Systemic Mastocytosis: Symptoms, Subtypes, Treatment

Systemic mastocytosis is a rare health condition in which too many mast cells (a type of immune system cell) build up in the body, causing allergic reactions and other health issues. This disorder encompasses various subtypes, each presenting unique challenges and symptoms.

This article will help readers understand systemic mastocytosis, its symptoms, diagnostic process, and available treatments. It also provides information on managing the condition, recognizing triggers, and finding support.

Defining Systemic Mastocytosis

Systemic mastocytosis happens when a type of white blood cell called mast cells builds up too much in the body’s tissues. These cells are made in the bone marrow, where they usually help with allergic reactions and inflammation.

In most cases of systemic mastocytosis, these mast cells have a change in a gene called KIT. The KIT gene gives instructions for making a protein that tells mast cells when to grow and divide. When the KIT gene is mutated in systemic mastocytosis, the protein switch is always stuck in the “on” position. This causes the mast cells to grow too much and gather in the bone marrow, gastrointestinal tract, lymph nodes, spleen, or liver.

Mast cells in systemic mastocytosis are triggered by:

• Changes in temperature
• Rubbing or injury
• Surgeries
• Insect bites
• Vaccines
• Anxiety
• Certain medicines like aspirin or painkillers

When triggered, mast cells release proteins that start an immune response. This can cause symptoms like itching, flushing, stomach pain, or severe allergic reactions.

There are five subtypes of systemic mastocytosis:

• Indolent Systemic Mastocytosis (ISM)
• Smoldering Systemic Mastocytosis (SSM)
• Aggressive Systemic Mastocytosis (ASM)
• Mast Cell Leukemia (MCL)
• Systemic Mastocytosis with an Associated Hematologic Neoplasm (SM-AHN)

Indolent Systemic Mastocytosis

Indolent systemic mastocytosis (ISM) is the most common and typically less severe form of systemic mastocytosis. In indolent systemic mastocytosis, mast cells accumulate in various organs but do not cause significant organ damage or dysfunction. Symptoms may be mild and usually include skin lesions and gastrointestinal issues. The life expectancy for people with ISM is similar to that of the general population.

Mast Cell Activation Syndrome (MCAS)

MCAS is a related disease of systemic mastocytosis, but it is not one of its subtypes. It is a non-cancerous condition characterized by frequent and excessive release of chemicals by mast cells, leading to recurrent and severe allergic reactions.

The main difference is that MCAS involves the inappropriate activation of normal mast cells, causing them to release their mediators excessively and inappropriately, leading to symptoms. The number of mast cells is typically normal.

However, with systemic mastocytosis, mast cells abnormally accumulate in various tissues, including the skin, bone marrow, and internal organs. These mast cells may also behave abnormally.

Other Variants

Other variants of systemic mastocytosis, starting with the least severe, include:

Smoldering Systemic Mastocytosis

SSM is an intermediate form between indolent and aggressive types characterized by a higher number of mast cells compared to indolent systemic mastocytosis. It commonly presents with symptoms like bone marrow abnormalities, an enlarged spleen, and skin lesions. It may also progress to ASM or mast cell leukemia (MCL) over time. Close monitoring is essential.

Aggressive Systemic Mastocytosis

ASM involves a rapid and extensive accumulation of abnormal mast cells in multiple organs, leading to severe symptoms such as organ dysfunction, bone fractures, and potentially life-threatening complications. Examples of organ dysfunction include low white blood cells, liver dysfunction, anemia, and low platelets.

ASM requires intensive treatment to manage its aggressive nature and preserve organ function.

Mast Cell Leukemia

MCL is an exceptionally rare and highly aggressive subtype in which mast cells rapidly multiply in the bone marrow and bloodstream. This results in severe symptoms such as high mast cell levels in the blood, organ failure, and a significantly reduced life expectancy. Treatment for MCL is challenging and often focuses on managing symptoms and improving quality of life.

