Fig. 1. Newly formed large blisters on the right hand	Fig. 2. Aspect after rupture of blisters on the left hand	Fig. 3. Extensive blistering on both feet	Fig. 4. Skin lesion on the left foot, reminiscent of aplasia cutis

Fig. 9. TEM: Blistering at the base of the basal lamina	Fig. 10. TEM: Basal lamina is attached to the detached epidermis	Fig. 11. TEM: No anchoring fibrils can be demon-strated	Fig. 12. Skin condition at discharge (age 6 weeks): presence of older and newer skin lesions	Fig. 13. Skin condition at discharge (age 6 weeks)

Discussion

Epidermolysis bullosa (EB), a heterogeneous group of genetic skin disorders, is characterized by fragility and formation of blisters following minor trauma. The group includes up to thirty clinical-genetic entities (1) with both autosomal recessive and autosomal dominant inheritance. The clinical manifestations vary widely from a severe, mutilating condition to a relatively mild disorder, with a marked variability within each major subtype (2). The most severe forms are multiorgan disorders with a poor prognosis (3).

Based on the level of tissue separation, EB can be described as simplex or epidermolytic (in case of blistering in the epidermis), junctional (within the lamina lucida of the basement membrane zone) and dystrophic or dermolytic (if located between basal lamina and dermis) (4). Currently specific mutations in ten distinct genes expressed within the cutaneous basement membrane zone (BMZ) are known. In the simplex forms, the disorders lie in genes coding for keratins, in the junctional ones mutations are found in the laminin genes or in the genes coding for other components of the basement membrane. In the dystrophic forms, the genes affected are normally responsible for the development of the anchoring fibrils (collagen VII). Precise diagnosis is based on morphological and histological examination of the skin, as well as molecular analysis. This allows for a prenatal diagnosis in pregnancies at risk (6).

Despite improved disease characterization, specific treatment is still missing. One major goal of symptomatic treatment is to reduce blistering and to enhance wound healing. Treatment of EB is therefore based on meticulous wound care. An international support organization for families and patients, called DebRA (Dystrophic epidermolysis bullosa Research Association), has been in existance for more than 20 years (see also www.debra.org). In the severe mutilating forms of EB, frequent complications include local skin infections, amputations as well as the occurrence of squamous cell carcinomas (5). In mouse models of EB, attempts at gene therapy are in progress (7).