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

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Last updated: April 26, 2025View editorial policy

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From the Guidelines

Treatment for Mast Cell Activation Syndrome (MCAS) should prioritize a multi-faceted approach, including H1 antihistamines like cetirizine or fexofenadine, combined with H2 antihistamines such as famotidine or ranitidine, to effectively manage symptoms and prevent mast cell degranulation, as recommended by the most recent guidelines 1. The cornerstone of treatment includes:

  • H1 antihistamines like cetirizine (10mg daily) or fexofenadine (180mg daily) to relieve symptoms caused by secreted histamine, with the option to increase doses up to 2 to 4 times the standard dose if necessary 1
  • H2 antihistamines such as famotidine (20mg twice daily) or ranitidine (150mg twice daily) to help attenuate gastrointestinal and cardiovascular symptoms 1
  • Mast cell stabilizers like oral cromolyn sodium (200mg four times daily before meals) or ketotifen (1-2mg twice daily) to prevent mast cell degranulation and manage cutaneous, gastrointestinal, and neurologic symptoms 1 For acute flares, patients should have rescue medications available, including:
  • Fast-acting antihistamines
  • Injectable epinephrine (EpiPen) for severe reactions 1 Additional considerations include:
  • Leukotriene modifiers such as montelukast (10mg daily) for patients with respiratory symptoms 1
  • Avoidance of non-steroidal anti-inflammatory drugs, which can trigger reactions in many MCAS patients 1
  • Dietary modifications to eliminate common triggers (alcohol, fermented foods, artificial preservatives) and lifestyle adjustments to avoid physical triggers (extreme temperatures, strong scents, stress) 1 Treatment should be individualized, starting with lower medication doses and gradually increasing as needed, with regular monitoring for effectiveness and side effects, as outlined in the guidelines 1.

From the FDA Drug Label

Cromolyn Sodium Oral Solution (Concentrate) is indicated in the management of patients with mastocytosis. Use of this product has been associated with improvement in diarrhea, flushing, headaches, vomiting, urticaria, abdominal pain, nausea, and itching in some patients. Four randomized, controlled clinical trials were conducted with Cromolyn Sodium Oral Solution (Concentrate) in patients with either cutaneous or systemic mastocytosis;

  • Treatment: Cromolyn Sodium Oral Solution (Concentrate) 200 mg QID can be used to treat Mast cell activation syndrome, as it has been associated with improvement in symptoms such as diarrhea, abdominal pain, urticaria, and pruritus 2.
  • Clinical improvement: can occur within 2-6 weeks of treatment initiation and may persist for 2-3 weeks after treatment withdrawal 2.
  • Alternative treatment: Chlorpheniramine (4 mg QID) plus cimetidine (300 mg QID) may also be effective for both cutaneous and systemic symptoms of mastocytosis 2.

From the Research

Treatment Options for Mast Cell Activation Syndrome

  • Symptoms of MCAS can be managed by blockade of mediator receptors (H1 and H2 antihistamines, leukotriene receptor blockade), inhibition of mediator synthesis (aspirin, zileuton), mediator release (sodium cromolyn), anti-IgE therapy, or a combination of these approaches 3
  • Acute episodes of mast cell activation require epinephrine, and prolonged episodes may be addressed with corticosteroids 3
  • Gastrointestinal symptoms of MCAS can be managed by modulating mast cell activation and the effects of the mediators, with many therapies being simple over-the-counter medications 4
  • H1-antihistamines have been shown to be effective in the treatment of primary MCAS, with significant improvements in quality of life, symptom control, and reduction in itching and whealing 5
  • Sunitinib, a multitargeted tyrosine kinase inhibitor, has been reported to be effective in treating life-threatening MCAS refractory to multiple agents, including imatinib 6
  • A diagnostic algorithm for MCAS includes typical clinical signs and symptoms of acute, recurrent, and systemic mast cell activation, increase in tryptase level, and response of MCA symptoms to antimediator therapy 7

Medications Used to Treat MCAS

  • H1-antihistamines (e.g. rupatadine) 5
  • H2-antihistamines 3
  • Leukotriene receptor blockers 3
  • Aspirin 3
  • Zileuton 3
  • Sodium cromolyn 3
  • Anti-IgE therapy 3
  • Epinephrine (for acute episodes) 3
  • Corticosteroids (for prolonged episodes) 3
  • Sunitinib (for life-threatening MCAS) 6

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

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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