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

Abstract

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 ≥ 2 chemically unrelated NSAIDs do not meet the current classification criteria. However, they may be considered as part of a cross-reactive type of acute HR, which is NSAID-induced urticaria/angioedema with/without respiratory and/or systemic symptoms of anaphylaxis (NIUAA). To evaluate patients reporting acute HRs to NSAIDs and classify them according to updated criteria. 414 patients with suspected HRs to NSAIDs were studied prospectively. NEFA/NIFA was diagnosed in those who met all the following criteria: 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 + NSAIDs; 3) positive allergy tests to the suspected foods; 4) negative drug challenges (DCs) with the NSAIDs involved. 252 patients (60.9%) were diagnosed with NSAID hypersensitivity, 108 of whom had NIUAA. NSAID hypersensitivity was excluded in 162 patients (39.1%) who tolerated DCs with the suspected NSAIDs, 9 of whom were diagnosed with NEFA and 66 with NIFA. Pru p 3 was implicated in 67 of these 75 cases. NEFA/NIFA accounts for about 18% of patients reporting HRs to NSAIDs, with Pru p 3 as 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.