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Hypersensitivity to Nonsteroidal Anti-inflammatory Drugs in Children and Adolescents: Cross-Intolerance Reactions


Blanca-López N1*, Cornejo-García JA2,3*, Plaza-Serón MC2, Doña I3, Torres-Jaén MJ3, Canto G1, Padilla-España L4, Kidon M5, Perkins JR2, Blanca M3

1Allergy Service, Infanta Leonor Hospital, Madrid, Spain
2Research Laboratory, IBIMA, Regional University Hospital of Malaga, UMA, Malaga, Spain
3Allergy Unit, IBIMA, Regional University Hospital of Malaga, UMA, Malaga, Spain
4Dermatology Service and Research Unit, Costa del Sol Hospital, Marbella, Spain
5Rheumatology, Immunology and Allergy Service, Department of Paediatric Medicine, Kandang Kerbau Children's Hospital, Singapore
*Both authors contributed equally to the manuscript

J Investig Allergol Clin Immunol 2015; Vol. 25(4): 259-269



Nonsteroidal anti-inflammatory drugs (NSAIDs) are used worldwide and are responsible for several types of drug hypersensitivity reactions (DHRs) in all age groups. The 2 major groups of DHRs to NSAIDs are those induced by immunological mechanisms (selective reactions) and those where inflammatory mediators are released through activation of the prostaglandin-leukotriene pathway without specific immunological recognition (cross-intolerance). In the present review, we focus on cross-intolerance reactions, which are the most frequent DHRs and are becoming a topic of major interest in children and adolescents.
Paracetamol and ibuprofen are the drugs that most frequently cause DHRs in children; other NSAIDs are responsible for reactions in adolescents. In vivo and in vitro tests are of limited diagnostic value, with some exceptions for the less common selective reactions. In cross-intolerance, the clinical history and controlled administration are in many instances the only way to establish a diagnosis and look for alternatives. The clinical history is diagnostic when consistent symptoms occur repeatedly after exposure to NSAIDs with different chemical structures.
Cutaneous and respiratory symptoms often co-occur in young children. The natural history of these reactions in children is unknown, and some patients can develop tolerance over time. Atopy remains a major risk factor for cross-intolerant reactions. The increasing interest in hypersensitivity to NSAIDs with improvements in patient phenotyping and the information provided by pharmacogenetics will improve our understanding and management of these reactions in the near future.

Key words: Hypersensitivity drug reactions. NSAIDs, cross-intolerance. Cysteinyl leukotrienes. NSAID-exacerbated respiratory disease. NSAID-exacerbated cutaneous disease. NSAID-induced urticaria/angioedema.