What to Know About MCAS, a Condition That Can Feel Like a Nonstop Allergic Reaction

In the most severe cases, anaphylaxis can happen seemingly at random.

By Erica SloanMedically reviewed by Kristin Sokol, MD, MS

December 3, 2024

circles resembling mast cells in the body

In 2015, Marla Barkoff, MD, was a healthy mom and board-certified endocrinologist practicing at the University of Illinois Hospital in Chicago when a bunch of debilitating symptoms landed her on the opposite side of an exam room. It all started when she came down with strep throat. A prescription for penicillin knocked out the infection, no problem—but within a month, “I was unrecognizable,” she tells SELF. She was swollen from head to toe and covered in hives, struggling to eat and even to remember her patients. An allergist put her on a round of steroids and an antihistamine, but the relief was short-lived. By the time another month had passed, she says she “couldn’t even walk down the street without gasping for breath” and was having near-constant diarrhea.

The doctor she’d seen insisted she had chronic hives, but Dr. Barkoff couldn’t help but suspect that it was something else, given the other symptoms she was experiencing. Ultimately, her research led to mast cell activation syndrome, or MCAS, a condition in which mast cells (a type of white blood cell) overreact for reasons that aren’t always clear. These infection-fighting cells love to hang out under your skin, near blood vessels, and in your lungs and intestines—and when they’re activated, they can release a potentially dangerous wave of substances like histamine. In some cases, these chemicals can lead to anaphylaxis, a life-threatening allergic reaction that can include hives, diarrhea, low blood pressure, difficulty breathing, swelling of your throat, and fainting.

At the time, MCAS was very much a medical newbie; an international group of experts had only come to a consensus on how to diagnose it a few years prior, in 2012. (The CDC didn’t even develop insurance codes for the condition until 2016.) So it’s no wonder Dr. Barkoff struggled to find a doc who would take her symptoms seriously—much less help her. It wasn’t until she got in touch with a specialist at the Brigham and Women’s Mastocytosis Center several months later that she would undergo testing and get diagnosed.

Fast-forward to now, and an influx of research on mast cells has helped clarify how and when they may go rogue. Though the “why” is still elusive and controversial in some scenarios, experts agree that the condition can be debilitating. But even today it can be hard to find a specialist who’s equipped to help—and it takes an average of four and a half years to get a diagnosis.

Another challenge: There’s no known cure for MCAS, though pinpointing and avoiding triggers that may push your mast cells into overdrive and taking medications to chill them out can help. Read on to find everything you need to know about the condition, including how it typically shows up and is diagnosed, and what a care plan might look like.

What is MCAS?

Technically, there are three types of MCAS. In the case of primary MCAS (a.k.a. mastocytosis), a genetic mutation causes your mast cells to clone themselves and proliferate, Cem Akin, MD, clinical professor of allergy and immunology at University of Michigan, tells SELF. Secondary MCAS is triggered by specific allergens, like foods, pet dander, or bee venom. But there’s also a third type, idiopathic MCAS, which doesn’t have a known cause, as in Dr. Barkoff’s case.

This mystery-cause form of MCAS has gained credence over the past several years as doctors have seen more cases that don’t fit the other two molds, Joshua Milner, MD, director of the Division of Pediatric Allergy, Immunology, and Rheumatology at Columbia University, tells SELF: “You have someone who goes into anaphylaxis more than once, and you can’t explain it [with an allergen], and you test them for mastocytosis, and it’s not that either.” So the only potential cause is one we don’t understand yet.

Sometimes MCAS seems to happen after a traumatic health event like an injury, illness, or surgery, Dr. Milner says. Take Dr. Barkoff’s run-in with strep. It’s not that the infection caused her mast cells to become chronically overzealous—but perhaps her immune system was depleted or somehow primed to be reactive, and the strep pushed it over the edge, she says.

A similar scenario happened to Caroline Cray, a healthcare recruiter and content creator with MCAS. She’d had severe food allergies since childhood, but after an anaphylactic reaction to nuts in her first year of college in 2017, she found herself in and out of the hospital on a near-weekly basis, her throat closing and her face puffing up in response to seemingly anything she ate, breathed, or touched. “I don’t even know how many EpiPens I took during that fall semester,” she tells SELF. When she was finally able to see a mast cell specialist and get diagnosed with the condition in 2018, the trickiest part to process, she says, was that she could react to a particular trigger—like a known allergen—or for no obvious reason at all.

What are the symptoms of MCAS?