Systemic Mastocytosis with an Associated Hematologic Neoplasm

SM-AHN is a rare subtype in which systemic mastocytosis coexists with another health condition, such as acute myeloid leukemia (AML). This combination poses diagnostic challenges and requires careful management due to the overlapping symptoms and complexities in treatment.

People with SM-AHN may experience symptoms related to both mastocytosis and other hematologic disorders, necessitating a multidisciplinary approach involving hematologists and oncologists for optimal care.

Possible Systemic Mastocytosis Symptoms

Systemic mastocytosis encompasses a spectrum of symptoms that can vary widely in severity and presentation across different people. These symptoms predominantly arise from the excessive activation and release of mast cells, affecting various organ systems in the body.

Emergency Systemic Mastocytosis Symptoms 

Emergency symptoms of systemic mastocytosis can be severe and require immediate medical attention. These include:

Anaphylaxis

A life-threatening allergic reaction is characterized by the sudden onset of symptoms such as difficulty breathing, swelling of the throat and tongue, rapid heartbeat, and a drop in blood pressure. Anaphylaxis requires prompt treatment with epinephrine to prevent potentially fatal outcomes.

Hypotension

Low blood pressure, or hypotension, can cause dizziness, fainting, and, in severe cases, shock. In systemic mastocytosis, low blood pressure happens because the chemicals released by extra mast cells, like histamine, cause blood vessels to widen and relax.

Skin and Rash Symptoms

Skin manifestations are common in systemic mastocytosis, often presenting as:

• Urticaria pigmentosa: Small, raised patches or spots on the skin that are reddish-brown and can itch when rubbed or scratched.
• Itching and flushing of the skin: Persistent itching of the skin, which can be localized or generalized. Flushing causes episodes of redness and warmth and can cause even more itching.

GI Symptoms

Gastrointestinal (GI) symptoms in systemic mastocytosis may include:

• Abdominal pain: Cramping or sharp pain in the abdomen, which can vary in intensity and duration. Abdominal pain is often associated with mast cell infiltration into the gastrointestinal tract, leading to inflammation and hypersensitivity.
• Diarrhea: Frequent, loose stools may be accompanied by urgency and abdominal discomfort. Diarrhea in systemic mastocytosis can result from increased intestinal motility triggered by mast cell mediators.
• Nausea and vomiting: Feelings of queasiness or an urge to vomit may occur occasionally or frequently.

Other Symptoms

Systemic mastocytosis can affect various other organ systems and manifest with diverse symptoms, including:

• Neurological symptoms: Mast cell activation, which affects the nervous system, may cause headaches and cognitive dysfunction (such as difficulty concentrating or memory problems).
• Respiratory symptoms: Wheezing, shortness of breath, and coughing may occur, particularly in response to mast cell activation in the respiratory tract.
• Bone and joint symptoms: Bone pain, osteoporosis (bone thinning), and joint pain can result from mast cell infiltration into bones and joints, causing inflammation.
• Psychological symptoms: Mast cell activation can trigger heightened anxiety levels and occasional panic attacks in affected individuals. Depression and mood changes may also occur.

Traits of Systemic Mastocytosis Symptoms

The onset of systemic mastocytosis symptoms can vary. Some people may experience symptoms suddenly and acutely, often triggered by specific environmental factors or stressors that activate mast cells. In contrast, others may have a slower onset, with symptoms gradually worsening over time as mast cell accumulation and activation progress. Early symptoms may be subtle and easily mistaken for other conditions, which may delay getting a proper diagnosis.

Symptom variability in systemic mastocytosis is further influenced by the specific subtype of the disease. Indolent systemic mastocytosis (ISM) may present with milder and more stable symptoms, whereas aggressive systemic mastocytosis (ASM) or mast cell leukemia (MCL) are associated with more severe and rapidly progressing clinical courses. The subtype dictates not only the intensity of symptoms but also the overall prognosis and response to treatment.

