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Under the Microscope: How would you diagnose this case?

A 66 year old man with hypothyroidism, vitamin D deficiency, type 1 diabetes, and 8 week history of severe diarrhea with 30 pound weight loss and evolving ascites. On colonoscopy, congested mucosa was observed. Below is a photo of the ascending colon. What is your diagnosis?

a) Graft versus host disease. d) Autoimmune colitis.
b) Active colitis. e) Normal colonic mucosa.
c) Lymphocytic colitis.

Answer: Autoimmune colitis.

The photomicrographs of the colon show a marked absence of the goblet cells and Paneth cells, intraepithelial lymphocytes present within the crypt epithelium, and numerous apoptotic bodies in the crypts. Interestingly, a concominant duodenal biopsy (above) showed a marked reduction in goblet and Paneth cells; typically, these patients have marked villous blunting which can simulate celiac disease.

Autoimmune enteropathy (AIE) is a syndrome of protacted diarrhea with autoantibodies to gut epithelium, along with extragastrointestinal manifestations. Most cases occur in infancy or the first year of life. Gastrointestinal symptoms are due to circulating anti-goblet cell or anti-enterocyte antibodies. Some of the other antibodies detected include anti-smooth muscle, antimitochondrial, and antiadrenal; these produce disease in organs such as the kidney, pancreas, and thyroid. AIE is associated with a high mortality rare, occurring in up to a third of patients. Changes in diet and steroid therapy usually have no effect, and immunosuppressants, such as cyclosporine or tacolimus, are often needed.

In this case, anti-goblet cells were detected by indirect immunofluorescence at The Children’s Hospital of Philadelphia. The patient was treated with steroids and the diarrhea immediately improved. He has been on steroids since early 2010 and is doing well.

Graft versus host disease is a T-cell mediated process that can produce similar histologic findings in bone marrow transplant patients in that there are numerous apoptotic bodies and intraepithelial lymphocytes in the colonic crypts; however, there would not be an absence of goblet or Paneth cells. The severity of diarrhea with weight loss and evolving ascites would be unusual for a case of lymphocytic colitis. In lymphocytic colitis, the intraepithelial lymphocytosis tends to be more prominent in the superficial epithelium rather that in the crypts, and goblet cells are not depleted. An autoimmune process is included in the differential of any gastrointestinal biopsy with increased intraepithelial lymphocytes.

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