Recessive dystrophic epidermolysis bullosa-generalized other

Alternate names

Autosomal recessive dystrophic epidermolysis bullosa generalisata mitis; Autosomal recessive dystrophic epidermolysis bullosa, generalized other; Generalized mitis RDEB; RDEB generalisata mitis; RDEB, non-Hallopeau-Siemens type; RDEB-O; RDEB-generalized other; Recessive dystrophic epidermolysis bullosa, non-Hallopeau-Siemens type; RDEB, generalized intermediate; Recessive dystrophic epidermolysis bullosa, generalized intermediate

Definition

Recessive dystrophic epidermolysis bullosa (RDEB)-generalized other, also known as RDEB non-Hallopeau-Siemens type, is a subtype of 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 RDEB, the first one being severe generalized RDEB (RDEB- sev gen).
• 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.

Cause

• 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.

Inheritance

Autosomal recessive inheritance, a 25% chance

Transmission is autosomal recessive.

Signs and symptoms

• 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 structures 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).

Diagnosis

• 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.

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.

NIH genetic and rare disease info

• NIH info on Recessive dystrophic epidermolysis bullosa-generalized other

Recessive dystrophic epidermolysis bullosa-generalized other is a rare disease.