Gastrointestinal Manifestations of MCAS with Dr. Leonard Weinstock as part of the Mast Cell Matters series

GI Manifestations of MCAS [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 fourth episode of Mast Cell Matters, where we go deep on all things related to mast cell activation syndrome or MCAS. We have a fantastic episode for you today with two World Class MCAS experts. The first is our guest host, Dr. Tania Dempsey, who is a Johns Hopkins trained specialist in complex chronic disorders of immune dysregulation. And thank you for hosting Dr. Dempsey. Which of your amazing mast cell expert colleagues did you bring with you today? [00:00:37] Dr. Tania Dempsey: Today I'm excited to have Dr. Lenny Westock with us here all the way from St. Louis. Dr. Weinstock was born and raised in New York but moved to St. Louis in 1985. He received his medical training in Rochester, New York and completed his gastroenterology fellowship at Washington University. He's board certified in both internal medicine and gastroenterology, and he's an associate professor of clinical medicine and surgery at the Washington University School of Medicine. Dr. Weinstock's lectures and research have been presented at national and international conferences on small intestinal bacterial overgrowth, low dose naltrexone, restless leg syndrome, rosacea, and mast cell activation syndrome. And we're really honored to have Dr. Weinstock here with us today to talk about all things mast cell and GI. Welcome. [00:01:25] Dr. Leonard Weinstock: Thank you. Thank you very much. [00:01:27] Jill Brook: I have to say, actually, I think that Dr. Weinstock's research might be the research that I end up talking about the most with my nutrition clients. I feel like I talk about you several times a day, so I don't know if your ears are ringing, but your research is so important. [00:01:41] Dr. Tania Dempsey: It really is. Yeah. [00:01:43] Dr. Leonard Weinstock: You're so welcome. So nice. [00:01:45] Dr. Tania Dempsey: So let's dig in. Dr. Weinstock. Why don't we start with a background about mast cells in the GI tract. And I kind of want to start there and then sort of, you know, go more systemic. But maybe we can just start there and you can tell us a little bit about their role manifestations and things like that. [00:02:02] Dr. Leonard Weinstock: Sure. Well, the fact is mast cells are many places, and there are many places where the environment meets the gut, environment meets the air. Environmental. Factors play a big role in activating the mast cell activation syndrome. And it is exceedingly common to have it in the gut if not as possibly always. Perhaps I have one patient out of 320 that had low counts, but virtually everybody else that I tested have what we call high counts. That's somewhat in debate these days, but nonetheless it's a very common factor and I think it is common because not only do the mast cells in the gut cause symptoms locally but distant because they secrete chemicals that are carried off in the bloodstream and create trouble wherever they go. [00:03:01] Dr. Tania Dempsey: Gotcha. Yep. I couldn't agree more with you about the systemic nature of it and the interaction between muscles and the gut and elsewhere. There are lots of conditions that occur in the GI tract and, and lots of conditions that overlap with mast cell activation syndrome. But you know, one of the things that I know you've spoken a lot about at different conferences is SIBO, right? Small intestinal bacterial overgrowth. And maybe we can talk a little bit about your experience with the interaction between SIBO and MCAS and how that also may lead to a more systemic effect. [00:03:32] Dr. Leonard Weinstock: Sure. Well I looked at approximately 125 patients with mast cell activation syndrome and then looked at their lactulose breath test. And found out that 30% of these patients who had undiagnosed irritable bowel symptom -like problems 30% had a positive breath test with hydrogen. 10% had a problem with methane, but there were a lot of other patients who had bloating without markers for bacterial imbalance, and discussed this at our meetings. Feel that it's the chemicals that create either a paralysis or fluid coming into the gut to fill up the small intestine with fluid kind of a secretory phenomenon, creating bloating and sometimes it's just paralysis and you get air and distension and other times it's actually fluid. And patients have no evidence for gas just by percussing and testing them for kind of that bloated sound. And so certainly chemicals play a big role. So the other issue about SIBO is that it creates inflammation. It activates the T and the B cells and the mast cells for even the normal mast cells. And it can also cause secretion of cytokines, which are inflammatory