Gastric sarcoidosis.

Sarcoidosis is a systemic disorder of uncertain etiology, characterized by accumulation of mononuclear inflammatory cells followed by the formation of noncaseating epithelioid granulomas at the site of involvement. The disease has a female preponderance, and is more common in the African-American population. (1) Virtually all organs of the body have been reported to be affected, but the most common site of involvement is the lung and mediastinal lymph nodes. Involvement of the skin, eyes, and lymphatic tissues is also common. Other organ involvement includes the heart (with infiltrative cardiomyopathy and conduction abnormalities), nervous system (with unilateral facial nerve palsy), and reticuloendothelial system (liver and spleen). Gastrointestinal manifestations excluding liver involvement (which occur in 40-70% of cases) are not commonly reported. (1) It is estimated that up to 10% of patients with pulmonary or cutaneous sarcoidosis have alimentary tract involvement, most of which is asymptomatic. An autopsy study of patients with sarcoidosis, however, reported gastroduodenal involvement in 4-10% of the cases. (2,3) Only 1% of cases of systemic disease have symptomatic gastric involvement.

In this issue of the Southern Medical Journal, Friedman et al (4) report a case of gastric sarcoidosis in a young woman who presented with weight loss and early satiety. This patient had been diagnosed with sarcoidosis of the lungs 6 months prior with mediastinal lymph node biopsy when she presented with chest pain. The authors report swift response to corticosteroid therapy and recurrence of symptoms upon its withdrawal. As in this case, the stomach is the most frequently affected alimentary organ with sarcoidosis; involvement of the esophagus, small bowel, and colon is rarely reported. Case reports of gastric sarcoidosis are scattered but date back more than 60 years. (5)

Patients with sarcoidosis typically display symptoms between the ages of 20 and 40 years. Gastrointestinal sarcoid, however, has been reported in the pediatric age group as well. The differential diagnosis of granulomas in the GI tract includes mycobacterium, syphilis, histoplasma infection, gastric cancer and lymphoma, Langerhans cell histiocytosis, as well as Crohn and Whipple diseases. (6) Clinical manifestations include epigastric fullness or pain, early satiety, nausea/vomiting, hematemesis and weight loss. Gastric involvement particularly affects the antrum. Endoscopic findings vary from diffuse mucosal hyperemia (thickening of gastric folds leading to narrowing of the lumen) to nodular or polypoid lesions. GI hemorrhage has been reported due to ulcers that look very similar to peptic ulcer disease. Thus, gastric biopsies are essential in making the diagnosis. (7) The submucosa of the stomach can have granulomas with mucosal sparing in early and asymptomatic cases.

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Reports of gastric sarcoidosis with no other sarcoid foci are rare. (8,9) Those cases often have a previous history of asymptomatic hilar adenopathy or subclinical pulmonary involvement. Even though there is no radiological evidence of lung disease, bronchoscopy and transbronchial biopsies can make the diagnosis in such cases. (6) Symptomatic small intestinal involvement is extremely rare. Duodenal obstruction by cicatrizing constriction of the granulomatous inflammation has been reported in a few cases. It is important to consider Crohn disease in the differential diagnosis especially in the younger age group. Both are granulomatous inflammatory diseases that present with weight loss and abdominal pain. Histologically, sarcoid granulomas are rather superficial compared with Crohn. Lack of perianal involvement or fistula formation and terminal ileal sparing suggest sarcoidosis. (2)

It has been suggested that there might be an overlap between sarcoidosis and Crohn disease, both being an autoimmune disorder of unknown etiology with indications of common pathogenesis and genetic basis. An expansion of T-cell subsets similar to sarcoidosis has been shown in Crohn disease with CD4 lymphocyte activation in intestinal mucosa. This suggests cell-mediated mechanisms in the gut similar to that displayed in pulmonary sarcoidosis. Just as sarcoid rarely involves the gut, Crohn disease also rarely involves the lungs and is mostly linked to treatment with sulfasalazine and mesalamine, manifesting as either eosinophilic pneumonia or alveolar fibrosis. The pathologic similarities may suggest a common inciting antigen triggering distinct immune responses. (10) The most common etiology behind bowel obstruction in sarcoidosis is external compression by abdominal lymphadenopathy. Lymph nodes in the abdomen are involved subclinically in up to 40% of cases of sarcoid.

