Genetic susceptibility to the cross-reactivity of aromatic antiepileptic drugs-induced cutaneous adverse reactions

• The HLA-A*2402 allele may be a protective marker for the cross-allergic reactions among aromatic AEDs.
• HLA-B*1502 is not a major responsible allele for the cross-reactivity of cADRs to aromatic AEDs.
• These patients with AEDs-induced SJS/TEN rarely exhibited another attack of SJS/TEN when converting to other AEDs.

SummaryBackgroudThe cross-allergic reactions among aromatic antiepileptic drugs (AEDs) are common, but little is known about the genetic mechanisms.PurposeThe aim of this study was to investigate the genetic associations of the human leukocyte antigen (HLA) genes with the cross-reactivity of cutaneous adverse drug reactions (cADRs) induced by different aromatic AEDs.MethodsWe reviewed 60 Chinese patients with a history of cADRs induced by an aromatic AED, and which re-challenged other aromatic AEDs as an alternative to the causative AED owing to some particular reasons. According to whether developing another episode of cADRs, these patients were automatically divided into the cross-reactivity group and tolerant control group. High-resolution HLA-A, -B, -DRB1 genotyping were performed for each patient.ResultsOne out of 10 patients (10%, 1/10) carried the HLA-A*2402 allele in the cross-reactivity group. However, 23 patients (46%, 23/50) carried this allele in the tolerant control group. The difference of the HLA-A*2402 allele between the two groups is statistically significant (P = 0.040, OR = 0.130, 95% CI: 0.015–1.108). In addition, the frequency differences of other HLA alleles between the two groups, including the HLA-B*1502 allele, did not reach statistical significance (P > 0.05).ConclusionsThe HLA genes contribute to the genetic susceptibility of the cross-reactivity of cADRs among aromatic AEDs. Our results suggest that HLA-B*1502 is not a major responsible allele for the cross-reactivity of cADRs to aromatic AEDs, but the HLA-A*2402 allele may be a protective marker for the cross-allergic reactions among aromatic AEDs in Han Chinese. Further studies are warranted to test the potential predictive value of the HLA-A*2402 allele in future.