Takeaway: Massage is unlikely to fix or cure MCAS, but with care, knowledge, and sensitivity, MTs can create an experience for clients that feels safe and supportive of their wellness goals.

In the last two or three years, several Pathology Perspectives columns have focused on poorly understood, chronic, difficult-to-treat, and even more difficult-to-live-with conditions. We have looked at long COVID, fibromyalgia, postsepsis syndrome, dysautonomia, postural orthostatic tachycardia syndrome (POTS), chronic Lyme disease, and more—each one a somewhat controversial situation that can be hard to identify, especially since there are often differences of opinions about what they are, or even whether they exist.

Mast cell activation syndrome (MCAS) fits into this category for several reasons. Although it has a strict set of diagnostic criteria, the majority of people who have the typical signs and symptoms of this condition do not meet that diagnostic standard—but that doesn’t mean they aren’t struggling. Also, MCAS occurs frequently with other long-term syndromes, and may be a contributing factor to them in ways that have yet to be discovered or confirmed. Or, it might be the other way around: Other disorders might set the stage for MCAS. 

It would be great to untangle this snarl of disorders and syndromes so that people who live with MCAS or any of its many partners might find some more useful management strategies. However, at this moment that’s not a realistic expectation.

In this article, we will explore MCAS and its relationship to other immune-system hypersensitivity syndromes (along with other conditions that at first glance have only a tenuous connection to MCAS) with an emphasis on where massage therapy might fit in this picture. Whether MCAS is common or not is a debatable question. But its signs and symptoms, which include extreme allergic reactions, fatigue, digestive discomfort, and more, are common. And while massage could be helpful for some clients with this condition, there are many ways our work might make it worse. That’s why we need to understand as much as we can to make safe and effective clinical decisions. 

What Is MCAS?

Mast cell activation syndrome is among a group of disorders that affects mast cells: immune system cells distributed throughout the body that are involved with inflammatory reactions. In MCAS, the number of mast cells stays constant but they become overreactive and secrete abnormally high levels of pro-inflammatory chemicals. This distinguishes MCAS from mastocytosis, another mast cell disease, but mastocytosis involves the cloning of abnormal mast cells in various tissues, which can lead to extreme symptoms and, in some cases, a type of leukemia. 

MCAS is a complex situation that affects multiple organ systems—usually some combination of the skin, respiratory tract, and gastrointestinal tract. It involves fluctuating and often unpredictable bouts of extreme inflammation that can be painful and even life-threatening if it leads to anaphylaxis.

What Causes MCAS?

To understand MCAS, we need to learn a bit about mast cells. These are large white blood cells born in the bone marrow and distributed in many tissues. They are especially populous near the skin, in the respiratory tract, and in the GI tract. This makes sense since these are parts of the body most likely to be on the receiving end of any environmental threats or invaders. 

When mast cells are stained and seen under a microscope, they show tiny granules—pockets of chemicals. For this reason, they are called granulocytes. When mast cells release these chemicals, this is called “degranulation.”

During degranulation, mast cells secrete a group of chemical mediators. These promote inflammatory responses, including vasodilation, local edema, flushing, excess mucus production, and other reactions often associated with allergic reactions. Histamine is a well-known mediator, but several others are also involved. Testing for high levels of these chemicals in the blood or urine is part of the diagnostic process for MCAS.

When mast cells behave normally, they degranulate in response to some stimulus. This is called secondary activation because it comes after a trigger. (Primary activation—degranulation without an initiating stimulus—is a sign of mastocytosis, which is potentially very serious.) 

Secondary mast cell activation is a normal, healthy response that protects us from the action of antigens—any bits of “non-self.” But when mast cells become hyperreactive, degranulating in response to a wide variety of changing triggers, it can become a problem that ranges from being mildly irritating to life-threatening. 

The causes of MCAS are not understood. One of its most mysterious features is that the triggers of episodes can vary and change over time. This makes it sound like multiple chemical sensitivity syndrome (MCSS), a condition in which a history of exposure to toxins appears to initiate a heightened tendency toward allergic reactions to an ever-widening collection of stimuli. The overlap of MCAS, MCSS, and several other conditions is discussed in the sidebar, “Partners in Inflammation.”

