Overview of Epidermolysis Bullosa

Epidermolysis bullosa is a group of rare diseases that cause the skin to be fragile and to blister easily. Tears, sores, and blisters in the skin happen when something rubs or bumps the skin. They can appear anywhere on the body. In severe cases, blisters and sores may also develop inside the body, such as in the mouth, esophagus, stomach, intestines, upper airway, bladder, and genitals.

Most people who have epidermolysis bullosa inherit a mutated (changed) gene from their parents. The gene mutation changes how the body makes proteins that help the skin bind together and remain strong. If you have epidermolysis bullosa, one of these proteins does not form correctly. The layers of the skin do not bind normally, making it easy for the skin to tear and blister.

The primary symptom of epidermolysis bullosa is fragile skin that leads to blistering and tearing. The symptoms of the disease usually begin at birth or during infancy and range from mild to severe.

There is no cure for the disease; however, scientists continue to research possible treatments and cures for epidermolysis bullosa. Your doctor treats the symptoms, which may include managing pain, treating wounds caused by the blisters and tears, and helping you cope with the disease.

Who Gets Epidermolysis Bullosa?

Anyone can get epidermolysis bullosa. It occurs in all racial and ethnic groups and affects males and females equally.

Types of Epidermolysis Bullosa

There are four major types of epidermolysis bullosa. The skin has a top or outer layer, called the epidermis, and a dermis layer that is underneath the epidermis. The basement membrane is where the layers of skin meet. Doctors determine the type of epidermolysis bullosa based on the location of the changes in the skin and the gene mutation identified. The types of epidermolysis bullosa include:

  • Epidermolysis bullosa simplex: Blisters occur in the lower part of the epidermis.
  • Junctional epidermolysis bullosa: Blisters occur in the top portion of the basement membrane, due to problems in attachment between the epidermis and basement membrane.
  • Dystrophic epidermolysis bullosa: Blisters occur in the upper dermis due to problems in attachment between the basement membrane and the upper dermis.
  • Kindler syndrome: Blisters happen in multiple layers of the skin, including the basement membrane.

Researchers have identified more than 30 subtypes of the disease, which are groupings under the four major types of epidermolysis bullosa. By knowing more about the subtypes, doctors can focus treatment of the disease.  

A fifth type of the disease, epidermolysis bullosa acquisita, is a rare autoimmune disorder that causes the body’s immune system to attack a certain type of collagen in the person’s skin. Sometimes, it happens with another disease such as inflammatory bowel disease. Very rarely, a medication causes the disease. Unlike the other types of epidermolysis bullosa, the symptoms may begin at any age, but many people develop symptoms during middle age.

Symptoms of Epidermolysis Bullosa

The symptoms of epidermolysis bullosa vary depending on the type you have. Everyone with the disease has fragile skin that blisters and tears easily. Other symptoms, by type and subtype, include the following.

  • Epidermolysis bullosa simplex is the most common form of the disease. People who have a mild subtype develop blisters on the palms of the hands and soles of the feet. In other more severe subtypes, the blisters occur over the entire body. Depending on the subtype of the disease, other symptoms may include:
    • Thickened skin on the palms of the hands and soles of the feet.
    • Rough, thickened, or absent fingernails or toenails.
    • Blisters inside the mouth.
    • Changes in the pigmentation (color) of the skin.
  • Junctional epidermolysis bullosa is usually severe. People who have the most serious form can have open sores on the face, trunk, and legs, which may become infected or cause severe dehydration due to fluid loss. Blisters also can develop in the mouth, esophagus, upper airway, stomach, intestines, urinary system, and genitals. Other symptoms and problems related to the disease may include:
    • Rough and thickened or absent fingernails and toenails.
    • Blisters on the scalp or loss of hair with scarring.
    • Malnutrition resulting from poor intake of calories and vitamins due to blistering in the mouth and gastrointestinal tract. 
    • Anemia.
    • Slow overall growth.
    • Poorly formed tooth enamel.
  • Dystrophic epidermolysis bullosa has slightly different symptoms, depending upon whether the disease is dominant or recessive; however, most people have the recessive subtype.
    • Recessive subtype: Symptoms tend to be moderate to severe and may include:
      • Blisters usually appear over large areas of the body; in some milder cases of the disease, blisters may only appear on feet, elbows, and knees.
      • Loss of nails.
      • Skin scarring, which may cause the skin to be thick or thin.
      • Milia, which are small white bumps on the skin.
      • Itching.
      • Anemia.
      • Slow overall growth.

Severe forms of the recessive subtype may lead to eye damage, tooth loss, blistering inside the mouth and gastrointestinal tract, and fusing together of the fingers or toes. There is also a high risk of developing skin cancer. This cancer tends to grow and spread faster in people with epidermolysis bullosa than in those without the disease.

    • Dominant subtype: Symptoms may include:
      • Blisters only on the hands, feet, elbows, and knees.
      • Change in shape of nails or nail loss.
      • Milia.
      • Blisters inside the mouth.
  • Kindler syndrome does not have any subtypes. The blisters usually appear on the hands and feet and, in severe cases, spread to other areas of the body, including the esophagus and bladder. Other symptoms include thin, wrinkled skin; scarring; milia; and sensitivity of the skin to sun damage.

Causes of Epidermolysis Bullosa

Mutations (changes) to genes that you inherit from your parents cause most forms of epidermolysis bullosa. Genes carry information that determines which features are passed to you from your parents. We have two copies of most of our genes—one from each parent. People with the disease have one or more genes that carry the incorrect instructions to make certain proteins in the skin.

There are two types of inheritance patterns:

  • Dominant, which means you inherit one normal copy and one copy of the gene that causes epidermolysis bullosa. The abnormal copy of the gene is stronger or “dominant” over the normal copy of the gene, causing the disease. A person with a dominant mutation has a 50% chance (1 in 2) of passing on the disorder to each of his or her children.
  • Recessive, which means that your parents do not have the disease, but both parents have an abnormal gene that causes epidermolysis bullosa. When both parents carry the recessive genes, there is a 25% chance (1 out of 4) per pregnancy of having a child with the disease. There is a 50% chance (2 out of 4) per pregnancy of having a child who inherits one abnormal recessive gene, making them a carrier. 

Researchers know that epidermolysis bullosa acquisita is an autoimmune disease, but they do not know what causes the body to attack the collagen in a person’s skin. Sometimes, people with autoimmune inflammatory bowel disease also develop epidermolysis bullosa acquisita. Rarely, medications cause the disease.