Gastric Sarcoidosis: Case Report and Literature Review David B. Liang, MD; Jennifer Cohen Price, MD; Haitham Ahmed, BS; Nicole Farmer, MD; Elizabeth A. Montgomery, MD; Samuel A. Giday, MD
Sarcoidosis involving the gastrointestinal tract is extremely rare. Clinically recognizable gastrointestinal system involvement occurs in 0.1% to 0.9% of patients with sarcoidosis. We encountered a 22-year-old African American female admitted to Johns Hopkins Hospital (Baltimore, Maryland) for a 2-week history of fever, chills, eye pain, and abdominal pain. Her abdominal CT scan showed multiple subcentimeter retroperitoneal lymph nodes. An upper endoscopy was performed and discovered an antral nodule that measured about 7 mm and antral gastritis in which biopsies showed active chronic necrotizing granulomatous gastritis. Biopsies of the antral polyp showed focal intestinal metaplasia and active chronic necrotizing granulomatous pattern. Stains for Helicobacter pylori, acid fast, and fungi were negative. A small-bowel series showed no abnormality. Ophthalmologic evaluation revealed panuveitis with bilateral optic disc edema. The patient was later prescribed 60 mg of prednisone by mouth once a day and subsequently her abdominal pain and fever resolved during follow-up 2 months later. This literature review demonstrates the importance in the diagnosis, pathophysiology, clinical manifestations, types of gastric sarcoidosis, major endoscopic findings, and management of gastric sarcoidosis. Keywords: ophthalmic n sarcoidosis n inflammation J Natl Med Assoc. 2010;102:348-351 Author Affiliations: Division of Gastroenterology and Hepatology (Drs Liang, Price, and Giday), Departments of Pathology (Dr Montgomery) and Internal Medicine, Johns Hopkins Hospital, Baltimore, Maryland (Drs Farmer and Giday, and Mr Ahmed); and Department of Medicine, Howard University College of Medicine, Washington, DC. Correspondence: Samuel A. Giday, MD, Johns Hopkins Hospital, Division of Gastroenterology and Hepatology, 1830 E Monument St, Room 424, Baltimore, MD 21205 ([email protected]
22-year-old African American woman presented to our hospital with complaints of a 2-week duration of fever, chills, eye pain, and epigastric abdominal pain. An abdominal and chest computed tomography scan showed multiple subcentimeter retroperitoneal and mediastinal lymph nodes along with 348 JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION
bilateral pulmonary infiltrates. An extensive infectious disease workup, including bacterial, mycobacterial, and fungal cultures, was negative. Serologies for histoplasma; aspergillus; human immunodeficiency virus; and spirochetal infection, including Lyme disease and syphilis, were also unrevealing. Serum angiotensin-converting enzyme (ACE) levels were normal. A gastric erythema and an antral nodule (Figure 1) were seen on an upper endoscopy performed as part of the evaluation of her abdominal pain. Histopathological examination revealed active chronic necrotizing granulomatous gastritis (Figure 2). Stains for Helicobacter pylori, acid fast, and fungi were negative. A small-bowel series showed no abnormality. Ophthalmologic evaluation revealed panuveitis with bilateral optic disc edema. Because of the absence of an infectious etiology coupled with the information obtained from the gastric biopsy, pulmonary finding, and ophthalmologic evaluation, the patient was started on systemic steroids for sarcoidosis with a significant clinical improvement.
