In early 2020, Wynde Dyer walked into the house that would transform her life. The Central California ranch sat on a cul-de-sac of gated homes and glittering aquamarine pools. It boasted private tennis and beach volleyball courts, a horse run, floor-to-ceiling windows, and a manicured lawn. The immaculate exterior masked what lay inside.
The owners of the house, wealthy pistachio farmers, had a hoarding problem. For decades, they’d accumulated mountains of items. Then they vacated, leaving it virtually untouched for six years. Dyer had accepted a job as their personal organizer. When she arrived, she faced rat droppings, moldy carpets, a garage full of agricultural chemicals and animal-care products, decades-old toiletries and makeup, endless boxes of scented candles, rotting wood and cardboard — and an unidentifiable animal carcass.
Dyer was good at her job, though. Thirty-nine years old at the time, she’d been organizing homes for years and was planning to take her business national. Expecting a job like any other, Dyer rolled up her sleeves.
But as she sifted through the mess, she started getting sick. Dyer had always been sensitive to her environment. In the past, she’d experienced minor symptoms — “a nose full of snot” and bouts of illness as a child, skin problems and extreme allergies when she organized other homes as an adult. But in this client’s house, Dyer’s symptoms intensified. Her exposed skin began to sear, as if it had been scalded with steam. When she ate, her insides burned, a sensation she likened to spilling rubbing alcohol on an open wound. Rashes crawled over her hands and her fingers swelled like bloated sausages, rings cutting into her flesh. Some days, she woke up swallowed by exhaustion. Alone in the house she was organizing, save for a stray cat she was caring for, she would sometimes pass out.
Dyer saw a dermatologist who told her, “It’s probably just eczema. Maybe a sunburn,” and sent her home with a tube of cortisone cream. A gastroenterologist was similarly unhelpful. Her primary care doctor was at a loss. Dyer took an allergy test, exposing her bare back to 80 pinpricks containing different allergens, and flared to all of them. The allergists were mystified — they’d never seen a patient react to everything.
Dyer remained uncannily task-oriented. She had to be — she was broke and had a partner at home counting on the income. But the instinct to press on was about more than money. “I couldn't figure out what was going on with my body,” Dyer says. “I couldn't figure out why I was so sick. But I could figure out [how to] get the stuff in order and get out of here.”
As her condition only worsened with every day she spent in the house, Dyer started combing the internet for answers. In the hours of scrolling on forums and blogs, her attention snagged on a website that described her exact symptoms. “Oh my god — this is me,” Dyer thought, “allergic to the modern world.” The site suggested something a couple of her doctors had mentioned in passing, but didn’t believe could match Dyer’s symptoms: that her mysterious illness might be caused by mast cells. These cells, critical first responders in the immune system, are present in connective tissues, which are essentially everywhere in the body: in our skin, lungs, gut, muscles, nerves, even in the brain. What we’re just beginning to understand about mast cells is that common exposures may cause them to activate when they shouldn’t, wreaking havoc across body systems. Scientists are still riddling out why.
Mast cells have been around since before the adaptive immune system developed in mammals 500 million years ago. But for such an old cell, we know relatively little about what it does. One of the first glimmers of understanding arrived in 1877 when a young German immunologist, Paul Ehrlich, was training to become a doctor.
Ehrlich was refining a new technique for staining cells, which made them more visible and therefore easier to study under a microscope. During this work, he discovered a cell whose tiny granules reacted with the dye. Under a microscope, these plump cells filled with colored sacs looked to Ehrlich like they nourished the surrounding cells. He named them mastzellen, or mast cells, because mast denotes a suckling or fattening function in German.
It wasn’t until the 1950s that we learned that mast cells release histamine, a powerful chemical responsible for the sneezing and runny nose of an allergy, as well as anaphylaxis, a life-threatening reaction caused when mast cells detect an allergen, and histamine and other chemicals erupt from the cell and into the bloodstream. Indeed, our abundant mast cells contain more than enough histamine to kill us, which is why “we have been inclined in the last 25 years to think that mast cells are bad guys,” says Mariana Castells, a Harvard Medical School professor, clinician, and mast cell researcher. Scientists saw the problems caused by mast cells but couldn’t decipher the function and importance of these cells in our bodies.
That’s changed in the last several decades as mast cell research has exploded. “We are at the beginning of understanding the physiological role of mast cells,” Castells says. We now know that mast cells are the frontline sentinels of the immune system, initiating inflammation and releasing not just histamine, but also hundreds of other chemicals, called mediators, that act as biological signals. When mast cells are behaving as they should, allergens and pathogens cause the body to produce specialized molecules, which bind to proteins studding the outsides of mast cells like jewels. In turn, the mast cells release their torrent of chemical signals, setting off a cascade of immune system processes. Thanks to other research by German scientists, we know that the sneezing, coughing, and itching of an allergy represent a protective benefit of mast cells: removing substances from the body and avoiding them in the future.
