Current Pharmacogenetic Perspective on Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis

Abstract

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?

Effectiveness and Safety of Early Short-Course, Moderate- to High-Dose Glucocorticoids for the Treatment of Stevens–Johnson Syndrome/Toxic Epidermal Necrolysis: A Retrospective Study

“…In recent years, reports of adverse reactions to traditional Chinese medicine have increased at home and abroad, with drug eruption the most common adverse reaction. 11,12 More than 170 countries and regions around the world use traditional Chinese herbal medicines and medicines derived from plants and animals. These medicines were generally considered to be safer to use and had fewer adverse reactions.…”

Erythema multiforme in children

“…All 3 are immune-mediated epidermal conditions with variable clinical presentations; however, SJS and toxic epidermal necrolysis each have high mortality and lack an effective treatment. 5 While in the past these conditions were considered to be on a continuum, they are now recognized as having distinct features and diverse outcomes, resulting in the need for different management strategies. Erythema multiforme is mostly considered to be papular and generally has target-like lesions; SJS usually contains widespread erythematous or purpuric macules with blisters.…”

Rare vardenafil-associated Stevens-Johnson syndrome: toxic epidermal necrolysis

“…At least 200 drugs have been reported to be associated with the onset of the disease, including nonsteroidal anti-inflammatory drugs, sulfa-derived medications, lactam antibiotics and anticonvulsants. 7 SCARs like SJS/TEN are type IV delayed-type hypersensitivity reactions, mediated either by direct cytotoxicity of CD8 +T cells or by release of CD4 +derived cytokines via antigen presenting cells, such as macrophages and dendritic cells. 7 Macrophages are major cellular producers of ferritin and remarkable serum ferritin was observed in the patient, in the setting of ongoing inflammation, together with other acute-phase reactants, such as ESR and CRP.…”

“…7 SCARs like SJS/TEN are type IV delayed-type hypersensitivity reactions, mediated either by direct cytotoxicity of CD8 +T cells or by release of CD4 +derived cytokines via antigen presenting cells, such as macrophages and dendritic cells. 7 Macrophages are major cellular producers of ferritin and remarkable serum ferritin was observed in the patient, in the setting of ongoing inflammation, together with other acute-phase reactants, such as ESR and CRP. 8 Sexual and reproductive health is a significant public health issue, and the COVID-19 quarantine had an impact in mental and physical health and to the best of our knowledge, this is the first vardenafil-induced SJS case.…”

“…Severe cutaneous adverse reactions (SCARs) are uncommon and potentially life-threatening immune-mediated ADRs, with diverse clinical phenotypes, including SJS/TEN. At least 200 drugs have been reported to be associated with the onset of the disease, including nonsteroidal anti-inflammatory drugs, sulfa-derived medications, lactam antibiotics and anticonvulsants 7…”