6.1.3 Epidermolysis Bullosa

1.2 in 100000 live births worldwide; estimated 500000 cases worldwide (Orphan disease). Epidermolysis bullosa simplex the most common sub-type of epidermolysis diseases (>90%) followed by dystrophic epidermolysis bullosa (5%) and junctional epidermolysis bullosa (1-2%).

Several subtypes depending on location of defective protein and level of blister formation in the skin: epidermolysis bullosa simplex, junctional epidermolysis bullosa, dystrophic epidermolysis bullosa. Clinically mild and severe forms.

• Epidermolysis bullosa simplex: most cases are inherited in an autosomal dominant pattern, caused by defect in the genes encoding keratin 5 and keratin 14. Clinically it is characterized by blisters with an erythematous halo, caused by friction and exacerbated by sweating and excessive heat.

• Junctional epidermolysis bullosa: cleavage occurs within the lamina lucida at the dermo-epidermal junction. Most case are due to mutation in laminin genes-, collagen XVII or α6β4 integrin. The mode of inheritance is autosomal recessive, and the distribution of lesions can be localized or generalized. Clinically, it is characterized by blisters, erosions, skin dystrophy, hypoplasia of dental enamel and caries. On healing, the blisters leave atrophic scars.

• Dystrophic epidermolysis bullosa: caused by the mutation in collagen VII gene. Blisters may be localized or generalized, and the lesions hesitates in dystrophic scars. The inheritance pattern can be autosomal dominant or autosomal recessive (the more severe, but the less common). Clinically, milia and nail dystrophy are commonly observed, as well as the involvement of mucous membranes.

Epidermolysis bullosa simplex: intraepidermal cleavage (keratin 5 and 14 defects).

Junctional epidermolysis bullosa: cleavage at the dermo-epidermal junction (lamina lucida). Dystrophic epidermolysis bullosa: subepidermal cleavage (collagen VII).

Histology and immunofluorescence mapping allow for the identification of the plane of cleavage as well as determination of semiquantitative protein expression.

Other blistering disorders (pemphigoid, pemphigus, linear IgA bullous dermatosis, epidermolysis bullosa acquisita), peeling skin syndrome, congenital localized absence of skin, Bart’s syndrome (rare inherited disorder characterized by the localized absence of the skin, blister formation, and nail deformity; it is a variant of aplasia cutis congenita with epidermolysis bullosa), suction blisters and mechanical blisters by friction and trauma.

The treatment of inherited EB is mainly supportive. Intensive skin care, avoidance of pressure and friction. Prevention of secondary infections. No specific systemic therapy available. Treatments are mainly focused on the prevention of lesions and complications. There are currently two FDA-approved therapies for dystrophic epidermolysis bullosa: beremagene geperpavec is a herpes-simplex virus type 1 vector-based in vivo gene therapy. It contains two copies of COL7A1 cDNA under the control of the human cytomegalovirus immediate early promoter. The vector does not penetrate intact epidermis, and thus topical application is restricted to wounds. FFilsuvez® has been approved for use in EB by the FDA, EMA and UK Medicines and Healthcare Products Regulatory Agency. It is a topical wound healing therapy containing birch triterpenes as its active ingredients, which promote wound healing. Gene therapy of stem cells in combination with advanced tissue- engineering techniques for severe forms of junctional and dystrophic epidermolysis bullosa under development. Patient support groups very helpful. Prademagene zamikeracel.