Mastocytosis

Mastocytosis is a rare disease that happens when the body produces too many mast cells, which are white blood cells that normally protect against bacteria and allergens. When these cells become abnormal and multiply uncontrollably, they release chemicals that cause unusually intense or long-lasting allergic reactions throughout the body.

Table of contents

• What is mastocytosis?
• Types of mastocytosis
• How common is mastocytosis?
• What causes mastocytosis?
• Symptoms of mastocytosis
• What triggers mastocytosis symptoms?
• How is mastocytosis diagnosed?
• Treatment and management
• Outlook and prognosis
• Living with mastocytosis

What is mastocytosis?

Mastocytosis is a rare disease that occurs when your body makes too many mast cells, which are a type of white blood cell that forms part of your immune system^[1]. Mast cells are found throughout your body, mostly in your skin, bone marrow, lungs and the lining of your intestine^[1].

Under normal circumstances, mast cells protect your body from intruders like bacteria and allergens. They do this by releasing histamine, a chemical that helps cells communicate and triggers your body’s allergic reactions^[1]. Mast cells also help produce stomach acid^[1]. Normally, mast cells stop reacting once they have dealt with the intruders.

In mastocytosis, abnormal mast cells multiply and build up in your body. As they multiply, they release more histamine^[1]. This means that if you have mastocytosis, your body overreacts to allergens, and you may experience unusually intense or long-lasting allergic reactions^[1].

Healthcare providers cannot cure mastocytosis, but they can treat its symptoms and the complications the condition causes^[1]. Most people can manage symptoms with medication and by avoiding activities and environments that trigger the condition^[1]. However, all people with mastocytosis have an increased risk of anaphylaxis, which is a severe allergic reaction that can be life-threatening^[1].

Types of mastocytosis

There are two main types of mastocytosis^[2]:

Cutaneous mastocytosis is a type where mast cells gather in the skin but are not found in large numbers elsewhere in the body^[2]. This type typically affects infants and toddlers but may also affect adults^[1]. In cutaneous mastocytosis, abnormal mast cells build up in your skin and create itchy sores that may be red or dark red, brown or a combination of red and brown^[1]. The most common symptom is abnormal growths on the skin, such as bumps and spots, which can form on the body and sometimes blister^[2].

Systemic mastocytosis is a type where mast cells gather in body tissues, such as the skin, internal organs and bones^[2]. This type typically affects adults^[1]. In systemic mastocytosis, abnormal mast cells build up in your bone marrow, bones, digestive system and lungs^[1]. Abnormal mast cells that build up in your bone marrow may affect blood cell production. Abnormal mast cells that build up in your organs affect how they work^[1]. For example, if there are unusually large numbers of mast cells in your stomach, they may produce too much stomach acid and cause ulcers^[1].

There are several subtypes of systemic mastocytosis, depending on the symptoms^[2]. Indolent systemic mastocytosis is the most common type and usually does not include organ dysfunction. Symptoms are usually mild to moderate and vary from person to person. Indolent systemic mastocytosis accounts for around 90 percent of adult systemic mastocytosis cases^[2].

Smoldering systemic mastocytosis is associated with more significant symptoms and may include organ dysfunction and worsening disease over time^[9]. Individuals with smoldering mastocytosis may have more organs affected and more severe features than those with indolent mastocytosis^[2].

The severe types include 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^[2]. This type is rare and more severe, with significant symptoms, and is usually associated with progressive organ dysfunction and damage^[9].

Systemic mastocytosis with an associated blood disorder is where a condition that affects the blood cells also develops^[2]. Mast cell leukemia is an extremely rare and aggressive form of systemic mastocytosis^[9].

Mastocytosis can occur at any age. It is more serious in adults and usually mild in children, who often outgrow it^[5]. Cutaneous mastocytosis usually affects children when they are newborns^[1]. Systemic mastocytosis affects adults age 50 and older^[1].

How common is mastocytosis?

