Drug hypersensitivity reactions (DHRs) are associated with high global morbidity and mortality. Cutaneous T cell–mediated reactions classically occur more than 6 hours after drug administration and include life‐threatening conditions such as toxic epidermal necrolysis, Stevens‐Johnson syndrome, and hypersensitivity syndrome. Over the last 20 years, significant advances have been made in our understanding of the pathogenesis of DHRs with the identification of human leukocyte antigens as predisposing factors. This has led to the development of pharmacogenetic screening tests, such as HLA‐B*57:01 in abacavir therapy, which has successfully reduced the incidence of abacavir hypersensitivity reactions. We have completed a PRISMA‐compliant systematic review to identify genetic associations that have been reported in DHRs. In total, 105 studies (5554 cases and 123 548 controls) have been included in the review reporting genetic associations with carbamazepine (n = 31), other aromatic antiepileptic drugs (n = 24), abacavir (n = 11), nevirapine (n = 14), trimethoprim‐sulfamethoxazole (n = 11), dapsone (n = 4), allopurinol (n = 10), and other drugs (n = 5). The most commonly reported genetic variants associated with DHRs are located in human leukocyte antigen genes and genes involved in drug metabolism pathways. Increasing our understanding of genetic variants that contribute to DHRs will allow us to improve diagnosis, develop new treatments, and predict and prevent DHRs in the future.

中文翻译：

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与 T 细胞介导的皮肤药物不良反应相关的遗传变异：符合 Prisma 的系统评价 – EAACI 立场文件

药物超敏反应 (DHR) 与高全球发病率和死亡率相关。皮肤 T 细胞介导的反应通常发生在给药后 6 小时以上，包括危及生命的疾病，例如中毒性表皮坏死松解症、史蒂文斯-约翰逊综合征和过敏综合征。在过去的 20 年中，随着人类白细胞抗原作为易感因素的鉴定，我们对 DHR 发病机制的理解取得了重大进展。这导致了药物遗传学筛查测试的发展，例如阿巴卡韦治疗中的 HLA-B*57:01，它成功地降低了阿巴卡韦超敏反应的发生率。我们已经完成了符合 PRISMA 的系统评价，以确定 DHR 中报告的遗传关联。总共，105 项研究（5554 例病例和 123548 例对照）已被纳入评价报告与卡马西平（n = 31）、其他芳香类抗癫痫药（n = 24）、阿巴卡韦（n = 11）、奈韦拉平（n = 14）的遗传关联、甲氧苄啶-磺胺甲恶唑 (n = 11)、氨苯砜 (n = 4)、别嘌醇 (n = 10) 和其他药物 (n = 5)。最常报道的与 DHR 相关的遗传变异位于人类白细胞抗原基因和参与药物代谢途径的基因中。增加我们对导致 DHR 的遗传变异的了解将使我们能够改进诊断，开发新的治疗方法，并在未来预测和预防 DHR。奈韦拉平 (n = 14)、甲氧苄啶-磺胺甲恶唑 (n = 11)、氨苯砜 (n = 4)、别嘌醇 (n = 10) 和其他药物 (n = 5)。最常报道的与 DHR 相关的遗传变异位于人类白细胞抗原基因和参与药物代谢途径的基因中。增加我们对导致 DHR 的遗传变异的了解将使我们能够改进诊断，开发新的治疗方法，并在未来预测和预防 DHR。奈韦拉平 (n = 14)、甲氧苄啶-磺胺甲恶唑 (n = 11)、氨苯砜 (n = 4)、别嘌醇 (n = 10) 和其他药物 (n = 5)。最常报道的与 DHR 相关的遗传变异位于人类白细胞抗原基因和参与药物代谢途径的基因中。增加我们对导致 DHR 的遗传变异的了解将使我们能够改进诊断，开发新的治疗方法，并在未来预测和预防 DHR。