Root Causes & Treatment of Mast Cell Disease

hypersensitive Mast Cell Activation and the unregulated degranulation and release of mediators may be an underlying cause of illness for patients with many diagnoses Mast Cell Activation disorders may present as episodic inflammatory symptoms that come and go over time making them difficult to diagnose these fluctuating symptom patterns include allergic type responses and non-specific symptoms ranging across the cardiovascular endocrine gastrointestinal dermatologic and respiratory systems chronic diseases and lifestyle choices May influence mast cell dysregulation and overall immune system activation it's challenging testing but honestly why would we expect it to be simple I mean if there were anything about this disease that were easy or simple we would have figured it out a long time ago the only problems left to be solved are the complicated ones and it does not get any more complicated than mast cell disease [Music] on this episode of Pathways to well-being a Pioneer in mast cell disease research Dr Lauren Safran to provide Insight on treating this complex disorder Dr afren we're thrilled to have you we're eager to learn about how you've been working with patients in your practice welcome to the show thanks appreciate the opportunity I know this is a a complex topic that is beloved to you in many ways and like I mentioned you are a Pioneer in this field we're so fortunate to be able to speak with you so to kick off our conversation I thought we could explore the biologic purpose of mast cells in the body and discuss healthy mast cell function versus an unregulated hyperactive release I think we have the potential to to villainize mast cells but they do serve some important purposes can you start with maybe a little primer about mast cell degranulation and the release of mediators we've heard of like histamine sure mast cells are there for a reason uh their normal functioning is an important part of our immune system we depend on them to help us resist and recover from assaults upon the body traumas infections and so on and so forth the mast cells ordinarily sit in all the different tissues in the body uh fairly quietly just sensing the environment around them uh largely doing nothing as long as we're healthy uh but the moment they sense an assault upon the body they swing into action uh producing and releasing various and Sundry of there are many many many uh different mediators various signaling chemicals that then waft out into the surrounding tissues and when they come to doth or bind with other cells in the vicinity uh that binding then influences the other cells to begin adjusting their functioning as is appropriate to help the body best resist and recover from whatever the specific insult uh that was suffered and the whole system works very well actually mast cells are the front line Sentinels of assaults upon the body they respond to assault upon the body faster than any other type of immune cell mast cells actually swing into action in sub-second time compared to minutes to hours or other types of immune cells um and as long as they're putting out the right mediators and the right amounts right times right durations right places in the body all as well and we have an amazing capacity to resist and recover from assaults but sometimes at least some of the mast cells start misbehaving and there can be a lot of reasons for that but when they start putting out the wrong mediators wrong amounts wrong times wrong durations wrong places in the body the other cells and tissues on the receiving ends of those mediators they don't they of course don't know they're getting the wrong signals they're just biologically programmed to react in particular ways one particular mediators come at them so the situation you get with a Mast Cell Activation disorder uh dominantly Mast Cell Activation Syndrome or MCAS is that you have all these different tissues and organs and systems in the body that are reacting in ways they should not be reacting at the time and that doesn't help us resist and recover from anything it doesn't help us maintain or improve health it actually just makes us sick and the particular fashions in which any given mast cell patient is ill at any particular point is entirely dependent on which mediators are coming out of these dysfunctional mast cells in which amounts which times which durations which places in the body so extraordinarily complex system most doctors are taught in their you know decade or so of training that the mast cells produce uh a couple of mediators histamine and tryptase we have a fairly good idea what histamine does in the human body for example causing itching but we've been studying tryptase for more than 60 years now and we still don't really have a good grasp on what the principal role of tryptas is in human biology and that just helps you understand how challenging some of this research is so that's what doctors are taught in in a decade's worth of training in which they get one minute of teaching about Mast Cell Biology and disease they get just one minute because we really didn't start to understand that Mast Cell Activation Syndrome and even existed up until about 16 years ago the only other mast cell disease we knew about for the last century or so was the extremely rare disease uh a cancer of the Mast Cell called mastocytosis that most doctors will never see a case of in training in a decade of training three or four Decades of practice so if if you're never going to see a disease of the Mast Cell at least any disease that you know of then why spend much time in the training but now that we're starting to understand oh there's this other Mast Cell disorder