What is mastocytosis?
Mastocytosis is a rare condition caused by excessive amounts of mast cells gathering in body tissues. These cells release large amounts of histamine and other chemicals into the blood, causing symptoms such as a skin rash, itchy skin and hot flushes.
Mast cells play an important role in the immune system and are found in certain parts of the body, such as the skin and the lining of the lungs and stomach.
Types of mastocytosis
There are two main types of mastocytosis:
In cutaneous mastocytosis, mast cells gather in the skin. It usually only affects children – three-quarters of cases develop in children aged one to four. It is also known as paediatric mastocytosis.
The most common symptom of cutaneous mastocytosis is abnormal growths (lesions) on the skin, such asand spots which can form a rash on the body.
In systemic mastocytosis, mast cells gather in body tissues, such as the skin, organs and bones and can affect any part of the body. The condition mainly affects adults.
People with the condition experience attacks, lasting 15-30 minutes, when their symptoms are severe. During an attack they may have:
- , such as itching and flushing
- gut symptoms, such as vomiting and
- pain in muscles and joints
- changes in mood, headaches and episodes of severe fatigue (tiredness)
These attacks are often triggered by:
- physical exertion
- certain medications, such as or
- stress or emotional upset
Systemic mastocytosis is also known as mast cell disease.
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There are three subtypes of systemic mastocytosis, described below.
- indolent mastocytosis (accounting for 90% of cases) – symptoms are usually mild to moderate and vary from person to person
- aggressive mastocytosis – mast cells invade organs such as the spleen, liver and digestive system, so symptoms are more wide ranging and severe (but skin lesions are less common)
- systematic mastocytosis with associated haematological (blood) disease – the person also develops a condition affecting blood cells, such as
Theis not fully known although there is thought to be an association with a genetic mutation known as the c-KIT mutation. A genetic mutation happens when normal instructions carried in certain genes become ‘scrambled’. This means some of the body’s processes will not work in the normal way.
Severe allergic reaction
Because of the excessive amounts of mast cells and their potential to release large amounts of histamine into the blood, people with mastocytosis have an increased risk of experiencing a severe and life-threatening allergic reaction known as.
If you or your child are diagnosed with mastocytosis, you may need to carry an adrenaline injection kit, which can be used to prevent the symptoms of anaphylaxis from getting worse.
Symptoms of cutaneous mastocytosis usually improve over time. In most cases the disease goes away 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. Some people develop a serious haematological condition, such as chronic leukaemia.
There is no cure for mastocytosis. Treatment is based on trying to relieve symptoms with medication.
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How common is mastocytosis?
Cutaneous mastocytosis is the most common form of the condition, but is still rare in general terms. It is estimated only one in every 1,000 visits to a dermatologist (specialist in treating skin conditions) is due to cutaneous mastocytosis.
Systemic mastocytosis is thought to be much rarer, although exactly how rare is uncertain.
Mastocytosis causes a wide range of symptoms which can vary depending on whether you have cutaneous or systemic mastocytosis.
The main symptom of cutaneous mastocytosis is skin lesions. A skin lesion is any type of abnormality that affects the skin. 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)
- (collections of fluid that develop inside the upper layer of the skin)
Lesions normally develop on the trunk (the body, excluding head, neck and limbs). The lesions, known as urticaria pigmentosa, are usually yellow-tan to reddish-brown in colour, and can range from 1mm to several centimetres in size.
The number of lesions that develop on the skin vary widely. In some cases, only one lesion was reported whereas in another case, the person had more than 1,000 lesions.
Stroking the affected areas of skin can make it swollen, itchy and red.
If you have systemic mastocytosis you will have sudden attacks of symptoms that last around 15-30 minutes. Most common symptoms during an attack are:
- hot flushing – described as a dry feeling of heat, rather than the sort of wet heat you experience when sweating
- palpitations (irregular heartbeat)
Less common symptoms during an attack include:
- shortness of breath
- chest pain
Once the attack has passed, you will probably feel lethargic (sluggish) for several hours.
