Details of Disease

General Information of Disease (ID: DISVOTZQ)

• Disease Name: Epidermolysis bullosa
• Synonyms: EB; acantholysis bullosa; epidermolysis bullosa
• Disease Class: EC3Z: Epidermolysis bullosa
• Definition: Epidermolysis bullosa (EB) is a group of genetic skin diseases that cause the skin to blister very easily. Blisters form in response to minor injuries or friction, such as rubbing or scratching. There are four main types of epidermolysis bullosa: dystrophic epidermolysis bullosa Epidermolysis bullosa simplex Junctional epidermolysis bullosa Kindler Syndrome Identifying the exact type can be hard because there are many subtypes of EB. Within each type or subtype, a person may be mildly or severely affected. The disease can range from being a minor inconvenience to completely disabling, and fatal in some cases. Most types of EB are inherited. The inheritance pattern may be autosomal dominant or autosomal recessive. Management involves protecting the skin, reducing friction against the skin, and keeping the skin cool.
• Disease Hierarchy:
  DISV4VFZ: Vesiculobullous skin disease
  DISVOTZQ: Epidermolysis bullosa
• ICD Code:
  ICD-11: ICD-11: EC3Z
  Expand ICD-11: 'EC3Z
  Expand ICD-10: 'Q80-Q89; 'Q81; 'Q81.9
• Disease Identifiers:
  MONDO ID: MONDO_0006541
  MESH ID: D004820
  UMLS CUI: C0014527
  MedGen ID: 41832
  SNOMED CT ID: 61003004

Drug-Interaction Atlas (DIA) of This Disease

This Disease is Treated as An Indication in 2 Approved Drug(s)

Drug Name	Drug ID	Highest Status	Drug Type	REF
Filsuvez	DMHJBPG	Approved in EU	NA	[1]
Coenzyme Q10	DM8D9H5	Phase 4	Small molecular drug	[2]

This Disease is Treated as An Indication in 9 Clinical Trial Drug(s)

Drug Name	Drug ID	Highest Status	Drug Type	REF
APZ-2	DM3K95H	Phase 3	Cell therapy	[3]
Beremagene geperpavec	DM8J3VY	Phase 3	Gene therapy	[4]
CCP-020	DMWJZ8O	Phase 3	NA	[2]
BPM 31510	DMIW5P1	Phase 2	Lipid-drug conjugate	[6]
GBT-101	DMD9C1E	Phase 2	NA	[2]
RGN-137	DMB9DST	Phase 2	Peptide	[7]
Allo-APZ2-EB	DM39Y9O	Phase 1/2	Cell therapy	[8]
QR-313	DMNIPCO	Phase 1/2	NA	[2]
LAMB3-transduced autologous epidermal stem cells	DM1C4UM	Phase 1	NA	[9]

This Disease is Treated as An Indication in 1 Drugs in Phase 2 Trial

Drug Name	Drug ID	Highest Status	Drug Type	REF
Mesenchymal stem cells	DMOUEY7	Phase 2/3 Trial	Cell therapy	[5]

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

Drug Name	Drug ID	Highest Status	Drug Type	REF
Type VII collagen	DMN26WK	Investigative	NA	[10]

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 3 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
COL7A1	TTBCOKN	Disputed	Genetic Variation	[11]
ITGA6	TT165T3	Strong	Genetic Variation	[12]
LAMC2	TTNS7H3	Strong	Genetic Variation	[13]

This Disease Is Related to 2 DME Molecule(s)

Gene Name	DME ID	Evidence Level	Mode of Inheritance	REF
TGM3	DEOEB3Q	Strong	Genetic Variation	[14]
TGM5	DEW8QEH	Strong	Genetic Variation	[14]

This Disease Is Related to 15 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
EXPH5	OTOMXDUO	Limited	Genetic Variation	[15]
ITGA3	OTBCH21D	Limited	Biomarker	[16]
PLEC	OTU4XDEG	Limited	Biomarker	[17]
PLOD3	OTT00T7Q	Limited	Genetic Variation	[18]
DST	OTHZBM4X	Disputed	Genetic Variation	[19]
LAD1	OT6YGTVX	Disputed	Altered Expression	[20]
DSC2	OTODVH8K	Strong	Genetic Variation	[21]
ERBIN	OTNWTUA8	Strong	Biomarker	[22]
FERMT1	OT626PBA	Strong	Genetic Variation	[23]
ITGB4	OT28UK84	Strong	Genetic Variation	[12]
KLHL24	OTWZSX5C	Strong	Genetic Variation	[24]
KRT14	OTUVZ1DW	Strong	Genetic Variation	[25]
KRT5	OTVGI9HT	Strong	Biomarker	[26]
LAMA3	OTFME7HT	Strong	Genetic Variation	[27]
RPS27A	OTIIGGZ2	Strong	Genetic Variation	[28]

