Dr. David Kaufman on ME/CFS, MCAS, POTS and complex disorders - Mast Cell Matters Series

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Jill Brook: Hello fellow mast cell patients and marvelous people who care about mast cell patients. I'm Jill Brook and today we have another amazing not to be missed episode of Mast Cell Matters with our incredible guest host, Dr. Tanya Dempsey, a Johns Hopkins trained physician, researcher, and world renowned expert on MCAS.

Dr. Dempsey, thank you so much for hosting today and which of your illustrious colleagues did you bring with you today?

Dr. Tania Dempsey: Oh, I am thrilled to have my good friend, Dr. David Kaufman here today. This is going to be a really fun podcast. We're going to take some really deep dives. I'll do a quick intro on Dr. Kaufman. He has such an interesting background. He actually started in the, in the, I guess, filmmaking world.

He got a BFA from NYU, and MA from Teachers College, Columbia University in Education, and then his MD from New York Medical College, and then he completed his internal medicine residency training at [00:01:00] St. Vincent's Hospital in New York City. And he began his internal medicine practice in Greenwich Village in New York City just around the time

of the HIV AIDS epidemic. And so he was deeply involved in the care of HIV patients and in research aimed at discovering ways to treat both the opportunistic infection they were dying from and the virus that was causing the destruction of their immune system. And actually, that sort of, I think, paved the way for his practice, which evolved over time and evolved, evolved into taking care of patients with complex diseases like Lyme disease, fibromyalgia, chronic viral diseases, vitamin and nutrient deficiencies. And, you know, eventually he really became an expert in ME CFS dysautonomia, autoimmune diseases, tick borne infections, and Mast Cell Activation [00:02:00] Syndrome.

In 2017, he opened his clinic, the Center for Complex Diseases, and he's doing some great stuff. He's a working member of the U. S. ME CFS Clinical Coalition and part of the Guideline Committee, and he helped write the Consensus Recommendations published in the Mayo Clinic Proceedings. Dr. Kauffman, it's a pleasure and honor to have you here today.

Dr. David Kaufman: Well, thank you. That's quite an introduction. Thank you very much, Tanya. I could pretty much say all the same things about you. So, this will be an interesting hour to spend together, especially since you probably know more about Mast Cell than I do, but let's see how this interview goes.

Dr. Tania Dempsey: Oh, oh, I don't know about that.

Dr. David Kaufman: I think so.

I'm sure we're gonna wander all over the map.

Dr. Tania Dempsey: We will, we will, because what I really love is just your perspective on, you know, it's not so much about just the MCAS, it's, it's how MCAS is involved in these complex [00:03:00] diseases that you're, that you're treating. Right? And, you know, one of the areas that I really wanted to chat with you about, because it's an area that we've, we've talked about before, and we continue to talk about is this sort of spectrum of, of conditions the septad.

The pentad, the decad, I called it a decad recently in a conference because it just keeps exploding, but I'd love to sort of talk to you about what it is, how you see it, how it plays a role in these patients, how MCAS fits into that. Maybe we can kind of dive into that.

Dr. David Kaufman: Sure. Sure. So, as you know, I mean, the whole septad concept is, I don't know if passion is too strong a word, but certainly something I have great, strong feelings about, because I think it's an incredibly valuable concept and roadmap for looking at our chronic complex illness patients. You know, the first thing that it drives home, which I think is fundamental, is our patients don't have just one thing wrong, and that, [00:04:00] that flies in the face of the way you and I were educated.

You know, we, we were taught in medical school, you're taught by organ systems, and then you go on, you have clerkships, and you do cardiology, and you do neurology, and you do urology, and infectious disease, and everything is kind of these separate systems. To be negative about it, they're silos, and that works.

It works if you're having a heart attack, and it works if you have a brain tumor, and it works if you have, you know, multiple sclerosis, but it doesn't work if you have multiple complex pathologies that are occurring together and interacting together. So that, that's why for me septad is so important. Beyond that, it lays out, it, it's, it's not something we invented to make patients fit into it. It really comes from, actually from Andy Maxwell initially, Dr. Maxwell, who's talked about a pentad because in the very beginning after our Northern California MCAS meeting, the first meeting we [00:05:00] had, you know, shortly after that we put the listserv together, there's 25, 30 doctors, now there's 550, okay?

So, and I just, I still remember his email, which was kind of a, you know, aha eureka, why do all of our patients who come with mast cell also have EDS and gastrointestinal motility and POTS and on and on and on. So, that's where it came from, and since then it's, you know, evolved into this 7 piece thing, although I agree we could keep going up and up, but I still find 7 just works easiest. And as a clinician, you know, when I meet a new patient, these patients are really complicated, okay? They don't just come in and say, or they may come in and say, I have ME CFS, but, but then when you take your history, as you well know starting from the beginning, there's just layer upon layer upon layer of quasi pathology, quasi problems, [00:06:00] background noise that doesn't sound like illness, and then all of a sudden, bam, they explode and they're sick as they're very sick.

Dr. Tania Dempsey: Yep.

Dr. David Kaufman: And, and then the septad provides a roadmap, both for how I can ask, take a history, and how I can explain to patients, which in some ways I think is the most valuable piece, how I can plan out a workup, because when you, when you're looking at so many different pathologies, there's a lot of different kinds of testing you want to do, and then of course how to plan treatment.

So I find it just an invaluable roadmap to understand these patients.

