Dr. Afrin, a world expert in all things mast cell, talks in depth about issues with the first MCAS “consensus” statement and the need for a second MCAS consensus statement so that patients can be treated even if their lab tests don’t show an elevation of tryptase levels. This opens the diagnostic door to many additional patients so that they can get the treatment that they need.

You can read the transcript for this episode here: https://tinyurl.com/potscast129

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[00:00:00] Jill Brook: Hello, mast cell patients and lovely people who care about mast cell patients. I’m Jill Brook, and this is our third episode of Mast Cell Matters, where we go deep on all things related to mast cell activation syndrome or MCAS. We have an incredible episode for you today with two rockstar MCAS experts. Our guest host is Dr. Tania Dempsey, who will lead a conversation with Dr. Lawrence Afrin. She will introduce him. But first, let me remind you that Dr. Dempsey herself is a top MCAS physician and researcher in New York State, educated at Cornell and Johns Hopkins. She specializes in complex chronic disorders and immune dysregulation, and I will hand it off to her. Thanks for being our host today, Dr. Dempsey.

[00:00:49] Dr. Tania Dempsey: Well, thank you. I’m so excited to have this opportunity today to interview my esteemed colleague, Dr. Afrin. After earning a Bachelor of Science degree in computer science, in graduating Summa Cum Laude and valedictorian from Clemson University, Dr. Afrin pursued medical school, internal medicine residency and clinical and research fellowships at the Medical University of South Carolina, M U S C. While there on the hematology oncology faculty, he also served in several senior institutional positions and won numerous recognitions for his educational and research efforts. He transitioned to the University of Minnesota’s Hematology Oncology faculty in 2014 to further his developing clinical research and educational interests in mast cell diseases, particularly MCAS or mast cell activation syndrome. In 2017, he joined me at my practice, Armon Integrative Medicine in Armon, New York to pursue with me the development of an independent center for advancing care, research and education regarding mast cell disease, especially MCAS. And reflecting the practices updated approach and engineered to accommodate the MCAS patient population, Ames Center for Personalized Medicine was opened in New York in mid 2020. And Dr. Afrin has published extensively in the peer review medical literature several of which I was fortunate enough to co-author on as well. I’m excited to have Dr. Afrin here today to discuss MCAS and in particular, we’re going to look at the diagnostic criteria that we have renamed the Consensus two criteria. So we’re going to dive in and Dr. Afrin, you along with me, and something like 38 other of our colleagues published a peer reviewed article called The Diagnosis of Mast Cell Activation Syndrome, A Global Consensus 2. And so I was hoping we can talk a little more about that.

[00:02:50] Dr. Larry Afrin: Sure. Look forward to the opportunity.

[00:02:53] Dr. Tania Dempsey: What was the impetus for publishing this.

