Epidermolysis bullosa

Epidermolysis bullosa
Classification and external resources
ICD-10	Q81
ICD-9	757.39
DiseasesDB	31928 33248 29580 4338 32146 31929 29579 4334 33249 33564
eMedicine	derm/124
MeSH	D004820

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. It is caused by a mutation in the keratin or collagen gene.

As a result, the skin is extremely fragile. Minor mechanical friction or trauma will separate the layers of the skin and form blisters. People with this condition have an increased risk of cancers of the skin, and many will eventually be diagnosed with it as a complication of the chronic damage done to the skin.

The skin has two layers; the outer layer is called the epidermis and the inner layer the dermis. In individuals with healthy skin, there are protein anchors, made of collagen, between the 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, and any action that creates friction between the layers (like rubbing or pressure) will create blisters and painful sores. Sufferers of EB have compared the sores with third-degree burns.

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. In the United States, the same could be said of the powerful 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.

Children with the condition have also been described as "Cotton Wool Babies," and in South America, "Crystal Skin Children" is the term used.

Epidemiology

An estimated 50 in 1 million live births are diagnosed with EB, and 9 in 1 million are in population. 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 Junctional, to 1 in 450 for Dystrophic. Carrier frequency for Simplex is not indicated in this article, but 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.

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. However, the severe immunosuppression that bone marrow transplantation requires causes a significant risk of serious infections in patients with large scale blisters and 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 a small group of patients treated so far.

Classification

A five-year-old boy with congenital epidermolysis bullosa

Epidermolysis bullosa refers to a group of inherited disorders that involve the formation of blisters following trivial trauma, and which may be divided into the following types:

Epidermolysis bullosa simplex

• Epidermolysis bullosa simplex

• 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

• Junctional epidermolysis bullosa

• 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

• Dystrophic epidermolysis bullosa

• Dominant dystrophic epidermolysis bullosa (Cockayne-Touraine disease)
• Recessive dystrophic epidermolysis bullosa (Hallopeau-Siemens variant of epidermolysis bullosa)

Other genetic

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

Other

• Epidermolysis bullosa acquisita

Treatment

Recent research has focused on changing the mixture of keratins produced in the skin. There are 54 known keratin genes, 28 type I intermediate filament genes and 26 type II, which work as heterodimers. Many share substantial structural and functional similarity, but are specialized for different cell types or conditions under which they are normally produced. If a drug can shift the balance of production toward an intact keratin gene, symptoms can 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).

External links

• GeneReviews/NCBI/UW/NIH entry on Epidermolysis Bullosa Simplex
• Epidermolysis bullosa at the Open Directory Project
• Spendenprojekt zum Aufbau einer Hilfedatenbank für Schmetterlingskids