Updating the classification and routine diagnosis of NSAID hypersensitivity reactions: A WAO Statement

Abstract

Hypersensitivity reactions to non-steroidal anti-inflammatory drugs (NSAIDs) have been classified as immediate (or acute) and delayed. Immediate reactions can be further classified into 4 clinical types: NSAID-exacerbated respiratory disease (N-ERD), NSAID-exacerbated cutaneous disease (NECD), NSAID-induced urticaria/angioedema (NIUA), and single NSAID-induced urticaria/angioedema/anaphylaxis (SNIUAA). Specifically, the NIUA type references reactions to ≥2 NSAIDs belonging to different chemical groups, involving urticaria and/or angioedema in patients with no underlying chronic spontaneous urticaria. However, there are patients meeting cross-reactive criteria for NIUA phenotype who report reactions that involve 2 organ systems (eg, cutaneous and respiratory; cutaneous and gastrointestinal) and have been termed "blended". In pediatrics, this type of reaction is recognized and has been termed NSAID-induced urticaria/angioedema/anaphylaxis (NIUAA), an acronym we suggest be extended now to adults. There are small subgroups of N-ERD patients who also report skin symptoms and, alternatively, NECD patients who report respiratory symptoms. These 2 subgroups could be diagnosed as having mixed N-ERD and mixed NECD, respectively. In fact, they are patients suffering from N-ERD or NECD who have had reactions consistent with anaphylaxis. In the current classifications of NSAID hypersensitivity, the reactions in which NSAIDs act as aggravating factors or cofactors in subjects with sensitization to foods are not included. Recently, this type of reactions has been defined as NSAID-exacerbated food allergy (NEFA) and NSAID-induced food allergy (NIFA), respectively. This Statement of the World Allergy Organization (WAO) aims to update both the classification of hypersensitivity reactions to NSAIDs and their diagnosis, addressing the novel issues.

Keywords: Drug challenge; NSAID-Exacerbated or -induced food allergy (NEFA/NIFA); NSAID-Induced urticaria/angioedema/anaphylaxis (NIUAA); Patch tests; Skin tests; Update.

Fig. 1

Diagnostic algorithm for patients with histories of immediate reactions to non-steroidal anti-inflammatory drugs ASA, acetylsalicylic acid; COX-1, cyclooxygenase-1; CRSwNP, chronic rhinosinusitis with nasal polyps; CSU, chronic spontaneous urticaria; DC, drug challenge; NECD, NSAID-exacerbated cutaneous disease; NEFA, NSAID-exacerbated food allergy; N-ERD, NSAID-exacerbated respiratory disease; NIFA, NSAID-induced food allergy; NIUAA, NSAID-induced urticaria/angioedema and/or anaphylaxis; NSAID, non-steroidal anti-inflammatory drug; SNIUAA, single NSAID-induced urticaria/angioedema or anaphylaxis; SPTs, skin prick tests; STs, skin tests. ∗See text. ^# or with another potent COX-1 inhibitor (e.g., ibuprofen or ketoprofen) if ASA is the suspected drug

Fig. 2

Diagnostic algorithm for patients with histories of delayed reactions to non-steroidal anti-inflammatory drugs AGEP, acute generalized exanthematous pustulosis; DC, drug challenge; dIDT, delayed-reading (after 24–48 h) intradermal test; DIHS, drug-induced hypersensitivity syndrome; dSPT, delayed-reading (after 24–48 h) skin prick test; DRESS, drug reaction with eosinophilia and systemic symptoms; FDE, fixed drug eruption; GBFDE, generalized bullous fixed drug eruption; MDE, morbilliform drug eruption; NSAID, non-steroidal anti-inflammatory drug; SDRIFE, symmetrical drug-related intertriginous and flexural exanthema; SJS, Stevens-Johnson syndrome; TEN, toxic epidermal necrolysis. ∗See Table 4