the Activation Syndrome which is incredibly prevalent now there arises a need for doctors to understand a whole lot more about the biology of this and it's turning out what the biologists have long known the doctors aren't taught this not not yet but what the biologists have long known is that the mast cells produce not just two mediators but actually more than a thousand Each of which has a huge range of very potent effects on different you know different systems different tissues in the body and this is the fundamental reason why this one disease so to speak just in a myriad different variance why this one disease is actually capable of presenting in so many different Fashions at a superficial clinical level I think that was a beautiful introduction we're understanding why this is so complex now even with that brief introduction I want to revisit a few things you said because I think you you mentioned some trivia in there that many of us are naive to so number one being that mast cells May release a thousand different mediators you're right we didn't learn that in school that is absolutely not common knowledge the other the other thing you mentioned which I thought was fascinating was that mast cells have a sub-second response to an assault which that I really had to pause and think about that for a moment because that is actually profound when we look at those assaults I I know that there's a wide variety of things that might elicit a mast cell response what are some of the things that come to your mind first what might be some of the underlying causes of uh of an inappropriate Mast Cell release well the research to date I mean please understand we've only known about this disease for 16 years now since the publication of the first case reports now this it's not that it's a new disease it's just a newly recognized disease and uh you know 16 years is not much time for research uh and in truth not much research has been done yet in this area and I think it's only fair to characterize all of the limited research has been done so far as preliminary but all those caveats haven't been stated what seems to be emerging from the preliminary research fairly consistently in the studies that have actually looked at this particular aspect of the disease is that in almost every mcast patient we're actually able to find and presently this can only be done in the research laboratory not in any clinical laboratories but we're actually able to find a bevy of different mutations in various genes inside the dysfunctional mast cells various genes that are of importance in regulating the behaviors of the mast cells and it's the research also makes clear that pretty much every different MCAS patient has a different uh total set of these mutations uh there might be some overlap from one patient to the next but by and large each patient seems to have a unique set of mutations and it's that it's that that totality the the net result of the particular set of mutations that are present in any given patient that drives a certain Baseline level of misbehavior of those dysfunctional mast cells and we're not saying that all the mast cells are mutated in fact we know that it's only a minority of them that are mutated and we also know these mutations by and large are not inherited they're largely acquired at various stages in the patient's life and we're still trying to work out how and why they get acquired but these mutations create a certain Baseline level of misbehavior of the mast cells and then when you add into the mix the exposures that different people have to different elements of the environment different things they take in their body different exposures outside their body that these dysfunctional mast cells will excessively react to you multiply all these variables together and you get an almost infinite number of permutations of different ways this disease can behave in in different people so it sounds like you mentioned that these are largely or appear to be acquired mutations rather than inherited mutations so as a functional medicine practitioner I want to believe that there's some lifestyle factors that we may be able to modify in the future do you see that happening do you see us getting to a place where we might be able to predict what kind of you mentioned some environmental exposures what kind of modifiable behaviors might influence those mutations and make some recommendations in a predisposed patient I don't think we're anywhere close at this point it was wishful thinking well it's the disease behaves so differently in every patient there are some general themes to this I I don't want to mislead anybody into thinking that uh that there's no way to to see any patterns of this there actually are patterns and they follow pretty much along the lines of the general types of effects of the majority of the mediators that are produced by the mast cell I mean the the the symptoms of the disease are all consequent to the effects of the mediators and given that a substantial uh fraction of this large set of mediators have effects that we would kind of generically categorize as inflammatory that's why the chronic multi-system inflammation means to be sure waxing and waning all the time and there are you know uh acute spikes of inflammatory issues from time to time but chronic multi-system inflammation is the universal constant clinical feature of this disease a couple of other patterns we often see with this um I say chronic multi-system inflammation plus minus allergic type issues that's the second broad theme with this disease because many of the mediators bring about symptoms that we would broadly classify as allergic uh and then there's a third broad theme to this