Diagnostic Algorithm and Real-Life Data in Pediatric Patients Suspected of NSAID Hypersensitivity

Background Nonsteroidal anti-inflammatory drugs (NSAIDs) are frequently used in children, but NSAID hypersensitivity (NSAID-H) presents a heterogeneous clinical profile. Pediatric diagnostic approaches and real-life data after drug challenges (DCs) remain limited. Objective We aimed to evaluate the diagnostic algorithm for suspected pediatric NSAID-H and examine real-life drug use. Methods Children (1-18 years) evaluated for NSAID-H using WAO guidelines at a tertiary pediatric allergy center (Jan 2022-Nov 2025) were included. Clinical histories, co-morbidities, and DC outcomes were recorded. Patients were classified as having single- or multiple-NSAID induced hypersensitivity. Positive patients underwent DCs for safe alternatives, and real-life tolerance was assessed. Results Of 62 included children, five had suspected immediate paracetamol reactions (one confirmed). Fifty-seven reported reactions to ≥2 unrelated NSAIDs; six were diagnosed via history alone. Of 51 children challenged with ASA/ibuprofen, 14 (27.5%) were positive. Angioedema was the most frequent reaction; one experienced anaphylaxis following ibuprofen provocation. Single- and multiple-NSAID hypersensitivity rates were 20% (1/5) and 35.1% (20/57), respectively. Five patients already used paracetamol safely. For the remaining 14, safe alternatives identified were nimesulide (n=6) and meloxicam (n=4). One reacted to both, but tolerated codeine. Among 41 patients with excluded NSAID-H, 37 were contacted; 36 (97.3%) safely reused the culprit drug in real-life (one avoided due to maternal fear). Of 14 confirmed NSAID-H patients, 11 were contacted, all reporting safe alternative use without reactions. Conclusion Structured diagnostic algorithms and drug challenges ensure accurate diagnosis, reducing unnecessary NSAID restrictions and enabling safe real-life drug use in children. Key Words Acetyl salicylic acid, Children, Cyclooxygenase, Diagnosis, Drug allergy, Drug challenge, NSAID Hypersensitivity, Safe alternative, Real life.