Mastocytosis is a rare condition. Studies vary but estimate that mastocytosis affects 1 in 10,000 to 20,000 people^[1][7]. Most cases of mastocytosis are limited to the skin, and 80 percent of them appear during childhood^[8].

What causes mastocytosis?

Mastocytosis is an acquired genetic disorder, meaning you do not inherit the condition^[1]. The cause or causes of mastocytosis are not fully known, but there is thought to be an association with a change in genes known as the KIT mutation^[2].

The condition happens when KIT genes mutate, or change. KIT genes play a role in developing certain cell types, including blood cells and mast cells^[1]. In mastocytosis, mutated KIT genes order mast cells to multiply uncontrollably^[1].

The KIT mutation makes the mast cells more sensitive to the effects of a signaling protein called stem cell factor. This protein plays an important role in stimulating the production and survival of certain cells, such as blood cells and mast cells, inside the bone marrow^[2].

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^[2]. The most common mutation, called KIT D816V, produces a receptor that is constantly activated, resulting in continuous growth and activation of mast cells^[13]. This mutation is present in approximately 90 percent of adults with systemic mastocytosis, compared with 35 percent in pediatric mastocytosis^[6].

Symptoms of mastocytosis

The symptoms of mastocytosis can vary depending on the type^[2]. This abnormal growth of mast cells causes a range of symptoms^[1].

Common symptoms include^[1][3]:

• Flushing, when skin all over the body turns red
• Itchy bumps on your skin or itching
• Red or brown patches on your skin, or hives
• Abdominal pain
• Diarrhea, nausea or vomiting
• Bone pain
• Muscle and joint pain
• Headache
• Lightheadedness from a drop in blood pressure
• Fainting
• Feeling anxious
• Mood changes or problems concentrating
• Tiredness

Some people with systemic mastocytosis may experience episodes of severe symptoms, often with specific triggers such as physical exertion or stress^[2]. Many people do not have any problems^[2].

Signs and symptoms of systemic mastocytosis depend on the part of the body affected by excessive mast cells. Too many mast cells can build up in the skin, liver, spleen, bone marrow or intestines. Less commonly, other organs such as the brain, heart or lungs may also be affected^[3].

Additional symptoms may include enlarged liver, spleen or lymph nodes, anemia or bleeding disorders, and depression^[3].

Severe allergic reaction

People with mastocytosis have an increased risk of developing a severe and life-threatening allergic reaction known as anaphylaxis^[2]. 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^[2]. Nearly half of individuals with systemic mastocytosis will experience severe allergic reactions^[7].

In a few patients, the extra mast cells cause a serious reaction, like a bad allergy reaction. The blood pressure may suddenly drop to a low level and cause fainting. The person may have trouble breathing. This reaction can cause death if treatment is not started right away, although this kind of severe reaction is very rare^[5].

What triggers mastocytosis symptoms?

There are dozens of potential mastocytosis triggers and not everyone with mastocytosis reacts the same way^[1]. When mast cells are triggered, they release substances that can cause signs and symptoms similar to those of an allergic reaction^[3].

Some activities or experiences that trigger the condition include^[1][3]:

• Having something touch or rub on your skin so it causes friction or skin irritation
• Participating in exercise and physical activity
• Being bitten or stung by an insect
• Changes in temperature, including cold or heat
• Spicy foods
• Alcohol
• Certain medications
• Emotional stress

Symptoms may be triggered by cold or heat, certain medicines, emotional stress and insect bites. The triggers are not the same in every person^[5]. People have different triggers, but the most common ones include alcohol, skin irritation, spicy foods, exercise, insect stings and certain medications^[3].

How is mastocytosis diagnosed?

The symptoms of mastocytosis can be like the symptoms of many other health problems^[5]. A physical examination of the skin is the first stage in diagnosing cutaneous mastocytosis^[2]. Your doctor or skin specialist may rub the affected areas of skin to see if they become red, inflamed and itchy. This is known as Darier’s sign^[2].