These attacks are caused by the mast cells suddenly releasing excessive amounts of histamine, usually after you are exposed to certain triggers. Triggers known to cause attacks include:
- physical factors, such as heat, cold, fatigue and physical exertion
- emotional factors, such as stress and excitement
- certain foods, such as cheeses, shellfish and spices
- , such as flea bites or a wasp sting
- infection, such as the cold or
- certain medications, such as , and
Abnormal mast cells in your bone marrow and organs can also cause related symptoms, including:
- stomach pain caused by
- loss of appetite
- weight loss
- swelling of the liver, which can cause (yellowing of the skin and eyes) and make you feel lethargic
- swelling of the spleen, which can cause abdominal (tummy) and shoulder pain
- joint pain
- swelling of the lymph nodes
- changes in mental state, such as confusion, irritability, poor attention span and impaired memory
- urinary symptoms (needing to pass urine frequently, or pain when passing urine)
Low blood pressure (hypotension)
Some people with severe symptoms will experience a sudden drop in blood pressure during an attack. Low blood pressure (hypotension) can trigger a number of associated symptoms, such as:
- fainting (a sudden, temporary loss of consciousness)
- blurred vision
- general weakness
If you have either cutaneous or systemic mastocytosis, you have an increased risk of(a severe allergic reaction). Therefore it is important to look out for the initial symptoms of anaphylaxis, which include:
- breathing difficulties
- swollen eyes, lips, genitals, hands, feet and other areas (called angio-oedema)
- itchy skin or nettle rash (hives)
- a strange metallic taste in the mouth
- sore, red, itchy eyes
- changes in heart rate
- a sudden feeling of extreme anxiety
- unconsciousness due to very low blood pressure
- abdominal cramps, vomiting or diarrhoea
If you think you are experiencing anaphylaxis, you should administer your adrenaline auto-injector (if you have one) and call immediately for an ambulance.
The cause (or causes) of mastocytosis are uncertain, although genetic mutations are known to be involved.
A genetic mutation occurs when normal instructions carried in certain genes become ‘scrambled’. This means some of the body’s processes will not work in the normal way.
The c-KIT mutation
There is evidence that most people with either cutaneous or systemic mastocytosis have a genetic mutation known as the c-KIT mutation. This makes their bodies more sensitive to the effects of a type of protein called stem cell factor (SCF).
SCF plays an important role in stimulating production of certain cells, such as blood cells and mast cells, inside the bone marrow. Bone marrow is the soft, jelly-like tissue found in the hollow centre of all large bones. It contains stem cells, capable of producing specialist cells, such as mast cells.
When the bone marrow is exposed to SCF, it produces more mast cells than the body can cope with, which leads to symptoms of mastocytosis.
In a number of cases of mastocytosis, it appears the c-KIT mutation was inherited (passed down through families). However, in most cases the mutation was spontaneous (that is, it happened for no apparent reason).
There are several tests available to confirm a diagnosis of mastocytosis, depending on which type you have.
The first stage in diagnosing cutaneous mastocytosis is to carry out a physical examination of the skin. Your child’s doctor or dermatologist (specialist in treating skin conditions) may rub affected areas of the skin to see if it becomes red, inflamed and itchy (known as Darier’s sign).
A diagnosis can usually be confirmed by carrying out a. This involves removing a small sample of affected skin and checking under a microscope to see if the skin contains an abnormally high number of mast cells.
Five tests are commonly used to diagnose systemic mastocytosis. They are described below.
Full blood count (FBC)
A full blood count is a type of. A small blood sample is taken from a vein in your arm and different types of blood cells in the sample are measured. Unusually low levels of blood cells could be caused by excessive amounts of mast cells in your bone marrow.
Blood tryptase levels
The levels of an enzyme called tryptase in your blood are measured using a blood test. Tryptase is produced by mast cells. Having more than 20 nanograms of tryptase (a nanogram is a billionth of a gram) in a millilitre of blood would suggest you have excessive amounts of mast cells in your bone marrow or other organs.
Ancan be used to check whether your liver and spleen are swollen, which can occur in some cases of systemic mastocytosis. An ultrasound scanner uses high-frequency sound waves to create an image of part of the inside of the body.
Ais a type of X-ray that measures the amount of calcium in bones. Low levels of calcium usually indicate your bones have become weak and brittle ( ), which could be the result of excessive amounts of mast cells accumulating inside your bones. Mast cells release substances that cause the bones to thin.
Bone marrow test
If the tests suggest you may have systemic mastocytosis, it is likely you will be referred for a bone marrow test. You will be given a local anaesthetic to numb an area of skin and underlying tissue. A long needle is inserted into your skin and pushed into the bone underneath.
The needle is used to remove a small sample of bone marrow which can be studied to see if it contains an abnormally high number of mast cells. The bone marrow can also be tested for the c-KIT mutation, known to be associated with most cases of systemic mastocytosis (read about thefor more information).
The treatment options for mastocytosis depend on which type you have, and how severe your symptoms are.
Mild to moderate cases of cutaneous mastocytosis can be treated with steroid cream (). Steroid cream prevents mast cells releasing histamine and triggering inflammation inside the skin.
Side effects of steroid cream include:
- thinning of the skin, which can sometimes result in permanent stretch marks
- discolouration of the skin
- the affected area of skin bruising easily
To reduce the risk of side effects, you should only apply the cream to areas of skin affected by lesions.
Antihistaminesmay also be used to treat symptoms of cutaneous or indolent mastocytosis, such as itchiness and redness of the skin. Antihistamines are a type of medication that block the effects of histamine. They are widely used in the treatment of allergic conditions.
