The Role of Mast Cells in Health and Disease: Part 2
Mast Cell Diseases: MCAS, Mastocytosis, Hereditary Alpha Tryptasemia & More
Mast cells play a role in many processes and diseases, including allergies, anaphylaxis, wound healing, infections, gastrointestinal disorders and more. While mast cells are involved in many conditions, mast cell diseases are defined as a group of complex disorders that involve abnormal mast cell activation and/or proliferation.
Mast Cell Diseases Include:
Mast Cell Activation Syndrome (MCAS)
Mastocytosis
Cutaneous
Systemic
Mast Cell tumors (mastocytoma and sarcoma)
Hereditary Alpha Tryptasemia (HATs)
Mast Cell Leukemia (MCL)
Disease and Disorder are often used interchangeably to refer to mast cell conditions. Sometimes, MCAD is used to describe mast cell activation disorders.
Mast Cell Activation Syndrome (MCAS)
MCAS is a condition caused by abnormal activation of mast cells in various tissues and organs throughout the body. Mast cells can be viewed as overly sensitive, reacting to various triggers to release mediators. Sometimes, the triggers are unknown. This can lead to a wide range of symptoms that can affect multiple organ systems
Symptoms of MCAS include: rashes, hives, itching, flushing, abdominal pain, diarrhea, nausea, heart palpitations, low blood pressure, wheezing, shortness of breath, headaches, brain fog, anxiety and fatigue. Anaphylaxis, a severe and potentially life-threatening allergic reaction can also occur.
A diagnosis of MCAS is often made from clinical presentation and improvement of symptoms with mast cell stabilizing medications. Sometimes, a diagnosis is made based on laboratory tests for mast cell mediators. However, these tests (such as serum tryptase) have many limitations and normal results do not exclude the possibility of MCAS. There are some controversial views when it comes to what tests are necessary for diagnosis (see consensus 1 and consensus 2 papers) Unfortunately, despite clear evidence of the condition, some professionals dismiss its existence or severity.
Treatment options for MCAS include antihistamines, mast cell stabilizers, leukotriene Inhibitors, immune modulators/monoclonal antibody biologics, epinephrine auto-injectors, avoidance of triggers, and dietary and lifestyle adjustments.
Mastocytosis
Mastocytosis is a group of rare and complex disorders characterized by abnormal accumulation and activation. Mastocytosis can present as cutaneous mastocytosis (the accumulation of mast cells is primarily limited to the skin) and systemic mastocytosis (SM)(excess mast cells in various organs and tissues beyond the skin).
SM can present similarly to MCAS, but has a different underlying cause. SM is usually diagnosed through a combination of bloodwork, bone marrow biopsy and genetic testing. The main difference between MCAS and SM is that MCAS involves the overactivity of mast cells, while in systemic mastocytosis, there are too many mast cells being made on top of their overactivity. Mutations in the KIT gene (most commonly D816V) are the cause of most cases of mastocytosis.
Mastocytoma and mast cell sarcoma are used to describe rare instances of a mass of mast cells. Mastocytomas are benign masses, more frequently seen in the skin in cutaneous mastocytosis. Mast cell sarcomas, although rare, is a cancerous mass of mast cells.
Treatments for the various types of mastocytosis can depend on the underlying condition and symptoms. Antihistamines and epinephrine may be used. More aggressive forms of systemic mastocytosis may require interferon, immune modulators or chemotherapy.
Hereditary Alpha Tryptasemia (HAT)
HAT is a genetic trait found in 4% to 6% of the general population. It is defined as excess copies of the alpha-tryptase gene, TPSAB1. Tryptase, a mediator released from mast cells when they are activated, causes allergic-like symptoms. Elevated basal serum tryptase occurs in HAT. However, only 1/3 of people with HAT have symptoms associated with it.
It was suggested that HAT is the cause of the 'trifecta' of hypermobility, MCAS, and dysautonomia when it was first discovered. However, these studies lack convincing evidence to support HAT as an underlying cause, especially given the majority of people with HAT do not have any symptoms. It is possible that HAT may be playing a role as a contributing factor, but it is likely not the only genetic factor at play.
Mast Cell Leukemia
Mast Cell Leukemia (MCL) is an extremely rare and aggressive form of cancer that involves the uncontrolled production of mast cells in the bone marrow and other tissues. MCL is characterized by the presence of high levels of mast cells (mastocytosis) in the peripheral blood and bone marrow, along with other clinical and laboratory findings.
Symptoms and complications associated with MCL can include anemia, thrombocytopenia (low platelet count), hepatosplenomegaly (enlarged liver and spleen), skin lesions, bone pain, and potentially life-threatening symptoms related to mast cell activation.
Treatment typically involves a combination of chemotherapy, targeted therapies, and supportive care. Stem cell transplantation may also be considered in some cases.
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References and Resources
Hereditary alpha tryptasemia is not associated with specific clinical phenotypes
Mast cell sarcoma: new cases and literature review
https://www.aaaai.org/conditions-treatments/related-conditions/systemic-mastocytosis
Mast Cell Activation Syndrome: Tools for Diagnosis and Differential Diagnosis
Mast cell activation syndrome: Proposed diagnostic criteria
Proposed Diagnostic Algorithm for Patients with Suspected Mast Cell Activation Syndrome
Diagnosis of mast cell activation syndrome: a global “consensus-2”