Department of Neurology, West China Hospital, Sichuan University, Chengdu, Sichuan Province 610041, China.
Epilepsy Res. 2010 Dec;92(2-3):226-30. doi: 10.1016/j.eplepsyres.2010.10.006. Epub 2010 Nov 10.
Antiepileptic drugs including lamotrigine (LTG) and carbamazepine (CBZ) are among the most common causes of cutaneous adverse reactions (cADRs). Human leukocyte antigen (HLA)-B1502 has been strongly associated with CBZ-induced Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN). To investigate this relationship, we performed high-resolution HLA genotyping on LTG-tolerant controls, healthy volunteers, and patients affected by LTG-induced cADRs, ranging from maculopapular exanthema (MPE) to SJS/TEN. Patients with LTG-induced cADRs (n=25, including three with SJS/TEN and 22 with MPE), 21 LTG-tolerant controls, and 71 healthy volunteers were enrolled. The differences in the starting dosage of LTG among the SJS/TEN, MPE, and LTG-tolerant control groups were not statistically significant. HLA-B1502 frequency was 33.3% (1/3; LTG-induced SJS/TEN group), 9.1% (2/22; LTG-induced MPE group), 4.8% (1/21; LTG-tolerant group), and 8.5% (6/71; healthy volunteers). There was no significant difference in the frequency of subjects with the HLA-B1502 allele between the SJS/TEN group and LTG-tolerant group (p=0.239, OR=10.0, 95% CI 0.44-228.7), and healthy volunteers (p=0.26, OR=5.42, 95% CI 0.43-68.8), MPE and LTG-tolerant groups (p=1.0, OR=1.08, 95% CI 0.20-5.8), and healthy volunteers (p=1.0, OR=2.0, 95% CI 0.17-23.9). None of the HLA alleles detected were associated with LTG-induced cADRs. In conclusion, HLA-B1502 and other HLA alleles are not directly associated with LTG-induced MPE. The possibility that HLA-B*1502 is associated with an increased risk of LTG-induced SJS/TEN could not be excluded.
包括拉莫三嗪 (LTG) 和卡马西平 (CBZ) 在内的抗癫痫药物是引起皮肤不良反应 (cADR) 的最常见原因之一。人类白细胞抗原 (HLA)-B1502 与 CBZ 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) 密切相关。为了研究这种关系，我们对 LTG 耐受对照、健康志愿者和 LTG 诱导的 cADR 患者进行了高分辨率 HLA 基因分型，这些患者的 cADR 从斑丘疹性皮疹 (MPE) 到 SJS/TEN 不等。入组患者 25 例，包括 3 例 SJS/TEN 和 22 例 MPE，LTG 耐受对照 21 例，健康志愿者 71 例。SJS/TEN、MPE 和 LTG 耐受对照组之间 LTG 的起始剂量无统计学差异。HLA-B1502 频率分别为 33.3%（1/3；LTG 诱导的 SJS/TEN 组）、9.1%（22/22；LTG 诱导的 MPE 组）、4.8%（1/21；LTG 耐受组）和 8.5%（6/71；健康志愿者）。SJS/TEN 组与 LTG 耐受组（p=0.239，OR=10.0，95%CI 0.44-228.7）和健康志愿者（p=0.26，OR=5.42，95%CI 0.43-68.8）之间 HLA-B1502 等位基因频率无显著差异，MPE 和 LTG 耐受组（p=1.0，OR=1.08，95%CI 0.20-5.8）和健康志愿者（p=1.0，OR=2.0，95%CI 0.17-23.9）。未发现任何 HLA 等位基因与 LTG 诱导的 cADR 直接相关。结论：HLA-B1502 和其他 HLA 等位基因与 LTG 诱导的 MPE 无直接关系。不能排除 HLA-B*1502 与 LTG 诱导的 SJS/TEN 风险增加有关的可能性。
