What is epidermolysis bullosa with congenital absence of skin?
Epidermolysis bullosa (EB) with congenital absence of skin was previously known as Bart syndrome. It has also been known as 'type VI aplasia cutis congenita and epidermolysis bullosa'.
EB with congenital absence of skin was originally described by Bruce Bart in 1966 after observing a large family of six generations with a symmetrical congenital absence of skin on the lower legs, blistering affecting mainly acral skin and sometimes mucous membranes, and nail dystrophy [1]. In 1986, Ilona Frieden proposed a classification of aplasia cutis congenita in which conditions were classified into nine groups according to location of lesions and presence of other anomalies [2]. Under the Friedan classification system, Bart syndrome was classified as type VI aplasia cutis congenita by its combination of a congenital localised absence of skin, epidermolysis bullosa, and nail dystrophy [2].
In 2014, a working group of experts in EB suggested a new classification of EB based on molecular features [3]. They suggested substituting eponymous names with descriptive terms and recommended Bart syndrome be known as EB with congenital absence of skin [3].
Who gets epidermolysis bullosa with congenital absence of skin?
EB with congenital absence of skin is rare and its exact incidence is unknown. Aplasia cutis congenita is seen in 1–2 per 10,000 births [4].
EB with congenital absence of skin can be considered a rare form of aplasia cutis congenita, but the proportion of aplasia cutis congenita that can be classified as EB with congenital absence of skin is unknown.
What causes epidermolysis bullosa with congenital absence of skin?
EB with congenital absence of skin is a familial condition with an autosomal dominant pattern of inheritance, but isolated cases have also been recognised [5].
The aetiology and pathogenesis is complex as the EB can affect different membranes of the skin; it may be epidermal (simplex), junctional, or dermal (dystrophic). The original family described by Bart had dystrophic EB with ultrastructural changes in the anchoring fibrils in the dermis. The genetic abnormality in that family has been identified as related to the COL7A1 gene on chromosome 3, which codes for collagen type VII [6,7].
The congenital absence of skin is thought to be secondary to the skin fragility and in utero trauma, explaining the symmetrical distribution on the lower legs that may rub together, rather than as a failure to form the skin [7].
What are the clinical features of epidermolysis bullosa with congenital absence of skin?
EB with congenital absence of skin is a clinical triad that consists of:
- Congenital absence of skin on the lower legs
- Any type of EB elsewhere on the body
- Nail changes, such as the congenital absence of nails or nail dystrophy.
The areas of absent skin are usually symmetrical and bilateral, typically involving the medial or dorsal surface of the distal lower limbs including the tops of the feet. They are sharply demarcated, glistening red areas of ulceration [8].
In the original family described by Bart, the phenotype showed some variability, with not all affected members showing all features of the triad [7].
EB with congenital absence of skin may also be associated with other anomalies, such as:
- Pyloric atresia (obstruction of the pylorus or lower stomach)
- Rudimentary ear development
- A flattened nose
- A broad nasal root (top of the nose)
- Wide-set eyes [5,8].
What are the complications of epidermolysis bullosa with congenital absence of skin?
Complications of EB with congenital absence of skin include infection and haemorrhage. Hypothermia, hypoglycaemia, and disorders of fluid balance may complicate large defects [4,8]. Severe mucosal involvement has caused early death [7].
How is epidermolysis bullosa with congenital absence of skin diagnosed?
EB with congenital absence of skin is a clinical diagnosis. Histological evaluation of the skin confirms the diagnosis and categorises the EB type.
Biopsy has revealed a subepidermal blister with an inflammatory infiltrate in the dermis in some cases [8]. In Bart's original series of cases, the split in the skin was below the lamina densa on electron microscopy, indicating a dermal dystrophic EB [7]. In other cases, electron microscopy findings of separation of the dermal–epidermal junction and interruption of the basal lamina are similar to that seen in junctional EB [9]. In several cases, the split has been above the basement membrane indicating the epidermal simplex type [7].
What is the differential diagnosis for epidermolysis bullosa with congenital absence of skin?
The differential diagnoses of EB with congenital absence of skin are included below.
- Other forms of aplasia cutis congenita — aplasia cutis is a rare congenital anomaly characterised by an absence of skin that occurs most commonly on the scalp and cranial vault. The depth of lesions can range from superficial erosion to absence of all skin layers. There are nine subtypes of aplasia cutis congenita; EB with congenital absence of skin has been classified as type VI.
- Other forms of EB — EB is a group of rare inherited disorders characterised by blister formation due to increased skin and mucous membrane fragility. Four major types of EB have been described according to the level of skin cleavage at the ultrastructural level. EB is further classified based on inheritance, clinical findings, and molecular defects.
- Adams–Oliver syndrome — Adams–Oliver syndrome is a rare condition characterised by aplasia cutis congenita of the scalp with transverse defects of the limbs and mottling of the skin.
What is the treatment for epidermolysis bullosa with congenital absence of skin?
The management of EB with congenital absence of skin is usually conservative. The aim is to accelerate healing of the affected areas of skin, to prevent infection or other complications, and to reduce the risk of scarring.
Topical antibacterial ointment and wet dressings are the mainstays of treatment [8]. Prophylactic systemic antibiotics are not recommended. Occasionally surgical intervention with a skin graft or flap repair may be needed for a large defect [9].
What is the outcome for epidermolysis bullosa with congenital absence of skin?
In general, the prognosis of EB with congenital absence of skin is good. Most areas of congenital absence of skin heal within weeks or months with no long-term sequelae [7,10]. However, when the original family described by Bart was revisited, many adults had continued to develop blisters, and milia and mild scarring were noted at sites of blistering. The sites of the congenital absence of skin had healed with atrophic hairless scars [7]. The nails did not recover.