General Information about Epidermolysis Bullosa

What is Epidermolysis Bullosa (EB)?

A child with Epidermolysis Bullosa (EB) is afflicted with a type of inherited skin disorder that causes blisters after even the mildest trauma. Most commonly, EB causes blisters on the skin, but EB can also affect the mouth, esophagus, lungs, muscles, eyes, nails and teeth. Depending on the type of EB, the effects of the disease can be mild, disabling, or life threatening. EB is never contagious because it is a genetic disease.

There are three types of EB, all caused by a different genetic mutation: EB simplex (EBS), Junctional EB (JEB) and Dystrophic EB (DEB). EB simplex is the mildest and most common form of EB, while Junctional EB and Dystrophic EB are relatively less common and affect the patient more severely.

What are some symptoms of EB?

Blisters on the skin, usually beginning in infancy
Blisters or sores on the mucous membranes (mouth, throat, respiratory tract)
Thickened skin on the palms of the hands or soles of the feet
Thickening or absence of fingernails/toenails
Anemia (more common in severely affected individuals)

How common is EB?

Based on statistics collected through the National Epidermolysis Bullosa Registry, EB is estimated to occur in 20 newborns per 1 million live births in the United States. The exact number of persons with EB is unclear, but estimates suggest that 25,000 - 50,000 people in the United States have EB.

How is EB treated?

Many patients with mild forms of EB require little or no treatment. In fact, people with the most common form of EB, the Weber-Cockayne Subtype of EB Simplex rarely seek medical help. However, patients with severe forms of EB require hours of daily intense care that is usually provided by their families. The care given to these patients is similar to the care provided for burn victims; blisters are wrapped in dressings and the dressings are changed daily. Currently, treatment for severe forms of EB is focused on promoting wound healing, preventing infection, protecting the skin from trauma, decreasing blister occurrence, minimizing deformities, alleviating pain, attending to nutritional needs, and providing psychological support for the family. With the more severe forms of EB, it is often necessary to have several physicians involved in the care of the patient, including a dermatologist, a primary care doctor, dentist, hand surgeon, gastrointestinal specialist, and pain specialist. Additional help is provided by nutritionists, physical and occupational therapists, social workers, and other health care professionals. This multidisciplinary approach is needed for children with severe EB.

Forms of EB:

EB simplex

There are many types of EB Simplex and most are caused by an autosomal dominant gene mutation that leads to a defective keratin protein. Keratin proteins function as the scaffolding for the skin, and so when this scaffolding is not formed correctly, the skin is more likely to fall apart and form blisters. EB Simplex can be split up into two main types, Generalized and Localized. In Generalized EB Simplex, blistering occurs all over the body, and in the more common Localized EB Simplex blistering only occurs in areas that receive the most trauma, usually the hands and feet.

Junctional EB

Junctional EB is an autosomal recessive condition that is caused by mutations in the genes that code for collagen17 or laminin-5. Collagen17 and laminin-5 are proteins that help anchor the skin together. Without them the skin separates easily, causing blisters. There are many types of Junctional EB, and all of them cause widespread blistering. Some forms of Junctional EB improve as the patient gets older, while a rare form of Junctional EB can be fatal in infancy. Because this disease is autosomal recessive, parents can carry the genetic mutations and be completely healthy. Afflicted patients receive one copy of the abnormal gene from each parent (see "How is EB inherited?" below).

Dystrophic EB

Dystrophic EB is caused by a mutation in the collagen7 gene and can be dominant or recessive. The collagen gene codes for the collagen7 protein that anchors the deeper layer of skin, called the dermis, to the epidermis, or superficial layer of skin. When an individual has an abnormal collagen protein, the skin is fragile and separates easily, forming blisters. Both dominant and recessive forms of Dystrophic EB cause scarring. An individual with dominant Dystrophic EB generally experiences mild to moderate blistering of the skin, but only a small amount of blistering of the mouth, esophagus, and GI tract. This type rarely causes pseudosyndactyly, a deformity of the hands or feet caused by the fusion of the fingers or toes. The recessive form of Dystrophic EB is the most severe, chronic type of EB. Blistering begins at birth or shortly afterwards. Much of the skin is covered in blisters and there is extensive internal blistering. Children can develop deformities caused by the recurrent scarring of the fingers and toes (pseudosyndactyly) and the hands and arms become fixed in stiff positions (contractures). It is painfully difficult for a child with recessive Dystrophic EB to ingest food due to the internal blistering that occurs in the mouth, esophagus, and gastrointestinal tract.

How is EB inherited?

EB is a disease that is passed to a child from the mother and/or father's chromosomes. All of the genes that cause EB are autosomal, meaning the genes are X and Y chromosomes. You can think about the process of inheriting genes by imagining chromosomes as two sets of instruction manuals that contain information on how to make everything in your body. One instruction manual is from your mother and the other manual is from your father. Genes on chromosomes are like pages or sections of the instruction manual that focus on a specific part of the body, how to make hair or what color to make it.

In individuals with EB, some of the pages of one or both instruction manuals are missing or incorrect. These pages should contain the information on how to make the proteins that hold the skin together. Faulty instructions lead to proteins that are either absent or abnormal. Without these proteins, the skin is not as strong as it should be. Depending on the form of EB, either one or two sets of bad instructions are needed to produce disease.

Autosomal Dominant Inheritance:

When only one abnormal gene is needed to produce disease, that disease is autosomal dominant. The abnormal gene is able to disrupt the function of the normal gene, causing disease. Most forms of EB Simplex and Dominant Dystrophic EB are autosomal dominant.

A person with a dominant form of EB has a 50% chance of passing the disease onto their children each pregnancy.

A person may have a dominant form of EB and not have an affected parent. In these cases, a new mutation in the egg or sperm of one parent occurred.

Autosomal Recessive Inheritance:

When two abnormal genes are needed to produce disease, that disease is autosomal recessive. All forms of Junctional EB and Recessive Dystrophic EB are autosomal recessive. A person can have one abnormal copy of the gene for the disease be completely healthy. This individual is called a carrier. If an individual that carries one recessive gene for the disease has a child with another carrier for the same disease, their child may be afflicted.

When two carriers for a disease produce a child, there is a 25% chance the child will have the disease, a 50% chance the child will be a carrier, and a 25% chance the child will have completely normal genes. This information is most useful to parents who have had one child with a recessive form of EB in determining their risk of having another affected child in the future.