Dystrophic epidermolysis bullosa (ORPHA:303)
A group of inherited epidermolysis bullosa (EB) characterized by cutaneous and mucosal fragility resulting in blisters and superficial ulcerations that develop below the lamina densa of the cutaneous basement membrane and that heal with significant scarring and milia formation. Dystrophic epidermolysis bullosa (DEB) comprises four major and several rare sub-types with the three most common being intermediate dominant DEB, severe recessive DEB and intermediate recessive DEB.
Epidemiology
DEB is the second most common form of EB, the first being EB simplex. Based on recent data, the prevalence in Europe ranges between 1/120,000-350,000.
Clinical description
The clinical picture varies widely, ranging from mild localized to severe generalized involvement. Onset is usually at birth but a delayed onset in infancy, childhood or adolescence can also be observed in milder subtypes. Skin lesions, forming spontaneously or in response to friction, may show a generalized or a localized distribution, particularly on the hands, feet or pretibial areas. Healing of blisters is associated with atrophic or, more rarely, hypertrophic scarring, albopapuloid lesions, milia formation and dystrophic nails. Excessive scarring can lead to highly disabling hand/foot deformities. Mucosal involvement is common and most frequently manifests with oral cavity lesions and esophageal strictures. The eyes and the genitourinary tract can also be affected. Skin and mucosal involvement can lead to anemia, iron deficiency, osteopenia/osteoporosis, growth delay and, rarely, renal failure. DEB patients are also at a higher risk of occurrence of squamous cell carcinomas (SCC).
Etiology
DEB is caused by mutations in the COL7A1 (3p21.31) gene encoding type VII collagen. Mutations are either autosomal dominant (dominant DEB) or recessive (recessive DEB), and alter the function or reduce or disrupt the production of collagen VII. This impairs its assembly into anchoring fibrils that anchor the basement membrane to the underlying dermis, resulting in a cleavage plane below the lamina densa, within the upper papillary dermis. In the case of severe recessive DEB there is no collagen VII production.
Diagnostic methods
Diagnosis is suspected at clinical examination. It is confirmed by biopsy of skin samples by immunofluorescence antigen mapping and/or transmission electron microscopy (showing a blister cleavage plane beneath the lamina densa of the cutaneous basement membrane zone), and by COL7A1 mutation screening.
Differential diagnosis
The differential diagnosis includes other forms of EB. During the neonatal period and infancy, it may also include aplasia cutis congenita, herpes simplex infection, epidermolytic ichthyosis, bullous impetigo, staphylococcal scalded skin syndrome, linear IgA bullous dermatosis, bullous pemphigoid, neonatal pemphigus and pemphigoid gestationis. For rare forms of DEB with a late onset, differential diagnosis includes acquired skin disorders such as lichen planus or autoimmune bullous diseases.
Antenatal diagnosis
Antenatal diagnosis should be offered to affect families with recessive severe DEB.
Genetic counseling
Genetic counseling should be offered to affect families and depends on the inheritance type and form of DEB.
Management and treatment
Management is preventive and symptomatic and requires an inter- and multidisciplinary approach. Protective padding of the skin and careful wound care reduces blistering, scarring and prevents secondary infection. Treatment of pain and itching is highly warranted but partly limited in effectiveness. Physiotherapy and occupational therapy are necessary to delay gradual loss of mobility and autonomy. Hand deformities can be treated surgically, but have a high recurrence. Nutritional requirements should be evaluated by a dietitian and gastrostomy feeding may be necessary. Esophageal strictures are treated by balloon dilatation with fluoroscopic guidance. Transfusions, iron supplementation, and erythropoietin administration improve anemia and iron deficiency. A regular follow-up with complete skin checks and biopsies is necessary for the surveillance of SCC development. Psychological support should be offered.
Prognosis
Prognosis depends on the subtype. Patients with dominant DEB usually have a normal life expectancy. Patients with severe recessive DEB are at high risk of mortality primarily from metastatic SCC, less frequently from chronic renal failure, sepsis and dilated cardiomyopathy.

                            Last update: 
                            May 2021


                            - Expert reviewer(s): 
                            Pr Martin LAIMER | ERN-Skin*


                                * European Reference Network