Gastric sarcoidosis has been described as causing irritable bowel syndrome in a patient with previous pulmonary sarcoid. This young male patient met the Rome II criteria for constipation-predominant IBS. Significant symptomatic relief with corticosteroid and azathioprine therapy was described. (11) Kawaura et al (12) reported three cases of gastric sarcoidosis with and without pulmonary involvement with spontaneous resolution of symptoms and evidence of resolution on endoscopic inspection but not histologically. (5,12)

Although histologic regression has not been consistently documented with corticosteroid therapy, symptomatic and endoscopic regression has been repeatedly reported. Whether it is all related to appetite stimulation effects of corticosteroid or actual direct theraputic mechanism is also difficult to determine. However, it is fair to conclude at this point that corticosteroids should be used in cases with severe symptoms, especially weight loss or intestinal obstruction. Otherwise, a trial of proton pump inhibitor with close symptomatic follow-up is reasonable. (7,13)

References

1. Newman LS, Rose CS, Marier LA. Sarcoidosis. N Engl J Med 1997;336:1224-1234.

2. Noel JM, Katona IM Pineiro-Carrero VM et al. Sarcoidosis resulting in duodenal obstruction in an adolescent. J Pediatr Gastroenterol Nutr 1997;24:594-598.

3. Palmer ED. Note on silent sarcoidosis of the gastric mucosa. J Lab Clin Med 1958;52:231-234.

4. Friedman M, Ali MA, Borum ML. Gastric sarcoidosis. South Med J. 2007;100:301-303.

5. Sato Y, Enjoji M, Ito K, et al. Gastric sarcoid without other sarcoid lesions [letters to the editor]. J Clin Gastroenterol 2002;35:359.

6. Fireman Z, Sternberg A, Yarchovsky Y, et al. Multiple antral ulcers in gastric sarcoid. J Clin Gastroenterol 1997;24:97-99.

7. Chlumsky J, Krtek V, Chlumsky A, et al. Sarcoidosis of the stomach: endoscopic diagnosis and possibilities of conservative treatment. Hepatogastroenterology 1985;32:255-257.

8. Panella VS, Katz S, Kahn E, et al. Isolated gastric sarcoidosis, unique remnant of disseminated disease. J Clin Gastroenterol 1998;10:327-331.

9. Teichman RF, Brandt-Rauf PW. Gastric sarcoidosis. J R Soc Med 1991;84:50-51.

10. Storch Ian Rostoff L Katz S, et al. Sarcoidosis and inflammatory bowel disease [letters to the editor]. J Clin Gastroenterol 2001;33:345.

11. Leeds S McAlindon ME Lorenz E, et al. Gastric sarcoidosis mimicking irritable bowel syndrome: cause not association? World J Gastroenterol 2006;12:4754-4756.

12. Kawaura K Takahashi T Kasaka K, et al. Spontaneously identified gastric sarcoidosis: a report of three cases. J Int Med Res 2003;31:239-243.

13. Korsager S. Sarcoidosis of the stomach: a case report. Scand J Resp Dis 1979;60:24-27.

There is meaning in every journey that is unknown to the traveler.
--Dietrick Bonhoeffer

Maen Alqdah, MD, and Robert Lenox, MD

From State University of New York, Upstate Medical University, Syracuse, NY.

Reprint requests to Robert Lenox, MD, SUNY Upstate Medical University, 750 East Adams Street, Syracuse, NY 13201. Email: [e-mail]

Accepted November 7, 2006.