NSAID or nonsteroidal anti-inflammatory drug hypersensitivity reactions encompasses a broad range of allergic or allergic-like symptoms that occur within minutes to hours after ingesting aspirin or other NSAID nonsteroidal anti-inflammatory drugs. Hypersensitivity drug reactions differ from drug toxicity reactions in that drug toxicity reactions result from the pharmacological action of a drug, are dose-related, and can occur in any treated individual (see nonsteroidal anti-inflammatory drugs section on adverse reactions for NSAID-induced toxic reactions); hypersensitivity reactions are idiosyncratic reactions to a drug.[1] Although the term NSAID was introduced to signal a comparatively low risk of adverse effects,[2] NSAIDs do evoke a broad range of hypersensitivity syndromes. These syndromes have recently been classified by the European Academy of Allergy and Clinical Immunology Task Force on NSAIDs Hypersensitivity.[3]
Classification
The classification organizes the hypersensitivity reactions to NSAIDs into the following five categories:
NSAIDs-exacerbated respiratory disease (NERD) is an acute (immediate to several hours) exacerbation of bronchoconstriction and other symptoms of asthma (see aspirin-induced asthma) in individuals with a history of asthma and/or nasal congestion, rhinorrhea or other symptoms of rhinitis and sinusitis in individuals with a history of rhinosinusitis after ingestion of various NSAIDs, particularly those that act by inhibiting the COX-1 enzyme. NERD does not appear to be due to a true allergic reaction to NSAIDs but rather at least in part to the more direct effects of these drugs to promote the production and/or release of certain mediators of allergy. That is, inhibition of cellular COX activity deprives tissues of its anti-inflammatory product(s), particularly prostaglandin E2 while concurrently shuttling its substrate, arachidonic acid, into other metabolizing enzymes, particularly 5-lipoxygenase (ALOX5) to overproduce pro-inflammatory leukotriene and 5-Hydroxyicosatetraenoic acid metabolites and 15-lipoxygenase (ALOX15) to overproduce pro-inflammatory 15-Hydroxyicosatetraenoic acid metabolites, including eoxins; the condition is also associated with a reduction in the anti-inflammatory metabolite, lipoxin A4, and increases in certain pro-allergic chemokines such as eotaxin-2 and CCL7.[4][5][6][7][8]
NSAIDs-exacerbated cutaneous disease (NECD) is an acute exacerbation of wheals and/or angioedema in individuals with a history of chronic urticaria. NECD also appears due to the non-allergic action of NSAIDs in inhibiting the production of COX anti-inflammatory metabolites while promoting the production 5-lipoxygenase and 15-lipoxygenase pro-inflammatory metabolites and the overproduction of certain pro-allergic chemokines, e.g. eotaxin-1, eotaxin-2, RANTES, and interleukin-5.[9][10]
NSAIDs-induced urticarial disease (NEUD) is the acute development of wheals and/or angioedema in individuals with no history of chronic NSAIDs-induced urticaria or related diseases. The mechanism behind NEUD is unknown but may be due to the non-allergic action of NSAIDs in promoting the production and/or release of allergy mediators.[11]
Single NSAID-induced urticarial/angioedema or anaphylaxis (SNIUAA) is the acute development of urticarial, angioedema, or anaphylaxis in response to a single type of NSAID and/or a single group of NSAIDs with a similar structure but not to other structurally unrelated NSAIDs in individuals with no history of underlying relevant chronic diseases. SNIUAA is due to a true IgE-mediated allergy reaction.[3][12]
^ abcKowalski ML, Asero R, Bavbek S, Blanca M, Blanca-Lopez N, Bochenek G, et al. (October 2013). "Classification and practical approach to the diagnosis and management of hypersensitivity to nonsteroidal anti-inflammatory drugs". Allergy. 68 (10): 1219–32. doi:10.1111/all.12260. PMID24117484. S2CID32169451.
^Claesson HE (September 2009). "On the biosynthesis and biological role of eoxins and 15-lipoxygenase-1 in airway inflammation and Hodgkin lymphoma". Prostaglandins & Other Lipid Mediators. 89 (3–4): 120–5. doi:10.1016/j.prostaglandins.2008.12.003. PMID19130894.
^Ledford DK, Wenzel SE, Lockey RF (2014). "Aspirin or other nonsteroidal inflammatory agent exacerbated asthma". The Journal of Allergy and Clinical Immunology: In Practice. 2 (6): 653–7. doi:10.1016/j.jaip.2014.09.009. PMID25439353.
^Choi JH, Kim MA, Park HS (February 2014). "An update on the pathogenesis of the upper airways in aspirin-exacerbated respiratory disease". Current Opinion in Allergy and Clinical Immunology. 14 (1): 1–6. doi:10.1097/ACI.0000000000000021. PMID24300420. S2CID205433452.
^Mullol J, Picado C (May 2013). "Rhinosinusitis and nasal polyps in aspirin-exacerbated respiratory disease". Immunology and Allergy Clinics of North America. 33 (2): 163–76. doi:10.1016/j.iac.2012.11.002. PMID23639706.
^Simon RA, Dazy KM, Waldram JD (March 2015). "Update on aspirin desensitization for chronic rhinosinusitis with polyps in aspirin-exacerbated respiratory disease (AERD)". Current Allergy and Asthma Reports. 15 (3): 508. doi:10.1007/s11882-014-0508-7. PMID25663486. S2CID23740152.
^Himly M, Jahn-Schmid B, Pittertschatscher K, Bohle B, Grubmayr K, Ferreira F, Ebner H, Ebner C (April 2003). "IgE-mediated immediate-type hypersensitivity to the pyrazolone drug propyphenazone". The Journal of Allergy and Clinical Immunology. 111 (4): 882–8. doi:10.1067/mai.2003.163. PMID12704373.
^Rozieres A, Vocanson M, Saïd BB, Nosbaum A, Nicolas JF (August 2009). "Role of T cells in nonimmediate allergic drug reactions". Current Opinion in Allergy and Clinical Immunology. 9 (4): 305–10. doi:10.1097/ACI.0b013e32832d565c. PMID19474707. S2CID20616655.
