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Severe generalized recessive dystrophic epidermolysis bullosa

Orpha number ORPHA79408
Synonym(s) Autosomal recessive dystrophic epidermolysis bullosa generalisata gravis
Autosomal recessive dystrophic epidermolysis bullosa, Hallopeau-Siemens type
RDEB generalisata gravis
RDEB, Hallopeau-Siemens type
RDEB-sev gen
Severe generalized RDEB
Prevalence <1 / 1 000 000
Inheritance
  • Autosomal recessive
Age of onset Neonatal/infancy
ICD-10
  • Q81.2
OMIM
UMLS -
MeSH -
MedDRA -
SNOMED CT -

Summary

Severe generalized recessive dystrophic epidermolysis bullosa (RDEB-sev gen) is the most severe subtype of dystrophic epidermolysis bullosa (DEB, see this term), formerly known as the Hallopeau-Siemens type, and is characterized by generalized cutaneous and mucosal blistering and scarring associated with severe deformities and major extracutaneous involvement.

The reported prevalence varies between populations, from 1/1,250,000 inhabitants in Scotland to 1/2,381,000 inhabitants in the Unites States.

Blisters develop at birth or during the neonatal period and affect all the body as well as the oral and gastrointestinal mucosa. Healing of lesions occurs with retracting scars or milia. Excessive scarring can lead to adhesion of fingers and toes resulting to pseudosyndactyly, and to joint contractures that further cause disabling hand and foot deformities (''mitten deformities''). Scarring alopecia of the scalp and permanent loss of nail plates are also observed. Eye involvement is frequent and includes blepharitis, loss of eyelashes, ectropion, symblepharon, and corneal blisters that can lead to loss of vision. In the oral cavity, fusion of the tongue to the mouth floor (ankyloglossia), obliteration of the oral vestibules and progressive restriction of oral aperture (microstomia) cause difficulties in chewing and swallowing. Dental caries are numerous. Esophageal stricture is frequent and result in severe dysphagia. Anal and perianal erosions cause major pain during defecation and therefore self-induced constipation. Oral, esophageal, and anal involvement induce a state of chronic malnutrition which contributes to growth retardation typical of the disease, delayed puberty, osteopenia and osteoporosis. Refractory anemia, iron deficiency and hypoalbuminemia are also observed. Nearly all patients develop at least one aggressive squamous cell carcinoma (SCC; see this term), more often during the third-fourth decade of life.

The disease is caused by null mutations within the type VII collagen gene (COL7A1) that usually lead to a lack of functional collagen VII, the main constituent of anchoring fibrils that anchor the basement membrane to the dermis.

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.

The differential diagnosis includes other forms of EB. In the neonatal period also herpes simplex infection, congenital erosive and vesicular dermatosis, epidermolytic ichthyosis, bullous pemphigoid, neonatal pemphigus and pemphigoid gestationis, and staphylococcal scalded skin syndrome (see these terms) may need to be considered.

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

Transmission is autosomal recessive.

Protective padding of the skin reduces the blistering and careful wound care helps in preventing secondary infections. Hand and foot deformities can be treated by surgery. Due to recurrence, regular physiotherapy is necessary to maintain intraoperative results, but additional treatments are always required. Follow-up by a dietitian is essential and gastrostomy feeding may be necessary in patients unable to maintain adequate nutrition. 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 is necessary for the surveillance of SCC, whose treatment is surgical.

Life expectancy is significantly reduced, mostly due to the development of aggressive SCC with frequent metastases. Mortality from metastatic SCC within five years of the time of diagnosis of the first SCC is of 87% by age 45. Other complications that affect the prognosis include chronic renal failure, and more rarely, dilated cardiomyopathy.

Expert reviewer(s)

  • Dr Giovanna ZAMBRUNO

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Detailed information

Summary information
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Article for general public
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