Epidermolysis bullosa (EB) is an inherited connective tissue disease causing blisters in the skin and mucosal membranes, with an incidence of 1/50,000. Its severity ranges from mild to lethal.
| Epidermolysis bullosa | |
|---|---|
| Specialty | Medical genetics  |
The human skin consist 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.[1] Furthermore, as a complication of the chronic skin damage, people suffering from EB have an increased risk of malignancies (cancers) of the skin.
The condition was brought to public attention in the UK through the Channel 4 documentary The Boy Whose Skin Fell Off, chronicling the life and death of Jonny Kennedy, an English man with EB.[2] 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 [3] , "Cotton Wool Babies,",[4][5] or (in South America) as "Crystal Skin Children".[6]
Epidemiology
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.[7][8]
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.[9] 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.
Classification
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.[10] They have been classificated into the following types[11][12]: 596 :
Epidermolysis bullosa simplex (EBS)
-
- Generalized epidermolysis bullosa simplex (Koebner variant of generalized epidermolysis bullosa simplex)
- Localized epidermolysis bullosa simplex (Weber-Cockayne variant of generalized epidermolysis bullosa simplex)
- Epidermolysis bullosa herpetiformis (Dowling-Meara epidermolysis bullosa simplex)
- Epidermolysis bullosa simplex of Ogna
- Epidermolysis bullosa simplex with muscular dystrophy
- Epidermolysis bullosa simplex with mottled pigmentation
Junctional epidermolysis bullosa (JEB)
-
- Junctional epidermolysis bullosa gravis (Epidermolysis bullosa lethalis, Herlitz disease, Herlitz epidermolysis bullosa, Lethal junctional epidermolysis bullosa)
- Mitis junctional epidermolysis bullosa
- Generalized atrophic benign epidermolysis bullosa
- Cicatricial junctional epidermolysis bullosa
- Junctional epidermolysis bullosa with pyloric atresia
Dystrophic epidermolysis bullosa (DEB)
-
- Dominant dystrophic epidermolysis bullosa (Cockayne-Touraine disease)
- Recessive dystrophic epidermolysis bullosa (Hallopeau-Siemens variant of epidermolysis bullosa)
Other genetic
| OMIM | Name | Locus | Gene |
|---|---|---|---|
| Template:OMIM2 | epidermolysis bullosa, lethal acantholytic | 6p24 | DSP |
Other
Treatment
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).[13]
See also
References
- ^ Mary E. O'Brien, M.D. "Caroline". The Columbia Observer. Retrieved 2008-07-22. [dead link]
- ^ "Series 1 - The Boy Whose Skin Fell Off". Channel 4. 2004. Retrieved 2009-02-28.
- ^ 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.
- ^ Suellen Hinde, Health reporter (2006-11-26). "Little girl's life of pain". HeraldSun.com.au. Retrieved 2008-07-22.
- ^ By Robyn Gobert, Past President of DEBRA Australia Inc. (2002). "Times change - A family's story about living with EB". e-bility.com. Retrieved 2008-07-22.
{{cite web}}: Unknown parameter|month=ignored (help) - ^ Gena Brumitt Gruschovnik, DEBRA International Executive Committee. "DEBRA Chile website".
- ^ M Peter Marinkovich, MD, Associate Professor, Department of Dermatology and Program in Epithelial Biology, Stanford University Medical Center (December 3, 2007). "Epidermolysis Bullosa". Bullous Diseases. emedicine.com. Retrieved 2008-07-22.
{{cite web}}: Unknown parameter|coauthors=ignored (|author=suggested) (help)CS1 maint: multiple names: authors list (link) - ^ 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.
- ^ Josephine Marcotty (2008-07-03). "Long-shot stem-cell treatment gives two brothers a future". Star Tribune. Retrieved 2008-07-22.
- ^ 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
- ^ James, William; Berger, Timothy; Elston, Dirk (2005). Andrews' Diseases of the Skin: Clinical Dermatology. (10th ed.). Saunders. ISBN 0-7216-2921-0.
- ^ Freedberg, et al. (2003). Fitzpatrick's Dermatology in General Medicine. (6th ed.). McGraw-Hill. ISBN 0-07-138076-0.
- ^ Michael 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.
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