Mastocytosis is a type of disorder that can occur in both children and adults. It is a rare disease that develops when too many mast cells (white blood cells) build up in the body. When these cells continue to grow, they may build up in the bone marrow, the skin, or in other organs. This may cause a number of symptoms; in rare cases, it may lead to organ failure. People with mastocytosis can also be at greater risk for severe symptoms like anaphylaxis. Anaphylaxis is an allergic reaction that has the potential to be life-threatening.
What Are Mast Cells?
Mast cells are a type of white blood cell (myeloid cell) that are part of the immune system. These cells help keep us healthy by fighting off infections. They also trigger an immune response to help heal any injuries or damage to the body’s tissues.
Mast cells play a key role in the body’s inflammatory response process. This response occurs when the mast cells are activated and substances, called mediators, are released. These mediators live within small containers, called granules, inside the mast cell. When mast cells are activated, the granules release mediators like histamine and tryptase. The release of these mediators may cause symptoms such as swelling and itching.
Types of Mastocytosis
Mastocytosis can appear in 2 forms: cutaneous mastocytosis and systemic mastocytosis.
Cutaneous mastocytosis (CM) occurs when mast cells build up in the skin. It is more common in young children and is usually not life-threatening. CM may be caused when there is a mutation in the KIT gene. Most cases develop at random and are not inherited or passed down from one generation to the next. People with CM may not develop symptoms at all or may only develop discoloration of the skin (pigmentation). Not all cases of CM need treatment. In fact, CM in children often resolves on its own.
There are 3 subtypes of CM:
- Maculopapular cutaneous mastocytosis (MPCM)
- Diffuse cutaneous mastocytosis (DCM)
- Cutaneous mastocytoma
Previously known as urticaria pigmentosa, MPCM is the most common subtype of cutaneous mastocytosis. MPCM may be present during birth or may develop slowly over the years. It is usually seen in infants or children. Most adults who develop MPCM are likely to also have systemic mastocytosis.
There are 2 subvariants of MPCM:
- The monomorphic variant is usually seen in adults and in some children. It is seen in adults when there is a mutation in the KIT gene. Children with the monomorphic variant have a higher chance of developing systemic mastocytosis as they get older.
- The polymorphic variant is mostly seen in children. When this variant is found in children, it is likely that the disease will resolve without treatment.
DCM appears in children during infancy. It affects most or all areas of the skin. The skin will appear thick, and blisters may occur intermittently or at random. Blistering can be severe and, in some cases, life-threatening.
Signs of cutaneous mastocytoma are usually present at birth. A mastocytoma is a single elevated lesion (cluster of mast cells). When stroked by a doctor this lesion may turn into hives. This is known as Darier’s sign. Cutaneous mastocytoma may resolve on its own over time.
Systemic mastocytosis (SM) occurs when too many mast cells grow and build up in the body. These cells may begin to grow in only one area of the body, like in the bone marrow, or in multiple tissues or organs. This form of mastocytosis is more common in adults. Symptoms of SM are typically treated with drugs like antihistamines. Antihistamines block the mediators found in the mast cells from being released.
The different types of SM (also known as variants) can be either non-advanced or advanced. Indolent and smoldering SM are non-advanced variants. Indolent means that the disease is growing slowly. These types of SM are usually linked to mast cell activation. Advanced variants of SM are linked to the overgrowth of mast cells. Advanced variants can lead to organ failure.
There are 2 types of non-advanced SM:
BMM is an indolent form of SM. It usually does not cause skin lesions. BMM has a higher chance of causing anaphylaxis.
SSM is an indolent form of SM. It has a higher chance of becoming an aggressive form of SM, but this is rare.
There are 3 types of advanced SM:
- Systemic mastocytosis with an associated hematologic neoplasm (SM-AHN)
- Aggressive SM
- Mast cell leukemia (MCL)
People with SM-AHN have both SM and a cancer. The cancer is typically MDS (myelodysplastic syndrome), MPN (myeloproliferative neoplasm), or AML (acute myeloid leukemia). SM-AHN patients require treatment for both the SM and their cancer.
Aggressive means that the disease is fast growing. Aggressive SM is rare but can be life-threatening. In some rare cases, aggressive SM may develop into mast cell leukemia. Mast cell leukemia is a cancer that forms in the blood and bone marrow.
MCL is the rarest form of SM and occurs in less than 1% of cases. Even though it is rare, MCL can lead to more severe symptoms.
Risk factors are things that can increase the chance of developing a disease. People can avoid some cancer risk factors, such as smoking. Other risk factors, like a person’s age or family history, cannot be changed. Having one or even many risk factors does not mean that a person will get the disease.
Risk factors for mastocytosis include:
Cutaneous mastocytosis occurs more often in infants and children. A person’s risk of developing systemic mastocytosis increases as they get older.
