What is epidermolysis bullosa?
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 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.
- 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.
- 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.
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 there may be more that have not yet been identified.
Read more about the symptoms of epidermolysis bullosa.
In most cases, symptoms of EB are obvious from birth or soon after. If it is suspected that your child has the condition, they will be referred to a skin specialist (dermatologist) who will carry out tests to determine the type of EB and will help to come up with a treatment plan.
Read more about diagnosing epidermolysis bullosa.
Why does EB happen?
EB is caused by faulty genes inherited from one or both parents.
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 without realising it.
If you or your partner is known to be a carrier of a mutated gene associated with EB and there is a risk of your child developing a severe form of the condition, it is possible to test an unborn baby at about 11 weeks into pregnancy.
Read more about the causes of epidermolysis bullosa.
Who is affected?
EB is a rare condition. EB affects both sexes equally.
How is EB treated?
There is currently no cure for EB, so treatment aims to relieve the symptoms and prevent complications developing, such as blisters becoming infected.
You will be helped by a team of medical specialists to decide what treatment is best for your child. They will also offer advice about living with the condition.
Most treatments can be done at home, such as lancing blisters with a sterile needle, and avoiding things that make the condition worse, such as heat and solid foods.
Medicines are only really used to treat infection or reduce pain. Surgery can be used if EB causes physical problems, such as narrowing of the airways due to scarring.
Read more about treating epidermolysis bullosa.
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 distressing and 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 can lead to skin cancer in later life.
The outlook for a very rare type of junctional epidermolysis bullosa (JEB) called Herlitz JEB is poor. As many as nine out of 10 children with this form of the condition will die from a serious complication developing during the first two years of life.
Epidermolysis bullosa symptoms
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 and nose
- blisters on the hands and soles of the feet
- scarred skin, sometimes with small white spots called milia
- thickened skin and nails
Symptoms of epidermolysis bullosa simplex (EBS)
The symptoms of the most common variants of epidermolysis bullosa simplex (EBS) are described below.
Localised (Weber-Cockayne) EBS
Localised EBS is the most common form of EBS. It is 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 is not uncommon for them to develop on other parts of the body as well, such as the buttocks or inner thighs, after they have 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.
Köbner type EBS (generalised)
In this form of generalised EBS, blisters can form anywhere on the body in response to friction or trauma.
The symptoms of this type of generalised EBS 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 of this form of EBS 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.
Dowling-Meara EBS is the most severe type of EBS, where children experience widespread blistering across their entire body. 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 of Dowling-Meara EBS usually develop at birth, but the blistering tendency gradually improves through childhood and adolescence so that adults with this form of EBS may only experience occasional blistering.
However, it is 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.
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 of non-Herlitz JEB 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 is not properly formed in non-Herlitz JEB, which means teeth may be discoloured, fragile and prone to tooth decay. Extensive dental reconstruction is often necessary. The mouth is also frequently affected by blisters and ulcers, which may make eating difficult.
Some patients also develop:
- osteoporosis (weakening and thinning of the bones)
- anaemia, where there are not enough red blood cells in the body, resulting in tiredness and breathlessness
- problems with the urinary tract, where there is blistering or scarring of the urethra (tube urine passes through from the bladder)
The symptoms of non-Herlitz JEB usually develop at birth or shortly afterwards and can improve with age.
As adults, people with non-Herlitz JEB have an increased risk of developing skin cancer, so regular review by a dermatologist (skin specialist) familiar with EB is recommended.
This is the most severe type of JEB, although it is 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:
- tooth enamel defects and decay
- malnutrition and delayed growth
- breathing difficulties
Because of these complications, the outlook for children with Herlitz JEB is very poor. Around 40% of children with the condition will die during their first year of life, and almost all children with the condition will die by the time they are five.
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.
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 also 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.
Severe generalised recessive DEB (Hallopeau-Siemens)
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:
- oesophagus (tube connecting the mouth and stomach)
Tooth decay is common, as is repeated scarring in and around the mouth. 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.
Epidermolysis bullosa causes
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 that cause them can be passed down through families in two ways:
- autosomal dominant inheritance – this is where it only takes one mutated gene for you to develop the symptoms of a particular genetic condition. The parent who you inherited the mutated gene from will also have symptoms of the condition.
- autosomal recessive inheritance – this is where both genes in the pair need to have the same mutation before you develop symptoms of the condition, so 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.
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.
Occasionally, 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 will 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 do not 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 is 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, any children you have will 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.
To have a better understanding of the causes of EB, it is useful to learn a little more about the skin.
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 that is then filled with fluid to form a blister.
Epidermolysis bullosa diagnosis
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.
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 is a risk of your child developing a severe form of the condition, it is possible to test an unborn baby at about 11 weeks into pregnancy.
If the test confirms your child will have EB, you will be offered counselling and advice so you can make an informed decision about how you wish to proceed with the pregnancy.
Your doctor will ask about your child's skin. For example, they may ask about what causes your child's blisters and how easily their skin is damaged.
They will also ask whether you or your partner have a family history of EB.
Your doctor will assess where your child's blisters are, how big they are and how much of their body is affected.
They will also check for blisters on other areas of your child's body, such as in their mouth and eyes. Your child's nails, teeth and hair may also be examined.
Following the examination, if your doctor suspects EB it is likely your child will be referred to a dermatologist (skin specialist) for further testing.
Further testing is used to confirm the diagnosis of EB and determine which variant your child has. These tests are discussed briefly below.
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 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.
Read more about genetics.
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 International is a worldwide network of national groups working on behalf of people affected by EB.
