Epidermolysis bullosa

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Epidermolysis bullosa
Other namesButterfly children [1]
Iraqi-boy-epidermolysis bullosa-090216-M-8096M-001.jpg
A five-year-old boy displaying characteristic blisters of epidermolysis bullosa
Specialty Dermatology
Symptoms Painful skin blisters [2] [3]
Complications Esophageal narrowing, squamous cell skin cancer, amputations [4] [5]
Usual onsetAt birth [5]
DurationOften lifelong [5]
Types Epidermolysis bullosa simplex, dystrophic epidermolysis bullosa, junctional epidermolysis bullosa, Kindler syndrome [2]
Causes Genetic [2]
Diagnostic method Skin biopsy, genetic testing [6]
Differential diagnosis Bullous pemphigoid, pemphigus vulgaris, friction blisters, insect bites [5]
Treatment Wound care, pain control, controlling infections, nutritional support [2]
Prognosis Death usually occurs during early adulthood
Frequencyaround 1 in 500,000 [5]

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. [7] Inherited EB is a rare disease with a prevalence in the United States of 8.2 per million live births. [8] 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.[ medical citation needed ]

Contents

EB is due to a mutation in at least one of 16 different genes. Some types are autosomal dominant while others are autosomal recessive. [2] The underlying mechanism is a defect in attachment between or within the layers of the skin. Loss or diminished function of type VII collagen leads to weakness in the structural architecture of the dermal–epidermal junction (DEJ) and mucosal membranes. [9] There are four main types: epidermolysis bullosa simplex (EBS), dystrophic epidermolysis bullosa (DEB), junctional epidermolysis bullosa (JEB), and Kindler syndrome. The diagnosis is suspected based on symptoms and confirmed by skin biopsy or genetic testing.

There is no cure for the condition. Management involves wound care, pain control, controlling infections, nutritional support, and prevention and treatment of complications. [7] About half a million people are affected globally. [5] It occurs equally commonly in males and females. [10]

Classification

Epidermolysis bullosa refers to a group of disorders that involve the formation of blisters following trivial trauma. Over 300 mutations have been identified in this condition. [11] They have been classified into the following types: [12] [13] : 596 

Epidermolysis bullosa simplex

Epidermolysis bullosa simplex (EBS) is a form of EB that causes blisters at the site of rubbing. It typically affects the hands and feet, and is typically inherited in an autosomal dominant manner, affecting the keratin genes KRT5 and KRT14. Therefore, there is a failure in keratinization, which affects the integrity and the ability of the skin to resist mechanical stresses.[ citation needed ]

Junctional epidermolysis bullosa

Junctional epidermolysis bullosa (JEB) is an inherited disease affecting laminin and collagen. This disease is characterized by blister formation within the lamina lucida of the basement membrane zone [13] : 599  and is inherited in an autosomal recessive manner. It also presents with blisters at the site of friction, especially on the hands and feet, and has variants that can occur in children and adults. Less than one person per million people is estimated to have this form of EB. [14]

Dystrophic epidermolysis bullosa

Dystrophic epidermolysis bullosa (DEB) is an inherited variant affecting the skin and other organs. DEB is caused by genetic defects (or mutations) within the human COL7A1 gene encoding the protein type VII collagen (collagen VII). [15] DEB-causing mutations can be either autosomal dominant or autosomal recessive. Epidermolysis bullosa pruriginosa and albopapuloid epidermolysis bullosa (Pasini disease) are rare subtypes of this disease. [16]

Other genetic variants

OMIM NameLocusGene
609638 epidermolysis bullosa, lethal acantholytic 6p24 DSP

Epidermolysis bullosa acquisita

Acral peeling

Pathophysiology

The human skin consists of two layers: an outermost layer called the epidermis and a layer underneath called the dermis. In individuals with healthy skin, there are protein anchors between these two layers (Dermo epidermal junction) that prevent them from moving independently from one another (shearing). In people born with EB, the two skin layers lack the protein anchors that hold them together, resulting in extremely fragile skin—even minor mechanical friction (like rubbing or pressure) or trauma will separate the layers of the skin and form blisters and painful sores. [17] EB individuals manifest unremitting skin blistering that evolves into chronic wounds, inflammation, and fibrosis. [18] People with EB have compared the sores with third-degree burns. Furthermore, as a complication of the chronic skin damage, people with EB have an increased risk of malignancies (cancers) of the skin. [19] Virtually any organ lined or covered by epithelium may be injured in inherited EB. External eye, esophagus, upper airway, and genitourinary tract are the epithelial surfaced tissues that are at particular risk. [20]