One of the stickiest things about MCAS is the massive range of symptoms linked to it, which makes it easy for a doctor to mistake it for another condition or plop you in the mast-cell bucket preemptively while missing whatever else is at play. That’s why it’s also controversial; some experts think that MCAS is overdiagnosed, particularly when patients have a bunch of seemingly unrelated symptoms, and tests don’t add up. All the recent chatter about MCAS on social media—there are more than 130 million videos on #mcas and #mastcellactivation on TikTok and over 21,000 users in the r/MCAS subreddit—may also be leading some folks to wrongly self-diagnose, particularly if they’ve been long searching for answers. No one is sure exactly how many people have it—estimates range from less than 1% to as much as 17% of the population.

Although some people who think they might have MCAS report nonspecific symptoms like fatigue, chest pain, headaches, hearing loss, and brain fog, only those issues falling into four specific categories—cardiovascular system, skin, lungs, and gastrointestinal tract—are actually noted as relevant for diagnosis in the 2012 expert consensus. “That’s because most mast cells mature and set up their defense in tissues that interact with the outside world,” Dr. Barkoff explains. Here are the common MCAS symptoms in each pillar:

Cardiovascular: Low blood pressure, lightheadedness, fainting
Skin: Itching, swelling, hives, flushing
Lungs: Shortness of breath, throat tightness, wheezing, sneezing, congestion
GI tract: Vomiting, diarrhea, abdominal pain

Technically, an MCAS diagnosis requires you to have symptoms in at least two of the four body systems above. And often those symptoms have to be so severe that they resemble anaphylaxis. However, there’s some debate around exactly how bad or consistent they must be to “count.” The diagnostic consensus simply notes that they should be “recurrent or permanent” and “require a therapeutic intervention.”

MCAS symptoms might also change or worsen with time, as was the case for Jenna Gestetner, an entrepreneur and content creator. Throughout childhood, she dealt with a variety of seemingly random but minor health issues, which she says were labeled as sensitivities: Her GI discomfort was due to a sensitive stomach, while her flushing was caused by overreactive skin. But as the years passed, she began reacting more frequently, even to things like the linen in her bed sheets.

It wasn’t until she broke out in full-body hives and struggled to breathe on a walk a few years ago that a doctor first mentioned mast cells to her. And when she finally got the diagnosis from a mast cell specialist about a year later, she tells SELF that it gave her the kind of “proof” she’d been searching for—an understanding of her body that felt deeply validating.

How exactly is MCAS diagnosed?

It’s tricky to prove a mast-cell overreaction; evidence only lurks around in your blood for a few hours after an episode of symptoms, and even then, lab work often doesn’t reveal black-and-white answers. There’s also still controversy over the best diagnostic criteria to use; the 2012 consensus hasn’t been universally accepted, and some physicians may rely on less stringent measures, which just adds to the confusion.

According to that consensus, however, there are three core criteria that sound the alarm for any type of mast cell activation syndrome:

You’re having symptoms in at least two of the four areas of the body noted above.
Your blood shows a substantial spike in a chemical (typically tryptase) released by mast cells within four hours of a symptomatic episode.
Your symptoms largely respond to medications that block or slow the release of the chemicals found in mast cells.

From there, your doctor may do a workup to check for the gene mutation linked with mastocytosis (primary MCAS) or a severe underlying allergy (secondary MCAS). If neither of these routes turns up anything, then you’d wind up with the diagnosis of idiopathic MCAS. Though that might seem simple enough, the truth is, there’s still some tricky things to navigate.

Take the symptoms, for starters. They can be due to a whole host of other conditions; for instance, chronic hives and irritable bowel syndrome (IBS) could plague you with bouts of itchy skin and GI discomfort, but that doesn’t necessarily mean you have MCAS, Dr. Milner says. There’s also substantial overlap with POTS—a.k.a. postural orthostatic tachycardia syndrome, Dr. Milner says, which commonly leads to MCAS-like symptoms such as lightheadedness, palpitations, and fainting—and Ehlers-Danlos Syndrome (EDS), a group of genetic disorders affecting connective tissue that, like MCAS, can cause GI issues and chronic pain. The lines get blurrier when you consider that these three conditions commonly crop up in the same people (though research hasn’t identified a biological link).

Also, to have MCAS, your blood tryptase test should show a spike of 20% above your baseline, plus two nanograms per milliliter. The challenge? You have to do the test within four hours of when an episode strikes, Dr. Milner says, or else, your tryptase will have leveled out. (The question of when to test is also muddied by the fact that some folks feel crappy all the time and don’t have as clearly defined symptomatic episodes as others, Dr. Barkoff notes.) Gestetner says it was “honestly luck” that she got a positive result: She happened to go to an outpatient center post-flare where they tested her blood right away.