plus minus abnormalities in growth and development in potentially any tissue in the body what we medically call dystrophisms and I say plus minus for the allergic type issues and the dystrophisms because actually there are plenty of Mast Cell Activation Syndrome patients who don't have a speck of allergic type issues or dystrophic issues in them and then there are the Mast Cell patients at the opposite end of those spectrums there are those unfortunately those thank goodness fairly few uh Unfortunate Souls who with regard to the uh allergic type issues they are in virtually 24 by seven uh by 365 anaphylaxis if you can even imagine such misery and then other patients who are suffering an extraordinary array of dystrophic issues fortunately almost always benign but occasionally malignant uh so you've got these vast spectrums of the allergic issues and the dystrophic issues but it's the inflammation uh that is the universal constant to this disease now to be clear there are lots of other mediators too that have effects that really don't fit well into any of those three categories so the disease certainly can drive a lot of other symptoms as well but but if you're looking for a broad description of the disease um then chronic multi-system inflammation plus minus allergic issues plus minus dystrophisms that that that's the the hundred thousand foot view of what this disease looks like clinically it's just that when you dive into the details uh the the the specific inflammatory issues that are going on in any patient the specific types of allergic issues uh the specific dystrophic issues it is a unique assortment of specific issues in every mast cell patient incredibly unique and really presents some challenges for the primary care doctor who might not see this in practice with frequency although I will challenge you on that they do see it with frequency they just don't recognize it right there you go yep I mean the the preliminary reason the preliminary epidemiologic research in this area is suggesting that it may be as prevalent as about 17 to 20 percent of the population and if you think about the implications of that it means that every doctor and I do mean every doctor has been seeing this left and right all day long every day their whole career they just couldn't previously recognize it for what it is because number one they haven't been taught that such a disease exists and the other big factor the other big confounding Factor impeding diagnosis is that the biology is so complex that it's it's guaranteed to present in a thousand and ten thousand different ways of The Superficial clinical level and how do you learn the patterns uh to that I mean that's what diagnosis is whether you're a doctor or a car mechanic you know you go to school you learn the different diseases the way they operate and most diseases have one or two ways that they operate whether it's a disease of the human body a disease of the car so then when the patient comes in you take a history you do a physical you may run a test or two you match up all those data points against your learned database of the the different disease patterns and that's how you make a diagnosis and that all works fine for most diseases but now there comes this disease and I say that facetiously because it's not a new disease but now now we have to start learning how to recognize this disease whose fundamental biology is such that it's pretty much guaranteed to present in a thousand different ways I mean this is a real challenge not only for individual doctors but if you think about it for the educational system the medical educational system too how do you didactically teach this in the classroom how do you even teach it in the clinical training experiences especially when the teachers themselves in the education system don't yet have any familiarity with this I mean well we'll get there you know eventually but it nobody should fool themselves that it's going to happen anytime quickly you know it almost seems like the pattern is that it defies our pattern recognition everything we thought we knew well it it can be difficult learning about it on your own but um once you start to understand like I said the these this Broad pattern uh I I described a moment ago um and then a patient comes in and you look at what's typically a long problem list that the patient has accumulated over the past you know 10 30 60 years and so many of the items on the problem list are itis itis itis itis you know inflammation inflammation inflammation in one system one tissue One organ after another and then you look at the allergy list and you see the patient has quite the array of allergies and sensitivities many of which really don't make any sense at all you know those drugs or almost always extremely well tolerated and and then you start looking further at the problem listen you realize the the their dystrophysms here that usually benign and minor but nobody's ever explained them before that's when you start real ah okay maybe this is the one of those patients listen I'm not about to say that MCAS is the explanation for every patient with chronic mysterious multi-system illness that'd be dumb what I'm trying to say is We Now understand that there exists this disease that is capable of behaving in this fashion so now when a doctor sees a patient who superficially has these features I've been describing it now becomes reasonable to at least consider the possibility that maybe what's at the root of maybe the patient really isn't so uniquely unlucky as to have coincidentally acquired so many different problems all them developing independently of one another and maybe what's been going on is just one thing that really is biologically