MAST CELL / MCAS EDUCATION

Aug 25, 2024

8 min read

Updated: 2 days ago

Mast cell activation (MCAS) comes up in our Lyme groups all the time, and the same questions follow. What is it? What are the signs? How do doctors decide if someone has it? Is it connected to Lyme? Doctors do not all agree on the answers, so I pulled together the basics from the MCAS specialists and Lyme organizations I trust. Always take your own questions to your doctor.

Short on time or energy? A quick-view graphic with the key points is at the bottom of this post.

POSSIBLE SOLUTIONS

https://www.riseabovelyme.com/post/mast-cell-solutions

WHAT IS MCAS?

Dr. Tania Dempsey describes mast cells as "our soldiers, our first line of defense against the world around us." They sit in tissues that are in direct contact with our environment. When they are working normally, they react to things like viruses, bacteria and parasites, and some of the chemical messengers they release (called mediators) also help with growth and development and with protecting against osteoporosis.

In MCAS, Dr. Dempsey explains, the mast cells are not resetting, so they keep reacting, which causes inflammation and symptoms that stick around. She says allergies on their own are not MCAS and other symptoms are needed too. She describes the effects as three themes: allergy-type reactions, inflammation, and problems with growth and development, such as osteoporosis, cysts or nodules. Not everyone has all three, and not having allergy symptoms does not rule MCAS out.

She says inflammation is probably the most common, and it can show up in any organ or tissue. Mast cells can release thousands of different mediators, which is a big reason MCAS looks so different from person to person.

HOW COMMON IS IT?

Dr. Dempsey points to research out of Germany suggesting about 17 percent of people have MCAS, and says rounding up to 20 percent would mean potentially one in five or six people. Dr. Leonard Weinstock says 15 to 20 percent of the country, and a June 2026 review by Dr. Lawrence Afrin, Dr. Dempsey, Dr. Weinstock and colleagues says roughly 17 to 20 percent of people in Western countries. Dr. Dempsey also says women are probably affected more than men, and that hormonal shifts, such as puberty, are a common time for it to show up.

These are estimates, and that review says MCAS research is still in its early stages. An earlier set of criteria, called consensus-1, described MCAS as rare, so doctors do not all agree.

COMMON SIGNS AND SYMPTOMS

MCAS can affect many parts of the body at once, and it looks different for everyone. These are the ones the doctors I follow talk about most:

Gut: diarrhea, belly pain, bloating, changes in bowel habits, reflux, trouble swallowing, and food intolerances

Skin: hives, itching and rashes, and possibly eczema

Head and brain: headaches and migraines, brain fog, and trouble with memory and finding words

Nerves: tingling, and neuropathy (nerve pain, burning or numbness, often from small fiber neuropathy)

Whole body: fatigue and muscle aching

Mood: anxiety, depression, OCD and other mood changes

Eyes and ears: vision changes, including double vision, and ringing in the ears

Body control (autonomic): changes in heart rate, blood pressure, body temperature, sweating and sleep, including POTS

Sensitivities: reactions to certain chemicals, foods and additives

Dr. Dempsey says reactions can show up late, and two to three days later is not an uncommon timeframe. She also describes some people having flare-ups she calls "spells." Under the newer criteria, severe allergic reactions (anaphylaxis) are uncommon with MCAS.

MCAS also shows up alongside POTS and hypermobile Ehlers-Danlos syndrome (EDS). Dr. Dempsey says the connection with POTS is mast cells producing inflammation in the autonomic nervous system. Dr. Weinstock calls MCAS, EDS and POTS together the "evil triad." In a group of 180 MCAS patients he studied, about 20 percent had POTS and about 20 percent had EDS. The June 2026 review also says signs of mast cell activation are commonly seen in hypermobile EDS.

MCAS AND NEUROPATHY

Overactive mast cells can affect the nerves too, and the link to neuropathy is a strong one.

-In a 2022 study by Dr. Peter Novak and Dr. Matthew Hamilton, skin biopsies found small fiber neuropathy in 81% of people with MCAS, and in 80% of people with hereditary alpha tryptasemia, an inherited mast cell condition.

-Dr. Leonard Weinstock and colleagues (2023) include sensory neuropathies among the nerve symptoms of MCAS. They suggest the chemicals mast cells release may affect the small nerve fibers.

-I lived this. Calming my mast cells, especially with H1 and H2 blockers, is what finally helped my neuropathy.

Learn more in my neuropathy posts:

https://www.riseabovelyme.com/post/neuropathy

https://www.riseabovelyme.com/post/neuropathy-solutions-ideas

HOW DO DOCTORS DECIDE?

