ANTIEPILEPTIC drugs accounted for almost one quarter of reported Stevens Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) cases worldwide, according to a systematic review and meta analysis, reinforcing the role of these medicines as a leading trigger of severe drug hypersensitivity reactions.
Researchers conducted a systematic review and meta analysis to determine the proportion of Stevens Johnson syndrome and toxic epidermal necrolysis cases associated with antiepileptic drugs. Fifty experimental and observational studies involving 4,403 patients were included. Patient level data were analysed using a random effects meta-analysis, with subgroup analyses performed according to age group and geographic region.
Across the included studies, single drug triggers accounted for 88% of cases (95% CI:83–92). Overall, antiepileptic drugs were responsible for 23% of Stevens Johnson syndrome and toxic epidermal necrolysis cases (95% CI:19–26), highlighting their substantial contribution to severe drug induced hypersensitivity reactions.
Almost all antiepileptic drug associated cases involved aromatic antiepileptic drugs, which accounted for 96% of cases (95% CI:92–99). Carbamazepine was the most frequently implicated medicine, accounting for 39% of antiepileptic drug associated cases (95% CI:29–50). This was followed by phenytoin at 19% (95% CI:11–28) and lamotrigine at 15% (95% CI:8–22). In contrast, nonaromatic antiepileptic drugs were rarely associated with Stevens Johnson syndrome and toxic epidermal necrolysis, representing only 2% of cases (95% CI:0–4).
The analysis also identified marked regional variation. The proportion of antiepileptic drug associated Stevens Johnson syndrome and toxic epidermal necrolysis ranged from 42% in West Asia (95% CI:26–59) to 10% in Africa (95% CI:0–33; P<0.001).
Children Experienced Higher Rates
Subgroup analyses demonstrated that antiepileptic drug associated Stevens Johnson syndrome and toxic epidermal necrolysis occurred more frequently in children than adults. The pooled proportion reached 35% among children (95% CI:22–48), compared with 23% among adults (95% CI:20–27).
The authors concluded that antiepileptic drugs were responsible for nearly one quarter of Stevens Johnson syndrome and toxic epidermal necrolysis cases reported worldwide, with aromatic agents accounting for almost all antiepileptic drug associated cases. These findings support the preferential use of nonaromatic antiepileptic drugs when clinically appropriate and may help inform prescribing decisions aimed at reducing the risk of these severe hypersensitivity reactions.
Reference
Lee EY et al. Proportion of antiepileptic drug–associated Stevens-Johnson syndrome and toxic epidermal necrolysis: a meta-analysis. JAMA Dermatol. 2026;DOI: 10.1001/jamadermatol.2026.2473.
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