chemicals, creating an inflammatory condition in the body, which is why I think we see a lot of issues with restless leg syndrome and rosacea in general. Rosacea's not a big one for MCAS, but certainly restless leg syndrome is. In any event, SIBO plays a role in treating that is at least a correctable problem that would reduce the inflammation that some of our MCAS patients have. [00:05:25] Dr. Tania Dempsey: Great. And what would your approach be to that. We don't have to go into like great, great detail, but it would be nice to sort of understand from a gastroenterologist perspective how you might approach a patient who has MCAS and who you find this condition SIBO in. [00:05:41] Dr. Leonard Weinstock: Right. So often the SIBO causes Or amplifies the bloating, amplifies the abdominal pain, diarrhea, constipation sometimes it really holds to the truth of hydrogen excess causes bloating and diarrhea and methane overgrowth causes bloating and constipation. And bloating, constipation due to methane may just be an overgrowth of the methane in the colon, but not in the small intestine. So there are different patterns that are seen with bacterial imbalance and the treatment is different. We also have another bad actor, hydrogen sulfide. And you know, you get at that by talking to the patient about the gas and saying, does it ever have a rotten egg odor or sulfuric smell. And then that's treated yet a different way with different antibiotic therapy or herbal therapy such as oregano. [00:06:42] Jill Brook: Dr. Weinstock, I know there's a lot of listeners who have POTS or MCAS and they feel like they get bloated so often after no matter what they eat. And they're probably wondering right now if I bloat, does that mean I have MCAS or does that mean I have SIBO? And in your experience, Is bloating something that can be caused by a hundred different underlying problems, or is it pretty diagnostic of MCAS and or SIBO? [00:07:11] Dr. Leonard Weinstock: Wow, that's a big question. That's a loaded question, but the fact is, is that it varies quite a bit, as you say. So I'm going to get a MCAS and have bloating because abdominal pain associated with the release of chemicals can cause this natural relaxation of the abdominal muscle. So it's like you've eaten too much of Thanksgiving, you've gotta find room to put all that and basically the belly bloats out because the abdominal wall muscles relax and the diaphragms go down. And so people will show me pictures of themselves bloated out, but it doesn't mean that they have bacterial overgrowth. In fact, those patients with MCAS cells I'll see them, they'll have a trigger, one thing or another. One woman has a trigger. Before she was treated and diagnosed of course of driving to see me on rough roads from Southern Illinois and just that vibration would cause an attack and bloated, and she'd come in really distended and she didn't have SIBO, but treating aggressively, treating her MCAS, got rid of that. And certainly certain foods could trigger. Now if you take one population who are just plain old SIBO, they had post-infectious irritable bowel syndrome and they have bacterial overgrowth because of the antivenculin antibody that slows down the migrating motor complex, allowing for bacterial overgrowth. Well, those patients will, let's say, have gluten or sugar. They'll feed the bacteria and they'll blow it up accordingly. Whereas if it's strictly MCAS only and the gluten, which is often a really tough product to handle, will cause an attack and an activation of the mast cells will then they'll bloat up and be distended as well, but it's for a different reason. And then finally you'll have a mix of the two, that you'll have a carbohydrate load for somebody with SIBO and MCAS, and they get a double whammy of bloating, pain, inflammation. And maybe they're also going to have symptoms elsewhere, like hives for instance or itching or edema as a full blown attack. [00:09:37] Dr. Tania Dempsey: Yeah, that was a great answer. And so then, how do you approach these patients to try to figure out which one or more of those conditions are really happening in the patients, or what's your thought process and also workup process for these? [00:09:50] Dr. Leonard Weinstock: Right. So I will ask about the bad odor to the gas and if they don't have it, then I will just run 'em through a regular lactulose breath test, looking at hydrogen and methane. I pretty much do it on virtually every person. Unless somebody says, no, this is just spontaneous bloating. You know, a lot of things are going on. I'm having an attack and then I spontaneously bloat. I may not do a breath test for that patient because I'm really thinking that it's primarily a mast cell activation phenomenon. In fact, if you look at Dr. Moldering's