[00:02:56] Dr. Larry Afrin: Well, an alternative thought construct for how to go about diagnosing this inherently quite complex and heterogeneous disease had been developing since very shortly after the disease first came to be recognized. There was one contingent of investigators who Fairly strongly that if the patient did not have an elevated tryptase level, that there was just no way there could be any significant dysfunction with the patient’s mast cells. And therefore those patients even if they had symptoms a long history strongly suggestive of mast cell activation as likely the unifying issue for all their problems, nevertheless, without an elevated tryptase level they would be told that no, there cannot be a mast cell disorder here and we don’t know what else is going on, but there’s nothing else we can do to help in these patients, unfortunately, will be largely released with no other direction provided for them diagnostically or therapeutically and myself and some others particularly Dr. Gerhard Molderings probably, in my opinion, the world’s number one authority in mast cell activation disorders at the University of Bond in Germany. We were in disagreement with that approach. It was quite clear that the mast cell produces many hundreds of mediators. There’s been argument over time, is it a few hundred? Is many hundred as a more than a thousand? That’s an discussion for another time. But it was clear that the mast cell was producing many, many mediators. And it also had been clear in the literature for quite some time that even though originally back in the eighties the tryptase level was originally described as a marker of mast cell activation in patients with mastocytosis, as more research was done, it was becoming increasingly clear that actually the tryptase level is a fairly poor marker for the general mast cell activation state in a human being. It became understood that what the tryptase level typically represented was simply the number of mast cells in a patient’s body. So if you have a malignancy of the mast cell, if you have mastocytosis in one form or another, Where you have gross over proliferation of the mast cells and you would expect to have a strongly increased tryptase level in that indeed is what is typically seen in mastocytosis. There, of course, are occasional exceptions. There are exceptions, every rule, but that’s what’s typically seen in most mastocytosis patients. But the issue in mast cell activation syndrome is not a gross over proliferation of mast cells. It’s a chronic inappropriate activation of the mast cells where there’s relatively little to even sometimes just no excessive proliferation of the mast cells. But, Nobody should go thinking that just because you don’t have an increased proliferation of the mast cells, that you can’t have any problem from the mast cells. Actually, the mediators that are produced by the mast cells are so potent in their actions once those mediators are released from the mast cells, that there’s a phenomenal amount of chaos in the body that the mediators can produce when inappropriately released. And so with the mast cell understood to produce many hundreds of mediators. And furthermore, findings by Dr. Molderings and his team based in Bonn that what seemed to be at the root of most cases of MCAS was a very wide Array… a real menagerie of mutations in various genes inside the dysfunctional mast cells, various genes of importance in regulating the behavior of those mast cells. But it was also quite clear from his research that you had very different patterns of these mutations in different mast cell patients. And so it just kind of made sense that with the dysfunctional mast cells in different mast cell patients having different sets of mutations, these mast cells would be misbehaving in quite different ways. They’d be releasing quite different sets of mediators in very different abberant patterns, and it just seemed unlikely that tryptase could be expected to be a reliable indicator of mast cell activation. There also was research developing at the time, showing that, as I said, tryptase is not so reliable a marker of activation. And instead what’s actually happening to, to generate the tryptase levels we see in most people is that there is regardless of whether the mast cells are activated or not, there is a constant baseline level. What is medically called a constitutive production or expression of tryptase from all mast cells. So if you have a cancer of the mast cell, we have this grossly excessive number of mast cells. Then you multiply the little bit of baseline production, the constant baseline production of tryptase by a vastly increased number of mast cells, and that’s what’s going to get you the very high tryptase level you see as kind of a regular thing in patients who have mastocytosis. But when you don’t have such a great number of mast cells and since Tryptase is not such a great marker of activation of the mast cells, therefore, in patients who have the activation syndrome, typically tryptase is not elevated at all. In fact, the published research suggests the tryptase is elevated and only about 15% of MCAS patients. And even in those 15%, we now understand there’s something else going on besides mast cell activations actually driving the modest elevation of tryptase. We find in the great majority