Classification of Drug Hypersensitivity into Allergic, p-i, and Pseudo-Allergic Forms

Drug hypersensitivity reactions (DHR) are clinically and functionally heterogeneous. Different subclassifications based on timing of symptom appearance or type of immune mechanism have been proposed. Here, we show that the mode of action of drugs leading to immune/inflammatory cell stimulation is a further decisive factor in understanding and managing DHR. Three mechanisms can be delineated: (a) some drugs have or gain the ability to bind covalently to proteins, form new antigens, and thus elicit immune reactions to hapten-carrier complexes (allergic/immune reaction); (b) a substantial part of immune-mediated DHR is due to a typical off-target activity of drugs on immune receptors like HLA and TCR (pharmacological interaction with immune receptors, p-i reactions); such p-i reactions are linked to severe DHR; and (c) symptoms of DHR can also appear if the drug stimulates or inhibits receptors or enzymes of inflammatory cells (pseudo-allergy). These three distinct ways of stimulaPublished online: December 14, 2016 Correspondence to: Prof. Werner J. Pichler ADR-AC GmbH Holligenstrasse 91 CH–3008 Bern (Switzerland) E-Mail Werner.pichler @ adr-ac.ch © 2016 The Author(s) Published by S. Karger AG, Basel www.karger.com/iaa Th is article is licensed under the Creative Commons AttributionNonCommercial-NoDerivatives 4.0 International License (CC BYNC-ND) (http://www.karger.com/Services/OpenAccessLicense). Usage and distribution for commercial purposes as well as any distribution of modifi ed material requires written permission. D ow nl oa de d by : 54 .7 0. 40 .1 1 11 /2 0/ 20 17 3 :4 3: 26 P M