Reeducating Mast Cells with Anne Maitland, MD, PhD

[00:11] Jennifer Milner: Welcome back to Bendy Bodies with the Hypermobility MD, where we explore the intersection of health and hypermobility, focusing on dancers and other aesthetic athletes. This is co-host Jennifer Milner here with the founder of Bendy Bodies, Dr. Linda Bluestein.

[00:27] Dr. Linda Bluestein: Our goal is to bring you state-of-the-art medical information to help you live your best life. Please remember to always consult with your own healthcare team before making any changes to your routine. Our guest today is Dr. Anne Maitland, MD, PhD, Chair of the Allergy and Immunology Working Group for the International Consortium on EDS and HSD. Dr. Maitland, hello and thank you so much for being here today.

[01:02] Anne Maitland, MD, PhD: I am so delighted to join you ladies. This is an exciting opportunity, especially for a person who always likes to sit in the back of the classroom. This is new media, and my daughter thinks I'm rather cool that I'm actually moving outside of my comfort zone.

[01:20] Jennifer Milner: Well, we are happy to have you here and happy to have you at the front of the class today to share your wisdom with us. Before we dig in, can you share a little bit about your background? Just give us a brief bio.

[01:37] Anne Maitland, MD, PhD: I've always wanted to be a physician. My father was a physician. He was part of the 2% that serviced the 15%, meaning he's an African American physician who actually trained at Meharry Medical College and went on to be a surgeon. He actually was on the surgical team that saved Martin Luther King when he was stabbed in Harlem, and he always— he saw no limitations for a little brown girl from the Bronx to go into science and medicine, so always encouraged me along the way.
[02:17] I thought it was going to be a fairly straight shot: go to a good high school, go to a good college. And then in the middle of college, when I'm starting to think about formally applying, he said, I don't want you to go into medicine. And that was a full stop. The reason why is because he started to appreciate that medicine was no longer becoming a profession, but a business. And he felt that it would be more important for me to go into graduate school. So I actually worked for three years to understand what it meant to go into graduate school. And then I eventually landed at University of Pennsylvania in their MD-PhD combined degree program.
[02:59] I've been actually studying the immune system since before HIV got a name in the mid-'80s. And now here we are in the midst of another immune-mediated pandemic. In many ways, I'm part of the minority because there is a national shortage of allergy and immunology specialists in the country. So I've had the pleasure of meeting individuals who really don't have as much of a grasp of the immune system. It really is almost like another language. Trying to appreciate how the immune system becomes tolerant or loses tolerance has been at the forefront of trying to understand what happens in individuals that have a connective tissue disorder.
[03:51] This is a very relevant conversation on many levels, and I look forward to sharing some of the experiences I've learned along the way. Currently, I'm in a very exciting position. Mount Sinai South Nassau Community Hospital just formed the first inpatient and outpatient center that addresses Chiari, connective tissue disorders, and mast cell dysfunction. I've had the pleasure of working with Drs. Eileen Ruhoy as well as Dr. Paolo Bolognese. We're trying to build it from the ground up, and hopefully it'll be a safe haven for patients who feel that they can't find a medical home.

[04:32] Jennifer Milner: That is really interesting. We have spoken with Dr. Eileen Ruhoy before and love her and the work that she is doing. There are so many avenues we could go down with you and talk about, so many things that you mentioned that I want to explore. But today we want to talk about mast cells and all things mast cell related. So, starting with the very basic: what are mast cells and why are they important? Why are we having this conversation?