References

• [1] EU Approved Drug Products from EU Official Website.
• [2] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [3] ClinicalTrials.gov (NCT05838092) A Double-blind, Randomized, Placebo-controlled, Interventional, Multicenter, Phase III Clinical Trial to Investigate the Safety and Efficacy of ABCB5-positive Mesenchymal Stromal Cells (ABCB5+ MSCs) on Epidermolysis Bullosa (EB). U.S.National Institutes of Health.
• [4] ClinicalTrials.gov (NCT04491604) A Phase III Efficacy and Safety Study of Beremagene Geperpavec (B-VEC, Previously "KB103") for the Treatment of Dystrophic Epidermolysis Bullosa (DEB). U.S.National Institutes of Health.
• [5] FDA Approved Drug Products from FDA Official Website. 2019. Application Number: (FDA ORPHAN DRUG) 427014
• [6] ClinicalTrials.gov (NCT02793960) Topical BPM31510 3.0% Cream in Patients With Epidermolysis Bullosa. U.S. National Institutes of Health.
• [7] ClinicalTrials.gov (NCT03578029) Evaluation of the Safety and Efficacy Study of RGN-137 Topical Gel for Junctional and Dystrophic Epidermolysis Bullosa (CELEB). U.S. National Institutes of Health.
• [8] ClinicalTrials.gov (NCT03529877) An Interventional, Multicenter, Single Arm, Phase I/IIa Clinical Trial to Investigate the Efficacy and Safety of Allo-APZ2-EB on Epidermolysis Bullosa (EB). U.S.National Institutes of Health.
• [9] Long-Term Stability and Safety of Transgenic Cultured Epidermal Stem Cells in Gene Therapy of Junctional Epidermolysis Bullosa. Stem Cell Reports. 2014 January 14; 2(1): 1-8.
• [10] The ChEMBL database in 2017. Nucleic Acids Res. 2017 Jan 4;45(D1):D945-D954.
• [11] Epidermolysis Bullosa (EB) Acquisita in an Adult Patient with Previously Unrecognized Mild Dystrophic EB and Biallelic COL7A1 Mutations.Acta Derm Venereol. 2018 Apr 16;98(4):411-415. doi: 10.2340/00015555-2851.
• [12] Heterozygosity for a Novel Missense Mutation in the ITGB4 Gene Associated With Autosomal Dominant Epidermolysis Bullosa. JAMA Dermatol. 2016 May 1;152(5):558-62. doi: 10.1001/jamadermatol.2015.5236.
• [13] Genome-wide meta-analysis implicates mediators of hair follicle development and morphogenesis in risk for severe acne.Nat Commun. 2018 Dec 12;9(1):5075. doi: 10.1038/s41467-018-07459-5.
• [14] Transglutaminases in autoimmune and inherited skin diseases: The phenomena of epitope spreading and functional compensation.Exp Dermatol. 2018 Aug;27(8):807-814. doi: 10.1111/exd.13449. Epub 2018 Feb 26.
• [15] Next generation sequencing identifies double homozygous mutations in two distinct genes (EXPH5 and COL17A1) in a patient with concomitant simplex and junctional epidermolysis bullosa.Hum Mutat. 2018 Oct;39(10):1349-1354. doi: 10.1002/humu.23592. Epub 2018 Aug 3.
• [16] Constitutional absence of epithelial integrin 3 impacts the composition of the cellular microenvironment of ILNEB keratinocytes.Matrix Biol. 2018 Dec;74:62-76. doi: 10.1016/j.matbio.2018.07.001. Epub 2018 Jul 3.
• [17] Laryngeal lesion associated with epidermolysis bullosa secondary to congenital plectin deficiency.Eur Ann Otorhinolaryngol Head Neck Dis. 2019 Jun;136(3):203-205. doi: 10.1016/j.anorl.2019.02.009. Epub 2019 Mar 15.
• [18] Mutations in PLOD3, encoding lysyl hydroxylase 3, cause a complex connective tissue disorder including recessive dystrophic epidermolysis bullosa-like blistering phenotype with abnormal anchoring fibrils and type VII collagen deficiency.Matrix Biol. 2019 Aug;81:91-106. doi: 10.1016/j.matbio.2018.11.006. Epub 2018 Nov 18.
• [19] BPAG1, a distinctive role in skin and neurological diseases.Semin Cell Dev Biol. 2017 Sep;69:34-39. doi: 10.1016/j.semcdb.2017.06.005. Epub 2017 Jun 13.
• [20] The 97 kDa linear IgA bullous dermatosis antigen is not expressed in a patient with generalized atrophic benign epidermolysis bullosa with a novel homozygous G258X mutation in COL17A1.J Invest Dermatol. 1998 Nov;111(5):887-92. doi: 10.1046/j.1523-1747.1998.00363.x.
• [21] Desmosomal genodermatoses.Br J Dermatol. 2012 Jan;166(1):36-45. doi: 10.1111/j.1365-2133.2011.10640.x.
• [22] Disruption of ERBB2IP is not associated with dystrophic epidermolysis bullosa in both father and son carrying a balanced 5;13 translocation.J Invest Dermatol. 2005 Oct;125(4):700-4. doi: 10.1111/j.0022-202X.2005.23875.x.
• [23] Focal adhesions in the skin: lessons learned from skin fragility disorders.Eur J Dermatol. 2017 Jun 1;27(S1):8-11. doi: 10.1684/ejd.2017.3039.
• [24] Stabilizing mutations of KLHL24 ubiquitin ligase cause loss of keratin 14 and human skin fragility. Nat Genet. 2016 Dec;48(12):1508-1516. doi: 10.1038/ng.3701. Epub 2016 Oct 31.
• [25] Revertant mosaicism in junctional epidermolysis bullosa due to multiple correcting second-site mutations in LAMB3.J Clin Invest. 2007 May;117(5):1240-8. doi: 10.1172/JCI30465.
• [26] The Role of Collagen IV and Cytokeratin 5/6 Immunohistochemistry in Identifying Subtypes of Hereditary Epidermolysis Bullosa.Appl Immunohistochem Mol Morphol. 2018 Sep;26(8):586-590. doi: 10.1097/PAI.0000000000000471.
• [27] Detection of novel LAMA3 mutation in Herlitz junctional epidermolysis bullosa in a Jordanian family.Australas J Dermatol. 2013 Aug;54(3):218-21. doi: 10.1111/j.1440-0960.2012.00945.x. Epub 2012 Sep 11.
• [28] Epidermolysis bullosa - a group of skin diseases with different causes but commonalities in gene expression.Exp Dermatol. 2012 Jul;21(7):526-30. doi: 10.1111/j.1600-0625.2012.01519.x.