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 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.

Epidermolysis bullosa (EB) is a group of genetic skin diseases that cause the skin to blister and erode very easily. In people with EB, blisters form in response to minor injuries or friction, such as rubbing or scratching. There are four main types of EB, which are classified based on the depth, or level, of blister formation:

• Epidermolysis bullosa simplex
• Dystrophic epidermolysis bullosa
• Junctional epidermolysis bullosa
• Kindler Syndrome

EB may then be further classified based on severity and specific symptoms, such as distribution (localized or generalized) and whether parts of the body other than the skin are affected. Specific sub-types may then be determined based on identifying the exact protein that is defective in a person with EB. This may be done by tests performed on a skin biopsy, or when possible, genetic testing. Identifying the exact sub-type can be hard because there are many sub-types of EB. A person with any main type of EB may be mildly or severely affected, and the disease can range from being a minor inconvenience requiring modifying activities, to completely disabling and even fatal in some cases.

EB may be caused by changes (mutations) in at least 18 genes that play various roles in the structure, integrity, and repair of the skin. Inheritance may be autosomal dominant or autosomal recessive depending on the type and subtype of EB a person has. Management involves a multidisciplinary team of health care providers and involves wound care, pain control, controlling infections, nutritional support, and prevention and treatment of complications.

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.

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

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. If one parent has a recessive mutation of the gene, all their children will carry an abnormal gene but will not necessarily have epidermolysis bullosa.

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.

Inheritance of epidermolysis bullosa (EB) may be either autosomal dominant or autosomal recessive, depending on the type and subtype of inherited EB present:

• Epidermolysis bullosa simplex (EBS, the most common type of EB) is almost always inherited in an autosomal dominant manner, but rare autosomal recessive forms have been reported.
• Dystrophic epidermolysis bullosa (DEB) can be inherited in an autosomal dominant or autosomal recessive manner, depending on the subtype present. However, dominant DEB is the second most common type of EB.
• Junctional epidermolysis bullosa is autosomal recessive.
• Kindler syndrome is autosomal recessive.

A condition is autosomal dominant if having only one changed (mutated) copy of the responsible gene in each cell is enough to cause symptoms of the condition. When a person with an autosomal dominant condition has children, each child has a 50% chance to inherit the mutated copy of the gene. While many people with an autosomal dominant form of EB have a parent with EB, some cases result from a new mutation, occurring for the first time (called a de novo mutation). A person with a de novo mutation still has a 50% chance to pass the mutation on to each of his/her children.

In autosomal recessive inheritance, a person must have a mutation in both copies of the responsible gene in each cell to have EB. Typically, a person with EB inherits one mutated copy of the gene from each parent, who are referred to as carriers. Carriers usually do not have symptoms of the condition. When two carriers of an autosomal recessive condition have children, each child has a 25% chance to be affected, a 50% chance to be an unaffected carrier like each parent, and a 25% chance to not be a carrier and not be affected.

Epidermolysis bullosa acquisita (an acquired form of EB) is a rare autoimmune disorder and is not inherited.

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 blisters 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.
  • Thin appearance to the skin.
  • 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 vary from mild 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 or rough or thick 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, and the blisters can form in all layers of the skin. 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.

Doctors usually diagnose epidermolysis bullosa by:

• Asking about family and medical history, because most types of epidermolysis bullosa are inherited.
• Completing a physical exam and closely examining the skin, which can help doctors identify where the skin is separating to form blisters.
• Performing a skin biopsy and reviewing the tissue sample using special microscopic techniques, which helps doctors identify which layers of the skin are affected and determine the type of epidermolysis bullosa you have.
• Ordering genetic testing to identify specifically which gene mutations you may have. This helps doctors diagnose the specific type and subtype of the disease. People who have genetic testing should see a specialist or genetic counselor to help them understand the test results.

Epidermolysis bullosa (EB) can have either an autosomal dominant or autosomal recessive mode of inheritance in epidermolysis bullosa simplex (EBS) and dystrophic epidermolysis bullosa (DEB). Kindler syndrome and junctional epidermalysis bullosa (with the exception of one report, to our knowledge) are autosomal recessive. The mode of inheritance in a given family is usually established by analyzing the family history (pedigree analysis).

EBS in families in which only one child is affected (and the parents are unaffected) could be either autosomal dominant (as the result of a de novo gene mutation) or autosomal recessive. A de novo dominant mutation is the more likely mode of inheritance. The two modes of inheritance can usually be distinguished based on results of immunohistochemistry testing.

The only accurate method to determine the mode of inheritance in a person with DEB is molecular genetic testing to identify the responsible mutation(s). Symptoms, severity, and other types of lab results alone are not sufficient. Until recently, mutations in the responsible gene were considered 100% penetrant (meaning that all people with mutations would be affected). However in several affected families, a person with a mutation for dominant DEB had no signs of the disease.

People with questions about the inheritance of their condition and genetic risks to themselves or family members should speak with a genetics professional.

There is no cure for epidermolysis bullosa. The goals of treatment are to prevent and control symptoms by:

• Managing pain and itch.
• Protecting skin and caring for blisters and wounds.
• Treating and preventing infection.
• Maintaining or restoring mobility.
• Maintaining good nutrition.