of that 15%, and if you want, we can discuss a little bit later what that other issue is. But in the 85% or so of MCAS patients who don’t have an elevated tryptase, it’s instead these other markers of mast cell activation that you have to go looking for to prove that. Yeah, there, there really is a problem here with these mast cells. They are inappropriately producing and releasing excessive amounts of various mediators. So Dr. Molderings and I back in 2011, we published a paper. There had been a paper first back in late 2010 that first proposed some diagnostic criteria for MCAS that really focused on tryptase elevations and dr. Molderings and I wrote a paper just a few months later in 2010 that suggested an alternative approach looking at a broader array of mediators, which, if elevated, we felt would be reasonable to accept as clear evidence of a mast cell activation problem. As the years went on the first group, so to speak, they came out with some occasional updates to their criteria. Though in general it still remained pretty much, a tryptase focused set of criteria. And Dr. Molderings and I, over time, we saw needs to tweak our criteria. We came out with some other papers over time and ultimately we got to a point where it was a little concerning that the first group in their first follow-up paper in 2012, they had declared that their criteria were so-called consensus criteria, which, I mean, if you think about it, that word has a lot of significant implications to it. It kind of implies people are just going to accept when they hear that word that, oh, all the doctors who are interested in this field, they got together and there was just a lot of agreement from most of the doctors involved in this area that this is the most reasonable way to regard this area. And yet we knew that in truth, there was no consensus and we were seeing quite a number of doctors who were being influenced to think that the first approach was really the only acceptable approach to diagnosing this. And as I said before, unfortunately this was leading to a lot of patients whose symptoms were strongly suggestive that MCAS was at the root of their problems. But nevertheless, they had a normal tryptase level, even when they were having terrible flares of the disease, they had a normal tryptase level and therefore they were being told that, no, you can’t have a mast cell disorder. And then some of those patients would come to some of the doctors who were looking at the disease from the perspective of the other diagnostic criteria. And they were having a broader range of diagnostic testing run and finding that, oh yeah, there it is. There’s the evidence right there of mast cell activation. But this word consensus was a real issue that there were so many doctors out there thinking there was only one consensus. Even if the group involved with the first consensus, even if they wouldn’t be happy about it, and even if they wouldn’t be in agreement with any other approach to diagnosing the disease, we thought it was most important for the patients and the other doctors attending to those patients to understand that there was an alternative approach to looking at this. There was an alternative consensus. No, it’s still not at a stage where there’s one big happy global agreement on this and there probably won’t be for a long time to come. But the two different approaches. Different enough. And it has enough impact on patient wellbeing that we felt it was important to make more folks aware that there was a different approach to diagnosing this and it was an approach that had already been adopted by quite a greater number of doctors than had originally signed on to that original consensus. So we felt it was appropriate to sort of update our criteria and to label it as just an alternative consensus. And if you consider the first consensus to be consensus one, then our consensus was consensus two. And it was kind of a play on words too, because we felt that our consensus was a consensus. Two t o o. It was also a consensus and just as legitimate a consensus as the first consensus. It’s a very, very biologically complex disease. And to be honest, we’re just at an embryonic state in the development of the science in this area. Our scientific understanding of how this works, so, Shouldn’t be any surprise at all that different investigators are going to have considerably different thoughts about how this disease operates. Lots of different guesses as to the unknown science in this area. I don’t think anybody should be thinking that consensus one is the only right way to think about this and I also don’t think that anybody should go thinking that consensus two is the only right way to think about how to diagnosis. They are just different options for diagnosing a very complex and variable disease at a point in our understanding of the disease’s behavior that is just very early. you know, As time goes on, the, the research will advance our understanding of the biology will advance the sophistication of the testing will advance. And I suspect that within the next, I don’t know, 10, 20, 30 years, we will get to a point where we’ll have moved beyond just diagnosing MCAS per se, and we’ll start to move into the realm where we’re diagnosing this particular variant of MCAS and from the information we’ll have learned from the