apa Asia Pacific Allergy Asia Pac Allergy 2233-8276 2233-8268 Asia Pacific Association of Allergy, Asthma and Clinical Immunology 10.5415/apallergy.2020.10.e8 apa-10-e8 Current Review Drug hypersensitivity reactions in Asia: regional issues and challenges ThongBernard Yu-Hor 1 * LucasMichaela 2 KangHye-Ryun 3 ChangYoon-Seok 4 LiPhilip Hei 5 TangMin Moon 6 YunJames 7 FokJie Shen 8 KimByung-Keun 9 NagaoMizuho 10 RengganisIris 11 TsaiYi-Giien 12 ChungWen-Hung 13 YamaguchiMasao 14 RerkpattanapipatTicha 15 KamchaisatianWasu 16 LeungTing Fan 17 YoonHo Joo 18 ZhangLuo 19 LatiffAmir Hamzah Abdul 20 FujisawaTakao 21 ThienFrancis 22 CastellsMariana C. 23 DemolyPascal 24 WangJiu-Yao 25 PawankarRuby 26 Department of Rheumatology, Allergy and Immunology, Tan Tock Seng Hospital, Singapore Department of Immunology, Pathwest and Sir Charles Gairdner Hospital, Medical School, University of Western Australia, Perth, Australia Institute of Allergy and Clinical Immunology, Seoul National University Medical Research Center, Department of Internal Medicine, Seoul National University College of Medicine, Drug Safety Center, Seoul National University Hospital, Seoul, Korea Division of Allergy and Clinical Immunology, Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea Division of Rheumatology and Clinical Immunology, Department of Medicine, Queen Mary Hospital, University of Hong Kong, Hong Kong Hospital Kuala Lumpur, Kuala Lumpur, Malaysia Faculty of Medicine and Health, The University of Sydney, Division of Medicine, Nepean Hospital, Sydney, Australia Department of Respiratory Medicine, Box Hill Hospital, Eastern Health, Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, Australia Department of Internal Medicine, Korea University Medical Center Anam Hospital, Seoul, Korea Allergy Center of Mie National Hospital, Tsu, Japan Department of Internal Medicine, Faculty of Medicine Universitas Indonesia – Cipto Mangunkusumo Hospital, Jakarta, Indonesia School of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan Department of Dermatology, Drug Hypersensitivity Clinical and Research Center, Chang Gung Memorial Hospital, Keelung and Linkou Branches, College of Medicine, Chang Gung University, Taipei, Taiwan Division of Respiratory Medicine and Allergology, Department of Medicine, Teikyo University School of Medicine, Tokyo, Japan Allergy, Immunology and Rheumatology Division, Department of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand Department of Pediatrics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Ratchathewi, Bangkok, Thailand Department of Paediatrics, The Chinese University of Hong Kong, Hong Kong Department of Internal Medicine, Hanyang University College of Medicine, Seoul, Korea Department of Otolaryngology Head and Neck Surgery, Beijing TongRen Hospital, Capital Medical University, Beijing Key Laboratory of Nasal Diseases, Beijing Institute of Otolaryngology, Beijing, China Allergy & Immunology Centre, Pantai Hospital, Kuala Lumpur, Malaysia Allergy Center of Mie National Hospital, Tsu, Japan Eastern Health, Melbourne; Monash University, Melbourne, Australia Division of Rheumatology, Immunology, and Allergy, Department of Medicine, Mastocytosis Center, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA Division of Allergy, Department of Pulmonology, Hôpital Arnaud de Villeneuve, University Hospital of Montpellier, Montpellier, UPMC Univ Paris 06, UMRS 1136, Equipe – EPAR – IPLESP, Sorbonne Universités, Paris, France Graduate Institute of Medical Sciences, China Medical University, Taichung, Taiwan Department of Pediatrics, Nippon Medical School, Tokyo, Japan Correspondence to Bernard Yu-Hor Thong Department of Rheumatology, Allergy and Immunology, Tan Tock Seng Hospital, 11 Jalan Tan Tock Seng, Singapore 308433. Tel: +65-63577822 Fax: +65-63572686 E-mail: bernard_thong@ttsh.com.sg 01 2020 04 01 2020 10 1 e8 27012020 27012020 Copyright © 2020 Asia Pacific Association of Allergy, Asthma and Clinical Immunology 2020 This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. Abstract

