Olmesartan-Associated Sprue-Like Enteropathy

Abstract

Introduction: We present a case of olmesartan-associated sprue-like enteropathy presenting with chronic diarrhea. Although this has been previously reported, it is critical to raise awareness of this rare side effect. A 67-year-old female with history of asthma, insulin-dependent diabetes, remote Clostridium difficile colitis, and hypertension presented with 1 month of severe, watery diarrhea accompanied by abdominal bloating and distention. Initial work-up was notable for mild hypokalemia with normal liver panel, lipase, and complete blood count. Infectious stool studies including fecal leukocytes, Clostridium difficile toxin PCR, rotavirus ELISA, bacterial cultures, as well as giardia and cryptosporidium antigen testing all returned negative. Fecal fat staining returned abnormal. Tissue transglutaminase IgA antibody testing was negative for celiac disease. Colonoscopy to the distal ileum was normal, finding 2 tubular adenomas, normal colonic mucosa, and biopsies negative for microscopic colitis. Her diarrhea persisted, and GI was reconsulted. A review of her medicines revealed she had been taking olmesartan for 2 years. Olmesartan-associated sprue was suspected, and EGD revealed duodenal mucosal changes consistent with sprue-like enteropathy with moderate villous blunting, mild active inflammation, and increased intraepithelial lymphocytes (IELs) by CD3 immunohistochemical staining. Improvement in diarrhea was seen after 1 week of discontinuation of olmesartan, and complete resolution was observed at 1 month. Olmesartan is 1 of several angiotensin II receptor antagonists available for the treatment of hypertension. In 2012, Rubio-Tapia et al identified 22 patients treated with olmesartan who developed clinical features of chronic diarrhea, weight loss, and sprue-like enteropathy, evidenced by villous atrophy and mucosal inflammation on intestinal biopsy. All cases demonstrated negative serologic testing for celiac disease by IgA tissue transglutaminase, and a majority had failed prior therapy with gluten-free diet. Notably, all 22 patients experienced resolution of symptoms with withdrawal of olmesartan and discontinuation of gluten-free diet. The mean duration of exposure to olmesartan was 3.1 years, suggesting a potential drug-induced cell-mediated damage rather than a type I hypersensitivy reaction. Our case report matches prior descriptions of olmesartan-associated sprue-like enteropathy. Though rare, clinicians should be aware of the association between olmesartan and sprue-like illness.