capable of driving most or all of the issues the patient has been suffering I've had the great privilege in the last 15 years of assisting a growing number of doctors come to recognize this disease in their first one or two or three patients and an interesting pattern has observed has emerged in that many of those doctors then take their valuable time to contact me again uh you know a year or two later specifically to tell me I I can see it now I I've I've been seeing these patients left and right my whole career I just couldn't previously recognize them for what they are but now that I can recognize them thank goodness there's testing that's available to prove that this is what's going on and once a diagnosis is established it's like any other diagnosis you apply the right treatment for the right diagnosis and the patient actually gets better I mean not a hundred percent but but nevertheless significantly better and you know what a concept give the right treatment for the right diagnosis the patient gets better yeah personalized medicine that's that's what we're what we really believe in here in the functional medicine world you mentioned that there's some testing available and I feel like this is a great source of confusion and intimidation for many clinicians will you give us a little bit of insight about what you might be looking for just in a at a standard lab work up and then what are some other biomarker clues that might signal dysregulated mast cell activity and uh you know the standard or routine testing you know routine blood counts routine chemistries routine uh uh you know thyroid function tests and and so on a routine nutritional tests quite often are utterly unrevealing in these patients or at worst demonstrate very modest abnormalities that the clinician knows in his or her clinical Hearts really can't even begin to explain the severity of any of the patients symptoms and one instead has to look fairly specifically for the the mediators and you can't even go looking for just any mediators the Mast Cell puts out the fact is the great majority of the mediators produced by the mast cell actually can't even be measured in The Clinical Laboratory at present they can be measured in the research laboratory that's how we know they exist but only a minority can be measured in The Clinical Laboratory and of the minority we can measure in The Clinical Laboratory the great majority of those are not particularly specific to the mast cells so for example yes I can go measuring in The Clinical Laboratory a level of interleukin-6 and it's a potent inflammatory mediator and if I find an elevated level of il-6 in the blood of the urine then yes there's a significant inflammatory stage in that patient and yes the mast cell does produce a lot of il-6 but so too do a lot of other cells so if I find an elevated level of idle six in somebody it doesn't even begin to tell me that the mast cells are the root of the trouble so instead you know you can't look at the non-specific mediators it turns out that out of the thousand a thousand plus they're only roughly 10 that we can measure in The Clinical Laboratory and which are relatively specific to the mast cells so that's what we measure but I'll be the first to acknowledge this is technically challenging testing there are a lot of biological and logistical reasons why we might go to all the effort and expense to run one round of blood and urine testing on a patient with suspected MCAS and it's easily possible we might get back a set of all negative results no matter how symptomatic the patient is uh on the day that we're collecting the specimens but I've learned the hard way with this disease there's nothing about a set of negative results on one round of this challenging testing that even begins to invalidate to refute or negate even a single element of their histories which usually have long been at least shouting if not screaming Mass Cell Activation to any clinician who has actually learned what that shout sounds like and looks like and and that's the problem it's an educational problem come back in 50 years every doc coming out of training will know about this like today they know about diabetes and hypertension but it's going to take a long time to get there so we run these mediator tests sometimes we find the evidence we're looking for in the first round of testing my own style of practice and I know different doctors have different styles my own style I tend to go up to about three rounds of non-invasive testing before we then think about doing something invasive like GI tract biopsies but honestly most of these patients have had enough uh GI troubles or somewhere along the way that they already had seen one or more gastroenterologists they had already had uh upper and or lower endoscopies done they had biopsies obtained and you know you can't go back to old blood and urine specimens to retest then they they have no shelf life they get thrown out almost immediately but fortunately the Pathologists hang on to the old biopsies for about 10 to 20 years and you can go back to the old biopsies and get them retested with the special processing that's required to see the mast cells there is you have to understand with the routine processing that the pathologist supplies to these tissues they actually cannot see the mast cells in the tissues well sorry correction with the routine processing the pathologist sees the cells that are the mast cells but he cannot recognize that they are mast cells because with the routine processing what clinicians are taught is hematoxylin and EOS and staining h e staining with the routine processing the mast cells very reliably masquerade as other types of cells that are