Sarcoidosis is a multisystem granulomatous disease of unknown etiology that affects individuals worldwide.1 The exact prevalence (estimated at 10-20/100 000 population) and annual incidence of sarcoidosis are not known with certainty.1 The lifetime risk of sarcoidosis in blacks in the United States is 2.4%, compared with a lifetime risk of 0.85% in whites.2 Up to 1% of patients with sarcoidosis can have a clinically evident involvement of the gastrointestinal (GI) tract.3 Gastric sarcoidosis, first described by Schaumann in 1936, is the most common form of GI tract sarcoidosis. Sarcoidosis can also appear in the esophagus,4 liver,5 rectum,6 pancreas,7colon,8 and appendix.9 Involvement of the gastric antrum has been reported in up to 10% of patients with systemic disease.3
Clinical presentation of gastric sarcoidosis varies depending on the intensity of granulomatous inflammation and anatomic location of the gastric involvement Gastric sarcoidosis can present as an ulceration of the gastric mucosa, a polypoid lesion or a diffuse infiltrative VOL. 102, NO. 4, APRIL 2010
area with associated fibrosis. In some patients, this fibroUlcerative gastric sarcoidosis usually presents with sis may lead to gastroparesis and a presentation similar to epigastric pain. Gastric ulcer formation occurs in areas in linitis plastica.10 Most patients, though, have a normal which mucosa is infiltrated with granulomatous inflamappearing or minimal gastric inflammation. The most mation.15 Although ulcerative gastric sarcoidosis can present throughout the stomach, it tends to occur more frecommon presenting symptom is epigastric pain (75%). quently in antral mucosa, pylorus, and lesser curvature.16 This pain can be associated with other nonspecific comSarcoid ulcers can also lead to the formation of gastric plaints, including nausea and vomiting, especially in those patients with fibrostenosing disease because of partial Figure 1. Gastric Nodule and Minimal Antral Erythema or severe complete gastric outlet obstruction. Most patients who present with abdominal pain and weight loss are first considered to have malignancy, especially when linitis plastica is found during subsequent evaluation.10 Patients with disseminated GI tract sarcoidosis may also report diarrhea due to involvement of the small or large bowel. About 25% of patients with gastric sarcoidosis can also present with symptoms of upper GI bleeding.11
Most patients with gastric sarcoidosis do not have any referable symptoms. It is usually incidentally discovered after finding noncaseating granuloma on gastric mucosal biopsy. During endoscopy, the gastric mucosa may appear either normal or hyperemic with superficial nodularity. Mucosal involvement in gastric sarcoidosis has also been reported to be patchy, and a diagnosis of gastric sarcoidosis can be missed if mucosa appears normal.12Atrophic gastritis also has been described in patients with chronic gastric sarcoidosis. This type of gastric sarcoidosis is usually benign. Palmer et al followed 6 patients with gastric sarcoidosis diagnosed by biopsy for a period of 18 months. During follow-up, these patients did not develop GI-related symptoms, and there was no change in biopsy patterns.13,14
Figure 2. Necrotizing Epithelioid Granuloma
Note the giant cell in the lower center portion of the field. A collection of neutrophils embedded in necrotic tissue appears on the left side of the field. Original magnification, 100x.
JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION
VOL. 102, NO. 4, APRIL 2010 349
outlet obstruction or bleeding. Thrombocytopenia—secondary to hypersplenism, portal hypertension, and esophageal varices—and gastric ulcer associated with antral stasis are among contributing factors to GI hemorrhage in sarcoidosis patients.15 Infiltrative gastric sarcoidosis can be localized or diffuse. Localized infiltrative gastric sarcoidosis is dominant in the distal part of the stomach resulting in smooth, coned-shaped antral narrowing and deformity.17 Diffuse infiltration of gastric mucosa with granulomatous inflammation may result in linitis plastica-like appearance. This type of gastric sarcoidosis should be differentiated from gastric carcinoma. If granulomatous inflammation is confined to submucosa and deeper layers of stomach, superficial biopsies through endoscope may miss the diagnosis of gastric sarcoidosis. In these types of situations a deep submucosal biopsy or a full-thickness surgical biopsy may lead to a conclusive diagnosis, especially in ruling out malignancy. Other tests such as endoscopic ultrasonography may be beneficial in these scenarios mainly in the acquisition of deep samples and evaluation of perigastric and celiac lymphadenopathy. Polypoid gastric sarcoidosis is rare. Single and multiple gastric polypoid lesions have been reported in the literature.18It has been proposed that polypoid gastric sarcoidosis represents an early phase or atypical appearance of diffuse-type gastric sarcoidosis.