There’s also the fact that you need to know your baseline tryptase level to know what qualifies as a spike—and there’s a lot of variability there. (You’ll have to do another blood test at least 24 hours after an episode to get your baseline if you haven’t had that done previously.) Making it murkier still, a genetic condition called hereditary alpha tryptasemia can cause some people to have above average tryptase levels, Dr. Milner adds. This can be totally asymptomatic, but it could also increase your risk for mastocytosis and more severe symptoms of anaphylaxis.

Even if you take all of the above into account, a lack of a post-reaction rise in tryptase still doesn’t fully rule out MCAS. When mast cells spring into action, they can also spurt out other chemicals, like histamine, leukotriene, and prostaglandin, which could be triggering your symptoms, Dr. Barkoff says. (Some blood and urine tests can also check for these.) But because other non-mast cells can release all of these substances too, there’s no established level that confirms MCAS. Similarly, if you find relief with a drug that negates one of these chemicals, it could be proof of a mast cell issue or a problem with other cells pumping out these same substances.

How do you manage symptoms of MCAS?

If there’s any chance MCAS is behind your symptoms, you’ll get prescribed an EpiPen to use in case of anaphylaxis. This is an injector pen you give yourself (once you feel symptoms like shortness of breath or throat tightening) that contains epinephrine, a medication that relaxes muscles in your airway and constricts blood vessels to tame the reaction before you can get medical attention. Beyond that, there are a couple categories of medications that your doctor might prescribe you to take on a regular basis to make symptoms more manageable:

Receptor blockers: These drugs prevent mast-cell-released chemicals from binding to receptors, where they wreak their havoc. As Dr. Barkoff puts it, they won’t keep your mast cells from “spilling their inflammatory contents,” but once those are floating around, the drugs help “mop up the mess.” The most commonly used types are various classes of antihistamines (Allegra and Zyrtec for skin and respiratory symptoms; Pepcid for GI) and antileukotrienes (Singulair, Monalast), and both Cray and Gestetner take a couple of these meds on a daily basis.
Mast cell stabilizers: Just like they sound, these meds help tame hyperreactive mast cells. Dr. Barkoff describes them as plastic wrap: They keep those cells from leaking out some of their reaction-causing substances. A common option is cromolyn sodium, which is available in inhalable and ingestible forms (e.g., NasalCrom or Gastrocrom) and can work locally on the cells in those areas, Dr. Akin says. For instance, Cray takes a liquid dose of Gastrocrom before each meal and ahead of going to sleep to stave off GI reactions.

Another potential therapy that’s distinct from the above is omalizumab (Xolair), which is an injection you give yourself: It blocks a particular kind of antibody called immunoglobulin E (IgE)—which is produced en masse in folks with allergies—from binding to and triggering mast cells, Dr. Akin says. (Because of that mechanism, omalizumab is typically used for conditions like allergic asthma and severe food allergies, but a few case reports suggest it could also help folks with MCAS who might not have a known underlying allergy.) Cray, for one, credits her biweekly injections of omalizumab as “one of the biggest reasons why I haven’t been hospitalized in over five years.”

At the same time, it’s often helpful to search for triggers and try to avoid them, Dr. Barkoff says, though this can be really tricky, especially in very severe cases like Cray’s. When she was hospitalized for an anaphylactic episode in 2019, she started to react to everything she tried to eat, with the exception of oatmeal. Five years later, she’s still working with her care team to reincorporate foods into her extremely limited diet. (Her many co-occurring food allergies make this more complicated than is typical for MCAS.) Gestetner also has a short list of just 14 foods she doesn’t react to, including things like white fish and watermelon.

Beyond diet, triggers can extend to things like airborne allergens (pet dander, fragrances, pollen), certain fabrics, or even day-to-day stress, temperature changes, exercise, or sleep deprivation—all of which can be tough to identify and avoid. And of course, the nature of an idiopathic condition means you might not be able to figure out anything specific that sets your mast cells off. This is where all the experts point to the massive need for more thorough and objective studies on MCAS. Finding an underlying cause, for instance, could crack open a trove of new solutions.

While Dr. Barkoff has made ample progress in her own treatment journey through a variety of medications, she says she still steers clear of certain foods and has to pace herself on an everyday basis because of “post-exertional malaise”—a crushing fatigue that hits after a few hours of physical activity. Despite these limitations, she sees patients daily and says she “leads a full life.” (She started the Mast Cell Disease Society’s physician training program and runs a private endocrinology practice that includes care for MCAS.) Most of all, she’s grateful to be believed and to be in the position to both validate and care for others in the same boat. “We have a long way to go,” she says, “but it’s a much less lonely experience than it was nine years ago.”