What is Systemic Mastocytosis?

Systemic mastocytosis (SM) is a rare disease in which immune cells known as mast cells abnormally build up in the bone marrow and other parts of the body. In healthy people, mast cells produce histamine and other so-called “mediators” that help activate the immune system and direct disease-fighting blood cells to where they are needed. In SM, however, the abnormal build-up of mast cells leads to high levels of these mediators, and can cause symptoms that resemble allergies including hives, flushing, shortness of breath and anaphylactic shock. In some patients, mast cells also build up in the organs, impairing organ function and triggering symptoms including abdominal bloating, nausea, pain, fever and fatigue.

SM is typically diagnosed in adulthood. In almost all patients with SM, a genetic mutation known as KIT D816V is believed to be the root cause of the disease. The genetic mutation is not hereditary, and it is highly unusual for SM to run in families.

The signs, symptoms and severity of SM can vary widely from person to person. Depending on the nature of your disease, you may be diagnosed with a specific sub-type, or form, of the disease. These sub-types of the disease can be broadly grouped into two categories: indolent and advanced.

Indolent systemic mastocytosis (ISM)

Indolent systemic mastocytosis (ISM) is the most common type of systemic mastocytosis. People with ISM experience varying degrees of symptoms, including skin lesions, nausea, pain, fever and anaphylactic shock. But organ function is not impaired and life expectancy is not affected. Smoldering systemic mastocytosis (SSM) is a type of ISM that is often associated with an enlarged liver or spleen and is more likely to progress to advanced disease.

Advanced systemic mastocytosis

Advanced systemic mastocytosis includes:

  • Aggressive systemic mastocytosis (ASM)
  • SM with associated clonal hematologic non-mast cell disease (SM-AHNMD)
  • Mast cell leukemia (MCL)

These forms of the disease are associated with high levels of mast cell build-up in the organs, including the bone marrow, spleen, liver and gastrointestinal tract, that results in the impairment or loss of organ function and may shorten life expectancy[NA1] . People with advanced SM can also experience symptoms triggered by histamine and other mediators produced by mast cells. In SM-AHNMD, patients have a distinct disorder of the blood or bone marrow in addition to SM. MCL is the most severe form of SM and is a blood cancer driven by the aggressive infiltration of mast cells into the bone marrow.