Mastocytosis: What is It and How Is It Treated?

Key Takeaways:

  • Mastocytosis can affect many organs, including the skin, bone marrow, liver, and spleen, when too many malfunctioning immune cells accumulate in the tissues.
  • A new, targeted drug has been approved for three forms of advanced systemic mastocytosis.

Mastocytosis is a rare type of mast cell disorder characterized by the abnormal accumulation of mast cells in various organ systems such as the skin, liver, spleen, intestine, or bone marrow. It is one of two major types of mast cell disorders; the other major, more common type is mast cell activation syndrome.

To keep us healthy, mast cells protect our body from foreign threats, such as infections, and help repair its tissues once the threat is gone. As part of their role in the immune system, they create histamine — neurotransmitters that react to those threats and allergens, such as bee stings. Histamine is also released in response to allergens, causing reaction symptoms such as inflammation and even anaphylaxis, a severe, potentially life-threatening kind of reaction.

What triggers mastocytosis?

Mastocytosis is caused by a genetic mutation in which the body accumulates too many mast cells — white blood cells that are part of the immune system and help fight infections.

Systemic mastocytosis, which is also known as systemic mast cell disease, is mostly present in adults. It occurs when mast cells have infiltrated the body’s organs, such as the gastrointestinal tract, bone marrow, liver, spleen, and lymph nodes.

Systemic mastocytosis is diagnosed through a bone marrow aspiration and biopsy and may involve care by a hematologist/oncologist.

Systemic mastocytosis has three forms:

  • Indolent systemic mastocytosis (the most common) and smoldering mastocytosis, which progress slowly and often do not require therapy
  • Aggressive systemic mastocytosis, which is fast-growing

Some forms of systemic mastocytosis may also be associated with a second blood disorder, such as myeloproliferative or myelodysplastic disorders. The rarest form of systemic mastocytosis is mast cell leukemia, characterized by a high number of mast cells in the bone marrow. These aggressive forms of systemic mastocytosis or mast cell leukemia are generally treated with chemotherapy.

Daniel Deangelo, MD, PhD.
Daniel Deangelo, MD, PhD.

In June 2021, the U.S. Food and Drug Administration approved a precision drug, avapritinib (Ayvakit), to treat aggressive systemic mastocytosis, systemic mastocytosis with an associated hematological neoplasm, and mast cell leukemia. The drug targets a mutation in the KIT  gene that is the main molecular cause of the disease.

“Since avapritinib is able to selectively target the primary driver of the disease, it has the potential to fundamentally change the outlook for patients with advanced systemic mastocytosis,” says Daniel DeAngelo, MD, PhD, chief of the Division of Leukemia at Dana-Farber.

Signs and symptoms of mastocytosis

In many cases, urticaria pigmentosa — the appearance of dark pigments on the skin — is the first visible symptom of mastocytosis. Recurrent anaphylactic reactions is another common symptom. There are a myriad of other symptoms usually associated with the area of the body where the mast cells have infiltrated, including:

  • Recurrent anaphylactic reactions (to insect stings, general anesthetics, intravenous contrast media, and other drugs and foods)
  • Pruritus and flushing
  • Symptoms and signs of gastroesophageal reflux disease (GERD)
  • Abdominal pain is the most common gastrointestinal symptom, followed, by diarrhea, nausea, and vomiting
  • Anemia and coagulopathy

Learn more about treatment for blood disorders from the Hematologic Oncology Treatment Center at Dana-Farber/Brigham and Women’s Cancer Center.