Research for the Future: MCAS and Long Haul

Tania Dempsey, MD, ABIHM

And I think, but I’ve certainly seen lots of patients you know consult with me and I think the key was that they were already being treated for immune dysfunction, mast cell activation syndrome. So even though some of them had prolonged some prolonged illness, they didn’t really turn into long haul thankfully the majority or maybe all um because I believe that we have been doing things to maybe you know, support them better. And a lot of people out there didn’t have that support.

Eric Gordon, MD

I think that’s true. I mean, again, just from the experience that our patients did not, not many of, even the ones who got covid they were they were taking, you know, generally things that modulated their immune response and that prevented this unbridled immune response from getting started and from carrying on. Again, we don’t have enough numbers. But I can say, yeah, our patients did not get long covid. I yeah, that is true. You know, and so the what you’ve seen because I think that what’s so important is that I remember right in the beginning there were reports from England. I mean, one of some of the doctors there were saying like, you know, oh this is mast cell activation, you know that they felt that long covid was. And I think it’s more complicated than that, but maybe just let’s step back for a minute and tell people a little bit what mast cell activation is.

Tania Dempsey, MD, ABIHM

Yeah I think it’s important to start there and sort of evolve into it. But the reality is that mast cells are part of your immune system, they’re your first line of defense against the environment, right? Your body, you know, breathes in lots of things, swallows lots of things that could potentially be dangerous. So your mast cells are in these locations all over your body ready to defend and they’re in the respiratory tract. So if you breathe in a virus they’re there, if you breathe in a toxin they’re in the GI Tract and they’re in the skin. They’re basically in all tissue and all organs.

Everyone has them. The way I like to think about it is if you have normal mast cells, they can react to things that are foreign. So you get a virus, let’s say covid, you have normal mast cells, your immune system is normal. You get covid and these mast cells see the virus, they tell the other immune cells come on help me out here, and they all you know kind of pitch in and help to clear the virus. Then after this happens everything sort of resets, the immune system resets.

You know one of the ways mast cells defend us is actually they explode. They degranulate, they produce these granules of different chemicals, inflammatory mediators, and they explode. And that’s how they’re trying to kill, let’s say the virus. In a normal person the mast cells will do that and they do other things too. But they return to normal and they wait for the next offense, right? Something that’s going to attack. 

But in people who have a syndrome, Mast Cell Activation Syndrome, they have what we’ll call abnormal or aberrant reacting mast cells. So these mast cells are not just ready to, are primed to react to the virus but they may even at baseline be reacting to things that they shouldn’t be reacting to. You know, maybe a food, maybe a medication, a scent. There are all these things that it’s getting these signals crossed, essentially. Reacting, releasing these chemicals, these chemicals are inflammatory. If you have this reaction, let’s say in your respiratory tract, you might have asthma, trouble breathing, wheezing. The mast cells are reacting in the stomach or the GI tract, you might be nauseous, you might have diarrhea or constipation. If they’re reacting in the skin you might have hives, in the nervous system, you might have numbness, tingling, dizziness, migraines.

So the point is that some people who have these abnormal mast cells, they are already reactive. Then they see something like Covid. So they’re already primed, then they’re really primed and now they’re seeing this virus in a way that is just a little bit more exaggerated. The response is more exaggerated. The response to the rest of the immune system may be more exaggerated. And patients with mass cell activation syndrome will never return back to normal after they’re done with Covid or anything else. Those mast cells will always be abnormal, but they’ll go back to maybe their baseline, hopefully, and not a higher baseline. So I think that what’s important about mast cell activation syndrome is that it is really a condition that is multi system, because it can affect every organ tissue in the body and it’s inflammatory. And again it can present to be problematic for infections like Covid, but it’s problematic if you’re reacting to the environment abnormally.

Our environment unfortunately is very toxic and you know at some point our bodies have to kind of deal with our environment. But patients who have this are constantly fighting, you know, they’re in this constant state of everything around them is poison. And so I hope that kind of explains.

Eric Gordon, MD

It summed it up just that these mast cells are too easy to be triggered. You know, I always compare them to like an irritable child. You know, we want your mast cells to be adult like and instead you’ve got a five year old that’s been up too late. And that’s what makes it so frustrating because many of the things that they’re reacting to are not inherently bad for us, the mast cell becomes confused and everything becomes the enemy. And what people I think need to understand is that you’ve got different types. 

