ObjectiveIt has been reported that many different kinds of antiepileptic drugs (AEDs) induced cutaneous adverse drug reactions (cADRs) are associated with human leukocyte antigen (HLA) genes. However, previous studies mainly focused on the traditional AEDs. There are very few research focused on the new AEDs, especially levetiracetam (LEV). This study aimed to evaluate the clinical characteristics of LEV-induced cADRs and to explore its possible genetic association with the HLA alleles. MethodsNine cases with LEV-induced cADRsfrom September 2011 to December 2014 were recruited. Demographic and clinical information of these cases was summarized. Additionally, cases were matched with LEV-tolerant controls (1 : 4).High-resolution HLA-A, -B, -DRB1 genotyping were performed for each subject. The allele frequencies between the cases and controls were compared. ResultsNine cases with LEV-induced cADRs formed the LEV-cADRs group. And 36 epilepsy patients who had received or have been receiving LEV treatment for at least 3 months without any adverse drug reactions formed the LEV-tolerant controls group. All LEV-induced cADRs were mild skin rashes whichoccurred within 30 days of LEV exposure. The mean latency from LEV exposure to skin rash was (15.67±5.41) days (ranging 6~27). Two patients in the LEV-cADRs group carried the HLA-DRB1*0405allele, while none subjects in the control group carried this allele. The carrier rate of HLA-DRB1*0405 allele between the LEV-cADRs group and control group was statistical significant [P=0.036, OR=13.875, 95%CI(1.273, 151.230)]. ConclusionsSafety monitoring was necessary within four weeks after the initiation of LEV treatment, although it has been regarded as a safe AED.Our study suggested thatHLA-DRB1*0405 allele may be a risk factor for LEV-induced cADRs. However, the Further studies with large samples are needed to clarify this hypothesis and the genetic and immunological mechanisms of LEV-induced cADRs should also be further explored in the future.