questionnaire, he specifically says spontaneous bloating is one of the check marks, which is more of an MCAS problem. [00:10:39] Dr. Tania Dempsey: Gotcha. And then after you've asked these questions and you've done a SIBO test in some of those patients, then what's your next step? [00:10:48] Dr. Leonard Weinstock: So let's say it's hydrogen only. And then I'll try to get rifaximin for them. Some people do pretty well with herbal antibiotics and there's some that are better situated for hydrogen plus methane, hydrogen alone or methane by itself. And then if they do happen to be tested with a trio, smart for hydrogen sulfide, then you use high dose oregano. For that or a three week course of rifaximin. I think that you also think about motility, I think a little less about motility cause is because the mast cells, not only they liked living in the environmental surfaces, but they also like living next to nerves. And that's been shown in a number of ways, including anatomically. And so when they show next to the nerves, then they throw off the parasympathetic balance and they may have decreased peristalsis because of that and bacterial overgrowth. And I think in that situation, what you're trying to do is to get control over MCAS and you won't necessarily need the prokinetic therapy that we need in regular run of the mill SIBO. [00:12:11] Dr. Tania Dempsey: Right, right. And so what would your approach with MCAS in these patients be? What's your sort of first line? [00:12:18] Dr. Leonard Weinstock: Okay. So step one therapy is H one, H two blocker, BID, twice a day. It's vitamin C and vitamin D, it's quercetin or lin, and it is low dose naltrexone. So basically five over-the-counter product. And one prescription for Naltrexone. [00:12:44] Dr. Tania Dempsey: Great. This is a great segue because I really wanted to talk more about low dose naltrexone because obviously this is a interest of yours, it's an interest of mine as well, and I use quite a bit of it in my practice. So I'd love to hear from you how you're treating patients with it, what the current research is with LDN. [00:12:59] Dr. Leonard Weinstock: Okay. Right. Well, when you look at the actual potential physiology of how naltrexone and the downstream effects of naltrexone can work. Then you want to think about the fact that there are toll receptors on the activating side of mast cells, and naltrexone is a toll receptor blocker. So on inflammatory cells, it binds to the Toll receptor and decreases cytokine production. And when you're decreasing cytokine production by mast cells or other inflammatory cells, then you're reducing the things that could activate mast cells and normal mast cells and aggressively unregulated mast cells that are the basis of MCAS. So that's one thing. Then the other thing is that after the Naltrexone binds for six hours this end comes off. You get a burst of endorphins and endorphins reduce inflammation, reduce T-cell and B-cell activation. And T-cells have these microparticles that activate mast cells. Which therefore would be decreasing the cytokines and reducing again the inflammatory diseases that we see and the activation of mast cells, both normal and abnormal. So there are a couple things that are clearly mapped out on paper that you can say, okay, this makes sense. This is not just hands waving, this is real. This is phenomenon that you can find in research papers. Now, how does it really work out for the patient? So I did look at 116 of my first patients that were given naltrexone. Gave them a handout with a questionnaire and 60% found significant benefit from naltrexone. 20% didn't help. And also with respect to side effects try to ramp up slowly. But even with that people can have side effects. There's no 100% drug, there's no 90% drug. There's no 70%. So 60% is pretty good. And also with respect to side effects, try to ramp up slowly. But even with that people can have side effects and have to either go down on their dose or they have to stop. And in general, as we know, mast cell patients are just much more sensitive to any therapy. So it's kind of amazing that you could give somebody famotidine and they'd be sick for the famotidine, which is pretty basic. Now, is it due to the famotidine or is it due to the excipients? The preservatives, food dyes, the packaging material. Could be all three. Yeah, but rarely the actual drugs, I've had patients respond poorly just to compounded medication. [00:16:06] Dr. Tania Dempsey: Yes. [00:16:07] Dr. Leonard Weinstock: Of course naltrexone is compounded, but still some people can't endure the endorphin rush, if you will. And that's part of the problems with LDN. But I've had a number of MCAS patients who tell me you know, they ran out of their naltrexone for a few days and they really started feeling