A prospective study of 336 children and adolescents with a history of hypersensitivity reactions (HRs) to NSAIDs, evaluated using drug challenge per international guidelines to classify NSAID hypersensitivity/allergy (NH/A) phenotypes and identify clinical/immunologic predictors, including the novel NEFA and NIFA phenotypes.
NH/A was confirmed in 104/336 patients (31%); the most common phenotypes were single-NSAID-induced urticaria/angioedema/anaphylaxis (55.8%) and cross-reactive NSAID-induced urticaria/angioedema/anaphylaxis (22.1%). In 69% of patients, the NH/A label was removed. Of 232 patients without NH/A, 48 (14.3% of total) were diagnosed with NEFA/NIFA; Pru p 3 sensitization was strongly linked to NEFA/NIFA. Antipyretic use (OR 5.92), urticaria (OR 3.06), and younger age (OR 0.64 per 6-year increment) predicted non-allergic reactions. The predictive model showed good discrimination (AUROC 0.82).
Internal validation only (no external cohort); single-center or registry design not fully described; retrospective history reliance for initial phenotype classification before challenge.
Most children labeled NSAID-allergic (~69%) can have that label safely removed after structured challenge — reactions during fever/antipyretic use are often infection-related, not true NSAID hypersensitivity. In children with unexplained food-triggered reactions and NSAID use, test for Pru p 3 sensitization to screen for NEFA/NIFA.
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