[05:10] Anne Maitland, MD, PhD: I find mast cells fascinating — and here's the thing, I'm a T-cell biologist by training, and I had to unlearn what I learned to understand a cell population that we can't be born without. So you can actually be born without T cells, you can be born without neutrophils, but you cannot be born without mast cells. And interestingly enough, that amounted to one or two lectures in first year of medical school many, many moons ago.
[05:38] It's an interesting population because you really don't see them in the blood, so standard blood tests won't pick it up. They start in the bone marrow, kind of like a man or woman who joins the police academy. And then after they get their initial education — you're going to be a mast cell — they get their marching orders. They basically go to every single part of the body and act as the first line of defense for that community of cells that face the environment. So, you can imagine a man or woman assigned to work in Times Square versus a small town in New York State. They have to learn how to meet the needs of that community. It is the community that educates the mast cell on what its job is in order to better serve and protect that community.
[06:29] Unfortunately, we know relatively little about mast cells compared to other cells of the immune system and even the body itself. But in many ways, the mast cell has a lot of key jobs. They have receptors to recognize tissue injury and damage, which happens with higher frequency in individuals that have hypermobility issues. And they have the ability to coordinate the immune response to that damage. Not all damage is the same — kind of like if a man or woman sees a fire versus somebody down. You want to call the fire department, not the SWAT team. Or you want to call an ambulance if somebody's down, as opposed to the cavalry on horseback. So the mast cell makes the decision: is it a mechanical injury? Is it an infectious insult? Is it a toxic exposure? They're hardwired for recognizing certain dangers, and depending on what they recognize, they will release chemicals.
[07:40] So mast cell orders are: recognize tissue injury, respond to it. And once the harm is contained, help coordinate the repair. If these chemicals get released inappropriately — like if your body thinks peanut is a parasite — you have these chemicals that go out that have the ability to kill, detoxify, recruit other help. It's like a false alarm that goes off all the time.
[08:12] And what is interesting is that individuals who are bendy — and understand, it's a prevalent issue, as much as a lot of my colleagues don't want to acknowledge it — people who are hypermobile, it's prevalent in this society. Which suggests to me that Mother Nature has endowed them with skills that really served their ancestors well before the world changed. Understand, a lot of people did not become symptomatic in the '50s and the '60s. It was more of a pronounced issue starting in the '80s and '90s.
[08:46] Kind of like — and we're all contemporaries here. I grew up in the Bronx and Harlem, and I have to tell you, peanut butter and jelly on Wonder Bread with a glass of milk was everywhere. But milk was still delivered to our back doors in glass bottles. Food sources came locally and were either wrapped in paper, tin, or glass. We weren't turning on air conditioning. If it was cold, you put on a sweater. If it was hot, you opened up the window and turned on the fan. There wasn't a car everywhere. We spent a lot more time outdoors. And within 20 years — kind of like an Avengers: Endgame Thanos snap — our environment completely changed. So our bodies, which were designed to fight certain dangers, in less than 50 years have become completely confused about what is truly danger and what is not.
[10:37] In my mind, mast cell orders are to help protect and respond to injury, but the nature of the dangers has changed, and these systems that are hardwired haven't been able to change course and restore that type of balance that says: this is when those chemicals should be out, this is when they should not. So you go from mast cell orders to mast cell disorders.
[10:37] Under that umbrella of mast cell activation disorders, you have some individuals that have, in my opinion, two or more organ systems involved. So the definition of mast cell activation syndrome in my mind is: you have misbehaving mast cells in at least two body systems. Somebody who has hives and brain fog, or somebody who has interstitial cystitis and hypersensitivity to foods, or anybody who has joint involvement and trouble breathing. All of those represent somebody with an increased susceptibility to having those chemical mediators out there inappropriately.
[11:11] If we can at least give people that working definition — MCAD, MCAS, MCAD-ish — you then give people the power to understand what is going on in their bodies. And then with that understanding, you'll be able to chart out both pharmacologic and non-pharmacologic interventions to help them feel better.

[11:38] Jennifer Milner: I'm going to need a couple of days to process that because it was so rich. That description was extremely helpful for me. I feel like I know more about mast cells than the average person just from all of this work that we do, but to look at it as something that has been hardwired a certain way and can no longer work correctly — it's like when our fire alarm goes haywire because it smells smoke from burned toast, and it goes, "oh my gosh," and then it turns on the sprinklers, and you're like, no, no, no, we don't need the sprinklers. That was an inappropriate response to what's going on here, right?
[12:27] So that's really helpful to look at it that way, and also to recognize that there's more than one way that mast cell disorders — or disorganization, or however people want to talk about it — can come through. It's not just hives. Not everybody thinks about joint pain as being mast cell related. The brain fog, all of these things that can walk hand in hand with dysautonomia and that general sense of, well, I can't really point to one thing that keeps me in bed, but I do get kind of hivesy and my eyes are itchy and my joints ache and sometimes I have a little trouble breathing. Sometimes those little things are such underlying issues for so long that we just learn to live with them and don't realize: hey, this is the thing. Maybe we could find someone to talk to about it.

