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Epidermolysis bullosa dystrophica

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(Redirected from Hallopeau–Siemens disease)

Epidermolysis bullosa dystrophica
Other namesDystrophic EB
The legs of an individual with dystrophic epidermolysis bullosa.
SpecialtyMedical genetics Edit this on Wikidata

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

"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

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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 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

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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

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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

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Classification

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Name Locus & 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, pretibial 3p21.3 (COL7A1) 131850
Epidermolysis bullosa pruriginosa 3p21.3 (COL7A1) 604129
Epidermolysis bullosa with congenital localized absence of skin and deformity of nails 3p21.3 (COL7A1) 132000
Transient bullous dermolysis of the newborn (TBDN) 3p21.3 (COL7A1) 131705

Treatment

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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

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This section is an excerpt from Birch triterpenes.[edit]
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 such as skin reactions at the application site, infections, pruritus (itching), and hypersensitivity.[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]

References

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  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. ^ [1], 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. ^ a b 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. ^ a b c "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. Public Domain This article incorporates text from this source, which is in the public domain.

Sources

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  • Freedberg IM, Eisen AZ, Wolff K, Austen KF, Goldsmith LA, Katz SI, eds. (2003). Fitzpatrick's Dermatology in General Medicine (6th ed.). McGraw-Hill. ISBN 978-0-07-138076-8.
  • James W, Berger T, Elston D (2005). Andrews' Diseases of the Skin: Clinical Dermatology (10th ed.). Saunders. ISBN 978-0-7216-2921-6.
  • Rapini RP, Bolognia JL, Jorizzo JL (2007). Dermatology: 2-Volume Set. St. Louis: Mosby. ISBN 978-1-4160-2999-1.
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