Allopurinol‐Induced Stevens–Johnson Syndrome and Toxic Epidermal Necrolysis: A Systematic Review of Case Reports and Case Series

Background: Allopurinol is a known cause of mucocutaneous adverse drug reactions, including Stevens–Johnson syndrome and toxic epidermal necrolysis. The aim of this systematic review was to characterize the clinical presentation, identify risk factors, and evaluate the best treatment strategies for allopurinol‐induced severe skin reactions. Methods: The PubMed, Embase, and Scopus databases were systematically searched to identify English case reports and case series of allopurinol‐induced Stevens–Johnson syndrome and toxic epidermal necrolysis. Animal studies, reviews, book chapters, randomized and nonrandomized human studies, observational studies, and conference abstracts were excluded. The Joanna Briggs Institute (JBI) critical appraisal checklists were used to assess the quality of the included studies. Results: Forty‐seven case reports and 21 case series were included in the analysis, which reported 91 individual patient datasets. The reaction occurred after a median of 16 days (8.5 days in those with prior reactions to allopurinol). Rapid dose escalation was observed in half of the patients (21 of 43) for whom dose‐increment schedules were reported. Mucosal involvement was observed in 72 (90.0%) patients. Corticosteroids, IVIG, cyclosporine, and plasma exchange were the most common treatment modalities. Twenty‐one patients (23.6%) died, and 68 (76.4%) were discharged. Conclusion: Although gout is 2–3 times more common in men, the numbers of cases were similar in both sexes, likely due to higher reporting rates in women. Rapid dose escalation is a risk factor for the occurrence of severe skin reactions. Corticosteroids, IVIG, and plasma exchange appear to be reasonable treatment options.