Pharmacogenetic screening of carbamazepine-induced severe cutaneous allergic reactions

Recent studies associated the HLA-B∗1502 allele with carbamazepine (CBZ)-induced Stevens–Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) in patients from China, Thailand and Malaysia. No association has been found in patients from Europe or Japan. Linkage summary reports from East and South-east Asia predict a highly significant odds ratio (OR) of 84.75 (95% confidence interval [CI] = 42.53–168.91; p = 8.96 × 10[–15]) with sensitivity and negative predictive values of 92% and 98%, respectively. The higher prevalence of HLA-B∗1502 allele among certain Asian populations (10–15%) compared to Caucasians (1–2%) may explain a 10-fold to 25-fold higher incidence of CBZ-SJS/TEN in patients from Asia. Screening for HLA-B∗1502 before using CBZ can prevent SJS/TEN in certain populations, but screening may be less beneficial in populations with low HLA-B∗1502 allele frequency and in patients exposed to CBZ for more than 2 months. A retrospective study demonstrated that the costs of HLA-B∗1502 screening were less than those of SJS treatment. This article reviews possible benefits and concerns of HLA-B∗1502 screening in clinical practice.