Systemic mastocytosis (SM) is a rare blood disorder in which the body makes too many mast cells, a type of immune system cell. These cells can build up in organs, most commonly the bone marrow, but also the skin, liver, spleen, gastrointestinal tract and lymph nodes.

When they release chemicals called mast cell mediators (such as histamine, tryptase and cytokines), they can cause a wide range of symptoms. These symptoms can come and go, and their pattern can vary from person to person. As a result, diagnosing SM is challenging.

Types of systemic mastocytosis

Doctors classify systemic mastocytosis into six subtypes, grouped as non-advanced and advanced.

Non-advanced forms

These are more common and usually progress slowly.

• Indolent SM (ISM): The most common type of SM. Patients may have no symptoms or mild or moderate issues, such as skin rash, flushing, diarrhea, brain fog, or severe allergic reactions.
• Bone marrow mastocytosis (BMM): Mast cells are mostly in the bone marrow. It often has fewer symptoms than ISM.
• Smoldering SM (SSM): Higher numbers of mast cells than ISM. Organs may be affected over time, but the damage is not yet severe.

Advanced forms

These types grow more aggressively and can affect multiple organs, requiring closer monitoring and treatment.

• Aggressive SM (ASM): There is organ damage, such as to the liver, spleen or bones.
• Mast cell leukemia (MCL): A rare and aggressive disease. Abnormal mast cells are found in the blood and bone marrow and can progress quickly.
• SM with an associated blood disorder (SM-AHN): SM occurs alongside another blood or bone marrow condition, like certain leukemias, myeloproliferative syndromes or lymphomas.

In addition to subtypes, doctors use B and C findings to guide care. These findings help describe how much disease is present and whether organs are affected.

• B findings show that mast cells are elevated or that organs are enlarged without causing damage, such as a high number of mast cells in the bone marrow or a spleen that is enlarged but still functioning normally. These findings are most often associated with non-advanced forms of SM. Treatment may be needed, but it is usually focused on symptom control rather than treating organ damage.
• C findings show that mast cells are starting to affect how organs work and require more intensive, disease-directed treatment. These findings define advanced forms of SM and include problems such as low blood counts, liver dysfunction, bone disease, or digestive difficulties.

Who gets systemic mastocytosis

• Age: Usually diagnosed in adulthood, though some forms can appear in children.
• Sex: Both men and women can be affected.
• Genetics: More than 90% of people with SM have a mutation in the KIT gene, which helps control how cells grow and survive.

Living with systemic mastocytosis

Most people with non-advanced forms can live full, active lives if they carefully manage symptoms.

• Avoid triggers that can activate mast cells (e.g., extreme temperatures, insect stings, certain medications, physical activity, stress). Reactions may be allergic or happen even without an allergy.
• Carry emergency medications such as epinephrine if at risk for severe allergic reactions.
• Follow a regular treatment plan and attend all scheduled medical appointments.
• Participate in support groups, counseling and patient education to help cope with symptoms and emotional stress.
• Maintain a healthy lifestyle with balanced nutrition, regular exercise and enough sleep.
• Keep a detailed record of symptoms, triggers and medications to guide discussions with your healthcare provider.

Symptoms may fluctuate or appear occasionally and do not always match how much the disease is affecting your body. Some people may feel relatively well even if organs are affected, while others experience severe symptoms early on.

Survival rates

People with milder forms of SM generally have a normal or near-normal life expectancy.

If the disease is more advanced, it can affect life expectancy, but newer treatments may help improve outcomes.

Systemic Mastocytosis Symptoms

Symptoms of systemic mastocytosis can vary widely depending on the number of mast cells that have accumulated in the body and the organs that are affected. Early recognition and diagnosis are important as they allow patients to manage the disease more effectively and reduce the risk of complications. Symptoms may include:

• Flushing or redness of the skin
• Itching or hives
• Stomach problems such as nausea, diarrhea, or abdominal pain
• Fatigue or unexplained tiredness
• Headaches or dizziness
• Bone pain, fractures or osteoporosis
• Low blood pressure or fainting
• Brain fog
• Severe allergic reactions

Symptoms may come and go and may not always reflect how severe the disease is.