research by that point, we’ll know that okay, this particular variant behaves in this particular clinical fashion because of these particular biological features. And therefore it’s these particular drugs that make sense to try for those variants. That’s all going to just be kind of organic natural development in this field in the years and decades to come. But the good news is even though we know very little about this disease so far, thank God we know enough that we actually can identify the patients who likely do have one form or another of chronic inappropriate mast cell activation at the root of their typically very wide assortment of problems. So we can actually diagnose this kind of, regardless of which set of criteria you choose to use. We can identify the patients who have this disease maybe not perfectly yet, but still fairly good recognition. And thank goodness we already have a boatload of drugs that have already been found helpful in a great many of these patients. And so, strikes me and many others in the consensus two effort that it would be kind of a shame to have somebody who pretty clinically obviously has a mast cell activation syndrome and we have all these drugs that are reasonable to try for them. And yet we would not go trying them because they don’t have a diagnosis because their tryptase level is not elevated. Because one out of the many hundreds of mast cell mediators is not behaving in a particular way that’s seen in a small fraction of MCAS patients. It seems like it’s really doing the majority of MCAS patients a disservice. And yeah, no question about it. , we don’t have any reliable ways yet to predict which treatments are best going to help the individual mast cell patient. There’s no question it’s far more trial and error in trying different medications in present in the individual patient to figure out which treatments are going to best serve the individual patient. But nevertheless, if both the patient and the treating doctor are sufficiently patient and persistent and methodical about working through these medication trials, most of these patients actually do sooner or later stumble across some cocktail of mast cell targeted treatment, which actually does get them to the goal of feeling significantly better than the pre-treatment baseline the majority of the time. And given that they’ve typically been sick for many years honestly, typically many decades. It’s a good thing when you can finally make the right diagnosis. Many of these patients, of course, have long been dismissed, as just having psychosomatic symptoms. They’ve been gaslit. But when you can make the right diagnosis and then sooner or later figure out effective treatment. What do you know? They actually start getting better. Even though they’ve actually been symptomatic for decades, they actually do start getting better. You can’t recover for them the time of their lives they’ve lost to the symptoms, but nevertheless, they tend to live a normal lifespan. So whatever decades they have ahead of them are typically going to be better quality years and times for them. So, Just would be kind of ashamed to not provide them that opportunity, especially given that the preliminary research in this area, is increasingly showing just how prevalent a disease is. This is not the rare disease that mastocytosis is a very prevalent disease. So given all these factors, it’s best to make physicians aware. There are competing schools of thought for this, and there’s nothing wrong with having different approaches to thinking about a complex subject where the science is far from resolved. But if in the end it winds up helping more people sooner rather than later. my opinion anyway is that that’s a good thing. So that’s how Consensus two came about. Even though we were willing to consider that a much broader array of mast cell mediators in the diagnostic testing compared to just looking at tryptase, we knew there were a lot of places in the world where patients and their doctors would’ve trouble accessing that testing. So with conscious thought, we structured those criteria so that even if certain aspects of the mediator testing could not be accessed, there were still pathways through the consensus two criteria that you could wind up with having a definitive diagnosis, even without finding elevated levels of these Mediators. There’s no question that it’s a higher quality diagnosis, so to speak. If you can actually find elevated levels in the blood or the urine of these mediators that are relatively specific to the mast cell I mean, that’s unquestionably the most definitive demonstration of activation of the mast cells. But not everybody in the world can access those tests. So there are other approaches to diagnosing this that we consider to be good enough, so to speak, so that these patients would not just be told, nope. We understand you got symptoms that are consistent with mast cell activation, but nope. Sorry. You just don’t meet criteria, so therefore you don’t have a diagnosis and without a diagnosis, we can’t justify trying you on the treatments for this. We just didn’t think that was right. So, so there are multiple pathways through the criteria to get to the diagnosis, but the mediator testing is probably the best way to go through it. That’s a ridiculously long answer for a simple question.