Certain genetic mutations can cause mastocytosis. Genes make up a person’s DNA and are inherited from their birth parents. A change in the DNA is called a mutation. For mastocytosis, mutations in the KIT gene can increase a person’s chance of developing the disease. The KIT gene helps control cell growth. Mutations in this gene can lead to an overgrowth and build-up of mast cells in the body. These unhealthy mast cells tend to live longer than healthy mast cells in the body.
Signs & Symptoms
The signs and symptoms people experience with mastocytosis may differ depending on the subtype they have. These symptoms may be more likely to occur after the person experiences certain situations.
These situations can occur when certain substances cause the mast cells to release their mediators. Trying to control exposure to certain substances can be challenging. But it is important to recognize them to avoid severe reactions or anaphylaxis. If you are diagnosed with mastocytosis, make sure your family, friends, and healthcare team are aware so they can act quickly if anaphylaxis occurs.
Some examples of substances that may cause symptoms include:
- Venom released from insect or animal bites (hornet, yellowjacket, wasp, honeybee, and fire ant)
- Some drugs or medications (opioids, antibiotics, pain relievers, or NSAIDs)
- Some food items
- Environmental factors (pollen or animal dander)
- Sudden changes in temperature
- Exposure to the sun and sunlight
- Irritation of the skin
- Stress (emotional, physical, or environmental)
General signs and symptoms of mastocytosis include:
- Swelling of the skin
- Red and/or itchy raised rash on the skin
- Abdominal pain
- Rapid heart rate
- Fainting or lightheadedness
- Low blood pressure (hypotension)
- Bone and/or muscle pain
- Weak and/or soft bones (Osteoporosis)
- Reddening of the face (flushed skin)
- Shortness of breath, wheezing, or trouble breathing
- Psychological changes, such as irritability or difficulty concentrating or brain fog
Other symptoms related to cutaneous mastocytosis include:
- Tan or reddish-brown spots on the skin
- Nausea and vomiting
- Thickening of the skin
- A single raised lesion or reddish-brown or tan lesions on the skin
Other symptoms related to systemic mastocytosis include:
- Skin lesions
- Nausea and vomiting
- Acid reflux or heartburn
- Nasal congestion
- Irregular heartbeat (heart palpitations)
- Anemia (low red blood cells) which can lead to fatigue
- Enlarged liver and/or spleen (with or without loss of function)
To diagnose mastocytosis and the subtype, a doctor may perform a number of tests. These tests may include a physical exam, blood and/or urine tests, and biopsies. A blood or urine test may be given to test for the serum tryptase level. Tryptase is a substance released from mast cells. The doctor may also use this test to see how well the body’s organs are working. During a physical exam, they will look for any skin lesions or spots that could be a sign of the disease.
A doctor may perform a tissue biopsy or a colonoscopy to see if mast cells have built up in the GI tract. A colonoscopy is an outpatient procedure done in a hospital. During the colonoscopy, the doctor will insert a camera on a long, flexible tube through the anus and rectum to look at the colon. They may also check to see if the liver, spleen, or any lymph nodes are enlarged. This will require a CT scan or ultrasound.
To test for CM, a doctor will perform a skin biopsy on any lesion that is present on the skin. During this skin biopsy, a small sample of the tissue is removed and looked at under a microscope. The tissue is examined to see if clusters of mast cells are present.
To diagnose CM, the doctor will also test for Darier’s sign. When testing for Darier’s sign, they will use a tool to gently rub an existing lesion on the skin. After a few minutes the doctor will look to see if a wheal and flare reaction occurred. This reaction can include swelling, itching in the nearby area, and redness of the skin. Testing for Darier’s sign should only be performed by a doctor because of risk of anaphylaxis.
If there are no lesions on the skin, the doctor may want to test for SM. SM is diagnosed by a bone marrow biopsy. During this process, tissue from the bone marrow is removed and looked at under a microscope. This will show if large clusters of mast cells are present in the bone marrow. If there are signs of SM, the doctor may suggest a bone density scan to check for any weakening or damage (osteoporosis).
To develop the best treatment plan for your diagnosis, you may have a team of healthcare professionals from different backgrounds working together. You may see a dermatologist, a gastroenterologist, a hematologist, and an allergist or an immunologist. Mastocytosis is often misdiagnosed because it is rare. It is important to find a doctor who has experience diagnosing and treating mastocytosis. You may need to travel to find a specialist or center that focuses on treating this disorder.
Your doctors will recommend treatment options based on the type of mastocytosis you have, your overall health, symptoms, and your treatment preferences. Talk with your doctors about developing a treatment plan that includes managing your diagnosis in the short term and the long term. It is okay to seek a second opinion to discuss your diagnosis or treatment options. Do not worry about hurt feelings.