[13:25] Anne Maitland, MD, PhD: Well, here's the thing. I thank God that we have more resources and redundancy in our system. If you think about what a police officer has in order to respond to danger — and in many ways, I guess this is also a relevant conversation in our society regarding tolerance and intolerance — you don't want a police officer pulling their gun out to get the cat out of the tree. And if they're going to be upset about somebody who's jaywalking, you'd prefer they just take out their ticket book.
[14:06] So mast cells have very potent chemicals. They have the ability to detoxify venom from poisonous snakes, frogs, any other creature you can think of from Jumanji. They have the ability to alter blood flow because they release heparin and platelet activating factor. I actually had one gentleman who had anaphylaxis to ibuprofen, which was complicated with a very horrific bleeding issue. He started to clot and bleed at the same time — called disseminated intravascular coagulation — simply from taking ibuprofen. And he actually had a history of reactions to Aleve, and his doctor didn't know that Aleve and ibuprofen were related in that way.
[14:58] So in many ways, people who have mast cell activation disorders — meaning those chemicals are being kicked out — all we're saying is that you are susceptible to having those chemicals out there when they shouldn't be. Instead of saying "allergies," meaning let me identify what the trigger is, why don't we identify whether or not your mast cells are misbehaving? It's a simple question.
[15:22] And understand, mast cells are in every single part of your body. So what does mast cells misbehaving look like in the gut? Bloating, diarrhea, constipation, can't absorb — what some people call leaky gut. What does it look like if those chemicals are inappropriately released in your brain? Mood lability, difficulty with concentration, difficulty with speaking, difficulty with organizing one's thoughts. What does it look like if it happens in the joints? Pain, swelling, discoordination. What if it happens in the skin? Flushing, itch, frank hives or swelling.
[16:07] And here's the thing — what is going to force all of us very resilient individuals — and that's what I find in individuals that have connective tissue disorders. Their level of resilience is amazing. Like, oh, my leg is broken? I'm just going to go back out and finish this performance and then I'll take care of it. So I find that this sensitivity that a lot of folks with connective tissue disorders have has been present, but it was only — if I were to use a Richter scale like earthquakes — maybe a 1.2. They're like, I can deal with it.
[16:55] By the time they make their way to an allergy immunology specialist — or a hematologist oncologist, because that's where mast cell disorders were classically found — they're pretty sick. A lot of primary care providers don't even know how to refer to an allergy immunology specialist. There's plenty of data that shows there are only 80 training programs in allergy immunology in the country, which means there are plenty of people who go through nursing school and medical school who've never had direct contact with an allergy immunology specialist. They never saw one, never did one, never knew how to refer to one.
[17:29] So they end up using whatever they were taught. Let me just give you a medication. Let me just give you a medication. And then people get tired of it: I don't want to keep taking medication. So they'll go to functional medicine or integrative medicine. And I don't consider myself a dysfunctional medicine practitioner, but the lack of knowledge of what the immune system is about is as prevalent in allopathic medicine as it is in other specialties. Eastern medicine, I would say, has a better grasp of it. They just have a different vocabulary.
[18:23] So to pivot back — I think the first question people should ask if they're having different symptoms is: do I have signs or symptoms of mast cells misbehaving, whether it's in my brain, my gut, my skin, my joints, or my bladder? That's the first question.
[18:45] Second question: do you get better? Not cured, but do you get better if you take a histamine blocker or take quercetin? The American Academy of Allergy, Asthma, and Immunology doesn't recognize quercetin or luteolin as mast cell stabilizers, but classically, do you get better if you take over-the-counter histamine blockers? That's the second question.
[19:12] Third question, which I find to be the hardest, is: are you able to demonstrate that those chemical mediators are out there inappropriately? That's the hardest thing to do because most emergency departments don't want to order it or don't know how to order it. And I think you need to be patient — just like, Linda, if somebody's having a heart attack, how do we evaluate it? We do a rule-out. We keep you in the hospital for 24 hours, check your EKG three times, check your cardiac enzymes three times. We might even get an echo or put you through a stress test. Well, that's the same thing for a mast cell attack. Let's look at you over a period of time to see whether or not those chemicals are out there inappropriately. Because again, you don't want them out there unless you really need them — like if you got stung by a bee, or better yet, if you got bitten by a poisonous snake. You want those mast cells out there.

[20:14] Jennifer Milner: You want those mast cells on the wall because you need them on the wall.