Dr. Tania Dempsey: Yeah, I agree. And how do you see the MCAS piece? Is it, is it do you think that the MCAS is driving these conditions? Do you think that these conditions are potentially driving MCAS? Do you have a sense of, because I have, I have my own kind of way of thinking about it. I'm curious where you are on that.

Dr. David Kaufman: So, [00:07:00] you know, as I said a little earlier about the septad I think a key piece is that it's all interactive. You know, I have this diagram I made for some talk, I think with Eileen Ruhoi, and you know, it's got seven circles and their name for the different septad components, but then there's just a million arrows all the arrows you know, because it all interacts.

So, so yes, let's let you answer your question directly. So if a person has MCAS for a variety of reasons, which we can dive into, that's going to provoke or may provoke worsening POTS, worsening motility disorder, certainly brain fog. I believe it makes their EDS get progressively worse or even creates connective tissue disorder.

So it's all interactive. If the question is, how often do I see it as a component in septad patients? At least 80 percent of the time. Yeah. Of that 80%, I, I can't say that each, all, every patient has been, [00:08:00] quote, confirmed by labs. But they tend to be confirmed by response to treatment.

Dr. Tania Dempsey: So, do you have a sense, and I want to talk a little bit about root cause, right? So, I, I kind of think about this as, you know, is it is it that these patients are just vulnerable? They have genetic vulnerability or other, other something that makes them develop MCAS and then maybe these other conditions, or they have the genetic predisposition for, let's say, EDS, and then they wind up getting other things?

Are there, are there things in the environment, you know where I'm leading you, infection, other things, where do you see, how much do you see these other pieces, actually, as the, as the root of the septad

let's say.

Dr. David Kaufman: So I do think that there's probably a genetic predisposition. I don't know what that is, what the genetic mutation or whatever is. And as you know, when [00:09:00] we take a history, or when I take a history, Let me, let me back up. So a patient comes in and they say, I was completely fine until I was 33 and I got mono and I've never been the same since.

And then you take their history and it turns out that from, you know, the first in their infant and toddlerhood years, say 0 to 3, they had rashes, they had colic, they reacted to foods, they had allergies, okay, and then from 3 to 8, they had more allergies, and then they start getting these infections and sinus infections, and they had asthma, and all of those in my mind become hints of early MCAS.

Not MCAS disabling the way it is in the patients you and I now see, but just say allergies. I mean, you know, it's like background noise that's not disabling enough to upset the patients, the families, and the doctors. It's kind of like, well, that's just growing up, you [00:10:00] know. And then something happens, and it's usually an infection.

That kicks off major, you know, significant Mast Cell Activation Syndrome. And that infection may be the mono that I just mentioned, an EBV viral infection it could certainly be a vector borne infection, Lyme disease, Bartonella Babesia but that becomes a new driver of MCAS, which then causes inflammation and kind of on and on and on in the cascade.

I don't think. Actually, I'm curious to ask you. Have you ever had a patient who only had Mast Cell Activation Syndrome and nothing else?

Dr. Tania Dempsey: No.

Dr. David Kaufman: Okay, that's my answer too. I don't see it.

Dr. Tania Dempsey: Because I think you can just obviously just concentrate on this one, even though MCAS is a huge thing, right? But the more we dig, the more we, we understand this, it's just so clear to me that the environment, and how we think about this environment is such a [00:11:00] key player in this, and, and without addressing those things, you, you just, it's just much harder to, to get the patients

Dr. David Kaufman: Right, I agree.

Dr. Tania Dempsey: And the environment is just, I mean, that's just like a garbage bag filled full of, like, lots of things, because I think that I think of environment as, you know, let's say early childhood traumas, or where they live, what kind of home they lived in, whether it was moldy, or there were other chemicals, or whether they grew up on a farm where there were, you know, spraying pesticides, or near farmland where they were spraying pesticides, or they got, you know, infected early on with various viruses, or tick borne or vector borne infections, right?

It's so huge, and the more I learn, the more I don't know, the more I see that there's just so much more. But there has to be I think the set, I think that sets the stage so [00:12:00] that these patients won't have MCAS, they can't have MCAS alone because they have all these other things that caused it and are causing other things.

Dr. David Kaufman: I completely agree. Maybe this is because I'm totally immersed in this world of complex illness, but it seems to me that the world of complex illness patients is exploding, okay? Now, there's no question that's true because of Long COVID. That's an instant explosion. Epic explosion if you think about the numbers, it's millions of people and that's, that disease or illness to me is virtually the same as ME CFS and I've, I've, I literally have only met one Long COVID patient so far who didn't have a septad picture and didn't have a pre existing history that was consistent with what I've seen in ME CFS and septad and, and, Long COVID patients. And I think you're right. Part of the problem and part of the reason I think there is so much [00:13:00] growth in this complex illness world is that our environment is polluted and contaminated and, you know, overused word, but filled with toxins. Our food supply is contaminated. Our air is contaminated.

And that's only getting worse. And, you know, to make it simplistic, I think it it's obvious that our immune system is going to respond to that. And once that happens, that sort of starts the stage. So I think you can't separate the two. I mean, you can't separate MCAS and this chronic illness from what's happening in the larger environment.

Dr. Tania Dempsey: And I think it's going to get worse.

Dr. David Kaufman: Yeah, I absolutely think it's going to get worse. I hate to say it.

Dr. Tania Dempsey: I think it's inevitable with COVID in the mix, of course, that that's, I think precipitating like a explosion. But then I think just in general, people are just going to be sicker.

