Epidermolysis bullosa is a group of blistering skin conditions. The skin is so fragile in people with epidermolysis bullosa that even minor rubbing may cause blistering. At times, the person with epidermolysis bullosa may not be aware of rubbing or injuring the skin even though blisters develop. In severe epidermolysis bullosa, blisters are not confined to the outer skin. They may develop inside the body, in such places as the linings of the mouth, esophagus, stomach, intestines, upper airway, bladder, and genitals.
The skin has an outer layer called the epidermis and an underlying layer called the dermis. The place where the two layers meet is called the basement membrane zone . The main forms of epidermolysis bullosa are epidermolysis bullosa simplex (EBS), junctional epidermolysis bullosa (JEB), and dystrophic epidermolysis bullosa (DEB). Epidermolysis bullosa simplex occurs in the outer layer of skin; junctional epidermolysis bullosa and dystrophic epidermolysis bullosa occur in the basement membrane zone. These major types of epidermolysis bullosa, which will be described throughout this text, also have many subtypes.
Epidermolysis bullosa occurs in all racial and ethnic groups and affects males and females equally. The disease is not always evident at birth. Milder cases of epidermolysis bullosa may become apparent when a child crawls, walks, or runs, or when a young adult engages in vigorous physical activity.
Most people with epidermolysis bullosa have inherited the condition through faulty genes they receive from one or both parents. Genes are located in the body's cells and determine inherited traits passed from parent to child. They also govern every body function, such as the formation of proteins in the skin. Several genes are known to underlie the different forms of epidermolysis bullosa. Genes are located on chromosomes, which are structures in each cell's nucleus.
In an autosomal dominant form of epidermolysis bullosa, the disease gene is inherited from only one parent who has the disease, and there is a 50-percent (1 in 2) chance with each pregnancy that a baby will have epidermolysis bullosa. In the autosomal recessive form, the disease gene is inherited from both parents.
Neither parent has to show signs of the disease; they simply need to "carry" the gene, and there is a 25-percent (1 in 4) chance with each pregnancy that a baby will have epidermolysis bullosa. Epidermolysis bullosa can also be acquired through a mutation (abnormal change) in a gene that occurred during the formation of the egg or sperm reproductive cell in a parent. Neither the sex of the child nor the order of birth determines which child or how many children will develop epidermolysis bullosa in a family that has the faulty gene.
Although epidermolysis bullosa simplex can occur when there is no evidence of the disease in the parents, it is usually inherited as an autosomal dominant disease. In epidermolysis bullosa simplex, the faulty genes are those that provide instructions for producing keratin, a fibrous protein in the top layer of skin. As a result, the skin splits in the epidermis, producing a blister.
In junctional epidermolysis bullosa, there is a defect in the genes inherited from both parents (autosomal recessive) that normally promote the formation of anchoring filaments (thread-like fibers) or hemidesmosomes (hem-ee-DES-mo-soms) (complex structures composed of many proteins). These structures anchor the epidermis to the underlying basement membrane. The defect leads to tissue separation and blistering in the upper part of the basement membrane.
There are both dominant and recessive forms of dystrophic epidermolysis bullosa. In this condition, the filaments that anchor the epidermis to the underlying dermis are either absent or do not function. This is caused by defects in the gene for type VII collagen, a fibrous protein that is the main component of the anchoring filaments.
Epidermolysis bullosa acquisita (EBA) is a rare autoimmune disorder in which the body attacks its own anchoring fibrils with antibodies, the special proteins that help fight and destroy foreign substances that invade the body. In a few cases, it has occurred following drug therapy for another condition; in most cases, the cause is unknown.
Dermatologists can identify where the skin is separating to form blisters and what kind of epidermolysis bullosa a person has by doing a skin biopsy (taking a small sample of skin that is examined under a microscope). One diagnostic test involves use of a microscope and reflected light to see if proteins needed for forming connecting fibrils, filaments, or hemidesmosomes are missing or reduced in number. Another test involves use of a high-power electron microscope, which can greatly magnify tissue images, to identify structural defects in the skin.
