Is It MCAS or Something Else? Key Signs & Treatment Tips

Piecing Together the Puzzling Symptoms of Mast Cell Activation Syndrome

• What Is MCAS?|
• Symptoms|
• Is it Something Else?|
• Diagnosis|
• Treatments|
• Simple Solutions|

MCAS, or mast cell activation syndrome, is a condition that can sometimes make you feel like you’re reacting to practically everything you eat, touch, or inhale.

Although the prevalence of MCAS is unknown [1], one estimate based on about 30 million people suggested that only 6.2 (0.0062%) of every 100,000 people have it [2]. At the other end of the spectrum, some estimates suggest up to 17% of the population is affected, at least mildly [3].

The cause of MCAS symptoms is an immune system that’s in overdrive. The symptoms, which move around the body and come and go, can affect the skin, brain, gut, and joints. What causes them are immune cells called mast cells being triggered into action too often.

Though the internet has plenty of generic information on MCAS, it can be hard to find the practical advice and guidance needed to navigate this complex condition.

In this article, I aim to change that by sharing some of my clinical experience with MCAS, including how I approach diagnosis, and the treatment steps that help my clients the most. Let’s start with what the symptoms of MCAS can look like and what causes them.

What Is Mast Cell Activation Syndrome?

Mast cells are white blood cells that release inflammatory substances that call the immune system into action when needed [4].

Triggers for MCAS symptoms can include many things we experience regularly, such as:

• Stress [5]
• Foods [6]
• Alcohol [5]
• Excipients (coloring agents, preservatives, or fillers) in medications [7]
• Infections [8]
• Toxins [8]
• Allergic reactions [9]
• Strong odors (like perfumes, smoke, or cleaners) [5]
• Large temperature fluctuations [5]
• Certain drugs (like morphine, NSAIDs, antibiotics, or aspirin) [5] 
• Exercise [8]
• Bug bites [9]

When something triggers a mast cell, it degranulates, which means it bursts and releases a bunch of chemical mediators, or compounds that participate in inflammation. The most significant of these chemicals is histamine, which can cause inflammation flares throughout the body, including the brain.

In people with MCAS, mast cells sometimes degranulate on a large scale, flooding the body with histamines and other compounds, causing multiple allergy-type or intolerance-type reactions.

MCAS may be caused by a mutation in what’s called the KIT gene or by an allergy (say to a drug, food, or insect bite) [8]. But usually, its origin is unknown, which is called idiopathic MCAS [10].

MCAS Symptoms

Next is a list of common symptoms that can occur during an MCAS flare. The severity of symptoms can be unpredictable, affecting many organ systems and migrating around the body.

• Dermatologic (skin) symptoms
  • Flushing [5, 11] 
  • Itching [5]
  • Sweating [5]
  • Hives (aka urticaria, a common skin rash) [5, 11]
  • Dermatographia (aka skin writing, when a light scratch on the skin causes a raised red line) [5, 11]
• Respiratory symptoms
  • Runny nose [5]
  • Itchy or swollen throat [5]
  • Shortness of breath [5, 11]
  • Wheezing [5]
• Gastrointestinal symptoms
  • Abdominal cramping or pain [5, 11]
  • Diarrhea that often alternates with constipation [5, 11]
  • Nausea [5, 11]
  • Bloating [5]
• Heart symptoms
  • Heart palpitations (heartbeat feels rapid, strong, or irregular) [5, 11]
  • Dysfunctional autonomic nervous system (eg. postural orthostatic tachycardia syndrome, dizziness upon standing up, swings in blood pressure and heart rate, and body temperature that doesn’t reflect the environmental temperature) [5, 11]
• Nervous system symptoms
  • Headache [5, 11]
  • Sensory neuropathy (weird sensations like pins and needles, tingling, or numbness) [5, 11]
  • Brain fog [5, 11]

All this means that MCAS is very hard to diagnose. So, before jumping to the conclusion that a client has MCAS, I always work with them to figure out if there could be other causes of their symptoms. 

Is It MCAS or Something Else?

A helpful way to find out if MCAS is a possibility for you is to visit Beth O’Hara’s site, Mast Cell 360, and take her MCAS Symptoms Survey. Note that some conditions look a lot like MCAS, but aren’t. An MCAS specialist will want to rule these out before making an MCAS diagnosis.

