What Is Systemic Mastocytosis?

Systemic mastocytosis (SM) is a rare blood disorder in which the body produces too many mast cells. Part of the immune response, mast cells are a type of white blood cell that releases histamine in response to bacteria and allergens.

In systemic mastocytosis, mast cells accumulate in the bone marrow, digestive system, lungs, and other organs, causing a variety of symptoms.

There are six types of systemic mastocytosis. Each type has different symptoms, but in general, the higher the abnormal mast cell accumulation, the greater the likelihood of serious health complications.

Indolent Systemic Mastocytosis (ISM)

Indolent (slower growing) systemic mastocytosis is the most common form of systemic mastocytosis in adults. People usually have milder symptoms that develop over many years. Skin and gastrointestinal issues are common, and usually other organs aren’t affected.

For people with ISM, the chances of progressing to more advanced disease are low — about 5 percent in a 10-year period, says Nikolai Podoltsev, MD, PhD, an associate professor of internal medicine specializing in hematology at Yale Medicine in New Haven, Connecticut.

Smoldering Systemic Mastocytosis (SSM)

SM With Associated Hematologic Neoplasm (SM-AHN)

Aggressive Systemic Mastocytosis (ASM)

In aggressive systemic mastocytosis, mast cells infiltrate organs such as the liver, spleen, bone marrow, lymph nodes, and small intestine.

Mast Cell Leukemia (MCL)

Mast Cell Sarcoma (MCS)

Indolent and smoldering SM are less aggressive forms of the disease, whereas SM-AHN, ASM, MCL, and MCS are all considered advanced systemic mastocytosis (advSM), says Dr. Podoltsev.

Systemic mastocytosis can cause a variety of symptoms, depending on the type of disease and the location of mast cell buildup.

• Skin issues: People may experience lesions, rashes, hives, or itchy bumps on the skin. These symptoms occur because mast cells release histamine, which causes the skin to react.
• Gastrointestinal problems: Abdominal pain, nausea, vomiting, diarrhea, or acid reflux are common due to excess mast cells in the digestive tract.
• Fatigue and weakness: Symptoms can include headache, lightheadedness, fatigue, and overall weakness.
• Respiratory issues: Wheezing, difficulty breathing, or coughing due to the effect of excess mast cells in the lungs or airways can occur.
• Bone pain or fractures: Excessive mast cell accumulation in the bones can lead to pain or even fractures, as the bone structure becomes weakened.
• Anxiety: People with all types of SM can feel anxious.

Often, people with indolent or smoldering SM (the less severe forms of the condition) may actually experience more of those types of “allergic reaction” symptoms, says Podoltsev.

When people get to the more advanced state, they can have severe symptoms and complications related to impacted organs, he says. For example, if there’s a buildup of mast cells in the liver that results in liver disease, it could cause symptoms such as nausea, vomiting, changes in stool and urine, weight loss, and mental changes.

Risk factors for developing mastocytosis haven’t been identified and there’s no known, obvious predisposition to it, says Jason Gotlib, MD, a professor of hematology at Stanford University School of Medicine and a hematologist at Stanford Health Care in California.

“It’s like many cancers,” Dr. Gotlib says. “Although there are some [genetic mutations known to raise the risk of certain] cancers — such as BRCA for breast cancer — that are inherited, most cancers are basically acquired genetic mutations that ultimately cause a cell to turn from normal to malignant.”

Mastocytosis is no different, meaning that a person develops a mutation, and in some cases, other mutations in addition to KIT, that cause the development of mastocytosis, says Gotlib.

“This is a very rare disease, and many doctors aren’t familiar enough with the condition to recognize it. Because of that, many people can go undiagnosed for years,” says Gotlib.

Typically, doctors will begin with a physical exam and a thorough review of symptoms. If mastocytosis is suspected, several diagnostic tests may be used:

• Blood tests: Elevated levels of certain markers, such as tryptase (a protein released by mast cells), can suggest mastocytosis.
• Bone marrow biopsy: A sample of bone marrow may be taken to check for abnormal mast cells.
• Genetic testing: Tests to detect mutations in the KIT gene can help confirm a diagnosis of systemic mastocytosis.
• Imaging studies: CT scans, MRIs, bone scans, or ultrasounds may be used to check for organ involvement.

  [9]

There is no single treatment for systemic mastocytosis. For people with indolent and smoldering SM, treatment focuses on managing symptoms and preventing and controlling inflammation, says Gotlib.

In people with advanced systemic mastocytosis, treatment plans are highly individualized and may involve a combination of approaches, including targeted cancer therapies and symptom management that help people live longer and may even change the course of the disease, he says.

Medications

Over-the-counter and prescription medications may be used to manage symptoms of systemic mastocytosis. These include:

• Epinephrine Because of the risk of anaphylaxis, it's recommended that people with mastocytosis carry two epinephrine self-injectors at all times.
• Antihistamines These are often prescribed to manage symptoms like itching, hives, and gastrointestinal discomfort caused by the release of histamine.
• Bisphosphonates These are used to treat osteoporosis.
• Corticosteroids These can help reduce inflammation and control symptoms, especially in more severe cases.
• Pain Medication Both over-the-counter and prescription pain medicines can help treat pain.
• Proton Pump Inhibitors These help with peptic ulcer disease that can occur with systemic mastocytosis.
• Cromolyn Sodium This can help relieve flushing, headaches, diarrhea, vomiting, nausea, hives, abdominal pain, and itching.

  [10]

• Monoclonal Antibodies For people with recurrent anaphylaxis or anaphylaxis that doesn’t respond to treatment, monoclonal antibodies, especially omalizumab, may be used.

