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Gastroenterol Rep (Oxf). 2019 Jun;7(3):162-167. doi: 10.1093/gastro/goz019. Epub 2019 Jun 1.

Angiotensin II receptor blockers and gastrointestinal adverse events of resembling sprue-like enteropathy: a systematic review.

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Department of Medicine, Division of Gastroenterology, Johns Hopkins University, Baltimore, MD, USA.
Johns Hopkins, Department of Surgery and Surgical Sciences, Johns Hopkins University, Baltimore, MD, USA.
Division of Gastroenterology, Beth Israel Deaconess Medical Center, Boston, MA, USA.
Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.



Olmesartan, an angiotensin II receptor blocker (ARB), is associated with gastrointestinal symptoms resembling sprue-like enteropathy. Some have proposed that enteropathy may be a class effect rather than olmesartan-specific. We performed a systematic review to identify literature of sprue-like enteropathy for all ARBs.


Case reports, case series and comparative studies of ARBs were searched on PubMed and Embase databases through 21 November 2018 and then assessed.


A total of 82 case reports and case series as well as 5 comparative studies, including 248 cases, were selected and analysed. The ARBs listed in the case reports were olmesartan (233 users; 94.0%), telmisartan (5 users; 2.0%), irbesartan (4 users; 1.6%), valsartan (3 users; 1.2%), losartan (2 users; 0.8%) and eprosartan (1 user; 0.4%). The periods between ARB initiation and onset of symptoms ranged from 2 weeks to 13 years. Histologic results were reported in 218 cases, in which 201 cases (92.2%) were villous atrophy and 131 cases (60.1%) were intraepithelial lymphocytosis. Human leucocyte antigen (HLA) testing was performed in 147 patients, among whom 105 (71.4%) had HLA-DQ2 or HLA-DQ8 haplotypes. Celiac-associated antibodies were tested in 169 patients, among whom 167 (98.8%) showed negative results. Gluten exclusion from the diet failed to relieve symptoms of enteropathy in 127 (97.7%) of 130 patients with information. Complete remission of symptoms after discontinuation of ARB was reported in 233 (97.4%) of the 239 patients with information. Seven cases (2.8%) reported recurrence of symptoms after restarting olmesartan; rechallenge was not reported for the non-olmesartan ARBs. The retrospective studies conducted worldwide had inconsistent study designs (e.g. differences in periods of study and case definition) and findings.


Although enteropathy is rare, clinicians should remain vigilant of this potential adverse event even years after medication initiation.


angiotensin II receptor blockers; diarrhea; enteropathy; olmesartan

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