Definition

Epithelial adhesion disorders (EAD), also known as epidermolysis bullosa (EB), are a group of heritable skin diseases, which are typified by chronic fragility and blistering of the skin and mucous membranes. The blisters and erosions are mostly induced by minimal trauma or, sometimes, occur spontaneously. The disorders are caused by mutations in genes, encoding for proteins involved in maintaining the integrity and stability of epithelial tissues.

These diseases have a high personal, medical and socio-economic impact on the affected individuals and their families. Complications may occur since many organs can be secondarily affected, necessitating daily skin and wound care, protective measures, and other medical treatments throughout their lives. Currently, no specific cure is available for EAD.

Symptoms / Signs 

The skin on the hands and feet, as well as other parts of the body, mucous membranes, and digestive tract, are prone to blistering due to reduced adhesion between the skin layers (epidermis and dermis), making the skin vulnerable to even slight mechanical stress. The blisters can contain clear fluid (serum) or blood. The involvement of deeper layers of skin may cause scarring and deformities during the healing process, which can lead to contractures in the hands and feet.

Symptoms of EAD vary widely, depending on the subtype, ranging from minimal skin fragility to very severe symptoms with general complications and involvemnt of internal organs (e.g. esophagus, lungs, gastrointestinal tracts). Nails, hair, and teeth may also be affected in some forms of EAD. 

Causes

The various types of EAD are attributed to genetic mutations in the genes coding for protein components of the dermal-epidermal junction zone. This results in skin cells producing either dysfunctional or no proteins at all. Due to the lack of the protein or its impaired functionality, the skin's ability to withstand mechanical stress and shearing forces is reduced.

Main groups

The main groups of EAD are:

Epidermolysis bullosa simplex (EBS). This is in general a mild form. Blister formation usually occurs more during childhood than in adulthood, and the healing of the blisters occurs without scarring or skin atrophy.

Junctional epidermolysis bullosa (JEB). Very different forms of JEB exist, both mild and moderate forms, but also early lethal forms of JEB. Healing without scarring is usually observed; however, skin atrophy, nail dystrophy and hair involvement often develop.

Dystrophic epidermolysis bullosa (DEB). DEB can either take a mild or a more severe form. Healing with scars is usual, because the deeper layers of the skin and mucous membranes are affected by blistering. In severe cases, bad scarring can cause mutilation and contractures of the hands and feet.

Kindler syndrome (KS). KS is a rare EAD subtype, which shows a changing picture with age. In early childhood, the symptoms include skin blistering and sensitivity to sun light. These improve with age, but variations of skin pigmentation and atrophy (thin skin) develop. Sometimes, thickened skin of palms and soles, and inflammation and mild scarring of mucous membranes are observed.

Diagnosis

External observation is not sufficient to determine the level of skin blistering in EAD. Thus, a skin biopsy is necessary to microscopically identify the specific EAD subtype. However, to obtain a definitive, accurate diagnosis, a genetic mutation analysis must be performed, which requires a blood sample.