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Biomarkers in Drug Hypersensitivity BIOMARKERS IN DRUG HYPERSENSITIVITY EDITED BY : José A. G. Agúndez, Silvia Selinski, Emanuela Corsini, Klaus Golka and Elena García-Martín PUBLISHED IN : Frontiers in Pharmacology Frontiers Copyright Statement About Frontiers © Copyright 2007-2017 Frontiers Media SA. All rights reserved. Frontiers is more than just an open-access publisher of scholarly articles: it is a pioneering All content included on this site, approach to the world of academia, radically improving the way scholarly research such as text, graphics, logos, button icons, images, video/audio clips, is managed. The grand vision of Frontiers is a world where all people have an equal downloads, data compilations and software, is the property of or is opportunity to seek, share and generate knowledge. 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All copyright, and all rights therein, Frontiers Research Topics are very popular trademarks of the Frontiers Journals Series: are protected by national and international copyright laws. they are collections of at least ten articles, all centered on a particular subject. With their The above represents a summary unique mix of varied contributions from Original Research to Review Articles, Frontiers only. For the full conditions see the Research Topics unify the most influential researchers, the latest key findings and historical Conditions for Authors and the Conditions for Website Use. advances in a hot research area! Find out more on how to host your own Frontiers ISSN 1664-8714 Research Topic or contribute to one as an author by contacting the Frontiers Editorial ISBN 978-2-88945-226-2 DOI 10.3389/978-2-88945-226-2 Office:[email protected] Frontiers in Pharmacology 1 July 2017 | Biomarkers in Drug Hypersensitivity BIOMARKERS IN DRUG HYPERSENSITIVITY Topic Editors: José A. G. Agúndez, University of Extremadura, Spain Silvia Selinski, Leibniz Research Centre for Working Environment and Human Factors at TU Dortmund (IfADo), Germany Emanuela Corsini, Università degli Studi di Milano, Italy Klaus Golka, Leibniz Research Centre for Working Environment and Human Factors at TU Dortmund (IfADo), Germany Elena García-Martín, University of Extremadura, Spain Biomarkers, especially those based on pharmacogenomics testing, have proved to be extremely useful for type A adverse drug reactions. Clinical practice guidelines based on biomarker testing are presently being developed and updated for type A adverse drug reactions. In contrast, little attention has been paid to the potential use of biomarkers in type B adverse reactions, charac- terized by the occurrence of reactions not directly related to the pharmacological properties of the drug. Drug-induced hypersensitivity belongs to those type B reactions. Drug-induced hypersensitivity reactions involve complex mechanisms that include, among oth- ers, the metabolic activation and haptenization of drug metabolites. Hence, factors that influence the pharmacokinetics of drug and metabolites may contribute to the development of some drug-induced hypersensitivity reactions. This implies that processes such as ADME (absorp- tion, distribution, metabolism and excretion) that are typically involved in type A adverse drug reactions, may have a role in hypersensitivity reactions too. In addition to metabolic activation, several signal transduction pathways participate and modulate the development and the clinical presentation of drug hypersensitivity. The diverse mechanisms underlying such drug-hypersensitivity reactions lead to four major groups of reactions according to the Gell and Coombs classification: immediate, cytotoxic, immune complex and delayed. The enormous complexity of drug-hypersensitivity reactions is a consequence of the variety of mechanisms involved, which may be related, among others, to drug metabolism, generation of antigenic signals, stimulation and maturation of dendritic cells, presentation of haptens and mechanisms of cytotoxicity. In addition, a plethora of possible clinical presentations exists, including urticaria, angioedema, anaphylaxis, cytopenias, nephritis, serum sickness, vasculitis, contact dermatitis, drug rash, eosinophilia and systemic symptoms, Stevens–Johnson syndrome, toxic epidermal necrolysis and acute generalized exanthematous pustulosis. The rapid progress in the field in recent years indicates that the combination of sev- eral disciplines is essential to understand the mechanisms involved in this particular, and not completely understood, type of adverse drug reactions. Frontiers in Pharmacology 2 July 2017 | Biomarkers in Drug Hypersensitivity The objective of this Research Topic is to present insights obtained from both basic and clinical scientists, which may include studies related to the identification, validation, refinement and clinical implementation of biomarkers for drug-induced hypersensitivity. The Topic aims to include recent findings related, but not limited to, potential phenomic, genomic, proteomic, metabolomic and signal transduction biomarkers. These biomarkers could eventually be used in clinical practice and/or these might contribute, as a proof of concept, to our understanding of the complex events leading to drug hypersensitivity reactions. In addition the Topic will cover recent developments and methodological advances in the diagnosis, prevention and therapeutic management of drug-induced hypersensitivity. Citation: Agúndez, J. A. G., Selinski, S., Corsini, E., Golka, K., García-Martín, E., eds. (2017). Bio- markers in Drug Hypersensitivity. Lausanne: Frontiers Media. doi: 10.3389/978-2-88945-226-2 Frontiers in Pharmacology 3 July 2017 | Biomarkers in Drug Hypersensitivity Table of Contents 06 Editorial: Biomarkers in Drug Hypersensitivity José A. G. Agúndez, Silvia Selinski, Emanuela Corsini, Klaus Golka and Elena García-Martín Section 1: Genetic testing 09 Pharmacogenetics and Predictive Testing of Drug Hypersensitivity Reactions Ruwen Böhm and Ingolf Cascorbi 20 HLA-B*58:01 for Allopurinol-Induced Cutaneous Adverse Drug Reactions: Implication for Clinical Interpretation in Thailand Chonlaphat Sukasem, Thawinee Jantararoungtong, Parnrat Kuntawong, Apichaya Puangpetch, Napatrupron Koomdee, Patompong Satapornpong, Patcharin Supapsophon, Jettanong Klaewsongkram and Ticha Rerkpattanapipat 28 MinION: A Novel Tool for Predicting Drug Hypersensitivity? Eng Wee Chua and Pei Yuen Ng Section 2: Phenotyping 35 Asthma and Rhinitis Induced by Selective Immediate Reactions to Paracetamol and Non-steroidal Anti-inflammatory Drugs in Aspirin Tolerant Subjects Diana Pérez-Alzate, Natalia Blanca-López, Inmaculada Doña, José A. Agúndez, Elena García-Martín, José A. Cornejo-García, James R. Perkins, Miguel Blanca and Gabriela Canto 41 Biomarkers in DILI: One More Step Forward Mercedes Robles-Díaz, Inmaculada Medina-Caliz,
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