Systematic allergological evaluation enables NSAID allergy delabeling and identification of safe alternatives in adults.

BACKGROUND: Hypersensitivity reactions to nonsteroidal anti-inflammatory drugs (NSAIDs) are a frequent reason for allergy referral and a major diagnostic challenge. In everyday practice, overdiagnosis contributes to unnecessary drug avoidance, restricting therapeutic access to first-line analgesic and anti-inflammatory treatments and impacting clinical care. OBJECTIVE: To determine the true prevalence of confirmed NSAID hypersensitivity in adults with suspected reactions through systematic allergological evaluation and assess its clinical impact on therapeutic access through safe delabeling and identification of alternative agents. METHODS: We conducted a prospective, cross-sectional study including adults ≥18 years with suspected NSAID hypersensitivity evaluated at a tertiary referral center in Mexico between March and November 2025. All patients underwent standardized assessment including detailed clinical history, skin testing (prick and intradermal), and controlled drug provocation tests (DPTs) with acetylsalicylic acid, the implicated NSAID, and celecoxib. Clinical phenotypes were classified according to EAACI/ENDA guidelines. Associations between clinical variables and confirmed hypersensitivity were analyzed. RESULTS: Thirty-three patients were included; 72.7% were women, and 42.4% were aged 18-30 years. Atopy was present in 63.6%. Urticaria/angioedema predominated (69.7%). Ibuprofen and diclofenac were most frequently implicated (45.5%). Skin testing showed low diagnostic yield (6.1% prick; 21.2% intradermal). DPT was positive in 24.2%, mainly inducing urticaria. Celecoxib was tolerated in all patients with multiple hypersensitivity. Overall, 48.5% had no confirmed hypersensitivity and were successfully delabeled, restoring access to NSAID therapy. Multiple hypersensitivity occurred in 39.4% and selective reactions in 12.1%, with NIUAA as the predominant phenotype (33.4%). Atopy (p = 0.002) and recurrent episodes (p < 0.001) were associated with multiple hypersensitivity. CONCLUSION: Nearly half of adults labeled as NSAID-allergic were not truly hypersensitive. These prospective Mexican data demonstrate the clinical impact of systematic evaluation in reducing overdiagnosis and improving therapeutic access.