Comparative Impact of <scp>NSAIDs</scp> Versus Acetaminophen on Mortality in Stevens–Johnson Syndrome and Toxic Epidermal Necrolysis: A Retrospective Cohort Study of 2484 Patients From a Nationwide Inpatient Database

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe and life-threatening mucocutaneous disorders, primarily triggered by medications. Despite the frequent need for antipyretic and analgesic therapy, the impact of nonsteroidal anti-inflammatory drugs (NSAIDs) and acetaminophen on clinical outcomes in patients with SJS/TEN remains unclear. This study aimed to compare the effects of NSAIDs and acetaminophen use on in-hospital mortality, infection-related events, and renal outcomes, with particular attention to the presence or absence of chronic kidney disease (CKD). We conducted a retrospective analysis using a nationwide administrative database of over 1200 acute care hospitals in Japan between July 2010 and March 2022. Adult patients diagnosed with SJS or TEN who received either NSAIDs or acetaminophen within the first 5 days of hospitalization were included. Patients who received both drugs or neither were excluded. Among 8301 eligible patients, 2484 met inclusion criteria. Overall mortality did not differ significantly between groups (4.1% vs. 4.6%; risk difference [RD], -0.6%; 95% confidence interval [CI], -2.5% to 1.4%). In patients without CKD, NSAID use was associated with lower mortality (2.6% vs. 4.3%; RD, -1.7%; 95% CI, -3.4% to 0.0%). Conversely, in patients with CKD, acetaminophen use was associated with lower mortality (12.0% vs. 38.2%; RD, 26.2%; 95% CI, 5.0% to 47.4%). In conclusion, NSAID use may be associated with relatively improved survival compared with acetaminophen in patients without CKD, while acetaminophen appears safer in those with CKD, suggesting that renal function may inform the selection of antipyretic or analgesic therapy when such treatment is unavoidable. As both drugs are known causative agents of SJS/TEN, these results should be interpreted with caution. Further studies are warranted to validate these observational findings.