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In Vitro Methods for Diagnosing Nonimmediate Hypersensitivity Reactions to Drugs


C Mayorga,1 ML Sanz,2 P Gamboa,3 MC Garcia-Aviles,4 J Fernandez,5 MJ Torres,1 on behalf of the Spanish Society of Allergy and Clinical Immunology (SEAIC) Immunology and Drug Allergy Committee

1Allergy Service, Carlos Haya Hospital, Malaga, Spain
2Department of Allergology and Clinical Immunology, Navarra University Clinic, Pamplona, Spain
3Allergy Service, Basurto Hospital, Bilbao, Spain
4Allergy Service, Moncloa Hospital, Madrid, Spain
5Allergy Service, Alicante General Hospital, Alicante, Spain

J Investig Allergol Clin Immunol 2013; Vol. 23(4): 213-225



Nonimmediate drug hypersensitivity reactions (DHRs) are difficult to manage in daily clinical practice, mainly owing to their heterogeneous clinical manifestations and the lack of selective biological markers. In vitro methods are necessary to establish a diagnosis, especially given the low sensitivity of skin tests and the inherent risks of drug provocation testing. In vitro evaluation of nonimmediate DHRs must include approaches that can be applied during the different phases of the reaction. During the acute phase, monitoring markers in both skin and peripheral blood helps to discriminate between immediate and nonimmediate DHRs with cutaneous responses and to distinguish between reactions that, although they present similar clinical symptoms, are produced by different immunological mechanisms and therefore have a different treatment and prognosis. During the resolution phase, in vitro testing is used to detect the response of T cells to drug stimulation; however, this approach has certain limitations, such as the lack of validated studies assessing sensitivity. Moreover, in vitro tests indicate an immune response that is not always related to a DHR.
In this review, members of the Immunology and Drug Allergy Committee of the Spanish Society of Allergy and Clinical Immunology (SEAIC) provide an overview of the most widely used in vitro tests for evaluating nonimmediate DHRs.

Key words: Nonimmediate. Drug hypersensitivity. Diagnosis. Lymphocyte. In vitro.