Ehlers-Danlos Syndrome

What are the Ehlers-Danlos syndromes?

The Ehlers Danlos syndromes (EDS) are a group of conditions usually (although not always) inherited from your parents. People with EDS have a problem with the formation and structure of connective tissue in the body. Connective tissue is a particularly important component of skin, muscles and ligaments, blood vessels and heart valves.

Whilst the symptoms of EDS may be mild and undiagnosed, for some people with EDS, symptoms can be severe, life-changing, and even life-threatening.

Most forms of EDS affect the skin (which can be unusually stretchy and, sometimes, fragile) and the joints which can be 'double-jointed' (hypermobile). Many types also cause general symptoms such as tiredness, generalised pain, and poor sleep. Some affect other parts of the body, including blood vessels, the digestive system, the eyes, the teeth and the heart valves.

What causes the Ehlers Danlos syndromes?

The syndromes are genetic conditions. The genes which cause most types of EDS have been clearly identified and can be tested for. However, the most common form of EDS, hypermobility EDS (hEDS), is an exception to this, as the gene which causes it has not yet been identified.

In some cases, the faulty gene is inherited from an affected parent. However, a person may also be affected if there is a new mutation in the gene. In which case EDS may occur in people with no history of the disorder in their family.

The more common types of EDS show autosomal dominant inheritance, meaning if you have one faulty gene, from one of your parents, you will have the condition (and your parent will also have the condition). Rarer types of EDS show autosomal recessive inheritance.

Ehlers-Danlos syndrome or syndromes?

Until fairly recently, the name 'Ehlers-Danlos syndrome' was used to describe all forms of the condition. However, there are many different types of EDS and so it was felt that this was not one syndrome, but many. EDS is now therefore called 'the Ehlers-Danlos syndromes'.

How common are the Ehlers-Danlos syndromes?

It is estimated that EDS can occur in between 1 in 5,000 and 1 in 250,000 births.

What are the symptoms of Ehlers-Danlos syndrome?

Symptoms range from mild to very severe, and vary with which type of EDS you have. Milder forms of EDS are often not diagnosed until early adulthood, as it can take some time before the symptoms and signs become noticeable. The more severe types, however, are diagnosed mainly in childhood. Some types have been seen so few times that it is hard to generalise about what symptoms are normal for them. Below are the main symptoms seen in the different types of EDS.

Joint changes

Joints are often loose and 'double-jointed' (hypermobile), so that they have a greater than normal range and degree of movement.

Ehlers-Danlos syndrome finger hyperreflexia

By Piotr Dołżonek, CC BY-SA 4.0, via Wikimedia Commons

Dislocations of joints may easily occur, and people with EDS can often put their own joints back into place because the tissues are so stretchy. Joint pains are also common.

Skin changes

In all types of EDS except the vascular type, the skin feels soft and is unusually stretchy.

Ehlers-Danlos syndrome hyperelastic skin

By Whitaker JK, Alexander P, Chau DY, Tint NL, CC BY 2.5, via Wikimedia Commons

The picture shows how easy it is to pull the skin downwards and away from the body. When you let go, the skin immediately returns to its normal position.

Many affected people find that their skin splits and bruises easily and that skin injuries heal slowly. People with some types of EDS have scars that tend to become wide and thin. Blood vessels near to the skin surface can be very delicate and can be damaged easily.

Mobile lumps can develop under the skin of people with EDS, particularly around the elbows and knees, and tiny hard lumps may also form around the heel.

In the vascular type of EDS, the skin is not stretchy but it may look slightly transparent, so that you can see blood vessels underneath the skin.

Muscles and skeleton

The muscles of people with many forms of EDS tend to be floppier and less strong than those of people without EDS. This may be noticed because of difficulty with walking, such as falling over frequently, or because of problems with balance. In more severe cases, people find it helpful to use a stick or a wheelchair to help them get about.

Poor grip and difficulty writing are sometimes a problem. Special aids may be needed at school, in the kitchen and in other places where grip is important. Sometimes the voice tires easily when shouting, singing or talking loudly. Easy tiring of the muscles is common.

People with EDS are more prone to hernias in the groin and in surgical scars. In some types of EDS, curvature of the spine (scoliosis) can develop.

