Current understanding of genetic associations with delayed hypersensitivity reactions induced by antibiotics and anti-osteoporotic drugs

Chih-Hsuan Wung; Chuang-Wei Wang; Kuo-Chu Lai; Chun-Bing Chen; Wei-Ti Chen; Shuen-Iu Hung; Wen-Hung Chung; Taiwan Severe Cutaneous Adverse Reaction Consortium

doi:10.3389/fphar.2023.1183491

Current understanding of genetic associations with delayed hypersensitivity reactions induced by antibiotics and anti-osteoporotic drugs

Front Pharmacol. 2023 Apr 26:14:1183491. doi: 10.3389/fphar.2023.1183491. eCollection 2023.

Authors

Chih-Hsuan Wung¹, Chuang-Wei Wang^{2

3

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5}, Kuo-Chu Lai^{6

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8}, Chun-Bing Chen^{2

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12}, Wei-Ti Chen^{2

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9}, Shuen-Iu Hung^{2

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13}, Wen-Hung Chung^{2

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4

5

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16}; Taiwan Severe Cutaneous Adverse Reaction Consortium

Affiliations

¹ Chang Gung Memorial Hospital, Taoyuan, Taiwan.
² Department of Dermatology, Drug Hypersensitivity Clinical and Research Center, Chang Gung Memorial Hospital, Taipei and Keelung, Taiwan.
³ Cancer Vaccine and Immune Cell Therapy Core Laboratory, Department of Medical Research, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
⁴ Chang Gung Immunology Consortium, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan.
⁵ Department of Dermatology, Xiamen Chang Gung Hospital, Xiamen, China.
⁶ Department of Physiology and Pharmacology, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
⁷ Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
⁸ Division of Hematology and Oncology, Department of Internal Medicine, New Taipei Municipal TuCheng Hospital (Built and Operated by Chang Gung Medical Foundation), New Taipei City, Taiwan.
⁹ College of Medicine, Chang Gung University, Taoyuan, Taiwan.
¹⁰ Whole-Genome Research Core Laboratory of Human Diseases, Chang Gung Memorial Hospital, Keelung, Taiwan.
¹¹ Immune-Oncology Center of Excellence, Chang Gung Memorial Hospital, Linkou, Taiwan.
¹² Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
¹³ Institute of Pharmacology, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.
¹⁴ Department of Dermatology, Beijing Tsinghua Chang Gung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, China.
¹⁵ Department of Dermatology, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
¹⁶ Genomic Medicine Core Laboratory, Chang Gung Memorial Hospital, Linkou, Taiwan.

Abstract

Drug-induced delayed hypersensitivity reactions (DHRs) is still a clinical and healthcare burden in every country. Increasing reports of DHRs have caught our attention to explore the genetic relationship, especially life-threatening severe cutaneous adverse drug reactions (SCARs), including acute generalized exanthematous pustulosis (AGEP), drug reactions with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN). In recent years, many studies have investigated the immune mechanism and genetic markers of DHRs. Besides, several studies have stated the associations between antibiotics-as well as anti-osteoporotic drugs (AOD)-induced SCARs and specific human leukocyte antigens (HLA) alleles. Strong associations between drugs and HLA alleles such as co-trimoxazole-induced DRESS and HLA-B*13:01 (Odds ratio (OR) = 45), dapsone-DRESS and HLA-B*13:01 (OR = 122.1), vancomycin-DRESS and HLA-A*32:01 (OR = 403), clindamycin-DHRs and HLA-B*15:27 (OR = 55.6), and strontium ranelate (SR)-SJS/TEN and HLA-A*33:03 (OR = 25.97) are listed. We summarized the immune mechanism of SCARs, update the latest knowledge of pharmacogenomics of antibiotics- and AOD-induced SCARs, and indicate the potential clinical use of these genetic markers for SCARs prevention in this mini review article.

Keywords: Stevens-Johnson syndrome; delayed hypersensitivity reactions; drug reactions with eosinophilia and systemic symptoms; human leukocyte antigens; toxic epidermal necrosis.

Publication types

Review

Grants and funding

This work was supported by grants from the National Science and Technology Council, Taiwan (NSTC 109-2320-B-182A-008 -MY3, 110-2320-B-182A-014-MY3, 111-2314-B-182A-113-MY3, and 111-2326-B-182A-003-), and Chang Gung Memorial Hospital (CIRPG3M0061-2, CLRPG3N0021 and CMRPG3M1081). Additionally, the Figure 1 is created with BioRender.com.