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

Sep 30, 2026

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Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe, medication-triggered mucocutaneous disorders, yet the clinical impact of antipyretic/analgesic choice—nonsteroidal anti-inflammatory drugs (NSAIDs) versus acetaminophen—remains uncertain. This retrospective cohort used Japan’s nationwide inpatient administrative database from July 2010 to March 2022 to assess in-hospital mortality and related outcomes. Among 2484 eligible adults receiving either NSAIDs or acetaminophen within 5 days, overall mortality was similar, but effects diverged by chronic kidney disease (CKD) status. In CKD-free patients, NSAIDs showed lower mortality, whereas in patients with CKD, acetaminophen showed lower mortality, suggesting renal function may guide therapy when treatment is unavoidable.

LanguageEnglish

CategoryHealthcare

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Abstract

Introduction

The Journal of Dermatology ORIGINAL ARTICLE OPEN ACCESS Comparative Impact of NSAIDs Versus Acetaminophen on Mortality in Stevens–Johnson Syndrome and Toxic Epidermal Necrolysis: A Retrospective Cohort Study of 2484 Patients From a Nationwide Inpatient Database Rino Toyoshima1 | Shotaro Aso2 | Hiroki Matsui3 | Kiyohide Fushimi4 | Natsumi Hama5 | Riichiro Abe5 | Hideo Yasunaga3 | Shinichi Sato1 | Sayaka Shibata1 1Department of Dermatology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan | 2Department of Health Services Research, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan | 3Department of Clinical Epidemiology and Health Economics, School of Public Health, The University of Tokyo, Tokyo, Japan | 4Department of Health Policy and Informatics, Institute of Science Tokyo Graduate School, Tokyo, Japan | 5Division of Dermatology, Graduate School of Medicine, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan Correspondence: Sayaka Shibata ([shibatas-der@h.u-tokyo.ac.jp](shibatas-der@h.u-tokyo.ac.jp)) Received: 29 July 2025 | Revised: 27 October 2025 | Accepted: 19 November 2025 Keywords: acetaminophen | chronic kidney disease (CKD) | nonsteroidal anti-inflammatory drugs (NSAIDs) | Stevens–Johnson syndrome (SJS) | toxic epidermal necrolysis (TEN) ABSTRACT 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. | Abbreviations: ASD, absolute standardized difference; BMI, body mass index; CI, confidence intervals; CKD, chronic kidney disease; DPC, Diagnosis Procedure Combination; ICD-10, International Classification of Diseases, Tenth Revision; ICU, Intensive Care Unit; JCS, Japan Come Scale; NSAIDs, nonsteroidal antiinflammatory drugs; RD, risk differences; SD, standard derivatives; SJS, Stevens–Johnson syndrome; TEN, Toxic epidermal necrolysis. | | --- | | This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
© 2025 The Author(s) . The Journal of Dermatology

FAQs

What was the study’s main objective?

To compare NSAID and acetaminophen use on in-hospital mortality and related clinical outcomes in patients with SJS/TEN, with emphasis on whether chronic kidney disease (CKD) was present.

How were patients selected for the analysis?

Adults diagnosed with SJS or TEN who received either NSAIDs or acetaminophen within the first 5 days of hospitalization were included, while patients receiving both drugs or neither were excluded.

Did NSAIDs and acetaminophen differ in overall mortality?

Overall in-hospital mortality did not differ significantly between the groups. However, mortality patterns differed when stratified by CKD status.

How did results change depending on CKD status?

In patients without CKD, NSAID use was associated with lower mortality, while in patients with CKD, acetaminophen use was associated with lower mortality, indicating renal function may help guide antipyretic/analgesic selection.

Sep 30, 2026

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