bad and they needed it back. And it's a great drug because you can stop it if you need to. If you're having surgery and you're going to get an opioid. No withdrawal no issues it can then, can be restarted right away. So as an antinarcotic opioid antagonist, I feel like, and it's almost a homeopathic dosing, if you will. I find it'll be a very good modality to try. [00:16:56] Jill Brook: Well, Dr. Weinstock, I think a lot of people wonder about LDN versus sodium cromolyn because I think they have it in their head that sodium cromolyn is the go-to GI medicine for MCAS. But I just wanted to clarify that you're saying you actually go to LDN first? [00:17:16] Dr. Leonard Weinstock: I do, and part of that is the expense. And the fact that there are other things that cromolyn won't do because you know, how often do we see muscle aching and fatigue as major issues? I guess I view cromolyn more as gut specific, although the fact is, is that it can help other things. If you're getting a lot of distant phenomenon from cytokines caused by eating and so forth. And it's expensive. And then you also have to worry about activation caused by high dose cromolyn. So you have to gear up and start slowly, and I just find it a little trickier. I definitely do a lot of it. I definitely have seen a number of patients say it's a wonder drug for them. And I prescribed it today to a patient. So I do it on a regular basis, but why do I do Naltrexone first? I just feel it's much more bang for the buck, and I'm going to come to it sooner than later. [00:18:21] Dr. Tania Dempsey: It sounds like most of us who use LDN know that there has to be some ramp up with it as well, but it's maybe not quite the ramp up we do with cromolyn. Typically, where do you usually start and where do you end? Because I've been feeling in my own practice that I'm pushing the boundaries. I'm going higher on the LDN that I had in the past, and for some patients I'm starting lower because of how sensitive they are. So I'm curious about what your approach is. [00:18:45] Dr. Leonard Weinstock: I will try one milligram and increase it every four to seven days and get up to four, and then they report back to me and then we go to 4.5. If I truly think that there's a major, major element of concomitant chronic fatigue syndrome, Then I'll think about doing four and a half at night and one in the morning. So I do normally start with one milligram in the morning. And I know for prescribers of LDN from a study that I did just inquiring from LDN prescribers, that about Two-thirds to three quarters of people started at night. I usually started in the day just because I think there's less side effects from it that if you're going to get the endorphin rush and it's at the noon, that some of it will wear off, but you're getting some of the benefits no matter what. The people who are hooked on the idea of nighttime, they're playing into the circadian rhythm. Where most is released normally at four in the morning, but you know what, if you boost that too much, then maybe you'll get the dreams and insomnia. And so that's part of the problem. So it's an issue. And, it's an art not necessarily a science. Now, as far as going higher, right off the bat, going a six or eight or 10. I generally don't. [00:20:17] Dr. Tania Dempsey: Gotcha. So you feel that as you go up in dosage, you're sort of changing the pharmacokinetics, so to speak, of the drug. [00:20:25] Dr. Leonard Weinstock: Yes, yes. Yeah. [00:20:28] Dr. Tania Dempsey: Okay, great. If there's anything else to talk about LDN let's do that now, because then I want to talk a little bit about diet and food specifically with MCAS patient. So, are there specific diets that you talk to your patients about? Specific foods that you talk to them about? You know, we have Jill here who's a nutritionist, and I know she has an approach, right? I have an approach. And I'm curious from the gastroenterologists in the group here what do you talk to patients about, in terms of their diet? Or do you? [00:20:55] Dr. Leonard Weinstock: I do well and it's in my manual that I give them as well. But the fact is, is that I didn't come up with this. I followed Dr. Moldering's advice and his big compendium of therapy. He goes through basically suggesting that they go on a gluten-free, dairy-free, and a yeast-free diet for three to four weeks and look for triggers and look for high, high histamine foods to avoid. Now, that's a lot to deal with, but they can really make a difference. As far as the winners, I think in terms of what to exclude, it's the dairy and gluten. [00:21:41] Dr. Tania Dempsey: Yeah. [00:21:41] Dr. Leonard Weinstock: and, and I think that people have their bad days with high histamines as well. But that's probably going to be bad for most patients with