Epidermolysis Bullosa (EB) – Definition, Causes, and Treatments.

Definition

Epidermolysis Bullosa (EB) is a group of rare genetic skin conditions, which is characterized by extremely fragile skin and recurrent blister formation, resulting from minor mechanical friction or trauma. The skin has two layers; the outer layer is called the epidermis and the inner layer called the dermis. Normally, there are ‘anchors’ between the two layers that prevent them from moving independently from one another. In people with EB, the two skin layers lack the anchors that hold them together, and any action that creates friction between the layers (like rubbing or pressure) will create blisters and painful sores. Sufferers of EB have compared the sores to third-degree burns.

In many countries, Butterfly Children is a term often used to describe younger patients because their skin is as fragile as a butterfly’s wings. Sometimes, children with the condition are also described as Cotton Wool Babies. And in South America, Crystal Skin Children is the term used.

Types of EB

There are four major types of EB based on the site of blister formations within the skin layers as follows:

Epidermolysis bullosa simplex (EBS)

In this type, blistering occurs in the upper layer of the skin called the epidermis. It is characterized by a lack of adhesion of the skin directly above the basement membrane (the basal layer). EBS usually is inherited in an autosomal dominant manner, meaning that a defective gene inherited from a parent. The blistering may develop either on hands or feet (localized EBS) or all over the body (generalized EBS).

Junctional epidermolysis bullosa (JEB)

In this type, blistering occurs in a skin layer called the lamina lucida within the basement membrane zone, which is situated at the junction between the epidermis (upper layer of the skin) and the dermis (lower layer). JEB is the most severe type of EB. Like EBS, JEB also is inherited in an autosomal recessive manner.

Dystrophic epidermolysis bullosa (DEB)

In this type, blistering occurs in the lamina densa, which is a component of the basement membrane zone between the lamina lucida and the underlying dermis of the skin. DEB is characterized by the scarring of the healed wounds, resulting in contraction of the joints, fusion of the fingers and toes, contraction of the mouth membranes, and narrowing of the esophagus. It may be inherited in a recessive or dominant manner.

 

Kindler syndrome

In this type of EB, blistering may occur at multiple levels within the basement membrane zone, or in skin layers beneath it. This syndrome is rare within this disease and characterized by blisters on the hands and feet, altered skin coloring, and damage to the inner lining of areas such as the mouth, intestines, or eyes.

Epidermolysis bullosa acquisita (EBA)

Another rare type of EB is called epidermolysis bullosa acquisita. EBA is a non-genetic autoimmune disease, caused by the development of antibodies (proteins that attack foreign substances) against type VII collagen, an essential skin protein. An examination of skin blisters will show antibodies deposited in the basement membrane between the epidermis and dermis. This form of EB is very rare, is not inherited, and usually develops during adulthood.

Pathophysiology

EB is caused by mutations involving at least 18 genes encoding structural proteins within keratin intermediate filaments, focal adhesions, desmosome cell junctions, and hemidesmosome attachment complexes, which form the intraepidermal adhesion and dermoepidermal anchoring complex within the basement membrane zone (BMZ) of the skin and mucosae. The molecular aberrations interfere with the functional and structural integrity of the BMZ (which is a highly specialized interface between epithelial cells and the underlying matrix) that is crucial for cell adhesion, proliferation, and differentiation; tissue repair; and barrier function and leads to cell and tissue dehiscence

Causes of Epidermolysis Bullosa

• Epidermolysis bullosa (EB) is almost always caused by a genetic mutation that makes the skin extremely fragile. In rare conditions, it’s not inherited but is caused by the immune system.
• Genetic causes of EB include the presence of a defective (or mutated) gene that is inherited from one or both parents, or it occurs as a spontaneous mutation, making the child the first in the family to have the disease.
• Non-genetic reasons for EB a type that results from the immune system attacking the body’s healthy tissue by mistake. In this case, the body produces antibodies (proteins that act against foreign substances) against its own molecules causing autoimmune disorders.

