Evaluation and Updated Classification of Acute Hypersensitivity Reactions to Nonsteroidal Anti-Inflammatory Drugs (NSAIDs): NSAID-Exacerbated or -Induced Food Allergy.

Background: There are hypersensitivity reactions (HRs) to foods in which nonsteroidal anti-inflammatory drugs (NSAIDs) act as aggravating factors (NSAID-exacerbated food allergy [NEFA]) or cofactors (NSAID-induced food allergy [NIFA]), often misdiagnosed as HRs to NSAIDs. Urticarial/angioedematous and/or anaphylactic reactions to two or more chemically unrelated NSAIDs do not meet current classification criteria. However, they may be considered part of a cross-reactive type of acute HR, which is NSAID-induced urticaria/angioedema with or without respiratory or systemic symptoms of anaphylaxis.

Objective: To evaluate patients reporting acute HRs to NSAIDs and classify them according to updated criteria.

Methods: We prospectively studied 414 patients with suspected HRs to NSAIDs. For all whom met these criteria, NEFA/NIFA was diagnosed: (1) mild reactions to (NEFA) or tolerance of (NIFA) the suspected foods without taking NSAIDs; (2) cutaneous and/or anaphylactic reactions to the combination foods plus NSAIDs; (3) positive allergy tests to the suspected foods; and (4) negative drug challenges (DCs) with the NSAIDs involved.

Results: A total of 252 patients were given the diagnosis of NSAID hypersensitivity (60.9%), 108 of whom had NSAID-induced urticaria/angioedema with or without respiratory or systemic symptoms of anaphylaxis. We excluded NSAID hypersensitivity in 162 patients (39.1%) who tolerated DCs with the suspected NSAIDs, nine of whom received a diagnosis of NEFA, and 66 of NIFA. Pru p 3 was implicated in 67 of those 75 patients who received a diagnosis of NEFA or NIFA.

Conclusions: NEFA and NIFA account for about 18% of patients reporting HRs to NSAIDs, in which Pru p 3 is the main responsible food allergen. Therefore, patients with cutaneous and/or anaphylactic reactions to NSAIDs should be carefully questioned about all foods ingested within 4 hours before or after NSAID exposure, and targeted food allergy tests should be considered in the diagnostic workup of these patients. If testing is positive, DCs with the suspected NSAIDs should also be considered.