Understanding Systemic Mastocytosis

What is systemic mastocytosis?

Systemic mastocytosis, or SM, is a rare disease that results from too many abnormal mast cells spreading throughout the body.1

Mast cells are a type of white blood cell that’s a key part of the immune system. They’re designed to help keep the body safe from diseases and infections.2,3

If mast cells become abnormal and grow in an uncontrolled way, they often increase or spread throughout the body, releasing substances that may trigger symptoms of allergic reactions, inflammation, and other immune responses.1,4

What causes SM?

In about 95% of cases, SM begins because of a mutation in the KIT gene known as KIT D816V.5-7

This mutation leads to the production of too many abnormal mast cells.8

Doctors can help you identify the type of SM by ordering certain tests.

Symptoms of systemic mastocytosis2,4

People with SM may experience different symptoms that may be unexplained, unpredictable, recurring, and severe.4

For example:

Skin rashes

Hives, rashes that look like "spots," or flushing that lasts more than a few minutes.

Gut issues

Diarrhea, nausea, heartburn, abdominal cramps, or sensitivities to food.

Respiratory

Shortness of breath, wheezing.

Whole body

Severe or whole-body allergic reactions, weakness, bone pain, or bone health issues.

Neuropsychiatric

Brain fog, unexplained fatigue, anxiety, and depression.

Cardiovascular

Low blood pressure, rapid heart rate.

This is not an exhaustive list of symptom categories.

Types of SM

To get the most optimal care, it’s important to talk to your doctor about the type of SM you may have.

Non-advanced SM4,9-13

  • Indolent systemic mastocytosis (ISM) is believed to be the most common form of non-advanced SM. Symptoms can be widespread and unpredictable, varying from person to person. Many areas of the body can be affected, including the whole body with fatigue; the skin with spots, flushing, and rashes; and in the gut with abdominal pain, nausea, and diarrhea. ISM may also lead to bone loss. In about 5% of cases, ISM can progress to smoldering SM (SSM) or advanced SM (AdvSM).
  • Bone marrow mastocytosis (BMM) is a type of non-advanced SM where the person does not experience skin symptoms.
  • Smoldering SM (SSM) involves more mast cell production, more significant whole-body symptoms, and may affect organs like the liver. In about 9% of cases, SSM can progress to AdvSM.

Advanced SM9,12-13

  • SM with associated hematologic neoplasm (SM-AHN) where an additional blood disorder may be present.
  • Aggressive systemic mastocytosis (ASM), which is associated with progressive organ damage.
  • Mast cell leukemia (MCL), which is an extremely rare and aggressive form of SM that affects the bone marrow and blood.

Next steps for diagnosed patients

See what to expect after getting an SM diagnosis.

Explore the options

Get help talking about your diagnosis

Support to help you feel understood and supported is available.

Decode your experience

FAQs

Yes. Many people with SM report bone or joint pain, which can result from the buildup of abnormal mast cells in the bone marrow.9 Let your doctor know if this is a symptom you are experiencing. There may be ways to help manage it.

The treatment plan depends on the type of SM you have and your overall health.1 Take a look at possible treatment options and ask your doctor about which ones may be right for you.

  1. Pardanani A, et al. Am J Hematol. 2023;98(7):1097-1116.
  2. American Academy of Allergy, Asthma & Immunology. Accessed January 14, 2026. https://www.aaaai.org/conditions-treatments/related-conditions/systemic-mastocytosis
  3. Metcalfe DD. Blood. 2008;112(4):946-956.
  4. Jennings SV, et al. Immunol Allergy Clin North Am. 2018;38(3):505-525.
  5. Kristensen T, et al. Am J Hematol. 2014;89(5):493-498.
  6. Ungerstedt J, et al. Cancers. 2022;14(16):3942.
  7. Garcia-Montero AC, et al. Blood. 2006;108(7):2366-2372.
  8. Kristensen T, et al. J Mol Diagn. 2011;13(2):180-188.
  9. Jankovski L, et al. Int J Mol Sci. 2025;26(12):5649.
  10. Trizuljak J, et al. Allergy. 2020;75(8):1927-1938.
  11. Zanotti R, et al. J Clin Med. 2021;10(7):1420.
  12. WHO Classification of Tumours Editorial Board. Haematolymphoid tumours [Internet]. Lyon (France): International Agency for Research on Cancer; 2024 [cited April 24, 2024]. (WHO Classification of Tumours Series, 5th ed.; vol. 11). Available from: https://tumourclassification.​iarc.who.int/chapters/63
  13. Arber DA, et al. Blood. 2022;140(11):1200-1228.