Details of Disease

General Information of Disease (ID: DISIWPFR)

• Disease Name: Toxic epidermal necrolysis
• Synonyms: Stevens-Johnson syndrome/toxic epidermal necrolysis spectrum; Lyell syndrome; Lyell's syndrome; SJS-TEN; TEN; toxic epidermolysis
• Definition: Toxic epidermal necrolysis (TEN) is an acute and severe skin disease with clinical and histological features characterized by the destruction and detachment of the skin epithelium and mucous membranes.
• Disease Hierarchy:
  DISW5398: Toxic dermatosis
  DISIWPFR: Toxic epidermal necrolysis
• Disease Identifiers:
  MONDO ID: MONDO_0019810
  MESH ID: D013262
  UMLS CUI: C0014518
  MedGen ID: 4501
  Orphanet ID: 95455
  SNOMED CT ID: 768962006

Drug-Interaction Atlas (DIA) of This Disease

This Disease is Treated as An Indication in 1 Approved Drug(s)

Drug Name	Drug ID	Highest Status	Drug Type	REF
Infliximab	DMH7OIA	Approved	Antibody	[1]

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 22 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
ALB	TTFNGC9	Limited	Therapeutic	[2]
CSF3	TT5TQ2W	Limited	Therapeutic	[3]
HSPG2	TT5UM29	Limited	Biomarker	[4]
MIF	TT6804T	Limited	Biomarker	[5]
NOS2	TTF10I9	Limited	Genetic Variation	[6]
PTGER3	TTPNGDE	Limited	Genetic Variation	[7]
CAV1	TTXUBN2	Strong	Biomarker	[8]
CCL17	TTMPHAE	Strong	Altered Expression	[9]
COPS5	TTSTNJR	Strong	Biomarker	[8]
EP300	TTGH73N	Strong	Biomarker	[8]
FSHB	TT13GFV	Strong	Genetic Variation	[10]
HLA-A	TTHONFT	Strong	Biomarker	[11]
IFNA2	TTSIUJ9	Strong	Biomarker	[8]
NEDD4	TT1QU6G	Strong	Biomarker	[8]
NUCB1	TT6A5ZL	Strong	Biomarker	[8]
PARP1	TTVDSZ0	Strong	Biomarker	[8]
PML	TTLH9NY	Strong	Biomarker	[8]
PTGIS	TTLXKZR	Strong	Biomarker	[8]
SGSH	TTPJ2SH	Strong	Biomarker	[12]
TLR3	TTD24Y0	Strong	Genetic Variation	[13]
VCP	TTHNLSB	Strong	Biomarker	[8]
CD37	TTFCW29	Definitive	Biomarker	[14]

This Disease Is Related to 2 DME Molecule(s)

Gene Name	DME ID	Evidence Level	Mode of Inheritance	REF
CYP2C18	DEZMWRE	Strong	Altered Expression	[15]
UPP1	DEFZWAX	Strong	Altered Expression	[16]

This Disease Is Related to 31 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
PCM1	OTFM133C	Limited	Genetic Variation	[17]
ARIH1	OTO3XDR2	Strong	Biomarker	[18]
BAG6	OT4Z0S2U	Strong	Genetic Variation	[19]
BCL2L10	OTYXQJ3I	Strong	Altered Expression	[20]
CCL27	OTUZYC61	Strong	Altered Expression	[21]
CCR10	OT7ZWSSD	Strong	Biomarker	[22]
CELF2	OTLJJ4VT	Strong	Biomarker	[8]
CUL1	OTXPE1UZ	Strong	Biomarker	[8]
CUL4A	OTTBV70J	Strong	Biomarker	[8]
DDX39B	OTEVCFVU	Strong	Genetic Variation	[23]
DERL1	OTJUS74N	Strong	Biomarker	[8]
DSP	OTB2MOP8	Strong	Biomarker	[24]
ELMO1	OTY2ORXK	Strong	Biomarker	[8]
FBXO6	OT58MKP3	Strong	Biomarker	[8]
GNLY	OTZJKA8C	Strong	Biomarker	[25]
HCP5	OTV0YRI8	Strong	Genetic Variation	[26]
HDLBP	OTKDEEYX	Strong	Biomarker	[27]
HLA-C	OTV38BUJ	Strong	Biomarker	[28]
IKZF1	OTCW1FKL	Strong	Genetic Variation	[13]
MPRIP	OT5FV5NS	Strong	Altered Expression	[29]
PANK2	OTFBW889	Strong	Biomarker	[12]
PLXNA3	OTMZIBVG	Strong	Biomarker	[30]
POU5F1	OTDHHN7O	Strong	Genetic Variation	[31]
PSMC5	OTJOORMR	Strong	Biomarker	[8]
PSORS1C1	OT9HK436	Strong	Genetic Variation	[31]
RB1	OT9VMY7B	Strong	Biomarker	[8]
RBX1	OTYA1UIO	Strong	Biomarker	[8]
SETX	OTG3JNOQ	Strong	Biomarker	[32]
SPTBN2	OTDMJ75N	Strong	Biomarker	[33]
TCF19	OT7NKLF9	Strong	Genetic Variation	[31]
TRAF3IP2	OTLLZERL	Strong	Genetic Variation	[34]

