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Epidermolysis bullosa (EB)

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Epidermolysis bullosa (EB)



Introduction 

Epidermolysis bullosa (EB) is a general term used to describe a group of rare inherited skin disorders that cause the skin to become very fragile.

In people with EB, any trauma or friction to the skin can cause painful blisters.

 



Types of epidermolysis bullosa

There are three main types of EB, which are described below. The condition is classified according to where in the various layers of skin the blistering takes place.



Epidermolysis bullosa simplex (EBS), where blistering occurs in the upper layer of the skin (the epidermis). This is the most common type of EB, accounting for 70% of cases, and tends to be milder than the other types.



Dystrophic epidermolysis bullosa (DEB),where blistering occurs below the basement membrane zone in the upper part of the dermis. DEB accounts for around 25% of cases.



Junctional epidermolysis bullosa (JEB), where blistering occurs at the junction between the epidermis and the dermis (lower layer of the skin) in a layer of skin known as the basement membrane zone. JEB accounts for around 5% of cases and is usually considered the most severe type of EB.



There are many variants of these main types of EB, each with slightly different symptoms. So far, researchers have classified 27 variants of the condition and more may be identified in the future.

In most cases, symptoms of EB are obvious from birth or soon after. If it's suspected your child has the condition, they'll be referred to a skin specialist (dermatologist). The specialist will carry out tests to determine the type of EB and help to come up with a treatment plan.

 

Why does EB happen?

EB is caused by faulty genes. In most cases these are inherited from one or both parents but sometimes the fault occurs spontaneously.

In some cases, one or both parents will have the condition. However, there are many cases when neither parent has EB, but their child does. This happens when both parents are 'carriers' of the faulty genes.

If you or your partner is known to be a carrier of a mutated gene associated with EB, and there's a risk of your child developing a severe form of the condition, it's possible to test an unborn baby at about 11 weeks into pregnancy.

 

Who is affected?

EB is a rare condition. It's estimated one in every 17,000 children born in the UK will have EB. In the UK, there are currently an estimated 5,000 people living with it.

EB affects both sexes equally.

How is EB treated?

There's currently no cure for EB, so treatment aims to relieve symptoms and prevent complications developing, such as infection.

A team of medical specialists will help you decide what treatment is best for your child and offer advice about living with the condition.

Most treatments can be done at home, such as popping blisters with a sterile needle, applying protective dressings and avoiding things that make the condition worse.

Medicines can be used to treat infection or to reduce pain. Surgery can be used if EB causes narrowing of the foodpipe or problems with the hands.

 

Outlook

The outlook for EB can vary widely depending on the type and variant of EB a child has.

Epidermolysis bullosa simplex (EBS) carries a low risk of causing serious complications. However, it can often be a frustrating condition to live with, as it can interfere with daily activities.

Some cases of dystrophic epidermolysis bullosa (DEB) are mild and cause no serious complications, while others are severe and may affect general health or possibly lead to skin cancer in later life.

The outlook for a very rare type of junctional epidermolysis bullosa (JEB-severe generalised) is poor. Around 40% of children with the condition will not survive the first year of life, and most will not survive more than five years.

 

Epidermolysis bullosa acquisita

Epidermolysis bullosa acquisita (EBA) is an acquired form of epidermolysis bullosa (EB), with similar symptoms.

Like EB, EBA causes the skin to blister easily. It can also affect the mouth, throat and digestive tract.

However, EBA is not inherited. EBA is an autoimmune disease which doesn't usually appear until later life. It's not known exactly what causes it.

EBA is more common in people over the age of 40, but overall it's a very rare condition.

 

Symptoms of epidermolysis bullosa 

Symptoms of epidermolysis bullosa (EB) can vary in severity, ranging from mild to life-threatening.

Although specific symptoms depend on the type of EB, there are some common features, including:



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



 

Types of EBS

Read information about symptoms of:



EBS (localised)



EBS (generalised intermediate)



EBS (generalised severe)



Junctional EB (localised)



Junctional EB (generalised)



Dystrophic EB (dominant)



Dystrophic EB (recessive, severe generalised)



Symptoms of epidermolysis bullosa simplex (EBS)

The symptoms of the most common variants of epidermolysis bullosa simplex (EBS) are described below.

 

EBS (localised)

Localised EBS is the most common form of EBS. It's characterised by painful blisters on the palms of the hands and soles of the feet that develop after mild or moderate physical activity, such as walking, gardening or playing sport.