Tiredness and sleep disturbance

Tiredness, getting tired easily after physical activity (fatiguability) and dizziness are very common in EDS of many types. Sleep disorders are also common. EDS can seem similar to, and is often mistaken for, chronic fatigue syndrome and/or fibromyalgia.

Pain

Widespread pain or pain in the limbs is a common feature of most types of EDS. This typically gets worse with exercise. Many patients have frequent headaches.

Mood

Difficulties with mood, particularly anxiety, panic disorder and depression, are common conditions in the general population but they are more commonly experienced by people with EDS.

Heart

An uncomfortable feeling of thudding of the heart (palpitations) and noticeable extra beats are symptoms experienced by many people but they are more common in EDS. Many people experience dizziness and a fast pulse rate when they stand quickly.

Some people with EDS have problems with their heart valves, particularly as they get older, and may develop a murmur.

In the rare vascular type of EDS, serious complications involving blood vessels can develop, including aneurysms and blood vessel rupture. This risk can be lowered by medication.

Lungs

Asthma-like symptoms can occur in some forms of EDS, particularly the hypermobile type.

Digestive system

Constipation and diverticulosis (in which there are bulges in the wall of the large intestine) are more common in people with EDS. Hiatus hernia and irritable bowl syndrome are also more common than in the general population, and many people with EDS experience 'heartburn' (dyspepsia). Nausea is commonly noticed, and people with EDS are more than usually prone to travel sickness. Prolapse of the bowel (rectal prolapse can occur) is quite common.

Bowel rupture is a possible (rare) complication of some rare types of EDS.

Eyes, ears and teeth

Tinnitus is common in several types of EDS. Many people also have dizziness (vertigo).

Some very rare types of EDS affect the eyes. The areas around the pupils (sclera) may be blue rather than white and the eyeballs themselves may be very fragile. One rare subtype also affects the gums and teeth.

Children's health

Children with EDS often show delay in crawling, walking and standing. They tend to be more floppy than usual. Some rare types of EDS can affect growth and cause early joint dislocations.

Women's health

Prolapse of the womb (uterus) is more common in EDS. Prolapse is a common condition in women who have children; however, it is seen in EDS in women who have not had children more commonly than you would otherwise expect.

How do the Ehlers Danlos syndromes affect pregnancy?

Problems that can occur when pregnant

These include:

• Varicose veins, haemorrhoids and vulval varicosities.
• Reflux, which tends to get worse: many people with EDS have ongoing reflux and symptoms may worsen during pregnancy.
• Swelling of legs and hands, which is common in pregnancy but tends to be worse in EDS.
• Carpal tunnel syndrome, which is common in pregnancy in EDS.
• Women with EDS - may be more than usually prone to morning sickness.
• Many people with EDS experience regular headaches and these tend to get worse in early pregnancy.
• Many people with EDS have tinnitus due to instability of the bones in the middle ear. Pregnancy may exacerbate this condition.
• Women with EDS who need to protect their joints throughout pregnancy.
• Women with EDS who often have worse aches and pains in pregnancy, including:
• Pelvic girdle pain (symphysis pubis dysfunction).
• Back pain.
• Generalised aches and pains.
• Palpitations and extra heartbeats, which may increase in pregnancy.
• Breast changes which occur in most pregnant women. The stretchy skin of EDS means that extra support is important. People with EDS are more prone to stretchmarks generally.
• People with EDS, who are more prone to anxiety and depression. This can be made worse by pregnancy.

Problems that can occur during delivery

These include:

• Early breaking of the waters - preterm rupture of membranes (PROM).
• Women with EDS, who often have a poor response to lidocaine (used in epidurals). You should see an anaesthetist before your labour to talk about what options might be effective for you.
• Delivery of your baby which can be fast in EDS because your tissues 'give' easily and don't resist pushing the baby out. It's important for your midwife to keep it slow and controlled, for your baby and for you.
• Abnormal position of the baby, which is more common, as the baby is not held so tightly by your tissues, but this does not generally make labour more difficult in EDS.
• Rarely, the womb (uterus) can rupture during labour.

Problems that can occur after delivery

These include:

• Bleeding after delivery.
• If you have fragile skin, it is more prone to tearing and may take longer to heal.
• If you need stitches, dissolvable stitches may dissolve too early, so silk sutures are recommended.

How are the Ehlers-Danlos syndromes diagnosed?

