Ahmed Ali Fadhel, Sukasem Chonlaphat, Sabbah Majeed Arsheed, Musa Nur Fadhlina, Mohamed Noor Dzul Azri, Daud Nur Aizati Athirah
Discipline of Clinical Pharmacy, School of Pharmaceutical Sciences, Universiti Sains Malaysia, Pulau Pinang 11800, Malaysia.
Department of Pathology, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok 10400, Thailand.
J Pers Med. 2021 May 7;11(5):383. doi: 10.3390/jpm11050383.
Adverse drug reaction (ADR) is a pressing health problem, and one of the main reasons for treatment failure with antiepileptic drugs. This has become apparent in the event of severe cutaneous adverse reactions (SCARs), which can be life-threatening. In this review, four hypotheses were identified to describe how the immune system is triggered in the development of SCARs, which predominantly involve the human leukocyte antigen (HLA) proteins. Several genetic variations in HLA genes have been shown to be strongly associated with the susceptibility to developing SCARs when prescribed carbamazepine or phenytoin. These genetic variations were also shown to be prevalent in certain populations. Apart from the HLA genes, other genes proposed to affect the risk of SCARs are genes encoding for CYP450 drug-metabolising enzymes, which are involved in the pharmacokinetics of offending drugs. Genetic variants in CYP2C9 and CYPC19 enzymes were also suggested to modulate the risk of SCARs in some populations. This review summarizes the literature on the manifestation and aetiology of antiepileptic-induced SCARs, updates on pharmacogenetic markers associated with this reaction and the implementation of pre-emptive testing as a preventive strategy for SCARs.
药物不良反应（ADR）是一个紧迫的健康问题，也是抗癫痫药物治疗失败的主要原因之一。这在严重皮肤不良反应（SCARs）的情况下已变得很明显，严重皮肤不良反应可能会危及生命。在本综述中，确定了四种假说来描述免疫系统在SCARs发生过程中是如何被触发的，这主要涉及人类白细胞抗原（HLA）蛋白。已表明，当使用卡马西平或苯妥英时，HLA基因中的几种基因变异与发生SCARs的易感性密切相关。这些基因变异在某些人群中也很普遍。除了HLA基因外，其他被认为会影响SCARs风险的基因是编码CYP450药物代谢酶的基因，这些酶参与了致病药物的药代动力学。还表明，CYP2C9和CYPC19酶的基因变异在某些人群中也会调节SCARs的风险。本综述总结了关于抗癫痫药物诱发SCARs的表现和病因的文献、与该反应相关的药物遗传学标志物的最新情况以及作为SCARs预防策略的前瞻性检测的实施情况。