Diagnosis

EB can be diagnosed either by a skin (punch) biopsy at the edge of a wound with immunofluorescent mapping, or via blood sample and genetic testing.[ citation needed ]

Treatment

Treatment of the epidermolysis bullosa by transplantation of laminin5 modified stem cells Treatment of the epidermolysis bullosa by transplantation of laminin5 modified stem cells..jpg
Treatment of the epidermolysis bullosa by transplantation of laminin5 modified stem cells

Research has focused on changing the mixture of keratins produced in the skin. There are 54 known keratin genes—of which 28 belong to the type I intermediate filament genes and 26 to type II—which work as heterodimers. Many of these genes share substantial structural and functional similarity, but they are specialized to cell type and/or conditions under which they are normally produced. If the balance of production could be shifted away from the mutated, dysfunctional keratin gene toward an intact keratin gene, symptoms could be reduced. For example, sulforaphane, a compound found in broccoli, was found to reduce blistering in a mouse model to the point where affected pups could not be identified visually, when injected into pregnant mice (5 μmol/day = 0.9 mg) and applied topically to newborns (1 μmol/day = 0.2 mg in jojoba oil). [21]

As of 2008, clinical research at the University of Minnesota has explored allogeneic bone marrow transplantation for RD and junctional EB, treating a two-year-old child who is one of two brothers with EB. A second transplant has also been performed on the child's older brother. A Missouri boy has also successfully undergone the transplant, as well as a 5 year old boy from Alabama. So far there have been 12 successful transplants. [22] Another transplant is scheduled for a California baby. A clinical trial is planned for 30 subjects. [23] However, the immune suppression that bone marrow transplantation requires causes a risk of serious infections with large scale blisters and skin erosion. [24] Indeed, at least four people have died in the course of either preparation for or institution of bone marrow transplantation for EB, out of only a small group of patients treated so far. [24] The mechanism of action of this therapy is unclear as hematopoietic stem cells are not thought to contribute to epithelial lineages. Rather, it is speculated that cross-correction from tissue-resident graft-derived immune cells contributes to the observed clinical benefit. [25]

A pilot study performed in 2015 suggests that systemic granulocyte-colony stimulating factor (G-CSF) may promote increased wound healing in people with dystrophic EB. [26] Transplanting skin derived from genetically modified stem cells onto the wound surfaces has been studied with a report of improvements in one person. [27]

A 2017 clinical trial with male RDEB (recessive dystrophic EB) patients conducted successful grafting of type VII gene corrected keratinocytes (COL7A1 gene correction using retrovirus transduction), without any serious adverse effects. Type VII collage formation was observed at the dermis-epidermis junction in significant amounts. [28]

A 2020 study demonstrated the safe allogenic grafting of acellular dermal matrix/scaffolds in EB patients without any observed infection or necrosis and instead noted fewer required dressing changes, promoted wound healing, pain reduction, and an overall improvement in the quality of life of the patients. [29]

In 2022, a pharmaceutical gel made out of birch bark extract from Betula pendula and Betula pubescens was approved by the European Union as a treatment for epidermolysis bullosa. [30] [31]

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. [32] [33] The active ingredients are triterpenes extracted from the outer bark of silver birch (Betula pendula) and downy birch (Betula pubescens). [34]

The most common side effects include wound complications such as skin reactions at the application site, infections, pruritus (itching), and hypersensitivity. [33]

Birch triterpenes was approved for medical use in the European Union in June 2022, [33] and in the United States in December 2023. [35] [36]

