{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T10:53:10Z","timestamp":1789901590509,"version":"4.0.1"},"reference-count":50,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2016,12,18]],"date-time":"2016-12-18T00:00:00Z","timestamp":1482019200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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-\u03b1 (TNF-\u03b1), 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.<\/jats:p>","DOI":"10.3390\/ijms17122135","type":"journal-article","created":{"date-parts":[[2016,12,23]],"date-time":"2016-12-23T04:09:09Z","timestamp":1482466149000},"page":"2135","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":60,"title":["Review of Toxic Epidermal Necrolysis"],"prefix":"10.3390","volume":"17","author":[{"given":"Victoria","family":"Harris","sequence":"first","affiliation":[{"name":"Sydney Medical School\u2014Northern, University of Sydney, 2065 Sydney, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9234-9116","authenticated-orcid":false,"given":"Christopher","family":"Jackson","sequence":"additional","affiliation":[{"name":"Sutton Arthritis Research Laboratory, Kolling Institute, University of Sydney, 2065 Sydney, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan","family":"Cooper","sequence":"additional","affiliation":[{"name":"Dermatology Department, Royal North Shore Hospital, 2065 Sydney, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2016,12,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1046\/j.1523-1747.2000.00061.x","article-title":"SCORTEN: A severity-of-illness score for toxic epidermal necrolysis","volume":"115","author":"Fouchard","year":"2000","journal-title":"J. Investig. Dermatol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1111\/j.1365-2133.1956.tb12766.x","article-title":"Toxic epidermal necrolysis: An eruption resembling scalding of the skin","volume":"68","author":"Lyell","year":"1956","journal-title":"Br. J. Dermatol."},{"key":"ref_3","first-page":"1019","article-title":"Correlations between clinical patterns and causes of erythema multiforme majus, Stevens\u2013Johnson syndrome, and toxic epidermal necrolysis: Results of an international prospective study","volume":"138","author":"Mockenhaupt","year":"2002","journal-title":"Arch. Dermatol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1097\/00000372-199704000-00005","article-title":"Erythema multiforme and toxic epidermal necrolysis: A comparative study","volume":"19","author":"Paquet","year":"1997","journal-title":"Am. J. Dermatopathol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"526","DOI":"10.1001\/archpedi.1922.04120120077005","article-title":"A new eruptive fever associated with stomatitis and ophthalmia: Report of two cases in children","volume":"24","author":"Stevens","year":"1922","journal-title":"Am. J. Dis. Child."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"726","DOI":"10.1111\/j.1346-8138.1997.tb02524.x","article-title":"Stevens\u2013Johnson syndrome and toxic epidermal necrolysis are severity variants of the same disease which differs from erythema multiforme","volume":"24","author":"Roujeau","year":"1997","journal-title":"J. Dermatol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1194","DOI":"10.1111\/bjd.14530","article-title":"UK guidelines for the management of Stevens Johnson syndrome\/toxic epidermal necrolysis in adults 2016","volume":"174","author":"Creamer","year":"2016","journal-title":"Br. J. Dermatol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1001\/archderm.1991.01680050083008","article-title":"Toxic epidermal necrolysis and Stevens\u2013Johnson syndrome: An epidemiologic study from West Germany","volume":"127","author":"Rzany","year":"1991","journal-title":"Arch. Dermatol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1016\/0895-4356(96)00035-2","article-title":"Epidemiology of erythema exsudativum multiforme majus, Stevens\u2013Johnson syndrome, and toxic epidermal necrolysis in Germany (1990\u20131992): Structure and results of a population-based registry","volume":"49","author":"Rzany","year":"1996","journal-title":"J. Clin. Epidemiol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1197","DOI":"10.1038\/jid.2012.510","article-title":"Comprehensive survival analysis of a cohort of patients with Stevens\u2013Johnson syndrome and toxic epidermal necrolysis","volume":"133","author":"Sekula","year":"2013","journal-title":"J. Investig. Dermatol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"49","DOI":"10.2165\/11593240-000000000-00000","article-title":"Incidence of toxic epidermal necrolysis and Stevens\u2013Johnson syndrome in an HIV cohort an observational, retrospective case series study","volume":"13","author":"Mittmann","year":"2012","journal-title":"Am. J. Clin. Dermatol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1600","DOI":"10.1056\/NEJM199512143332404","article-title":"Medication use and the risk of Stevens\u2013Johnson syndrome or toxic epidermal necrolysis","volume":"333","author":"Roujeau","year":"1995","journal-title":"N. Engl. J. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1038\/sj.jid.5701033","article-title":"Stevens\u2013Johnson Syndrome and toxic epidermal necrolysis: Assessment of medication risks with emphasis on recently marketed drugs. The EuroSCAR-study","volume":"128","author":"Mockenhaupt","year":"2008","journal-title":"J. Investig. Dermatol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1097\/00006454-200102000-00022","article-title":"Stevens\u2013Johnson syndrome and toxic epidermal necrolysis after vaccination: Reports to the vaccine adverse event reporting system","volume":"20","author":"Ball","year":"2001","journal-title":"Pediatr. Infect. Dis. J."