Dr. David Kaufman: Well, they'll be sicker. I mean, you know, to just climate change alone it's already demonstrated. It's increasing the incidence of [00:14:00] the tick population and therefore Babesian and Lyme and Bartonella. It's like, it's kind of staring us in the face. And that's going to increase the incidence of various viral diseases.

You know, some of the things that we think of as South American or Latin America or the Caribbean, they're all going to come north because it's getting warmer.

Dr. Tania Dempsey: So, but I want to give people hope and I, and I do think there is hope. That's why we do the work we do, because we, we can help people and but we need, we need, obviously people in politics and in policy and whatever to be doing the big, there's a lot of big stuff to be done, but we can do it on the individual level, right?

So let's talk a little bit about the ME CFS portion of did I say that right? ME CFS portion of the septad. You know, and how you feel that relates to MCAS specifically, how do you [00:15:00] approach ME CFS? Do you approach it from the MCAS perspective? Or are there other things that you're thinking about?

Dr. David Kaufman: Well again, that's, that's why I find the septad concept so helpful, okay. So in one of the first talks I gave at our second MCAS meeting in Boulder I did a chart review of my own charts and my practice, so already very skewed, but literally 80 percent of the patients who had a ME CFS diagnosis, 80 percent had Mast Cell Activation Syndrome. That's an enormous number. And I may have missed the other 20 percent for all I know. So I always look for it. I've learned the hard way that if the history isn't suggestive, that doesn't mean they don't have it. It just means I've missed it. If the labs are negative, it doesn't mean they don't have it.

So translate that into I have a very high index of suspicion with every new complex patient that they may well have Mast [00:16:00] Cell. Until proven otherwise. I'll go out on that limb and just say, until proven otherwise. And, and, as an example, when I have a new patient, you know, I take a long history, I spend a lot of time, as, as you do, and ask a million questions, drive them crazy, do my exam, and then go over what I think is going on and order a ridiculous amount of tests, you know, 30, 40 tubes of blood. But treatment wise, I tend not to make too many decisions because I don't have enough data. But I routinely do three things, almost with every patient. I ask they do a trial of histamine 1 receptor blockers, antihistamines, histamine 2 receptor blockers, like, Pepcid, Thuminidine, and I start them on LDN if they're not on low dose naltrexone.

Okay? So, the fact that I'm doing those H1, H2 blockers with no data, no data, no labs, tells you how suspicious I am. Okay, and I, and I'll take it a step further. [00:17:00] If they don't improve, that doesn't rule it out to me. Right? It's, it's, it's great if they improve, because now I have one clear answer.

Dr. Tania Dempsey: Then if they don't improve, right, so what are, what are your next steps?

Dr. David Kaufman: Well, I think I'd say that it depends on how much new information I get. So certainly if I get some positive labs, then I'm gonna start ratcheting up the treatment. I'll add more Mast Cell stabilizing type drugs and products or interventions, work on triggers, try to identify what might be making them worse, but then go into the rest of the septad and look, you know, very deep dive for infection, I, you know, fully disclose I have a great bias towards infection as a driver for all of this.

So, you know, so to me that's a major piece to the point where I'll almost say if the patient has an active infection of any kind, their mast cells not going to get better. I think one drives the other. And infection, just to be clear, can be tick [00:18:00] borne infections, but it can be reactivated EBV or reactivated HHV 6 or HHV 7, Mycoplasma, Chlamydia, Pneumonia.

Those are kind of the biggies. And of course COVID is now in the mix as well.

Dr. Tania Dempsey: Yeah, let's talk, let's talk about COVID because, because this is a really, really important topic now. And you mentioned early on that you really think of Long COVID as ME CFS. You really see those as equal in terms of, right, they're, they seem to be the same process, right?

Dr. David Kaufman: Well, think about it. ME CFS is a diagnosis made by checking some boxes. We don't have a biomarker. We don't have a blood test. We don't have a X-ray. So I use the, you know, the, the Institute of Medicine criteria from 2015, which is literally a bunch of check boxes. Does the patient have fatigue greater than six months?

Do they have post exertional malaise, et cetera, et cetera. And if you take that, that diagnostic [00:19:00] screen, it, it's true for the Long COVID patients. It's identical, right? It's not like they come in and they say, I have Long COVID, but I absolutely don't have ME CFS. It just doesn't work that way, you know, and I think that tells us something about the underlying pathology of the illness or at least may help us figure out what directions to aim research at.

Okay, which is, you know, one of the few silver linings in the COVID, Long COVID sky, which is now finally maybe we'll get some dollars spent on research that will help the millions of ME CFS that haven't been addressed, haven't been looked at.

Dr. Tania Dempsey: There are two areas that I'm really interested in and I'm curious what you think. One is the connection, not just to ME CFS, but also to MCAS. Right, and so what role MCAS is playing. And again, it's, it's related to all these things we've been talking about, but maybe we can just talk about it a little more specifically to Long COVID.

And then my other question is going to be about the [00:20:00] underlying things like underlying infections in patients who get COVID and then develop Long COVID. Because that's one thing that I see a lot of is that development of reactivation of they had Lyme, they didn't know it, or they knew it, and then they got worse, things like that.

So I want to explore those, those areas a little bit.