Side effects of antihistamines include:
- dry mouth
- dry nose
These side effects should pass quickly.
Sodium cromoglicate (Nalcrom) is a medication used to treat allergic conditions of the eye, rhinitis and food allergy. It is also used as an unlicensed medication for the treatment of mastocytosis.
It 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, itching and flushing of the skin.
A case report published in 2010 describes a patient with mastocytosis whose symptoms improved after taking antihistamines and sodium cromoglicate capsules. Their bone pain, fatigue and headache improved further after also taking inhaled sodium cromoglicate.
Nausea, skin rashes and joint pains have been reported in some people taking sodium cromoglicate. A topical form (applied to the skin) is available which may help with itching.
The more severe symptoms of cutaneous mastocytosis, such as severe itchy skin, may require a type of treatment known as psoralen plus ultraviolet A (PUVA). PUVA involves taking a medication 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 remove lesions from the skin.
The patient can only receive a limited number of PUVA sessions as using the treatment too many times (thought to be around 200-250 sessions) increases their risk of developing skin cancer.
During times when symptoms such as itchiness are particularly severe, tablets containing corticosteroids () may be prescribed on a short-term basis.
For example, a short course of corticosteroid tablets may be recommended if you have bone pain or a previous history of anaphylaxis (severe allergic reaction).
Side effects of oral corticosteroids used on a short-term basis include:
- an increase in appetite
- weight gain
- fluid retention
- mood changes, such as feeling irritable or anxious
Bisphosphonates and calcium supplements
If you have osteoporosis (weakened bones) due to abnormal mast activity in your bones, you will be given a type of medication 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 (calcium helps strengthen the bones).
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If you have symptoms of stomach pain due to peptic ulcers, you will be given a medication called a H2-receptor antagonist. This blocks the effects of histamine in the stomach (histamine stimulates the production of stomach acid, which damages the lining of the stomach).
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Originally designed to treat cancer, interferon alpha has proved effective in treating some cases of aggressive mastocytosis. Exactly why this is the case is uncertain, although it appears the medication reduces the production of mast cells inside the bone marrow.
Interferon alpha is given by injection. Most people will have flu-like symptoms such as chills, a high temperature and joint pain when they first start taking interferon alpha. However symptoms should improve over time as your body gets used to the medicine.
Nilotinib and dasatinib
Nilotinib or dasatinib may be tried when people do not respond to treatment with imatinib. They work in much the same way, blocking the effects of tyrosine kinase.
The medication will make you more vulnerable to infection, so report possible symptoms of infection to your doctor immediately.
Cladribine was originally designed to treat leukaemia (cancer of the white blood cells), but has since proved effective in treating aggressive systematic mastocytosis.
Cladribine suppresses the activity of your immune system. It is given by infusion, which means it is slowly released into your body via a drip in your arm over the course of two hours.
Again, cladribine will make you more vulnerable to the effects of infection, so you should report possible symptoms of infection to your doctor immediately.
There's evidence that cladribine can rarely cause serious liver injury, usually within 8 weeks of starting your first treatment. Therefore your doctor will check your liver levels before each treatment and during treatment if they feel it is necessary.
Let them know if you've had any problems with your liver in the past or had a reaction of your liver to other medicines. Talk to your doctor straight away if you develop any signs of liver problems such as pain in the upper right area of your stomach, yellowing of your skin or the white part of your eyes, loss of appetite, feeling or being sick, dark urine, or widespread itching.
An alternative medication to interferon alpha is imatinib tablets. Imatinib 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 c-KIT mutation (see), and it does not work for all cases of mastocytosis.
Imatinib can also make you more vulnerable to infection. Contact your doctor immediately if you develop possible signs of an infection, such as:
- high temperature (fever) of or above 38ºC (101.4ºF)
- aching muscles
Treatments for haematological (blood) disease
Systemic mastocytosis with associated haematological disease will be treated in the same way as aggressive systematic mastocytosis (with either interferon alpha, imatinib, nilotinib or cladribine) with a number of additional treatments for the related haematological condition.
For more information on treating the most common haematological conditions, see:
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 injection pen to use in an emergency. Adrenaline is a hormone that helps block the effects of histamine while also relieving breathing difficulties. Each pen contains a single dose of adrenaline (0.3mg for adults or 0.15mg for children). There are two types:
- EpiPen – this needle releases adrenaline when jabbed against the outer thigh
- Anapen – you hold the syringe against the outer thigh and push a button, which plunges the adrenalin-loaded needle into your thigh. After injecting, the syringe should be held in place for 10 seconds
The injections can be given through clothing.
If you are given an adrenaline injection pen it is important to keep an eye on its expiry date as it will not be effective beyond this date.