Monitoring

The Epidermolysis Bullosa Disease Activity and Scarring index (EBDASI) is a scoring system that objectively quantifies the severity of EB. The EBDASI is a tool for clinicians and patients to monitor the severity of the disease. It has also been designed to evaluate the response to new therapies for the treatment of EB. The EBDASI was developed and validated by Professor Dedee Murrell and her team of students and fellows at the St George Hospital, University of New South Wales, in Sydney, Australia. It was presented at the International Investigative Dermatology congress in Edinburgh in 2013 and a paper-based version was published in the Journal of the American Academy of Dermatology in 2014. [37]

Prognosis

A 2014 study classified cases into three types—EBS, JEB and DEB—and reviewed their times of death. The first two types tended to die in infancy and the last in early adulthood. [38] In a survey of 11 families affected by the disease, lack of awareness of the disease by both the public and health care providers raised concerns about the care provided. [5]

Epidemiology

An estimated 20 per million live births are diagnosed with EB, [39] and 9 per million people in the general population have the condition. Of these cases, approximately 92% are EBS, 5% are DEB, 1% are JEB, and 2% are unclassified. Carrier frequency ranges from 1 in 333 for JEB, to 1 in 450 for DEB; the carrier frequency for EBS is presumed to be much higher than JEB or DEB.[ citation needed ]

The disorder occurs in every racial and ethnic group and affects both sexes. [40] [41]

Society and culture

In 2010, Emma Fogarty, a campaigner for DEBRA Ireland (the EB charity), was awarded a People of the Year Award. [42] Actor Colin Farrell has campaigned with Fogarty on behalf of affected people. [43]

In 2014, Pearl Jam lead vocalist Eddie Vedder together with his wife Jill McCormick co-founded the EB Research Partnership, [44] a non-profit organization dedicated to finding a cure for EB. [45] McCormick is childhood friends with Ryan Fullmer, whose son, Michael, was born with EB. Vedder, McCormick, Ryan Fullmer, and his wife Heather founded Heal EB. In 2014, they merged Heal EB with the Jackson Gabriel Research Foundation to create the EB Research Partnership. The EBRP hosts several annual fundraising events. To date, they have raised $12 million to fund research to find a cure. [46]

On 1 March 2019, heavyweight boxer Luis Ortiz was named an honorary ambassador for the EB community by the EB Research Partnership. Ortiz's daughter, Lismercedes, was born with EB. [47]

Television

The condition was brought to public attention in 2004 in the UK through the Channel 4 documentary The Boy Whose Skin Fell Off, chronicling the life and death of Jonny Kennedy, an Englishman with EB. [48] In the United States, HBO ran a documentary, My Flesh and Blood , in 2003.[ citation needed ] Additionally, the film Butterfly Girl follows Abigail Evans with the disease. [49] In Canada, The Sports Network's award-winning documentary on Jonathan Pitre led to extensive coverage on the boy's disease, treatment, and death. [50] [51]

Other names

Other terms used to describe those affected include "butterfly children" as the skin is fragile as a butterfly's wings, [52] "cotton wool babies", [53] [54] or "crystal skin children". [55]

Related Research Articles

<span class="mw-page-title-main">Epidermolytic hyperkeratosis</span> Medical condition

Epidermolytic ichthyosis (EI), is a severe form of dry scaly skin, that initially presents with redness, blisters, erosions, and peeling in a newborn baby. Hyperkeratosis typically develops several months later. Other symptoms include itch, painful fissures, strong body odor, and absence of sweat. Symptoms vary in severity and extent of skin involvement. The two main types are divided into one involving palms and soles and the other without.

Type II keratins constitutes the Type II intermediate filaments (IFs) of the intracytoplasmatic cytoskeleton, which is present in all mammalian epithelial cells. The type 2 cytokeratins consist of basic or neutral, high molecular weight proteins which in vivo are arranged in pairs of heterotypic Type I and Type II keratin chains, coexpressed during differentiation of simple and stratified epithelial tissues. It has been seen that Type II Keratins are developed before Type 1 keratins during human embryonic development.

<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.

DEBRA is the name of an international medical research charity dedicated to securing effective drug treatments and ultimately cures for every type of epidermolysis bullosa, with national groups in over 40 countries including in the United Kingdom and the United States.

