Autoimmune Enteropathy and Bullous Pemphigoid

Abstract

Introduction: Autoimmune enteropathy (AIE) is a rare condition characterized by intractable diarrhea, malabsorption, villous atrophy and enterocyte autoantibodies. A predisposition to autoimmune diseases has been reported in association with AIE. We report the first case of a patient with AIE presenting with bullous pemphigoid. Case Report: A 67-year-old man with recently diagnosed bullous pemphigoid was referred for evaluation of chronic, large volume, watery diarrhea and a 30 lb weight loss. A gluten free diet and empiric courses of metronidazole, tetracycline and rifaxamin failed to improve the diarrhea. He denied abdominal pain, nausea, vomiting and fever. He had no allergies. His medications included esomeprazole 40 mg daily, prednisone 10 mg three times daily, olmesartan-hydrochlorothiazide 20/12.5 mg daily and cetirizine 10 mg daily. Physical examination was unremarkable except for large bullous lesions on the trunk and upper extremity. Laboratory investigations revealed low serum immunoglobulins. IgA was 78 mg/dl (82-453), IgG was 26 mg/dl (46-304) and IgM was 563 mg/dl (751-1560). Stool studies and serology for HIV, HLA-DQ 2 and HLA-DQ 8 were negative. Colonoscopy to the terminal ileum was normal, and random biopsies were negative for microscopic colitis. Esophagogastroduodenosocopy revealed erythema in the duodenum, and small bowel biopsies showed severe villous blunting, intraepithelial lymphocytes, increased crypt apoptosis and focal active inflammation. Anti-enterocyte antibodies were present on immunohistochemical stains. The bullous pemphigoid and diarrhea resolved with prednisone 60 mg daily after two weeks of therapy; however, diarrhea recurred with a steroid taper. Prednisone was restarted at 40 mg daily in addition to 6-Mercaptopurine 1.5/mg/kg daily. A slow steroid taper was performed over 3 months, and at 6 months follow-up, he is without diarrhea or skin lesions. Discussion: Chronic diarrhea, malabsorption, villous atrophy and enterocyte autoantibodies in the absence of celiac disease or a primary immunodeficiency are hallmarks of AIE. Predisposition to autoimmunity is well described in the literature; however, there are no reported cases of an association with bullous pemphigoid. Little is known regarding the epidemiology, natural history and therapeutic options for AIE. Treatment is primarily guided by anecdotal experience, and diarrhea tends to be unremitting without aggressive immunosuppresion. Steroid dependent patients require additional immunomodulators for induction and maintenance of remission. Infliximab, tacrolimus, azathioprine and cyclophosphamide have been used with varying success.