HLA genotype and carbamazepine-induced cutaneous adverse drug reactions: a systematic review

Abstract

Carbamazepine (CBZ) therapy is associated with cutaneous adverse reactions in up to 10% of patients. Predisposition to these hypersensitivity reactions has been linked to the human leukocyte antigen (HLA) genotype. This systematic review determines the strength of these associations and accuracy of proposed genetic screening. We determined that carriage of HLA-B*1502 in Asian patients was associated with a pooled odds ratio (OR) of 113.4 (95% confidence interval (CI) = 51.2-251.0, P < 1 × 10(-5)) for CBZ-induced Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). A total of 461 patients would need to be screened for HLA-B*1502 to prevent one episode of SJS/TEN. HLA-A*3101 is significantly associated with all phenotypes of CBZ hypersensitivity in multiple ethnicities with a pooled OR of 9.5 (95% CI = 6.4-13.9, P < 1 × 10(-5)). Between 47 and 67 patients would need to be tested for HLA-A*3101 to prevent one episode of hypersensitivity. Our findings suggest that HLA testing before carbamazepine therapy would be effective at identifying individuals at risk of hypersensitivity and applicable to multiple populations providing hope for prevention in the future.