commonly seen in those tissues and it's not until the special and frankly somewhat uh expensive processing is done uh cd-117 staining tends to be the best uh it's not until that special processing is done on the tissues that the pathologist suddenly realizes oops it looks like a lot of those cells that I had thoughts were lymphocytes and plasma cells and macrophages and histiocytes and spindle cells nope what they actually are are mast cells but he's just got no reason to go doing that special and again somewhat expensive processing unless he's been told by the by the gastroenterologist or or you know whoever is obtaining the the biopsies unless that clinician has told the pathologist that there is a clinical suspicion of mast cell disease then the pathologist has no reason to go doing this special processing so I've had cases where we were able to go back to biopsies that were sitting in the pathologist's archive for 20 years and You Haul out those dust-covered specimens uh and you take a fresh slice and and you're you do the special processing and there it is there's the evidence it was sitting there for 20 years it's just that nobody knew to look for it in in the past so I'll be the first to acknowledge it's challenging testing but honestly why would we expect it to be simple uh I mean if there were anything about this disease that were easy or simple we would have figured it out a long time ago the only problems left to be solved are the complicated ones and it does not get any more complicated than mast cell disease I'm understanding that more and more as this conversation goes on I have a really great gastroenterologist who I refer to here in the Seattle area and I've actually had their office send me back reports with I think they reported back as mast cells per high power field is how I normally see it on the report and I I haven't even had to ask for it they have just done it but I hear from other clinicians it's very hard to get them to do it I mean is this still controversial or is this becoming more mainstream you have remarkably enlightened Pathologists or gastroenterologists I don't know who's sparking than testing in your case whether it's the GI doctor asking for it or the pathologist just having the insight to do it on their own but uh your uh you're very lucky uh in in your area there is some controversy about this area still persisting there are some doctors who feel that I mean they've published that in their opinion there is no number of mast cells you could count in a tissue which they would consider to be abnormal position which I just respectfully have to disagree with um uh but then there's another group of doctors large and growing who to be fair the data on this are uh far less than perfect there is ample room Apple need for much more rigorous and definitive study in this area but you piece together all the flawed studies that have been done in this area over the last no roughly 20 years or so and uh a threshold of somewhere around 20 mast cells per high power field is probably a reasonable threshold for distinguishing between normal being below 20 and abnormal being above 20. um but you know it's not called a Mast Cell Activation Syndrome for nothing and you have to understand I mean all the issues in the disease are coming about not because there's any increased number of mast cells but all the symptoms are coming about because of the inappropriate activation of the masses the inappropriate production and release of all these different mediators and the truth of the matter is that under the microscope at least in the routine Clinical Pathology laboratory there is nothing you can do Under the microscope that will give you a clear indication of what the activation State actually is of any muscle you've identified under the scope so you know when we take an increase number of mast cells as a piece of laboratory evidence contributing toward or or supporting a diagnosis of MCAS let's be clear that we are inferring from that increased number of mast cells that if there is something already going awry with mast cell biology in that patient to lead to an increased number of mast cells than probably there's also increased activation of those mast cells but you can't actually see the activation under the microscope it's the elevated levels in the blood of the urine of these few mediators that are relatively specific to the Mast Cell that's really the definitive evidence of Activation so even once I've found increased numbers of mast cells in a biopsy or two from one of these patients it's my own style to still at least try make it make a diligent effort in the blood and urine testing to find at least one or two elevated mediator levels to complement the um this suggestive biopsy findings and in fact the way the uh the diagnostic criteria at least there are two different sets of diagnostic criteria out there in the literature present the the so-called consensus to uh diagnostic criteria by which I tend to abide um uh you don't even need biopsy evidence to make the diagnosis uh just just finding um uh elevated mediator levels the loan is is sufficient together with of course a history that's consistent with the disease and absence of any other disease that could better explain what's going on in the patient um you know the the that's how we make the diagnosis I'm gonna go out on a limb and ask this question to you of you know if we if we collect a really thorough history on a patient and we see that they have migraines and um IBD and they have dermatographia can we just make the Assumption this patient has problems in activation of their mast cell and just treated do we need to do all the testing yeah that's an excellent question