MCAS Signs, Symptoms, and Diagnosis

The primary signs and symptoms of MCAS involve frequent, often extreme allergic reactions that affect more than one body system. The respiratory tract, gastrointestinal tract, and the skin are most at risk for these reactions. 

The main driver for these signs and symptoms is histamine. This chemical mediator causes dilation of both small and large blood vessels, which causes skin reddening, flushing, hives, itching, and pain. In the respiratory tract, histamine causes excess mucus production, runny and itchy nose, congested sinuses, and tightened airways, which leads to wheezing, shortness of breath, and a specific breath-sound called stridor. In the GI tract, histamine causes excessive acid production and inflammation in the intestines, leading to nausea, vomiting, diarrhea, constipation, and cramping. Other general symptoms can include chronic pain, headaches, and fatigue.

The most serious consequence of excessive histamine release is anaphylaxis(from Greek for “guarding against”). This is a system-wide situation with a rapid drop in blood pressure, faintness, tachycardia, and swelling in the extremities. Anaphylaxis is a medical emergency, and people with MCAS are at high risk for anaphylactic episodes.

The triggers for MCAS episodes appear to come and go, or change over time. They can include substances like the chemicals used in fragrances, or certain foods, or they can arise with environmental factors, like exposure to sunlight or a sudden change in temperature—which makes exercising a challenge for many people. 

The symptomatic profile for MCAS is not uncommon, but the diagnostic process is quite strict. To get an official diagnosis, a person must meet these criteria: 

• Have severe, recurrent symptoms of mast cell activation that affect at least two organ systems

• Show signs of mast cell activation in the form of elevated serum tryptase compared to baseline

• Respond to treatment with mast cell stabilizing drugs or drugs that target mast cell mediators

According to at least one study, a surprisingly small percentage of people who report MCAS symptoms meet these criteria;¹ another indicator that several related conditions have overlapping symptoms but may need to be treated with differing strategies.

How is MCAS Treated?

The first and most important strategy in managing MCAS is to identify the worst triggers and avoid them as much as possible. These can be chemical exposures, including molds, but also the rapid temperature changes that occur with exercise, exposure to sunlight, and histamine-rich or histamine-releasing foods. Aggravating foods include, but are not limited to, fermented, aged, smoked, or dried vegetables or meat; alcohol and fermented drinks; eggplant, tomatoes, and green peppers; avocados, bananas, papayas, citrus fruits, and most berries; shellfish, spinach, beans, and more. The food restrictions for MCAS can be extreme and are usually not meant for long-term use, but once an elimination diet is established, a person can reintroduce various foods to check for reactions.

Some medications are triggers and must also be avoided. They include some nonsteroidal anti-inflammatory drugs, certain high blood pressure medications, and narcotic analgesics. 

Medications that can help people with MCAS include type 1 and type 2 antihistamines and epinephrine in case of anaphylaxis. 

Implications for Massage Therapy Practice

Trying to sort out mast cell activation syndrome from multiple chemical sensitivity syndrome, histamine intolerance, hypermobility Ehlers-Danlos syndrome, POTS, fibromyalgia, and associated chronic pain syndromes is like trying to untangle knotted up fishing line—many threads lead in promising directions. Does it start with thalamic glial cells? Distorted connective tissue? Diamine oxidase (DAO) deficiency? Or, are they all snarled up with each other? Yank on one, and everything else comes along for the ride.

At this point, it isn’t possible to delineate between MCAS and related conditions, or to design an organizational chart to lay out how they relate to each other. It would be nice to be able to do that so people who are affected might have better options to manage them, but we aren’t there yet.

What does this mean for massage therapists? As with all confusing situations, we must fall back on core principles: We identify the variables that will allow us to offer safe, effective work. 

What are the risks if a massage therapist is uninformed about MCAS and not conscientious about meeting clients’ needs?

We could:

• Create an uncomfortable environment with the use of fragrances (candles, incense, perfume or scented deodorant, air fresheners, detergents, fabric softeners, surface cleaners, etc.) or other irritating chemicals. 

