The risk of cutaneous adverse reactions among patients with the HLA-A* 31:01 allele who are given carbamazepine, oxcarbazepine or eslicarbazepine: a perspective review

Carbamazepine is a drug that is widely used for the treatment of epilepsy, trigeminal neuralgia and bipolar disorder. This drug is also known to cause cutaneous adverse drug reactions (cADRs) in up to 10% of patients. The recent progress in pharmacogenetics has revealed that human leukocyte antigen (HLA) genotypes are associated with a susceptibility to the cADRs caused by particular drugs. For carbamazepine-induced Stevens-Johnson syndrome and toxic epidermal necrolysis, very strong associations with HLA-B*15:02 have been found mainly in patients of Southeastern Asian origin. In some countries, prescreening HLA-B*15:02 allele has already been put to practical use as a biomarker to avoid the life-threatening adverse drug reactions. In this review, another risk factor for carbamazepine-induced cADRs is discussed, namely HLA-A*31:01. We compare the strength of the association between HLA-A*31:01 and carbamazepine-induced cADRs based on reports for various ethnic populations; discuss the difference between the HLA-A*31:01 and HLA-B*15:02 biomarkers and the usefulness of prescreening HLA-A*31:01 to detect patients at high risk for carbamazepineinduced cADRs; and refer to points that remain to be resolved.