It is usually possible to confirm a diagnosis by carrying out a biopsy, where a small skin sample is taken and checked for mast cells^[2]. Your doctor removes a small piece of skin and puts it under a microscope to look for extra mast cells^[5].

The following tests are commonly used to look for systemic mastocytosis^[2]:

• Blood tests, including a full blood count 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^[2]. When an adult gets mastocytosis, a bone marrow biopsy may be needed to look for other blood diseases that might come along with the mastocytosis^[5].

If you do not have a rash but you have other symptoms, like diarrhea, your doctor may do a blood test or a urine test^[5].

Treatment and management

There is no cure for mastocytosis, so the aim of treatment is to try to relieve the symptoms^[2]. Treatment options will depend on the type of mastocytosis and the severity of the symptoms^[2]. Therapy for systemic mastocytosis is primarily symptomatic^[14].

Treatment can stop your mast cells from releasing histamine. It can also keep the histamine from causing problems^[5]. The principles of treatment include control of symptoms with measures to decrease mast cell activation^[14].

Medications for symptom control

Antihistamines, which are often used to treat allergies, are helpful and are part of initial pharmacologic treatment in systemic mastocytosis^[5][14]. H1 antagonists are used to treat itching and flushing. Nonsedating antihistamines may be recommended for daytime use, and sedating ones for nighttime use^[14].

H2 receptor blockers have been used to treat stomach problems and peptic ulcer disease associated with systemic mastocytosis^[14]. Proton pump inhibitors are also useful for this^[14].

Cromolyn sodium has demonstrated multiple benefits in systemic mastocytosis. It has proved useful for relieving abdominal pain and diarrhea, itching, whealing and flushing, and impaired cognition^[14]. For some patients, an extra dose of H1 blockers and H2 blockers can help prevent a more serious attack^[16].

Aspirin can be used in patients with flushing that is unresponsive to antihistamines^[14].

Corticosteroids have been used to control malabsorption, ascites, abdominal pain refractory to cromolyn, bone pain, and diffuse cutaneous disease refractory to topical therapy, and to prevent anaphylaxis^[14]. Mild to moderate cases of cutaneous mastocytosis can be treated with steroid cream for a limited length of time^[10]. A short course of corticosteroid tablets may be recommended if you have bone pain caused by mastocytosis or a severe allergic reaction^[10].

Other treatments

More severe symptoms of cutaneous mastocytosis, such as severe itchy skin, may require a type of treatment called psoralen plus ultraviolet A (PUVA)^[10]. 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, which helps reduce lesions in the skin^[10]. You can only have a limited number of PUVA sessions as using the treatment too many times may increase your risk of developing skin cancer^[10].

If you have weakened bones (osteoporosis) resulting from abnormal mast cell activity in your bones, you will be given a medicine called bisphosphonates^[10]. 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^[10].

For patients with anaphylaxis that is recurrent or refractory to conventional therapies, omalizumab (anti-immunoglobulin E), a humanized monoclonal antibody that inhibits the binding of IgE to mast cells, reduced the frequency of anaphylaxis in some patients with systemic mastocytosis^[14].

Leukotriene antagonists, such as zafirlukast and montelukast, have also been used in the treatment of systemic mastocytosis^[14].

Originally designed to treat cancer, interferon alpha has proved effective in treating some cases of aggressive mastocytosis. It appears the medicine reduces the production of mast cells inside the bone marrow^[10].

Imatinib is an alternative medicine to interferon alpha^[10].

The preclinical and clinical development of KIT-D816V-targeting drugs, such as midostaurin or avapritinib, mark a milestone in improving management, the quality of life and survival in patients with systemic mastocytosis^[6]. These agents induce major responses or even remission in people with advanced systemic mastocytosis and lead to rapid improvement of mediator-related symptoms and quality of life in symptomatic patients^[6].

