Cancer Vaccine and Immune Cell Therapy Core Laboratory, Department of Medical Research, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan, Taiwan.
Department and Institute of Pharmacology, National Yang Ming Chiao Tung University, Taipei, Taiwan.
Nat Rev Dis Primers. 2024 Apr 25;10(1):30. doi: 10.1038/s41572-024-00514-0.
Severe cutaneous adverse reactions (SCARs), which include Stevens-Johnson syndrome and toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms (also known as drug-induced hypersensitivity syndrome), acute generalized exanthematous pustulosis, and generalized bullous fixed drug eruption, are life-threatening conditions. The pathogenesis of SCARs involves T cell receptors recognizing drug antigens presented by human leukocyte antigens, triggering the activation of distinct T cell subsets. These cells interact with keratinocytes and various immune cells, orchestrating cutaneous lesions and systemic manifestations. Genetic predisposition, impaired drug metabolism, viral reactivation or infections, and heterologous immunity influence SCAR development and clinical presentation. Specific genetic associations with distinct SCAR phenotypes have been identified, leading to the implementation of genetic screening before prescription in various countries to prevent SCARs. Whilst systemic corticosteroids and conventional immunomodulators have been the primary therapeutic agents, evolving strategies, including biologics and small molecules targeting tumour necrosis factor, different cytokines, or Janus kinase signalling pathways, signify a shift towards a precision management paradigm that considers individual clinical presentations.
严重的皮肤不良反应（SCARs），包括史蒂文斯-约翰逊综合征和中毒性表皮坏死松解症、伴有嗜酸性粒细胞增多和全身症状的药物反应（也称为药物诱导的超敏综合征）、急性泛发性发疹性脓疱病和全身性大疱性固定性药疹，是危及生命的疾病。SCARs 的发病机制涉及 T 细胞受体识别由人类白细胞抗原呈递的药物抗原，触发不同 T 细胞亚群的激活。这些细胞与角质形成细胞和各种免疫细胞相互作用，协调皮肤损伤和全身表现。遗传易感性、药物代谢受损、病毒再激活或感染以及异源免疫影响 SCAR 的发展和临床表现。已经确定了与不同 SCAR 表型相关的特定遗传关联，导致在许多国家实施处方前遗传筛查以预防 SCARs。虽然全身性皮质类固醇和传统免疫调节剂一直是主要的治疗药物，但包括针对肿瘤坏死因子、不同细胞因子或 Janus 激酶信号通路的生物制剂和小分子在内的不断发展的策略标志着向个体化临床表型为导向的精准管理范式的转变。
