphylaxis occurring through cutaneous absorption of grass pollen allergens. Methods: Retrospective chart reviews. Case 1: A 12 year old male with a history of asthma and seasonal allergic rhinoconjunctivitis presented with an anaphylactic reaction after playing tag for 20 minutes in tall grass while wearing shorts during grass season. He developed a sensation of warmth and then pruritus of his palms that became generalized, a scratchy tight throat, nasal congestion, hives and dyspnea. He was taken by ambulance after being given diphenhydramine. He received corticosteroids, famotidine and IV fluids and improved. He denied any insect sting or prior ingestion of nuts to which he is allergic. In vitro IgE to grass pollen was positive as was prick skin testing (10 mm wheal with satellites and pseudopods). Case 2: A healthy 4 year old male wearing only his bathing suit presented with anaphylaxis after vigorous play with his father who was squirting him with a hose as he ran and played on grass in late June. He developed a pruritic rash on his chest and arms followed by facial redness and angioedema. He was driven to an ER where he developed cough and shortness of breath and was treated with epinephrine, diphenhydramine, corticosteroids and IV fluids. He was initially thought to have had an insect sting as a red lesion was noted on his head. Venom skin test and in vitro IgE testing elsewhere was negative. Skin test was strongly positive for grass pollen. Discussion: Severe allergic reactions are most often caused by food, stinging insect, drug and latex allergies. These 2 cases demonstrate the importance of considering grass pollen allergy in the differential diagnosis of anaphylaxis in patients with direct cutaneous exposure to grass during pollen season. This has important implications on management and prevention of such severe allergic reactions.

P141 CHURG-STRAUSS: AN ATYPICAL PRESENTATION. M. Relan*, M. Sands, Buffalo, NY. Introduction: Churg-Strauss syndrome (CSS), also known as allergic angiitis and granulomatosis, is a multiorgan disease that affects approximately 35 out of one million adult asthmatics. Patients usually present in their 3rd to 4th decade of life. Cardinal features include asthma, eosinophilia, neuropathy, nonfixed pulmonary infiltrates, paranasal sinus disease, and extravascular eosinophils (eos) on biopsy. Case: 73-year-old male patient hospitalized for acute onset of productive cough, diffuse myalgia, WBC 24.5K/mm3 (Nl 4.410.7), with 77% eos (Nl 0.7-6.6) and absolute eos count 21K/mm3 (Nl 0.10.5), hemoglobin 14.5g/dL (Nl 13.5-17) and platelets 145K/mm3 (Nl 140-375). He had previous diagnoses of allergic rhinitis, recurrent non-aspirin sensitive nasal polyps, recurrent intermittent eosinophilia (10 to 30%) since age 55 and asthma onset at age 61. Bone marrow biopsy at age 66 was unremarkable. Numerous ANCA profiles, ABPA screen, and hypersensitivity pneumonitis serologic evaluations were negative. At age 72, his eos count was zero in the absence of systemic steroids. Data: Pertinent PE: afebrile, lungs CTAB, tender left quadriceps, and within days, development of erythema to left lower leg; patient complained of progressive numbness and painful dysaesthesias of his distal extremities. Additional labs: CRP 50.21mg/L (Nl 0-3), CPK 335U/L



ABSTRACTS: POSTER SESSIONS (Nl 21-232), aldolase 7.9U/L (Nl 1.2–7.6), total serum IgE 1034IU/mL (Nl 0100). CXR: hyperinflation; CT thorax: atelectasis, left pleural effusion, chronic interstitial changes with focal pleural thickening bilaterally. Punch biopsy of rash: upper- and mid-dermal perivascular and interstitial eosinophilic infiltrate. Marrow biopsy: hypercellularity with markedly increased eos. EMG and nerve conduction studies consistent with mononeuritis multiplex. Nerve biopsy: several small blood vessels surrounded and partially infiltrated with lymphocytes, plasma cells, and prominent eos, diagnostic of vasculitis. Conclusion: We describe an atypical case of CSS in an older individual with stable, non-steroid-dependent asthma and relapsing/remitting eosinophilia with a severely prolonged prevasculitic stage. This case underscores the wide potential clinical spectrum of Churg-Strauss vasculitis. Although a rare disease, CSS should be included in the differential of adult asthmatics with severe eosinophilia, since prompt initiation of immunosuppressive treatment is required to prevent mortality.


bellar and brainstem lesions. Subcortical ring enhancement lesions were also noted. The dominant lesion within the right cerebellar hemisphere demonstrates hemorrhage with mild mass effect. EEG was suggestive of moderate encephalitis. Cerebrospinal fluid (CSF) evaluation showed nucleated cells of 8 cells/ul 95 % lymphocytes, protein of 129 mg/dl and glucose of 58 mg/dl. CSF was negative for aerobic and anaerobic cultures, Mycoplasma pneumonia culture, cryptococcal antigen, and myelin basic protein. CSF PCR testing was negative for CMV, EBV, HSV, VZV, JC virus, but positive for Toxoplasma gondii. Sulfadiazine and pyrimethamine were initiated. Neurologic symptoms started to improve within 3 days. Repeat MRI on day 9 showed decrease enhancement of lesions, repeat CSF was negative for toxo after 5 weeks. Discussion: CNS infections are very rare complications of AT and symptoms can be masked by baseline neurologic findings. In our case, increased sleepiness despite proper treatment of pneumonia alerted us to further investigate the cause of deterioration. Conclusion: CNS infections should be considered in AT patients who present with new neurologic findings or acute worsening of baseline CNS symptoms

AUTOIMMUNE PROGESTERONE DERMATITIS: AN UNUSUAL PRESENTATION OF A RARE DISORDER. J.L. Hill*, T.F. Carr, Tucson, AZ. Background: Autoimmune progesterone dermatitis (AIDP) is an unusual allergy to progesterone characterized by cyclic cutaneous eruptions coincident with the luteal phase of the menstrual cycle. Although typically related to a peak in endogenous progesterone, cases precipitated by exogenous progesterone have been reported. We describe a case of iatrogenic AIPD presenting with multiple types of hypersensitivity. Case Presentation: A 26-year-old pregnant female at 7 weeks gestation following in-vitro fertilization (IVF) presented for evaluation of urticaria that developed after intramuscular (IM) progesterone in oil (PIO) injections. The urticaria began as a localized reaction, developing within 2 minutes of PIO injections. Later in her therapy, the reaction expanded to involve concurrent urticaria on her thighs and abdomen. The lesions lasted for several hours, resolving without bruising. As an alternative to PIO, she was prescribed intravaginal progesterone suppositories that caused vaginal pruritus and blistering lesions. Additionally, she described the development of a fixed, erythematous, papular, and pruritic rash in response to topical progesterone creams suggestive of a delayed hypersensitivity reaction. On presentation, she did not have skin lesions present; however, provided photographs that were consistent with urticaria. Skin prick testing performed using full strength progesterone in sesame oil and sesame extract with saline and histamine controls, revealed a positive reaction to PIO. Sesame extract was non-reactive. She was diagnosed with immediate hypersensitivity to progesterone. Although delayed type hypersensitivity to topical progesterone was also suspected based on her clinical history, confirmatory patch testing was deferred. She was treated with a 13-step, rapid desensitization protocol using IM PIO and subsequently completed five additional, uncomplicated weeks of progesterone therapy, thus sustaining her pregnancy. Conclusion: We report one of the few cases of iatrogenic AIDP in the literature. Further, our case is unique in that the patient displayed both immediate and suspected delayed hypersensitivity reactions to progesterone. Given the frequent use of synthetic progesterone in infertility therapy, iatrogenic AIDP could represent an increasingly prevalent entity and clinicians should be aware its causes as well as its various presentations.

P143 A RARE CNS COMPLICATION OF ATAXIA TELANGIECTASIA. R. Chaiban*1, A. Tarabishy1, Y. Yilmaz Demirdag2, 1. Morgantown, WV; 2. New York, NY. Introduction: Ataxia-Telangiectasia (AT) is an autosomal recessive DNA repair defect affecting multiple organs including the immune system. The most common immunologic abnormality is antibody deficiency resulting in recurrent bacterial respiratory tract infections. Here we present an unusual infectious complication of AT. Case Presentation: An 8 year-old boy with AT who has been on subcutaneous immunoglobulin therapy presented with increased work of breathing, high fever, and increased sleepiness. One week prior to presentation, Cefdinir was started for pneumonia. He had a temperature of 104 F, decreased air entry bilaterally, drowsiness, bilateral ptosis, bilaterally dilated but reactive pupils, and severe truncal ataxia. Laboratory evaluation revealed a WBC of 28.3Kcells/ul and 75% polymorphonuclear cells. Brain MRI with IV contrast read multifocal and extensive white matter signal changes involving the medial thalami (Figure A, asterix), brainstem and right cerebellar hemisphere (Figure B, arrow) along with involvement of the subcortical white matter of the left frontal and left temporo-occipital lobes (Figure A, arrow). There was associated irregular patchy and discontinuous enhancement of the cere-


P144 POLYARTHRITIS AS A PRESENTATION OF INFLAMMATORY BOWEL DISEASE. K.G. Conner*, J. Moy, Chicago, IL. Introduction: Inflammatory bowel disease (IBD) has varied presentations making it difficult to diagnose. We highlight a case of polyarthritis as a presentation of IBD. Case: A 15 year old boy presented to the emergency room with difficulty ambulating. He reported a two and a half week history of polyarthritis of his right heel, right knee, and left wrist as well as 5 minutes of morning stiffness. He injured these joints after sliding down a set of stairs. Review of systems was remarkable for subjective fevers, decreased appetite, and a twentypound weight loss over the one month prior to admission. He denied a past medical history, history of sexual activity, or a history of recreational or IV drug use. Examination showed warm, right knee and ankle effusions and a slightly warm, right wrist. No dactylitis was appreciated. Synovial fluid analysis of the right knee was yellow, cloudy, 2,350 RBC, 5,000 WBC, no crystals, and no growth on culture. Laboratory evaluation demonstrated WBC 10.1, Hg 7.2 MCV 74.1 RDW 15.4%, ESR 110, CRP 18.04, and normal C3, C4, ANA, RF, and ASO titers. Ketonuria was noted without UTI. X-ray of the right knee showed a moderate suprapatellar joint effusion. Several days into the hospital course, the patient passed bloody stools. CT abdomen showed a nonspecific prominence of the mesenteric and pelvic lymph nodes. Colonoscopy revealed erythematous, edematous, and thickened mucosa of the entire colon. Biopsy samples revealed evidence of acute and chronic inflammation as well as cryptitis in the cecum, ascending, transverse, and sigmoid colon. Inflammation and microabscesses in the lamina propria with hemorrhage were noted in the rectum. Discussion: Polyarthritis as a presentation of IBD is uncommon. Only 1.8% of patients with IBD present with arthritis, such as our patient did. Although rare, IBD should always be considered in the differential diagnosis of polyarthritis.

P145 STEVENS-JOHNSON SYNDROME ASSOCIATED WITH RITUXIMAB AND BENDAMUSTINE. T. Gavrilova*, A. Wolff, Newark, NJ. Introduction: Stevens-Johnson syndrome (SJS) is a severe, life-threatening condition associated with a widespread destruction of the epidermis and mucous membranes.(1) Due to its high mortality rate, prompt diagnosis and treatment


ABSTRACTS: POSTER SESSIONS is crucial. Although medications are the most common culprits of SJS(2), rituximab and bendamustine chemotherapeutic agents have rarely been linked with SJS. We report a patient with SJS associated with rituximab and bendamustine. Case Report: A 78 year old Caucasian man with follicular lymphoma presented for hospital admission with an altered mental status, fever, an extensive erythematous rash. He received three cycles of outpatient chemotherapy with rituximab and bendamustine, and developed a sore throat and rash on his upper chest wall one day after his third cycle. His symptoms were not relieved with twice daily use of triamcinolone 0.1% cream and desonide 0.05% cream that was initially prescribed for a suspected drug eruption. His rash progressed during the week to become generalized, extensive desquamation as well as a bullous eruption on his legs. He was admitted to the intensive care unit for treatment. His home medications at the time were aspirin, amlodipine and a stool softener. He did not have any recent bouts of acute infections. Pertinent physical exam findings at the time of evaluation included a fever of 102.4 and somnolence. His physical exam showed erythema and desquamation of the eyelids, lips, torso, bilateral upper and lower extremities, and conjunctival injection. There was no evidence of oral mucosal lesions on exam. Laboratory findings showed anemia (hemoglobin-8.8mg/dL) and thrombocytopenia (platelets-95K). Peak eosinophil count was 1.1K but subsequently returned to zero. Blood and fungal cultures were negative. The clinical presentation was consistent with SJS associated with rituximab and bendamustine. Since both agents were administered during the same treatment cycle, it was not possible to determine which one was specifically responsible for his disease. Discussion: Steven-Johnson syndrome is a severe life-threatening condition involving the epidermis and mucous membranes. Rituximab and bendamustine association with SJS has rarely been reported.(3) Early detection of SJS and discontinuation of possible offending agents is critical in the diagnosis and treatment of this condition.

P146 ANGIOTENSIN RECEPTOR BLOCKER-INDUCED INTESTINAL ANGIOEDEMA. P. Thalanayar*1, I. Ghobrial1, A. Petrov2, 1. Mckeesport, PA; 2. Pittsburgh, PA. Introduction: Angioedema is a rare complication of angiotensin receptor blocker (ARB) therapy. However, isolated visceral angioedema has not been previously reported with ARB treatment. Methods: We performed Pubmed search for intestinal or visceral angioema associated with ARB therapy. Case Report: 31 y/o African-American woman with history of recurrent abdominal pain, hemodialysis-dependent end-stage renal disease (ESRD) and hypertension, presented to the hospital with another bout of severe abdominal pain, nausea, vomiting, and diarrhea. She had diffuse pain and tenderness over the epigastrium and right lower quadrant without guarding or rigidity. Bowel sounds were hypoactive. CBC, BMP, LFTs and lipase were normal. For hypertension, she was on nifedipine, losartan, and clonidine. Review of records indicated that the onset of her abdominal pain coincided with starting lisinopril 6 years ago. Previous non-contrast abdominal CTs were remarkable only for peri-hepatic fluid. The diagnosis remained elusive. Five years later, she experienced some dry cough and was transitioned to losartan. The transition from lisinopril to losartan resulted in the resolution of her cough but the gastrointestinal symptoms persisted. 6 months into losartan therapy, she continued to present with abdominal symptoms. Abdominal CT scan with contrast was obtained and it revealed small bowel wall edema, a classic ‘Target sign’ and peri-hepatic fluid. C1-inhibitor and C4 levels were normal. Losartan was discontinued and the patient’s symptoms resolved. Sustained relief of symptoms over a year after stopping losartan supported the diagnosis of ARB-induced visceral angioedema. Conclusions: We report the first case of ARB-induced isolated intestinal angioedema in the setting of previous angiotensin converting enzyme (ACE) inhibitor treatment. In our case, visceral angioedema most likely occurred after administration of lisinopril and again after administration of losartan. Clinicians should be aware that cross-reactivity of angioedema between ACEinhibitors and ARBs, albeit low, can affect visceral organs and cause significant morbidity.

P147 SEQUELAE OF DELAYED DIAGNOSIS OF HYPER-IGM SYNDROME AS AN ADULT IN ABSENCE OF KNOWN GENETIC MUTATIONS. A. Thakor*, B. Geng, M. Braskett, Los Angeles, CA. Hyper-IgM syndromes are a group of immunologic syndromes associated with defective class-switch recombination. Patients present with severe recurrent childhood infections and normal/elevated serum IgM with reduced IgG, IgA and IgE levels. Diagnosis is made by clinical signs, lab findings, and genetic testing for known mutations. Definitive treatment is bone marrow transplantation. Delayed recognition leads to morbidity and mortality secondary to endorgan failure and overwhelming infections. A 22 year old man with history of Evan’s Syndrome (ITP, autoimmune hemolytic anemia) and prior diagnosis of Common Variable Immunodeficiency presented with respiratory failure, bacteremia/viremia and anasarca. He had cryptogenic cirrhosis with severe hypoxemia secondary to intrapulmonary shunting from hepatopulmonary syndrome. On exam, he had anasarca with 3+ pitting edema in all extremities and clubbing of all digits. Also present were splenomegaly and petechiae. Immunoglobulin levels were IgG 297 mg/dl, IgA <8mg/dl, IgM 1450 mg/dl (repeat 1810 mg/dl). Flow cytometry revealed a normal number of B cells which were all immature and no evidence of class-switched cells. T cell panel showed CD4 lymphopenia (278), low memory CD4 cells and increased activated CD8 cells. Bone marrow biopsy was negative for leukemia/lymphoma. Investigations also demonstrated culture positive CMV viremia, strep viridans bacteremia, acinetobacter pneumonia, influenza B and pseudomonas UTI. Liver transplant evaluation was initiated but patient was denied given multiple comorbidities. Lab findings and clinical presentation supported a clinical diagnosis of HyperIgM Syndrome. Genetic studies for known Hyper-IgM syndrome mutations were all negative including CD40LG, CD40, UNG, and AICD. Whole exome sequencing is being considered. Hyper-IgM syndrome is often considered a pediatric illness, but should be considered in young adults with characteristic clinical and lab abnormalities. Hematopoietic stem cell transplant and/or liver transplant may have been an option in absence of significant comorbidities including multiple severe infections and end organ failure. Our case is most consistent with the Hyper-IgM phenotype, complicated by sequelae of delayed recognition, and presents the possibility of a novel genotype for Hyper-IgM Syndrome.

P148 PROTAMINE SULFATE ALLERGY: ANAPHYLAXIS DURING AN INTRADERMAL SKIN TEST AND A SUCCESSFUL DESENSITIZATION PROTOCOL. B. Hronek*, H.J. Wedner, St. Louis, MO. Introduction: Protamine sulfate is a cationic polypeptide used clinically to reverse heparin anticoagulation during procedures including cardiopulmonary bypass. Adverse reactions to protamine have been reported, including IgE-mediated allergy. The evaluation and management of protamine allergy are not well defined, and there are no published desensitization protocols. Case: A 59 yearold man presented to his local hospital with chest pain and was found to have a non-ST elevation myocardial infarction. His past medical history was significant for obesity, obstructive sleep apnea, and a prior vasectomy. He did not have diabetes, had never received subcutaneous insulin, and had no prior procedures requiring intravenous heparin or protamine. Coronary catheterization was performed which showed extensive three vessel disease requiring coronary artery bypass grafting. Due to a reported salmon allergy the local anesethesiologist requested an allergy evaluation out of concern for potential protamine allergy. As an inpatient, prick testing to protamine was performed at a concentration of 1 mg/ml, which was negative. Intradermal testing with the same concentration was positive, but was complicated by diffuse pruritus, coughing, and wheezing treated with antihistamines, albuterol, and steroids. This concentration had been shown to be irritating, but there are no published reports of adverse reactions from skin testing. The patient was referred to our Cardiothoracic Surgery and Allergy departments for further evaluation and treatment. The patient declined further skin testing and due to the urgency of surgery, a 12-step desensitization with premedication was performed the day of surgery. Cardiopulmonary bypass was initiated 30 minutes following completion of the last dose. Protamine was given for heparin reversal with no adverse reactions noted. The surgery was successful and he was discharged to home. Discussion: This is the first report of protamine anaphylaxis during intradermal skin testing, and we propose that the concentration of protamine used for skin testing should be less than 1 mg/ml. This is also the first report of a detailed,



ABSTRACTS: POSTER SESSIONS successful protamine desensitization, which can be used for future management of protamine allergic patients.

P149 A CASE OF AORTIC ANEURYSM IN A 47 YR OLD MAN WITH XLA. K.K. Brar*, R. Chakraverty, S. Kumar, S.R. Gottesman, R. Joks, Brooklyn, NY. Introduction: While rare, medium and large vessel vasculopathy has been reported in primary immunodeficiency syndromes. Etiopathogenesis of vascular manifestations in these disorders is poorly understood and is not immediately explained by the infections to which these patients are vulnerable. We report the first case of a large vessel (aortic) aneurysm in patient with Xlinked agammaglobulinemia (XLA). Presentation: A 47 yr old African American male with XLA, on monthly IVIG therapy, atrial fibrillation (normal cardiac catheterization), recurrent leg ulcers, and asthma presented with shortness of breath and chest pain to the ER. The patient was in atrial fibrillation with a ventricular rate of 170 beats per minute, and blood pressure of 132/82 mm Hg. Atrial fibrillation was controlled with amiodarone and metoprolol. Serum troponins were normal, ruling out acute coronary syndrome. A chest CT angiography ruled out pulmonary embolus, but showed aortic root dilatation of 6.2 cm in diameter consistent with ascending aortic aneurysm. A transthoracic echocardiogram revealed annuloaortic ectasia, without the presence of bicuspid aortic valve, with mild-moderate aortic regurgitation. Left ventricular ejection fraction was decreased to 30% to 35% Due to the presence of aortic regurgitation, as well as aneurysm size greater than 6 cm, the patient underwent graft replacement of the aortic valve, aortic root, and ascending aorta with reimplantation of the coronary arteries to the graft. Results. Pathology revealed minimal cellular infiltration, and myxoid degenerative changes (patchy loss of elastin and smooth muscle fibers) of the aortic wall, a non-specific finding, making etiology of the aneurysm unclear. Blood culture evaluation for “Flexispira”-Like Organism, a curved Gram-negative rod bacterial infection associated with leg ulcers in patients with XLA, was negative. Conclusion: Aortic aneurysms have previously been described in two cases of CVID, five cases of Wiskott-Aldrich Syndrome, and are now a well-recognized phenomenon of the Hyper IgE syndromes. This is the first description of aortic aneurysm in XLA. The pathologic mechanisms for development of this connective tissue manifestation have yet to be determined.

P151 LIFE-THREATENING AUTOIMMUNE HISTAMINERGIC ANGIOEDEMA. S. Waqar*1, S. Farzan2, 1. Dix Hills, NY; 2. Great Neck, NY. Introduction: Angioedema is the most common cause of hospital admission among acute allergic diseases. Autoimmune urticaria and angioedema, as evidenced by a positive anti-Fc Epsilon receptor antibody, does not typically present with life-threatening symptoms. Here we describe the presentation, diagnosis, and clinical course of a patient with suspected histamine-mediated autoimmune angioedema, which caused several life-threatening episodes. Methods: A 37-year-old female, two weeks post-partum, with PMH significant for IVF and anti-cardiolipin antibody positive thrombophilia presents with recurrent idiopathic angioedema. CG reports an initial episode of upper airway angioedema while self-administrating Ganirelix and estrogen for an IVF procedure. She then develops several episodes of angioedema involving her mouth and tongue immediately post-partum. One episode occurred one hour after ingestion of Xanax, which she had tolerated in the past. Acute episodes were treated with IV Benadryl, Pepcid and IV and/or oral corticosteroids. CG had moderate control of her symptoms with a regimen of oral H1- and H2-blockers as an outpatient. In order to determine if her symptoms are histamine or bradykinin mediated, she received a bradykinin antagonist during an acute episode, without relief. Results: CG was admitted to the hospital with tongue and speech involvement for monitoring and further work-up of recurrent idiopathic angioedema. Her physical exam was notable for lower lip angioedema and lingual swelling. Laryngoscopy revealed uvular swelling. Extensive laboratory work-up showed normal C4, C2, C1q, and C1 esterase inhibitor level and function. Limited Factor XII genetic testing for Type III hereditary angioedema was normal. Tryptase, rheumatoid factor, anti-CCP IgG and angiotensin converting enzyme-1 were normal. She was found to have an elevated anti-Fc epsilon receptor antibody level and an elevated ANA titer (1:160 speckled). Rheumatology evaluation was unremarkable. Given her laboratory profile and lack of response to a bradykinin antagonist, it was determined that her symptoms were likely histamine-mediated. Conclusion: In patients with life-threatening recurrent angioedema with laboratory findings suggestive of an autoimmune etiology, histamine-mediated angioedema should be considered. Use of a bradykinin antagonist during an acute episode can rule out bradykinin-mediated angioedema.

P152 P150 A CASE OF APPARENT CONTACT DERMATITIS ACTUALLY CAUSED BY TOXOCARA INFECTION. R. Qualizza*, C. Incorvaia, A. Maraschini, Milan, Italy. Background: Several reports highlighted the ability of Toxocara infection to present with apparently allergic manifestations. We report a case, thus far undescribed, of a diagnosis of contact dermatitis from nickel actually caused by Toxocara infection. Methods: The patient was a 53 year-old woman presenting from 10 years a dermatitis affecting head, neck and thorax. Patch tests were initially performed, with a positive result only for nickel. The patients avoided any possible contact with nickel, but dermatitis recurred regularly at intervals of 4-6 months. In 2005 dermatitis also affected the sole of the right foot and was treated with topical steroids, but in the following years also edema of the foot with difficulty in walking occurred. The patients referred to our Allergy service in 2010 because of the development of dermatitis also to the left foot. Patch testing confirmed the positive result for nickel sulfate, the patients also complained recurrent headache and asthenia especially in the morning. By routine blood tests, only peripheral of eosinophilia and total IgE levels were abnormal. We required other immunological tests including ANA, ENA and anti-Toxocara antibodies, with a positive results to Western blotting and ELISA for the latter. Results: Following the diagnosis of Toxocara infection, treatment with mebendazole 100 mg b.i.d for 3 days was started, achieving immediate efficacy on feet dermatitis and edema. Other 3 courses of Mebendazole treatment were performed, dermatitis showing a mild reoccurrence, while headache and asthenia disappeared. Also peripheral eosinophilia turned to normal value. Then, two courses of treatment with Albendazole 400 mg b.i.d for 5 days were performed, that were followed by complete regression of dermatitis, accompanied by negativization of ELISA and Western blotting for Toxocara antibodies. Conclusions: This report adds another misleading presentation of Toxocara infection as apparent contact dermatitis. Only the correct diagnosis allowed to cure the 10-year long symptoms of the patient, the causative role of Toxocara being confirmed by the immunological laboratory results.


OCULAR IRRITATION SECONDARY TO TAMSULOSIN. B.T. Kelly*1, B.A. Locke1, K.J. Kelly2, 1. Milwaukee, WI; 2. Chapel Hill, NC. Introduction: Tamsulosin (an α1a-selective α-blocker) is a commonly used medication for the treatment of benign prostatic hypertrophy (BPH). It is generally a well tolerated medication with few adverse effects if taken as directed. Common occular adverse effects include: blurred vision, intraoperative floppy iris syndrome (IFIS), and amblyopia. We report the first case of persistent severe non-purulent conjunctivitis secondary to Tamsulosin. Case Description: 59 year old Caucasian male referred to the allergy clinic by his Ophthalmologist due to chronically irritated right eye. Past medical history was remarkable for BPH, rosacea, hypercholesterolemia, and recurrent HSV stomatitis. Family and social history were unremarkable. Symptoms started two years prior to evaluation and included conjunctivitis, pain, and clear drainage. He was initially treated with tobramycin/dexamethasone eye drops by his ophthalmologist, which resolved the symptoms. However, each time the eye drops were discontinued the irritation returned. The patient revealed that he began taking Tamsulosin about the same time his ocular symptoms started. Stoppage of Tamsulosin resulted in complete clearing of the conjunctivitis. To ascertain cause and effect, a drug challenge was scheduled. Approximately 20 minutes after ingestion of 0.4mg of Tamsulosin, the patient experienced typical symptoms of pain, itching, and scleral injection. On physical examination, there was marked bilateral scleral injection with dilated scleral vessels right worse than left. These findings were compatible with a unique local conjunctivitis secondary to Tamsulosin. Conclusion: This case illustrates a unique and previously unreported adverse reaction to Tamsulosin, a popular BPH medication. While not an anaphylactic reaction, this drug eruption caused significant morbidity for the patient. The eye drops likely worked by decreasing inflammation. Our case highlights the importance of a thorough history and thoughtful use of diagnostic challenge.







Introduction: Administration of Alemtuzumab (CAMPATH), a humanized anti-CD52 monoclonal antibody, can cause serious adverse reactions including rigors, fever, nausea, vomiting, dyspnea, and hypotension. We report a successful desensitization protocol to Alemtuzumab used for a patient with a prior history of anaphylactic symptoms to this monoclonal antibody. Methods: Case report; literature review of anaphylaxis and adverse reactions to Alemtuzumab. Results: EC is a 26 year old female with severe Crohn’s Disease that presented for allogeneic stem cell transplantation for refractory disease. Alemtuzumab was administered as part of her conditioning regimen prior to transplantation. Prior to infusion, she was premedicated with acetaminophen, diphenhydramine, and intravenous methylprednisolone. However, she developed hypotension during infusion along with symptoms of urticaria, throat tightness, and dyspnea post-infusion consistent with a severe hypersensitivity reaction to the medication. Her symptoms resolved with administration of diphenhydramine and intravenous corticosteroids. Given the lack of a suitable alternative medication, she underwent desensitization to Alemtuzumab utilizing a modified 3 step protocol consisting of premedication along with slow infusions of the monoclonal antibody in 1:100, 1:10, and 1:1 dilutions. Using this desensitization protocol, she tolerated the total dose of Alemtuzumab with only subjective symptoms of chest burning and epigastric pain at the goal infusion rate. Conclusion: Infusion-related acute reactions to Alemtuzumab are proposed to be secondary to cytokine release of IFNγ, TNFα, IL-6, and IL-10 likely from natural killer cells. Adverse reactions primarily occur with the first dose and can be reduced on subsequent doses with premedication with diphenhydramine, acetaminophen, and corticosteroids. Our patient developed severe symptoms concerning for anaphylaxis during and after Alemtuzumab infusion despite appropriate premedication. This case demonstrates the successful use of a modified desensitization protocol in a patient with a prior severe adverse reaction to Alemtuzumab.

Rational: Eosinophilic granulomatosis with polyangitis (EGPA) accounts for 10% of ANCA associated vasculitis. It is most commonly associated with asthma and eosinophilic infiltration of many organs including renal, myocardium, musculoskeletal, and skin. We present an atypical presentation of lower extremity weakness in a patient with stable asthma that is ultimately diagnosed with EGPA. Methods: Case Presentation Results: A 69 year old man with a past medical history of well controlled moderate persistent asthma presented with a ten day history of intractable hiccups accompanied with fever, chills, and weakness in the lower extremities for 3-4 days. He denied any rash, cough, hemoptysis, dyspnea, arthralgia, or sinusitis and was adherent to fluticasone/salmeterol and an albuterol inhaler which he rarely used. Physical exam was notable for a fever of 102.4 F and left lower extremity weakness with normal cardiac, pulmonary, and skin exam. Laboratory evaluation showed white blood cells 28.49 K/ul, with eosinophils 37.9% (10.960 K/ul absolute count), AST 67 u/L, ALT 76 u/L, and elevated CK 1378 (u/L) and normal renal function. Infectious evaluation included negative blood and urine cultures, and normal chest x-ray . Serologies for Hep B, Hep C and HIV were negative as well. On day five after admission he complained of new onset paresthesias in his right hand with persistence of weakness in the lower extremities and had difficulty ambulating, leukocytosis (total WBC 24 K/ul) and eosinphilia (44% 10.5 K/ul). Immune work up at that time showed positive P-ANCA 35.7 u/ml, IgE 154 kU/ml and negative ANA. Bone marrow biopsy showed a slightly hypercellular marrow with eosinophilia and slightly increased plasma cells. Muscle biopsy showed active necrotizing vasculitis affecting small arteries or large arterioles and focal myofiber atrophy with infiltrating eosinophils consistent with EGPA. The patient was subsequently treated with cyclophosphamide in addition to prednisone and he had significant improvement with his lower extremity weakness, downtrending WBC counts (18.87 K/ul) including normal eosinophil count. Conclusion: Eosinophilic granulomatosis with polyangitis can present atypically with musculoskeletal weakness in patients with well controlled asthma.

P154 UNDERLYING MALIGNANCY AS A POTENTIAL RISK FACTOR FOR ANGIOTENSIN CONVERTING ENZYME INHIBITOR ASSOCIATED ANGIOEDEMA: A CASE REPORT. J.A. Savitz*, S. Gada, Bethesda, MD. Introduction: Angiotensin converting enzyme inhibitor (ACE-I) associated angioedema is a potentially life-threatening form of angioedema with a predilection for the tongue and face that may occur days to years after initiation of ACE-I therapy. Known risk factors for ACE-I-associated angioedema include African-American race, smoking, increasing age, and female sex. We present a case of new-onset severe angioedema in a patient treated with an ACE-I who was found to have rectal adenocarcinoma, suggesting that underlying malignancy may be an additional risk factor leading to the manifestation of ACE-I-associated angioedema. Case Report: A 66-year-old African American male presented to our ER after awakening in the middle of the night with angioedema of the lips, hoarse voice, and difficulty with secretions. He was admitted for observation after treatment with antihistamines, steroids, and epinephrine led to only a small improvement in his symptoms. He had no family or previous personal history of angioedema. His past medical history was significant for type 2 diabetes and essential hypertension, for which he had been on an ACE-I for the past 7 years. He was given the diagnosis of ACE-Iassociated angioedema, and started on an angiotensin receptor blocker. Surprisingly, initial laboratory evaluation revealed a microcytic anemia, and despite a normal virtual colonoscopy 8 months prior, a workup to include colonoscopy revealed a rectal mass with pathology consistent with adenocarcinoma. He is currently undergoing radiation therapy and has had no further episodes of angioedema. Conclusions: We describe a case of ACE-I-associated angioedema after 7 years of treatment in a patient with rectal adenocarcinoma. Although it is unknown why some patients develop angioedema from ACE-I therapy while others are spared, this case serves to demonstrate that underlying malignancy may be an additional risk factor for ACE-I angioedema, and we believe this association requires further study.

P156 A WOMAN WITH BOTH SELECTIVE ANTIBODY DEFICIENCY AND PRIMARY CILIARY DYSKINESIA. L. Li*, C.L. Holland, Ann Arbor, MI. Introduction: Selective antibody deficiency and ciliary dyskinesia are both associated with recurrent sinopulmonary infections. Here we report a unique case of a young woman with debilitating sinopulmonary infections, whose workups yielded two diagnoses: selective antibody deficiency and primary ciliary dyskinesia. She was treated with immunoglobulin replacement, an effective intervention. Descriptioin: Patient is a 23-year-old Caucasian woman who has had frequent sinopulmonary infections since childhood, including otitis media, pneumonia and sinusitis, requiring multiple typanostomies and sinus surgeries. Family history is negative for primary immunodeficiency. Initial workups were normal for immunoglobulin levels, sweat chloride, alpha-1 antitrypsin level, tetanus and diphtheria titers. Six weeks after immunization with a polysaccharide vaccine, Pneumovax, her pneumococcal titer showed optimal response (>=1.3 mcg/ml) to only 4 of the 14 serotypes tested (23%). With her clinical history and suboptimal response to the polysaccharide antigen, she was diagnosed with selective antibody deficiency with normal immunoglobulin levels. Her recurrent infections have been debilitating with significant symptomology, and they seemed out of proportion to a single diagnosis of selective antibody deficiency. She underwent further diagnostic procedures, specifically nasal ciliary biopsy. The light microcopy showed very small percentage of cilia with active movements. Electronic microscopy showed ultrastructural abnormality in 72% of cilia examed, specifically central microtubual doublet disruptions, consistent with primary dyskinesia defect. In consideration of her severe clinical picture, she was started on immunoglobulin replacement with IVIG. She responded to the therapy with significant improvement, with only a few infections annually, and her quality of life also improved markedly. Discussion: This case demonstrates the existence of dual immunodeficiency disorders. In this patient with such frequent and debilitating infections, after establishment of selective antibody deficiency, it may be necessary to further investigate additional causes, such as ciliary dyskinesia, in this case. Further




Cross Section of Cilia with Disrupted Central Microtubule Pair

serositis may not be recognized until children become verbal. While cases have been described in patients as young as 4-months old, FMF is not often diagnosed before children are 2-years old. We describe the presentation, clinical course, and evaluation of a patient who presented with symptoms of Familial Mediterranean Fever at 5-weeks-old. As FMF can be complicated by secondary amyloidosis that can result in renal failure, it is important to include in the differential diagnosis of infants with recurrent fevers. Methods: A 6-month-old Ashkenazi Jewish male presented for an evaluation of recurrent fevers. He was a full-term, healthy newborn. He first developed a fever when he was 5weeks-old. He had vague symptoms and was diagnosed with a viral infection. The fever resolved within two days without treatment. Two weeks later, he again had a fever and was treated with antibiotics for a presumed upper respiratory infection. When he was 8-weeks-old, he was evaluated in the Emergency Department for a fever and had a negative infectious workup. One week later, he again had a fever and was admitted to the hospital. The infectious workup was again negative and he was discharged after 48 hours of negative cultures. Since then, he has continued to have fevers every 1-2 weeks and occasionally appears uncomfortable during these episodes. He was started on cimetidine by his pediatrician without resolution in his symptoms. His family background is from Poland and his older sister also had frequent fevers when she was younger. Results: Laboratory testing for Familial Mediterranean Fever revealed two copies of the V726A mutation in the pyrin (MEFV) gene. He was started on colchicine prophylaxis. Conclusions: FMF can manifest as early as 5-weeksold. Because symptoms may be difficult to recognize in non-verbal children, FMF should be included in the differential diagnosis of unexplained recurrent febrile episodes. Early diagnosis and initiation of prophylaxis is important to reduce morbidity and prevent amyloidosis.



A MISTAKEN CASE OF ANGIOEDEMA. A. Keswani*, A.T. Peters, Chicago, IL.

LYMPHOPENIA INDUCED BY ETANERCEPT. N. Talreja1, G.M. Cowan*2, M.C. Glaum3, R.F. Lockey3, 1. Wichita, KS; 2. Lutz, FL; 3. Tampa, FL.

more, the treatment with immunoglobulin replacement has led to marked improvement in her health and quality of life.

Case Presentation: ST is a 55 year old woman with rosacea, hypothyroidism and diabetes who presented with non-painful, non-pruritic periorbital edema. Her symptoms consisted of daily upper and lower eyelid swelling and erythema, without urticaria or oropharyngeal edema. These symptoms initially began 7 years ago and resolved after bilateral blepharoplasties. The edema returned 8 months ago. She denied the use of cosmetics or any recent changes in her skin care, laundry, or medication regimens. She denied any association with food. ST had previously been treated with prednisone for one month during which she had resolution of the edema. Upon discontinuation of prednisone, the edema returned. Topical steroids were ineffective. Her rosacea was previously treated with minocycline for several years but she self-discontinued therapy one year ago. ST’s physical exam was notable for non-pitting edema with erythema of the bilateral eyelids and erythematous papules over her bilateral cheeks and forehead. She was previously found to be allergic to nickel and fragrance on patch testing; however, complete avoidance of these contact allergens did not change her periorbital edema. Aeroallergen testing was unremarkable. Her blood tests demonstrated a normal C4 level, negative ANA and rheumatoid factor, normal TSH, normal albumin, normal creatinine, and mildly elevated ESR. ST was diagnosed with solid facial edema due to rosacea, known as Morbihan disease. Discussion: It is essential to consider many diagnoses when evaluating a patient with periorbital edema. This patient’s daily, isolated periorbital edema was not classic for angioedema. Her symptoms were unlikely due to contact dermatitis as they persisted despite complete avoidance of the allergens. Morbihan disease should be considered in patients with rosacea or acne vulgaris who present with persistent solid facial edema. It is a rare complication and can occur at any stage of disease, including mild disease. It is crucial to control disease activity, as persistent facial edema has been reported to cause visual impairment in severe cases. Short courses of oral steroids have been used successfully, as well as the combination of systemic isotretinoin with ketotifen or clofazimine. Blepharoplasty to excise the redundant edematous eyelid tissue has been reported to improve visual impairment; however, as in this case, the periorbital edema may return if the underlying disease is not treated.

P158 MANIFESTATION OF FAMILIAL MEDITERRANEAN FEVER IN EARLY INFANCY: A CASE REPORT. D. Hirsch*, V. Bonagura, Great Neck, NY. Rationale: Familial Mediterranean Fever (FMF) is an autosomal recessive disease characterized by intermittent episodes of fever and serositis. Diagnosing FMF in early infancy can be difficult because the pain associated with


Introduction: Current guidelines do not recommend routine complete blood counts (CBC) with the use of tumor necrosis factor alpha (TNF-α) inhibitors. Several case reports of neutropenia and thrombocytopenia are reported in the literature. This is the first case report of significant lymphopenia associated with the use of etanercept. Case History: A 64-year-old female with seronegative non-erosive rheumatoid arthritis (RA) and rheumatoid associated lung disease presents to the clinic with leukopenia. She has been on prednisone, 20 mg daily and leflunomide, 20 mg daily, each by mouth, for the past 6 months. She was treated previously for 2 years with methotrexate and adalimumab, the former of which was stopped six months ago for a open lung biopsy and the latter of which was stopped because of neuropathy. She received 5 doses of etanercept over a period of 5 weeks but stopped this therapy secondary to injection site reactions. She was asymptomatic with an absolute lymphopenia of 307 cells/mL (850 – 3900 cells/mL), low CD3 134 cells/mL (840 – 3060 cells/mL), CD4 45 cells/mL (490 – 1740 cells/mL), CD8 76 cells/mL (180 – 1170 cells/mL) and CD19 58 cells/mL (110 – 660 cells/mL) and a normal total leucocyte count on two occasions. Folate, B12 and methylmalonic acid levels were normal. Her lymphopenia resolved after discontinuation of etanercept for three months. The patient is currently on abatacept 250 mg IV once monthly and prednisone 3 mg by mouth daily. Conclusion: TNF-α inhibitors may cause cytopenia as TNF-α regulation is related to cellular differentiation of immune cells through the expression of other cytokines. There may be a need to monitor the CBC in patients on TNF-α inhibitors because of reported neutropenia, thrombocytopenia and, in this case, lymphopenia.

P160 A 3 YEAR OLD MALE WITH DNA LIGASE IV DEFICIENCY. M. Paul*, M.B. Bober, M.L. DeFelice, Wilmington, DE. Introduction: Ligase IV deficiency is a rare AR disorder due to mutations in the DNA ligase IV gene. Ligase IV protein is critical in repair of DNA double-stranded breaks through non-homologous end-joining. Depending on the mutation, ligase IV deficiency generally presents in 2 ways: a syndrome of primordial dwarfism, pancytopenia, and cellular radiosensitivity with mild immune defects or a radiosensitive SCID without developmental defects. We present the unique case of a child with microcephalic primordial dwarfism (MPD) who also has an immune phenotype consistent with T-B-NK+ SCID. Methods: The patient is a 3 year old male with MPD who underwent genetic evaluation as well as investigation of immune function. Lifetime infection history includes 1 AOM, 1 UTI, 2 episodes of bronchitis, 1 pneumonia, and 3


ABSTRACTS: POSTER SESSIONS episodes of severe viral gastroenteritis requiring hospitalization. Infections have increased in severity over time. Exam findings include a proportionately shortstatured male with height, weight, and head circumference >2 SD below the mean, dysmorphic facies, hyponasal speech, and small tonsils. Results: Genetic testing revealed a truncating hypomorphic compound heterozygous nonsense mutation (R814X) of the ligase IV gene, along with undetectable levels of ligase IV on Western blot. There was marked radiosensitivity on colony survival assay consistent with a DNA repair disorder. Immune evaluation revealed leukopenia, thrombocytopenia, low IgG 366 mg/dL (477-1334 mg/dL), failure to mount a polysaccharide response, normal IgA and IgM, protective tetanus and diphtheria titers, and normal complement pathway function. Lymphocyte enumeration showed CD3+ T cells 465 cells/mcL (1400-3700 cells/mcL), CD4+ T cells 165 cells/mcL (700-2200 cells/mcL), CD8+ T cells 170 cells/mcL (4901300 cells/mcL), CD19+ B cells 30 cells/mcL (390-1400 cells/mcL), and normal CD16+CD56+ NK cells for age. The number of recent thymic emigrants was reduced. Lymphocyte proliferative response to mitogens was decreased compared to control. Conclusion: Patients with previously reported nonsense mutations in ligase IV have presented with syndromic features and only mild immune defects, if any. This patient is distinct in that he has both the syndromic features of ligase IV deficiency and an immune phenotype consistent with radiosensitive SCID. Given the progressive nature of this disease, he will undergo bone marrow transplant.

P161 DELAYED AND PROLONGED ANAPHYLAXIS SECONDARY TO LIDOCAINE. J. Moreau*, S. Farzan, Great Neck, NY. Introduction: Anaphylaxis is a life-threatening event that can vary in presentation. Reactions occur within seconds to minutes of exposure to an allergen. Triggers include food, insect stings, and medications. We report a novel case of a patient who experienced delayed and prolonged anaphylaxis after endoscopy, secondary to lidocaine. Methods: We describe the case of GC, a 44year-old woman who underwent endoscopy. The endoscopy tools were sterilized with Cidex (glutaraldehyde) and she received propofol and lidocaine. GC awoke the next day with facial angioedema, dysphagia, and shortness of breath. She received epinephrine, anti-histamines, and steroids and was sent home after observation in the ER. Two days after endoscopy, GC developed abdominal pain and urticaria on her lower extremities, and was admitted. Her symptoms resolved with H1-, H2-blockers and corticosteroids. She was discharged on a prednisone taper, cetirizine, fexofenadine, famotidine, proton pump inhibitor, and sucralfate. Results: During hospitalization, laboratory evaluation revealed an elevated tryptase level on two occasions (27.5 ng/mL and 35.8 ng/mL respectively). ANA, RF, C4, C1 esterase level and function were within normal limits. Repeat laboratory studies as an outpatient demonstrated an elevated IgE receptor antibody (19.7%) and normal tryptase levels (3.5 ng/mL and 4.3ng/mL, respectively). Thyroid function tests and anti-thyroid antibodies were normal. Skin prick testing to diluted and full strength concentrations of Cidex and propofol were negative. Skin prick testing to diluted and full strength concentrations of lidocaine were also negative. However, she developed a delayed reaction (wheal and erythema) to full strength subcutaneous lidocaine one hour after intradermal placement. Conclusions: Physicians should consider the possibility of delayed anaphylaxis in patients presenting with multiple organ system involvement and obtain tryptase levels during and subsequent to its occurrence. Our patient’s presentation is atypical of an acute allergic reaction considering its delayed onset (>12 hours) and prolonged presentation of symptoms. However, the skin, gastrointestinal, and respiratory manifestations, elevated tryptase levels and delayed reaction on intradermal skin testing support the diagnosis of a delayed anaphylactic reaction.

year old male with two prior episodes of urticaria presented for evaluation of acute isolated tongue swelling. The patient was initially seen at an outside emergency room on two separate visits where he was administered steroids, epinephrine, and antihistamines with only a minor and transient improvement. He was subsequently transferred to the intensive care unit for airway protection where he was administered fresh frozen plasma (FFP), C1 esterase inhibitor, corticosteroids, antihistamines, and epinephrine prior to consultation with the allergy/immunology service. The patient had no signs of respiratory distress, but he was unable to swallow his secretions. He was otherwise well appearing and afebrile. Results: Physical exam showed asymmetric erythematous tongue swelling without exudate and without uvula or soft palate involvement. The floor of the mouth was firm to palpation. The dentition was poor. Complement studies were within normal limits but tempered by the recent infusion of FFP. A CBC revealed a leukocytosis with a mild left shift compatible with recent administration of corticosteroids. A CT scan showed heterogeneous low-attenuation with asymmetric swelling of the tongue and cervical lymphadenopathy, suggestive of infection. Blood cultures grew Micromonas (Peptostreptococcus) micros, an oral anaerobe. Conclusion: This patient initially presented with findings on physical exam suggestive of AE but both the history of his illness and his response to treatment cast doubt on this diagnosis. An infectious etiology was eventually substantiated by the positive blood culture and the CT scan. He was treated intravenously with broad spectrum antibiotics and had rapid improvement in symptoms. While acute onset of swelling of the tongue may be due to AE, other potentially life-threatening causes of swelling such as infection (e.g. Ludwig’s angina) must be considered.

P163 TRANSIENT RASH ATTRIBUTED TO HAEMOPHILUS B ANTIGEN AFTER VACCINATION. R. Sporter*, B. Kaplan, Great Neck, NY. Rationale: Although serious immune-mediated reactions to vaccines are rare, pediatricians and allergists are often confronted with the management of a patient who has experienced a minor reaction to vaccination. Determination of the causative agent is often difficult, as most vaccines contain multiple antigens and excipients, and several vaccines are often administered simultaneously. We present the case of a 5-month-old girl who was referred for a skin rash after vaccination, which we determined to be due to haemophilus b antigen, as well as a logical methodology for evaluating such reactions. Methods: Case report Results: A 5-month-old girl was referred after experiencing a blotchy skin rash 5 minutes after receiving two vaccines, which resolved after 20 minutes without treatment. There was no associated shortness of breath or wheeze. We opted not to perform skin testing due to the mild nature of the reaction and the desire to avoid excessive skin tests in this very young patient. We administered the vaccine antigens individually, each at the next recommended dosing interval, in challenge doses. We selected alternative preparations to administer based on subsequent reactions and components of the individual vaccines, using the CDC’s Vaccine Excipient & Media Summary which lists all components of commercially available vaccines (see table). Haemophilus b antigen was determined to be the causative agent. Conclusions: Identifying the causative agent in a patient with a vaccine reaction is critical to minimize the chance of reaction recurrence which, if IgE-mediated, could be life-threatening upon reexposure. Concurrently, the necessity of immunization cannot be overstated. Many reactions are often attributed to vaccine excipients. In this case, careful evaluation demonstrated that the rash was in response to the hemophilus b antigen itself. We present a logical methodology to ascertain the causative agent(s) following a minor vaccine reaction, so that they may be avoided when possible, while allowing for safe administration of the necessary immunizations.

P162 CASE REPORT: LUDWIG’S ANGINA PRESENTING AS ANGIOEDEMA. W.C. Anderson*1, R.W. Vandivier2, S.C. Dreskin2, 1. Denver, CO; 2. Aurora, CO. Background: Angioedema (AE) is a self-limited, localized, often asymmetric swelling of the subdermis or submucosa that may involve the oropharynx. The differential diagnosis of AE includes hereditary, acquired, and idiopathic. Ludwig’s angina is a rare, rapidly spreading, and potentially life-threatening cellulitis of the sublingual and submaxillary spaces. Here we present a patient who was initially diagnosed with acute onset of idiopathic AE and was finally determined to have Ludwig’s angina. Case History: A 23







IGG4-RELATED DISEASE: A NOVEL PROTEAN SYNDROME IN EVOLUTION. J.G. Ghably*1, T.R. Borthwick1, J.M. Litchfield1, T.J. Oneil1, H.S. Mostafavipour1, P. Datta2, G. Krishnaswamy1, 1. Johnson City, TN; 2. Washington, DC.

Introduction: A presentation of exacerbation of systemic lupus erythematosus (SLE) as symptoms of nausea, emesis, fevers and abdominal pain along with decrease in complement levels and increase in inflammatory markers, amylase, triglyceride and lipase levels. Case: Seven year old female with a past medical history significant for SLE and stage 1 nephritis who presented with symptoms of decreased appetite, joint pains, emesis, nausea, and fevers for 3 days. Labs showed C3 level of 36 mg/dL and C4 levels of 4 mg/dL as well as elevated CRP of 2.2 mg/dL and ESR of 120 mm/hr. She was given pulse dose steroids due to concern of SLE exacerbation. She then received daily steroids at a higher dose then her home dose. Her initial symptoms along with abdominal distension returned after initial improvement. Labs showed elevated amylase level of 806 U/L, lipase of 1706 U/L, and triglycerides 683 mg/dL. CT imaging of the abdomen was consistent with acute pancreatitis. She was given one dose of cyclophosphamide. She was kept NPO per surgery recommendations and was given pain medications and IV fluids. Her repeat lab work revealed normal C3 and C4 levels as well as improvement in inflammatory markers and amylase, lipase, and triglycerides. She was started on cyclophosphamide every 2 weeks. All of her symptoms improved except for intermittent abdominal pain. A pancreatic pseudocyst was found on repeating imaging. She was kept NPO for 6 weeks and then had corrective surgery after which all of her abdominal symptoms resolved. Discussion: SLE exacerbations can be quite varied in presentation and usually include fevers, arthralgias, worsening pleural or pericardial effusions, seizures or altered mental status, and worsening of lab values such as decrease in complement levels and increase in inflammatory markers or worsening anemia. Pancreatitis is not a very common presentation of SLE exacerbations and is something that should be considered in patients with SLE and presentation of symptoms consistent with pancreatitis like our patient. Aggressive treatment with high dose pulse steroids as well as cyclophosphamide has been shown to resolve acute exacerbations of pancreatitis from SLE exacerbations.

P165 AN UNUSUAL CASE OF CRYPTOCOCCAL MENINGITIS IN AN IMMUNOCOMPETENT PATIENT WITH HYPEREOSINOPHILIC SYNDROME. M.A. Slack*, P.U. Ogbogu, Columbus, OH. Introduction: Hypereosinophilic Syndrome (HES) is a unique group of disorders featuring persistently elevated serum eosinophils (>1.5X109) without evidence of secondary cause, and eosinophilic end organ involvement. A subset of patients have lymphocytic variant HES (17%) where activated clonal or aberrant T lymphocytes produce cytokines that induce eosinophil hematopoiesis. Oral corticosteroids are the mainstay of treatment in this disorder. The third most common cause of morbidity in HES is infection, however, to our knowledge there have been no reported cases of HES –associated cryptococcal meningitis. Case Description: The patient is a 33-year-old female with a history of lymphocytic variant HES (absolute eosinophil count 800-21,700) maintained on chronic low dose oral steroid therapy. She presented with complaints of one week of neck pain, nausea, fever, blurred vision, headache, and progressive altered mental status. She had a white blood cell count (WBC) of 10,600, eosinophil count of 800, and lymphocyte count of 800. Lumbar puncture revealed elevated opening pressures of >60mmHg, elevated CSF WBC and total protein, and low CSF glucose. She was treated with empiric antibiotics for bacterial meningitis. Subsequently CSF and peripheral blood cultures revealed budding encapsulated yeast consistent with Cryptococcus neoformans. Her laboratory evaluation indicated an elevated CSF cryptococcal antigen level. She was started on Amphotericin B and Flucytosine. Her prednisone dose was slowly decreased from 20mg daily to 5mg daily. The patient’s confusion resolved over the course of 1 month on antifungal therapy. Conclusion: Cryptococcal meningitis is known to occur in higher frequency in immunocompromised patients (e.g. HIV or solid organ transplant recipients). While there are case reports of cryptococcal meningitis in patients on high dose steroid therapy for acute liver disease, CLL, and systemic lupus erythematosus, it has not been reported in a patient with HES. The risk factors for developing cryptococcal meningitis associated with HES or HES treatment are currently unknown. This case illustrates the need for heightened awareness of this opportunistic infection in patients with HES.


Introduction: IgG4-related disease (IgG-4 RD) is a novel syndrome with protean manifestations-including autoimmune pancreatitis, salivary gland disease and pulmonary complications. Case report: A 59 year old male was admitted for indolent pancreatitis, weight loss, and night-sweats. He was first hospitalized 4 years previously with pressure-like chest pain with negative stress test. PFT’s at the time revealed obstruction leading to a diagnosis of COPD. Soon afterwards, he began to experience recurrent episodes of profuse rash diagnosed as leukocytoclastic vasculitis on biopsy. At the time, dermatology diagnosed possible Churg-Strauss vasculitis but workup a year later refuted this diagnosis. This workup only revealed positive RF, but normal PFTs, chest xray, eosinophil count, compliment levels, CRP, ESR, IgE, and negative ANCA. A year later, he presented to our institution with recurrent abdominal pain and nausea for over 3 months duration. Elevated serum lipase, ESR, CRP, eosinophils, and creatinine were seen. Abdominal US showed minimally dilated common bile duct and no gallstones. MRI revealed diffuse pancreatic involvement, bilateral renal inflammatory masses, and biliary duct thickening /dilatation. Further workup revealed positive RF and ANA, but negative hepatitis panel and auto-immune antibodies, decreased complement levels, elevated IgE and IgG (class 1, 2, and 3) and elevated liver function tests. Serum protein electrophoresis demonstrated polyclonal hyperglobulinemia. A CT chest showed inflammatory lung nodules and mediastinal lymph nodes. Clinical Immunology was consulted due to multisystem disease. At their recommendation, a renal biopsy by interventional radiology was carried out and following special stains, the diagnosis of IgG4-RD was made. He was started on prednisone with full recovery, with plans made for Rituximab infusion soon. Conclusion: IgG4RD is in the differential for multisystem disease such as vasculitis, sarcoidosis or granulomatous infections. A careful assessment, tissue biopsy and requesting special stains for IgG4-expressing plasma cells is required to confirm the diagnosis. Glucocorticoid therapy leads to rapid improvement but frequent relapses are also likely. Newer data suggests remarkable efficacy for Rituximab, and anti-B cell therapy. Untreated, the disease can culminate in end-stage fibrotic complications and organ failure.

P167 DEVELOPMENT OF A MYELOID SARCOMA IN ASSOCIATION WITH SYSTEMIC MASTOCYTOSIS. T. Campbell*, F. Hsieh, Cleveland, OH. Introduction: Systemic mastocytosis (SM) is characterized by the abnormal growth and accumulation of mast cells in one or more extracutaneous organs. Mastocytosis is clinically heterogeneous and patients who have SM coexisting with an associated hematologic non-mast cell lineage disorder are designated as having SM-AHNMD. A variety of myeloid, myelodysplastic, and lymphoproliferative diseases have been associated with SM-AHNMD. Methods: Retrospective chart review of one subject over a five-year period. Results: We report a case of an 87 year old female with SM-AHNMD where the AHNMD was a myeloid sarcoma that presented five years after the initial diagnosis of systemic mastocytosis. The subject initially presented at age 82 with abdominal enlargement and abdominal CT demonstrated splenomegaly with enlarged intra-abdominal lymph nodes; a lymph node biopsy and subsequent bone marrow examination performed at an outside hospital was read as myelofibrosis. She then developed a chest wall nodule which was biopsied and diagnosed as mastocytosis with additional dysmyelopoietic changes. A repeat bone marrow biopsy and review of outside slides demonstrated systemic mastocytosis without meeting full criteria for AHNMD. c-kit D816V gene mutation analysis was positive and the serum tryptase was 519 ng/mL. As she had no symptoms outside of abdominal swelling and no target organ damage, a diagnosis of indolent systemic mastocytosis was made. She did well and three years later had combined aortic and mitral valve surgery at our hospital with no complications. Five years after diagnosis she presented with an enlarging, painful axillary mass developing from pea to tennis ball size over 3 months. A needle biopsy demonstrated a myeloid sarcoma. Despite therapy with cytarabine the sarcoma continued to enlarge and a 2nd sarcoma developed on the lower back. Palliative X-ray therapy failed to control these lesions and the patient expired 2 months later. Conclusions: SM is often misdiagnosed as other hematologic disease. Although transformation of indolent SM to more aggressive disease classifi-


ABSTRACTS: POSTER SESSIONS cations is uncommon, it can occur. Mortality in patients with SM-AHNMD is generally determined by the AHNMD portion of their disease. To the best of our knowledge, this is the first documented case of SM-AHNMD where the AHNMD was a myeloid sarcoma.

