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


Blanca-López N1*, Cornejo-García JA2,3*, Pérez-Alzate D1, Pérez-Sánchez N3, Plaza-Serón MC2, Doña I3, Torres MJ3, Canto G1, Kidon M4,5, 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
4Pediatric Allergy Clinic, Safra Children's Hospital, Chaim Sheba Medical Center, Tel Hashomer, Israel
5Faculty of Pediatric Medicine, Sackler Medical School, Tel Aviv University, Tel Aviv, Israel
*Both authors contributed equally to the manuscript.

J Investig Allergol Clin Immunol 2015; Vol. 25(6): 385-395



Nonsteroidal anti-inflammatory drugs (NSAIDs) are used throughout the world to treat pain and inflammation; however, they can trigger several types of drug hypersensitivity reactions (DHRs) in all age groups. Although most such reactions occur through activation of the leukotriene pathway without specific immunological recognition (cross-intolerance), a significant number of DHRs to NSAIDs are due to immunological mechanisms (selective reactions [SRs]). SRs are thought to be induced by specific IgE antibodies or by T cells. In this manuscript, we focus on SRs, which are of great concern in children and adolescents and comprise a heterogeneous set of clinical pictures ranging from mild entities such as urticaria/angioedema to potentially life-threatening conditions such as Stevens-Johnson syndrome/toxic epidermal necrolysis.
Paracetamol and ibuprofen are the most frequent elicitors of IgE-mediated SRs, although pyrazolones have also been implicated. T cell– mediated reactions are infrequent in children but have been associated with ibuprofen, naproxen, and dipyrone.
In this review, we analyze the available literature on SRs in children and adolescents, with emphasis on epidemiological data, mechanisms, and drugs involved, as well as on diagnostic procedures.

Key words: Drug hypersensitivity reactions. NSAIDs. Single NSAID–induced urticaria/angioedema or anaphylaxis. Single NSAID–induced delayed reactions.