Bloody diarrhea—a new complication of sulfasalazine

Bloody diarrhea—a new complication of sulfasalazine

450 B r i e f clinical and laboratory observations REFERENCES 1. Williams HE: Inhalation pneumonia, Aust Paediatr J 9:279, 1973. 2. Ribaudo CA, and ...

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B r i e f clinical and laboratory observations

REFERENCES 1. Williams HE: Inhalation pneumonia, Aust Paediatr J 9:279, 1973. 2. Ribaudo CA, and Grade W J: Pulmonary aspiration, Am J Med 50:510, 1971: 3. Danus O, Casar C, Lorrain A, and Pope CE: Esophageal reflux--an unrecognized cause of recurrent obstructive bronchitis in children, J PEDIATR 89:220, 1976. 4. Head MA: Foreign body reaction to inhalation of lentil soup: Giant cell pneumonia, J Clin Pathol 9:295, 1956.

Bloody diarrhea-a new complication of sulfasalazine Steven L. Werlin, M.D.,* and Richard J. Grand, M.D.,** Boston, Mass.

SULFASALAZINE has been s h o w n to be effective in m a i n t e n a n c e t r e a t m e n t o f ulcerative colitis? It is m e t a b o iized by colonic microflora to 5-aminosalicylate a n d sulfapyridine. T h e 5-aminosalicylate is excreted in the stool while the sulfapyridine is a b s o r b e d a n d is excreted in the urine. 2 The m a j o r side effects whidh limit its use are nausea, vomiting, a b d o m i n a l pain, b o n e m a r r o w suppression, hemolysis, a n d fever, a n d all have b e e n related to the sulfapyridine blood level? O t h e r m u c h less c o m m o n l y seen side effects, pancreatitis ~ a n d lung d a m a g e ? seem to be idiosyncratic. Instances of" neurotoxicity" a n d toxic epidermal necrolysis 7 are less well d o c u m e n t e d . W e report two children with ulcerative colitis who experienced a previously u n r e c o r d e d side effect o f SAS: r e p e a t e d episodes of fever, vomiting, a n d bloody d i a r r h e a unrelated to the activity o f the ulcerative colitis. CASE REPORTS Patient 1. An ll-year-old girl was well until age 9V2 years, when she developed the sudden onset of bloody diarrhea, From the Department o f Pediatrics, Harvard Medical School, and the Department o f Medicine (Gastroenterology), the Children ~ Hospital Medical Center. *Supported in part by United States Public Health Service Fellowship Grant No. 1F32A M052 74. **Recipient of Academic Career Development A ward No. AM-44590 from the National Institute of A rthritis, Metabolism and Digestive Diseases. Reprint address: Richard J. Grand, M.D.e Division of Gastl'oenterology, Children's Hospital Medical Center, 300 Longwood Ave., Boston, MA 02115.

The Journal o f Pediatrics March 1978

5. Emery JL: Two cases of lentil pneumonitis, Proc R Soc Med 53:942, 1960. 6. Crome L, and Valentine JC: Pulmonary nodular granulomatosis caused by inhaled vegetable particles, J Clin Pathol 15:21, 1962. 7. Knoblich R: Pulmonary granulomatosis caused by vegetable particles, Am Rev Resp Dis 99:380, 1969.

abdominal pain, fever, and weight loss. A diagnosis of ulcerative colitis was made and on SAS, 4 gm/day, her condition deteriorated as she lost 20 pounds over the next week. Ulcerative colitis was then confirmed by sigmoidoscopy, rectal biopsy, and barium enema. SAS was discontinued and prednisone, 40 rag, was begun to which she responded. Over the next nine months she did well on a tapering dose of prednisone. While still on prednisone (15 mg/day), SAS was reintroduced and she immediately developed fever, nausea, vomiting, and bloody diarrhea. Hospitalization was required, and she became anemic (hemoglobin 7 gm/dl) but the symptoms rapidly resolved when SAS was discontinued. She was then well for six months and prednisone Was again discontinued. Four weeks later, she relapsed and prednisone (40 mg/ day) Was begun but two weeks after that she was admitted to the hospital because of continuing disease. She appeared to be chronically ill and had a diffusely tender abdomen. Rectal examination was painful and the stool was grossly bloody. She responded rapidly t ~ fluids, blood transfusion, and continuation of the corticosteroids. Two days after admission she was apparently well, afebrile, and had normal appearing stools. Two days later she was given SAS, 500 mg, as a test dose. Within 12 hours she developed fever, vomiting, and bloody diarrhea, and required intravenous fluids. The episode lasted 12 hours and subsided with no other therapy. Abbreviation used SAS: sulfasalazine Patient 2. A 13-year-old girl was well until age 8 years when she developed cramping pain and bloody diarrhea. The diagnosis of ulcerative colitis was made after sigmoidoscopy and barium enema. Initial treatment with prednisone (30 rag/day) was successfully tapered to 5 rag/day over one year. Subsequently, prednisone was discontinued, relapse ensued, and prednisone (30 rag/day) was reinstituted a month later without benefit. ACTH was then given intramuscularly for one month with a good response. Four months later while in clinical remission prednisone (30 rag/day) and SAS (2 gin/day) were begun. Within 24 hours the pati6nt developed a rash, fever (103 ~ C) and bloody diarrhea. SAS was discontinued and the episode resolved within two days. She was then well until about 1 year later when, 12 hours after the ingestion of a test dose of SAS (250 mg), she developed vomiting, cramping pain, and bloody diarrhea. Intravenous fluids were administered and the episode resolved within 24 hours. 0022-3476/78/0392-0450500.20/0 9 1978 The C. V. Mosby Co.