P168 TREATMENT OF ADULT HYPER-IGD SYNDROME WITH CANAKINUMAB. C. Curtis*, C.C. Fox, Columbus, OH. Background: Hyper-IgD syndrome (HIDS) is a rare autoinflammatory disease characterized by lifelong recurrent episodes of systemic inflammation and elevated IgD levels. This periodic fever syndrome frequently presents in the first year of life with intermittent fevers and elevated serum inflammatory markers. Associated symptoms may include abdominal pain, diarrhea, rashes, arthralgias, aphthous ulcers and lymphadenopathy. HIDS is caused by mutations in the gene encoding mevalonate kinase (MVK), an enzyme involved in isoprenoid biosynthesis; this results in elevated levels of IL-1β . We present a case of HIDS which was successfully treated with canakinumab, a fully humanized anti-IL-1β monoclonal antibody. Case: A 35 year old female was referred for evaluation of immunodeficiency. The patient reported multiple admissions for periodic fevers associated with mucosal ulcers, myalgias, arthralgias, abdominal pain, and lymphadenopathy. Abdominal CT scan demonstrated splenomegaly and retroperitoneal and mesenteric lymphadenopathy. Lymph node biopsy showed no abnormal lymphocyte populations. Previous workups were negative for autoimmune, malignant, or infectious etiologies of fevers. Our evaluation found elevated inflammatory markers, as well as an elevated IgD level of 69 mg/dL (normal <10 mg/dl). Further testing identified I268T and V377I mutations in the MVK gene, confirming the diagnosis of mevalonate kinase deficiency with resultant HIDS. Trials of multiple therapeutic agents provided little benefit. Febrile episodes continued to worsen in frequency and duration until she was receiving nearly continuous steroid courses. She was started on canakinumab 150 mg subcutaneously every 8 weeks, resulting in significant reductions in febrile episodes and associated symptoms, with minimal adverse effects of therapy. Conclusions: This case is unique in two aspects. Firstly, the diagnosis of HIDS in this patient was delayed until the 4th decade. Furthermore, while canakinumab has been used successfully in a limited number of cases in Europe, to our knowledge this is the first report of use of this therapy for HIDS in the United States. Gathering data on such patients is crucial in that other therapies for HIDS are inconsistently effective or limited due to side effect profiles. This case demonstrates the safety and efficacy of canakinumab for treatment of HIDS.

P169 POST-SURGICAL PLEURAL EFFUSION AS THE INITIAL PRESENTATION OF NICKEL HYPERSENSITIVITY AND RAPID RESOLUTION WITH CORTICOSTEROID TREATMENT. M. Korah-Sedgwick, L. Wall*, K. Paris, New Orleans, LA. Purpose: Hypersensitivity to surgical metal implants is well described in orthopedic literature. However, methods for pre-surgical evaluation, diagnosis, and treatment are not well established. We report a case of a patient with no prior history of metal hypersensitivity or other atopic disease who developed signs of implant intolerance and was treated successfully with minimal intervention. Methods: Skin testing was performed using a commercially available rapid use epicutaneous patch test. Results: A 16 year old male presented with a one week history of fever and shortness of breath, 21 days after surgical correction of pectus excavatum involving implantation of a stainless steel bar (Nuss procedure). Evaluation revealed leukocytosis, eosinophilia, elevated ESR, CRP, and pleural effusion. A chest tube was placed and IV antibiotics were started. Clinical improvement was demonstrated by decreased shortness of breath and fever resolution. Despite negative blood and pleural fluid cultures, chest tube drainage remained significant. Pleural fluid showed lymphocyte and eosinophil predominance, and a hypersensitivity reaction to the implanted steel bar was suspected. Patch testing confirmed Type IV Hypersensitivity to nickel. With nickel hypersensitivity thus identified, antibiotics were discontinued and oral Prednisone initiated (1mg/kg/day for 5 days, then tapered for 14 days total) which produced rapid cessation of the chest tube drainage. He remains asymptomatic one year following treatment. Conclusion: This case emphasizes that clinically significant hypersensitivity reaction to implanted metal hardware may occur in patients without a history of atopy, rash, or metal intolerance. Rarely, metal hypersensitivity following the Nuss procedure may manifest as pleural effusion without overlying dermatitis, offering few clues to the diag-

nosis. In this case, diagnosis was demonstrated by eosinophilia in pleural fluid, positive patch test to nickel, and response to corticosteroids. Although treatment methods have not been standardized, we clearly document that resolution may be achieved and maintained with a brief course of oral corticosteroids. Therefore, more aggressive treatment including higher dose and prolonged course of corticosteroids, or surgical implant removal, may not be necessary.

P170 SAFETY OF ZOSTER LIVE VACCINE IN AN ADULT WITH α-GAL ALLERGY. M.L. Bandino*, R. Gomez, K. Waibel, San Antonio, TX. Rationale: Immunoglobulin (Ig) E antibodies to galactose-α-1,3-galactose (α-Gal) are associated with delayed anaphylaxis to mammalian food products and gelatin-based foods. The live zoster vaccine, which contains 15,580 mg porcine gelatin per 0.65 mL dose, is approved for adults ages 50 years and older has been reported to cause allergic reactions. However, it is not known whether these patients had clinical α-Gal allergy. Herein, we report a patient with αGal allergy who successfully tolerated the live zoster vaccine. Case Report: A 58 year-old Caucasian male with α-Gal allergy whose initial presentation included multiple delayed anaphylaxis episodes after ingestion of lightly cooked ground beef. He denied clinical reactions to thoroughly cooked beef, pork, chicken, or turkey. The patient was referred to our clinic to assess the safety of gelatin-containing vaccines. Results: The patient had a positive skin prick test to beef jerky, positive intradermal skin tests to beef and pork, and positive sIgE to pork, beef, and α-Gal. Skin and immunoblot testing to pork and the live zoster vaccine were negative. After obtaining informed consent, the patient was administered a single, live zoster vaccine dose; no immediate or delayed reaction resulted. Conclusions: α-Gal allergy is a well characterized specific IgE reaction to mammalian protein; however, much is still unknown regarding this patient cohort. We report a single α-Gal allergy case who was clinically reactive to lightly cooked beef and had positive skin testing and sIgE to beef and pork, but tolerated the live zoster vaccine without reaction. Since porcinederived gelatin-containing vaccines may have the potential to elicit IgE mediated reactions in patients with α-Gal allergy, further safety studies should be considered.

P171 NON-COMPLEMENT DEFICIENCY ANGIOEDEMA RESPONSIVE TO C1 ESTERASE INHIBITOR REPLACEMENT. D.K. Bayer*, M.M. DeGuzman, I.C. Hanson, Houston, TX. Angioedema can be characterized as either complement-associated angioedema, designated type I and II hereditary angioedema (HAE), and noncomplement-associated, designated as type III HAE or non-histaminergic idiopathic angioedema. Medical record and literature review were completed. A 13 year old Caucasian pre-menstrual female presented in early childhood with daily, painful, non-pruritic angioedema without urticaria, wheezing, or anaphylaxis. Her exam revealed ocular and lip edema and hyperextensible joints without arthritis or enthesitis. She denied use of any medication. Family history was positive for autoimmune disease including thyroiditis, trypsin deficiency, and SLE but negative for angioedema. Laboratory evaluation revealed low titer positive ANA (1:160 FANA), negative autoantibodies to nuclear antigens, normal C-reactive protein, serum tryptase, serum IgE, absolute eosinophil count, free T4, thyroid stimulating hormone, thyroid autoantibodies, C1 esterase inhibitor level and function, and complement levels. Her clinical course included progressive and more generalized angioedema throughout grade school and pre-teen years. A diagnosis of type III HAE was entertained despite her young age, lack of estrogen association, and normal Factor XII studies. She was unresponsive to H1/H2 inhibitors, steroids (oral or IV, including pulse), epinephrine, monteleukast, hydroxychloroquine, cyclosporine, or methotrexate. After 2 doses of C1 esterase inhibitor replacement, her angioedema significantly improved, including improvement of ocular and lip swelling. C1 esterase inhibitor replacement has documented efficacy in type I and II HAE through a mechanism that modulates production of kinins and vasoactive mediators that allow for tissue permeability. Kinin inhibitors have shown some efficacy in Type III HAE or idiopathic angioedema. Our patient with non-complement deficiency-driven angioedema responded to complement supplementation with marked improvement. The mechanism for her response is unclear but suggests that even in the face of normal complement levels and function, C1 esterase inhibitor may impact vasoactive amines and diminish tissue permeability. We suggest that this patient’s clinical response should prompt further evaluation of C1 esterase inhibitor use in non-complement-driven angioedema states.








Hypereosinophilic syndrome (HES) is characterized by heterogeneous clinical presentations depending on the specific organ involvement. Cardiovascular complications are the most common cause of mortality and morbidity in HES patients. Here we describe a 15 y/o patient with HES who had recurrent massive cardiovascular thrombo-embolic disease. Case report: A 15-year-old female with a history of persistent peripheral blood eosinophilia, multiple DVTs and pulmonary embolisms (PEs) was hospitalized after collapsing at school with massive PE involving the right atrium (RA). She underwent open-heart surgery with thrombus resection and embolectomy. She had been maintained on Lovenox therapy and prednisone 30 mg daily with questionable compliance. She was started on sc interferon-gamma (INFg) half a million unit with gradual increase to 3 million units daily over 4 weeks. Anticoagulants were continued. The patient was readmitted 3 weeks later with increased RA thrombus size and IVC thrombus detected by routine follow up echocardiogram. Imatinib 100mg was added for the possibility of Myelodysplastic Syndrome (MDS). Despite treatment, subsequent echocardiograms showed further increase in the size of the right atrial thrombus. Compassionate use of Mepolizumab was approved and she was started on 750 mg IV every month. Subsequently the dose of oral prednisone was tapered to 15 mg with stable peripheral blood absolute eosinophil count (AEC) of 150/mm3. Laboratory tests revealed AEC ranging between 1400 and 2900/mm3 since 2011 with increased counts during acute thrombotic events, normal serum tryptase level (7.9 ng/ml), and decreased CD19 count 36/mm3). Testing for mutations in JAK2, BCR/ABL, and CHIC-2 was negative. Bone marrow biopsy showed eosinophilia and 8% of cells with Trisomy 8. Work- up for connective tissue disease and hypercoagulable states was normal with negative lupus anticoagulant, negative ANA, and normal C3 and C4. Conclusion: Hypereosinophilia is one of the known predisposing factors to thrombosis. Diagnosis remains a challenge for atypical cases with abnormal cytogenetics. In our patient, treatment was further complicated by poor compliance to prescribed medications. Normalization of AEC by various therapeutic strategies as well as anticoagulation remains the main stay of treatment for thrombo-embolic events in patients with HES.

Introduction: Determining the etiology of severe eosinophilia (>5000 cells/mL) can be difficult, and has important implications for treatment. The differential diagnosis includes hypereosinophilic syndrome, malignancy, ChurgStrauss Syndrome, and infection (fungal or parasitic). Treatments range from conservative to high-risk chemotherapy. We report the case of a boy with severe eosinophilia who was ultimately diagnosed with Toxocariasis through serial serologic examination. Case Description: A 6 year old Caucasian boy presented with a 3 week history of fatigue, vomiting, diarrhea, and 3kg weight loss. The past medical history was unremarkable. There was no family history of inflammatory bowel disease. Social history indicated that he lived in a suburban community with his parents, brother, and two reportedly healthy dogs. Physical examination was normal. There was no abdominal tenderness, bruising, oral ulcers, or rash. Ophthalmologic exam was normal. Laboratory evaluation revealed an absolute eosinophil count of 5796 (normal < 500 cells/mL). Because of his eosinophilia he was admitted to the hospital for further diagnostic evaluation. Serial eosinophil counts peaked at 15,700 before trending lower. Stool guiac was positive. Metabolic panel, liver function tests, ESR, Troponin level, stool ova and parasites evaluations were all negative. Computed Tomography of the abdomen and pelvis revealed circumferential thickening at the terminal ileum. EGD, colonoscopy, and Echocardiogram were normal. Fluorescent in situ hybridization for FIP1L1 mutation was normal. ELISAs for various parasitic antibodies revealed progressive elevation in specific IgG for Toxocara. He remained asymptomatic in the hospital and was discharged home without antihelminthic therapy as his symptoms were mild. Dogs were treated for the parasites, and his eosinophilia resolved. Conclusion: Parasitic infection is an important yet often overlooked cause of severe eosinophilia. Toxocariasis in this case was most likely secondary to infection by the roundworm Toxocara canis. Stool ova and parasite evaluation is unhelpful in this disease as the parasite resides in tissue and can be missed without serologic examination. Our case highlights the importance of performing serologic testing for parasites in acute severe eosinophilia.


P173 ABSENCE OF B-CELLS IN CVID EXPLAINED BY USE OF RITUXIMAB TO TREAT AIHA/ITP COMPLICATIONS OF CVID. S.C. Minnicozzi*1, J. Kennedy2, N. Schroeder2, L. Borish2, 1. Baltimore, MD; 2. Charlottesville, VA. A 27-yo female was admitted to the ICU for fever, rigors, and altered mental status. Her PMHx was significant for recurrent sinus infections and pneumonias since childhood. She also carried the diagnosis of autoimmune hemolytic anemia (AIHA) and idiopathic thrombocytopenia (ITP) during early teenage years, which was then ascribed to Evans syndrome and treated with intravenous immunoglobulin (IVIG). The IVIG resolved her hemolytic anemia, however her ITP persisted and she subsequently received a course of Rituximab. At no time were immunoglobulin levels checked despite the history of frequent and severe infections and, unfortunately, she underwent a splenectomy in 2008. She subsequently developed a third autoimmune disease, autoimmune sensorineural hearing loss. 2 months prior to our evaluation she was admitted to the ICU for facial cellulitis. During her current evaluation immunoglobulins were finally checked and demonstrated an IgG 259.0, IgA, 38.9, IgM 4.2 (mg/dl). Flow cytometry was striking for revealing a CD19 of 0%, along with normal CD16 (13%), CD3 86%, CD4 (46%; absolute n=430), and CD8 37%. She was treated with antibiotics and started on IVIG for CVID. CT scan did not demonstrate thymoma, ruling out Good’s syndrome. This case identifies a patient with undiagnosed CVID since childhood who received rituximab (anti-CD20 antibodies), for the CVID complications of AIHA/ITP. This treatment led to the eradication of her B cells. Absence of B cells in hypogammaglobulinemia patients raises the suspicion of X-linked (BTK) or autosomal recessive congenital B cell deficiency or Good’s syndrome. However, genetic B cell deficiency is ruled out by her having developed autoimmune antibody-mediated diseases. Rituximab does not normally cause long-term eradication of B cells. However this case points out that B cell eradication occurs in patients with underlying CVID. In addition, this case again emphasizes the importance of avoiding splenectomy in patients who have hypogammaglobulinemia.


IGA NEPHROPATHY IN A CHILD WITH CHRONIC GRANULOMATOUS DISEASE. S. Ho*, F.C. Schmalstieg, Galveston, TX. Introduction: Chronic Granulomatous Disease (CGD) is a rare primary immunodeficiency in which phagocytes have defective oxidative burst predisposing those afflicted to bacterial and fungal infections with granuloma formation. There has been some evidence that patients with CGD have an increased rate of autoimmune disease including IgA nephropathy1. Here we report a case of an 8 year of boy with CGD and IgA nephropathy. Only two other cases of CGD associated IgA nephropathy have been reported1,2. Case Report: An 8 year old male with X-linked CGD on prophylactic trimethoprim/sulfamethoxazole and itraconozole presented to clinic for a one week history of dark colored urine with associated polyuria as well as two days of congestion, clear rhinorrhea and malaise. Several weeks prior to the onset of dark urine, the child had a viral gastroenteritis necessitating a brief hospital stay for intravenous hydration. He denied skin rashes, sore throat, body aches, fevers, back pain, dysuria, abdominal pain, diarrhea or swelling. Physical exam was unremarkable except for 2-3+ tonsils without erythema or exudate. In clinic his urine was noted to be tea colored. Urine dipstick revealed positivity for bilirubin, leukocyte esterase as well as 250 RBCs, and 2+ protein. The patient was admitted to the hospital for expedited workup with concern for glomerulonephritis. The initial differential included post-streptococcal glomerulonephritis, IgA nephropathy, interstitial nephritis, and vasculitis. Labwork obtained was only significant for anemia (hemoglobin 10.5), decreased GFR (69%), and elevated creatinine (1.0). Other workup including renal ultrasound, serum complement levels and urine eosinophils were within normal limits. Renal biopsy was performed and the findings were consistent with IgA nephropathy. The patient was started on high dose prednisone with resolution of proteinuria and dark urine within a few weeks, and normalization of creatinine 2 months after initiation of treatment. Discussion: A mechanism linking IgA nephropathy and CGD is unclear. Although it is possible that the child’s preceding viral gastroenteritis or current upper respiratory tract infection led to an increased production of IgA and IgA deposition onto the glomerulus, the time frame between onset of his dark urine do not correlate with either viral illness. The


ABSTRACTS: POSTER SESSIONS link between IgA nephropathy and oxidative stress has been well documented in animal models and human studies 3-10. Markers of oxidative stress such as increased levels of nitric oxide and lipoperoxide along with decreased levels of superoxide dismutase, catalase and glutathione peroxidase may lead to a predisposition of those with CGD to develop of IgA nephropathy. Conclusion: We report a case of IgA nephropathy in a child with CGD. We hypothesize that CGD may predispose patients to IgA nephropathy due to decreased ability to metabolize reactive oxygen species.

P176 FAMILIAL MEDITERRANEAN FEVER IN A CHINESE PATIENT. S. Siddique*1, J. Hochfelder2, V. Bonagura2, 1. Brooklyn, NY; 2. Great Neck, NY. Introduction: Familial Mediterranean Fever (FMF) is a hereditary inflammatory disorder caused by mutations in the MEFV gene, typically causing symptoms including abdominal pain, joint involvement, pleuritis, myalgias, and intermittent fevers with no source. FMF usually affects people originating from around the Mediterranean Sea. Here we describe a case of a Chinese boy diagnosed with FMF after presenting with atypical symptoms of aphthous stomatitis and cervical lymphadenitis. Methods: Case report. Results: A 7-year-old male of Chinese descent presented with chronic cervical lymphadenitis, aphthous stomatitis recurring in a monthly-bimonthly pattern for 3 years, and an intermittent, non-cyclical fever history. The patient had a history of a positive PPD with a negative chest x-ray and was treated with isoniazid at 1 year of age with negative yearly PPD tests since that time. At age 2 years, the patient developed chronic right cervical lymphadenitis and had a negative lymph node biopsy with a positive Epstein Barr titer. He has maintained his weight at 50th percentile and height at 90th percentile. Family history was noncontributory. The evaluation included negative HSV 1 and 2 IgG, negative Coxsackie virus antibodies, sufficient levels of Vitamins B1, B2, B6, and B12, a normal CBC, and comprehensive metabolic panel. The patient was found to be homozygous positive for the E148 mutation in the MEFV gene indicating FMF. He was also found to have an insufficient Vitamin D 25 hydroxy level at 27.3 ng/mL. Conclusions: Familial Mediterranean Fever should be considered in patients with aphthous stomatitis, intermittent fevers, and cervical lymphadenopathy. Though there are some controversial reports that FMF may exacerbate PFAPA (Periodic Fever, Aphthous Stomatitis, Pharyngitis, and Adenitis Syndrome), this link has not clearly been established, thus we consider this patient’s clinical phenotype as an unusual presentation of FMF. Recurrent fevers can be treated with a short course of oral steroids, and colchicine should be considered if more overt symptoms of FMF develop. While vitamin D insufficiency was identified, this may be a comorbid, unrelated condition that should also be treated.

P177 PATIENT WITH PYRIDOSTIGMINE HYPERSENSITIVITY: A CASE REPORT OF SUCCESSFUL DESENSITIZATION. K.C. Sokol*, R.S. Bonds, Galveston, TX. Introduction: Pyridostigmine is a cholinesterase inhibitor and usual firstline treatment for patients with myasthenia gravis (MG). It is available under the trade name Mestinon. Allergy to pyridostigmine is exceedingly rare, as there are only two prior cases and one desensitization previously reported. Methods: We report the case of an 84-year old man with history of MG and atrial fibrillation, with reported allergy to pyridostigmine, who presented to our clinic for evaluation at the request of his neurologist. The patient stated that 10 years ago he was diagnosed with MG and prescribed Mestinon while traveling. There was a break in treatment before finding a neurologist at home who restarted the medication. Within hours of his second dose after restarting it he developed an urticarial pruritic rash. Once he stopped Mestinon the rash resolved. For the past 10 years, his disease has been controlled on Mytelase (ambenonium chloride), also a cholinesterase inhibitor. Recently, the manufacturer stopped producing Mytelase in the US, and his neurologist wished to restart Mestinon at the dose of 60 mg four times daily. After admission to the MICU, we performed rush desensitization with increasing doses of an oral solution of pyridostigmine beginning with 1/10,000th of the prescribed dose, a concentration which was not achieved in the published report of pyridostigmine desensitization. We proceeded in 20 minute intervals, with a total administered dose of 120 mg. He complained of abdominal cramping and diarrhea after completion (known side effects). Discussion: Given our patient’s age and comorbid condition of atrial fibrillation, a traditional graded dose challenge would have increased his risk of poor outcome in the event of a severe IgE-mediated reaction. We did not perform skin prick as a prior report found no correlation between prick result and clinical reactiv-

ity. Intradermal testing was avoided due to concerns about potential false positive due to acetylcholine effect. Therefore we performed rapid desensitization in a monitored setting. Desensitization was successful without any immediate hypersensitivity reactions. Conclusion: We report the case of an 84-year old man with hypersensitivity to pyridostigmine and subsequent successful desensitization. This case has allowed us to alert the allergist to a rare allergy and formulate an original desensitization protocol.

P178 TREATMENT OF A PATIENT WITH MAST CELL ACTIVATION SYNDROME USING OMALIZUMAB. N.G. Parikh*, A. Rafi, J. Yusin, W. Klaustermeyer, Los Angeles, CA. Introduction: Mast Cell Activation Syndrome (MCAS) is a disorder describing the clinical effect of significant mast cell degranulation lacking an obvious trigger or evidence of abnormal mast cell proliferation. Per recent guidelines, criteria includes ruling out primary and secondary causes of mast cell activation, evidence of an increase in a validated urinary or serum marker of mast cell activation during an episode, improvement in symptoms with antimediator therapy, and episodic symptoms consistent with mast cell mediator release affecting ≥ 2 organ systems. Treatment of MCAS with anti-mediator therapy will often improve symptoms/episodes but impact on quality of life can still be severe. We present a patient with MCAS who achieved significant therapeutic control with omalizumab. Case Presentation: This is a 17 year-old female with no significant known past medical history who was referred for a 5 year history of recurrent episodes of abdominal pain, nausea, fatigue, flushing, and dizziness. The patient also had intermittent episodes of urticaria. On history, no obvious environmental, food, or physical trigger was identified. Percutaneous and intradermal for common food and aeroallergen extracts were all negative, with complete blood count, total IgE, tryptase level, thyroid studies, ESR, and CRP all within normal limits. Patient was started on Zyrtec, Zantac, as well as montelukast for suspected chronic urticaria Patient’s urticaria improved, but she continued to have episodes of abdominal pain, nausea, flushing, dizziness. Tryptase remained normal, however 24-hour urinary prostaglandin D2 levels were elevated 467 pg/ml with repeat during other episode elevated 512 pg/ml. Bone marrow biopsy showed normal marrow morphology with no aberrant mast cell population or spindle-shaped mast cells (CD25 staining negative). Patient was subsequently placed on oral steroids which had mild therapeutic benefit, but adverse effect of diffuse body swelling. Patient was started on omalizumab 200 mg subcunatenously every 4 weeks. Patient had reduction in frequency of episodes from once every 3-4 days to once a month. Conclusion: MCAS is a disorder of mast cell degranulation of unkown etiology. Without known triggers or cause, treatment has been limited in efficacy to antimediator therapies. This case demonstrates the potential benefit of omalizumab in treating this rare condition.

P179 OMALIZUMAB TREATMENT FOR ASTHMA IN PATIENTS WITH LOW TOTAL IGE. J.A. Quirt*1, J.Y. Chen2, J.K. Lee3, 1. Hamilton, ON, Canada; 2. Kingston, ON, Canada; 3. Toronto, ON, Canada. Omalizumab, a monoclonal antibody to IgE, is a treatment for patients with moderate to severe persistent asthma. Currently in North America it is indicated for use in patients with skin prick test or in vitro reactivity to perennial aeroallergens, whose symptoms are inadequately controlled with inhaled corticosteroids, and who have total serum IgE 30-700 IU/mL(1). It is unclear how the lower limit was determined. Previous data suggests that pretreatment total IgE is predictive of response to omalizumab (2,3), however case studies suggest benefit of omalizumab in patients with low total IgE(4-7). We present two cases of successful omalizumab treatment in patients with low total IgE. Patient 1, a 29-year-old female with asthma, was symptomatic despite treatment with montelukast 10mg daily, budesonide/formeterol 200mcg two inhalations three times daily, and triamcinolone nasal spray 1-2 sprays each nostril daily. She reported frequent ventolin use, nighttime symptoms, unscheduled physician visits and often missed work. Skin prick testing was 2+ positive to grass, dustmite, weed mix, cat and horse. Total IgE was 30 IU/mL. Despite her low IgE level, omalizumab was initiated given her clinical picture, positive skin prick testing and lack of asthma control. Within seven months, she reported a 3040% improvement in her symptoms. Patient 2, a 31-year-old female type I diabetic suffered from uncontrolled asthma symptoms including frequent nighttime symptoms, missed workdays, and unscheduled physician visits. She received multiple courses of oral steroids in the year prior to assessment and



ABSTRACTS: POSTER SESSIONS had difficulty managing glycemic control. Her medications included montelukast 10mg daily, fluticasone/salmeterol 250/50mcg twice daily and budesonide/formeterol 200mcg/6 mcg two inhalations twice daily. She had 2+ positive skin prick tests to dust mite, grass and mold. Total IgE was 4.16 IU/mL. Given her clinical picture and positive skin prick tests, omalizumab was initiated despite her low IgE level. She has to this date required no further systemic steroids and is maintained on budesonide/formeterol 200mcg/6mcg two inhalations twice daily without need for montelukast. While previous dosing data suggests that a serum total IgE level less than 30 IU/mL is not an indication for omalizumab, we present two cases of successful asthma control with the addition of omalizumab in patients with low serum total IgE.

P180 18 YEARS OLD WITH CHRONIC COUGH: AN ATYPICAL PRESENTATION OF CYSTIC FIBROSIS. A.S. Nickels*, M. Park, Rochester, MN. Background: Chronic cough in the adolescent population can present a difficult diagnostic dilemma and management challenges. When treatment fails or atypical signs are present, rare causes of a chronic cough should be entertained. Case Presentation: An 18 year old female presented to the Allergy Clinic in October 2012 for worsening chronic cough that had been present since early childhood. Recently, the cough had become mildly productive, worsens with exercise and associated with mild nasal congestion and heartburn. At age 11 she had normal pulmonary function test (PFTs), exhaled nitric oxide (eNO), and skin prick testing (SPT) for environmental allergens. Since that time, the patient had used numerous inhaled and intranasal steroids, as well as, antihistamines without satisfactory response. In the recent months prior to our evaluation, she had PFTs showing mild obstruction with positive methacholine challenge and negative eNO. Upper endoscopy showed duodenitis and gastritis with reflux related to her cough. ENT evaluation revealed polypoid lesions on the right middle turbinate and left uncinate process. CT sinus revealed pansinusitis. Recent treatment included a proton pump inhibitor, antibiotics for sinusitis, and inhaled and intranasal steroids without relief of her symptoms. Her past medical, social, and family histories were noncontributory. Her growth curves had tracked along the 50th percentile since age 11. She was overall well with a normal cardiopulmonary exam and no clubbing. SPT was negative. Given the patient’s suboptimal response to numerous treatment approaches, as well as her nasal/sinus disease, we recommended sweat chloride test which was elevated to 96 on the right and 95 on the left (normal <39). Genetic testing confirmed heterozygous deleterious mutations, CF- deltaF508 and R347P, confirming the diagnosis of Cystic Fibrosis. Conclusion: Cystic fibrosis is a wellestablished cause of lung disfunction and failure to thrive in the pediatric population. Our case highlights an atypical presentation of Cystic Fibrosis in an adolescent with chronic cough that seemed to have a multifactorial etiology and was poorly responsive to treatment. Cystic Fibrosis should be entertained in the young adult population who are presenting with sino-pulmonary symptoms that do not response to typical treatment.

tions are common in patients with XLA, but the increased frequency of these infections since his diagnosis of HIV despite rapidly achieving an undetectable viral load and maintaining CD4 counts well above 500 is concerning. We postulate the HIV is resulting in additional immune dysregulation despite the CD4/CD8 ratio remaining normal. It is also important to note that in patients with XLA, ELISA should not be used for diagnostic purposes as it is likely to be falsely negative. Instead, DNA PCR should be used for diagnostic or screening purposes. Conclusion: We report a patient with congenital X-linked agammaglobulinemia and a new diagnosis of HIV which has been previously unreported. This case is of interest to the allergist/immunologist because the progression of his clinical status with both conditions is unknown and as a reminder to use DNA PCR as the screening or diagnostic tool in these patients.

P182 A CASE OF SUBACUTE COMBINED DEGENERATION IN A PATIENT WITH COMMON VARIABLE IMMUNODEFICIENCY. S. Deol*, D. Khan, Dallas, TX. Introduction: Peripheral and central neuropathies are rarely reported in patients with CVID. We report a case of subacute combined degeneration in a patient with CVID. Methods: Case report. Data: A 33 yo woman with CVID and bronchiectasis on IVIG for 8 years presented with peripheral neuropathy and gait ataxia. Two years earlier she had developed a protein-losing enteropathy with villous atrophy of the small bowel. The enteropathy was partially responsive to oral budesonide, but due to persistent symptoms and concern for adverse effects, adalimumab was added as a steroid-sparing agent. After 3 months of therapy, adalimumab was discontinued due to new neurologic complaints. Neurological exam revealed a widebased, markedly ataxic gait, decreased lower extremity reflexes, and decreased sensation to pin prick, temperature, vibration, and proprioception in a stocking glove distribution. Laboratory results were notable for a mild macrocytic anemia, a lownormal vitamin B12, with normal protein, albumin, and IgG. B12 normalized with replacement therapy, but neurologic dysfunction progressed. MRI demonstrated abnormal signal within the dorsal columns of the cervical spinal cord and subtle linear enhancement of the cauda equina nerve roots. Signal abnormalities were also noted within the white matter tracts of the brain.A thorough workup was unrevealing for infectious, autoimmune, and neoplastic etiologies. Metabolic workup revealed a low ceruloplasmin (10.7mg/dL [16-45]), low serum copper (0.33 mcg/mL [0.75-1.45]), and low vitamin E (3.2 mg/L [5.5-17]), with normal zinc, B12, thiamine, folate, homocysteine, and MMA. After copper replacement and continued vitamin B12 supplementation, the patient had mild clinical improvement of her peripheral neuropathy and ataxic gait. Serial neurological examinations and repeat MRI will be performed to monitor for improvement of this demyelinating process. Conclusion:A&I specialists need to be aware of unusual complications in patients with CVID, including neurologic derangements. A stepwise approach to rule out infectious, autoimmune, neoplastic and metabolic etiologies should be conducted. A low-normal B12 without anemia should not exclude B12 deficiency as an etiology of myelopathy. Copper deficiency occurs in patients with malabsorption and can mimic the myelopathy seen in B12 deficiency.





Introduction: Patients with congenital X-linked agammaglobulinemia are more susceptible to encapsulated bacteria and commonly develop enteroviral infections. They have not been noted to be at increased risk for HIV. Patients with XLA with subsequent development of HIV infection have not been reported. Methods: We report the case of a 23 year old male with congenital XLA controlled with IVIG infusions presenting with cough, unintentional weight loss, night sweats, fever, fatigue, and vomiting. Evaluation for Tuberculosis, Histoplasmosis, Giardia, CMV, and HCV was negative. Chest radiograph was negative. Bronchoscopy was consistent with his agammaglobulinemia and cytology and culture were unremarkable. HIV DNA PCR was negative, but he reported a recent HIV diagnosis in his partner. Repeat HIV DNA PCR was positive 6 weeks later. ELISA was negative. After susceptibility testing, Stribild was started resulting in an undetectable viral load in one month. His CD4 count remained above 500. Since his HIV diagnosis, he has been hospitalized more frequently with recurrent Helicobacter cellulitis and gastric ulcers, Campylobacter sepsis, as well as fever and cough of undetermined etiology. Discussion: Although patients with congenital XLA and those with HIV are not rare in themselves, it is previously unreported for a patient with XLA to also have HIV infection. Helicobacter and Campylobacter infec-

Hyperimmunoglobulin M (HIGM) syndrome is a heterogenous immunodeficiency characterized by impaired class-switch recombination due to different molecular defects. The most common genetic defect is due to mutations of the CD40LG gene and is inherited as an X-linked trait. The estimated frequency of CD40L deficiency is 2:1,000,000 males. Other gene defects include CD40, activation-induced cytidine deaminase (AICDA), and uracil N-glycosylase (UNG) which are all inherited as an autosomal recessive trait. But, about 20 percent of cases are still genetically undefined. We present a female with HIGM who presented at age 31 years. She had history of pneumonia several times in the past but most recently was having chronic sinusitis and recurrent ear infections. Her immunoglobulin levels were as follows: IgG <20 mg/dL, IgA <5 mg/dL, IgE <2 mg/dL, and IgM 1441 mg/dL. She has protective IgG to tetanus, diphtheria, rubella, or varicella. We suspected that she had AID deficiency but her exon 1 could not be amplified. She now receives subcutaneous immunoglobulin and has had less frequent infections. HIGM is very rare, particularly in females, as the most common form is inherited as an X-linked trait. This case report illustrates HIGM in a female, and though we could not identify the exact molecular defect, her case stimulates discussion on the pathogenetics of HIGM in females. The pathogenesis of



ABSTRACTS: POSTER SESSIONS HIGM in females may involve extreme lyonization with a mutation of the CD40L gene; autosomal recessive inheritance of CD40 deficiency, AID deficiency, HIGM4, and UNG deficiency; or autosomal dominant inheritance of AID deficiency, C-terminus variant.



Introduction: Aspirin desensitization for AERD is often underutilized as a therapeutic option. We describe a patient with AERD and possible concomitant IgE mediated aspirin sensitivity treated with aspirin desensitization. Methods: The patient has a history of throat fullness, respiratory symptoms and 4 intubations following ingestion of as little as 20.25 mg of aspirin. He has adult onset steroid dependent severe persistent asthma and nasal polyposis s/p multiple polypectomies. He has failed omalizumab, zafirlukast and montelukast. His chronic steroid regimen has included oral methylprednisone and hydrocortisone. At the time of evaluation, he was on methylprednisone 16 mg QOD, high dose budesonide/formoterol and aspirin/NSAIDs avoidance. Results: Prior to aspirin desensitization, he had an infection associated asthma exacerbation with a fall of FVC from 5.14 L to 3.71L; FEV1 from 2.50 L to 1.87 L; and FEV1/FVC from 99 to 75. He was started on methylprednisolone 16mg daily With this his peak flows improved to 450-470 L/min representing 85% projected for patient’s height and his FVC increased to 4.29 L, FEV1 2.38L and FEV1/FVC to 56%. Given that his history could not exclude a prior history of IgE mediated aspirin sensitivity, the patient underwent aspirin desensitization using a 17 step procedure, administering sequential increased doses orally at 20 min intervals achieving a goal dose of 650 mg BID. His symptomatic provocative dose occured at 162 mg, cumulative dose of 324 mg, where he noted diffuse sinus fullness and headache without respiratory symptoms or symptoms consistent with prior exposures. Post desensitization peak flow was 510 L/min representing 94% projected and he subjectively had marked improvement in anosmia and voice quality. He was able to sustain these peak flows while weaning methylprednisolone to 8mg QOD. One month following the desensitization, he noted symptoms of acute sinusitis and his FVC was 5.03L, FEV1 2.15L, and FEV1/FVC 43% representing less impairment on spirometry with concurrent illness compared to prior. Conclusions: We demonstrate that a 17 step 20 minute interval aspirin desensitization is effective for a patient with AERD. It is unclear if the patient truly had IgE mediated aspirin disease superimposed on a diagnosis of AERD. We do not believe that there are previously published reports of desensitization in such individuals.

IN VITRO CYTOKINE ASSAY TO IDENTIFY THE MEDICATIONS RESPONSIBLE FOR A DRUG ERUPTION. J.R. Zaragoza*, G. Ghaffari, F.T. Ishmael, Hershey, PA. Introduction:There is a lack of diagnostic assays available to characterize drug hypersensitivity reactions. We have developed an in vitro assay to profile cytokine expression in peripheral blood mononuclear cells (PBMCs) after exposure to suspected drugs as a means to characterize T-cell mediated hypersensitivity reactions. We report a case of a patient with a photosensitive rash that occurred while being treated with sertraline and lamotrigine, the use of an assay to characterize the cytokine responses to these medications. Methods: Blood was obtained from the patient and a negative control subject, PBMCs were isolated by Ficoll preparation and incubated with each medication. A gene expression array was used to quantify cytokine expression by real time polymerase chain reaction (PCR). Case Report: A 15 year old female patient with a history of depression and mood disorder treated with Sertraline for four months was started on lamotrigine one month prior to developing a severe rash. She presented with malaise, a confluent erythematous maculo-papular rash over sun-exposed areas, and generalized pruritus one day after being exposed to sun light. A shave-biopsy report was consistent with a drug-induced photosensitive rash. Since the patient was on two medications at the same time, it was not clear which induced the reaction. The in vitro cytokine gene expression assay employed showed a greater than 5-fold increase in expression of the following cytokines in the patient’s cells but not the negative control subject: sertraline: IL-2, IL-4, IL -5, IL-6, IL-17A, GM-CSF, TNF-α, IFN-γ; lamotrigine: IL-5, IL-17A, GM-CSF, TNF-α . Given the increase in cytokine response with both medications, we hypothesized that both medications acted in concert to produce the rash, possibly triggered by sun exposure. The rash improved after holding the medications. Sertraline was restarted and was subsequently tolerated. Conclusion:This case highlights the use of in vitro cytokine gene expression testing as a tool to evaluate drug reactions, and raises the question of whether some drug reactions may be due to immunologic reactions to more than one medication.


P186 PROPHYLAXIS FOR HAE WITH NORMAL C1INH; A NOVEL THERAPEUTIC OPTION. R. Steele*, J.M. Sher, M.A. Davis-Lorton, Mineola, NY. Rationale: Hereditary angioedema with normal C1-Inhibitor (HAE with Normal C1INH) is a physiologically distinct type of HAE, with a preserved level and function of C1INH. These patients present both a diagnostic and therapeutic challenge, particularly in prophylaxis of future attacks. Case Report: A 22 year old female presented with a three month history of facial and tongue swelling. She denied pruritis, but reported intermittent abdominal pain without diarrhea or vomiting. She denied use of non-steroidal anti-inflammatory medications or ACE-inhibitors. Her medications included quetiapine, and a low dose estrogen containing OCP. Her mother and maternal grandmother have a history of recurrent non-medication related angioedema. An evaluation for secondary causes of her symptoms was unrevealing. Allergic workup included negative allergen specific IgE and negative autoimmune/rheumatic serologies. A serological examination (drawn during an angioedema attack) revealed a C4 of 20 mg/dL (16-38 mg/dL), C1INH of 27 mg/dL (21-39 mg/dL, and C1INH function of 98% (>=40%) with factor XII SNP analysis pending. The patient had been started on a regimen of high dose fexofenadine and cetirizine, hydroxyzine and epinephrine as needed for three months without improvement. Given the history, physical, and laboratory findings the patient met recently published criteria for HAE with Normal C1INH. Results: The patient clinically worsened, using her epinephrine auto-injectors eight times in one week for worsening symptoms of throat closing. She was given a trial of purified human C1INH as prophylaxis at dose of 1,000 Units. After two doses she saw no improvement in her daily symptoms, however, on her third dose it was increased to 1500 Units every other day. On this regimen, she had a complete resolution of her daily symptoms. Her OCP was subsequently switched to a progesterone only containing preparation. Conclusions: Empirical treatment with purified human C1INH in HAE with Normal C1INH is a novel prophylaxis use, particularly in increased dosing. Existing functional assays for C1INH do not examine disease specific pathways to determine enzymatic activity, and there may be an unidentified role for C1INH in the pathogenesis of



ABSTRACTS: POSTER SESSIONS this type of HAE. Further examination of the role of C1INH in HAE with Normal C1INH is warranted, and the purified inhibitor may be a viable prophylaxis option in these patients.

P187 HEMP SEED ANAPHYLAXIS. P. Gill*, S. Betschel, G. Sussman, P. Vadas, Toronto, ON, Canada. Rationale: We report a series of patients presenting with anaphylaxis after ingestion of hemp fibre or hemp seeds. Pollens from the Cannabis plant have been implicated in prior research as aero-allergens relating to lipid transfer proteins; however, reports of anaphylaxis after ingestion of Cannabis sativa are rare. We present these cases to highlight the possibility of Cannabis related plant-food allergy causing systemic reactions. Methods: Three individuals presented with severe systemic reactions after exposure to hemp fibre or hemp seeds by ingestion, and underwent skin prick testing for further investigation. Case #1) This 51 year old male presented with laryngioedema, hives, and decreased level of consciousness after ingestion of hemp seeds; symptoms resolved with epinephrine and prednisone treatment. Case #2) A 31 year old female’s symptoms manifested as angioedema, hives, upper airway obstruction and light-headedness after unintentional ingestion of hemp fibres. She was treated with epinephrine and her symptoms subsided within minutes. Case #3) A 35 year old female with a prior history of marijuana use developed hives, shortness of breath, dizziness and abdominal pain within ten minutes of ingesting hemp protein powder. She was treated with intravenous steroids and her symptoms resolved. Results: In all three cases, the clinical history in addition to allergy testing by skin prick method was consistent with anaphylaxis secondary to hemp seed exposure. Case #1) Skin prick testing was positive (51mm) to hemp seed. Case #2) Initial skin prick test to extract prepared from hemp fibers was negative, with subsequent strongly positive skin prick testing to hemp seeds. Case #3) Skin prick testing indicated a positive reaction (10mm) to the hemp protein powder that was implicated. Conclusions: Cannabis sativa contains allergens including lipid-transfer proteins which may convey allergenicity through a plant-food association, not only as aeroallergens from pollen, but also from direct contact. As the Cannabis sativa plant gains notoriety worldwide for its claimed health benefits, this report highlights the importance of identifying its allergenic potential and the spectrum of reactions it may trigger. Individuals who experience anaphylaxis secondary to hemp should be advised to carry an Epinephrine auto-injector in addition to avoiding all forms of exposure to hemp and its related products.


hospital with similar complaints led to the diagnosis of disseminated cryptococcosis based on positive cryptococcal antigen in CSF and serum, along with presence of Cryptococcus in lung biopsy. His pertinent examination revealed a cachectic man, with several brown orange scaly plaques on abdomen, forearms and legs. Laboratory investigations were significant for lymphopenia (absolute lymphocyte 195/mm3), positive ANA (211 AU/ml), anti-dsDNA (211 AU/ml), anti-centromere antibodies, elevated ACE (128 U/L), CD4+ 28% (105 cell/mm3), negative HIV tests. Search for other autoimmune disorders, malignancy and other immunodeficiency diseases remained unrevealing. Delayed hypersensitivity reaction to Candida, Trichophyton, tetanus toxoid and PPD were negative. CT of chest and abdomen revealed pleural and pericardial effusion, hepatosplenomegaly, and adenopathy. Biopsied skin, bone, liver and lymph node exhibited noncaseating granulomas. Mycobacterium and fungal cultures remained negative. Discussion: Noncaseating granulomas and elevation of ACE, suggests the diagnosis of sarcoidosis. Even though low titers of ANA or lymphopenia are reported in sarcoidosis but by demonstrating serositis and presence of anti-ds DNA antibodies, this case showed an overlap syndrome with SLE. Coexistence of sarcoidosis, which has polarized Th1 immune responses and SLE, predominantly Th2-mediated disease, suggests unusual dysregulation of Th1/Th2 immunity in this situation. Concurrently the two connective tissue diseases might impact T cell function, which seems to be the most significant risk factor for disseminated cryptococcosis. Conclusion: Sarcoidosis and SLE should be included in differential diagnosis of HIV-negative patients presenting with cryptococcal infection and lymphopenia. Concurrent autoimmune diseases are seen in patients with sarcoidosis. Therefore, diagnostic screening for accumulating autoimmune diseases in these patients should be considered.

P189 A CASE OF YELLOW URTICARIA IN ASSOCIATION WITH EBV INFECTION. A. Crans Yoon*, M. Kaplan, J. Sheikh, B. Goldberg, Los Angeles, CA. Yellow urticaria is a rare type of urticaria associated with elevated bilirubin, and described in patients with Hepatitis B and C, end-stage liver disease, and obstructive jaundice due to malignancy. We report a case of acute EBV infection complicated by yellow urticaria without jaundice. Case Presentation: A 26 year old female presented with 2 weeks of sore throat, cough, and intermittent fever to 102°F. 1 month prior she had traveled to Argentina and Uruguay. Vitals were significant for blood pressure of 98/67. Physical exam was unremarkable. Significant labs were WBC 5.0 x103/mL (22% bands, peripheral blood smear significant for moderate reactive lymphocytes), Hgb 13.6 g/dL,AST 505 U/L,Alkaline Phosphatase 467 U/L, total serum bilirubin 4.1 mg/dL, direct serum bilirubin 2.30 mg/dL.Abdominal ultrasound showed mild hepatosplenomegaly. 6 hours later she became febrile to 101.5 °F, and 1 hour later complained of severe pruritis on her bilateral lower extremities. A raised, erythematous urticarial rash on a yellow base was observed. Oral antihistamines gave some relief. Over the hospital course she had several urticaria episodes with lessening severity. Transaminases downtrended and total bilirubin peaked at 14.4 mg/dL (direct 9.04 mg/dL) on day 4. Hemoglobin declined to 8.4 g/dL and haptoglobin was low at 21 mg/dL with LDH 499 IU/L, suggesting a hemolytic etiology; however, direct Coombs was negative. EBV IgM was positive, indicating acute EBV infection, which is known to cause cholestatic hepatitis. CMV IgM was 1.16(positive ≥1.11); however, as EBV IgM can cross react with CMV, this was thought to be a false positive rather than a CMV co-infection. She clinically improved and had no further urticaria episodes after discharge with gradual return of her lab values to normal. Discussion: Infectious Mononucleosis due to EBV has been reported to cause urticaria due to circulating immune complexes; this is likely in our patient given that she had hemolytic anemia.Yellow urticaria has no known mechanism, but is thought to involve bilirubin preferentially depositing in the dermis due to increased vascular permeability. The patient never developed typical clinical signs of jaundice despite significantly elevated bilirubin, consistent with previously reported cases of cholestatic hepatitis caused by EBV. Thus, yellow urticaria may have diagnostic value as a physical sign of hyperbilirubinemia.

DISSEMINATED CRYPTOCOCCAL INFECTION AS INITIAL PRESENTATION OF AN OVERLAP SYNDROME OF SYSTEMIC SARCOIDOSIS AND SYSTEMIC LUPUS ERYTHEMATOSUS. K. Chotikanatis*, J. Moallem, Brooklyn, NY. Introduction: Cryptococcal infection has been reported as a rare complication of sarcoidosis or SLE, while on immunosuppressants. Case: 51-year-old African American man presented with confusion, weakness and brown orange scaly plaques on the skin. His prior admission, two weeks before, in a local




P190 A CASE OF PROLONGED HYPOGAMMAGLOBULINEMIA AFTER RITUXIMAB TREATMENT IN A CHILD WITH UNDERLYING IGA DEFICIENCY. K.M. Edelman*, A. Alvarez, A. Irani, Richmond, VA. Introduction: Transient peripheral B-cell depletion is expected with rituximab use, but rarely does secondary prolonged hypogammaglobulinemia ensue. We present a case of prolonged hypogammaglobulinemia after rituximab treatment for nonparaneoplastic limbic encephalitis in a child with underlying IgA deficiency. Case Description: A nine-year-old Caucasian male presented to us for evaluation of rituximab-induced hypogammaglobulinemia after treatment of limbic encephalitis. Previously healthy, he first presented at age five with seizures associated with ataxia, dysarthria, and fevers of unknown origin. At seven, he was diagnosed with anti-Hu antibody associated nonparaneoplastic limbic encephalitis. He also had recurrent sinopulmonary infections and was diagnosed with selective IgA deficiency (IgA<15 mg/dl, normal IgG and IgM). In light of his steroid-responsive epilepsy and CSF immunophenotyping which revealed expansion of CD19+ B-cells, the decision was made to treat with rituximab. Two months prior to rituximab initiation, his total serum IgG level was 576 mg/dl (normal 633-1280 mg/dl), IgM 53.4 mg/dl (normal 48-207 mg/dl) and IgA < 6.7 mg/dl. He received four doses of rituximab after which his epilepsy and behavioral issues improved. However, he developed symptomatic pan-hypogammaglobulinemia as well as absent peripheral CD19+ B cells associated with chronic sinusitis. Lymphocyte analysis revealed normal T-cell numbers and antigen stimulation profile. He was treated with monthly IVIG and prophylactic antibiotics for over five years. B-cells reappeared in the peripheral blood (8%, absolute count 152 mm3) and IVIG was discontinued. However, he failed to produce protective antibody titers after immunization with tetanus and pneumococcal vaccines and his IgG level dropped to 321 mg/dl. IVIG was resumed and he was ultimately switched to subcutaneous IG. Conclusion: Prolonged hypogammaglobulinemia secondary to rituximab is a known though rare complication and usually only seen in patients exposed to chemotherapy agents or stem cell transplantation. This is a curious case of either hypogammaglobulinemia secondary to rituximab use or selective IgA deficiency progressing to common variable immunodeficiency, perhaps confounded by rituximab use, raising the question of whether rituximab can aggravate underlying hypogammaglobulinemia.

P191 SERUM SICKNESS-LIKE SYNDROME TO MINOCYCLINE PRESENTING AS URTICARIA WITH NORMAL SERUM COMPLEMENT LEVELS. C. Parrish*, A. Wong, S. Thobani, M. Li, L. Scott, Los Angeles, CA. Introduction: Classic serum sickness, the prototypic Gell and Coombs type III allergic reaction, presents with rash, fever, arthralgias, and lymphadenopathy. Clinical diagnosis may be challenging, especially when cardinal features are lacking or laboratory findings are not suggestive of immune complex deposition. Methods: Case Report. Results: A 15 year old boy with history of Hodgkin’s lymphoma in remission for six years noticed erythematous, itchy patches of skin on his neck and arm two weeks after starting minocycline for acne. The rash spread and he sought care in the pediatric emergency department. Urticaria were scattered on the extremities and trunk. Antihistamines and corticosteroids temporarily improved his symptoms, and minocycline was discontinued. Over the next three days the rash progressed, with new fever and arthralgias. Loratadine, famotidine, acetaminophen and calamine lotion were added. On the fifth day the rash spread to palms and soles with fever, and arthralgias. The rash was diffuse, blanchable, mildly tender, involving the face, trunk and all four extremities including the palms and soles. Mucosae were uninvolved and there was no lymphadenopathy. He was tachycardic and febrile, so cultures were drawn and he was admitted due to concern for sepsis. Cardiopulmonary, abdominal, and joint exams were normal except for tachycardia. Laboratory results revealed normal levels of C3 and C4, negative antinuclear antibody, and nonreactive RPR. Cultures of the blood, urine, and throat were all negative. C-reactive protein was elevated. The constellation of urticaria, fevers, and arthralgias led to suspicion of serum-sickness-like syndrome secondary to minocycline. With ibuprofen and cessation of minocycline, the patient’s symptoms rapidly improved over a three-day hospitalization. One week later CRP level had normalized and the patient was asymptomatic. Conclusions: Minocycline was first reported to cause serumsickness-like syndrome in 1990 and rare cases have been reported since. This

case illustrates the difficulty in establishing a clinical diagnosis when only one cardinal feature is present initially. Review of known medication adverse effects and timing of symptom onset can be essential to diagnosis, especially when the classic laboratory findings of hypocomplementemia are absent.

Intensely pruritic, urticarial rash on upper chest and arm.

P192 A CASE OF URTICARIAL VASCULITIS MASQUERADING AS LYME DISEASE. A.K. Wong*, C. Parrish, S. Thobani, M. Li, L. Scott, Los Angeles, CA. Background: Urticarial vasculitis (UV) is a rare dermatologic eruption that classically resembles urticarial wheals, but histologically shows leukocytoclastic vasculitis of the small vessels. Skin biopsy is required for diagnosis. Treatment recommendations include antihistamines, NSAIDS, and glucocorticoids. Methods: Case report. Results: 37 year old Hispanic female with asthma presented with worsening skin rash. She was “bitten by a bug” 5 days prior to admission and developed two red, pinpoint-sized “bumps” on her left thigh which were later surrounded by red “rings.” She presented to the Emergency Department (ED) 2 days later with the rash spreading over her back, shoulders, face, extremities, groin and buttocks. On exam, the physician noted erythematous lesions with target-like central clearing. He diagnosed infectious etiology, such as Lyme disease, versus allergic reaction. Patient was discharged home with oral hydroxyzine, topical hydrocortisone, prednisone, and doxycycline. The next day outpatient Dermatology performed a punch biopsy and recommended to continue all prescribed medications. She returned to the ED within 2 days because her rash became progressively pruritic, at which time she was admitted for intravenous hydrocortisone, hydroxyzine, diphenhydramine, topical steroids, and specialty consultation. ANA, C3, C4, ESR, and CRP were within normal limits. Allergy and Immunology was consulted for diagnosis. Detailed history obtained from the patient described her lesions as painful, burning and each lesion persisting longer than 24 hours. Physical exam revealed hyperpigmentation in areas of resolved wheals. With this description, UV was the most likely etiology. The consult team recommended loratadine and famotidine for H1 and H2 receptor blockade to better manage the patient’s pruritus. At outpatient follow-up, skin biopsy results were consistent with UV. Conclusions: UV may present anywhere on the body with lesions that are classically similar to urticarial wheals. Burning, tenderness and lesions lasting longer than 24 hours can help to distinguish UV lesions. This particular case report highlights additional variability in presentation of UV. The above patient presented with a history and target-like skin lesions similar to Lyme disease,



ABSTRACTS: POSTER SESSIONS but failed to respond to antibiotics. Appropriate diagnosis and treatment of UV requires thorough history, physical examination, and skin biopsy.

Target-like erythematous wheals of urticarial vasculitis

P193 B- AND T-CELL IMMUNODEFICIENCY WITH AN OLIGOCLONAL T-CELL POPULATION ASSOCIATED WITH PURE RED CELL APLASIA AND SEVERE HEMOLYTIC ANEMIA. J. Dara*1, B. Raphael1, A. Verma2, A. Rubinstein2, 1. New York, NY; 2. Bronx, NY. Introduction: 26-year-old male with a B and T cell deficiency and developed a severe anemia from pure red cell aplasia (PRCA) and hemolysis. Bone marrow studies revealed oligoclonal cell proliferation suggestive of early/lowgrade lymphoma. Methods: Immunological, hematological, and genetic evaluation of a patient, ZD, with underlying B and T cell deficiency, history of measles and varicella post vaccination, and lymphopenia after acute EBV infection. Results: ZD had a history of measles and chickenpox post MMR and varicella immunization. He was hospitalized at 18 years for acute EBV infection then developed marked elevation of serum IgG (2012 mg/dL) and IgM (624 mg/dL). Over time IgM decreased to normal, IgG decreased to 555-680 mg/dL with low IgG2 (94 mg/dl) and IgG4 (2 mg/dL). At the same time, he developed a persistent lymphopenia (568-686/mL) with low CD4+ T-cells (246/ml), low naïve T-cells (CD4+CD45RA+), high memory T-cells (CD4+CD45RO+) and low B-cells (3-5%, 36/dL). He failed to mount antibody responses to all pneumococcal serotypes after PPSV, PCV7, and PCV13. Whole genome sequencing did not reveal any relevant mutations. At 26 years, he had recurrent respiratory infections and was started on IVIg. Four months into therapy, he was found to have severe anemia (3.7g/dL) with elevated LDH (270 IU/L), undetectable haptoglobin, low reticulocyte count, and negative direct and indirect Coombs. Bone marrow analysis revealed PRCA and oligoclonal T-cell infiltration. Repeat analysis at the National Cancer Institutes revealed a minor T-cell clone suggestive of a lymphoproliferative disorder. He was started on high dose steroids then mycophenolate mofetil with an increase of haptoglobin levels and B-cells (39-45%, 214-238/mL) but no effect on the anemia or reticulocyte counts. He was started on cyclosporine with resolution of the aplastic anemia but persistence of low haptoglobin and of B-cell lymphopenia (5%, 36cells/mL). Repeat bone marrow showed a persistent 25% oligoclonal gamma/delta T-cell population. Conclusion: We report of a case of B- and T-cell deficiency aggravated by severe EBV infectioncomplicated by a gamma/delta T-cell proliferative clone. The role of the T-cell clone in the development of PRCA and its relationship to the B-cell dysfunction is of great interest.


P194 HEREDITARY ANGIOEDEMA INDUCED TAKOTSUBO CARDIOMYOPATHY. M. Mortezavi*1, V. Packianathan2, S. Vishwanath2, M. Sands2, 1. Rochester, NY; 2. Buffalo, NY. Purpose: We describe a patient with Hereditary Angioedema (HAE)-related Takotsubo cardiomyopathy. Takotsubo cardiomyopathy is a stress-induced cardiomyopathy that presents with features mimicking a ST elevation myocardial infarction (STEMI). It is frequently seen in post-menopausal women after an exposure to a physiological or emotional stressor, hence inspiring the name “broken heart syndrome.” The precise pathogenic mechanism remains unclear but is postulated to be a stress-induced catecholamine mediated cardiotoxicity. It is characterized by transient wall motion abnormalities in the apical and mid-portions of the left ventricle (LV), electrocardiogram (ECG) changes, and troponin elevation with no evidence of obstructive coronary disease on angiography. The prognosis is favorable and LV ejection fraction rapidly improves over days to weeks. Methods: 41 year old female with known history of HAE on C1 inhibitor prophylaxis, presented with abdominal pain, genital swelling and lip swelling. She required emergent intubation on presentation for airway protection. On the day of admission, her telemetry monitoring showed acute ST elevations, prompting further evaluation. Elevated troponins and ST segment elevations on ECG lead to a preliminary diagnosis of acute STEMI. Results: Her troponins peaked at 4.16 ng/mL (Ref: 0-0.06 ng/mL). Echocardiogram showed severely depressed LV ejection fraction of 25-30% and apical hypokinesis consistent with Takotsubo cardiomyopathy. Cardiac catheterization revealed minimal coronary artery disease with no obstructive lesions. 72 hours later, repeat echocardiogram showed improvement of LV systolic function to 40%. Conclusion: Our patient’s presentation of acute ST elevations, troponin leak, apical hypokinesis, and cardiac catheterization showing minimal coronary artery disease points to a diagnosis of Takotsubo cardiomyopathy with her angioedema flare the likely precipitating factor. Although attacks of HAE may be sporadic; trauma, physical or emotional stress can often precipitate exacerbations. Interestingly, the same stressors can induce Takotsubo cardiomyopathy. The stress mediated response to her angioedema flare likely caused a catecholamine surge precipitating her Takotsubo cardiomypathy. Takotsubo cardiomyopathy should therefore be considered an important differential in a patient with an angioedema flare and concurrent presentation of cardiac compromise.

P195 VICKS VAPORUB AS A CAUSE FOR ALLERGIC CONTACT DERMATITIS IN THE NASAL AREA. J.A. Mendez*, S. Nazario, San Juan, Puerto Rico. Introduction: Vicks VapoRub is a mentholated ointment marketed as a cough suppressant. In spite instructions to avoid its use in nostrils, some patients apply it to this area in an attempt to reduce nasal congestion. A previous report described a case of allergic contact dermatitis after application of Vicks VapoRub in the neck area. Here, we report the first case of nasal and facial allergic contact dermatitis caused by application of Vicks VapoRub in nostrils. Case description: A 47 year-old woman without systemic illness was evaluated for nasal and facial edema, erythema, and tenderness. Symptoms had been present for about 1 year, were fairly constant, and persisted despite discontinuation of facial cosmetics. She referred some worsening of symptoms during hot weather and after sun exposure. Besides occasional application of Vicks VapoRub in nostrils to relieve nasal congestion, she denied using other topical facial products. Physical examination was remarkable for nasal and facial edema and erythema. Laboratory workup was unremarkable, including a total serum IgE level of 8.4 IU/mL. The patient was patch-tested to the North American Baseline Series of 50 allergens (Dormer Laboratories, Inc.) and to Vicks VapoRub. The results of patch testing after 72 hours revealed positive results to Vicks VapoRub and Fragrance Mix II. Symptoms resolved completely after discontinuation of Vicks VapoRub. Conclusion: Vicks VapoRub is a commonly used ointment that contains multiple potential sensitizing ingredients. Nasal edema and erythema may occur through an allergic contact dermatitis mechanism after application of Vicks VapoRub in nostrils. This is the second report describing allergic contact dermatitis secondary to Vicks VapoRub, and the first involving the nose and facial area.



