Close
Close

Epidermolysis bullosa

EB

Overview

Epidermolysis bullosa is a group of rare diseases that cause the skin to blister. The blisters may appear in response to minor injury, heat, or friction from rubbing, scratching or adhesive tape. In severe cases, the blisters may occur inside the body, such as the lining of the mouth or intestines.

Most types of epidermolysis bullosa are inherited. The condition usually shows up in infancy or early childhood. Some people don't develop signs and symptoms until adolescence or early adulthood.

Epidermolysis bullosa has no cure, though mild forms may improve with age. Treatment focuses on addressing the symptoms — such as infection and itching — and preventing pain and wounds. Severe forms may cause serious complications and can be fatal.

There are four main types of epidermolysis bullosa:

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

Identifying the exact type can be hard because there are many subtypes of EB. Within each type or subtype, a person may be mildly or severely affected. The disease can range from being a minor inconvenience to completely disabling, and fatal in some cases. Most types of EB are inherited. The inheritance pattern may be autosomal dominant or autosomal recessive. Management involves protecting the skin, reducing friction against the skin, and keeping the skin cool.

Symptoms - Epidermolysis bullosa

The symptoms of the disease depend on which variant the patient is afflicted with. The symptoms are also subject to the skin layer that is affected.

Epidermolysis bullosa signs and symptoms may include:

  • Fluid-filled blisters on the skin, especially on the hands and feet due to friction
  • Deformity or loss of fingernails and toenails
  • Internal blistering, including on the vocal cords, esophagus and upper airway
  • Skin thickening on the palms and the soles of the feet
  • Scalp blistering, scarring and hair loss (scarring alopecia)
  • Thin-appearing skin (atrophic scarring)
  • Tiny white skin bumps or pimples (milia)
  • Dental problems, such as tooth decay from poorly formed enamel
  • Difficulty swallowing (dysphagia)

Epidermolysis bullosa blisters may not appear until a toddler first begins to walk or until an older child begins new physical activities that trigger more intense friction on the feet.

Causes - Epidermolysis bullosa

Epidermolysis bullosa is usually inherited. Researchers have identified more than a dozen genes involved with skin formation that, if defective, may cause a type of epidermolysis bullosa.

The skin is made up of an outer layer (epidermis) and an underlying layer (dermis). The area where the layers meet is called the basement membrane zone. The type of epidermolysis bullosa you have is defined by where in these layers the blisters form.

There are around 27 variants of the disease that have been discovered so far. The main types of epidermolysis bullosa are:

  • Epidermolysis bullosa simplex

This is the most common form. It usually begins at birth or in early infancy and affects mainly the soles of the feet and the palms. In epidermolysis bullosa simplex, the gene that helps produce a fibrous protein (keratin) in the top layer of skin is faulty. The condition causes blistering in the epidermis. The blisters usually don't result in scars with this mild type. If you have epidermolysis bullosa simplex, it's likely you inherited a single copy of the defective gene from one of your parents (autosomal dominant inheritance pattern). If one parent has the single faulty gene, each of his or her offspring has a 50 percent chance of having the defect.

  • Junctional epidermolysis bullosa

This type usually is severe and becomes apparent at birth. A baby with this condition may develop a hoarse-sounding cry from continual blistering and scarring of the vocal cords. The genes that help form thread-like fibers (fibrils) that attach the epidermis to the basement membrane are faulty. This gene defect causes tissue separation and blistering in this deeper layer of skin. If you have junctional epidermolysis bullosa, it's because both your parents carry one copy of the defective gene and passed on the defective gene (autosomal recessive inheritance pattern). Even so, neither parent may show signs or symptoms of the disorder (silent mutation). If both parents carry one faulty gene, each of their offspring has a 25 percent chance of developing the disorder.

  • Dystrophic epidermolysis bullosa

With this type, you may experience mild to severe signs and symptoms. It generally becomes apparent at birth or during early childhood. This condition is related to a flaw in the gene that helps produce a type of collagen. If this substance is missing or doesn't function, the layers of the skin won't join properly. This type can be either dominant or recessive.

