Epidermolysis bullosa dystrophica

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Epidermolysis bullosa dystrophica
Other namesDystrophic EB
Dystrophic type of epidermolysis bullosa.jpg
The legs of an individual with dystrophic epidermolysis bullosa.
Specialty Medical genetics   OOjs UI icon edit-ltr-progressive.svg

Epidermolysis bullosa dystrophica or dystrophic EB (DEB) is an inherited disease affecting the skin and other organs. [1] [2]

Contents

"Butterfly child" is the colloquial name for children born with the disease, as their skin is seen to be as delicate and fragile as the wings of a butterfly. [3]

Signs and symptoms

The deficiency in anchoring fibrils impairs the adherence between the epidermis and the underlying dermis. This deficiency occurs due to the genetic mutation(s) in the COL7A1 gene in chromosome 3. The COL7A1 gene in chromosome 3 is responsible for coding for type VII collagen, a protein that assists in helping anchor the epidermis and dermis. Thus the skin of DEB patients is thus highly susceptible to severe blistering.[ citation needed ] Collagen VII is also associated with the epithelium of the esophageal lining, and DEB patients may have chronic scarring, webbing, and obstruction of the esophagus. Affected individuals are often severely malnourished due to trauma to the oral and esophageal mucosa and require feeding tubes for nutrition. They also have iron-deficiency anemia of uncertain origin, which leads to chronic fatigue.[ citation needed ]

Open wounds on the skin heal slowly or not at all, often scarring extensively, and are particularly susceptible to infection. Many individuals bathe in a bleach and water mixture to fight off these infections.[ citation needed ] The chronic inflammation leads to errors in the DNA of the affected skin cells, which in turn causes squamous cell carcinoma (SCC). The majority of these patients die before the age of 30, either of SCC or complications related to DEB.[ citation needed ]

The chronic inflammatory state seen in recessive dystrophic epidermolysis bullosa (RDEB) may cause small fiber peripheral neuropathy (SFN); [4] RDEB patients have reported the sensation of pain in line with neuropathic pain qualities. [5]

Causes

DEB is caused by genetic defects (or mutations) within the human COL7A1 gene encoding the protein type VII collagen (collagen VII). [6] DEB-causing mutations can be either dominant or recessive. [7] Most families with family members with this condition have distinct mutations. [8]

Collagen VII is a very large molecule (300 kDa) that dimerizes to form a semicircular looping structure: the anchoring fibril. Anchoring fibrils are thought to form a structural link between the epidermal basement membrane and the fibrillar collagens in the upper dermis.[ citation needed ]

Pathophysiology

In the absence of mutations of the COL7A1 gene, an autoimmune response against type VII collagen can result in an acquired form of epidermolysis bullosa called epidermolysis bullosa acquisita. [9]

There exist other types of inherited epidermolysis bullosa, junctional epidermolysis bullosa and epidermolysis bullosa simplex, which are not related to type VII collagen deficiency. These arise from mutations in the genes encoding other proteins of the epidermis or the basement membrane at the junction between the epidermis and the dermis. [10]

Diagnosis

Classification

NameLocus & Gene OMIM
Dominant dystrophic epidermolysis bullosa (DDEB)
Also known as "Cockayne-Touraine disease", this variant is characterized by vesicles and bullae on the extensor surfaces of the extremities. [11] [12]
3p21.3 (COL7A1) 131750
Recessive dystrophic epidermolysis bullosa (RDEB)
Also known as "Hallopeau–Siemens variant of epidermolysis bullosa" [13] and "Hallopeau–Siemens disease", [14] this variant results from mutations in the gene encoding type VII collagen, COL7A1, characterized by debilitating oral lesions that produce pain, scarring, and microstomia. [15] [12] It is named for François Henri Hallopeau and Hermann Werner Siemens.
3q22-q23 (COL7A1), 3p21.3 (MMP1) 226600
Epidermolysis bullosa dystrophica, pretibial3p21.3 (COL7A1) 131850
Epidermolysis bullosa pruriginosa3p21.3 (COL7A1) 604129
Epidermolysis bullosa with congenital localized absence of skin and deformity of nails3p21.3 (COL7A1) 132000
Transient bullous dermolysis of the newborn (TBDN) 3p21.3 (COL7A1) 131705

