More than a one-quarter of Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) cases worldwide are associated with antibiotics, most notably sulfonamide antibiotics, according to study findings published in Journal of the American Medical Association Dermatology.
Researchers conducted a systematic review and meta-analysis using the MEDLINE and Embase databases from inception through February 2022 to search for 64 experimental and observational studies that described SJS/TEN risks selected by 2 independent reviewers. They employed eligibility criteria that included clearly diagnosed SJS/TEN, clearly described study setting, specific information on antibiotic triggers, sufficient descriptors of culprit medications associated with SJS/TEN, and sample sizes of at least 30 patients with SJS/TEN recruited consecutively during the course of at least 1 year.
Researchers described patient-level associations using a random-effects model, used subgroup analyses to examine heterogeneity, and used Joanna Briggs Institute checklist to assess risk for bias. Reviews, editorials, conference abstracts, surveys, and case reports were excluded from the final analysis.
A total of 38 studies that described patient-level associations and the prevalence of single antibiotics associated with SJS/TEN in the final meta-analysis.
Among all SJS/TEN cases, 86% (95% CI, 0.80-0.92) were associated with a single medication. Unknown medication names, infections, multiple potential medication triggers, or unknown causes associated with the remaining 14%. Other common triggers for SJS/TEN included nonsteroidal anti-inflammatory drugs, allopurinol, and anticonvulsants.
Researchers noted a prevalence of 28% (95% CI, 0.23-0.33) with moderate certainty of evidence in the pooled proportion of antibiotics associated with SJS/TEN. The antibiotic-associated SJS/TEN included an association with the macrolide class (2%; 95% CI, 0.01-0.05) of cases, fluoroquinolones (4%; 95% CI, 0.01-0.07), cephalosporins (11%; 95% CI, 0.06-0.17), penicillins (22%; 95% CI, 0.17-0.28), sulfonamides (32%; 95% CI, 0.22-0.44; all P <.001). It was observed that the pooled proportion of medication-associated SJS/TEN triggered by antibiotics was 35% (95% CI, 0.29-0.40), and the pooled proportion of sulfonamide antibiotics triggering medication-associated SJS/TEN was 11% (95% CI, 0.07-0.16).
The statistically significant heterogeneity was possibly partially explained by the statistically significant difference in the proportion of antibiotics when stratified by continents in subgroup analysis. There was a low overall risk for bias. There was no difference in the proportion of antibiotics associated with SJS/TEN between adult (n=1028) and pediatric (n=208) groups.
Limitations of the study include the stringent eligibility criteria that excluded significant numbers of studies causing selection bias, and the fact that meta-regression was not performed on primary outcomes to further explore heterogeneity.
“Antibiotics were associated with more than one-quarter of SJS/TEN cases described worldwide, and sulfonamide antibiotics remained the most important association,” researchers conclude. “The study highlights the importance of using antibiotics judiciously and limiting sulfonamide antibiotics to only specific indications and durations, as well as early recognition and prompt discontinuation of the implicated drugs to reduce morbidity and mortality associated with SJS/TEN.”
Disclosure: One study author declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.
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 Dermatol. Published online February 15, 2023. doi:10.1001/jamadermatol.2022.6378