EDS is usually suspected because you have the typical symptoms of one of the types. The doctor may ask about close family members and any problems they may have had with their skin or joints. Once the condition is suspected, specialist testing, including genetic testing, may be offered to determine which type of EDS you have.

The exception to this is double-jointed (hypermobility) EDS (hEDS), the most common type, for which there is so far no genetic test. The diagnosis of hEDS is made from discovering you have a very specific set of symptoms. This is described under the description of hEDS below.

What is the treatment for the Ehlers-Danlos syndromes?

There is no cure for EDS. Treatment is aimed at trying to protect the skin and the joints from further damage, and to managing other symptoms which arise. For most people with EDS, generally speaking:

• Physiotherapy can be very helpful to build strength and help balance, as well as to provide support for joints by strengthening muscles.
• The 'talking therapy' known as cognitive behavioural therapy (CBT) is often recommended for anyone living with a chronic condition that affects their life.
• For patients with fragile skin, injuries should ideally be stitched by a plastic surgeon who understands EDS, and stitches should be left in twice as long as usual.
• Anti-inflammatory tablets and analgesics may be required to control pain.
• Ascorbic acid is sometimes recommended to reduce bruising.

More detail about managing EDS is given under the description of each type, below.

What is the outlook for the Ehlers-Danlos syndromes?

The outlook (prognosis) is variable and depends on which type of EDS a person has. Most forms of EDS do not affect a person's lifespan, and people with milder symptoms are able to live their their lives without any restrictions. However, the need to protect the skin and joints in those with more marked symptoms can limit a person's chosen activities - particularly those hoping to take part in activities with a risk of physical injury, such as rugby - and can cause significant disability.

Many people with EDS have more severe symptoms and may have significant disabilities and therefore a severe restriction of their lives.

If someone has the rare type of EDS that affects the blood vessels (the vascular type) then there is a risk of bursting (rupture) of large blood vessels or internal organs, and therefore premature death.

The thirteen Ehlers-Danlos syndromes

The classification of EDS into different types has changed several times over the years. In 2017 there was a major change to the current classification. This divides EDS into 13 types. They are classified by what they are like to experience and to examine (their presentation) and also by the gene changes that cause them.

Under the new classification a few people previously diagnosed with hEDS may find that their conditions no longer 'fit' the new rules. People who already have a diagnosis should keep their diagnosis, even if the 'fit' to the new definition is not perfect.

Hypermobile Ehlers-Danlos syndrome

This is the most common form of EDS. It is inherited but so far no gene has been identified as the cause. It can be mild and is probably often undiagnosed.However many people with hEDS have significant or even severe pain and disability.

The main symptoms of hEDS are stretchy skin (which is not fragile but which may heal slowly) and unusually flexible joints.

Many people with hEDS have tiredness, pain and mood changes. The symptoms may include include:

• Sleep disturbance and tiredness.
• Fast heart rate.
• Dizziness and fainting on standing up quickly.
• Unexplained tummy pains, constipation and irritable bowel syndrome.
• Tendency to nausea.
• Anxiety and depression and panic attacks.
• Problems with passing urine.
• Widespread pain in the muscles and/or limbs.
• Headaches.
• Prolapse affecting the bladder, womb (uterus) or back passage.

How is hEDS diagnosed?

hEDS can be quite difficult to diagnose, as there is no specific test for it. As a result it often goes undiagnosed.

When symptoms are relatively mild, hEDS may be similar to benign joint hypermobility syndrome (BJHS). Some doctors think that the two conditions may be different degrees of the same thing.

Criterion 1: generalised joint hypermobility (GJH)
This is detected by doctors using a series of stretching and joint-bending tests which lead to the 'Beighton score'. GJH is diagnosed if you have a score or 5 or more (if you're aged under 18 years), 5 or more (if you're aged 18-50 years) and 4 or more (if you're aged over 50 years). Some doctors also use the 'five-point questionnaire' which asks you:

• Can you, or could you ever, put your hands flat on the floor without bending your knees?
• Can you, or could you ever, bend your thumb to touch your forearm?
• As a child, could you contort your body into strange shapes, or do the splits?
• As a child or teenager, did your shoulder or kneecap dislocate more than once?
• Do you consider yourself 'double-jointed'?

A 'yes' answer to two or more questions suggests you probably have hypermobile joints.