Table of laboratory trends with pronounced leukocytosis, eosinophilia, hyponatremia, hypoalbuminemia, transaminitis, and anemia.

P197 VOGT-KOYANAGI-HARADA SYNDROME IN 14-YEAR OLD NATIVE AMERICAN. Q. Rashid*, F. Schmalsteig, Galveston, TX. Allergic contact dermatitis in nose and facial area after application of Vicks VapoRub in nostrils.

P196 A PEDIATRIC CASE OF CO-TRIMOXAZOLE-INDUCED DRUG REACTION WITH EOSINOPHILIA AND SYSTEMIC SYMPTOMS (DRESS). P. Wong*1, D.F. Muench2, F. Lewis2, D. Moffitt2, 1. San Antonio, TX; 2. Tacoma, WA. The evaluation and diagnosis of severe cutaneous eruptions in pediatric patients can be challenging. DRESS is a rare but life-threatening hypersensitivity syndrome characterized by a severe cutaneous eruption, leukocytosis and eosinophilia, and multi-organ involvement. Case: One week after completing a 14-day course of co-trimoxazole for a urinary tract infection, a 9-year-old Caucasian female presented to the pediatric service with recurrent fevers, diffuse rash, and multiple organ involvement to include hepatitis with hepatomegaly, generalized ascites, severe hyponatremia, pulmonary edema, generalized lymphadenopathy, hemolytic anemia, atypical lymphocytosis, and eosinophilia. Her diffuse morbilliform rash consisted of prominent erythroderma punctuated with fine sandpaper-like perifollicular papules and a few vesicles, sparing the mucosal surfaces. Laboratory studies were notable for a WBC of 71,000/mL with 18% atypical lymphocytes and 16% eosinophils, and a severe hyponatremia (sodium 116 mmol/L). Over subsequent days, she developed marked hepatomegaly with hepatitis (ALT 410 units/L, AST 815 units/L), ascites with hypoalbuminemia (1.9 g/dL), tubulointerstitial nephritis, pulmonary edema, generalized lymphadenopathy, and a hemolytic anemia (hemoglobin 7.6 g/dL) (Figure 1). DRESS was diagnosed based on clinical findings assisted by skin biopsy. Human herpes virus-6 (HHV-6) PCR was positive. Treatment required six months of prednisone due to the recurrence of rash. The child subsequently returned to baseline health. Discussion: This case highlights the late onset of symptoms, leukocytosis, eosinophilia, hepatitis, lack of mucocutaneous involvement, and association with HHV-6 specific to DRESS. This patient uniquely demonstrated a severe hyponatremia, which has not been previously highlighted. While treatment requires prompt drug removal and supportive care, early systemic corticosteroid therapy in DRESS is vital. This distinguishing and life-saving feature highlights the importance of increased clinical awareness in previously healthy children to whom co-trimoxazole is commonly prescribed for urinary tract infections and methicillin-resistant Staphylococcus aureus infections, and argues for increased discretion with co-trimoxazole given its association with DRESS and its associated potential morbidities.

Introduction: Vogt-Koyanagi-Harada Syndrome (VKHS) is a rare systemic disorder characterized by panuveitis, aseptic meningitis, alopecia, and vitiligo resulting from a T cell-mediated autoimmune attack on melanocytes in the choroids, meninges, inner ear and integumentary system. It commonly manifests in third to fourth decade of life, and is rarely seen in children. Methods: A 14 year old Native American female presented with complaints of vision loss in her left eye, and a five week history of blurred vision, bilateral floaters, and severe left-sided retro-orbital pain. She denied skin discoloration, hearing loss, joint pain, or oral ulcers. Physical exam was positive for bilateral central visual field defects, macular edema, mild retinal detachment, and granulomatous precipitate in the anterior chambers consistent with panuveitis. Optical coherence tomography showed bilateral macular serous detachment consistent with VKHS. HLA-DR4 and HLA-Dw53, markers commonly associated with VKHS, were negative. The patient’s symptoms partially improved after treatment with highdose glucocorticoids. Discussion: VKHS predominately occurs in Asians, Hispanics, and Native Americans. It is more common in women, with a 2:1 female:male ratio. Four clinical stages of VKHS have been described: the prodromal stage includes headache, fever, and photophobia and may mimic a viral infection; the acute uveitic stage includes bilateral uveitis, hearing loss, and meningitis; the convalescence stage includes vitiligo, and alopecia and can last for weeks or months; and the chronic recurrent stage marked by repeated bouts of uveitis. Hearing loss ranges from mild impairment to complete unilateral or bilateral deafness and progressively worsens with subsequent flares. The prognosis for vision is generally favorable with prompt diagnosis and appropriate treatment. The goal of treatment is to suppress intraocular inflammation and prevent visual impairment. Early and aggressive treatment with systemic corticosteroids remains the mainstay of initial therapy for VKHS. However, in the last 10-15 years biologic drugs have emerged as a therapeutic alternative for patients refractory to treatment with steroids. Conclusion: VKHS is a rare multi-system inflammatory disorder. A high index of suspicion in patients of all ages is required to make a prompt diagnosis, as delay in treatment can result in permanent loss of vision and hearing.

P198 CLINICAL RELEVANCE OF SENSITIZATION TO INDIVIDUAL COW’S MILK PROTEINS. T. Lee*, S. Bunyavanich, New York, NY. Cow’s milk allergy is the most common food allergy in children, affecting about 2 percent of children under 4 years old. Most patients with cow’s milk allergy are sensitized to the major milk proteins, casein and whey (alpha-lactalbumin, beta-lactoglobulin). Co-sensitization is also common. In formula-



ABSTRACTS: POSTER SESSIONS fed infants, extensively hydrolyzed or amino acid-based infant formulas are typically recommended. We present a 7 month old female with history of eczema who presented with anaphylaxis after eating cow’s milk yogurt. Several weeks after the incident, her skin test to cow’s milk and cow’s milk yogurt were positive. She was advised to switch from the Gerber Good Start formula,which she had been taking since 10 weeks of age, to Neocate. Her serum IgE levels then returned: milk at 8.01 kU/L, beta-lactoglobulin <0.35 kU/L, alpha-lactoglobulin <0.35 kU/L, and casein 23.4 kU/L. With this additional data, we thought that she would likely be able to tolerate whey-based formulas; therefore, she was switched back to Good Start without problem. In conclusion, when milk allergy is specific to selected cow’s milk proteins, formula selection may not have to be as restrictive. This case highlights the benefits of testing for individual cow’s milk proteins.

Evaluation for end organ dysfunction with echocardiogram, troponin, and liver function tests were normal. Studies evaluating for parasites were negative. RSV antigen test was again negative. A CT chest showed diffuse ground glass opacities of the bilateral upper lobes. He was started on prednisone 2 mg/kg/day and budesonide 0.5 mg nebulized BID. AEC decreased to 0/mm3 and his hypoxemia and wheezing resolved. He was discharged home to complete a week long prednisone taper and continue budesonide. At one month follow-up, he was doing well with no respiratory symptoms although AEC increased to 984/mm3. He continued to use budesonide 0.5 mg nebulized daily. Conclusions: This case highlights the diagnosis and treatment of PIE in a young infant. It also suggests continued monitoring of the AEC after clinical resolution of symptoms.


AN UNUSUAL PRESENTATION OF KIMURA DISEASE AND RESPONSE TO LOW-DOSE STEROID. A. Kleva*1, R. Sporter1, L. Sulica2, B. Kaplan1, 1. Great Neck, NY; 2. New York, NY.

EOSINOPHILIC GASTROENTERITIS AFTER ASPIRIN DESENSITIZATION IN A PATIENT WITH ASPIRIN-EXACERBATED RESPIRATORY DISEASE. C.H. Feng*1, N. Kim2, S. Teuber2, 1. Davis, CA; 2. Sacramento, CA. Background: Aspirin-exacerbated respiratory disease (AERD) is an uncommon disease found in 0.3 to 0.9% of the population, which can be successfully treated with aspirin desensitization. Eosinophilic gastroenteritis is an even rarer clinical entity occurring in 28 out of 100,000 people. Here we report the case of a patient with both AERD and eosinophilic gastroenteritis. Case Report: A 42-year-old male with asthma, sinusitis, aspirin sensitivity, and nasal polyps was diagnosed with AERD. He had no previous history of atopy. He subsequently had three polypectomies, underwent successful aspirin desensitization, and was maintained on aspirin 650 mg twice daily. However, one year and one month after desensitization, the patient presented to clinic with nausea, vomiting, abdominal pain, and diarrhea. Esophagoduodenoscopy was performed, and pathology from the stomach, duodenum, and ileum revealed increased intramucosal eosinophils (>80/high powered field) and crypt abscesses, consistent with eosinophilic gastroenteritis. White blood cell count was 10.2 K/uL with 38% eosinophils, and quantitative IgE was 262. Tests for parasites including Strongyloides IgG, Giardia lamblia antigen, and stool ova and parasites were negative. Skin prick testing to a panel of standard aeroallergens and 52 foods was also negative. The patient was placed on a prednisone taper and a six food elimination diet. Aspirin was discontinued because of his gastrointestinal discomfort. One month after starting treatment for eosinophilic gastroenteritis, the patient reported an improvement in his gastrointestinal symptoms, without any worsening of his upper or lower respiratory symptoms from AERD. Conclusions: To the best of our knowledge, this is the first case report of a patient with eosinophilic gastroenteritis after undergoing aspirin desensitization for AERD. The exact relationship between AERD and eosinophilic gastroenteritis, and what role aspirin desensitization plays in the onset of eosinophilic gastroenteritis, is unclear, as AERD reactions reflect non-allergic hypersensitivities that are usually not IgE-mediated. More case descriptions are necessary to determine whether there is a true relationship between these two diseases.

P200 PULMONARY INFILTRATES WITH EOSINOPHILIA (PIE) IN A 7 WEEK OLD MALE INFANT. C. Pope*1, A. Hall2, N. Dave2, A.Yates2, 1. Ridgeland, MS; 2. Jackson, MS. Introduction: PIE syndromes are a group of heterogeneous disorders having the common findings of lung disease and eosinophilia in the peripheral blood, bronchoalveolar lavage fluid, or pulmonary interstitium. They are rare in childhood and few cases have been reported. To our knowledge, there has only been one case reported in a patient this young. Case: A term 7-week-old African American male was admitted for hypoxemia, wheezing, and respiratory distress. Symptoms initially started at 3 days of life with increased respiratory rate, wheezing, cough and retractions. No history of fever. He was evaluated at the UMMC Pediatric ED two weeks prior to admission. He had a negative rapid RSV test and negative B. pertussis PCR. Chest radiograph showed a slight peribronchial infiltrate in the right upper lobe. He was diagnosed with bronchiolitis and sent home. On admission physical exam, significant inspiratory and expiratory wheezing was heard with subcostal retractions. No rash was present. Complete blood count showed total white blood cell count of 31,100/mm3, hemoglobin 10.3 g/dL, platelet 489,000/mm3, 33% neutrophils, 4% bands, 35% lymphocytes, 13% monocytes, 12% eosinophils, 1% basophils, and 2% myeloctes. Absolute eosinophil count (AEC) peaked at 5,497/mm3.



Background: Kimura disease is an uncommon chronic inflammatory condition, primarily reported in Asian males. It typically presents with large subcutaneous head and neck masses, tissue and peripheral blood eosinophilia, and elevated IgE. Lymphoid hyperplasia, proliferation of vascular endothelium, and eosinophilic infiltration are observed histologically. Standard treatment involves surgical resection and occasionally steroids and radiotherapy. We describe a case of Kimura disease localized to the epiglottis, larynx and pharynx presenting with hoarseness and transient respiratory obstruction. Case Report: A 53-year-old Caucasian female with recurrent otitis media, sinusitis, and gastroesophageal reflux presented with a one-year history of progressive hoarseness and transient respiratory obstruction. Strobovideolaryngoscopy revealed prominent lesions of the lateral pharyngeal wall and supraglottic larynx. Biopsy of the lesions demonstrated a reactive lymphocytic and eosinophilic infiltrate accompanied by plasma cells and benign germinal centers, consistent with Kimura disease. Results: Patient was referred for an immune evaluation. Laboratory testing was significant for peripheral eosinophilia (2.8 K/uL, 16%). IgE was normal (15 IU/ml). Evaluation otherwise revealed normal IgG, IgM, IgA, specific antibody titers, and hemolytic complement level. Therapy with low-dose prednisone (10mg daily) was prescribed, and resulted in significant improvement in voice quality and regression of the lesions on subsequent laryngoscopy. Conclusion: Kimura disease is a benign inflammatory process that could result in airway obstruction if localized to the laryngopharyngeal space. Kimura disease involving the epiglottis and paraglottic area is rare and difficult to diagnose. It should be considered in the differential diagnosis of chronic dysphonia that has eluded diagnosis in the absence of the typical subcutaneous lesions, and should also be considered in patients who are not of Asian descent. Low-dose steroids can be highly effective in the treatment of laryngopharyngeal Kimura disease, and may obviate the need for surgical resection.

P202 A CASE OF CHRONIC RHINOSINUSITIS WITH POLYPS AND STEROID-DEPENDENT ASTHMATIC WHO EXPERIENCED ACTIVE, GENERALIZED GRANULOMATOSIS WITH POLYANGIITIS (GPA) WITH ANCA-NEGATIVE SEROLOGY. D.A. Nayak*, A.T. Peters, Chicago, IL. Introduction: Approximately 90% of patients with pauci-immune glomerulonephritis are anti-neutrophil cytoplasmic antibody (ANCA) positive. However, there remains a subset of patients who are ANCA-negative. We report a patient with a prior history of chronic rhinosinusitis with polyps and steroiddependent asthma who experienced active, generalized granulomatosis with polyangiitis (GPA) with ANCA-negative serology. Methods: Case report; chronic rhinosinusitis, asthma and ANCA-negative renal vasculitis. Results: RH is a 54 year old male with chronic rhinosinusitis with polyps, steroid-dependent asthma, specific antibody deficiency and allergic rhinitis who presented with a 2 week history of progressively worsening cough, shortness of breath and wheezing accompanied with intermittent, small-volume hemoptysis. He was noted to be acutely anemic and in acute renal failure with nephrotic range proteinuria. Chest radiography revealed bilaterally pulmonary infiltrates concerning for an acute infectious process or possible pulmonary hemorrhage. ANCA serologies were negative and serum complements were normal. Bronchoscopy was deferred due to increased risk of complication. Renal biopsy revealed a focal proliferative form of necrotizing glomerulonephritis consistent with anti-glomerular basement membrane antibody (anti-GBM antibody)


ABSTRACTS: POSTER SESSIONS disease or GPA. His anti-GBM antibody was negative and a diagnosis of GPA was made. On Day 3, he was started on methylprednisolone 1g IV daily for 3 days and cyclophosphamide 750 mg/m2 IV monthly. On Day 4 his hemoptysis resolved and he required no supplemental oxygen. He was discharged on Day 8 with a long-term oral steroid taper and cyclophosphamide infusions monthly for 6 doses. He significantly improved over the next 10 days with resolution of his hemoptysis, dyspnea and wheezing. 2 weeks following discharge, his serum creatine improved and CT chest 4 months later revealed resolution of pulmonary infiltrates. Conclusion: Patients with chronic rhinosinusitis and severe asthma may present with clinical features of systemic vasculitis despite negative serologies. Obtaining prompt tissue sampling from the suspected involved organ may help guide clinicians to expeditiously treat a life-threatening disease.

P203 A CASE OF ANCA NEGATIVE EOSINOPHILIC GRANULOMATOSIS WITH POLYANGIITIS (CHURG- STRAUSS) PRESENTING WITH MYOCARDITIS AND PULMONARY INFILTRATES. N. Fenny*, K. McGrath, Chicago, IL. Eosinophilic granulomatosis with polyangiitis (EGPA) formerly known as Churg Strauss is classified as a vasculitis of small and medium sized arteries. EGPA is a multisystem disorder characterized by chronic rhinosinusitis, asthma and peripheral blood eosinophilia. The lung is the most commonly involved organ, however, EGPA can affect any organ. Cardiac involvement accounts for approximately 50% of deaths caused by EGPA. ANCA are found in 40-60% of patients with EGPA. In a series of patients newly diagnosed with EGPA, a positive ANCA was associated with renal involvement and biopsy proven vasculits, while a negative ANCA was associated with heart disease and fever. We describe a 44-year old female with uncontrolled asthma for 6 months, chronic sinusitis and hypothyroidism seen for evaluation of pulmonary infiltrates and eosinophilia. She initially presented with severe lower extremity, shoulder and neck pain as well as epigastric pain. A CXR performed during her workup revealed pulmonary infiltrates and she was treated with moxifloxacin and steroids. An outpatient physician reviewed her blood work performed in the emergency department and noted eosinophilia. Subsequently she was admitted and a CT chest and neck showed right upper lobe and right lower lobe infiltrates with hilar lymphadenopathy and partial opacification of the ethmoid sinuses. She was subsequently treated with azithromycin and ceftriaxone without improvement. She was also found to have elevated troponins. Subsequent workup included a TTE which showed an ejection fraction of 30-35% and regional wall motion abnormalities. A cardiac MRI showed findings consistent with myocarditis likely secondary to the eosinophilic infiltrates. She was started on solumedrol with dramatic improvement in her eosinophil count, troponin and epigastric pain. ANCA was negative, but based on her clinical features, findings and an overwhelming response to systemic steroids, EGPA was strongly suspected and a VATS open lung biopsy was performed with pathology showing foci of eosinophil enriched granulomatous vasculitis consistent with EGPA. The patient was discharged home on high dose oral steroids and continued to improve. She followed up with Allergy, Rheumatology and Cardiology as an outpatient. This case illustrates the complex pathology and multisystem nature of EGPA.

P204 SUCCESSFUL ALGLUCOSIDASE ALFA DESENSITIZATION IN A 16-MONTH OLD INFANT. H. Bhatti*, E. Secord, P. Poowuttikul, Detroit, MI. Background: Pompe disease (PD) is a rare glycogen storage disease caused by lysosomal acid alpha glucosidase deficiency. The only available medical treatment is alglucosidase alfa enzyme replacement. Alglucosidase alfa improves progressive metabolic myopathy, ventilator-free survival, and cardiac and motor function, especially in severe infantile PD which is known to have high morbidity and mortality. Adverse reactions to alglucosidase alfa are not uncommon (1% cardiac arrest/anaphylaxis required life-support interventions, 14% allergic reactions involved two organ systems from post-marketing safety studies). Only few successful desensitization procedures are previously reported, in two preschoolers and an adult, and there is no standardized protocol for this. Objective: We report successful alglucosidase alfa desensitization in a 16month old infant. Case Report: A child with infantile PD began alglucosidase alfa infusion at age 9 months and tolerated it well until age 16 months. The reactions were angioedema, urticaria, tachycardia and desaturation on several

infusions. The alglucosidase alfa IgE and skin prick testing were negative but intradermal testing was positive at the 1:10 concentration of 5 mg/mL alglucosidase alfa with two negative adult controls. An 11-step (7.5 hours) desensitization protocol started by administering a reduced dose of alglucosidase alfa (10 mg/kg weekly), with gradual dose escalation via serial microdilutions; this was performed successfully in PICU. Dosing was then adjusted to 20 mg/kg every 2 weeks, given in only five steps (3.5 hours) in an outpatient setting, with no reactions. Discussion: Alglucosidase alfa is necessary for the survival of patients with infantile PD; however, severe allergic reactions to alglucosidase alfa may prevent patients from receiving this crucial therapy. Reports of successful desensitization to alglucosidase alfa were made in two preschoolers (infantile PD and less severe, juvenile onset PD; infusion time 6.5 hours) and an adult (less severe, late onset PD; infusion time 12-14 hours). Desensitization in infants with PD is more challenging as infants are unable to convey their symptoms adequately and underlying cardiomyopathy restricts amount of fluid intake allowed. We report of a patient younger than those already reported who has undergone significantly shorter desensitization procedures to alglucosidase alfa successfully.

P205 A CURIOUS CASE OF PERSISTENT T-CELL CLONALITY FOLLOWING CLINICAL RESOLUTION OF TOXOCARIASIS. A. Alvarez*, S. Kumar, Richmond, VA. Introduction: Toxocariasis is a parasitic infection typically acquired from infected feces of dogs or cats. Though parasitic infection is a known but infrequent cause of eosinophilia, resultant T-cell clonality is less well studied. We present a case of persistent T-cell clonality following treatment in a patient with Toxocariasis. Case Description: A 13 year old male presented with fatigue, fevers, abdominal pain, facial and scrotal swelling. Initial workup including CT scans of the chest, abdomen, and pelvis showed multifocal airspace nodules with ground-glass halos as well as numerous hepatic hypodensities and diffuse lymphadenopathy. His laboratory exam was significant for a mild leukocytosis with eosinophilia. Infectious and malignant etiologies were entertained, and he was evaluated for a variety of possible conditions including blood and tissue cultures, viral and fungal serum markers, autoimmune studies, complement levels, and inflammatory markers which were unremarkable. An immune workup showed normal immunoglobulins, and a lymphocyte enumeration panel slightly elevated T-cell marker. Tissue diagnosis was pursued with colonic biopsy and liver FNA failing to provide a diagnosis. He then underwent a lung biopsy which showed non-specific perivascular and interstitial inflammation with immunohistochemistry showing mixed B and T-cells. Though he was discharged with symptomatic improvement, he continued to have fatigue and low grade fevers. Upon review he was noted to have continued eosinophilia, and a workup for hypereosinophilia was initiated. FIP1L1/PDGFRA analysis, B-cell clonality, Trichinella, and Strongyloides antibodies were negative. Toxocara antibody was positive, as was T-cell clonality testing. He completed a course of Albendazole with prompt resolution of his symptoms. Subsequent CT imaging showed interval resolution of his pulmonary nodules, liver lesions and lymphadenopathy. Despite clinical and imaging resolution, his T-cell clonality remained positive and unchanged. Discussion: There is paucity of literature on T-cell clonality in parasitic infections. Given the clinical response, we believe this patient’s T-cell clonality was due to the parasitic infection. We are unsure if his persistent Tcell clonality will resolve with time. Parasitic infection should be in the differential diagnosis for any patient with T-cell clonality and eosinophilia.

P206 MONOCLONAL B-CELL LYMPHOCYTOSIS. A. Gonzalez-Estrada*, A. Klein, R. Dean, R.I. Siles, Cleveland, OH. Introduction: Monoclonal B-cell lymphocytosis (MBL) is an asymptomatic precursor for chronic lymphocytic leukemia (CLL). A diagnosis of CLL can lead to hypogammaglobulinemia. We present a case of hypogammaglobulinemia secondary to underlying MBL with no evidence of CLL. Methods: A case report Results: 61 year old man presented to our department for evaluation of recurrent sinus infections. Computed tomography showed air fluid level within the right maxillary sinus. No cultures were obtained. He had received allergen immunotherapy for allergic rhinitis during adolescence. He had no history of frequent, recurrent or unusual infections. His physical exam was unremarkable with no evidence of lymphadenopathy or hepatospenomegaly. Humoral evaluation demonstrated low IgG (433 mg/dL), low IgA (55 mg/dL) and low IgM (42 mg/dL) with protective response to past tetanus and diphtheria vaccines. Pre-pneumococcal titers were present for 4/14 serotypes, which increased to



ABSTRACTS: POSTER SESSIONS 6/14 pneumococcal serotypes post vaccination. A decision was made to manage the patient conservatively given response to medical treatment and patient’s preference. Subsequent flow cytometry evaluation demonstrated an elevated number of CD19 positive B cells (1320 per microliter), with a reference range of 75-660 cell/uL. Enumeration of T cells and NK cells were normal. Serial evaluation demonstrated a gradual rise in the absolute number of circulating B cells to 1950 cell per microliter. Further analysis revealed an abnormal immunophenotype of B cells expressing CD5, CD19, CD20, CD23, and CD45 with subset expression of monotypic kappa surface light chain immunoglobulin. The B-cells were negative to other markers. This is consistent with monoclonal B-cell lymphocytosis as he had no clinical manifestation of CLL. The patient is closely being followed. Conclusions: This case report demonstrates the presence of humoral defects that can precede a diagnosis of CLL. To our knowledge, this is the first case of hypogammaglobulinemia secondary to monoclonal B cell lymphocytosis in the literature.

melanin positive hyphae. Cultures from the sinus and abscesses grew Curvularia. HIV ELISA was negative and there was no evidence of diabetes. IgA, IgG, and IgM were normal. IgE was significantly elevated at 4509 IU/ml. RAST specific testing for Curvularia illustrated elevated levels of IgE and IgG antibodies. Skin prick testing was positive for Curvularia. The patient completed an extended course of antifungals as well as oral steroids. Discussion: “Is this aggressive allergic fungal sinusitis or is this invasive fungal sinusitis?” Invasive fungal sinusitis is typically seen in immunocompromised patients leading to tissue necrosis with high morbidity and mortality. Allergic fungal sinusitis is defined as being a non-invasive disease with a more hypersensitivity response to the presence of extra-mucosal sinus fungal hyphae. While bony erosions have been described in literature in association with allergic fungal sinusitis, progression to intracranial abscess is a rare complication. The comparison between these possibilities as illustrated by this patient perhaps represents a spectrum of the two diseases.



A CASE OF LYMPHOCYTOPENIA DUE TO LYMPHATIC MALFORMATION. M. Goodman*, J.S. Tan, K.A. Risma, F.X. McCormack, A.W. Lindsley, Cincinnati, OH.


The evaluation of patients presenting with lymphocytopenia poses a unique diagnostic challenge given the large differential encompassed by such a finding. The most common causes to consider are bacterial sepsis, postoperative state, malignancy, use of glucocorticoids, chemotherapy/radiation therapy, trauma, and primary or secondary immunodeficiency. While rare, lymphatic malformations (LM), have previously been reported as a cause of lymphocytopenia, and are often associated with a poor prognosis. Here we describe an unusual case of lymphocytopenia associated with a left lower lobe pulmonary lymphangiomatosis, demonstrating the diagnostic challenges associated with linking lymphocytopenia to LM. A 30 year-old, non-smoking, male initially presented to Allergy and Immunology clinic for immune evaluation due to a 5 year history of progressively worsening productive cough, noisy breathing at night, and persistent “pneumonia.” The patient would frequently cough up balls of a string-like white material. Lab evaluation showed chronic lymphocytopenia with low CD4, CD8, and CD19 cells, low-normal NK cells, and an expanded gamma/delta T cells population. He also developed hypogammaglobulinemia during an acute respiratory decompensation following a diagnostic VATS procedure. Pulmonary biopsy showed desquamating interstitial pneumonia, but subsequent whole-body lymphoscintigraphy revealed lymphatic telangiectasiae of the left lower mediastinum with fistulous connection to the lower lobe of the left lung. A diagnosis of lymphocytopenia due to LM was then made. This case is notable for the fact that it illustrates an uncommon but severe etiology of lymphocytopenia, lymphatic malformations. The initial lab abnormalities were suggestive of an underlying primary immunodeficiency; his pulmonary complications the result of respiratory infections. It was only through looking at the patient in a broader context, and further investigation of his atypical symptoms, that the correct diagnoses of LM was elucidated. This case illustrates the importance of considering lymphatic malformations when evaluating cases of lymphocytopenia.

P208 AGGRESSIVE OR INVASIVE ALLERGIC FUNGAL SINUSITIS? F. Tabatabaian*, H. Niebur, M. Ballow, M. Sher, St. Petersburg, FL. Introduction: Allergic fungal sinusitis is a form of chronic rhinosinusitis, which is associated with atopic individuals with nasal polyposis, characteristic CT findings of bony erosions, eosinophilic mucin on pathology, and positive fungal smear or culture. This is a case of allergic fungal sinusitis, a typically non-invasive disease with an uncommon complication of multiple epidural abscesses. Methods: Description of clinical presentation, lab, radiographic, and pathology data. Case Presentation: A 16-year-old African American male with a two year history of chronic congestion and anosmia developed severe headache, fever, and right sided facial numbness. He was initially diagnosed with acute sinusitis and was started on amoxicillin. Despite therapy, his symptoms persisted and on re-examination he was found to have evidence of nasal polyposis and left sided facial weakness. CT scan of the head illustrated extensive chronic rhinosinusitis, bony erosion into the anterior cranial fossa from frontal, sphenoid and ethmoid sinuses with formation of bilateral frontal epidural abscesses and right temporal abscess. He emergently underwent debridement under stereotactic guidance. Microscopic analysis of mucosal fragments illustrated eosinophilic infiltration, chronic inflammation and branching, septated


Introduction: Prevalence of food allergy has been increasing over the last several years. Causative foods include peanut, soy, wheat and seafood with symptoms developing 5-30 minutes after ingestion. However, in 2009 Cummings et al. described delayed allergic reactions, typically waking people from sleep, to red meat with similar symptoms. Reactions occurred with beef, pork and lamb ingestion in patients sensitized to galactose-alpha-1,3-galactose (alphagal) who also had a history of bites caused by Amblyomma americanum, a species of tick usually found in Southern states. This case report documents a history and evaluation suggestive of a food-dependent exercise-induced anaphylaxis (FDEIA) related to an alpha-gal allergy. To our knowledge this is the first case report specific to this entity. Case Description: A 73 year-old white male presented to a clinic in Minnesota with a history significant for four episodes of anaphylaxis. The first two episodes occurred several hours after eating cashews and peanuts, respectively. Testing showed borderline sensitivity towards nuts. He avoided all nuts, but had two more similar episodes. His fourth episode occurred on a camping trip after eating steak that woke him from sleep. On further questioning, it was noted that all of his previous episodes were associated with physical activity and he remembered episodes of urticaria after hunting in Missouri. Currently, he is a retired and lives in Minnesota. Exam was unremarkable, Skin Prick Testing to nuts was repeated and negative, tryptase was negative. Given his history, ImmunoCAP to alpha-gal was performed and positive Therefore, it was concluded his anaphylaxis was induced by a combination of exercise with a proven food allergy to alpha-gal. Currently, he avoids beef and has not had another episode. Conclusion: Anaphylaxis caused by an allergy to alpha-gal is difficult to diagnose since it occurs 4-6 hours after ingestion. This case was unique in that the patient had to have concomitant beef ingestion and moderate activity to elicit anaphylaxis. It is always imperative to take a good history when evaluating patients for etiologies of anaphylaxis, but history of tick exposure needs to be included even if the patient does not live in the typical area. Without a detailed history of past exposure this diagnosis may not have been considered. To our knowledge, this is the first reported case of alpha-gal allergy associated with FDEIA.

P210 AUTOIMMUNE LYMPHOPROLIFERATIVE SYNDROME: A GROUP OF THREE PATIENTS. C.T. Quezada-Chalita*, I.D. Castillo, S. Enciso-Peláez, M. Moreno, Mexico City, DF, Mexico. Autoimmune lymphoproliferative syndrome (ALPS) is a disorder of T cell dysregulation caused by defective Fas-mediated apoptosis. Testing for ALPS should be considered in patients with unexplained lymphadenopathy, hepatosplenomegaly and/or autoimmunity. An increased number of a T cell population termed “double negative T cells” (DNTs) are present. CASE 1 : A 12-year old male with epistaxis, easy bruising and gingival bleeding. At admission severe neutropenia and thrombocytopenia were found with multiple lymphadenopathies in neck. Bone marrow aspiration showed left shift in myeloid cells, hyperplasic mature megakaryocytes, unremarkable lymphoid cells. EBV serology was positive. ANA, anti-DNA, direct Coombs and lupus anticoagulant were positive, IgG elevated. Thoracic-abdominal CT showed diffuse lymphadenopathy. A cervical lymph node was biopsied and atypical cortical and paracortical hyperplasia with progressive transformation of germinal centers was found. The DNTs cells were elevated (41.4 %). After prednisone treatment


ABSTRACTS: POSTER SESSIONS cytopenias remitted. CASE 2 : A 13-year old male with splenomegaly and bicytopenia. Bone marrow aspiration showed normal cellularity, hyperplasic megakaryocytes, and abundant plasma cells. ANA with a homogeneous pattern, anti-DNA, c-ANCA and lupus anticoagulant with a direct Coombs were positive. DNTs elevated with 20 % . He developed sepsis and neutropenic colitis requiring IVIG and wide spectrum antibiotics. Because of persistent bicytopenia mophetil mycofenolate was started. CASE 3 : A 11-year old male with epistaxis, gingival bleeding and bruising. Admitted with fever and otorrhea. Physical exam was positive for splenomegaly. He had pancytopenia, positive direct Coombs, and polyclonal hypergammaglobulinemia. Bone marrow aspiration reported hypercellularity with hyperplasic immature megakaryocytes and maturation arrest in the myeloid serie. ANA with a speckled pattern was positive as well as lupus anticoagulant. IgG serology for EBV was positive. High levels of vitamin B12. DNTs were also elevated with 3.02 %. ALPS is a rare syndrome caused by defective lymphocyte apoptosis with a wide range of symptoms including cytopenias. This diagnosis should be considered in any child with autoimmune cytopenias and lymphoproliferation findings.

P211 EFFICACY AND SAFETY OF INTRAVENOUS IMMUNOGLOBULIN IN ELDERLY PATIENTS WITH PRIMARY IMMUNE DEFICIENCY. J. Romm*, E. Gascoigne, M. MacKechnie, T. Aldwinckle, Elstree, United Kingdom. Introduction: There is little published on the use of intravenous immunoglobulin in specific populations such as elderly subjects, many of whom have existing co-morbidities. This post-hoc analysis of data from a previous clinical study evaluated the efficacy and safety of intravenous immunoglobulin in elderly patients with primary immune deficiency (PID). Methods: Data were extracted from listings for a clinical study (study code: GMX01) in which patients with PID received a 5% (w/v) intravenous immunoglobulin at doses of 300 to 800 mg/kg per infusion, every 21 or 28 days for a period of up to 1 year. IRB approval and informed consent was obtained from all research subjects. Results: Efficacy and safety were evaluated in elderly patients aged >60 years (mean age 69.3 years; range 61 to 78 years; n = 12) compared with younger adults (mean age 41.2 years; range 19 to 57 years; n = 31). Of the 12 patients aged >60 years, 11 (91.7%) had a documented co-morbidity1, compared with 13/31 (41.9%) patients aged 19 to 57 years. Median exposure to intravenous immunoglobulin was 351 days in both patient groups; all 12 patients aged >60 years completed the study, whereas 3/31 patients aged 19 to 57 years withdrew due to adverse events (paraesthesia, bronchospasm and pregnancy). Dose per infusion ranged from 307 to 647 mg/kg in those aged >60 years and from 300 to 790 mg/kg in patients aged 19 to 57 years. The specified maximum infusion rate (0.08 mL/kg/min) was achieved by all 12 patients aged >60 years and by 30/31 patients aged 19 to 57 years. Key safety data are summarised in the Table below. No serious acute bacterial infections were observed in either patient group. 75.0% of patients aged >60 years experienced an infection at some point, compared with 80.6% of those aged 19 to 57 years. Patients aged >60 years also reported lower mean study days on therapeutic systemic antibiotics, but 91.7% of older subjects visited a physician or hospital due to an infection or other medical problem compared with 77.4% of the younger group. Conclusions: In conclusion, these preliminary data indicate that intravenous immunoglobulin is effective and well tolerated in elderly PID patients with co-morbidities. 1. Elixhauser A et al. Medical Care, 1998; 36: 8 – 27. Footnote: The brand name of the intravenous immunoglobulin used in this research was Gammaplex®.

Key Safety Findings

P212 PHARMACOKINETICS OF INTRAVENOUS IMMUNOGLOBULIN IN CHILDREN. J. Romm*1, E. Gascoigne1, S. Leach1, C. Brindley2, T. Aldwinckle1, 1. Elstree, United Kingdom; 2. Quothquan, United Kingdom. Introduction: There is little published on the pharmacokinetics (PK) of intravenous immunoglobulin (IVIG) in specific populations, such as children. This research compared the PK of IVIG in two populations, namely children/adolescents and adults with primary immune deficiency (PID). Methods: Noncompartment analysis (WinNonlin) was used to calculate IgG PK using unadjusted serum IgG data from a previous study on a 5% (w/v) IVIG in adults with PID (study code: GMX01) and an ongoing study in children (study code: GMX04). Both studies specified doses of 300 to 800 mg/kg per infusion, with identical PK blood sampling after 6 months’ dosing. IRB approval and informed consent was obtained from all research subjects. Results: The pediatric population (aged 4 to 16 years) comprised 19 PID subjects (18 from GMX04 and 1 from GMX01), and the adult population (aged 17 to 78 years) comprised 22 PID subjects from GMX01. The mean dose per infusion was 3.6% higher in children than in adults (mean values of 497.7 mg/kg and 480.2 mg/kg respectively). Systemic exposure to IgG at steady state (AUCo-τ and Clearance, CL) in children was not statistically significantly different to that in adults. By contrast, Maximum Concentration (Cmax) and Cmax/Dose in children were 12% and 17% lower respectively than in adults; the between-group differences were statistically significant. The age-related difference in Cmax/Dose was largely explained by including Body Mass Index (BMI) in a statistical model. Volume of Distribution (Vss) in children was 40% greater than in adults (28% greater when BMI was included in a statistical model), and the difference was statistically significant. The larger Vss in children was reflected in a longer apparent terminal half-life (geometric means of 36.9 and 29.9 days in children and adults respectively). Over the entire age range of 4 to 78 years, CL, Vss and Half-life tended to decrease with increasing age, whilst Cmax/Dose and AUC0-τ tended to increase with increasing age. Conclusions: Although these age-related correlations were statistically significant, the serum IgG profile of IVIG in children was not appreciably different to that in adults. Furthermore, primary measures of exposure (AUC0-τ and CL) were not statistically different, with no appreciable differences in dosage requirements. Footnote: The brand name of the intravenous immunoglobulin used in this research was Gammaplex®.

P213 SAFETY AND TOLERABILITY OF INTRAVENOUS IMMUNOGLOBULIN IN PEDIATRIC PATIENTS WITH PRIMARY IMMUNE DEFICIENCY. J. Romm*, E. Gascoigne, S. Leach, M. Stratford Bobbitt, T. Aldwinckle, Elstree, United Kingdom. Introduction There is little published data on the tolerability of intravenous immunoglobulin products in specific populations such as children with primary immune deficiency (PID). The objective of this research was to compare the safety and tolerability of a intravenous immunoglobulin (IVIG) in two patient populations, namely children/adolescents and adults with PID. Methods Adverse reaction data from a previous study on a 5% (w/v) IVIG in mainly adults with PID (study code: GMX01) was compared with that from an ongoing study in children with PID (study code: GMX04). The two studies were similar in terms of design and data capture, with subjects receiving IVIG at doses of 300 to 800 mg/kg per infusion, every 21 or 28 days for a period of up to one year. IRB approval and informed consent was obtained from all research subjects. Results Study GMX01 recruited 50 PID subjects with a mean age of 44.0 years (range: 9 to 78 years) receiving 703 infusions. At the time of data analysis (Jan-



ABSTRACTS: POSTER SESSIONS uary 2013), study GMX04 had recruited 21 PID subjects, with a mean age of 10.8 years (range: 4 to 16 years) receiving 285 infusions. Product-related adverse reactions were reported by 24/50 (48.0%) of subjects in the GMX01 study, compared with 10/21 (47.6%) of pediatric subjects (GMX04 study). One subject in the GMX01 study, with pre-existing risk factors, experienced two product-related serious adverse events (thrombosis and chest pain); there were no reports of product-related serious adverse events in the pediatric population (GMX04 study). Number and percent of subjects with the most frequent product-related adverse reactions are summarised in the Table below. The incidence of hypotension appeared to be higher in the pediatric population, emphasising the importance of adequate hydration prior to intravenous immunoglobulin infusion. Conclusions In conclusion, the interim analysis of an ongoing study on intravenous immunoglobulin in children with PID suggests that overall tolerability in the pediatric population is comparable to that in adults. However, whilst the overall incidence of product-related adverse reactions appears to be somewhat greater in the adult population (GMX01), analysis of the pediatric study (GMX04) is based on interim data in fewer subjects. Footnote: The brand name of the intravenous immunoglobulin used in this research was Gammaplex®. Most Frequent Adverse Reactions to Intravenous Immunoglobulin

P214 A NOVEL STAT1 MUTATION MANIFESTING AS MYCOBACTERIUM FORTUITUM CERVICAL ADENITIS. T.J. Owens*1, D. Sutter1, J. Quinn1, S. Holland2, 1. JBSA - Lackland, TX; 2. Bethesda, MD. Introduction: M. fortuitum is rarely the cause of recurrent infection in an immunocompetent patient as it is weakly pathogenic. The finding of weakly pathogenic mycobacteria may raise the suspicion for Mendelian susceptibility to mycobacterial diseases (MSMD). STAT 1 deficiencies are a rare group of genetic defects within the family of MSMD. Case Report: A 4 year old boy with a history of failure to thrive (FTT) and recurrent infections diagnosed with M fortitum adenitis was referred to our service for further evaluation. His course was complicated by relocations and incomplete records. His mother reported a normal pregnancy, delivery, and peripartum course. His first year of life was remarkable for FTT despite numerous interventions including NG feeding and TPN. Extensive evaluations did not reveal a diagnosis for his FTT. He had frequent thrush responsive to therapy. He first had pneumonia at 1 year of age. Subsequently his course was remarkable for recurrent otitis media requiring PET, mucocandidiasis, recurrent pneumonia, recurrent perianal abscesses, and cervical adenitis. He was noted to have mild delay of speech and developmental milestones. He was fully vaccinated and tolerated live viral vaccines. Prior immunologic laboratory evaluations demonstrated intermittent mild lymphopenia and normal evaluations of quantitative immunoglobulins, CH50, AH50, neutrophil oxidative burst, and antibody response to diphtheria, tetanus and isohemagglutinins. He was HIV negative. Flow cytometry reported normal numbers of T and B cells, but decreased NK cells. Mitogen stimulation was reported as decreased. Culture of an excised lymph node was positive for M fortuitum. Repeat immunologic evaluation at referral was notable for a normal WBC count 13,300 cells/m3; lymphopenia 1,769 cells/m3; and reduced T cells 974 cells/m3, CD4 cells 493 cells/m3, and NK cells 46 cells/m3. Mitogen stimulation was normal to PHA, PWM, and Con A. STAT1 gene analysis at the National Institute of Health revealed a single base transition, c.853 C>A, causing substitution of lysine for glutamine at amino acid 285. Conclusion: We report a novel mutation in the STAT1 gene with resultant immunodeficiency. This lysine for glutatmine substitution at position 285 is consistent with an autosomal dominant STAT1 deficiency and is similar to mutations in STAT1 that have been reported at the adjacent amino acids.


P215 AN OMEN OF OMENN SYNDROME. F. Khan*, C. Chang, Wilmington, DE. Background: Omenn syndrome is a form of severe combined immunodeficiency (SCID) characterized by erythroderma, hepatosplenomegaly, lymphadenopathy, eosinophilia, alopecia, failure to thrive and chronic diarrhea. These patients present with recurrent infections. Laboratory findings typically reveal absence of B cells and the presence of oligoclonal autoreactive T cells. These T cells target organs such as skin and gut, resulting in the erythroderma and colitis respectively. Bone marrow transplant (BMT) is the firstline therapy for most forms of SCID, including Omenn syndrome. Case Description: SS is a 1 day-old Amish female, 2850 gram born at home without complications. She is the youngest of 10 siblings, with 2 siblings diagnosed with RAG1 SCID. Her eldest sibling, born 20 years ago, died of unknown causes. At birth, SS was found to have erythroderma and a desquamative skin rash. She was immediately transferred to AIDHC and placed on reverse isolation. Laboratory studies revealed a homozygous RAG1 mutation, absolute eosinophil count of 8500 and TRECS of 0. T cell phenotyping revealed CD4+CD45RA+ and CD4+CD62L+CD27+ to be 0 cells/mcL and an overall decreased mitogen stimulation response. On admission, she was placed on antimicrobial prophylaxis and IVIG infusions every 2 weeks. Two matched siblings were never immunized and were positive to varicella, cytomegalovirus (CMV) and Epstein-Barr virus (EBV), causing a delay in BMT. After 8 weeks of hospitalization, myeloablative therapy was initiated in preparation for BMT with donor matched sibling. The donor had recovered from a primary varicella infection during which he was viremic for EBV (peak viremia 17 copies). After a month, the increasing risk of infection from further delay coupled with a reduction in donor viremia motivated the decision to complete BMT on hospital day 70. Post transplant, the infant was started on prophylaxis for graft versus host disease and remained stable. Discussion: This case illustrates the importance of identifying an at risk child in a population who may be genetically predisposed for rare but potentially lethal diseases. Prompt diagnosis is crucial in identifying infants with SCID, because early BMT can be life-saving. Our case illustrates management challenges including finding a donor match sibling for BMT who is negative for CMV, EBV and/or varicella. Our case also emphasizes the need for mandatory newborn screening for SCID.

P216 NATURAL KILLER CELL DEFICIENCY. J. Greiwe*, J. Fernandez, L. Pien, Cleveland, OH. Introduction: NK cell deficiency syndromes are rare disorders in which either the number, function, or both are abnormal. These syndromes can be divided into three categories: absolute, classical, and functional. They are characterized clinically by susceptibility to severe and/or recurrent viral infections, especially herpes viruses. A large majority of these patients die from complications in childhood, however there is a small minority of adult patients who often go undiagnosed. Methods: A case report Results: A 31 year old female presented to clinic after a recent hospitalization with pancytopenia -suspected to be secondary to a viral infection. She was confirmed to have West Nile virus meningitis and presumed HSV meningitis. Lab work was remarkable for low immunoglobulins at that time, and she presented to our clinic for further workup. The patient has a self-reported history of recurrent infections requiring intermittent antibiotics since childhood. Additional complaints include chronic fatigue and persistent viral infections with recurrent “cold sores” on the outside of her lips (~2 times/month) that clinically seemed to be consistent with HSV. She has no history of atopy or recurrent CMV, EBV, or zoster infections. Humoral immunity was re-evaluated a few months after hospitalization and showed persistent abnormalities: IgG 589 mg/dL, IgA 63, and IgM 31. There was normal responses to diphtheria/tetanus vaccines, but only 1/14 protective pneumococcal titers 18 months after receiving the pneumovax vaccine. Flow cytometry was repeated multiple times which consistently showed low levels of NK cells: 1% and 32 cells/mcl. An NK cell cytotoxicity assay was performed and showed decreased NK cell absolute counts and cytotoxic activity. Based upon clinical history and lab results, the diagnosis of NK cell deficiency was made. She was started on prophylactic acyclovir 400mg PO BID for a 3 month trial period. After only a few weeks of treatment, the patient noted significant improvement in viral-related symptoms. Conclusion: This case report confirms that in addition to a detailed clinical history and a high level of suspicion, flow cytometry followed by NK cell cytotoxicity testing is a simple and effective way to evaluate NK cell deficiencies. It also highlights the impor-


ABSTRACTS: POSTER SESSIONS tance of keeping this disorder in the differential diagnosis, especially in cases of unexplained recurrent viral infections.

be considered mainly for patients with recurrent respiratory and/or ear infections prior to IVIG therapy in pediatric group.





Hyper-IgE Syndrome (HIES, ‘Job’s Syndrome’) is a rare primary immunodeficiency characterized by eczema, skin abscesses, candidiasis, recurrent pulmonary infections, and formation of pneumatoceles (1). Mutations in STAT3 have been shown to be the cause of autosomal dominant HIES (2). We report the case of 61-year-old female who presented to our institution for treatment of invasive pulmonary aspergillosis. Laboratory investigation revealed an elevated total IgE (4758 kU/L). Her infectious history is notable for oral candidiasis, several pneumonias caused by Staphylococcus aureus and Pseudomonas aeruginosa, and an aspergilloma that required lobectomy due to severe hemoptysis. Additional clinical manifestations included mild eczema, retained primary teeth, scoliosis, and hyperextensible joints. She had a score of 50 according to the NIH clinical HIES scoring system, which suggests HIES (3). Immunologic studies showed normal lymphocyte phenotyping with NK marker; normal IgA, IgG, and IgM; and protective antibody titers for diphtheria, tetanus, and pneumococcus. CH50 and AH50 were unremarkable. TH17 cells were marginally decreased (0.3% of CD4 cells). DNA sequencing of the STAT3 gene revealed a heterozygous transition from A to G in Exon 21 (c. 1934A>G), resulting in an amino acid change, p. Leu645Pro. This variant has not been reported in the literature or NCBI database. One predictive protein modeling program suggests that Leucine to Proline is not a tolerated amino acid change at position 645. Both of the patient’s parents were healthy, and none of her ten siblings have similar medical concerns, suggesting a spontaneous in utero STAT3 mutation. Her son and three granddaughters have clinical histories characteristic of HIES, including eczema, severe pneumonias, retained primary teeth, pathologic fractures, and skin abscesses. To date, her son has not agreed to confirmatory genetic testing for himself or his three daughters. 1. Buckley RH, Wray BB, Belmaker EZ. Extreme hyperimmunoglobulinemia E and undue susceptibility to infection. Pediatrics 1972;49:59–70. 2. Holland, S.M., F.R. DeLeo, H.Z. Elloumi, et al. 2007. STAT3 mutations in the hyperIgE syndrome. N. Engl. J. Med. 357:1608–1619. 3. Grimbacher B, Schaffer AA, Holland SM, Davis J, Gallin JI, Malech HL, et al. Genetic linkage of hyperIgE syndrome to chromosome 4. Am J Hum Genet 1999;65:735-44.

Background: Before 1968, severe combined immunodeficiency (SCID) was a universally fatal diagnosis in infants who succumbed to fulminant infections. Early diagnosis and hematopoietic stem cell transplantation (HSCT) has led to improved outcomes. However, some patients may have persistent infectious complications despite complete immune reconstitution. Here we report 2 cases of recalcitrant verrucae in two siblings with SCID after HSCT. Case presentation: Two half-brothers, ages 9 and 12, both with X-linked SCID due to genetic defects in common gamma chain, successfully underwent haplotype identical donor HSCT, with maternal peripheral blood cells at birth and maternal bone marrow aspirate at 3 months of age respectively. Both siblings have demonstrated complete reconstitution of cellular and humoral immunity by peripheral blood analysis. Laboratory analysis include normal quantitative immunoglobulins, cellular immune panels (total CD3 counts 2419, 2673, and total NK cell counts 145, 365 respectively), as well as robust lymphocyte proliferation response to mitogen (PHA, PWM) and antigen (candida, tetanus). However, both boys have recalcitrant verrucae vulgaris on trunk and extremities, as well as verrucae planae on their face, many years after HSCT despite multiple topical and systemic treatments. Conclusion: HSCT is a life-saving treatment for SCID, however, there is evidence for persistence of partial immunodeficiency associated with significant infections, including severe human papillomavirus (HPV) disease in X-linked SCID. The cause for increased susceptibility to warts after HSCT in SCID patients remains unknown, although certain genetic defects in the natural-killer cell, or IL-2Rgamma-c/JAK-3 dependent signaling in keratinocytes, likely play a role in the immune response against HPV. (1-3) References: 1. Laffort C et al. Severe cutaneous papillomavirus disease after hematopoietic stem-cell transplantation in patients with severe combined immune deficiency caused by common gamma-c cytokine receptor subunit or JAK-3 deficiency. Lancet. 2004;363(9426):2051-4. 2. Neven B et al. Long-term outcome after hematopoietic stem cell transplantation of a single-center cohort of 90 patients with severe combined immunodeficiency. Blood. 2009;113:4114. 3.Leidig JW, Holland SM. Warts and all: Human papillomavirus in primary immunodeficiencies. JACI. 2012;130(5):1030-1048.


Peripheral Blood Analysis:

PROFOUND HYPOGAMMAGLOBULINEMIA WTH ADEQUATE VACCINE RESPONSE IN A 9 YEAR OLD BOY. L. Zhou*, R. Rodriguez, Jackson, MS. Introduction: The prevalence of immunodeficiency disorders is much higher than generally thought. Most primary immune-deficiencies (PID) become manifest during early childhood. Most of the PI primarily involves the humoral immunity followed by cell-mediated immunity, combined humoral and cell-mediated immunity, phagocytic defects, and diseases involving the complement system. We report a 9 year old boy with recurrent infections since one year of age and profound hypogammaglobulinemia with adequate vaccine response. Method: A 9 year old boy was referred to our immunology clinic at the age of 8 years old and with careful monitoring over time with serial immunoglobulin and T-cell subset measurement and reassessment of his antibody response to vaccine. Results: One 9 year old male who presented with recurrent rhinosinusitis and pneumonia since one year of age referred to our clinic for evaluation at 8 years of age. Serial immunoglobulins throughout his life reveal low IgG (157mg/dl, 172mg/dl, and 140mg/dl at age of 10m, 7y, and 8y, respectively), IgA (10mg/dl, 12mg/dl, and 15mg/dl at age of 10m, 7y, and 8y, respectively) with normal IgM. Lymphocyte subset reveals normal CD4, CD8, with slightly decreased CD19 (231cells/ul). His antibody titer (IgG) to tetanus and diphtheria vaccine was within protective range at age of 7y. His pre and post antibody titers showed a good response to HiB and pneumococcal vaccines. Due to the persistent hypogammaglobulinemia even in the presence of good antibody response he was started an amoxicillin 500mg PO QD prophylactic treatment 8 months ago and reported no pneumonia or rhinosinusitis infection since antibiotic prophylactic treatment. We plan to follow up with this patient long term. Conclusions: Symptomatic hypogammaglobulinemia in childhood may be the initial finding of PID. Antibiotic prophylaxis should

Complete immune reconstitution as measured by peripheral blood analysis of lymphocyte subsets and proliferation response to mitogens and antigens. PWM, pokeweed mitogen; PHA, phytohemagglutinin




P220 CLINICAL STABILIZATION OF A NEWBORN WITH ADA-SCID USING SUBCUTANEOUS IMMUNE GLOBULIN PRIOR TO GENE THERAPY. N.L. Rider*1, K.A. Strauss2, E. Puffenberger2, D.H. Morton2, 1. Carlisle, PA; 2. Lancaster, PA. Introduction: At present, subcutaneous IgG replacement is indicated for children aged 2 years and older. However, newborn screening for Severe Combined Immunodeficiency allows for disease identification and intervention at earlier ages. We present evidence for the safety and efficacy of subcutaneous IgG replacement in a newborn with Adenosine Deaminase Deficiency. Methods: Adenosine Deaminase Deficiency/Severe Combined Immunodeficiency was diagnosed at birth in an Amish infant. The child was managed comprehensively as an outpatient using PEG-ADA, antimicrobial prophylaxis and subcutaneous IgG replacement. IgG replacement therapy (100mg/kg-week) commenced within the first week of life. Steady state serum IgG, metabolic parameters and clinical status were recorded in our practice until she qualified for entry into a gene therapy trial. Results: Molecular analysis confirmed a known pathologic ADA 646 A>G variant, thus IgG replacement was initiated and serum levels maintained at 884±238mg/dL throughout the first two years of life. No serious bacterial infections were observed. The child underwent gene transfer at 18 months of life without reconstitution of the B-cell compartment. She requires ongoing IgG replacement therapy via the subcutaneous route and remains in good condition. Conclusion: Subcutaneous IgG replacement is effective in newborn infants with life threatening immunodeficiencies.

P221 PLASMA CELL MYELOMA PRESENTING AS GASTROENTERITIS. I. Cohen*, S. Qazi, P. Mustacchia, M. Frieri, East Meadow, NY. Introduction: Immunologists and gastroenterologists should be familiar with plasma cell myeloma, or multiple myeloma, the second-most common hematologic malignancy in the US after non-Hodgkin’s lymphoma. It develops in 1-4 per 100,000 per year and nearly 45,000 Americans live with the malignancy. Patients can present with hypercalcemia, renal insufficiency, anemia and bone lesions. Case: The patient was an 83-year-old Hispanic female with a medical history of hypertension, type two diabetes mellitus and diverticulosis who presented with a complaint of nausea, vomiting, diarrhea and abdominal pain for four days. Vomiting was non-bilious, diarrhea was watery and abdominal pain was localized to the epigastric region. She denied fevers, night sweats, hematemesis, hematochezia, or melena, but did have a 10 pound of unintentional weight loss over the past 2months, frequent chills and urinary hesitancy. Similar symptoms occurred 2-months prior, which resolved and she was diagnosed with acute gastroenteritis and acute renal failure. Methods: Physical examination revealed dry mucous membranes, decreased skin turgor, pallor, generalized abdominal tenderness without rigidity, rebound tenderness or guarding. A WBC count was 5 K/mm3 without differential shift, 9.7 gm/dL Hgb, 9.8 mg/dL calcium, 5.3 gm/dL TP of 48 mg/dL BUN and a rising 7.8 mg/dL creatinine. Fractional sodium excretion was 10.12%. Serum and urine protein electrophoresis both produced a free kappa light chain. Bone survey showed multiple punched-out lytic skull lesions and small focal lesions in the ischia bilaterally. Bone marrow biopsy revealed, plasma cells with >30 percent of the nucleated cells, kappa and CD-138+. Kidney biopsy findings were consistent with light chain cast nephropathy. Conclusion: She was diagnosed with PCM and initially started on Bortezomib, a proteasome inhibitor, that exerts its effects through NF-κB inhibition and on cell survival pathways, such as the p44/42 MAP kinase pathway, and inhibitory effects on IL6, TNF-α, and VEGF and dexamethasone along with hemodialysis 3 times per week. She eventually received 7 cycles of plasmaphoresis to reduce free light chains. Gastrointestinal symptoms improved with therapy. In patients who present with renal failure, nausea, vomiting and other uremic symptoms, a differential diagnosis should include monoclonal gammopathies even if calcium levels are not elevated.


Bone marrow biopsy from this patient showing plasma cells comprising greater than 30 percent of the nucleated cells.

P222 PASTEURIZED, NANOFILTERED C1-ESTERASE INHIBITOR FOR ANGIOEDEMA DUE TO ACQUIRED C1-INH DEFICIENCY. H. Farkas*, K. Molnar, L. Horvath, D. Csuka, Z. Zotter, L. Varga, S. Benedek, Budapest, Hungary. Angioedema due to acquired C1-INH deficiency (AAE-C1-INH) is a rare disease characterized by recurrent edematous episodes in the subcutis and/or submucosa. AAE-C1-INH is often associated with lymphoproliferative disorders. Low C1-INH activity leads to the activation of plasma cascade systems, resulting in bradykinin release. C1-INH inhibits these processes. C1-INH concentrate is a potential option for the treatment of AAE-C1-INH; however, only limited data are available with this treatment. In this study, we assessed the efficacy and safety of a pasteurized, nanofiltered C1-esterase inhibitor (pnfC1INH, Berinert®, CSL Behring, Marburg, Germany) administered as acute treatment and short-term prophylaxis in four patients (3 males, 1 female) with AAE-C1-INH. The onset of their symptoms was at the age of 58 years on average. All patients had a negative family history, along with low C4, C1q, C1-INH levels, and C1-INH functional activity. Different types of autoantibodies against C1-INH could be detected in two patients’ serum. Three patients had non-Hodgkin lymphoma, and a male subject suffered from multiple myeloma. All patients were hypertensive and used ACEIs at the time of diagnosis. The first step of management was to withdraw the ACEIs. Tranexamicacid was introduced for long-term prophylaxis in a single patient. Three patients received pnfC1-INH 1000 U/attack on 31 occasions. One patient with anti- C1INH antibodies required higher doses (2000-2500 U/attack) for acute therapy on 41 occasions. Mean time to the onset of symptom relief was 1.5 hours, and the symptoms resolved in all cases within 24 hours on average. No drug-related adverse events were observed. Short-term prophylaxis with 1000 U was administered to two patients on 12 occasions before dental procedures, and on one occasion before iliac crest biopsy. All procedures were uneventful. Any underlying disease has been treated in all patients. Two patients received Rituximab, one underwent autologous stem cell transplantation, and splenectomy was performed in another. The treatment of underlying disease improved the symptoms also of AAE-C1-INH. pnfC1-INH can be used effectively and safely for acute treatment and short-term prophylaxis in AAE-C1-INH. Higher doses are needed in some cases. The elimination of potential trigger factors and the therapy of any underlying disease are essential.



