DISEASE CARD

Definition

The term epidermolysis bullosa (EB) describes a clinically and genetically heterogeneous spectrum of rare inherited conditions that are characterized by a marked mechanical fragility of epithelial tissues with blistering and erosions occurring after minor trauma. There are four major types of EB: EB simplex (EBS), dystrophic EB (DEB), junctional EB (JEB), and Kindler-syndrome.

Authors: Prof. Johann Bauer, MD Christine Prodinger

Dystrophic or dermolytic epidermolysis bullosa (DEB) is characterized by tissue separation within the upper papillary dermis. The cleft formation occurs at the sub-lamina densa level, where collagen VII forms the anchoring fibrils (AF). DEB is divided into two major categories, the dominant (DDEB) and recessive (RDEB) forms, according to the mode of inheritance. Further subclassifications are made by clinical phenotype and severity of disease^.1 DDEB is subdivided into four subtypes (Table) with the intermediate subtype (DDEB-intermed) representing the prototype of DDEB.² All forms of DEB are caused by mutations in the COL7A1 gene (3p.21.31).

DDEB subtypes

Clinical Description

Dominant DEB presents with a generally milder phenotype compared to recessive DEB or junctional EB, but there is a considerable clinical overlap. Blistering starts at birth or soon thereafter, ranging from mainly acral involvement to disseminated lesions, frequently limited to areas of trauma such as the hands, feet, knees and elbows. Wound healing results in milia formation, atrophic scars and loss of nails. Mucosal involvement is rare, but severe strictures in the esophageal tract can occur. Teeth are usually normal. Disease activity commonly diminishes with advancing age and life expectancy is normal.^1,2,3

In DDEB pruriginosa skin fragility and blistering starts at infancy. Wounds heal with milia formation and atrophic scarring. The onset of pruritus is delayed and often does not appear until adolescence or adulthood. With the onset of pruritus the clinical picture worsens with development of nodular prurigo-like lesions and in some cases albopapuloid lesions on the trunk. Scratching due to pruritus may aggravate the disease on the shins and forarms. Nail dystrophy is almost always present.^1,2,3

In localized DDEB, solely nail, acral or pretibial lesions can become manifest. As they are often papular or plaque-like, sometimes violaceous ((in particular pretibial), the diagnosis of lichen planus may be suggested. Bullae and scarring are clinical symptoms and nail dystrophy is characteristic, involving both fingernails and toenails (without pterygium as in lichen planus).^1,2,3

Self-improving DDEB shows generalized blister formation at birth or shortly thereafter. Oral cavity can be affected. Blisters heal with mild atrophic scarring and milia formation. The disease usually ceases after 6 to 24 months of life. Yet, nail dystrophy and skin fragility can persist until adulthood.^1,2,3

Pathogenesis

In DDEB, heterozygous glycine substitution mutations in the Gly-X-Y repeat triplet sequence within the collagenous domain of the pro-a-chain of the type VII collagen homotrimer interfere in a dominant-negative manner with collagen synthesis and impair its secretion or the fibrillogenesis of anchoring fibrils.⁴ Since the defective as well as the wildtype alleles are expressed, some anchoring fibrils are functionally intact, accounting for the relatively mild course of DDEB.^1,2,3

Diagnosis

Clinical features together with a family history (the majority of cases (about 70%) show a clear family history) point towards the diagnosis. Confirmation can be reached with DNA sequencing of the COL7A1 gene, revealing a heterozygous pathogenic variant. Examination of a skin biopsy with direct immunofluorescence for specific cutaneous markers and histologic examination, showing cleavage below the basal lamina, may be helpful for diagnosis. A typical finding in electron microscopy is a paucity of hypoplastic anchoring fibrils at the subbasal lamina region.^1,3

Treatment

Currently no causative therapy is available for neither form of DEB and treatment is primarily preventive (e.g. protective padding) and symptomatic. Wound care management is paramount in order to prevent secondary infections and to reduce scarring. In rare cases of esophageal strictures/obstruction, endoscopic balloon dilatation may become necessary. 

References

Prof. Johann Bauer, MBA

Professor of Dermatology

University Hospital of the Paracelsus Medical University Salzburg, Austria 

Head of the EB Research Unit, EB House Austria, Salzburg

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