Case Presentation: A 74-year-old female with a history of hypertension on olmesartan presents to the emergency department with acute worsening of chronic watery diarrhea and is hospitalized for failure to thrive.The diarrhea has been ongoing for a year but has progressively worsened over the past month, with large volume watery bowel movements unrelated to oral intake now occurring every hour, both day and night. She has lost 80 pounds in a year and required initiation of TPN during her most recent hospitalization.She has had extensive workup with EGD at symptom onset showing gastritis and duodenitis. Histopathology was notable for duodenal intraepithelial lymphocytes and villous atrophy. Colonoscopy was unremarkable, and celiac serologies were negative. Stool infectious testing was negative. She has tried loperamide, diphenoxylate/atropine, dicyclomine, cholestyramine, pancreatic enzymes, and rifaximin previously without improvement in symptoms. She did not find relief with a 6-month trial of a gluten-free diet either.During this admission, she undergoes MRCP which shows bowel wall thickening and mucosal hyperenhancement. Enteroscopy reveals diffuse flat atrophic ulcers mostly in the duodenum. Histological evaluation shows duodenal mucosa with crypt atrophy and severe villous blunting.She has been taking olmesartan daily for four years. As drug-related enteropathy is suspected, the olmesartan is discontinued and oral budesonide is started. Her diarrhea diminishes immediately following drug discontinuation. A month after discharge, the diarrhea is resolved and she has gained 15 pounds. Follow-up EGD two months later reveals improvement in duodenal mucosal atrophy, with biopsies showing normal small bowel villi and crypts.

Discussion: Angiotensin receptor blocker (ARB)-induced enteropathy was first reported in 2012 in a case series from Mayo Clinic. The sprue-like enteropathy is defined by abnormal small bowel villous architecture and chronic diarrhea. It can thus mimic celiac disease, but the distinguishing features are negative celiac serologies and no response to a gluten-free diet.The pathophysiology of ARB-induced enteropathy is unknown. The delay in the onset of symptoms after initiation of ARB may indicate damage from cell-mediated immunity. This hypothesis is supported by reports of increased aggregation of CD8+ cells in the mucosa. It most often occurs with olmesartan, but other ARBs have also rarely been implicated. The reported latency of the disease ranges from months to years. Gross endoscopic findings are non-specific, so pathologic evaluation is important. Of note, there is no sole cardinal histopathological finding that can distinguish ARB-induced injury from other conditions; therefore, an appropriate clinical context is needed. The most common pathologic findings include total intestinal villous atrophy with more variable intraepithelial lymphocytosis and crypt hyperplasia.Complete resolution of both clinical and histologic features may be achieved after discontinuing the inciting agent. Corticosteroids may be used for symptom control after clinical response is achieved with suspension of the drug. Recovery is on the order of weeks to months, for both clinical symptoms and histologic mucosal healing.

Conclusions: ARB-induced enteropathy may currently be underdiagnosed and should be considered in all patients with unexplained chronic diarrhea and unintentional weight loss who are taking olmesartan.

IMAGE 1: Duodenal atrophy