Criterion 2: two or more of the following (A-C) MUST be present

• A: you have at least FIVE of the following:
• Unusually soft or velvety skin.
• Mild skin hyperextensibility.
• Unexplained stretchmarks.
• Piezogenic papules (little hard lumps under the skin) of the heel.
• Recurrent or multiple abdominal hernia(s).
• Thinned scarring in at least two places.
• Any sort of prolapse without another reason, such as childbirth.
• Tooth crowding and high, narrow palate.
• Long, slender fingers (arachnodactyly).
• Unusually long arms.
• Floppy mitral (heart) valve.
• Stretched aortic (heart) valve.
• B: you have a close family member diagnosed with EDS.
• C: you have at least one of the following:
• Pain in two or more limbs, daily for at least three months.
• Widespread pain for ≥3 months.
• Recurrent joint dislocations or instability.

Criterion 3: all the following MUST be the case

• Skin must NOT be unusually fragile (this suggests other types of EDS).
• No other medical explanation for symptoms.

Some of the common symptoms of hEDS, such as tiredness and tummy pain, are not included in the list of symptoms needed for diagnosis. This is because they are commonly found in many other conditions too, including other sorts of EDS, so they don't help identify hEDS specifically.

How is hEDS managed?

• Regular gentle exercise and keeping your weight within the recommended range for your height will help keep you fit and stabilise your joints with good, working muscles. Pilates can be beneficial in helping maintain core stability and maintaining good posture.
• Some activities are better avoided, in order to protect the skin and joints from injury. Contact team sports, such as rugby and football, increase the risk of injury to joints, and it is better to choose less high-risk activities such as tennis or swimming.
• Some people benefit from seeing specialists in pain management, rheumatology, physiotherapy or occupational therapy.
• Painkillers may be helpful for generalised pains.
• Some patients find talking therapies such as CBT helpful.

Is hEDS the same as joint hypermobility syndrome?

Some doctors believe that hEDS is a more severe form of hypermobility syndrome and there is certainly an overlap in symptoms. However, hypermobility syndrome mainly affects joints. EDS is more likely to be the diagnosis where there are associated, more serious conditions, such as heart valve problems, prolapse or repeated dislocations.

Classical Ehlers-Danlos syndrome

Classical EDS (cEDS) affects 1 in 20,000-50,000 people. It is autosomal dominant genetic condition, which means that if you inherit one affected gene (one from either parent will do) then you will have the condition.

cEDS is similar to hEDS but in addition patients have very fragile skin, which is prone to splitting, particularly over the forehead, elbows, knees and chin. Those affected also have a tendency to form particularly thin scars. People also get rolled-up skin around joints which can be easily injured, little mobile nodules under the skin and easy bruising. Floppy muscles can be a feature, and children with cEDS may be slow to stand and walk.

cEDS is suspected if you have skin hyperextensibility and thin scars, PLUS joint hypermobility. The other possible effects of cEDS include tiredness, poor sleep, tummy pains and prolapse. Sometimes there are problems with the heart valves, which can become floppy, causing a heart murmur.

Management of cEDS

The main way in which management of cEDS differs from hEDS is in the need to protect the fragile skin. The important things are:

• Protecting the skin to minimise injuries, with clothing and, when needed, protective pads and helmets.
• If you have an injury that needs stitching, this should be done by a plastic surgeon. Stitches need to be left in place for longer than usual and wounds need extra support, with Steri-strips® or bandaging.
• Children with cEDS need to find a balance between restrictions and risks. Contact sports such as rugby, ice hockey, boxing and martial arts, and high-impact activities like trampolining, are high-risk for injury and may need to be avoided. Lower-impact physical activities such as badminton, table tennis, bowling and swimming are better alternatives.
• Regular gentle exercise is appropriate. Tiredness and joint pain can be part of cEDS and regular gentle exercise helps to reduce these effects.
• Adults with cEDS may find Pilates helpful to build strength and help protect joints.
• Physiotherapy is helpful when joint hypermobility is making joints slip out of place.
• Occupational therapy can suggest aids to daily living and advise on pacing activities to avoid the extreme fatigue that can follow a period of over-activity.
• There are some increased risks in pregnancy which are discussed in the separate section 'How do the Ehlers-Danlos syndromes affect pregnancy?', above.

