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      Drug hypersensitivity reactions in Asia: regional issues and challenges

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          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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          Clinical classification of cases of toxic epidermal necrolysis, Stevens-Johnson syndrome, and erythema multiforme.

          To conduct a prospective case-control study about causative factors of severe bullous erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis, we needed to define criteria for classifying the cases and standardize the collection of data so that cases could be reliably diagnosed according to this classification. Based on review of case histories and photographs of patients, a group of experts proposed a classification based on the pattern of erythema multiforme-like lesions (categorized as typical targets, raised or flat atypical targets, and purpuric macules) and on the extent of epidermal detachment. An atlas illustrating this classification that included photographs and schematic drawings was developed. We compared the evaluations of 28 cases by four nonphysicians relying on the atlas with the evaluations of the same cases by five experts not using the atlas to determine the usefulness of this atlas for classifying cases according to our nosologic schema. The following consensus classification in five categories was proposed: bullous erythema multiforme, detachment below 10% of the body surface area plus localized "typical targets" or "raised atypical targets"; Stevens-Johnson syndrome, detachment below 10% of the body surface area plus widespread erythematous or purpuric macules or flat atypical targets; overlap Stevens-Johnson syndrome-toxic epidermal necrolysis, detachment between 10% and 30% of the body surface area plus widespread purpuric macules or flat atypical targets; toxic epidermal necrolysis with spots, detachment above 30% of the body surface area plus widespread purpuric macules or flat atypical targets; and toxic epidermal necrolysis without spots, detachment above 10% of the body surface area with large epidermal sheets and without any purpuric macule or target. Using the atlas, the nonexperts showed excellent agreement with the experts. This study suggests that an illustrated atlas is a useful tool for standardizing the diagnosis of acute severe bullous disorders that are attributed to drugs or infectious agents. Whether the five categories proposed represent distinct etiopathologic entities will require further epidemiologic and laboratory investigations.
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            Evaluation and Management of Penicillin Allergy

            β-Lactam antibiotics are among the safest and most effective antibiotics. Many patients report allergies to these drugs that limit their use, resulting in the use of broad-spectrum antibiotics that increase the risk for antimicrobial resistance and adverse events.
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              Antibiotic allergy

              Antibiotics are the commonest cause of life-threatening immune-mediated drug reactions that are considered off-target, including anaphylaxis, and organ-specific and severe cutaneous adverse reactions. However, many antibiotic reactions documented as allergies were unknown or not remembered by the patient, cutaneous reactions unrelated to drug hypersensitivity, drug-infection interactions, or drug intolerances. Although such reactions pose negligible risk to patients, they currently represent a global threat to public health. Antibiotic allergy labels result in displacement of first-line therapies for antibiotic prophylaxis and treatment. A penicillin allergy label, in particular, is associated with increased use of broad-spectrum and non-β-lactam antibiotics, which results in increased adverse events and antibiotic resistance. Most patients labelled as allergic to penicillins are not allergic when appropriately stratified for risk, tested, and re-challenged. Given the public health importance of penicillin allergy, this Review provides a global update on antibiotic allergy epidemiology, classification, mechanisms, and management.
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                Author and article information

