Institute for Immunology and Infectious Diseases, Murdoch University, Murdoch, Western Australia, Australia.
J Allergy Clin Immunol. 2011 Mar;127(3 Suppl):S60-6. doi: 10.1016/j.jaci.2010.11.046.
Severe cutaneous adverse reactions include syndromes such as drug reaction with eosinophilia and systemic symptoms (DRESS) or drug-induced hypersensitivity syndrome (DIHS) and Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN). An important advance has been the discovery of associations between HLA alleles and many of these syndromes, including abacavir-associated hypersensitivity reaction, allopurinol-associated DRESS/DIHS and SJS/TEN, and SJS/TEN associated with aromatic amine anticonvulsants. These HLA associations have created the promise for prevention through screening and have additionally shed further light on the immunopathogenesis of severe cutaneous adverse reactions. The rollout of HLA-B∗5701 into routine clinical practice as a genetic screening test to prevent abacavir hypersensitivity provides a translational roadmap for other drugs. Numerous hurdles exist in the widespread translation of several other drugs, such as carbamazepine, in which the positive predictive value of HLA-B∗1502 is low and the negative predictive value of HLA-B∗1502 for SJS/TEN might not be 100% in all ethnic groups. International collaborative consortia have been formed with the goal of developing phenotypic standardization and undertaking HLA and genome-wide analyses in diverse populations with these syndromes.
严重的皮肤不良反应包括药物反应伴嗜酸性粒细胞增多和全身症状（DRESS）或药物诱导的超敏反应综合征（DIHS）和史蒂文斯-约翰逊综合征（SJS）/中毒性表皮坏死松解症（TEN）等综合征。一个重要的进展是发现了 HLA 等位基因与许多这些综合征之间的关联，包括阿巴卡韦相关过敏反应、别嘌醇相关 DRESS/DIHS 和 SJS/TEN 以及芳香胺类抗惊厥药相关的 SJS/TEN。这些 HLA 相关性为通过筛查进行预防创造了希望，并进一步阐明了严重皮肤不良反应的免疫发病机制。HLA-B∗5701 作为一种遗传筛选测试纳入常规临床实践，以预防阿巴卡韦过敏，为其他药物的转化提供了路线图。在将卡马西平等其他许多药物广泛转化方面存在许多障碍，例如 HLA-B∗1502 对卡马西平的阳性预测值较低，并且 HLA-B∗1502 对 SJS/TEN 的阴性预测值在所有种族群体中可能并非 100%。已经成立了国际合作联盟，旨在制定表型标准化，并在具有这些综合征的不同人群中进行 HLA 和全基因组分析。
