What is mast cell activation syndrome?

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From the Guidelines

Mast cell activation syndrome (MCAS) is a primary clinical condition characterized by spontaneous episodic signs and symptoms of systemic anaphylaxis concurrently affecting at least 2 organ systems, resulting from secreted mast cell mediators. According to the most recent and highest quality study 1, MCAS is defined by the presence of multi-system symptoms, including flushing, hives, gastrointestinal issues, and respiratory problems, which occur in association with the secretion of mast cell products such as tryptase, histamine, prostaglandin D2, and leukotriene C4.

Key Characteristics of MCAS

  • Spontaneous episodic signs and symptoms of systemic anaphylaxis
  • Involvement of at least 2 organ systems
  • Resulting from secreted mast cell mediators
  • Symptoms improve with medications that block binding of these products to receptors or their production

Diagnosis and Management

The diagnosis of MCAS is based on the presence of clinical symptoms, increased levels of secreted mediators or their metabolites, and improvement with medications that block or reduce mast cell mediator release 1. Management of MCAS typically involves a combination of H1 and H2 antihistamines, mast cell stabilizers, and lifestyle modifications.

Treatment Options

  • H1 antihistamines: cetirizine 10mg daily or loratadine 10mg daily
  • H2 antihistamines: famotidine 20mg twice daily or ranitidine 150mg twice daily
  • Mast cell stabilizers: sodium cromolyn 200mg four times daily before meals
  • Breakthrough symptoms: diphenhydramine 25-50mg as needed
  • Severe cases: montelukast 10mg daily to block leukotrienes
  • Acute flares: corticosteroids like prednisone, starting at 40mg daily and tapering over 1-2 weeks

Lifestyle Modifications

  • Identifying and avoiding triggers (certain foods, temperature extremes, strong odors, stress)
  • Maintaining a low-histamine diet
  • Reducing stress through mindfulness practices

By prioritizing the most recent and highest quality study 1, we can provide a clear and concise definition of MCAS, as well as evidence-based treatment options and lifestyle modifications to improve symptoms and quality of life.

From the Research

Definition and Characteristics of Mast Cell Activation Syndrome

  • Mast cell activation syndrome (MCAS) is a group of disorders with diverse causes presenting with episodic multisystem symptoms as the result of mast cell mediator release 2
  • MCAS is thought to be a common, yet under-recognized, chronic multi-system disorder caused by inappropriate mast cell activation 3
  • Mast cells are found in all tissues and express numerous surface receptors allowing them to sense and respond to allergic, autoimmune, environmental, neurohormonal, pathogenic and stress triggers 4

Symptoms and Diagnosis

  • Symptoms of MCAS can be managed by blockade of mediator receptors, inhibition of mediator synthesis, mediator release, anti-IgE therapy, or a combination of these approaches 5
  • Gastrointestinal symptoms are frequently reported by patients with MCAS and are often mistaken by physicians as functional gastrointestinal disorders 3
  • Diagnosis of MCAS can be made by medical history and measurable biomarkers 3

Treatment and Management

  • Treatment of MCAS involves avoiding triggers and modulating mast cell activation and the effects of the mediators 3
  • Many therapies for MCAS are simple over-the-counter medications 3
  • Administering chemotherapy to patients with MCAS remains challenging, but a staged approach to chemotherapy administration and utilization of a desensitization regimen can reduce the risk of immediate and delayed hypersensitivity sequelae 6

Related Conditions

  • Mast cell activation diseases (MCADs) include primary, secondary and idiopathic conditions, especially MCAS, but mast cells are activated in many other disorders making the diagnosis and treatment challenging 4
  • Patients with clonal mast cell activation syndromes (MCAS) including cutaneous and systemic mastocytosis (SM) may present with symptoms of mast cell activation, but in addition can have organ damage from the local effects of tissue infiltration by clonal mast cells 5

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Mast cell activation syndromes.

The Journal of allergy and clinical immunology, 2017

Research

Mast cell activation: beyond histamine and tryptase.

Expert review of clinical immunology, 2023

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

Safe administration of chemotherapy in mast cell activation syndrome.

Journal of oncology pharmacy practice : official publication of the International Society of Oncology Pharmacy Practitioners, 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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