Path to Systemic Mastocytosis Diagnosis

Your healthcare provider will gather a detailed medical history and conduct a physical examination to identify symptoms. Specialists involved in diagnosis typically include allergists, dermatologists, gastroenterologists, and hematologists. It is a good idea to keep detailed records of your symptoms so you don’t forget anything when you speak with your providers. 

A skin biopsy is often the first step if cutaneous mastocytosis is suspected. A small sample of the affected skin is examined under a microscope. The number of mast cells in the sample is counted to confirm the diagnosis.

Another diagnosis method is a bone marrow biopsy. This procedure involves numbing the skin and inserting a needle into the bone to extract marrow cells. These cells are then analyzed microscopically to identify any abnormal accumulation of mast cells.

In some cases, a biopsy from other tissues, such as the gastrointestinal tract, may be necessary to make the diagnosis. 

Laboratory tests are critical for confirming systemic mastocytosis, including:

• Tryptase level test: This blood test measures the level of tryptase, a protein mast cells produce.
• Genetic testing: Tests to identify specific genetic mutations, such as the KIT mutation, and help confirm the diagnosis.

Home Remedies Without a Systemic Mastocytosis Diagnosis

If you have systemic mastocytosis symptoms, seeing your provider for treatment options is essential. But in addition to your established treatment plans, you may want to ask your provider about additional alternative approaches you can take at home, such as:

• Acupuncture
• Mind-body techniques such as yoga or medication to lower stress levels

Talk to your provider about other home remedies to help with your symptoms.

Treatment With a Systemic Mastocytosis Diagnosis

Once diagnosed, treatment options may include:

• Topical emollients: To keep skin moisturized
• Antihistamines: These drugs help counteract the effects of histamine released by mast cells, alleviating symptoms like itching, hives, and gastrointestinal discomfort
• Mast cell stabilizers: Medications like cromolyn sodium can prevent mast cells from releasing histamine and other chemicals, reducing symptoms and flare-ups
• Proton pump inhibitors (PPIs) and H2 blockers: These are used to reduce stomach acid production and help manage gastrointestinal symptoms
• Leukotriene inhibitors: These medications can help reduce inflammation and manage symptoms, particularly in the respiratory system.
• Corticosteroids: In severe cases, corticosteroids may be prescribed to reduce inflammation and control symptoms.
• Tyrosine kinase inhibitors (TKIs): For aggressive forms of SM, drugs like imatinib may be used to target specific genetic mutations in mast cells
• Blood transfusions: Help with anemia and low platelet counts.
• Chemotherapy or stem cell transplant: Used in severe cases like mast cell leukemia.

Systemic Mastocytosis Triggers

Mastocytosis can worsen due to triggers that prompt mast cells to release histamine and other chemicals. While triggers can vary among individuals, common ones include:

• Exposure to extreme temperatures
• Intense exercise or physical activity
• Rubbing or scratching the skin
• Spicy foods, alcohol, and foods high in histamine or tyramine (such as aged cheeses and fermented products)
• Artificial colors and preservatives
• Nonsteroidal anti-inflammatory drugs
• Stings from bees, wasps, and hornets
• Pollen, dust, and mold
• Anxiety or stress

Continued Reading and Systemic Mastocytosis Support

Living with systemic mastocytosis can be challenging, but understanding the condition and connecting with supportive resources can make a significant difference. Here are some recommended avenues for further reading and support:

• The Mast Cell Disease Society, Inc.
• Online forums, support groups, and social media communities
• Articles, books, and YouTube videos about living with systemic mastocytosis

Summary

Systemic mastocytosis is a complex condition characterized by the abnormal accumulation of mast cells in various organs. Symptoms can vary widely and often flare, making diagnosis challenging. Understanding the diagnostic process and available treatments is crucial for managing this condition. By avoiding triggers and utilizing support resources, individuals with systemic mastocytosis can often improve their quality of life. Talk to your healthcare provider for more information.