Mast cell activation syndrome (MCAS) was found far more often in people with both postural orthostatic tachycardia syndrome (POTS) and Ehlers-Danlos syndrome (EDS) in one study, but researchers disagree on how often and why. A Mayo Clinic review01704-X/fulltext) found no patient who met the established MCAS criteria. The answer depends on how MCAS is defined.
If you’ve lived with POTS for a while, you may have been handed a second label along the way. Maybe a doctor or a support group suggested MCAS. Maybe someone told you it’s all the same thing, and someone else told you MCAS isn’t real. You’ve heard promises and dismissals both, and you have every right to ask hard questions.
If you want the MCAS basics first, start with What Is MCAS?.
What are MCAS and POTS, in plain terms?
POTS is a condition of the autonomic nervous system, the part of you that runs heart rate, blood pressure, digestion and temperature without asking you. In POTS, heart rate climbs abnormally when you stand. The mechanics are in why heart rates surge while standing.
MCAS involves mast cells, immune cells that release chemicals such as histamine. According to PoTS UK, MCAS is caused by abnormal mast cells or abnormal release of the chemicals contained within them. Mast cells sit in tissues throughout the body, so symptoms can show up in many places at once.
Think of the autonomic nervous system as the thermostat and wiring of a house, and mast cells as smoke alarms scattered through every room. They’re separate systems, yet a fault in one can set off noise in the other. That’s a picture, not a mechanism, but it explains why finding both in one person raises questions.
How often do MCAS and POTS show up together?
The number depends on who is counting and how. Studies using different definitions of MCAS land on very different figures, and the table shows how far apart they are.
| Study | What it looked at | What it reported |
|---|---|---|
| UT Health San Antonio, 2021 | 195 medical records of patients with autonomic dysfunction | MCAS in 31% of the POTS and Ehlers-Danlos syndrome (EDS) group versus 2% of the non-POTS and EDS group |
| Frontiers in Neurology, 2025 | 100 young patients meeting POTS criteria | MCAS in 2% to 87%, depending on which criteria were used |
| Mayo Clinic review, Journal of Allergy and Clinical Immunology01704-X/fulltext) | 110 adults with hEDS and/or POTS and suspected MCAS | Most had unconfirmed MCAS labels (95%); none met the established diagnostic criteria for MCAS |
The first study found a strong statistical link. Its authors reported an odds ratio of 32.46, which means that people in the POTS and EDS group were far more likely to have MCAS than people outside it. The second showed that the same patients can look almost free of MCAS or almost entirely affected, depending on the yardstick. The Mayo Clinic review01704-X/fulltext) found that the label was common, but the confirmed diagnosis wasn’t.
That doesn’t say your symptoms aren’t real. It says that in that group the formal criteria for MCAS weren’t met, and the authors called for further research using standardized, validated diagnostic criteria.
Why would the two conditions overlap?
Nobody has settled this. Researchers have proposed several explanations, and none of them is the whole story yet.
One idea is that the immune and autonomic systems talk to each other constantly. The Frontiers authors write that many reports have established the relationship and that some have proposed mechanisms by which each induces the development of the other. The EDS Clinic describes recent research as suggesting a substantial overlap and raising questions about shared pathophysiology (the shared biology underneath) and potential treatment approaches.
Another is plain symptom overlap. PoTS UK puts it plainly: the two conditions are not very well understood and the overlap between them is complicated.
A third is that something else sits underneath both. Joint hypermobility, meaning joints that stretch beyond the normal range, shows up in these clusters too. A Houston Methodist report on POTS, MCAS and hypermobility with severe digestive symptoms found 73% of its patients were diagnosed with POTS. We don’t know whether that cluster reflects shared biology or the way these patients get diagnosed.
Does one condition cause the other?
Not that anyone can show today. The research describes two conditions that occur together, and it doesn’t establish that one produces the other. If a source tells you MCAS definitely causes your POTS, it’s claiming more than the studies above support.
The uncertainty cuts both ways, since no one can tell you the two are unrelated either. Treat the question as open.
