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大疱性类天疱疮发病相关药物的探索:一项全国性研究

Exploration of Drugs Associated With the Development of Bullous Pemphigoid: A Nationwide Study.

作者信息

Kim Min Jae, Kim Bo Ri, Lee Kun Hee, Ju Hyun Jeong, Bae Jung Min, Choi Chong Won, Youn Sang Woong

机构信息

Department of Dermatology, Seoul National University Bundang Hospital, Seongnam, Republic of Korea.

Department of Dermatology, Seoul National University College of Medicine, Seoul, Republic of Korea.

出版信息

J Dermatol. 2025 Aug;52(8):1304-1313. doi: 10.1111/1346-8138.17809. Epub 2025 Jul 4.

DOI:10.1111/1346-8138.17809
PMID:40613611
Abstract

Bullous pemphigoid (BP) is an autoimmune blistering skin disorder with an increasing incidence, particularly among older adults. Given the role of medications in developing drug-associated BP (DABP), exploring drugs that cause DABP is crucial for prescribing appropriate drugs to prevent BP development. This study aimed to identify drugs associated with DABP. In this nationwide retrospective cohort study, we compared 5066 patients newly diagnosed with BP with 10 132 matched controls. We first established a comprehensive drug list of all medications used in our country and conducted a case-control study to identify candidate drugs associated with DABP. To validate these associations, we performed a separate cohort study, enrolling patients with a confirmed diagnosis of BP and matched controls. In the screening stage, 88 drugs were associated with an increased risk of DABP, while 27 drugs were linked with a reduced risk. Validation confirmed that 78 drugs increased the risk of DABP, whereas 22 drugs lowered it. Among the candidate drugs, anti-diabetic medications, including dipeptidyl peptidase-4 (DPP4) inhibitors and sulfonylureas, neuropsychiatric drugs such as benserazide and carbidopa (used for Parkinson's disease) and donepezil and memantine (for Alzheimer's disease), increased the risk of DABP. Conversely, several anti-inflammatory medications, including meloxicam and celecoxib and lipid-lowering agents, such as rosuvastatin and atorvastatin, have been found to lower the risk of DABP. Lastly, diazepam, diltiazem, and Ginkgo biloba extracts exhibited protective effects against DABP development. This nationwide study, employing an unbiased analysis of all medications in our country, highlights a substantial number of medications linked to the development of DABP. Our study provides practical insights for drug selection to prevent the development of DABP in elderly patients.

摘要

大疱性类天疱疮(BP)是一种自身免疫性水疱性皮肤病,发病率呈上升趋势,在老年人中尤为明显。鉴于药物在药物相关性BP(DABP)发病中的作用,探索导致DABP的药物对于开具适当药物以预防BP发生至关重要。本研究旨在确定与DABP相关的药物。在这项全国性回顾性队列研究中,我们将5066例新诊断为BP的患者与10132例匹配的对照进行了比较。我们首先建立了我国使用的所有药物的综合药物清单,并进行了一项病例对照研究,以确定与DABP相关的候选药物。为了验证这些关联,我们进行了一项单独的队列研究,纳入确诊为BP的患者和匹配的对照。在筛查阶段,88种药物与DABP风险增加相关,而27种药物与风险降低相关。验证证实,78种药物增加了DABP风险,而22种药物降低了DABP风险。在候选药物中,包括二肽基肽酶-4(DPP4)抑制剂和磺脲类药物在内的抗糖尿病药物、用于帕金森病的苄丝肼和卡比多巴以及用于阿尔茨海默病的多奈哌齐和美金刚等神经精神药物增加了DABP风险。相反,包括美洛昔康和塞来昔布在内的几种抗炎药物以及瑞舒伐他汀和阿托伐他汀等降脂药物被发现可降低DABP风险。最后,地西泮、地尔硫䓬和银杏叶提取物对DABP的发生具有保护作用。这项全国性研究对我国所有药物进行了无偏分析,突出了大量与DABP发生相关的药物。我们的研究为预防老年患者发生DABP的药物选择提供了实用的见解。

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