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目的多种抗癫痫药物(AEDs)所致皮肤不良反应(cutaneous adverse drug reactions,cADRs)发现与HLA等位基因密切相关。但研究主要集中在对传统AEDs的研究上,而对新型AEDs,特别是对于左乙拉西坦(Levetiracetam,LEV)所致cADRs与HLA等位基因相关性的研究较少。因此,研究探索LEV所致cADRs的临床特点,以及其与HLA等位基因之间可能的相关性。方法纳入2011年9月-2014年12月期间于四川大学华西医院门诊及住院部连续登记的LEV所致cADRs患者共9例,详细收集患者的流行病学信息及临床资料。同时,按1∶4的比例收集服用LEV未出现过敏反应的患者组成对照组。每例受试者均进行HLA-A,-B和-DRB1位点的高分辨率分析,并对每种基因在病例组和对照组中的携带率进行比较。结果 9例服用LEV出现cADRs的患者组成病例组,36例耐受LEV的患者组成对照组。全部LEV所致的cADRs均为轻度皮疹,且出现在用药的30 d内。从使用LEV到出现皮疹的平均天数为(15.67±5.41)d(范围:6~27 d)。病例组中,有2例患者(2/9,22.2%)携带HLA-DRB1*04:05等位基因,对照组中没有患者携带该基因,HLADRB1*04:05等位基因的携带率在病例组和对照组的差异有统计学意义[P=0.036,OR=13.875,95%CI(1.273,151.230)]。结论虽然LEV是较为安全、cADRs发生频率较低的AEDs,但使用LEV治疗癫痫时仍应密切监测cADRs的发生,特别是在起始用药的4周内。研究提示HLA-DRB1*04:05等位基因可能是LEV所致cADRs的危险因素之一。由于研究样本量较小,仍需大样本研究进一步证实。
OBJECTIVE: Various cutaneous adverse drug reactions (cADRs) induced by various anti-epileptic drugs (AEDs) were found to be closely related to HLA alleles. However, the research mainly focuses on the traditional AEDs, but few studies on the association of new AEDs, especially levotiracetam (LEV) with the alleles of cADRs. Therefore, the study explored the clinical features of LEV-induced cADRs and their possible association with HLA alleles. Methods Nine patients with LEAD-induced cADRs enrolled in Outpatient and Inpatient Department of West China Hospital of Sichuan University from September 2011 to December 2014 were included in this study. Epidemiological information and clinical data of patients were collected in detail. At the same time, patients in LEV-free allergic reactions were collected at a 1: 4 ratio to make up a control group. High-resolution analyzes of HLA-A, -B, and -DRB1 sites were performed on each subject, and the carriage rate of each gene in the case group and the control group was compared. Results Nine of the patients taking corticosteroids (LEVs) with cADRs formed a case-control group and the other 36 patients who tolerated LEVs formed a control group. All LEV-induced cADRs were mild rashes and appeared within 30 days of treatment. The average number of days from LEV to rash was (15.67 ± 5.41) days (range: 6 to 27 days). In the case group, 2 patients (2/9, 22.2%) carried the HLA-DRB1 * 04: 05 allele, and none of the patients in the control group carried the gene. The carrier rate of HLADRB1 * 04: 05 allele was in the cases The difference between the two groups was statistically significant (P = 0.036, OR = 13.875, 95% CI (1.273, 151.230)]. Conclusions Although LEVs are safer and AEDs with lower incidence of cADRs, the incidence of cADRs should be monitored closely when LEV is used in the treatment of epilepsy, especially within 4 weeks of initial dosing. Studies suggest that HLA-DRB1 * 04: 05 allele may be one of the risk factors for LEV-induced cADRs. Due to the small sample size, large sample studies still need further confirmation.