Maybe you want to speak to this a little bit, different types of mast cells in different parts of the body? Because that’s what most doctors think about mass cells, just in terms of a rash or an acute allergy. I think that’s where people get disappointed when they go to their physicians and say I have mast cell activation. And the doctor just kind of like, eyes glaze over and goes, well you don’t have mastocytosis, which is a cancer, and you’re not wheezing, so what are you talking about? 

So how can people talk to their doctors? I just realized that that’s something that is frustrating I think. Sometimes when people listen to these summits, they come away with information because we’re so used to talking about it and we forget what it sounded like the first time we heard it from a patient. 

So is there any way you could think that people could begin to have this conversation with a doctor who is not on board yet?

Tania Dempsey, MD, ABIHM

I’m gonna do the first one, then I’m gonna do the second one. Okay, so mast cells again, they’re your line of defense for the environment, right? And I didn’t mention that mast cells are really what’s responsible for allergy. Now, allergy is not Mast Cell Activation Syndrome. Allergy is really that you have these mast cells in the respiratory tract, let’s say. And let’s say you have an allergy to pollen and you breathe in the pollen and you’re allergic to pollen. 

You have these antibodies that are against pollen trying to fight pollen. And those antibodies actually bind to the mast cell. There are these like antennas, receptors we call them, and it binds to the mast cell and says bad pollen is here and it sends that signal that the mast cells have to explode. And one of the chemicals that mast cells make is histamine. So you have a release of histamine. And people who have allergies know that when they have this release of histamine in the respiratory tract they get congested, they get runny itchy eyes, and they might have asthma or trouble breathing. They may get a rash if it’s on their skin. So mast cells are involved in that, right? But an allergy, it’s really just that it’s an allergic response and the rest of the time the mast cells are quote unquote normal, they’re not reacting abnormally to anything else. Everything is just allergy.

But in Mast Cell Activation Syndrome, we’re talking about other parts of the body that are releasing different types of chemicals. Sometimes it’s histamine, but there are thousands of chemicals that mast cells can make. And every part of the body might have different mast cells making different chemicals and causing a different response. Inflammation is by far the biggest response. So inflammation in the respiratory tract obviously is gonna cause these symptoms we discussed that look like allergy. Some patients have this allergic like reaction, but they go to the allergist and they’re told they don’t have an allergy. So they can’t, the allergy tests are normal, so that’s impossible. They’re really not allergic to anything. So they’re imagining their symptoms, right? But really it’s an inflammatory response, it’s not in that case, in their case allergy, but it’s it’s it’s a process. It’s still sending a signal to the mast cells. Bad. Something’s bad. Let’s fight. Again explode, degranulate, we say, releasing these different chemicals causing inflammation. 

So the symptoms can be different in different parts of the body. And I think that’s important to note. And I think that one of the things that’s difficult for patients, sort of tying it into your second question, is that again, if they don’t have typical symptoms of what doctors were taught related to mast cells, then they’re discounted, right? If you have anxiety, migraines, joint pain, all these different symptoms, stomach pains, nausea, right? That’s not on their radar, that’s not on the doctor’s radar, right. The doctor’s not thinking, oh, mast cells could be involved in all those things. They’re thinking, patient has a stomach problem. The patient has migraines, the patient has an anxiety problem. So, I’m gonna send them to the psychiatrist and all of a sudden the patient now has this multiple problem list. But they’re all related. 

And so, how do patients talk to this difficult question? Right. I think one of the things that I really encourage patients to do is to come armed with information. Right. There’s literature, you know, I published, Dr. Afrin has published, we’ve published a lot together. There is lots of literature, there’s enough now that you can print those articles out or send the links to your doctors and let them start to read and start to understand that it’s not a made up disease. We have medical data, we have medical, you know, support in the literature that respects this diagnosis. But it’s difficult. You know you can’t change every doctor’s mind about this, right? 

