Epidermolysis Bullosa

Excerpt

Epidermolysis bullosa (EB) defines a prototypic group of rare, inherited dermatoses, characteristically featuring skin fragility secondary to structural defects in the dermo-epidermal junction. This skin fragility creates an impaired tolerance to mechanical stress. Trivial mechanical trauma and shear stress can provoke skin blistering, erosions, and ulceration. This places patients with certain forms of epidermolysis bullosa at a greater risk of infection, disabling deformities secondary to heavy scarring, and aggressive cutaneous malignancy, leading to early fatality in some cases. An extensive phenotypic range is described, ranging from fragility and blistering localized to areas of weight-bearing or pressure to widespread generalized involvement, including extracutaneous disease. Thus, certain subtypes of EB confer high morbidity, with a risk of increased mortality due to multi-system pathology.

Sixteen genes have been implicated in underpinning at least 30 observed epidermolysis bullosa subtypes. Each subtype features varying phenotypic severity and impact on morbidity and mortality. These subtypes have been organized into 4 major groups based on the ultrastructural plane within the dermo-epidermal junction that the defect impacts:

Epidermolysis Bullosa Simplex (EBS) comprises around 70% of all epidermolysis bullosa cases and features a fragility defect in the epidermis, mostly inherited in an autosomal dominant pattern.

Junctional Epidermolysis Bullosa (JEB) is an autosomal recessive fragility defect seen specifically within the lamina lucida and makes up around 5% of all epidermolysis bullosa cases.

Dystrophic Epidermolysis Bullosa (DEB) represents around 25% of all epidermolysis bullosa cases and may be autosomal dominant or recessive. Dystrophic epidermolysis bullosa features a fragility defect below the lamina densa of the basement membrane zone.

Kindler Epidermolysis Bullosa (KEB) is the rarest of the 4 major epidermolysis bullosa types inherited in an autosomal recessive pattern. The kindlin-1 protein is affected in Kindler epidermolysis bullosa, resulting in fragility in any plane of the dermo-epidermal junction. Around 400 cases have been reported worldwide.

Inherited epidermolysis bullosa is distinct from epidermolysis bullosa aquisita, a separate, non-inherited, immunobullous disorder characterized by antibodies against type VII collagen.