Although the blisters often form on the hands and feet, it's not uncommon for them to develop on other parts of the body as well, such as the buttocks or inner thighs, after they've been subjected to friction during activities such as riding a bike.

Excessive sweating can make the blisters worse, so localised EBS is often more noticeable during the summer. The blisters usually heal without scarring.

Symptoms usually become apparent during early childhood, although mild cases may go undiagnosed until early adolescence. 

Some adults with localised EBS may experience thickening of the skin on their palms and the soles of their feet, as well as their fingernails and toenails.

 

EBS (generalised intermediate)

In this form of EBS, blisters can form anywhere on the body in response to friction or trauma. The symptoms are also usually more troublesome during hot weather.

There may be mild blistering of the mucus membranes, such as the inside of the nose, mouth and throat.

Scarring and milia (small white spots) may occur on the skin, but this is uncommon.

The symptoms usually begin during birth or infancy. As with localised EBS, adults may experience thickening of the skin on their palms and the soles of their feet, as well as their fingernails and toenails.

 

EBS (generalised severe)

This form of EBS is the most severe type, where children experience widespread blistering. In the most severe cases, a child can develop up to 200 blisters in a single day.

The widespread blistering can make the skin vulnerable to infection and affect an infant's normal feeding pattern, which means they may not develop at the expected rate.

Painful blisters on the soles of the feet can affect an infant's ability to walk and may mean they start to walk later.

Blisters can also develop inside the mouth and throat, making eating – and sometimes speaking – difficult and painful. Thickening or loss of the fingernails and toenails is another common symptom.

The symptoms usually develop at birth, but the blistering gradually improves through childhood and adolescence – so adults may only experience occasional blistering.

However, it's common for the skin of the palms and soles to become progressively thicker with age, and this may make walking or activities using the hands difficult or painful.

Symptoms of junctional epidermolysis bullosa (JEB)

There are two main variants of junctional epidermolysis bullosa (JEB), discussed below.

 

JEB localised (non-Herlitz)

Non-Herlitz JEB causes widespread blistering of the skin and mucus membranes. Blistering of the scalp is common and may lead to scarring and permanent hair loss.

Other common symptoms include:



long-term injuries to the skin and underlying tissue, especially of the lower legs



scarring of the skin



deformity or loss of fingernails and toenails



pigmented (coloured) areas of skin that look like large, irregular moles



Tooth enamel isn't properly formed, which means teeth may be discoloured, fragile and prone to tooth decay. The mouth is also frequently affected by blisters and ulcers, which may make eating difficult.

Some patients also develop problems with the urinary tract, such as blistering or scarring of the urethra (tube urine passes through from the bladder).

The symptoms usually develop at birth or shortly afterwards and can improve with age.

As adults, people with this form of EB have an increased risk of developing skin cancer, so regular review by a dermatologist (skin specialist) familiar with EB is recommended.

 

JEB generalised (Herlitz)

This is the most severe type of JEB, although it's incredibly rare.

Herlitz JEB causes widespread blistering of both the skin and the mucus membranes. In particular, the following areas of the body are affected by blistering and chronic ulcers:



the genitals and buttocks



around the nose and mouth



the fingertips



the toes



the neck



inside the mouth and throat



the eyes



Complications of Herlitz JEB are common and include:



anaemia



tooth enamel defects and decay



malnutrition and delayed growth



dehydration



breathing difficulties



sepsis



Because of these complications, the outlook for children with Herlitz JEB is very poor. Around 40% of children with the condition won't survive the first year of life, and most won't survive more than five years.

Sepsis and respiratory failure (due to blistering and narrowing of the airways) are the most common causes of death.

Symptoms of dystrophic epidermolysis bullosa (DEB)

The three most common variants of dystrophic epidermolysis bullosa (DEB) are discussed below.

 

Dystrophic EB (dominant)

Dominant DEB causes blistering at places on the body that experience trauma, often the hands, feet, arms and legs, which usually results in scarring. Milia (tiny white spots) often form at the site of the blisters.

The nails will usually become thickened and abnormally shaped, or even lost altogether. The mouth is often affected, which can make eating or cleaning teeth painful. 

Some people with dominant DEB have mild symptoms with very few blisters, and the only sign of the disease may be misshapen or missing nails.

The symptoms of dominant DEB usually develop at birth or shortly afterwards, but may not occur until later in childhood.

 

Dystrophic EB (recessive, severe generalised)

Severe generalised recessive DEB is the most severe type of DEB. It causes severe and widespread skin blistering that often leaves areas covered with persistent ulcers.