But I think that helping them understand, you know, there’s one article we published looking at how to diagnose Mast Cell Activation Syndrome. And in that article, there’s a huge appendix on all the symptoms, hundreds, hundreds of symptoms. You know you could print that out and say look I have this one, this one, this one, maybe this explains is it? I think this is one way.

Eric Gordon, MD

It is difficult and I think just armed with the idea that when you walk into the average doctors office and it’s just knowledge based. I mean to be fair, we’re taught you know we’re taught a whole bunch of stuff in medical school and unless a new drug comes out that has enough money behind it to teach all the doctors about something new. They don’t learn, because you’re running on what you already know. 

When it comes to something like mast cell activation no drug company has yet got on the bandwagon. So doctors are still operating under the idea that mast cells either are involved with allergy, and in the definition that they’re taught in medical school, is allergy involves IgE This immunoglobulin that protects your body to, as Dr. Dempsey was saying pollen and extraneous things from the environment. And if the IgE Is not elevated, or your blood tests for IgE Allergies aren’t positive then they discount the idea that mast cells have anything to do with anything. So just be aware that you’re gonna run into that and just smile and the good thing is now doctor Dr. Dempsey and Dr. Afrin and others have articles that are available and readable and they’re not that intimidating. And if you have if your doctor has no interest, you really have to find another doctor unfortunately. 

When it comes to long haul Covid, what has been your experience with treating people with some of the mast cell interventions?

Tania Dempsey, MD, ABIHM

You know, again, I think that the MCAS is a piece of that puzzle of long haul covid there’s no doubt in my mind. There’s some literature now, people are starting to look at it. They’re starting to see that mast cell targeted therapy is helping some patients. I’m the first to say that it may not be the only thing that explains long haul covid. There’s so much more. This is such a complex problem. And so I hope that research continues and all these other realms you know. 

But the part that I know that I can help patients with is to help to modulate their immune response. So, if their mast cells are dysfunctional, and they continue to be dysfunctional after Covid, and they don’t reset to normal they’re going to be in an inflammatory state. They may just have fatigue as their main symptom, they may have breathing issues. That’s the one that we see very very commonly. They may have GI Issues or persistent GI issues and a host of other neurologic issues etcetera.

Every system can be involved of course. So we’re taking these patients and we’re using mast cell targeted therapy. We are first testing them and, I think this is something that we will have to publish, is first we’re proving that these long haul patients have Mast Cell Activation Syndrome. Okay. And I can’t say 100% because the testing is difficult and sometimes we can’t get the answers. But a large percentage, you know, we’re probably at about 90%, have evidence of dysfunctional mast cells and Mast Cell Activation Syndrome. 

Now, does that explain all their symptoms? Maybe, and in some cases I think it does, in some cases it’s so much more complex. They have other things going on. Also maybe affecting the mast cells but also affecting other parts of the immune system. But if I prove that they have MCAS, I’m going to go through my protocol of mast cell targeted therapy, trying to figure out what’s the right thing to start with. Whether it’s pharmacologic, whether it’s nutraceutical, whether it’s lifestyle, whether it’s limbic retraining, we can go through all these different things that I do, but I have found that to be incredibly helpful for a lot of patients. 

So I know it’s a piece, you know, I’ll say, I don’t know if I should bring this up here, but you know, I think that some of these patients have other things. They’ve been sick actually probably for a while before they had covid. Many of them say that they were perfectly healthy before they had Covid. And many of them say that, you know, we see athletes, professional athletes, you know, perfectly healthy and then they have Covid. Well, when we take a history, there’s actually a flavor of stuff that was going on before, but they were highly functional. And so for whatever reasons, they were able to sort of control this immune dysfunction until covid sort of spun it out of control. So a lot of those patients not only need mast cell support to get them through this, but it’s looking at the other stuff that they may have been affected with as well. Maybe they have a history of Lyme disease they didn’t know about, and another infection. And this was just, Covid was like the icing on the cake, and it just was, bad analogy, but, you know, it just brought it all out. 

Eric Gordon, MD

I mean this is what you’re bringing up is I think a crucial point that, in this series where you address several times, but I think it has to be emphasized over and over again. Is that you never, not 100%, but so many people who thought they were healthy. They were, but their bodies were working a little bit over time to control an underlying source of inflammation. That and you know, because chronic, we all have it basically, chronic inflammation in my mind is how we all wind up eventually dying.