Dr. David Kaufman: I, again, I think it's the same picture that patients come in, there's something about post viral fatiguing illnesses that seems to include leading and causing Mast Cell Activation. And likely that something is that the infection provokes inflammatory response, probably changes gut motility and gut microbiome and that leads to leaky gut and that cause, and those things cause constant immune activation, which by definition is one of the things that's going to activate [00:21:00] mast cells. I had COVID, so why didn't my mast cells stay over activated? I don't have that answer. I think I just was lucky that I didn't progress to Long COVID.

Dr. Tania Dempsey: Were you lucky or did you just not have underlying dysfunctional mast cells before you got COVID.

Dr. David Kaufman: Yeah, so I think, thank you, I think that's true because that's why I said I've only met one Long COVID patient where I couldn't pull any history whatsoever suggesting previous mast cell disorder. Okay, so that's, that's correct. Right. What it is specific, so, so if the question is why does a COVID slash Long COVID patient develop Mast Cell Disorder, I think it's related to this level of inflammation in already primed or vulnerable mast cells.

You know, and, and, and again it's bidirectional, which is, you know, something I'm constantly trying to think about and explain to people. In a similar way to Mast Cell. If we accept that there [00:22:00] might have been something happening that wasn't significant enough, and I constantly use this term background noise, not silence, noise, okay, like, I have chronic sniffles, that's not nothing.

It's nothing if you're otherwise healthy and, you know, et cetera, but it's noise. So, Long COVID kicks that off for mast cells, and in the same way, it just, Long COVID or COVID, causes a profound disturbance of the immune system and that means immune competence may decrease even though at the same time there may be so called cytokine storm, okay, and that allows or may allow reactivation of anything pre existing that's just hanging around in a latent state.

So you and I were taught from day one of, almost day one of medical school, that the herpes family of viruses never leave our bodies, we never get, we can't kill them with our immune system. We all get EBV. We all get HHV 6. We all get [00:23:00] CMV. But it becomes inactivated and latent. Okay, I like to use a simplistic image of locked up in a cell.

They're in jail, cellular jail. But the implication of that is that whenever the jailer is gone or not, is sleeping on the job, all that EBV wants to do is break out and reactivate. So, you know, it wasn't a surprise that suddenly people realized that COVID led to EBV reactivation. It's like a no brainer, if you think about it.

And you and I would argue, or do argue, that the same thought process is true for the tick borne infections. That's not well accepted in mainstream medicine. Maybe one day it will be. But I've seen it too many times, you've seen it too many times. A patient says, oh, I never had a tick bite. I just grew up in Connecticut and I did hiking and fishing.

I rode horses, and I had a cat and a dog and ticks in the house, but I never had a tick attachment, never been diagnosed. And then lo and behold, they have positive testing and they're [00:24:00] sick. They undoubtedly were infected as a kid or an adult, and then, you know, their immune system took care of it, and then it reactivates with the insult of COVID.

And that's why one has to look for that. So when I see a Long COVID patient, sometimes they'll look at me like, Why are you looking for tick borne infections? I'm here for Long COVID. What does COVID have to do with tick?

Jill Brook: And are patients going to have symptoms of that reactivated virus, or it's only upon testing for it that you would find it?

Dr. David Kaufman: So the question is, how do you sort out the symptoms? How do I, you know, it's easy when you have, let's say, let me change your question to Lyme disease just for a second, okay? So do they have symptoms of Lyme? Well, you know, it's easy when somebody has acute Lyme disease, they come back, they have a, you know, a target lesion and they have joint pain or, or, and fever and flu syndrome, you have Lyme disease, treat them and they're better.

But 30 years later, those symptoms are not necessarily what will, how the reactivated [00:25:00] organism will present. You know, it's, I, I can't sort that out. I would just say it adds to the whole mess of what the patient feels. Which is why you have to look. This is no easy symptom picture. You agree with that, Tania right?

Dr. Tania Dempsey: Yeah, yeah, absolutely. And sometimes when you take that history, you will get that history, not just of their exposures, but that there were these low level symptoms that, yeah, sometimes we, you know, it is an MCAS situation. Sometimes it really is, you know, suspicious for Lyme, suspicious for Babesia or Bartonella.

They have these low level symptoms that are bothersome enough. that they notice it, but not enough that they really went to anybody to diagnose it, right? So they, they went to some doctors, they told them maybe they had anxiety, that's why they were having palpitations, but maybe it really was something else going on.

So you often see like a flavor when you take that [00:26:00] history of stuff that was there before COVID. And then COVID is, is in some cases the straw that breaks the camel's back, and then it's all out. Sometimes the history is a little more subtle, and it's a little bit harder to see how those conditions were, you know, were manifested before.

But I would say more often than not, it does become a little bit more obvious that there were things that, that patients had. And that the, you know, the story that I see quite often is that the patients come in with this, I can't tell you how many times I've seen this really, they, they say I was perfectly healthy

before I had COVID. That's, that's their sort of

presentation, right? I was, I was healthy. I've seen athletes, professional athletes, that were quote unquote healthy because they were athletes, right? But, but when you go through their history, they were just very high functioning athletes who had very, you know, significant medical [00:27:00] problems that were sort of masked in some ways.

Dr. David Kaufman: Yeah. I see that all the time. I mean, I said earlier, I've only had one Long COVID patient where I couldn't get that history. One. Every other history that's, like you said, starts at, doc, I was fine until I got COVID. Not true. I mean, it's true, but, but then if you look hard enough and ask enough questions and start far enough back, there's other stuff there. I want to come back to your question, Jill, because it's a really important question. So, you're right, one of the, one of the I was going to say conflict, but that's not the right word, one of the puzzles here is, in these patients, their symptoms are not always consistent with what you might say is causing infection, whether that's reactivated EBV or Lyme or Babesia.

