How common is antibiotic-associated Stevens-Johnson syndrome and toxic epidermal necrolysis?

Antibiotics are known to be an important risk factor for the development of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). SJS and TEN are the most severe types of drug hypersensitivity reactions, with a mortality rate of up to 50%. These severe drug-associated reactions are characterized by mucosal erosion, epidermal detachment and necrosis. Short- and long-term morbidity and mortality include visual impairment and adverse effects on mental health and quality of life. SJS/TEN can occur at any age. Symptoms of drug-related SJS/TEN usually begin within four to 28 days of continuous exposure to a culprit drug. Commonly implicated drugs include allopurinol, aromatic anticonvulsants, antibiotics and nonsteroidal anti-inflammatory drugs. Prompt cessation of the culprit drug is associated with a decreased risk of death compared with SJS/TEN of unknown cause. The first systematic review and meta-analysis has now been undertaken to evaluate the prevalence of antibiotic-associated SJS/TEN worldwide and the relative prevalence of each antibiotic class triggering antibiotic-associated SJS/TEN. The review included studies that adequately described SJS/TEN origins and specified the antibiotics associated with SJS/TEN. Results showed the following: A total of 64 studies were included in the systematic review. Of these 64 studies, 38 described patient-level associations; the meta-analysis included these 38 studies with 2,917 patients to determine the prevalence of single antibiotics associated with SJS/TEN. The pooled proportion of antibiotic-associated SJS/TEN was 28% (95%CI, 24%–33%), with moderate certainty of evidence. Among antibiotic-associated SJS/TEN, the sulfonamide class was associated with 32% (95%CI, 22%–44%) of cases, followed by penicillins (22%; 95%CI, 17%–28%), cephalosporins (11%; 95%CI, 6%–17%), fluoroquinolones (4%; 95%CI, 1%–7%) and macrolides (2%; 95%CI, 1%–5%). The authors conclude that in this global systematic review and meta-analysis, antibiotics were associated with more than one-quarter of SJS/TEN cases. Sulfonamide antibiotics had the highest association with the development of SJS/TEN, while macrolides were the least frequent cause among the top five globally prescribed antibiotic classes. This study supports the ongoing effort to avoid unnecessary antibiotic use and restrict sulfonamide antibiotics to specific indications and durations to help prevent SJS/TEN. These findings also highlight the importance of antibiotic stewardship, clinician education and awareness of SJS/TEN, and conducting a risk-benefit assessment of antibiotic choice and duration prior to prescribing. Reference 1. Lee EY, Knox C, Phillips EJ. Worldwide prevalence of antibiotic-associated Stevens-Johnson syndrome and toxic epidermal necrolysis. A systematic review and meta-analysis. JAMA Dermatology 2023; Published online February 15, 2023. (accessed February 21, 2023).

How common is antibiotic-associated Stevens-Johnson syndrome and toxic epidermal necrolysis?

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