Tania Dempsey, MD, ABIHM

Actually, that’s true, that’s right. Yeah, accumulation of inflammation over time.

Eric Gordon, MD

And so we all have it and, but so many people, especially high functioning folks managed to push through it. Maybe they’re not getting out of bed with the enthusiasm they did before, but as soon as they hit the ground they’re going, you know, I mean, it’s subtle. And again and again, we see the chronic how that, you know, that mono that you had lasted a little longer when you were a teenager. Your B cells haven’t quite, well your t cells actually, haven’t quite kept that in check. And all it takes is an infection to lose the control. 

I think that’s one of the things I just want to point out to people and the point that you’ve been making over and over again, is that mast cell isn’t everything. But because mast cells engage almost all the rest of the immune system, they’re a good indication of immune dysregulation. You can have a T cell that doesn’t work right, or a B cell that doesn’t work right, or even some neutrophils that are a little off. But at the end of the day, the mast cells are the one that kind of coordinate and are your first responders to almost everywhere in the body. That’s what makes them have so much noise. 

One thing, I’d just like to go back to is, you talked about the neurologic findings and how do you tie in the neurologic changes that people have? You know, the cognitive little brain fog and you know, and when it’s mild it’s easy to write off too. I’m just getting older, but when it gets a little more noticeable people go, oh, this is an issue. So how do you tie that in with mast cells?

Tania Dempsey, MD, ABIHM

You know, I’ve actually given quite a few lectures on this. I’ve spoken about it on another podcast, but as I mentioned, you know, mast cells are everywhere, literally every tissue in the body, right? Every organ. So your nervous system is covered with, I think about it like if this is a nerve, the nerve is like a wire, you have mast cells surrounding that nerve the whole way, you have all these mast cells in the brain. And so you can imagine if the mast cells activate and they release these inflammatory chemicals, these cytokines/chemicals/mediators, they will send a message to the nervous system, they’re so close there, right there. They send a message to the nerves. They may send a message to, there’s another immune cell in the brain called the astrocyte, they might send a message there or the microglia. They’re sending a message there and those cells are sending messages back to the mast cell which is maybe causing more inflammation. But it’s this sort of vicious cycle of inflammation. The signals are bad signals. They’re leading to more inflammation.

Now, if you have inflammation in the brain, it’s going to affect your cognitive ability. It’s gonna affect behavior, could affect mood in psychiatric neuropsychiatric symptoms in the peripheral nervous system, a lot of neuropathy, small fiber neuropathies of various kinds. So the nerves are everywhere. I mean the mast cells are everywhere the nerves are and the mast cells are sending these aberrant signals to the nerves. The nerves are then releasing their own set of signals and neurotransmitters inappropriately. And then that’s telling the mast cell okay keep doing that and then again you get into this very vicious cycle. So the neurological effects because again the whole your whole body is covered. You know the nerves run everywhere, right? Different types of nerves. The mast cells are all there. And so you can imagine that that could lead to significant neurologic manifestations in patients.

So I have to say that’s probably the number one thing we see. And I would lump fatigue actually into that neurologic symptom because many of those patients have fatigue that they describe as, it’s a combination of brain fog and fatigue. 

Eric Gordon, MD

I mean you know for so many people I think the best way that they understand that fatigue is how we all feel on that first or second day of a bug. You know, any kind of cold. It’s just like where you know you can tell people what you know off the top of your head but if you have to dig further than the top of your head there’s nothing there. And that’s what brain fog is like on a lot of levels. And that’s what you said, that’s the inflammation and we get there lots of different ways. But when the mast cells are activated. Yeah it’s one of the problems. Are there particular you know of the antihistamines and mast cell stabilizers and the as you say the nutraceuticals, are there particular ones that you have found are more helpful for let’s say brain fog fatigue or just people with long covid in general?