Managing Pain and Itch

Your doctor may recommend a pain medication to help manage pain due to blisters and open wounds on the skin or in other areas of the body.

Some types of epidermolysis bullosa cause itching. To help prevent scratching, which can cause fragile skin to tear, your doctor may prescribe medications to help control itch.

Protecting Skin and Caring for Blisters and Wounds

Skin care is an important part of treating epidermolysis bullosa. Because the blisters can be large, it is important to care for the blisters and wounds to help prevent loss of body fluid from the blister and prevent infection of any wounds.

Changing bandages is an important step in protecting the skin and caring for blisters and wounds. Your health care team will give you directions on changing the bandages. When possible, use non-adhesive bandages. Sometimes, bandages still stick to the skin. If this happens, your doctor may recommend soaking the area in warm water to help loosen the bandages.

Treating and Preventing Infection

Some wounds and blisters can become infected. To treat infection, your doctor may prescribe oral or topical antibiotics. Wounds that are not healing may require medicated coverings or bandages.

You can help lower the chance of developing an infection by staying as healthy as possible by:

• Washing your hands before providing skin care or changing dressings.
• Applying topical antibiotic creams as recommended by your doctor.
• Staying healthy by eating a nutritious diet and following your doctor’s recommendations.

Even if you take precautions, an infection may still develop. If you see any signs of infection, including increased redness, increased pain in a skin lesion, red streaks coming from the wound or blister, pus, or fevers, contact your doctor right away.

Maintaining and Restoring Mobility

For some people, scarring can create contractures (abnormal tightening and shortening of muscles, tendons, or ligaments). This may happen in the hands and feet and limit your ability to move or use those muscles. A physical or occupational therapist can help improve, restore, or maintain your ability to move.

Maintaining Good Nutrition

Some people with epidermolysis bullosa may have blisters in the mouth, esophagus, and intestines, making it difficult to chew, swallow, and digest foods and drinks. Your health care provider may refer you to a dietician to help identify recipes and foods that are nutritious and easy to consume. Some options may include:

• Soft foods that are easy to chew and swallow.
• Foods that are warm or cool; you should avoid hot foods and drinks.
• Foods that help prevent constipation or diarrhea.

Some people may need additional treatments to treat and correct problems from epidermolysis bullosa.

• If you develop anemia, your doctor may recommend specific treatments to manage the complication.
• If scarring causes narrowing in the body, such as the esophagus or urinary tract, surgery can widen and open up the passageways.
• People who are not getting proper nutrition may need surgery to insert a tube that provides a direct access for food to go directly into the stomach.
• Some scarring can cause fingers or toes to fuse together. If this happens, surgery may be needed to release them.

You may see one of the following specialists:

• Dermatologists, who specialize in conditions of the skin, hair, and nails.
• Clinical geneticists, who diagnose and treat children and adults with genetic disorders.
• Nurse educators, who specialize in helping people understand their overall condition and set up their treatment plans.
• Occupational therapists, who teach how to perform activities of daily living safely.
• Pediatricians, who diagnose and treat children.
• Physical therapists, who teach ways to build muscle strength while keeping the skin protected.
• Primary care physicians, who diagnose and treat adults.
• Registered dietitians, who teach about nutrition and meal planning.

Living with epidermolysis bullosa can be hard; however, taking steps to care for your skin to help prevent blisters from forming and getting help to cope can help.

To minimize friction, and to stop tears and blisters from forming, your health care team may recommend the following:

• Keep your skin cool. Never apply anything hot to the skin, and avoid using water higher than your body temperature when bathing.
• Wear loose fitting, soft clothing to avoid rubbing against the skin or causing friction.
• Avoid overheating by keeping rooms at a cool, even temperature.
• Apply lotion to the skin to reduce friction and keep the skin moist.
• Use sheepskin on car seats and other hard surfaces.
• Wear mittens at bedtime to help prevent scratching while asleep.

Managing and caring for epidermolysis bullosa may be hard. You may find it helpful to find a community or online support group. Some people may find it helpful to speak to a mental health professional about coping with the disease.

Patients with epidermolysis bullosa frequently have oral involvement, with blisters that form in the mouth and esophagus. In some people, these lesions are likely to cause difficulty in chewing and swallowing food and drinks. If breast or bottle feeding results in blisters, infants may be fed using a preemie nipple (a soft nipple with large holes), a cleft palate nipple, an eyedropper, or a syringe. When the baby is old enough to take in food, adding extra liquid to pureed (finely mashed) food makes it easier to swallow. Soups, milk drinks, mashed potatoes, custards, and puddings can be given to young children. However, food should never be served too hot.

In patients with oral involvement, hard or brittle foods and foods with high acid content (eg, tomatoes, orange juice) should be avoided. Ingestion of these foods may injure the mucosa and cause new lesions.

It is important for individuals with epidermolysis bullosa to consult with a dietitian who can identify high-caloric and protein-fortified foods and beverages that help replace protein lost in the fluid from draining blisters. They can suggest vitamin and mineral nutritional supplements that may be needed, and show how to mix these into the food and drinks of young children. Dietitians can also recommend adjustments in the diet to prevent gastrointestinal problems, such as constipation, diarrhea, or painful elimination.