Physiology
15 March 2012

Epidermolysis Bullosa

Childhood is a time of wonderment in any human’s life. It is a time for frolicking and having fun. A time to explore, to discover, to interact with other children, a time to be carefree…or so one would think. But imagine a child who will never know that it is like to run and jump, to play games with other children because even the slightest physical contact will damage his or her skin. Imagine a child who can subsist on only a diet of soft food and liquids due to lesions and scarring in his or her esophagus. Imagine a child who cannot be hugged tightly by a loving parent because this contact will cause their skin to burn and blister. These children have come to be known as “Butterfly Children” as their skins are as frail and delicate as that of a butterfly’s wing. This is the nightmare of living with a disease known as Epidermolysis bullosa.

Epidermolysis bullosa is in a group of inherited diseases that are characterized by blistering lesions on the skin’s surface and also in the mucous membranes. These lesions may occur elsewhere on the body but most commonly occur at areas more apt to friction and minor trauma such as the hands and feet (Ngan, 2011). In severe cases, blisters are not confined to the outer layers of the skin. They can also occur inside the body in places such as the lining of the mouth, esophagus, stomach, intestines, upper airway, bladder, and the genitals (Fine, 2009). There are three main types of inherited Epidermolysis bullosa:

• Epidermolysis bullosa simplex (EBS)
• Junctional epidermolysis bullosa (JEB)
• Dystrophic epidermolysis bullosa (DEB)

Depending on the type present, Epidermolysis bullosa varies in its severity from minor blisterings to a lethal form involving the organs of the body. The one that I will be focusing on is the more severe and often times, lethal form called Dystrophic epidermolysis bullosa.

Causes

The skin is composed of an outer layer called the epidermis and an underlying layer called the dermis. The area where the two layers meet is called the basement membrane zone (Fine, 2003). All forms of hereditary Epidermolysis bullosa are caused by structural abnormalities in the skin. Usually this abnormality occurs within a protein molecule called keratin which then causes weakness of the cells. The dystrophic forms, both recessive and dominant, are usually due to collagen VII defects in the upper dermis. This molecule forms a structure of anchoring fibrils that are responsible for attaching the epidermis firmly to the dermis.
Blister formation of EB Simplex occurs in the epidermis and Junctional EB is seen in the lamina lucida within the basement membrane zone. Dystrophic EB is a very scarring form of EB which occurs in the deeper layers of the skin known as the lamina densa or upper dermis (Bayliss et al, 2012). Children with EB have usually inherited the condition through defective genes that they have received from one or both parents. Genes are located in the cells of the body and determine traits that are passed on from parent to child. The genes are located on chromosomes, which are structured inside a cell’s nucleus (Fine, 2009). A dominant form means that the offspring could have inherited the gene or train from one affected parent. Anyone who has dominant Dystrophic EB, whether male or female, can pass the condition on to his or her child or children. Each time a pregnancy occurs, there is a one in two chance that the child will be born with the disease. The recessive form means that both parents must have the gene to pass it on to their child even though they are unaffected. This is the form of Epidermolysis Bullosa that tends to be the most severe and often times, lethal (Bayliss et al, 2012).

Signs and Symptoms

The onset of Dystrophic Epidermolysis Bullosa occurs at birth or in early childhood. Some of the characteristics of this condition is the formation of large, fluid-filled blisters that develop over considerable areas of the body due to minor trauma to the skin. Chafing, rubbing and even temperature changes may cause blisters to arise. Because of the severity of the disease, scarring after the appearance of blisters can result in deformities. Such deformities can include the fusion of the fingers with the hand which is also known as “webbing”. This can cause the hands or feet to become lodged in a contracted position resulting in the inability to extend the arms and legs fully. If the disease affects the body internally for instance, such as lesions erupting in the esophagus, this will results in the narrowing of the tube due to build-up of scar tissue. This will likely cause difficultly in swallowing so that the child will have to resort to a diet of soft foods or even liquid to prevent choking as food may easily become lodged in the throat. Severe itching and tingling is also associated with EB as when the sores heal, they tend to itch more. If there is an infection present, this will cause the skin to itch even more. Scratching causes further damage and should be avoided as much as possible.

The eyes may also suffer with blisters and corneal abrasions which is extremely painful. Problems with teeth and tooth decay can arise as oral hygiene in severe cases of EB is hard to treat. If tooth loss occurs, dentures are not an option as the gums are often blistered and fragile. Other indicators of the disease can involve the GI tract which may include lesions in the mouth (again causing difficulty in eating and swallowing) all the way to the anal region.

Diagnosis

Recent techniques now make it possible to identify defective genes in EB patients and their families. Doctors can detect the disease by identifying, in the presence of blistering, where the skin is separating to form the blisters and what kind of EB the patient has by performing a kin biopsy and examining the sample under a microscope. A high-powered electron microscope can greatly magnify images to identify defects in a sample of skin with regards to defects and abnormalities. Another test involves utilizing a microscope and reflected light to see if the proteins required for forming connective fibrils, filaments, and hemidesmosomes (these are adhesive structures involved in the anchoring of structures to the basement membrane and the underlying dermis) are absent or have diminished in number (Fine, 2009). Other ways to detect the disease is by using immunofluorescence and gene mapping and immunohistochemical staining with EB-specific monoclonal antibodies (Puvabanditsin, 2011).

Since underlying genetic defects have been linked with the disease, doctors investigate family history of Epidermolysis bullosa and the patient’s geographic and/or racial ancestry (Puvabanditsin, 2011). Prenatal diagnosis can now be achieved by way of amniocentesis (the removal of a small amount of amniotic fluid by insertion of a long needle in the womb of a pregnant woman) and testing for the disease as early as the tenth week of development (Fine, 2009).