Repeated scarring to hands and feet can result in the loss of nails. Spaces between fingers and toes can fill with scar tissue so hands and feet take on a mitten-like appearance.

Extensive blistering can also occur on the mucus membranes, particularly inside the:



mouth



oesophagus (tube connecting the mouth and stomach)



anus



Tooth decay and repeated scarring in and around the mouth are both common. This can often cause problems with speaking, chewing and swallowing. Repeated blisters on the scalp may also reduce hair growth.

As a result, many children with this form of DEB will experience anaemia, malnutrition and delayed or reduced growth. The eyes can also be affected by blistering and scarring, which is painful and can lead to vision problems.

The symptoms of severe generalised recessive DEB are usually present at birth. There may be areas of missing skin at birth, or blistering developing very shortly afterwards.

People with this type of DEB have a high risk of developing skin cancer at the site of repeated scarring. It is estimated that more than half of people with severe generalised recessive DEB will develop skin cancer by the time they are 35.

Therefore, awareness of this problem and frequent check-ups (possibly twice a year) with a dermatologist are recommended.

Causes of epidermolysis bullosa 

Epidermolysis bullosa (EB) is caused by an inherited genetic mutation that makes skin more fragile.

A genetic mutation occurs when instructions carried in certain genes become 'scrambled'. This results in some of the body's processes not working in the normal way.

 

How EB is inherited

All genes in your body come in pairs. You receive one half from your mother and the other half from your father.

Genetic conditions such as EB and the mutations which cause them can be passed down through families in two ways:



 it takes only one mutated gene for you to develop the symptoms of a particular genetic condition. The parent you inherited the mutated gene from will also have symptoms of the condition – this is known as autosomal dominant inheritance



both genes in the pair need to have the same mutation before you develop symptoms of the condition. You would need to inherit one mutated gene from your mother and another from your father. In this case, neither parent would have any symptoms of the condition as they would only be a carrier of the mutated gene – this is known as autosomal recessive inheritance.



In EB, some variants are autosomal dominant and others are autosomal recessive.

Epidermolysis bullosa simplex

Epidermolysis bullosa simplex (EBS) is an autosomal dominant condition. If you have EBS, one of your parents also has a history of the condition and has passed the mutated gene to you. However, if their symptoms are mild, their condition may not have been diagnosed.

You may be the first in your family to be affected. In these cases, the mutation will have occurred in the womb before you were born. Neither of your parents carries the mutation and you have a new mutation.

If you go on to have children, they'll have a 50% chance of developing EBS.

 

Junctional epidermolysis bullosa

Junctional epidermolysis bullosa (JEB) is an autosomal recessive condition. If you have JEB, both your parents are carriers of the mutated gene but they don't have symptoms.

Your children are only at risk of developing JEB if your partner is also a carrier of a mutated gene known to be associated with JEB. It's difficult to estimate exactly how many people are carriers of the various JEB mutated genes, but the number is thought to be low.

If you and your partner are both carriers of a JEB mutated gene, your children have a one-in-four chance of developing the condition.

 

Dystrophic epidermolysis bullosa

Depending on the particular variant, dystrophic epidermolysis bullosa can be either autosomal recessive or dominant.

Dominant DEB is autosomal dominant and the other types are autosomal recessive.

 

Skin layers

Human skin is made of three layers:



epidermis – the outer layer of skin



dermis – the middle layer of skin



subcutis – the deepest layer of skin, mainly made up of fat



The epidermis and dermis meet at a point known as the basement membrane zone (BMZ). This contains specialised proteins that keep the two layers stuck securely together.

Faulty genes can cause one or more proteins in the BMZ to not work properly. This means trauma or friction to an area of skin could result in the epidermis and dermis becoming unstuck. If the two layers become separated, a space is created which fills with fluid to form a blister.

Diagnosing epidermolysis bullosa 

Epidermolysis bullosa (EB) is usually diagnosed in babies and children.

However, symptoms of some types of EB can be mild and develop later, so may not be diagnosed until adulthood.

Prenatal testing

In some cases, EB may be diagnosed in an unborn child.

If you or your partner is known to be a carrier of a mutated gene associated with EB, and there's a risk of your child developing a severe form of the condition, it's possible to test an unborn baby at about 11 weeks into pregnancy. 

If the test confirms your child will have EB, you'll be offered counselling and advice to help you make an informed decision about how you wish to proceed with the pregnancy.

Prenatal tests include amniocentesis and chorionic villus sampling.