P223 CASE REPORT OF A PATIENT WITH COMMON VARIABLE IMMUNODEFICIENCY (CVID), MANNOSE BINDING LECTIN DEFICIENCY WITH PERSISTENT EBV INFECTION AND RECURRENT EBV INDUCED LEIOMYOSARCOMA. A. Kochin*, A. Rubinstein, Bronx, NY. Introduction: Primary hepatic mesenchymal tumors are rare. Leiomyosarcoma represent 8% to 10% of all sarcomas. It has been reported that these neoplasms are strongly associated with EBV infection. The majority of cases of EBV associated leiomyosarcomas were reported after liver or kidney transplantation and in HIV infected patients. We report of a primary hepatic EBV positive leiomyosarcoma in a patient with CVID. Four years after partial liver resection the patient had a recurrence of the leiomyosarcoma which was treated with a liver vessel embolization. Methods:A 33-year old woman was evaluated for a history of recurrent infections; bronchitis, sinusitis, and pneumonias since early infancy. In addition, she had a history of Infectious Mononucleosis with persisting EBV viremia, she also suffered from recurrent episodes of shingles, CMV infection, HPV infection, onychomycosis and developed a Pneumocystis Jirovecii pneumonia post five weeks of treatment with Enbrel for severe psoriaisis. In addition she suffered from hypothyroidism. Leiomyosarcoma of the liver was diagnosed in 2005 with a recurrence in 2009. She was diagnosed by us with CVID, poor specific antibody responses, a T cell deficiency and absent MBL. She received intravenous gammaglobulin (IVIG) since 2005 and since then has not had recurrence of her infections and her psoriasis has improved. Results: Immune studies. Serum immunofixation was normal with no monoclonal bands; Serum IgA 35 mg%;Serum IgG 320 mg%; Serum IgM 104 mg%. Pneumococcal IgG responses were not protective to all 14 serotypes EBV serology suggested a reactivation pattern, with persistently positive EBV PCR at 100 copies/ml. Lymphocyte mitogenic responses to phytohemagglutinin, Concanavalin A, and Pokeweed mitogen, Staphylococcal Cowan A were markedly decreased.Genetic studies for TACI, AIRE and RAG mutations were completed and no mutations were found. CD27 mutations pending. Conclusion: KM is a patient with a B and T cell deficiency, MBL deficiency and autoimmune disorders who is currently maintained on IVIG. Due to the persistent EBV viremia a liver transplant is not feasible. Attempt will be made to eradicate her EBV infection with EBV primed CTLs followed by a bone marrow and liver transplant.

P224 X-LINKED SEVERE COMBINED IMMUNODEFICIENCY SECONDARY TO IL-2 RECEPTOR MUTATION IN A NEWBORN INFANT. T. Dy*1, P. Patel1, A. Rubinstein1, R. O’Reilly2, 1. Bronx, NY; 2. New York, NY. Introduction: T cell receptor excision circles (TRECs) are a biomarker for newly produced, naïve T lymphocytes that have emigrated into peripheral blood from the thymus and can be measured by PCR. These assays have been implemented in Newborn Screening Programs in a number of states to identify patients with severe combined immunodeficiency (SCID). One type of X linked SCID occurs due to mutations in the IL-2 receptor (IL-2R) gene. The proliferation and differentiation of naïve T lymphocytes are driven by IL-2. Methods: We describe a male infant diagnosed with X-linked severe combined immunodeficiency who initially presented with a low TREC level as reported by the New York State Newborn Screen Program. Results: A male infant was born at 37 weeks gestation following an uncomplicated pregnancy and delivery. His TREC level result was reported as 65 copies/ml blood (normal > 150). His physical examination was benign, and he was well appearing with normal progression of his growth parameters, and family history was negative for immunodeficiency. Quantitative enumeration of lymphocytes was significant for profound T cell lymphopenia: CD3+ T cells 207 cells/ml, 14% (801-2684;5582%); CD4+T cells 175 cells/ml, 13% (447-1682; 30-53%); CD8 + T cells 25 cells/ml, 2% (259-973, 13-34%); CD19+B cells 851 cells/ml, 55% (66-1053; 8-36%); CD16+CD56+NK cells 470 cells/ml, 30% (6-368, 1-15%). The mitogen proliferation screen was normal: PHA 111,896 cpm (>93,000), Con A 99,181 cpm (>76,000), and PWM 224,229 cpm (>85,000). Genetic testing performed at Correlagen was significant for a hemizygous nonsense mutation (c.982C>T) in the IL-2R gene. Following an episode of severe CMV infection, he was referred to an outside institution at 2 months of age where he underwent bone marrow transplantation. His course was complicated by graft versus host disease and CMV colitis. Conclusion: Based on the results of his newborn screen, this patient was referred promptly for evaluation and man-

agement. He underwent successful and lifesaving transplantation for X-linked SCID secondary to an IL2RG mutation. Early screening allowed for proper anticipatory guidance regarding isolation precautions and avoidance of live vaccine administration. This case demonstrates the clinical utility of TREC newborn screening followed by lymphocyte subset enumeration.

P225 PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY (PML) AND INTERMITTENT NEUTROPENIA IN A PATIENT WITH CHRONIC MUCOCUTANEOUS CANDIDIASIS (CMC) DUE TO STAT1 GAIN-OF-FUNCTION MUTATION. C.B. Santos*1, A.P. Hsu2, S.M. Holland2, R.K. Katial1, 1. Denver, CO; 2. Bethesda, MD. Introduction: CMC comprises a heterogeneous group of disorders characterized by persistent Candida infection of the skin, nails, and mucous membranes. Only recently, several causative genetic mutations have been identified, and the variable clinical features associated with these mutations continue to be elucidated. Case: A 32-year-old Hispanic male with mental retardation and CMC presented with a childhood history of recurrent thrush and onychomycosis due to C. albicans. Initial immune workup revealed normal CBC, metabolic panel, thyroid function, lymphocyte quantity/function, and delayed-type hypersensitivity to Candida. He was successfully treated with topical and systemic antifungals. Over ten years later, he returned to clinic, describing a history of progressive ataxia. He had recently presented to an outside hospital with altered mental status and dizziness, and brain MRI revealed cerebellar atrophy. He had no history of new infections. Our repeat workup revealed pancytopenia, normal immunoglobulins, normal response to pneumococcal, tetanus, and diphtheria vaccines, normal lymphocyte stimulation to mitogens and Candida, and normal delayed-type hypersensitivity to Candida. Evaluation for HIV and hepatitis was negative. Serial CBCs revealed intermittent neutropenia and persistent lymphopenia. Bone marrow biopsy was normal. Sequences of the AIRE, Dectin-1, Dectin-2, and CARD9 genes were normal. STAT1 sequencing revealed a c.821 G>A (R274Q) mutation of the coiled-coil domain, consistent with an autosomal dominant gain-of-function mutation. He further deteriorated, and repeat brain MRI showed an enhancing lesion in the left frontal lobe. Brain biopsy revealed JC virus-associated PML. The patient declined treatment, and he expired within 3 months. Conclusion: To our knowledge, this is the first reported case of STAT1 gain-of-function mutation resulting in cerebellar atrophy and PML, combined with lymphopenia and intermittent neutropenia, in the absence of opportunistic infections other than CMC. This mutation has been described in another patient who had PML and CMC, as well as disseminated histoplasmosis. STAT1 gain-of-function mutation predisposes to CMC as well as neurologic and hematopoietic sequelae.

P226 PREVALENCE OF ATOPIC DISEASES IN HUMORAL PRIMARY IMMUNODEFICIENT PATIENTS IN THE USIDNET REGISTRY. A.M. Jongco*, L. Helfner, V.R. Bonagura, Great Neck, NY. Rationale: Humoral primary immunodeficiency (PID) patients are hypothesized not to develop atopy due to inherent defects in B-cell class switch recombination or maturation. Thus these patients are expected to have low or undetectable levels of serum IgE, and are not expected to develop IgE-mediated atopic diseases. We determined the prevalence of atopic diseases in select primary humoral immunodeficiency patients enrolled in the USIDNET registry. Methods: Patients enrolled in the USIDNET registry with the following diagnoses were included in the analysis: X-linked agammaglobulinemia (XLA), idiopathic agammaglobulinemia, selective IgA deficiency, IgG subclass deficiency, specific antibody deficiency, and HyperIgM syndrome. Common variable immunodeficiency patients were excluded. The presence of atopic diseases, including the type and trigger of allergic reaction, and IgE evaluation were queried. Results: Of 3,282 patients in the registry, 136 (4.1%) unique humoral PID patients with one of the eligible diagnoses had at least one reported atopic disease. In decreasing prevalence, the PID diagnoses of these 136 patients are XLA (58.4%), HyperIgM syndrome (38.7%), and idiopathic agammaglobulinemia (2.9%). In decreasing prevalence, the atopic diagnoses of these 136 patients are asthma (22.8%), drug allergy (11.0%), atopic dermatitis (6.6%), environmental allergies (3.7%), and food allergy (2.2%). Serum IgE was documented in 100 (73.5%) patients. In decreasing prevalence, the PID diagnoses of these 100 patients are HyperIgM syndrome (52.0%), XLA (44.0%), and idiopathic agammaglobulinemia (4.0%). Eleven (11.0%) of those 100 patients with



ABSTRACTS: POSTER SESSIONS reported IgE had undetectable IgE, 7 (63.6%) of whom had HyperIgM syndrome and 4 (36.4%) had X-linked agammaglobulinemia. Conclusions: Humoral PID patients may develop atopy. Surprisingly, 89.0% of these patients were reported to have detectable IgE. This may represent data quality limitations with registry data or be true biological phenomena. Further research is needed to elucidate the mechanisms for development of atopic diseases in humoral PID patients.

P227 HEREDITARY ANGIOEDEMA ATTACKS IN A NEWBORN: A CASE OF RECURRENT ERYTHEMA MARGINATUM. I. Martinez-Saguer*, W. Kreuz, Morfelden-Walldorf, Germany. Background: Hereditary angioedema (HAE) is a rare genetic disease characterized by recurrent episodes of severe edema (swelling) in various body tissues, sometimes preceded by prodromal symptoms like erythema marginatum. Initial symptoms usually occur during the first decade of life and can even manifest in infants. Case Description: A 3-days-old girl developed a profound erythema marginatum that subsided without treatment. Due to positive family history of HAE, the newborn was tested when the erythema marginatum recurred after 3 weeks. Type I HAE was confirmed with a C1 esterase inhibitor (C1 INH) activity of 13%, and a sonography revealed minor edema around the liver. The symptoms were not treated. At the age of 4 weeks, an erythema marginatum developed as a prodrome of a potential HAE attack, which was being treated with C1 INH concentrate (Berinert®, CSL Behring Marburg, Germany), resulting in onset of relief within 30 minutes after treatment, complete recovery after 7 hours, and freedom from symptoms for 7 days. The girl suffered recurrent erythema until an age of 18 months but remained free of edema and was not being treated. The symptoms attenuated with each episode, and as of June 2013, the patient has been free of symptoms for 12 months. Conclusions: This case of very early manifestation of symptoms of HAE underlines the need to educate and sensitize parents with a known family history of HAE to the importance of early diagnosis of HAE in their offspring to allow for an optimal management of the disease.

P229 INFANT WITH CRYOPYRIN ASSOCIATED PERIODIC SYNDROME (CAPS) AND IMMEDIATE RESPONSE TO ANAKINRA. K.C. Sokol*1, A. Tinana2, F. Schmalstieg1, 1. Galveston, TX; 2. Corpus Christi, TX. Introduction: Cryopyrin-Associated Periodic Syndromes (CAPS) are members of a rare family of autoinflammatory conditions consisting of familial cold autoinflammatory syndrome (FCAS), Muckle-Wells Syndrome (MWS), and Neonatal-Onset Multisystem Inflammatory Disease (NOMID). The inflammation in CAPS is driven by an excess release of interleukin-1β (IL-1β) due to genetic mutations in the NLRP3 gene, which encodes cryopyrin. This leads to constitutive activation of the inflammasome. This overproduction of IL-1β causes many CAPS symptoms to be present at birth or in early infancy, and persist throughout life. Methods: We report the case of a 12-week old Caucasian male who was referred to the allergy and immunology clinic for a rash present since birth and recurrent fevers since the age of 5 weeks. Fevers accompanied flares of the rash. At the time of presentation, the infant had been admitted to the hospital twice for high fevers, with a negative work-up for sepsis. In addition, a bone marrow and a skin biopsy were performed, both of which were unrevealing. He was noted to have high inflammatory markers, including ESR and CRP, in addition to a chronic leukocytosis and anemia. He was started on iron supplementation with minimal improvement. Physical examination revealed a non-pruritic urticarial-like rash mainly on his trunk. In addition, his eye exam revealed a preferential gaze to the right and lack of focus. Discussion: Given this patient’s history of recurrent fevers and rash since birth, we considered possible immunodeficiency, including a hypomorphic, or “leaky,” SCID. However, flow cytometry of his lymphocyte subpopulations and PHA-P mitogen stimulation were normal. Because of the non-pruritic urticarial rash, a cryopyrinassociated periodic syndrome, specifically NOMID, was considered. Treatment with Anakinra, an IL-1 receptor antagonist, was started resulting in complete resolution of his fevers and rash. Conclusion: We report a 12-week old patient presenting to the allergy and immunology clinic with recurrent fevers and a non-pruritic urticarial-like rash, typical of a cryopyrin-associated periodic syndrome. This report alerts the allergist/immunologist to be cognizant of this family of autoinflammatory conditions, which are rare and not well recognized.

P228 BARKING UP THE WRONG TREE: THE CLINICAL IMPLICATIONS OF SEVERE HYPOGAMMAGLOBULINEMIA. G. Panchal*, G. Youngberg, C. Crisostomo, G. Krishnaswamy, Johnson City, TN. Introduction: Chronic Variable Immunodeficiency (CVID) is characterized by low immunoglobulin level, immune dysregulation and resultant severe infections which may be fatal. Correct diagnosis is important for appropriate management. We present a patient who was misdiagnosed as CVID. Methods: Medical records were reviewed, laboratory and pathological data collected and analyzed and the medical literature surveyed for renal disease, hypogammaglobulinemia and management. Results: A 45 year old female referred for hypogammaglobulinemia and recurrent respiratory tract infections. She had been receiving monthly immunoglobulin infusion for 3 years but this was discontinued due to onset of hypertensive emergency during her last infusion with subsequent port and subclavian thrombosis and secondary sepsis. The patient suffered from obesity, hypertension, dyslipidemia and sleep apnea. Physical examination demonstrated obesity and 3+ pitting edema on both lower limbs. Serum chemistry demonstrated decreased total protein and albumin. IgG level was 396 mg/dL (normal- 791-1643 mg/dL), with normal IgA and M. ANA, rheumatoid factor, SS-A, SS-B, anticardiolipin antibody as well as lupus anticoagulant were negative. Due to peripheral edema and low total protein, a thorough renal or protein-loss work up was initiated. Urine analysis showed 300 mg% protein with moderate blood and 3-5 RBC. 24 hour urinary protein showed 10 gm proteinuria with hematuria,suggestive of nephrotic syndrome. Kidney biopsy was done which showed paramesangial staining of Ig G, M, C3, C4 as well as kappa lambda light chains, suggestive of membranous nephropathy. She was started initially on cyclophosphamide, but due to intolerance was switched to mycophenolate and prednisone which she received for 2 years. Slow and progressive decrease in proteinuria and improved IgG levels were seen, without IVIG therapy. Conclusion: Hypogammaglobulinemia requires careful and aggressive evaluation and management. A low albumin, especially in the presence of peripheral edema, is suggestive of protein-losing states, such as nephrotic syndrome and malabsorption. This case represents the need for careful history, physical evaluation and work up of patients presenting with immunological abnormalities. Misdiagnosed CVID can lead to iatrogenic complications and rapid progression of underlying protein-losing states.


Urticarial-appearing non-pruritic rash in 12 week old infant male

P230 CHRONIC INFLAMMATORY DEMYELINATING POLYNEUROPATHY IN A PATIENT WITH ADENOSINE DEAMINASEDEFICIENT SEVERE COMBINED IMMUNODEFICIENCY: A CASE REPORT. D.A. Petty*, M.E. Conley, N. Shah, D.B. Lew, C.F. Michael, Memphis, TN. Introduction: Adenosine deaminase (ADA) deficiency is a type of severe combined immunodeficiency (SCID) that involves about 15% of all SCID cases. This form of SCID has low B cells, T cells, and NK cells. This condition is complex with many possible complications including neurological abnormalities. Guillain-Barre syndrome is an acute inflammatory disease of the periph-


ABSTRACTS: POSTER SESSIONS eral nerves that involves an autoimmune attack on myelin resulting in demyelination. Chronic Inflammatory Demyelinating Polyneuropathy is a chronic form of Guillain-barré syndrome that presents with progressive symptoms. Case: TT is a 14 year old female with ADA-SCID who was diagnosed at 4 months of age and started on polyethylene glycol adenosine deaminase. She had normal immunoglobulin levels and has never been treated with immunoglobulin replacement. She presented to Le Bonheur Children’s Hospital June 15, 2012 with a 1 day history of bilateral lower extremity tingling and numbness. Due to concern for Guillain-Barre syndrome she was admitted to the Intensive Care Unit to monitor for respiratory failure. Her neurological exam quickly progressed to involve her upper extremities, as well as breathlessness and autonomic instability with variable heart rate and blood pressure. She had a prolonged hospital course that involved extensive work up to try and find an infectious cause which only found a positive urinary histoplasma with a negative blood test. She was treated with IVIG for 5 days, and plasmapheresis for 5 treatments which were both unsuccessful. After starting Amphotericin B and prednisone 2 mg/kg BID and still without recovery, it was decided to start rituximab infusions weekly for 4 doses. This decreased her CD19 from 2% prior to rituximab to <1%.This treatment finally produced sustained improvement and she was able to be discharged. She was seen in outpatient follow up and 1 year later she reported 99% of her strength had returned. Conclusion: Chronic Inflammatory Demyelinating Polyneuropathy should be added to neurological complications that can occur in ADA-SCID patients. In this case it was successfully treated using anti CD 20 monoclonal antibody rituximab.

P231 CLINICAL OUTCOMES OF IMMUNOGLOBULIN THERAPY IN PATIENTS WITH SPECIFIC-ANTIBODY DEFICIENCY. S.R. Kumar*1, M. Riedl2, 1. Los Angeles, CA; 2. San Diego, CA. Introduction: Specific-Antibody Deficiency (SAD) is characterized by an impaired response to immunization with polysaccharide antigens in the presence of normal immunoglobulin (Ig) and IgG subclass concentrations. Recurrent sinopulmonary complications of SAD may include bacterial infections such as otitis media, bronchitis, and pneumonia, though the natural course of SAD is not well-defined. Management of SAD often begins conservatively with vaccination and prophylactic oral antibiotic therapy, but little data exists on the need for Ig therapy in adult patients with SAD and severe infectious complications. Methods: We conducted a retrospective chart review in a tertiary-care adult immunology clinic spanning a 3 year period to identify adult patients diagnosed with SAD and prescribed Ig therapy due to severe or refractory infectious complications. IRB approval was obtained for the study; this included a waiver for research subject consent. Results: We identified 5 patients with SAD and severe clinical courses due to infection who ultimately required Ig therapy to achieve clinical improvement. Prior to Ig therapy, 3 had documented sinopulmonary infection with Pseudomonas, 3 had undergone sinus surgery for severe symptoms, and 4 had infections requiring hospitalization with intravenous antibiotic therapy. In this patient cohort, 3 received subcutaneous Ig and 2 received intravenous Ig therapy. Adverse reactions to Ig therapy included flu-like symptoms, lower extremity edema, and hyperviscosity syndrome. Subsequent to Ig replacement, the number of antibiotic courses and documented infections for each patient decreased. Conclusion: Specificantibody deficiency in adults may be associated with infectious complications of varying severity. We identified a small cohort of patients developing at least one serious clinical complication including sinopulmonary Pseudomonas infection/colonization, recurrent or refractory sinusitis necessitating surgery, bronchiectasis with concurrent pneumonia, and the need for IV antibiotic therapy. In these cases, Ig replacement therapy was prescribed with resultant clinical improvement, though side effects occurred and antibiotic therapy was still required in some cases. Further studies on adult SAD are needed to better define the frequency of serious clinical complications and optimal treatment strategies for this immunodeficient population.

P232 PROPHYLACTIC ANTIBIOTICS AS ADJUNCTIVE MANAGEMENT FOR ANTIBODY DEFICIENCY SYNDROMES: IS THERE A ROLE? M.E. Kuruvilla*, M.T. de la Morena, Dallas, TX. Rationale: While the mainstay of treatment in antibody deficiency syndromes (ADS) is IgG replacement, use of prophylactic antibiotics (APx) is common. Empiric guidelines for use have included frequent infections, declining lung function, bronchiectasis or refractory chronic sinusitis. We performed

a retrospective analysis on the use of APx in patients with ADS. Primary objective was to describe settings where APx were prescribed and to evaluate clinical benefit defined as need for breakthrough antibiotic use despite APx. Secondary objective - to identify other variables associated with clinical benefit from APx. Methods: Retrospective chart review at a single referral academic institution from January 2008 to December 2012. Patients with diagnosis of ADS were included in analysis if they received at least 3 months of APx therapy in the following settings - recurrent antibiotic use (>3 episodes in the preceding 6 months), bronchiectasis, chronic sinusitis, persistent cough, or transitioning off from IgG replacement. Each patient acted as their own control. The period for comparison included one year before and after implementation of APx. Statistical analysis was performed using Chi-square and Fisher’s exact tests. Results: Of 150 patients with ADS, 78(52%) received APx. 47(31%) patients (74.5% male, mean age 8.3± 5.4 years) receiving APx met inclusion criteria: six with agammaglobulinemia (12.8%), 7, CVID (14.9%), 6, transient hypogammaglobulinemia of infancy (12.8%), 16, hypogammaglobulinemia (40.4%), 5, IgA deficiency (12.7%) and 3 with selective antibody deficiency with normal Igs (6.4%). Azithromycin was the most frequent antibiotic used (89.3%). The most common clinical reason for breakthrough antibiotic use was recurrent sinusitis (74%). No difference in breakthrough antibiotic use was seen before or 1 year after implementation of APx (p=0.494). No association was noted between efficacy of APx according to primary diagnosis. Multivariate analysis showed no benefit in APx for patients with atopy, daycare exposure, prior tonsillectomy, adenoidectomy or myringotomy, asthma or chronic sinusitis. Conclusion: Small numbers and retrospective design limit accurate identification of ADS phenotypes that would benefit from APx. Prospective, controlled trials on APx use in ADS patients may identify populations that may best benefit from such practice.

P233 A CASE OF EVAN’S SYNDROME AND CVID COMPLICATED BY LARGE B-CELL LYMPHOMA. E. Sarid*, S.R. Gottesman, Y. Rao, R. Joks, Brooklyn, NY. Introduction: Evan’s Syndrome is a chronic relapsing combined autoimmune hemolytic anemia (AIHA) and thrombocytopenia associated with significant morbidity and mortality. Immunodeficiency and lymphoid malignancy are associated disorders leading to complicated disease progression. Presentation: A 41 year old female with a history of Evan’s Syndrome and Common Variable Immunodeficiency (CVID) since childhood received regular care including periodic blood product transfusions and monthly intravenous immunoglobulin infusions. She presented to the emergency department complaining of several days of unexplained bruising throughout her body. On examination, she was found to have multiple petechiae and ecchymoses over her extremities as well as supraclavicular lymphadenopathy. Laboratory evaluation revealed anemia (hemoglobin: 8.8 g/dL ref: 12.0-15.5 g/dL) and thrombocytopenia (platelets: 53 k/uL ref: 150-400 k/uL). Results: Peripheral blood smear revealed lymphocytosis. A supraclavicular lymph node biopsy demonstrated diffuse, large B-cell lymphoma and the patient was referred for treatment of her malignancy. The patient continues to require monthly intravenous immunoglobulin for her hypogammaglobulinemia as well as regular blood product transfusions to control her primary autoimmune hemolytic anemia and thrombocytopenia. She is followed for continued prevention and monitoring of all complications related to her syndrome. Conclusion: This case illustrates the association of Evan’s Syndrome with common variable immunodeficiency and lymphoid malignancies. In spite of the propensity for polyclonal expansion of lymphoid cells in these underlying disorders, special attention for malignancy should be paid to any patient developing concerning hematologic signs or symptoms or lymphadenopathy.

P234 COMBINED VARIABLE IMMUNODEFICIENCY AND AUTOIMMUNE NEUTROPENIA. S. Yee*1, S.C. Dreskin2, 1. Denver, CO; 2. Aurora, CO. Introduction: Common variable immunodeficiency (CVID) is a humoral immunodeficiency characterized by hypogammaglobulinemia involving two or more immunoglobulin isotypes and impaired functional antibody responses. While increased susceptibility to respiratory and other infections is common, the presence of autoimmune complications is recognized in up to two-thirds of patients. Among the autoimmune manifestations reported, autoimmune cytopenias are the most common. A case of a patient with CVID and recalcitrant neutropenia is presented. Method: Case description. Results: DR is a 26



ABSTRACTS: POSTER SESSIONS year old female with a history of idiopathic thrombocytopenia (ITP), and two episodes of autoimmune hemolytic anemia (AIHA) (Evan’s Syndrome), who was admitted for cellulitis of the thumb with septicemia. On admission, she was found to be severely leukopenic with a WBC of 0.7 and an absolute neutrophil count of zero. She also had low levels of IgG (173 mg/ml) and IgA (<8 mg/ml). CAT scans were remarkable for diffuse pulmonary nodular opacities and hepatosplenomegaly. A liver biopsy was unremarkable. Two bone marrow biopsies were performed, both of which showed agranuloctyosis and no evidence of malignancy. She was started on IVIG to treat suspected CVID. Treatment for agranulocytosis included high dose corticosteroids and G-CSF which was administered for 1 week at 300mcg daily with no effect such that her neutrophil counts remained at zero. Towards the end of this 3 month hospitalization, she was given an additional course of G-CSF at 480mcg daily and rituxin (anti-CD20) (~375 mg/m^2) was added. After 1 day of receiving rituxin and 5 days after restarting G-CSF, her neutrophil count improved. As an outpatient, she was continued on several more cycles of rituxin. She had recurrence of neutropenia and was given G-CSF on several occasions. Conclusion: This 26 year old female with CVID and a very strong history of autoimmune cytopenias (ITP and AIHA) presented with severe neutropenia that, based on the clinical setting and the response to rituxin, was likely also autoimmune in etiology.

Laboratory findings in two CVID patients with <1% peripheral B cells

P236 P235 DIVERSE CHARACTERISTICS IN CVID PATIENTS WITH <1% PERIPHERAL B CELLS: TWO CASE REPORTS. K. Todoric*, M. Hernandez, M. Jerath, 1. Chapel Hill, NC. Introduction: Several classification schemes for CVID have been proposed focusing on differences in peripheral B cell populations. The most recent of these, the multicenter EURO class trial, sought to unify these classifications but only included patients with >1% peripheral B cells. However, approximately 5-10% of CVID patients have <1% peripheral B cells, and phenotypes in this group are not well-defined. Here, we describe clinical characteristics of two patients, ages 8 and 63, who fall within this minority group. Case Discussion/Data: Our pediatric and adult patient suffered recurrent sinopulmonary infections, starting at birth and around age 60, respectively. Our pediatric patient had no personal history of autoimmunity, but our adult patient had Sjogren’s syndrome, ulcerative colitis, and cryoglobulinemic vasculitis. There was no history of immunodeficiency in either family. Immunizations were up-to-date for both. Our pediatric patient’s exam was essentially unremarkable. Prior studies included CXR with scarring of the right lung, and x-ray showing chronic sinusitis. Our adult patient was ill-appearing with temporal wasting, lower extremity edema, and dry crackles on lung exam. CXR and chest CT showed persistent infiltrate, and bronchoscopy revealed mucopurulent secretions and debris suggestive of alveolar damage. Our pediatric patient had immeasurable immunoglobulins (mg/dL, IgG 67, IgM<25, IgA<1, IgE<2) while our adult patient had very low IgG (<135mg/dL) and IgM (<25mg/dL) but normal IgA (40mg/dL). Both had minimally protective protein vaccine titers and less than appropriate numbers of protective post-vaccination pneumococcal serotypes. Both patients had <1% peripheral B cells. T cell numbers were normal in our child, but our adult patient had an inverted CD4/CD8 ratio. Additional workup in our pediatric patient showed normal BTK and an increased percentage of transitional B cells with essentially no isotype-switched memory B cell populations. Immunoglobulin replacement was initiated without further delay for both. Conclusion: These two cases highlight the diversity of CVID phenotypes seen even in patients with severely reduced peripheral B cells. More research is clearly needed to further elicit differing mechanisms of this complex disease that will ultimately improve our understanding of CVID and aid in prognosis and treatment/screening recommendations.


A CASE OF DIFFUSE GIANT MOLLUSCUM PRESENTING IN AN ADULT PATIENT WITH HISTORY OF X-LINKED SCID. E. Karlin*, J. Fahrenholz, Nashville, TN. Introduction: Molluscum contagiosum is a poxvirus that causes chronic localized infection of the skin and is often a self-limited disease of childhood. In the immunocompetent patient, lesions typically present as flesh-colored, dome-shaped papules on the skin and spontaneously resolve within several months. However, in immunocompromised patients, multiple extensive voluminous lesions may be present that are often resistant to topical therapies. Case Presentation: A 28 year old male with history of X-linked Severe Combined Immunodeficiency status-post bone marrow transplant in infancy presented to our clinic with a new skin eruption that had been progressing over several months. He had been followed in our clinic for hypogammaglobulinemia and was on treatment with monthly intravenous immunoglobulin replacement. The lesions initially presented on his trunk with further spreading to his arms, legs, and face. Examination revealed multiple, umbilicated, partly coalescing, pink papules and nodules involving the face, abdomen, trunk, upper and lower extremities. The individual lesions varied in size with diameters of 2-8 cm. Laboratory evaluation revealed lymphocyte count of 2,394 cells/mL, CD4+ T-cell count of 694 cells/mL, and CD8+ T-cell count of 1772 cells/mL. B-cells were low at 24 cells/mL and NK cells were absent. Serum IgG (trough) was normal at 739 mg/dL. Antibodies to HIV and HIV-1 RNA were not detected. Urine was negative for blastomycoses antigen. Skin biopsy of a right forearm lesion revealed findings consistent with molluscum contagiosum. Due to the diffuse nature of this patient’s disease, a trial of interferon-alpha was initiated. Conclusion: Molluscum contagiosum infection causes smooth-surfaced pearly papules that are typically seen in young children. They usually average 3-4 mm in size and resolve within months, often without treatment. However, those with giant molluscum can measure up to several centimeters in diameter and have been reported primarily in patients with Acquired Immunodeficiency Syndrome. Molluscum has also been reported in patients with primary immunodeficiencies, particularly those with hyper-immunoglobulin E recurrent infection syndromes. To our knowledge, we report the first case of diffuse giant molluscum infection in an adult patient with history of X-linked Severe Combined Immunodeficiency Disorder.




P237 DELAYED SEPARATION OF THE UMBILICAL CORD: NOT JUST A LEUKOCYTE ADHESION DEFECT. A.T. Hampton*, R. Herzog, New York, NY. Delayed separation of the umbilical cord often prompts evaluation for leukocyte adhesion defect, a condition that is often associated with leukocytosis. However, in the presence of neutropenia, evaluation of other underlying etiologies such as other immune deficiency syndromes, viral infection, auto or alloimmune neutropenia, congenital neutropenia, or cyclic neutropenia, is warranted. We present two patients with delayed separation of the umbilical cord and the finding of neutropenia as the sole underlying abnormality, in which its resolution led to cord separation. These cases illustrate the importance of the complete blood count (CBC) as well as the absolute neutrophil count (ANC) as part of the evaluation of these patients. Case Report: 7 week old and 2 month old males presented with delayed separation of the umbilical cord. Birth history and growth and development were normal, with no history of infection. Results: Laboratory evaluation revealed persistent neutropenia (500 cells/ul). Anti-granulocyte antibody, neutrophil elastase (ELANE) and HS1-associated protein X1(HAX1) sequence analysis for cyclic and congenital neutropenia were negative, bone marrow aspirate and biopsy revealed normal number of myeloid precursors up to the metamyelocyte stage. The number of bands and neutrophils was low, comprising only 15% of all cells (normal: 25-30%), and the marrow had an otherwise normal cellular composition. Flow cytometry was normal and neutrophil morphology did not suggest Chediak-Higashi, myeloid dysplasia, leukemia or bone marrow failure. Cytogenetic analysis revealed a regular male karyotype, and immunoglobulins and lymphocyte subsets were normal as well. Clinical and laboratory follow up revealed resolution of neutropenia at several month of age and separation of umbilical cord. Conclusion: Persistent or transient neonatal neutropenia can present with delayed separation of the umbilical cord. A CBC and ANC should be included in the evaluation of these patients in order to inform workup and to explore etiologies beyond leukocyte adhesion defect.

Introduction: PANS is characterized by acute onset of neuropsychiatric symptoms, which appear to be triggered by various infections. A subset of PANS children referred to our clinic exhibit low and/or gradual decline of Ig levels. This study addressed whether this subset of PANS children (defined as PANS test group) exhibit clinical and/or laboratory findings different from PANS children with normal or stable Ig levels (PANS control) and age-matched normal controls. Methods: In the PANS test group (N=13), innate and adaptive immune responses were evaluated in comparison with PANS controls (N=19) and normal controls (N=20). Ig levels, memory B-cell numbers, specific antibody levels, and cytokine production by peripheral blood mononuclear cells (PBMCs) in response to toll like receptor/dectin-1 agonists, and recall antigens, were evaluated. Clinical features were compared between the PANS groups. IRB approved signed consent forms were obtained from the study subjects. Results: There was no significant difference in the prevalence of neuropsychiatric symptoms between the PANS groups. The prevalence of allergic rhinitis is higher in the PANS control than the PANS test group (42% vs. 8%, respectively). Prevalence of sinopulmonary infections did not differ between the PANS groups, although many were on prophylactic antibiosis. Numbers of B cell subsets did not differ between the PANS groups. In contrast, cytokine production profiles in response to stimuli of innate immunity significantly differ between the PANS test and PANS control groups. PBMCs from the PANS test group revealed lower production of IL-1β (with a dectin-1 agonist) and CCL7 (with dectin-1 and TLR 2/6 agonists) as compared to normal controls. PANS control group showed lower CCL7 production with stimuli of TLR/dectin-1 agonists compared to normal controls. PBMCs from the PANS test group revealed lower production of IL-6/ IL-10 in response to a TLR2/6 agonist than the PANS control group. Conclusion: The results indicate that although there may not be distinct differences in clinical features of PANS, the PANS test group exhibits distinct immune abnormalities as compared to the PANS control group in addition to low Ig and/or declining Ig levels. It remains to be seen how such immune abnormalities are associated with the disease outcomes.

P239 PREDICTION OF ADEQUATE OR INADEQUATE SPECIFIC ANTIBODY RESPONSE TO POLYSACCHARIDE PNEUMOCOCCAL VACCINATION BASED UPON BASELINE CLINICAL AND LABORATORY FINDINGS. N.N. Patel*1, Z. Jacobs2, 1. Overland Park, KS; 2. Kansas City, MO. Background: A common evaluation performed in an allergy/immunology clinic is evaluation of recurrent infections. A key component of this is obtaining pre and post PPV23 specific antibody levels to S. pneumo serotypes to test polysaccharide specific antibody response. Objective: To retrospectively review if there are any clinical features or laboratory findings that could predict an adequate or inadequate response to PPV23. Methods: A chart review was performed for all patients who had pre and post PPV23 S. pneumo specific antibody testing performed since 2011 for recurrent infections. All patients who underwent this evaluation and had <70% of serotype specific antibody levels above 1.3 mcg/mL were included in the analysis. IRB approval was obtained. Clinical histories, baseline laboratory findings and serotype specific antibody levels pre and post vaccine were collected and analyzed for statistical significance. It was considered statistically significant if p ≤ 0.05. Results: Vaccine responders had a statistically significant higher total IgG level (1002 mg/dl) than non-responders (783 mg/dl) with p = 0.05. Total IgA and IgM levels were not significant. Non-responders had a statistically significant lower percentage (22%) of serotype specific antibody levels higher than 1.3 mcg/mL pre PPV23 than responders (35%) with p=0.05. Analysis of clinical histories between the two groups was not significant. Conclusion: Patients who had IgG levels above 1000 mg/dl were more likely to adequately respond to PPV23. Patients who were considered to have an inadequate response had lower levels of S. pneumo specific antibody pre PPV23 compared to adequate responders. There was no difference in the clinical histories between the two groups, but the sample size was small. Some individual serotypes appeared to be more antigenic than others. It might be possible to predict a patient’s response to polysaccharide vaccine, but further prospective studies are needed.



ABSTRACTS: POSTER SESSIONS Comparison between non-responders and responders based on clinical history

cells cultured with lactobacilli cell walls, to view the effects of lactobacilli on various leukocytes . A significant immunomodulatory effect was induced by the studied lactobacilli strains as well as isolated lactobacilli cell walls. Conclusion: Lactobacilli cell wall components stimulate reactive oxygen species formation by neutrophils; enhance the expression of CD80 molecules; and increase production of TNF-α. There are inter-strain variations in the immune modulation induced by lactobacilli. These characteristics suggest that select lactobacilli strains could be employed to influence human immune responses.


P240 ASSESSMENT OF SERUM IL-12, IL-10, IL-8, AND IFN-γ IN PATIENTS WITH ORAL MUCOSAL LICHEN PLANUS. A. Kurchenko*1, G. Drannik1, R. Rehuretska1, L.M. DuBuske2, 1. Kiev, Ukraine; 2. Gardner, MA. Background: Oral lichen planus is a chronic inflammatory, immune-mediated, mucocutaneous disease which rarely regresses spontaneously. The erosive form tends to progress, frequently relapses, and can become chronic leading to malignancy. This study assesses a T-helper cell cytokine IL-12, a T-regulatory cytokine IL-10, an anti- viral proliferative cytokine IFN-γ, and a pro-inflammatory cytokine with chemokine activity, IL-8, in patients with frequent relapses of erosive oral lichen planus. Methods: 97 patients age 18 to 60 years were studied including 35 with erosive oral lichen planus, 32 with nonerosive oral lichen planus and 30 healthy control subjects of similar age. The levels of serum cytokines (IL-12, IL-10, IL-8, IFN-γ) were determined by enzyme-linked immunosorbent assay (“Immunotech”; France). Results: During relapse of erosive oral lichen planus there is a marked increase in select cytokines compared with control group levels including: IL-12, 2.0 fold rise (15.3±1.1 pg/ml versus 8.6±0.6 pg/ml); IL-8, 2.8 fold rise (83.1±2.3 pg/ml versus 30.1±1.2 pg/ml); and IL-10, 1.6 fold rise (80.2±1.5 pg/ml versus 49.5±3.2 pg/ml). IFN- γ ( 0.5±0.2 pg/ml) however is reduced 4.6 fold versus the control group. In remission IL-12 increases 1.2 fold, IL-8 increases 2.3 fold, and IL10 increases 1.1 fold, while IFN- γ decreases to 0.8±0.2 pg/ml, being less than in healthy controls, and 1.6 fold less than in disease relapse (p<0.05). Conclusions: Acute relapse and chronic stages of lichen planus of the oral mucosa are characterized by immunological changes detectable in peripheral blood serum including increases in concentrations of IL-12, IL-8, IL-10 and reduction in concentration of IFN-γ, characteristic of development of a recurrent inflammatory immune response.

P241 STIMULATORY EFFECTS OF LACTOBACILLI ON HUMAN PERIPHERAL BLOOD LEUKOCYTE IMMUNE RESPONSES. L. Titov*1, A. Murashko1, A. Hancharou1, N. Golovnyova1, I. Naidenko1, L.M. DuBuske2, 1. Minsk, Belarus; 2. Gardner, MA. Introduction: Probiotics are natural microbial products which have been recently been proposed for use in patients with allergic diseases. The mechanisms of action of probiotics are not well understood. This study assesses the influence of different lactobacilli strains and their cell wall components on function of human immune cells in vitro. Methods: 14 lactobacilli strains were assessed. Lactobacilli were labeled with FITC for phagocytosis assays. Blood from healthy volunteer subjects was obtained for assessment of neutrophil, lymphocyte, monocyte and macrophage functions influenced by the lactobacilli and their cell wall components. Reactive oxygen species (ROS) production by neutrophils cultured with lactobacilli cell walls and cell lysates was studied, as well as various surface molecules. Monoclonal antibodies to CD11b, CD14, CD66b, CD69, CD80 were used to label cells studied by flow cytometry. TNFα production was assessed. Results: Cluster analysis has shown the presence of inter-strain variations in the ability of lactobacteria to be phagocytosed by neutrophils and monocytes. There were 2 clusters with high and low numbers of cells which phagocytosed the lactobacilli. Lactobacteria cell wall components induced substantial activation of neutrophils and stimulation of generation of ROS. A weak effect of lactobacilli cell wall components on expression of CD69 by lymphocytes was seen. Lactobacilli cell walls enhanced production of TNF-α and expression of CD80 by macrophages See figures A – macrophages; B – neutrophils (exclusion gate); C – unstimulated cells; and D-


Introduction: Common variable immunodeficiency (CVID) is a heterogeneous disorder characterized by impaired B cell differentiation with defective immunoglobulin production. B cell maturation and toll-like receptor 7 and 9 function are impaired. CVID is associated with infectious, inflammatory, autoimmune and malignant conditions. Neurologic manifestations of CVID are reported in the literature, but clinical descriptions of Central Nervous System (CNS) vasculitis are limited. Case Report: A 24year old female with history of immunodeficiency, type 1 diabetes mellitus, and autoimmune disorder referred to clinic for evaluation. Around age 10 years refractory Immune Thrombocytopenic Purpura with platelet count of 3000 manifested as easy bruising, non-responsive to Intra Venous Immunoglobulin (IVIG) prompted splenectomy. Over the next few years she developed recurrent sinopulmonary and genital Herpes Simplex Virus (HSV) infections, chronic lymphadenopathy, hypogammaglobulinemia, anergy to vaccines and was diagnosed with CVID. A year after diagnosis she had acute left sided headache with narrowed vision and photophobia. Brain MRI revealed a left frontal mass of unknown etiology. Neurosurgical evaluation considered brain biopsy; but on reimaging, the lesion resolved, which ruled out suspected cancer. Migraine prophylaxis and abortive treatment, was associated with radiographic resolution of the lesion. 9 months later she developed seizures. EEG was normal but a new hyperintense flair enhancing signal was identified in the right cerebellar hemisphere. Differential diagnosis included hemangioblastoma versus glioma. Her seizures were well controlled with seizure and anti-inflammatory medications. No behavioral changes, weakness or alterations of gait, balance or coordination were reported except headache. After extensive evaluation (MRI with and without gadolinium) enterovirus infection, HIV, neurosarcoid and malignancy, spinal cord lesions were ruled out. Repeat MRI two weeks later revealed resolution of the right cerebellar lesion, consistent with resolution of an inflammatory process. Conclusion: Clinical features and MRI findings suggest a CNS inflammatory process secondary to autoimmunity which is not uncommon in CVID. Clinical descriptions of CNS vasculitis in CVID are limited. Clinicians should consider vasculitis in the differential diagnosis when evaluating neurologic symptoms in CVID.

P243 EFFICACY AND SAFETY OF RECOMBINANT HUMAN C1 ESTERASE INHIBITOR FOR ACUTE ATTACKS OF HEREDITARY ANGIOEDEMA: AN OPEN-LABEL STUDY. H. Li*1, D. Moldovan2, J. Bernstein3, A. Reshef4, G. Porebski5, M. Stobiecki5, J. Baker6, R. Levy7, Y. Hardiman8, A. Relan9, M. Cicardi10, M. Riedl8, 1. Chevy Chase, MD; 2. Tîrgu Mures, Romania; 3. Cincinnati, OH; 4. Ramat Gan, Israel; 5. Krakow, Poland; 6. Lake Oswego, OR; 7. Atlanta, GA; 8. San Diego, CA; 9. Leiden, Netherlands; 10. Milan, Italy. Rationale: Hereditary angioedema (HAE) due to C1esterase inhibitor deficiency is an autosomal dominant disorder characterized by recurrent attacks of subcutaneous/submucosal edema. Recombinant human C1 esterase inhibitor (rhC1INH) has been shown to be effective for treatment of acute HAE attacks, including repeated treatments for multiple attacks. The current study evaluated safety and efficacy of rhC1INH for repeated treatment of acute HAE attacks in an open-label extension of a randomized controlled study. Methods: Patients experiencing eligible angioedema attacks at any anatomical location were treated with rhC1INH (50 IU/kg up to 4200 IU). The time to onset of symptom relief at the primary attack location was assessed as time from start of study drug infusion to onset of sustained beneficial effect, using a Treatment Effect Questionnaire. Time to minimal symptoms for all attack locations was assessed for


ABSTRACTS: POSTER SESSIONS the first 3 attacks. Safety evaluations comprised adverse events and laboratory results. Results: As of this analysis, 44 patients were treated with rhC1INH for 170 HAE attacks (range 1-15 attacks/patient). The median (95% confidence interval [CI]) time to onset of symptom relief following treatment for all attacks was 75 min (64, 90) and median (95% CI) time to minimal symptoms for all assessed attacks (first 3 per patient) was 303 min (211, 449). When evaluated by attack number, median times to onset of relief and minimal symptoms were comparable across attacks, suggesting no loss of efficacy with repeat administration. The majority (97 %) of attacks were treated with a single rhC1INH dose. A total of 64% of patients experienced at least 1 treatment-emergent adverse event (TEAE). Most TEAEs were mild/moderate in intensity; no increase in TEAE incidence was observed with increasing numbers of rhC1INH administrations. Overall, rhC1INH was well tolerated, with no thromboembolic events, neutralizing antibodies, or anaphylaxis following repeated treatments over a period of 20 months. No patients developed antibodies to rabbit dander IgE. Conclusions: Consistent with previous studies, results of this open-label extension study support continued efficacy of rhC1INH after repeated treatments for multiple HAE attacks, without increasing the incidence of adverse events after repeated rhC1INH exposure.

P244 HEALTHCARE PROVIDERS’ PERCEPTIONS OF SUBCUTANEOUS IMMUNOGLOBULIN COMPARED WITH INTRAVENOUS IMMUNOGLOBULIN. A. Bullinger*, A. Zampelli, King of Prussia, PA. Introduction: Immunoglobulin (IgG) is used for the treatment of primary immunodeficiency disease (PIDD), neurologic disease, and other disorders. Administration of IgG subcutaneously is chosen as the preferred route with increasing frequency. To this point, the views of healthcare providers regarding the relative merits of treatment with subcutaneous IgG (SCIG) versus intravenous IgG (IVIG) have not been examined. Methods: At recent immunology- and/or infusion-related conferences, 26 immunologists and 51 nurses (total of 77 participants) completed surveys to assess their use and perceptions of SCIG and IVIG therapy. Results: Most respondents (57.1%) have been in practice >20 years. The majority of the patients treated by the respondents were receiving SCIG for PIDD, although some also received SCIG for the treatment of neurologic disorders, immunothrombocytopenic purpura, and other conditions. A steady-state IgG level was ranked as the most important benefit of SCIG compared with IVIG by the greatest number of respondents (44.2%), followed by patient independence/convenience (19.5%), and the lack of a need for venous access (15.6%). Unexpectedly, SCIG therapy was thought to be more efficacious than IVIG by 41.6% of respondents, while 51.9% viewed them as equivalent (Figure). However, the most important factors motivating the choice of SCIG were IVIG adverse effects and patient lifestyle. The majority of respondents (66.2%) believed that SCIG therapy was better tolerated (Figure) and improved patients’ quality of life (89.6%) compared with IVIG. In addition, 72.7% of respondents felt that patients were more satisfied with SCIG than IVIG. Most respondents (88.3%) were of the opinion that high-concentration SCIG has advantages over lower-concentration formulations, namely lower administration volume and fewer infusion sites. Conclusions: Many healthcare providers believe that SCIG has several advantages over IVIG such as maintenance of consistent steady-state IgG levels, better efficacy and tolerability, as well as improved quality of life and patient satisfaction. Specific benefits were seen with high-concentration, low volume, SCIG products.

P245 CAMPYLOBACTER JEJUNI LEG ULCER IN A PATIENT WITH AGAMMAGLOBULINEMIA. M. Ramesh*, P.J. Maglione, C. Cunningham-Rundles, New York, NY. A 24 year old male with agammaglobulinemia on immunoglobulin replacement therapy presented with a left lower extremity ulcer. He had initially presented to vascular surgery with pain and dependent edema of his left lower extremity and diagnosed with superficial venous insufficiency. He was treated with endovascular laser therapy of the left greater saphenous vein. He developed a small ulcer subsequently and was treated as a chronic venous stasis ulcer with conservative measures. However, over the subsequent 13 months the ulcer did not heal and grew to 6 inches in diameter. The patient lost approximately 20 kg of body weight. He was in excruciating pain requiring opiates and unable to walk without assistance. He was admitted, blood and wound cultures sent. He had white count of 13.9×103/ ml with 92% neutrophils, microcytic anemia, ESR of 97 mm Hg and CRP of 107.6 mg/L. His IgG was 689mg/dL, IgA <5mg/dL and IgM was <5mg/dL. He had no B cells on flow cytometry and an absolute T cell count of 1537/ ml. Skin biopsy was suggestive of a neutrophilic dermatosis. The blood and wound cultures grew Campylobacter jejuni. Nuclear imaging showed a soft tissue ulcer without bone involvement. He was treated successfully with ertapenem and gentamycin with complete resolution of the infection and no recurrences. This case highlights Campylobacter and Helicobacter bacteremia and skin ulcers, a rare infectious complication seen in patients with agammaglobulinemia that is often associated with significant diagnostic delay.

Image of left lower extremity showing ulcer.




P246 CUTANEOUS LEUKOCYTOCLASTIC VASCULITIS IN A CHILD WITH SALMONELLA INFECTION AND INTERLEUKIN-12 RECEPTOR BETA-1 DEFICIENCY. E.E. Castelan*, O.J. Saucedo-Ramirez, M. Nava-Frias, B.E. Del RioNavarro, Mexico City, DF, Mexico. We report the case of a 2 years 9 months female, product of the fourth pregnancy, with no evidence of inbreeding, and no history of familiar pulmonary tuberculosis infection, BCG given at 7 months. At 1 year 3 months old, she presented a right axillary lymphadenopathy, treated with Dicloxacillin by a general practitioner. At 2 years 4 months she was admitted into a state hospital for a cervical abscess, where she was diagnosed typhoid fever, receiving medical treatment and was discharged. At 2 years 9 months she was admitted again for fever, purpuric skin lesions on lower extremities and cervical lymphadenopathy, an excisional biopsy was performed, reporting an acute lymphadenitis abscess, and she was sent to our institution. Physical examination revealed multiple lymphadenopathy (cervical, submandibular, inguinal and axillary); hepatosplenomegaly, purpuric lesions in the lower limbs, with pain on movement of knees and ankles. In the initial laboratory tests with anemia, high IgG and IgE, a normal flow cytometry, C4 protein of the complement depleted, no response following full immunization for hepatitis B; bone marrow culture positive for group D Salmonella, so therapy with ceftriaxone was initiated. A nitroblue tetrazolium oxidation test was performed with a good respiratory burst response. We performed PCR for mycobacteria in the previous node biopsy, and after a positive result, treatment for tuberculosis was initiated and the patient was discharged. Three weeks after the start of antituberculosis drugs the purpuric lesions were exacerbated, so was the knee and ankle joints pain. A skin biopsy was performed, reporting leukocytoclastic vasculitis that improved upon the initiation of nonsteroidal anti-inflammatory drugs. Five months later because of persistent fever and recurring purpuric she was readmitted, and another bone marrow culture was performed, resulting positive for group D Salmonella, so ceftriaxone-amikacine was initiated. A flow cytometry compatible with IL12Rβ1 deficiency was performed and gamma interferon treatment was initiated. Although Leukocytoclastic vasculitis has been rarely reported as a complication of salmonella gastroenteritis, there is an increasing number of case reports documenting a relation between both of them in patients with bacteremia and IL-12Rβ1 deficiency, so more investigation is needed.

P247 COMPLEMENT DEFICIENCY CASE SERIES. J.M. Camacho*, P.J. Maglione, S. Agarwal, C. Cunningham-Rundles, New York, NY. Introduction: Complement deficiencies are a rare group of disorders in which markedly low complement levels can result in immunodeficiency. The phenotype of complement deficiency is broad, ranging from asymptomatic to recurrent serious illnesses; the specific presentation of this disease is dependent on the type of complement that is reduced. Here we present a case series of complement deficiencies in the classical pathway and comparison of their clinical courses. Methods: Cases were obtained from medical records of patients seen at the Allergy and Immunology Clinic at Mount Sinai Hospital from 2008 – 2013. Results: Patient 1 is a 5 year old boy with a history of multiple infections at an early age including cellulitis, pneumonia and pneumococcal meningitis. The patient was diagnosed with a C2 deficiency as his complement levels were notable for undetectable levels of C2 and low CH50. The patient was placed on daily prophylactic antibiotics and his immunizations for meningococcal and pneumococcal vaccinations were updated. Patient 2 is a 58 year old female in good health with a sister who died of group B streptococcus sepsis at age 54 years. The patient was diagnosed with a C2 deficiency as her complement levels were notable for undetectable levels of C2 and low CH50. Her immunoglobulin levels were notable for a marginally low IgG 650 mg/dl (7001600 mg/dl) with normal IgA and IgM levels. She did not have protective titers for Hib, pneumococcus or meningococcus after vaccination. We advise that IgG subclass levels be evaluated and the urgent use of antibiotics for any infections. Patient 3 is a 38 year old female with recurrent lung and sinus infections and numerous hospitalizations in childhood. She was diagnosed with a complement 4 deficiency based on low C4 2 mg/dL (9-36) and CH50 levels with a marginally low C2 and C3 level. She has protective titers for pneumococcus; ANA titer was positive. She was vaccinated for hib and meningococcus and further diagnostic studies are scheduled to include C4 functional testing, C4 genotyping and measurement of C4 split products (C4a and C4d). Conclu-


sion: Patients with complement deficiencies have a broad clinical presentation. They may be asymptomatic, have poor response to vaccine titers or have serious recurrent infections that require prophylactic antibiotics.

P248 GOOD’S SYNDROME: A RARE FORM OF IMMUNODEFICIENCY ASSOCIATED WITH THYMOMA. R. Gandhe*1, R. Divekar2, N. Amar3, R. Bonds1, J.A. Grant1, 1. Galveston, TX; 2. Rochester, MN; 3. Waco, TX. Introduction: Good’s syndrome (GS) is a rare form of immunodeficiency associated with thymoma first described in 1954 by Robert Good. Patients commonly present between the ages of 40 and 70 years with infectious complications, with or without autoimmune manifestations in the presence of a thymoma. Diagnostic work up usually reveals low to absent B cells, hypogammaglobulinemia, and defects in cell-mediated immunity. Methods: We present a 48 year old male who was admitted to our hospital with history of chronic productive cough and dyspnea. Patient reported multiple episodes of pneumonia requiring frequent hospitalizations, several intubations, and numerous courses of antibiotics. His problem began about 5 years ago after he underwent thymectomy for a benign thymoma causing mass-associated respiratory symptoms. He also had intermittent flaky, scaly skin rash and intermittent diarrhea. The rash was diagnosed as Tinea corporis based on skin biopsy. Allergy/Immunology service was consulted to evaluate for immunodeficiency. Initial work up revealed leukopenia, normocytic, normochromic anemia and significantly low immunoglobulin levels: IgG – 160, IgA – 55 and IgM- 7. CT scan of the chest revealed evidence of extensive bronchiectasis with mucus plugging. Respiratory culture of bronchial secretions obtained by bronchoscopy grew pseudomonas aeruginosa and streptococcus viridans. Further immunological work-up revealed very low CD 19+ cells [<1], low CD4 T cells [219], normal CD8 T cells [257] with CD4/CD8 ratio of 0.8, low CD3 cells [476] and low CD 16+56 cells [46]. Base on the history and lab findings, a diagnosis of GS was made. Patient was started on monthly IVIG replacement. He responded dramatically and has not reported any infection or hospitalizations since. Discussion: GS affects both humoral and cellular aspects of immunity predisposing patients to severe, recurrent sinopulmonary and opportunistic infections. GS has a poor prognosis mainly because of infectious complications. Immunoglobulin replacement has been reported to decrease infections, hospitalizations and use of antibiotics in these patients. Conclusion: We report a case of GS, a rare form of immunodeficiency disorder associated with thymoma. We as allergist/immunologists should be cognizant of such rare immunodeficiency conditions. Appropriate work up and treatment should be promptly considered to improve the outcome.

P249 CILIARY APLASIA IN A CAUCASIAN MALE WITH RECURRENT SINOPULMONARY DISEASE. J. Abraham*, J. Horbal, D. Jhaveri, J. Sterbank, T. Tim-aroon, S. DeBrosse, R. Rezaee, R. Hostoffer, H. Tcheurekdjian, Cleveland, OH. Background: Bardet-Biedl syndrome (BBS) is characterized by retinal dystrophy, truncal obesity, post axial polydactyly, cognitive impairment, hypogonadism and renal abnormalities. The genes associated with this syndrome are implicated in the structure and function of cilia, however testing for known BBS genes only identify a portion of patients. BBS is typically associated with a defect in primary cilia, with no reports of cases with abnormalities in both primary and motile cilia. We introduce an interesting patient with BBS who has an absence of all cilia. Methods: A 29 year-old Caucasian male with retinal dystrophy, obesity, post axial polydactyly and developmental delay presents with a history of recurrent pneumonias from two weeks of age and bronchiectasis. Clinical diagnosis of BBS was made in childhood when genetic testing was not available. Testing for immunodeficiencies and select known mutations associated with BBS was performed to elucidate a cause for the patient’s symptoms. Results: Immunodeficiency workup was significant only for mannose binding lectin deficiency, which is not consistent with the patient’s clinical presentation. Five known BBS genes were tested for and were normal, however these genes only identify 66% of patients with BBS. Ciliary dysfunction is commonly associated with BBS and due to the patient’s recurrent pneumonias and bronchiectasis, a full thickness nasal inferior turbinate biopsy was obtained. The biopsy specimen demonstrated complete absence of both primary and motile cilia. Conclusions: BBS has been a clinical diagnosis until recently, when genetic testing has become available. However, these tests only


ABSTRACTS: POSTER SESSIONS identify a portion of patients with BBS. The absence of cilia in this patient is a novel finding that has not been previously reported in patients with BBS and may be a new clinical presentation of this syndrome. Whole exome sequencing is being performed currently to try and identify a genetic cause for our patient’s symptoms.


iectasias, a presumptive diagnosis of AT was made, given her early onset ataxia, significant speech delay, elevated AFP, poor T cell function, and low serum IgA and IgG. Mutation testing later revealed one inherited mutation in the ATM gene, further supporting the diagnosis. Conclusion: Although cutaneous noninfectious granulomas are uncommonly associated with primary immune deficiencies, AT should be considered when such granulomas are present along with combined immunodeficiency, even in the absence of the classic features of this syndrome.