Jonathan "Jonny" Kennedy was a British man who had a rare inherited condition known as dystrophic epidermolysis bullosa. Kennedy ultimately died of skin cancer, a complication of EB.

<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">Junctional epidermolysis bullosa (veterinary medicine)</span> Genetic disorder of horses

Junctional epidermolysis bullosa (JEB) is an inherited disorder that is also known as red foot disease or hairless foal syndrome. JEB is the result of a genetic mutation that inhibits protein production that is essential for skin adhesion. Therefore, tissues, such as skin and mouth epithelia, are affected. Blisters form over the entire body causing pain and discomfort, and open sores leave newborn foals highly susceptible to secondary infection. The condition can be categorized into two types of mutations: JEB1 and JEB2. JEB1 is found in Belgian Draft horses, as well as other related Draft breeds. In contrast, JEB2 is found in American Saddlebred horses.

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

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

<span class="mw-page-title-main">Genodermatosis</span> Genetic skin disease

Genodermatosis is a hereditary skin disease with three inherited modes including single gene inheritance, multiple gene inheritance and chromosome inheritance. There are many different types of genodermatosis; the prevalence of genodermatosis ranges from 1 per 6000 people to 1 per 500,000 people. Genodermatosis has influence on the texture, color and structure of skin cuticle and connective tissue, specific lesion site and clinical manifestations on the body vary depending on the type. In the spite of the variety and complexity of genodermatosis, there are still some common methods that can help people diagnose. After diagnosis, different types of genodermatosis require different levels of therapy including interventions, nursing interventions and treatments. Among that, research of therapy for some new, complex and rare types are still in the developing stage. The impact of genodermatosis not only can be seen in body but also can be seen in all aspects of patients' life, including but not limited to psychological, family life, economic conditions and social activities. Accordingly, the patients need treatment, support and help in these areas.

<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.

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.

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.

A coma blister, or coma bullae, is a skin lesion or blister that typically arises due to pressure in an individual with impaired consciousness. They vary in size, ranging from 4 to 5 centimeters in diameter, and may appear hemorrhagic or blood filled. Coma blisters are usually found in the extremities and trunk. These types of blisters have been associated with the overdose of central nervous system (CNS) depressants especially barbiturates, but also tricyclic antidepressants, hypnotics, benzodiazepines, opiates, antipsychotics, and alcohol. However, studies have found that coma blisters are not caused by the toxicity of these drugs, but due to hypoxia and external pressure on the comatose individual's skin from being immobilized. Coma blisters have been frequently found on individuals who have overdosed on drugs, but have also been found on individuals with chronic kidney failure, hypercalcemia, diabetic ketoacidosis, and a variety of neurologic conditions. Coma blisters are more frequent in adults and less common among children as demonstrated by the few cases published in literature.

Scioderm, acquired by Amicus Therapeutics in 2015, was a rare disease company focused on developing a treatment for Epidermolysis Bullosa (EB), a rare genetic disease characterized by extremely fragile skin and recurrent blister formation. There are currently no approved therapies for EB. Scioderm was developing a topical treatment known as SD-101, or Zorblisa, aimed at triggering wound reduction and closure, and a reduction in body surface area coverage of blisters and lesions.

