Autosomal recessive generalized dystrophic epidermolysis bullosa, intermediate form (ORPHA:89842)
A rare dystrophic epidermolysis bullosa (DEB) characterized by generalized cutaneous and mucosal blistering that is not associated with severe deformities.
Epidemiology
Its exact prevalence is unknown but this sub-type represents the second most common recessive DEB (RDEB), the first one being severe RDEB. The prevalence of all RDEB sub-types, with the exclusion of severe RDEB, has been estimated at 1/2,000,000 in the United States.
Clinical description
Under the term intermediate RDEB are grouped a spectrum of phenotypes, showing highly variable severity of the cutaneous and mucosal involvement. The disease manifests at birth or during the neonatal period with generalized blistering. Aplasia cutis congenita (congenital absence of the skin) can also be observed at birth. Healing of blisters results in the development of milia, atrophic scarring (less severe than in severe RDEB), dystrophic nails, and, occasionally, albopapuloid lesions (ivory-white colored, scar-like papules) and scalp abnormalities. In some patients, the scarring phenomena can lead to a certain degree of pseudosyndactyly and loss of nail plates. Extracutaneous involvement is similar but less severe than in severe RDEB with no hand/foot deformities associated with this disease. Oral cavity lesions and excessive dental caries are common. Patients have a lower risk of esophageal strictures and corneal injury than severe RDEB. Growth delay and anemia are rare. Genitourinary tract involvement is rare. The risk of developing squamous cell carcinomas (SCC) is also increased but less common than in severe RDEB and occurs later in adulthood.
Etiology
The disease is caused by mutations within the type VII collagen gene (COL7A1; 3p21.31) that lead to an alteration of function or a reduction in the amounts of collagen VII. This impairs collagen VII assembly into anchoring fibrils, which anchor the basement membrane to the underlying dermis. This in turn causes reduced skin resistance to minor trauma.
Diagnostic methods
Diagnosis is suspected at clinical examination and is confirmed by immunofluorescence antigen mapping and/or transmission electron microscopy on skin samples. Genetic testing confirms the diagnosis.
Differential diagnosis
The differential diagnosis includes other forms of EB. In the neonatal period, aplasia cutis congenita, herpes simplex infection, congenital erosive and vesicular dermatosis, epidermolytic ichthyosis, linear IgA bullous dermatosis, bullous pemphigoid, neonatal pemphigus and pemphigoid gestationis, bullous impetigo, and staphylococcal scalded skin syndrome may need to be considered.
Antenatal diagnosis
Antenatal diagnosis can be recommended in families with this RDEB subtype, depending on the individual degree of severity.
Genetic counseling
The pattern of inheritance is autosomal recessive. Genetic counseling should be offered to at-risk couples (both individuals are carriers of a disease-causing mutation) informing them of the 25% risk of having an affected child at each pregnancy.
Management and treatment
Management is preventive: protective padding of the skin reduces blistering and careful wound care prevents secondary infection and reduces scarring. Oral hygiene is important for management of caries. Nutritional requirements should be evaluated by a dietitian. Esophageal strictures are treated by balloon dilatation with fluoroscopic guidance. A regular follow-up is necessary for the surveillance of SCC. The treatment of SCC is surgical and involves full-thickness excision with wide margins.
Prognosis
In most cases, life expectancy is normal. However, there is an increased risk of development of metastasizing squamous cell carcinomas with a cumulative risk of mortality of 21.5% by age 55.

                            Last update: 
                            May 2021


                            - Expert reviewer(s): 
                            Pr Carmen SALAVASTRU | ERN-Skin*


                                * European Reference Network