Mast Cell Activation Syndrome (MCAS) is a complex illness that describes a plethora of symptoms affecting nearly every system of the body. Patients with MCAS experience symptoms that seem unrelated but do have one common factor—the over-stimulation of mast cells, one type of cell with an important immune system function.


What are mast cells? They are a lesser known type of immune system cell that connect the immune system and nervous system. They help organize the immune response to threats like infections or toxins. Mast cells primarily are found in the sinuses, throat, respiratory passages, digestive tract, skin, and genitourinary tract, but smaller numbers of mast cells can be found in every part of the body. Mast cells are one of the body’s first lines of defense against pathogens.


Mast cells contain several components called “granules,” the most relevant being histamine, serotonin, and tryptase, and are prepared to release these granules at a moment’s notice. In a body that is overloaded by toxins or infection, mast cells become hyper-stimulated and overreact to the slightest change in their environment. A food, smell, chemical, light, sound, or movement that was previously tolerated may suddenly trigger a strong reaction due to this hypersensitivity. In contrast, another time the stimuli is encountered, there may be no noticeable reaction. The unpredictability of mast cells’ response is one of the most frustrating things about this condition.


Patients grow used to being dismissed by well-meaning family or healthcare professionals as “overreacting” or “just being too sensitive,” when in reality, their mast cells are too sensitive. It is truly possible for a severe MCAS patient to react negatively to drinking a glass of water. There’s a valid biological reason for every symptom.


Some of the symptoms associated with MCAS include:

  • intense anxiety and depression
  • severe pain that can localize to joints, muscles, tendons, and/or bones
  • unusual neurological symptoms, like numbness and tingling in different parts of the body, paralysis, and pseudo seizures
  • headaches
  • ringing in the ears (tinnitus)
  • sensitivity to a wide variety of stimuli, such as touch, sound, smells, foods, chemicals, and electromagnetic fields (EMF)
  • sore throat
  • swollen lymph glands
  • indigestion, including diarrhea, constipation, bloating, gas, dissension, and heartburn (especially when symptoms occur within 5 minutes of consuming food or drink)
  • chronic debilitating fatigue
  • insomnia
  • cognitive difficulties, including brain fog and decreased focus, memory, and concentration
  • pelvic pain
  • interstitial cystitis (a painful inflammation of the bladder)
  • shortness of breath
  • “air hunger”
  • skin rashes
  • difficulties with equilibrium and balance

(list compiled by Dr. Neil Nathan)


While some of these symptoms seem similar to those of common allergies, there are distinct differences. Allergies are consistent reactions to the same stimuli, involving IgE antibodies. In contrast, mast cells release granules like histamine in response to seemingly random or inconsistent stimuli.


Diagnosis of MCAS can be complicated due to the unpredictable nature of the illness. The trademark granules like histamine can be in and out of the body within minutes, and accurate diagnosis depends on catching them within that short time frame. Some of the current diagnostic tests include:

  • Total serum tryptase
  • Chromogranin A
  • Plasma heparin and/or histamine
  • Urinary N-methylhistamine
  • Urinary PGD2 or its metabolite, 11-beta-PGF2-alpha
  • Leukotriene E4
  • Antibodies to IgE (anti-IgE IgG) and antibodies to IgE receptors are not currently seen as diagnostic of mast cell activation syndrome, but rather a hint that autoantibody-mediated mast cell activation may be present.
  • Tissue biopsy may be re-examined after staining with CD117 to look at mast cell population in that specimen

(list compiled by Dr. Neil Nathan)

The first approach to treating MCAS after diagnosis should be diagnosing the root cause, then reducing the patient’s sensitivity by calming the immune and nervous systems, and identifying the underlying cause(s) of mast cell hyper-sensitization. There are several protocols that may accomplish this, including elimination diets, treatment of bacterial or viral overgrowth, and detoxing from mold or heavy metals, if present. The exact protocol will vary from person to person to account for biological and toxicity differences among patients. The most common underlying causes for MCAS include toxic mold and Bartonella (a confection of Lyme disease), and its treatment will also vary depending on what the patient tolerates best.