• Risk triggering an allergic or even anaphylactic reaction from our lubricant. Sometimes these are delayed by several hours, so clients may not know the source of their hives, shortness of breath, or other symptoms.

• Make any tendency toward itchiness or hives worse with overstimulation of the skin in those areas.

• Ignore or miss signals that our client needs to consult a primary health-care provider—dizziness, faintness, or tachycardia, for instance.

• Try to diagnose, label, or offer out-of-scope medical or nutritional advice to a client who lives with MCAS or one of its many associated conditions.

• Assume the client’s unpredictable symptoms are simply the product of their emotional instability.

What possible benefits could we offer to a person who has the symptoms of MCAS?

 We could:

• Create an environment where they can be confident of not having an allergic reaction, and they can experience their body in a positive way.

• Focus our work on their most troublesome symptoms that are likely to respond to massage: stress, fatigue, anxiety, depression, congested sinuses, digestive upset—if we can do so without exacerbating itching or other skin symptoms.

• Be supportive and compassionate about their struggles to manage their very challenging condition.

How can we minimize risks, and maximize the benefits our work has to offer? 

We could:

• Make sure our priorities for massage align with our clients’ priorities.

• Create a scent-free, allergen-free setting to the best of our ability.

• Partner with clients to create a trigger-free environment. That might mean inviting them to provide their own linens if they don’t tolerate our detergent and finding a lubricant that is soothing and not irritating—they may have suggestions for that.

• Manage the air quality in our workspace with appropriate air filters or purifiers.

• Ask about other accommodations we can make, like helping them deal with POTS, dizziness, or other symptoms as they get up after their session.

It seems clear that with MCAS and other associated disorders, massage is unlikely to fix or cure anything. But with care, knowledge, and sensitivity, we can probably create an experience for clients that feels safe and supportive of their wellness goals. 

Note

1. Thomas Buttgerit, “Idiopathic Mast Cell Activation Syndrome Is More Often Suspected Than Diagnosed—A Prospective Real‐Life Study,” Allergy (April 1, 2022): https://doi.org/10.1111/all.15304.

Partners in Inflammation

MCAS or MCAS-like symptoms are seen in conjunction with a host of other conditions. Often the associations are not hard to follow, but sometimes the links are obscure even though the pattern of MCAS alongside certain other conditions is predictable.

• Fibromyalgia and associated conditions

MCAS symptoms are often seen with people who have fibromyalgia, chronic fatigue syndrome, irritable bowel syndrome, chronic pelvic pain syndrome, and migraine. One theory suggests mast cells in the central nervous system are affected, and this may lead to the release of inflammatory cytokines in the skin that irritate neurons. This may link MCAS to both peripheral and central sensitization. If this finding is confirmed, it may lead to new treatment options for these challenging conditions. 

• Hypermobility Ehlers-Danlos syndrome (h-EDS), and postural orthostatic tachycardia syndrome (POTS) 

These conditions frequently overlap, and it turns out that a substantial portion of people living with h-EDS and POTS also have symptoms of MCAS. The link isn’t clear, but one theory suggests h-EDS alters the formation of connective tissue, and that may change the behavior of mast cells that are located within the connective tissue framework. POTS is discussed in the January/February 2020 issue of Massage & Bodywork magazine, and h-EDS is discussed in the November/December 2019 issue.

• Multiple chemical sensitivity syndrome (MCCS), idiopathic environmental intolerance, and chemical intolerance

These conditions may have slightly different presentations of the same thing, or they may be distinct from each other. They are described as situations that arise from a history of exposure to toxic substances—a single, large-scale exposure, or multiple smaller exposures—and this leads to multi-system symptoms in response to triggers that are not problematic for other people, just like MCAS. MCSS and its associated syndromes may be the result of a combination of immune system, respiratory system, and central nervous system functions. Symptoms may be worsened by anxiety (some researchers suggest that symptoms may be caused by anxiety and dysfunctional coping skills). Another line of thought suggests these are a type of central sensitization, with altered processing of stimuli that leads to headache, rash, asthma, muscle and joint pain, fatigue, and cognitive problems. 