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1007\/BF02113442","article-title":"Toxic epidermal necrolysis associated with Mycoplasma pneumoniae infection","volume":"14","author":"Fournier","year":"1995","journal-title":"Eur. J. Clin. Microbiol. Infect. Dis."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"710","DOI":"10.1111\/j.1365-2133.1996.tb06976.x","article-title":"Apoptosis as a mechanism of keratinocyte death in toxic epidermal necrolysis","volume":"134","author":"Paul","year":"1996","journal-title":"Br. J. Dermatol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1001\/archderm.1993.01680250078010","article-title":"Cutaneous T-cell recruitment in toxic epidermal necrolysis: Further evidence of CD8+ lymphocyte involvement","volume":"129","author":"Correia","year":"1993","journal-title":"Arch. Dermatol."},{"key":"ref_18","first-page":"225","article-title":"Blister fluid in T lymphocytes during toxic epidermal necrolysis are functional cytotoxic cells which express human natural killer cell (NK) inhibitory receptors","volume":"119","author":"Delaire","year":"2000","journal-title":"Clin. Exp. Immunol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1209","DOI":"10.1016\/j.jaci.2004.07.047","article-title":"Toxic epidermal necrolysis: Effector cells are drug-specific cytotoxic T cells","volume":"114","author":"Nassif","year":"2004","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1171","DOI":"10.1111\/bjd.14682","article-title":"Toxic epidermal necrolysis: The past, the guidelines and chellenges for the future","volume":"174","author":"Wolkenstein","year":"2016","journal-title":"Br. J. Dermatol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1097\/ACI.0b013e3283630cc2","article-title":"Toxic epidermal necrolysis: The year in review","volume":"13","author":"Lee","year":"2013","journal-title":"Curr. Opin. Allergy Clin. Immunol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1343","DOI":"10.1038\/nm.1884","article-title":"Granulysin is a key mediator for disseminated keratinocyte deathin Stevens-Johnson Syndrome and toxic epidermal necrolysis","volume":"14","author":"Chung","year":"2008","journal-title":"Nat. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1126\/science.282.5388.490","article-title":"Inhibition of toxic epidermal necrolysis by blockade of CD95 with human intravenous immunoglobulin","volume":"282","author":"Viard","year":"1998","journal-title":"Science"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1515","DOI":"10.1016\/S0002-9440(10)64284-8","article-title":"Toxic epidermal necrolysis and Stevens-Johnson syndrome are induced by soluble Fas Ligand","volume":"162","author":"Abe","year":"2003","journal-title":"Am. J. Pathol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"992","DOI":"10.1016\/j.jaci.2008.06.013","article-title":"Increased soluble Fas Ligand levels in patients with Stevens-Johnson syndrome and toxic epidermal necrolysis preceeding skin detachment","volume":"122","author":"Murata","year":"2008","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1111\/j.1365-2133.2005.06721.x","article-title":"Toxic epidermal necrolysis and Stevens-Johnson syndrome: Current evidence, practical management and future directions","volume":"153","author":"Chave","year":"2005","journal-title":"Br. J. Dermatol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"173e1","DOI":"10.1016\/j.jaad.2013.05.003","article-title":"Toxic epidermal necrolysis. Part I. Introduction, history, classification, clinical features, etiology, and immunopathogenesis","volume":"69","author":"Schwartz","year":"2013","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1134","DOI":"10.1056\/NEJMoa1013297","article-title":"HLA-A*3101 and carbamazepine-induced hypersensitivity reactions in Europeans","volume":"364","author":"McCormack","year":"2011","journal-title":"N. Engl. J. Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1034","DOI":"10.1093\/hmg\/ddq537","article-title":"Genome-wide association study identifies HLA-A*3101 allele as a genetic risk factor for carbamazepine-induced cutaneous adverse drug reactions in Japanese population","volume":"20","author":"Ozeki","year":"2011","journal-title":"Hum Mol Genet"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1038\/tpj.2013.40","article-title":"HLA-A 31:01 and different types of carbamezipine-induced severe cutaneous adverse reactions: An international study and meta-analysis","volume":"14","author":"Genin","year":"2014","journal-title":"Pharmacogenom. J."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Somkrua, R., Eickman, E.E., Saokaew, S., Lohitnavy, M., and Chaiyakunapruk, N. (2011). Association of HLA-B*5801 allele and allopurinol-induced Stevens Johnson syndrome and toxic epidermal necrolysis: A systematic review and meta-analysis. BMC Med. Genet., 12.","DOI":"10.1186\/1471-2350-12-118"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1097\/FPC.0b013e3282f3ef9c","article-title":"A European study of HLA-Bin Stevens\u2013Johnson Syndrome and toxic epidermal necrolysis related to five high-risk drugs","volume":"18","author":"Lonjou","year":"2008","journal-title":"Pharmacogenet. Genom."