What is the treatment for Mast Cell Activation Syndrome (MCAS)?

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Last updated: June 9, 2025View editorial policy

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From the Guidelines

The treatment for Mast Cell Activation Syndrome (MCAS) typically involves a multi-faceted approach targeting symptom relief and mast cell stabilization, with first-line treatments including H1 antihistamines, H2 antihistamines, and mast cell stabilizers, as recommended by the most recent guidelines 1. The goal of treatment is to reduce the inappropriate release of inflammatory mediators from mast cells, which are immune cells that release histamine and other chemicals during allergic and inflammatory responses.

  • First-line treatments include:
    • H1 antihistamines such as cetirizine (10mg daily), loratadine (10mg daily), or fexofenadine (180mg daily) to block histamine receptors, with the option to increase the dose to 2 to 4 times the standard dose if necessary 1.
    • H2 antihistamines like famotidine (20mg twice daily) or ranitidine (150mg twice daily) to help attenuate gastrointestinal and cardiovascular symptoms.
    • Mast cell stabilizers such as oral cromolyn sodium (200mg 30 minutes before meals and at bedtime) or ketotifen (1-2mg twice daily) to prevent mast cell degranulation.
  • For breakthrough symptoms, patients may use leukotriene modifiers like montelukast (10mg daily) or other agents such as aspirin or omalizumab, as indicated by the patient's specific symptoms and laboratory results 1.
  • In severe cases, low-dose corticosteroids like prednisone (5-10mg daily) may be prescribed for short periods, with careful monitoring of side effects and tapering of the dose as soon as possible 1. Non-pharmacological approaches are equally important, including:
  • Identifying and avoiding personal triggers (certain foods, chemicals, temperature extremes, stress)
  • Maintaining a low-histamine diet
  • Gradual desensitization to unavoidable triggers Treatment effectiveness varies significantly between individuals, so a personalized approach with careful monitoring and adjustment is essential, as emphasized by the recent guidelines 1.

From the FDA Drug Label

Cromolyn sodium inhibits sensitized mast cell degranulation which occurs after exposure to specific antigens. Cromolyn sodium acts by inhibiting the release of mediators from mast cells.

The treatment for Mast Cell Activation Syndrome (MCAS) may involve the use of cromolyn sodium, which has been shown to inhibit mast cell degranulation and the release of mediators from mast cells 2.

  • Key points:
    • Cromolyn sodium has been found to inhibit both the immediate and non-immediate bronchoconstrictive reactions to inhaled antigen.
    • It also attenuates bronchospasm caused by various triggers.
    • The dosage of cromolyn sodium may need to be adjusted based on the patient's response to treatment 2.

From the Research

Treatment for Mast Cell Activation Syndrome (MCAS)

The treatment for MCAS involves a multi-faceted approach, including:

  • Avoiding triggers that can cause mast cell activation 3
  • Modulating mast cell activation and the effects of the mediators 3
  • Using over-the-counter medications to manage symptoms 3
  • Blockade of mediator receptors, such as H1 and H2 antihistamines, and leukotriene receptor blockade 4
  • Inhibition of mediator synthesis, such as aspirin and zileuton 4
  • Mediator release inhibition, such as sodium cromolyn 4
  • Anti-IgE therapy 4
  • Epinephrine for acute episodes of mast cell activation 4
  • Corticosteroids for prolonged episodes of mast cell activation 4

Management of Symptoms

Symptoms of MCAS can be managed using a variety of approaches, including:

  • H1-antihistamines, which have been shown to be effective in reducing symptoms of MCAS, including itching, wheals, and flares 5
  • H2-antihistamines, which can be used in combination with H1-antihistamines to manage symptoms 5
  • Oral cromolyn sodium, which can be used to manage gastrointestinal symptoms 5
  • Second-generation H1-antihistamines, such as rupatadine, which have been shown to be effective in improving quality of life and symptom control in patients with MCAS 5

Diagnostic Approach

The diagnosis of MCAS requires a comprehensive approach, including:

  • Clinical evaluation to identify typical signs and symptoms of acute, recurrent, and systemic mast cell activation 6
  • Increase in tryptase level to >20% + 2 ng/mL within 1-4 hours after onset of the acute crisis 6
  • Response of MCA symptoms to antimediator therapy 6
  • Classification of MCAS using highly sensitive and specific methodological approaches for the assessment of clonal bone marrow mast cells at low frequencies 6

Research Needs

There are many gaps in knowledge regarding MCAS, including:

  • The underlying mechanisms and pathways that lead to mast cell activation in MCAS patients 7
  • The contextualization of MCAS and MCAS-like endotypes and related diagnostic evaluations 7
  • Mechanistic research to understand the causes of MCAS 7
  • Management of typical and refractory symptoms 7
  • MCAS-specific education for patients and health care providers 7

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

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

Clinical Approach to Mast Cell Activation Syndrome: A Practical Overview.

Journal of investigational allergology & clinical immunology, 2021

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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