• Histamine intolerance

This is a poorly understood situation in which mast cells release too much histamine, leading to exaggerated inflammation. Histamine intolerance may be related to a lack of diamine oxidase (DAO), an enzyme that helps break down histamine. This condition is associated with certain medications, leaky gut syndrome (a situation that allows incompletely broken-down nutrients to enter the bloodstream), inflammatory bowel disease, and bacterial overgrowth in the GI tract (see “Small Intestine Bacterial Overgrowth,” Massage & Bodywork, May/June 2019).

• Others

MCAS or other histamine-related imbalances are also associated with other long-term inflammatory conditions, like long COVID (see “Unpacking the Long Haul: What You Need to Know about Massage Therapy and Long COVID,” Massage & Bodywork, January/February, 2022), alpha-gal syndrome (see “Tick-Borne Meat Allergies,” Massage & Bodywork, November/December 2018), lipedema (see “The Skinny on Painful Fat,” Massage & Bodywork, January/February 2021), gastroesophageal reflux disorder, anxiety, depression, and many others. 

Resources

AAAAI.org. “Mast Cell Activation Syndrome (MCAS).” American Academy of Allergy, Asthma & Immunology. www.aaaai.org/conditions-treatments/related-conditions/mcas. 

Afrin, Lawrence B. et al. “Characterization of Mast Cell Activation Syndrome.” The American Journal of the Medical Sciences 353, no. 3 (2017): 207–15. https://doi.org/10.1016/j.amjms.2016.12.013.

Azuma, Kenichi et al. “Chemical Intolerance: Involvement of Brain Function and Networks After Exposure to Extrinsic Stimuli Perceived as Hazardous.” Environmental Health and Preventive Medicine 24, no. 1 (2019): 61. https://doi.org/10.1186/s12199-019-0816-6.

Conti, Pio et al. “Impact of Mast Cells in Fibromyalgia and Low-Grade Chronic Inflammation: Can IL-37 Play a Role?” Dermatologic Therapy 33, no. 1 (2020): e13191. https://doi.org/10.1111/dth.13191.

Ehlers-Danlos.com. “Mast Cell Disorders in Ehlers-Danlos Syndrome (for Non-Experts).” The Ehlers-Danlos Society. www.ehlers-danlos.com/2017-eds-classification-non-experts/mast-cell-disorders-ehlers-danlos-syndrome-2.

Healthline.com. “Histamine Intolerance: Causes, Symptoms, and Diagnosis.” Updated March 7, 2019. www.healthline.com/health/histamine-intolerance.

Kohn, Alison and Christopher Chang. “The Relationship Between Hypermobile Ehlers-Danlos Syndrome (h-EDS), Postural Orthostatic Tachycardia Syndrome (POTS), and Mast Cell Activation Syndrome (MCAS).” Clinical Reviews in Allergy & Immunology 58, no. 3 (2020): 273–97. https://doi.org/10.1007/s12016-019-08755-8.

Miller, Claudia S. et al. “Mast Cell Activation May Explain Many Cases of Chemical Intolerance.” Environmental Sciences Europe 33, no. 1 (2021): 129. https://doi.org/10.1186/s12302-021-00570-3.

Monaco, Ashley et al. “Association of Mast-Cell-Related Conditions with Hypermobile Syndromes: A Review of the Literature.” Immunologic Research 70, no. 4 (2022): 419–31. https://doi.org/10.1007/s12026-022-09280-1.

Russek, Leslie. (2018) “Is It Really Fibromyalgia? Recognizing Mast Cell Activation, Orthostatic Tachycardia, and Hypermobility.” Pain Management 30, no. 3 (2018): 8.

Theoharides, Theoharis C., Irene Tsilioni, and Mona Bawazeer. “Mast Cells, Neuroinflammation and Pain in Fibromyalgia Syndrome.” Frontiers in Cellular Neuroscience 13 (2019): 353. https://doi.org/10.3389/fncel.2019.00353.