Antibiotic Drug Use and the Risk of Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis: A Population-Based Case-Control Study

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare, life-threatening mucocutaneous adverse drug reactions. Sulphonamide antibiotics are commonly accepted as one of the primary causes of SJS/TEN. This notion is based on results from two hospital-based case-control studies that identified the combined antibiotic cotrimoxazole (sulfamethoxazole and trimethoprim) as the cause of several SJS/TEN cases. Associations were also reported for penicillins, quinolones, cephalosporins, macrolides, tetracyclines, and metronidazole. Using data from the UK-based Clinical Practice Research Datalink, we conducted a 1:4-matched case-control study including 480 previously validated SJS/TEN cases (1995-2013) to quantify the association between SJS/TEN and antibiotics. We further quantified absolute risks of SJS/TEN within separate cohorts of antibiotic users and assessed causality in each exposed case using an adapted version of the algorithm of drug causality in epidermal necrolysis (ALDEN). We observed a strong association between SJS/TEN and trimethoprim alone (odds ratio=9.44, 95% CI 3.83-23.25; absolute risk: 0.98 cases/100'000 users), which suggests that the previously reported association between cotrimoxazole and SJS/TEN is at least partly attributable to the non-sulphonamide antibiotic trimethoprim, which is frequently prescribed as a single agent in the UK. Our study further corroborates previously reported associations between SJS/TEN and use of penicillins, quinolones, cephalosporins, and macrolides.