Dystrophic Epidermolysis Bullosa

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Retrieved

2021-01-23

Source

Orphanet

Trials

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Genes

COL7A1, MMP1, GRIP1, STS, BMP1, COL1A1, EGFR, FN1, IFNG, IGFBP3, IL2, IL6, NHS, TNF, ERBIN

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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Dystrophic epidermolysis bullosa (DEB) is a form 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. It comprises ten sub-types with the three most common being generalized dominant DEB (DDEB), severe generalized recessive DEB (RDEB- sev gen) and RDEB generalized-other (see these terms).

Epidemiology

DEB is the second most common form of EB, the first being EB simplex. The overall reported prevalence varies from 1/49,000 inhabitants in Scotland to 1/420,168 in the United States.

Clinical description

The clinical picture varies widely, ranging from mild to severe. Onset is usually at birth but a delayed onset in infancy, childhood or adolescence can also be observed. 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 (''mitten deformities'' typical of RDEB- sev gen). 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 and growth delay. 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 the type VII collagen protein. Mutations in this gene alter the function, reduce or disrupt the production of collagen VII. This impairs its assembly into anchoring fibrils that anchor the basement membrane to the underlying dermis.

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 (see these terms). For rare forms of DEB with a late onset, differential diagnosis includes acquired skin disorders such as lichen planus.

Antenatal diagnosis

Prenatal genetic diagnosis can be performed for at-risk pregnancies by direct or indirect (linkage analysis) DNA mutational analysis if the causal mutation has been identified or not in the family respectively.

Genetic counseling

Transmission is autosomal dominant or autosomal recessive. Sporadic cases can result from de novo mutations.

Management and treatment

Management is preventive: protective padding of the skin and careful wound care reduce blistering, scarring and prevent secondary infection. 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. The treatment of SCC is surgical.

Prognosis

Prognosis depends on the subtype. Patients with DDEB usually have a normal life expectancy. Patients with RDEB-sev gen are at high risk of mortality primarily from metastatic SCC, less frequently from chronic renal failure and dilated cardiomyopathy.