We’re still learning why mast cells misbehave. Under one working theory, someone might be exposed to a big dose, or repeated low doses of a chemical, and mast cells would respond to the toxicants, producing mild allergic symptoms. (Toxicants are human-made substances, like pesticides, while toxins, like snake venom, are found in nature.) But the mast cells would be permanently changed, now sensitive to a host of environmental triggers, like “cellular PTSD,” Dyer says. The name for this phenomenon is mast cell activation syndrome, or MCAS. Depending on where the cells activate, someone might start fainting, break out in hives, have near constant diarrhea, or develop a rapid heart rate and breathing difficulties — seemingly unrelated symptoms that share the same root cause.
While extreme cases like Dyer’s are relatively rare, many people suffering from MCAS experience moderate or mild symptoms. One prominent MCAS doctor, Lawrence Afrin, spent decades in academic medical centers before joining a private clinic in Purchase, New York, to focus on MCAS. He estimates that, over his career, he has treated thousands of patients with the disease. Because the symptoms of MCAS can vary so widely, and since so few physicians are yet aware of the existence of what Afrin says may well be a very prevalent disease, “It’s almost always the case that it goes unrecognized for decades, if not the patient's entire life.”
One of Afrin’s first patients had spent a decade with undiagnosed fatigue, as well as sudden bouts of itching across her body. By the time she saw Afrin, she had bounced from doctor to doctor, and accumulated a mountain of diagnoses, from blood cancer to anemia. None of the many associated treatments had helped. Afrin ordered lab tests for MCAS, which eventually showed that the patient’s mast cell activity was off the charts.
As word got out that Afrin and a small but growing number of doctors were able to diagnose patients who had gone much of their lives without explanation or effective treatment of their symptoms, more people poured in to see them. Afrin’s own reported cases included: a 34-year-old schoolteacher, always tired and cold; a 24-year-old with chronic headaches and waxing and waning lupuslike symptoms; several patients diagnosed with sickle cell anemia who had unusually severe courses of that disease because they were also suffering from undiagnosed and untreated MCAS; and a 50-year-old hospital worker with night sweats, aching, itching, eye irritation, and weight gain. All of them, according to symptoms, lab tests, and treatment, ultimately were determined to suffer from MCAS.
Today, research suggests that MCAS affects a dizzying number of people — up to 17 percent of the population in industrialized countries — and could potentially explain a host of medically mysterious symptoms, from benign rashes to gastrointestinal symptoms, fatigue, swelling, runny nose and wheezing, and more.
But Afrin’s belief that MCAS is a widespread problem is still controversial.
Castells worries that doctors are jumping to an MCAS diagnosis before ruling everything else out. MCAS can be slippery to diagnose, especially since diseases like COVID-19 and Lyme can also trigger mast cell activation. Even for those who specialize in complex chronic conditions, teasing apart overlapping symptoms is like untangling a mat of gummed hair. Castells stresses that each MCAS patient required far more time than what is typically allotted for a clinical visit. “We need more people to embrace the evaluation of those patients,” Castells says, but “those patients take time.”
Cem Akin, a clinical professor and mast cell expert at the University of Michigan Medical School, notes the 17 percent figure for MCAS prevalence uses diagnostic criteria that are “too broad.” Gerhard Molderings, a doctor and professor at the University of Bonn, Germany, and his team of researchers arrived at the estimate by asking a random sample of German citizens to report their symptoms in a questionnaire, rather than by doing extensive lab tests needed to confirm MCAS. That approach could lump patients with myriad different problems under the same MCAS umbrella, Akin says.
When Akin himself reviewed insurance claims representing 30 million patients in 2018, he found that fewer than 1 in 10,000 patients had MCAS. While he acknowledges that that number may have grown as patient advocacy groups have fought for better awareness of the disease, he still believes the 17 percent estimate is high. “It wouldn't be incorrect to say that 17 to 20 percent of the population will have mast cell activation locally,” Akin says — meaning rashes and sneezes caused by mast cells activating in those tissues — but “we wouldn't call that mast cell activation syndrome.”
Akin doesn’t doubt that his patients are suffering. “They have a real problem, a real disease or a group of diseases,” he says. “They have real symptoms.” But he relies on objective criteria — symptoms, laboratory evidence and response to treatment — to make an MCAS diagnosis.
Afrin, though, argues that overly narrow diagnostic criteria risk excluding patients with the disease. MCAS doesn’t follow one single pattern, which makes the disease challenging to recognize and diagnose. Some labs aren’t equipped to handle the tests and often deliver false negatives. Because of that, doctors sometimes diagnose MCAS based only on symptoms and response to treatment — the same way other diseases, including Parkinson’s, are diagnosed.
