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

血管紧张素Ⅱ受体阻滞剂与胃肠道不良反应(口炎性腹泻样肠病):系统综述

作　　者：Ayesha Kamal Christopher Fain Angela Park Peiqi Wang Eduardo Gonzalez-Velez Daniel A.Leffler Susan M.Hutfless 

机构地区：[1]Department of Medicine,Division of Gastroenterology,Johns Hopkins University,Baltimore,MD,USA [2]Johns Hopkins,Department of Surgery and Surgical Sciences,Johns Hopkins University,Baltimore,MD,USA [3]Division of Gastroenterology,Beth Israel Deaconess Medical Center,Boston,MA,USA [4]Department of Epidemiology,Johns Hopkins Bloomberg School of Public Health,Baltimore,MD,USA

出　　处：《Gastroenterology Report》2019年第3期162-167,I0001,共7页胃肠病学报道（英文）

摘　　要：Background: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.Methods:Case reports,case series and comparative studies of ARBs were searched on PubMed and Embase databases through 21 November 2018 and then assessed.Results: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.Celiacassociated 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.Conclusions:Although enteropathy is rare,clinicians should remain vigilant of this potential adverse event even years after medication initiation.背景:奥美沙坦,一种血管紧张素Ⅱ受体阻滞剂(ARB),会引起口炎性腹泻样肠病这一胃肠道不良反应。有学者提出,该肠病可能是ARB这一类药物的普遍效应,而不是奥美沙坦特异性不良反应。我们对各种ARB药物所引起的口炎性腹泻样肠病的相关文献进行了系统综述。方法:截至2018年11月21日,于PubMed和Embase数据库中检索因服用ARB引起的口炎性腹泻样肠病的病例报告、病例系列和对照研究,并对这些研究进行评估。结果:筛选出82篇病例报告或病例系列文献,以及5篇对照研究文献纳入分析,共包含248例病例。这些病例应用的ARB包括:奥美沙坦(233例;94.0%),替米沙坦(5例;2.0%),厄贝沙坦(4例;1.6%),缬沙坦(3例;1.2%),氯沙坦(2例;0.8%)和依普沙坦(1例;0.4%)。开始服用ARB至症状出现的间隔时间为2周至13年。218例病例报告了组织学结果,其中绒毛萎缩201例(92.2%),上皮内淋巴细胞增多131例(60.1%)。147例患者进行过人白细胞抗原(HLA)测试,其中105例(71.4%)为HLA-DQ2或HLA-DQ8单倍型。169例患者进行了乳糜泻相关抗体检测,其中167例(98.8%)结果呈阴性。130例接受无麸质饮食的患者中,127例(97.7%)肠病症状未获缓解。239例病例报道停用ARB的情况,其中233例(97.4%)停药后症状完全缓解。7例(2.8%)患者再次使用奥美沙坦后,出现症状复发;而其他ARB药物则未出现再次使用后的症状复发。值得注意的是,全球各地所进行的回顾性研究,其研究设计(如研究时间和对病例的定义都有差异)和研究结果不尽相同。结论:尽管口炎性腹泻样肠病临床罕见,但临床医生应该对奥美沙坦可能引起的这种不良事件保持警惕,哪怕是在用药后多年。

关 键 词：angiotensinⅡreceptor blockers OLMESARTAN ENTEROPATHY diarrhea 

分 类 号：R57[医药卫生—消化系统]