And that's probably because it's not the only thing going on. There's so much else going on. But I, I, I will tell you that it makes me, there are situations where [00:28:00] I feel anxious and doubtful, am I right to be treating this because the patient doesn't have any symptoms that I can say, this is from that, okay?

The, the easier example for me is often the EBV reactivation where the patient, it's not like the patient says, well I have a sore throat and swollen lymph glands and low grade fevers. They don't have anything. They have Long COVID. They have fatigue and PEM and brain fog, but now they have an EBV that's PCR positive with a high, you know, viral DNA in their blood.

I can't ignore that. It has to be part of the problem, even if they're not giving the classic symptoms. And same with, same with the tick borne infections. It's, but as a physician, and I know Tania feels this way, as a physician it's challenging because it means I'm going to be giving them antivirals, which have side effects, or two or three antibiotics for months and months and months, and am I really doing the right thing?

They don't have classic symptoms, but I have labs, so it's, it's not an easy road.

Dr. Tania Dempsey: Yeah, and that's why it really has to be so [00:29:00] personalized and individualized, right? Because you're treating the labs, you're treating the patient, right? So we go back and forth on that. I think it's, I think it's really, really, really tough. And I think testing, of course, is also, you know, with without it, with, with lots of issues, right?

Dr. David Kaufman: In fact, let's, let's talk about that. That's a great conversation piece right there. So, I will say to a patient what I just said to you, to both of you, about my personal anxiety I experience as a physician making a clinical decision. And, and to put it in a context, I'll say, look, if I had a completely normal patient, normal meaning no complaints, they came in because they thought I did physicals, you know, annual physicals or whatever, and they have no complaints, not COVID, nothing, okay?

And for some reason, I'm stupid enough to waste their money on tick borne disease testing at any of the labs you and I use. And I get back positive results, what would I do? And my answer is, I'd do [00:30:00] nothing. Alright? Almost for sure, I'm just going to explain this to them and say, look, you clearly have been infected at some point in your life, I don't think it's active, you're a healthy person, I'm not going to treat this.

But you should know, it could reactivate at some point in the future.

Okay, so the study I'd love to see is a hundred patients from Connecticut, people, not patients, people from Connecticut with no symptoms whatsoever of anything, and a hundred from Texas, and a hundred from Florida, and see what he gets.

See what is the background level of positivity or negativity in those tests. Because until we figure that out, We're never going to get mainstream medicine on board with how significant this problem is.

Dr. Tania Dempsey: And I think, right, I think we need the studies for that, but I think that just anecdotally, I think, and, and I, and I say this to my patients sometimes, you know, I, I, I use this analogy, I'll say, [00:31:00] you know, if I pulled a hundred people off the street right outside the office, and I brought them in here, and I did testing for tick borne infections, I think 80%...

Dr. David Kaufman: Yeah, well, look where you live. Right.

Dr. Tania Dempsey: Exactly. Well, exactly. 80 percent for Lyme. I think probably more for Bartonella. And I think, I think what would be interesting to see is, you know, what's the, what's the rate of positivity in Texas for Bartonella? Because my guess is it would be the same as Connecticut and New York, but maybe Lyme would be, would be lower, right?

And, and, and what about Babesia, right? These are things that we need to know because my guess is that, that we, this is a huge problem, and I know it is but when you get these positive tests, the problem with mainstream medicine is that they can't imagine that all these people are, are positive. That's what we're up against all the time.

Dr. David Kaufman: Exactly. I mean, you're saying just what I was saying. It's a huge issue. And if you go to antibody testing as opposed to direct positive testing, PCR, etc. [00:32:00] Antibody testing is even more confusing. You know, if you, if you run antibody testing at GALAXY or IGENIX, on Bartonella, the positivity rate is mind boggling,

okay? It's mind boggling. And, and this is in patients who don't necessarily have active Bartonella infection, but they have it in them. And the funny thing about mainstream is it's widely accepted that everything you and I just said is true for EBV, HSV 1, CMV, meaning we all have it. By the time we're 20 or 12, 12 years old or 20 years old, 80, 90 percent of the humans have these infections and they are not regarded as a significant problem, but every, most doctors do know about the risk of reactivation.

I think we're only now beginning to appreciate more completely how significant that risk of reactivation is, and what it can do, witness the, you know, the quote discovery that MS may be caused by EBV. [00:33:00] I mean, that actually is not new news as far as I remember. I remember hearing that years ago. But now, it suddenly means something.

COVID with reactivated EBV. I see that all the time. That is now a starting lab test when I meet a Long COVID patient. That is not insignificant and may have a big role. EBV is a nasty virus when it's active. So I think, I think we're going to, as we sort of said earlier, more and more complex illness problems as we see more and more of these reactivated illnesses begin to occur.

Dr. Tania Dempsey: Yeah, and sort of to, to sort of, piggyback on this idea of reactivation, maybe we can talk about persistence of infection and how that may relate to not only the vector borne infections and the viruses, but also COVID specifically. Because because there's now more research showing, right, that COVID is maybe persisting

in some patients. And we know that people have had treatment [00:34:00] for Lyme disease, but they still have Lyme disease. So let's talk a little bit.

Dr. David Kaufman: Sure, sure, sure, sure. So, yeah, I'm glad you're asking because you can't really talk about reactivation without talking about persistence, okay? And let's take the easy example first. Let's take EBV again.