[00:24:40] Dr. Tania Dempsey: No, that was actually a complex question, so I appreciate you walking us through that. Obviously the publication of this paper was given a lot of thought . Over years from you and many of us who have been trained by you and alongside of you. So thank you for that. And I want to follow up then with this concept of, we know MCAS is a complex multisystem disease. In the paper we talk about three themes that MCAS typically presents as. And patients often can have some combination, either one or multiple of these themes, right? And we talk about having allergic phenomena or not having allergic phenomena. We talk about inflammatory issues and we talk about dystrophisms right? Those are sort of the three themes. And I’d like to dig in a little bit to the allergic theme, because at least in my practice, that’s the question that comes up the most from patients and from other practitioners about, if a patient doesn’t have allergic symptoms, doesn’t have anaphylactoid or anaphylaxis type symptoms, can they still have MCAS? Love to hear your take and how you respond to that.

[00:25:51] Dr. Larry Afrin: Yeah. I was trained like every other doctor is trained and you’re in the one minute of teaching, you get about mast cell biology and disease in the roughly 10 years of a physician’s training, you’re taught that there are only two diseases that mast cells can cause. You’re taught that it causes this ultra rare cancer of the mast cell called mastocytosis, where the classic symptom is mysterious anaphylaxis that just comes outta nowhere. And the only other disease you’re taught about that the mast cell produces is allergy… allergic phenomena, which actually is a very prevalent phenomena. Roughly about 10 20% of the world population suffers allergies to one extent or another. So, as I was just starting to wrap my head around this emerging concept of mast cell activation syndrome I was puzzled initially, because many of my initial patients, I came to figure out what was really at the root of their troubles was a mast cell. I got the clear evidence of mast cell activation and yet they had very little and in some cases just no allergic type reactivity. And yet, very clearly what they all had and I’ve seen this now across thousands of mast cell patients in the last 16 years now I’ve been spiraling down this mast cell rabbit hole. Very consistently seeing that the universal constant clinical feature of this disease is chronic multisystem inflammation. Every single MCAS patient has got multisystem inflammation in one fashion or another. I do understand that in many patients especially in their earlier years, it can be quite mild. Sometimes if at many times it’s so mild. Patients don’t even think of themselves as inflamed. It’s just mild quote, bothersome, occasionally mildly bothersome issues like a runny nose or a little bit of a cough, a little catch in their throat now and then, or a little bit of a rash that pops up now and then, and they don’t even really have a reason to go thinking about it as an inflammatory problem, even though in truth, that’s exactly what it is. And so that chronic multisystem inflammation is the universal constant, and it’s no surprise that that is the universal constant for this disease because so many of the mast cell mediators, these hundreds of mediators produced by the mast cell. If you dive into what the biologists have discovered about what the effects of these mediators are, you would kind of classically label the dominant effects of many of these mediators as inflammatory in nature? I mean, what are the symptoms of inflammation? Well, we’re taught early in our training that it’s pain, it’s swelling, it’s redness, it’s temperature or fever. It’s not to say that you necessarily get all of those symptoms in every inflammatory setting, but those are the classic features of inflammation. And that indeed is in one subset or another, those symptoms in one part of the body or another. That’s what so many of the mast cell mediators drive. And we’re not even saying that these patients are suffering these symptoms all the time. Quite often this is a waxing and waning phenomenon. So patients may have some periods, maybe days, maybe weeks, in which they have some worsening of some of these symptoms, and then things settle down again. Maybe these symptoms go away entirely. Maybe they just subside to a lower level that is kind of their baseline where they’re not even thinking about it as a problem. because a long ago just came to accept it as, oh, that’s my normal and that’s just the way I’m put together. Even though in truth it’s not Really a completely healthy state. So that’s what’s going on there with the inflammation. So that’s why these patients accumulate lists in their doctor’s charts where so many of the problems wind up having a suffix of itis. -itis is the medical suffix for inflammation. So they get bronchitis, sinusitis arthritis. It just goes on and on and on with all these itises and that’s where it’s coming from. Now, the mediators that drive the allergic phenomena I began seeing early on with my patients. Yeah, there’s some mast cell patients who have got allergic type phenomena to ,one degree or another. Many of these