 

Initial diagnosis

In most cases, EB is detected at birth by the neonatal team, who then refer your child to a specialist EB team.

For older children, your GP will ask about your child's skin. For example, what causes the blisters and how easily their skin is damaged.

You'll also be asked whether you have a family history of EB.

Your child's blisters will be examined, along with their nails, teeth and hair. Your GP may also check for blisters on other areas of your child's body, such as in their mouth and eyes.

If your GP suspects EB is likely, your child will be referred to a specialist EB team for further assessment and testing.

 

Further testing

Further testing is used to confirm EB and determine which variant your child has.

Biopsy

A biopsy involves taking a small sample of skin and examining it under powerful microscopes. Looking at exactly where blisters have developed in the various layers of skin can determine the type of EB your child has.

 

Genetic testing

Genetic testing involves taking a sample of your child's blood and sending it to a specialist genetic laboratory.

A sample of DNA can be extracted from the blood and checked for mutations associated with EB.

A sample of both your blood and your partner's may also be taken to help determine whether you are a carrier of one of the various EB mutations.

 

Charities and support groups

If your child is diagnosed with EB it can be a frightening and overwhelming experience. A natural response is to find out as much as possible about the condition and available treatments.

DEBRA is a national charity that provides help, advice and support for people in the UK living with EB.

DEBRA International is a worldwide network of national groups working on behalf of people affected by EB.

Support for carers

It's also important not to neglect your own health and wellbeing when caring for a child with a complex and demanding condition, such as EB.

 

Treating epidermolysis bullosa 

There's currently no cure for epidermolysis bullosa (EB), but treatment can help ease and control symptoms.

Treatment also aims to:



avoid skin damage



improve quality of life



reduce the risk of developing complications, such as infection and malnutrition



Specialist centres

Due to the rarity of EB, parents and children are usually referred to a specialist centre that employs staff with expertise and experience in treating the condition. In England, there are four specialist centres:



Birmingham Children's Hospital



Solihull Hospital



Great Ormond Street Children's Hospital, London



St Thomas' Hospital, London



After the initial diagnosis, it's likely you and your child will have regular follow up appointments at a specialist centre so a detailed treatment plan can be drawn up.

Once your child's symptoms improve or stabilise, it may be possible to arrange for treatment to be provided locally, so you'll only need to visit the specialist centre occasionally.

However, with more serious types of EB, such as Herlitz JEB or severe generalised recessive DEB, this arrangement may not always be possible.

 

Multidisciplinary teams

Children with EB often have complex needs, particularly if they have a severe form of the condition. They'll need to be treated by a diverse team of medical specialists working together.

These types of teams are called multidisciplinary teams (MDTs) and can include:



a dermatologist, a doctor who specialises in treating skin conditions



a dentist



a dietitian



a physiotherapist



a play specialist, who uses playful activities to help improve a child's physical and psychological wellbeing



a specialist nurse, who usually acts as the contact between you and other members of the MDT



 

General advice

An important part of your child's treatment plan will be practical advice about how to prevent trauma or friction to your child's skin to help reduce the frequency of blistering. This advice will vary depending on the type of EB and the severity of your child's symptoms.

This advice may include:



Not walking long distances, because this can cause blisters to form on the soles of your child's feet.



Avoid everyday knocks, bumps and scratches. This may mean having a carer when out in the playground and minimising contact sports. However, it's important your child doesn't avoid physical activities or contact with other children. Your physiotherapist should be able to recommend activities unlikely to result in blistering, such as swimming.



Avoid rubbing your child's skin. You may have to change the way you lift your child.



Keep your child as cool as possible in warm weather.



Avoid clothes that fit tightly or rub against the skin to avoid blistering. Wearing clothes made from natural fabrics, such as cotton, will also help your child keep cool.



Choose comfortable shoes that fit well and don't have lumpy seams inside.



 

Skin care

Your MDT will be able to advise about caring for your child's skin. For example:



when and how to puncture new blisters (see below)



how to care for wounds left by blisters and prevent infection



whether to leave wounds uncovered or use dressings



what types of dressing to use, how to apply and remove them, and how often to change them



whether to use moisturising creams on your child's skin



It's usually recommended that new blisters are punctured (lanced) using a sterile needle. Your GP will be able to provide you with a supply of sterile needles. Lancing the blisters will prevent them getting bigger. Large blisters can leave large, painful wounds which take longer to heal.

It's usually recommended to leave the skin on top of the blister to protect the lower layers of skin.

