抗癫痫药物所致重症皮肤过敏反应与HLA-B~* 1502基因的关联性

Association between HLA-B~* 1502 Gene and Severe Skin Allergy Induced by Antiepileptic Drugs

目的探究抗癫痫药物所致重症皮肤过敏反应与HLA-B* 1502基因的关联性,为抗癫痫药物所致重症皮肤过敏反应的防治提供理论依据。方法本研究观察对象为2015年6月-2017年2月期间于我院治疗的40例癫痫患者,所有患者均采用卡马西平(CBZ)或拉莫三嗪(LTG)治疗,CBZ致Stevens Johnson综合征(SJS)5例,致中毒性表皮坏死溶解症(Toxic epidermal necrolysis,TEN)3例,SJS/TEN 4例,LTG致TEN 2例,SJS/TEN 2例,共16例患者出现重症皮肤过敏反应,设为过敏组,将24例未发生过敏反应者设为耐受组,同期25例体检的健康自愿者设为对照组。通过顺序特异性引物聚合酶链反应(PCR-SSP)检测所有人员的HLA-B* 1502基因分型,并进行关联性研究。结果 CBZ致SJS者HLA-B* 1502基因型阳性4例,基因频率80.00%;CBZ致SJS/TEN者HLA-B*1502基因型阳性3例,基因频率75.00%;CBZ致TEN者HLA-B*1502基因型阳性3例,基因频率100.00%;LTG致TEN、SJS/TEN者HLA-B*1502基因型阳性均为2例,基因频率100.00%;耐受组HLA-B*1502基因型阳性2例,基因频率8.33%;对照组HLA-B*1502基因型阳性3例,基因频率12.00%;两种药物引起的各型重症皮肤过敏反应者HLA-B*1502基因频率均显著高于耐受组与对照组,有统计学差异(P<0.05)。结论抗癫痫药物LTG及CBZ所致重症皮肤过敏反应发生率较高,且与HLA-B*1502基因的表达具有明显的相关性。

Objective To investigate the relationships between HLA-B＊ 1502 gene and severe skin allergy caused by antiepileptic drugs so as to contribute to the prevention and treatment of severe skin allergy caused by antiepileptic drugs.Methods The subjects were 40 cases of patients with epilepsy treated in our hospital between June 2015 and February 2017. All these patients were treated with either carbamazepine（ CBZ） or lamotrigine（ LTG）. There were 5 cases of Stevens Johnson syndrome（ SJS） caused by CBZ,3 cases of toxic epidermal necrolysis（ TEN）,4 cases of SJS/TEN,2 cases of TEN induced by LTG,2 cases of SJS/TEN,so a total of 16 cases had severe skin allergy,which served as the allergy group. 24 cases who did not develop any allergy served as the tolerance group,and another 25 cases of healthy volunteers confirmed by physical examinations in the same period were used as the control group. HLA-B＊ 1502 genotyping was detected with sequence specific primers polymerase chain reaction（ PCR-SSP）,and correlations were studied. Results There were 4 cases of positive HLA-B＊ 1502 genotype in SJS patients induced by CBZ with a gene frequency of 80%,3 cases of positive HLA-B＊ 1502 genotype in SJS/TEN patients caused by CBZ with a gene frequency of 75%,and 3 cases of positive HLA-B＊ 1502 genotype in TEN patients caused by CBZ with a gene frequency of 100%. TEN and SJS/TEN induced by LTG resulted in 2 cases of positive HLA-B＊ 1502 genotype separately with a gene frequency of 100%. In the tolerance group,there were 2 cases of positive HLA-B＊ 1502 genotype with a gene frequency of 8.33%. compared to 3 cases with a gene frequency of 12% in the control group. HLA-B＊ 1502 gene frequency induced by these two drugs among patients with severe skin allergy was much higher than that of the tolerance group and control group,and the difference was of statistical significance（ P〈0.05）. Conclusion The incidence of severe skin allergy caused by antiepileptic drugs such as LTG and CBZ is high,which is markedly related to HLA-B~＊ 1502 gene expression.