Systemic mastocytosis [11]: In this rare condition, too many mast cells build up in the skin, bone marrow, digestive tract, or other organs. The resulting symptoms can look a lot like MCAS, but they can lead to organ damage [13].

Histamine intolerance [6]: Symptoms of histamine intolerance can arise when too much histamine builds up in the body because the body can’t break it down properly. Potential causes include:

• Having low gut levels of diamine oxidase (DAO), the enzyme that breaks down histamine
• Eating too many high-histamine foods, such as
  • Fermented foods (aged cheeses, wine, kimchi, sauerkraut)
  • Avocado, citrus, strawberries, kiwi, papaya, pineapple, dried fruit
  • Tomatoes, spinach, eggplant
  • Fish, shellfish, canned fish, aged beef, cured meats
  • Leftovers
• Having gut microbes that create too much histamine when metabolizing histidine, a normal amino acid in dietary proteins

Many other conditions can also create MCAS-type symptoms. These may include (but aren’t limited to) [6]:

• Inflammatory bowel disease
• Celiac disease
• Other autoimmune disorders
• SIBO (small intestinal bacterial overgrowth)
• Chronic pain and fatigue syndromes
• Fibromyalgia
• Chronic Lyme disease syndrome
• Panic disorders
• Hormone- or digestion-related cancers

When clients come to me suspecting MCAS or with MCAS-like symptoms of uncertain cause, I start with the general protocol outlined in the following 5 steps. 

1. First, we improve their gut health and reduce dietary histamine levels.
2. If symptoms persist, we experiment with natural antihistamine therapies, including probiotics, vitamin C, and quercetin. 
3. If symptoms still persist, I have them fill out an MCAS questionnaire, based on the Afrin and Molderings diagnostic questionnaire [14].
4. If they score above 8, I refer them to an MCAS specialist to firm up a diagnosis.

This procedure moves the client through helpful actions that can generally improve their symptoms while helping us narrow down whether MCAS is the likely problem or not. It’s not uncommon for people to get a lot of relief from gut health treatments and natural antihistamines, regardless of their eventual diagnosis.

Closing in On an MCAS Diagnosis 

If you decide that it makes sense to pursue further testing, an MCAS specialist can then help you figure out whether you meet the diagnostic criteria for MCAS.

An MCAS specialist can make a positive MCAS diagnosis if:

• You have periodic, repeating symptoms of mast cell reactivity that affect at least 2 organ systems [1].
• After taking antihistamines, leukotriene blockers, or mast cell stabilizers (see next section), your symptoms resolve or become less frequent or severe [1].
• You take a blood test during a flare (rarely easy to do) that shows positive results for tryptase (an enzyme stored in mast cells) or high levels of other compounds from mast cells [6]. 

Treatments to Combat Excess Histamine

Let’s now look at some basic steps that may reduce mast cell reactivity and excess histamine levels. I usually recommend that my clients with MCAS-like symptoms get started on these, whether they have a firm MCAS diagnosis or not. 

Sometimes, just avoiding triggers and improving poor gut health is enough to make MCAS-type symptoms go away without needing a specific diagnosis. 

1. Avoiding Triggers 

As you start to learn what your triggers are (allergic reactions, infections, toxins, certain foods, strong odors, temperature changes, stress, alcohol, certain drugs, exercise, insect stings or bites), you can do your best to avoid them. The ideal way to find out what’s setting off flares is to start tracking, perhaps on paper, in a spreadsheet, or in a symptom-tracking app.

2.  Diet and Gut Health Improvements

Next, I consider gut health when it comes to suspected MCAS because the gut and mast cell disorders are interconnected. Improving one usually improves the other.

For example, IBS, which is the most common functional gut disorder, is associated with a 16-times greater risk of MCAS [15]. And SIBO is three times more common in people with MCAS than in healthy people [16]. 

In addition, research suggests that hyperactive mast cells may offset the balance of gut microbes and contribute to inflammatory bowel disease [17]. And the chemicals that mast cells release could disrupt gut immunity and motility (how food moves through the gut) [16].

When it comes to MCAS specifically, we have evidence from animal and cell studies that suggests a low-histamine diet [6] or a low-FODMAP diet [6, 18, 19] might help MCAS. 

Human research hasn’t yet tested the effects of either a low-histamine or a low-FODMAP diet in people with MCAS, but studies do show these diets can reduce histamine levels in humans [20, 21]. The low-FODMAP diet can also reduce the levels of tryptase, an enzyme from mast cells that may play a role in inflammation [18]. 

