Mastocytosis

Mastocytosis is a rare condition caused by an excess number of mast cells gathering in the body's tissues.

There are 2 main types of mastocytosis:

• cutaneous mastocytosis, which mainly affects children – where mast cells gather in the skin, but are not found in large numbers elsewhere in the body
• systemic mastocytosis, which mainly affects adults – where mast cells gather in body tissues, such as the skin, internal organs and bones

There are also several subtypes of systemic mastocytosis, depending on the symptoms.

Mast cells

Mast cells are produced in the bone marrow, the spongy tissue found in the hollow centres of some bones, and live longer than normal cells. They're an important part of the immune system and help fight infection.

When mast cells detect a substance that triggers an allergic reaction (an allergen), they release histamine and other chemicals into the bloodstream.

Histamine makes the blood vessels expand and the surrounding skin itchy and swollen. It can also create a build-up of mucus in the airways, which become narrower.

Symptoms of mastocytosis

The symptoms of mastocytosis can vary depending on the type.

Cutaneous mastocytosis

The most common symptom of cutaneous mastocytosis is abnormal growths (lesions) on the skin, such as bumps and spots, which can form on the body and sometimes blister.

Systemic mastocytosis

Some people with systemic mastocytosis may experience episodes of severe symptoms, often with specific triggers such as physical exertion or stress. Many people do not have any problems.

During an episode you may have:

• skin reactions – such as itching and flushing
• gut symptoms – such as diarrhoea and vomiting
• muscle and joint pain
• mood changes, headaches and tiredness (fatigue)

There are 3 main subtypes of systemic mastocytosis. They are:

• indolent systemic mastocytosis – symptoms are usually mild to moderate and vary from person to person; indolent systemic mastocytosis accounts for around 90% of adult systemic mastocytosis cases
• aggressive mastocytosis – where mast cells multiply in organs, such as the spleen, liver and digestive system; the symptoms are more wide-ranging and severe, although skin lesions are less common
• systemic mastocytosis with associated blood (haematological) disease – where a condition that affects the blood cells, such as chronic leukaemia, also develops

Severe allergic reaction

People with mastocytosis have an increased risk of developing a severe and life-threatening allergic reaction. This is known as anaphylaxis.

The increased risk of anaphylaxis is caused by the abnormally high number of mast cells and their potential to release large amounts of histamine into the blood.

If you or your child has mastocytosis, you may need to carry an adrenaline auto-injector, which can be used to treat the symptoms of anaphylaxis. 

Read more about the symptoms of mastocytosis.

Causes of mastocytosis

The cause or causes of mastocytosis are not fully known, but there's thought to be an association with a change in genes known as the KIT mutation.

The KIT mutation makes the mast cells more sensitive to the effects of a signalling protein called stem cell factor (SCF).

SCF plays an important role in stimulating the production and survival of certain cells, such as blood cells and mast cells, inside the bone marrow.  

In very few cases of mastocytosis it appears the KIT mutation is passed down through families. However, in most cases the mutation happens for no apparent reason.

Diagnosing mastocytosis

A physical examination of the skin is the first stage in diagnosing cutaneous mastocytosis.

Your GP or skin specialist (dermatologist) may rub the affected areas of skin to see if they become red, inflamed and itchy. This is known as Darier's sign.

It's usually possible to confirm a diagnosis by carrying out a biopsy, where a small skin sample is taken and checked for mast cells.

The following tests are commonly used to look for systemic mastocytosis:

• blood tests – including a full blood count (FBC) and measuring blood tryptase levels
• an ultrasound scan to look for enlargement of the liver and spleen if it seems likely
• a DEXA scan to measure bone density
• a bone marrow biopsy test – where a local anaesthetic is used and a long needle is inserted through the skin into the bone underneath, usually in the pelvis

A diagnosis of systemic mastocytosis is usually made by finding typical changes on a bone marrow biopsy.

Treating mastocytosis

There's no cure for mastocytosis, so the aim of treatment is to try to relieve the symptoms.

Treatment options will depend on the type of mastocytosis and the severity of the symptoms.

Mild to moderate cases of cutaneous mastocytosis can be treated with steroid cream (topical corticosteroids) for a short time.

Steroid cream reduces the number of mast cells that can release histamine and trigger swelling (inflammation) in the skin.

Antihistamines can also be used to treat the symptoms of cutaneous or indolent mastocytosis, such as red skin and itchiness.

Antihistamines are a type of medicine that block the effects of histamine and are often used to treat allergic conditions.

Read more about treating mastocytosis.

Complications of mastocytosis

In children, the symptoms of cutaneous mastocytosis usually improve over time, but remain stable in adults.

In many cases the condition gets better on its own by the time a child has reached puberty.

The outlook for systemic mastocytosis can vary, depending on the type you have.

Indolent systemic mastocytosis should not affect life expectancy, but other types can. 

A few people develop a serious blood condition, such as chronic leukaemia, over their lifetime.

 Symptoms Mastocytosis 

Mastocytosis causes a wide range of symptoms, which can vary depending on the type of mastocytosis you have.

