Epidermolysis bullosa

In medicine (dermatology) Epidermolysis bullosa (EB) is a rare genetic disease characterized by the presence of extremely fragile skin and recurrent blister formation, resulting from minor mechanical friction or trauma. This condition is not contagious. 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 English sufferer Jonny Kennedy.

Forms

There are three main forms of inherited EB. These different subtypes are defined by the depth of blister location within the skin layers, and the location of the dissolution of the skin.

EB Simplex (EBS) -- ABOVE the basement membrane

Blister formation of EB simplex is within the basal keratinocyte of the epidermis. Sometimes EB simplex is called epidermolytic. There are four subtypes of EBS:

EBS - Weber-Cockayne (EBS-WC)
EBS - Koebner (EBS-K)
EBS - Dowling-Meara (EBS-DM) -- caused by missense mutation in KRT5 (E477K) or one of two missense mutations in KRT14 (R125C and R125H)
EBS - Mottled Pigmentation (EBS-MP) - caused by one missense mutation in KRT5 (I161S) or by missense mutations in the plectin gene (Koss-Harnes et al., 1997;Koss-Harnes et al., 2002).

Junctional EB (JEB) -- THROUGH the basement membrane

Blister formation in Junctional EB is seen at the level of the lamina lucida within the basement membrane zone.

Dystrophic EB (DEB) -- UNDER the basement membrane

Dystrophic EB (DEB) forms which can lead to scarring occur in a deeper tissue level; the sub-lamina densa region(the beneath the lamina densa) within the upper dermis. The disease DEB is caused by genetic defects (or mutations) within the molecule type VII collagen (collagen VII). Collagen VII is a very large molecule (780 nm) that dimerizes to forms 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.

Collagen VII is also present in the epithelial tissue of the esophagus, which leads to chronic scarring, webbing, and obstruction. Affected individuals are often severely malnourished due to trauma to the oral and esophageal mucosa and require feeding tubes for nutrition. They also suffer from iron-deficiency anemia of uncertain origin, which leads to chronic fatigue.

Open wounds on the skin heal slowly and are particularly susceptible to infection. Many individuals bathe in a bleach and water mixture to fight off these infections.

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.

Epidemiology

An estimated 2 out of every 100,000 live births are affected with some type of EB. The disorder occurs in every racial and ethnic group throughout the world and affects both sexes equally.

External links

DebRA - the Dystrophic Epidermolysis Bullosa Research Association of America
DebRA - UK site. There are similar sites in Canada, Australia, New Zealand and Ireland to find more local information and support.
EBMRF - Epidermolysis Bullosa Medical Research Foundation
NIH article about EB
Genetic basis of EBS
Medical details of EB
emedicine.com's article on epidermolysis bullosa

Congenital genetic disorders | Rare diseases