What is mast cell activation syndrome (MCAS)?

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Last updated: April 21, 2025View editorial policy

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From the Guidelines

Mast cell activation syndrome (MCAS) should be treated with a combination of H1 antihistamines, H2 antihistamines, and mast cell stabilizers, as well as avoidance of personal triggers and consideration of a low-histamine diet, as recommended by the most recent guidelines 1. Mast cell activation occurs when mast cells release inflammatory mediators like histamine, prostaglandins, and leukotrienes in response to various triggers.

  • Treatment typically involves:
    • H1 antihistamines (such as cetirizine 10mg daily or fexofenadine 180mg daily)
    • H2 antihistamines (like famotidine 20mg twice daily)
    • Mast cell stabilizers (such as cromolyn sodium 200mg four times daily)
  • For acute reactions, epinephrine auto-injectors should be available for severe symptoms.
  • Patients should identify and avoid personal triggers, which commonly include:
    • Certain foods
    • Medications
    • Temperature extremes
    • Alcohol
    • Stress
  • A low-histamine diet may help reduce symptoms.
  • For more severe cases, additional medications like montelukast (10mg daily) or low-dose aspirin therapy may be considered, as supported by recent guidelines 1. Mast cell activation occurs because these cells are part of the immune system and can become hypersensitive, releasing their inflammatory contents inappropriately.
  • This cascade of chemical mediators causes symptoms affecting multiple body systems, including:
    • Skin (flushing, hives)
    • Gastrointestinal (nausea, diarrhea)
    • Respiratory (wheezing)
    • Cardiovascular (blood pressure changes) systems.

From the Research

Mast Cell Activation Syndrome

Mast cell activation syndrome (MCAS) is a condition characterized by the activation of mast cells, leading to the release of various mediators that can cause a range of symptoms.

  • The symptoms of MCAS can affect multiple organ systems, including the skin, gastrointestinal, cardiovascular, respiratory, and neurologic systems 2.
  • Patients with MCAS may experience episodic symptoms, such as urticaria, angioedema, flushing, nausea, vomiting, diarrhea, abdominal cramping, hypotensive syncope, tachycardia, wheezing, conjunctival injection, pruritus, and nasal stuffiness 2.

Diagnosis of MCAS

The diagnosis of MCAS is based on a combination of clinical symptoms and laboratory tests.

  • Laboratory tests may include measurements of urinary or serum markers of MCAS, such as histamine metabolites, PGD2 or its metabolite, and 11-β-prostaglandin F2 alpha 2.
  • An increase in serum tryptase levels above 15 ng/mL or an increase in tryptase levels above baseline value on one occasion may also be indicative of MCAS 2.
  • A substantial transient increase in serum total tryptase or increase in other mast cell-derived mediators, such as histamine or PGD2, or urinary metabolites, may also be used to diagnose MCAS 2.

Treatment of MCAS

The treatment of MCAS typically involves the use of medications that block the effects of mast cell mediators or inhibit their release.

  • H1 and H2 antihistamines, leukotriene receptor blockers, and mast cell stabilizers may be used to manage symptoms of MCAS 3, 4.
  • In some cases, corticosteroids or epinephrine may be necessary to manage acute episodes of mast cell activation 3.
  • Second-generation H1-antihistamines, such as rupatadine, may be effective in improving quality of life and symptom control in patients with MCAS 4.

Research Needs

Despite the growing recognition of MCAS, there are still many gaps in our understanding of the condition.

  • Further research is needed to elucidate the underlying mechanisms and pathways that lead to mast cell activation in MCAS patients 5.
  • Large, well-designed clinical trials are necessary to investigate the effectiveness and safety of different treatments for MCAS, including second-generation H1-antihistamines 4.
  • The development of new diagnostic tests and treatments for MCAS is also an area of ongoing research 6.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Mast Cell Activation Syndrome.

Clinical reviews in allergy & immunology, 2018

Research

Mast Cell Activation Syndrome and Mastocytosis: Initial Treatment Options and Long-Term Management.

The journal of allergy and clinical immunology. In practice, 2019

Research

Mast cell activation syndrome: Current understanding and research needs.

The Journal of allergy and clinical immunology, 2024

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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