What does systemic mastocytosis feel like?

People with SM may have no symptoms or experience episodes of sudden warmth, itching, flushing, cramping, bloating, nausea or pain. Severe cases can cause ongoing symptoms that limit daily activities, especially if organs such as the liver, spleen, bones or digestive system are affected.

Other conditions with similar symptoms

SM can look like other conditions involving mast cells, including mast cell activation syndrome (MCAS) and hereditary alpha-tryptasemia (HAT). These conditions can overlap with SM, making diagnosis more complex.

• Mast Cell Activation Syndrome (MCAS): Mast cells release chemicals too easily, causing symptoms such as flushing, hives, stomach problems or low blood pressure. Does not involve large numbers of mast cells building up in organs.
• Hereditary Alpha-Tryptasemia (HAT): Caused by extra copies of the TPSAB1 gene. Up to 15–20% of SM patients also have HAT. People with HAT may have mild or no symptoms, but some experience flushing, itching, gastrointestinal issues, fatigue or allergic-type reactions, similar to MCAS.

Just because your tryptase level is high doesn’t automatically mean you have SM, and having a normal level doesn’t rule SM out. These conditions can occur at the same time, making diagnosis more complicated.

When to see a doctor

See your doctor if you have:

• Recurrent flushing or hives
• Unexplained fatigue or weight loss
• Low blood pressure, dizziness, or fainting
• Persistent stomach problems
• Unexplained bone pain

Early evaluation helps guide care and improve outcomes.

Systemic Mastocytosis Diagnosis

Diagnosing SM can be challenging because its symptoms often resemble other, more common conditions, including allergies, gastrointestinal disorders, autonomic dysfunction, connective tissue disorders, and cardiovascular or renal disease. For many people, it can take several years from when symptoms first appear to receive a clear diagnosis.

The diagnostic process may include:

• Blood tests: Measure tryptase, a protein released by mast cells. Elevated levels do not always mean SM; normal levels don’t rule it out.
• Bone marrow or tissue biopsy: Usually required to definitively diagnose or exclude SM. The sample is examined by specialists using special stains, molecular tests and other advanced lab studies to confirm the diagnosis.
• Genetic testing for KIT mutations: Helps guide diagnosis, but sometimes it may not detect the mutation even if it’s there. Results can depend on where the sample comes from and how many abnormal cells are present.

Systemic Mastocytosis Treatment

Treatment depends on the type of SM, severity and organs affected. In most cases, the goal is symptom control and quality-of-life improvement, rather than removing all mast cells.

First-line symptomatic therapy includes:

• H1 and H2 antihistamines
• Mast cell stabilizers
• Leukotriene modifiers and neuromodulators
• Short courses of corticosteroids for flares (used sparingly due to bone health risks)
• Epinephrine auto-injectors for all patients

Targeted therapy:

Targeted therapy may be considered if symptoms don’t get better with standard treatment.

Targeted therapy drugs are designed to stop or slow the growth or spread of cancer. This happens on a cellular level. Cancer cells need specific molecules, often in the form of proteins to survive, multiply and spread. These molecules are usually made by the genes that cause cancer as well as the cells themselves. Targeted therapies are designed to interfere with or target these molecules or the cancer-causing genes that create them.

Clinical trials at UT MD Anderson

For patients whose symptoms aren’t fully controlled by current treatments, clinical trials may offer additional options. UT MD Anderson runs studies for both non-advanced and advanced SM, and many are open to patients who have previously received certain therapies.

Thanks to growing awareness, better ways to diagnose SM, and new treatment options, patients now have more ways to manage their symptoms and care for their health. Working closely with your healthcare team can help you manage your condition and improve outcomes.