What is Mast Cell Activation Syndrome (MCAS)?

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Last updated: May 30, 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 lifestyle management and avoidance of triggers, as recommended by the most recent guidelines 1. The treatment of MCAS typically involves a combination of medications, including:

  • H1 antihistamines, such as cetirizine 10mg daily or loratadine 10mg daily, which can be increased to 2 to 4 times the standard dose if necessary 1
  • H2 antihistamines, such as famotidine 20mg twice daily or ranitidine 150mg twice daily, which can help alleviate gastrointestinal symptoms 1
  • Mast cell stabilizers, such as cromolyn sodium 200mg four times daily, which can help reduce abdominal bloating, diarrhea, and cramps 1 Additionally, lifestyle management is crucial, including:
  • Identifying and avoiding triggers, such as certain foods, medications, temperature extremes, stress, and strong odors
  • Following a low-histamine diet to reduce symptoms
  • Using epinephrine auto-injectors, such as EpiPen 0.3mg or 0.15mg for children, for acute flares 1 It is also important to note that MCAS can be difficult to diagnose, as symptoms overlap with many other conditions, and laboratory tests may show elevated tryptase or histamine metabolites during flares 1. The condition occurs because mast cells, which normally protect against pathogens, become dysfunctional and release inflammatory chemicals without appropriate triggers, leading to chronic inflammation and various symptoms, including:
  • Flushing
  • Hives
  • Gastrointestinal issues
  • Respiratory problems
  • Cardiovascular symptoms, such as tachycardia or hypotension 1 Overall, the goal of treatment is to alleviate symptoms, improve quality of life, and reduce the risk of complications, such as anaphylaxis 1.

From the Research

Definition and Diagnosis of Mast Cell Activation Syndrome

  • Mast cell activation syndrome is a chronic multi-system disorder caused by inappropriate mast cell activation, often mistaken for functional gastrointestinal disorders 2.
  • The diagnosis of mast cell activation syndrome is defined by three criteria: typical clinical signs and symptoms of acute, recurrent, and systemic mast cell activation, increase in tryptase level, and response of symptoms to antimediator therapy 3.
  • Gastrointestinal symptoms are frequently reported by patients with mast cell activation syndrome, including apparent irritable bowel syndrome, dyspepsia, chronic or cyclical nausea, and heartburn 2.

Classification and Management of Mast Cell Activation Syndrome

  • Patients with mast cell activation syndrome can be classified into primary, secondary, and idiopathic MCAS, based on the etiology of mast cell activation 4.
  • Management of mast cell activation syndrome involves avoiding triggers, modulating mast cell activation, and treating the effects of mediators, often with simple over-the-counter medications 2.
  • Therapies for mast cell activation syndrome include blockade of mediator receptors, inhibition of mediator synthesis, and anti-IgE therapy, as well as epinephrine and corticosteroids for acute episodes 5.

Treatment Options for Mast Cell Activation Syndrome

  • H1-antihistamines have been shown to be effective in the treatment of primary mast cell activation syndromes, with significant improvements in quality of life and symptom control 6.
  • Second-generation H1-antihistamines, such as rupatadine, have been found to be effective in reducing itching, whealing, and other symptoms of mast cell activation syndrome 6.
  • A diagnostic algorithm and practical evaluation and management of patients with suspected mast cell activation syndrome have been proposed, including the use of the Spanish Network on Mastocytosis score to select candidates for bone marrow studies 3.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

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

Journal of investigational allergology & clinical immunology, 2021

Research

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

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

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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