and again different doctors have different styles I get that I'll tell you that's not my style and there are a number of reasons for it but perhaps the most important reason that I strongly prefer to uh go to quite a bit of effort to obtain the laboratory evidence that will uh finally nail down the diagnosis per the peer-reviewed published diagnostic criteria the reason I do this is that these patients it's not me they're having to convince that they've got a massive Activation Syndrome I've come you know to see thousands of these patients and as you'd expect of anybody who sees thousands of cases of any disease I think I've gotten to a point where I can smell this disease at a thousand Paces um so it it's not me they have to convince they've likely got this but the problem is that with the education about this disease at its present virtually nil state and the fact that most of these patients are not going to have any doctor relatively close by who has any significant expertise in this disease and so fundamentally they're going to have to be working with their local doctors not only now but for the rest of their lives to manage the issues that come about the multi-system issues that come about from this disease so therefore they're going to have to be convincing they're local doctors for the rest of their lives that they've got this disease that most of their local doctors have never even heard of and even if they have heard of it they probably don't have much familiarity with it yet and my experience has shown that yeah these patients can come see me or some other expert in this area they can get a letter in their chart that says yeah they they likely have the disease but there's nothing that's going to um uh a test uh to the patient's local doctors that the patient really does have a mass Cell Activation Syndrome there's nothing that's going to attest louder than the laboratory evidence it's a laboratory evidence that's going to speak the loudest by far on the patient's behalf in convincing the local doctors the patient really has this disease and you see it's when the local doctors uh the the other doctors the patient is seeing when when they don't believe the patient has this or or even if they kind of it's some superficial level they they accept that the patient has this but they don't understand they don't take the heart that it's the root issue that's when it starts becoming all too easy for those doctors to start making treatment decisions that are not going to be in the patient's best interests because of the mast cell disease and the way it behaves so I've learned you've got to really convince the local doctors that the patient has this disease if the doctors have never heard of before and you can imagine that the bar is high for convincing a doctor who's been through a long and hard education at the hands of you know some of the best teachers in the business and in all that time all that effort they were never taught that such a disease exists uh the the bar is high and it's the laboratory evidence that helps um best with convincing the other doctors that the patient really has this disease and it is something that the other doctors they may not want to have to learn about a new disease uh but nevertheless if they're going to serve the patient the best they do need to learn about this disease and how it operates this makes good sense to me data speaks and like you said patients have likely been carrying around this narrative that they're unlucky or that they that there's a psychosomatic component which maybe there are in some folks but I think that that's really beautifully stated that we're we're building a case here For Better or For Worse we knew that this conversation could go on for days even and we have one hour and I know we're approaching the end of our time together and I want to look ahead I know everyone is really interested in well what do we do now when we have our diagnosis now what do we do so are there some therapeutic modalities that you're willing to highlight for us some of your favorites I'm sure that you know there's a vast variety of treatment plants that you could choose from but we've seen some research that talk about some antihistamine therapies things like vitamin C and quercetin some of our favorites in the functional medicine world have you seen any benefit to these Therapeutics or do you have some favorites that you would share with us highly different with each patient as you might expect because the disease is fundamentally biologically behaving in quite different ways in different patients we tend to start with at least from a pharmacologic perspective we tend to start with uh the antihistamines both the H1 blockers and the H2 blockers because in most Mast Cell patients some combination of H1 and H2 blocker really does bring significant Improvement in at least some of their symptoms and these drugs are cheap and they are long-term safe so since you have to start your trials of these many many different drugs that have been shown helpful in various Mast Cell patients since you have to start your trials somewhere it kind of makes all the sense in the world to start with the antihistamines yes they're occasional patients where you can find reasons to start somewhere else but but if you're looking for generalities we we tend to start at least pharmacologically speaking with the antihistamines but actually I don't even regard the antihistamines as step one in managing this disease step one that I teach to all my patients is to identify their triggers as precisely as they can and then to do their best to avoid them for the simple reason that it's actually kind of hard for any drug to gain good sustained control