What is Mast Cell Activation Syndrome?

What is Mast Cell Activation Syndrome?

“Traditionally, Mast Cell Activation Syndrome (MCAS) was considered a rare disease generally focusing on the mast cell mediators tryptase and histamine and the blatant symptoms of flushing and anaphylaxis. New research indicates that it plays a large role in many chronic health conditions. Mast cells are coordinators of our immune systems response to allergens, infections, and toxins. When activated they secrete over 200 chemical mediators, the most well known is histamine, serotonin and tryptase. A wide variety of stimuli can activate them, including, chronic infections, such as Lyme disease, mold toxicity, viruses, parasites, and environmental toxins.” Dr. Denise Clark, Mast Cell & Tick-Borne Disease Specialist.

What Are The Symptoms Of Mast Cell Activation Syndrome?

“Symptoms of MCAS can be similar to many other diseases, which makes it difficult to diagnose. The most common symptom is rapid onset after eating of flushing, palpitations, itching, tongue swelling, wheezing, gas, bloating, nausea, vomiting, abdominal pain, and dizziness. Research indicates that it is an under recognized contributor to neurologic and psychiatric symptoms, as well as multiple chemical sensitivities. A key to diagnosis is if water or food, any food, sets off a reaction and in 3-5 minutes reproducible symptoms occur.”– Dr. Denise Clark, Mast Cell & Tick-Borne Disease Specialist

Other symptoms of MCAS may include:

  • Malnutrition, vitamin & mineral deficiency
  • Dehydration
  • Migraine headache
  • Random itching
  • Tingling sensation
  • Nausea
  • Intolerance of heat or cold
  • Swelling in potentially any part of the body
  • Eye irritation
  • Difficulty taking a deep breath
  • Reflux of stomach acid
  • Brain fog
  • Rashes & hives
  • Throat irritation & swelling
  • Excessive sweating
  • Environmental allergies, medication and chemical sensitivities
  • Chest discomfort or pain
  • Diarrhea or constipation
  • Difficulty swallowing
  • Vision disturbances
  • Urinary frequency or hesitancy
  • Poor wound healing
  • Unexplained weight gain or loss
  • Urge to cough
  • Anxiety and panic
  • Heavy and painful menstrual cycle
  • Asthma
  • Hair thinning and loss
  • Depression
  • Sinusitis
  • Fatigue
  • Insomnia
  • Sense of urinary tract infection even though urine tests show no infection
  • Tremor
  • Frequent infections
  • Sores in the mouth
  • Easy bleeding or bruising
  • Enlargement and tender lymph nodes

Symptoms may come and go over time.

How is Mast Cell Activation Syndrome Diagnosed?

  1. Clinical presentation- does the patient’s history and symptoms lineup with MCAS?
  2. Elevated biopsies or laboratory evidence of mast cell activation.
  3. Ruling out all other possible disease.

MCAS can be difficult to diagnose and is often missed due to its complexity and the fact that standard testing may not reveal anything abnormal at the time. As of right now there is no standard diagnosing protocol set for MCAS.

Lab Tests for Mast Cell Activation Syndrome (MCAS)


Tests for Mast Cell Activation Syndrome (MCAS) Tests for MCAS may include:

  • Serum tryptase
  • Serum chromogranin A
  • Plasma histamine
  • Plasma PGD2
  • Plasma heparin
  • Urine for PGD2
  • Urine for 11-beta-PGF2-alpha
  • Urine for N-methylhistamine
  • GI and GU biopsies

Tryptase is an enzyme that is released from a mast cell during activation. This test is usually normal in patients with MCAS but may be elevated sometimes. The 2017 study “Characterization of Mast Cell Activation Syndrome” by Lawrence B. Afrin, MD*, Sally Self, MD, Jeremiah Menk, MS, & John Lazarchick, MD showed that only 16% of 400 mast cell activation syndrome patients had elevated tryptase levels. (American Journal of the Medical Sciences, 353(3), 207-215.)

High levels of chromogranin A can suggest MCAS, but you must first rule out other causes such as heart failure, renal insufficiency, neuroendocrine tumors and proton pump inhibitor use.

Heparin is a very sensitive and specific marker for mast cell activation, but due to its quick metabolism, continuous specimen chilling and an ultra-sensitive plasma heparin assay are usually needed to detect the levels of heparin released by mast cells.

Prostaglandin D2 is produced by several other cell types, but mast cell release is responsible for the dominant amount found in the body. Accurate measurement of PGD2, like heparin, requires continuous specimen chilling.

“In MCAS patients, gastrointestinal or genitourinary tract biopsies may show increased mast cells (best identified by CD117 staining), just not in the numbers, or in the abnormal patterns, seen in mastocytosis. Though there’s still some controversy to this, many doctors feel 20 mast cells per high-power (400x) field under the microscope is a reasonable threshold distinguishing normal from abnormal mast cell counts in the GI and GU biopsies.”-Lawrence B. Afrin, M.D, Mast Cell Disease Specialist

Some of the mast cell mediators are very sensitive to heat, requiring continuous chilling of specimens sent for mediator testing. Make sure to discuss all your current medications (and supplements) with your doctor as some medications may interfere with levels of certain mediators.