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1538","DOI":"10.1016\/j.jaci.2014.12.1916","article-title":"IKZFI, a new susceptibility gene for cold medicine- related Stevens\u2013Johnson syndrome\/toxic epidermal necrolysis with severe mucosal involvement","volume":"135","author":"Ueta","year":"2015","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1126","DOI":"10.1056\/NEJMoa1009717","article-title":"Carbamazepine-induced toxic effects and HLA-B*1502 screening in Taiwan","volume":"364","author":"Chen","year":"2011","journal-title":"N. Engl. J. Med."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1016\/S1081-1206(10)61112-X","article-title":"Steven\u2013Johnson syndrome and toxic epidermal necrolysis: A review of the literature","volume":"94","author":"Letko","year":"2005","journal-title":"Ann. Allergy Asthma Immunol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/j.jaad.2006.04.048","article-title":"Toxic epidermal necrolysis","volume":"56","author":"Pereira","year":"2007","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"853","DOI":"10.1111\/j.1365-2230.2010.03826.x","article-title":"Toxic epidermal necrolysis: Retrospective analysis of 21 consecutive cases managed at a tertiary centre","volume":"35","author":"Rajaratnam","year":"2010","journal-title":"Clin. Exp. Dermatol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"144","DOI":"10.2340\/00015555-0214","article-title":"Dexamethasone pulse therapy for Stevens Johnson syndrome\/toxic epidermal necrolysis","volume":"87","author":"Karduan","year":"2007","journal-title":"Acta Derm. Venerol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1016\/j.jaad.2013.04.007","article-title":"Methylprednisolone pulse therapy for Stevens Johnson syndrome\/toxic epidermal necrolysis: Clinical evaluation and analysis of biomarkers","volume":"69","author":"Hirahara","year":"2013","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1111\/j.1365-2133.2012.10965.x","article-title":"The efficacy of intravenous immunoglobulin for the treatment of toxic epidermal necrolysis: A systematic review and meta-anlaysis","volume":"167","author":"Huang","year":"2012","journal-title":"Br. J. Dermatol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"630","DOI":"10.1016\/j.jaad.2011.12.014","article-title":"Toxic epidermal necrolysis: Five years of treatment experience from a burn unit","volume":"67","author":"Firoz","year":"2012","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1304","DOI":"10.1111\/bjd.12607","article-title":"The role of intravenous immunoglobulin in toxic epidermal necrolysis: A retrospective analysis of 64 patients managed in a specialised centre","volume":"169","author":"Lee","year":"2013","journal-title":"Br. J. Dermatol."},{"key":"ref_43","first-page":"1657","article-title":"European Guidelines (S1) on the use of high-dose intravenous immunoglobulin in dermatology","volume":"30","author":"Enk","year":"2016","journal-title":"JEAVD"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"941","DOI":"10.1016\/j.jaad.2014.07.016","article-title":"Retrospective review of Stevens\u2013Johnson syndrome\/toxic epidermal necrolysis treatment comparing intravenous immunoglobulin with cyclosporine","volume":"71","author":"Kirchhof","year":"2014","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_45","first-page":"847","article-title":"Open trial of ciclosporin treatment for Stevens Johnson syndrome and toxic epidermal necrolysis","volume":"163","author":"Wolkenstein","year":"2012","journal-title":"Br. J. Dermatol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1046\/j.1365-2133.2002.46833.x","article-title":"Antitumour necrosis factor-\u03b1 antibodies (infliximab) in the treatment of a patient with toxic epidermal necrolysis","volume":"146","author":"Fischer","year":"2002","journal-title":"Br. J. Dermatol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1016\/j.jaad.2014.04.044","article-title":"Entanercept therapy for toxic epidermal necrolysis","volume":"71","author":"Paradisi","year":"2014","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1016\/j.jaci.2005.06.029","article-title":"Rapid resolution of toxic epidermal necrolysis with anti-TNF \u03b1 treatment","volume":"116","author":"Hunger","year":"2005","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1586","DOI":"10.1016\/S0140-6736(98)02197-7","article-title":"Randomised comparison of thalidomide versus placebo in toxic epidermal necrolysis","volume":"352","author":"Wolkenstein","year":"1998","journal-title":"Lancet"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"860","DOI":"10.1111\/j.1365-2133.2009.09585.x","article-title":"Granulocyte colony-stimulating factor in toxic epidermal necrolysis and Chelseas Westminster TEN protocol","volume":"162","author":"Williams","year":"2010","journal-title":"Br. J. Dermatol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/17\/12\/2135\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T19:28:51Z","timestamp":1760210931000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/17\/12\/2135"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,12,18]]},"references-count":50,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2016,12]]}},"alternative-id":["ijms17122135"],"URL":"https:\/\/doi.org\/10.3390\/ijms17122135","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,12,18]]}}}