Phenytoin Induced Toxic Epidermal Necrolysis: A Systematic Review and Meta-Analysis

Background: Toxic epidermal necrolysis (TEN) is a rare but life-threatening severe cutaneous adverse reaction (SCAR), most commonly triggered by drugs. Among anticonvulsants, phenytoin remains a significant contributor, particularly in developing countries. Objective:To systematically evaluate the incidence, clinical characteristics, risk factors, and outcomes of phenytoin-induced TEN and synthesize available evidence through meta-analysis. Methods: A systematic search of PubMed, MEDLINE, and EMBASE databases was performed up to March 31, 2026. Studies including observational studies, case series, and case reports of phenytoin-induced TEN were included. Meta-analysis was conducted using pooled proportions for incidence, mortality, and risk factors. Results: A total of 34 studies comprising 1,248 patients with drug-induced TEN were included, of which 162 cases were attributed to phenytoin. The pooled proportion of phenytoin-associated TEN among all TEN cases was 12.8% (95% CI: 9.6–16.5). Mortality in phenytoin-induced TEN was 28.4% (95% CI: 22.1–35.3). Significant associations were identified with HLA-B*1502 positivity, rapid dose escalation, and concomitant valproate therapy. Conclusion: Phenytoin is a major causative drug for TEN with high mortality. Genetic screening and cautious dosing strategies are essential preventive measures. Early withdrawal and intensive supportive care remain the cornerstone of management.