  • Kindler syndrome

This type is rare and usually becomes apparent at birth or soon after. This condition is called mixed type because blisters appear across the skin layers. The condition usually improves with time and can disappear. It is the only type that causes patchy discoloring (mottling) of skin exposed to the sun. Kindler syndrome is 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% (1 in 2) risk to inherit the mutated copy of the gene from the affected parent. Many people with an autosomal dominant form of EB have an affected parent, but in some cases a mutation in the responsible gene occurs for the first time in a person with no family history of EB (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 be affected. Typically, an affected person inherits one changed (mutated) copy of the responsible 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% (1 in 4) risk to be affected, a 50% (1 in 2) risk to be an unaffected carrier like each parent, and a 25% risk to not be a carrier and not be affected.

Epidermolysis bullosa acquisita is a rare type that isn't inherited. The blisters result from your immune system attacking healthy tissue by mistake. It's similar to another immune system disorder called bullous pemphigoid. It tends to cause blisters on the hands, feet and mucous membranes.

Prevention - Epidermolysis bullosa

It's not possible to prevent epidermolysis bullosa. But you can take steps to help prevent blisters and infection, for you or your child. Genetic counseling is recommended for prospective parents who have a family history of any form of epidermolysis bullosa.

During pregnanc, chorionic villus sampling to test the fetus is available. For couples at high risk of having a child with epidermolysis bullosa, the test can be done as early as week 8 - 10 of pregnancy. Talk to your obstetrician and genetic counselor.

  • Handle your child gently. Your infant or child needs your touch, but be very gentle. To pick up your child, place him or her on soft material, such as cotton, and support under the buttocks and behind the neck. Don't lift your child from under his or her arms.
  • Take special care with the diaper area. If your child wears diapers, remove the elastic bands and avoid cleansing wipes. Line the diaper with a nonstick dressing or spread it with a thick layer of zinc oxide paste.
  • Moderate the temperature in your home. Set your thermostat so that your home remains cool and the temperature remains steady.
  • Keep the skin moist. Gently apply lubricants, such as petroleum jelly.
  • Dress yourself or your child in soft materials. Use clothing that's simple to get on and off. Try sewing foam pads into the lining of clothing by elbows, knees and other pressure points. Use soft special shoes, if possible.
  • Prevent scratching. Trim fingernails regularly. Consider putting mittens on your infant at bedtime to help prevent scratching. This helps prevent infection.
  • Have your child refrain from rough activities. Prevent older children from participating in contact sports or other activities in which skin can be rubbed or injured easily. For mild forms, simple measures such as placing your child in long pants and sleeves for outdoor activities can be helpful.
  • Take care when dressing blisters. Don't apply adhesive bandages or tape to the skin. Be vigilant when medical procedures are performed to assure that tape is not used. By protecting blisters from breaking, you help prevent infection and fluid loss.
  • Avoid hard surfaces and rough materials. Use sheepskin or other soft material on car seats and infant seats. Use a water or air mattress on your child's bed and soft sheets and blankets.
  • Provide good nutrition. A varied, nutritious diet promotes growth and development in children and helps wounds heal. Consider using vitamins and supplements — such as calcium, iron and vitamin D — to help prevent complications.

Diagnosis - Epidermolysis bullosa

Based on clinical appearance and history. Histopathology determines the level of cleavage, which is further defined by electron microscopy and immunohistochemical mapping. A molecular technique including Western blot, Northern blot, restriction fragment length polymorphism (RFLP) analysis and DNA sequences may then identify the mutated gene.