Tania Dempsey, MD, ABIHM

Such a good question. And unfortunately the answer is no because there are so many different types of mast cells. Every person has multiple types of mast cells making different chemicals. And then my mast cells are gonna be different from your mast cells. And so every patient is so different. And because the receptors on their surface the chemicals that they’re making are so different. Unfortunately we’re at the point where we were kind of it’s a lot of trial and error eventually I think what would what would really change this is if we could do genetic testing on the mast cells and then understand what these mast cells are really making. And if we could do a test on everyone and and then we can target it directly but that we’re not there yet for that. So I think what I do usually is, I just start with some of the basics right? And some of the basics are are things that can make a big difference. And that’s why I think it’s important to start there. 

Some patients are gonna require more trials and and get a little bit more aggressive with therapy. Some patients we’re gonna hit it the first time. I think generally speaking I’ll tell you a couple of things before I even talk about drugs or or just general vitamins that are for histamine and mast cell stabilization.

Vitamin D. I want to I want to talk about vitamin D, it’s the number one thing that I do and sometimes it makes a huge difference. Mast cells have vitamin D receptors on their surface. If you are vitamin D deficient, that’s a signal for the mast cell, something’s wrong. So if their vitamin D deficient, the first thing I’m gonna do is try to figure out how to get vitamin D into them as a way to stabilize the mast cell. So that is like number one and then of course there are other things that I’m doing with the patient’s, because there’s always a lot of other issues that sometimes come up. But the next would be, sometimes it’s as simple as an over the counter antihistamine. We call them H1 blockers. You know over the counter, there’s Claritin, Zyrtec, Allegra and Zeisel.

And those are like the, we’ll call them the second generation. The first generation are like more sedating and make you more sleepy. That’s Benadryl, that’s over the counter. And so patients can try all of them and I walk them through you know one at a time, small dosage. There are different formulations of each. You know what I find with MCAS patients that sometimes they’re sensitive, not to just the drug, but the excipients, the fillers that are made, you know, when you read a label. You grab a Claritin, there are few different Claritins on the market. One will have lactose, one will have mannitol, one will have magnesium stearate. And sometimes patients do well with one brand and one formulation or another. So we walk through that and we work through the trial and errors. You know. But generally I think it’s not a bad place to start, especially if they have respiratory symptoms or more allergic type symptoms. For the brain fog,  it’s very very hit or miss. 

Sometimes, yes, an antihistamine can help. Sometimes I have to move on to the next line of things. There’s H1 blockers I mentioned, there’s H2 blockers and those are histamine blockers that are mostly in the GI Tract but somewhat elsewhere in the body. And those are drugs like Pepcid, Tagamet, the old Zantac which I think is coming back. Those block different histamine receptors and might help if a histamine is the issue. It might help some of the symptoms. Too much histamine in the brain from the mast cell, maybe these will help. 

And then there are these other drugs. Very often I’ll use cromolyn. Cromolyn is a really interesting drug and I will say that I have some really great responses. I have a handful of patients who have had amazing responses to cromolyn for brain fog and cognitive issues. And it’s interesting because cromolyn is a drug that is not absorbed. So it’s a liquid and it’s a prescription, you put it in water and you drink and the teaching and if you look at the pharmacologic information it doesn’t get absorbed into the body. So it just acts on the mast cells in the GI Tract.

And so you know some of my patients when I started giving it to them for let’s say GI symptoms related to MCAS, they would start to say that their anxiety was better. Right? And you think well how is that possible? 

So what’s interesting is that mast cells communicate with other mast cells everywhere in the body in addition to communicating with the rest of the immune system. So the mast cells being calmed down in the GI tract is sending a signal. We also make a lot of neurotransmitters in the GI tract. Maybe that’s playing a role. Maybe it’s sending signals to the rest of the nervous system, “alright calm down”. So maybe that’s why anxiety gets better or brain fog gets better. 

But it’s interesting, that’s an interesting drug that I sometimes see, like when it works, it’s really really nice. Doesn’t work for everyone. Ketotifen is the other drug that I’ll sometimes find to be incredibly helpful. Sometimes you have to start low and slow. Same with cromolyn, it has to be compounded. It’s not commercially available as a pill, only as an eye drop. But Ketotifen is a mast cell stabilizer, cromolyn is a mast cell stabilizer. But they just work differently. It’s sort of like how is their mast cell going to respond to this drug? How is it going to bind to the drug? What signal is it going to get and how it’s going to calm things down? So those would be like first line pharmacologic. You know sometimes we use quercetin, quercetin is a natural anti histamine. Vitamin C is a natural anti histamine. Quercetin also stabilizes mast cells. There are lots of other things. I think it’s just sort of like, what I think the patient is going to respond to. Maybe it’s not gonna be right. Maybe again trial and error.