Upper endoscopy should be performed in patients with sarcoidosis and persistent epigastric symptoms. The diagnosis of gastric sarcoidosis depends upon histologic evidence of noncaseating granulomas on biopsy with clinical and pathologic evidence of sarcoidosis affecting other organ systems. Specimens should be carefully interpreted because Crohn’s disease, Whipple’s disease, tuberculosis, fungal infections, syphilis, and foreign-body reactions may yield similar pathology. The diagnosis of gastric sarcoidosis is difficult to establish in the absence of multisystem involvement. Major endoscopic findings may reveal nodular changes, diffuse erythematous mucosa, gastritis, thickened mucosa, greater or lesser curvature deformities, or benign- or malignant-appearing or multiple ulcers.3,19 Nodular mucosal irregularities are common, and mucosal polyps may occasionally be present.10 Segmental mucosal thickening and nondistensibility that mimics the linitis plastica variety of gastric cancer are the most common abnormalities on upper GI series. The presence of granulomatous inflammation in the stomach should lead one to investigate other systemic disease processes. In one report, the most common cause of granulomatous inflammation in the stomach was noted to be gastric Crohn’s disease.20 Shapiro et al showed 42 patients with granulomas on gastric biopsy specimens who were seen at the Cleveland Clinic
350 JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION
between 1975 and 1994. The most common diagnoses were Crohn’s disease (55%), sarcoidosis (21%), distal esophageal adenocarcinoma and chronic active gastritis (5%), mucosa-associated lymphoid tissue (MALT lymphoma) (5%), peptic ulcer complications (5%), hypertrophic gastropathy (2%). Other possible causes include infections (tuberculosis, histoplasmosis, Whipple’s disease, tertiary syphilis, anisakiasis, H pylori), tumors (adenocarcinoma, lymphoma), vasculitis (Wegener’s granulomatosis), and foreign bodies (usually due to the infiltration of foreign material or gastric juice into a gastric ulcer crater, which later becomes engulfed in the repair process, causing a foreign-body reaction).
The decision to treat GI sarcoidosis is based upon the activity and extent of disease. Glucocorticoids are the mainstay of treatment. Corticosteroid therapy produces a dramatic clinical response in about 66% of patients with systemic gastric sarcoidosis.21 Prednisone, 30-40 mg, given daily as a single dose followed by a maintenance dose of 10-15 mg over 6 months results in an effective response.22 The disease is monitored clinically, radiographically, and by measuring serum ACE levels if abnormal at the time of diagnosis. Although histologic regression has not been documented consistently with corticoidsteroid therapy, symptomatic and endoscopic regression has been repeatedly reported. Corticoidsteroids should be used in symptomatic patients, especially with weight loss or abdominal pain. Otherwise, a trial of proton pump inhibitor with close symptomatic follow-up is reasonable.19Surgery frequently is required in patients with pyloric stenosis or GI hemorrhage.
GI sarcoidosis is an extremely rare disease. Up to 1% of patients with sarcoidosis can have a clinically evident involvement of the gastrointestinal tract.4 It is important to recognize the disease and perform endoscopy for patients with persistent abdominal pain and evaluate histologic evidence of granulomas consistent with gastric sarcoidosis. This literature review demonstrates the importance in the diagnosis, major endoscopic findings, and management of gastric sarcoidosis.