Diagnostic techniques make it possible to identify defective genes in epidermolysis bullosa patients and their family members. Prenatal diagnosis can now be accomplished by amniocentesis (removing and examining a small amount of amniotic fluid surrounding the fetus in the womb of a pregnant woman) or sampling the chorionic villus (part of the outer membrane surrounding the fetus) as early as the 10th week of pregnancy.
The major sign of all forms of epidermolysis bullosa is fragile skin that blisters, which can lead to serious complications. For example, blistering areas may become infected, and blisters in the mouth or parts of the gastrointestinal tract may interfere with proper nutrition.
Following is a summary of some of the characteristic signs of various forms of epidermolysis bullosa.
A generalized form of epidermolysis bullosa simplex usually begins with blistering that is evident at birth or shortly afterward. In a localized, mild form called Weber-Cockayne, blisters rarely extend beyond the feet and hands. In some subtypes of epidermolysis bullosa simplex, the blisters occur over widespread areas of the body. Other signs may include thickened skin on the palms of the hands and soles of the feet; rough, thickened, or absent fingernails or toenails; and blistering of the soft tissues inside the mouth. Less common signs include growth retardation; blisters in the esophagus; anemia (a reduction in the red blood cells that carry oxygen to all parts of the body); scarring of the skin; and milia, which are small white skin cysts.
This disease is usually severe. In the most serious forms, large, ulcerated blisters on the face, trunk, and legs can be life-threatening because of complicated infections and loss of body fluid that leads to severe dehydration. Survival is also threatened by blisters that affect the esophagus, upper airway, stomach, intestines, and urogenital system. Other signs found in both severe and mild forms of junctional epidermolysis bullosa include rough and thickened or absent fingernails and toenails; a thin appearance to the skin (called atrophic scarring); blisters on the scalp or loss of hair with scarring (scarring alopecia); malnutrition and anemia; growth retardation; involvement of soft tissue inside the mouth and nose; and poorly formed tooth enamel.
The dominant and recessive inherited forms of dystrophic epidermolysis bullosa have slightly different symptoms. In some dominant and mild recessive forms, blisters may appear only on the hands, feet, elbows, and knees; nails usually are shaped differently; milia may appear on the skin of the trunk and limbs; and there may be involvement of the soft tissues, especially the esophagus. The more severe recessive form is characterized by blisters over large body surfaces, loss of nails or rough or thick nails, atrophic scarring, milia, itching, anemia, and growth retardation. Severe forms of recessive dystrophic epidermolysis bullosa also may lead to severe eye inflammation with erosion of the cornea (clear covering over the front of the eye), early loss of teeth because of tooth decay, and blistering and scarring inside the mouth and gastrointestinal tract. In most people with this form of epidermolysis bullosa, some or all the fingers or toes may fuse (pseudosyndactyly). Also, individuals with recessive dystrophic epidermolysis bullosa have a high risk of developing a form of skin cancer called squamous cell carcinoma. It primarily occurs on the hands and feet. The cancer may begin as early as the teenage years. It tends to grow and spread faster in people with epidermolysis bullosa than in those without the disease.
People with mild forms of epidermolysis bullosa may not require extensive treatment. However, they should attempt to keep blisters from forming and prevent infection when blisters occur. Individuals with moderate and severe forms may have many complications and require psychological support along with attention to the care and protection of the skin and soft tissues. Patients, parents, or other care providers should not feel that they must tackle all the complicated aspects of epidermolysis bullosa care alone. There are doctors, nurses, social workers, clergy members, psychologists, dietitians, and patient and parent support groups that can assist with care and provide information and emotional support.
In many forms of epidermolysis bullosa, blisters will form with the slightest pressure or friction. This may make parents hesitant to pick up and cuddle young babies. However, a baby needs to feel a gentle human touch and affection. Parents can learn the best ways to handle babies to minimize the chances of blisters.
A number of things can be done to protect the skin from injury. These include:
When blisters appear, the objectives of care are to reduce pain or discomfort, prevent excessive loss of body fluid, promote healing, and prevent infection.
