儿童抗癫痫药物所致重症药疹与HLA基因的关系

Relationship between severe drug eruption and HLA genes caused by antiepileptic drugs

目的:明确西北地区汉族儿童抗癫痫药物所致重症药疹与人类白细胞抗原(HLA)基因多态性的关联性。方法:收集2018年1月1日至2023年6月30日应用抗癫痫药物所致重症药疹的住院患儿20例为病例组,应用抗癫痫药物3个月以上未出现皮肤不良反应的患儿55例为耐受组,正常体检的40例儿童为正常对照组,采用序列特异性引物-聚合酶链反应法(PCR-SSP)检测外周血HLA-B^(*)1502、HLA-A^(*)2402、HLA-A^(*)3101 3个等位基因,分析等位基因分布频率在三组之间的差异。结果:重症药疹平均发病年龄(6.78±3.28)岁,平均潜伏期15天。三组总体基因分布频率有统计学差异(P<0.05)。病例组HLA-B^(*)1502等位基因分布频率与耐受组及正常对照组有统学差异(P<0.05),HLA-A^(*)2402及HLA-A^(*)3101基因分布频率在三组之间无统计学差异(P>0.05)。病例组HLA-B^(*)1502等位基因分布频率在卡马西平组与非卡马西平组有统计学差异(P<0.05)。结论:抗癫痫药物引发的重症药疹学龄前及学龄期儿童高发,潜伏期长。卡马西平所致重症药疹与HLA-B^(*)1502等位基因密切相关,建议患者服用抗癫痫药物前筛查HLA基因型,避免重症药疹的发生。

Objective:To investigate the relationship between severe drug eruptions caused by antiepileptic drugs in Han children in Northwest China and human leukocyte antigen(HLA) gene polymorphisms.Methods:The peripheral blood of all study subjects was collected,including 20 children with severe drug eruption caused by antiepileptic drugs,55 children who had been treated with antiepileptic drugs for more than 3 months without adverse skin reactions,and 40 children with normal physical examination.The three alleles of HLA-B~*1502,HLA-A~*2402 and HLA-A~*3101 were detected by PCR-SSP,and the differences in allele distribution frequencies between the three groups were analyzed.Results:The average age of onset of severe drug eruptions was 6.78±3.28 years old,the average incubation period was 15 days.There was a statistical difference in the overall gene distribution frequency among the three groups(P<0.05).The distribution frequency of HLA-B~*1502 alleles in the case group was statistically different from that of the tolerance group and the normal group(P<0.05).There was no statistical difference in the distribution frequencies of HLA-A~*2402 and HLA-A~*3101 genes among the three groups.differences(P>0.05).In the case group,the distribution frequency of HLA-B~*1502 alleles was statistically different between the carbamazepine group and the non-carbamazepine group(P<0.05).Conclusion:Severe drug eruption caused by antiepileptic drugs is more common in preschool and school-age children and has a long incubation period.Severe drug eruptions caused by carbamazepine are closely related to the HLA-B~*1502 allele.It is recommended that patients screen HLA genotypes before taking anti-epileptic drugs,which will help avoid the occurrence of severe drug eruptions.