Hu Fa-Yun, Wang Wei, Ren Jie-Chuan, An Dong-Mei, Chen Jia-Ni, Zhou Dong
Department of Neurology, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China.
Department of Neurology, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China.
Epilepsy Res. 2016 Aug;124:12-5. doi: 10.1016/j.eplepsyres.2016.04.008. Epub 2016 May 2.
This study aimed to evaluate the clinical characteristics of levetiracetam (LEV)-induced cutaneous adverse drug reactions (cADRs) and to explore its possible genetic association with the human leukocyte antigen (HLA) genes.
Nine cases with LEV-induced cADRs were recruited. Demographic and clinical information of these cases was summarized. Additionally, cases were matched with LEV-tolerant controls (1:4). High-resolution HLA class I and class II genotyping was performed for each participant. The allele frequencies between the cases and controls were compared.
All LEV-induced cADRs were mild skin rashes which occurred within 28 days of LEV exposure. The mean latency from LEV exposure to skin rash was (15.67±5.41) days (ranging 6-27). The carrier rates of the two alleles, HLA-DRB10405 and HLA-DQB10401, were higher in cases compared with controls (the same P=0.036, OR=13.875, 95% CI: 1.273-151.230). The association between the HLA-C*0304 allele and LEV-induced cADRs was boundary (P=0.05, OR=5.2, 95% CI: 1.086-24.897). However, the above-mentioned HLA alleles didn't reach statistical significance after multiple comparisons.
Safety monitoring was necessary within four weeks after the initiation of LEV treatment, although it has been regarded as a safe antiepileptic drug. Our study failed to show any potential link between HLA alleles and LEV-induced cADRs in Han Chinese. Further studies are needed to clarify the genetic and immunological mechanisms of LEV-induced cADRs.
本研究旨在评估左乙拉西坦(LEV)所致皮肤不良反应(cADRs)的临床特征,并探讨其与人类白细胞抗原(HLA)基因的可能遗传关联。
招募9例LEV所致cADRs患者。总结这些患者的人口统计学和临床信息。此外,将患者与耐受LEV的对照者按1:4进行匹配。对每位参与者进行高分辨率HLA I类和II类基因分型。比较患者和对照者之间的等位基因频率。
所有LEV所致cADRs均为轻度皮疹,发生于LEV暴露后28天内。从LEV暴露至出现皮疹的平均潜伏期为(15.67±5.41)天(范围6 - 27天)。与对照者相比,患者中两个等位基因HLA - DRB10405和HLA - DQB10401的携带率更高(P均 = 0.036,OR = 13.875,95%CI:1.273 - 151.230)。HLA - C*0304等位基因与LEV所致cADRs之间的关联接近临界值(P = 0.05,OR = 5.2,95%CI:1.086 - 24.897)。然而,经过多重比较后,上述HLA等位基因未达到统计学意义。
尽管LEV被认为是一种安全的抗癫痫药物,但在开始LEV治疗后的四周内进行安全监测是必要的。我们的研究未能显示HLA等位基因与汉族人群中LEV所致cADRs之间存在任何潜在联系。需要进一步研究以阐明LEV所致cADRs的遗传和免疫机制。