References

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• [2] Protein-losing cytomegalovirus gastritis in a patient with Stevens-Johnson syndrome.Digestion. 2002;65(4):234-7. doi: 10.1159/000063818.
• [3] Toxic epidermal necrolysis in a patient with severe aplastic anemia treated with cyclosporin A and G-CSF.J Med. 2001;32(1-2):31-9.
• [4] Development and Validation of a Risk Prediction Model for In-Hospital Mortality Among Patients With Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis-ABCD-10.JAMA Dermatol. 2019 Apr 1;155(4):448-454. doi: 10.1001/jamadermatol.2018.5605.
• [5] The role of macrophage migration inhibition factor in toxic epidermal necrolysis.Int J Dermatol. 1997 Oct;36(10):776-8. doi: 10.1046/j.1365-4362.1997.00043.x.
• [6] The apoptosis pathway and the genetic predisposition to Achilles tendinopathy.J Orthop Res. 2012 Nov;30(11):1719-24. doi: 10.1002/jor.22144. Epub 2012 May 15.
• [7] Expression of prostaglandin E(2) receptor 3 in the eyelid epidermis of patients with Stevens-Johnson syndrome/toxic epidermal necrolysis.Br J Ophthalmol. 2020 Jul;104(7):1022-1027. doi: 10.1136/bjophthalmol-2018-313587. Epub 2019 Apr 18.
• [8] Systems pharmacological analysis of drugs inducing stevens-johnson syndrome and toxic epidermal necrolysis. Chem Res Toxicol. 2015 May 18;28(5):927-34. doi: 10.1021/tx5005248. Epub 2015 Apr 3.
• [9] The thymus and activation-regulated chemokine (TARC) level in serum at an early stage of a drug eruption is a prognostic biomarker of severity of systemic inflammation.Allergol Int. 2018 Jan;67(1):90-95. doi: 10.1016/j.alit.2017.06.001. Epub 2017 Jun 22.
• [10] Novel FSH mutation in a male patient with isolated FSH deficiency and infertility.Eur J Med Genet. 2017 Jun;60(6):335-339. doi: 10.1016/j.ejmg.2017.04.004. Epub 2017 Apr 6.
• [11] Drug allergy.Allergy Asthma Proc. 2019 Nov 1;40(6):474-479. doi: 10.2500/aap.2019.40.4275.
• [12] Genetic testing for prevention of severe drug-induced skin rash.Cochrane Database Syst Rev. 2019 Jul 17;7(7):CD010891. doi: 10.1002/14651858.CD010891.pub2.
• [13] Results of Detailed Investigations Into Stevens-Johnson Syndrome With Severe Ocular Complications.Invest Ophthalmol Vis Sci. 2018 Nov 1;59(14):DES183-DES191. doi: 10.1167/iovs.17-23537.
• [14] Cyclooxygenase and lipoxygenase gene expression in the inflammogenesis of breast cancer.Inflammopharmacology. 2018 May 7. doi: 10.1007/s10787-018-0489-6. Online ahead of print.
• [15] Association of CYP2C9*3 with phenytoin-induced Stevens-Johnson syndrome and toxic epidermal necrolysis: A systematic review and meta-analysis.J Clin Pharm Ther. 2018 Jun;43(3):408-413. doi: 10.1111/jcpt.12660. Epub 2017 Dec 23.
• [16] Correlation between chemosensitivity and mRNA expression level of 5-fluorouracil-related metabolic enzymes during liver metastasis of colorectal cancer.Oncol Rep. 2006 Apr;15(4):875-82.
• [17] Hematopoietic neoplasms with 9p24/JAK2 rearrangement: a multicenter study.Mod Pathol. 2019 Apr;32(4):490-498. doi: 10.1038/s41379-018-0165-9. Epub 2018 Nov 6.
• [18] Improved multiparametric MRI discrimination between low-risk prostate cancer and benign tissues in a small cohort of 5-reductase inhibitor treated individuals as compared with an untreated cohort.NMR Biomed. 2017 May;30(5):10.1002/nbm.3696. doi: 10.1002/nbm.3696. Epub 2017 Feb 6.