patients, as best as I can tell, they don’t have a speck of allergy to them. And then there are the most unfortunate souls. Thank God, very few of them who honest to God are suffering a absolute, flagrant anaphylaxis 24 by seven. In fact, I was just on the phone earlier today with a doctor out in Texas who is dealing with one such patient who’s having to use an EpiPen like a dozen times a day. And she can’t even find any antihistamines to control her because she keeps reacting to every antihistamine she gets tried on. And yeah, we can talk later about excipient reactivities if you want to, because that’s probably what’s going on in her. But nevertheless, she’s just incredibly reactive in an allergic type fashion. So you got those polar opposite ends of the allergy spectrum that you can find different MCAS patients at different ends of the spectrum. And then you got every other MCAS patient that fits in somewhere in the middle in that vast spectrum. So that’s why when I describe this disease, I say it is a disease of chronic multisystem inflammation plus minus allergic type phenomena. And then there’s the one other plus minus to this. In terms of general themes, yeah, you can find all sorts of oddball issues in these patients to tack on. But if you’re looking for a general description, it the inflammation that’s the constant plus minus the allergic issues, plus minus the dystrophic issues, the abnormalities in growth and development that you can see in any tissue in the body. Now, thank God most of these growth abnormalities are benign but sometimes they are malignant. There’s so many mast cell mediators that are integrally involved in guiding growth and development in so many different tissues in the body that it shouldn’t be any surprise that you actually can see a vast array. It’s possible to see a vast array of abnormalities in growth and development, potentially any tissue, any organ, any system in the body. In fact, many times we don’t even think about these things as abnormalities in growth. For example, many patients with mast cell disease turn out to have some difficulties in healing. They suffer a cut or a wound or a bruise. They go through surgery and they have trouble healing from something as simple as a little paper cut. And you don’t think that healing is a function of tissue growth and development, but it is. Listen, as long as normal mast cells that are putting out the right growth guiding mediators in the right amounts, right times, right durations, right places in the body, you’re going to get normal healing. But when you get dysfunctional mast cells that are putting out the wrong growth guiding mediators, wrong amounts, wrong times, wrong durations, wrong places in the body, Nobody’s going to be surprised if you’re going to get abnormal growth and development. Sometimes you get undergrowth of various issues. That’s kind of the category that poor healing would fit into. Sometimes you get overgrowth. Now again, thank God, usually that’s benign. But there are many types of overgrowths that you can get in this disease. A couple of the most common types are cysts. Oh. These patients develop lots of troubles with cysts. Breast cysts, ovarian cyst, lung cyst, pancreatic cyst, liver cyst, kidney cyst, thyroid cyst ,brain cyst, spinal cysts. They also develop a lot of abnormal scar tissue. What’s medically called fibrosis. How many times have surgeons gone into the belly of a patient who has never had abdominal surgery before and found all this scarring, all this fibrosis just scattered all about the belly and they just scratched their heads and looking at this, say, how could all this have happened? we haven’t even done any surgery in the belly before that would give these tissues any reason to go scarring up and fibrosing. They’re not aware that, yeah, there is a disease that can drive abnormal growth of tissues in a fashion that results in scarring. So again, there are great many mast cell patients who don’t have a speck of dystrophism to them. And then at the opposite end of that spectrum, boy, they’re an awful lot of patients who have an awful lot of dystrophism. Thank God. Usually it’s benign. Usually it’s very modest. It usually doesn’t cause any clinically obvious problems, but nevertheless it is abnormal. And the only question then becomes, why, how, how did this come about? So those are the opposite ends of that spectrum. And then of course, is everybody else with a disease who’s somewhere in the middle on that spectrum between those polar opposite ends. So those are the broad themes of the disease. Yeah. There are plenty of other mediators that cause lots of other goofball issues. You could talk about endocrinologic issues, various hormone fluctuation issues. You could talk about various coagulation system issues, mast cell patients who keep having troubles with excessive bleeding or excessive clotting. It just goes on and on and on. But if you’re looking for the one sentence broadest description of this, I’ve been thinking about this for years, and the best description I’ve been able to come up with so far is chronic multisystem illness of general themes of inflammation plus minus allergic issues, plus minus dystrophisms. Another ridiculously long answer.