Classical-like Ehlers-Danlos syndrome

This is also called tenascin-X deficient Ehlers-Danlos syndrome (clEDS).

This very rare condition is similar to cEDS, except that affected people do not make wide scars. It is autosomal recessive, which means that in order to inherit it you need to inherit one faulty gene from EACH of your parents. If a parent has only one faulty gene each, they will generally NOT have the condition. If they only have one faulty gene each, they will generally NOT have clEDS.

The other features of clEDS which are less common in other types of EDS are long thin fingers, 'flat' feet (pes planus), swollen legs, nerve compression syndromes (such as carpal tunnel syndrome), diverticular disease and wasting of the muscles in the hands and feet.

Management of clEDS

clEDS is managed like cEDS, above. It is specifically recommended to avoid smoking.

Vascular Ehlers-Danlos syndrome

Vascular EDS (vEDS) is the most serious form of EDS. It affects about 1 in 50,000-200,000 people.

vEDS has autosomal dominant inheritance so just one copy of the defective gene from either parent will cause the condition. A person may also be affected if there is a new mutation in the gene, and so vEDS may occur in people with no history of the disorder in their family.

The main risk people with vEDS face is leaking or bursting (rupture) of medium/large arteries. There is also a small risk of rupture of the large bowel (colon), and of the womb (uterus) during labour, and of spontaneous pneumothorax (caused by popping of an air space in the lungs). These are life-threatening effects, which usually occur in young adulthood, making this an extremely difficult diagnosis to be given.

Other features of vEDS include early varicose veins, premature skin ageing on the hands and feet, and fine, thinning hair, pointing and thinning of the cornea (the transparent front of the eye), and a characteristic facial appearance with small or absent earlobes.

Management of vEDS

Treatment with a medicine called celiprolol greatly reduces the risk of arterial rupture. It may also be possible to repair blood vessels at risk of rupture before they do. This is a very specialised area.

vEDS patients should wear a medical alert bracelet, necklace or similar. The EDS National Diagnostic Service has produced a medic alert sheet with the information that may be needed in case of an emergency. It is best to avoid invasive tests or invasive treatments unless strictly necessary, because of the risk of damage to skin and blood vessels.

Cardiac-valvular Ehlers-Danlos syndrome

Cardiac-valvular EDS (cvEDS) causes problems with the heart valves, in addition to other, clEDS-like symptoms. It is a rare condition and in order to inherit it you need to inherit one faulty gene from EACH of your parents. (If they only have one faulty gene each then they will generally NOT have cvEDS.)

Management is as for cEDS but with regular heart scans and monitoring, as the heart valves may need repair or replacement.

Arthrochalasia Ehlers-Danlos syndrome

Arthrochalasia EDS (aEDS) is a very rare, severe type of EDS in which the joints are very, very much looser than they should be. It has autosomal dominant inheritance so just one copy of the defective gene from either parent will cause the condition. It is usually diagnosed soon after birth, as babies are born with two dislocated hips. They also tend to have rather weak, floppy muscles, and particularly stretchy loose skin. Only around 30 cases have ever been described.

In addition to the severe joint problems, affected people also have fragile skin and, sometimes, a tendency to curvature of the spine.

Management of aEDS

The most important problem for children with aEDS is the early hip dislocation, since this severely affects mobility. Most of the usual surgical treatments for this condition do not work, so it is helpful if the diagnosis of aEDs is made before the hips are treated, in order that a method that will succeed is chosen first.

Repeated dislocation of other joints can slow children from progress in standing and walking. The symptoms are worst in infancy and tend to improve with age, so that some children manage to use orthoses (such as braces and calipers) to assist in walking later on.

Dermatosparaxis Ehlers-Danlos syndrome

Dermatosparaxis EDS (dEDS) is an extremely rare type of EDS which has been described only around 10 times. Affected people have extremely fragile, sagging skin. It is usually diagnosed before the age of 2 years. Fragility, bruising and sagging of the skin are severe but, surprisingly, the skin heals well. Like the other rare types, in order to inherit it you need to inherit one faulty gene from EACH of your parents. If a parent has only one faulty gene, they will generally NOT have the condition.

Affected children tend to have a characteristic facial appearance. They often have other features seen in classical EDS, such as hypermobile joints, hernias, tiredness, 'thinning' of the bones, floppy muscles, constipation and tummy pain. They can also experience abnormalities of the teeth, gums and vision, requiring spectacles.