Rationale: Griscelli syndrome (GS) is an autosomal recessive disorder that results in partial albinism with variable cellular immunodeficiency and/or neurologic deficits. GS type 2 (GS2) is secondary to a mutation in RAB27A, which encodes a small GTPase protein implicated in vesicle fusion and trafficking. Patients develop immunodeficiency from dysfunctional secretion of cytotoxic granules in natural killer (NK) cells and cytotoxic lymphocytes.This immune dysfunction often results in hemophagocytic lymphohistiocytosis (HLH), which leads to death in the absence of bone marrow transplant. Our patient was homozygous for a novel missense mutation in the RAB27A gene. The mechanism of this inheritance pattern is explained by uniparental disomy. A pattern not previously associated with GS. Results: A term newborn infant was born to nonconsanginous parents (Mongolian/Chinese mother and mixed European descent father) via uncomplicated pregnancy and delivery. At birth, she was noted to have silver hair, prompting further evaluation including microscopy of her hair which showed irregular melanin pigment clumping, concerning for GS. Complete blood count showed normal absolute neutrophil and lymphocyte count. Blood smears showed no evidence of giant lysosomal inclusion bodies. Flow cytometry forT, B, and NK cell numbers were within normal limits for her age. NK cells showed decrease cytotoxicity with abnormal chromium release assay. Perforin/granzyme presences in cells were normal. RAB27A sequencing showed homozygous missense variant, c.37T>G (p.Leu13Val). This has not been described in association with GS. However, this mutation has been recognized in the database of Single Nucelotide Polymorphisms. Although no allele frequency information is available for this variant. Father was a carrier for the same mutation in the RAB27A gene. The inheritance pattern is explained by uniparental disomy. Currently, there are no known cases of uniparental disomy resulting in GS. Conclusion:This patient demonstrates both partial albinism and evidence of reduced NK cell function in the setting of a variant mutation in RAB27A. Given the phenotypic findings of GS, this RAB27A variant should be included in the disease associated mutations.This case shows a new mutation in RAB27A with uniparental disomy leading to phenotypic Griscelli Syndrome type 2.

P251 CUTANEOUS GRANULOMAS PRESENTING AS PRIMARY IMMUNE DEFICIENCY. G. Ram*, J. Heimall, Philadelphia, PA. Introduction: Cutaneous granulomas are uncommon in primary immune deficiency. We report an unusual case of a 3-year-old girl presenting with multiple ulcerated non-infectious cutaneous granulomas who underwent several hospitalizations and extensive work-up before being diagnosed with ataxia telangiectasia (AT). AT is an autosomal recessive chromosomal breakage syndrome characterized by progressive cerebellar neurodegeneration, radiosensitivity, predisposition to lymphoid malignancies, and a variable degree of immunodeficiency. It is associated with mutations in the ATM gene. Our case demonstrates the variable presentation of AT and emphasizes difficulty in early diagnosis. Case Presentation: A 3-year-old female presented to the ED with a history of chronic nasal congestion, poor feeding, failure to thrive, developmental delay and worsening of chronic skin lesions on bilateral upper extremities. Family history was limited, but there was no known consanguinity. Past medical history was remarkable for premature birth at 32 weeks and upper extremity skin lesions since 1 year of age. She had no previous hospitalizations, surgeries, or known prior infections. Physical exam revealed a small nonverbal girl with thick nasal discharge, diffuse lymphadenopathy, wide-based unsteady gait, and multiple large ulcerated annular plaques with heaped-up hyperpigmented borders and serosanguinous crusting. Skin biopsy showed caseating granulomas with negative results for numerous infectious pathogens. Brain MRI revealed vermian hypoplasia. AFP level was elevated at 86. Immunologic evaluation revealed IgG 354, IgA 24, and IgM 72. Pneumococcal and diphtheria titers were poor and did not respond to booster vaccination. Lymphocyte flow cytometry was normal (CD3:2514, CD4:456, CD8:1788). All mitogen responses were poor. Despite the absence of oculocutaenous telang-

HISTAMINE H3-ANTAGONISTS MODULATE CYTOKINE SYNTHESIS IN VIVO AND IN VITRO IN ACUTE SENSORINEURONAL HEARING LOSS PATIENTS. R. Khanferyan*1, R. Lazareva2, L.M. DuBuske3, 1. Moscow, Russian Federation; 2. Krasnodar, Russian Federation; 3. Gardner, MA. Introduction. Acute sensorineuronal hearing loss (ONT) may benefit from use of histamine H3 receptor antagonists. Betahistine (BH) possesess a very strong affinity for H3 receptors increasing levels of neurotransmitters released from the nerve endings. BH has a weak affinity for histamine H1 receptors. This study investigates modulation of cytokine synthesis in ONT patients treated with BH. Methods. Concentration of pro- and anti-inflammatory cytokines (IL1β, TNFα, IL4 and INFγ) were assessed by ELISA in sera of patients before treatment on day 1 of the disease and on the 7th and 14th days of treatment with BH. Cytokine synthesis was investigated in supernatants of peripheral blood mononuclear cells (PBMC) pre-treated with the H3/4 antagonist Imoproxifan (IMP) (10-5M/ml) as well as with BH. Results. Decreased sera levels of proinflammatory cytokines (IL1β, TNFα and INFγ) were noted especially on the 14th day of treatment in comparison with non-treated patients. Both IMP and BH increased sera levels of IL4 and IL4 synthesis by PBMC of patients with ONT. Pre-treatment of PBMC by IMP or BH decreased IL1β, TNFα and INFγ synthesis, most noted with IMP pre-treated cells. IMP and BH induced a more pronounced effect on cytokine production in BH treated patients who responded well to treatment versus those with a low response to treatment. Conclusions. H3 as well as H3/4 antagonists modulate pro-and anti-inflammatory cytokine synthesis in patients with ONT. This investigation suggests that histamine H3 receptors may have a role in the pathogenesis of ONT.

P253 CELLULAR IMMUNITY AND NUTRITIONAL STATUS OF WEIGHT LIFTERS IN THE RUSSIAN FEDERATION. E. Trushina1, O. Mustaphina1, D. Nikityuk1, K. Gapparova1, R. Khanferyan1, L.M. DuBuske*2, 1. Moscow, Russian Federation; 2. Gardner, MA. Introduction: While elite athletes may not demonstrate clinical evidence of immune deficiency, immune cell subpopulations and regulatory cytokines may be impacted by the effects of prolonged intense exercise leading to subclinical secondary immune deficiency. This study assesses immune parameters in weight lifters related to daily nutrient intake and lipid metabolism. Methods: 30 weight lifters (18 females and 12 males) and 14 individuals who did not engage in sport were assessed. All subjects were from the Russian Federation and were assessed at the Institue of nutrition of the Russian Academy of Medical Sciences in Moscow, Russia. Lymphocyte subpopulations were studied by flow-cytometry (Cytomics FC500, Beckman Coulter). Results: Decreased immunoregulatory index of CD4/CD8 (0.89+0.08 in women and 0.77+0.11 in men; p<0.05) mainly due to an increased number of cytotoxic CD3+CD8+ cells and reduction of helper CD3+CD4+ cells occurred in 17% of female and 42% of male athletes. There was an imbalance in the athletes’ diet with unfavorable ratio of proteins, fats and carbohydrates of 1:1.7:3 in women and 1:1.4:2.9 in men along with an increase in low-density lipoproteins and decrease in highdensity lipoproteins. Conclusions: Athletes engaging in prolonged intensive physical activities can exhibit subclinical secondary immune deficiency which together with an associated imbalance in dietary intake of proteins, fats and carbohydrates may lead to a deleterious imbalance in lipoproteins. This change in lipoproteins may also impact immune parameters in these elite athletes.




P254 FEMALE TEENAGER WITH GRISCELLI SYNDROME TYPE 3: A CASE REPORT. R. Muriel-Vizcaino*, E. Sandoval, M.A. Rosas, B.E. del Rio, Mexico City, DF, Mexico. Background: Griscelli syndrome (GS) is a rare autosomal recessive disorder characterized by different degrees of skin and hair hypopigmentation. The phenotypical main feature is the gray-silver colored hair and it is classified in base of the accompanied affection. The GS type I presents with neurological impairment mostly global neurodevelopmental delay, due to the lack of the MyosinVa (MyoVa) protein. The second type is associated with an immune defect, leading to episodes of an uncontrolled T lymphocyte and macrophage activation syndrome. Recently it has been described a third type of GS (GS3) that only shows the skin and hair hypopigmentation. To date there are two genes involved in GS3, the melanophilin (Mlph) gene and the F-exon of MyoVa gene. In GS the capture and mobilization of melanosomes is altered as it requires absolute interaction of the complex formed by MLPH-MyoVaRAB27A, that’s why the 3 subtypes share pigmentary defects. We present the case of a female teenager product of consanguineous parents who was referred to our department with allergic rhinitis. Featuring a characteristic phenotype of silver-hair with skin hypopigmentation. No serious or repeated infections were referred and have normal neurodevelopment. All studies reported in normal ranges: CBC, immunoglobulins, flow cytometry, and peripheral blood smear. The clinical phenotype with the consanguinity and absence of neurological or immune impairment raised the suspicion of a GS3. Skin biopsy and hair microscopy was requested reporting the characteristics findings described in the GS. In collaboration with Dr. William A. Gahl of the National Human Genome Research Institute (NIH), the gene was sequenced, finding a homozygous deletion in exon 2 of the gene encoding for Mlph, which is consistent with previously described mutations in the GS3. In order to normal neurological development and function the MyoVa (at least in the form F-exonMyoVa) is essential, as well as RAB27A is for the cytotoxic granules exocytosis of T lymphocytes and NK cells since cytotoxic cells do not express MLPH or MyoVa, and as the Mlph is only essential for proper pigmentation. Conclusion: The molecular study of patients with silvery hair phenotype at early ages, in which the three types may be indistinguishable, is critical because it helps to guide management, prognosis and genetic counseling before the accompanying condition appears.

a newborn referred for low TRECs detected on newborn screening who was found to have T- and B-cell lymphocytopenia but no evidence for SCID. The patient presented with initial average TRECs of 14, repeat of 0. He was born at 35 4/7 weeks because of premature rupture of membranes. Both parents are natives of Macedonia. They are not related and healthy. The patient has a two year old healthy sister. The family history is negative for immune deficiencies. After birth he was diagnosed with Hirschsprung’s disease and underwent surgical resection and colostomy. His physical exam was significant for mild micromelia. The diagnosis of Hirschsprung’s, his immune dysfunction and physical features incited genetic screening. The patient was diagnosed with cartilage hair hypoplasia. Both parents are carriers. At presentation at the age of six weeks the patient’s absolute B-cell number was 350/cuMM (432-3345/ cuMM), absolute T-cell number 513/ cuMM (1460-5440/cuMM). At second follow up at 6 months his absolute B-cells had normalized at 691/cuMM and T-cells increased 684/cuMM. At 9 months his absolute B-cells continued to be normal at 481/cuMM and T-cells stagnated at 588/cuMM. His repeated TREC levels varied between 0 and 270 with no trend noticeable. Prophylactic antibiotics were continued three times per week. He has received childhood vaccines except for live viral vaccines. He continued to be well appearing with no major infections. The physical features of cartilage-hair hypoplasia have become more prominent since his initial presentation. Newborn screening for severe combined immunodeficiency has been initiated in New York State in the fall of 2011 to allow for early detection of a severe curable disease. Apart from detecting cases of SCID other dysfunctions of the immune system have been detected. This allowed for faster diagnosis of certain genetic syndromes or other underlying disorders. Therapeutic or preventative measures as prophylactic antibiotics and delaying of live vaccines were initiated early and decreased morbidity and improved long-term outcomes.

P256 VACCINE STRAIN VARICELLA ZOSTER VIRUS-INDUCED CENTRAL NERVOUS SYSTEM VASCULOPATHY AS THE PRESENTING FEATURE OF DOCK8 DEFICIENCY. A. Sabry*, P. Hauk, E. Gelfand, Denver, CO. Background: Patients with mutations in the gene encoding the dedicator of cytokinesis 8 (DOCK8) experience recalcitrant atopic dermatitis, food allergies, recurrent respiratory infections and asthma, diverse central nervous system (CNS) disorders, and recurrent fungal and viral infections. We describe a child with a novel compound heterozygous mutation in DOCK8 who developed CNS vasculopathy caused by Oka vaccine strain varicella zoster virus (VZV). Methods: Advanced CNS imaging was used to visualize the vasculopathy. VZV in cerebrospinal fluid (CSF) was detected by quantitative polymerase chain reaction (PCR). The VZV genotype was determined by Förster Resonance energy transfer PCR that targets multiple vaccine markers. Comparative genomic hybridization and DOCK8 gene sequencing were used to study disease-causing mutations. DOCK8 protein expression was assessed by Western blot. Results: CNS vasculopathy complicated by infarction was produced by reactivation of the Oka vaccine strain of VZV. DOCK8 deficiency was confirmed by the absence of protein and deletion of exons 1 to 13 on one allele and a single base pair mutation on the opposite allele. Conclusions: A young patient with significant atopic disease and widespread infarction produced by stenosis of multiple large cerebral arteries was shown to express novel mutations on both alleles of the DOCK8 gene. For the first time, VZV vasculopathy was shown to be due to the vaccine strain. This case highlights the importance of considering the potential for significant immune deficiency in the context of severe allergic disease and the potential risks for VZV vaccinerelated vasculopathy.

P257 P255 CASE OF CARTILAGE-HAIR HYPOPLASIA DETECTED BY NEW YORK STATE NEWBORN SCREENING FOR SEVERE COMBINED IMMUNODEFICIENCY. D.A. Andreae*, C. Cunningham-Rundles, New York, NY. Universal newborn screening for severe combined immunodeficiency (SCID) using T-cell receptor excision circles (TRECs) was implemented in New York State in 2011. Apart from identifying patients with SCID, newborns with other defects of the immune system were detected. We describe a case of


IMPACT OF WINTER SPORTS ON LYMPHOCYTE SUB-POPULATIONS AND SERUM CYTOKINES IN ELITE ATHLETES FROM THE RUSSIAN FEDERATION. R. Khanferyan1, E. Trushina1, O. Mustafina1, G. Azizbekyan1, V. Kodentzova1, N. Beketova1, A. Samoilov1, L.M. DuBuske*2, 1. Moscow, Russian Federation; 2. Gardner, MA. Introduction. Prolonged intense exercise may cause depression in various lymphocyte subpopulations and cytokine production. The degree and duration of immune suppression is related to the intensity and duration of exercise. Dietary deficiencies of macro- and micro-nutrients including antioxidant vitamins may also impact immune function in athletes. This investigation assesses


ABSTRACTS: POSTER SESSIONS sub-populations of blood lymphocytes and serum level of cytokines along with antioxidant vitamin serum levels in winter sport elite athletes. Methods. 26 elite athletes including 10 women and 17 men from the Russian Federation specialized in biathlon and snowboard/skeleton were assessed at the Scientific Institute of nutrition, Moscow, Russia. Lymphocyte subpopulations were assessed by flow-cytometry (Cytomics FC500, Beckman Coulter). Levels of pro-inflammatory cytokines (IL1β, TNFα) in sera were measured by ELISA. Vitamin A, C, E, β-carotene and carotenoid levels in serum were assessed by HPLC. Results. Decrease in the immunoregulatory index (CD4+/CD8+) was noted in 7/26 athletes due to decreased CD4+ helper cells. 3 athletes had marked reduction in CD8+ cells. 40% of athletes had reduced numbers of NK lymphocytes (CD3+16+56+). Most athletes after intense exercise had decreased numbers of activated T-cells (CD25+). Pro-inflammatory cytokines (IL1β, TNFα) increased more than 3 to 4 fold in most athletes. Changes in lymphocyte subpopulations may be related to low levels of anti-oxidative micronutrients. 40% of athletes had a deficiency of β-carotene and about 50% had decreased levels of total carotenoids. Conclusions. Immune suppression reflected in altered lymphocyte sub-populations in winter sport elite athletes enduring prolonged intense exercise was mainly seen in T-helper and NK cell sub-populations. Intense exercise increased production of pro-inflammatory cytokines IL1β, and TNFα. Factors augmenting immune suppression maybe low serum levels of anti-oxidative carotenoids and β-carotene. Low levels of anti-oxidative nutrients may increase immune suppression induced by intense physical activity by winter sport elite athletes.

P258 CONGENITAL NEPHROTIC SYNDROME AND PNEUMOCOCCAL ANTIBODIES DEFICIENCY. A.B. Teodoro*, V. Johnson, R. Herzog, New York, NY. Introduction: Nephrotic syndrome (NS) comprises of several signs and symptoms that denote kidney damage, which include proteinuria, hypoalbuminemia, hyperlipidemia, and edema. In addition, immune abnormalities have been reported to be associated with NS. We present 3 patients with congenital NS who demonstrate unique patterns of immune deficiency and illustrate the importance of immune evaluation in this condition. Case Report: Three 4-yearold patients (two males and one female) presented with chronic nasal congestion, recurrent otitis and a history of frequent relapsing idiopathic minimal change NS. Immune evaluation revealed normal lymphocyte subsets, IgA and IgM, as well as protective antibody titers for tetanus and diphtheria. However, they were found to have IgG 300-400 (463-1236 mg/dL) and non-protective pneumococcal antibodies despite vaccination. Variability was present in lymphocyte mitogen stimulation test with low pokeweed mitogen simulation response. Conclusion: Children with NS may have a high prevalence of impaired antibody response to pneumococci and pneumococcal polysaccharide vaccine, which may lead to susceptibility to bacterial infections, particularly pneumococci. Thus, immune evaluation is warranted in this condition regardless of remission state.

P259 DOES THE DEGREE OF LYMPHOPENIA INDUCED BY ANTITHYMOCYTE GLOBULIN IMPACT OUTCOMES IN PEDIATRIC LUNG TRANSPLANT RECIPIENTS WITH BRONCHIOLITIS OBLITERANS? J.V. Lorbert*, S. Sweet, C. Huddleston, A. Faro, St. Louis, MO. Purpose: Antithymocyte globulin (ATGAM) is a polyclonal antibody preparation that decreases the number of circulating lymphocytes and is frequently used to treat post-lung transplant bronchiolitis obliterans (BO). However, little is known about the overall efficacy of the drug for this purpose and no guidelines exist as to what extent of immunosuppression optimizes treatment benefits without placing patients at further risk for acquiring life-threatening infections or malignancies. We investigated the degree to which ATGAM induced lymphophenia correlated with treatment responses. Methods: We retrospectively analyzed data from lung transplant patients who received ATGAM therapy at our center between 2000 and 2011 (n = 53). IRB approval was obtained. Informed consent was not required as it was a retrospective chart review. Data were collected from electronic medical records and our center’s database. We compared groups with ATGAM induced absolute lymphocyte counts (ALCs) below 500 to those with ATGAM induced ALCs over 500. We analyzed time to death, time to retransplantation, graft survival, development of post-transplantation lymphoproliferative disorder (PTLD), episodes of acute rejection, development of infections, changes in FEV1, and changes in chest

CT and VQ scans following ATGAM therapy. Results: We found no significant associations. Of note, although not statistically significant, all three patients who developed PTLD following ATGAM therapy had ALCs less than or equal to 100. Conclusions: Our findings suggest that the degree of lymphopenia induced by ATGAM does not affect outcomes. However, as the presumed mechanism of action of ATGAM in treating BO is augmented immunosuppression, the lack of a difference in outcomes between the two groups raises concerns as to the efficacy of ATGAM in treating BO. A limitation of this study was sample size. Multi-centered controlled trials are needed to further investigate the efficacy of ATGAM and its potential association with increased risk of infection and malignancy. This may be particularly important in evaluating the risk for PTLD.

P260 RELAPSING POLYCHONDRITIS PRECEDED BY PULMONARY, CARDIAC AND GASTROINTESTINAL SYMPTOMS. R. Kreiner*, A. Rubinstein, Bronx, NY. Introduction: Relapsing Polychondritis (RPC) is a rare immune mediated condition associated with inflammation of cartilaginous tissues throughout the body. We report the case of a 21-year-old patient with RPC who initially presented with respiratory distress, parotitis, hemorrhagic colitis and chest pain. Methods: We evaluated a 21-year-old female with RPC preceded with unusual multiple inner organ involvement eventually presenting with auricular cartilage inflammation typical for RPC. Results: 19-yr-old female CP was referred for evaluation after developing pulmonary symptoms suggestive of Bronchiolitis Obliterans with Organizing Pneumonia based on chest CT and lung biopsy. PFTs at the time were 30% of normal. She was treated with steroids noting significant clinical and radiographic improvement but relapsed a month off steroids. She then developed painful swelling of her parotid glands responding to steroids but failing upon dose tapering. CP concomitantly developed chest pain with EKG, Holter monitor and ECHO showing sinus tachycardia, PVCs and a pericardial effusion. Mycophenolate Mofetil was introduced with resolution of chest pain, of parotitis and normalization of lung CT and PFTs. While on Mycophenolate she developed a hemorrhagic ulcerative colitis. Mycophenolate was discontinued and she responded to steroids and Asacol. Upon resolution of these symptoms she developed otalgia and inflammation of ear lobe cartilage typical for RPC which responded to steroids and Mycophenolate. Further treatment options include Imuran, Rituxan, anti-TNF, or Anakinra. Conclusion: This is the first case report describing a patient with RPC with a confounding initial presentation of inner organ disorders (pulmonary symptoms, parotitis, ulcerative colitis and pericarditis)-all probably secondary to inner organ chondritis.

P261 A 22-YEAR REPLACEMENT THERAPY FOR AN ADENOSINE DEAMINASE (ADA) DEFICIENT PATIENT. H.M. Tartibi*1, M.S. Hershfield2, S.L. Bahna1, 1. Shreveport, LA; 2. Durham, NC. Introduction: ADA activity is highest in the thymus; its deficiency leads to accumulation of deoxyadenosine nucleotides (dAXP) which are toxic to T and B cells, causing severe combined immunodeficiency (SCID) presenting within the first months of life. Replacement therapy with PEG-ADA is used when HLA-matched stem cell donor is not available. Case: A full-term newborn with APGAR score 4-6 and pulmonary infiltrate had WBC 3,100/ml; 82% poly, 3% mono, 1% lymph, 14% eos. No FHx of early deaths or immunodeficiencies. At 3 wk had oral thrush, diaper rash, cough and diarrhea. At 3.5 mo had fever; WBC 9,800/ml; 66% P, 4% M, 2% L, 19% E, and 610,000 platelets. Serum IgG <189, IgA <7 & IgM <6 mg/dL, and IgE <9 IU/mL. Infant and mother were HIV negative. His lymphocyte subsets were very low: total 288/ml; B cells 4.6% (13/ml; Nl 50-540), T cells 48% (139/ml; Nl 730-2790), Th 4.7% (13/ml; Nl 310-1920), Ts 17% (49/ml; Nl 200-1320), Th/Ts 0.3 (Nl > 1), NK 15% (43/ml; Nl 30-300), IL2-R1 1.4% (4/ml; 3-30). SCID was diagnosed; heterozygote for 2 missense mutations A179D and R211H. In addition to antibiotics and antifungal, received IVIG for 5 mo, with clinical improvement. RBC ADA was barely detectable and dAXP were 20.6% of total adenine nucleotides (normal <1%), confirming ADA-deficient SCID. PEG-ADA 30 U/kg biweekly and prophylactic trimethoprim/sulfa began. Within 1 mo CD4 increased from 109 to 418/ml. At 1 yr T cells showed adequate response to mitogens and candida. At 16 mo (6 mo after IVIG D/C) had IgG 475, IgA 19, IgM 59 mg/dL. PEGADA dose was periodically adjusted for weight, maintaining plasma ADA at



ABSTRACTS: POSTER SESSIONS 25-101 mmol/h/ml during the first year, 27-211 at 1-5 yr, 73-163 at 6-10 yr, 18-95 at 11-20 yr. His recent level at 22 yr was 40 mmol/h/ml and the dose was increased from 11 to 15 U/kg biweekly. Major events since infancy were pneumonia at 35 mo, meningoencephalitis at 3.5 yr, staph bacteremia at 4 yr, membranous glomerulonephritis at 18 yr, and tinea corporis at 20 yr. During the past few years, he had no major infections and good humoral immunity [IgG 604, IgA 111 & IgM 48 mg/dL, and specific antibody titers], but lymphopenia (570/ml) and low T cell numbers (CD3, 447; CD19, 64; CD56/16, 49/ml; CD4/CD8, 0.64). Conclusion: ADA-deficient SCID infants can have satisfactory control of infections through adulthood by early and regular replacement with PEG-ADA.

observed at 5 min following LPS stimulation. and activation of NF-κβ were observed at 5 minutes of LPS and extent of activation of stimulated cells of the control. The expression of NEMO, and phosphorylation of Iκβα, and activation of NF-κB in the patient was comparable to control. Conclusions: This patient with hypogammaglobulinemia and anhidrotic ectodermal dysplasia has no defect in the expression of NEMO, or phosphorylation of Iκβα and activation of the NF-κB pathway, excluding a possibility of mutations of NEMO or Iκβα. Therefore, this is the first case of hypogammaglobulinemia and EDA in an adult without a defect in the NF-κB pathway.



MOSAIC MONOSOMY 7 IS ASSOCIATED WITH AN ABNORMAL TREC SCREEN. L.V. Buyantseva*, A. Horwitz, T. Fausnight, Hershey, PA. Introduction: Testing for T-cell receptor excision circles (TREC), a DNA biomarker of normal T-cell development, is used to screen newborns for severe combined immunodeficiency (SCID) and syndromes associated with T cell lymphopenia (DiGeorge syndrome, ataxia-telangectasia, and Jacobsen syndrome). It has also identified other conditions which have more non-specific immune dysfunction, such as Trisomy 21. We present a case of an infant with an abnormal TREC screen who was later diagnosed with mosaic monosomy of chromosome 7, a rare disorder associated with myelodysplastic syndrome (MDS) and multiple congenital anomalies. Methods: PubMed literature review was performed using a combination of the following terms: monosomy 7, mosaic monosomy 7, lymphopenia, TREC, Test for T-cell receptor excision circles. Case Report: We describe a 3 month-old boy born at 27 weeks of gestation by C-section for a low biophysical profile and severe intra-uterine growth retardation. Amniocentesis showed 46 XY karyotype. He had multiple congenital abnormalities including ambiguous genitalia, congenital adrenal hypoplasia, an atrial septal defect, and spina bifida with associated ventriculomegaly. His NICU course was complicated by hypotension, hypoglycemia, persistent acidosis, electrolyte imbalances and pancytopenia. Newborn SCID screening at birth was inconclusive, but when repeated at 40 week adjusted age revealed undetectable TRECs. A microarray study performed after the second abnormal newborn screen revealed mosaic monosomy 7. Additional testing showed low but present T, B and NK cells. His IgG and IgM were low; IgA was normal. Based on his poor prognosis, the family withdrew support and the patient died at 41 weeks of age. Literature Review: There are 2 published case reports of mosaic monosomy 7 associated with MDS and severe aplastic anemia, but not lymphopenia. Conclusions: Population-based TREC screening has been helpful in identifying cases of SCID and T-cell lymphopenia. As screening increases, other syndromes with variable degrees of lymphopenia are being diagnosed. The practitioner should consider microarray testing in a child with an abnormal TREC newborn screen and multiple congenital abnormalities. This is the first published report of a patient with mosaic monosomy 7 and an abnormal TREC screen.

P263 HYPOGAMMAGLOBULINEMIA AND ANHIDROTIC ECTODERMAL DYSPLASIA IN AN ADULT WITH NORMAL NF-κB SIGNALING PATHWAY. A. Gharib*1, S. Gupta2, S. Agrawal2, 1. Pacific Palisades, CA; 2. Irvine, CA. Background: Anhidrotic Ectodermal dysplasia with immunodeficiency (EDA-ID) is a primary immunodeficiency disorder in children with a multitude of phenotypical findings including but not limited to anhidrotic ectodermal dysplasia (EDA). This is associated with abnormal NF-κB signaling pathway as a result of a mutations in Iκκγ(NEMO) or Iκβα. Here we investigated an adult 49 year old male with hypogammaglobulinemia and EDA for NF-κB signaling pathway deficiency. Methods: Peripheral blood mononuclear cells were isolated from patient and control donor. 2 million cells per milliliter were incubated with LPS for 5,10,30 minutes. Cells were fixed and permeabilized with Perm Buffer III. Cells were stained with NEMO, phospho- Iκβα, and phospho-p65 antibodies. Cells were washed, and 10,000 cells were acquired by FACSCalibur and analyzed by FlowJo software. Isotype controls were used as a negative control. Protocol was approved by the Institutional Review Board of the University of California, Irvine Results: Activation of NF-κB as measured by phosphorylation of its p65 subunit, and phosphorylation of Iκβα were


P264 Introduction: Immunodeficiency has been associated with many genetic syndromes. A neonate presenting with a phenotype of infection, lymphopenia, and dysmorphic features should prompt evaluation and treatment for primary immunodeficiency. We describe our neonate with a severe form of immunoosseous dysplasia. Case description: A 4 month old Caucasian male with history of IUGR, hydrocephalus, failure to thrive, erythematous rash, and skeletal abnormalities presented to our Pediatric ICU in acute respiratory failure. Laboratory evaluation revealed a low IgG level, profound hypothyroidism, adenoviral infection, and bone marrow failure with marked lymphopenia. Lymphocyte analysis revealed low circulating T cells, low B cells, and normal NK cells. Urinalysis was normal. Notable physical characteristics included normal hair and nails, profound shortening of the hands, feet, fingers, and toes, capillary hemangiomas of the eyelids, upslanted palpebral fissures, flat nasal bridge, anteverted nares, and undescended testicles. He remained markedly hypothyroid and lymphopenic. Despite absent B cells, immunoglobulin production appeared normal . The infant died at 9 months life secondary to cardiorespiratory failure. Discussion: This report presents a rare case of a severely affected neonate with immunoosseous dysplasia. Sixty percent of individuals with the clinical features of Schimke Immunoosseous Dysplasia (SIOD) have a mutation in the SMARCAL 1 gene. SIOD is characterized by lymphopenia (80% with T cell deficiency), bone marrow failure, spondyloepiphyseal dysplasia, hypothyroidism, and nephropathy. Conclusion: Our patient had a rapidly progressive form of immunoosseous dysplasia. Schimke’s Immunooseous Dysplasia (SIOD) and Cartilage Hair Hypoplasia (CHH) are the only forms of immunoosseous dysplasia described in the literature. Our patient’s phenotype fits most closely with a diagnosis of SIOD with the unique features of profound B cell deficiency and lack of nephropathy. Although onethird of SIOD patients do not have an identifiable gene defect, these forms will likely be elucidated with advancement in exome sequencing interpretation.

P265 CHARACTERIZING A UNIQUE IMMUNOLOGIC HYPERIMMUNOGLOBULIN M PHENOTYPE. A. CaJacob*, T. Atkinson, L. Xiao, Y. Vaid, Birmingham, AL. Introduction: The Hyperimmunoglobulin M (HIGM) syndromes are a heterogeneous group of diseases characterized by normal or elevated levels of IgM but variably decreased levels of IgG, IgA and IgE. Several genes have been identified in which loss-of-function mutations result in HIGM syndrome, two with relatively selective B cell deficiency (AID and UNG deficiency), two with combined T and B cell functional defects (CD40, CD154 deficiency), and at least one type with a diffuse defect in leukocyte activation affecting T and B lymphocytes, NK cells, and phagocytes (IKBKG encoding the NFkB Essential Modulator, NEMO). Methods: Commercial sequence analysis of NEMO (IKBKG) was performed. Results: JV and TM are twenty-one and eleven year old unrelated African-American males with markedly elevated IgM occasionally exceeding 3 gm/dL, and essentially absent IgG, IgA, and IgE. No family history of recurrent infection was identified in either patient. They have both had lifelong problems with bacterial infections that have been prominently respiratory, but have also included persistent Salmonella gastroenteritis in JV and Pseudomonas cervical lymphadenitis in TM for over one year despite repeated attempts at antibiotic treatment. These bacterial infections have been associated with severe reactive regional lymphadenopathy. Progressively severe T and B cell lymphopenia has occurred in both patients, with persistently positive EBV viremia documented in one of them. Normal DNA sequence results were obtained on both patients for CD40L and on one patient for CD40, UNG, and AICDA. Additional sequencing on both patients revealed an intronic


ABSTRACTS: POSTER SESSIONS IKBKG mutation 1056-6T>C, a polymorphism that has been found in up to thirteen percent of the normal population. Conclusions: The HIGM syndromes are characterized by mutations in several genes, the most common of which are mutations in the X-linked genes IKBKG (NEMO) and CD40L. One subtype of the Hyper-IgM syndromes, HIGM4, is characterized by lymphoid hyperplasia, recurrent bacterial infections, and a proclivity towards autoimmunity, but T cell populations and function are normal while both our patients have developed severe T cell lymphopenia. The genetic basis for this HIGM subtype, which has features of both AID and IKBKG deficiency, is unclear.

P266 META-ANALYSIS OF THE EFFICACY OF ORAL IMMUNOTHERAPY FOR TREATMENT OF EGG ALLERGY IN CHILDREN. T. Gavrilova*, M.E. Weinstein, A.H. Wolff, Newark, NJ. Introduction: Egg allergy is one of the more common food allergies encountered in the pediatric population, affecting approximately 2.6% by 2.5 years of age.(1) Oral immunotherapy (lT) is a relatively new approach to treatment of food allergy.(2) This meta-analysis reviews the success of oral immunotherapy in inducing tolerance in children with egg allergy. Methods: Data were extracted via a PUBMED search of the literature available until June 2013. The search terms used were oral immunotherapy, egg allergy and children. The search yielded 60 results. We included four studies. Inclusion criteria were double-blind, randomized, placebo-controlled studies of children with egg allergy comparing the success of tolerance induction in those who received oral immunotherapy versus those maintained on elimination diets. Exclusion criteria were those studies that were not double-blind and placebo-controlled. Statistical analyses were performed using Review Manager (RevMan) 5. Results: A total of 193 patients were identified from 4 included studies. Eighty four of 119 patients who underwent oral immunotherapy to egg successfully passed the oral food challenge as compared to 25 of 74 patients who underwent elimination diets. Desensitization protocols varied and included maintenance with 1.6gm of Hen’s egg protein per day, 2gm egg white powder per day, and even a diet consisting of non-measured egg products after an initiation protocol with measured egg product has been completed.(1, 3-5) These trials showed that oral IT was more successful in inducing tolerance to egg allergy than a strict elimination diet. (odds ratio [OR], 4.63; 95% confidence interval [CI]2.57 to 8.35). Conclusion: According to our meta-analysis of the studies reviewed, oral desensitization seems to be a more successful treatment of egg allergy when compared to elimination diets. Further studies are needed to further establish the benefits of this approach to treatment.

n=190). For challenges to foods for which tolerance typically is developed (e.g. milk, egg, wheat, soy), the Ratio for those who failed their challenge was not higher than the Ratio for those who passed (n=102). For challenges to foods for which tolerance typically is not developed (e.g. peanut, tree nut, shellfish, seed), the Ratio for those who failed their challenge was significantly higher than the Ratio for those who passed (0.91% vs. 2.58%, P<.0001, n=88). This trend was also independently observed for peanut and tree nut challenges. The AUC representing the Ratio was significantly larger than that of sIgE alone (0.64 vs. 0.50, P=.01). For challenges to foods for which tolerance typically is developed, the AUC was no different between the Ratio and sIgE alone (0.50 vs. 0.50). In contrast, for challenges to foods for which tolerance typically is not developed, the AUC representing the Ratio was significantly larger than that of sIgE alone (0.75 vs. 0.50, P=.001). This trend was also individually observed for peanut and tree nut challenges. Conclusion: The Ratio of sIgE to total IgE is more accurate than sIgE alone in predicting tolerance to a food allergen, especially to peanut and tree nut. The Ratio may be a useful clinical indicator to identify patients most likely to pass an oral food challenge.

P268 ALPHA GAL ALLERGY AND CROSS-REACTIVE RED MEAT ALLERGY: ANALYSIS OF CLINICAL DATA. L. Flebbe-Rehwaldt*, H. Wells, J. Hester, M. Altrich, Lee’s Summit, MO. Introduction: Galactose-alpha-1,3-galactose (alpha-gal), is a cross-reactive carbohydrate moiety found in red meats such as beef, pork and lamb and is associated with a delayed IgE response, leading to urticaria and/or anaphylaxis. Methods: A retrospective review of national laboratory data was performed over eighteen months of the testing for IgE to Beef, Pork, Lamb, and Alpha Gal utilizing data with de-identified patient health information. Data was compiled into groups based on a cutoff of 0.1 kU/L as a positive test. Results: Thirty two percent of samples contained IgE antibodies against all 4 allergens, while 53 percent contained no detectable antibodies to any of the 4 allergens. Seven percent of samples were positive for at least one red meat (beef, pork, and/or lamb) but were negative for Alpha Gal. An additional 2 percent of samples were positive for IgE recognizing all three red meats but were negative for IgE to Alpha Gal. Interestingly, 4 percent of samples were positive for low levels (<1kU/L) of Alpha Gal IgE, but negative for IgE recognizing any of the three meats. Conclusions: Analysis of results testing for red meat and Alpha Gal reactive IgE revealed that a large portion of samples contained antibodies to both red meats and alpha gal, supporting the inter-related nature of these allergies. Surprisingly, 4 percent of samples were positive for Alpha Gal (albeit low levels) and negative to all three red meats. This suggests that the level of alpha gal contained in commercial products testing for red meat IgE are not sufficient to detect Alpha Gal IgE when present in low levels. Additionally a small portion of samples were negative for Alpha Gal reactive IgE, but positive for IgE recognizing some or all of the red meats. This indicates there are IgE antibodies that bind meat proteins and not the Alpha Gal carbohydrate, thus testing to red meat and Alpha Gal is important to gain a complete clinical picture. Further analysis may reveal if certain demographics (age or sex) contribute to this population of samples.

P269 P267 RATIO OF ALLERGEN-SPECIFIC IGE TO TOTAL IGE IN PREDICTING TOLERANCE TO FOOD ALLERGENS. R. Gupta*, C.H. Lau, A. Donnell, R. Hamilton, K. Newhall, Chicago, IL. Rationale: Allergists typically use allergen-specific Immunoglobulin E (sIgE) levels or skin prick test wheal size as indicators of tolerance to a food allergen (e.g. readiness to proceed with an oral food challenge). Although studies have shown the value of these tests in predicting tolerance, both have high rates of false positive results. The objective of this study was to examine the accuracy of the ratio of sIgE to total IgE (the “Ratio”) in predicting tolerance to a food allergen. Methods: Medical records of food allergic patients participating in an oral food challenge at an allergy outpatient clinic (2009–2013) were reviewed. Mann-Whitney U-tests assessed statistical correlations between challenge outcome and the Ratio. Receiver Operator Characteristics (ROC) curves and Area Under the Curve (AUC) were computed to compare the predictive value of the Ratio versus sIgE alone in predicting tolerance. Results: The overall Ratio for those who failed their oral food challenge was significantly higher than the Ratio for those who passed (1.08% vs. 1.94%, P<.001,

A MUFFIN A DAY KEEPS ALLERGIES AWAY…. OR NOT? A. Fiocchi*1, L. Dahdah1, C. Riccardi1, P.L. Koch1, S. Mancini1, P. Restani2, 1. Rome, Holy See (Vatican City State); 2. Milan, Italy. Background: Introducing baked egg (BE) in children with egg allergy (EA) increase the variety of products consumed, reduce parental anxiety, nutritional problems, child’s discomfort in social situations, and could shorten the time to tolerance. The present study casts prudence on this practice. Methods: 59 children referred for immediate reactions to egg were prospectively evaluated. Sensitization was assessed at SPT with native egg (cut-off: 3 mm wheal diameter) and at hen’s egg (HE)-ImmunoCAP® test (cut-off 0.35 kU/L). EA was confirmed at blinded challenges. A BE challenge (Pavesini biscuits) was done in EA children, who were allowed to consume BE-containing goods if negative. Their parents were interviewed after 2-4 months on allergic reactions to the newly introduced foods. Results: 38 children [22M, 16F, median age 3.2 years, range 13-62 months] had EA. All were SPT and/or sIgE positive with egg. 15 (group A) were reactive to Pavesini; 23 [13M, 10F, median age 4.0 years, range 16-62 months] passed the BE challenge. Products with baked milk were kept off the diet of 11 children with CMA. During the follow-up, 7 reactions to BE goods were reported in 3/23 children (group C): 3 urticaria, 2



ABSTRACTS: POSTER SESSIONS urticaria+angioedema, 1 urticaria + rhinitis, 1 anaphylaxis. Provoking foods were: Plum-cake Giusto Giuliani; Kinder fetta al latte Ferrero (two reactions in different children); Colombina Motta; Pan di Stelle cake Mulino Bianco Barilla; Ringo Pavesi biscuits. The anaphylactic reaction was due to Pandoro Paluani. The 3 children in group C tolerated a number of different BE products, but reacted at the first administration of the indicated foods. Sensitization in groups A, B (Pavesini-tolerant without reactions to other baked products) and C was: SPT wheal mean diameter, 10.8 vs. 7.2 vs. 8.8 mm respectively; hen’s egg sIgE, 61.5 vs. 7.8 vs. 18.8 kUI/L; egg yolk sIgE, 23.7 vs. 3.6 vs. 12.9 kUI/L. Comments: Children tolerant of the specific product used in challenges may react to different BE-containing goods. This may be due to sensitization characteristics (group C showed higher sensitization values) and to intrinsic characteristics of foods. Pending data on specific sensitization characteristics of our children and on the impact of different baking processes on the allergenicity of baked goods, we advise a negative BE challenge to be followed by the introduction of the specifically used product only.

P270 INCIDENCE OF FOOD ALLERGY AND BIRTH ORDER. M.Z. Blumberg, N. McComb*, Richmond, VA. Nicholas McComb Douglas S Freeman High School and Michael Z. Blumberg, M.D., MHA Allergy Partners of Richmond-Virginia Commonwealth University Richmond, VA The purpose of this project was to determine if birth order has an effect on the incidence of food allergies. The hypothesis tested was that first-borns are more likely to have a food allergy. An initial local survey of 194 subjects was sent out. This was done to verify that the experiment would be valid if done on a larger scale. After the local survey proved to be valid, a second survey was sent out to 176 food allergy support groups across the United States. The 2,179 survey responses were filtered to 2,000 participants to ensure that each respondent had a doctor-diagnosed food allergy, had one of the top eight most common food allergies, and had stated their birth order. A chi square test was performed on the data. In order to calculate the chi square values, the percentage of people with food allergies for each birth order was calculated using National Vital Statistics birth order data. The computed chi square value was 218.92, and the tabular chi square value was 11.0705. This indicates a statistically-significant effect with p<0.001. Therefore, we find a likely correlation between birth order and food allergies. The first born subjects had a much greater chance of developing a food allergy than any other birth order with a 40.44% chance of developing a food allergy. The other percentages are as follows: second born 32.50%, third born 16.91%, fourth born 6.70%, fifth born 2.44%, and sixth born 0.98% These results could be caused by a difference in the maternal immune system, a difference that is innate to the offspring or due to unique environmental exposures.

P271 THE MAJORITY OF EGG ALLERGIC PATIENTS TOLERATE EGG BAKED IN PRODUCT AT ORAL FOOD CHALLENGE. B. Buelow*, C. Lee, H. Zafra, M. Dasgupta, R. Hoffmann, M. Vasudev, Milwaukee, WI. Introduction: Egg is a common food allergen with an estimated prevalence of 1-2%. Most children outgrow their egg allergy by late adolescence, and it is very important to determine when oral tolerance is achieved, to avoid financial burden, social stress, personal anxiety, bullying and nutritional obstacles associated with this condition. Oral food challenges (OFC) can determine presence of food allergy or tolerance. OFC are not always widely available. We sought to retrospectively review the number of egg allergic patients who passed egg baked in product (EBP) OFC in an outpatient setting as a way to determine if we can consider recommending EBP OFC at home. Methods and Results: 43 patients underwent EBP OFC from January 2011 to December 2012. 9 patients were excluded who did not have a prior history of symptomatic egg ingestion. Of the remaining 34 patients, the mean age of patients was 71.3 months (14-165 months) and 22 (64.7%) were male. 23 (68%) had allergic rhinitis, 16 (47%) had asthma, 16 (47%) had atopic dermatitis and 1 (3%) had eosinophilic esophagitis. If known, the average age of first reaction to egg was 12.9 months (6-24 months) with a mean time of 56.3 months (8-159 months) between first reaction and EBP OFC. On initial egg exposure, 17 had cutaneous manifestations, 9 had one system involved (not a cutaneous manifestation), 1 had multisystem symptoms not related to egg ingestion whereas 7 had multisystem manifestations related to egg ingestion. 19 patients had accidental exposures and 9 were asymptomatic, 8 had one system involved, and 2 had multisystem manifestations. 28 of 34 patients (82.4%) passed the EBP OFC while


4 (11.8%) failed and 2 (5.9%) could not be determined. Of the 4 patients who failed, none required epinephrine. Conclusions: EBP OFC is a valuable tool to assess tolerance. The majority of our patients passed EBP OFC with continued consumption 2 weeks after challenge. OFC should be considered as a clinical tool to expand a patient’s diet and to improve quality of life. Recent literature suggests egg allergic patients consuming EBP may tolerate plain egg more quickly than egg allergic patients strictly avoiding egg. Since OFC in the outpatient setting has limited availability and long waiting times, further prospective studies are necessary to determine the ideal patient for home-based EBP OFC.

P272 EMERGENCY ROOM VISITS AND HOSPITALIZATIONS FOR FOOD-INDUCED ANAPHYLAXIS IN ILLINOIS, 2008-2010. R. Gupta*, T.L. Smith, A.A. Dyer, J. Cartland, Chicago, IL. Background: Food allergy prevalence affects an estimated 8% of children in the United States with over a third of children with food allergy reporting a history of a severe reaction. Studies have suggested that annual rates of Emergency Department (ED) visits and hospitalizations for food-induced anaphylaxis increased during the first half of the decade. To understand utilization of ED and inpatient services in Illinois, we must better describe the pediatric population experiencing severe reactions that lead to the utilization of such services. The goal of this study is to describe the population of Illinois children aged 0-19 years who presented to the ED and/or were hospitalized for foodinduced anaphylaxis, determine if the rate increased from 2008-2010 and identify what factors are associated with hospitalization that are indicative of a severe reaction. Methods: Anaphylaxis cases were identified from hospital discharge data using applicable ICD-9 codes. Univarite analysis was conducted to determine differences in rates by year. Logistic regressions were used to examine co-variates of hospital admission. Data were de-identified. Results: The rate of ED visits/hospitalizations in Illinois for food-induced anaphylaxis has increased from 6.3 per 100,000 in 2008 to 9.0 per 100,000 in 2010. For the three year period, the rate is highest among children aged 0-4 years (14.5 per 100,000), Asians (13.2 per 100,000) and males (9.5 per 100,000). Chicago children are also more likely to visit the ED or be hospitalized (13.0 per 100,000) compared to rural areas of the state (2.8 per 100,000). Logistic regression determined that adolescents aged 15-19 years are 1.8 times more likely to be admitted to the hospital for anaphylaxis compared to children aged 0-4. Conclusions: ED/hospitalization rate for food-induced anaphylaxis is increasing in Illinois. Children who are under 4 years, Asian, and reside in Chicago are at higher risk of having an ED visit or hospitalization due to anaphylaxis. Though the ED visit and hospitalization rate for children aged 0-4 years is the highest among the age groups, the adolescents appear to have the most severe reactions. Increasing education and awareness of food allergy and food allergy reaction management is needed, especially for adolescents.

P273 PARENTAL EMPOWERMENT AND FOOD ALLERGY-RELATED QUALITY OF LIFE. R. Gupta*, C.M. Warren, E. Oh, M.W. Sohn, C.H. Lau, J. Pongracic, X. Wang, Chicago, IL. Rationale: Given the limited treatment options, ubiquity of food in the social environment and absence of a cure, living with food allergy has been found to strain familial relationships, limit social activities and diminish quality of life among families. Past studies on the psychosocial consequences of food allergy on caregivers have focused almost exclusively on the impact of a child’s food allergy on maternal caregivers. The objective of this study was to describe the impact of a child’s food allergy on both mothers and fathers, as well as to assess the relationship between parental empowerment and food allergy-related quality of life. Methods: 940 families of children with food allergy were included as part of a family-based food allergy cohort. Food allergy was determined by objective symptoms developing within 2 hours of ingestion, skin prick testing, and specific IgE testing. Levels of empowerment and food allergy-related quality of life were collected through a questionnaire-based interview. Levels of mothers were compared with those of fathers using the t-test. Multivariate regression models were estimated to examine the association of parental empowerment with quality of life. Results: Mothers reported significantly higher degrees of empowerment (P<.001) and a significantly reduced food allergyrelated quality of life (P<.0001) than fathers, regardless of the child’s allergy severity or type. Analyzing mothers and fathers together, we found that food allergy-related quality of life scores increased significantly (P=.001) as care-


ABSTRACTS: POSTER SESSIONS givers reported increasing agreement with: “I feel like my family life is under control.” Additionally, greater educational achievement predicted poorer food allergy-related quality of life (P=.006) in mothers but not fathers. After controlling for age, gender, race, number of siblings, education and insurance status in multivariate regression models, we did not find parental empowerment to predict caregiver food allergy-related quality of life overall. However, when analyzing mothers and fathers separately, increasing parental empowerment was associated with a higher food allergy-related quality of life in mothers, but not fathers. Conclusion: Mothers and fathers of children with food allergy have significant differences in their level of empowerment and quality of life. Increased empowerment leads to increased quality of life among mothers.

P274 THE EPIDEMIOLOGY OF PEANUT ALLERGY IN US CHILDREN. A. Dyer1, R. Gupta*1, B. Schmeltzer1, D. Perumal2, B. Smith1, 1. Chicago, IL; 2. Wellesley, MA. Rationale: Peanut allergy is one of the most common and severe food allergies among children in the US. Better understanding racial differences and trends in diagnosis can help us understand the etiology of food allergy. The objective of this study is to determine the distribution of peanut allergy as well as reaction history and diagnosis trends among US children. Methods: Data was collected through a randomized, cross-sectional survey administered to parents belonging to a representative sample of US households with children between June 2009 and February 2010. 38,480 parents were surveyed regarding demographic characteristics, allergic symptoms associated with food ingestion, and methods used to diagnose food allergy were collected and analyzed as weighted proportions. Adjusted models were estimated to examine association of these aspects with the odds of peanut allergy. Results: 754 of the 3,218 food allergic children in the sample of US households were reported as having peanut allergy (23.4%). Though evenly distributed by gender, peanut allergies were most commonly reported in children aged 6 to 10 years (25.5%). There were no significant differences in peanut allergy prevalence among by race, gender, age or household income. However, children living in homes with an annual household income of less than $50,000 were significantly less likely (OR=0.6) to receive a formal physician diagnosis than children living in homes with a >$50,000 annual income. 53.7% of all cases of peanut allergy reported severe allergic reactions, a significantly higher instance in comparison to food allergy in general (p<0.001). The three most common symptoms reported were hives (63.1%); swelling of lips, eyes or face (53.6%); and trouble breathing (35.2%). Conclusion: Childhood peanut allergy impacts almost 1 in 4 children with food allergy. Peanut allergy is also the most common childhood food allergy and is evenly distributed by gender, race, and socioeconomic status. Given that over half of these children experience severe allergic reactions upon exposure, it is critical to improve awareness of prevention and management strategies in households, schools and communities.

P275 ALLERGY TO FISH ROE: A CASE REPORT. D. Baum*1, R. Herzog2, 1. Brooklyn, NY; 2. New York, NY. Introduction: Fish allergy is one of the most common IgE mediated food sensitivities in the US. Roe is commonly consumed from many popular fish including cod, herring and salmon (Salmo salar). Currently, several cases in Japan have been reported whereby an IgE mediated fish roe allergy occurred with no presence of a fish allergy. The IgE cross-reactivity was limited to fish roe, with other animal eggs such as chicken eggs, testing negative in patients experiencing anaphylaxis after consumption of salmon roe. We present a young patient with allergic reaction after eating salmon. This case demonstrates the importance of consideration of roe allergy in the differential diagnosis of reaction to fish. Case: A 15 month old female developed generalized urticarial skin eruption after the consumption of salmon. The patient had reportedly been eating a variety of fish including tuna, cod, and salmon prior to this reaction. The patient underwent skin prick testing and immunoCAP which were found to be negative for salmon (<0.35 kU/L). Due to the significance of the clinical reaction, immunoCAP was performed for salmon roe, with results revealing 6.5 kU/L (negative<0.35). The patient was then successfully passed food challenge with fish including salmon and had no further reaction to food while eliminating fish roe. Conclusion: Fish roe may cause IgE-mediated sensitization without concomitant fish allergy and may be associated with a clinical allergic reaction and anaphylaxis. Hence, when evaluating for allergic reactions to fish, roe allergy should be considered in the differential diagnosis.

P276 A CASE OF AN ALLERGIC REACTION TO JAMAICAN JACK FRUIT (ARTOCARPUS INTEGRIFOLIA) IN A CANADIAN PATIENT WITH POLLEN-FOOD ALLERGY SYNDROME (ORAL ALLERGY SYNDROME). T.J. Pitt*, Toronto, ON, Canada. Introduction: Jamaican Jack Fruit or Artocarpus Integrifolia is the largest tree born fruit in the world weighing as much as 80 lbs. It is found in Caribbean countries such as Jamaica as well areas such as Africa, Asia, India and South America. Jack fruit is a member of the Moraceae family containing proteins homologous to Bet v 1 and may represent a clinically relevant birch pollenassociated food. A few cases of allergy to Jack fruit in patients with PollenFood Allergy Syndrome have been reported outside of North America. This is a case of a 39 year old Canadian patient with a history of Pollen-Food Allergy Syndrome who reported a recent allergic reaction to Jack fruit, a fruit which was intermittently tolerated in the past. Methods: Epicutaneous skin testing was performed to birch tree extract, fresh apple and fresh Jackfruit. A positive test was defined as 3 mm greater than the negative saline control. Results: S: Skin testing to birch tree extract, fresh apple and fresh jack fruit was positive to birch tree extract, fresh apple and fresh jack fruit. The patient has been instructed to avoid Jack fruit,consume apple only in the cooked form and was provided a chart with other foods in the birch pollen family. Conclusions: Allergic reactions to Jack fruit have been noted in patients with Pollen- Food Allergy Syndrome predominantly in Asia and Europe. This is one of the first case reports of a Pollen-Food Allergy Syndrome patient from North America having a reaction to Jack fruit. North Americans often travel to the Caribbean, particularly in the winter months and may be exposed to this fruit. Pollen-Food Allergy Syndrome patients should be warned about possible reactions to Jack fruit. Further research is needed to determine whether true isolated Jack fruit allergy (in patients without the Pollen-Food Allergy Syndrome) exists, particularly where this fruit is endemic.

P277 ORANGE SEED ALLERGY. V. Ta*, A. White, San Diego, CA. Introduction: Citrus fruits are widely consumed, but there are not many well-documented cases of allergic reactions to their seeds. Fruit allergy testing by serum specific immunoglobulin IgE and skin prick test (SPT) identifies the allergen in most cases; however, these tests use extract from the fruit and fail to identify reactions to the seed, which may be more severe. This case, which is the first reported case of orange seed allergy in a patient with pistachio anaphylaxis, highlights the need to consider fruit seeds as a potential cause of severe allergic reactions. Case Report: The patient is a three-year-old girl with a history of atopic dermatitis and anaphylaxis to pistachio and sensitization to peanut and tree nuts who developed lip angioedema when she ingested an orange seed. The patient had eaten oranges on several occasions without any issues but had never swallowed orange seeds before. Skin prick testing against a panel of suspected food allergens revealed positivity to orange seed and tree nuts, (table). Discussion: Fruit seed allergy is uncommon, likely because ingestion is usually not intentional. A limited number of case reports identified children who were able to tolerate fruit pulp but developed anaphylaxis to fruit seeds. Coexisting peanut and tree nut sensitization was also observed in these children. Consistent with this case, the evidence suggests a possible association between allergy to fruit seeds and nuts. The risk associated with eating fruit pulp that is clearly “cross contaminated” with the seed is unknown. This patient only clinically reacted to ingestion of the seed itself. It is also unclear whether peanut or nut allergen leads to cross reactivity with fruit seeds. In this case, the patient was clinically allergic to pistachio. In light of other reported cases, it is possible that nut allergy led to co-sensitization to orange seed. This case highlights the need to consider fruit seeds as a potential cause of severe allergic reactions to fruit. Because testing for fruit allergy uses extracts from the fruit pulp rather than the seed, clinicians might be falsely reassured about the safety of fruits in a patient allergic to fruit seeds. In summary, in rare cases fruit seeds appear to cross-react with peanuts and tree nuts; therefore, we recommend considering fruit seed allergy as a cause of apparent idiopathic anaphylaxis in patients with nut allergies.



ABSTRACTS: POSTER SESSIONS 44). This study demonstrates the remarkable safety of the UAS immunotherapy protocol. We conclude that the utilization of the UAS SCIT protocol is safe in the pediatric population in both the office and self-administered home setting.

Skin Prick Test


SPT to orange seed extract was tested on 6 healthy controls and was negative.

P278 A CASE OF DELAYED PRESENTATION OF VITAMIN D DEFICIENT RICKETS IN THE SETTING OF MILK ALLERGY. K. Welch*, J. Wang, New York, NY. Introduction: Calcipenic rickets has varied manifestations in the pediatric population, including delayed closure of the fontanelles, frontal bossing, and lateral bowing of the femur and tibia. While rickets is widely prevalent in many parts of the developing world, it is relatively rare in the U.S. due to the fortification of infant formula and cow’s milk with vitamin D or vitamin D supplementation with breastfeeding. Case presentation: A 5 year-old African-American girl was evaluated by orthopedics for bowing of her legs. The child had been breastfed until 3 months of age, when her mother transitioned her to a milk-based formula. She then developed urticaria and was changed to juice and water only, with no vitamin D supplementation starting at the age of 4 months. The child had no other past medical history and had her first tooth eruption at 4 months and walked at the appropriate age, with no limits on her mobility. Her physical exam on presentation at age 5 years was notable for bilateral genu varum. Results: Lab work revealed vitamin D deficiency (vitamin D 25-OH 13ng/mL), with a low-normal calcium level of 8.6mg/dL, and radiographic films of the lower extremities were consistent with demineralization of the osseous structures and widening of the growth plate. Further allergic work-up revealed a milk IgE level of >100kIU/L. The mother does not recall being instructed on vitamin D supplementation in the absence of milk intake. On evaluation at the age of 5 years, she was started on vitamin D 6,000 units daily, with vitamin D level improved to 40ng/mL 2 months later. Corrective orthopedic surgery is planned once her vitamin D stores are fully replete. Conclusions: The presentation of this patient’s bony deformities relatively late in development and in the setting of other normal developmental milestones is a very unusual example of rickets. It is possible that she had adequate maternal stores or dietary intake from non-dairy sources that prevented a flagrant presentation at a younger age. In summary, this case represents a striking example of how allergic disease may lead to dietary restrictions that severely impact the metabolic development of the pediatric patient and that close work with dieticians is a crucial part of food allergy care.

