Systemic mastocytosis is a rare and complex disorder that involves an overproduction of mast cells, a type of blood cell that accumulates abnormally in multiple tissues. These mast cells are part of our immune system and play a vital role in inflammation and allergy responses.
In systemic mastocytosis, the excess mast cells can infiltrate various organ systems such as the skin, bone marrow, liver, spleen, and gastrointestinal tract. This infiltration can lead to a range of symptoms, often varying in severity, from skin rashes and abdominal discomfort to more severe complications like organ damage.
As with many other medical conditions, early diagnosis can prevent serious complications. However, even with proper management, systemic mastocytosis can sometimes worsen over time.
Understanding Systemic Mastocytosis
Systemic mastocytosis is a disorder caused by a mutation in the KIT gene. This gene regulates the growth and development of mast cells. The mutation leads to an overproduction of mast cells, which accumulate in tissues throughout the body.
Mast cells are primarily responsible for immediate allergic reactions. They contain granules packed with substances like histamine and tryptase; when released, they cause inflammation, itching, and swelling.
In a person with systemic mastocytosis, the excessive presence of mast cells causes an overreaction to allergens, leading to severe reactions. As the condition progresses, the mast cells can infiltrate and damage multiple organ systems, eventually causing organ damage.
“A more common sign of progression is organ dysfunction,” said Aaron T. Gerds, MD, MS, associate professor of medicine and deputy director for clinical research at the Cleveland Clinic Taussig Cancer Institute and medical director for the clinical research office at Case Comprehensive Cancer Center. Dr. Gerds noted that the liver, gut, bone, and bone marrow are the most commonly involved organs.
Common Signs and Symptoms
Some individuals with systemic mastocytosis may experience mild or no symptoms, whereas others have more severe complications.
The most common signs and symptoms of systemic mastocytosis include:
Flushing
Hives or skin rashes
Abdominal pain
Nausea and vomiting
Diarrhea or constipation
Bone pain or fractures
Fatigue and weakness
Indicators of Disease Progression
If you notice an increase in the severity or frequency of existing symptoms, it may be a sign that your systemic mastocytosis is worsening. The emergence of symptoms you have not experienced before may also indicate progression.
The following may suggest a need for further evaluation and treatment:
Persisting or worsening skin rashes or flushes that previously responded well to treatment
Increasing frequency or severity of abdominal discomfort, nausea, vomiting, or changes in bowel habits
Unexplained weight loss, which could suggest malabsorption or other gastrointestinal complications
New onset of bone pain, which could indicate bone marrow involvement
Increasing fatigue, weakness, or shortness of breath, potentially indicating anemia or other systemic complications
Frequent infections, which may suggest a compromised immune system due to the overburdening of the body's mast cells
Sudden unexplained anaphylactic reactions, which could signal an increase in mast cell activity
These symptoms don't always mean your condition is getting worse, but they warrant a discussion with your healthcare provider.
Diagnostic Procedures
If you're experiencing new or worsening symptoms, your provider may suggest one or more of the following tests:
Blood tests
Blood analyses can check your complete blood count and assess the levels of certain substances, such as tryptase, a marker substance that is often elevated in systemic mastocytosis.
Bone marrow biopsy
If systemic mastocytosis is suspected to have infiltrated the bone marrow, your healthcare provider may conduct a bone marrow biopsy. This test involves extracting a small bone marrow sample for laboratory examination.
Skin biopsy
For patients with skin symptoms, a biopsy may be performed. This involves removing a small skin sample to look for an excess of mast cells.
Imaging tests
Radiological imaging, such as computerized tomography (CT) scans or magnetic resonance imaging (MRI), can evaluate the extent of organ involvement and detect any related complications.
Gastrointestinal endoscopy
If gastrointestinal symptoms persist or worsen, your provider may recommend an endoscopy to evaluate the stomach and intestines.
Management
Your treatment plan may need adjusting if your condition progresses despite initial management strategies. Your provider may recommend the following:
Increased dosage or change in medication
Your provider may recommend increasing the dose of your current medication or switching to a different drug that may be more effective. Medications to control the symptoms caused by mast cell activation may include mast cell stabilizers, antihistamines, or corticosteroids.
Chemotherapy
If the disease has significantly progressed or is aggressive, chemotherapy may reduce the number of mast cells, alleviate symptoms, and potentially slow disease progression.
Targeted Therapy
Targeted drugs, called KIT inhibitors, block a mutation in the KIT gene that is present in most SM cases, are the front line of treatment for indolent and advanced SM. The KIT inhibitors midostaurin and avapritinib were approved by the U.S. Food and Drug Administration (FDA) for advanced disease in 2017 and 2021, respectively.
Bone marrow transplant
When the bone marrow is significantly affected, transplant may be necessary. The procedure involves replacing diseased bone marrow with healthy marrow from a donor.
“Patients may require chemotherapy pills or, in severe situations, stem cell transplantation,” said Daniel Landau, MD, a board-certified medical oncologist and hematologist at Orlando Health Cancer Institute. Dr. Landau emphasized that many patients do well long-term, but some may require more aggressive treatment options.
Self-Care and Lifestyle Changes
In addition to medical treatments, self-care and lifestyle changes can have a significant impact on the body.
Here are some strategies that might help alleviate symptoms and improve your quality of life:
Avoiding triggers
Certain foods, medications, physical stimuli (like heat or cold), or emotional stress can trigger mast cell activation. Identifying and avoiding these triggers can help manage symptoms.
Healthy diet
A balanced, nutrient-dense diet can support overall health and immune function. Some individuals find that certain dietary modifications, like reducing histamine-rich foods or alcohol, can help minimize symptoms.
Regular exercise
Regular physical activity can help improve energy levels, reduce stress, and strengthen the body. However, vigorous exercise can sometimes trigger symptoms, so it's essential to find a balance that works for you.
Rest and stress management
Ensure you're getting enough rest and practicing stress management techniques such as mindfulness, yoga, or meditation. These can promote relaxation and potentially lessen mast cell activation.
Regular follow-up care
Keep up with your regular medical appointments, and don't hesitate to report new or worsening symptoms to your healthcare provider.
Moving Forward After Progression
A diagnosis of systemic mastocytosis can be overwhelming, especially when your condition is advanced. However, many individuals can effectively manage their disease and lead fulfilling lives.
Don't be discouraged if your symptoms worsen or if new ones arise. Keep an open line of communication with your healthcare provider, continue advocating for your health, and explore additional treatment options.
You may also wish to seek a second or third opinion from other treatment specialists who have experience with systemic mastocytosis. If you're unsure which providers to consult, consider contacting a patient advocacy group for recommendations. A second opinion is your right as a patient and can significantly improve your treatment journey.
“It’s important to work with a physician who understands mastocytosis well and is comfortable managing the complex therapies used for treatment,” Dr. Landau concluded.