I usually find it best for my clients to start with a nutrient-rich, whole-food diet (like a Paleo or Mediterranean diet) while watching out for any reactions related to eating high-histamine foods (see list above). Sometimes, cleaning up the diet to this degree is enough to help people’s immune systems calm down.

However, more targeted elimination diets may be appropriate, depending on a person’s specific MCAS-like symptoms. From my clinical experience:

• A low-FODMAP diet may work best if IBS symptoms (bloating, diarrhea, constipation, abdominal pain, or early fullness) are most noticeable [6].
• A low-histamine diet is a good choice if symptoms seem strongly triggered by high-histamine foods [6].
• A liquid elemental diet could be the right choice if MCAS-like symptoms are severe and triggered by many foods [6]. An elemental diet can give the gut a rest and allow the immune system to calm down before slowly reintroducing foods.

Useful cooking tip: Histamine levels usually increase when you fry or grill, but boiling has no effect on—or may even reduce—histamine levels [22].

Probiotics

We still don’t know how probiotics affect people with MCAS, specifically. The only direct research on how probiotics affect MCAS is in cell and mouse studies that suggest probiotics might reduce mast cell activity, including degranulation, in humans [23, 24]. 

However, in the clinic, we’ve found that improving gut microbiome health with probiotics seems to help mitigate high-histamine symptoms. In fact, a meta-analysis showed that probiotics can reduce histamine-related symptoms of seasonal allergies [25], so it wouldn’t be surprising if they can help with histamine overload in MCAS patients, too.

3. Antihistamine Self-Help

It can be helpful to take over-the-counter (OTC) antihistamines when trying to get MCAS or similar flares under control. The two common OTC antihistamines, available at any pharmacy, are H1 receptor blockers, namely cetirizine (Zyrtec), and loratadine (Claritin). 

Vitamin C may also be worth taking: One clinical study found that patients with infectious or allergic diseases who received intravenous vitamin C had meaningful reductions in histamine [26]. Studies on oral vitamin C supplements and histamine levels in humans are lacking, but C is generally a safe vitamin that is okay to take in doses up to 2,000 mg a day [27].

Although we’ll have to wait for human studies to confirm, cell and animal research suggest other supplements might also improve mast cell signaling and histamine release. These include:

• Quercetin [28]
• Vitamin D [28]
• Vitamin E [28]
• Selenium [28]
• Omega-3 fatty acids [28]
• Luteolin [28]
• Caffeic acid [28]
• Kaempferol [28]
• Myricetin [28]
• Curcumin [28]
• Butyrate [29]

4. Prescription Medications

If you have a clear MCAS diagnosis and severe symptoms that don’t improve with OTC medicines, a specialist doctor, such as an allergist or immunologist, may want to try a variety of drugs. Depending on the body systems involved, these could include [5]:

• Mast cell stabilizers, like cromolyn sodium or ketotifen
• Leukotriene blockers, like the asthma drug montelukast, brand name Singulair
  • Like histamine, leukotrienes are inflammatory agents that mast cells release.
• Corticosteroids for life-threatening reactions like anaphylaxis
• Anti-IgE medications such as omalizumab, brand name Xolair
  • Anti-IgE meds interfere with the function of IgE, an antibody in the immune system.
• Higher doses of the natural antihistamine, quercetin

Simple Solutions for a Complex Condition

In conclusion, MCAS is confusing because it can cause a huge array of symptoms that don’t happen predictably, have hard-to-identify triggers, and are hard to separate from other things going on in the body.

However, whether you have a validated diagnosis of MCAS or MCAS-like symptoms doesn’t really matter, as the treatment approach remains the same. 

Improving gut health, usually with an elimination diet and probiotics, is a great place to start when managing many cases of MCAS and MCAS-like symptoms. 

Perhaps the best way to gain confidence when dealing with MCAS, diagnosed or suspected, is to figure out what triggers your symptoms and avoid those triggers. Another empowering strategy is to have a couple of reliable antihistamine supplements or (ideally doctor-approved) medications on hand for flares.

Ultimately, though, MCAS and other forms of mast cell activation disorders can be too difficult to resolve alone. If you have or suspect you may have MCAS or something similar, you can reach out to one of our experienced health practitioners for help.

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