I can't get rid of EBV in any living organism, any living person, okay? Neither can you. None of us can, okay?

So when I give or suggest an antiviral, I'm just trying to make up for the immune system's disturbance or, or loss of competence and suppress that virus back into their cellular jail long enough that hopefully the immune system recovers. So that's a persistent infection. That model is totally accepted in medicine.

The easier one to talk about is shingles that, you know, those of us who didn't get vaccinated, which is, I assume, all of us on the screen,

for chickenpox, okay, we got chickenpox as kids. That chickenpox virus, I mean this is mind boggling if you think about it, that varicella virus, the [00:35:00] chickenpox virus that we got, that I got when I was five, could give me shingles tomorrow.

That same virus, it's in there, waiting to do it. So I think the persistence concept is, is critical and it applies just as much in tick borne infection. I had a conversation with with Bob, Bob Mazziani.

The conversation, I'll simplify it and, and, and paraphrase, Bob, how the hell am I going to cure these people? You know, when do you know when, how do you know when to stop, okay, because it's, it's a brutal infection. And his answer, which is what I thought, but it's nice to hear it from him, is, you don't necessarily have to cure them.

You just have to get lower the burden of infection enough, while improving their immune competence, that they live with this infection in some persistent state. Which we do with thousands of bacteria and viruses in our body. So, you know, it kind of brings you back to the immune system, which is so key.

Jill Brook: So are you implying that there's a part of the immune system that is [00:36:00] failing to keep down the Epstein Barr or whatever virus it is? And so, that then triggers the mast cells, which are now becoming overactive as almost like an overcompensating for something. How come the mast cells can't just make up for the, the immune system and help put everything back?

I guess, I mean, this is probably way too simplistic, but it seems like one part of the immune system is failing and the other part's now overactive.

Dr. David Kaufman: So, so in it, let's split it into two pieces. So the first part of your question is am I saying that there's a, a decline in immune competence allowing this to happen? I can't imagine any other explanation for that. It's not like the EBV sits in its hibernated state lifting weights and gets stronger and stronger and more and more virulent and breaks out of jail.

That's not what's happening. I mean, it's, it's literally latent. It's not doing anything. But it's kept that way, or the jail cell is kept locked because of a competent immune system. And to be [00:37:00] clear, that decrease in competence can be COVID, it can be Lyme disease, it can be death of a loved partner or family member, it can be a major fight, it can be pneumonia, it can be surgery, it can be prednisone, steroids, chemotherapy.

Whatever impairs immune function may allow that to happen. Which does raise a question, which is probably EBV reactivation happens way more than we understand in, quote, healthy people, alright? So once in a while I may wake up with a little sore throat, maybe it's because I didn't sleep well and EBV reactivated for 24 hours.

I don't, we don't have that data. I, the only data we have is that we all have EBV. The second part before I leave that, so that's why I think viral suppression in our sick patients, using meds to suppress the virus, and whatever possible interventions we can do to strengthen the immune system and go after the rest of the septad or whatever else is going on, which includes [00:38:00] mast cells.

Mast cells will get activated by the immune, the inflammation and immune activation against the EBV that's now broken out. That will activate or may activate mast cells. They can mount inflammatory response, but they are a first line, you know, innate immune system, so I don't think they have antiviral function. So I don't know if that's what you were asking, Jill, but, but at least that would be nice. If we had overactive mast cells, at least that would help get rid of the infection, but it doesn't.

Jill Brook: Interesting. Okay. Thanks.

Dr. Tania Dempsey: Do you think that people with MCAS sort of, I guess, kind of talking about the immune system here a little bit. So if you, do you think people with MCAS have, are immunosuppressed, immunodeficient? Do you think that there is part of the immune system that isn't? It's kind of like what Jill was saying, but do you think there's a part that isn't working or, or is it different in everybody?

Dr. David Kaufman: So I'm not an immunologist, okay? So my thinking is somewhat simplistic on this. [00:39:00] I think anyone who has reactivation infection has some kind of disturbance in their immune competence. But, but, but I can't say they have immunosuppression. And, in fact, in most of these patients, if I look at their immunoglobulin levels and their IgA and their IgM and their T cell subsets and their B cells, they're all normal, right?

So it's not obvious in the easy testing. I'm sure there's immunologic testing that dives deeper into how the T cell responds to viral antigens or whatever that may show a problem.

So, you know, I don't, I don't know how to demonstrate the incompetence other than the fact that you're not supposed to have EBV floating around.

Dr. Tania Dempsey: Right. No, I agree. I just, I wish there was a way to, to identify it, right?

Dr. David Kaufman: Well, I think there are things we can do to improve immune competence.

Dr. Tania Dempsey: Yeah. So what's your approach?

Dr. David Kaufman: Well, it goes back a little bit to what Jill said that you know, if they have mast cell activation, also I'm going to want to control that because that's [00:40:00] going to further, harm or impair their immune system.

You know, let, we should throw in a concept here. We, you know, we have these incredibly elegant bodies and immune and including the immune system and just amazing products of evolution. But the fact remains that all of these systems, the hormonal system, immune system, they can, they can wear out, they can get burnt out, literally.

You can have t-cell exhaustion. You can have adrenal exhaustion or adrenal insufficiency, if you want to say adrenal fatigue, you can have that. So, I think that's part of what we see in our complex illness patients. The systems just get kind of run down, you know. There's a reason that virtually every ME CFS patient and every Long COVID patient has a disorder of their hypothalamic pituitary adrenal axis with low cortisol.