Cutaneous mastocytosis

Skin lesions are a characteristic of cutaneous mastocytosis. Types of lesions known to occur in cutaneous mastocytosis include:

• small areas of skin that change colour (macules)
• small, firm, raised bumps (papules)
• larger raised, red bumps (nodules)
• large raised areas of skin noticeable to the touch (plaques)
• blisters – which mainly affect young children with mastocytomas (tumours consisting of mast cells) or diffuse cutaneous mastocytosis (a rare form of cutaneous mastocytosis)

Lesions usually develop on the trunk and limbs rather than the head and neck.

The lesions, known as urticaria pigmentosa, are usually reddish-brown in colour, and can range from 1mm to several centimetres in size.

The number of lesions that develop on the skin can vary widely.

Stroking the affected areas of skin can make it swollen, itchy and red over the lesion.

Systemic mastocytosis

If you have systemic mastocytosis, you may experience episodes of symptoms. However, many people do not have any problems.

The most common symptoms experienced during an episode are:

• hot flushes
• a forceful or rapid heartbeat (heart palpitations)
• feeling lighthead

Less common symptoms during an episode include:

• headache
• chest pain
• feeling sick
• diarrhoea

The episodes are caused by the mast cells suddenly releasing excessive amounts of histamine, usually after you're exposed to certain triggers.

Triggers known to cause episodes include:

• physical factors – such as heat, overheating, cold, fatigue and physical exertion
• emotional factors – such as stress and excitement
• insect bites or stings
• infection – such as a cold or flu
• alcohol
• certain medications – such as ibuprofen, aspirin and antibiotics
• certain foods – such as cheese, shellfish and spices

Abnormal mast cells in your bone marrow and organs can also cause related symptoms, including:

• stomach pain caused by peptic ulcers
• joint pain
• weakness
• fatigue
• changes in mental state – such as confusion, irritability, poor attention span and impaired memory

In more severe cases of mastocytosis, the following symptoms may occur:

• weight loss
• swelling of the lymph nodes
• swelling of the liver – which can cause jaundice and make you feel lethargic
• swelling of the spleen – which can cause tummy and shoulder pain

Low blood pressure (hypotension)

Some people with severe symptoms experience a sudden fall in blood pressure during an attack. 

Low blood pressure (hypotension) can trigger a number of associated symptoms, such as:

• dizziness
• fainting
• blurred vision
• confusion
• generally feeling weak

Severe allergic reaction

If you have systemic mastocytosis or extensive cutaneous mastocytosis, your risk of a severe allergic reaction (anaphylaxis) is increased.

It's important to look out for the initial symptoms of anaphylaxis, which include:

• itchy skin or a raised, red rash
• swollen eyes, lips, hands and feet
• feeling lightheaded or faint
• narrowing of the airways, which can cause wheezing and breathing difficulties
• stomach pain
• feeling and being sick

Dial 112 immediately and ask for an ambulance if you think you or someone else is experiencing symptoms of anaphylaxis.

 Treatment Mastocytosis 

The treatment options for mastocytosis depend on which type you have and how severe your symptoms are.

Nearly all medicines used to treat mastocytosis are unlicensed. This means the manufacturers haven't applied for a licence for their medicine to be used to treat mastocytosis.

In other words, the medicine has not undergone clinical trials to see if it can treat mastocytosis effectively and safely.

Many experts will use an unlicensed medicine if they think it will be effective and the benefits of treatment outweigh any associated risk.

Steroid cream

Mild to moderate cases of cutaneous mastocytosis can be treated with a very strong steroid cream (topical corticosteroids) for a limited length of time.

Steroid cream reduces the number of mast cells that can release histamine and trigger inflammation inside the skin.

Side effects of steroid cream when used too much include:

• thinning of the skin, which can sometimes result in permanent stretch marks
• a temporary reduction in the pigmentation of the skin
• the affected area of skin bruising easily

You should only apply the cream to areas of skin affected by lesions to reduce the risk of side effects.

Antihistamines

Antihistamines can also be used to treat symptoms of cutaneous or indolent mastocytosis, such as itchiness and skin redness.

Antihistamines are a type of medicine that block the effects of histamine. They're widely used to treat allergic conditions.

Side effects of some "classical" antihistamines include:

• headache
• dry mouth
• drowsiness

However, these side effects should pass quickly once you're used to the medicine. Modern antihistamines do not usually cause these side effects.

Sodium cromoglicate

Sodium cromoglicate is a medicine used to treat conjunctivitis, asthma and food allergy. It may also be used to treat gut symptoms of mastocytosis, but is not absorbed well from the bowel.

Sodium cromoglicate is a mast cell stabiliser, which means it reduces the amount of chemicals released by the mast cells. This helps relieve symptoms such as diarrhoea and stomach pain.

Some people taking sodium cromoglicate have reported feeling sick and getting joint pain.

A form of sodium cromoglicate applied to the skin is available that may help with itching. However, it's not routinely available on prescription.

