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Mast Cell Activation: Causes, Symptoms & Treatment

Mast cell activation describes the process by which mast cells of the immune system are triggered to release chemical mediators, causing inflammatory and allergic reactions throughout the body.

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Things worth knowing about "Mast Cell Activation"

Mast cell activation describes the process by which mast cells of the immune system are triggered to release chemical mediators, causing inflammatory and allergic reactions throughout the body.

What is Mast Cell Activation?

Mast cell activation refers to the process by which specialized immune cells known as mast cells become stimulated and release a wide range of chemical mediators. Mast cells are found primarily in tissues that interface with the external environment, including the skin, mucous membranes, airways, and gastrointestinal tract. They play a key role in immune defense but can cause significant health problems when activated excessively or inappropriately.

Causes of Mast Cell Activation

Mast cells can be activated by a wide variety of triggers, including:

Allergens (e.g., pollen, animal dander, foods)
Infections caused by bacteria, viruses, or parasites
Physical stimuli such as heat, cold, pressure, or UV radiation
Medications (e.g., certain painkillers, antibiotics, or contrast agents used in imaging)
Psychological stress and emotional strain
Alcohol and certain foods (e.g., histamine-rich foods)
Hormonal fluctuations

In Mast Cell Activation Disease (MCAD) or Mast Cell Activation Syndrome (MCAS), mast cells are chronically or excessively activated, often without a clearly identifiable external trigger, or they respond disproportionately to minor stimuli.

Mechanism of Action

When mast cells are activated, they release both pre-stored and newly synthesized mediators in a process called degranulation. The key mediators released include:

Histamine: causes itching, redness, swelling, and mucosal reactions
Tryptase: an enzyme used as a biomarker for mast cell activation
Prostaglandins and leukotrienes: amplify inflammatory responses and affect the airways and blood vessels
Cytokines: regulate further immune responses throughout the body

These mediators act on multiple organ systems, producing the characteristic symptoms associated with mast cell activation.

Symptoms

The symptoms of mast cell activation are diverse and can affect nearly every organ system:

Skin: flushing, hives (urticaria), itching, wheals
Respiratory system: shortness of breath, coughing, bronchospasm, runny nose
Gastrointestinal tract: abdominal pain, nausea, vomiting, diarrhea, bloating
Cardiovascular system: palpitations, low blood pressure, dizziness, fainting
Nervous system: headaches, brain fog, fatigue, anxiety
Eyes: redness, tearing, itching

In the most severe cases, mast cell activation can trigger anaphylaxis -- a life-threatening allergic shock reaction requiring immediate medical attention.

Diagnosis

Diagnosing mast cell activation can be challenging due to the nonspecific and variable nature of its symptoms. Common diagnostic approaches include:

Blood tests: measurement of serum tryptase levels (elevated levels suggest mast cell activation)
Urine tests: detection of mast cell mediators such as N-methylhistamine, prostaglandin D2, or leukotrienes
Allergy testing: skin and blood tests to identify specific allergens
Bone marrow biopsy: used when systemic mastocytosis is suspected
Symptom diary: documenting triggers and reactions over time

Mast Cell Activation Syndrome (MCAS) is diagnosed according to internationally recognized criteria, which include characteristic symptoms, elevated mediator levels, and a positive response to mast-cell-targeting therapies.

Treatment

Treatment of mast cell activation focuses on reducing mediator release and blocking the effects of released mediators:

Trigger Avoidance

Consistently avoiding known triggers is the most important management strategy. This often includes following a low-histamine diet and avoiding medications that are known to activate mast cells.

Pharmacological Treatment

Antihistamines (H1 and H2 blockers): block the effects of histamine at its receptors
Mast cell stabilizers (e.g., cromolyn sodium): inhibit mast cell degranulation
Corticosteroids: reduce inflammation in severe cases
Leukotriene antagonists (e.g., montelukast): block leukotriene activity
Epinephrine auto-injector: used in emergencies for severe anaphylactic reactions
Tyrosine kinase inhibitors (e.g., imatinib): used in advanced systemic mastocytosis

Complementary Measures

Stress reduction, regular physical activity within individual tolerance, and dietary adjustments can help reduce the frequency and severity of mast cell activation episodes.

References

Valent P. et al. - Definitions, Criteria and Global Classification of Mast Cell Disorders with Special Reference to Mast Cell Activation Syndromes. International Journal of Molecular Sciences, 2012.
Afrin L.B. - Presentation, Diagnosis and Management of Mast Cell Activation Syndrome. In: Murray D.B. (ed.), Never Bet Against Occam. Sisters Media, 2016.
Akin C. et al. - Mast cell activation syndrome: Proposed diagnostic criteria. Journal of Allergy and Clinical Immunology, 2010.

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