MCAS. It's an issue. And as far as gas problems, if they don't have SIBO, but they are expelling a lot of gas, you could just say, okay, just do the low fodmap diet. And, and that could be helpful. And if they have SIBO I don't go into long issues with that in terms of being very strict, but certainly long term, no high fructose corn syrup because if there are remaining bacteria, they just love to eat the fructose. [00:22:23] Dr. Tania Dempsey: But even fruit has fructose too. Would you say that that could be problematic for these patients? [00:22:29] Dr. Leonard Weinstock: It's not so much the fruit, it is more of the high fructose corn syrup was really, very high doses, not more concentrated. Yeah. [00:22:39] Dr. Tania Dempsey: It really sounds like there's no right diet for everyone. I think that's sort of the way I see it with my patients too, you know? Overall gluten and dairy are the big. Big ones that we have to eliminate, but after that, right, it's very, very individualized. What about the patient that has a very limited diet because of their MCAS they can only tolerate three foods, five foods. How do you approach those patients in terms of then expanding their diet? [00:23:05] Dr. Leonard Weinstock: Well one of these things is to get hold of the MCAS and get it better because, and I think those patients, I'm very quick to start on cromolyn. [00:23:16] Dr. Tania Dempsey: Okay. Yeah. [00:23:18] Dr. Leonard Weinstock: Okay. So that's number one. So that really has made a difference. I do worry about the patients and you know, those are the patients that I'm going to suggest they do supplement maybe even Neocate Jr. Which is expensive, but it's elemental diet. They can often tolerate. If their body weight is low, MCT oil on top of things for the fat, they're probably avoiding. And sometimes pea protein or Kate's farm can be helpful to. [00:23:50] Dr. Tania Dempsey: Right? But the bottom line is you have to stabilize their immune system and their mast cells specifically, right? [00:23:57] Dr. Leonard Weinstock: right sure. [00:23:59] Dr. Tania Dempsey: So I want to jump back a little bit. We were talking about SIBO and actually one of the other things I was thinking about that would be good to cover is this sort of entity called SIFO or fungal overgrowth. Can we talk a little bit about its relationship to MCAS and what the approach might be for that and do you see that with SIBO together? [00:24:21] Dr. Leonard Weinstock: Right. So it can be together. Dr. Rao in Augusta has done some great work in terms of culturing the duodenum for fungus and has found lots of coexisting organisms. And I'm just getting into some of the companies to look for cultures for fungal elements in the stool. But the problem is they may not make it down in the stool. They may live mainly in the small intestine, obviously with SIFO what do I deal with? I ask patients who either fail to respond to SIBO therapy with a positive breath test. I ask them, have they been treated for years with on and off with the antibiotics? Have they have vaginal yeast infections frequently? And do they have gas? And yet it is not foul smelling and they've got the bloating and maybe sugar rushes. And then at the end of the day, it's really guesswork. And I'll often, when I'm stuck try 'em on therapy and usually it's fluconazol with the protocol that Satish Raj came up with, which is 100 daily for 21 days. and it can be a winner sometimes for sure. And I have a patient with MCAS. I was just thinking about this, who with neem and nystatin. She's gone from Three Foods, two 25 foods. I just heard from her from the other day. And she said, can I change the doses? But there you go. That's an example of treating some underlying cause to allow the gut lining to heal and then going from there. And then there are other things that you do to heal the gut lining, because why are we having so much trouble with particular foods? Is it because it's specifically, you have too many mast cells, but again, usually they're down deeper. But the leaky gut, increased intestinal permeability, bacterial overgrowth, or just damage to the gut lining. We're getting larger pieces of the food coming through and therefore they're activating the white blood cells down below. And so I think we have to think about modalities like s p E and zinc and Endozin zinc carnosine that will help heal the gut lining [00:26:59] Dr. Tania Dempsey: And the first thing you mentioned is that bovine immunoglobulins. I, I don't, [00:27:03] Dr. Leonard Weinstock: Yeah, serum bovine immunoglobulin, [00:27:06] Dr. Tania Dempsey: Okay. [00:27:07] Jill Brook: Dr. Weinstock can I ask you, are you having patients have any success with some of the probiotics that claim to help with mast cell activation syndrome? because there's