Generalized Dominant Dystrophic Epidermolysis Bullosa

Watchlist

(log in to enable)

Retrieved

2021-01-23

Source

Orphanet

Trials

—

Genes

COL7A1, IGAN1

Drugs

Allantoin, Allogeneic adipose-derived adult mesenchymal stem cells contained in a fibrin-based bioengineered dermis, Allogeneic human dermal fibroblasts

Allantoin, Allogeneic adipose-derived adult mesenchymal stem cells contained in a fibrin-based bioengineered dermis, Allogeneic human dermal fibroblasts, Allogeneic skin-derived ABCB5-positive mesenchymal stem cells, Antisense oligonucleotide targeting exon 73 in the COL7A1 gene, Autologous genetically modified human dermal fibroblasts, Autologous skin equivalent graft composed of keratinocytes and fibroblasts genetically corrected by CRISPR/Cas9-mediated excision of mutation-carrying COL7A1 exon 80, Bilayer engineered skin composed of keratinocytes (patient autologous) and fibroblasts (donor allogeneic) in a plasma matrix, Diacerein, Dry extract from Betulae cortex (birch bark), Ex-vivo-expanded autologous fibroblasts transduced with lentiviral vector containing the COL7A1 gene, Ex-vivo-expanded autologous keratinocytes transduced with retroviral vector containing the COL7A1 gene, Expanded Allogeneic Human Dermal Fibroblasts In Hypothermosol(R)-Frs, Human dermal fibroblasts cultured on a bioresorbable polyglactin mesh, Losartan, Recombinant human alpha 1 chain homotrimer of type VII collagen, Recombinant human collagen alpha-1 (VII) chain homo-trimer (rC7), Skin equivalent graft genetically corrected with a COL7A1-encoding SIN retroviral vector, ex-vivo-expanded autologous human keratinocytes containing epidermal stem cells transduced with a COL7A1-encoding retroviral vector

Interested in hearing about new therapies?

Generalized dominant dystrophic epidermolysis bullosa (DDEB-gen) is a subtype of dystrophic epidermolysis bullosa (DEB, see this term), formerly known as DDEB, Pasini and Cockayne-Touraine types, characterized by generalized blistering, milia formation, atrophic scarring, and dystrophic nails.

Epidemiology

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 (see these terms) may need to be considered.

Clinical description

The clinical picture is milder than that of the autosomal recessive generalized EB forms. DDEB-gen manifests usually at birth with the development of blisters, primarily affecting the limbs. Aplasia cutis congenita (congenital absence of the skin) can also be observed, more frequently on the lower part of the legs. Blisters heal by developing numerous milia and atrophic scars, particularly evident on the elbows, knees, and backs of hands. Multiple ivory-white colored papules and plaques, known as albopapuloid lesions, may occur, more frequently on the trunk. Nail dystrophy, always present, can lead to loss of nail plates. Blisters develop in the mucosa, mainly in the oral cavity and, less commonly, the esophagus, where they can cause strictures. Dental caries are relatively frequent. Corneal and genitourinary tract involvement, anemia, and growth delay are rare.

Etiology

DDEB-gen is caused by mutations within the type VII collagen gene (COL7A1) that lead to an alteration of function or a reduction in the amount 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 showing a cleavage plane located below the lamina densa of the cutaneous basement membrane zone. 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, bullous impetigo, incontinentia pigmenti, linear IgA bullous dermatosis, bullous pemphigoid (see these terms) may need to be considered.

Antenatal diagnosis

DNA-based prenatal diagnosis is possible for at risk pregnancies.

Genetic counseling

DDEB-gen follows an autosomal dominant pattern of inheritance.

Management and treatment

Management is preventive: protective padding of the skin and appropriate lifestyle measures reduce blistering, and careful wound care prevents secondary infection and reduces scarring. Oral hygiene is important for the management of caries. When present, esophageal strictures can be treated by balloon dilatation with fluoroscopic guidance. In a minority of patients, a follow-up by a dietitian can be required to evaluate nutritional requirements.

Prognosis

Life expectancy is normal.