COVID-19 and severe cutaneous allergic reactions to sulfonamides

Abstract

Background: Sulfonamides are associated with severe cutaneous adverse reactions (SCARs). Coronavirus disease 2019 (COVID-19) triggers an immune response, which may increase the likelihood of developing a hypersensitivity reaction. Objectives: We sought to explore the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection on the probability of developing SCARs and/or erythema multiforme (EM) reactions to sulfonamides. Methods: In the propensity score-matched cohort study by using the de-identified TriNetX Research data base, patients who had an exposure to antibiotic or non-antibiotic sulfonamides between March 1, 2020, and January 1, 2023, were divided into two groups based on the presence or absence of a previous COVID-19 infection within 6 months of starting the sulfonamide agent. The outcomes studied were the 30-day risk of developing SCARs or EM (Stevens-Johnson syndrome, toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms, or EM) within 3 months of sulfonamide exposure. Cohorts were matched based on baseline demographics; malignant lymphoid neoplasms; human immunodeficiency virus; systemic lupus erythematosus; bone marrow transplantation; diabetes; psoriasis; seizures; gout; solid organ or stem cell transplantation; COVID-19 vaccination; and exposure to risk medications, including allopurinol, levetiracetam, carbamazepine, lamotrigine, oxcarbazepine, phenytoin, phenobarbital, abacavir, nevirapine, piroxicam, tenoxicam, or mexiletine. Results: When comparing 345,119 patients on sulfonamides and with previous COVID-19 to an equal number of sulfonamides users without a previous COVID-19, patients with COVID-19 had a lower risk of developing any form of SCARs (relative risk 0.39 [95% confidence interval, 0.26, 0.58]; p < 0.001). Conclusion: Previous SARS-CoV-2 infection seems to be associated with a lower probability of developing SCARs or EM among patients using sulfonamides.

Figure 1.

(A) The proportion of patients (per 1000) who developed the different forms of SCARs and/or EM among the patients with exposure to sulfonamides according to COVID-19 diagnosis status. There was a significantly reduced proportion of patients with COVID-19 who developed all forms of SCARs or EM, SJS/TENS, and all forms of EM compared with the controls. (B-E) A Kaplan–Meier survival curve of developing all SCARs or EM, DRESS, SJS or TENS, and EM among the patients using sulfonamides with or without previous COVID-19. The results shown are after propensity score matching. SCARs = Severe cutaneous adverse reactions; EM = erythema multiforme; COVID-19 = coronavirus disease 2019; SJS = Stevens-Johnson syndrome; TENS = toxic epidermal necrolysis syndrome; DRESS = drug reaction with eosinophilia and systemic symptoms.