HLA-A*24:02/B*51:01 haplotype and lamotrigine-induced cutaneous adverse drug reactions in Koreans

ABSTRACT

Antiepileptic drugs (AEDs) have been known to induce cutaneous adverse drug reaction (cADR), ranging from a mild maculopapular eruption (MPE) to potentially life-threatening cADRs such as Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). Despite studies examining mechanisms associated with human leukocyte antigen (HLA), the association between lamotrigine (LTG)-induced cADR and HLA alleles still has room to investigate. We investigated HLA-A,-B, and -C alleles in LTG-induced cADR. The medical records of four patients with LTG-induced cADR were retrospectively reviewed. All patients were treated with LTG for epilepsy. All recovered from cADR after stopping LTG treatment and receiving intensive care. HLA-A, -B, and -C genotyping was performed in all four patients using a PCR-sequence-based typing (SBT) method. Two patients had SJS, and the other two had MPE due to LTG. The range of latency to cADR after the initial LTG dose was 19–42 days. Two patients experienced cross-reactivity with other aromatic or new AEDs. Expression of the HLA-A*2402/B*5101 haplotype was detected in three (75%) patients with LTG-induced cADR. The other patient carried homozygous HLA-B*5801 alleles. The results suggest that Korean individuals with the HLA-A*2402/B*5101 haplotype may be susceptible to LTG-induced cADR. Further investigations are necessary to confirm these findings.