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. ↑ Fine JD, Hintner H (2009). Life with Epidermolysis Bullosa (EB): Etiology, Diagnosis, Multidisciplinary Care and Therapy. Springer Science & Business Media. p. 242. ISBN   9783211792711. Archived from the original on 3 November 2021. Retrieved 21 November 2020.
  2. 1 2 3 4 5 "Epidermolysis bullosa". rarediseases.info.nih.gov. Archived from the original on 16 May 2018. Retrieved 16 May 2018.
  3. ↑ "Epidermolysis Bullosa". National Institute of Arthritis and Musculoskeletal and Skin Diseases. 11 April 2017. Archived from the original on 4 October 2017. Retrieved 16 May 2018.
  4. ↑ "Epidermolysis Bullosa". National Institute of Arthritis and Musculoskeletal and Skin Diseases. 11 April 2017. Archived from the original on 4 October 2017. Retrieved 16 May 2018.
  5. 1 2 3 4 5 6 7 Tabor A, Pergolizzi JV J, Marti G, Harmon J, Cohen B, Lequang JA (May 2017). "Raising Awareness Among Healthcare Providers about Epidermolysis Bullosa and Advancing Toward a Cure". The Journal of Clinical and Aesthetic Dermatology. 10 (5): 36–48. PMC   5479476 . PMID   28670357.
  6. ↑ "Epidermolysis Bullosa". National Institute of Arthritis and Musculoskeletal and Skin Diseases. 11 April 2017. Archived from the original on 4 October 2017. Retrieved 16 May 2018.
  7. 1 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. Archived from the original on 18 November 2020. Retrieved 26 September 2020.
  8. ↑ FINE JD, JOHNSON LB, WEINER M, STEIN A, CASH S, DeLEOZ J, et al. (November 2004). "Genitourinary Complications of Inherited Epidermolysis Bullosa: Experience of the National Epidermylosis Bullosa Registry and Review of the Literature". Journal of Urology. 172 (5): 2040–2044. doi:10.1097/01.ju.0000143200.86683.2c. PMID   15540785.
  9. ↑ Vanden Oever M, Twaroski K, Osborn MJ, Wagner JE, Tolar J (1 November 2017). "Inside out: regenerative medicine for recessive dystrophic epidermolysis bullosa". Pediatric Research. 83 (1–2): 318–324. doi: 10.1038/pr.2017.244 . ISSN   0031-3998. PMID   29593249. S2CID   4447720.
  10. ↑ "Epidermolysis Bullosa". National Institute of Arthritis and Musculoskeletal and Skin Diseases. 11 April 2017. Archived from the original on 4 October 2017. Retrieved 16 May 2018.
  11. ↑ Koshida S, Tsukamura A, Yanagi T, Nakahara S, Takeuchi Y, Kato T, et al. (2013). "Hallopeau-Siemens dystrophic epidermolysis bullosa due to homozygous 5818delC mutation in the COL7A gene". Pediatr Int. 55 (2): 234–7. doi:10.1111/j.1442-200X.2012.03638.x. PMID   23679163. S2CID   24238328.
  12. ↑ James, William; Berger, Timothy; Elston, Dirk (2005). Andrews' Diseases of the Skin: Clinical Dermatology. (10th ed.). Saunders. ISBN   0-7216-2921-0.
  13. 1 2 Freedberg, et al. (2003). Fitzpatrick's Dermatology in General Medicine. (6th ed.). McGraw-Hill. ISBN   0-07-138076-0.
  14. ↑ "Junctional epidermolysis bullosa". Genetics Home Reference. NIH. Archived from the original on 12 October 2013. Retrieved 11 October 2013.
  15. ↑ Varki R, Sadowski S, Uitto J, Pfendner E (1 March 2007). "Epidermolysis bullosa. II. Type VII collagen mutations and phenotype–genotype correlations in the dystrophic subtypes". Journal of Medical Genetics. 44 (3): 181–192. doi:10.1136/jmg.2006.045302. ISSN   0022-2593. PMC   2598021 . PMID   16971478.
  16. ↑ McGRATH J, Schofield O, Eady R (1 May 1994). "Epidermolysis bullosa pruriginosa: dystrophic epidermolysis bullosa with distinctive clinicopathological features". British Journal of Dermatology. 130 (5): 617–625. doi:10.1111/j.1365-2133.1994.tb13109.x. ISSN   1365-2133. PMID   8204470. S2CID   5958915.
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  19. ↑ Mallipeddi R (November 2002). "Epidermolysis bullosa and cancer". Clinical and Experimental Dermatology. 27 (8): 616–623. doi:10.1046/j.1365-2230.2002.01130.x. ISSN   0307-6938. PMID   12472531. S2CID   40006559. Archived from the original on 8 March 2022. Retrieved 8 March 2022.