Because when you're stressed, it's all pouring cortisol out, and after a while the adrenals say, bye bye, I can't do it anymore. So you asked me [00:41:00] about the immune system, and I got off topic.

Dr. Tania Dempsey: No, no, no. It's good. This is all good.

Dr. David Kaufman: So I think you need to look at what else is going on. So, can you, can we quiet down the mast cells? Are there any other infections going on?

Alright, when there's you remember back in school and residency If you had a patient with an STD, a sexually transmitted infection, that came in with gonorrhea, what's the first thing you're supposed to do? Look for syphilis, look for herpes, right? Look for the whole flock of STDs. So, if I see a patient with Long COVID, which I'll call a viral infection, sort of a post viral infection.

I'm going to look for other things. EBV, tick borne infection. So you, you need to look for, you need to look a lot. You have a wide net, okay? So mast cell infection, if they have POTS, Dysautonomia, which again, almost every Long COVID patient I've seen has. Actually, every single patient I've ever seen with Long COVID has POTS.

Or has a [00:42:00] disorder of their hemodynamic regulatory system. How's that?

Dr. Tania Dempsey: Kind of autonomic dysfunction, right?

Dr. David Kaufman: So POTS is going to cause inflammation if for no other reason than it's going to cause stress to the person which will ignite the stress pathways, etc. etc. So you want to control their POTS. Same with their gut and if they have SIBO, Small Intestinal Bacterial Overgrowth with a leaky gut. That's going to drive illness constantly. That'll continue to drive mast cell activation. That'll continue to harm the immune system from overactivity. Just, just think about leaky gut for a minute.

And Tania, I know you know how nuts I am about this. So that leaky gut which is a term that I used to roll my eyes at back in New York before I kind of understood all this. What leaks is bacterial cell wall debris, and what's leaking is lipopolysaccharide, LPS, okay?

LPS is what causes sepsis. It's what causes people to end up in the ER with a 50 percent mortality rate from sepsis. That's what it is, LPS. So in leaky gut, [00:43:00] that's what's leaking. Obviously not at that level of volume. It's a slow leak instead of a firehose and that's causing immune activation inflammation, leaky blood brain barrier, driving mast cell activation and wearing down the system.

So you know, it's another thing that needs to be fixed. And again, not to be a broken record, this is why I love the septad, because I can just go down the list and answer to your question, what can we do to help the immune system? Go down the list first, each item in the septad. You know, and then we can, after that, you can look at nutrition and supplements and vitamins and some specific drugs and kind of go out there a little on the frontier with, you know, rapamycin and stem cells and plasmapheresis and exosomes.

That's another, another podcast.

Dr. Tania Dempsey: Oh, no, I want to talk about those things too. I love that. No, let's, let's talk a little bit about, about your approach. I mean, I, I, [00:44:00] listen, I think that we we definitely have a lot of similarities in how we think about the patients. And I, I, I, couldn't agree more with everything you've said, but I think there's some things that you're doing that are really unique.

And I, I want to talk a little bit about rapamycin because it's obviously gotten a lot of sort of hype in the longevity world. People thinking about it as this sort of anti aging solution, but, but you're using it in some of these patients with chronic complex illness. So, I'd love to hear you're thinking on it.

What do you think it's doing?

Dr. David Kaufman: So I came, came at it, at Rapamycin specifically, and now a bigger picture, but Rapamycin is the first example, actually from the anti aging longevity world, okay? I, I, you know, we, we're friends and we talk a lot. I spend a pretty significant amount of time reading, listening, podcasting, studying, looking at the papers in, in that world, and, you know,

truthfully, I did it partly [00:45:00] because of me, you know, I'm getting old and I'd like to see what can be done, right? But it hit me or has really struck me in the process that, wait a minute, the pillars of aging, you know, can be simplified into anything that causes chronic inflammation, okay? Mitochondrial dysfunction and metabolic issues, and there's all 12 of them. Well, those all are what apply to our patients. That's the problem. Our patients have chronic inflammation, they have metabolic disorders, and they have mitochondrial pathology. So, could the world of anti aging and in those interventions apply to our patients?

That's kind of where I'm spending a lot of brain time these days. And Rapamycin is a great example. So, as we get older our autophagy system begins to decline. Autophagy is a evolved biologic house cleaning mechanism that we all have, where junky, [00:46:00] crappy cells that don't die and hang out in our bodies are cleaned up and disposed of through lysosomes and all this other fancy stuff.

Okay? As we get older, that, that process gets worse and worse. Which is terrible because as we get older you have more and more junky cells, so it's, it's kind of a double whammy. Rapamycin inhibits mTOR, which is a nutrient sensing protein in the cells. I think it's every cell except red blood cells in our body.

And by the way, in every other living organism on the planet, that's how important mTOR is. And by inhibiting mTOR, specifically mTOR1, that increases autophagy. Not clear why exactly, I mean, why did evolution decide to do that? I don't know. But it increases autophagy. Well therefore, if there's any truth to what I think about our patients, they have impaired autophagy.

Which is contributing to this [00:47:00] mess that might be causing their chronic inflammation and their mast cell activation and their worsening connective tissue. So anything to increase autophagy may be beneficial. That's why I started looking at Rapamycin. Alright? It's more than autophagy, it also affects the immune system and restores balance and homeostasis and things like that.

