Department of Dermatology, Drug Hypersensitivity Clinical and Research Center, Chang Gung Memorial Hospital, Keelung and Linkou Branches, College of Medicine, Chang Gung University, Taiwan.
J Dermatol Sci. 2012 Jun;66(3):190-6. doi: 10.1016/j.jdermsci.2012.04.002. Epub 2012 Apr 11.
Stevens-Johnson syndrome (SJS) and toxic epidermal necrosis (TEN) are rare but life-threatening severe cutaneous adverse reactions (SCARs), which are majorly (65-75%) induced by a variety of drugs. SJS/TEN could be recognized as SCARs or drug immune reactions, if the reactions are elicited by drugs. The recent studies suggested that SJS/TEN is a specific immune reaction initiated by the cytotoxic T lymphocytes (CTLs) via human leukocyte antigens (HLAs)-restricted pathway. The patho-mechanism involving HLA-restricted presentation of a drug or its metabolites for T-cell activation is supported by the findings of strong genetic associations with HLA alleles (e.g. HLA-B15:02 and carbamazepine-SJS/TEN, and HLA-B58:01 and allopurinol-SJS/TEN). However, the genetic associations of SJS/TEN or drug induced cutaneous immune reactions are complex, which are drug specific and ethnicity specific. The genetic polymorphisms and diversity of HLA alleles may provide different binding affinities for drug antigens to launch the activation of specific CTLs responses, further leading to the unique clinical manifestations in SJS/TEN. Fas-FasL and perforin/granzyme B have been advocated mediating the epidermal necrosis in SJS/TEN. Our recent study showed that granulysin, a cytotoxic protein produced by CTLs or natural killer (NK) cells, is the key mediator for disseminated keratinocyte death in SJS/TEN. From the point of view of a physician, the profounder understanding of the genetic predisposition and patho-mechanism we discover, the better strategies for prevention, clinical management, and therapeutic methods of SJS/TEN we can develop in the near future.
史蒂文斯-约翰逊综合征（SJS）和中毒性表皮坏死松解症（TEN）是罕见但危及生命的严重皮肤不良反应（SCARs），主要由各种药物引起（65-75%）。如果反应是由药物引起的，SJS/TEN 可被视为 SCARs 或药物免疫反应。最近的研究表明，SJS/TEN 是一种由细胞毒性 T 淋巴细胞（CTLs）通过人类白细胞抗原（HLA）限制性途径启动的特异性免疫反应。该病理机制涉及 HLA 限制的药物或其代谢物呈递以激活 T 细胞，这一发现得到了与 HLA 等位基因（例如 HLA-B15:02 和卡马西平-SJS/TEN，以及 HLA-B58:01 和别嘌醇-SJS/TEN）的强烈遗传关联的支持。然而，SJS/TEN 或药物引起的皮肤免疫反应的遗传关联是复杂的，具有药物特异性和种族特异性。HLA 等位基因的遗传多态性和多样性可能为药物抗原提供不同的结合亲和力，以启动特定 CTL 反应的激活，从而导致 SJS/TEN 中独特的临床表现。Fas-FasL 和穿孔素/颗粒酶 B 被认为介导 SJS/TEN 中的表皮坏死。我们最近的研究表明，颗粒溶素，一种由 CTL 或自然杀伤（NK）细胞产生的细胞毒性蛋白，是 SJS/TEN 中角质形成细胞弥散性死亡的关键介质。从医生的角度来看，我们对遗传易感性和病理机制的理解越深，我们就能在不久的将来开发出更好的 SJS/TEN 预防、临床管理和治疗方法的策略。