There are geographical, regional, and ethnic differences in the phenotypes and endotypes of patients with drug hypersensitivity reactions (DHRs) in different parts of the world. In Asia, aspects of drug hypersensitivity of regional importance include IgE-mediated allergies and T-cell-mediated reactions, including severe cutaneous adverse reactions (SCARs), to beta-lactam antibiotics, antituberculous drugs, nonsteroidal anti-inflammatory drugs (NSAIDs) and radiocontrast agents. Delabeling of low-risk penicillin allergy using direct oral provocation tests without skin tests have been found to be useful where the drug plausibility of the index reaction is low. Genetic risk associations of relevance to Asia include human leucocyte antigen (HLA)-B*1502 with carbamazepine SCAR, and HLA-B*5801 with allopurinol SCAR in some Asian ethnic groups. There remains a lack of safe and accurate diagnostic tests for antituberculous drug allergy, other than relatively high-risk desensitization regimes to first-line antituberculous therapy. NSAID hypersensitivity is common among both adults and children in Asia, with regional differences in phenotype especially among adults. Low dose aspirin desensitization is an important therapeutic modality in individuals with cross-reactive NSAID hypersensitivity and coronary artery disease following percutaneous coronary intervention. Skin testing allows patients with radiocontrast media hypersensitivity to confirm the suspected agent and test for alternatives, especially when contrasted scans are needed for future monitoring of disease relapse or progression, especially cancers.

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Summary Table

Beta-lactam allergy
  · Risk stratification of the likelihood of penicillin allergy based on history and non–IgE-mediated type of clinical manifestations of the index adverse drug reaction, form the basis of safe direct oral amoxicillin/penicillin challenge for low-risk patients without the need for skin tests.
  · Delabeling and de-escalation encourage appropriate narrow-spectrum antimicrobial use, preventing the
  · Delabeling and de-escalation encourage appropriate narrow-spectrum antimicrobial use, preventing the increasing incidence of antimicrobial resistance.
Severe cutaneous adverse reactions
  · The most commonly implicated drugs in Asia are antiepileptic drugs (carbamazepine, phenytoin, lamotrigine), allopurinol and antimicrobials.
  · Although HLA-B*1502 (carbamazepine), HLA-B*5801 (allopurinol) and HLA-B*5701 (abacavir) testing prior to drug initiation may reduce the risk of severe cutaneous adverse reaction (SCAR), a recent Cochrane review found no eligible evidence on genetic testing for severe drug-induced skin rash in relation to different drugs and classes of drugs.
Antituberculous drug allergy
  · Many antituberculous drug hypersensivity reactions are SCARs.
  · Desensitization or any re-exposure is of much higher risk. Desensitization protocols involving sequential re-introduction of antituberculous drugs are commonly used given the paucity of well-validated in vitro and in vivo tests to identify the causative drug to restart during induction combination therapy.
Nonsteroidal anti-inflammatory drug hypersensitivity
  · The phenotype in children and adolescents tends to have overlapping features, with a much lower prevalence of nonsteroidal anti-inflammatory (NSAID) exacerbated respiratory disease compared to adults.
  · Low-dose aspirin desensitization (up to 100 mg/day) for coronary artery disease has been found to be effective and safe in patients with NSAID hypersensitivity.
Radiocontrast media hypersensitivity
  · Radiocontrast media (RCM) drug hypersensitivity reactions (DHR) may be allergic or nonallergic, immediate or non-immediate (delayed); nonionic and hyperosmolar agents are associated with higher risks of DHR.
  · Skin tests are increasingly useful in the management of patients with RCM DHR, especially those who may require repeat contrasted imaging.
  · Negative intradermal tests are used to select alternative RCM to prevent recurrent DHR. International guidelines suggest changing RCM within the same class of low-osmolar RCM.