over dysfunctional mast cells as long as the patient is simultaneously and persistently ingesting or otherwise exposing herself or himself to a trigger I mean over time these patients May well regain some measure of tolerance to to things that previously had become intolerable but but that's over time you know so to begin with identify your triggers as precisely as you can do your best to avoid them in some people it's certain substances and some people certain activities in some people certain physical forces and some people various uh physical or even psychological stressors so the the triggers can really be all over the map and it often takes just an awful lot of diligence in you know every time you have a flare of any of your symptoms then yeah no you you can't think when you're in the middle of a flare you're sick but after you've recovered um you have to have the diligence to uh many many patients what what they find helpful is just maintaining a little diary uh you don't have to be elaborate about it but every time you have a flare of symptoms then after you've recovered you put a short entry in the diary so where you had been at the time what you were doing at the time what you had most recently ingested what the weather was like in the area at the time any noticeable odors or other major sensory stimuli that have been in the area of the time any major stressors uh physical or psychological they had been suffering at the time so they may not be able to pin down at the moment what the trigger of that flare of symptoms was but hopefully over time the patterns will start to become more apparent so step one identify triggers the best they can do their best to avoid them and let me also mention in that context another important thing for Mast Cell patients to understand uh that'll last a good lesson that'll last them well for the rest of their lives it's quite common actually for Mast Cell patients to suffer adverse reactions to medication products particularly fairly soon out of the Starting Gate you know within the first few doses of trying any new product but when such adverse reactions happen it's actually almost never the drug in the product that is triggering their dysfunctional mast cells to further activate and further spew out all these potent mediators that are actually causing all the symptoms and instead it's almost always one or more of what we call the excipients the fillers the binders the dyes the preservatives and so forth almost always one or more of the excipients it's actually triggering the reaction by the mast cells so anytime an patient's having an adverse reaction to a product being newly tried and this even includes refills if you notice that the pharmacist has inadvertently switched You from One formulation of a given drug to a different formulation of a different drug but when you're when you're taking a new product and pretty soon you start having an adverse reaction you don't give up on the drug you give up on the product and then you work with a pharmacist to look at the full ingredient list on the Troublesome product you do your best uh do the best you can to try to figure out which excipient was likely to trigger and I'll be the first to acknowledge this can be challenging for a lot of reasons and sometimes there's a lot of guesswork involved you do the best you can but once you finally think you've got some idea of what the trigger is then you work with a pharmacist to find some other formulation of the same drug same dose that just does not have the suspected offending excipient in the mix and you try that product and if you have a better experience with that product you just proved it's not the drug that's the problem it's the excipients and at that point it's the excipient you put on your allergy list not the drug and frankly at that point you then have got another job to do because you then got to look at the full ingredient list for everything else you're taking to make sure they don't contain even a trace amount of that triggering excipient because let me tell you something Mast Cell patients can easily go from looking and feeling the picture of Health to looking and feeling like death warmed over within minutes sometimes even within seconds of exposure to even a trace amount of whatever it is that's a trigger for them so step one identify their trigger as best they can do their best to avoid them step two identify their optimal antihistamine regimen and and I there there's a number of these H1 blockers available a number of H2S available I understand why anybody might initially think oh they're all just different H1s they probably all work about the same and the same with the a H2S but I'm telling you it's been my pretty consistent experience intending to many thousands of these patients over the last 15 years when the individual patient actually does the diligence this systematically try the different H1s and the different H2S they almost always come back from that set of experiments and they tell me oh yeah no question about it it's this particular H1 and this particular H2 that clearly serves me better than the other H1s and the other H2S my problem is I've been doing this for 15 years now haven't even begun to figure out how to reliably predict which H1 and which H2 is going to best serve the individual patient and if they're likely going to live another few decades you know why would you want to make do for another few decades with what might be a sub-optimal antihistamine regimen so it takes you know a few months to work through uh the trials of these different drugs but if in the end I mean many of these patients they come back and they tell me their best H1 or H2 is serving them starkly better