Risk factors

• A positive family history of Epidermolysis Bullosa increases one’s risk of this condition
• It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.
• Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

Clinical manifestations

The main symptoms of all types of EB include:

• Skin that blisters easily
• Blisters inside the mouth
• Blisters on the hands and soles of the feet
• Scarred skin, sometimes with small white spots called milia
• Thickened skin and nails

• Alopecia (hair loss)
• Blisters around the eyes and nose
• Blisters in or around the mouth and throat, causing feeding problems or swallowing difficulty
• Painful urination resulting from blistering in the urinary tract.
• Dental problems such as tooth decay
• Hoarse cry, cough, or other breathing problems
• Tiny white bumps on the previously injured skin
• Nail loss or deformed nails

Complications of Epidermolysis Bullosa

A number of serious complications are associated with EB:

• Blisters can lead to infection and open sores
• Skin cancer is more common. Patients with DEB have a higher chance of developing squamous cell carcinoma before the age of 35 years. This is an aggressive form of skin cancer.
• Deformities can occur, for example, the fusion of the fingers in people with DEB.
• Vision loss is possible if the conjunctiva and other parts of the eye are affected.
• Malnutrition can happen if the patient cannot swallow easily.
• Anemia may develop due to chronic inflammation and blood loss.
• Some of the complications of EB, such as dehydration, infection, internal blisters, malnutrition can be fatal, especially in young infants.

Diagnosis and test

The following procedures may be used to diagnose Epidermolysis Bullosa:

• A thorough evaluation of the individual’s medical history and a complete physical examination including of the skin, mouth, face, and other body regions
• During history-taking the physician may want to know the following:
• When the symptoms began and whether they are becoming worse
• About one’s personal and family history of skin diseases, birth moles, etc.
• The appearance of the skin, together with the family history may help in making a preliminary diagnosis of Epidermolysis Bullosa

Test

• Skin biopsy: In this procedure, the physician removes a sample of the skin tissue and sends it to the laboratory for a histopathological examination. The pathologist examines the biopsy under a microscope and arrives at a definitive diagnosis after a thorough evaluation of the clinical and microscopic findings, as well as by correlating the results of special studies on tissues (if any performed).
• Specialized tests, which will help in diagnosing the specific type of EB, include electron microscopy, immune-fluorescent mapping, and other studies
• Genetic testing: a Blood sample is analyzed for mutations associated with EB
• Prenatal testing: Families with a history of epidermolysis bullosa may want to consider prenatal testing and genetic counseling.

Other tests that may be required depending on the clinical situation include:

• Wound culture for bacterial infection
• Upper gastrointestinal endoscopy
• Blood tests for nutritional deficiencies
• Blood tests, such as complete blood count, to determine one’s overall well-being

Treatment and medications

Epidermolysis bullosa (EB) has no cure and its treatment takes several factors into consideration, including areas affected physiological response to healing, infection, and involvement of other organ systems. Treatment aims to:

• Avoid skin damage
• Improve the quality of life
• Reduce the risk of developing complications, such as infection and malnutrition

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 to treat this condition may include:

• Skin grafting in places where sores are deep
• Dilation (widening) of the esophagus if there is a narrowing
• 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.
• Repair of hand deformities
• Removal of any squamous cell carcinoma (a type of skin cancer) that develops

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.

Home remedies

Follow these guidelines at home:

• Take good care of your skin to prevent infections.
• Follow your provider’s advice if blistered areas become crusted or raw. You might need regular whirlpool therapy and to apply antibiotic ointments to wound-like areas. Your provider will let you know if you need a bandage or dressing, and if so, what type to use.
• You may need to use oral steroid medicines for short periods of time if you have swallowing problems. You may also need to take medicine if you get a candida (yeast) infection in the mouth or throat.
• Take good care of your oral health and get regular dental check-ups. It is best to see a dentist who has experience treating people with EB.
• Eat a healthy diet. When you have a lot of skin injury, you may need extra calories and protein to help your skin heal. Choose soft foods and avoid nuts, chips, and other crunchy foods if you have sores in your mouth. A nutritionist can help you with your diet.
• Do exercises a physical therapist shows you to help keep your joints and muscles mobile.

Prevention of Epidermolysis Bullosa

• Wearing clothing that does not rub or irritate, for example, simple cotton
• Using lubricants on the skin to reduce friction
• Keeping room temperatures cool to prevent overheating.
• Putting sheepskin on hard surfaces and car seats and wearing mittens while sleeping to prevent scratching.
• A person with EBS can prevent blisters to the feet by avoiding long walks. Those with DEB or JEB should be extremely careful to avoid scratches and knocks to the skin.
• Blisters or pain in the mouth can be helped by avoiding spicy foods and food items that may cut and scratch, such as potato chips.
• 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.
• To pick up an infant with EB, it is better to place one hand under their buttocks and the other behind their back.
• Care should be taken that eyeglasses do not cause blistering around the nose and ears.