Pharmacogenetic Testing for Prevention of Severe Cutaneous Adverse Drug Reactions

Chih-Jung Chang; Chun-Bing Chen; Shuen-Iu Hung; Chao Ji; Wen-Hung Chung

doi:10.3389/fphar.2020.00969

Pharmacogenetic Testing for Prevention of Severe Cutaneous Adverse Drug Reactions

Front Pharmacol. 2020 Jul 2:11:969. doi: 10.3389/fphar.2020.00969. eCollection 2020.

Authors

Chih-Jung Chang^{1

2}, Chun-Bing Chen^{1

2

3

4

5

6}, Shuen-Iu Hung^{1

3}, Chao Ji⁷, Wen-Hung Chung^{1

2

3

4

5

8

9}

Affiliations

¹ Department of Dermatology and Drug Hypersensitivity Clinical and Research Center, Chang Gung Memorial Hospital, Linkou, Taipei and Keelung, Taiwan.
² Central Research Laboratory, Department of Dermatology and Xiamen Chang Gung Allergology Consortium, Xiamen Chang Gung Hospital, School of Medicine, Huaqiao University, Xiamen, China.
³ Cancer Vaccine and Immune Cell Therapy Core Laboratory, Department of Medical Research, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
⁴ College of Medicine, Chang Gung University, Taoyuan, Taiwan.
⁵ Whole-Genome Research Core Laboratory of Human Diseases, Chang Gung Memorial Hospital, Keelung, Taiwan.
⁶ Graduate Institute of Clinical Medical Sciences, Chang Gung University, Taoyuan, Taiwan.
⁷ Department of Dermatology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China.
⁸ Department of Dermatology, Beijing Tsinghua Chang Gung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, China.
⁹ School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

Abstract

Severe cutaneous adverse reactions (SCAR), such as Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug rash with eosinophilia and systemic symptoms (DRESS), are idiosyncratic and unpredictable drug-hypersensitivity reactions with a high-mortality rate ranging from 10% to over 30%, thus causing a major burden on the healthcare system. Recent pharmacogenomic studies have revealed strong associations between SCAR and the genes encoding human-leukocyte antigens (HLAs) or drug-metabolizing enzymes. Some of pharmacogenetic markers have been successfully applied in clinical practice to protect patients from SCAR, such as HLA-B*15:02 and HLA-A*31:01 for new users of carbamazepine, HLA-B*58:01 for allopurinol, and HLA-B*57:01 for abacavir. This article aims to update the current knowledge in the field of pharmacogenomics of drug hypersensitivities or SCAR, and its implementation in the clinical practice.

Keywords: T cell receptor; drug hypersensitivity; human-leukocyte antigen; pharmacogenetics; severe cutaneous adverse reactions.

Publication types

Review