P280 THE SAFETY OF THE UNITED ALLERGY SERVICES IMMUNOTHERAPY PROTOCOL FOR PEDIATRIC PATIENTS. F.M. Schaffer*1, A. Naples2, M. Ebeling1, T. Hulsey1, L. Garner2, 1. Charleston, SC; 2. San Antonio, TX. Introduction: Subcutaneous immunotherapy (SCIT) induced systemic reactions (SR) are reported to range from 3 to 34% among pediatric patients (Pediatrics 2013:131, 1155). We conducted one of the largest pediatric SCIT studies to contrast the safety of the United Allergy Services (UAS) SCIT protocol, characterized by a slower build-up phase, to previous reports. Methods: Basic survey techniques were used for assessment. RESULTS: We report our findings from 4,894 pediatric patients (< 18 y/o) who underwent 432,918 injections. The SR rates were: (WAO) Anaphylaxis Grade I- 7, Grade II- 7, and no Grade III to V reactions or deaths occurred in approximately 433,000 injections. Discussion: Thus, the UAS SR rate is only 0.29% (per patient) & 0.003% (per injection) for all patients while patients on home immunotherapy demonstrated SR rates of only 0.19% (per patient) & 0.002% (per injection). These results are significantly below (p < 0.0001) previous reports (of up to 4.6% per injection; Pediatrics 2013:131, 1155 & Pediatr Allergy Immunol 1995:6,


Introduction: Physicians frequently try to limit the number of injections/visit due to concern for patient discomfort. There are no data to support the practice of minimizing the number of immunotherapy (IT) injections/visit for patient comfort or compliance. Methods: De-identified surveys about IT history and injection number preference were given to all IT patients to complete voluntarily. The parents of patients < 18 years old were asked to complete the survey for their child. IRB approval and participants’ consents were obtained. Results: There were 344 of 363 (94.8%) IT patients (4-80 years) who completed surveys. There were 81.7% (276/338) on aeroallergen IT, 15.1% (51/338) on venom IT, 3.2% on both (11/338), and 6/344 did not answer. Patients were receiving 1 (39.6%, 135/341), 2 (41.9%, 143/341), 3 (16.7%, 57/341), or > 3 (1.8%, 6/341) injections at each visit and 3/344 did not answer. Before starting IT, 88.7% (305/344) of allergists informed their patients of the number of injections they would be receiving. For the patients that were receiving 1 injection, 94.7% (234/247) reported that they would either not decline IT or that it did not matter to them if they had to get 2 or 3 injections. If they were receiving 2 injections, 93.8% (226/241) would either not decline IT or it did not matter if they had to get 3 injections. Of those receiving 2 or 3 injections, 6.8% (16/234) would not prefer to receive fewer injections, 60.3% (141/234) felt that it did not matter, and 32.9% (77/234) of patients would prefer at most receiving 1 or 2 injections. When asked what the maximum number of injections they would be willing to receive (1, 2, 3, 4, 5, or > 5), 174 patients responded. Of these, 8.6% (15/174), 19.0% (33/174), 23.0% (40/174), 25.9% (45/174), 8.0% (14/174) and 15.5% (27/174) responded with a maximum number of 1, 2, 3, 4, 5, or > 5 shots, respectively. The majority of the patients, 72.4% (126/174), were willing to receive ≥ 3 injections. Conclusion: This is the first survey investigating patient preference regarding number of injections for IT. The data indicates that the majority of patients are willing to receive ≥ 3 injections at a visit. Rather than potentially excluding clinically important allergens, allergists should include their patients in the decision regarding the number of IT injections/visit.

P282 COMPARING SYSTEMIC REACTION RATES AND TIME TO MAINTENANCE FOR INHALANT AEROALLERGENS IN CLUSTER VERSUS STANDARD IMMUNOTHERAPY IN AN ACADEMIC AFFILIATED HOSPITAL: A PRELIMINARY ANALYSIS. R. Minocha*1, P.F. Detjen2, D. Masood1, R.E. Story1, E. Schafer1, 1. Evanston, IL; 2. Kenilworth, IL. Introduction: Subcutaneous immunotherapy (SCIT) has a proven safety and efficacy profile for the treatment of allergic rhinitis. However, the time commitment and compliance required by the patient can deter initiating therapy. The purpose of this study is to compare the rate of systemic reactions (SR) and time to maintenance (TTM) for inhalant aeroallergens in patients receiving Cluster or Standard SCIT. We hypothesize that Cluster SCIT will be associated with a shorter TTM and have a tolerable safety profile, thus increasing adherence with therapy. Methods: A retrospective analysis in an academic affiliated hospital was performed for patients receiving SCIT from 2009 to 2012. IRB approval was obtained prior to starting the review. Any patient offered SCIT was given the option to undergo either a Cluster or Standard protocol. Potential confounders including the presence of asthma, age, sex, prior to admission antihistamines (PTAA), and adherence were recorded. SR was defined by the WAO grading system. Results: In this preliminary analysis, 115 patient charts were reviewed. Three patients were excluded secondary to noncompliance. Out of the remaining 112 patients, 84 received Standard SCIT and 28 received Cluster SCIT. There were no significant differences between the two groups with respect to asthma, age, sex and PTAA. The mean TTM was 35.6 weeks for Standard SCIT and 18.44 weeks for Cluster SCIT (p <0.0001). The rate of SR was 12.2% for Standard SCIT versus 35.7% for Cluster SCIT (p < 0.005). In a multivariate regression analysis controlling for asthma, age, and sex, Cluster SCIT was associated with a sig-


ABSTRACTS: POSTER SESSIONS nificantly shorter TTM (p <0.0001) but a significantly higher rate of SR (p <0.05). Ten of the original 28 Cluster patients dropped out of the Cluster group and switched to Standard SCIT secondary to personal preference. Only 1 of these patients withdrew secondary to SR grade higher than 2. Conclusions: Cluster SCIT is associated with a significantly shorter TTM but increased rate of SR. We experienced a higher rate of SR with Cluster SCIT than reported in the literature, however the rate of adherence to this protocol demonstrates a tolerable safety profile to the patient. This supports Cluster SCIT in patients wanting a shorter TTM.

P283 STABILITY OF ALLERGENIC EXTRACTS OF DERMATOPHAGOIDES PTERONYSSINUS USED IN IMMUNOTHERAPY IN ALLERGY SERVICES OF MEXICO CITY HOSPITALS. D. Sanchez*1, G.A. Guidos Fogelbach2, C. Sandino2, 1. Naucalpan de Juarez, DF, Mexico; 2. Mexico City, DF, Mexico. Allergic diseases affect 10 to 42% of Mexico’s population, rising among the 10 principal morbidity causes. Immunotherapy with specific allergens is the only treatment proven to be effective for this condition. Such effectiveness relies on the stability of the allergenic proteins and their concentration. Dermatophagoides species are amidst the first causes of prick test positivity, with a 52% prevalence rate. The objective of this study is to evaluate protein stability of Dermatophagoides pteronyssinus allergenic extracts used in immunotherapy, in the nine major allergic disease treating public hospitals of Mexico City. The samples were analyzed in different conditions of time, temperature, and dilution (1:100 W/V and 1:1000 W/V). As control samples ALK ABELLO USA and IPI ASAC Mexico standardized allergens were obtain directly from the companies. A real time stability study with a length of 7 days was designed, with samples recollection at 0 and 7 days. Absorbance peaks and morphology of the patterns obtained using Reverse Phase High Pressure Liquid Cromatography were analyzed. Descriptive and tendency analysis were performed. Protein absorbance peaks were obtained in all samples, with important variations in pattern morphology and peak height for both dilutions kept in optimal conditions, compared to the reference extracts. Statistically significant protein degradation, abrupt changes in the protein pattern, and absence of some of the major peaks were found in many samples analyzed after being held by seven days under a 28.5 C temperature, compared with the control allergens. Changes in the protein pattern suggests protein degradation and/or the presence of other protein compounds secondary to: Allergen quality, storage temperature, extract contamination with other protein compounds, preservatives, stabilizers, dilution making process, proteases presence, lyophilization, stabilizers (human seric albumin, glycerol, phenol), diluents and vial material (allergen absorption activity loss).

P284 ASSESSMENT OF EFFICACY OF ALLERGEN SPECIFIC SUBLINGUAL IMMUNOTHERAPY IN PATIENTS WITH RESPIRATORY ALLERGIC DISEASE. L. Maslova*1, L. Titov1, L.M. DuBuske2, 1. Minsk, Belarus; 2. Gardner, MA. Background: Subcutaneous allergen specific immunotherapy can be inconvenient and carries the risk of frequent local and rare but very serious anaphylactic reactions. The development of sublingual immunotherapy offers the potential for a safer and more convenient alternative. Methods: 60 patients with grass pollen and house dust mite allergic rhinoconjunctivitis with or without asthma received allergen specific immunotherapy with standardized allergen extracts (Sevapharma, Czechrepublic) administered sublingually for two years. The diagnosis of respiratory allergy was made by clinical history, positive skin prick tests to standardized grass pollen and dust mites extracts and the presence of specific IgE to grass pollens and dust mites of at least Class 3. Sublingual immunotherapy (SLIT) involved an up-dosing phase and maintenance phase with a maximum dose (10000 JSK, PNU; 10 drops 3 times in the week) achieved. Efficiency was assessed using symptom relief score analysis(very good/good/moderate/poor/no effect). Specific IgE by immunoblot (R-Biopharm, Germany) and IgG4 by ELISA (Dr. Fooke, Germany) were assessed at baseline and after 2 years of treatment. Results: SLIT was effective reducing overall symptom scores and rescue drug intake, with a highly significant reduction of more than 80% achieved. After 2 years of SLIT allergen specific serum IgE to both grass pollens and dust mites level were significantly decreased. Levels of specific IgG4 to grass pollens and dust mites increased (p 0.001). Adults with rhinitis without asthma had lower specific IgE and IgG4 than adults with both rhinitis and asthma (P= 0.05). Laboratory results corresponded to clinical improvement. Adverse effects were limited to a small number of patients having mild local oral reactions. Conclusion: SLIT for adults with allergic rhinoconjunctivitis and asthma is a highly effective treatment for carefully selected patients with respiratory allergy. It has shown significant efficacy over 2 years of continuous treatment and demonstrates immune modulation of allergen specific IgG and IgE responses. SLIT is safe and effective, offering added convenience of therapy.

P285 POSITIVE SKIN PRICK TEST (SPT) CONTROL: EFFECT OF HISTAMINE (H) STRENGTH, DEVICE AND METHOD FOR MEASURING WHEAL SIZE. G. Plunkett*, J. Young, T. Moore, Round Rock, TX. Introduction: A histamine control is used in skin testing to determine if the patient is able to have a valid wheal/erythema response to allergens. Several factors can influence the conclusion for a valid SPT; the histamine concentration, the device used, the size cutoff for a positive, and SPT suppressive drugs like antihistamines and antidepressants. We have found that the measuring technique is important. A new skin test device with a purported pain control design has also been introduced. The purpose of this study was to evaluate some of these factors measuring wheals with a standard SPT ruler or outlining with ink. Methods: SPT was performed on subjects with informed consent using a glycerin-saline negative control, 6mg/mL and 1mg/mL H base with 2 devices from Lincoln Diagnostics and 1 device from Jubilant Hollister-Stier Laboratories (JHS). Some of the subjects were tested before and after a single dose of cetirizine. Wheals were measured using a ruler or following tracing with an ink pen and transferring to a recording sheet using tape. The average width was measured from the inside of the circle. A 5mm or greater wheal cutoff was recorded as positive for the Lincoln Diagnostics devices and a 3mm wheal size was used for the JHS devices. Results: Wheals sizes were about a 1 – 3mm greater for the 6mg/mL H. The 1 mg/mL H was below the cutoff for each device more often than the 6 mg/mL in the suppressed subjects regardless of the devices. The 2 Lincoln devices had similar wheal sizes and were about 2mm greater than the JHS devices justifying the 5mm and 3mm cutoffs. There was a surprising 33% increase in wheal size by measuring directly on the skin with a ruler which reduced the number of false negatives compared to the transfer method. Conclusions: Decisions on whether the positive control is identifying a valid test must take into account the device used as well as the method of measurement. The larger wheal using a ruler may explain the variation of wheal sizes reported in the literature. To minimize false negatives it may be necessary to lower the size cutoff for positive results. The 1 mg/mL histamine is appropriate for identifying suppressed patients in the Lincoln devices. A pos-



ABSTRACTS: POSTER SESSIONS itive SPT may occur with 6 mg/mL histamine resulting in a false negative allergen response. 6 mg/mL is suitable for the JHS device.

P286 RUSH IMMUNOTHERAPY FOR HARMONIA AXYRIDIS (LADYBUG) ALLERGY. A. Ravi*, D. Maddox, Rochester, MN. Rationale: Although rare, ladybug allergy does occur and can be treated with rush immunotherapy. In review of the literature, this is the first report of rush immunotherapy for ladybug. Case Presentation: A 24 year old female with history of rhinitis was evaluated for onset of significant pruritic bilateral periorbital edema during a camping trip. Component microarray IgE testing was negative to all the standard allergens. Later, she recognized that with exposure to ladybugs, she had episodes of acute urticaria, angioedema, and sense of shortness of breath. Skin testing to ladybug was performed at 1:10,000, 1:1,000, 1:100, and 1:10 and found positive at all these concentrations. Our patient underwent preparation for rush allergen immunotherapy with omalizumab (Xolair) conditioning: 3 doses given once monthly. Subsequently, prior to the rush immunotherapy day, she received dexamethasone, fexofenadine, montelukast, theophylline, indomethacin, and ranitidine. Morning of the procedure, she received dexamethasone, fexofenadine, ranitidine, zileuton, indomethacin, and theophylline. With ladybug rush allergen immunotherapy, she received 8 increasing doses of allergen until achieving concentrate dose. Then she received 4 increasing volumes of the allergen concentrate maintenance dosing to reach 0.5mL. Along with the last injection of the rush immunotherapy, she received PO dexamethasone. Results: On rush immunotherapy day, she reached her maintenance dose levels without severe reactions. She had no reactions until she got up to the 1:10 dilution of extract. She then had some local erythema at the injection sites and with one injection she had a 10mm wheal. That evening, she sought ER evaluation for mild flushing and generalized pruritus without any other systemic symptoms. Then she was able to receive once monthly maintenance injections, starting with 0.1mL concentrate and gradually increasing to 0.5mL injection in the 5th month. Discussion: The major allergens in ladybugs are Har a 1 and Har a 2, which are contained in the externalized hemolymph and “reflex bleeding” from their tibiofemoral joints. Ladybug allergic individuals may display a single or combination of symptoms: allergic rhinoconjunctivitis, asthma, pruritus, urticaria, angioedema, and anaphylaxis. For ladybug allergic patients with likely future exposure, ladybug rush immunotherapy may be considered.

P287 DEVELOPMENT OF A NOVEL MODIFIED RAGWEED IMMUNE-ADJUVANTED VACCINE FOR ULTRA SHORT ALLERGEN IMMUNOTHERAPY. L.M. DuBuske*1, T. Holdich2, P. Patel3, W. Howland4, K. Fischer von Weikersthal-Drachenberg5, H. Kaiser6, 1. Gardner, MA; 2. West Sussex, United Kingdom; 3. Missassauga, ON, Canada; 4. Austin, TX; 5. Munich, Germany; 6. Minneapolis, MN. Background: Conventional subcutaneous allergen immunotherapy needs many injections over several years and can cause anaphylaxis. Modification of allergens (MA) decreases allergenicity; tyrosine absorption (TA) increases Th1 versus Th2 immune responses; and monophosphoryl lipid A (MPL) augments speed and intensity of allergen-specific Th1 response induction. Methods: A MATA ragweed vaccine was created including 50mcg/injection MPL, 2% tyrosine, and glutaraldehyde polymerization of epsilon-amino lysine residues of ragweed pollen extract, given as 4 consecutive doses once a week. The vaccine was assessed in a dose response study to optimize the MA dosage. A doubleblind placebo-controlled field study of 993 ragweed allergic subjects was conducted to assess the vaccine’s impact on combined symptom medication scores (CSMS), quality of life (RQLQ) and allergen specific IgG immune responses in natural setting. A double-blind placebo-controlled environment exposure chamber (EEC) study using 4 daily 3 hour ragweed pollen exposures before and after treatment of 228 ragweed allergic subjects allowed assessment of symptom score (SS) reduction, and RQLQ-EEC impact Results: Dose-ranging assessment of ragweed- specific IgG responses established the doses of 300/ 700/ 2000/ 6000 SU consecutively of MA as the optimal dose schedule. The field study demonstrated a 13.5% reduction in CSMS over the entire pollen season in the 381 subject cohort receiving the complete dosage, with a midseason improvement of 0.5 in 7/8 RQLQ domains, and a 11-fold increase in ragweed-specific IgG. The EEC study demonstrated a 42% mean SS reduction from baseline, a 48% mean reduction in SS versus placebo, 82% median


reduction of SS versus placebo, significant improvement in Overall and Global Assessment in RQLQ-EEC and a 6-fold increase in ragweed- specific IgG and 41 fold increased specific IgG4. No study subject experienced anaphylaxis. Conclusion: This novel modified allergen, tyrosine depot, MPL- adjuvanted ragweed vaccine has demonstrated freedom from anaphylaxis with rapid clinical and immunologic efficacy using a 4 injection ultra-short regimen. Environmental exposure chamber assessment provided optimal demonstration of the vaccine’s efficacy versus placebo avoiding the vagaries of unpredictable pollen exposure which can impact field studies of allergen vaccine efficacy.

P288 EXTREME SENSITIVITY TO INSECT VENOM IN A PATIENT WITH NEGATIVE IN VITRO TESTING. C. Adkins*1, J. Tripple2, J. Bonner2, A. CaJacob2, 1. Hoover, AL; 2. Birmingham, AL. Introduction: Stinging insect hypersensitivity is estimated to cause severe allergic reactions in about 3% of adults. Diagnosis is made by history and supported by skin or in vitro testing. Venom immunotherapy (VIT) is indicated for high risk patients. Although difficult, VIT was executed in a patient with systemic reactions to skin testing despite a negative RAST. Methods: A 44 year old female with history of severe reactions to stinging insects was evaluated after a wasp sting resulted in anaphylaxis and hospitalization. She had past history of 10 stings (wasp and yellow jacket) with symptoms of face and lip tingling, sensation of throat swelling, dyspnea, chest tightness, generalized itching, and syncope within 5 minutes of the stings. Results: Skin prick testing (SPT) was negative to yellow jacket and honeybee, but positive to wasp (welt > 50 mm at test site with flushing and stridorous respirations). RAST for all three insect venoms were negative, tryptase was < 2.0 mg/L, and IgE was 2 IU/mL. SPT and intradermal testing (ID) at 0.01 mg/mL to honeybee and yellow jacket were negative. ID at 0.1 mg/mL resulted in anaphylaxis. VIT to wasp was started at 0.05 mL of 0.01 mg solution, but the patient developed systemic symptoms. VIT was tolerated at 0.001 mg/mL dilution, but at 0.3 mL symptoms recurred. A trial of omalizumab for 6 months failed to prevent systemic symptoms with VIT and ID remained positive to all venoms. Placebo IT was given to exclude any psychogenic element of her symptoms. She had no reaction. At the proposal of Dr. Robert Reisman, VIT for yellow jacket at a starting dose of 0.1 mL at 0.0000001 mg/mL was given (Figure 1). After 18 months, maintenance dose was achieved without severe reactions. Discussion: This case demonstrates that VIT can be given to highly sensitive patients using a very conservative protocol. The discrepancy between skin and RAST testing in this patient is unexplained. SPT is more sensitive than RAST; however in our patient a totally negative in vitro test is unexpected. Possible reasons are failure of the in vitro test to include the culprit antigen, or mast cell activation by venom content via a non-immunologic mechanism. In summary, VIT is effective in preventing anaphylaxis and should not be withheld in highly sensitive patients at high risk of severe reactions.

Figure 1. Initial VIT Schedule. The patient started on VIT with yellow jacket only. Maintenance dosing of 100 mg/mL was achieved over the course of 18 months increasing the dose by 0.05 mL weekly.



P289 QUALITY OF LIFE IN PATIENTS WITH HEREDITARY ANGIOEDEMA RECEIVING NANOFILTERED C1 INHIBITOR FOR PROPHYLAXIS: RESULTS OF A RANDOMIZED, PLACEBOCONTROLLED, CROSS-OVER STUDY. W.R. Lumry*1, D.P. Miller2, K. Beusterien3, E. Hautamaki3, D. Fitts4, J. Dayno4, 1. Dallas, TX; 2. San Francisco, CA; 3. Bethesda, MD; 4. Exton, PA. Background: We evaluated the health-related quality of life (HRQoL) of patients with hereditary angioedema (HAE) while they were receiving nanofiltered C1 inhibitor (C1 INH-nf) either as prophylactic therapy or for the acute treatment of individual attacks in a clinical trial setting. Methods: Patients ≥6 years old with a confirmed diagnosis of HAE and a history of ≥2 attacks per month and who provided informed consent/assent were eligible for this randomized, placebo-controlled, cross-over, IRB-approved study in the US. Patients received intravenous injections of 1000 U C1 INH-nf or placebo every 3 to 4 days for 12 weeks and then crossed over to the other treatment arm for a second 12-week period. Patients could receive open-label C1 INH-nf (1000 U) for the acute treatment of attacks in either arm of the study. Patients completed the SF-36 V 1.0 questionnaire before the first treatment period and at the end of both periods. A mixed-model ANOVA with a period effect, a treatment effect, and adjustment for the baseline score was used to evaluate the differences in SF-36 scores while patients received C1 INH-nf or placebo. Norm-based SF-36 scores were computed for comparison with the score for the general population (mean 50, SD 10). Results: Of the 22 patients evaluated for efficacy, 16 completed SF-36 questionnaires for both treatment periods. Eighty-eight percent of patients were female; the mean age was 41.7 years. At baseline, the mean physical and mental component summary scores were 36.4 and 49.9 respectively. Statistically significant differences in least-square mean SF-36 scores between C1 INH-nf and placebo were observed at followup in the physical function, role physical, bodily pain, social function, mental health, vitality, and general health domains and in both the physical and mental component summary scores despite the availability of open-label C1 INH-nf for the acute treatment of individual attacks (see table). Social function, bodily pain, and role physical had the greatest magnitude difference. Conclusion: In a clinical trial setting, C1 INH-nf therapy for routine prophylaxis of HAE was associated with more favorable HRQoL outcomes relative to C1 INH-nf dosed for the acute treatment of individual angioedema attacks in the absence of routine prevention. Least-square mean differences (C1 INH-nf minus placebo) in norm-based SF-36 scores at follow-up

P290 CLINICAL USAGE OF A C1 ESTERASE INHIBITOR CONCENTRATE (BERINERT) FOR HEREDITARY ANGIOEDEMA: INTERIM ANALYSIS FROM AN ONGOING INTERNATIONAL REGISTRY. M. Rojavin*1, A. Bygum2, P. Busse3, W. Lumry4, I. Martinez5, T. Machnig6, J. Edelman1, 1. King of Prussia, PA; 2. Odense, Denmark; 3. New York, NY; 4. Dallas, TX; 5. Frankfurt-Morfelden, Germany; 6. Marburg, Germany. Background: Hereditary angioedema (HAE) is a rare disease caused by a qualitative or quantitative deficiency of C1 esterase inhibitor (C1-INH). The C1-INH concentrate Berinert is used for prophylactic and acute therapy of HAE. Methods: A registry was initiated in April 2010 at 32 US and 5 EU sites for retrospective and prospective surveillance of the clinical safety of Berinert (CSL Behring GmbH, Marburg), licensed for the treatment of acute HAE attacks and, in Europe, for short-term prophylaxis. Reasons for administration of Berinert (acute or prophylactic therapy), dose administered, body location and inten-

sity of attacks, home or office administration of Berinert (and reasons for change), and adverse events (AEs) were recorded in the registry by the investigators. IRB/IEC approval and informed consent (or IRB/IEC approved waiver for some retrospective cases where consenting was not feasible) was obtained from all patients. Results: As of April 2013, the 130 patients captured in the registry were treated with 3,189 infusions: for acute HAE attacks (119 patients, 1,608 infusions) and/or for prophylaxis (42 patients, 1,581 infusions). The majority of HAE attacks (72.4%) were mild or moderate. Median doses for acute attacks and prophylaxis were 17.9 IU/kg and 16.6 IU/kg, respectively, with more than half of the infusions (53.4%) administered at doses close to 20 IU/kg. Almost 40.9% of the infusions were done at dose levels of <15 IU/kg. In 5.7% of the infusions for acute attacks, Berinert doses ≥25 IU/kg were used. 86.5% of all infusions were administered by the patients or their caregivers at home. The most frequent attacks were abdominal (63.8%) and peripheral (43.1%) attacks. Facial (3.8%) and laryngeal (3.1%) attacks were rare, but were experienced at least once by a significant share of HAE patients (27.3% and 22.3%, respectively). The overall safety was favorable: 7 of 299 AEs (including 2 cases of thromboembolism) were at least possibly related to administration of C1-INH concentrate. Conclusions: This interim analysis indicates that self-administration of Berinert is a suitable option, and that individualized dosing is commonly used for acute therapy. Overall, results from the ongoing registry support the safety of Berinert as a first-line on-demand and prophylactic treatment option for HAE.

P291 CLINICAL DECISION-MAKING AND TREATMENT APPROACHES FOR HEREDITARY ANGIOEDEMA: RESULTS OF A NATIONAL SURVEY. J. Chiao*, J. Hirsh, L.M. Landmesser, J. Dayno, Exton, PA. Background: Treatment approaches for the management of hereditary angioedema (HAE) include acute treatment of angioedema attacks and prophylactic treatment. Methods: Between October 2011 and January 2012, we conducted a survey of physicians who were identified as prescribers of attenuated androgens for HAE. In a discussion format, willing participants were asked about the criteria they use to make treatment decisions for patients with HAE. Results: Of the 52 physicians originally identified, 31 agreed to participate and completed interviews. These physicians reported that they treated a combined total of 415 HAE patients. Most participants (n=30) specialized in allergy, but some reported that pediatrics, internal medicine, general practice, and rheumatology were areas of specialty. Eleven physicians were managing 10 or more patients, accounting for 80% of the total number of patients. Of these 11, 6 reported an academic affiliation. Physicians reported that they were treating 47% of patients with prophylaxis either alone or in combination with acute treatment. The 4 most important factors that physicians considered in starting either acute or prophylactic treatment were attack frequency, attack severity, attack type/location, and impact on quality of life. Among physicians who managed fewer than 10 patients, attack frequency was the most commonly reported factor in their decision to choose prophylaxis. Among physicians who managed 10 or more patients, attack severity was the most commonly reported factor in their decision to choose prophylaxis. Physicians with fewer than 10 patients were most likely to report that decreasing the frequency of attacks was the single most important factor influencing their choice of a prophylactic therapy; whereas, physicians with 10 or more HAE patients were equally likely to choose decreasing the frequency or severity of attacks. Conclusion: Based on the pattern of responses to this survey, physicians with less experience treating HAE rely on attack frequency as a single parameter in considering prophylactic treatment. Physicians with more experience consider multiple factors that comprise overall disease burden, such as attack frequency, severity, and impact on quality of life.

P292 C1 INHIBITOR PROPHYLAXIS FOR IDIOPATHIC NONHISTAMINERGIC ANGIOEDEMA. S. Matto*1, M. Stahl2, 1. Beavercreek, OH; 2. Dayton, OH. Introduction: Angioedema, can be broadly divided into two types, histamine-mediated and bradykinin-mediated. Treatment of histamine-mediated forms is well established; however, therapeutic options for bradykinin-mediated forms have only recently emerged. Nanofiltered plasma derived C1 inhibitor (C1INHnf, Cinryze) is FDA-approved for long-term prophylaxis of hereditary angioedema (HAE). However, the use of C1INHnf in other forms of non-histaminergic angioedema has not been well studied. Case Report: A



ABSTRACTS: POSTER SESSIONS 32 year-old female presented to the ED with progressive facial, tongue and lip swelling. History was negative for urticaria, pruritus, new medications, medication allergies, changes in diet/exposures, or family history of similar episodes. She was admitted to the ICU requiring intubation. Symptoms were unresponsive to steroids, H1/H2 blockers, epinephrine and fresh frozen plasma. Levels of C4, C1INH and C1INH function were normal. Swelling gradually improved over four days, but underlying etiology remained unknown. Repeat labs were unremarkable and genetic testing negative. Over the next 15 months, she had 22 ED visits, 12 inpatient admissions and 2 additional intubations. Prophylaxis with danazol, tranexamic acid, progestin, sulfasalazine and hydroxychloroquine were unsuccessful. Prophylaxis with C1INHnf resulted in no further inpatient admissions (one ER visit) and a decrease in acute therapy from 5-7/month to 1.5/month. Discussion: HAE is a disease characterized by recurrent episodes of swelling, without urticaria or pruritus, most commonly affecting the face, abdomen and extremities. HAE Types I/II are due to a defect in the C1INH protein. HAE Type III is characterized by normal C1INH quantity and function, with increased predilection for the face and larynx, and frequent association with increased estrogen. Spontaneous genetic mutations have not been described in HAE Type III. Therefore, without a family history, this patient would be more accurately described as idiopathic nonhistaminergic angioedema. Patients with this condition are non-responsive to steroids and anti-histamines. Historically, therapeutic options for prophylaxis involved attenuated androgens or tranexamic acid. To our knowledge, this is the first reported case of C1INHnf use for prophylaxis in idiopathic nonhistaminergic angioedema.

P293 BARRIERS TO SELF-ADMINISTRATION IN HEREDITARY ANGIOEDEMA: A NURSE’S PERSPECTIVE. L.C. Tuong*, K. Olivieri, T.J. Craig, Hershey, PA. Background: Presently, the movement of care for hereditary angioedema (HAE) is out of the clinic, emergency room and hospital and into the home. There is an increasing effort to make self-administration of HAE treatment available, effective and safe. As much of the transition relies on specially trained medical professions, our goal is to assess the comfort of nurses with teaching self-administration and to identify barriers they anticipate or have noted in an effort to improve patient care. Methods: A survey consisting of 21 questions related to nurse’s experience in HAE treatment and teaching of self-administration was sent to nurses who provide home care for patients and family members. Results were collected anonymously and data analyzed. The study met an IRB exception. Results: Survey participants felt that there is a definite need for teaching patients self-administration of therapies. However, most feel that physicians are hesitant to have patients self-administer. As far as nurses training experience, the majority feels very comfortable in teaching patients, trouble-shooting problems and are versed in teaching self-administration of both subcutaneous and intravenous medications. Most prefer to have self-infusion taught at home by a visiting nurse at set sessions. Patients aged 18 to 40 most easily acquire self-administration skills and having a care partner in self-administration training was very helpful. Less than 10% of patients refused selfadministration after initially being taught. Most cited fear of injection (pain, anxiety, bruising) and lack of skills (dexterity) as the major reasons for refusing to self-administer. Following initial training, most patients are able to demonstrate the skills required for self-administration on that same day; however, it took in general 3 to 5 times in order to properly train a patient. Conclusion: Self- administration of HAE treatment is increasingly more accessible and should be offered to patients as a safe and practical option. Specially trained nurses are essential for home-based teaching of the skills required for injection/infusion and for addressing patient’s concerns regarding treatment. Moving to self or home treatment and nursing education will improve patient’s quality of life, improve independence, lead to earlier therapy and reduce cost associated with care.

P294 SEROPREVALENCE OF CYTOMEGALOVIRUS AMONG BLOOD DONORS AND OTHER INVESTIGATED GROUPS. F. Alsharif*, O. Al-Jiffri, Z. El-Sayed, Jeddah, Saudi Arabia. Cytomegalovirus (CMV) is found worldwide in all geographical locations and socio-economic groups and is the virus most frequently transmitted to a developing child before birth. The aim of this study was to determine the seroprevalence of antibodies to CMV among repeated abortion females, immunecompromised patients, dialysis patients and healthy blood donors and to evaluate different methods of diagnosis as ELISA, latex agglutination and


complement fixation tests. Blood samples were collected from four investigated groups (repeated abortion females, immune-compromised patients, dialysis patients and healthy blood donors). Highest positive cases were detected by latex agglutination test (63.3 %.), followed by ELISA and complement fixation test (61 and 53.3%) respectively. Non significant association (P>0.05) was recorded between positive cases and different methods. Antibodies for cytomegalovirus was mostly prevalent among blood donors (91.4 and 82.9%) by both latex agglutination and ELISA and immune-compromised patients with (75%) by both ELIZA and CFT. There was a statistically significant difference (P< 0.05) between positive cases among different investigated groups. The validity test of latex agglutination proved sensitivity, specificity and accuracy with (94.7, 97 and 95.6%) respectively more than that detected by CFT (91.7, 73.8 and 83.3%) respectively. The seroprevalence of CMV appears to be very high in this environment among healthy blood donors, also high seropositivity rates were detected among different investigated groups. Latex agglutination test proved higher sensitivity, specificity and accuracy than CFT. ELISA and latex agglutination test are reliable, easy and rapid methods of cytomegalovirus diagnosis. Furthermore, the routine screening of blood donors for CMV antibodies should be recommended for the prevention and/or reduction of CMV.

P295 FACTITIOUS ANGIOEDEMA: A CASE SERIES. M. Feldman*, I. Warrier, D. Wierzbicki, D. Khan, Dallas, TX. Introduction: Angioedema is a common entity encountered by allergists, ER physicians, and primary care physicians. Angioedema can be broadly categorized as 1) allergic, 2) idiopathic, 3) ACE inhibitor associated, 4) hereditary, and 5) acquired. We describe the only published cases of Factitious Angioedema. Methods: Patients were diagnosed by one or more of the authors at one of the UT Southwestern affiliated hospitals. The diagnosis was made after all known etiologies of angioedema were excluded. Data: The three patients ranged in age from 11 to 34. Two patients were Caucasian, and one was Middle Eastern. Two patients were male, and one was female. Two patients manipulated their tongues to achieve a dusky purple color. Two patients were administered multiple auto-injectable epinephrine doses without improvement. Two patients had a total tryptase checked during an “attack”, both of which were normal. All patients had normal C4, C1 esterase inhibitor level, and C1 esterase inhibitor function studies at the time of an “attack”. All patients “failed” high dose antihistamine therapy. Two patients also “failed” multiple second line immunomodulatory therapies. One patient had genetic testing for a factor XII mutation which was normal. Two patients were hospitalized >3 times for tongue swelling. Multiple intubations and an emergent tracheostomy were performed in one patient. One patient was taking 100mg Benadryl IV q2 hours and 40mg methylprednisolone IV q12 hours via PICC line for “attack” prevention. During an “attack”, a normal facial MRI was noted in two patients and a normal laryngoscopic exam was noted in one patient. Spontaneous replacement of the tongue while speaking was noted in one patient, manual replacement during exam of the tongue was achieved in another patient, and both manual and spontaneous replacement (after gag-reflex testing) occurred in the third patient. Underlying psychiatric disease was suspected in all three patients. Two patients approved formal psychiatric evaluation with Factitious Disorder confirmed in both. Conclusion: We describe the first case series of Factitious Angioedema, a previously unrecognized entity. Factitious Angioedema should be considered in cases of seemingly refractory isolated angioedema with a negative workup for more commonly encountered causes. Underlying psychiatric disease should be considered in these “refractory” patients.

P296 RESULTS FROM A MULTICENTER RANDOMIZED CONTROLLED TRIAL OF ECALLANTIDE FOR THE ACUTE TREATMENT OF ANGIOTENSIN CONVERTING ENZYME INHIBITOR INDUCED ANGIOEDEMA. C. Graffeo*1, L.M. Lewis2, P. Crosley3, H.A. Klausner4, C.L. Clark5, A.J. Frank6, J. Miner7, R. Iarrobino8, Y. Chyung9, 1. Norfolk, VA; 2. St. Louis, MO; 3. Decatur, GA; 4. Detroit, MI; 5. Royal Oak, MI; 6. Greenville, NC; 7. Minneapolis, MN; 8. Burlington, MN; 9. Burlington, MA. Introduction: Angiotensin converting enzyme inhibitor induced angioedema (ACEIA) is a potentially life-threatening condition associated with the use of ACE-inhibitors. It is thought to be mediated by elevations in bradykinin. Ecallantide is a plasma kallikrein inhibitor that suppresses bradykinin production. The purpose of this study was to compare the safety and efficacy of conven-


ABSTRACTS: POSTER SESSIONS tional therapy with ecallantide against conventional therapy with placebo for ACEIA. Methods: In this phase 2 double-blind study, subjects were randomized 1:1:1:1 to receive conventional therapy with a single subcutaneous dose of ecallantide (10, 30, or 60 mg) or placebo. Adults presenting to the emergency department within 12 hours of onset of ACEIA of the head/neck were eligible. The primary endpoint was defined as meeting a predetermined set of 6 discharge eligibility criteria within 6 hours of treatment. Results: 176 subjects were planned for enrollment. An interim analysis of blinded study data indicated that a majority of subjects overall were meeting the primary endpoint, and the study was halted. In total, 76 eligible subjects were treated. Most patients had mild (45%) or moderate (42%) ACEIA at the time of presentation; 45% of patients were Ishoo Class I (facial rash, facial edema, lip edema), 5% were Class II (soft palate edema), 41% were Class III (tongue edema), and 8% were Class IV (laryngeal edema). The primary endpoint was met by 72% (13/18) of the placebo group, and by 85% (17/20), 89% (17/19), and 89% (17/19) of the 10, 30 and 60 mg ecallantide groups, respectively. Comparing all dosages of ecallantide to placebo, there was a non-significant absolute difference of 15.7% (95%CI -10.9 to 41.2) in favor of ecallantide. No new safety signals were identified. ICU admission rate was low and not significantly different between ecallantide and placebo groups (8.6% [5/58] vs 16.7% [3/18] respectively; p=0.385). Conclusion: Compared with conventional therapy alone, the addition of ecallantide did not demonstrate a significant benefit in this small study of ACEIA patients. The majority of patients met the discharge eligibility criteria within 6 hours of ED presentation regardless of intervention.

periodontitis. The aim of this study is to determine the prevalence of periodontal disease in patients older than 15 years with respiratory allergy. Method. We performed an observational, transversal and comparative study that assessed two groups. Group 1 included patients with a diagnosis of respiratory allergy, with sensitization to aeroallergens identified by skin tests. Group 2 (control) included non-allergic subjects with negative skin tests to aeroallergens. All subjects were evaluated by the Periodontal Clinic to identify the presence of periodontal disease. Subjects with periodontal disease were divided into 4 subgroups (I: gingivitis, II: mild periodontitis, III: moderate periodontitis, and IV: advanced periodontitis). Results. We included a total of 60 subjects (30 in each group). The mean age was 30 years in both groups (p = 0.4). There was no difference in relation to gender (p = .78). Allergic diseases in Group 1 included: allergic rhinitis (100%), asthma (66%), and atopic dermatitis (33%). All subjects in both groups had some degree of periodontal disease. Within the group of allergic patients, the distribution according to the degree of periodontal disease was: grade I, 13% (n = 4); grade II, 0%; grade III, 70% (n = 21); and grade IV, 17% (n = 5). In the control group, the distribution by degree of periodontal involvement was: grade I, 0%; grade II, 0%; grade III, 80% (n = 24); and grade IV, 20% (n = 6) (Graphic 1). No association was found between the degree of periodontal disease with gender, duration of respiratory allergic disease, or a history of previous dental cleaning. Conclusions. The high prevalence of periodontal disease found in our study population did not identify differences between the groups evaluated. We suggest further studies with larger sample population and study design modifications.

P297 ADVERSE DRUG REACTIONS: FACTORS THAT PLAY A ROLE IN READMISSION. M.H. Chong*, S. Wang, B. Malone, M. Aquino, M. Davis-Lorton, L. Fonacier, Mineola, NY. Introduction: An estimated 5.3% of hospitalizations are related to adverse drug reactions (ADRs); however, there is little data on the readmission rate of patients experiencing these reactions. Our objective was to determine the rate and factors affecting readmission (within 30 days) after being discharged from an ADR-related hospitalization. Methods: A retrospective chart review of 238 patients with ADRs identified through pharmacy records over a 12-month period was conducted with IRB approval. The severity of the ADR was based on treatment, length of stay and/or disability. Patients were separated into an inpatient and outpatient group based on whether the initial ADR occurred in the hospital or community setting. Only patients who were admitted solely for the ADR were included for analysis. Results: A total of 111 outpatients and 78 inpatients were analyzed. The readmission rate for ADRs in the community was 16.2% versus 17.9% in the inpatient setting (p=0.8). Readmission related to the initial ADR was seen in 4 inpatients (ie. bradycardia, neutropenia) and 5 outpatients (ie. renal failure, hypoglycemia). Both inpatients and outpatients who were readmitted had a mean number of 8.0 concurrent medications. The mean age for readmission was 74.7 years (outpatient group) versus 70.0 years (inpatient group). COPD was the most common comorbidity in ADR-related readmissions (55.5%) while diabetes was most common in non-ADR-related readmissions (52.2%). More serious initial ADRs occurred in the community usually from anticoagulants and angiotensin converting enzyme inhibitors (ACEIs)/angiotensin II receptor blockers (ARBs). Contrast dye and opioids were predominant causes of ADRs in the hospital. The ADR severity in the initial admission did not increase the likelihood of an ADR-related readmission. Conclusion: The readmission rates for ADRs in the community versus hospital were nearly identical. The severity of the initial ADR did not affect the readmission rate. Patients with COPD and diabetes are more likely to experience readmission thus we suggest careful review of discharge criteria in these populations.

P298 PREVALENCE OF PERIODONTAL DISEASE IN PATIENTS WITH RESPIRATORY ALLERGY. I.V. Yanez-Pérez*, M. Calva-Marino, A. Arias-Cruz, S.N. Gonzalez-Díaz, G. Martínez-Sandoval, G. Chapa-Arizpe, L.E. Gonzalez-Martínez, L. Leal-Villarreal, J.I. Canseco-Villarreal, H. Hernandez-Sanchez, L. Rangel-Garza, Monterrey, NL, Mexico. Background. Periodontal disease results from childhood exposure and accumulation of bacteria at the gingiva and teeth. In contrast to the “hygiene hypothesis”, several studies have found an association between respiratory allergy and

P299 IMPLEMENTING A COMPREHENSIVE STANDARDIZATION PROCESS (DEFINE, INTERVENE, ANALYZE, CLOSE THE LOOP) LEADS TO BOTH SHORT-TERM AND LONG-TERM CHANGES IN CLINICAL PRACTICE. R. Pyle*, M. Park, Rochester, MN. Introduction: We present a comprehensive process (Define, Intervene, Analyze, Close the loop) to standardize clinical practice and improve patient care. Methods: We implemented a comprehensive process (Define, Intervene, Analyze, Close the loop) in order to standardize our penicillin and cephalosporin allergy evaluation. Define: Inconsistent evaluation of patients with a history of anaphylaxis to penicillin; amoxicillin allergy; cephalosporin allergy. Intervene: A literature search was conducted regarding the defined problem and the studies presented to all providers. A consensus was achieved and practice parameter was written and reviewed addressing the problem. Analyze: Those who participated in the defined process (intervention group) and control group (providers who did not participate) were tested on the material with 4 questions with different clinical scenarios addressing the defined problem. Close the loop: Both groups were then tested six months later to evaluate for long-term retention of the material and change in practice. Results: Correct answers to the 4 questions from the intervention group (n=7) compared to control group (n=6) were as follows: Question 1(86% vs. 0%), 2 (86% vs. 67%), 3 (86% vs. 33%), 4 (57% vs. 0%) shortly after intervention. The same questionnaire was administered to both groups 6 months later: Question 1 (100% vs. 40%), 2 (100% vs. 100%), 3 (100% vs. 60%), 4 (66% vs. 40%). Conclusion: Implementing a comprehensive standardization process (Define, Intervene, Analyze, Close the loop) can lead to both short-term and long-term changes in clinical practice compared with controls.







AN EXPLORATORY, RANDOMIZED, PLACEBO-CONTROLLED, DOUBLE-BLIND, CROSSOVER STUDY OF FP01 LOZENGES IN SUBJECTS WITH CHRONIC REFRACTORY COUGH. M. Sher*1, A. Goldsobel2, S. Birring3, A. Das4, B. Canning4, P. Dicpinigaitis5, I. Paul6, R. Casper4, H. Fraser4, R. Mazhari4, J. Vornov4, B. Paterson4, 1. St. Petersburg, FL; 2. San Jose, CA; 3. London, United Kingdom; 4. Baltimore, MD; 5. New York, NY; 6. Hershey, PA.

Introduction: Circulating IgG antibody to the IgE receptor has been noted in 40-60% of patients with chronic urticaria. The presence of this same antibody in patients with angioedema has not been routinely described. We report a case in which antibody to the IgE receptor was found to be positive in a patient with isolated angioedema. Case Report: A 16 year old female with past medical history of Celiac disease presented with recurrent episodes of angioedema. Episodes were noted to occur with upper respiratory illnesses and involved abdominal pain along with angioedema of the lips, periorbital areas, and tongue. None of these episodes involved urticaria. Also noted was a reduction in these episodes when she developed dysmenorrhea. Examination revealed no evidence of dermatographism. Results: Laboratory evaluation showed negative antithyroglobulin antibody and normal thyroid function. CH50, C4, C1 esterase inhibitor function and level, and serum tryptase were within normal limits. Factor XII SNP testing was also negative. Of note, antibody to the IgE receptor was found to be positive. Despite treatment with fexofenadine 180 mg twice a day, levoceterizine 5 mg twice a day, montelukast 10 mg daily, hydroxyzine 25 mg daily, cromolyn sodium 200 mg three times a day and prednisone bursts followed by tapers, she continued to have episodes of angioedema. Conclusion: About 10% of patients experience angioedema without urticaria. The presence of antibody to the IgE receptor with isolated angioedema raises the question of whether there is a similar process responsible for episodes of angioedema, in addition to the known role of this antibody in chronic urticaria.

P301 USE OF NOVEL SOCIAL MEDIA AND CLOUD-BASED SERVICES FOR SCHOLARLY COLLABORATION FOCUSED ON ALLERGY AND IMMUNOLOGY DURING RESIDENCY AND MEDICAL SCHOOL. A.S. Nickels*1, R. Wolf2, V. Dimov2, 1. Rochester, MN; 2. Chicago, IL. Introduction: In 2011, a newly formed Allergy and Immunology Interest Group (AIIG) at the University of Chicago began using novel social media and cloud-based services to promote scholarly collaboration and activity. Here we describe our approach, limitations, and outcome. Methods: Starting in August 2011, the AlIG began using the online Google Plus social network to share messages between members regarding scholarly activity. These messages were private and allowed separation of professional and personal accounts, unlike other social media. In December 2011, the AIIG starting using a privately shared Google Document to provide an overview of the AIIG activity and allow the posting of new ideas, editing current projects, updating progress (i.e. IRB status), and expressing interest in ongoing projects. Results: Google plus intervention had 15 participants and 16 private group specific posts. The Google document with scholarly activity has been shared amongst 12 participants. Seven members have updated the document a total of 38 times and listed 28 unique projects. Since August 2011, members have generated and published 2 peer reviewed articles, 7 national abstract presentations, 1 book chapter, a successful grant application, and 5 research projects are currently underway. Two members have successfully matched in Allergy/Immunology fellowship; there are 3 current applicants, and 2 have future plans to apply. Conclusion: Novel social media tools and cloud based sharing tools have the potential to improve scholarly collaboration. Benefits include a quick, simple, and centralized way to organize research ideas and promote interest in Allergy/Immunology for scholarly collaboration. Using a cloud based, shared document is conducive to ethical sharing of scholarly ideas. Google Plus allows message sharing among researchers in an environment that protects the online privacy of trainees, allowing separation of personal and professional activities. Limitations include lack of face-to-face interaction (siloing effect) and limits in sharing protected health information. The Allergy and Immunology Interest Group application of this novel technology has yielded a significant amount of scholarly activity amongst the residents and attendings that have engaged in this technology.


FP01, an investigational treatment for cough, is an oral lozenge form of memantine hydrochloride (MMT) designed for accelerated absorption and local demulcent effect. MMT has been shown to significantly reduce cough in guinea pigs challenged with inhaled citric acid and bradykinin. The present study was designed to explore the clinical efficacy, safety, and tolerability of FP01 lozenges in patients with chronic cough patients. Methodology: 83 subjects were enrolled in this multi-center, randomized, crossover, double-blind, placebo-controlled study. Subjects were randomized to receive FP01 lozenges 6, 12, or 18 mg or matching placebo three times / day (TID) for 2 weeks, and after a 2 week washout, crossed over to receive matching placebo or FP01 lozenges 6, 12 or 18 mg TID for 2 weeks. Assessment of tolerability and balance of completed subjects between groups was performed at intervals during conduct of the trial. Automated cough counting with the Leicester Cough Monitor, Visual Analogue Scale (VAS), Cough Severity Diary (CSD), and Leicester Cough Questionnaire (LCQ) were performed at the beginning of the study and upon conclusion of the first treatment period, washout, and the second treatment period. Safety was assessed through monitoring adverse events, vital signs and physical examinations. Blood was drawn for plasma concentrations of FP01 on the last day of each treatment period. IRB approval and informed consent was obtained from all research subjects Diagnosis and Main Criteria for Inclusion: Chronic refractory cough of > 8 weeks where underlying etiology had been treated and yet cough persists. Subjects were required to have a cough severity (VAS) > 35 mm & mean CSD frequency domain score > 3.0 at screening and enrollment. Outcome Measures: The primary outcome was change in start-to-end difference in cough frequency, active vs. placebo treatment periods. Statistical Methods: For both per protocol and ITT populations, efficacy was assessed by comparing the change in cough frequency, LCQ, CSD and VAS scales during each treatment period (Visit 3 vs. 2, Visit 5 vs. 4). The mean difference was tested for statistical significance using a Wilcoxon Sign Rank test (for paired differences). Additional exploratory analyses were conducted. Results: The results of the study will be presented.

P303 THE CCR4 CHEMOKINE RECEPTOR ANTAGONIST CCX6239 FOR THE TREATMENT OF ALLERGIC DISEASES. Z. Miao, Y. Wang, M. Leleti, D. Dairaghi*, M. Walters, T. Sullivan, S. Miao, T. Schall, J. Jaen, J. Powers, Mountain View, CA. Introduction: Lymphocytes expressing CCR4 have long been known to be associated with allergic disorders such as atopic dermatitis (AD), rhinitis and asthma and, as such, there has been considerable interest in developing small molecule antagonists against this chemokine receptor; however, few CCR4 antagonists are in clinical development. Our objective was to identify an orally bioavailable small molecule that selectively targets CCR4 and that possesses an overall profile suitable for clinical development. Methods: The potency and selectivity of CCX6239 was assessed in vitro by inhibition of lymphocyte chemotaxis to chemokines, including the CCR4 chemokines CCL17 and CCL22, or to AD skin biopsy extracts. The ability of CCX6239 to inhibit allergic disorders in vivo was assessed by mouse models of contact sensitivity and allergic airway inflammation. Results: CCX6239 potently inhibits CCR4 under physiologically relevant conditions (i.e., in the presence of 100% human serum), inhibiting both CCL17 and CCL22-induced chemotaxis of human lymphocytes with a potency (A2 value) of 20 and 26 nM, respectively. In addition, CCX6239 significantly reduced cell chemotaxis towards AD skin biopsy extracts. CCX6239 is highly selective for CCR4, showing no cross-reactivity with other chemokine receptors and no significant activity against the hERG potassium channel or CYP isozymes. CCX6239 also inhibits murine CCR4 in 100% serum with a potency of 60 nM. CCX6239 was effective in murine models of contact hypersensitivity and allergic airway inflammation. Doses of CCX6239 that resulted in plasma levels higher than its in vitro A10 value resulted in a significant reduction in ear thickening in the DTH model, as well as reduction in the number of leukocytes recovered by bronchoalveolar lavage and levels of Th2 cytokines. Pharmacokinetic profiles in preclinical species and resultant allometric scaling to humans indicate that a single oral daily dose of CCX6329


ABSTRACTS: POSTER SESSIONS would provide serum-adjusted A10 coverage of the receptor in humans. Conclusions: CCX6239 is a potent and selective antagonist of CCR4 that can be dosed orally and is in late stage preclinical development. This molecule displays pharmaceutical properties suitable for its use in the treatment of allergic diseases such as AD, rhinitis and asthma.

Responses to application of BRNS - ITT Population (n = 26)

P304 LCB 03-0110, A NOVEL MULTI-KINASE INHIBITOR TARGETING KINASES INVOLVED IN INFLAMMATORY AND FIBROTIC CELL SIGNALING INHIBITS ACTIVATION AND EMT OF A549 CELLS AND SUPPRESSES COPD IN MICE. B. Yang*, X. Sun, Seoul, Korea, Republic of. Fibrotic airway remodeling is associated with chronic obstructive pulmonary disease (COPD) and effective treatments are still lacking for this disorder. Recent evidence suggests that the abnormal activation of airway epithelium contribute to the pathological airway remodeling and epithelial-mesenchymal transition (EMT) plays an important role in this process. Inflammatory mediators, growth factors and extracellular matrix proteins are suggested as factors to induce activations and EMT of airway epithelial cells and in particular TGF β is suggested as the prominent factor to induce EMT. We have developed a small molecular ATP-competitive kinase inhibitor, LCB 03-0110 which is a thieno-pyridine derivative targeting simultaneously multiple kinases involved in inflammatory and fibrotic cell signaling. LCB 03-0110 potently inhibits inflammatory non-receptor tyrosine kinases such as src family, syk1, and btk1 and fibrotic receptor kinases such as TGFBR-II and discoidin domain receptor family with in vitro IC50 of 1-20 nM. When LCB 03-0110 was treated into A549 human airway epithelial cells stimulated with TNF-α and IL-1β, the induction of various inflammatory mediators, reactive oxygen species and the production of mucine 5A were significantly suppressed with IC50 of 0.3-1mM. This suppression was associated with the inhibition against the activations of p38, JNK, Akt1, and NF-κB. In addition, LCB 03-0110 inhibited TGF β1induced epithelial-mesenchymal transition (EMT) of A549 cells with IC50=1 mM. When 10 ml of 0.1% LCB 03-0110 was injected intratracheally into the lung of smoke-induced COPD mice, suppression of airspace enlargement, neutrophil infiltration, wall thickening, inflammation around alveolar were observed. These results suggest that LCB 03-0110 could be an effective therapeutic agent for COPD by suppressing EMT of airway epithelial cells and this activity is associated with its simultaneous inhibition against both inflammatory and fibrotic cell signaling.

P305 OBJECTIVE AND SUBJECTIVE RESPONSES TO AN EXTERNAL NASAL DILATOR IN CONGESTED CHILDREN. E.O. Meltzer*1, W. Becker2, G. Shanga2, 1. San Diego, CA; 2. Parsippany, NJ. Background: Breathe Right® Nasal Strips (BRNS) are mechanical external nasal dilators which are applied to the outside of the nose to provide temporary relief from nasal stuffiness. The purpose of this study was to explore the effect of a child sized BRNS on nasal patency using Peak Nasal Inspiratory Flow (PNIF). Subjective responses were also collected using a questionnaire. Methods: This study was a single-center assessment of BRNS in 26 congested children aged 6-12 with allergic rhinitis. Following IRB approval, parental informed consent and subject assent, medical history was obtained including a nasal examination by the investigator. After blowing their nose gently, each subject was asked to report their perception of their nasal breathing after being seated for at least 3 minutes (subjective baseline). Following this, the baseline PNIF was measured (3 times) using the In-Check PNIF meter and small pillow facemask (patency baseline). After a 3-minute break, the subjects repeated this process in a supine position. The subjects then had the BRNS applied by the investigative staff and the same measurements described above were repeated (in both the sitting and supine positions). Results: Part 1 of the Table below shows peak nasal inspiratory flow. The BRNS showed a statistically significant change from baseline in the seated position, but not the supine. Part 2 of the Table below shows the subjective responses. The questionnaires used in the study were exploratory, because there were no validated questions available for use with children in these endpoints. Conclusions: In conclusion, the BRNS provided a significant objective improvement in seated PNIF, and improvement in subjective responses for both seated and supine positions among children ages 6 – 12 with allergic rhinitis.

P306 ANTIBIOTIC USE FOR CHRONIC RHINOSINUSITIS: SEASONAL VARIABILITY AND COMPARISON TO CONTROLS. J. Hsu*, A.T. Peters, L.C. Grammer, B.K. Tan, R.K. Chandra, D.B. Conley, R.C. Kern, R.P. Schleimer, P.C. Avila, Chicago, IL. Introduction: Antibiotics are often used for chronic rhinosinusitis (CRS) with seasonal variation, but magnitude of use is unknown. We determined frequency and seasonality of antibiotic use for patients with CRS compared to controls. Methods: We performed a retrospective cohort study (2010-2012) using our center’s electronic medical records. CRS subjects were patients with >=1 medical encounter (2010-12) associated with an ICD9 &/or CPT code for CRS or nasal polyposis (NP). Controls were patients with >=1 medical encounter in 2010-12, but had no CRS- or NP-related ICD9 codes, CPT codes, or sinus CT scan. We excluded patients with cystic fibrosis or immunodeficiency. We calculated prescription rates for systemic antibiotics often used to treat sinusitis, and compared CRS to controls using logistic regression (adjusting for demographics, asthma, allergic rhinitis and tobacco use). We defined 4 equal-length calendar seasons and compared seasonal prescription rates between groups and within group using non-parametric statistics. Institutional Review Board approval was obtained. Results: Of 293343 subjects (21724 with CRS, 271619 controls), mean+/-SD age=49.9+/-17.7 yrs, 40.8% were male, and 64.3% were Caucasian. NP-associated ICD9 or CPT codes occurred in 4.4% of CRS subjects; CPT codes associated with CRS- or NP-related surgeries occurred in 6.5%. In 2010-12, a greater proportion of CRS subjects received sinusitis-associated antibiotic prescriptions vs. controls(21.4% vs. 5.8%,P<0.0005). Diagnoses of CRS with NP(odds ratio[OR]=4.14, 95% confidence interval[CI]=3.544.85) and of CRS without NP(OR=3.66, 95%CI=3.50-3.82) increased risk for antibiotic prescriptions compared to controls. Analysis of seasons showed antibiotic prescription rates were higher for CRS subjects than controls for all seasons(P=0.0003). Seasonality for antibiotic prescriptions was found only in CRS subjects, among whom the average monthly prescription rate peaked in Winter(Jan-Mar=49.1 prescriptions per 1000 office visits per month) compared to Spring(Apr-Jun=36.1,P=0.0005), Summer(Jul-Sep=26.9,P=0.0003), and Fall(Oct-Dec=35.9,P=0.004). Among controls, these rates varied little (Winter=14.2,Spring=13.1,Summer=12.3,Fall=14.0;P>0.05). Conclusion: Rate of antibiotic prescriptions for patients with CRS is 3.6 times greater than for controls. Rates were seasonal only for CRS patients, peaking in winter. Odds ratios (95% confidence intervals) for sinusitis-associated antibiotic prescriptions for subjects with CRS compared to controls (2010-2012)

CRS=chronic rhinosinusitis; NP=nasal polyposis. *P<0.0005 compared to control subjects (adjusted for age, sex, race/ethnicity, allergic rhinitis, asthma, and tobacco use).




P307 CARUNCULAR NODULARITY: NEW SIGN FOR SEASONAL ALLERGIC CONJUNCTIVITIS. T.M. Nsouli*, C.D. Schluckebier, S.T. Nsouli, N.Z. Diliberto, J.A. Bellanti, Washington, DC. Rationale: Seasonal Allergic Conjunctivitis (SAC) is an acute inflammatory condition often triggered by airborne allergens, mainly tree, grass and weed pollen. The diagnosis of this ocular allergic condition is usually clinical (Bielory L, Ann Allergy Asthma Immunol 2007; 98:105-115). We identified a novel ocular sign consisting of nodularity of the caruncle. Methods: One hundred and six adult patients (mean age 39 years) were evaluated in our allergy clinic for possible SAC. All patients were experiencing bilateral moderate to severe ocular itching, conjunctival hyperemia and epiphora. In addition, a prominent occurrence of nodularity of the caruncles was observed consisting of small, pale and elevated protuberances (fig.1). The magnitude and number of these caruncular nodules were directly related with the severity of SAC. All study patients underwent a careful allergy evaluation consisting of clinical history and physical exam. All patients had positive skin prick tests (SPTs) to seasonal environmental allergens. Results: Treatment of SAC with topical ophthalmic solutions of antihistamines (olopatadine, bepotastine) and oral second-generation anti-H1 agents resulted in significant improvement of SAC and resolution of the caruncular nodularity. Conclusion: Since the diagnosis of SAC is based mainly on clinical findings, this additional new clinical sign of caruncular nodularity could further help facilitate the diagnosis and treatment response of SAC.


