Diagnosing Nonsteroidal Anti-Inflammatory Drug-Hypersensitivity/Allergy and Nonsteroidal Anti-Inflammatory Drug-Exacerbated or Induced Food Allergy Phenotypes in Children and Adolescents.

Abstract

Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used in children. Hypersensitivity reactions (HRs) to NSAIDs represent a diagnostic challenge, particularly because NSAIDs may act as aggravating factors or cofactors as in two phenotypes recently named NSAID-exacerbated food allergy (NEFA) and NSAID-induced food allergy (NIFA). To diagnose NSAID hypersensitivity/allergy (NH/A) and NEFA/NIFA phenotypes in children and adolescents, classify HRs to NSAIDs according to updated international guidelines, and identify clinical and immunologic predictors of true NH/A. We prospectively studied 336 children and adolescents with a history of HRs to NSAIDs, following international guidelines, which include challenges with the suspected NSAIDs. Primary outcomes were identification of NH/A phenotypes and their predictors. Hypersensitivity or allergy to NSADISs was diagnosed in 104 of 336 patients (31%). The most frequent phenotypes were single-NSAID-induced urticaria, angioedema, or anaphylaxis (55.8%) and NSAID-induced urticaria, angioedema, or anaphylaxis (22.1%). We excluded NH/A in 232 patients (69%), 48 of whom received the diagnosis of NEFA/NIFA. Sensitization to Pru p 3 was strongly associated with NEFA/NIFA. Non-hypersensitive or allergic reactions were associated with antipyretic use (odds ratio [OR] = 5.92; 95% CI, 3.60-9.72), urticaria (OR = 3.06; 95% CI, 1.77-5.28), and younger age (OR per 6-year increment = 0.64; 95% CI, 0.47-0.89). Internal validation showed good discrimination (area under the receiver operating characteristic curve, 0.82; cross-validated area under the receiver operating characteristic curve, 0.79). Approximately one third of children with suspected reactions had confirmed NH/A, whereas 14.3% had NEFA/NIFA. In 69% of patients, the NH/A label was removed. Many reactions during antipyretic use appear to be related to infection rather than true NSAID hypersensitivity.