Treatment

In May 2023, the US Food and Drug Administration (FDA) approved Vyjuvek for the treatment of wounds in people with dystrophic epidermolysis bullosa with mutation(s) in the collagen type VII alpha 1 chain (COL7A1) gene. [16] [17]

Birch triterpenes

This section is an excerpt from Birch triterpenes.[ edit ]
Chemical structure of betulin, one of the primary constituents of birch triterpenes Betulin.svg
Chemical structure of betulin, one of the primary constituents of birch triterpenes

Birch triterpenes, sold under the brand name Filsuvez, is an extract of birch bark used as a topical medication for the treatment of epidermolysis bullosa. [18] [19] The active ingredients are triterpenes extracted from the outer bark of silver birch (Betula pendula) and downy birch (Betula pubescens). [20]

The most common side effects include wound complications. [19] Other common side effects include skin reactions at the application site, wound infections, pruritus (itching), and hypersensitivity (allergic) reactions. [19]

Birch triterpenes was approved for medical use in the European Union in June 2022, [19] and in the United States in December 2023. [21] [22]

Related Research Articles

<span class="mw-page-title-main">Epidermolysis bullosa</span> Rare medical conditions that result in easy blistering of the skin and mucous membranes

Epidermolysis bullosa (EB) is a group of rare medical conditions that result in easy blistering of the skin and mucous membranes. Blisters occur with minor trauma or friction and are painful. Its severity can range from mild to fatal. Inherited EB is a rare disease with a prevalence in the United States of 8.2 per million live births. Those with mild cases may not develop symptoms until they start to crawl or walk. Complications may include esophageal narrowing, squamous cell skin cancer, and the need for amputations.

<span class="mw-page-title-main">Keratin 14</span> Protein found in humans

Keratin 14 is a member of the type I keratin family of intermediate filament proteins. Keratin 14 was the first type I keratin sequence determined. Keratin 14 is also known as cytokeratin-14 (CK-14) or keratin-14 (KRT14). In humans it is encoded by the KRT14 gene.

<span class="mw-page-title-main">Hemidesmosome</span> Structures connecting keratinocyte cells to the extracellular matrix

Hemidesmosomes are very small stud-like structures found in keratinocytes of the epidermis of skin that attach to the extracellular matrix. They are similar in form to desmosomes when visualized by electron microscopy; however, desmosomes attach to adjacent cells. Hemidesmosomes are also comparable to focal adhesions, as they both attach cells to the extracellular matrix. Instead of desmogleins and desmocollins in the extracellular space, hemidesmosomes utilize integrins. Hemidesmosomes are found in epithelial cells connecting the basal epithelial cells to the lamina lucida, which is part of the basal lamina. Hemidesmosomes are also involved in signaling pathways, such as keratinocyte migration or carcinoma cell intrusion.

<span class="mw-page-title-main">Epidermolysis bullosa simplex</span> Medical condition

Epidermolysis bullosa simplex (EBS) is a disorder resulting from mutations in the genes encoding keratin 5 or keratin 14. It is one of the major forms of epidermolysis bullosa, a group of genetic conditions that cause the skin to be very fragile and to blister easily.

<span class="mw-page-title-main">Kindler syndrome</span> Medical condition

Kindler syndrome is a rare congenital disease of the skin caused by a mutation in the KIND1 gene.

<span class="mw-page-title-main">Keratin 5</span>

Keratin 5, also known as KRT5, K5, or CK5, is a protein that is encoded in humans by the KRT5 gene. It dimerizes with keratin 14 and forms the intermediate filaments (IF) that make up the cytoskeleton of basal epithelial cells. This protein is involved in several diseases including epidermolysis bullosa simplex and breast and lung cancers.

<span class="mw-page-title-main">Collagen, type XVII, alpha 1</span> Mammalian protein found in humans

Collagen XVII, previously called BP180, is a transmembrane protein which plays a critical role in maintaining the linkage between the intracellular and the extracellular structural elements involved in epidermal adhesion, identified by Diaz and colleagues in 1990.

The lamina densa is a component of the basement membrane zone between the epidermis and dermis of the skin, and is an electron-dense zone between the lamina lucida and dermis, synthesized by the basal cells of the epidermis, and composed of 1) type IV collagen, 2) anchoring fibrils made of type VII collagen, and 3) dermal microfibrils.