than even their second best so when you when you see see those sorts of differences I mean say hey take the time figure out your best H1 and H2 and then I mean that's step two optimal antihistamines and then steps three through n are to try try try try try try try try and then try some more these many many many many many other drugs which have been found helpful in various patients I mean some people are so lucky they find very helpful treatment very quickly and cheaply others are literally working on this for a few years uh but you also have to keep in mind that with almost every drug that makes sense to try for this disease we figure out in only about a month whether any given drug is going to bring the patient's significant benefit or not and if you get a month or two into trying some drug for this disease and the best the patient can say about it is yeah I'm maybe a little bit better that's not nearly good enough to warrant keeping the drug in the regimen for the rest of the patient's life you gotta ditch it you dump it you got to be ruthless about it and you move on and try something else I learned quite some time ago that um it's a pretty good bet that when the treating doctor and the patient together the two of them stumble across the particular drugs that is the particular molecules that just happen to be the right molecular keys for fitting in to the particular molecular law that is the individual Mast Cell patients particular variant of this highly variable disease they'll come back in just a month and the dock will walk in the exam room and as huddle spin 360 it'll be so obvious how much better they are you got to be realistic very complex disease there's no way any one drug is going to fix all their problems you know one drug helps some problems over time you find other Keepers that significantly help other problems and in that fashion you piece together or what in the end is usually a pretty small cocktail of mass cell targeted drugs that gets the patient to the goal of feeling significantly better than the pre-treatment Baseline the majority of the time that's the best you can do we're not curing this we're not going to get them perfect but most of them have been sick enough long enough in enough different ways that when you tell them the goal is getting them significantly better than the pre-treatment Baseline the majority of the time they're delighted with that as the goal and and many of them are able to get back to a a good life uh even though they may not have perfect control over it so it really takes in from the patient this therapeutic partnership you've described where both the practitioner and the patient have to be diligent in the investigation I think is one of my most important takeaways from what we've spoken about today and it sounds like I was going to ask you you know in your 15 years of experience treating MCAS patients is recovery possible but I think you've just answered my question that we can get to an improved state of quality improved quality of life now we are in spite of how ridiculously immature the state of the science in this areas I wouldn't even characterize it as infantile or neonatal I think we're at an embryonic state in our understanding of this but in spite of that we're blessed to already have a boatload of treatments that have already been found helpful in various Mast Cell patients and I've been quite tickled as you might imagine to have experienced the that the large majority the great majority of patients who have this disease have both the patient and the treating doctor both of them can be sufficiently patient and persistence in working through the trials of these different treatments patient and persistent and methodical trying to make one change at a time that you don't have to spend long with trying each uh each intervention but you do have to try to do one change at a time as best you can because the moment either the patient or the doc starts making two or more changes around the same time and then the patient gets either Better or Worse neither the doc nor the patient has any idea which change is making the patient better yeah there are emergencies now and then when the patient and the doc have no choice but to make multiple changes around the same time you know that's life and you deal with it but as much as possible one change at a time and it just doesn't take long so you don't persist with something for you know four months six months a year if you're just not seeing a significant Improvement that is not the right molecular key for fitting into the lock that is the individual Mast Cell patient's particular variant of this highly variable disease so you figure out the keys and in my experience most of these patients actually do sooner or later piece together some cocktail usually a pretty unique cocktail to the individual patient but they usually eventually piece together some cocktail that really does get them to the goal that I just mentioned well I I think it's appropriate to close on that note of empowerment so Dr Afrin thank you so much for being with us I feel so fortunate we've been able to tap into your wealth of knowledge on this topic today you've given us so much to think about and I hope I can check back with you in 15 years and see how we have evolved in that time thank you so much for being on the show you're welcome thank you to join the conversation on this topic visit ifm's pages on Facebook and Instagram for more information about functional medicine visit ifm.org [Music]

Channel: The Institute for Functional Medicine

Views: 41,706

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Id: m6neGwYf6_g

Length: 57min 53sec (3473 seconds)

Published: Tue Feb 28 2023