a number of products out there and a lot of people are trying them, but I haven't really seen any data. Are you getting a feel of whether those are effective? [00:27:26] Dr. Leonard Weinstock: We had somebody post a list of beneficial bacteria in terms of reducing histamine output on our recent webinar. But it's on my list of things to do for natural products because a lot of people do want more natural and less drug-induced drug mediated products. But I haven't seen definitive benefit yet, but I'm just getting started. I would being more pro probiotic. How is that?. [00:27:53] Dr. Tania Dempsey: And I'll add my 2 cents on that. Where I think those probiotics are helpful is in a patient who's very sensitive, who is particularly histamine sensitive or they are histamine intolerant, or histamine is one of the main mediators that their mast cell makes. And so you have to think about the histamine component. You know, they need some probiotics, but they are very sensitive to probiotics, whether that's because of the SIBO or whether it's because of their MCAS. And so some of those probiotics, like I might start with like lactobacillus remnosis. One strain I know that it's going to be helpful at breaking down histamine. but in terms of like the long term effects of how it's helping their gut overall, right. I think it's still early. Like, I don't know if I have the data to say that, but I know that I've been really successful at getting patients on some of those probiotics when they have not been able to tolerate probiotics in the past. So that's my 2 cents. I think there's some benefit, but you know what? It's not measurable right now, and so I don't know exactly what it's doing. Overall, I think it's a piece of the puzzle. I don't think I can say that that alone is the intervention that turns them around, but I think it's part of that process of helping with the leaky gut, helping with the microbiome, but it's small, like it's a baby step, I think. [00:29:05] Dr. Leonard Weinstock: Well, part of the problem is that number one, most bacteria in the gut are anaerobic and there really are not anaerobic products around. And so, as soon as you take it, it's exposed to air and acid and so you're going to break it down. So how much of it gives through is really a question. Now, if you can get spore formed it's [00:29:28] Dr. Tania Dempsey: Yeah, I was just going to say, I think spores probably make more sense, right? And I think patients tolerate that a little better. I think the MCAS patients seem to tolerate the spore once, but, right. Everyone's different. [00:29:40] Dr. Leonard Weinstock: And IBS, you mentioned [00:29:42] Dr. Tania Dempsey: Yeah, I wanted to dig into that too. Yes, please. Let's go. [00:29:45] Dr. Leonard Weinstock: Yeah. What is IBS? IBS is a bunch of stuff. It's really in terms of causes, you know just saying somebody has IBS is doing a disservice. I just have to say, you have a syndrome of typical symptom for one thing or another, but basically we have to dissect the cause. We have to cut up the pie and take the slices that have names to them out of the pie of IBS and therefore say, okay, this slice of pie is SIBO. Take it out of the pie pan. It's not IBS anymore. It's IBS SIBO. Same thing for MCAS, and I think take a big portion of the pie out of the pie pan. And put it in your MCAS dish because that's what we're dealing with. I just see so many patients who over the years, decades, have been told they have irritable bowel syndrome, but you start treating 'em, for SIBO everything melts away and goes away. it's the same thing for celiac, for gluten sensitivity. For food sensitivity. You know, these things are lumped together. And it's easier for doctors to deal with it because they weren't taught all these things. Very few people know about MCAS, and it's what I keep on saying and keep on wishing in a way, is that some dean of a medical school has a daughter, granddaughter, who has MCAS, who has POTS and then they'll change what it's taught at the medical school. But if that's what it's going to take, I mean, it's going to take something on a personal basis for the person in charge of what is taught in medical school. [00:31:33] Dr. Tania Dempsey: I couldn't agree more. And unfortunately, right, because IBS is a sort of like, Basket garbage pail term. I don't know how what's the best way to describe it? So the problem is that patients are often sort of then thought to have, it's a psychiatric thing, it's anxiety, it's not because it doesn't really have the research to support it like SIBO. So that really does a disservice to patients to not have a truly true diagnosis. So hopefully that will change over time. Right. So what is your approach then? So, IBS right. So you said it could be a different things. So what