“Weight Loss Syndrome”: A Case of Olmesartan-Associated Enteropathy

Abstract

Blood pressure control aims to reduce the risk of long-term cardiovascular events. Olmesartan medoxomil is an oral prodrug that belongs to the angiotensin II receptor blockers (ARBs) family and blocks the renin-angiotensin-aldosterone system by antagonizing the angiotensin II (AT) type 1 receptor. 1 Olmesartan-associated enteropathy (OAE), was described for the first time in 2012 by Rubio-Tapia et al. in 22 patients with chronic diarrhea and weight loss treated with olmesartan. Serological screening tests for celiac disease were negative, and there was no response to a gluten-free diet. Endoscopic biopsy showed villous atrophy and mucosal inflammation similar to sprue-like enteropathy. Clinical response was demonstrated in all patients after drug discontinuation. In July 2013 the U.S. Food and Drug Administration issued a postmarketing warning highlighting the importance of this new entity. 2 We present a case of a 76-year-old man with a history of arterial hypertension treated with olmesartan/hydrochlorothiazide 40/12.5mg/daily during 2 years, who presented with 2-month history of weight loss of 15 kg, vomiting and watery diarrhea, up to 4 stools per day, without bleeding, mucus or pus, and afebrile. Stool sample culture found no microbiological isolations. Laboratory tests showed hemoglobin 14 g/dL, white blood cells 9,100/mcL, platelets 259,000/mcL, creatinine 0.7 mg/dL with no electrolyte imbalance, albumin 3.0 g/dL, C-reactive protein 1.5 mg/dL, thyroid-stimulation hormone 0.5 mUI/L and T4-free 1.3 nanogram/dL. Biomarkers were normal. Autoimmune tests with anti-nuclear antibodies and anti-DNA antibodies were negative. Serological tests for celiac disease (CD) were negative. Human leukocyte antigen (HLA) DQ2 typing was positive. Abdominal computed tomography showed a diffuse thickening throughout the entire colon and terminal ileum. Gastroscopy and colonoscopy evinced villous atrophy in duodenum and unspecific recto-colon-ileitis, respectively. Biopsy samples from gastric, ileum and colon showed no malignancy but severe chronic nonspecific inflammatory damage with the presence of lymphocytes, plasma cells and granulocytic infiltration. Helicobacter pylori was not visualized (Figure 1).During hospitalization, watery diarrhea persisted in spite of a gluten-free diet. Parenteral nutrition was required initially due to severe weight loss and oral intolerance. Clinical remission was observed after withdrawal of olmesartan. Control

Systematic review: Clinical phenotypes, histopathological features and prognosis of enteropathy due to angiotensin II receptor blockers

“…p < 0.05 were considered statistically significant. Ninety-four were case reports or case series of enteropathy due to ARBs (86 case reports or case series with less than five patients and eight case series with five or more patients 5,11,[99][100][101][102][103][104] ) corresponding to a total of 183 patients (101 F, mean age at diagnosis 69 ± 10 years) published between 2012 and 2023, with most cases being reported in Europe (93 cases) 11,13,17,18,20,21,23,24,26,27,[30][31][32][33][34]40,44,45,50,51,[55][56][57][61][62][63][64]67,68,70,73,75,77,80,[83][84][85][89][90][91]…”

“…Finally, three patients showed macroscopic abnormalities at colonoscopy, including one case of ulceration of the proximal colon, 29 one case of non-specific pan-colitis and ileitis 70 and one patient presented erosive ileitis. 103…”

“…11 Whether a follow-up OGD was performed or not was reported for 144 patients (78.7%). 5,11,[13][14][15][16][17][18][19][20][21][23][24][25][26][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42][43][44][45]47,48,51,54,56,[58][59][60][61][62][63][65][66][67][68][69][70]72,[...…”

“…5,11,[13][14][15][16][17][18][19][20][21][23][24][25][26][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42][43][44][45]47,48,51,54,56,[58][59][60][61][62][63][65][66][67][68][69][70]72,[76][77][78]…”

“…All these patients had a normal gastric biopsy at follow -up 5,11,38,61,77,80,92,93,102 with the exception of one. 102 Of the 39 patients with colon mucosal changes at baseline, 5,14,16,20,21,23,26,29,34,36,38,42,48,52,[60][61][62]70,80,84,[91][92][93][99][100][101]103,104 only six (15%) repeated a follow-up colonoscopy with biopsies after a median of 6 months (IQR 5-6). 20,48,61,70,93 Resolution of either microscopic colitis, 20,48,93 non-specific chronic inflammation of the colon 61,70 or ileal VA 20 was reported in all these patients.…”