Emergency treatment

Epinephrine is used in acute anaphylaxis^[14]. Acute anaphylaxis can be treated with 0.3 mL of a 1:1000 dilution of epinephrine. In children, the dose is 0.01 mL/kg (up to 0.3 mL) administered every 10 to 15 minutes as needed^[14].

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^[2]. In all adults with mastocytosis and in pediatric patients with severe cutaneous mastocytosis, a persistently elevated serum tryptase level and anaphylaxis in medical history, equipping with epinephrine autoinjector for use in case of anaphylaxis is recommended^[12].

Many patients feel less anxious about their disease when they have EpiPens (or other epinephrine auto injector) and other rescue medications with them. You should carry them in something that is easily identifiable so that helpers can find them in an emergency^[16]. Mast cell disease experts generally recommend that patients carry two EpiPens at all times^[16].

Outlook and prognosis

Individuals with the milder forms of the condition generally have a normal or near normal life expectancy, while those with the more severe forms typically survive months or a few years after diagnosis^[7]. The prognosis for advanced systemic mastocytosis is daunting: it most often includes a shortened life expectancy and difficult-to-manage symptoms^[18].

The prognosis of cutaneous mastocytosis and non-advanced systemic mastocytosis is mostly favorable, whereas prognosis and survival in advanced systemic mastocytosis and mast cell sarcoma are poor^[6].

Most of the cases of mastocytosis are limited to the skin, and 80 percent of them appear during childhood. By adolescence, the majority of them improve or resolve completely^[8]. It is usually mild in children, and they often outgrow it^[5].

Living with mastocytosis

A healthy lifestyle is especially important when you have mastocytosis. Following the basic recommendations on a balanced, healthy diet and regular physical activity is incredibly important for a disease of this nature^[18]. Not only will this improve your overall health and quality of life, it may also make you eligible for more treatment options^[18].

Identifying and avoiding triggers

The best treatment for mastocytosis may be to stay away from the things that trigger your symptoms^[5]. It may help if you and your doctor list all the things that cause your symptoms. Did your symptoms start after you were exposed to heat or cold? Emotional stress? A medicine? An insect bite? Share what you learn with your doctor^[5].

Identifying and avoiding triggers may not be easy^[17]. You are in a good position to be a detective to discover what makes you feel worse and what makes you feel better, and you can do a lot to keep yourself safe^[16].

Taking medications

Unless instructed by your doctor, do not stop taking your medications just because you are feeling better. You may well be feeling better because of them^[16]. Consider using a pill organizer with boxes for each day of the week. It is very important that you can see whether you have taken your regular medications on schedule. If you take meds while out and about, develop a system of where you will put them^[16].

If your doctor has advised you to try a new medication to treat your mast cell disease, ask if you should start slowly. Always have a responsible person nearby when you try a new medication so that if you react you have someone to help you. If you have been given epi-pens, keep those to hand as well^[16].

Emergency preparedness

Carry emergency medications with you at all times^[16]. Find a carrier that works for you: a bright zipped case in your handbag, briefcase, or nappy bag; a bum bag or something similar. Keep EpiPens out of the sun. Consider an insulated bag if you know you will be out in the heat^[16].

A medical alert bracelet speaks for you in a medical emergency when you cannot speak^[16]. You will want to find one that is comfortable and long-wearing. Some patients find that a medical alert bracelet gives them more credibility in a circumstance where emergency personnel are not sure what to do^[16].

If you are with a larger group, make sure at least one person there knows about your condition and how to help if you experience symptoms^[17]. Make sure the people you are closest with know the signs and protocols (for example, how to administer an EpiPen if needed or get you immediately to the emergency room if necessary)^[17].

Support and communication

Communication is one of the most important elements when it comes to managing systemic mastocytosis. Being open and honest with those around you may help create a support network that can aid in your journey^[17].

Your innermost circle can be your strongest supporters. While asking for help can be difficult sometimes, it is important to know your family and friends care about your well-being. Sharing how your symptoms affect your life may help others understand you^[17].