Epidermolysis bullosa

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Epidermolysis bullosa
Classification and external resources
Iraqi-boy-epidermolysis bullosa-090216-M-8096M-001.jpg
A five-year-old boy with congenital epidermolysis bullosa
ICD-10 Q81
ICD-9 757.39
DiseasesDB 31928 33248 29580 4338 32146 31929 29579 4334 33249 33564
MedlinePlus 001457
eMedicine derm/124
Patient UK Epidermolysis bullosa
MeSH D004820

Epidermolysis bullosa (EB) is an inherited connective tissue disease causing blisters in the skin and mucosal membranes, with an incidence of 1 in 50,000. It is a result of a defect in anchoring between the epidermis and dermis, resulting in friction and skin fragility. Its severity ranges from mild to lethal.

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.[1] In the United States, the same could be said of the HBO documentary My Flesh and Blood from 2003.

"Butterfly Children" is a term often used to describe younger patients (because the skin is said to be as fragile as a butterfly’s wings,[2] "Cotton Wool Babies",[3][4] or (in South America) as "Crystal Skin Children".[5]

Classification[edit]

Epidermolysis bullosa refers to a group of inherited disorders that involve the formation of blisters following trivial trauma. Over 300 mutations have been identified in this condition.[6] They have been classified into the following types:[7][8]:596

Epidermolysis bullosa simplex[edit]

Epidermolysis bullosa simplex is a form of epidermolysis bullosa 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.

Junctional epidermolysis bullosa[edit]

Junctional epidermolysis bullosa is an inherited disease affecting laminin and collagen. This disease is characterised by blister formation within the lamina lucida of the basement membrane zone[8]: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 per million people are estimated to have this form of epidemolysis bullosa.[9]

Dystrophic epidermolysis bullosa[edit]

Dystrophic epidermolysis bullosa is an inherited variant affecting the skin and other organs. "Butterfly children" is the term given to those born with the disease, as their skin is seen to be as delicate and fragile as a butterfly's wings. Dystrophic epidermolysis bullosa is caused by genetic defects (or mutations) within the human COL7A1 gene encoding the protein type VII collagen (collagen VII).[10] DEB-causing mutations can be either autosomal dominant or autosomal recessive.

Other genetic[edit]

OMIM Name Locus Gene
609638 epidermolysis bullosa, lethal acantholytic 6p24 DSP

Other[edit]

Pathophysiology[edit]

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 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 only minor mechanical friction (like rubbing or pressure) or trauma will separate the layers of the skin and form blisters and painful sores. Sufferers of EB have compared the sores with third-degree burns.[11] Furthermore, as a complication of the chronic skin damage, people suffering from EB have an increased risk of malignancies (cancers) of the skin.

Treatment[edit]

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

Recent 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).[12]

Current clinical research at the University of Minnesota has included a bone marrow transplant to a 2-year-old child who is one of 2 brothers with EB. The procedure was successful, strongly suggesting that a cure may have been found. A second transplant has also been performed on the child's older brother, and a third transplant is scheduled for a California baby. The clinical trial will ultimately include transplants to 30 subjects.[13] However, the severe immunosuppression that bone marrow transplantation requires causes a significant risk of serious infections in patients with large scale blisters and skin erosions. Indeed, at least four patients have died in the course of either preparation for or institution of bone marrow transplantation for epidermolysis bullosa, out of only a small group of patients treated so far.

Epidemiology[edit]

An estimated 50 in 1 million live births are diagnosed with EB, and 9 in 1 million sufferers are in the general population. Of these cases, approximately 92% are epidermolysis bullosa simplex (EBS), 5% are dystrophic epidermolysis bullosa (DEB), 1% are junctional epidermolysis bullosa (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 throughout the world and affects both sexes.[14][15]

Monitoring[edit]

The Epidermolysis Bullosa Activity and Scarring index (EBDASI) is a scoring system that objectively quantifies the severity of epidermolysis bullosa. 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 American Academy of Dermatology in 2014.[16]

See also[edit]

References[edit]

  1. ^ "Series 1 - The Boy Whose Skin Fell Off". Channel 4. 2004. Retrieved 2009-02-28. 
  2. ^ Roddy Isles, Head of Press (2005-05-12). "Dundee Scientists on road to cure for "Butterfly Children" condition". University of Dundee. Retrieved 2008-07-22. 
  3. ^ Suellen Hinde, Health reporter (2006-11-26). "Little girl's life of pain". HeraldSun.com.au. Retrieved 2008-07-22. 
  4. ^ By Robyn Gobert, Past President of DEBRA Australia Inc. (May 2002). "Times change - A family's story about living with EB". e-bility.com. Retrieved 2008-07-22. 
  5. ^ Gena Brumitt Gruschovnik, DEBRA International Executive Committee. "DEBRA Chile website". 
  6. ^ Koshida S, Tsukamura A, Yanagi T, Nakahara S, Takeuchi Y, Kato T, Tanaka T, Nakano H, Shimizu H (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
  7. ^ James, William; Berger, Timothy; Elston, Dirk (2005). Andrews' Diseases of the Skin: Clinical Dermatology. (10th ed.). Saunders. ISBN 0-7216-2921-0.
  8. ^ a b Freedberg, et al. (2003). Fitzpatrick's Dermatology in General Medicine. (6th ed.). McGraw-Hill. ISBN 0-07-138076-0.
  9. ^ "Junctional epidermolysis bullosa". Genetics Home Reference. NIH. Retrieved 11 October 2013. 
  10. ^ 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". J. Med. Genet. 44 (3): 181–92. doi:10.1136/jmg.2006.045302. PMC 2598021. PMID 16971478. 
  11. ^ Mary E. O'Brien, M.D. "Caroline". The Columbia Observer. Retrieved 2008-07-22. [dead link]
  12. ^ Michelle Kerns et al. (2007-09-04). "Reprogramming of keratin biosynthesis by sulforaphane restores skin integrity in epidermolysis bullosa simplex". Proc Natl Acad Sci U S A. 104 (36): 14460–14465. doi:10.1073/pnas.0706486104. PMC 1964870. PMID 17724334. 
  13. ^ Josephine Marcotty (2008-07-03). "Long-shot stem-cell treatment gives two brothers a future". Star Tribune. Retrieved 2008-07-22. 
  14. ^ M Peter Marinkovich, MD, Associate Professor, Department of Dermatology and Program in Epithelial Biology, Stanford University Medical Center; Jean Paul Ortonne, MD, Chair, Department of Dermatology, Professor, Hospital L'Archet, Nice University, France; Michael J Wells, MD, Associate Professor, Department of Dermatology, Texas Tech University Health Sciences Center; Van Perry, MD, Assistant Professor, Department of Medicine, Division of Dermatology, University of Texas Health Science Center; Joel M Gelfand, MD, MSCE, Medical Director, Clinical Studies Unit, Assistant Professor, Department of Dermatology, Associate Scholar, Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania; William D James, MD, Paul R Gross Professor of Dermatology, University of Pennsylvania School of Medicine; Vice-Chair, Program Director, Department of Dermatology, University of Pennsylvania Health System (December 3, 2007). "Epidermolysis Bullosa". Bullous Diseases. emedicine.com. Retrieved 2008-07-22. 
  15. ^ Ellen Pfendner, Jouni Uitto and Jo-David Fine (2000-11-07). "Epidermolysis Bullosa Carrier Frequencies in the US Population". Journal of Investigative Dermatology. nature.com. Retrieved 2008-07-22. 
  16. ^ Development, reliability, and validity of a novel Epidermolysis Bullosa 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.

External links[edit]