Epidermolysis Bullosa (EB)

Genetic mutations cause epidermolysis bullosa.

Epidermolysis bullosa is a group of inherited conditions that affect the supporting tissue of the skin and mucosa. It often appears at birth or during infancy and is characterized by severe skin fragility, erosions, and blisters.

Epidermolysis bullosa is due to one or multiple defective genes that normally synthesize structural proteins that are involved in the adherence of the epidermis (the superficial layer of skin) to the dermis (the deeper layer of the skin). Another term for this group of conditions is "mechanobullous disease," which distinguishes it from conditions that may appear superficially similar but are produced by autoimmune destruction of some of the same proteins that are defective in epidermolysis bullosa.

Epidermolysis bullosa acquisita (another condition) is an inappropriately named example of an autoimmune problem that really does not belong in the discussion of mechanobullous diseases.

There are four distinct clinical forms of this condition, and each is associated with different defective proteins:

1. Epidermolysis bullosa simplex (EB simplex)
   • EBS localized (Weber-Cockayne), generalized other EBS, Dowling Meara EBS, EBS with muscular dystrophy, EBS with mottled pigmentation, EBS Ogna, EBS with pyloic atreseia, EBS circinate migratory, lethal acantolythic EB, EBS superficialis (EBSS), and plakophilin deficiency
2. Junctional epidermolysis bullosa (junctional EB)
   • Herlitz JEB and JEB-other (including JEB with pyloric atresia, non-Herlitz JEB, and many other subtypes)
3. Dystrophic epidermolysis bullosa (dystrophic EB)
   • Recessive DEB (RDEB)
     • Hallopeau-Siemens
   • Dominant DEB (DDEB)
4. Kindler syndrome

Since mechanobullous diseases are hereditary, the presence of a family history of this condition is the major risk factor.

Mechanobullous diseases are rare. Their prevalence in the U.S. population is estimated to be about eight cases per million. Mechano-bullous diseases have been attributed to at least 1,000 different mutations in 20 separate genes that code for various structural proteins near the junction of the epidermis and the dermis (the top layers of skin).

Some of the proteins involved include:

• keratin,
• laminin,
• type VII collagen,
• type VII collagen,
• integrins,
• lectin,
• desmoplakin,
• plakophilin, and
• plakoglobin.

Epidermolysis bullosa is not contagious.

The commonality in the presentation of all the mechanobullous diseases includes the following symptoms:

• fragile skin,
• erosions of skin, and
• blister formation.

Healthcare professionals most frequently note these findings in areas of friction where shear forces are greatest. Elbows, knees, hands, and feet are generally involved, although EB affects any anatomical area. EB may affect the lining tissues within the mouth. Although often evident at birth, the condition may occasionally appear in young adults depending on the gene involved.

There can be a spectrum of severity so that some affected individuals may have localized disease and reach adulthood with few problems, while others with a more severe form are likely to die during infancy. There are associated conditions in some patients, including muscular dystrophy, pyloric atresia, and reno-urinary defects. In dystrophic epidermolysis bullosa, there is a predisposition to scarring, milia formation, and occasionally squamous cell carcinoma.

In an infant for whom this diagnosis is considered, it is vital to exclude other treatable diseases first. In addition, it is often impossible to come to an accurate diagnosis based on the clinical appearance of the patient. It is often necessary to involve a dermatologist with special expertise in pediatrics to evaluate the affected infant.

Special tests on the skin biopsy specimens are required to determine which component of the skin is defective. Immunofluorescence mapping and electron microscopic evaluation may be necessary to pinpoint precise structural defects.

Newly available genetic tools can detect the presence of defective genes in the patient and family members. In families with a history of mechanobullous disease, prenatal testing is available. Such tests are likely to be available only at university medical centers.

Since the problem in all mechanobullous diseases is an absent or defective structural protein, there is no cure. At this time, there is also no specific treatment other than supportive care. The care would be similar to that given in a burn center environment except that the condition never resolves.

Pain, metabolic abnormalities, and infection are major problems in these patients. Preventing erosions is a constant challenge. Occasionally, skin cancer can develop at the site of erosions.

Attempts to produce the normal proteins by bone marrow transplantation, local fibroblast transplantation, or the addition of stem cells to affected patients have met with limited success. Such interventions are available only through participation in investigational studies.

In mild localized cases, it is possible to care for the erosions as one would care for any superficial wound. Additionally, it is important to consider techniques for minimizing friction in areas predisposed to blisters and erosions.

The prognosis of epidermolysis bullosa is almost entirely dependent on the specific structure of the genetically altered protein. That is why it is of the utmost importance to make an accurate diagnosis. Mild localized forms of epidermolysis bullosa simplex exist. Most of these patients can expect to live into adulthood.

The only conceivable way to prevent this or any other genetic disease is by identifying genetic carriers and insuring that any offspring they produce are free from the mutations. Families with a history of mechanobullous disease should seek genetic counseling to insure that they understand the risks involved in procreation.