Dystrophic epidermolysis bullosa

Synonyms

4

Overview

Epidermolysis bullosa is a group of genetic conditions that cause the skin to be very fragile and to blister easily. Blisters and skin erosions form in response to minor injury or friction, such as rubbing or scratching. Dystrophic epidermolysis bullosa is one of the major forms of epidermolysis bullosa. The signs and symptoms of this condition vary widely among affected individuals. In mild cases, blistering may primarily affect the hands, feet, knees, and elbows. Severe cases of this condition involve widespread blistering that can lead to vision loss, disfigurement, and other serious medical problems.

Researchers classify dystrophic epidermolysis bullosa into three major types. Although the types differ in severity, their features overlap significantly and they are caused by mutations in the same gene.

Autosomal recessive dystrophic epidermolysis bullosa, Hallopeau-Siemens type (RDEB-HS) is the most severe, classic form of the condition. Affected infants are typically born with widespread blistering and areas of missing skin, often caused by trauma during birth. Most often, blisters are present over the whole body and affect mucous membranes such as the moist lining of the mouth and digestive tract. As the blisters heal, they result in severe scarring. Scarring in the mouth and esophagus can make it difficult to chew and swallow food, leading to chronic malnutrition and slow growth. Additional complications of progressive scarring can include fusion of the fingers and toes, loss of fingernails and toenails, joint deformities (contractures) that restrict movement, and eye inflammation leading to vision loss. Additionally, young adults with the classic form of dystrophic epidermolysis bullosa have a very high risk of developing a form of skin cancer called squamous cell carcinoma, which tends to be unusually aggressive and is often life-threatening.

A second type of autosomal recessive dystrophic epidermolysis bullosa is known as the non-Hallopeau-Siemens type (non-HS RDEB). This form of the condition is somewhat less severe than the classic type and includes a range of subtypes. Blistering is limited to the hands, feet, knees, and elbows in mild cases, but may be widespread in more severe cases. Affected people often have malformed fingernails and toenails. Non-HS RDEB involves scarring in the areas where blisters occur, but this form of the condition does not cause the severe scarring characteristic of the classic type.

The third major type of dystrophic epidermolysis bullosa is known as the autosomal dominant type (DDEB). The signs and symptoms of this condition tend to be milder than those of the autosomal recessive forms, with blistering often limited to the hands, feet, knees, and elbows. The blisters heal with scarring, but it is less severe. Most affected people have malformed fingernails and toenails, and the nails may be lost over time. In the mildest cases, abnormal nails are the only sign of the condition.

Symptoms

The signs and symptoms can vary widely among affected people. In mild cases, blistering may primarily affect the hands, feet, knees, and elbows. Severe cases often involve widespread blistering that can lead to vision loss, disfigurement, and other serious medical problems.

Symptoms:

  • Abnormal blistering of the skin
  • Abnormality of the fingernails
  • Abnormality of the toenails
  • Aplasia/Hypoplasia of the skin
  • Cheilitis

Causes

DEB is caused by changes (mutations) in the COL7A1 gene and may be inherited in an autosomal dominant or autosomal recessive manner depending on the subtype. This gene provides instructions for making a protein that is used to assemble type VII collagen. Collagens are molecules that give structure and strength to connective tissues, such as skin, tendons, and ligaments, throughout the body. 

Mutations in the COL7A1 gene cause all three major forms of dystrophic epidermolysis bullosa. This gene provides instructions for making a protein that is used to assemble type VII collagen. Collagens are molecules that give structure and strength to connective tissues, such as skin, tendons, and ligaments, throughout the body. Type VII collagen plays an important role in strengthening and stabilizing the skin. It is the main component of structures called anchoring fibrils, which anchor the top layer of skin, called the epidermis, to an underlying layer called the dermis.

COL7A1 mutations alter the structure or disrupt the production of type VII collagen, which impairs its ability to help connect the epidermis to the dermis. When type VII collagen is abnormal or missing, friction or other minor trauma can cause the two skin layers to separate. This separation leads to the formation of blisters, which can cause extensive scarring as they heal. Researchers are working to determine how abnormalities of type VII collagen also underlie the increased risk of skin cancer seen in the severe form of dystrophic epidermolysis bullosa.

Prevention

It's not possible to prevent epidermolysis bullosa. But you can take steps to help prevent blisters and infection, for you or your child.

  • 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

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.

Treatment

New blisters should be lanced, drained, and protected. Some patients need nutritional support, supplements, occupational therapy and/or surgery depending on the associated features of the disease.

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

  • NIH
  • Mayo Clinic
  • Genetics Home Reference