Recessive Dystrophic Epidermolysis Bullosa, Generalized Intermediate

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Retrieved

2021-01-23

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Orphanet

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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, Angiotensin (1-7), 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

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Recessive dystrophic epidermolysis bullosa (RDEB)-generalized other, also known as RDEB non-Hallopeau-Siemens type, is a subtype of DEB (see this term) 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 RDEB, the first one being severe generalized RDEB (RDEB- sev gen; see this term). The prevalence of all RDEB sub-types, with the exclusion of RDEB-sev gen, has been estimated at 1/2,040,816 in the United States.

Clinical description

Under the term RDEB-other 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 RDEB- sev gen), 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 generalized 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 RDEB-sev gen. Growth delay and anemia are uncommon. Genitourinary tract involvement is rare. Patients have an increased risk of developing squamous cell carcinomas (35.8% by age 50 according to the U.S. EB national registry).

Etiology

The disease is caused by mutations within the type VII collagen gene (COL7A1) 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 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, 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.

Antenatal diagnosis

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

Genetic counseling

Transmission is autosomal recessive.

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 according to the U.S. EB national registry.