  20. ↑ Anderson TR, Slotkin TA (15 August 1975). "Maturation of the adrenal medulla--IV. Effects of morphine". Biochemical Pharmacology. 24 (16): 1469–1474. doi:10.1016/0006-2952(75)90020-9. ISSN   1873-2968. PMID   7.
  21. ↑ Kerns ML, DePianto D, Dinkova-Kostova AT, Talalay P, Coulombe PA (4 September 2007). "Reprogramming of keratin biosynthesis by sulforaphane restores skin integrity in epidermolysis bullosa simplex". Proceedings of the National Academy of Sciences. 104 (36): 14460–14465. Bibcode:2007PNAS..10414460K. doi: 10.1073/pnas.0706486104 . ISSN   0027-8424. PMC   1964870 . PMID   17724334.
  22. ↑ "My Skin is Killing Me - Epidermolysis Bullosa | Extraordinary People Documentary | Reel Truth". YouTube . 29 June 2018.
  23. ↑ Josephine Marcotty (3 July 2008). "Long-shot stem-cell treatment gives two brothers a future". Star Tribune. Archived from the original on 11 February 2009. Retrieved 22 July 2008.
  24. 1 2 Souillet G, Guffon N, Maire I, Pujol M, Taylor P, Sevin F, et al. (10 June 2003). "Outcome of 27 patients with Hurler's syndrome transplanted from either related or unrelated haematopoietic stem cell sources". Bone Marrow Transplantation. 31 (12): 1105–17. doi:10.1038/sj.bmt.1704105. PMID   12796790. S2CID   30326472.
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  26. ↑ Fine JD, Manes B, Frangoul H (July 2015). "Systemic granulocyte colony-stimulating factor (G-CSF) enhances wound healing in dystrophic epidermolysis bullosa (DEB): Results of a pilot trial". Journal of the American Academy of Dermatology. 73 (1): 56–61. doi:10.1016/j.jaad.2015.04.015. ISSN   0190-9622. PMID   25956659.
  27. ↑ Hirsch T, Rothoeft T, Teig N, Bauer JW, Pellegrini G, De Rosa L, et al. (16 November 2017). "Regeneration of the entire human epidermis using transgenic stem cells". Nature. 551 (7680): 327–332. Bibcode:2017Natur.551..327H. doi:10.1038/nature24487. PMC   6283270 . PMID   29144448.
  28. ↑ Siprashvili Z, Nguyen NT, Gorell ES, Loutit K, Khuu P, Furukawa LK, et al. (1 November 2016). "Safety and Wound Outcomes Following Genetically Corrected Autologous Epidermal Grafts in Patients With Recessive Dystrophic Epidermolysis Bullosa". JAMA. 316 (17): 1808–1817. doi:10.1001/jama.2016.15588. ISSN   1538-3598. PMID   27802546. Archived from the original on 8 March 2022. Retrieved 8 March 2022.
  29. ↑ Pliszczyński J, Nita M, Kowalewski C, Woźniak K, Eljaszewicz A, Moniuszko M, et al. (September 2020). "Transplantation of a New Biological Product in Rare Diseases, Such as Epidermolysis Bullosa: Response and Clinical Outcome". Transplantation Proceedings. 52 (7): 2239–2243. doi:10.1016/j.transproceed.2020.02.119. ISSN   1873-2623. PMID   32334796. S2CID   216555379. Archived from the original on 8 March 2022. Retrieved 8 March 2022.
  30. ↑ "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.
  31. ↑ "European Commission Approves Filsuvez for the treatment of Dystrophic and Junctional EB" (Press release). Amryt Pharma plc. 23 June 2022. Archived from the original on 23 June 2022. Retrieved 6 July 2022.
  32. ↑ "Filsuvez- birch triterpenes gel". DailyMed. 14 February 2024. Retrieved 3 March 2024.
  33. 1 2 3 "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.
  34. ↑ "Filsuvez, common birch bark extract" (PDF). European Medicines Agency (EMA). Archived (PDF) from the original on 15 July 2024. Retrieved 1 February 2024.
  35. ↑ "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.
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  37. ↑ Development, reliability, and validity of a novel Epidermolysis Bullosa Disease Activity and Scarring index (EBDASI). 2014. Loh CH, Kim J, Su JC, Daniel BS, Venugopal SS, Rhodes LM, Intong LR, Law MG, Murrell DF. January 2014. JAAD, 70, 1pp.
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