title: Review of Toxic Epidermal Necrolysis.
abstract: Toxic epidermal necrolysis (TEN) is a rare but life threatening mucocutaneous reaction to drugs or their metabolites. It is characterised by widespread keratinocyte apoptosis and sloughing of the skin, erosions of the mucous membranes, painful blistering, and severe systemic disturbance. The pathophysiology of TEN is incompletely understood. Historically, it has been regarded as a drug-induced immune reaction initiated by cytotoxic lymphocytes via a human leukocyte antigen (HLA)-restricted pathway. Several mediators have been identified as contributors to the cell death seen in TEN, including; granulysin, soluble Fas ligand, perforin/granzyme, tumour necrosis factor-α (TNF-α), and TNF-related apoptosis-inducing ligand. Currently, granulysin is accepted as the most important mediator of T cell proliferation. There is uncertainty around the accepted management of TEN. The lack of definitive management guidelines for TEN is explained in part by the rarity of the disease and its high mortality rate, which makes it difficult to conduct randomised control trials on emerging therapies. Developments have been made in pharmacogenomics, with numerous HLA alleles identified; however, these have largely been ethnically specific. These associations have translated into screening recommendations for Han Chinese.
authors.affiliation: Sydney Medical School-Northern, University of Sydney, 2065 Sydney, Australia. vharrisderm@gmail.com.
authors.forename: Victoria
authors.initials: V
authors.lastname: Harris
authors.affiliation: Sutton Arthritis Research Laboratory, Kolling Institute, University of Sydney, 2065 Sydney, Australia. chris.jackson@sydney.edu.au.
authors.forename: Christopher
authors.initials: C
authors.lastname: Jackson
authors.affiliation: Dermatology Department, Royal North Shore Hospital, 2065 Sydney, Australia. alanjco@tpg.com.au.
authors.forename: Alan
authors.initials: A
authors.lastname: Cooper
mesh_terms: D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism*; D017209:Apoptosis / Q000502:physiology*; D016572:Cyclosporine / Q000627:therapeutic use; D064420:Drug-Related Side Effects and Adverse Reactions / Q000276:immunology / Q000473:pathology*; D004817:Epidermis / Q000473:pathology; D053222:Fas Ligand Protein / Q000378:metabolism; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use; D053804:Granzymes / Q000378:metabolism; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000627:therapeutic use; D000069285:Infliximab / Q000627:therapeutic use; D015603:Keratinocytes / Q000473:pathology*; D009092:Mucous Membrane / Q000473:pathology*; D054353:Perforin / Q000378:metabolism; D013262:Stevens-Johnson Syndrome / Q000188:drug therapy* / Q000473:pathology*; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D000945:Antigens, Differentiation, T-Lymphocyte; C505661:FASLG protein, human; D053222:Fas Ligand Protein; C075005:GNLY protein, human; D016756:Immunoglobulins, Intravenous; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; D014409:Tumor Necrosis Factor-alpha; D054353:Perforin; D016179:Granulocyte Colony-Stimulating Factor; D016572:Cyclosporine; D000069285:Infliximab; D053804:Granzymes
keywords: drug reaction; inflammatory dermatoses; toxic epidermal necrolysis