If an open wound needs dressing, it's best to use one that doesn't stick to the skin and is easy to remove. To hold a non-stick dressing in place, you may be advised to use a sock, cotton bandage or tubular bandage. Regular sticking plasters should be avoided.

 

Infections

Open wounds or raw patches of skin can often become infected and need to be treated. Signs that an area of skin has become infected include:



redness and heat around an area of skin



the area of skin leaks pus or a watery discharge



crusting on the surface of the wound



a wound does not heal



a red streak or line is spreading away from a blister or collection of blisters



a high temperature (fever) of 38C (100.4F) or above



If you think your child has a skin infection, inform your GP as soon as possible. Left untreated, a skin infection can often quickly spread to other parts of the body, particularly with the more severe variants of EB.

Treatment for skin infections include:



antiseptic creams or ointments



antibiotic creams or lotions



antibiotic tablets



specially designed dressings to help stimulate the healing process



 

Pain relief

The need for pain relief will vary depending on the severity of your child's symptoms. The blisters and wounds they leave can be painful and may make simple activities such as moving and walking difficult.

Milder variants of EB such as EBS may only require painkillers available over the counter, such as paracetamol or ibuprofen. In more severe types of EB, stronger painkillers such as morphine may be needed, either for background pain or for procedures like dressings, changes, or bathing.

Children under the age of 16 should never be given aspirin as there's a small risk it could trigger a serious condition called Reye's syndrome.

Some types of EB that cause long-term (chronic) pain may require different medicines, such as amitriptyline or gabapentin. These were originally designed to treat depression and epilepsy but they later proved effective in treating chronic pain.

 

Dental care

Soreness caused by blisters inside your child's mouth can make cleaning their teeth difficult. Good dental hygiene with a soft toothbrush and fluoride-containing mouthwash, as well as regular visits to a dentist, is important.

 

Nail care

Your child's fingernails and toenails may become thicker than normal and difficult to cut, especially if blisters form under the nail.

Your hospital team should be able to recommend creams which soften nails and make them easier to cut.

 

Eye care

Children with Herlitz JEB and recessive DEB often experience blistering and irritation in and around their eyes. This usually requires treatment with eye drops and ointments to keep the eyes moist. 

 

Feeding and nutrition

If your baby has blisters in their mouth, it can cause problems with feeding. Your MDT should be able to give you advice about how to overcome feeding problems. For example:



feeding a baby or infant using a syringe, eyedropper or 'artificial nipple'



adding liquid to mashed food to make it easier to swallow (once your child is old enough to eat solids)



including lots of soft food in your child's diet



not serving food too hot, as it could cause further blistering



If your child is older, your MDT will also be able to give you advice about their diet. The healing process makes great demands on the body and a healthy diet is important to help heal your child's skin wounds and avoid malnutrition.

Your child may also need supplements in the form of milk-based drinks or puddings that have high levels of protein and/or calories. Supplements of vitamins, iron or zinc may also be required if they're found to be deficient in these on blood tests. Your dietitian will be able to advise about this.

Constipation can be a common problem for children with EB, particularly if they find it difficult to digest high-fibre foods, such as wholemeal bread or muesli. If your child regularly experiences constipation, they may benefit from having a fibre supplement.

 

Surgery

Surgery may be required to treat some complications that can arise in cases of EB.

The different types of surgery are described below:



If your child's fingers and toes have become fused together by scar tissue, creating a 'mitten' effect, surgery may be required to separate them.



If your child's oesophagus (the tube in the throat that food passes through) has become narrowed by scarring, surgery may be required to widen it. This is done by placing a balloon inside the oesophagus and inflating it to widen the narrowed area.



If poor weight gain and reduced growth have occurred because symptoms of EB make eating impossible, surgery can be used to implant a feeding tube into the body through an incision (cut) in the surface of the stomach or abdomen (tummy).



Research

A great deal of research is being carried out to try to find a cure, or at least more effective treatments, for EB.

Areas of research include:



applying proteins directly to the skin to prevent the layers of skin becoming unstuck



adding 'corrected' copies of certain genes to badly affected areas of skin to try to regulate the production of skin cells



adding a type of cell known as fibroblasts – grown from a small sample of your child's skin – to the skin to help strengthen it



using bone marrow transplants to stimulate production of healthy skin cells



identifying medication that can improve and accelerate the process of wound healing



Initial results in all of these areas have been promising, but it may take several years until researchers come up with safe and effective treatments.

See the clinical trials page to search for relevant trials through the UK and worldwide.

 


Epidermolysis bullosa (EB)