Amy O'Neill

What Is Epidermolysis Bullosa?

EB is a group of blistering skin conditions. The skin is so fragile in people with EB that even minor rubbing may cause blistering. At times, the person with EB may not be aware of rubbing or injuring the skin even though blisters develop. In severe EB, blisters are not confined to the outer skin. They may develop inside the body, in such places as the linings of the mouth, esophagus, stomach, intestines, upper airway, bladder, and the genitals.

The skin has an outer layer called the epidermis and an underlying layer called the dermis. The place where the two layers meet is called the basement membrane zone (See diagram). The main forms of EB are EB Simplex, Junctional EB, and Dystrophic EB. EB Simplex occurs in the outer layer of skin; Junctional EB and Dystrophic EB occur in the basement membrane zone. These major types of EB, which will be described throughout this text, also have many subtypes.

Who Gets Epidermolysis Bullosa?

It is estimated that 2 to 4 out of every 100,000 people, or up to 12,000 people in the United States, have some form of EB. It occurs in all racial and ethnic groups and affects males and females equally. The disease is not always evident at birth. Milder cases of EB may become apparent when a child crawls, walks, or runs, or when a young adult engages in vigorous physical activity.

What Causes Epidermolysis Bullosa?

Most people with EB have inherited the condition through faulty genes they receive from one or both parents. Genes are located in the body's cells and determine inherited traits passed from parent to child. They also govern every body function, such as the formation of proteins in the skin. More than 10 genes are known to underlie the different forms of EB. Genes are located on chromosomes, which are structures in each cell's nucleus.

In an autosomal dominant form of EB, the disease gene is inherited from only one parent who has the disease, and there is a 50 percent (1 in 2) chance with each pregnancy that a baby will have EB. In the autosomal recessive form, the disease gene is inherited from both parents. Neither parent has to show signs of the disease; they simply need to "carry" the gene, and there is a 25 percent (1 in 4) chance with each pregnancy that a baby will have EB. EB can also be acquired through a mutation (abnormal change) in a gene that occurred during the formation of the egg or sperm reproductive cell in a parent. Neither the sex of the child nor the order of birth determines which child or how many children will develop EB in a family that has the faulty gene.

Although EB Simplex can occur when there is no evidence of the disease in the parents, it is usually inherited as an autosomal dominant disease. In EB Simplex, the faulty genes are those that provide instructions for producing keratin, a fibrous protein in the top layer of skin. As a result, the skin splits in the epidermis, producing a blister.

In Junctional EB, there is a defect in the genes inherited from both parents (autosomal recessive) that normally promote the formation of anchoring filaments (thread-like fibers) or hemidesmosomes [hem-ee-DES-mo-soms] (complex structures composed of many proteins). These structures anchor the epidermis to the underlying basement membrane. The defect leads to tissue separation and blistering in the upper part of the basement membrane.

There are both dominant and recessive forms of Dystrophic EB. In this condition, the filaments that anchor the epidermis to the underlying dermis are either absent or do not function. This is due to defects in the gene for type VII collagen, a fibrous protein that is the main component of the anchoring filaments.

Epidermolysis bullosa acquisita (EBA) is a rare autoimmune disorder where the body attacks its own anchoring fibrils with antibodies, the special proteins that help fight and destroy foreign substances that invade the body. In a few cases, it has occurred following drug therapy for another condition; in most cases, the cause is unknown.

How Is Epidermolysis Bullosa Diagnosed?

Dermatologists can identify where the skin is separating to form blisters and what kind of EB a person has by doing a skin biopsy (taking a small sample of skin that is examined under a microscope). One diagnostic test involves use of a microscope and reflected light to see if proteins needed for forming connecting fibrils, filaments, or hemidesmosomes are missing or reduced in number. Another test involves use of a high-power electron microscope, which can greatly magnify tissue images, to identify structural defects in the skin.

Recent techniques make it possible to identify defective genes in EB patients and their family members. Prenatal diagnosis can now be accomplished by amniocentesis (removing and examining a small amount of amniotic fluid surrounding the fetus in the womb of a pregnant woman) or sampling the chorionic villus (part of the outer membrane surrounding the fetus) as early as the tenth week of pregnancy.

What Are the Symptoms of Epidermolysis Bullosa?

The major sign of all forms of EB is fragile skin that blisters, which can lead to serious complications. For example, blistering areas may become infected, and blisters in the mouth or parts of the gastrointestinal tract may interfere with proper nutrition.

Following is a summary of some of the characteristic signs of various forms of EB.

EB Simplex (EBS)--A generalized form of EBS usually begins with blistering that is evident at birth or shortly afterward. In a localized, mild form called Weber-Cockayne, blisters rarely extend beyond the feet and hands. In some subtypes of EBS, the blisters occur over widespread areas of the body. Other signs may include thickened skin on the palms of the hands and soles of the feet; rough, thickened, or absent fingernails or toenails; and blistering of the soft tissues inside the mouth. Less common signs include growth retardation; blisters in the esophagus; anemia (a reduction in the red blood cells that carry oxygen to all parts of the body); scarring of the skin; and milia, which are small white skin cysts.

Junctional EB (JEB)--This disease is usually severe. In the most serious forms, large, ulcerated blisters on the face, trunk, and legs can be life-threatening due to complicated infections and loss of body fluid that leads to severe dehydration. Survival is also threatened by blisters that affect the esophagus, upper airway, stomach, intestines, and the urogenital system. Other signs found in both severe and mild forms of JEB include rough and thickened or absent fingernails and toenails; a thin appearance to the skin (called atrophic scarring); blisters on the scalp or loss of hair with scarring (scarring alopecia); malnutrition and anemia; growth retardation; involvement of soft tissue inside the mouth and nose; and poorly formed tooth enamel.

Dystrophic EB (DEB)--The dominant and recessive inherited forms of DEB have slightly different symptoms. In some dominant and mild recessive forms, blisters may appear only on the hands, feet, elbows, and knees; nails usually are shaped differently; milia may appear on the skin of the trunk and limbs; and there may be involvement of the soft tissues, especially the esophagus. The more severe recessive form is characterized by blisters over large body surfaces, loss of nails or rough or thick nails, atrophic scarring, milia, itching, anemia, and growth retardation. Severe forms of recessive DEB also may lead to severe eye inflammation with erosion of the cornea (clear covering over the front of the eye), early loss of teeth due to tooth decay, and blistering and scarring inside the mouth and gastrointestinal tract. In most people with this form of EB, some or all the fingers or toes may fuse (pseudosyndactyly). Also, individuals with recessive DEB have a high risk of developing a form of skin cancer called squamous cell carcinoma. It primarily occurs on the hands and feet. The cancer may begin as early as the teenage years. It tends to grow and spread faster in people with EB than in those without the disease.

How Is Epidermolysis Bullosa Treated?

Persons with mild forms of EB may not require extensive treatment. However, they should attempt to prevent blisters from forming and prevent infection and care for the skin when blisters occur. Individuals with moderate and severe forms may have many complications and require psychological support along with attention to the care and protection of the skin and soft tissues. Patients, parents, or other care providers should not feel that they must tackle all the complicated aspects of EB care alone. There are doctors, nurses, social workers, clergy members, psychologists, dietitians, and patient and parent support groups that can assist with care and provide information and emotional support.