<span class="mw-page-title-main">Collagen, type VII, alpha 1</span> Protein found in humans

Collagen alpha-1(VII) chain is a protein that in humans is encoded by the COL7A1 gene. It is composed of a triple helical, collagenous domain flanked by two non-collagenous domains, and functions as an anchoring fibril between the dermal-epidermal junction in the basement membrane. Mutations in COL7A1 cause all types of dystrophic epidermolysis bullosa, and the exact mutations vary based on the specific type or subtype. It has been shown that interactions between the NC-1 domain of collagen VII and several other proteins, including laminin-5 and collagen IV, contribute greatly to the overall stability of the basement membrane.

<span class="mw-page-title-main">Laminin, beta 3</span> Protein-coding gene in the species Homo sapiens

Laminin subunit beta-3 is a protein that in humans is encoded by the LAMB3 gene.

Anchoring fibrils extend from the basal lamina of epithelial cells and attach to the lamina reticularis by wrapping around the reticular fiber bundles. The basal lamina and lamina reticularis together make up the basement membrane. Anchoring fibrils are essential to the functional integrity of the dermoepidermal junction.

Epidermolysis bullosa acquisita, also known as acquired epidermolysis bullosa, is a longterm autoimmune blistering skin disease. It generally presents with fragile skin that blisters and becomes red with or without trauma. Marked scarring is left with thin skin, milia and nail changes. It typically begins around age 50.

<span class="mw-page-title-main">Erythrokeratodermia variabilis</span> Medical condition

Erythrokeratodermia variabilis is a rare autosomal dominant disorder that usually presents at birth or during the first year of life. To date, it is thought to be caused by mutations in genes encoding for connexin channels proteins in the epidermis, leading to the misregulation of homeostasis in keratinocytes.

Bart syndrome, also known as aplasia cutis congenita type VI, is a rare genetic disorder characterized by the association of congenital localized absence of skin, mucocutaneous blistering and absent and dystrophic nails.

Junctional epidermolysis bullosa is a skin condition characterized by blister formation within the lamina lucida of the basement membrane zone.

Transient bullous dermolysis of the newborn (TBDN) is a skin condition that presents in newborns. It is characterized by blister formation secondary to even mild trauma.

<span class="mw-page-title-main">Dermoepidermal junction</span> Interface between the epidermal and dermal layers of the skin

The dermoepidermal junction or dermal-epidermal junction (DEJ) is the interface between the epidermal and the dermal layers of the skin. The basal cells of the epidermis connect to the basement membrane by the anchoring filaments of hemidesmosomes; the cells of the papillary layer of the dermis are attached to the basement membrane by anchoring fibrils, which consist of type VII collagen.

<span class="mw-page-title-main">Daniel S. Greenspan</span> American biomedical scientist

Daniel S. Greenspan is an American biomedical scientist, academic and researcher. He is Kellett professor of Cell and Regenerative Biology at the University of Wisconsin-Madison School of Medicine and Public Health. He has authored over 120 publications. His research has mainly focused on genes encoding proteins of the extracellular space and possible links between defects in such genes and human development and disease.

Beremagene geperpavec, sold under the brand name Vyjuvek, is a gene therapy for the treatment of wounds. Beremagene geperpavec is the first approved gene therapy to use herpes-simplex virus type 1 as a vector. Beremagene geperpavec is a genetically modified herpes-simplex virus used to deliver normal copies of the COL7A1 gene to the wounds.

<span class="mw-page-title-main">Birch triterpenes</span> Medication

Birch triterpenes, sold under the brand name Filsuvez, is an extract of birch bark used as a topical medication for the treatment of epidermolysis bullosa. The active ingredients are triterpenes extracted from the outer bark of silver birch and downy birch.

