A case of Olmesartan-induced enteropathy

Abstract

Clinical Scenario: A 60 year old African American gentleman with a history of high blood pressure on olmesartan for the past 7 years presents with a 6 month history of diarrhea consisting of 3-4 loose, non-bloody bowel movements a day, associated with a ten pound weight loss over that time period. He has no known personal or family history of inflammatory bowel disease, Celiac disease, or colon cancer. Physical exam was normal. On laboratory evaluation, with the exception of an albumin of 3.3 and Hgb 12.6 (MCV 89), CBC, CMP, ESR, CRP, and TSH were within normal limits. Testing for Celiac disease was negative or normal including TTG, anti-endomysial antibody, total IgA, DQ2 and DQ8. MRI of the abdomen with contrast showed diffuse enhancement and bowel wall thickening of the proximal jejunum with associated prominent mesenteric lymph nodes. Duodenal biopsies from EGD had near total villous blunting with increased intraepithelial lymphocytes, but no clonality (see figures 1-2). Colonoscopy with biopsies demonstrated increased intraepithelial lymphocytes of the colon and terminal ileum, which also had marked villous blunting. Patient was empirically placed on a gluten free diet prior to completion of the above work up, which did not improve his symptoms. He was then started on a trial of budesonide, which caused his stools to become more formed, but did not change the frequency. Stool studies that had not been sent initially were obtained and were positive for Clostridium difficile infection, which was treated with a 2 week course of Flagyl, but not thought to explain the findings on imaging and endoscopic evaluation. Patient's antihypertensive medication was switched from olmesartan to amlodipine, resulting in complete resolution of symptoms. Discussion: Olmesartan is associated with a spruelike enteropathy consisting of chronic diarrhea, weight loss, negative Celiac testing, and lack of response to a gluten free diet. Symptoms characteristically resolve with histologic improvement after withdrawal of olmesartan. A recently published retrospective study of 22 patients with olmesartan associated enteropathy reported a median age at diagnosis of 69.5. Most patients were taking 40 mg/day, with a mean duration of exposure of 3.1 years (range 0.5-7). In addition to diarrhea and weight loss, presenting symptoms included nausea and vomiting (68%), abdominal pain (50%), bloating (41%), and fatigue (68%). Histologic examination of the small bowel demonstrated villous atrophy, with a thick band of subepithelial collagen deposition (collagenous sprue) in 7. Out of 13 patients who underwent colonoscopy, 5 had evidence of microscopic colitis. Of the 14 patients in whom gastric biopsies were obtained, 5 had lymphocytic gastritis and 2 had collagenous gastritis. All patients responded clinically to withdrawal of olmesartan, with histologic recovery documented by duodenal biopsies in 17 out of 18 patients. Though the mechanism of olmesartan induced enteropathy is unknown, inhibition of TGF-B (involved in gut immune homeostasis) is thought to play a role. More studies will need to be done to determine if other angiotensin receptor blockers in addition to olmesartan are also associated with spruelike enteropathy. (Figure Presented)