Proportion of Antiepileptic Drug–Associated Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis: A Meta-Analysis

Lee EY, Knox C, Sugumar C, Phillips EJ. JAMA Dermatol. Published online July 22, 2026. doi:10.1001/jamadermatol.2026.2473

Key Points

Question  What is the global proportion of antiepileptic drug–associated Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN)?

Findings  In this systematic review and meta-analysis of 50 studies including 4403 patients, 23% of SJS/TEN cases were attributed to antiepileptic drugs. Nearly all antiepileptic drug–associated cases involved aromatic agents (96%), most commonly carbamazepine (39%), phenytoin (19%), and lamotrigine (15%).

Meaning  These findings support the view that antiepileptic drugs are a major cause of SJS/TEN worldwide and reinforce the preferential use of nonaromatic alternatives when clinically appropriate.

Abstract

Importance  Antiepileptic drugs (AEDs) are frequently implicated in Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), which are the most severe type of drug hypersensitivity reaction, with a mortality rate up to 50%. However, the overall proportion of these cases attributed to AEDs has not been systematically reviewed.

Objective  To evaluate the proportion of AED-associated SJS/TEN.

Data Sources  The MEDLINE and Embase databases were searched from inception through March 17, 2026, with results limited to English-language publications and human participants.

Study Selection  All experimental and observational studies that reported patient-level triggers of SJS/TEN were included.

Data Extraction and Synthesis  Two reviewers independently screened studies and extracted data using a predefined template. To estimate the proportion of AED-associated SJS/TEN, a random-effects meta-analysis was performed, calculating the pooled proportions with 95% CIs. Subgroup analyses by age group (children vs adults) and geographic region were performed to explore heterogeneity.

Main Outcomes and Measures  To estimate the proportion of AED-associated SJS/TEN.

Relative Proportions of Specific Antiepileptic Drugs (AEDs)
Among AED-Associated Stevens-Johnson Syndrome (SJS)
and Toxic Epidermal Necrolysis (TEN)

Results  This systematic review and meta-analysis included 50 studies with 4403 patients that reported patient-level triggers of SJS/TEN. Single-drug triggers accounted for 88% (95% CI, 83-92) of cases. The pooled proportion of SJS/TEN cases attributed to AEDs was 23% (95% CI, 19-26). Nearly all AED-associated cases were due to aromatic AEDs (96%; 95% CI, 92-99), most commonly carbamazepine (39%; 95% CI, 29-50), followed by phenytoin (19%; 95% CI, 11-28), and lamotrigine (15%; 95% CI, 8-22). Nonaromatic AEDs were rarely implicated (2%; 95% CI, 0-4). Significant geographic variation was observed in the proportion of AED-associated SJS/TEN, ranging from 42% (95% CI, 26-59) in West Asia to 10% (95% CI, 0-33) in Africa (P < .001). The proportion of AED-associated SJS/TEN cases was significantly higher in children (35%; 95% CI, 22-48) than in adults (23%; 95% CI, 20-27).

Conclusions and Relevance  In this systematic review and meta-analysis of observational studies, AEDs accounted for nearly one-quarter of SJS/TEN cases reported worldwide, predominantly involving aromatic AEDs, such as carbamazepine, phenytoin, and lamotrigine. These findings suggest aromatic AEDs as leading contributors to SJS/TEN and support the preferential use of nonaromatic AEDs when clinically appropriate.

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