Management of dEDS

Management is as for cEDS. A specialist dentist will need to be involved if there are tooth and gum problems, and an ophthalmologist if there are eye problems.

Kyphoscoliotic Ehlers-Danlos syndrome

This is a rare type of EDS which has been described only around 60 times. Like the other rare types, in order to inherit kyphoscoliotic EDS (kEDS), you need to inherit one faulty gene from EACH of your parents. If a parent has only one faulty gene each, they will generally NOT have the condition. It causes worsening (progressive) curvature of the spine (kyphoscoliosis).

Babies with kEDS are very floppy and they stand and walk late. Eyes are also affected and may have a thin surface (sclera) which appears slightly blue and which can (very rarely) rupture. Some affected children have hearing problems. Other signs of this type of EDS include thin bones and long thin fingers

Joints are very hypermobile and there may be frequent dislocations. Skin may be stretchy, soft and fragile, bruise easily and form widened, atrophic scars.

Management of kEDS

This is as for classical EDS but with particular focus on trying to keep the back growing straight and involving a specialist optician to look after the eyes.

Brittle cornea syndrome

In this rare type of EDS the front coverings of the eye are thinner and less strong than usual and the white of the eye (sclera) may appear blue. Like the other rare types, in order to inherit it you need to inherit one faulty gene from EACH of your parents. If a parent has only one faulty gene, they will generally NOT have the condition.

People with brittle cornea syndrome are generally very short-sighted, and the globe of the eye is at risk of rupturing. They also have the typical skin and joint features of classical and hypermobility types of EDS.

Management of brittle cornea syndrome

This is as for cEDS, with additional care needed for the eyes.

Spondylodysplastic Ehlers-Danlos syndrome

Spondylodysplastic EDS (spEDS) is a severe EDS. Like the other rare types, in order to inherit it you need to have inherited one faulty gene from EACH of your parents. If a parent has only one faulty gene each, they will generally NOT have the condition. It is marked particularly by short stature and weak floppy muscles. Bowing of limbs is common.

Unlike other types, there may be learning difficulties in children. Some of the features of EDS that affect eyes, bones, joints, blood vessels or the lungs may be present and there is a characteristic facial appearance.

Management of spEDS

Management involves the approaches used in cEDS towards skin and joints, together with specialist physiotherapy as your child grows up - to help maximise their bone growth and strength. It is not possible to generalise about the degree of learning education difficulty children experience, as the condition is so rare.

Musculocontractural Ehlers-Danlos syndrome

Musculocontractural EDS (mcEDS) is a rare type of EDS in which muscles in the legs and arms are severely tightened and shortened - these are called muscle contractures. The skin is severely affected too, being very stretchy, fragile and easily bruised, with the atrophic scars seen in clEDS. It can also affect bones, eyes, the digestive system and the kidneys. Like the other rare types, in order to inherit it you need to inherit one faulty gene from EACH of your parents. If a parent has only one faulty gene, they will generally NOT have the condition.

Management of mcEDS

Management of this condition follows the patterns detailed above for cEDS, with special attention to any of the eye, bone, kidney or digestive symptoms.

Myopathic Ehlers-Danlos syndrome

Myopathic EDS (mEDS) is a milder subtype of EDS which causes very floppy muscles which may seem very poorly developed at birth, but which improve with age. It is possible to inherit mEDS if just one of your parents is affected, although some 'versions' of mEDS seem to require you to inherit a faulty gene from both parents.

Management of mEDS

Management is as for the other types, with a focus on physiotherapy and muscle strengthening.

Periodontal Ehlers-Danlos syndrome

Periodontal EDS (pEDS) causes dental problems, particularly inflamed or absent gums and poor tooth development, on top of typical features of cEDS. It is rare but can be inherited from one parent only, as only one faulty gene is needed to develop the condition.

Management of pEDS

Management of pEDS is as for management of hEDS and cEDS but with additional, specialist dental care.

Summary

EDS is a very varied condition, which primarily affects skin and joints but which can also affect many other organs. Thirteen subtypes have now been classified.

There is no specific cure for EDS but if symptoms are interfering with your life, physiotherapy, gentle exercise, talking therapies and, sometimes, pain relief are the mainstays of treatment.

Dr Mary Lowth is an author or the original author of this leaflet.