P308 EVALUATION OF RISK FACTORS, ETIOLOGY, PRIMARY AND SECONDARY DIAGNOSTIC METHODS IN 1 TO 24-MONTH-OLD WHEEZY INFANTS. Öner. Özdemir1, A.F. Cetin*2, S.P. Isguven1, 1. Adapazar, Turkey; 2. Istanbul, Turkey. Purpose: In this study, the specific diagnosis group and recurrent wheezing groups were compared for risk factors, etiology and diagnostic methods. Materials/Methods: Between 2010-12, wheezing infants, varying from 1 to 24month-old, having recurrent wheezing ≥x3 or a wheezing lasting longer than 1 month were retrospectively examined at Istanbul Medeniyet University Göztepe Research/Training Hospital. 970 patient files were screened and 76 of them were enrolled in this study. History, socio-economic / demographic features, physical exam findings, laboratory and MR-CT scan results were recorded. Results: 21/76 was female and 55/76 was male. 60% of patients’ mothers were ≤29-year-old. In 76 patients with recurrent wheezing, 16% were transient early, %21 were persistent atopic, 25% were non-atopic and 38% were the patients having specific diagnosis. Echography was performed in 79%, thorax CT in 26%, video-fluoroscopy in 5%, esophagus-stomach-duodenum graphs in %25, pHmetre in 34%, sweat test in 81% and bronchoscopy in 8%. 29 patients were diagnosed with a specific disease. In 29 cases, gastro-esophageal reflux disease (GERD) was detected in 44%, secondary aspiration pneumonia due to GERD in 7%, GERD+oropharyngeal dysfunction in 10%, bronchopulmoner dysplasia in 10%, foreign body aspiration in 7%, secondary aspiration pneumonia due to gastric volvulus in 3%, bronchogenic cyst in 3%, bronchiectasis in 3%, dilated cardiomyopathy in 3%, and hypereosinophilic syndrome in 3% and cystic fibrosis in 3% were detected. In these patients, attacks were repeated


most of the time during winter. The patients had their first attack up to 6 months of age. When the groups were compared for growth retardation, there was a statistically significant difference for specific diagnosis group. There were significantly more smokers and more humidity at home in recurrent wheezing groups than the specific diagnosis group. If total IgE levels were compared, there was a significant difference for persistent atopic wheezers among recurrent wheezing groups. Eosinophil count was significantly lower in transient early wheezers when compared with other groups. Conclusions: In the recurrent wheezing groups; the family should pay attention to humidity and smokers at home. In the specific diagnosis group, growth retardation was significantly different.

P309 CASE REVIEW: A 12 YEAR OLD MALE PATIENT WITH COMPLICATED BILATERAL KERATOCONUS WITH CORNEAL HYDROPS TREATED WITH IMMUNOTHERAPY TO DUST MITES. B. Di Giorgi*, S. Nazario, C. Ramos, San Juan, Puerto Rico. Introduction: Keratoconus is a degenerative eye disorder with structural changes within the cornea. Causes thinning and a more conical shape. The cause of this condition is still largely unknown; association between keratoconus and many conditions has been suggested: atopy, eye rubbing, and contact lens wear. Case: A 12 year old with “eye allergy” for 8 years, followed up by ophthalmologist, referred to allergist but never evaluated. He refers ocular pruritus, blurry vision, clear rhinorrhea, nasal congestion and pruritus. Pending corneal transplant, poor candidate due to eye rubbing. Physical exam eye rubbing, photophobia, bilateral keratoconus, hazy corneas with erosions, eyelid edema and eye pain, edematous/pale nasal turbinates with obstruction. Skin prick test positive to dust mites. He was started on subcutaneous immunotherapy (SCIT). On follow up, right bluish hazy cornea was noted. Patient reports sudden eye pain, blurry vision and minimal eye sight. Patient was diagnosed with corneal hydrops by ophthalmologist. Discussion: Study suggest vigorous eye rubbing contributes to the progression of keratoconus and decreased vision. Keratoconic corneas show signs of increased activity by proteases and reduced expression of protease inhibitor. Bulging of the cornea can result in a localized rupture of Descemet’s membrane, leading to seeping of aqueous humor into the cornea. Patient experience pain, clouding of vision, with a translucent milky-white appearance known as a corneal hydrops. Conclusion: Atopy may contribute to keratoconus, due to associated pruritus. Rubbing exposes the thinner or weakened cone apex to high intraocular pressure that tends to promote ectasia. In advanced keratoconus, the cornea may become scarred causing worsening vision and may require corneal transplant. Keratoconus needs a multidisciplany approach. Treatment includes: topical vasoconstrictors, antihistamines, mast cell stabilizers, NSAIDs, and steroids. Patient was started on SCIT and had significant improvement of pruritus and eye rubbing.

P310 ONCE-DAILY TREATMENT WITH BECLOMETHASONE DIPROPIONATE NASAL AEROSOL (80 mG) DOES NOT AFFECT HYPOTHALAMIC-PITUITARY-ADRENAL AXIS FUNCTION IN CHILDREN WITH PERENNIAL ALLERGIC RHINITIS. F. Hampel*1, N.A. Nayak2, N. Segall3, C.J. Small4, J. Li4, S.K. Tantry4, 1. New Braunfels, TX; 2. Normal, IL; 3. Atlanta, GA; 4. Frazer, PA. Rationale: Beclomethasone dipropionate (BDP) nasal aerosol has a wellestablished efficacy and safety profile for the treatment of allergic rhinitis (AR) in adolescents and adults. A previous study demonstrated that BDP nasal aerosol was not associated with hypothalamic-pituitary-adrenal axis (HPA) suppression in adolescent and adult patients with perennial AR (PAR) (Ratner Ann Allergy Asthma Immunol 2012). The effect of 6 weeks of once-daily treatment in the morning with BDP nasal aerosol versus placebo on HPA function in children with PAR was evaluated in this study. Methods: In this double-blind, placebo-controlled, parallel-group study, patients (6-11 years old) with PAR were randomized (2:1 ratio) to treatment with BDP nasal aerosol 80 mg/d (n=67) or placebo (n=32). The primary endpoint was change from baseline in the 24hour serum cortisol weighted mean for BDP nasal aerosol versus placebo after 6 weeks of treatment, analyzed in the per-protocol (PP) population. Results: The PP population consisted of 97 patients (66, BDP nasal aerosol; 31 placebo); mean age was 9.0 years. Baseline geometric mean serum cortisol weighted mean values were similar in the BDP nasal aerosol 80 mg/d and placebo treatment groups (5.97 and 6.47 mg/dL, respectively). After 6 weeks of treatment,


ABSTRACTS: POSTER SESSIONS the geometric mean values were 6.19 and 7.13 mg/dL, respectively, with no decrease from baseline in either group. The geometric mean serum cortisol ratio for BDP nasal aerosol 80 mg/d to placebo was 0.91 (95% CI: 0.81, 1.03), indicating predefined noninferiority. Overall, serum cortisol concentrationtime profiles were similar for the placebo and BDP nasal aerosol 80 mg/d treatment groups at baseline and at week 6. The safety profile of BDP nasal aerosol 80 mg/d was similar to that of placebo. Conclusions: Twenty-four-hour serum cortisol profiles were comparable for BDP nasal aerosol and placebo in pediatric patients with PAR, indicating that once-daily BDP nasal aerosol treatment was not associated with HPA axis suppression in children.

P311 ALLERGEN SENSITIVITY AND OCULAR AND NASAL SYMPTOMS (ONS) IMPLICATIONS FROM THE U.S. NATIONAL HEALTH AND NUTRITION EXAMINATION SURVEYS (NHANES) N-II AND N-III. Q. Meng1, P. Koutsoupias2, L. Bielory*2, 1. Piscataway, NJ; 2. New Brunswick, NJ. Background: Allergen skin test (IST) results from NHANES have been published, but the trends in ONS and positive IST prevalence have not been thoroughly investigated across regions and age groups. Methods: IST data was assessed for the 6 allergens (Ag) common to N-II (1976-1980; n=11,044) and N-III (1988- 1994; n=10,833): cat, ragweed (R), perennial rye(PR), oak (O), Bermuda grass, and A. alternata. (+IST = delta mean of the wheal length and width of IST and negative control was ≥ 3mm) and linked to ocular symptoms (OS), nasal symptoms (NS), and ONS. Wilcoxon tests were performed between differences in NHANES II vs III for OS, NS, ONS (α= 0.05) and Bonferroni correction for multiple comparisons (e.g. age groups and regions). Results: For the overall population, 19.4% (n=2144/11044) had +IST >1Ag tested during N-II, and 41.9% (n=4538/10833) during N-III (α=0.025). +IST increased in all regions and age groups from N-II vs N-III: from 26.1% in the South to 22.1% in the West; and from 25.1% (ages 41-50) to 20.9% (ages 610). +IST (6 Ags tested) increased from N-II vs N-III; ranging from 22.1% for cat, to 1.9% for O. The increases were significant for all Ag (α=0.0042) except O. ONS increased (α=0.0014) among N-II vs N-III +IST populations ranging from 20.6% for PR to 26.2% for O. NS alone significantly increased only for R and PR; none was seen for OS. In the –IST population: ONS increased (α=0.0014) @20% for the overall N-II vs N-III population; NS alone also increased (α=0.0014) @8%; with insignificant increase in OS. ONS increase ranged from 20-30% in all regions for +IST populations and ranging from 1020% in all regions for -IST populations. All increases were significant. For +IST population, the increase in ONS was varied across different age groups. Age 11- 30, ONS increased (α=0.00035) for at least 4/6 Ags. For -IST population, a 20% increase in ONS was significant across all age groups (α=0.0002). Conclusion: From N-II to N-III, +IST population increased from 19.4% to 41.9% to specific Ags. For +IST and -IST populations, ONS increased for all regions with age group differences. For +IST populations, ONS significantly increased for age 11-30. Minor ONS increases were observed for older and younger people. However, for -IST populations, a 20% increase in ONS was significant across all age groups.

P312 ONCE-DAILY TREATMENT WITH BECLOMETHASONE DIPROPIONATE NASAL AEROSOL IMPROVES NASAL SYMPTOMS OF PERENNIAL ALLERGIC RHINITIS, REGARDLESS OF SYMPTOM SEVERITY AT BASELINE. E.O. Meltzer*1, R. Jacobs2, L. Janka3, S.K. Tantry3, 1. San Diego, CA; 2. San Antonio, TX; 3. Frazer, PA. Rationale: Beclomethasone dipropionate (BDP) nasal aerosol, a nonaqueous formulation with a well-established efficacy and safety profile, is approved in the United States for the treatment of allergic rhinitis (AR) in adolescents and adults. Previously published results (Meltzer Allergy Asthma Proc 2012) demonstrated that BDP nasal aerosol significantly improves nasal and ocular symptoms compared to placebo with a similar adverse event (AE) profile in patients with perennial AR (PAR). The objective of this post hoc analysis was to evaluate the effectiveness of BDP nasal aerosol based on baseline symptom severity in PAR patients. Methods: In this 6-week, double-blind, placebo-controlled, parallel-group study, patients (≥12 years) with PAR were randomized (1:1 ratio) to treatment with BDP nasal aerosol 320 mg/d (n=236) or placebo (n=238). In this post hoc subgroup analysis, efficacy measures of change from

baseline in average patient-reported AM and PM reflective and instantaneous total nasal symptom scores (rTNSS and iTNSS) were evaluated by patient nasal symptom severity at baseline: less severe (with baseline rTNSS < baseline median [9.0]) and more severe (rTNSS ≥ baseline median [9.0]). Results: At week 6, treatment with BDP nasal aerosol resulted in greater improvement in average AM and PM rTNSS compared to placebo in patients with more severe symptoms at baseline (least squares [LS] mean [95% CI] difference: –0.86 [–1.4, –0.3]; P = 0.004), as well as in patients with less severe baseline symptoms (LS mean [95% CI] difference: –0.80 [–1.3, –0.3]; P = 0.002). Treatment with BDP nasal aerosol also resulted in greater improvement in average AM and PM iTNSS compared to placebo in patients with more severe symptoms at baseline (LS mean [95% CI] difference: –0.78 [–1.3, –0.2]; P = 0.005), as well as in those with less severe baseline symptoms (LS mean [95% CI] difference: –0.75(–1.1, –0.4) P < 0.001). BDP nasal aerosol was well-tolerated and AE profiles were similar in patients compared with placebo. Conclusions: Results of this post hoc analysis showed that treatment with BDP nasal aerosol provides greater improvement in nasal symptoms compared to placebo in PAR patients, regardless of symptom severity at baseline.

P313 THE UTILITY OF POST-PROVOCATION LARYNGOSCOPY IN PATIENTS WITH DYSPNEA AND HISTORIES SUGGESTIVE OF VOCAL CORD DYSFUNCTION. K.A. von Elten*, C. Gould, S. Schwabacher, P. Brenner, A. Nations, A. Lipton, S. Coles, S. Gada, Bethesda, MD. Introduction: Paroxysmal vocal fold motion, also known as vocal cord dysfunction (VCD), is the abnormal movement of the vocal cords during inspiration resulting in functional airway obstruction. Although history and pulmonary function testing may be strongly suggestive of a diagnosis of VCD, definitive diagnosis involves demonstration of abnormal vocal cord motion under direct laryngoscopy after stimulus provocation. We present three patients from our multidisciplinary VCD clinic with provocation studies that showed normal vocal cord motion and elucidated alternative diagnoses. These patients demonstrate the utility of post-provocation laryngoscopy in the evaluation of VCD. Cases: The first patient is a 39 year old female with symptoms of throat tightness, inspiratory stridor, and globus sensation after exercise. Exercise provocation led to a diagnosis of deconditioning when vocal cord motion was found to be normal. The patient was referred to a trainer for treatment. The second case is a 13 year old athletic female who presented with 6 months of shortness of breath and high pitched inspiratory stridor during exercise. Upon exercise provocation, the patient developed inspiratory stridor and tachypnea with a ventilation rate of 60 breaths per minute. She demonstrated normal post-provocation spirometry and laryngoscopy. A diagnosis of hyperventilation syndrome was made and the patient was treated by speech pathology with focused breathing and relaxation techniques. The third case is a 60 year old female who experienced the sensation of throat closure with exposure to strong odors such as cologne. Although laryngoscopy after provocation with smelling salts demonstrated normal movement of the vocal cords, significant retractions and narrowing of the musculature surrounding the hypopharynx was noted. She was referred to speech pathology to assist in relaxation of the accessory muscles of inspiration. Conclusion: VCD is often suspected in patients who experience respiratory distress with inciting stimuli. The three cases presented show that the diagnosis cannot be made by history alone and reinforce the need for direct laryngoscopy following provocation testing. As demonstrated by our series of patients, the correct diagnosis is essential in guiding appropriate therapy.

P314 CURRENT ALLERGIC RHINITIS EXPERIENCES SURVEY: CONSUMERS’ AWARENESS, ATTITUDES AND PRACTICES. L.M. Fromer*1, M.S. Blaiss2, J.A. Jacob-Nara3, R.M. Long4, K.M. Mannion4, L.A. Lauersen3, 1. Los Angeles, CA; 2. Memphis, TN; 3. Parsippany, NJ; 4. Baltimore, MD. Rationale:Allergic Rhinitis (AR) affects around 60 million people in the United States (US). The consumer arm of the Current Allergic Rhinitis Experiences Survey (CARES) evaluated awareness, attitudes and behaviors of AR sufferers to manage their condition. Methods: This US based survey evaluated 1600 adult AR sufferers to assess their perception of AR diagnosis, treatment preferences and interaction with healthcare professionals (HCPs). Two consumer groups of AR sufferers were assessed; over the counter (OTC) users only (n=1020) and prescription (Rx) users +/- OTC use (n=580). The Rx group had 451 intranasal steroid (INS) users. Results: 82% of respondents indicated that



ABSTRACTS: POSTER SESSIONS they require no to minimal HCP guidance to manage AR; 51% have not visited an HCP in past 2 years specific to AR. 86% of sufferers agreed they can confidently self-recognize AR symptoms and 69% suspected allergies prior to diagnosis. On suspecting nasal allergies, 52% of sufferers went to the store for an OTC medication. 64% of OTC only users perceived they can completely manage their nasal allergies, and 85% typically took one or more OTC medications prior to any HCP interaction. AR sufferers (69%) consider nasal allergies as a nuisance and not a serious problem. The most frequent symptoms included rhinorrhea and nasal congestion. The most bothersome ones were sleep disturbances(64%), headache(59%) and nasal congestion(58%). 82% of sufferers indicate being comfortable with self-education on AR, with only 23% noting they learned anything new about AR from their last HCP visit. 72% of AR sufferers are likely to go to an HCP if symptoms persist after having tried multiple OTC options. Sufferers showed good awareness about different OTC and Rx medications for AR treatment. High level of awareness about INS brands existed among both OTC and Rx users. Rx users perceived INSs to be more beneficial in treating AR and showed high level of satisfaction (7.4 score out of 10). 48% of AR sufferers still felt the need for more efficacious OTC medications to better manage their AR symptoms. Conclusion: The CARES study indicated that AR sufferers perceive that they self-recognize AR symptoms and initiate their management with OTC options. The availability of OTC medications did not deter AR sufferers from visiting HCPs for advice when symptoms worsen. Nonetheless, more efficacious OTC options are still desired.

P315 CURRENT ALLERGIC RHINITIS EXPERIENCES SURVEY: PRACTITIONERS’AWARENESS, ATTITUDES AND PRACTICES. M.S. Blaiss*1, L.M. Fromer2, J.A. Jacob-Nara3, R.M. Long4, L.A. Lauersen3, K.M. Mannion4, 1. Memphis, TN; 2. Los Angeles, CA; 3. Parsippany, NJ; 4. Baltimore, MD. Rationale: Allergic Rhinitis (AR) continues to be a common health problem in United States (US) despite the availability of many over the counter (OTC) medications. The healthcare practitioners’ (HCPs) arm of the Current Allergic Rhinitis Experiences Survey (CARES) assessed HCPs perceptions around how AR is currently being managed. Methods:This US based national survey included 375 Primary Care Physicians and 375 Nurse Practitioners/ Physician Assistants (who were representative of their populations at ≤ 5% margin of error). Participants were screened to ensure they treat at least 15 AR sufferers per month during an allergy season. Results:The majority of HCPs (86%) agreed that AR patients can easily recognize allergy symptoms after diagnosis and pointed out that 57% of their patients come to them self-recognizing their symptoms as AR. 82% of HCPs strongly agreed that patient history/symptoms and a physical exam are primary ways to diagnose a patient with AR. HCPs also reported that AR patients do not typically undergo diagnostic testing until after they have attempted some medication. HCPs reported that 77% of mild and 63% of moderate to severe AR patients can easily manage nasal allergies once treatment is established. HCPs reported that AR sufferers (71%) visit them to specifically discuss AR two times or less a year, while follow-up visits to evaluate the effectiveness of the medication generally do not occur. Treatment recommendations by HCPs for nasal allergies do not always depend upon the cause. According to surveyed HCPs, OTC medication should precede a prescription (Rx) medication for AR management. HCPs are comfortable with AR patients educating themselves about AR (65%), using OTC medications (70%), self-selecting OTC medications (62%) and knowing if their AR medication is working to provide symptom relief (75%). 82% HCPs considered intranasal steroids (INSs) to be the gold standard treatment for AR. HCPs have very minimal safety concerns around INS use and rarely monitor patients for potential side effects. Conclusion: HCPs perceive that patients easily recognize their AR symptoms and can self-manage the same. Patient history/symptoms and physical exam are the primary way of AR diagnosis. INSs are considered the gold standard for treatment of AR. However, most HCPs feel OTC medication should be tried prior to Rx medication for AR management.


P316 CURRENT ALLERGIC RHINITIS EXPERIENCES SURVEY: UNDERSTANDING HCP-CONSUMER INTERACTION. M.S. Blaiss*1, L.M. Fromer2, J.A. Jacob-Nara3, R.M. Long4, L.A. Lauersen3, K.M. Mannion4, 1. Memphis, TN; 2. Los Angeles, CA; 3. Parsippany, NJ; 4. Baltimore, MD. Rationale: The incidence of allergic rhinitis (AR) has continued to rise dramatically over the years. Presently, AR affects around 60 million people in the United States (US). The Current Allergic Rhinitis Experiences Survey (CARES) assessed AR sufferers and healthcare practitioners (HCPs) perspectives of how AR is perceived, diagnosed and managed in the US. Methods: A US based survey was conducted among 1600 adult AR sufferers including over the counter (OTC) users only (n=1020), prescription (Rx) users with/without OTC use (n=580) and 750 HCPs including 375 primary care physicians (PCPs), and 375 Nurse Practitioners/Physician Assistants (NP/PAs). The samples for PCPs, NP/PAs, and each AR sufferer group were representative of their populations at ≤ 5% margin of error. Research questionnaires asked participants about the impact, diagnosis and management of AR. Results: The majority of HCPs (82%) strongly agreed that the diagnosis of AR symptoms is commonly based on discussion of current and/or past AR symptoms and through physical exam. HCPs also indicated that AR patients do not typically undergo diagnostic testing until they have used some medication. AR sufferers agreed they were very likely to visit a HCP if dissatisfied with their OTC treatment (51%) or if their allergy symptoms became severe (72%). According to HCPs, 70% of patients typically request a medication during an office visit. Also, 43% of HCPs agree with the statement that AR is undertreated because HCP office visits are too expensive. AR sufferers note that their symptoms impact daily activities with an average of 12.0 days missed per year due to nasal allergies. AR sufferers are aware of both OTC and Rx medications currently available for the treatment of AR. Significantly more Rx users are aware of INS brands than OTC only users. AR sufferers prefer OTC medications for ease of access (56%), convenience (47%), and decreased cost (38%). 48% of sufferers agree they could manage their allergy symptoms better if they had more effective medications available in OTC domain. Conclusion: The CARES study demonstrated that the majority of AR sufferers would visit an HCP if symptoms persist after having tried OTC options. However, some dissatisfaction with currently available OTC medications remains. More efficacious OTC medications can further improve access, consumer satisfaction, and overall AR management.

P317 EVALUATION OF THE PATIENTS WITH RECURRENT CROUP. S. Asilsoy1, B. Usta Guc*2, F.G. Cihan2, R. Kutlu2, 1. Adana, Turkey; 2. Konya, Turkey. Background: In this study, we aimed to question the causes and affecting factors of recurrent croup. Methods: The recurrent croup patients were evaluated between May 2009 - 2012. Minimum three episodes of croup annually, was defined as recurrent croup. Patients’ medical history, physical examination findings, presence of atopy (asthma, allergic rhinitis, atopic dermatitis in patients, parents or siblings), symptoms like heart-burn, and/or bad taste in the mouth were all evaluated. Allergy skin prick testing was performed in all patients and gastroesophageal scintigraphy was done in patients experiencing heartburn, and/or bad taste in the mouth. Results: 100 patients (77% male) between 0,4-14 (4,55 ± 2.76) years old, were included. In 63 of the patients (63%), wheezing accompanied the croup complaints. There was spasmodic croup in 24 patients (24%), it was triggered by viral infections in 18 patients (18%), it had sudden onset (spasmodic croup) and/or induced by viral infections in 58 patients (58%). There was co-morbiding laryngotracheobronchitis (54%), atopic dermatitis(12%) and atopic family history (46%). Total IgE was 184 ± 230 kU/L and total eosinophil count was 277 ± 237/mm3. Gastroosephagial reflux was suspected in 82 patients, and 34 (41,5%) of them was detected positive. Skin prick tests were performed in 100 of the patients, and atopy was diagnosed in 36 of them (36%). Atopy was 3.378 times more prevalent in male patients. Laryngotracheobronchitis was 2 times more prevalent in atopic patients. Croup symptoms were persistent in 25 patients. There was no statistically significant relation between persistent croup and age, IgE level, total eosinophil count, GER, atopy presence. Direct laryngoscopy was conducted in these patients, and an anomaly was identified in 12 patients. Five of the patients with recurrent croup were under 1 year old; in these patients reflux was searched by barium swallowing test for a probable vascular ring and anatomical anomaly, and apparent reflux was detected in four patients. Conclusion: Recurrent croup is a clinical concept. Even thought it is frequent in pediatric population, its eti-


ABSTRACTS: POSTER SESSIONS ology, natural course and epidemiology is not clear yet. The underlying pathologies and other contributing factors should be carefully examined. GER and atopy should be scanned. Recurrent croup patients with atopy should be followed closely for developing bronchial asthma.

P318 THE ALLERGIES, IMMUNOTHERAPY AND RHINOCONJUNCTIVITIS (AIRS) PROVIDER SURVEY: HOW PROVIDERS DIFFER. L. Bielory*1, M. Blaiss2, T. Craig3, B. Leatherman4, M. Dykewicz5, F. AllenRamey6, N. Walstein7, J. Hadley8, G. Ortiz9, D. Skoner10, 1. Springfield, NJ; 2. Germantown, TN; 3. Hershey, PA; 4. Gulfport, MS; 5. WinstonSalem, NC; 6. West Point, PA; 7. Phoenixville, PA; 8. Naples, FL; 9. El Paso, TX; 10. Pittsburgh, PA. Introduction: Allergic Rhinoconjunctivitis (ARC) is one of the most common chronic diseases in the US. Management of ARC encompasses avoidance, pharmacologic agents, and use of specific immunotherapy (SIT). The Allergies, Immunotherapy & RhinoconjunctivitiS (AIRS) provider survey was designed to assess provider’s perceptions of allergy symptoms, allergy testing and SIT. Methods: A telephone survey was administered to 500 healthcare providers offering outpatient care to >1 ARC patient per week. Providers were randomly selected from professional society lists by specialty to yield completed surveys from 100 Allergy/Immunology (AI), 100 Otolaryngology (ENT), 75 Family Medicine (FM), 75 Pediatric (PED) and 50 Ophthalmology/Optometry (OPH/OPT) physicians along with 50 Nurse Practitioners (NP) and 50 Physician Assistants (PA). Results: Overall, providers reported itchy eyes (62%) as the primary reason allergy patients sought treatment followed by nasal congestion (58%). Specialty-level results showed nasal congestion as the most frequent symptom among patients seen by AI (79%), FM (64%), and ENT (85%) with itchy eyes as the second most common (64%, 51%, 45%, respectively). Eye symptoms were the most common for OPH/OPT. Nearly all providers (>90%) reported at least a moderate amount of impact of allergies on a patients’ quality of life. Allergy testing was performed primarily by AI (95%) and ENT (63%) versus other specialists (OPH/OPT: 4% - FM: 37%). Greater than 90% of all specialists agreed that patients with severe symptoms should be treated with SIT. AI recommended SIT to the largest proportion of ARC patients (adult: 41%; pediatric: 39%) while FM recommended to the smallest proportion (adult: 11%, pediatric: 10%). Likewise, AI reported SIT as being currently used by the greatest number of their patients (adult: 33%, pediatric: 28%) and least by FM (adult: 8%, pediatric: 8%). Fewer OPH/OPT(86%) either provided or referred for SIT compared to other specialists with >95% provide or refer for SIT. One of the major barriers for not recommending SIT was that providers (N=64) did not feel it was in their scope of practice. Conclusions: Provider differences exist for diagnosis and management of ARC. Targeted educational efforts and development of collaborations across provider specialties could maximize care and enhance appropriate use of SIT for allergy patients.

days. Reflective total ocular symptom score (rTOSS; AM + PM; Max = 18) was an important secondary endpoint. Results: Patients aged 12-17 yrs treated with MP29-02 experienced a 4.29 point mean improvement from baseline in their rTNSS, significantly more the 2.06 point improvement observed in those treated with placebo (diff: 2.23; 95% CI: 3.23; 1.22; p<0.0001). Similarly, in this adolescent patient population treatment with MP29-02 produced a significant mean improvement in the rTOSS of 2.23 points from baseline compared to 1.04 points with placebo (diff: 1.19; 95% CI: 2.06, 0.32; p=0.0080). Conclusion. These results show that adolescent SAR patients treated with MP2902 experience significant relief from both their nasal and ocular symptoms. Similar beneficial effects may be expected in pediatric patients.

P320 MP29-02 RELIEVES ALL INDIVIDUAL NASAL AND OCULAR SYMPTOMS IN SEASONAL ALLERGIC RHINITIS (SAR) PATIENTS, PARTICULARLY NASAL CONGESTION AND OCULAR ITCH. W. Carr*1, U. Munzel2, N. Ruiz3, P. Lieberman4, 1. Mission Viejo, CA; 2. Bad Homburg, Germany; 3. Somerset, NJ; 4. Memphis, TN. Introduction: Nasal congestion is the most bothersome nasal symptom of SAR, but any symptom can predominate in a given patient. Ocular symptoms, particularly itch, have the greatest impact on quality of life. Here, we assess the efficacy of MP29-02 (a novel intranasal formulation of azelastine hydrochloride [AZE] and fluticasone propionate [FP]) in providing individual nasal and ocular symptom relief, plus relief for patients with a predominant symptom. Methods: 610 patients (≥ 12 years old) with moderate-to-severe SAR were randomized into a double-blind, 14-day, parallel-group trial comparing MP29-02, AZE, FP or placebo (PLA) nasal sprays (1 spray/nostril bid; total daily doses: AZE 548 mg; FP 200 mg). Change from baseline (CFB) in nasal and ocular symptom scores was assessed by ANCOVA. CFB in patients’ predominant symptom was assessed post-hoc. Patients were defined as congestion-, itching-, rhinorrhoea- or sneezing-predominants based on max. symptom scores at baseline. Results: MP29-02 provided superior relief from all individual and predominant symptoms of congestion, nasal itch, rhinorrhoea, sneezing and ocular itch than either AZE or FP. The magnitude of this effect was particularly evident for congestion and ocular itching (Table). Conclusion: MP29-02 universally relieves all symptoms associated with SAR, especially nasal congestion and ocular itch, including those patients who present with nasal congestion or ocular itch predominantly. Compared to AZE or FP alone, MP2902 is a superior SAR treatment.

P319 MP29-02 EFFECTIVELY RELIEVES BOTH NASAL AND OCULAR SYMPTOMS IN ADOLESCENTS AGED 12-17 YEARS: RESULTS FROM 4 RANDOMIZED CONTROLLED SEASONAL ALLERGIC RHINITIS (SAR) TRIALS. E. Sher*1, C. Maccia2, S. Gawchik3, U. Munzel4, N. Ruiz5, S. Goldstein6, 1. Ocean City, NJ; 2. Warren, NJ; 3. Upland, PA; 4. Bad Homburg, Germany; 5. Somerset, NJ; 6. New York, NY. Introduction: Two large pediatric studies are currently underway in the United States to investigate the efficacy and safety of MP29-02 (Dymista) in children, with a view to extending its indication to those aged ≥ 6 years. In line with FDA recommendations, these studies compare MP29-02 to placebo. In preparation for these clinical trial results, and in order to mimic the clinical trial design of these on-going pediatric studies, this meta-analysis assessed all the data available for moderate-to-severe SAR patients aged 12-17 years, who received either MP29-02 or placebo in the same vehicle and device. Methods: Data from 4 multi-centre, parallel-group, randomized, double-blind, placebocontrolled, 14-day studies were pooled. A total of 97 patients aged 12-17 yrs received MP29-02 (a novel intranasal formulation of azelastine hydrochloride [AZE] and fluticasone propionate [FP]) 1 spray/nostril bid (total daily dose: AZE 548 mcg; FP 200 mcg) and 112 patients received placebo spray 1 spray/nostril bid. The primary efficacy variable was change from baseline in reflective total nasal symptom score (rTNSS; AM +PM; MAX=24), over 14-

+ [1-(FP or AZE - PLA)/(MP29-02 - PLA)] x 100 * significant vs PLA

P321 TYMPANOMETRIC ALTERATIONS IN PATIENTS FROM 12 TO 20 YEARS OF AGE WITH ALLERGIC RHINITIS. L. Rangel*, L.A. Dominguez-Sansores, S.N. Gonzalez-Diaz, A. Arias-Cruz, J.A. Buenfil-Lopez, I.V. Yanez-Perez, H. HernandezSanchez, Monterrey, Nuevo Leon, Mexico. Background: Allergic rhinitis is an inflammatory process of the nasal mucosa,caused by exposure to allergens in previously sensitized individuals.



ABSTRACTS: POSTER SESSIONS Otitis media with effusion is among the main conditions associated with allergic rhinitis which can lead to tympanometric alterations Objective: To determine the tympanometric alterations that occurs in adolescent patients with allergic rhinitis and compared with a control group. Method: We included 55 patients aged 12 to 20 years which were divided in two groups: a group of patients with allergic rhinitis (29 patients) and a control group without allergic rhinitis (27 patients), both groups underwent skin tests with aeroallergens, ISAAC survey was applied. Additionally all patientts underwent tympanometry. Using SPSS 20 program we analyzed nominal and ordinal variables, frequencies and percentages, plus contingency tables and correlation of variables with Pearson test and Chi-square; being considered statistically significant a P < 0.05. Results: The mean age of patients included in the study was 18.1 years. Symptoms in patients with perennial allergic rhinitis were predominantly perennial and the average time of evolution was 9 years. In all control subjects, skin tests were negative. The allergen to which were sensitized with more frequency the patients with allergic rhinitis was Dermatophagoides pteronyssinus. Tympanometric alterations were identified in only 3.4% of patients with allergic rhinitis and in 7.7% of subjects in the control group (p = 0.6). No difference in the frequency of tympanometric alterations in relation to the duration of allergic rhinitis or the number of positive allergen skin tests was found. Conclusion: We found no statistically significant difference in the frequency of tympanometric alterations between the group of patients with allergic rhinitis and control groups.

PAR were initiated on BDP nasal aerosol. Web-based surveys were used for patient follow-up. INS treatment satisfaction was assessed at baseline when used within the prior 2 years and at follow-up if INS was being used. The validated brief Treatment Satisfaction Questionnaire for Medication (TSQM-9) consisted of 9 items in 3 subscales: Effectiveness, Convenience and Global Satisfaction with medication. Each subscale was scored from 0-100 with higher scores representing greater satisfaction with INS. Results: The 43 study centers enrolled 824 patients; mean age was 38.0 years, 61.7% female; 85.9% Caucasian; and their mean duration of PAR was 15.7 years. Of those enrolled, 491 (59.6%) had used a prior INS and completed the TSQM-9 at baseline. The mean baseline Effectiveness score was 50.2 (Standard Deviation [SD]: 16.5); the mean baseline Convenience score was 67.6 (SD: 16.9); and the mean baseline Global Satisfaction score was 53.3 (SD: 19.4). At three months, 227 (46.2%) patients completed the TSQM-9 and 194 (85.5%) were continuing to use BDP nasal aerosol. Their mean change from baseline for the Effectiveness subscale was 14.5 (Standard Error [SE]: 1.8; 95% Confidence Interval [CI]: 10.8-18.1); mean change from baseline for the Convenience subscale was 10.4 (SE: 1.6; 95% CI: 7.2-13.6); and mean change from baseline for the Global Satisfaction subscale was 12.4 (SE: 1.9; 95% CI: 8.8-16.1). Conclusions: BDP nasal aerosol was associated with three-month improvement in patient-perceived treatment effectiveness, convenience and global satisfaction compared to previous INS use.


P322 AN ELECTRONIC PATIENT DATA ACQUISITION TABLET (EPDAT) IDEAL FOR RAPID ONSET-OF-ACTION DATA COLLECTION. A. Salapatek*, V. Nelson, D. Wilson, P. Patel, Mississauga, ON, Canada. Introduction: The onset of action (OOA) of allergy medication relief is an important measure to both patients and researchers. To date, the use of paper diary cards has limited the ability to capture the earliest post-treatment time point and thereby the earliest OOA. An Electronic Patient Data Acquisition Tablet (ePDAT) has been created which allows for rapid, easy collection of patient-reported outcomes (PRO). Methods: Sixty-four subjects with a confirmed history of allergic rhinitis to ragweed allergen participated in a 6 hour Environmental Exposure Chamber (EEC) visit. During their exposure patients recorded Total Nasal Symptom Scores (TNSS) using the ePDAT at 0, 15, 30 minutes and every 30 minutes thereafter for the remainder of the visit. ePDAT is an electronic PRO (ePRO) system that has an intuitive graphical user interface to display fully customizable questionnaires or visual analog scales on a touch-screen tablet. Results: We have developed an ePDAT that is fully validated and CFR21 part 11 compliant for use in our EEC, mobile EEC (mEEC) and at home. During a 6 hour exposure period in an EEC our ePDAT captured over 5800 unique study data values at specific time points. 93% of all instantaneous TNSS (including nasal itching, rhinorrhea, sneezing and congestion) data values were captured within a minute of the symptom score assessment time, and 100% of all TNSS were captured within 4 minutes and therefore 100% patient compliance was obtained within 4 minutes. Conclusions: ePDAT is an innovative ePRO device that allows patients to report their symptoms rapidly and accurately. This will improve the quality of PRO and will lead to a better understanding of the drug response time course and ensure patient compliance.

P323 BECLOMETHASONE DIPROPIONATE NASAL AEROSOL FOR PERENNIAL ALLERGIC RHINITIS: SATISFACTION WITH INTRANASAL CORTICOSTEROIDS AFTER THREE MONTHS. R.D. O’Connor*1, K.K. Sheth2, D.A. Bukstein3, W.R. Reisacher4, M.S. Lepore5, G.H. Gopalan5, P.O. Buck5, 1. San Diego, CA; 2. Lafayette, IN; 3. Milwaukee, WI; 4. New York, NY; 5. Frazer, PA.

REAL-WORLD USE OF BECLOMETHASONE DIPROPIONATE NASAL AEROSOL BY PATIENTS WITH PERENNIAL ALLERGIC RHINITIS: EFFECTIVENESS ON RHINITIS CONTROL AFTER THREE MONTHS. K.K. Sheth*1, D.A. Bukstein2, R.D. O’Connor3, W.R. Reisacher4, M.S. Lepore5, G.H. Gopalan5, P.O. Buck5, 1. Lafayette, IN; 2. Milwaukee, WI; 3. San Diego, CA; 4. New York, NY; 5. Frazer, PA. Introduction: A prospective, observational, patient-centered outcomes registry, Investigation of the Real World Effectiveness of Beclomethasone Dipropionate (BDP) Nasal Aerosol in Perennial Allergic Rhinitis (PAR) Subjects (BALANCE), was implemented in 2012. BALANCE assessed monthly changes in patient-reported rhinitis control over six months. The objective of this analysis was to show the interim results for rhinitis control at three months. Methods: BALANCE study participants were enrolled at allergy, otolaryngology and primary care clinics in the US between July and December 2012. IRB approval and informed consent for all research subjects was obtained. Enrollees with a minimum one-year history of PAR were initiated on BDP nasal aerosol. Web-based surveys were used for patient follow-up. The primary outcome, rhinitis control, was measured by change from baseline on the validated Rhinitis Control Assessment Test (RCAT), with a clinically important difference of three points. Higher scores indicated better rhinitis control. Interim analyses, planned at three months of follow-up, are shown here. Results: The 43 study centers enrolled 824 patients. Mean age was 38.0 years; 61.7% were female; 85.9% were Caucasian; 75.6% also had seasonal allergic rhinitis (SAR); 48.2% had used other intranasal corticosteroids in the past two years; and their mean duration of PAR was 15.7 years. Of the 824 patients, 755 (91.6%) completed three-month follow-up surveys, and, of these, 655 (86.8%) continued using BDP nasal aerosol. The mean RCAT score at baseline was 15.8 (Standard Deviation [SD]: 3.4), and the mean 3-month change for all respondents was 5.8 (Standard Error [SE]: 0.2; 95% Confidence Interval [CI}: 5.4-6.2). For those continuing to use BDP nasal aerosol the mean change in RCAT score was 6.1 points (SE 0.2; 95% CI: 5.7-6.5) while for those who had stopped BDP nasal aerosol the mean change in RCAT score was 3.8 points (SE: 0.5; 95% CI: 2.84.7). The percent of responders to BDP nasal aerosol with at least three-point improvement on the RCAT at three months was 76.6% (95% CI: 73.4-79.9). Conclusions: The real-world effectiveness of BDP nasal aerosol on rhinitis control in patients with PAR was confirmed after three months of use.

Introduction: Beclomethasone Dipropionate (BDP) in a non-aqueous or “dry” aerosolized spray has been FDA-approved for treatment of nasal symptoms associated with perennial allergic rhinitis (PAR), and is being investigated in a prospective, observational, patient-centered registry, the BALANCE study. Outcome measures include treatment satisfaction with intranasal corticosteroids (INS). This analysis shows the interim results for patient-reported treatment satisfaction with INS after 3 months of use. Methods: BALANCE study participants were enrolled at allergy, otolaryngology and primary care clinics in the US between July and December 2012. IRB approval and informed consent for all subjects was obtained. Enrollees with a minimum one-year history of




P325 GRASS SUBLINGUAL IMMUNOTHERAPY TABLET TREATMENT IS ASSOCIATED WITH SIMILAR EFFICACY AND SAFETY IN CHILDREN AND ADULTS: SUBGROUP ANALYSIS OF DATA FROM A LARGE NORTH AMERICAN TRIAL. H. Nolte*1, D.I. Bernstein2, H. Nelson3, A. Kaur1, J. Maloney1, 1. Whitehouse Station, NJ; 2. Cincinnati, OH; 3. Denver, CO. Rationale: Trials of sublingual immunotherapy for allergic rhinitis with or without conjunctivitis (AR/C) in North American subjects are few, particularly among children. A previous North American pediatric trial found timothy grass sublingual immunotherapy tablet (Phleum pratense, 2800 BAU; 75,000 SQ-T) treatment to show efficacy and safety similar to that seen in a corresponding adult trial; however, other sublingual immunotherapy research has suggested treatment effect may be inconsistent between children and adults. Using data from a double-blind controlled trial including children and adults—the largest published immunotherapy study yet conducted—we evaluated a timothy grass sublingual immunotherapy tablet treatment in North American pediatric and adult subgroups with AR/C. Methods: North American subjects (5-65 yrs) with grass allergy were randomized 1:1 to once-daily grass immunotherapy tablet or placebo. The first dose was given on site; subsequent doses were self-administered. The primary efficacy endpoint was total combined score (TCS = rhinoconjunctivitis daily symptom score [DSS] plus daily medication score [DMS]) over entire grass pollen season (GPS). Approval was obtained from appropriate IRBs and informed consent obtained from all research subjects. Results: 1501 subjects were randomized; 283 (19%) were aged 5 to <18 years. Among subjects aged 5 to <18 years, the grass immunotherapy tablet was associated with a median reduction vs placebo of 32% (−1.32 score; 2.77 vs 4.09; P=.02) in TCS. Among subjects aged 18 to 65 years, the grass immunotherapy tablet was associated with a median reduction vs placebo of 21% (−0.9 score; 3.33 vs 4.24; P<.001) in TCS. Adverse event rates were similar between treatment groups and among age categories (73-80% and 65-84% for grass immunotherapy and placebo respectively among age categories). Most adverse events were self-limited, mild or moderate local application-site reactions. No severe systemic allergic events were reported. Conclusion: In this large North American trial, treatment with timothy grass sublingual immunotherapy tablet was effective and well tolerated in grass-allergic children and adults with AR/C. The 2800 BAU sublingual tablet was associated with similar efficacy and safety between pediatric and adult subgroups.

P326 EFFECT OF SUBLINGUAL IMMUNOTHERAPY TABLET TREATMENT ON DAILY MEDICATION SCORE USING ALTERNATIVE SCORING METHODS BASED ON WAO RECOMMENDATIONS. T. Casale*1, H. Nolte2, J. Maloney2, A. Kaur2, H. Nelson3, 1. Omaha, NE; 2. Whitehouse Station, NJ; 3. Denver, CO. Rationale: The efficacy of specific immunotherapy can be assessed by multiple means including effect on rescue medication use (daily medication score, or DMS). Trial designs have used different weighting models for rescue medication; the World Allergy Organization (WAO) has proposed standardized weighting to help facilitate comparison across studies. Methods: Data from 5 randomized trials of sublingual immunotherapy tablet treatment for subjects with allergic rhinitis with or without conjunctivitis (AR/C) were analyzed (3 trials including 2800 BAU/75,000 SQ-T sublingual tablets and placebo; 2 ragweed trials including 6 and 12 Amb a 1-U sublingual tablets and placebo). Approval was obtained from appropriate IRBs and informed consent obtained from all research subjects. As per protocols, all trials scored daily rescue medication use as follows: oral antihistamine, up to 6 pts; ocular antihistamine, up to 6 pts; intranasal corticosteroid, up to 8 pts; oral steroid, up to 16 pts. We analyzed DMS with an adjusted weighting based on WAO recommendations, but including the medications used in per-protocol DMS: oral antihistamine, up to 1 pt; ocular antihistamine, up to 1 pt; intranasal corticosteroid, up to 2 pts; oral steroid, up to 3 pts. The primary analysis period was entire pollen season in grass trials and peak season in ragweed trials. Results: The Table shows DMS in the 5 studies by per-protocol and adjusted scoring methods. DMS was consistently reduced by grass and ragweed sublingual tablets, by differences ranging from 26% (P=.084) to 45% (P=.0001) according to per-protocol scoring and 26% (P=.078) to 47% (P<.0001) according to adjusted scoring. Conclusions: Grass and ragweed sublingual immunotherapy tablet treatments were associated with lower medication use vs placebo. Analysis of DMS as per the adjusted scoring methods based on WAO recommendations showed results similar to the per-protocol weighting.

P327 EFFICACY AND SAFETY OF GRASS SUBLINGUAL IMMUNOTHERAPY TABLET TREATMENT IN A LARGE RANDOMIZED CONTROLLED TRIAL IN NORTH AMERICAN CHILDREN AND ADULTS. J. Maloney*1, D.I. Bernstein2, H. Nelson3, P. Creticos4, J. Hebert5, M. Noonan6, D. Skoner7, Y. Zhou1, A. Kaur1, H. Nolte1, 1. Whitehouse Station, NJ; 2. Cincinnati, OH; 3. Denver, CO; 4. Baltimore, MD; 5. Quebec, QC, Canada; 6. Portland, OR; 7. Pittsburgh, PA. Rationale: In North America, few studies have evaluated sublingual immunotherapy for allergic rhinitis with or without conjunctivitis (AR/C), and pediatric data are sparse. We report findings from the largest published immunotherapy trial yet conducted in adults and children. This multicenter trial evaluated grass sublingual immunotherapy tablet treatment in subjects with AR/C. Methods: North American subjects (5-65 yrs) with grass allergy were randomized 1:1 to once-daily grass immunotherapy tablet (Phleum pratense, 2800 BAU; 75,000 SQ-T) or placebo. Approval was obtained from appropriate IRBs and informed consent obtained from all research subjects. The primary efficacy endpoint was total combined score (TCS = rhinoconjunctivitis daily symptom score [DSS] plus daily medication score [DMS]) over entire grass pollen season (GPS). Key secondary endpoints included entire-season DSS and DMS and peak-season TCS and rhinoconjunctivitis quality-of-life questionnaire (RQLQ) scores. Safety endpoints included adverse events (AEs). Results: 1501 subjects were randomized; 85% were multisensitized and 25% had asthma. Grass immunotherapy tablet yielded improvements versus placebo of 23% in entire-season TCS (median difference: –0.98, P < .001), 29% in peakseason TCS (median difference: –1.33, P < .001), 20% in entire-season DSS (median difference: –0.64, P = .001), 35% in entire-season DMS (mean difference: –0.48, P < .001), and 12% in peak-season RQLQ (median difference: –0.13, P = .027). Efficacy was similar between children and adults. Most AEs were transient local application-site reactions, with no serious treatment-related AEs or anaphylactic shock. Three subjects (2 grass tablet, 1 placebo) had moderate systemic allergic reactions. Conclusion: In the largest published immunotherapy trial conducted to date, grass immunotherapy tablet was effective in grass-allergic North American children and adults with AR/C, confirming previous research.






REAL-WORLD EFFECTS OF BECLOMETHASONE DIPROPIONATE NASAL AEROSOL ON SLEEP QUALITY AMONG PATIENTS WITH PERENNIAL ALLERGIC RHINITIS. D.A. Bukstein*1, R.D. O’Connor2, K.K. Sheth3, W.R. Reisacher4, M.S. Lepore5, G.H. Gopalan5, P.O. Buck5, 1. Milwaukee, WI; 2. San Diego, CA; 3. Lafayette, IN; 4. New York, NY; 5. Frazer, PA.


Introduction: Perennial Allergic Rhinitis (PAR) is associated with disturbances of sleep. The BALANCE study, a prospective, observational, patient-centered registry assessed the real-world effect of non-aqueous beclomethasone dipropionate (BDP) nasal aerosol on sleep quality after 3 months of use. Methods: BALANCE study participants were enrolled at allergy, otolaryngology and primary care clinics in the US between July and December 2012. IRB approval and informed consent for all subjects was obtained. Enrollees with a minimum one-year history of PAR were initiated on BDP nasal aerosol. Web-based surveys were used for patient follow-up. Sleep quality was assessed with the validated, self-reported 19-item Pittsburgh Sleep Quality Index (PSQI); it generated 7 component scores: subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleeping medication, and daytime dysfunction. Scores ranged from 0-3 and could be combined for a global score ranging from 0-21 with lower scores indicating better sleep quality. Results: The 43 study centers enrolled 824 patients in the BALANCE study; mean age was 38.0 yrs; 61.7% female; 85.9% Caucasian; and mean duration of PAR was 15.7 yrs. At baseline, 815 patients completed the PSQI. Mean baseline component scores were: subjective sleep quality 1.4 (Standard Deviation [SD]: 0.7); sleep latency 1.6 (0.9); sleep duration 0.7 (0.9); habitual sleep efficiency 0.9 (1.1); sleep disturbances 1.7 (0.6); use of sleeping medication 0.7 (1.1); and daytime dysfunction 1.3 (0.8). At 3 months, 652 patients (80.0%) continued to use BDP nasal aerosol and completed the PSQI. Their mean change component scores from baseline were: subjective sleep quality -0.4 (95% Confidential Interval [CI]: -0.4, -0.3); sleep latency -0.5 (95% CI: -0.5, -0.4); sleep duration -0.3 (95% CI: -0.3, -0.2); habitual sleep efficiency -0.2 (95% CI: -0.3, -0.1); sleep disturbances -0.4 (95% CI: -0.4, -0.3); use of sleeping medication -0.3 (95% CI: -0.4, -0.2); and daytime dysfunction -0.4 (95% CI: -0.4, -0.3). The global mean PSQI score at baseline was 8.3 (3.6), with a mean change at 3 months of -2.3 (95% CI: -2.6, -2.1). Conclusions: BDP nasal aerosol was associated with patient-reported improvement in global sleep quality and each of the components of the PSQI after 3 months of use.

P329 RESULTS OF ALLERGY ASTHMA NETWORK MOTHERS OF ASTHMATICS (AANMA) ONLINE SURVEY OF PATIENTS USING NASAL CORTICOSTEROIDS (NCS). A. Nguyen*1, M. Shams1, N. Sander2, L. Ross2, S. Fineman1, 1. Atlanta, GA; 2. McLean, VA. Purpose: To investigate impressions and practices of patients using nasal corticosteroids (NCS). Methods: NCS users and caregivers voluntarily responded to an online patient survey developed and distributed by the Allergy Asthma Network Mothers of Asthmatics (AANMA) to social media networks, family and professional membership, and coalition lists including allergist offices over a two week period. Results: 1592 respondents completed surveys (74.9% for themselves and 25.1% as a caregiver). NCS users were adults (52.9%, 3160 years of age) and children (20.5%, 5-18 years of age). Respondents used the following medications: NCS seasonally or as needed (48.6%), other allergy medications (75%), asthma medications (57%), and inhaled corticosteroids (49%). NCS respondents relied on physicians to diagnosis and treat nasal symptoms (91%) and designated an allergist as the preferred physician (76.9%). NCS users reported satisfaction with their therapy: 43.7% satisfied, 31.9% very satisfied, 16.6% completely satisfied. Respondents knew why NCS was prescribed (97%), how quickly to expect results (79.4%), what to do if symptoms did not respond (69.1%) and when to see a physician for follow-up (68.2%). Respondents were instructed to aim nasal spray away from septum (77.7%) and to obtain annual eye exams (43.6%). Conclusions: Patients using NCS were generally satisfied with their NCS therapy and preferred to rely on allergists or other experienced physicians for accurate diagnosis and monitoring of treatment. Although most patients were instructed on the proper use of NCS, there may be room for improvement in patient education. Electronic surveys are a powerful technique to efficiently obtain patient preference practices.


Background: There is limited data regarding alternative treatments for antihistamine refractory chronic idiopathic urticaria (CIU), also recently termed chronic spontaneous urticaria. Patients with recalcitrant skin disease are often unable to gain satisfactory symptom control with standard therapies, such as antihistamines, and often require prolonged courses of oral corticosteroids. The success of sulfasalazine therapy in these patients has been supported by case series and reports. However, there is a lack of information describing the degree and duration of sulfasalazine’s efficacy, the frequency and nature of adverse reactions and the appropriate safety monitoring parameters for those undergoing sulfasalazine therapy. In this report, we present a case series detailing the efficacy and safety of sulfasalazine therapy in patients with CIU. Methods: A retrospective chart review was conducted of 39 sulfasalazine treated, CIU patients evaluated at Johns Hopkins Asthma and Allergy Center from October 2007 to March 2012. Eight subjects were excluded from analysis due to insufficient data or insufficient trial of sulfasalazine therapy. Results: Overall, 83.9% of patients (n=26) experienced an improvement in symptoms within the first 3 months, with 51.6% of patients (n=16) becoming asymptomatic within the first 6 months of starting sulfasalazine. Eleven (35.4%) patients ultimately achieved total relief of symptoms after a complete taper off of sulfasalazine therapy. This subset of patients received sulfasalazine for a mean of 68.6 weeks, averaging 38.2 weeks at therapeutic dosages prior to tapering. Five of the 31 patients (16.1%) failed treatment as defined by worsening symptoms and pursuit of an alternate therapy. In this series, 19.4% (6/31) of patients experienced a modified course of sulfasalazine therapy due to abnormal hematologic parameters. Serious adverse events leading to drug discontinuation occurred in 6.5% of patients (n=2) and included a patient with drug-induced leukopenia and one with rhabdomyolysis. Conclusion: This case series demonstrates that sulfasalazine is a highly effective treatment for patients with antihistamine resistant CIU. However, the frequency of adverse events leading to the alteration of the sulfasalazine treatment supports the need for close observation and monitoring of these patients.

P331 CASE REPORT: LONGSTANDING NON-SPECIFIC PRURITUS DIAGNOSED AS MASTOCYTOSIS: THE IMPORTANCE OF OBTAINING A SERUM TRYPTASE WHEN EVALUATING PRURITUS, RASHES AND URTICARIA. R.M. Harris*, M.S. Johnson, Beverly Hills, CA. This is a case report of a 90 year old female with persistent severe and diffuse pruritus lasting for over 8 months, poorly responsive to medications including cetirizine, and Doxepin. Her workup included a skin biopsy that showed perivascular mononuclear infiltrate with scattered eosinophils consistent with a drug reaction or a bite reaction on staining followed by CD-117 stain showing mildly increased mast cell numbers of “uncertain significance”. Her evaluation in our office showed no history of liver disease, no medication changes, no changes in household products, no supplements or herbal products. She did have an elevated sed rate and borderline positive ANA by history. On exam she had a diffuse, non specific, non hyper pigmented rash with significant excoriation over most of her body. Some of these lesions looked unusual and a deep pressure stroke of the skin over several the lesions caused an urticarial eruption, a positive Darrier’s sign. Further labs showed a tryptase of 70 (N=210) and a repeat Tryptase of 55. She was referred to Hematology-Oncology but due to her age it was decided that a bone marrow was not recommended. We prescribed Periaction (cyprohepatadine) and she had a partial response. It was suggested that she try p.o. Ketotifen (Zaditen) but was lost to followup. In all evaluations of persistent pruritis, rashes and urticaria we feel that it is important to always obtain a serum Tryptase level, and indeed we diagnosed a cutaneous Mastocytosis case later in the same year by tryptase levels.


ABSTRACTS: POSTER SESSIONS utes). The remaining 32.2% (95%, CI 22%-45%) answered “none of the above”. Of the 86 family physicians, 15.1% (95%, CI 9%-24%) indicated a preference for frequent bathing, (6 for daily bathing more than 10 minutes and 7 for daily bathing less than 10 minutes). In contrast, 66.3% (95%, CI 56%-75%) indicated a preference for limiting bathing, (5 for less than daily bathing for more than 10 minutes, and 52 for less than daily bathing for less than 10 minutes). The remaining 19.8% (95%, CI 13%-29%) answered “none of the above.” Conclusion:There is no consensus among PCPs in Maine regarding routine bathing in pediatric AD; although there is a tendency toward recommending limiting bathing to every other day or less. Studies are needed to evaluate whether frequency and/or duration of bathing makes any clinical difference.


P332 EFFICACY OF OMALIZUMAB, AN ANTI-IGE RECOMBINANT, HUMANIZED, MONOCLONAL ANTIBODY, FOR THE TREATMENT OF SEVERE CHRONIC IDIOPATHIC URTICARIA PATIENTS NOT CONTROLLED ON ORAL ANTIHISTAMINES. S.M. Nsouli*, Danville, CA. For Severe Chronic Idiopathic Urticaria (CIU) patients that remain symptomatic on an H1-Receptor Antagonist, Cetirizine, the addition of Omalizumab, a recombinant, humanized, chimeric, anti-IgE monoclonal antibody, may provide additional efficacy in sub optimally controlled Chronic Idiopathic Urticaria patients. In this open labeled 16 week trial, 60 adult patients with symptomatic Severe Chronic Idiopathic Urticaria using Cetirizine, 10 mg orally QD, were randomized to continue the existing therapy Cetirizine or to add on Omalizumab subcutaneously (every 2 weeks to 4 weeks) dosed according to patient’s weight, and baseline IgE levels to the existing therapy Cetirizine. The end points of the trial include: weekly itch severity score on a scale. The mean of measurements at the end of the 16-week trial revealed a significant improvement in all parameters examined in the treatment group receiving Omalizumab (as addon to the existing therapy), compared to the other group. In conclusion, the addition of Omalizumab to the combination of Cetirizine is more effective than Cetirizine, for the treatment of Severe Chronic Idiopathic Urticaria patients. It appears that when Omalizumab is added to the combination H1-receptor antagonist, Cetirizine, the end points and symptom scores are significantly improved.


Introduction: Autoimmune hepatitis (AIH) is a progressive variable immunemediated liver disorder of unknown etiology more common in women, characterized by autoantibodies. Anti-smooth muscle autoantibodies with F-actin reactivity have been considered specific markers. The clinical course may involve periods of decreased or increased activity. Initial treatment is prednisone, alone or in combination with azathioprine. Case: A 35 year old Hispanic female was referred to allergy clinic from the gastroenterology clinic for an intensely pruritic butterfly rash on the face, arms, chest and back for 3 months. She also complained of shoulder and neck joint pain .There was no headache, blurry vision, chest pain, fever, oral ulcers, abdominal pain, nausea, vomiting, recent sick contacts, seasonal or food allergies. Past medical history was significant for helicobacter pylori gastritis. AIH was diagnosed in 2011. Current medications included: Azathioprine 50mg, Prednisone 40mg daily, calcium with vitamin D. On physical examination, she was alert, orientated, afebrile with a BP of 113/70 mm Hg, P:72/min, RR:16/min. Cardiopulmonary and neurological examinations were normal. Skin revealed erythema on both cheeks, arms, chest and back. Methods:WBC:6.5K/mm3, elevated LRTs, AST:236U/L, ALT:98U/L. Hepatitis A/B/C serology was negative. Anti-smooth muscle and antinuclear antibodies were positive at titers of 1:80 and 1:160. Specific IgE tests for food and pollen were negative. She discontinued Azathioprine and started Benadryl 25mg every 6 hours. The rash gradually improved. Conclusion: Allergic dermatitis may occur as drug hypersensitivity. Patients usually present with an intensely pruritic rash. In chronic cases, dermatitis may have been present for months or years. Diagnosis relies mostly upon the history and physical examination. Therapy depends on the severity of the dermatitis. Avoidance of exposure to the offending agent will mostly result in control.. In our patient, the rash improved after discontinuation of Azathioprine. The pathogenesis of AIH may be due to genetic susceptibility, molecular mimicry, impaired immunoregulatory networks contributing to the initiation and perpetuation of autoimmunity. Liver damage is thought to be mediated primarily by CD4+ T-cells, and recent studies support the involvement of diverse populations, including Th17 cells.