Support for carers
It is also important not to neglect your own health and wellbeing when caring for a child who has a complex and demanding condition, such as EB.
Treating epidermolysis bullosa
There is 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
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.
After the initial diagnosis, it is likely that you and your child will need to spend some time at the specialist centre so a detailed treatment plan can be drawn up.
Once the plan takes effect and your child's symptoms improve or stabilise, it may be possible to arrange for treatment to be provided locally, so you will 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.
Children with EB often have complex needs, particularly if they have a severe form of the condition. They therefore 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 will usually act as the contact between you and other members of the MDT
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:
- Your child should avoid walking long distances, because this can cause blisters to form on the soles of their feet.
- It is important your child avoids everyday knocks, bumps and scratches. This will probably mean not taking part in playground games and contact sports. However, it is important your child does not completely avoid physical activities or contact with other children. Your physiotherapist will be able to recommend activities unlikely to result in blistering, such as swimming.
- Avoid eating hard or sharp foods, such as crisps or toast, if they cause blisters to develop.
- 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 do not have lumpy seams inside.
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 is usually recommended that new blisters are punctured (lanced) using a sterile needle. Your doctor 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 wounds that are more painful and take longer to heal.
After puncturing the blister, you can drain the fluid from it onto a sterile piece of gauze. If the blister refills with fluid, it may need to be drained several times. After a blister has been drained, it is important to look after the skin while it heals.
It is usually recommended that the skin on top of the blister is left in place to protect the lower layers of skin. There may be no need for a dressing, although you may be advised to dust the blister with cornflour to help dry it and reduce further friction.
If an open wound needs dressing, it is best to use one that does not 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.
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
- there is 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
- your child has a high temperature (fever) of 38ºC (100.4ºF) or above
If you think your child has a skin infection, inform your doctor as soon as possible. Left untreated, a skin infection can often spread quickly 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
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 that are available over the counter, such as paracetamol or ibuprofen. In more severe types of EB, stronger painkillers such as codeine or 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 is a small risk that it could trigger a serious condition called Reye's syndrome that can cause liver and brain damage.
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.
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.
Read more about dental care for babies and children.
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, such as sugar-free milkshakes, soup, mashed potatoes and bananas
- 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. Therefore, a healthy diet is very important to help heal your child's skin wounds and avoid malnutrition.
To help your child's wounds heal, you may be advised to give them a diet high in calories and to increase the amount of protein they eat. Your child may have difficulty eating large portions of food, but there are ways you can boost the nutritional content of smaller meals. For example:
- adding melted cheese or mayonnaise to high-calorie foods, such as potatoes, beans, eggs and pasta
- adding margarine or olive oil to vegetables
- adding pieces of soft fruit to yogurt
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 are 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.
In more severe or troublesome cases, an osmotic laxative may be required. This is a medication that helps to soften stools and makes them easier to pass. Read more about treating constipation.
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 usually achieved 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).
A great deal of research is currently 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.
Kayla Grant is a child with epidermolysis bullosa (EB). Her skin is so fragile she cannot be hugged. Her friends and family call her the butterfly girl, because her skin is as fragile as a butterfly wing. Her mother Brenda talks about their lives.
"My husband Paul and I had no idea that we both carry the gene that causes EB. When Kayla was born, she seemed healthy except for a few tiny blisters on her thumb and heel.
"When doctors checked her heart, I was horrified as they pulled the monitor pads off her body because skin came away. She was in and out of hospital for three months to try to find what was wrong. Eventually we went to Great Ormond Street, where our baby was diagnosed with EB.
"We were told Kayla's skin cells were damaged and there was no cure. Just cuddling or holding her caused her skin to blister. It got worse as she began trying to walk. Sometimes she would scream in agony. She never crawled because it would hurt her so much.
"Blisters form everywhere: under her hair, in her ears and her mouth. I became frightened to pick her up and dreaded having to get her dressed. In the beginning I think she resented me because I hurt her and I felt very guilty, but now she knows I am trying to help.
"Buying clothes is a nightmare because the fabric and seams rub against her skin. I have to modify almost everything she wears by cutting away tight cuffs and collars and she has a vest made from a soft bandage-like fabric. She has shoes because she wants to be like other little girls, but has to wear slippers most of the time.
"She sleeps in silk or Egyptian cotton sheets, which cause less friction. But every day I still have to lance the blisters that have formed overnight and cut away dead skin from the wounds that are healing, so that they don't become infected. Kayla takes morphine or a milder painkiller.
"We want her to have a normal life and experience the same things as other children as much as possible. I bind her hands and feet with bandages to save them from knocks and we allow her to run around and play on a slide, even though it can end up causing her pain.
"She loves swimming and we have a paddling pool in the garden, but she will never be able to play sports like tennis.
"It would be so easy to try to shield her but that would harm her. We want her to be in control of her own life and learn what she is capable of doing.
"She has a full-time carer and attends normal lessons, but even holding a pencil is sometimes too painful for her. Eating is a problem because blisters develop inside her mouth. She can't have anything like crisps. She'll normally have soup, yogurt and soft fruits such as bananas.
"I don't think I'll ever come to terms with seeing her in so much pain. We can't have a normal life and holidays are difficult. We took Kayla to Mauritius once but she had to fly home because the hot climate made her condition worse.
"Sometimes she gets very frustrated. The other night she had blisters on her ear and couldn't sleep. Despite all this, she has a wonderful sense of humour.
"Her older sister, Alana, who is eight and fortunately doesn't have EB, is great with Kayla. She sits reading with her for hours.
"We know that there will be health risks as Kayla gets older but we're determined to give her the best life possible."