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In this case of chronic intractable watery diarrhea, based on clinical and histologic features, the differential diagnoses included infectious gastroenteritis, celiac disease, Whipple’s disease, inflammatory bowel disease (IBD), irritable bowel syndrome (IBS), pancreatic insufficiency, medication induced colitis, ischemic colitis, common variable immunodeficiency (CVID), and graft versus host disease. Infectious gastroenteritis and Whipple’s disease were ruled out based on negative results for stool pathogen panel, negative ova and parasite exam, and absence of histologic evidence for infectious agents (Amoeba, Giardia and Tropheryma whipplei). Normal stool elastase and chymotrypsin levels and watery stools ruled out pancreatic insufficiency. Lack of response to gluten-free diet, absence of anti-tissue transglutaminase antibodies, intact duodenal villous architecture and no intra-epithelial lymphocytosis argued against celiac disease. Presence of plasma cells, lack of architectural distortion and granulomas ruled out CVID and IBD, respectively. Findings of increased crypt apoptosis and lymphocytosis in colon raised the possibility of GVHD and medication induced colitis but patient had no history of stem cell transplant, blood transfusions or offending medications. Patient had no risk factors for ischemic colitis. IBS is a diagnosis of exclusion.
The diagnosis of autoimmune enteropathy (AIE) was rendered based on complete lack of goblet and Paneth cells, colonic intra-epithelial and deep crypt lymphocytosis, and increased deep crypt apoptosis. The diagnostic criteria for AIE, based on two large case series include chronic diarrhea (> 6 weeks duration), malabsorption, histologic features of partial/complete villous blunting, deep crypt lymphocytosis, increased crypt apoptotic bodies, minimal intra-epithelial lymphocytosis, lamina propria expansion by mixed but predominantly mononuclear inflammation, neutrophilic cryptitis, loss of goblet and Paneth cells, presence of anti-enterocyte and/or anti-goblet cell antibodies, and exclusion of other causes of villous atrophy including celiac disease, refractory sprue and intestinal lymphoma. [1, 2]
AIE is a rare disease characterized by chronic intractable watery diarrhea, malabsorption, and presence of auto-antibodies. It is often associated with other autoimmune disorders, and with extra-intestinal systemic involvement. [3, 4] It primarily affects children, however, adult cases have also been reported, including rare cases in association with thymoma.[5,6] It can occur in isolated as well as in syndromic forms including IPEX syndrome (immune dysregulation, polyendocrinopathy, enteropathy and X linked syndrome) and autoimmune polyglandular syndrome (APS1).[ 3, 5, 7] Pathogenesis of AIE remains elusive and involves complex pathways of immune dysregulation including disruption of regularity T-cell homeostasis in thymus, immune-mediated intestinal injury by anti-enterocyte and anti-goblet cell antibodies, and abnormal expression of the FOXP3 gene. [8, 9, 10]
Patients with AIE develop malnutrition secondary to chronic diarrhea and require nutritional support in the form of total parenteral nutrition and a combination of immunosuppressive therapy including corticosteroids (budesonide and prednisone). Patients refractory to corticosteroids may need immunosuppressive therapy with azathioprine, 6-mercaptopurine, cyclosporine, mycophenolate mofetil, sirolimus, tacrolimus, infliximab, and rituximab. [3] Some patients may eventually require stem cell transplantation. [11]
List of References
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2. Masia R, Peyton S, Lauwers GY, Brown I. Gastrointestinal biopsy findings of autoimmune enteropathy: a review of 25 cases. Am J Surg Pathol. 2014;38(10):1319-1329. doi:10.1097/PAS.0000000000000317
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11. Moes N, Rieux-Laucat F, Begue B, et al. Reduced expression of FOXP3 and regulatory T-cell function in severe forms of early-onset autoimmune enteropathy. Gastroenterology. 2010;139:770–778