Bathing is an activity of daily living frequently addressed by primary care providers (PCPs) as part of a treatment plan for patients with atopic dermatitis (AD). However, there is a paucity of evidence as to how frequent, and for how long, a patient with AD should bathe. What PCPs are recommending concerning routine bathing in AD remains unknown. Methods: Providers attending the annual conferences of the Maine Chapter of the American Academy of Pediatrics and Maine Academy of Family Practice, were asked the following anonymous one-question survey: “As part of your general management of pediatric atopic dermatitis, along with moisturization, what do you counsel your patients to do about water exposure?” Answer choices included: a) frequent bathing at least daily for more than ten minutes per bath, b) frequent bathing at least daily for less than ten minutes per bath, c) limiting bathing to every other day or less for greater than ten minutes per bath, d) limiting bathing to every other day or less for less than ten minutes per bath, or e) none of the above. Results: A total of 145 providers responded to the survey (59 pediatric and 86 family practice). Of the pediatricians, 28.9% (95%, CI 19%-41%) indicated a preference for frequent bathing, (7 for daily bathing more than 10 minutes, and 10 for daily bathing less than 10 minutes). In contrast, 40.7% (95%, CI 29%53%) indicated a preference for limiting bathing, (8 for less than daily bathing for at least 10 minutes, and 16 for less than daily bathing for less than 10 min-




P335 CIPROFLOXACIN INDUCED ACUTE GENERALIZED EXANTHEMATOUS PUSTULOSIS. Z. Li*, D. Rajan, X. Wang, M. Frieri, East Meadow, NY. Introduction: Acute generalized exanthematous pustulosis (AGEP) is a rare, severe subtype of a drug eruption characterized by acute, extensive, non-follicular, sterile pustules on an erythematous background, with fever and leukocytosis that can be seen by Allergists Imunologists. Case: A 79 year-old white male presented for the first time with a diffuse rash for 4 days. The rash was first noticed on his trunk and arms, however quickly progressed to the bilateral legs and feet. The diffuse rash was best described as a red popular eruption that coalesced into plaques, studded with scattered, non-follicular pustules. The lesions were mildly pruritic, and painful, There was no chills, nausea or vomiting. His medical course in the hospital was significant for persistent leukocytosis and persistent temperature spikes. Past medical history included hypertension, controlled with diltiazem for several years. He had recently completed a 7 day course of ciprofloxacin for pneumonia which was diagnosed by his primary care physician. Methods: On admission he had a significant marked leukocytosis (30k /mm3). Punch skin biopsy of a lesion revealed subcorneal pustule s withalmost exclusively neutrophils surrounded by a spongiotic epithelium. Immunohistology showed no evidence of anti-tissue antibody, complement activation or immune complex deposition, which is consistent with a diagnosis of AGEP. The patient was treated with topical steroids, and hydroxyzine, which led to a gradual desquamation of the pustular lesions. Conclusion: AGEP is a relatively rare exfoliative dermatosis, characterized by numerous small, primarily non-follicular, sterile pustules, arising within large areas of edematous erythema, accompanied by fever, neutrophilia, and sometimes by facial edema, hepatitis and eosinophilia, In 90% of cases, AGEP is related to medication administration, especially antibiotics. Drug-specific T cells and the production of interleukin-8/CXCL8 play an important role in its pathogenesis. Spongiform subcorneal and/or intra-epidermal pustules are the histological key feature of AGEP. Diagnosis is dependent on clinical presentation and confirmatory histopathology. Anntibiotics most commonly cause AGEP.

and affects patient quality of life. Methods: Baseline characteristics of the study populations from three Phase III trials of omalizumab, an anti-IgE antibody in development for the treatment of patients with CIU/CSU who remain symptomatic despite antihistamine treatment, are described. Each study was a global, multicenter, randomized, double-blind, placebo-controlled study that included patients 12-75 years of age with CIU/CSU ≥ 6 months who remained symptomatic despite standard-dose H1 antihistamine treatment (2 studies) or despite H1 antihistamine treatment (up to 4 times the approved dose) and an H2 receptor blocker, and/or leukotriene receptor antagonist (1 study). IRB approval and informed consent was obtained from all research subjects. Results: A total of 975 patients (Asteria-I: n=318; Asteria-II: n=322; Glacial: n=335) were randomized and received at least one dose of study drug. Baseline demographic data and clinical characteristics of patients enrolled in each study are shown in the table. The demographic and clinical characteristics of the patient populations were similar among the studies. Most patients were white and female and the overall population had a mean body mass index >29. The average age was ~42 years and mean total IgE levels were elevated in patients from all three studies. There was a high degree of disease activity in the population (defined by high weekly itch severity and urticaria activity score during a 7-day period [UAS7] score at baseline) and angioedema was common. Conclusions: The patients enrolled in the omalizumab phase III trials on CIU/CSU are similar to the antihistamine-resistant patients seen in daily practice. Given the degree of uncontrolled disease, and the duration of symptoms, new and effective therapies are needed to improve symptom control.

UAS7, 7-day urticaria activity score


P336 BASELINE CHARACTERISTICS OF PATIENTS WITH REFRACTORY CHRONIC IDIOPATHIC/SPONTANEOUS URTICARIA ENROLLED IN THREE PHASE III, RANDOMIZED, PLACEBOCONTROLLED TRIALS OF OMALIZUMAB. K. Rosen*1, M.S. Bradley1, M. Ashby1, H.J. Hsieh1, P. Georgiou2, T. Casale3, M. Maurer4, 1. South San Francisco, CA; 2. Horsham, United Kingdom; 3. Omaha, NE; 4. Berlin, Germany. Background: Chronic idiopathic urticaria (CIU), also referred to as chronic spontaneous urticaria (CSU), is associated with significant healthcare burden


Introduction: Strongyloides stercoralis can cause occult infections that may last for several decades. Infected patients may be asymptomatic or may present with diarrhea, abdominal pain, or cough. Clinicians must recognize that pruritus and distinct types of skin rashes may occur in the setting of underlying Strongyloides infection. We describe an interesting case of Strongyloides infection associated with long-standing pruritus and severe, chronic eosinophilia. Methods: Case description; literature review Results: An 86 year-old male of Guyanese descent who moved to the United States 20 years prior to our evaluation, presented to our university-based Allergy clinic with chronic eosinophilia of 5 years duration and generalized pruritus for 3 months. The patient’s medical history was significant for chronic obstructive pulmonary disease with stable symptoms. Our exam was notable for excoriations on upper and lower extremities. The patient’s previous laboratory tests showed absolute eosinophil count of 1920 cells/mL (from 600-2010 cells/mL over the past 5 years), elevated serum total IgE (> 2000 IU/mL), and negative Strongyloides stercoralis IgG 4 years prior. Previous skin biopsy demonstrated superficial dermatitis with scattered lymphocytes and eosinophils. Given the patient’s chronic eosinophilia, bone marrow biopsy had previously been performed and was negative for malignancy. Laboratory testing following our visit revealed: positive Strongyloides stercoralis and Wuchereria bancrofti serologies; negative stool for ova and parasites; positive specific IgE for dust and cockroach; normal complement levels; negative hypersensitivity pneumonitis screen and negative serologies for Toxocara canis and Trypanosoma cruzi. The patient was treated with ivermectin for 2 days for presumed Strongyloides infection with decreasing in the eosinophil count and pruritus resolution. Discussion: Strongyloidiasis may present with cutaneous manifestations and severe eosinophilia. A high index of suspicion should exist in patients from endemic regions. Interestingly, cross-reactivity between Strongyloides and filarial antigens has been previously described, and likely explains the positive parasite serologies in this patient. Ivermectin


ABSTRACTS: POSTER SESSIONS is the mainstay of treatment for Strongyloides infection and commonly results in the rapid improvement of associated symptoms and eosinophilia.

P338 ACRODERMATITIS CONTINUA OF HALLOPEAU MASQUERADING AS CHRONIC ONYCHOMYCOSIS. E. Clayton*, B. Geng, V. Holland, A. Yang, M. Braskett, Los Angeles, CA. Acrodermatitis Continua of Hallopeau (ACH) is a rare variant of psoriasis characterized by eruption of sterile pustules on distal digit followed by inflammation and onychodystrophy. The condition is often misdiagnosed as refractory infection secondary to possible immunodeficiency. Case history: 45-yearold man presented with 10-year history of suspected onychomycosis. At symptom onset only a few nails were involved. Despite therapy with topical and systemic antifungals, the condition progressed to involve all his nails. There was no history of nail trauma prior to symptom onset. Inflammation became so painful that he could no longer work as a barber. On exam his fingertips and toes were swollen, erythematous and tender with profound induration and erythema around all nailbeds. Nails were dystrophic and hyperkeratotic. He had no other skin findings. CBC and metabolic panel were unremarkable. Nail bacterial culture was negative. He had no history of frequent or refractory systemic infections. Although there was initial suspicion for chronic mucocutaneous candidiasis (CMC), the presentation was not consistent with CMC. He denied history of thrush. Despite a decade of symptoms he never developed any endocrinopathies associated with Autoimmune polyendocrinopathy candidiasis-ectodermal-dystrophy (APECED), such as hypoparathyroidism or Addison’s disease. He had no medical conditions that would predispose him to secondary CMC, such as diabetes or HIV. Finally unlike CMC the degree of nailbed induration exceeded extent of hyperkeratosis. Nail biopsies revealed psoriasiform and spongiotic dermatitis with intracorneal and subcorneal neutrophilic pustules. Fungal and HSV stains were negative. This was consistent with a diagnosis of ACH. The initial treatment plan for this patient includes acitretin and topical steroids, although ACH often proves refractory to anti-psoriatic medication. ACH is rare variant of psoriasis that develops without the usual psoriatic plaques. Sterile pustules form on the distal digit and nailbed, leading to severe onychodystropy. Inflammation often spreads to the entire hand or foot, and longstanding disease may result in local osteitis and osteolysis. In contrast to CMC and APECED, ACH is remarkable for absence of systemic complications. This case illustrates an important differential diagnosis for refractory onychomycosis and underscores importance of early biopsy.

Distal digit inflammation and onychodystrophy in likely ACH

P339 DISSOCIATION BETWEEN HISTORY AND CHALLENGE IN A SUBSET OF PATIENTS WITH PHYSICAL URTICARIAS. H.D. Komarow*1, S. Arceo1, M. Young2, C. Nelson1, D.D. Metcalfe1, 1. Bethesda, MD; 2. Frederick, MD. Background: Physical urticarias are a unique form of hives that are induced by specific environmental or physical stimuli and comprise 20-30% of cases of chronic urticaria. Challenge testing procedures are essential to the determination of the correct diagnosis of a physical urticaria. We sought to determine the degree of consistency between a history of physical urticaria and the results of challenge testing. Methods: In a prospective study we evaluated 73 individuals, ages 3-77, diagnosed with a physically induced urticaria, primarily by a practicing allergist or dermatologist. All patients were evaluated using standard challenge testing for physical urticarias. Prior to evaluation, all subjects refrained from taking anti-histamines or any agent that could affect the outcome of the challenge tests. Challenge testing was directed toward the presenting diagnosis (e.g., cold urticaria), yet included other stimuli based on the history and a detailed 36 question clinical survey of physical urticarias. All subjects were tested for dermatographism and the majority of subjects were tested for 3 or more other entities. Results: Of the 73 subjects with a positive history of a physical urticaria, 45 (38%) were challenge negative to the presenting diagnosis and 19 (26%) were negative to all challenge testing. An additional 9 subjects (12%), although negative to the presenting diagnosis, did develop urticaria to a different stimulus consistent with the history upon further questioning. The proportion of negative challenge results based on the various types of physical urticaria indicates the percent negative was low (10%) in cold-induced, and delayed pressure urticaria (14%), yet high in cholinergic (52%) and solar urticaria (67%). Conclusion: In a survey of subjects referred for physical urticaria challenge testing, more than one-third of the subjects were negative to the presumed physical stimulus reported by history to provoke urticaria. Physicians that are unable to perform testing due to the cost of equipment, training and staff support requirements may consider referral to a tertiary care center for evaluation.

P340 AN ADULT WITH COLD URTICARIA AND SYSTEMIC SYMPTOMS. S. Mane*, A. Casillas, Shreveport, LA. Introduction: Cryopyrin-associated periodic syndromes are auto-inflammatory diseases, associated with mutations in the NOD-like receptor 3 gene (NLRP3) which encodes for cryopyrin, resulting in increased activation and secretion of interleukin 1 beta (IL-1β), causing systemic inflammation. Several mutations in this gene have resulted in familial cold auto-inflammatory syndrome (FCAS), a rare autosomal dominant disease characterized by fever, arthralgia, and urticaria 1-2 hrs after cold exposure. Most cases present in childhood, but cases of adult onset have been reported. We present a patient with overlapping features of systemic cold urticaria and FCAS. Case report: A 41 year old female was referred to our allergy clinic for an 8 yr history of urticaria. Her symptoms were initially characterized by rapidly progressing onset of pruritus and urticaria upon direct cold exposure with a rapid resolution. Over the course of 2 yrs, symptoms were increasingly delayed and systemic in nature. She described diffuse urticaria and shortness of breath upon inhalation of cold air, throat and tongue swelling after mucosal contact with cold foods or liquids, and abdominal pain and vomiting after ingestion of cold foods or liquids. Physical exam was normal except for a positive ice cube test. Epinephrine autoinjector, scheduled cyproheptadine and cold avoidance and precautions were recommended. Several years later, she returned to our clinic with new onset hair loss, night sweats, and chills. She reported fever of 99.9-101, fatigue and arthralgia 2 hrs after any form of cold exposure. Resolution took about 3 days. Family history was positive for arthralgia and cold-induced urticaria. Exam was normal. Laboratory data, including thyroid studies, ANA, rheumatoid factor, and tryptase levels were normal. Total IgE was slightly elevated (187 IU/ml; normal 1.6-165 IU/ml). Both systemic cold urticaria and FCAS were considered as diagnoses. Testing for NLRP3 mutation was negative; five overlapping fragments of exon 3 were analyzed. She continues to have symptoms. Further investigations and possible treatment with Anakinra, a recombinant IL1 receptor antagonist, are being considered for future. Conclusion: Positive ice cube test will confirm cold urticaria, but FCAS should be considered when cold urticaria is associated with systemic symptoms, especially since there have been reports of mutation negative FCAS.




P341 IMMUNOLOGICAL EVALUATION IN A PATIENT WITH FOLLICULITIS DECALVANS. E. Kim*1, D.W. Rosenthal2, 1. Manhasset, NY; 2. Great Neck, NY. Introduction: Folliculitis decalvans (FD) is a type of dissecting folliculitis characterized by papules and pustules on the scalp. In early lesions, acneiform infundibular dilatation and intrafollicular/perifollicular neutrophilic infiltrates are seen. As the disease progresses, the infiltrates become mixed with neutrophils, lymphocytes, plasma cells, and foreign-body giant cells, and may be found in the dermis and blood vessels of the superficial and mid-dermis. Methods: A 17-year-old male with eczema, recurrent scalp folliculitis, and recent hospitalization for worsening folliculitis presented for an immune deficiency evaluation. The patient was first diagnosed with eczema and folliculitis at age 10, and since then has been treated with various antibiotics for recurrent folliculitis, including cephalexin, clindamycin, cefadroxil, and daptomycin. He has had no other severe infections in the past. Other complaints included nasal congestion and ocular allergic symptoms. On physical examination, the patient had diffuse folliculitis with pustules throughout the entire body, more severe on posterior scalp with scarring and alopecia. Results: Laboratory evaluation showed normal CD3, CD4, CD19, IgG, IgA, IgM, and CH50 levels. Skin biopsy of the scalp showed follicular epithelium, surrounded by neutrophils, plasma cells, and histiocytes, which is consistent with FD. Conclusion: We report a rare case of Folliculitis decalvans in a young patient who has been treated with multiple antibiotics for a presumed recurrent folliculitis. Skin biopsy is the gold standard for the diagnosis of FD. It is hypothesized that the cytotoxic proteins secreted by Staphylococcus aureus may act as superantigens, and stimulate T cells. FD should be considered in patients with recurrent folliculitis who fail antibiotic treatments but have an intact immune system.

P342 SOLAR URTICARIA. R. Acosta*, A.M. Casillas, Shreveport, LA. Introduction: Solar urticaria (SU) is a rare IgE mediated photodermatosis caused by a photoallergen. It happens after exposure to UV-A, visible, less commonly UV-B, and rarely infrared radiation. Pruritus occurs within thirty seconds of sun exposure followed in minutes by urticarial lesions, erythema, and edema. Following large-scale exposure systemic symptoms may occur. Lesions disappear within one to three hours. This disease has been classified into six types depending on the wavelength of light required to produce urticaria and the ability to reproduce disease (historically) by passive transfer. Therapeutic options include avoidance of light exposure, use of antihistamines, steroids, protective clothing, and topical preparations to absorb or reflect light. We describe a patient with urticaria caused by sun exposure. Case report: The case subject is a 12 year old female who developed urticaria within minutes after direct sunlight exposure. Lesions disappeared spontaneously within twenty four hours. She had no residual changes. She took no medications, and her medical history was otherwise unremarkable. No laboratory tests were done before or after our evaluation. Her urticaria prevented her from participating in many activities. During her second outpatient visit she was asked to step outside for sun exposure, and after less than five minutes she developed urticaria on sun exposed skin with a sharp demarcation at her pant line. Heat, exercise, and sweating while indoors did not result in urticaria. Initial therapy consisted of cetirizine 10 mg by mouth daily. After several weeks of treatment, she was able to tolerate sunlight for periods up to thirty minutes. She remained on cetirizine and was advised to use Ultraviolet Protection Factor (UPF) protective clothing and sunscreen. Conclusion: This case demonstrates the importance of obtaining a detailed history for prompt diagnosis and treatment in order to improve quality of life. It is important to keep in mind that no single treatment is effective for all patients. With treatment, our patient was able to tolerate short periods of sun exposure.

After sun exposure

P343 PARENTAL PERCEPTION OF EFFICACY OF ANTIHISTAMINES FOR PRURITUS IN PEDIATRIC ATOPIC DERMATITIS. N.W. Wilson*, M.B. Hogan, G. Fenwick, A. Hooft, Reno, NV. Introduction: Pruritis associated with atopic dermatitis (AD) causes significant quality of life issues including sleeplessness. The role of antihistamines in the management of AD is controversial. A survey was performed to determine if parents perceived if antihistamines were efficacious in managing their children’s AD. Method: A descriptive anonymous survey was mailed to patients in a Pediatric Allergy clinic with a diagnosis of AD and a physician visit within the last 3 years. Questions included 4 point scale as to parental assessment of frequency of itch, whether antihistamines were helpful and frequency of use of antihistamines, topical steroids and emollients. Parents were asked to rank from 1 to 5, creams, emollients, topical steroids, antihistamines and topical calcineurin inhibitors with 1 being most helpful. Parents were also asked if child was allergic, age, and duration of AD. Study was IRB approved by institutional review board. Results: Age range of respondents was : 6% <1 yr. old, 55% 2-5 yrs. old, 28% 6-10 yrs. old, 15% > 10 yrs. old. Most children had AD for greater than 1 year (< 1 yr. 10%). 87% reported an identifiable allergic trigger. Parents reported that most children experienced itching: constant 21%, frequent 39%, occasional 26%, rarely 12%, never 1.5%. Antihistamines were perceived by a majority of parents to be helpful: 28% very much, 38% somewhat, 18% slightly, 10% very little, 6% not helpful. 53% of parents reported using antihistamines at least once per day, 32% as needed for itching, and 15% never used antihistamines for itching. Parents reported that antihistamines were used as frequently as topical steroids for pruritus. 42% ranked antihistamines either first or second most helpful compared to 49% for topical steroids. Conclusions: Pruritus is a common problem in children with AD. 66% of respondents reporting at least some itch relief with antihistamine use. 53% of parents used antihistamines consistently and 32% used it as needed. Parents generally perceived antihistamines to be useful for their child with atopic dermatitis and pruritus.

P344 CLINICAL PRACTICE PATTERNS FOR EVALUATION AND MANAGEMENT OF ATOPIC DERMATITIS: A COMPARISON OF PRIMARY CARE PHYSICIANS AND SPECIALISTS. M. Crites*, K. Mutgi, M.R. Rafeeq, J. Stausmire, Toledo, OH. Introduction: Atopic dermatitis (AD) is a genetically transmitted, chronic inflammatory skin disease that affects 10% to 20% of children and 1% to 3% of adults. The Joint Task Force on Practice Parameters recently published “Atopic dermatitis: A practice parameter update 2012”, a document that builds on the original 2004 publication. It is unclear to what extent physicians currently follow these recommendations. The purpose of our study was to evaluate and identify differences in clinical practice patterns of primary care physicians (PCPs) and specialists (SPs), and to compare these practices with current practice parameters. Method: After IRB approval, a prospective study of communitybased physicians was conducted between March 2013 and May 2013 using an



ABSTRACTS: POSTER SESSIONS online 24-question survey administered by Survey Monkey. All physicians in the northwest Ohio region currently listed in medical professional organizations were sent an email invitation with an internet link to participate in the survey. The survey could only be accessed via an email link and could only be completed once. The survey was programmed to include only respondents practicing in primary care (family medicine, internal medicine and pediatrics) and specialists (allergy/immunology and dermatology). Respondents in all other areas of practice were excluded from the study. Results: Of the 59 responses received, 18 were PCPs, 18 were SPs and the remaining 23 were physicians in other disciplines. Group differences that were significant with p<0.05 are reported. More PCPs than SPs identified food allergy as a common trigger for AD. However, SPs identified skin infection as a factor responsible for triggering AD more frequently. PCPs recommend blood tests for food and inhalant allergens more often than SPs. SPs prescribe antipruritic therapy and antibacterial therapy more often than PCPs. They use higher potency topical corticosteroids and topical calcineurin inhibitors more often than PCPs. SPs also recommend soapless cleansers, short warm baths and bleach baths more often compared to PCPs. Conclusion: There is high variability in practice patterns in the management of AD with significant differences between PCPs and SPs. Intensive efforts in ongoing physician education are needed to improve care of patients with AD.

P345 ANGIOEDEMA RESULTS FROM GLACIAL: A PHASE III, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY TO EVALUATE THE SAFETY AND EFFICACY OF OMALIZUMAB IN PATIENTS WITH CHRONIC IDIOPATHIC/SPONTANEOUS URTICARIA (CIU/CSU) RECEIVING CONCOMITANT H1 ANTIHISTAMINES, H2 ANTIHISTAMINES, AND/OR LEUKOTRIENE RECEPTOR ANTAGONIST (LTRA) TREATMENT. J. Zazzali*, K. Raimundo, M. Ashby, K. Rosen, South San Francisco, CA. Introduction: Angioedema, a symptom often associated with CIU/CSU, has a negative impact on patients’ health-related quality of life. This study describes the presence of angioedema and how patients managed it during the 24-week treatment period in GLACIAL. Methods: Subjects (n=335) were randomized 3:1 to receive omalizumab 300 mg or placebo at Baseline and every 4 weeks, for a total of 6 doses. All patients were allowed to take H1 antihistamines at up to four times the approved dose, plus H2 antihistamines, LTRAs, or both. Angioedema and angioedema management were assessed via the Urticaria Patient Daily Diary. We summarized the percent of patients reporting angioedema, the mean number of days with angioedema, and how patients managed it (response categories: did nothing; took medication; contacted health care provider; visited health care provider; went to the hospital emergency room; was hospitalized). Results: During the week prior to Baseline, angioedema was a prevalent symptom (54% vs. 49%; omalizumab 300mg vs. placebo, respectively); for those with angioedema, they reported having it approximately half of the days during that week (3.7 days vs. 3.3 days; omalizumab 300 mg vs. placebo, respectively). During the week prior to Week 24, a lower proportion of patients reported angioedema in the omalizumab 300mg arm than placebo (13% vs. 25%, respectively) and had reported angioedema for fewer days during that week (2.7 vs. 2.9 days, respectively). Angioedema management at Baseline and throughout the course of the treatment period generally consisted of low intensity interventions: most patients reported doing nothing or taking medication; some patients reported having called or visited their health care provider; and few patients reported visiting the hospital emergency room or being hospitalized for angioedema. Conclusions: Omalizumab was efficacious in reducing patientreported angioedema in patients with CIU/CSU who remained symptomatic despite H1 antihistamine treatment, plus H2 antihistamines and/or LTRAs.

P346 PERIORAL DERMATITIS ASSOCIATED WITH INTRANASAL STEROIDS: A COMMON MISDIAGNOSIS. J.L. Hill*, S. Patel, Tucson, AZ. Introduction: Perioral dermatitis (PD) is a common skin disorder characterized by an erythematous papulopustular eruption involving the nasolabial folds, chin, and perioral region, and sparing the vermillion border. Frequently, patients with PD have a history of topical, inhaled, or systemic steroid use. Cases associated with intranasal steroids are lacking in the literature and many clinicians are unaware of this common relationship. It is frequently misdiagnosed as contact or seborrheic dermatitis and consequently mistreated with topical corticosteroids, further exacerbating the condition. We present a case of PD related to intranasal steroid use. Case Presentation: A 29-year-old female with seasonal allergic rhinitis and remote history intranasal steroid use developed a pruritic, erythematous rash on the nasal labial folds approximately 2 months after initiation of fluticasone nasal spray, 50 mg (2 sprays in each nostril daily). The cutaneous eruption was characterized by small papules and papulovesicles on an erythematous background with areas of discrete scaling. She was evaluated by a dermatologist who suspected contact dermatitis and treatment with twice-daily hydrocortisone cream 0.1% to affected areas was initiated. This therapy resulted in burning, increasing pruritis, and spreading of the eruption to the chin and medial cheeks. The patient was then seen in allergy clinic where PD related to intranasal steroids was suspected. No other initiating factors such as contact irritants, allergens, or infection were identified. Steroid cream and intranasal steroid sprays were discontinued and she was treated with oral doxycycline 100 mg/day and twice daily metronidazole 0.75% cream to the affected areas. Within 1 month the rash completely resolved. Given persistent allergic rhinitis symptoms, six months later the patient tried budesonide intranasal spray, 32 mg (1 spray in each nostril daily), which resulted in reappearance of the pruritic rash within 1 week of therapy initiation. The medication was discontinued and the lesions resolved with use of topical metronidazole cream. Conclusion: PD is a common condition; however, diagnosis can be challenging especially to those unfamiliar with the disorder and its associated etiologies. Given frequent use of intranasal steroids, allergists should be aware of this underreported side effect and its potential therapies.

P347 LEVAMISOLE: FROM ANTIHELMINTHIC TO COCAINE CUTTER. N. Kharod*1, S. Patel2, Z. Alam3, 1. Orchard Park, NY; 2. Buffalo, NY; 3. Detroit, MI. Introduction: Levamisole, an antihelminthic and cancer drug, is now commonly being used to increase the affordability and profit from crack cocaine. Here we describe a case of levamisole-induced vasculitis with dermatological manifestations. Case Presentation: 56-year-old male with past medical history of hypertension, lupus anticoagulant, and crack cocaine abuse presented with multiple, irregular, purpuric macules and papules with erythematous border on both upper and lower extremities and both pinnae. Patient had a similar rash in June 2010 which was diagnosed as an insect bite. A urine toxicology screen was positive for cocaine and opiates. Throughout the admission he developed multiple new lesions over his forehead and upper extremities. Lesions on the arms showed desquamation with exposure of the underlying subcutaneous tissue. Skin biopsy showed epidermal necrosis with endothelial swelling and mild perivascular inflammation comprising of lymphocytes, rare neutrophils and eosinophils. Findings were consistent with thrombotic vasculopathy seen in levamisole-induced vasculitis. Lab tests done in previous admission showed the patient to be lupus anticoagulant positive, with C-ANCA>320 and ESR of 89 but he was never found to have neutropenia. Urine levamisole was never ordered. He was treated with a tapering dose of oral prednisone and topical fluocinonide. Discussion: The sudden onset of skin lesions, ANCA positivity, leukocytoclastic histology, and agranulocytosis suggest a levamisole-induced vasculopathy. Levamisole is an immunomodulator that was once used in rheumatoid arthritis and as an adjuvant in the treatment of colon cancer. Levamisoleinduced leukocytoclastic thrombotic vasculopathy is on the rise as 70% of the US cocaine supply is adulterated and there are over 2 million Americans who use cocaine each month, requiring physicians to be aware of this kind of a clinical picture in active cocaine abusers.



ABSTRACTS: POSTER SESSIONS urticaria versus localized cold urticaria. LCU has been previously identified in patients with a history of ragweed immunotherapy, insect bites, allergen immunotherapy, and cold injury. However all of the patients described did not have these preceding events. The cause of LCU is not well understood; however due to the involvement of noncontiguous tissue, humoral involvement and regional mast cell abnormalities is a less likely cause of etiology. The possibility of a localized abnormality in mast cells can be argued, however these studies have not been performed. Table #1: Cases of Localized Facial Cold Urticaria

P349 DESCRIPTIVE STUDY OF URTICARIA AND ANGIOEDEMA IN ALLERGY AND IMMUNOLOGY DEPARTMENT OF HOSPITAL GENERAL DE MéXICO “DR. EDUARDO LICEAGA”. D.A. Cariño Cartagena*, A. Velasco Medina, J.C. Fernandez de Cordova Aguirre, M. Arroyo Cruz, G. Velazquez Samano, Mexico City, DF, Mexico.

P348 LOCALIZED FACIAL COLD URTICARIA: A CASE PRESENTATION AND LITERATURE REVIEW. R. Patel*, A. Wolff, Newark, NJ. Introduction: Localized Cold Urticaria (LCU) is rare in both the pediatric and adult population. Usually cold urticaria causes hives on the skin after exposure to a cold stimulus. The diagnosis is made via an ice cube test, but the results are positive on any part of the body. We present a case of LCU and a comprehensive literature search of other LCU cases that were localized to the face. Methods: We present a 55 year old female who presented to the adult allergy clinic with a history of urticaria after exposure to cold weather for the past 30 years. Her face would break out in hives after a “few minutes” of cold weather exposure. She denied eruptions in other locations, shortness of breath, laryngeal swelling or angioedema. When the patient was not exposed to cold weather, she would not have urticaria. Ice pack challenge was performed on the left arm which yielded negative results, but a right facial cheek ice pack challenge yielded positive results. Results: An extensive literature review was performed via PubMed and Google, with only 6 cases of reported localized cold urticaria unrelated to a preceding cause, such as illness, food, insect sting or allergen immunotherapy. . The mean age at presentation was 31 years of age and a mean duration of symptoms were 6.5 years with 57% affected females and 43% affected males,. In each case, the cold test yielded positive results only to the face, and nowhere else on the body. Conclusion: LCU continues to be a rare phenomenon, but physicians should consider performing the cold ice cube challenge to the face as well as other locations to verify if their case is true cold


Introduction: Urticaria is a spontaneous or induced disease of the skin characterized by wheals, angioedema or both. The lesions are erythematous, they solve in hours without residual discoloration or visible scar, usually are itchy as they emerge, accompanied by burning or stinging. Angioedema is deep, pale, less defined, more painful than itchy and with a longer duration, resolved without sequelae. It is more common on the lips, eyelids and genitals but can occur anywhere on the skin. Methods: We performed a restrospective, analytical, descriptive study. The data were obtained from the records of patients treated at the Department of Allergy and Clinical Immunology for the first time in 2012. For statistical analysis we used central tendency measures such as mean, standard deviation, maximum and minimum. Results: 1913 patients attended our department, 186 (9.7%) patients were diagnosed with urticaria, angioedema, or both, of which 47 were men (25.2%) and 139 women (74.7%). The highest prevalence was found in the group of adults with a total of 168 patients (90.32%) corresponding 18 to the pediatric population (9.68%), the mean age was 37.4 years, 154 patients (82.7%) were diagnosed with urticaria, 21 (11.2%) angioedema and 11 (5.9%), urticaria and angioedema. Discussion: Urticaria affects 20% of the population at any age and in any presentation according to the international literature, contrasting with our results. It is important to distinguish the phenotype of the disease because treatment is different; urticaria without angioedema is the most common disease in our population.



Plates edema and erythema, erratic, fleeting, universal distribution, secondary to urticaria. Photographs: Diego Cariño. ®

P350 MASTOCYTOMA MASQUERADING AS FOOD ALLERGY. C. Ward*, M. Greenhawt, Ann Arbor, MI. Introduction: Systemic effects of solitary mastocytomas are well described and can have considerable symptom overlap with acute allergic reactions. We present the case of a 16-month-old infant referred due to concern for food allergies in the setting of post-prandial symptoms of rash, flushing, and diarrhea. Methods: A 16-month-old Caucasian male with a history of eczema was evaluated due to concern for symptoms urticaria, diarrhea, fussiness, and “spitting up” attributable to cow’s milk at 10 months of life. Substituting cow’s milk with lactose-free milk reproduced the same symptoms, and yogurt was attributable to non-pruritic facial flushing. Wheat, orange, and banana were also attributed to causing rash. Per mother, he also had a history of “some tumor” being biopsied from his flank at age five months. She noted he rubbed this area often when he fed. Results: Examination was unremarkable except for a 6 mm fleshcolored papule over the left chest wall (Figure 1). Skin prick testing was performed to milk, casein, wheat, banana, and orange. Results were negative with appropriate controls. Laboratory evaluation revealed an elevated tryptase level of 17.7 ng/mL and a normal blood count. Review of the skin biopsy indicated cutaneous mastocytosis consistent with a mastocytoma. He was referred to Hematology for a bone marrow biopsy, which was normal and without evidence of mast cell infiltration. His symptoms improved with scheduled cetirizine and ranitidine without any food elimination. Discussion: A solitary mastocytoma is classified as a benign cutaneous form of mastocytosis. The release of mast cell mediators can be provoked by physical stimuli, causing symptoms similar to systemic mastocytosis and IgE-mediated mast cell degranulation in allergic disease. The symptoms of flushing, pruritus, and diarrhea were ultimately attributed to systemic effects of a solitary mastocytoma, which the child provoked while drinking milk, mimicking symptoms of an allergic reaction. This case illustrates the importance of taking a careful history and performing a thorough skin exam when evaluating patients with food allergies or other presumed IgE-mediated allergic disease.

Flesh-colored mastocytoma over left lateral chest wall

P351 USE OF KETOTIFEN FOR THE TREATMENT OF CHRONIC IDIOPATHIC URTICARIA AND ANGIOEDEMA: A RETROSPECTIVE ANALYSIS. K.C. Sokol*, N.K. Amar, J.A. Grant, Galveston, TX. Introduction: Ketotifen, a benzocycloheptathiophene derivative, is an oral antiallergic drug initially marketed as an inhibitor of anaphylaxis. Ketotifen inhibits the release and/or activity of mast cell and basophil mediators, including histamine. Ketotifen has a chemical structure similar to first generation antihistamines such as cyproheptadine, and has been used and studied in patients with asthma, allergic rhinitis, allergic conjunctivitis, atopic dermatitis, and chronic urticaria. However, in the United States, ketotifen is available only as an ophthalmic solution. Methods: We sought to evaluate whether treatment with oral ketotifen provided symptomatic benefit in patients with refractory chronic idiopathic urticaria and idiopathic angioedema via retrospective analysis of the medical chart. IRB approval and informed consent was obtained from subjects. A total of 19 out of 51 patients prescribed ketotifen in the last 2 years agreed to participate in the study. Subjects were asked to complete a modified Urticaria Activity Score 7 (UAS 7) questionnaire to evaluate symptoms prior to and after starting ketotifen, and document the use of additional medications. Medication use was scored by a point system, with higher points assigned to more potent medications. Results: UAS7 scores improved in all 19 patients after starting ketotifen. No subjects thought that ketotifen made their symptoms worse, and 16 out of 19 subjects reported that ketotifen made their symptoms better. Sedation was the most frequent side effect reported. Additionally, medication scores in 14 of 19 subjects decreased, indicating the need for less medication after starting ketotifen. Most importantly, 5 out of 8 patients were able to stop systemic steroids after starting ketotifen. Discussion: Based on these results, ketotifen may be used as a favorable addition to medications in patients with refractory urticaria. Ketotifen’s side effects are nominal, and could minimize the need for other potentially harmful medications. Conclusion: This analysis adds to several case reports and small studies evaluating the efficacy of ketotifen in the management of chronic urticaria. We realize the power of this study is limited; however, a controlled prospective trial is planned to further the evidence that ketotifen has a beneficial effect in the treatment of chronic urticaria and angioedema.







Disclosures Abstracts and Posters ACAAI 2013 Annual Scientific Meeting November 7-11, 2013 Baltimore, Maryland Disclosure Policy and Disclosures As required by the Accreditation Council for Continuing Medical Education (ACCME) and in accordance with the American College of Allergy, Asthma and Immunology (ACAAI) policy, all educational planners, presenters, instructors, moderators, authors, reviewers, and other individuals in a position to control or influence the content of an activity must disclose all relevant financial relationships with any commercial interest that have occurred within the past 12 months. All identified conflicts of interest must be resolved and the educational content thoroughly vetted for fair balance, scientific objectivity, and appropriateness of patient care recommendations. It is required that disclosure be provided to the learners prior to the start of the activity. Individuals with no relevant financial relationships must also inform the learners that no relevant financial relationships exist. Learners must also be informed when off-label, experimental/investigational uses of drugs or devices are discussed in an educational activity or included in related materials. Disclosure in no way implies that the information presented is biased or of lesser quality. It is incumbent upon course participants to be aware of these factors in interpreting the program contents and evaluating recommendations. Moreover, expressed views do not necessarily reflect the opinions of the ACAAI. (Please note that posters were not certified for credit.) Aberer, W. – P84 Speaker: CSL Behring, Shire Abetz-Webb, L. – P89 Consultant/Advisory Board: Shire Aldwinckle, T. – P211, P212, P213 Employee: Bio Products Laboratory Allen-Ramey, F. – P318 Employee: Merck Altrich, M. – P29, P268 Employee and Stocks: Viracor-IBT Anagnostou, A. – 23 Employee: Immunomic Therapeutics Andritschke, K. – P88 Consultant/Advisory Board: CSL Behring Ashby, M. – P336, P345 Employee and Stocks: Genentech Aygoren-Pursun, E. – P88 Consultant/Advisory Board: CSL Behring

Berger, W. – P55 Consultant/Advisory Board, Speaker, Honorarium, Research Grant: Alcon, AstraZeneca, Genentech, GlaxoSmithKline, Meda, Merck, Novartis, Ora, Schering Plough, Sunovion, Teva

Blaiss, M. – P318, P314, P315, P316 Consultant/Advisory Board, Honorarium: Merck

Bernstein, D. – P325, P327 Consultant/Advisory Board: Merck; Research Grant: Greer, Merck, Stallergenes

Bonner, N. – P89 Consultant/Advisory Board: Shire

Bernstein, J. – P243, P90, 60 Investigator: Pharming Bethune, C. – P88 Consultant/Advisory Board: CSL Behring Beusterien, K. – P289 Consultant/ Advisory Board: ViroPharma; Employee: Oxford Outcomes

Baker, J. – P243 Investigator: Pharming

Bielory, L. – 64, P318 Consultant/Advisory Board, Speaker, Honorarium, Research Grant: Allergan, Bausch & Lomb, Dyax, Merck, Pharmacol

Baptista, J. – P83, P90 Employee: Shire

Bindslev-Jensen, C. – 54 Investigator: Novartis

Becker, W. – P305 Employee: GlaxoSmithKline

Birring, S. – P302 Investigator: Cerecor

Boccon-Gibod, I. – P88 Consultant/Advisory Board: CSL Behring

Bork, K. – P88 Consultant/Advisory Board: CSL Behring Bouillet, L. – P84, P88 Honorarium: CSL Behring, Pharming, Shire, ViroPharma; Research Grant: Shire, CSL Behring Boysen, H. – P88 Consultant/Advisory Board: CSL Behring Bradley, M. – 54, P336 Employee: Genentech Brindley, C. – P212 Consultant: Bio Products Laboratory Buatti Small, M. – P53, P57, P58 Employee: Teva Buck, P. – 11, P53, P57, P58, P323, P324, P328 Employee: Teva




Bukstein, D. – P323, P324, P328 Consultant: Teva Bullinger, A. – P244 Employee: CSL Behring Busse, P. – 49, 51, P290 Consultant/Advisory Board: ViroPharma; Research Grant: CSL Behring, ViroPharma Bygum, A. – P290 Consultant/Advisory Board: CSL Behring, Shire, Sobi, ViroPharma; Speaker: Shire, ViroPharma Caballero, T. – P84, P88, P89 Consultant/Advisory Board: CSL Behring, Shire, Sobi, ViroPharma; Speaker: Shire, ViroPharma; Clinical Trials: CSL Behring, Dyax, Pharming, Shire; Research Grant: CSL Behring, Shire Cancian, M. – P88 Consultant/Advisory Board: CSL Behring Canning, B. – P302 Consultant/Advisory Board: Almirall, Cerecor, Merck; Research Grant: Eli Lilly, GlaxoSmithKline, Palatin Technologies

Clark, C. – P296 Consultant/Advisory Board: Janssen; Research Grant: Alere, Biocryst, Cardiorentis, Dyax, GlaxoSmithKline, Janssen, Lundbeck, NexBio, Portola Coyne, T. – P33 Employee: Greer Craig, T. – P318, P88 Research Grant: Merck Creticos, P. – P327 Research Grant: Greer, Merck Crosley, P. – P296 Research Grant: Dyax Dairaghi, D. – P303 Employee: ChemoCentryx; Stocks: ChemoCentryx Das, A. – P302 Consultant/Advisory Board: Cerecor Davis-Lorton, M. – P186 Speaker: Dyax, ViroPharma; Principal Investigator: Dyax, ViroPharma

Ellis, A. – 59 Consultant/Advisory Board: Sanofi; Speaker: AstraZeneca, Merck, Pfizer, Sanofi; Honorarium: Merck; Research Grant: Circassia Fabien, V. – P84, P85 Employee: Shire Fischer von Weikersthal-Drachenberg, K. – P287 Employee: Allergy Therapeutics, Stocks: Allergy Therapeutics Fitts, D. – P289 Employee: ViroPharma; Stocks: ViroPharma Flebbe-Rehwaldt, L. – P268 Employee: Viracor-IBT Fraser, H. – P302 Employee: Cerecor Fromer, L. – P314, P315, P316 Consultant/Advisory Board: GlaxoSmithKline Garner, L. – P280 Consultant/Advisory Board: UAS

Dayno, J. – 49, 51, P289, P291 Employee: ViroPharma; Stocks: ViroPharma

Gascoigne, E. – P211, P212, P213 Employee: Bio Products Laboratory

Carr, W. – P320 Consultant/Advisory Board: Meda

Dicpinigaitis, P. – P302 Consultant/Advisory Board: Cerecor

Georgiou, P. – 54, P336 Employee: Novartis

Casale, T. – P326, P336 Consultant/Advisory Board: Stallergenes; Research Grant: Merck, Stallergenes; Speaker: ALK-Abello

Dorinsky, P. – P51 Former Employee: Aerocrine

Gever, L. – 62 Employee: Meda

Dotiwala, Z. – P57, P58 Employee: eMAX Health

Gillen, M. – P55 Employee: AstraZeneca; Stocks: AstraZeneca

Casciano, J. – P57, P58 Consultant: Teva Casper, R. – P302 Employee: Cerecor Chiao, J. – P291 Employee: ViroPharma; Stocks: ViroPharma Chyung, Y. – P296 Employee: Dyax Cicardi, M. – P88, P243 Consultant/Advisory Board: CSL Behring

DuBuske, L. – P287 Consultant/Advisory Board: Allergy Therapeutics; Speaker: Allergy Therapeutics; Honorarium: Allergy Therapeutics Duncan, E. – P33 Employee: Greer Dykewicz, M. – P318 Consultant/Advisory Board: Merck; Honorarium: Merck Edelman, J. – P290 Employee: CSL Behring el-Azhary, R. – 55 Consultant: Preventice



Goldsobel, A. – P302 Investigator: Cerecor Gopalan, G. – P53, P57, P58, P323, P324, P328 Employee: Teva Grier, T. – P33 Employee: Greer Grob, J. – 54 Consultant/Advisory Board: Novartis, Schering-Plough Gupta, R. – P272, P274 Speaker: Mylan; Investigator: Mylan


Hadley, J. – P318 Consultant/Advisory Board: Merck Hagan, J. – P47 Research: GlaxoSmithKline, MedImmune Hall, D. – P33 Employee: Greer Hampel, F. – P310 Research Grant: Amphastar, Array, Bausch & Lomb, Emergent, Forest, GlaxoSmithKline, Meda, MediciNova, Merck, Novartis, Ono, Pearl Therapeutics, Perrigo, Shionogi, Sunovion, Teva, Actavis

Hsieh, H. – P336 Employee: Genentech, Stocks: Genentech

Leleti, M. – P303 Employee: ChemoCentryx; Stocks: ChemoCentryx

Iarrobino, R. – P296 Employee: Dyax

Lepore, M. – 11, P323, P324, P328 Employee: Teva

Jacob-Nara, J. – P315, P314, P316 Employee: GlaxoSmithKline; Stocks: GlaxoSmithKline

Levy, H. – 49, 51 Employee: ViroPharma; Stocks: ViroPharma

Jaen, J. – P303 Employee: ChemoCentryx; Stocks: ChemoCentryx

Levy, R. – P243 Investigator: Pharming Lewis, L. – P296 Consultant/Advisory Board: MediciNova; Research Grant: Dyax, MediciNova

Janka, L. – 61, P312 Employee: Teva; Stocks: Teva

Hardiman, Y. – P243 Employee: Santarus

Kaiser, H. – P287 Research Grant: Allergy Therapeutics

Hautamaki, E. – P289 Employee: Oxford Outcomes; Consultant/Advisory Board: ViroPharma

Kaur, A. – P325, P326, P327 Employee: Merck

Hearl, B. – 23 Stocks: Immunomic Therapeutics; Stocks: Immunomic Therapeutics

Keith, P. – P88 Consultant/Advisory Board: CSL Behring Kemp, R. – P57, P58 Employee: eMAX Health

Hebert, J. – P88, P327 Consultant/Advisory Board: CSL Behring

Klausner, H. – P296 Research Grant: Dyax

Heiland, T. – 23 Employee: Immunomic Therapeutics

Kobayashi, R. – P130 Research Grant: Octapharma

Herje, N. – P51 Employee: Aerocrine

Krishnan, J. – P57, P58 Consultant/Advisory Board: eMAX Health

Hester, J. – P29, P268 Employee: Viracor-IBT Hirsh, J. – P291 Employee: ViroPharma; Stocks: ViroPharma Holdich, T. – P287 Employee: Allergy Therapeutics; Stocks: Allergy Therapeutics Hollander, D. – 58 Employee: Allergan Hom, M. – 64 Consultant/Advisory Board, Speaker, Honorarium, Research Grant: Allergan, Bausch & Lomb Howland, W. – P287 Research Grant: Allergy Therapeutics

Li, C. – P57, P58 Consultant/Advisory Board: eMAX Health Li, H. – 51, P83, 49, P243 Consultant/Advisory Board: CSL Behring, Dyax, Shire, ViroPharma; Speaker: CSL Behring, Dyax, Shire, ViroPharma; Research Grant: CSL Behring, Dyax, Shire, ViroPharma Lieberman, P. – P320 Consultant/Advisory Board: Meda Long, R. – P314, P315, P316 Consultant: GlaxoSmithKline

Lampl, K. – P55 Employee: AstraZeneca; /Stocks: AstraZeneca Landmesser, L. – P291 Employee: ViroPharma; Stocks: ViroPharma Lauersen, L. – P314, P315, P316 Employee: GlaxoSmithKline; Stocks: GlaxoSmithKline Leatherman, B. – P318 Consultant/Advisory Board: Merck, Sunovion; Speaker: Teva; Honorarium: ALK-Abello, Sunovion

Longhurst, H. – P85, P88, P89, P84 Consultant/Advisory Board: CSL Behring, Dyax, Shire and SOBI; Speaker: CSL Behring, Shire, SOBI, ViroPharma; Research Grant: CSL Behring, Shire, Pharming, ViroPharma Lumry, W. – P90, P290, 49, 51, P85, P83, P289 Consultant/Advisory Board: BioCryst, CSL Behring, Dyax, Shire, ViroPharma; Speaker: CSL Behring, Dyax, Shire, ViroPharma; Research Grant: CSL Behring, Dyax, Pharming, Shire, ViroPharma Machnig, T. – P290 Employee: CSL Behring MacKechnie, M. – P211 Employee: Bio Products Laboratory

Lee, J. – P179 Honorarium: Novartis; Research Grant: Novartis VOLUME 111, NOVEMBER, 2013



Mackler, B. – 23 Consultant/Advisory Board: Immunomic Therapeutics; Stocks: Immunomic Therapeutics Magerl, M. – P88 Consultant/Advisory Board: CSL Behring Maloney, J. – P44, P325, P326, P327 Employee: Merck Mannion, K. – P314, P315, P316 Consultant/Advisory Board: GlaxoSmithKline Marcus, J. – 14 Employee: Propeller Health Martinez, I. – P290 Consultant/Advisory Board: Bayer, Baxter, CSL Behring, Octapharma, Shire, Sobi; Honorarium: CSL Behring Martinez-Saguer, I. – P88, P227 Consultant/Advisory Board: CSL Behring Maurer, M. – 54, P84, P85, P89, P336 Consultant/Advisory Board: Genentech, Novartis; Speaker: Genentech, Novartis; Honorarium: Genentech, Novartis; Research Grant: Genentech, Novartis Mazhari, R. – P302 Employee: Cerecor McLaurin, E. – 58 Research Grant: Allergan Meltzer, E. – P305, P312 Consultant/Advisory Board: Alcon, Alexza, AstraZeneca, Bausch & Lomb, Boehringer Ingelheim, Forest, Johnson & Johnson, Kalypsys, Meda, Merck, Mylan, Optinose, Proctor & Gamble, Rigel, Sanofi, Sunovion, Teva; Research Grant: Alcon, Amgen, Apotex, AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, HRA, Kalypsys, MedImmune, Merck, Novartis, Ono, Proctor & Gamble, Rigel, Shionogi, Sunovion, Teva; Speaker: Alcon, Meda, Merck, Mylan, Sunovion, Teva.


Miao, S. – P303 Employee: ChemoCentryx; Stocks: ChemoCentryx Miao, Z. – P303 Employee: ChemoCentryx; Stocks: ChemoCentryx Miller, D. – P289 Employee: ICON; Consultant/Advisory Board: ViroPharma Miner, J. – P296 Research Grant: CSL Behring, Dyax, Hutchinson Technology, Trius Therapeutics; Speaker: Janssen Moldovan, D. – P243 Investigator: Pharming Moore, T. – P37, P285 Employee: ALK-Abello Munzel, U. – P319, P320 Employee: Meda Naples, A. – P280 Research Coordinator: UAS Neighbour, H. – 59 Research Grant: Circassia Nelson, H. – P325, P326, P327 Consultant/Advisory Board: Merck; Research Grant: Circassia Neri, S. – P88 Consultant/Advisory Board: CSL Behring Nolte, H. – P44, P325, P326, P327 Employee: Merck O'Connor, R. – P323, P324, P328 Consultant/Advisory Board: Teva Olson, G. – 62 Research Grant: Meda Opitz, D. – 64 Consultant/Advisory Board, Speaker, Honorarium, Research Grant: Allergan, Bausch & Lomb Ortiz, G. – P318 Consultant/Advisory Board: Genentech, Merck, Mylan, Teva, Sunovion; Speaker: Aerocrine, Genentech, Merck, Mylan, Teva, Thermo Fisher Scientific, Sunovion


Patel, P. – P287, P322 Employee: Inflamax Research Paterson, B. – P302 Employee: Cerecor Paul, I. – P302 Consultant/Advisory Board: Cerecor Petrov, A. – 30 Research Grant: CSL Behring Plunkett, G. – P37, P285 Employee: ALK-Abello Porebski, G. – P243 Investigator: Pharming Powers, J. – P303 Employee: ChemoCentryx; Stocks: ChemoCentryx Raimundo, K. – P76, P345 Employee: Genentech Ratner, P. – 62, 61 Research Grant: Amphastar, Bausch & Lomb, Circassia, GlaxoSmithKline, Meda, Pearl Therapeutics, Sunovion, Teva Reisacher, W. – P323, P324, P328 Consultant/Advisory Board: Teva Relan, A. – P243 Employee: Pharming Reshef, A. – P243 Investigator: Pharming Rickard, K. – P51 Employee: Aerocrine Rider, N. – P220 Speaker: CSL Behring; Honorarium: CSL Behring; Research Grant: CSL Behring Riedl, M. – 49, P83, P90, P243, 51, P85 Consultant/Advisory Board: BioCryst, CSL Behring, Dyax, Isis, Shire, Santarus, ViroPharma; Speaker: CSL Behring, Dyax, Shire, ViroPharma; Research Grant: CSL Behring, Dyax, Shire, Santarus, ViroPhamra


Rojavin, M. – P290 Employee: CSL Behring

Small, C. – P310 Employee: Teva

Vornov, J. – P302 Employee: Cerecor

Rosen, K. – 54, P76, P336, P345 Employee: Genentech; Stocks: Roche

Soteres, D. – 62 Research Grant: Meda

Walstein, N. – P318 Consultant/Advisory Board: Merck

Rossi, O. – P88 Consultant/Advisory Board: CSL Behring

Spector, S. – 54 Consultant: Novartis

Walters, M. – P303 Employee: ChemoCentryx; Stocks: ChemoCentryx

Rothenberg, M. – 33 Consultant/Advisory Board: Immune Pharmaceuticals; Stocks: Immune Pharmaceuticals; Royalties: Teva; Patents: Cincinnati Children's Hospital Ruiz, N. – P319, P320 Employee: Meda Saini, S. – P330, 54 Consultant/Advisory Board: Novartis, Genentech; Research Grant: Novartis, Genentech Sala-Cunill, A. – P88 Consultant/Advisory Board: CSL Behring Schaffer, F. – P280 Chief Medical Officer: UAS Schall, T. – P303 Employee: ChemoCentryx; Stocks: ChemoCentryx Segall, N. – P310 Research Grant: GlaxoSmithKline, Merck, Novella Clinical, Sanofi, Teva Shah, S. – 62 Research Grant: Meda

Steele, T. – 49, 51 Employee: ViroPharma; Stocks: ViroPharma Stobiecki, M. – P243 Investigator: Pharming Storms, W. – P56 Consultant/Advisory Board: Alcon, Amgen, AstraZeneca, Bausch & Lomb, Merck, Sunovion, Strategic Pharmaceutical Advisors, Teva; Speaker: Alcon, AstraZeneca, Genentech, Novartis, Bausch & Lomb, Merck, Sunovion, Teva; Grant Research: Amgen, Genentech, Novartis, GlaxoSmithKline, Bausch & Lomb, Meda, Sunovion, Teva

Wang, Y. – P303 Employee: ChemoCentryx; Stocks: ChemCentryx Wasserman, R. – 31 Consultant/Advisory Board: ADMA Biologics, Baxter, Biotest, BPL, CSL Behring, Kedrion, Green Cross; Research Grant: ADMA, Baxter, Biotest, BPL, CSL Behring, Kedrion, Green Cross; Speaker: ADMA, Baxter, Biotest, BPL, CSl Behring, Kedrion, Green Cross Weiner, L. – 23 Consultant/Advisory Board: Medical Director: Immunomic Therapeutics

Stratford Bobbitt, M. – P213 Employee: Bio Products Laboratory

Wells, H. – P29, P268 Employee: Viracor-IBT

Sullivan, T. – P303 Employee: ChemoCentryx; Stocks: ChemoCentrys

Williams, J. – 58 Employee: Allergan

Symons, C. – P88 Consultant/Advisory Board: CSL Behring Tantry, S. – 61, P310, P312 Employee: Teva

Yiannias, J. – 55 Consultant: Preventice Young, J. – P285 Employee: ALK-Abello Zampelli, A. – P244 Employee: CSL Behring

Shanga, G. – P305 Employee: GlaxoSmithKline

Thompson, J. – P43 Honorarium: Thermo-Fisher Scientific

Sher, M. – P302 Investigator: Cerecor; Speaker: GlaxoSmithKline, Meda

Trudo, F. – P55 Employee: AstraZeneca, Stocks: AstraZeneca

Zazzali, J. – P76, P345 Employee: Genentech

Sheth, K. – P323, P324, P328 Consultant/Advisory Board: Teva

Trzaskoma, B. – P76 Employee: Genentech

Zhou, Y. – P327 Employee: Merck

Silveira, F. – 30 Research Grant: CSL Behring

Uryniak, T. – P55 Employee: AstraZeneca, Stocks: AstraZeneca

Skoner, D. – P318, P327 Consultant/Advisory Board: Merck; Research Grant: Merck; Honorarium: Merck

Zanichelli, A. – P84 Consultant/Advisory Board: Shire; Speaker: CSL Behring, Shire, Sobi

Van Sickle, D. – 14 CEO: Propeller Health




The following have no relevant financial relationships with commercial interests to disclose: A Chouksey, A. – P77

Avila, P. – P306

Brown, M. – P30

A Kerr, A. – P91

Azizbekyan, G. – P257

Browne, S. – P116

Abdalgani, M. – P172

Bahna, S. – P261

Buchman, S. – P65

Abghari, P. – P81

Bajaj, K. – P133

Buelow, B. – P117, P271

Abi Fadel, F. – P5

Ballow, M. – P208

Buenfil-Lopez, J. – P321

Abraham, J. – P249

Bandino, M. – P170

Bukstein, D. – P72

Abramova, Z. – P66

Bang, K. – P52

Bullinger, A. – P244

Achar, K. – P27

Barion, F. – P53

Burden, A. – P53

Acosta, R. – P342

Barnes, C. – 57

Buyantseva, L. – P262

Adams, K. – P21

Bastian, J. – P219

Caimi, P. – P121

Adkins, C. – P288

Baum, D. – P275

CaJacob, A. – P265, P288

Agarwal, N. – P9

Bayer, D. – P171

Camacho, J. – P247

Agarwal, S. – P247

Beketova, N. – P257

Cameron, R. – P121

Agrawal, A. – P64

Bellanti, J. – P307

Camp, M. – P23

Agrawal, S. – P263

Beloglazov, V. – P67

Campbell, J. – P53

Al Atassi, K. – P96

Benedek, S. – P222

Campbell, T. – P167

Alam, Z. - P347

Bennett, G. – P13

Cano, P. – P40

Albin, S. – P104

Bernstein, J. – P38

Canseco-Villarreal, J. – P36, P298

Alfonzo, M. – P86, P87

Bertozzi, T. – P59

Cardona, I. – P333

Alghanmi, R. – P238

Bhargave, G. – P120

Carino-Cartegena, D. – P349

Alpan, O. – P30

Bhattacharjee, R. – P68

Cartland, J. – P272

Alsharif, F. – P294

Bhatti, H. – P204

Caruthers, C. – P64

Alvarado-Franco, N. – P78

Bielory, L. – P73

Castelan, E. – P246

Alvarez, A. – P205

Bina, S. – P17

Castilano, A. – P135

Amar, N. – P248

Blazine, A. – P19

Chaiban, R. – P143

Anastos, K. – P113

Bleecker, E. – P53

Chandra, R. – P306

Anderson, L. – P107

Blumberg, M. – P270

Chapa-Arizpe, G. – P298

Anderson, W. – P162

Boiani, A. – P12

Chatterjee, P. – P79

Andreae, D. – P255

Bonagura, V. – P79, P176, P226

Chen, P. – P68

Aquino, M. – P297

Bonds, R. – P248

Cheng, H. – P138

Arango, N. – P34

Bonner, J. – P136, P2