                Journal
                Asia Pac Allergy
                Asia Pac Allergy
                APA
                Asia Pacific Allergy
                Asia Pacific Association of Allergy, Asthma and Clinical Immunology
                2233-8276
                2233-8268
                January 2020
                30 January 2020
                : 10
                : 1
                : e8
                Affiliations
                [1 ]Department of Rheumatology, Allergy and Immunology, Tan Tock Seng Hospital, Singapore.
                [2 ]Department of Immunology, Pathwest and Sir Charles Gairdner Hospital, Medical School, University of Western Australia, Perth, Australia.
                [3 ]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.
                [4 ]Division of Allergy and Clinical Immunology, Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea.
                [5 ]Division of Rheumatology and Clinical Immunology, Department of Medicine, Queen Mary Hospital, University of Hong Kong, Hong Kong.
                [6 ]Hospital Kuala Lumpur, Kuala Lumpur, Malaysia.
                [7 ]Faculty of Medicine and Health, The University of Sydney, Division of Medicine, Nepean Hospital, Sydney, Australia.
                [8 ]Department of Respiratory Medicine, Box Hill Hospital, Eastern Health, Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, Australia.
                [9 ]Department of Internal Medicine, Korea University Medical Center Anam Hospital, Seoul, Korea.
                [10 ]Allergy Center of Mie National Hospital, Tsu, Japan.
                [11 ]Department of Internal Medicine, Faculty of Medicine Universitas Indonesia - Cipto Mangunkusumo Hospital, Jakarta, Indonesia.
                [12 ]School of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
                [13 ]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.
                [14 ]Division of Respiratory Medicine and Allergology, Department of Medicine, Teikyo University School of Medicine, Tokyo, Japan.
                [15 ]Allergy, Immunology and Rheumatology Division, Department of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
                [16 ]Department of Pediatrics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Ratchathewi, Bangkok, Thailand.
                [17 ]Department of Paediatrics, The Chinese University of Hong Kong, Hong Kong.
                [18 ]Department of Internal Medicine, Hanyang University College of Medicine, Seoul, Korea.
                [19 ]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..
                [20 ]Allergy & Immunology Centre, Pantai Hospital, Kuala Lumpur, Malaysia.
                [21 ]Allergy Center of Mie National Hospital, Tsu, Japan.
                [22 ]Eastern Health, Melbourne; Monash University, Melbourne, Australia.
                [23 ]Division of Rheumatology, Immunology, and Allergy, Department of Medicine, Mastocytosis Center, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
                [24 ]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..
                [25 ]Graduate Institute of Medical Sciences, China Medical University, Taichung, Taiwan.
                [26 ]Department of Pediatrics, Nippon Medical School, Tokyo, Japan.
                Author notes
                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, bernard_thong@ 123456ttsh.com.sg
                Author information
                https://orcid.org/0000-0002-6338-8482
                https://orcid.org/0000-0001-8881-9990
                https://orcid.org/0000-0002-2317-4201
                https://orcid.org/0000-0003-3157-0447
                https://orcid.org/0000-0002-9155-9162
                https://orcid.org/0000-0001-7760-3238
                https://orcid.org/0000-0002-3482-5663
                https://orcid.org/0000-0002-3450-0877
                https://orcid.org/0000-0001-5147-6306
                https://orcid.org/0000-0003-3557-8761
                https://orcid.org/0000-0001-8748-8544
                https://orcid.org/0000-0002-6744-1682
                https://orcid.org/0000-0003-1681-0959
                https://orcid.org/0000-0001-6167-0591
                https://orcid.org/0000-0002-6630-2795
                https://orcid.org/0000-0003-0839-7682
                https://orcid.org/0000-0002-6469-1926
                https://orcid.org/0000-0002-4645-4863
                https://orcid.org/0000-0002-0910-9884
                https://orcid.org/0000-0002-6304-0494
                https://orcid.org/0000-0002-9196-9436
                https://orcid.org/0000-0003-0925-6566
                https://orcid.org/0000-0001-6451-0163
                https://orcid.org/0000-0001-7827-7964
                https://orcid.org/0000-0003-4540-9822
                https://orcid.org/0000-0002-3091-7237
                Article
                10.5415/apallergy.2020.10.e8
                7016324
                32099830
                e1485825-5b79-41f3-a580-a79da82d2d48
                Copyright © 2020. Asia Pacific Association of Allergy, Asthma and Clinical Immunology.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( https://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.

                History
                : 27 January 2020
                : 27 January 2020
                Categories
                Current Review

                Immunology
                anaphylaxis,asthma,drugs,hypersensitivity, pharmacogenetics
                Immunology
                anaphylaxis, asthma, drugs, hypersensitivity, pharmacogenetics

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