PMID- 27999358 OWN - NLM STAT- MEDLINE DCOM- 20170407 LR - 20220318 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 17 IP - 12 DP - 2016 Dec 18 TI - Review of Toxic Epidermal Necrolysis. LID - 10.3390/ijms17122135 [doi] LID - 2135 AB - 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-alpha (TNF-alpha), 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. FAU - Harris, Victoria AU - Harris V AD - Sydney Medical School-Northern, University of Sydney, 2065 Sydney, Australia. vharrisderm@gmail.com. FAU - Jackson, Christopher AU - Jackson C AD - Sutton Arthritis Research Laboratory, Kolling Institute, University of Sydney, 2065 Sydney, Australia. chris.jackson@sydney.edu.au. FAU - Cooper, Alan AU - Cooper A AD - Dermatology Department, Royal North Shore Hospital, 2065 Sydney, Australia. alanjco@tpg.com.au. LA - eng PT - Journal Article PT - Review DEP - 20161218 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 RN - 0 (Antigens, Differentiation, T-Lymphocyte) RN - 0 (FASLG protein, human) RN - 0 (Fas Ligand Protein) RN - 0 (GNLY protein, human) RN - 0 (Immunoglobulins, Intravenous) RN - 0 (TNF-Related Apoptosis-Inducing Ligand) RN - 0 (TNFSF10 protein, human) RN - 0 (Tumor Necrosis Factor-alpha) RN - 126465-35-8 (Perforin) RN - 143011-72-7 (Granulocyte Colony-Stimulating Factor) RN - 83HN0GTJ6D (Cyclosporine) RN - B72HH48FLU (Infliximab) RN - EC 3.4.21.- (Granzymes) SB - IM MH - Antigens, Differentiation, T-Lymphocyte/*metabolism MH - Apoptosis/*physiology MH - Cyclosporine/therapeutic use MH - Drug-Related Side Effects and Adverse Reactions/immunology/*pathology MH - Epidermis/pathology MH - Fas Ligand Protein/metabolism MH - Granulocyte Colony-Stimulating Factor/therapeutic use MH - Granzymes/metabolism MH - Humans MH - Immunoglobulins, Intravenous/therapeutic use MH - Infliximab/therapeutic use MH - Keratinocytes/*pathology MH - Mucous Membrane/*pathology MH - Perforin/metabolism MH - Stevens-Johnson Syndrome/*drug therapy/*pathology MH - TNF-Related Apoptosis-Inducing Ligand/metabolism MH - Tumor Necrosis Factor-alpha/*antagonists & inhibitors/metabolism PMC - PMC5187935 OTO - NOTNLM OT - drug reaction OT - inflammatory dermatoses OT - toxic epidermal necrolysis COIS- The authors declare no conflict of interest. EDAT- 2016/12/22 06:00 MHDA- 2017/04/08 06:00 PMCR- 2016/12/01 CRDT- 2016/12/22 06:00 PHST- 2016/11/14 00:00 [received] PHST- 2016/12/09 00:00 [revised] PHST- 2016/12/12 00:00 [accepted] PHST- 2016/12/22 06:00 [entrez] PHST- 2016/12/22 06:00 [pubmed] PHST- 2017/04/08 06:00 [medline] PHST- 2016/12/01 00:00 [pmc-release] AID - ijms17122135 [pii] AID - ijms-17-02135 [pii] AID - 10.3390/ijms17122135 [doi] PST - epublish SO - Int J Mol Sci. 2016 Dec 18;17(12):2135. doi: 10.3390/ijms17122135.