Mast Cell Activation (MCA), Fibromyalgia, and Ehlers-Danlos Syndrome (EDS): The Overlapping Connection

By SWA

Understanding Mast Cell Activation Syndrome (MCAS): Symptoms, Testing, and Overlapping Conditions

Mast Cell Activation Syndrome (MCAS) is a complex and often underdiagnosed condition in which mast cells—a type of immune cell—release excessive amounts of chemical mediators, such as histamine, prostaglandins, and cytokines. These mediators affect multiple body systems and can lead to a wide range of chronic, fluctuating symptoms.

What Are Mast Cells?

Mast cells are immune cells found in connective tissues throughout the body, particularly in the skin, lungs, gastrointestinal tract, and blood vessels. Their normal role is to protect the body from allergens, infections, and injury. However, in MCAS, mast cells become abnormally reactive and release mediators too easily or excessively.

Skin-Related Symptoms of MCAS

The skin is one of the most commonly affected organs in MCAS. Symptoms can range from mild to severe and are often mistaken for common dermatological issues.

  • Itching (pruritus): A frequent complaint that can occur without visible rash.

  • Hives (urticaria): Raised, itchy welts that appear and disappear unpredictably.

  • Swelling (angioedema): Often seen in the face, lips, or extremities, caused by fluid leakage from blood vessels.

  • Flushing: Redness of the skin, particularly on the face, neck, or chest, due to blood vessel dilation.

  • Rashes: Can be diffuse or localized, and may mimic eczema or other skin disorders.

  • Other skin signs:

    • Migratory redness or blotchiness

    • Acne-like folliculitis

    • Striae (stretch marks) not related to weight gain or corticosteroids

Other Systemic Symptoms of MCAS

Mast cells are present throughout the body, so symptoms can affect nearly every organ system:

Gastrointestinal:

  • Abdominal pain

  • Diarrhea or constipation

  • Nausea and vomiting

  • Heartburn or acid reflux

Cardiovascular:

  • Low blood pressure (hypotension)

  • Rapid heartbeat (tachycardia)

  • Lightheadedness or fainting

  • Palpitations (especially during flares)

Respiratory:

  • Shortness of breath

  • Wheezing or asthma-like symptoms

  • Throat tightness

Neurological:

  • Headaches or migraines

  • Fatigue or brain fog

  • Anxiety or mood swings

  • Tingling or numbness

Musculoskeletal and Other:

  • Muscle cramps

  • Bone or joint pain

  • Enlarged lymph nodes

  • Sensitivity to temperature, light, or smells

Common Triggers for MCAS Symptoms

Identifying and avoiding triggers is key to managing MCAS. These can vary between individuals but may include:

  • Allergens: Pollen, pet dander, foods, fragrances, or chemicals

  • Stress: Emotional stress, sleep deprivation, or physical trauma

  • Medications: NSAIDs, opioids, certain antibiotics, or excipients in drugs

  • Infections: Viral or bacterial infections can worsen symptoms

  • Hormonal changes: Menstruation, pregnancy, menopause

  • Physical triggers: Heat, cold, friction, pressure, or exercise

Diagnosis of MCAS

Why Diagnosis Is Challenging

MCAS symptoms often overlap with other conditions like allergies, fibromyalgia, Ehlers-Danlos Syndrome (EDS), irritable bowel syndrome, and chronic fatigue. Lab values can fluctuate, and tests require precise timing and handling.

Most Effective Tests for MCAS

There is no single test that confirms MCAS, but several mast cell mediator tests are commonly used:

A. Mast Cell Mediators

  • Serum Tryptase

    • Drawn during a flare; elevated baseline (>11 ng/mL) or increase by 20% + 2 ng/mL from baseline supports diagnosis.

  • Urinary N-Methylhistamine (24-hour or random sample)

    • Stable histamine metabolite.

  • Plasma Histamine

    • Must be collected and frozen within minutes due to rapid breakdown.

  • Urine Prostaglandin D2 or 11-β-PGF2α

    • Key indicators of mast cell activation.

  • Urine Leukotriene E4

    • May reflect chronic activation.

B. Supporting Tests

  • Plasma or urinary heparin

  • Chromogranin A (non-specific but sometimes elevated)

C. Clinical Criteria

Diagnosis is based on:

  1. Symptoms involving two or more organ systems (e.g., skin + gut).

  2. Objective lab evidence of elevated mast cell mediators.

  3. Improvement with mast cell-targeted medications, such as H1/H2 blockers, mast cell stabilizers, or leukotriene inhibitors.

MCAS, Fibromyalgia, and Ehlers-Danlos Syndrome (EDS): An Overlapping Triad

Research and clinical observation have shown a strong link between MCAS, Fibromyalgia (FM), and Ehlers-Danlos Syndrome (EDS)—especially hypermobile EDS (hEDS).

Shared Features

  • Chronic pain

  • Fatigue and brain fog

  • Gastrointestinal distress (often labeled IBS)

  • Autonomic dysfunction (e.g., POTS – Postural Orthostatic Tachycardia Syndrome)

  • Sensitivity to foods, medications, and environmental factors

The Connection

  • In EDS, collagen defects make connective tissues more vulnerable; mast cells, which reside in these tissues, may be more likely to become dysregulated.

  • In Fibromyalgia, mast cells may contribute to widespread pain and neuroinflammation.

  • Many patients with EDS or FM report classic MCAS symptoms and benefit from mast cell-directed treatments.

Treatment Approaches

While there's no cure for MCAS, symptom control is achievable through a multi-pronged approach:

1. Medications

  • Antihistamines

    • H1 blockers: Cetirizine, Loratadine

    • H2 blockers: Famotidine, Ranitidine

  • Mast Cell Stabilizers

    • Cromolyn sodium, Ketotifen, Quercetin

  • Leukotriene Inhibitors

    • Montelukast

  • Low-dose Naltrexone (LDN)

    • May reduce inflammation and pain

  • Epinephrine autoinjector for anaphylaxis risk

2. Diet and Lifestyle

  • Low-histamine diet

  • Avoid known triggers

  • Stress management and pacing

  • DAO enzyme supplements to help break down histamine in the gut

Final Thoughts

Mast Cell Activation Syndrome (MCAS) is a systemic condition that often hides in plain sight, especially when overlapping with chronic illnesses like fibromyalgia and EDS. Its wide range of symptoms, particularly skin involvement, make it both complex and easily misdiagnosed.

If you suspect you have MCAS, early identification and a tailored treatment plan can significantly improve quality of life. Partner with a knowledgeable provider—ideally a specialist in immunology or mast cell disorders—for proper evaluation, testing, and symptom management.
What is Mast Cell Activation Syndrome (MCAS)
https://swaresearch.blogspot.com/2023/10/what-is-mast-cell-activation-syndrome.html

Dr. Maitland is considered one of the thought leaders in the emerging field of mast cell disorders. She currently serves on the medical and scientific advisory boards of the Ehlers-Danlos Society, the Mastocytosis Society, and the Bobby Jones Chiari & Syringomyelia Foundation. She is the former Past Chair of the Committee for the Underserved and the current Vice Chairperson for the Mast Cell Disorders Committee of the American Academy of Allergy, Asthma, and Immunology. She is also a member of the Allergy and Immunology Faculty of the National Medical Association.
https://www.youtube.com/watch?v=xGZIojcrjbY&t=1231s

© 2000-2025 Sieglinde W. Alexander. All writings by Sieglinde W. Alexander have a fife year copy right. Library of Congress Card Number: LCN 00-192742 ISBN: 0-9703195-0-9

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