Some patients are more accepting of the pharmacologic stuff and some are less accepting, maybe want to go a different route. There’s a supplement that is an enzyme called diamine oxidase which is an enzyme that breaks down histamine. And so some patients find that if histamine is their issue and their histamine bucket is too full, then they take this enzyme and it helps to break down Histamine and they and they feel better. And sometimes that histamine issue is related to food or something in the GI Tract and sometimes they take that and it’s breaking down histamine in their gut and then it’s helping their brain fog. So it’s just incredibly complex, fascinating. We’re still learning. I still learn every day. I learn something new from my patients. They teach me because we don’t know everything we need to know for sure.

Eric Gordon, MD

Yeah. And I think what I want to emphasize to people is just you know, not giving up. You know, I mean like you don’t wanna, on the other hand, you know, when you first get ill, there’s lots of possibilities when you look at, you know, you listen to summits or read things on on on lists and you know, everything sounds like you sometimes. I always tell people that in the old days one man’s Bartonella, you know, list of symptoms for Bartonella looks just like another man’s list from babesia, so you gotta be careful. You don’t fall in love with the diagnosis just because the list of symptoms fit you. But if you’re working with the doctor or practitioner and you really have good evidence that histamines or that mast cells are playing a role. Give yourself some time. 

Don’t give up just because you took one or two antihistamines and they didn’t work because you gotta give it time. And remember you might need to get them compounded if you just keep getting the same… If you feel really bad after you take these, you know or they flare your symptoms, get them compounded. It’s rare that the drug itself is making, drugs have side effects, but these guys generally don’t have many when they’re in their pure form. I mean it’s just everybody’s different but I have to have faith and keep trying.

So that was a great overview of the pharmacological approach to mast cell, maybe if we have time I might want to do a little bit more on the non-pharmacological. 

But before I get there, I want to have time for you to talk a little bit about another subject that I think that you’ve done a lot to teach people about is the – I don’t like to call it EDS. I think it’s more just you know kind of lax connective tissue, is my way of thinking of it. But you know this is something that we have seen ever since actually going back to Dr. Schumacher was the one who taught us to look for people with their with their upper limbs longer than their than their height and just for the hyper flexibility. He didn’t know why, but he just saw this and we did too. I was noticing, once he told me to look I have to admit, I need a little help. But I noticed that all my patients, I mean they’re hip flexors, not all of them but the vast majority of people who hadn’t done anything in years had hip flexors like they were doing yoga. You know like if they didn’t have bad arthritis, it was surprising their range of motion. And we see that connection, so talk a little bit about this thing that people are calling EDS and mast cells how it all connects.

Tania Dempsey, MD, ABIHM

So you know EDS or Ehlers Danlos syndrome. Ehlers Danlos Syndrome is a group of connective tissue disorders. Some of them have genetic markers that you can test for. What we’re talking about here though is really what we will call hypermobility syndrome. Sometimes it’s known as hyper mobile EDS. Because EDS is again it’s a huge huge sort of umbrella term with a lot of other disorders that evolved connective tissue. But in our patient population this hyper mobility is really significant. Now. Think about what I’ve been saying right, mast cells are everywhere. They’re an all tissue. Well they’re definitely in connective tissue. And mast cells that are normal right at baseline, they’re just hanging out there just waiting. We’re talking about patients who have dysfunctional mast cells at baseline that are releasing these chemicals very often to very little stimulus. And if these mast cells are reacting at the level of the connective tissue, you can imagine that this inflammatory cascade is now damaging the connective tissue on some level. And maybe, so in the majority we’re talking about it’s the hypermobility. We might see, well, let’s just be clear.

There are mast cell patients who don’t have any connective tissue issues, right? But there is this association that we’re starting to see that many patients have some level of connective tissue disorder. And I will say that I certainly have patients that are on the opposite end of the spectrum, they are stiff, tight beyond what you would expect. And I think that’s actually on the same spectrum of connective tissue. I think in them, the mast cell mediators are causing a different inflammatory response. And so maybe it’s scar tissue, maybe it’s something else and it’s actually contracting versus in some of these patients it’s sort of making it more lax, stretching it out. And so now they’re more, you know, limber more hyper mobile. So the association is there.