Psoralen plus ultraviolet A (PUVA)

More severe symptoms of cutaneous mastocytosis, such as severe itchy skin, may require a type of treatment called psoralen plus ultraviolet A (PUVA).

PUVA involves taking a medicine called psoralen, which makes the skin more sensitive to the effects of ultraviolet light.

The skin is then exposed to a wavelength of light called ultraviolet A (UVA), which helps reduce lesions in the skin.

You can only have a limited number of PUVA sessions as using the treatment too many times – around 150 sessions – may increase your risk of developing skin cancer over your lifetime.

Steroid tablets

If symptoms such as itchiness are particularly severe, corticosteroid tablets (oral corticosteroids) may be prescribed on a short-term basis. However, this is rare.

A short course of corticosteroid tablets may be recommended if you have bone pain caused by mastocytosis, or a severe allergic reaction (anaphylaxis).

Side effects of oral corticosteroids used on a short-term basis include:

• an increase in appetite
• weight gain
• insomnia
• fluid retention
• mood changes, such as feeling irritable or anxious

Bisphosphonates and calcium supplements

If you have weakened bones (osteoporosis) resulting from abnormal mast cell activity in your bones, you'll be given a medicine called bisphosphonates.

Bisphosphonates slow the process of bone breakdown while allowing production of new bone to continue as normal, which improves your bone density.

You may also be given calcium supplements, as calcium helps strengthen bones.

Read more about treating osteoporosis.

H2-receptor antagonists

If you have stomach pain caused by a stomach ulcer (peptic ulcer), you'll be given a medicine called an H2-receptor antagonist.

This blocks the effects of histamine in the stomach – histamine stimulates the production of stomach acid, which damages the stomach lining. 

Interferon alpha

Originally designed to treat cancer, interferon alpha has proved effective in treating some cases of aggressive mastocytosis.

It's not known exactly why this is, but it appears the medicine reduces the production of mast cells inside the bone marrow.

Interferon alpha is given by injection. You may have flu-like symptoms, such as chills, a high temperature and joint pain, when you start taking interferon alpha.

However, your symptoms should improve over time as your body gets used to the medicine.

Imatinib

Imatinib is an alternative medicine to interferon alpha. It's taken as a tablet and blocks the effects of an enzyme called tyrosine kinase, which helps stimulate production of mast cells.

However, imatinib should only be used for people who do not have the KIT mutation, and it does not work for most cases of mastocytosis.

Imatinib can also make you more vulnerable to infection. Contact your GP immediately if you develop possible signs of an infection, such as:

• a high temperature of or above 38C
• headache
• aching muscles
• diarrhoea
• tiredness

Nilotinib and dasatinib

Nilotinib or dasatinib may be recommended if you do not respond to treatment with imatinib. They work in much the same way, blocking the effects of tyrosine kinase.

The medicine will make you more vulnerable to infection, so report possible symptoms of infection to your GP immediately.

Midostaurin

Midostaurin is a licensed medicine that can be used to treat advanced systemic mastocytosis. It works by slowing down the growth of mast cells.

It can help to relieve some symptoms of advanced systemic mastocytosis and improve quality of life.

Side effects of taking midostaurin might include:

• diarrhoea and vomiting
• chills
• headaches
• weight gain

Cladribine

Cladribine is an alternative medicine to midostaurin. It was originally designed to treat cancer of the white blood cells (leukaemia), but it's also been shown to be useful in treating aggressive systemic mastocytosis.

Cladribine suppresses the activity of your immune system. It's given by infusion, which means it's slowly released into your body through a drip in your arm.

Like imatinib, nilotinib and dasatinib, cladribine will also make you more vulnerable to the effects of infection, so you should report possible symptoms of infection to your GP immediately.

Avapritinib

Avapritinib is a medicine that can be used to treat advanced systemic mastocytosis in adults.

It's taken as a tablet and blocks the effects of an enzyme called tyrosine kinase, which helps stimulate production of mast cells.

Treatments for haematological disease

Systemic mastocytosis with associated blood (haematological) disease will be treated in the same way as aggressive systemic mastocytosis, with a number of additional treatments for the related haematological condition.

For more information about treating the most common haematological conditions, see:

Treating acute myeloid leukaemia

Treating chronic myeloid leukaemia

Treating acute lymphoblastic leukaemia

Treating chronic lymphocytic leukaemia

Treating Non-Hodgkin lymphoma

Treating myeloma

Myeloproliferative neoplasms are also haematological disorders that can be associated with mastocytosis.

Using an adrenaline injection pen

Because of your increased risk of anaphylaxis, you may be given an adrenaline auto-injector to use in an emergency.

Adrenaline is a natural chemical that helps fight the effects of too much histamine, while also relieving breathing difficulties. Each pen contains a single dose of adrenaline.

There are 3 types:

• EpiPen
• Jext
• Emerade

These auto-injectors release adrenaline when jabbed or pressed against the outer thigh. The injections can be given through clothing.

If you're given an adrenaline auto-injector, you need to keep an eye on its expiry date because it will be less effective beyond this date.