Diagnosing Mast Cell Activation Syndrome (MCAS)

Diagnosing Mast Cell Activation Syndrome (MCAS)

A Living Signal Research Evidence Based Doctor Handout

Purpose:

To clarify the evidence based and evolving diagnostic methods for Mast Cell Activation Syndrome (MCAS) and to finally correct one of the most common misconceptions in modern medicine: that the only way to diagnose MCAS is by “catching” elevated blood levels in real time during a flare.

For thousands of patients with Ehlers Danlos Syndrome (EDS), Dysautonomia/POTS, and overlapping connective tissue or immune disorders, this narrow approach fails them. Mediator testing often comes back normal, not because mast cells aren’t active but because the activation is localized, tissue-based, and missed by serum testing alone.

Why This Handout Matters:

Too many patients have been told their bloodwork “looks fine” when the problem was never in their blood to begin with.

This handout bridges that gap, giving both patients and clinicians a clear, citation supported roadmap that explains:

• Why histamine and prostaglandin D₂ degrade within minutes if samples aren’t handled properly

• Why normal tryptase does not rule out MCAS

• How GI or bone marrow biopsies stained for CD117, tryptase, and CD25 can confirm mast-cell overactivity missed by routine pathology

• The differences between systemic vs. tissue-restricted activation

• The clinical danger of provocation testing and why it is not recommended for patients with autonomic or vascular instability

Inside This 4 Page PDF:

• Step-by-step breakdown of MCAS diagnostic pathways, from mediator testing to tissue staining
• Real case study: A colon biopsy reprocessed with CD117 revealing “39 mast cells per high power field” after standard histology found “no abnormalities”
• Myth vs. Reality section — direct quotes from Mayo Clinic Proceedings, Blood, and Clinical Therapeutics debunking outdated testing assumptions
• Histopathology guidelines — for communicating with labs and requesting proper stains
• Clinical snapshot section summarizing the full symptom spectrum, including multi-system hypersensitivity, extreme food intolerance, and medication reactivity

Who It’s For:

• Patients told “your mast cell test was normal” despite clear symptoms

• Clinicians seeking updated, peer-reviewed diagnostic standards

• Advocacy groups, EDS/POTS specialists, and pathologists coordinating care for complex connective-tissue patients

Format:

4 page printable PDF (8.5 × 11 in)

Professionally formatted · Fully citation supported · Designed to guide diagnostic discussions and improve accuracy in both patient and clinical settings