Working in medicine is akin to detective work. We follow clues the body offers as signs, include the symptoms experienced by the patient, and try to piece them together into a single cause. Some conditions can prove difficult to diagnose, especially if symptoms appear randomly, at multiple places in the body, and in varying severities. One such condition is mast cell activation syndrome (MCAS).
WHAT ARE MAST CELLS?
From the outside, the body may look like a single entity, when in fact, we are each formed by trillions of tiny cells, working together in unique ways to sustain us. While most cells have basic functions and processes, others, like immune cells, are nothing short of remarkable in both their complexity and their intelligence. Mast cells are immune cells—white blood cells that look like a sponge full of seeds. These “seeds” are tiny vesicles that store chemical mediators such as histamine, leukotrienes, and prostaglandins. Histamine is the primary and most abundant mediator in MCAS. Depending on its environment, histamine can increase blood flow, constrict airways, create mucus, mediate inflammation, and play a major role in allergic reactions. A runny nose, teary eyes, an itchy rash, and even indigestion are all results of histamine release by mast cells in the presence of an allergen they perceive as harmful. A mast cell in the absence of a threat, however, is just another cell quietly surveying the body for problems. The true wisdom of these cells is in knowing not only when to engage and attack but also when to be neutral and harmless. The moment the cell loses its ability to remain neutral, it becomes a liability.
MCAS
MCAS occurs when mast cells are overly active without a known mechanism.1 While the cause is still being researched, what has been observed is defective mast cells overproduce clone mast cells that spontaneously release their chemical mediators, resulting in various symptoms. Some patients may have mild symptoms for some time before seeing an increase in frequency or severity, while others may experience severe symptoms seemingly out of nowhere. Reactions seen in MCAS may be similar to anaphylactic reactions but differ in that anaphylactic reactions have a very clear cause and effect and occur within seconds to minutes of exposure. Anaphylactic reactions are caused by a known and singular antigen, while the causes of MCAS can be more ambiguous. Triggers of mast cell activation include exposure to heat/cold, viruses/bacteria, foods, toxins, and allergens, as well as physical or psychological stress. The diversity of symptoms, triggers, and varied frequency and severity make MCAS difficult to identify and diagnose.
A study observing more than 400 patients with MCAS in the United States found that the most common symptoms in both children and adults were:
- fatigue (83%)
- fibromyalgia-type pain (75%)
- dizziness/fainting (71%)
- hives/itchy skin (63%)
The table below lists other common symptoms categorized by different systems in the body:
Who’s at Risk?
MCAS can develop both in early life and in adulthood and is suspected to affect 10–30 percent of the North American population. A study conducted in 2016 researched the demographic information of over 400 patients diagnosed with MCAS and found that 69 percent of the patients were women and 75 percent were Caucasian.
Diagnosis
Since MCAS is part of a spectrum of mast cell disorders and mimics symptoms of anaphylaxis, there are diagnostic criteria that need to be met before reaching a conclusive diagnosis.
These criteria include:
- The presence of anaphylactic symptoms without a clear cause
- The elevation of mast cell mediators (normally tryptase) during an episode
- The resolution of symptoms with inhibitors of mast cell mediators
Testing at the time of an episode can prove to be difficult, and normal levels of mediators do not necessarily rule out MCAS, making diagnosis challenging. When these criteria are met, further testing is conducted to rule out similar mast cell disorders. Biopsies from the gut, bladder, or skin may be done to confirm high or abnormal numbers of mast cells. Currently, there are no genetic tests available for diagnosis, but research is ongoing.
Other possible conditions must be eliminated that might overlap with MCAS, such as myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), Lyme, and asthma. More than one of these conditions can coexist, making the detective work more difficult.
ALTERNATIVE TREATMENTS
The following treatments have been shown to help reduce MCAS symptoms with varying levels of success:
- Quercetin: This flavonoid is found naturally in stinging nettle leaves, grapefruits, onions, apples, black tea, leafy green vegetables, and beans. It’s a mast cell stabilizer, inhibiting the release of histamine, prostaglandins, and leukotrienes, which we know are the most common mediators in MCAS. Research shows that quercetin was more effective than the pharmaceutical mast cell stabilizer cromolyn sodium. Dr. Theoharides, an experienced mast cell researcher, has noted the importance of incorporating quercetin when treating MCAS.
- Green tea: The EGCG found in green tea inhibits calcium from entering mast cells. Without calcium, mast cells cannot release inflammatory mediators. It also prevents the production of leukotrienes, another mediator found in mast cells.
- Curcumin: This well-known anti-inflammatory also has antiallergic activity, as it inhibits the release of mediators in mast cells.
- Resveratrol: This phenol naturally found in grapes, berries, and peanuts reduces the expression of inflammatory markers interleukin-6 and interleukin-8 and inhibits IgE allergy reactions.
- Diamine oxidase (DAO) enzymes: These mast cell stabilizers are highly effective at breaking down histamine and are best taken with vitamin C for optimal absorption.
- Vitamin C: Research has found that when Vitamin C levels decrease in the blood, histamine levels increase exponentially; they fall again when Vitamin C levels are restored. There is little evidence, however, to support its use alone as a natural antihistamine.
- Probiotics: A balanced and diversified gut microbiome has been shown to reduce inflammation in the body and improve immune system health. Some probiotic strains have histamine-producing properties, and strains that have shown symptom improvement still require more research involving MCAS patients. The following probiotic strains have been shown to help the breakdown of histamine:
- Bifidobacterium adolescentis
- Bacteroides thetaiotaomicron
- Bacteroides fragilis
- Lactobacillus rhamnosus
- Other supplements to consider: Adequate levels of Vitamin D, zinc, and magnesium are important to be maintained in people with MCAS. Vitamin D is vital in immune regulation; zinc is responsible for proper mast cell signalling; and low levels of magnesium have been shown to increase the emergence of mast cells.
LIFESTYLE TIPS
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Avoid triggers: While identifying triggers can be taxing, avoiding triggers can decrease mast cell activation and reduce future flares. Keeping a journal of foods, environmental exposures, temperature changes, activities, and symptoms can lead to more insight.
- Modify your diet: Following a low-histamine or FODMAP diet and reducing blood sugar fluctuations has been shown to reduce the frequency of flares in some individuals.
- Reduce stress: Stress increases histamine production in the body. Incorporating stress-reducing techniques into everyday life, such as meditation, yoga, nature walks, and breathing exercises, can be beneficial in reducing flares.
- Avoid alcohol: Alcohol consumption encourages the release of histamine from mast cells and inhibits the DAO enzymes responsible for the breakdown of histamine.
The awareness of MCAS is growing in North America, yet a timely diagnosis is still some years away. No two people are likely to experience MCAS in exactly the same way, and the extent of symptoms can be substantial. The potential severity of symptoms along with the unpredictability of triggers can impact their lives, families, and careers considerably. But there is hope. Both naturopathic and pharmaceutical treatments can increase the quality of life of MCAS patients, and there is more research on the way to further our understanding and improve positive outcomes.
