Advanced Systemic Mastocytosis
Advanced systemic mastocytosis is a rare and serious blood disorder where abnormal mast cells build up uncontrollably in various organs, potentially causing organ damage and life-threatening complications.
Table of contents
- What is Advanced Systemic Mastocytosis?
- Signs and Symptoms
- What Causes This Condition?
- Types of Advanced Systemic Mastocytosis
- How is it Diagnosed?
- Treatment Options
- Possible Complications
- Living with Advanced Systemic Mastocytosis
What is Advanced Systemic Mastocytosis?
Advanced systemic mastocytosis is a rare form of blood disorder that affects how your body produces and controls mast cells, which are a type of white blood cell that helps your immune system work properly[1]. Mast cells are found throughout your body in tissues like your skin, stomach, and bone marrow. They normally help protect you from disease by releasing chemicals when they detect threats[1].
In advanced systemic mastocytosis, your body makes too many abnormal mast cells that build up in different organs. These cells can cause damage to organs, affecting how well they work[5]. This condition is part of a group of diseases called systemic mastocytosis, but the advanced form is more serious and can compromise life expectancy[3].
The condition is very rare, affecting approximately 1.5 cases per 100,000 people[3]. It most commonly affects adults and can cause a range of difficult symptoms that may worsen over time.
Signs and Symptoms
Advanced systemic mastocytosis can cause many different symptoms depending on where the abnormal mast cells build up in your body. When these cells are triggered, they release substances like histamine, a chemical that causes allergic reactions, leading to various symptoms throughout the body[1].
Common symptoms include skin problems such as rash-like lesions, flushing, itching, and hives[2][5]. Many people experience digestive issues including nausea, vomiting, diarrhea, and abdominal pain[2][5]. Some may develop peptic ulcer disease, which are painful sores in the stomach lining[2].
The condition can affect your bones, causing bone pain, osteoporosis (weak and brittle bones), or osteopenia (lower than normal bone density)[2]. Other symptoms may include low blood pressure (hypotension), headaches, extreme tiredness, shortness of breath, and mood changes including depression or difficulty concentrating[2][5].
More serious signs include swollen lymph nodes (lymphadenopathy), an enlarged liver and spleen (hepatosplenomegaly), reduced number of blood cells (cytopenia), and abnormal cell growth (dysplasia)[2]. Some people may experience severe whole-body allergic reactions called anaphylaxis, which can be life-threatening[5].
Certain things can trigger symptoms to worsen, including alcohol, spicy foods, insect stings, certain medications, skin irritation, and exercise[1]. People with the condition may suddenly develop several symptoms all at once, which doctors may call a mastocytosis attack or flare[4].
What Causes This Condition?
Advanced systemic mastocytosis is caused by changes in your genes that affect how mast cells grow and behave. In approximately 95% of cases, the condition is caused by a mutation, or change, in a gene called KIT D816V[5][4]. This mutation makes abnormal mast cells grow out of control[5].
The KIT gene normally acts like a switch that can be turned on and off to control how mast cells grow. When the KIT D816V mutation is present, this switch stays in the “on” position all the time, causing continuous growth and activation of mast cells[7].
These genetic changes happen during a person’s life and are not inherited from parents. The condition originates from abnormal cells in the bone marrow that then spread to other parts of the body[3].
Types of Advanced Systemic Mastocytosis
Advanced systemic mastocytosis includes three specific subtypes, each with different characteristics and levels of severity[5].
Aggressive Systemic Mastocytosis (ASM) occurs when the buildup of mast cells causes damage to organs and affects how well they function[6]. This type can affect your bone marrow and bones, with abnormal mast cells growing into bones and making them weak and more likely to break[4].
Systemic Mastocytosis with Associated Hematologic Neoplasm (SM-AHN) happens when excessive growth of mast cells combines with another blood disease, such as conditions where the bone marrow produces too many blood cells or acute myeloid leukemia, a type of blood cancer[6]. This type affects about one-fifth of people with systemic mastocytosis[4].
Mast Cell Leukemia (MCL) is the rarest and most aggressive form. Very rarely, systemic mastocytosis becomes mast cell leukemia, which is a form of acute myeloid leukemia[4].
How is it Diagnosed?
Diagnosing advanced systemic mastocytosis can be challenging because many of its symptoms are similar to other conditions. Many patients see multiple doctors across different specialties and often go undiagnosed for years, with the average delay to diagnosis being about 58 months[15].
