What are the specific tests to diagnose chronic pain syndrome versus mast cell activation syndrome?

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Last updated: June 14, 2025View editorial policy

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From the Guidelines

Diagnosing chronic pain syndrome and mast cell activation syndrome (MCAS) requires distinct testing approaches, with MCAS diagnosis relying on laboratory tests measuring mast cell mediators during symptomatic periods, as outlined in the 2019 study by the AAAAI Mast Cell Disorders Committee Work Group 1. To diagnose chronic pain syndrome, physicians primarily rely on clinical evaluation, with no specific laboratory tests available, using comprehensive pain assessments, medical history reviews, physical examinations, and sometimes imaging studies to rule out underlying causes. For MCAS diagnosis, key tests include:

  • Serum tryptase (preferably during flares)
  • 24-hour urine tests for N-methylhistamine, prostaglandin D2 or its metabolite 11β-prostaglandin F2α, and leukotriene E4
  • Blood tests for histamine levels and serum chromogranin A Tissue biopsies showing increased mast cells can support diagnosis in some cases. MCAS diagnosis typically requires demonstration of mast cell mediator release, characteristic clinical symptoms affecting multiple organ systems, and response to medications targeting mast cell mediators such as antihistamines, mast cell stabilizers, or leukotriene inhibitors, as recommended in the 2019 study 1. In contrast, the 2005 study on the diagnosis and management of anaphylaxis 1 provides less relevant information for diagnosing MCAS, as it focuses on anaphylaxis diagnosis and management. The most recent and highest-quality study, the 2019 AAAAI Mast Cell Disorders Committee Work Group report 1, should be prioritized for MCAS diagnosis and management. When evaluating patients with suspected MCAS, it is essential to measure mediator levels at baseline and during an acute episode, as outlined in the 2019 study 1. If the laboratory findings correlate with the presence of symptoms, then appropriate therapies should be implemented, and the symptoms should resolve with therapies directed at the increased mediator.

From the Research

Diagnostic Tests for Chronic Pain Syndrome and Mast Cell Activation Syndrome

  • There are no specific tests mentioned in the provided studies for diagnosing chronic pain syndrome.
  • For mast cell activation syndrome (MCAS), the diagnostic tests include:
    • Increase in tryptase level to >20% + 2 ng/mL within 1-4 hours after onset of the acute crisis 2
    • Increase in validated urinary or serum markers of mast cell activation, such as histamine or PGD2 or their urinary metabolites 3, 4
    • 24-h urine histamine metabolites, PGD2 or its metabolite, and 11-β-prostaglandin F2 alpha 3, 4
    • Baseline serum tryptase levels that are persistently above 15 ng/mL 3, 4
    • Response of clinical symptoms to agents that attenuate the production or activities of mast cell mediators 3, 4
  • The Spanish Network on Mastocytosis score has been used as a predictive model for selecting MCAS candidates for bone marrow studies based on a high probability of an underlying clonal mast cell disorder 2
  • A global definition, criteria, and classification for MCAS include typical clinical symptoms, a substantial transient increase in serum total tryptase level or an increase in other mast cell-derived mediators, and a response of clinical symptoms to agents that attenuate the production or activities of mast cell mediators 3, 4

Key Differences between Chronic Pain Syndrome and Mast Cell Activation Syndrome

  • The provided studies do not discuss chronic pain syndrome in detail, but MCAS is characterized by episodic symptoms consistent with mast cell mediator release affecting two or more organ systems 3, 4
  • MCAS can be classified into primary, secondary, and idiopathic, and its diagnosis requires a combination of clinical evaluation, laboratory tests, and response to treatment 2, 3, 4
  • The diagnosis of MCAS is complex and may involve multiple tests and evaluations, and two principal proposals for diagnostic criteria have emerged, including "consensus-1" and "consensus-2" 5

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: a review.

Current allergy and asthma reports, 2013

Research

Mast Cell Activation Syndrome.

Clinical reviews in allergy & immunology, 2018

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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