And you know, I’ll add that third piece, the trifecta. The other association we see very often is OTS or dysautonomia or postural orthostatic tachycardia syndrome. These three seem to go together for some patients. Again, every patient is different. And so maybe some patients will just have MCAS and some patients will really just have hypermobility. You know, I’m sure their patients out there, we’re not seeing them, right? Because you know, I’m attracting a certain patient population, but I’m sure in the general population there are people who are hyper mobile. You know, maybe there are ballerinas who, ballet dancers, who are flexible but are healthy and don’t have any issue. But what we’re starting to see is that many of these patients who are hyper mobile go on to present with other things that look like more of a chronic inflammatory syndrome which is MCAS.

So we’re starting to see these connections and that third piece I mentioned is this dysautonomia, which is really like a dysfunction of the nervous system, the autonomic nervous system. Your autonomic nervous system is automatic. You don’t think about your heart beating, you don’t think about, you don’t tell your stomach to digest food, everything’s sort of automatic, right? You don’t tell yourself to breathe, you just breathe automatically and you have mast cells in the nervous system as I said. And I’m not saying that Mast Cell Activation Syndrome is the only cause of this, but it’s one potential cause. Mast cell’s get dysfunctional, the level of the nervous system at this part of the nervous system leads to inflammation. Now this nervous system is reacting inappropriately. And then, you know, you may wind up with a problem like something called gastroparesis where the digestion is really slow, the signals are not getting there, that the food needs to go down, right? So patients feel full, they feel uncomfortable. It may present as POTS or postural orthostatic tachycardia syndrome where they change positions and their heart rate goes up to compensate for the inability to sort of regulate their blood pressure and they’re sort of their place in space.

So these are the things that, there are patients who have pots, they may not have hypermobility or mast activation syndrome, but more and more we’re seeing that many of them do, even if they didn’t realize it. We start to see, you know, there’s a there’s a pots community of of practitioners and patients and so, you know, for a long time they were sort of focusing on this condition, right?

But then, as those of us on the outside started to see these patients, but also see that and diagnose them with the MCAS, they started to realize, wait a second, there’s this connection, maybe the mast cell is the root of these various conditions. There’s certainly other things at play. There are certainly things that the mast cells are reacting to that’s probably spurring them on. Right. I think this is an important point. It can’t just be mast cell activation syndrome though. I have a hard time thinking that dysfunctional mast cells are constantly dysfunctional and causing this array of symptoms. I think it’s that those mast cells are dysfunctional AND there’s a mold exposure, there’s an infection, there’s some other trigger that really gets them going and then keeps them going until you take away that trigger. I think that’s really the way I’m starting to understand this.

Eric Gordon, MD

I mean that’s one of the reasons that I’m excited to meet you is because you agree with my bias, but more importantly, is that you’ve helped many people about that, mast cells, they can have a tendency to be activated, but without a constant irritant in majority of people, that’s not going to go anywhere.

You know, it’s just like this lax connective tissue, if you don’t have something that’s causing a lot of inflammation, it often doesn’t cause a lot of problems. You know, it’s minor, but when you add inflammation, then suddenly people start getting things like their dislocating their shoulders, they’re having problems with their necks that they didn’t have without the inflammation coming on. People don’t realize that because we see the body as pieces, as things that aren’t connected. That’s the beauty of your work. I know how much you’ve done to try to teach doctors how to think that this is a system, you’ve been working hard at that and I really appreciate that. The fact that you have actually written the papers and taken the time. I think patients have to understand how much extra work that is and how much dedication that takes to actually do that. But tying this up, there is, like you said, there’s so many pieces. You’ve seen the mast cell and the chronic infections. So do you have any thoughts for the future for long covid and anything that you’d like to see where the researchers should go and any, kind of like a prayer for the future.

