Genetic predisposition of life-threatening antiepileptic-induced skin reactions

Abstract

Importance of the field: Recent advances in pharmacogenetic studies have uncovered increasingly more genes that predispose individuals to adverse drug reactions. Aromatic antiepileptic drugs (AEDs) are a frequent cause of severe cutaneous adverse reactions (SCAR). A strong genetic association between HLA-B*1502 and carbamazepine (CBZ)-induced Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) has been shown in Han Chinese patients.

Areas covered in this review: This article reviews and updates genetic information associated with CBZ and other AEDs causing SCAR in different ethnic populations.

What the reader will gain: Independent studies from different countries confirmed that patients carrying the HLA-B*1502 are at high risk of SJS/TEN when exposed to CBZ. The US FDA and similar regulatory agencies in Canada and Taiwan have updated the CBZ drug label to include the genetic information. Available data also suggest that HLA-B*1502 is a risk allele for SJS/TEN caused by other aromatic AEDs with a similar structure to CBZ.

Take home message: Screening for HLA-B*1502 allele before starting treatment with CBZ is justified in patients from high-risk populations as recommended by regulatory agencies. Similar chemicals should also be avoided in individuals who test positive for HLA-B*1502.