1. Thomas KW, Hunninghake GW. Sarcoidosis. JAMA. 2003;289(24):33003303. 2. Rybicki BA, Major M, Popovich J et al. Racial differences in sarcoidosis incidence: a 5-year study in a health maintenance organization. Am J Epidemiol. 1997;145(3):234-241. 3. Fireman Z, Sternberg A, Yarchovsky Y, et al. Multiple antral ulcers in gastric sarcoid. J Clin Gastroenterol. 1997;24(2):97-99. 4. Murdock A, Jacob G. Sarcoidosis of the esophagus presenting macroscopically as Barrett’s esophagitis. Am J Gastroenterol. 2003;98(7):16611662. 5. Mayock RL, Bertrand P, Morrison CE, et al. Manifestations of sarcoidosis. Analysis of 145 patients, with a review of nine series selected from the litera-
VOL. 102, NO. 4, APRIL 2010
Gastric sarcoidosis ture. Am J Med. 1963;35:67-89. 6. Sprague R, Harper P, McClain S, et al. Disseminated gastrointestinal sarcoidosis. Case report and review of the literature. Gastroenterology. 1984;87(2):421-425. 7. Garcia C, Kumar V, Sharma OP. Pancreatic sarcoidosis. Sarcoidosis Vasc Diffuse Lung Dis. 1996;13(1):28-32. 8. Hilzenrat N, Spanier A, Lamoureux E, et al. Colonic obstruction secondary to sarcoidosis: nonsurgical diagnosis and management. Gastroenterology. 1995;108(5):1556-1559. 9. Munt PW. Sarcoidosis of the appendix presenting as appendiceal perforation and abscess. Chest. 1974;66(3):295-297. 10. Farman J, Ramirez G, Rybak B, et al. Gastric sarcoidosis. Abdom Imaging. 1997;22(3):248-252. 11. Ona FV. Gastric sarcoid: unusual cause of upper gastrointestinal hemorrhage. Am J Gastroenterol. 1981;75(4):286-288. 12. Friedman M, Ali MA, Borum ML. Gastric sarcoidosis: a case report and review of the literature. South Med J. 2007;100(3):301-303 13. Palmer CD. Note on silent sarcoidosis of gastric mucosa. J Lab Clin Med. 1958;52: 231-234. 14. Roth D, West B, Madison J, Cooper D. Gastric carcinoma in a patient with sarcoidosis of the gastrointestinal tract. Am J Gastroenterol. 1994;89(9):1589-1591.
JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION
15. Kremer RM, William JS. Gastric sarcoidosis: a difficult diagnosis. Am Surg. 1970; 36(11):686-690. 16. Panella VS, Katz S, Kahn E, et al. Isolated gastric sarcoidosis. Unique remnant of disseminated disease. J Clin Gastroenterol. 1988;10(3):327-331. 17. Konda J, Ruth M, Sassaris M, et al. Sarcoidosis of stomach and rectum. Am J Gastroenterol. 1980;73(6):516-518. 18. Kaneki T, Koizumi T, Yamamoto H, et al. Gastric sarcoidosis—a single polypoid appearance in the involvement. Hepatogastroenterology. 2001;48(40):1209-1210. 19. Chlumsky J, Krtek V, Chlumska A. Sarcoidosis of the stomach: endoscopic diagnosis and possibilities of conservative treatment. Hepatogastroenterology. 1985;32:255–257. 20. Shapiro JL, Goldblum JR, Petras RE. A clinicopathologic study of 42 patients with granulomatous gastritis. Is there really an “idiopathic” granulomatous gastritis? Am J Surg Pathol. 1996;20(4):462-470. 21. Chinitz MA Brandt LJ, Frank MS, et al. Symptomatic sarcoidosis of the stomach. Dig Dis Sci. 1985;30(7):682-688. 22. Vahid B, Spodik M, Braun KN et al. Sarcoidosis of gastrointestinal tract: a rare disease. Dig Dis Sci. 2007;52(12):3316-3320. Epub 2007 Apr 5. Review. n
VOL. 102, NO. 4, APRIL 2010 351
Join Us In...
JULY 31 – AUGUST 4
NATIONAL MEDICAL ASSOCIATION
2010 Annual Convention and Scientific Assembly
Photos courtesy of Orlando CVB