  [11]

• Tyrosine Kinase Inhibitors These drugs, which include midostaurin (Rydapt), avapritinib (Ayvakit), and imatinib mesylate (Gleevec), have really transformed treatment of advanced systemic mastocytosis, says Gotlib. “They are very effective in reducing and killing off the number of mast cells and reducing elevated tryptase levels, and sometimes reversing organ damage.”
• Chemotherapy Historically, before more targeted therapy was shown to be more effective, chemotherapy was used to try to kill off mast cells in advanced conditions.

Other Treatments

Depending on the severity and type of systemic mastocytosis, other treatments may be used.

• Venom immunotherapy: This may be recommended for people with SM with known strong reactions to venom, says Tsewang Tashi, MD, a hematologist and researcher at Huntsman Cancer Institute at the University of Utah Health in Salt Lake City.

  [12]

• Ultraviolet (UV) light: UV light is used to reduce skin lesions and relieve itching.
• Bone marrow transplant: Right now, this is the only potential cure for mastocytosis. A bone marrow transplant may be considered if patients have a donor and if they really need a transplant, says Gotlib.

Finding a healthcare team that is experienced in treating systemic mastocytosis is essential to managing the condition. Centers of Excellence for SM provide access to the latest treatments and even clinical trials, says Dr. Tashi.

In addition to medical treatments, there are things you can do on your own to reduce symptoms.

Avoiding Triggers

The most meaningful lifestyle change for systemic mastocytosis is avoiding the triggers that can lead to inflammation and organ damage. This is usually more important in people with indolent or smoldering SM than the more advanced forms of SM, says Gotlib.

• Rubbing or friction on your skin
• Exercise and physical activity
• Venom from bites and stings from fire ants, wasps, bees, jellyfish, snakes, fleas, and spiders
• Alcohol
• Spicy foods
• Certain medications, including opioids, nonsteroidal anti-inflammatory drugs (NSAIDs), some local anesthetics, and contrast dyes
• Sudden changes in temperature
• Stress, whether emotional, physical (including pain), or environmental
• Sunlight
• Infections (viral, bacterial or fungal)

Dietary Changes

Podoltsev doesn’t recommend any special diet specifically to help with systemic mastocytosis. A healthy and balanced diet can help support overall health, he says.

For some people, following an elimination diet, in which certain foods are eliminated from the diet for a few weeks and then slowly reintroduced, one at a time, can help to identify trigger foods. It’s best to work with a registered dietitian when trying an elimination diet.

Many people who have indolent or smoldering mastocytosis that hasn’t advanced can often have a near-normal life expectancy, says Gotlib.

The prognosis for individuals advanced systemic mastocytosis depends on several factors, including the extent of mast cell accumulation, the organs involved, and the person's overall health. Depending on the type, life expectancy may range between less than six months in people with very advanced disease, to three to four years for other subtypes, says Gotlib.

But the prognosis for advanced systemic mastocytosis has improved in the last decade thanks to new therapies, says Tashi.

“There has been a lot of research in the field, newer treatments, and several ongoing clinical trials. Overall, the prognosis has really improved,” Tashi says.

Not only do tyrosine kinase inhibitors help with symptoms, but there are also some indications that the drugs are modifying the disease trajectory, says Gotlib. “Patients who used to die within a few months or years seem to be living longer with these treatments,” he says.

Systemic mastocytosis can lead to several serious complications, which can include the following:

• Recurrent anaphylaxis: This is a severe allergic reaction that requires immediate medical attention. Anaphylaxis can cause a person to stop breathing or go into shock.
• Organ damage: Over time, the accumulation of mast cells in organs like the liver, spleen, or bone marrow can lead to dysfunction and organ failure.
• Bone fractures: Osteoporosis and bone weakening can result from abnormal mast cell activity.
• Blood disorders: These can include poor blood clotting and anemia.

  [8]

There doesn’t seem to be a difference in the number of men versus women, and no race or ethnicity has been identified as being at higher risk, says Gotlib.

Systemic mastocytosis is associated with several other medical conditions.

• Peptic Ulcer Disease People with mastocytosis are at higher risk of developing peptic ulcers, possibly caused by higher levels of histamine.
• Urticaria Pigmentosa This skin condition develops in many people with systemic mastocytosis. It looks like raised patches of brownish skin that sting or itch with contact or changes in temperature.
• Osteoporosis Aggressive systemic mastocytosis is associated with a loss of bone tissue and osteoporosis.
• Leukemia SM with associated hematologic neoplasm and mast cell leukemia both involve blood cell disorders or leukemia.
• Depression, Anxiety, and Memory Problems These are common in people with advanced systemic mastocytosis. In some cases, the memory issues or brain fog could be due to the many medications that a person is taking, says Gotlib.

Support groups, both in-person and online, provide a sense of community and can be a valuable resource for coping strategies, emotional support, and information about new treatments.

Leukemia and Lymphoma Society 

This nonprofit health organization focused on blood cancers has an online tool to help locate support groups in your community.

CancerCare

This national organization provides free support services and information for people living with cancer. They offer online support groups, and live support groups (in-person or via video conferencing) for residents of New York and New Jersey.

The Mast Cell Disease Society 

A support organization for support to patients, families, and medical professionals, the society offers an online tool to help you find a Center of Excellence in your area.

• Systemic mastocytosis is a rare condition in which the body produces an excessive number of mast cells, which can cause a range of symptoms.
• People with milder forms of SM typically have a good prognosis, while those with more advanced forms require targeted therapy and have a shorter life expectancy.
• Recent advancements in treatment, such as targeted therapies and clinical trials, have greatly improved outcomes.