The doctor may prescribe a mild analgesic to prevent discomfort during changes of dressings (bandages). Dressings that are sticking to the skin may be removed by soaking them off in warm water. Although daily cleansing may include a bath with mild soaps, it may be more comfortable to bathe in stages where small areas are cleaned at a time.
Blisters can become quite large and create a large wound when they break. Therefore, a medical professional will likely provide instructions on how to safely break a blister in its early stages while still leaving the top skin intact to cover the underlying reddened area. After opening and draining, the doctor may suggest that an antibiotic ointment be applied to the area of the blister before covering it with a sterile, nonsticking bandage. To prevent irritation of the skin from tape, a bandage can be secured with a strip of gauze that is tied around it. In milder cases of epidermolysis bullosa or where areas are difficult to keep covered, the doctor may recommend leaving a punctured blister open to the air.
A moderately moist environment promotes healing, but heavy drainage from blister areas may further irritate the skin, and an absorbent or foam dressing may be needed. There are also contact layer dressings where a mesh layer through which drainage can pass is placed on the wound and is topped by an outer absorbent layer. The doctor or other health care professional may recommend gauze or bandages that are soaked with petroleum jelly, glycerin, or lubricating substances, or may suggest more extensive wound care bandages or products.
The chances of 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, the doctor may recommend antibiotic ointments and soaks.
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. The 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.
Blisters that form in the mouth and esophagus in some people with epidermolysis bullosa 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.
Dietitians are important members of the health care team that assists people with epidermolysis bullosa. They can work with family members and older patients to find recipes and prepare food that is nutritious and easy to consume. For example, they 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.
Surgical treatment may be necessary in some forms of epidermolysis bullosa. Individuals with the severe forms of autosomal recessive dystrophic epidermolysis bullosa whose esophagus has been narrowed by scarring may require dilation of their esophagus for food to travel from the mouth to the stomach. Other individuals who are not getting proper nutrition may need a feeding tube that permits delivery of food directly to the stomach. Also, patients whose fingers or toes are fused together may require surgery to release them.
Epidermolysis bullosa is a difficult, sometimes painful, and often disfiguring disease. Most adults with signs of epidermolysis bullosa or who know they carry the gene would like to spare future generations, including their own potential offspring, from this condition. With the knowledge of specific gene mutations that cause epidermolysis bullosa, it is now possible to determine the specific gene mutation in the family and then to conduct prenatal tests on pregnant women with a fetus at risk of epidermolysis bullosa to determine the status of the fetus. A genetic counselor can test for gene mutations, provide information on the likelihood of passing the gene for epidermolysis bullosa to children, and provide advice on future childbearing. Genetic counseling can be a crucial step in helping families make decisions about their family planning.
At one time, research on epidermolysis bullosa was limited to describing the disease and understanding what happens in the layers of skin. Today, research focuses on finding gene mutations and their effect on the tissues, copying genes, reproducing gene mutations for research to correct them, inserting healthy genes to replace missing or mutated genes, and screening those who may have a gene mutation causing epidermolysis bullosa.
In one gene therapy study, investigators are looking at skin cells known as keratinocytes to find out if they can prevent the genes from expressing faulty keratin. In another study, researchers found through the use of mouse models that they can successfully deliver modified cells back into the host. They now are attempting to see if such gene therapy works in humans and, if it provides benefits, how long the benefits last. Also, scientists are attempting to transplant stem cells into the skin of mice affected by epidermolysis bullosa to see if such therapy can restore the basement membrane and reduce the fragility of the skin. And the possibility of using the stem cells extracted from a person affected by epidermolysis bullosa and transplanting them back into the host is being explored, perhaps setting the stage for future adult stem cell therapies.
Applying newer diagnostic techniques, investigators are beginning to link specific gene defects with the protein problems they produce. Now that the epidermolysis bullosa-causing gene mutations can be identified, doctors can identify ova (eggs) that do not contain an abnormal gene. These ova can be selected for in vitro fertilization, thus improving the chances of having healthy children in families with the epidermolysis bullosa gene.
Research on skin biology continues; researchers are looking at how skin cells form and which molecules regulate gene expression. Understanding how healthy skin develops will help researchers discover if and when development goes wrong and causes diseases.
-NIH
