Genetic predisposition for the development of lamotrigine-induced Stevens–Johnson syndrome/toxic epidermal necrolysis: a systematic review and meta-analysis

Abstract

Studies report an association between the expression of HLA alleles and lamotrigine (LTG)-induced Stevens–Johnson syndrome (SJS). This systematic review and meta-analysis evaluates the association between HLA alleles and LTG-induced SJS in different populations. Two alleles, HLA-B*0702 and HLA-C*0702, were deemed to be protective; five alleles, HLA-B*1502, HLA-B*4403, HLA-A*2402, CYP2C19*2 and HLA-B*38, may play a role in LTG-induced SJS, for which only data studying HLA-B*1502 could be extracted. The pooled odds ratio of 2.88, 95% CI of 1.60–5.17 and p-value of 0.0004 establish the presence of HLA-B*1502 as a major risk factor for the development of LTG-induced SJS/toxic epidermal necrolysis (TEN). Although multiple alleles that may play a role in the development of LTG-induced SJS/TEN were identified, the expression of the risk alleles may be ancestry-specific, and genetic screening is warranted for preventing this life-threatening adverse drug reaction.