Tryptase is the blood test most people hear about, but Dr. Weinstock says it is not commonly raised in MCAS, and the June 2026 review says the same. In a November 2023 interview, Dr. Afrin said the published research suggests tryptase is raised in only about 15 percent of MCAS patients.

The newer criteria, called consensus-2, ask for symptoms in two or more body systems that come from increased mast cell activity, plus at least one more clue, such as higher than normal mast cell chemicals in blood or urine, or symptoms that improve with medicines that calm mast cells, and no better explanation for the symptoms. Dr. Weinstock says someone with normal test results can still be diagnosed if they respond to mast cell treatment. He also says the tests he uses (four blood and three urine) need careful handling, such as keeping samples cold, so ask your doctor how and where to have them done.

The June 2026 authors say they have not seen over-diagnosis happen with the newer criteria, and that missed diagnosis is still a big problem. Dr. Afrin also says MCAS is still not mentioned in any medical school textbooks, and he encourages patients to go easy on their doctors and to find one who is willing to learn. He adds that he is not saying MCAS is the answer for every chronic mysterious illness.

In 2024, a review in the Journal of Allergy and Clinical Immunology by 24 specialists, including Dr. Cem Akin, Dr. Dean Metcalfe, Dr. Melody Carter, Dr. Joseph Butterfield, Dr. Matthew Hamilton and Dr. Clair Francomano, said it is not well understood whether MCAS is a syndrome of its own or a set of symptoms that show up inside other inflammatory, allergic or clonal conditions. They also say how mast cells get activated in MCAS is still being worked out, and they cover what research is needed on diagnosis, how it works, managing symptoms, and teaching patients and doctors.

A July 2026 review in the Fortune Journal of Health Sciences by Spencer Collins, Tyler Williams, Edgar Sanchez and Devendra Agrawal describes MCAS as an underrecognized disorder that affects many body systems. It walks through how mast cells get activated, through both allergy-type (IgE) and non-IgE routes, and the chemicals they release when they let go of their contents, including histamine, tryptase, heparin, leukotrienes and prostaglandins.

WHAT MAY SET IT OFF?

Dr. Steven Harris said in a Bay Area Lyme Foundation talk that mast cell activation can sometimes be driven by infections alone, but the cause is usually complicated.

Dr. Dempsey lists these as things that can trigger mast cells:

Temperature changes

Stress (emotional, physical or from the environment)

Exercise

Being run down or not sleeping well

Foods and drinks, including alcohol, and for some people foods higher in histamine

Certain medicines, such as opioids, NSAID pain relievers and antibiotics, and the fillers (excipients) in medicines and supplements

Perfumes and fragrances, cleaning products, smoke and other chemical odors

Weather and barometric pressure changes

Insect bites and stings

Infections (viral, bacterial or fungal)

Mold toxins

Gut changes, such as SIBO or an imbalance of gut bacteria

Hormones and sunlight

Implants, metal exposure and surgery

The June 2026 review adds that chemical exposures can be strong triggers for some people, even at low levels.

Dr. Jill Carnahan, in her MCAS article (first published in 2019 and updated in 2023), says no single factor has been shown to be the definitive cause of MCAS. She names mold and an elevated overall toxic burden as two major environmental triggers, and says various microbes can disrupt the immune system and send mast cells haywire. She also says mast cells have their own daily rhythm, which irregular sleep or poor sleep quality can throw off, and that chronic stress can push the immune system into overdrive. She suggests keeping a daily journal of emotions, events or activities that bring on symptoms.

MCAS AND LYME

In her own practice, Dr. Dempsey says the vast majority of her chronic Lyme patients have underlying mast cell dysfunction, even if they have not been formally diagnosed with MCAS. She explains that infections can trigger mast cells, so a long-lasting infection can keep them activated, and that mast cells often keep misbehaving even after an infection is cleared. She also says MCAS can be a driver of autoimmunity. She adds that treating an active infection, such as Bartonellosis or Babesiosis, could help MCAS, but MCAS might also get in the way of treating those infections, especially if it causes medicine or supplement intolerances.

LymeDisease.org, in a January 2025 research review, calls MCAS a complicating factor that is common in patients with chronic Lyme and says it can make people extremely sensitive to certain chemicals, foods and additives. A February 2022 LymeDisease.org article by Lonnie Marcum is upfront that there were no published surveys yet on the connection between MCAS and long Lyme. The June 2026 review also links MCAS to unusually severe courses of some infections, such as Covid-19.

Dr. Dempsey says MCAS is not presently curable, but there are many treatments known to help, and most patients who are accurately diagnosed can get significantly better. Dr. Carnahan also says there is no cure, but that you are not simply at the mercy of your mast cells. Our possible solutions post has the ideas people in our groups bring up most.