• [19] Association of ABCB1,CYP3A4,EPHX1,FAS,SCN1A,MICA, andBAG6 polymorphisms with the risk of carbamazepine-induced Stevens-Johnson syndrome/toxic epidermal necrolysis in Chinese Han patients with epilepsy.Epilepsia. 2014 Aug;55(8):1301-6. doi: 10.1111/epi.12655. Epub 2014 May 23.
• [20] Upregulation of miR-18a-5p contributes to epidermal necrolysis in severe drug eruptions.J Allergy Clin Immunol. 2014 Apr;133(4):1065-74. doi: 10.1016/j.jaci.2013.09.019. Epub 2013 Nov 1.
• [21] Diverse expression of TNF- and CCL27 in serum and blister of Stevens-Johnson syndrome/toxic epidermal necrolysis.Clin Transl Allergy. 2018 Apr 20;8:12. doi: 10.1186/s13601-018-0199-6. eCollection 2018.
• [22] Involvement of CCL27-CCR10 interactions in drug-induced cutaneous reactions.J Allergy Clin Immunol. 2004 Aug;114(2):335-40. doi: 10.1016/j.jaci.2004.04.034.
• [23] A whole-genome association study of major determinants for allopurinol-related Stevens-Johnson syndrome and toxic epidermal necrolysis in Japanese patients.Pharmacogenomics J. 2013 Feb;13(1):60-9. doi: 10.1038/tpj.2011.41. Epub 2011 Sep 13.
• [24] Pattern-Specific Loss of Desmoplakin I and II Immunoreactivity in Erythema Multiforme and its Variants: A Possible Aid in Histologic Diagnosis.Am J Dermatopathol. 2020 Feb;42(2):111-116. doi: 10.1097/DAD.0000000000001545.
• [25] Mutant GNLY is linked to Stevens-Johnson syndrome and toxic epidermal necrolysis.Hum Genet. 2019 Dec;138(11-12):1267-1274. doi: 10.1007/s00439-019-02066-w. Epub 2019 Oct 14.
• [26] Genome-wide DNA methylation analysis in ankylosing spondylitis identifies HLA-B*27 dependent and independent DNA methylation changes in whole blood.J Autoimmun. 2019 Aug;102:126-132. doi: 10.1016/j.jaut.2019.04.022. Epub 2019 May 23.
• [27] Human somatic cell mutagenesis creates genetically tractable sarcomas.Nat Genet. 2014 Sep;46(9):964-72. doi: 10.1038/ng.3065. Epub 2014 Aug 17.
• [28] Association of human antigen class I genes with cold medicine-related Stevens-Johnson syndrome with severe ocular complications in a Korean population.Br J Ophthalmol. 2019 Apr;103(4):573-576. doi: 10.1136/bjophthalmol-2018-313263. Epub 2019 Jan 31.
• [29] Regulation of RIP3 protein stability by PELI1-mediated proteasome-dependent degradation.BMB Rep. 2018 Oct;51(10):484-485. doi: 10.5483/BMBRep.2018.51.10.217.
• [30] Epidemiology and risk factors for drug allergy.Br J Clin Pharmacol. 2011 May;71(5):684-700. doi: 10.1111/j.1365-2125.2010.03774.x.
• [31] Genome-wide association study of Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis in Europe.Orphanet J Rare Dis. 2011 Jul 29;6:52. doi: 10.1186/1750-1172-6-52.
• [32] Associations between HLA class I and cytochrome P450 2C9 genetic polymorphisms and phenytoin-related severe cutaneous adverse reactions in a Thai population.Pharmacogenet Genomics. 2016 May;26(5):225-34. doi: 10.1097/FPC.0000000000000211.
• [33] Severe cutaneous adverse reactions induced by targeted anticancer therapies and immunotherapies.Cancer Manag Res. 2018 May 17;10:1259-1273. doi: 10.2147/CMAR.S163391. eCollection 2018.
• [34] A pharmacogenetics study in Mozambican patients treated with nevirapine: full resequencing of TRAF3IP2 gene shows a novel association with SJS/TEN susceptibility.Int J Mol Sci. 2015 Mar 12;16(3):5830-8. doi: 10.3390/ijms16035830.