Department of Dermatology Tehran University of Medical Sciences, Razi Hospital, Tehran, Iran.
Center for Research & Training in Skin Diseases & Leprosy, Tehran University of Medical Sciences, Tehran, Iran.
Dermatol Ther. 2022 May;35(5):e15393. doi: 10.1111/dth.15393. Epub 2022 Feb 28.
In this case-control study, class І and ІІ human leukocyte antigen (HLA) alleles in Iranian patients with benign and severe cutaneous adverse drug reactions (CADRs) due to aromatic anticonvulsants and antibiotics were evaluated. Patients diagnosed with CADRs (based on clinical and laboratory findings) with a Naranjo score of ≥ 4 underwent blood sampling and HLA-DNA typing. The control group comprised 90 healthy Iranian adults. Alleles with a frequency of more than two were reported. Deviations from Hardy-Weinberg equilibrium were not observed. Eighty patients with CADRs including 54 females and 26 males with a mean age of 41.49 ± 16.08 years were enrolled in this study. The culprit drugs included anticonvulsants (lamotrigine, carbamazepine, and phenytoin) and antibiotics (ciprofloxacin and co-trimoxazole). The comparison of allele frequencies in the Iranian healthy control group and the group with benign CADRs revealed that HLA-Cw04, and HLA-A24 were significantly associated with lamotrigine-induced maculopapular CADRs. Furthermore, HLA-B51 showed a significant correlation with carbamazepine-induced maculopapular CADRs. Significant associations were also detected between ciprofloxacin-induced urticarial CADRs with HLA-B40, and HLA-DRB114. In the severe group, HLA-B38 and HLA-DRB113 were significantly associated with lamotrigine-induced Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN). Moreover, HLA-A31 and HLA-Cw04 were significantly correlated with carbamazepine-induced drug reactions with eosinophilia and systemic symptoms (DRESS). HLA-B08 also showed a significant correlation with ciprofloxacin-induced acute generalized exanthematous pustulosis (AGEP). In conclusion, Lamotrigine-induced MPE was significantly correlated with HLA-Cw04, and HLA-A24. Similarly, lamotrigine-induced SJS/TEN was significantly associated with HLA-B38 and HLA-DRB113. Additionally, HLA-A*31 was associated with DRESS caused by carbamazepine. The most frequent CADR-inducing drugs were anticonvulsants.
在这项病例对照研究中，评估了伊朗芳香族抗惊厥药和抗生素致良性和严重皮肤不良反应（CADR）患者的Ⅰ类和Ⅱ类人类白细胞抗原（HLA）等位基因。根据临床和实验室发现诊断为 CADR（基于临床和实验室发现）且 Naranjo 评分为≥4 的患者进行了采血和 HLA-DNA 分型。对照组包括 90 名健康的伊朗成年人。报告了频率超过两个的等位基因。未观察到 Hardy-Weinberg 平衡偏离。本研究纳入了 80 名 CADR 患者，包括 54 名女性和 26 名男性，平均年龄为 41.49±16.08 岁。致病药物包括抗惊厥药（拉莫三嗪、卡马西平和苯妥英）和抗生素（环丙沙星和复方磺胺甲噁唑）。将伊朗健康对照组和良性 CADR 组的等位基因频率进行比较后发现，HLA-Cw04 和 HLA-A24 与拉莫三嗪诱导的斑丘疹性 CADR 显著相关。此外，HLA-B51 与卡马西平诱导的斑丘疹性 CADR 呈显著相关。还发现环丙沙星诱导的荨麻疹性 CADR 与 HLA-B40 和 HLA-DRB114 之间存在显著关联。在严重组中，HLA-B38 和 HLA-DRB113 与拉莫三嗪诱导的史蒂文斯-约翰逊综合征/中毒性表皮坏死松解症（SJS/TEN）显著相关。此外，HLA-A31 和 HLA-Cw04 与卡马西平诱导的伴有嗜酸性粒细胞增多和全身症状的药物反应（DRESS）显著相关。HLA-B08 也与环丙沙星诱导的急性全身性发疹性脓疱病（AGEP）显著相关。总之，拉莫三嗪诱导的 MPE 与 HLA-Cw04 和 HLA-A24 显著相关。同样，拉莫三嗪诱导的 SJS/TEN 与 HLA-B38 和 HLA-DRB113 显著相关。此外，HLA-A*31 与卡马西平引起的 DRESS 相关。最常见的 CADR 诱导药物是抗惊厥药。
