Generalized Bullous Fixed Drug Eruption: A Systematic Review

Generalized bullous fixed drug eruption (GBFDE) is a severe cutaneous adverse reaction characterized by widespread plaques with bullae. Although regarded as less severe than Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), emerging reports suggest GBFDE may be similarly life-threatening. Comprehensive characterization of GBFDE remains lacking.

To review the epidemiology, causative agents, clinical features, histology, outcomes, and management of GBFDE.

We conducted a systematic review according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We searched PubMed and Embase databases for studies from 1985 to October 27, 2024. Original observational cases of GBFDE were included. Studies without quantitative patient data were excluded. We assessed study quality using the Newcastle-Ottawa scale, analyzed data descriptively, and performed comparative analyses.

Of 347 publications reviewed, 83 studies composed of 430 cases were included, median age 56 years (interquartile range [IQR], 41-75 years). Common causative agents include nonsteroidal anti-inflammatory drugs (48.7%) available over the counter in many countries without prescription and antibiotics (30.9%). Median latency was 24 hours (IQR, 12-72 hours). Mucosal involvement occurred, but no cases involved ocular mucosa. Internal organ involvement was uncommon. Intensive care unit stay was required in 19.9%. Mortality was 15.2% and was significantly associated with age (P = .01). Median time to resolution was 11 days (IQR, 8-17 days). Post-inflammatory hyperpigmentation occurred in 54.3%. Corticosteroids were the most commonly used treatment (22.4% topical and 50.6% systemic). Data were heterogeneous, and the retrospective nature of reporting limited long-term outcome assessment.

Generalized bullous fixed drug eruption has a short latency. Nonsteroidal anti-inflammatory drugs and antibiotics are the commonest triggers. Systemic dysfunction is less common than in Stevens-Johnson syndrome/toxic epidermal necrolysis, but morbidity and mortality is significant, particularly in elderly people. The widespread availability of over-the-counter NSAIDs may pose a risk for GBFDE.