So I started using it. It's a little scary because I don't know what the right dose is. I use the dose that's in the literature from some clinical trials with people, obviously with mice too, but with people, and with what's talked about in the longevity world. But what I'm missing, or what we're missing, is a way to know is it the right dose.

So I have patients who take the target dose that I use from the literature. But they will tell me when they go, I taper up and when they go from say 4 to 5, they don't feel as good, so they stay at 4 and they feel better, they're getting benefit. So it's not one dose fits all, [00:48:00] you know, we have in medicine, we tend to say that, you know, if you look at a prescription, if you weigh 300 pounds or 150 pounds, you still get a Z Pak.

Well, maybe that's not right, you know. So we, but we don't have a marker. So there are some, as you know, I'm doing this trial where we're going, we think that we found a biologic marker, a biomarker, that tell, it relates to autophagy levels. Okay, so the marker is high when autophagy is low and vice versa.

And if that pans out to be true in people, it's true in mice, and it's been true in a certain survey, but in a treatment intervention trial, meaning giving the Rapamycin, if they, if our ME CFS patients start out high with this marker, and then with Rapamycin it goes down, and they feel better, that's a big deal, because then I'll know, well maybe I can, maybe I need more, maybe it didn't go down [00:49:00] enough so we need 10 mg, not 7 mg, that kind of thing.

So it's really a work in progress, and it's definitely kind of a little bit of cowboy medicine because it's totally off label, etc.

Dr. Tania Dempsey: No, but it's fascinating and makes a lot of sense actually to me. Are you measuring Rapamycin levels?

Dr. David Kaufman: I haven't been, I haven't been. And, and that's because it's given once a week, but the levels are, are based on daily treatment for transplant patients. So I don't know how to interpret those levels. In some of the aging literature, anti aging literature, they'll, they'll say maybe you do a level, a trough level, so if I take my Rapamycin on Sunday, do it on Saturday because you, you don't want it to be elevated the whole time. But I don't think we have the data yet, and actually, now that you're saying this, we probably should have had that part of this trial.

Jill Brook: This is so exciting. And I'm so just grateful that you think outside the box. And I know that you see the patients that have [00:50:00] already tried most of everything, and they're still not doing well, and they're desperate and, and, I wish we could have you talk for three more hours, but we only have a few more minutes.

So I want to make sure that any other priority things get in, and I hope you'll come back again soon, because this is amazing.

Dr. Tania Dempsey: So what, what do you want the audience to, to take home? What, what's your message to them?

Dr. David Kaufman: Well, that's a hard question to answer, Tania. I mean, my first message is talk to your doctors and get them to open their minds because we're desperate for doctors. You know, we don't have enough physicians or healthcare people to deal with what's now a crushing epidemic of Long COVID. You know, and we're only seeing the beginning.

We're still at the tip of the iceberg. So that's number one. Number two, I'll say what I've said in other venues. If you're sick with any of the illnesses that we're talking about, if you think of yourself as a complex illness patient, ME CFS, Long COVID, or whatever label you prefer, and your doctor says, [00:51:00] you just need to exercise more, I would say, thank you, goodbye, and never go back to that doctor.

And that I realized that may create anger in my colleagues, but I do think that patients shouldn't waste their time being gaslit like that. Those are my two takeaways.

Dr. Tania Dempsey: Thank you. Thank you. And no, I, I, I love that message. How can people find you? You have a website.

Dr. David Kaufman: I have a very primitive website, Tania. Nothing like yours. Yours is gorgeous. Mine is like Bella, my partner Bella Chetta. Dr. Chetta put it together one night with her 13 year old son, I think. It is just basically the office, the hours, the bios of the doctors. So there's that. Obviously I have a clinic email.

And I, I'm doing with Eileen Ruhoi, Dr. Ruhoi, this Patreon channel. So, we're doing a Patreon,

basically because we're both so frustrated that patients weren't getting the information and doctors weren't learning, we said, let's just do this.

So, it's a, [00:52:00] it's a, it's a video podcast, podcast, it's video on Patreon. And basically, it's called Unraveled: Understanding Complex Illness. And we have recorded now probably 35 hours of shows, and having an incredibly great time. It's so much fun. And discussing everything we're talking about. So, I mean, it ranges all over the map, but if you looked at the list of episodes, it's all the things we talked about multiplied by 100.

Dr. Tania Dempsey: Wonderful. So, we'll, we'll, we'll post it so that people know where to, where to listen.

Dr. David Kaufman: I think it's there, I mean, patients tell me it's very helpful, families find it helpful, and I wish we had more doctors looking. The few that look find it very helpful and the goal was education.

Dr. Tania Dempsey: Well, we just keep getting the word out and, and, and, and more and more, more and more doctors. Here's the positive part that I see, that there's still a lot that are really ignorant, but, but, one by one.

Dr. David Kaufman: [00:53:00] Well, yeah, I mean, look at Masterminds, right, our listserv, from 20 doctors to 550 doctors in, what, 3 years, 4 years?

Dr. Tania Dempsey: We're getting there.

Dr. David Kaufman: We'll get there.

Jill Brook: I just cannot thank you both enough. You do such amazing work. I think you do it evenings and weekends and all the time. I think you're always working on this and trying to make life better for your patients and you just are absolute groundbreaking giants. And I'm just so grateful and hey listeners, that's all for today. I'm going to stop gushing, but thank you for joining us, but may your health be good to you and please join us again soon.