Abstract
BackgroundOlmesartan, 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.MethodsCase reports, case series and comparative studies of ARBs were searched on PubMed and Embase databases through 21 November 2018 and then assessed.ResultsA 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.ConclusionsAlthough enteropathy is rare, clinicians should remain vigilant of this potential adverse event even years after medication initiation.
Highlights
Angiotensin II receptor blockers (ARBs) are among the most commonly used blood-pressure-lowering drugs in the world [1, 2]
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 ARBs listed in the case reports were olmesartan (233 cases; 94.0%), telmisartan (5 cases; 2.0%) [11,12,13,14], irbesartan (4 cases; 1.6%) [13, 16, 22], valsartan (3 cases; 1.2%) [13, 15], losartan (2 cases; 0.8%) and eprosartan (1 case; 0.4%) [17]
Summary
Angiotensin II receptor blockers (ARBs) are among the most commonly used blood-pressure-lowering drugs in the world [1, 2]. Discontinuation of olmesartan resulted in histologic recovery or improvement and remission of symptoms in these patients After this case series, more case reports described sprue-like disease with olmesartan use [6,7,8,9]. Similar histological findings together with sprue-like enteropathy were reported for the first time in a patient receiving telmisartan in 2014 [11], followed by 11 case reports of enteropathy after nonolmesartan ARB use [10,11,12,13,14,15,16,17] These case reports raised the possibility that ARB-related enteropathy may be a class effect rather than an effect specific to olmesartan [13]. Conclusions: enteropathy is rare, clinicians should remain vigilant of this potential adverse event even years after medication initiation
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