Tania Dempsey, MD, ABIHM

I’m an optimist. So I would like to think we’re going to figure this out. I think that doing large trials of mast cell targeted therapy in them and publishing on that would be amazing. At least we would understand. I mean, what I’m talking about is somewhat anecdotal, right? But I’m a big believer in evidence based medicine. So I want to be able to prove what we’re doing. You know? I think these patients have to be tested. So hopefully that’s for the future.

I’d really love to really understand the role of residual viral particles in the body, whether that’s what’s spurring on the mast cell, probably not live virus, but viral particles. I’d really like to understand better the underlying issues that these patients, like who are these patients who are the patients who wind up with long covid? And this may be a very diverse group and I certainly have a diverse group of MCAS patients, right? Every single patient is different. 

But I’d love for researchers to try to figure out how can we… Can we predict, is there anything we can use? So that preventatively, if we knew who were the highest risk, we know who the highest risk is for maybe getting covid and winding up in the hospital. But I don’t think we really know why people are getting long covid. Like, what is it about them? Again, I think it’s immune dysfunction and other things. We have a similar idea about that, but if we can measure that and people knew that they may be at higher risk, are there things that we can use preventatively? Again, we’re doing this work, some of it anecdotally right. Some of it is based on stuff that we know, but it would be nice to be able to help people to understand.

Some of these patients unfortunately had very mild covid by the way. The vast majority of long covid patients had mild symptoms, in their description, right? Most of them were not hospitalized, but their immune system didn’t stop and continue this inflammatory system. So to be able to understand that and being able to to predict, I think would be very, very helpful and then prevent, prevent, prevent, you know.

Eric Gordon, MD

That is, you know, since I’m an optimist, I like to think that this is in a way, a blessing if there is one of Covid is that it’s opened up the eyes of the medical community to this post viral. It doesn’t have to be a virus, but they’re hung up on it. We’ll call it post viral syndromes that have been a problem forever but have been ignored until recently because the symptoms that are provoked are ones that are easily ignored because their blood counts are normal. That is the problem. 

I’m with you, I’m a great believer in evidence based medicine, it’s just I’m – the people who heard these summits will hear – I’d like to call it evidence bought medicine because without the money it’s hard to collect the evidence. So my prayer is to have a way to actually harvest the information that primary care doctors or consultant doctors, like we are, get. I mean, just imagine if we actually could collect our data and have scientists and researchers look at it. I mean, it would be very hard because again, I’m going off here, but just so people understand. What makes medical science so difficult and makes it a science is because science likes experiments with single variables and you cannot do that with people.

So we’re kind of left with stuff that still sounds like anecdotes. It’s tough but to collect clean data often means to clean out the human piece, you know, and that’s why they study mice because it’s easy, they’re all the same. So anyway, just for people to understand that, that’s why medical research and things that really we care about, which is human health is so confusing and that’s why when you look at the stupid studies, which I call the stupid studies, the epidemiologic ones that look at population studies. That’s why one population study tells you eat meat, the next one says be vegetarian. The other one says drink coffee, the other one says don’t drink coffee because they’re asking the wrong questions and they’re getting garbage because there are some people who should eat meat. There are some people who would be better vegetarians. There’s some people who coffee is wonderful for. There are other people who it isn’t. We’re different and, until we get that through medicine, and figure out a way that really smart people can help us do experiments while we still can hold the variability.

That’s the human condition. I’m sorry to tirade about it, I want so much to have data. I want to be able to know how to help my patients. But at this point in time, a lot of it is just what seems to work. So anyway, prayers to all of us that through the massive amount of money that’s being thrown at this, that there’s going to be enough really good intentioned smart people are gonna get enough money and we’re gonna learn stuff. I hope some of it comes your way. I know you haven’t probably thought about applying for it because it seems overwhelming. But you know what you and Larry are doing. And with the groups that you work with, that would be a really wonderful service if you could gather some of this. Because this is a piece, as you say, it’s not the whole story. But the mast cell activation, long covid, chronic fatigue, right, chronic lyme. They’re all woven together and thank you for helping us unleash. We’ve at least some of the therapies.

Tania Dempsey, MD, ABIHM

Thank you. It’s my pleasure. 

Eric Gordon, MD

A pleasure. Dr. Dempsey.

Tania Dempsey, MD, ABIHM

Yeah, same here. Thank you for having me.