Volume 92 Number 3

Brief clinical and laboratory observations

DISCUSSION Both of our patients, young girls with ulcerative colitis, developed the onset of fever, vomiting, and bloody diarrhea after the ingestion of SAS. We believe that these symptoms were not secondary to the underlying ulcerative colitis because they were reproducible in each patient and resolution was more rapid than could be expected with ulcerative colitis. Patient 1 presented with symptoms characteristic of ulcerative colitis. When treated with SAS her condition deteriorated and did not improve until the SAS was discontinued. Symptoms returned during two subsequent challenges although she was clinically well on both occasions and in complete remission on one. Similarly Patient 2 developed symptoms each time she was treated with SAS. Her colitis was quiescent at the time of each challenge. Both patients tolerate aspirin without evidence of gastrointestinal bleeding or upset. Numerous side effects have been reported with both sulfonamides and salicylates, but the combination of fever, vomiting, and bloody diarrhea has not been among them 8. 9 nor has bloody diarrhea been previously reported with SAS. 1~ We have no explanation for the toxicity observed in our patients. Physicians caring for patients with inflammatory bowel disease should be aware that the onset of fever, vomiting, and bloody diarrhea may be due to SAS and not to a flare-up of the disease.

Barium enema: An outpatient procedure in the early diagnosis of acute appendicitis George A. Lewin, M.D.,* Victor Mikity, M.D., and Willis A. Wingert, M.D., Los Angeles, Calif.

THE DIFFICULTY in early diagnosis of acute appendicitis in children has changed little in the last 50 years. Although improvements in nutrition, use of antibiotics, From the Departments of Pediatrics and Radiology, University of Southern California School of Medicine, and the Los Angeles County-USC Medical Center Pediatric Pavilion. *Reprint address: 1129 North State St., Rm. 1D36A Los Angeles, CA 90033

0022-3476/78/0392-0451500.30/0 9 1978 The C. V. Mosby Co.

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REFERENCES 1. Misiewicz J J, Lennard-Jones JE, Connell AM, Baron JH, and Avery Jones F: Controlled trial of sulfasalazine in maintenance therapy for ulcerative colitis, Lancet 1:185, 1965. 2. Goldman P, and Peppercorn MA: Sulfasalazine, N Engl J Med 293:20, 1975. 3. Das KM, Eastwood MA, McManus JPA, and Sircus W: Adverse reaction during salicylazosulfapyridine therapy and the relation with drug metabolism and acetylator phenotype, N Engl J Med 289:491, 1973. 4. Block MB, Genant HK, and Kirsner JB: Pancreatitis as an adverse reaction to salicylazosulfapyridine, N Engl J Med 282:380, 1970. 5. Lead Article. Sulfasalazine induced lung disease, Lancet 2:504, 1974. 6. Wallace IW: Neurotoxicity associated with a reaction to sulfasalazine, Practitioner 204:850, 1970. 7. Strom J: Toxic epidermal necrolysis (Lyell's Syndrome) Scand J Infect Dis 1:209, 1969. 8. Woodbury DM, and Fingl E: Analgesic, antipyretics, antiinflammatory agents and drugs employed in the therapy of gout, in Goodman A, and Gilman AG, editors: The pharmacological basis of therapeutics, New York, 1975, The Macmillan Company, pp 325-358. 9. Weinstein LS: Antimicrobial agents, sulfonamides and trimethoprimsulfmethoxazole, in Goodman A, and Gilman AG, editors: The pharmacologic basis of therapeutics, New York, 1975, The Macmillan Company, pp 1113-1129. 10. Schinagl EF: Pharmacia Laboratories Inc., Personal communication.

anesthesia, and surgical techniques have contributed to a decreased mortality, morbidity continues at the same rate as in the preantibiotic era?, 2 Morbidity can be reduced only by appendectomy before perforation has occurred? With no reliable signs and only suggestive symptoms, APP is difficult to diagnose prior to perforation. When history, physical examination, laboratory data, and routine roentgenograms are equivocal, hospitalization for I

Abbreviations used APP: appendicitus BE: barium enema


observation is the rule, with increased costs and not infrequently, late perforation. Rates of 11 to 23% normal appendices removed at surgery are reported; ',~ approximately 15,000 normal appendices were removed in Great Britain in 19727 These children undergo the anesthetic risks and postoperative morbidity of abdominal surgery in an attempt to prevent the complications of perforation. The barium enema may be a useful procedure in children with equivocal findings to exclude the diagnosis of appendicitis or to delineate it clearly.~-1~ We evaluated this