References

  1. ↑ Reference GH. "dystrophic epidermolysis bullosa". Genetics Home Reference. Retrieved 3 April 2017.
  2. ↑ Bardhan A, Bruckner-Tuderman L, Chapple IL, Fine JD, Harper N, Has C, et al. (24 September 2020). "Epidermolysis bullosa". Nature Reviews Disease Primers. 6 (1): 78. doi:10.1038/s41572-020-0210-0. ISSN   2056-676X. PMID   32973163. S2CID   221861310.
  3. ↑ Pittman T (21 April 2015). "'Butterfly Child' With Rare, Painful Condition Displays Strength That Will Blow You Away". Huffington Post. Retrieved 14 July 2017.
  4. ↑ , Recessive dystrophic epidermolysis bullosa results in painful small fibre neuropathy.
  5. ↑ Schräder NHB, Yuen WY, Jonkman MF (2018). "Pain Quality Assessment Scale for Epidermolysis Bullosa". Acta Derm Venereol. 98 (3): 346–349. doi: 10.2340/00015555-2827 . PMID   29057428.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  6. ↑ Varki R, Sadowski S, Uitto J, Pfendner E (March 2007). "Epidermolysis bullosa. II. Type VII collagen mutations and phenotype–genotype correlations in the dystrophic subtypes". Journal of Medical Genetics . 44 (3): 181–92. doi:10.1136/jmg.2006.045302. PMC   2598021 . PMID   16971478.
  7. ↑ Pfendner EG, Lucky AW (13 September 2018), "Dystrophic Epidermolysis Bullosa", GeneReviews® [Internet], University of Washington, Seattle, PMID   20301481 , retrieved 29 October 2024
  8. ↑ Csikós M, Szőcs HI, Lászik A, Mecklenbeck S, Horváth A, Kárpáti S, et al. (May 2005). "High frequency of the 425A→G splice-site mutation and novel mutations of the COL7A1 gene in central Europe: significance for future mutation detection strategies in dystrophic epidermolysis bullosa". British Journal of Dermatology . 152 (5): 879–886. doi:10.1111/j.1365-2133.2005.06542.x. PMID   15888141. S2CID   44394902.
  9. ↑ Mihai S, Sitaru C (May–June 2007). "Immunopathology and molecular diagnosis of autoimmune bullous diseases". Journal of Cellular and Molecular Medicine . 11 (3): 462–481. doi:10.1111/j.1582-4934.2007.00033.x. PMC   3922353 . PMID   17521373.
  10. ↑ Fine JD, Eady RA, Bauer EA, Bauer JW, Bruckner-Tuderman L, Heagerty A, et al. (2008). "The classification of inherited epidermolysis bullosa (EB): Report of the Third International Consensus Meeting on Diagnosis and Classification of EB". Journal of the American Academy of Dermatology . 58 (6): 931–950. doi:10.1016/j.jaad.2008.02.004. PMID   18374450.
  11. ↑ James, Berger & Elston 2005 , p. 558
  12. 1 2 Freedberg et al. 2003 , p. 601
  13. ↑ Freedberg et al. 2003
  14. ↑ Rapini, Bolognia & Jorizzo 2007 , p. 458
  15. ↑ James, Berger & Elston 2005 , pp. 558–9
  16. ↑ Commissioner Oo (19 May 2023). "FDA Approves First Topical Gene Therapy for Treatment of Wounds in Patients with Dystrophic Epidermolysis Bullosa". FDA. Retrieved 1 June 2023.
  17. ↑ "Vyjuvek". U.S. Food and Drug Administration (FDA). 19 May 2023.
  18. ↑ "Filsuvez- birch triterpenes gel". DailyMed. 14 February 2024. Retrieved 3 March 2024.
  19. 1 2 3 4 "Filsuvez EPAR". European Medicines Agency (EMA). 13 April 2022. Archived from the original on 6 July 2022. Retrieved 6 July 2022. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  20. ↑ "Filsuvez, common birch bark extract" (PDF). European Medicines Agency (EMA). Archived (PDF) from the original on 15 July 2024. Retrieved 1 February 2024.
  21. ↑ "Novel Drug Approvals for 2023". U.S. Food and Drug Administration (FDA). 19 December 2023. Archived from the original on 21 January 2023. Retrieved 22 December 2023.
  22. ↑ "Drug Trials Snapshots: Filsuvez". U.S. Food and Drug Administration (FDA). 18 December 2023. Archived from the original on 15 July 2024. Retrieved 14 July 2024.PD-icon.svg This article incorporates text from this source, which is in the public domain.

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