What Is Epidermolysis Bullosa? What Causes Epidermolysis Bullosa?

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Main Category: Dermatology
Also Included In: Pediatrics / Children's Health
Article Date: 10 Nov 2009 - 0:00 PDT

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Epidermolysis bullosa (EB) is a rare group of inherited conditions of connective tissue that cause blisters in the skin and mucosal membranes in response to heat, friction, rubbing, scratching or minor injury. EB is caused by a fault (mutation) in the keratin or collagen gene. According to the CDC (Centers for Disease Control and Prevention), USA, it affects approximately 1 in every 50,000 people. In the UK approximately 1 live birth in every 17,000 has EB. About 5,000 people in the UK today have EB.

The skin of patients with epidermolysis bullosa is extremely fragile. Even very slight friction may cause blisters as layers of skin more independently and separate. EB severity can range from mild to life-threatening.

In it mildest form the blistering is confined to hands and feet. In its severest form the whole body is affected, wounds heal extremely slowly, there is significant scarring, physical deformity and disability. In its severest form EB is fatal in infancy. People with severe EB have a significantly high risk of developing skin cancers.

Normal human skin has two layers - the epidermis (outer part) and the dermis (inner part). Most of us have protein anchors in between the layers, made of collagen; they prevent the two layers from shearing - moving independently from one another. People with EB lack these protein anchors, so when there is any friction on the skin, the two layers rub against each other and separate, resulting in painful sores and blisters.

In some cases the blistering also occurs in the inner mucous membranes, such as the mouth and esophagus, making eating solids virtually impossible. Patients whose inner body linings (mucous membranes) are also affected may find urinating painful.

The term Butterfly children is sometimes used for younger individuals with EB, because their skin is said to be as fragile as the wings of a butterfly.

EB affects both males and females equally, as well as all ethnic groups. EB is incurable and treatment focuses on relieving the symptoms of pain, infection risk and some other potential complications.

There are three main types of EB:

• Epidermolysis Bullosa simplex (EBS) - the most common type. The CDC, USA says about 92% of EB cases are EBS, while the National Health Service (NHS), UK says it is 70%.
• Dystrophic Epidermolysis Bullosa (DEB) - the second most common.
• Junctional Epidermolysis Bullosa (JEB) - affects about 5% of EB patients.

Each EB type has several subtypes. According to The National Health Service (NHS), UK, there are over 25 known EB forms.

What are the signs and symptoms of epidermolysis bullosa?

A symptom is something the patient senses and describes, while a sign is something other people, such as the doctor notice. For example, drowsiness may be a symptom while dilated pupils may be a sign.

Symptoms are usually present very early in life, when the patient is a baby, and often fairly soon after birth. In very mild cases there may be no symptoms until later on.

In mild cases the blisters will heal and there will be either no scarring at all, or minimal scarring.

The skin of a patient with EB is extremely fragile and can be easily damaged at the slightest rub, gentle bump or knock, and also if clothing touches or rubs against it. Consequently, blisters form.

Typical signs and symptoms depend on the type of EB, and may include:

• Blistering of the skin
• Tearing of the skin
• The skin may appear very thin
• The skin falls off
• Alopecia - hair loss
• Blistering on the scalp
• Blistering around the eyes and nose
• Dysphagia (swallowing difficulties) - if blistering occurs around the mouth and throat
• Symptoms in the throat can cause voice hoarseness
• Blistering in the upper airway which may cause breathing problems
• Blistering in the urinary tract, resulting in painful urination
• Blistering which is present at birth
• Milia - very small, white bumps on the skin. Unlike blackheads or whiteheads they do not have an opening on the surface of the skin.
• Loss of fingernails/toenails, or deformity of nails
• Excessive sweating

What are the causes of Epidermolysis bullosa?

EB is caused by faulty (mutated) genes. The patient with EB can have the mutation(s) from two sources:

• Inheritance - a parent has the faulty genes and passes them onto their offspring. Both the parents of a patient with Junctional EB have/had the faulty genes and passed them on, for the other types of EB they can be inherited from just one parent.
• Faulty egg or sperm - neither parent has the genes. However, a mutation occurred in the egg or sperm of a parent when it was formed.

The mutated genes influence how our bodies produce and maintain skin tissue. Experts say the mutation occurs in the keratin or collagen gene.

Human skin has two layers:

• The epidermis (the outer layer)
• The dermis (the deeper, inner layer)

In healthy individuals there are protein anchors between the two layers. These anchors are made of collagen and they make sure the two layers move together - they stop the two layers from moving in different directions, or at different speeds (called shearing).

