Drug-Induced Severe Cutaneous Adverse Reactions: Insights Into Clinical Presentation, Immunopathogenesis, Diagnostic Methods, Treatment, and Pharmacogenomics

Therdpong Tempark; Shobana John; Pawinee Rerknimitr; Patompong Satapornpong; Chonlaphat Sukasem

doi:10.3389/fphar.2022.832048

Drug-Induced Severe Cutaneous Adverse Reactions: Insights Into Clinical Presentation, Immunopathogenesis, Diagnostic Methods, Treatment, and Pharmacogenomics

Front Pharmacol. 2022 Apr 20:13:832048. doi: 10.3389/fphar.2022.832048. eCollection 2022.

Authors

Therdpong Tempark^{1

2}, Shobana John^{3

4}, Pawinee Rerknimitr^{5

6}, Patompong Satapornpong^{7

8}, Chonlaphat Sukasem^{2

3

4

5

9

10}

Affiliations

¹ Division of Dermatology, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
² The Pediatrics-Thai Severe Cutaneous Adverse Drug Reaction (Ped-Thai-SCAR) Research Group, Bangkok, Thailand.
³ Division of Pharmacogenomics and Personalized Medicine, Department of Pathology, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
⁴ Laboratory for Pharmacogenomics, Somdech Phra Debaratana Medical Center (SDMC), Ramathibodi Hospital, Bangkok, Thailand.
⁵ The Thai Severe Cutaneous Adverse Drug Reaction (Thai-SCAR) Research Group, Bangkok, Thailand.
⁶ Division of Dermatology, Department of Medicine, Faculty of Medicine, Skin, and Allergy Research Unit, Chulalongkorn University, Bangkok, Thailand.
⁷ Division of General Pharmacy Practice, Department of Pharmaceutical Care, College of Pharmacy, Rangsit University, Pathum Thani, Thailand.
⁸ Excellence Pharmacogenomics and Precision Medicine Centre, College of Pharmacy, Rangsit University, Pathum Thani, Thailand.
⁹ Pharmacogenomics and Precision Medicine, The Preventive Genomics & Family Check-up Services Center, Bumrungrad International Hospital, Bangkok, Thailand.
¹⁰ MRC Centre for Drug Safety Science, Department of Pharmacology and Therapeutics, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, United Kingdom.

Abstract

SCARs are rare and life-threatening hypersensitivity reactions. In general, the increased duration of hospital stays and the associated cost burden are common issues, and in the worst-case scenario, they can result in mortality. SCARs are delayed T cell-mediated hypersensitivity reactions. Recovery can take from 2 weeks to many months after dechallenging the culprit drugs. Genetic polymorphism of the HLA genes may change the selection and presentation of antigens, allowing toxic drug metabolites to initiate immunological reactions. However, each SCARs has a different onset latency period, clinical features, or morphological pattern. This explains that, other than HLA mutations, other immuno-pathogenesis may be involved in drug-induced severe cutaneous reactions. This review will discuss the clinical morphology of various SCARs, various immune pathogenesis models, diagnostic criteria, treatments, the association of various drug-induced reactions and susceptible alleles in different populations, and the successful implementation of pharmacogenomics in Thailand for the prevention of SCARs.

Keywords: PGx implementation; SCARs; Thailand; immunopathogenesis of SCARs; pharmacogenomics; risk factors.

Publication types

Review