Current Pharmacogenetic Perspective on Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis
Adverse drug reactions are a public health issue that draws widespread attention, especially for Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) which have high mortality and lack of efficacious treatment. Though T-cell-mediated HLA-interacted immune response has been extensively...
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doaj-dab5d18c3e474210aee68f7f509311222021-04-26T09:02:25ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122021-04-011210.3389/fphar.2021.588063588063Current Pharmacogenetic Perspective on Stevens-Johnson Syndrome and Toxic Epidermal NecrolysisLin Cheng0Lin Cheng1State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, ChinaSchool of Ophthalmology and Optometry, Eye Hospital, Wenzhou Medical University, Wenzhou, ChinaAdverse drug reactions are a public health issue that draws widespread attention, especially for Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) which have high mortality and lack of efficacious treatment. Though T-cell-mediated HLA-interacted immune response has been extensively studied, our understanding of the mechanism is far from satisfactory. This review summarizes infection (virus, bacterial, and mycoplasma infection), an environmental risk factor, as a trigger for SJS/TEN. The mutations or polymorphisms of drug metabolic enzymes, transporters, receptors, the immune system genes, and T-cell-mediated apoptosis signaling pathways that contribute to SJS/TEN are discussed and summarized. Epigenetics, metabolites, and mobilization of regulatory T cells and tolerogenic myeloid precursors are emerged directions to study SJS/TEN. Ex vivo lymphocyte transformation test has been exploited to aid in identifying the causative drugs. Critical questions on the pathogenesis of SJS/TEN underlying gene polymorphisms and T cell cytotoxicity remain: why some of the patients carrying the risky genes tolerate the drug and do not develop SJS/TEN? What makes the skin and mucous membrane so special to be targeted? Do they relate to skin/mucous expression of transporters? What is the common machinery underlying different HLA-B alleles associated with SJS/TEN and common metabolites?https://www.frontiersin.org/articles/10.3389/fphar.2021.588063/fullHLApathogenesispharmacogeneticsStevens-Johnson syndrometoxic epidermal necrolysis |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Lin Cheng Lin Cheng |
spellingShingle |
Lin Cheng Lin Cheng Current Pharmacogenetic Perspective on Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis Frontiers in Pharmacology HLA pathogenesis pharmacogenetics Stevens-Johnson syndrome toxic epidermal necrolysis |
author_facet |
Lin Cheng Lin Cheng |
author_sort |
Lin Cheng |
title |
Current Pharmacogenetic Perspective on Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis |
title_short |
Current Pharmacogenetic Perspective on Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis |
title_full |
Current Pharmacogenetic Perspective on Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis |
title_fullStr |
Current Pharmacogenetic Perspective on Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis |
title_full_unstemmed |
Current Pharmacogenetic Perspective on Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis |
title_sort |
current pharmacogenetic perspective on stevens-johnson syndrome and toxic epidermal necrolysis |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Pharmacology |
issn |
1663-9812 |
publishDate |
2021-04-01 |
description |
Adverse drug reactions are a public health issue that draws widespread attention, especially for Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) which have high mortality and lack of efficacious treatment. Though T-cell-mediated HLA-interacted immune response has been extensively studied, our understanding of the mechanism is far from satisfactory. This review summarizes infection (virus, bacterial, and mycoplasma infection), an environmental risk factor, as a trigger for SJS/TEN. The mutations or polymorphisms of drug metabolic enzymes, transporters, receptors, the immune system genes, and T-cell-mediated apoptosis signaling pathways that contribute to SJS/TEN are discussed and summarized. Epigenetics, metabolites, and mobilization of regulatory T cells and tolerogenic myeloid precursors are emerged directions to study SJS/TEN. Ex vivo lymphocyte transformation test has been exploited to aid in identifying the causative drugs. Critical questions on the pathogenesis of SJS/TEN underlying gene polymorphisms and T cell cytotoxicity remain: why some of the patients carrying the risky genes tolerate the drug and do not develop SJS/TEN? What makes the skin and mucous membrane so special to be targeted? Do they relate to skin/mucous expression of transporters? What is the common machinery underlying different HLA-B alleles associated with SJS/TEN and common metabolites? |
topic |
HLA pathogenesis pharmacogenetics Stevens-Johnson syndrome toxic epidermal necrolysis |
url |
https://www.frontiersin.org/articles/10.3389/fphar.2021.588063/full |
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AT lincheng currentpharmacogeneticperspectiveonstevensjohnsonsyndromeandtoxicepidermalnecrolysis AT lincheng currentpharmacogeneticperspectiveonstevensjohnsonsyndromeandtoxicepidermalnecrolysis |
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