The Link between HLA-B Alleles and Causative Drugs in Vietnamese Patients with Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis

Tran Thi Huyen; Pham Dinh Hoa; Trinh Minh Trang; Nguyen Ba Khanh; Tran Ngoc Que; Nguyen Hoang Phuong; Nguyen Minh Hoang; Riichiro Abe; Nguyen Van Thuong; Pham Thi Lan; Michael Tirant

doi:10.3889/oamjms.2020.4906

Authors

Tran Thi Huyen Department of Dermatology and Venereology, Hanoi Medical University, Hanoi, Vietnam; Department of Skin diseases of Women and Children, National Hospital of Dermatology and Venereology, Hanoi, Vietnam
Pham Dinh Hoa Department of Dermatology and Venereology, Hanoi Medical University, Hanoi, Vietnam; Department of Skin diseases of Women and Children, National Hospital of Dermatology and Venereology, Hanoi, Vietnam
Trinh Minh Trang Department of Skin diseases of Women and Children, National Hospital of Dermatology and Venereology, Hanoi, Vietnam
Nguyen Ba Khanh Department of Dermatology and Venereology, Hanoi Medical University, Hanoi, Vietnam
Tran Ngoc Que Department of Stem cells, National Institute of Hematology and Blood Transfusion, Hanoi, Vietnam
Nguyen Hoang Phuong Center of Allergy and Clinial Immunology, Bach Mai Hospital, Hanoi, Vietnam
Nguyen Minh Hoang Center of Allergy and Clinial Immunology, Bach Mai Hospital, Hanoi, Vietnam
Riichiro Abe Department of Dermatology, Niigata University, Japan
Nguyen Van Thuong Department of Dermatology and Venereology, Hanoi Medical University, Hanoi, Vietnam; Department of Skin diseases of Women and Children, National Hospital of Dermatology and Venereology, Hanoi, Vietnam
Pham Thi Lan Department of Dermatology and Venereology, Hanoi Medical University, Hanoi, Vietnam; Department of Skin diseases of Women and Children, National Hospital of Dermatology and Venereology, Hanoi, Vietnam
Michael Tirant Department of Dermatology and Venereology, Hanoi Medical University, Hanoi, Vietnam

DOI:

https://doi.org/10.3889/oamjms.2020.4906

Keywords:

HLA-B allele, Stevens-Johnson syndrome/toxic epidermal necrolysis, Polymerase chain reaction-sequence-specific oligonucleotide, Carbamazepine, Traditional medicine, Allopurinol

Abstract

BACKGROUND: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe cutaneous adverse drug reactions. Human leukocyte antigens (HLA) may play an important role in the pathogenesis of SJS/TEN.

AIMS: This study aims to identify HLA-B alleles in Vietnamese patients with SJS/TEN and to investigate the possible link between HLA-B alleles and causative drugs.

MATERIALS AND METHODS: Sixty patients including SJS (30 patients) and TEN (30 patients) were enrolled in a cross-sectional descriptive study at two hospitals in Hanoi, Vietnam, from July 2018 to July 2019. Clinical features and laboratory findings were noted, HLA-B alleles were analyzed by the polymerase chain reaction (PCR)-sequence-specific oligonucleotide assay and Luminex^TMMultiplex Technology.

RESULTS: The most common HLA-B allele was HLA-B*15:02 (41.7%) followed by HLA-B*58:01 (25%) and HLA-B*46:01 (15%). Of the 25 patients possessing HLA-B*15:02 allele, culprit medicines were carbamazepine (13 patients; 52%), traditional medicine (two patients; 8%), and unknown drugs (seven patients; 28%). Of the 15 patients carrying HLA-B*58:01 allele, there were 13 patients whose offending medicine was allopurinol. Of the eight patients whose culprit drug was traditional medicine, there were 6 patients (75%) carrying HLA-B*51:02. Patients who carry HLA-B*15:02 were found to have 4 times higher risk of developing carbamazepine-induced SJS/TEN as compared with the tolerant control group (OR=4.17; 95% CI=2.07–8.37; p < 0.001).

CONCLUSION: HLA-B*15:02 was the most common HLA-B allele in Vietnamese patients with SJS/TEN. In traditional medicine-induced SJS/TEN patients, HLA-B*51:02 allele might play an important role. The link between the HLA-B genotypes and causative drugs may suggest physicians to avoid risk medications for certain patients.

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