[00:37:55] Dr. Tania Dempsey: No, thank you for that.

[00:37:56] Dr. Larry Afrin: It’s a complex disease. I used to apologize for it, that my answers are so long, but, the answers reflect the complexity of the disease, which stems from the complexity of the biology.

[00:38:12] Dr. Tania Dempsey: It is, and you really say so eloquently, you really explain this disease process because you’ve had time to really put it together. And, people who are listening are really appreciative, I’m sure of, of you putting it out there in this way and making it accessible.

[00:38:27] Dr. Larry Afrin: Happy to help. Education unquestionably is the most important thing. We are 16 years now since the publication of the first case reports in this. And to this day, at least to my knowledge This disease is still not mentioned in any medical school textbooks. It’s in no training curricula. The medical students, the residents, the fellows, by and large, they’re graduating to this day having never heard of this, and they’re going out into practice for the next 30, 40 years, having no awareness of this. Even though the research, at least the preliminary research done so far in this area, is showing this is present in about 20% of the population. Think about the implications. What that inescapably means is that every doctor has been seeing this left and right all day long, every day, their whole career. And every newly minted doctor is going to be seeing this. I don’t care if you’re a doctor, an MD, a DO, a PA, an NP, a nurse, physical therapist, whatever. Everybody is seeing these patients all damn day. It’s just that they haven’t been recognized for what they are. Most of them have the disease so mildly then I don’t think they’re ever going to need to be recognized as having MCAS at the root of their modest problems. Look, if they’ve got an occasional flare of an allergy or whatever, big deal, go to the drugstore, get some antihistamine take it for a few days. That’s that. But when you’re talking about 20%, I mean, unquestionably even a relatively small subset of that 20% that has the disease in a more significant fashion, that’s an awful lot of people who are really going to benefit by having it recognized for what it is, get it definitively diagnosed so that then they can legitimately access the medications that makes sense, make biological sense to try for this. So every doctor’s been seeing this and I’ve been very privileged in the years I’ve been spiraling down this hole. Very privileged to have been able to assist a growing number of physicians come to recognize this disease in their first one or two or three patients. They’ve come to diagnose this, and most of those doctors then follow up with me 6, 12, 24 months later. They take their valuable time to follow up with me simply to tell me, oh my God, you were right! I’ve been seeing these patients my whole career. I just couldn’t previously recognize ’em for what they are. But now that I can recognize ’em for what they are and now that I know that there is testing that can be done to definitively diagnose this, yeah, for the first time in their lives I can get them a diagnosis. And that alone quite often is transformative for these patients as they go from all their doctors and their families and friends thinking all their chronic complaining is just psychosomatic to suddenly understanding, no, there’s a real problem here. It may be a complex one, it may be a recently recognized one, but no, no, no, there’s a real problem here. And then boy, I’ve learned about ways to treat this and you start treating these people, they actually start getting better. And the doctors, I mean that, yeah, it’s great when the patients start feeling better that’s obvious. But this puts on the doctor’s faces when they are able to help these poor patients who previously they’ve seen so many doctors, had so many diagnosis, so many tests and treatments, never really made any significant progress. And now for the first time in their lives, they’ve got a diagnosis that makes sense and they’re clearly making therapeutic progress. That’ll put a smile on a doctor’s face too, so that that’s a good thing to see too.

