NSAID-induced reactions: classification, prevalence, impact, and management strategies

Abstract

Nonsteroidal anti-inflammatory drugs (NSAIDs) are the leading cause of hypersensitivity drug reactions. The different chemical structures, cyclooxygenase 1 (COX-1) and/or COX-2 inhibitors, are taken at all ages and some can be easily obtained over the counter. Vasoactive inflammatory mediators like histamine and leukotriene metabolites can produce local/systemic effects. Responders can be selective (SR), IgE or T-cell mediated, or cross-intolerant (CI). Inhibition of the COX pathway is the common mechanism in CI, with the skin being the most frequent organ involved, followed by the lung and/or the nose. An important number of cases have skin and respiratory involvement, with systemic manifestations ranging from mild to severe anaphylaxis. Among SR, this is the most frequent entity, often being severe. Recent years have seen an increase in reactions involving the skin, with many cases having urticaria and/or angioedema in the absence of chronic urticaria. Aspirin, the classical drug involved, has now been replaced by other NSAIDs, with ibuprofen being the universal culprit. For CI, no in vivo/in vitro diagnostic methods exist and controlled administration is the only option unless the cases evaluated report repetitive and consistent episodes with different NSAIDs. In SR, skin testing (patch and intradermal) with 24-48 reading can be useful, mainly for delayed T-cell responses. Acetyl salicylic acid (ASA) is the test drug to establish the diagnosis and confirm/exclude CI by controlled administration. Desensitization to ASA has been extensively used in respiratory cases though it can also be applied in those cases where it is required.

Keywords: NSAIDs; hypersensitivity drug reactions; management; mechanisms.

Figure 1

(Continued)

Figure 1

Groups and chemical structures of the different NSAIDs. Notes: *Tiaramide is considered an NSAID that does not inhibit the COX enzymes. Republished with permission from Blanca-López N, Somoza-Alvarez ML, Bellon T, et al. NSAIDs hypersensitivity: questions not resolved. Curr Opin Allergy Clin Immunol. 2018;18(4):291–301. https://journals.lww.com/co-allergy/Abstract/2018/08000/NSAIDs_hypersensitivity___questions_not_resolved.4.aspx. The Creative Commons license does not apply to this content. Use of the material in any format is prohibited without written permission from the publisher, Wolters Kluwer Health, Inc. Please contact permissions@lww.com for further information. Abbreviation: NSAID, nonsteroidal anti-inflammatory drug.

Figure 2

Diagnostic algorithm for NERD. Note: Reproduced with permission from Kowalski ML, Agache I, Bavbek S, et al. Diagnosis and management of NSAID-exacerbated respiratory disease (N-ERD)-a EAACI position paper. Allergy. 2019;74(1):28–39. Abbreviations: CRS, chronic rhinisinusitis; NERD, NSAID-exacerbated respiratory disease; NP, nasal polyposis; NSAID, nonsteroidal anti-inflammatory disease.