Treatment

In treating the disease, the goal is to prevent the formation of blisters and the ensuing complications. Depending on the severity of the disease, treatment can be minor to aggressive. It is vital to try and prevent any kind of trauma to the skin and to avoid extreme temperatures. Since blisters can form at the slightest pressure or frictions, parents may be hesitant to pick up their babies so the utmost care must be exercised when handling a baby or child with this disease. A number of things can be done to protect the skin from damage such as avoiding extreme temperatures, dressing the child in loose, soft clothing to keep friction on the skin to a minimum and applying lubricants to the skin to protect it and keep it moisturized (Fine, 2009).

If blistering does occur, the blister should be carefully pierced with a sterile needle. By puncturing the lesion and draining the fluid, build-up of fluid will be avoided and this will prevent the blister from spreading. Once the fluid is drained, ointments such as hydrogels, bacitracin or silver sulfadiazine can be applied topically and the area should be covered with gauze infused with white petroleum to assist in optimal healing (Puvabanditsin, 2011). If difficulty in swallowing is observed, the use of oral steroids for short periods of time may be administered. However, long-term use of steroids is not recommended. Dental hygiene is also very important in keeping the mouth healthy and free of infection so regular visits to a dentist is highly recommended.

A diet high in protein and calories is recommended as when the skin has been injured, the body requires more nutrients to assist in healing and recovery. It is advisable to work closely with a dietician or nutritionist where diet is concerned. These professionals can recommend adjustments to the diet to reduce GI tract upsets including constipation, diarrhea or painful elimination (Fine, 2009). In the case where deformities to the extremities have occurred, working with a physical therapist can be helpful in maintaining some range of motion in joint areas to reduce contractures.

Complications

Complications such as infection, malnutrition and dehydration can lead to death in infants. Infection to the skin can lead to sepsis (a toxic condition resulting from the spread of bacteria) and in the eye, where the cornea has been affected, blindness can result. Due to esophageal strictures, malnutrition can arise and severe anemia can ensue. In the case where there is extensive damage and ulceration to the skin, skin grafting may be necessary. Patients that do not have access to donor sites for skin grafting may need advanced therapy with bioengineered skin (Puvabanditsin, 2011).

If someone with Epidermolysis bullosa survives childhood, metastatic squamous cell cancer of the skin can develop and ultimately lead to death. The skin cancer often occurs in the patient with recessively inherited dystrophic EB. Cancer of the skin typically develops between the ages of 15 and 35, especially in areas where skin is exposed to the sun on a daily basis. Growth retardation can also occur in a severely affected individual, often in those with RDEB (Recessive Dominant Epidermolysis Bullosa) and children are monitored very closely by their doctors to watch for any sign of growth problems (Bayliss et al, 2012).

Occurrences

An estimated 1 out of every 50,000 births in the United States are affected with some type of Epidermolysis bullosa. The disease can affect persons throughout the world no matter what their race or ethnicity and it affects both sexes equally (Bayliss et al, 2012). The outcome of the disease depends on the severity. Mild forms such as EB Simplex often improve with age but of the three major forms of EB, two of them have a high mortality rate especially in the very young. The first is Junctional EB, which often causes death in newborns. This form affects the internal organs of the baby’s airway hence restricting breathing. The other form is Recessive Dominant Epidermolysis Bullosa. If the child is fortunate enough to live through childhood, they often do not live past their thirties. RDEB is considered to worsen with age due to contact breakdown of the skin which ultimately causes severe scarring.

Prognosis

Although there is no cure for Epidermolysis bullosa, many complications can be decreased or avoided through early intervention and treatment (Bayliss et al, 2012). At one time, research on Epidermolysis bullosa was limited to the description of the disease and understanding what happens in the layers of skin. Today research is being focused on seeking medications and their effect on tissues (Fine, 2009). Researchers at The Stanford University Medical School have been working on a way to insert DNA into skin cells taken from children with RDEB. These skin cells are then modified to form healthy skin which is then transplanted onto the skin of mice. To date, the most current breakthrough has been the development of a process to administer the gene by injection. Prior to this breakthrough, no other research group had been able to administer the modified gene into the stem cells where healthy skin is formed. Since the body renews skin cells every three months, the correction was lost in the sloughing off process. With further research, there is now a way to introduce the gene into the stem cells where the correction is now sustainable.

With amazing breakthroughs such as this, more positive prognoses can only follow and these “butterfly children” suffering with any form of this debilitating disease, can look forward to a day when they no longer have to suffer with the pain and scarring of Epidermolysis bullosa.

Works Cited

Ngan, Vanessa, staff writer. Epidermolysis Bullosa. New Zealand Dermatological Society
Inc. 28 June 2011. Web. 10 March 2012.

Puvabanditsin, Surasak, M.D. Pediatric Epidermolysis Bullosa. Medscape., 17 Aug 2011. Web. 10 March 2012.

Fine, Jo-David, M.D. Questions and Answers about Epidermolysis Bullosa. National Institutes of Health, Department of Health and Human Services. July 2009. Web. 10 March 2012.

Bayliss, Susan, Dr., Dr. Sharon Glick, Dr. Robert Meirowitz, Dr Alan Moshell Dr. Amy Paller, Dr. Ellen Pfendner Dr. Lawrence Schachner, Dr. Daniel Siegel, Dr. Alan R. Shalita, Dr. Mary K. Spraker. About EB. The Dystrophic Epidermolysis Bullosa Research Association of America. 2012. Web. 10 March 2012.