Mast Cell Triggers


  • Exercise.
  • Food or beverages (including alcohol & city or bottled water.)
  • Pharmaceutical drugs and contrast dyes.
  • Natural odors, chemical odors, cigarette smoke, pesticides, herbicides, perfumes and scents, fumes from preparing foods.
  • A venomous bite or sting from a bee, wasp, spiders, fire ants, snakes, jelly fish, biting insects, such as flies, mosquitos and fleas, etc.
  • Viral, bacterial or fungal infections.
  • Emotional or physical stress
  • Vibration, friction or mechanical irritation to skin.
  • Pollen
  • Pain
  • Sun/sunlight
  • Hot or cold climates and sudden temperature changes.
  • Environmental pollution and mold exposure.
  • Hormonal fluctuations
  • Additives in medications and food

How is Mast Cell Activation Syndrome TREATED?

Treatment for MCAS is a slow process that takes time, patience and understanding. One of the most important things when trying to treat MCAS is trying to find the underlying root cause of the MCAS. There are many pharmaceutical and natural treatment options available that have shown to be helpful in controlling dysfunctional mast cells and lessening symptoms. Due to the complexity of MCAS some patients may tolerate a certain treatment while another may not therefore each patient will have to go through a trial and error process of their own. Some patients may experience immediate reactions to a treatment while others may experience delayed reactions therefore it is encouraged to start by introducing one medication or supplement at a time within a reasonable amount of time.

MCAS is not an allergy. Something like toxins from Lyme or Mold comes in contact with activated mast cells and they release mediators.

 If you believe you have symptoms of MCAS it is important to identify and treat the underlying cause as you concurrently diffuse the MCAS. It can be treated by the use of mast cell stabilizers, interfering with the mediators so that they have less effect and reducing the unavoidable effects of mediators.” Dr. Denise Clark

Some treatments include:

1. A Low Histamine Diet (here is a histamine-restricted diet)

Here is a list of thing that it’s best to avoid 

  • Alcoholic beverages
  • Processed or smoked fish products. Use fresh wild caught fish instead.
  • Raw and cured sausage products.
  • Pickles.
  • Citrus fruits.
  • Instant Coffee & Black Tea.
  • Chocolate.
  • Nuts.
  • Yeast and yeast extracts.
  • Soy products.
  • Artificial food colorings & preservatives
  • Spices such as: cinnamon, cayenne pepper, cloves, nutmeg, curry powder.
  • Aged cheese
  • Large amounts of spinach or kelp.

2. Diamine oxidase enzymes with meals may help to break down histamines in food.

3. H1 and H2 Blockers

    • H1 Blockers
      • hydroxyzine, doxepine, diphenhydramine, cetirizine, loratadine, fexofenadine
    • H2 Blockers
      • Famotidine (Pepcid, Pepcid AC)
      • Cimetidine (Tagamet, Tagamet HB)
      • Ranitidine (Zantac)

4. Prescription, Natural Anti-histamines and Mast Cell Stabilizers

    • Quercetin
    • Ketotifen
    • Hyroxyurea
    • Ascorbic Acid
    • Cromolyn
    • Vitamin B6 (pyridoxal-5-phosphate)
    • Omega-3 fatty acids (fish oil, krill oil)
    • Alpha Lipoic Acid
    • N-acetylcysteine (NAC)
    • Vitamin D3
    • Methylation donors (SAMe, B12, methyl-folate, riboflavin)
    • Organic Medical Cannabis

5. Leukotriene Inhibitors

    • Montelukast (Singulair)
    • Zafirlukast (Accolate)

6. Tyrosine Kinase inhibitorsimatinib

7. Certain probiotics decrease histamine production

  • Lactobacillus rhamnosus and bifidobacter species

(Please Note this is for references purpose only, always consult your doctor before making any changes to your current medical routine.)

Diseases Associated with Mast Cell Activation Syndrome (MCAS)

  • Mold Toxicity
  • Tick-Borne Disease
  • Ehlers-Danlos
  • Chemical Sensitivity
  • Autism
  • Autoimmune diseases such as:
  • Hashimoto’s, Multiple Sclerosis, Bullous Pemphigoid, Systemic Lupus, Rheumatoid Arthritis along with others.
  • Celiac Disease
  • Chronic Fatigue Syndrome
  • Chronic Inflammatory Response Syndrome
  • Eosinophilic Esophagitis
  • Food Allergy & Intolerances
  • Gastroesophageal reflux
  • Infertility as mast cells in endometrium may contribute to endometriosis.
  • Irritable Bowel Syndrome
  • Migraine Headaches
  • Mood disorders – anxiety, depression, and insomnia
  • Dysautonomia
  • Postural Orthostatic Tachycardia Syndrome.
  • Interstitial Cystitis
  • Fibromyalgia


Looking for a support group?

Mast Cell & Tick-Borne Disease Awareness Group(This group focuses on Mast Cell Activation Syndrome & Tick-Borne Disease, including Alpha-Gal Syndrome)

Mast Movement (This group is open to Mastocytosis & Mast Cell Activation Syndrome)





What is Mast Cell Activation Syndrome?



Click to access MCAS-Afrin.pdf







Click to access Mast-Cell-Disorders-in-EDS-Nonexpert-S.pdf


A Tale of Two Syndromes – POTS and MCAS












Medical Disclaimer
This content is for informational and educational purposes only. It is not intended to provide medical advice or to take the place of such advice or treatment from a personal physician. All readers/viewers of this content are advised to consult their doctors or qualified health professionals regarding specific health questions. Ticked Off Mast Cells nor the publisher of this content takes responsibility for possible health consequences of any person or persons reading or following the information of content on this site.


  1. I have Fibromyalgia, IBS, heart disease, Alpha-gal Syndrome, and liver disease. I’m sensitive to latex, perfumes, soaps, some eye makeup. Antibiotics too.Have had depression most of my life.

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