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Immediate Reactions to More Than 1 NSAID Must Not Be Considered Cross-Hypersensitivity Unless Tolerance to ASA Is Verified

Pérez-Alzate D1*, Cornejo-García JA2,3*, Pérez-Sánchez N2, Andreu I4, García-Moral A5, Agúndez JA6, Bartra J5, Doña I2, Torres MJ2, Blanca M2, Blanca-López N1, Canto G1

1Allergy Service, Infanta Leonor University Hospital, Madrid, Spain
2Allergy Unit, Malaga Regional University Hospital-IBIMA, UMA, Málaga, Spain
3Research Laboratory, Malaga Regional University Hospital-IBIMA, UMA, Málaga, Spain
4Chemical Technology Institute, UPV-CSIC, Polytechnic University of Valencia, Valencia, Spain
5Allergy Unit, Pneumology and Allergy Service, Clinic Hospital, Barcelona, Spain
6Department of Pharmacology, University of Extremadura, Cáceres, Spain
*Both authors contributed equally to this manuscript.

J Investig Allergol Clin Immunol 2017; Vol 27(1) : 32-39
doi: 10.18176/jiaci.0080

Background: Individuals who develop drug hypersensitivity reactions (DHRs) to chemically unrelated nonsteroidal anti-inflammatory drugs (NSAIDs) are considered cross-hypersensitive. The hallmark for this classification is that the patient presents a reaction after intake of or challenge with acetylsalicylic acid (ASA). Whether patients react to 2 or more NSAIDs while tolerating ASA remains to be studied (selective reactions, SRs).
Objective: To identify patients with SRs to 2 or more NSAIDs including strong COX-1 inhibitors.
Methods: Patients who attended the Allergy Service of Hospital Infanta Leonor, Madrid, Spain with DHRs to NSAIDs between January 2011 and December 2014 were evaluated. Those with 2 or more immediate reactions occurring in less than 1 hour after intake were included. After confirming tolerance to ASA, the selectivity of the response to 2 or more NSAIDs was demonstrated by in vivo and/or in vitro testing or by controlled administration.
Results: From a total of 203 patients with immediate DHRs to NSAIDs, 16 (7.9%) met the inclusion criteria. The patients presented a total of 68 anaphylactic or cutaneous reactions (mean [SD], 4.2 [2.1]). Most reactions were to ibuprofen and other arylpropionic acid derivatives and to metamizole. Two different NSAIDs were involved in 11 patients and 3 in 5 patients.
Conclusions: Patients with NSAID-induced anaphylaxis or urticaria/angioedema should not be considered cross-hypersensitive unless tolerance to ASA is verified.

Key words: NSAID-hypersensitivity, Immediate reactions, Cross-hypersensitivity, Selective reactions