[00:43:15] Dr. Tania Dempsey: Absolutely. And I think I was one of those doctors when I found my first patient and we spoke, I think it was 2015, and then of course you joined me in 2017, which was really for me, a real turning point because I understand what these doctors are feeling. Once you see it, you can’t unsee it. And so once I saw it, once I understood it better. Once I had some guidance from you and then I sort of took off with it, then it was like the lens that I was seeing everything through, but in a good way. You have to be careful in medicine, right? Not to put all your eggs in one basket sometimes. But sometimes, understanding how everything is connected, is obviously going to be life changing for the patients. And that’s how it’s been for me too.

[00:43:57] Dr. Larry Afrin: You bring up some really important points. We are absolutely not saying that every chronically mysterious ill patient with multisystem inflammation and allergy and dystrophism necessarily has MCAS at the root of it.

[00:44:14] Dr. Tania Dempsey: Yes.

[00:44:14] Dr. Larry Afrin: what we’re saying is, Hey, here’s a disease that had never before been recognized. It’s not that it’s a new disease, but it’s a newly recognized disease and it turns out to be a really prevalent disease. And here’s the basic manner. Here’s the basic pattern in which it operates. So if you are now seeing a patient who fits the profile, all we’re saying is it now becomes reasonable to consider this diagnosis in the set of diagnoses that you would think about for that patient. And then at that point, you go pursuing the testing that’s appropriate to pursue, and you figure out either the patient does have it or does not have it. So no, we’re not saying this is the answer for every chronic mysterious illness out there, but 20% so it is a prevalent disease, and so it’s likely that it is the unifying diagnosis in many. I don’t know if many means 5% of the chronically mysteriously ill or 25% or 80%. Nobody’s done that research yet. We don’t know. But still there are an awful lot of folks out there who have this, and let’s also acknowledge that. Yeah, there are a great number of other diseases out there whose symptoms can pretty closely mimic and overlap with the symptoms that MCAS can drive. And boy, would it be a mistake to, as you said, just go assuming that the only thing going on in the patient is MCAS. The astute diagnostician has always gotta be on guard and thinking about what else might be going on here to maybe not account for everything, but maybe account for pieces and parts of what’s going on. And you can imagine if you don’t figure those things out, if they are present and you don’t figure them out, then I don’t care how well you’ve nailed down the mast cell diagnosis, you can go treating their mast cell disease till the cows come home. But you’re probably not going to make as much progress as you might expect to make if there’s something else going on there that has not yet been recognized and diagnosed. And you yourself, Tania, have done an excellent job teaching me about some aspects of that with regard to certain types of infection. And I thank you for that. I still don’t know anything about how to properly diagnose and treat those infections, but, just coming to understand that these are more prevalent complications in some of our mast cell patients than I had previously suspected based on my training and experience that’s been helpful to me. Everybody in a health profession’s career, we travel a unique path that is shaped by our training and our unique set of clinical experiences. And I’d like to think we all try to learn from our experiences, but fundamentally, we all take a unique path. And if the path you take is one that has not yet afforded you of a glimpse of this sort of larger spectrum of illness that the MCAS diagnosis captures, then I can see how you can keep going through the rest of your career continuing to see these patients in front of your face all day long for the rest of your career, and you would never come to suspect it. My first patient who had this. She had a very different set of symptoms than my second patient in whom I came to prove there was a mast cell activation syndrome at the root of her problems. Both of those patients had a very different set of symptoms than my third and fourth and fifth. I think I was roughly 70 patients or so into accumulating my series of MCAS patients before I stumbled across the first one that in my opinion, I thought, okay, this patient, I think bears some reasonable degree of similarity to one of the other patients I’ve seen. But that’s the degree of diversity and heterogeneity we’re dealing with. And that is something entirely new to most doctors. you go through your training, you learn 10,000 different diseases. You learn the one or two patterns that each disease behaves in and so that’s what you learn. And then the patient comes in, you take a history, you do a physical, you do a test or two, you take those data points, you match ’em up against your learned database of the patterns of how the different diseases behave. and that’s how you make a diagnosis. You may have to run another test or two to confirm it, but that’s how you diagnose. It’s an art in pattern recognition. So what’s the poor doctor supposed to do? Now that there comes along this new disease, so to speak, where it’s not going to present just in one or two patterns, it’s going to present in a hundred, in a thousand different patterns. How is the poor doctor supposed to learn to recognize that even though he is staring it in the face multiple times every day? And I I’m not saying it’s impossible to learn it. I mean, I learned it. You learned it. Many other doctors have now learned it, but I’m just saying it ain’t the easiest thing in the world, especially since it’s not yet being taught in a systematic, didactic fashion in any of the training programs. Yeah. All that’ll get fixed in time too. I understand that. But that’s the state of affairs today, and patients need to understand that and kind of go easy on their doctors. Their doctors have been doing the best they can operating within the box that was constructed for them. It’s just that no matter how long an expensive it was, It did not include MCAS. So go easy on your docs. And if you run into a doc that just doesn’t have any awareness of this, no understanding, and kind of more importantly is not even willing to learn about this, then okay, move on, find some other doctor who is going to be more willing to learn and more willing to at least try to help you with this from both diagnostic and therapeutic perspectives. So most patients out there, they’re not going to be able to find a local doctor who already knows about this. They’re going to have to find a local doctor who’s willing to learn and willing to try. And my experience has been that kind of no matter where you are in the world if an MCAS patient is sufficiently diligent in looking at the opportunities for care, the options for care, doctor shopping, if you will within a reasonable travel distance. Most patients who have this disease, no matter where they are in the world, they actually are able to find some doctor who’s willing to learn and willing to try. And the great thing is that once those doctors actually start learning and trying in their first MCAS patient, aha, the light bulb pretty quickly turns on over their head and they start realizing, I’ve been seeing this everywhere. And they’re actually quite energized and quite enthused that they now have a new way to help many patients who they previously had to just throw up their hands on. They couldn’t do anything to help ’em.

[00:52:49] Dr. Tania Dempsey: Thank you so much for your time today. I’m so happy to have had this opportunity and I’m assuming we’re going to do this again because I know you have so much more to talk about. I have so many more questions on my list that we didn’t cover, and we’ll have to do this as a part two. I’ll mention that. Our website is aimcenterpm.com. If they want to read more about our practice and I have a Facebook page, Dr. Tania Dempsey and Instagram, Dr. Tania Dempsey, md. We post a lot, blog a lot, show videos and podcasts and things like that there. Thank you so much.

[00:53:22] Dr. Larry Afrin: right.

[00:53:23] Dr. Tania Dempsey: We’ll see you in the office.

[00:53:24] Jill Brook: Well, Dr. Dempsey and Dr. Afrin, thank you so much for this information and for all you do to help MCAS patients, not just the ones in your own practice, but MCAS patients around the world. It’s a thrill to have you here together today, and we just so appreciate all you do. And hey listeners, that’s all for now, but we’ll be back again next week with a normal episode of the POTScast and we’ll be back again next month for another great episode of Mast Cell Matters. So until then, thank you for listening. May your mast cells behave themselves and please join us again soon.