Beyond A Gut Feeling: Confounding Severe Chronic Enteropathy. Autoimmune Or Not?

Summary: We present a 45-year-old male with APS and severe life-threatening chronic diarrhea with protein-losing enteropathy responsive to steroids. We will discuss the patient’s confounding presentation and diagnostic challenge. Autoimmune enteropathy (AIE) is a rare disorder characterized by chronic severe diarrhea and malnutrition that is refractory to dietary changes. AIE is proposed to be due to dysregulation of the gut humoral and cellular immune system from regulatory T-cell system defect 7. Although more common in young children, adult-onset has been reported. Systemic forms of autoimmune enteropathy have also been documented: Immunodysregulation Polyendocrinopathy Enteropathy X-linked (IPEX) or APECED (Autoimmune Phenomena, Polyendocrinopathy, Candidiasis, and Ectodermal Dystrophy). AIE is characterized into three categories: Type 1 with a mutation in the FOXP3 gene causing IPEX syndrome; type 2, similar to IPEX syndrome without being x-linked; and type 3, isolated autoimmune enteritis. Diagnostic criteria of AIE include features of malabsorption, serology findings of anti-enterocyte or anti-goblet cell antibodies, small bowel histology findings of villous blunting, and crypt lymphocytosis. Histopathologic findings commonly include intestinal villous atrophy with lymphocytic infiltration and loss of Paneth and goblet cells. Although anti-enterocyte antibodies highly support the diagnosis of AIE, studies have shown that anti-enterocyte antibodies can be negative in patients with AIE in the presence of hypogammaglobulinemia. Aside from diagnostic challenges, treatment of AIE is inconsistently successful with steroids and immunomodulators. Most patients with AIE require total parenteral nutrition (TPN) therapy. Aggressive immunosuppression is usually necessary for GI symptoms with some patients not responding to high-dose steroids. Immunomodulators such as Azathioprine, Cyclophosphamide, Tacrolimus, Cyclosporine, Infliximab, Vedolizumab, and Abatacept are also used.