Genetics of Severe Cutaneous Adverse Reactions

Shang-Chen Yang; Chun-Bing Chen; Mao-Ying Lin; Zhi-Yang Zhang; Xiao-Yan Jia; Ming Huang; Ya-Fen Zou; Wen-Hung Chung

doi:10.3389/fmed.2021.652091

Genetics of Severe Cutaneous Adverse Reactions

Front Med (Lausanne). 2021 Jul 15:8:652091. doi: 10.3389/fmed.2021.652091. eCollection 2021.

Authors

Shang-Chen Yang¹, Chun-Bing Chen^{1

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7}, Mao-Ying Lin¹, Zhi-Yang Zhang¹, Xiao-Yan Jia⁸, Ming Huang⁸, Ya-Fen Zou⁸, Wen-Hung Chung^{1

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Affiliations

¹ Department of Dermatology, Xiamen Chang Gung Allergology Consortium, Xiamen Chang Gung Hospital, Xiamen, China.
² Department of Dermatology, Drug Hypersensitivity Clinical and Research Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
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 Immune-Oncology Center of Excellence, Chang Gung Memorial Hospital, Linkou, Taiwan.
⁸ Department of Neurology, Xiamen Chang Gung Hospital, Xiamen, China.
⁹ Department of Dermatology, Beijing Tsinghua Chang Gung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, China.
¹⁰ Department of Dermatology, Ruijin Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.
¹¹ Genomic Medicine Core Laboratory, Chang Gung Memorial Hospital, Linkou, Taiwan.

Abstract

Severe cutaneous adverse reactions (SCARs) including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug rash with eosinophilia and systemic symptoms (DRESS) are T cells-mediated life-threatening immune reactions, most commonly induced by drug. The last decade has seen significant progress in SCARs research. Recent studies have unveiled the pathogenesis of SCARs involved in susceptible genes, including human leukocyte antigens (HLA) and drugs-T cell receptor (TCR) interaction that may trigger T cell activation with downstream immune signaling of cytokines/chemokines and specific cytotoxic proteins releases. Advances in identification of multiple genetic alleles associated with specific drugs related SCARS in different populations is an important breakthrough in recent years for prevention of SCARs. This article summarized the findings on genetic factors related to SJS/TEN, especially for HLA.

Keywords: Stevens–Johnson syndrome; genetic screen; pharmacogenomic; severe cutaneous adverse drug reactions; toxic epidermal necrolysis.

Publication types

Review