are you testing for in those patients? [00:32:11] Dr. Leonard Weinstock: I'm going back to what happened in medical school. You know, you take a history, you look at a review of system. The review systems used to drive me crazy because you have to ask all 50 questions. And as a person a little tongue tied. And as a medical student that was a bad thing. But now I've got a form. So I look at a form that people with complex symptoms have and a utilized Dr. Moldering's mast cell activation syndrome questionnaire. It's actually Mast Cell Mediator Release syndrome question. And I utilize that to do a framework. Well, is this suspicious for MCAS because they have hives, itching, anal itching, they have spots that are red and get worse with with a flare. And they have vertigo and they have ringing of the ears for no good reason and so forth. So you put all these things together and it starts to paint a picture, okay, this person is suspicious for MCAS along with their GI symptoms that any you know, Tom Dick or Harry Gastroenterologist is going to say, irritable bowel. Goodbye. See you in a year. But if you take that IBS patient back, and then you bring along the painted picture of what MCAS. Then you say, okay, could this IBS patient have MCAS and does that explain their functional GI symptoms? They've had upper endoscopy, colonoscopy, CAT scan, et cetera, et cetera. Everything's negative, but if you just put the story together, then you could do testing. And this is where I find that the blood tests and urine tests are really important. I think the last time I looked at it in 300 patients, it was close to 75% of my patients had one or more positive tests, which helps me believe in the diagnosis for them as MCAS, especially if they respond to therapy. And maybe it's swayed by the fact that I see a lot of patients who have seen two gastroenterologists and had their tests. So they don't have Crohn's disease, they don't have ulcerative colitis, they don't have celiac disease, so they have something else. And the fact is, many times it's MCAS. And why doesn't that surprise me? Well, a lot of these patients coming to me do have MCAS, mast cell activation syndrome. 70% of them had families with similar symptoms. [00:34:50] Dr. Tania Dempsey: Okay, well it's a self-selected group in a way, right? But I think the general population is probably afflicted 17% in Germany. But maybe more out there... [00:35:01] Dr. Leonard Weinstock: right. And maybe less, and maybe more in maybe more or lessened uh, America. But if you start looking at all the idiopathic namely unexplained syndromes, It's tremendous. I mean, you look at the interstitial cystitis, restless leg syndrome. You look at the mast cell activation syndrome, irritable bowel, migraine, fibromyalgia, chronic fatigue, and so forth. And you put all these things together. I mean, just by themselves. It's clearly 40% of the population. Very few people are normal. And so you know, and so in our MCAS patients, 40% had restless leg syndrome and normally seven to 10% of the population has restless leg syndrome. So that's one of the things that I ask. [00:35:52] Jill Brook: Dr. Weinstock, can I follow up? You have been mentioning a couple times the survey that you used that was created by Dr. Molderings and his colleagues. Do you just mind saying what that is and how you use it? [00:36:04] Dr. Leonard Weinstock: Sure. First of all, I have a number of patients who are filling up my spot saying, I think I have MCAS. That's what they tell my secretary. She writes it down possible MCAS. I say, okay, mail 'em the questionnaire and the review of systems. So it's a five page questionnaire and the review of systems is a two page questionnaire. And so what we're looking for are for the two pager review of systems, five or more systems affected by symptoms and for the mast cell activation questionnaire, which is really the mast cell mediator release syndrome questionnaire, which could be caused by mastocytosis. It could be caused by a person having 10 different diseases, which is usually not the case. But usually you are looking for an umbrella to put all these symptoms under so that you can make some sense out of it. Especially when you get a clinical story that adds to it. Then you're going to count up the points, you're going to look at the severity score, and that's going to help. So for instance a lot of people have seasonal allergies and there's spots to click off for the ringing of the ears, running nose, itchy eyes, sores in the mouth. That gives you one point. And yet, there are other questions that are higher point scales like flushing which can be more characteristic for mast cell activation syndrome. But you also look at the severity score. So one way I utilized this was in a long COVID study and