Part of the problem may also be lack of awareness — the world of doctors who treat MCAS is small. In 2018, a group of fewer than two dozen MCAS specialists convened in California and started a physician listserv to share knowledge among those treating the condition. The listserv has since grown to include more than 600 providers around the world, yet not many accept insurance. Insurance companies rarely reimburse for the many hours required to diagnose and treat MCAS patients, says Jill Schofield, a doctor who started a private clinic in Denver to treat MCAS and other complex conditions. “Our health care model doesn't fit with these problems.”
The internet and patient advocacy groups have accelerated awareness of MCAS, yet few doctors are formally trained to recognize the disease, since medical school curricula include only a glancing look at mast cell disorders. Some doctors, including some of Dyer’s, have barely heard of it. Afrin says he regularly gets calls from doctors who say, “Oh my God, you were right. I've been seeing this left and right my whole career. I just couldn't previously recognize it for what it was. I always dismissed these patients in the past as just being kind of crazy.”
Dyer grew up in a low-income version of the house whose environment triggered her symptoms as an adult. The ceilings sagged with water damage and mold turned the walls gray. Additionally, Dyer and her family lived within a mile of huge swaths of agriculture in California’s fertile Central Valley. Her grandpa had been a crop-duster in his younger days, and Dyer remembers the two of them driving through the fields and pausing to crane their heads out the window when planes flew overhead, showering the earth, and Dyer, with pesticides. To her, the crop dusters were magical, dipping down from the sky to spray the vegetables poking their leafy heads from the ground.
But it’s entirely possible that these exposures may have primed Dyer for the health catastrophe that would befall her decades later. When she stepped into the midcentury mansion with its garage full of pesticides and carpets reeking of water damage, her body reacted — or rather overreacted — with a massive immune response. Her mast cells released their granules of chemicals — histamine and heparin, proteases and prostaglandin, tryptase and chymase, and hundreds more molecular warning sirens — making Dyer sicker and sicker.
In some ways, Dyer is lucky. Before MCAS was identified, patients with what was then called “multiple chemical sensitivity” or “environmental illness” were assumed to be delusional. (And the physicians who took them seriously did so at their professional peril. In the 1950s, a doctor who treated such patients was ousted from Northwestern University’s medical school, for being a “pernicious influence on medical students.”) But a small number of researchers persisted. In the 1970s, Claudia Miller, an allergist and environmental scientist, was studying how toxicants affect people in industrial settings and began noticing strange symptoms emerging after certain kinds of chemical exposures. By the '90s, she observed that Gulf War veterans had been exposed to a cocktail of hazards while deployed, returning with a slew of symptoms: fatigue, headaches, joint pain, indigestion, insomnia, dizziness, respiratory disorders, and memory problems. Some veterans reported to Miller that they used to love the smell of the industrial lubricant WD-40: “It was like perfume to them,” she says. But after the war, a single whiff made them sick.
Miller also met people who’d been exposed to pesticides, breast implants, burn pits, and noxious fumes from chemical spills. Later, many grew hypersensitive to their environments, triggered by foods, fragrances, exhaust, and cleaning agents that hadn’t bothered them before. This pattern — sudden sickness affecting multiple parts of the body after an exposure — seemed to suggest a new model of disease.
Miller had no clues about the mechanism behind this phenomenon, until someone tipped her off to Larry Afrin’s work on MCAS. They began collaborating, crafting supplies that homed in on striking similarities between chemical intolerance and MCAS. Their patient groups experienced a wide range of symptoms across body systems, but no one had connected these groups before. Through careful assessments, Miller and Afrin found that people most likely to have mast cell activation syndrome were also highly likely to be chemically intolerant. At the high end of the scale, the overlap was nearly perfect — a breakthrough. After decades of work at the margins of medicine, these scientists had a likely mechanism for chemical intolerance: mast cell activation.
The link between chemical intolerance and mast cell activation was prescient (though scientists like Cem Akin are waiting for empirical data to prove the connection). Since the mid-2000s, the rate of diagnosed chemical intolerance has quadrupled, affecting more than 1 in 8 adults in the U.S. That translates to more than 25 million people, a group larger than the population of Texas. Over a quarter of the adults surveyed in the study report sensitivity to chemicals.
Those numbers will likely increase. Our world is filled with artifacts of industrialization — plastics, synthetic fragrances, fossil fuels, construction materials, and heavy duty chemicals. A 2021 Nature study led by Stanford University researchers shows that our exposure to pollen and mold is already increasing in our changing climate. Water damage from tropical storms, hurricanes, and flooding has led to an increased exposure to mold worldwide. A 2007 investigation by the CDC found increased fungal growth at levels harmful to human health after Hurricanes Katrina and Rita in New Orleans. Decades of research show that weeds flourish and pests thrive in response to more carbon dioxide and hotter temperatures, increasing the need for pesticides and herbicides. The global Pesticide Atlas reports that pesticide use increased by 80 percent from 1990 and 2017.
