Many newly diagnosed patients ask if systemic mastocytosis (SM) is an autoimmune disease.
In short: It isn’t. The underlying processes that drive SM and autoimmune disease are different.
The confusion may arise because both conditions involve immune cells and can cause similar symptoms. But while mastocytosisMastocytosis Rare disease caused by the buildup of mast cells. Cutaneous mastocytosis primarily affects the skin and is more common in children, while systemic mastocytosis affects internal organs and is more common in adults. and other mast cellMast cell A type of white blood cell produced in the bone marrow. They help defend against infections and play a key role in allergic reactions. In SM, mast cells become overactive and build up throughout the body. diseases are immune-related disorders, they’re not autoimmune disorders.
What is an autoimmune disease?
Autoimmune diseases are a group of disorders in which the immune system mistakenly attacks the body’s own cells or tissues, causing inflammation and damage.
There are over 100 different autoimmune diseases. Some examples you may be familiar with are type 1 diabetes, ulcerative colitis, Crohn’s disease and multiple sclerosis.
What type of disease is systemic mastocytosis?
SM is a hematologic neoplasm, sometimes called a blood cancer, in which abnormal mast cells build up in the bone marrow and sometimes other organs. Because these cells all arise from a single abnormal cell, this growth is called clonal.
The abnormal mast cells release inflammatory chemicals, leading to inflammation and tissue damage. In some forms of the disease, damage can also come from mast cells accumulating in organs.
SM’s behavior varies widely. Nonadvanced forms are often stable or slow to progress, while advanced forms may damage organs and require more intensive treatment.
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What do mast cells do?
Mast cells are tissue-resident immune cells found throughout the body, particularly in areas that come into contact with the external environment, such as the skin, lungs and lining of the digestive tract. They help protect the body by detecting potential threats and triggering an immune response.
When activated, mast cells release chemical mediators such as histamineHistamine A chemical released by mast cells when they are activated. Histamine causes many of the allergy-type symptoms in mastocytosis, including flushing, itching and hives., tryptaseTryptase A protein enzyme that is primarily produced by mast cells and stored in small pockets within the cells, known as granules. High levels of tryptase are a key indicator of SM., prostaglandins and leukotrienes. These substances help coordinate inflammation and other immune responses.
However, excessive mediator release can cause widespread symptoms, including itching, flushing, swelling, abdominal symptoms, breathing difficulties and changes in blood pressure. In advanced forms of SM, the buildup of mast cells in organs can also damage tissues and interfere with organ function.
Read more about mast cell mediators
What causes mast cells to grow abnormally in SM?
In about 90% to 95% of people with SM, abnormal mast cell growth is driven by a mutation called KIT D816V.
The KIT gene provides instructions for making the KIT receptor, a protein found on the surface of mast cells. Normally, a substance called stem cell factor binds to the receptor and activates signals that help control mast cell growth and survival.
The D816V mutation keeps the KIT receptor active without this usual signal, causing mast cells to survive, multiply and accumulate abnormally. It is a somatic mutation, meaning it develops during a person’s lifetime and is usually not inherited.
Why can SM seem like an autoimmune disease?
Since SM and autoimmune diseases can both cause inflammation and affect multiple parts of the body, they may produce similar symptoms.
Symptoms such as itching, swelling, abdominal complaints, dizziness and fatigue can occur in SM as well as in allergies, autoimmune diseases and other immune-related conditions.
This overlap can make the underlying cause difficult to identify based on symptoms alone.
Does the difference affect treatment?
Yes. SM treatment depends on the subtype, symptoms and whether the disease is affecting organ function.
In nonadvanced SMNonadvanced SM In these subtypes of SM, mast cells accumulate in the body but do not usually cause severe organ damage. Nonadvanced SM includes the subtypes indolent SM and smoldering SM., treatment often focuses on controlling mast cell-related symptoms and preventing serious reactions. This may include antihistamines, medications that block other mast cell mediators and epinephrine for anaphylaxisAnaphylaxis A severe allergic reaction that can turn fatal without treatment. Patients with SM are at a higher risk of developing anaphylaxis.. Some people with persistent symptoms may also receive treatment that targets KIT.
Advanced SMAdvanced SM In these subtypes of SM, mast cells begin to damage organs. Advanced SM includes the subtypes aggressive SM, mast cell leukemia and SM with an associated hematological neoplasm. may require treatment aimed at reducing the number of abnormal mast cells, including therapies that target the KIT pathway, because the disease can damage organs and interfere with their function.
Autoimmune disease treatment, by contrast, is directed at suppressing or modifying the misdirected immune response. The specific approach varies according to the disease.
