An Unusual Cause of Chronic Diarrhea

Abstract

Case: 79-year-old Caucasian woman with diabetes and chronic bronchiectasis was admitted with nine months of refractory nausea, vomiting and diarrhea, and associated weight loss. Had large volume stools with nocturnal symptoms, without blood or mucus. There was no coincident travel or new medications. Nasojejunal feeds were initiated for intractable emesis. Labs showed anemia with elevated ESR and CRP. She also had low albumin, hypovitaminosis D, and coagulopathy. Stool studies were negative for infection or inflammation. Fecal elastase was undetectable, with stool osmolar gap suggestive of osmotic diarrhea. Qualitative fecal fat was normal. Upper and lower endoscopy revealed multiple discrete ulcers in the proximal colon, otherwise unremarkable. Duodenal biopsies revealed total villous atrophy and extensive subepithelial collagen deposits on trichrome stain, with denuded surface epithelium, consistent with collagenous sprue. There was no increase in intraepithelial lymphocytes. Histology of colonic ulcers noted focal areas of fibrosis that did not meet criteria for collagenous colitis. Celiac serology was negative for anti-TTG and anti-endomysial antibodies with low IgG and IgA levels; genotyping for HLA-DQ2 was positive. Testing for anti-enterocyte antibodies was negative. The patient was started on a gluten free diet (GFD), pancreatic enzymes and systemic steroids. She noted decreased stool frequency and tolerance of oral diet by day 3, and was discharged on prednisone taper. At one month, she was in clinical remission, and steroids were discontinued. Three months after diagnosis, she remains asymptomatic on GFD and pancreatic enzymes, with improvement of nutritional lab markers. Discussion: Collagenous sprue (CS) is a rare condition, originally described as a refractory form of celiac disease (CD). It is now considered more heterogeneous, with links to CVID or as a paraneoplastic syndrome. Our patient did not have positive CD serology. Low initial immunoglobulin levels normalized with clinical remission. CS presents with chronic diarrhea, malabsorption and weight loss. Diagnosis is established on intestinal biopsy with a subepithelial collagen layer greater than 10 mu and inflammatory cells in the lamina propria. Evaluation for coexisting microscopic colitis should be performed. Diarrhea is classically unremitting without aggressive immunosuppression. Steroids are the mainstay of therapy along with GFD, with remission rates of up to 80%. However, the clinical course is unpredictable and often poorly responsive to medical therapy. Early recognition of CS is essential to prevent significant morbidity and mortality. However, more data are needed to optimize therapeutic strategies.