All of these exposures combine to create what experts call the “exposome”: the composite of everything we encounter in our environment, from conception to death, and how these exposures relate to health. While some people can tolerate more toxic exposures, others, like Dyer, are disabled by it.
Once Dyer’s online research suggested mast cells were the culprits of her illness, she wanted proof. For months, her doctors had dismissed her symptoms as exaggerated, psychosomatic, or unexplainable. She remembers being told “You just have a little hive,” when her skin burned and “We can’t find anything,” when she begged for answers. “There was no, like, ‘Why is this actually happening?’” Dyer says.
Months after she’d gotten sick, she implored her primary care doctor to refer her to one of the few mast cell specialists in the area. In the specialist’s office, Dyer detailed her complex matrix of symptoms, and the doctor listened attentively for hours, taking notes and asking the occasional question — about where Dyer grew up, when she first noticed health problems, how her symptoms progressed over time. It was the first time anyone took Dyer seriously.
She went home to complete the finicky diagnostic test, which would detect the histamine and prostaglandin her mast cells were releasing, fingerprints of MCAS. Over 24 hours, she collected her urine in a jug, which she shoved into the fridge to preserve the temperature-sensitive chemicals.
Then Dyer had to provide a final urine sample that mimicked a “flare,” when mast cells release a flood of mediators. From months of sickness, Dyer had learned to avoid the exposures that triggered her symptoms. Now, she intentionally sought them out. She sniffed a to-go cup of blue laundry detergent as she drove to a home improvement center. Then, she beelined to the lumber section, and her skin erupted with pain, “like somebody threw gasoline on it,” she says. She’d planned to stop at a department store perfume counter, but she’d already made herself miserably sick — a success — so she drove to the lab.
Her long-awaited results showed high prostaglandin levels, a telltale marker of MCAS. But she would have to repeat the test before she saw that her histamine levels, too, were six times the upper limit. Her mast cells were going haywire, releasing signals in response to perfume, detergent, and wood, which normal mast cells would treat as innocuous. Most of a year after her health spiral began, she learned she had mast cell activation syndrome.
Dyer’s doctor prescribed a simple treatment: an antihistamine. These drugs block histamine receptors on mast cells, keeping the histamine trapped inside. Dyer had tried over-the-counter antihistamines before, but she had reacted to the drugs themselves, likely because of fillers contained in the pills. Another treatment, mast cell stabilizers, such as cromolyn sodium, reduces the permeability of the mast cell’s membrane, preventing the chemicals from leaving the cell. When Dyer started taking prescribed antihistamines and stabilizers, her symptoms improved dramatically, though ordinary chemicals can still trigger an attack.
Thomas Plum, who studies immunology at the German Cancer Research Center, and led the groundbreaking study on the protective benefits of mast cells, hopes that his research will open the field for better treatments. “You first need to understand how something works in order to really interfere and design good therapies,” he says, which has “not adequately been done for the last half-century.” Now that we better understand the mast cell’s mechanism, we’re beginning to see innovative treatments that target these pathways. Monoclonal antibodies eliminate the signals that trigger mast cells. Certain vitamins can degrade histamine or even reduce mast cell proliferation. Some bioactive compounds like flavonoids, a class of chemicals present in many foods, including berries, may decrease mast cell activation.
Today, Dyer lives on the California coast and works in a health food store, allowing her affordable access to food that doesn’t make her sick. She no longer organizes houses — the risk to her health is too high. For years, Dyer tried to avoid all the things that she knew would trigger a flare. But over time, she wanted to reclaim parts of her previous life. She sleeps on a friend’s couch even when it smells of Febreze, wears makeup occasionally, and refuses to isolate herself. “There's no way to get around it unless you live in a bubble,” Dyer says. “And the only people who can afford to live in a bubble are people with money.”
Still, this disease derailed Dyer’s life. “I would describe myself as a person who had tremendous potential in this world,” she says, “and that potential has been hijacked by the mental, physical, and psychological impacts of this condition.”
She can’t do the work she loved as a personal organizer. She holds minimum wage jobs, making a fraction of what she did before. She doesn’t live in a mold-free house or follow an expensive low-histamine diet. She lives in and eats what she can afford. She hasn’t realized her dreams as an artist and entrepreneur — her career stalled when she got sick. Instead, she wakes up each day with the goal of staying alive.
It's not what she imagined, but her life before sickness no longer exists. “I have to close that door,” Dyer says. “I have to heal."
This article is not offering medical advice and should be used for informational purposes only.
This article appeared in the July and August 2025 print issue.
Kate Raphael is a San Francisco Bay area science writer.