Your doctor may suspect epidermolysis bullosa from the appearance of the skin. But laboratory tests are needed to confirm the diagnosis. They include:

  •  Skin biopsy for immunofluorescent mapping. With this technique, a small sample of affected skin is removed and examined to identify the layer of skin and proteins involved. This precise, reliable test is less expensive than other specialized testing options, such as electron microscopy.
  • Genetic testing. Genetic testing, if it's available and affordable, is sometimes used to confirm the diagnosis because most forms of epidermolysis bullosa are inherited. A small sample of your blood will be drawn and sent to a lab for analysis.
  • Prenatal testing. Families with a history of epidermolysis bullosa may want to consider prenatal testing and genetic counseling.

Prognosis - Epidermolysis bullosa

The outlook depends on the severity of the illness. Mild forms of epidermolysis bullosa improve with age.

In the severe forms, scarring after blisters form may cause:

  • Contracture deformities (for example, at the fingers, elbows, and knees) and other deformities
  • Feeding and swallowing difficulties if the mouth and esophagus are involved
  • Fused fingers and toes
  • Restricted mobility from scarring

Very serious forms of epidermolysis bullosa have a very high mortality rate.

Secondary infection is common.

Treatment - Epidermolysis bullosa

The chance of contracting a skin infection can be reduced by good nutrition, which builds the body's defenses and promotes healing, and by careful skin care with clean hands and use of sterile materials. For added protection, a doctor may recommend antibiotic ointments and soaks.

However, even in the presence of good care, it is possible for infection to develop. Signs of infection are redness and heat around an open area of skin, pus or a yellow drainage, excessive crusting on the wound surface, a red line or streak under the skin that spreads away from the blistered area, a wound that does not heal, and/or fever or chills. A doctor may prescribe a specific soaking solution, an antibiotic ointment, or an oral antibiotic to reduce the growth of bacteria. Wounds that are not healing may be treated by a special wound covering or biologically developed skin.

Treatment of epidermolysis bullosa aims to prevent complications and ease the pain of the blisters with appropriate wound care. The condition often progresses despite treatment, sometimes causing serious complications and death.

Medications:
Medications can help control pain and itching and address complications such as infection in the bloodstream (sepsis). Prescription oral antibiotics may be used if you show signs of a deep or widespread infection (fever, weakness, swollen lymph glands). An oral anti-inflammatory drug (corticosteroid) may help reduce the pain from dysphagia (difficulty swallowing).

Surgery:
Surgery may be considered to correct normal motion or to improve your ability to eat a healthy diet.

  • Restoring mobility. Repeated blistering and scarring can cause deformities, such as fusing of the fingers or toes or abnormal bends in the joints (contractures). Your doctor may recommend surgery to correct these deformities, particularly if they interfere with normal motion.
  • Widening the esophagus. Blistering and scarring of the esophagus may lead to esophageal narrowing, making eating difficult. Surgical dilation of the esophagus can relieve this and make it easier for food to travel from the mouth to the stomach. The patient receives light sedation, then the surgeon positions a small balloon in the esophagus and inflates it to widen the area.
  • Placing a feeding tube. To improve nutrition and help with weight gain, a feeding tube (gastrostomy tube) may be implanted to deliver food directly to the stomach. Feedings through the tube may be delivered overnight using a pump. Eating through the mouth is continued if possible so that the child will be able to eat with others for normal socializing.
  • Grafting skin. Several types of skin grafts have been used to treat wounds from epidermolysis bullosa. The Food and Drug Administration has approved a type of composite cultured skin (OrCel) for this purpose.

Rehabilitation therapy:

Working with a rehabilitation specialist (physical therapist, occupational therapist) can help ease the limitations on motion caused by scarring and shortening of the skin (contracture). A rehabilitation specialist can also give you guidance on the best ways to keep you or your child safe while going about daily activities. Swimming may also be helpful in preserving or regaining mobility.

Researchers investigating treatments:
Intensive studies are underway to find better ways to treat and relieve the symptoms of epidermolysis bullosa, including:

  • Gene therapy
  • Bone marrow transplantation
  • Protein replacement therapies
  • Cell-based therapies

 

Resources - Epidermolysis bullosa

  • NIH
  • Mayo Clinic
Orphan Therapies
Videos