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.
ObjectiveThe aim of this study was to investigate the pathogenesis of AED-induced SJS/TEN across the spectrum of HLA-A, -B and -DRB1 alleles, and to explore the different clinical characteristics of patients with and without the HLA-B*15:02 allele in the SJS/TEN group. MethodsA total of twenty-three patients exhibiting AED-induced SJS/TEN (16 CBZ-SJS/TEN, seven LTG-SJS/TEN) and fifty-two patients who exhibited tolerance to AEDs were recruited. High-resolution HLA genotyping was performed to estimate the prevalence of the HLA-A, -B and -DRB1 alleles for each subject. Patients in the SJS/TEN group were further divided to positive HLA-B*15:02 allele group and negative HLA-B*15:02 allele group depending on whether carrying the HLA-B*15:02 allele, and the clinical feathers were compared between the two groups. ResultsNine of twenty-three patients (39%) in the SJS/TEN group were male, and the mean age of this group was 32 (8-68) years old. Twenty-eight of fifty-four (54%) patients in the tolerant group were male, and the mean age of the tolerant group was 28 (9-64) years old.Fourteen subjects in the SJS/TEN group carried the HLA-B*15:02 allele, whereas only four subjects (7.7%) in the AED-tolerant group carried this allele; the carrier rate of HLA-B*15:02 was significantly different between the groups (P<0.001). Among the fourteen patients who carried the HLA-B*15:02 allele in the SJS/TEN group, composing the positive HLA-B*15:02 allele group, eight patients (57.1%) were female, whereas six of nine patients in the negative HLA-B*15:02 allele group were female. The difference of the gender didn't have statistical significance between the two groups, nor did the other clinical characteristics, including mean age, the dosage of the AEDs, the interval from the drug administration to the onset of the SJS/TEN, fever, allergic history, abnormal MRI and abnormal EEG results. ConclusionsThe pathogenesis of AED-induced SJS/TEN is a complex process, which may involve one or more alleles. The HLA-B*15:02 allele may be a genetic susceptibility factor of the AED-induced SJS/TEN. However, we didn't find significant difference of the clinical characteristics of SJS/TEN between the patients with and without the HLA-B*15:02 allele. Notably, further studies using larger samples are required to confirm these conclusions.