I looked at three groups long COVID patients and they scored their severity scale of this questionnaire, before and after Covid retrospectively. And then looking at a group of mast cell patients. They scored their symptoms two years before they were diagnosed. So they were all diagnosed within two years and before they were diagnosed, they filled out the questionnaire or retroactively filled it out. And then a general population control group who were just generally healthy, but if they had COVID ever or they were pregnant, they couldn't fill it out. And so it turns out that the score was about 10 for the general healthy group, but very minor symptoms severity, intensity. Whereas if you looked at the COVID folks before they ever had COVID, it was the same. So they were like control group, but with the MCAS patients, basically before they were ever treated and diagnosed for MCAS, they had very high numbers and high intensity scores. Equal to what you had when you had long COVID. So you know, nobody's normal. Nobody has a zero score just about. It's very uncommon. So somebody's going to have the sniffles or something, but if you really look at the total numbers if you're getting scores of 26 and 30 and they have intensity score of 10 or eight or seven for a lot of these things, you're going to show that the suspected MCAS patient is so much different than a normal person that you develop this painting, if you will, that just colors at MCAS. [00:39:36] Dr. Tania Dempsey: and so can I ask about the Covid group then that then the Covid group looked like the MCAS group is what you're saying? Gotcha. [00:39:43] Dr. Leonard Weinstock: Exactly. Yeah. They had virtually all the same set of symptoms and many of our long COVID patients do respond to mast cell therapy. But you know, it's complex because you know it's vascular, it's inflammatory, [00:39:59] Dr. Tania Dempsey: Multifactorial for sure. More complicated. But MCAS seems to be a piece of the puzzle. [00:40:04] Dr. Leonard Weinstock: Yes. [00:40:05] Dr. Tania Dempsey: Great. This has been great. We're probably just about at the end, so I'll ask you one more question. What's the take home message for the listeners? What would you like them to know? One last thing. [00:40:15] Dr. Leonard Weinstock: Be your own advocate, I guess is the best thing. Look hard to find somebody who has an open mind. Maybe it is worth the investment in a concierge doctor if you're getting nowhere for your first year or two, and then get a diagnosis and move on. Possibly. There are so many things that you can do actually that are over the counter that's worth even trying. So if you empirically find that changing your diet and taking a couple antihistamines and vitamins and flavonoids, which would be quercetin or Luteolin. And you find there's measurable improvement, that might be great evidence to be able to take to the doctor. And then finally unfortunately, diagnostic criteria is defined differently and you're just not going to be helped by a most allergist. I will say that. And that's, A problem. Now, you can get somewhere if you got hives and asthma you can get somewhere with many of the common folks. But unfortunately it's a bad situation because many of them will check things that are never going to be positive or very rarely, like a tryptase level. and yet is ingrained in the in the stone of their home so to speak. It's like the tablets the 10 Commandments. And you know, one of them is if you want to be considered a MCAS patient, you gotta have a high tryptase level. Well, that just doesn't happen very often. So I feel bad for that. I feel bad for patients. [00:42:08] Dr. Tania Dempsey: So the bottom line is that we have to train more doctors to understand this. Right. And like you said, maybe at the medical school level, we've gotta start teaching it because there's just not enough of us out there to treat all the patients who need it. [00:42:21] Dr. Leonard Weinstock: Very true. [00:42:22] Jill Brook: That's why we're so grateful you're doing this. Thank you. [00:42:25] Dr. Tania Dempsey: Dr. Weinstein, thank you so much for joining me today. I learned so much. I love hearing you speak and I was a real pleasure and an honor to have you. Thank. Next month we have Dr. Linda Bluestein, a Mayo Clinic trained expert in MCAS, pain and joint hypermobility syndromes, and she'll be joining us then. [00:42:45] Jill Brook: Dr. Dempsey and Dr. Weinstock, thank you so much for this great information and for all that you do to help MCAS patients. It is such a thrill to have you together today and we're just so grateful for 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 episode of Mast Cell Matters. Until then, thank you for listening. May your mast cells behave themselves and please join us again soon.