A person with EB does not have enough protein anchors; their two layers of skin do not move together properly. The resulting friction and separation damages tissue and causes blisters and painful sores.

Put simply - if there is not enough sticky stuff between the two layers of skin they will rub against each other and cause blisters and sores. If you rub the skin of somebody with EB, the outer layer may move faster than the inner layer, making the two layers rub against each other or separate, causing soreness.

Blisters can form in different parts of the skin, depending on the type of EB:

• EB simplex - blisters form on the epidermis (the outer layer).
• Dystrophic EB - blisters form in the epidermis (outer layer) and also the dermis (inner layer).
• Junctional EB - blisters form where the epidermis and dermis meet.

How is epidermolysis bullosa diagnosed?

In the majority of cases, diagnosis is reached when the patient is a baby or a very young child. Much more rarely, especially when symptoms are mild, diagnosis occurs later on in life.

The doctor may ask the patients or their parents some questions regarding signs and symptoms, such as the size, location(s) and severity of the blisters, as well as their causes (rubbing, clothing, etc).

The following diagnostic tests may be ordered:

• Biopsy - a small sample of affected skin tissue is taken and analyzed.
• Genetic test - in the form of a blood test. Blood samples from parents may also be taken. The blood test can help the doctor determine whether the condition was inherited from one parent, or both.

What is the treatment for epidermolysis bullosa?

EB is incurable. Current treatments focus on relieving symptom and preventing skin damage and complications.

Large blisters - the doctor may teach the patient or parent how to properly puncture (lance) a large blister with a needle. If it is done in a certain way, fluid can drain out without increasing the risk of infection or damaging the skin below it. A topical antibiotic may also be prescribed. Wound dressings should not stick to the skin.

Healing problems - if a lesion does not heal properly, skin grafts may be used. Covering the wound with skin may help the healing process.

Protecting the skin:

• EB simplex - avoid long walks, which can increase the likelihood of blisters developing on the soles of the feet. Avoid hot weather.
• Dystrophic or junctional EB - be extremely careful to avoid scratches and knocks to the skin.
• The mouth - if the patient has blisters and/or pain in the mouth, avoid foods which may cut and scratch, such as potato chips (UK: crisps) and highly condimented (spicy) foods.
• Holding a child - try to avoid picking a small child/baby up under the arms. The National Health Service (NHS), UK says it is better to place your hand under their bottom and the other behind their back.
• Eye glasses - parents should carefully check that spectacles (eye glasses) are not causing blistering around a child's nose and ears.

Repeated blistering and scarring - fusing of fingers and contractures (abnormal shortening of muscle tissue) may occur if blistering and scarring is severe and chronic. If such complications affect the patient's ability to perform everyday tasks, the surgeon may recommend surgery.

Dysphagia (swallowing problems) - if blistering in the esophagus makes it difficult for the patient to eat properly, the doctor may recommend surgery to widen the esophagus.

Gastrostomy tube - if the patient is unable to swallow food, a surgical opening is made into the stomach, through which the patient can be fed via a gastrostomy tube. An endoscope is passed through the mouth, throat and esophagus to the stomach, a small incision is made in the skin of the abdomen and an intravenous cannula is pushed through the skin into the stomach (stitches fix it there).

Sulforaphane - the compound sulforaphane, was demonstrated by Johns Hopkins scientists as helping patients with EB. The team turned to sulforaphane in their search for a chemical activator that would induce the production of missing keratins in basal epidermis. There are 54 "conserved" keratin proteins in mammals -- meaning that evolution favored their survival. Many of these keratins are closely related in their genetic sequences and their properties and by their distribution within epithelial tissues. The scientists reasoned that such a situation breeds "functional redundancy," meaning that the genetic loss of one keratin could be partially rescued by the overlapping functions of a keratin cousin. (read more)

What are the complications of epidermolysis bullosa (EB)?

• Cancer - people with EB have a higher risk of eventually developing some types of skin cancers.
• Deformities - in severe cases the fingers can fuse and the muscles around certain joints can become shorter (contracture).
• Premature death - unfortunately, some babies with severe signs and symptoms may die as a result of dehydration, infection, internal blisters, malnutrition (or a combination).
• Eyes - if the conjunctiva are affected, as well as other parts of the eye, there may be gradual vision loss.
• Infections - blisters and open sores make the risk of secondary infections greater.
• Nutrition - if the patient finds it hard to swallow and is not getting proper treatment and careful monitoring, there may be a risk of malnutrition.

Written by Christian Nordqvist
Copyright: Medical News Today
Not to be reproduced without permission of Medical News Today

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