When you talk to your doctor about your treatment options, ask about the goals of each option and how each option might affect the goals you have for your life. Think about what you want to be able to do. Do you want to continue working? How will your treatment affect your family and social relationships? Will you be able to do the things you enjoy? Think about any concerns you might have about suggested treatment options.
Ask your doctors questions if you do not understand something about your treatment or the medical terms they are using. Write down questions before your visits and take notes when your doctor talks so you can remember what was said. You may want to bring a friend or family member with you so they can take notes.
Questions to ask your doctor:
- What type of mastocytosis do I have? What is the subtype?
- Has my mastocytosis progressed?
- How will my diagnosis affect my quality of life?
- What type of treatment do you recommend?
- How often and where will this treatment take place? Will I have to stay overnight in the hospital for any part of this treatment?
- What are the goals of my treatment plan?
- Are there any potential side effects of treatment?
- Will I need someone to take care of me at any point during this treatment?
- Do you recommend a clinical trial?
- What will my treatment cost and how much will my insurance cover? Are financial resources available?
There is no cure for mastocytosis. In some cases, it may resolve on its own and treatment is not needed. Most treatment options for mastocytosis will focus on managing or treating the symptoms. This may include taking medications to help treat any allergy or skin-related conditions.
Other treatment options may include:
Chemotherapy (also called chemo) uses drugs to destroy or damage fast-growing cells like cancer cells. It is used to shrink tumors, slow cancer’s growth, relieve symptoms, or help people live longer. Chemotherapy drugs are given in different ways (intravenously, orally by a pill, or by injection). Chemotherapy should be considered if the mastocytosis has developed into an advanced variant of SM.
The doctor may recommend various treatments that are applied directly to the skin. Treatment may include applying topical steroid creams to the skin, which can be useful for children with diffuse cutaneous mastocytosis (DCM). Treatments that use light therapy may also be recommended.
Photochemotherapy (PUVA) is used to help treat any skin lesions that are present. During PUVA therapy a light is used to activate a chemotherapy drug taken orally. This treatment option can also help reduce skin itching.
UVB phototherapy is another type of treatment that uses light. UVB uses controlled amounts of ultraviolet light to target overgrown mast cells. This treatment helps stop the cells from growing out of control and spreading.
Targeted therapy uses drugs to target specific changes in cancer cells that help them grow, divide, and spread. Targeted therapy drugs are designed to be more precise. They fight cancer cells while causing less harm to other cells in the body.
Targeted therapy treatments can help stop the growth of mast cells without damaging healthy immune cells. Newer targeted therapy treatments, such as tyrosine kinase inhibitors, will target the KIT gene. This will help to reduce the number of mast cells growing in the body.
A stem cell transplant is an infusion of blood-forming cells (stem cells). It is not a surgery. The procedure has 2 parts. First, you will receive high doses of chemotherapy. This destroys blood cells. Next, stem cells are introduced into the bloodstream to replace the unhealthy blood cells.
A doctor may consider a stem cell transplant to treat mastocytosis if other treatment options are not effective.
Clinical trials are research studies to test new treatments or learn how to use existing treatments better. Be sure to ask your doctor about any clinical trials for mastocytosis that may be relevant to you.
Learn About Clinical Trials
Cancer clinical trials provide patients with access to new therapies: the next generation of treatment.
Cope With Side Effects
It helps to learn more about the side effects of treatment before you begin so you will know what to expect. When you know more, you can work with your healthcare team to manage your quality of life during and after treatment.
Everyone reacts differently to treatment and experiences side effects differently. There are many medications available to address these side effects. Talk to your healthcare team about any side affects you experience so they can help you feel better. Your doctor may discuss options such as lowering the dose of your treatment if side effects persist and are not easy to manage. You may also want to consult a palliative care doctor to help manage symptoms from cancer treatment and improve quality of life.
Learn More About Managing Side Effects
Mastocytosis can be challenging to live with. It can be both physically and mentally overwhelming. Talk to your healthcare team about how you are feeling. Ask about counseling or mental health services if you are feeling depressed, overwhelmed, or anxious. Having someone to talk to may help you find or maintain the energy you need to get through treatment. It may also help you keep up the energy to take the best possible care of yourself. It is a good idea to seek support early on so that you have somewhere to turn when you need it.
Think about people in your life who can help (your spouse or partner, friends, faith community, support group, or coworkers). Make a list of things you need (such as childcare, meal prep, laundry) and who can help with each task.
Keep Loved Ones Informed & Involved
Create your own private website to receive social, emotional, and practical support from friends and family during your treatment and beyond.
Manage the Cost of Care
Treatment and the potential need to travel for care can be costly, even with a healthcare plan. Keeping up with these costs might be overwhelming. Many people say that financial worries about treatment costs are a big source of stress, and they don’t know where to turn.