Can you have MCAS without POTS, or POTS without MCAS?
The studies here don’t answer the first half directly. The UT Health San Antonio study found MCAS in 2% of patients outside the POTS and EDS group, but that group can still include people with POTS, so it doesn’t show MCAS without POTS.
On the second half, the Frontiers study found MCAS in as few as 2% of young POTS patients under strict criteria, and the Mayo Clinic review01704-X/fulltext) found no confirmed MCAS among its patients with hEDS and/or POTS. A POTS diagnosis doesn’t mean you should assume MCAS, and a suspicion of MCAS doesn’t mean you must have POTS. Each deserves its own look.
What does a mast cell flare feel like?
It varies from person to person, which is part of why it’s hard to pin down. Because mast cells are spread through the body, reactions can touch skin, gut, breathing and heart rate. PoTS UK notes that an infection such as COVID-19 can cause an increase in symptoms.
The trouble is that this list also describes a POTS flare. A timeline of what happened before each episode is more useful than a symptom list alone.
How do clinicians check for MCAS?
They look for chemical evidence, not just symptoms. According to PoTS UK, possible tests include tryptase in serum or plasma and several urine markers, including methyl histamine and prostaglandins.
The Frontiers paper notes that most consensus-2 providers consider laboratory evidence of MCAS superior to relying on clinical response alone. That is part of why the overlap numbers swing so widely between studies.
Where does the whole-person view come in?
That pattern deserves one body-wide evaluation instead of a separate specialist for each piece, each working without the others’ notes.
The question I find most useful is how the autonomic nervous system, immune stress, digestion, sleep and pain regulation may be interacting. That is a clinical framework for understanding your whole experience. It points to a way of looking, and it makes no promise about any result. You can read how we approach this in how The Spero Clinic handles dysautonomia, and diet’s role in diet and neurological dysfunction.
I’ve also written a book on the EDS and POTS side of this picture, on the book’s page. Specialist care, including allergy and immunology, still has a place, and so does emergency care when you need it.
What are the common mistakes people make?
The easiest trap is treating a label as the answer. Many people in the Mayo Clinic cohort01704-X/fulltext) carried an MCAS label that was never confirmed, and a label without testing can send you down the wrong path for months, so ask your clinician what yours is based on.
The opposite trap catches people too. One negative review doesn’t close the topic, any more than one positive study opens it, and brushing off a mast cell question leaves you without a proper workup.
Be careful with medicines. Antihistamines such as cetirizine and famotidine are often discussed for MCAS, but whether they suit you depends on your other conditions and prescriptions, so take that conversation to your prescriber before changing anything.
Finally, chasing the flushing, the heart rate, the stomach and the fatigue with four separate plans that never speak to each other wears you out. Naming that fragmentation out loud is a good first step.
Frequently asked questions
Is POTS a symptom of MCAS?
No study has shown that. Research reports the two conditions together, but cause and effect remain unsettled.
What does a mast cell activation flare feel like?
It can involve skin, gut, breathing or heart rate, and POTS can cause similar symptoms. Noting what came before each episode helps your clinician tell them apart.
Can you have MCAS without POTS?
The evidence here doesn’t settle it. In the UT Health San Antonio records, MCAS appeared in 2% of patients outside the POTS and EDS group, which can still include people with POTS.
Can you have both POTS and MCAS?
Yes, though how often depends on the definition used. One 2025 study found MCAS in 2% to 87% of young POTS patients depending on the criteria. A Mayo Clinic review01704-X/fulltext) found none met the formal criteria.
What can you do today?
Write down a two-week timeline of your flares: what you ate, the weather, how you slept, and what you were doing before each episode. Bring it to the clinician who prescribes for you and ask what your MCAS label, if you have one, is based on. Questions like that are how a tangle of symptoms starts to make sense, and hope is still within your reach while you ask them. If you’d like us to hear the full picture, schedule a free discovery call, and we’ll listen to your story and tell you honestly whether Spero is a fit.
