Association of CYP2C9*3 with phenytoin-induced Stevens-Johnson syndrome and toxic epidermal necrolysis: A systematic review and meta-analysis.

WHAT IS KNOWN AND OBJECTIVE

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe cutaneous adverse reactions that can be induced by phenytoin (PHT). CYP2C93 is the key enzyme in PHT metabolism. The aim of this meta-analysis was to evaluate the association between CYP2C93 and PHT-induced SJS/TEN.

METHODS

An extensive search was performed in multiple databases, including the Cochrane Library, EMBASE, PubMed, OVID and EBSCO. Studies exploring the relationship between CYP2C9*3 and PHT-induced SJS and TEN were included. Odds ratios (ORs) with corresponding 95% confidence intervals (CI) were calculated for dichotomous data. Data analysis was performed using Review Manager (version 5.3).

RESULTS AND DISCUSSION

Four studies, with 117 PHT-induced SJS/TEN cases and 338 matched controls (PHT-tolerant patients) or 4231 population controls (general population), were identified. SJS and TEN were found to be significantly associated with the CYP2C9*3 allele, comparing both matched controls (OR, 8.93; 95% CI, 2.63-30.36; P = .0005) with substantial heterogeneity (I  = 46%) and population controls (OR, 8.88; 95% CI, 5.01-15.74; P < .00001).

WHAT IS NEW AND CONCLUSION

A significant association between CYP2C93 and PHT-induced SJS/TEN was identified, especially in a Thai population. CYP2C93 is thus a credible predictive genetic marker of PHT-induced SJS/TEN. Further multicenter studies and large prospective observational studies are, however, still required to determine the influence of CYP2C*3 on blood levels of PHT and its metabolites, and their association with SJS/TEN.