What is Systemic Mastocytosis? A Brief Overview
Systemic Mastocytosis (SM) is a rare disorder where the body produces too many mast cells, a type of immune cell that normally helps protect against infections and allergens. When these mast cells accumulate abnormally in organs like the skin, gastrointestinal (GI) tract, bone marrow, and liver, they can release large amounts of chemicals such as histamine, triggering a range of allergy-like symptoms.
For some individuals, this may lead to severe reactions like anaphylaxis—a potentially life-threatening immune response that causes swelling, hives, low blood pressure, and trouble breathing.
While SM is not an allergy, it often behaves like one.
Common symptoms of Systemic Mastocytosis may include
- Flushing or warm skin
- Itching or hives
- Abdominal pain, nausea, or diarrhea
- Fatigue and bone pain
- Episodes of anaphylaxis (in severe cases)
Learn more about common symptoms of systemic mastocytosis
What Causes Systemic Mastocytosis?
Most cases are caused by a mutation in the KIT gene, which controls mast cell growth. This mutation leads to the overproduction and accumulation of abnormal mast cells throughout the body.
How is it diagnosed?
Your provider may suspect this diagnosis when you first discuss symptoms, and they have examined you. Your provider will next order blood tests that are intended to look for signs of the disease but also potential early complications. When trying to initially diagnose Systemic Mastocytosis, labs should ONLY be obtained when you are at baseline health, not after a flare of symptoms, and can include:
- Tryptase level: Tryptase is an enzyme released by mast cells. High levels of tryptase (greater than 20 ng/mL) are a major sign that systemic mastocytosis may be the cause of the symptoms.
- Complete blood count (CBC): to look for abnormalities in blood counts, like red and white blood cells.
- Liver tests: to look for involvement of Mastocytosis in your liver where abnormal mast cells can accumulate. This may also be called a liver function test.
- Genetic testing of the KIT Gene: KIT is a receptor found on the surface of mast cells and is responsible for the production of mast cells. Systemic Mastocytosis most commonly occurs when there is a mutation in KIT; a specific blood test is able to test for this mutation which can be a key part of the
diagnosis.
If any of these tests are abnormal, then additional testing will be needed to definitively diagnose Systemic Mastocytosis. Based on guidance from the World Health Organization (WHO), tissue sampling, also known as biopsies, are required to confirm the diagnosis.
Biopsies can be obtained from the following areas for testing:
- Bone marrow (preferred option)
- Skin
- Gastrointestinal tract – This can be done via upper endoscopy
If the biopsy shows there is an abnormal number of mast cells – specifically, at least 15 cells that are clustered together – then this is sufficient to make the diagnosis. However, mast cell clusters may not be seen under the microscope in some patients, possibly because the tissue sample only gives us a small picture as to what is going on. In these situations, three of the following findings may still permit a diagnosis of Systemic Mastocytosis:
- Biopsy (from any tissue source listed above) that shows that at least 25% of the mast cells are considered abnormal in appearance.
- DNA testing that finds a specific mutation in the KIT gene (which is important for the production of mast cells).
- The mast cells in the biopsy express a specific marker on the cell surface called CD25, which tells us that there is an abnormal population of mast cells in the tissue that was biopsied.
- The blood test for “tryptase” is elevated above the normal level (greater than 20 ng/mL)
Types of Systemic Mastocytosis
SM can range from mild to aggressive. The main types include:
- Indolent SM (ISM): Most common; mild symptoms, no organ damage
- Smoldering SM (SSM): Higher mast cell burden but no organ failure
- SM with Associated Hematologic Neoplasm (SM-AHN): Also involves a blood cancer
- Aggressive SM (ASM): Organ damage occurs
- Mast Cell Leukemia (MCL): Extremely rare and severe
Learn about the types and their differences
What are some treatment options?
Treatment depends on the subtype and severity. Most people with ISM manage symptoms with:
- Antihistamines
- Mast cell stabilizers
- Avoiding triggers
- Emergency epinephrine (for anaphylaxis)
In 2023, the FDA approved Avapritinib (Ayvakit™) for adults with ISM, offering new hope for many patients.
Working with a Healthcare Provider
A partnership between a patient and their healthcare provider is essential when managing all chronic illnesses. Because the time spent with your healthcare provider is both limited and valuable, you can maximize it by following some simple guidelines before and after the visit.
- Have a list of other known chronic medical conditions: Because symptoms of Systemic Mastocytosis can occur all over the body it is important to discuss your known medical history at your visit.
- Have a list of Medications: medications you are currently taking (or have taken in the past) including prescriptions, over the counter, supplements and herbal preparations. These should include medications for all health conditions you have.
- Allergies: Before going to your appointment, be sure to create a list of all allergies to medications or other allergies and the type of reaction. This is especially important if you have experienced anaphylactic reactions or needed a hospital visit due to an allergic reaction.
- Consider bringing support: It is often helpful to ask a friend or relative to come to the visit with you for added support. They can assist in taking notes so you can fully attend the appointment.
Adapted from IFFGD Publication #901- Diagnosing Systemic Mastocytosis