To diagnose the condition, doctors will review your medical history and symptoms, then perform various tests to look for abnormal mast cells in your blood, bone marrow, and other organs[5][11].
Blood or urine tests can detect high levels of substances released by mast cells[11]. A bone marrow biopsy, where a small sample of bone marrow is removed and examined under a microscope, is often needed to confirm the diagnosis[11]. Doctors may also perform a skin biopsy if you have skin symptoms[11].
A KIT D816V blood test is helpful for diagnosis, as this genetic marker is found in approximately 95% of systemic mastocytosis cases[5]. High sensitivity tests may be required to detect the mutation[5].
Imaging tests such as X-rays, ultrasound, bone scans, and CT scans may be ordered to evaluate which organs are affected[11]. Doctors may also biopsy organs affected by the disease, such as the liver[11].
Treatment Options
Healthcare providers cannot cure advanced systemic mastocytosis, but treatment can help control symptoms, slow disease progression, and improve quality of life[4][3].
Treatment typically focuses on two main areas: managing symptoms caused by mast cell chemicals and reducing the number of abnormal mast cells.
For symptom management, antihistamines are commonly used to treat itching, flushing, and skin redness by blocking the effects of histamine[10]. Doctors may recommend non-sedating antihistamines for daytime use and sedating ones for nighttime[10]. Other medications include proton pump inhibitors or H2-receptor antagonists for stomach problems[10], and sodium cromoglicate for abdominal pain and diarrhea[9].
People with advanced systemic mastocytosis should carry self-injectable epinephrine and be trained to use it in case of severe allergic reactions or anaphylaxis[8].
For more advanced disease, targeted therapy medications called tyrosine kinase inhibitors work by blocking the abnormal KIT protein that causes mast cells to multiply[3]. Avapritinib is a selective KIT D816V inhibitor approved for treating advanced systemic mastocytosis[8]. Midostaurin is another medication active against both normal and mutant KIT that is approved for advanced disease[8].
Other treatment options may include corticosteroids for severe symptoms, bisphosphonates and calcium supplements for bone problems[9], and interferon alpha for some aggressive cases[9].
In some younger, carefully selected patients, doctors may consider allogeneic stem cell transplantation, where healthy stem cells from a donor are transplanted into the patient[8][3].
Possible Complications
Advanced systemic mastocytosis can lead to serious complications that significantly affect health and quality of life. One of the most dangerous complications is anaphylaxis, a severe allergic reaction that can lead to cardiovascular collapse and death[7]. People with the condition have a higher risk of experiencing anaphylaxis[4].
The disease can cause organ damage when abnormal mast cells build up and infiltrate organs. This may result in an enlarged liver or spleen, which can affect how these organs function[2]. Bone involvement can lead to weak bones that break easily, or severe bone loss[2].
Blood-related complications may include anemia, excessive bleeding, and reduced numbers of different blood cells[4]. Some people may develop associated blood disorders or, in rare cases, the condition may progress to forms of cancer[6].
The condition often causes significant mental health challenges, including depression, anxiety, and difficulty concentrating[5]. The chronic nature of symptoms and impact on daily life can greatly affect emotional well-being.
Living with Advanced Systemic Mastocytosis
Living with advanced systemic mastocytosis requires careful daily management and lifestyle adjustments. Following a healthy lifestyle is especially important and may include eating a balanced diet and engaging in regular physical activity as tolerated[14]. Maintaining overall health and wellness may make you eligible for more treatment options[14].
It is important to identify and avoid triggers that can cause symptoms to worsen. Common triggers include alcohol, spicy foods, extreme temperatures, stress, insect stings, and certain medications[1]. Keeping a diary of symptoms and possible triggers may help you and your doctor identify what to avoid.
Because the condition is rare and complex, you will likely need care from a team of healthcare providers. This may include specialists in blood disorders (hematologists), allergy specialists, and other doctors depending on which organs are affected[18].
Many people with advanced systemic mastocytosis experience a significant symptom burden that affects daily activities, work, and relationships. Seeking support from mental health professionals, patient support groups, and connecting with others who have the condition can be valuable[16].
Always carry your prescribed epinephrine auto-injector and make sure family members and close contacts know how to use it in case of emergency[8]. Wearing a medical alert bracelet can also be helpful to inform emergency responders about your condition.