[20:25] Anne Maitland, MD, PhD: Yeah, you need them on the wall because they detoxify the venom. That's why honey badgers can fight off poisonous African snakes. But you don't want them out there because you decided to have a loaf of bread you bought at the farmer's market and you didn't know it had almond flour in it.
[20:45] So I think the biggest hiccup we have is that most practitioners don't understand what it means to have a hypersensitivity disorder. I find that among specialists, the delay in diagnosis comes down to: well, you have a normal tryptase. And I'm like, well, I'm actually fine right now — it's when I went into the pharmacy and they were burning candles that I was not fine. So we're just trying to get a common language to say, can we determine whether the mast cells are misbehaving or not?
[21:19] Are your mast cells misbehaving? And then the question after that should be: why are your mast cells misbehaving? And this is where both children and adults with a connective tissue disorder — because they look fine — get overlooked. And as much as doctors, nurse practitioners, nurses, physician assistants, and physical therapists all try, we all profile, and the tools we use to profile are pretty dull. You come in with abdominal pain, the blood work is pristine. Well, mast cells — as I said — you can't really see them in the blood. Nobody thinks to check a histamine or tryptase level. The organ systems look normal under radiology.
[22:32] So in 100 years, we went from giving the patient the benefit of the doubt to relying on tests that inadequately assess whether or not mast cells are misbehaving. And so people have a medical odyssey for years until they run into somebody who says, you know, you look a little bendy — and I know that for people who are bendy, this can happen.
[23:10] Because we profile — for instance, as an African American woman, if I have chest pain and all the testing is normal, what do they normally say? It might not even be about being African American specifically; it's just women. They say you have an anxiety disorder. And unfortunately, in the old days, when you had an anxiety disorder, they would give you a tricyclic agent, which actually is a really good mast cell stabilizer. SSRIs don't do that. The Prozacs, the Zolofts, don't stabilize mast cells.
[23:48] And the antihistamines that were readily available over the counter — those first generation antihistamines — work better than the second generation antihistamines. I have patients in their 70s and 80s who have been on Benadryl since they were knee-high to a duck. They say, I sleep better, I'm less itchy. And I think, hmm, I wonder why. The Zyrtecs, the Allegras, the Claritins — those are second generation. They don't work as well, but they give longer action. So now we have fewer people operating under the influence of sedating medications. But when we become so tunnel-visioned regarding the types of medications we will use, we're missing the benefits of those medications that were so helpful for people who had these issues before the world changed.
[24:52] So if we can think about what mast cells are supposed to do and then let them know the world is not so dangerous — because as an allergist, how do I treat allergens that cause sinus disease or asthma? I give the allergen to you, but I give it to you in a shot form when you're relaxed. As relaxed as you can be with me coming at you with a needle.

[25:23] Jennifer Milner: Right.

[25:25] Anne Maitland, MD, PhD: So in my opinion, the treatment of mast cell disorders is to show the body it's in a safe space. And there are lots of ways you can approach that, both pharmacologically and non-pharmacologically. Reduce the tissue injury — which you need to do in individuals that are dancers and swimmers, because that's all you do: you keep pushing yourself to the point that you end up with more injury. So you want to stabilize those joints. You stabilize the joints, you reduce the susceptibility to that alarm going out.
[26:06] Just restraining the mast cells with medications — and by the way, you're only restraining one out of the hundreds of chemicals that mast cells release if you take histamine blockers. Cromoglycate, quercetin, and luteolin stabilize mast cell degranulation, making it much harder for the mast cells to degranulate. But again, if they're your police officers and your cleanup crew, do you really want to completely restrain them?
[26:44] And by the way, mast cells are found in shellfish, so they have lots of ways to figure things out. They're kind of like that main character from 24 — they will figure out a way to get around the restraints. Because they think they're trying to help. So if we can just change our mindset on what the mast cells are supposed to do and how we can let them know they don't need to do this in this circumstance, you can reinduce tolerance. Just like you can lose tolerance, I'm a believer that you can re-educate the system to restore it.

[27:31] Jennifer Milner: That's so interesting. You mentioned the anxiety attack, and I was thinking about how that parallels what you're talking about with mast cells. When someone has a panic attack, they're having feelings — their body is having this overcompensatory response relative to the actual stimulation. And you can't tell someone in a panic attack, just stop having those thoughts and feelings. You acknowledge that they are not proportionate to the level of challenge and help them move through it. And trying to encourage your mast cells — you are having an inappropriate response to what's going on; let's help you figure out how to have an appropriate response. Let's figure out how to stabilize it and have a more accurate response, right?
[28:20] So when we're looking at trying to get an MCAS diagnosis, it sounds like it's multifactorial but not impossible. Part of it is patient education — knowing that these things could all be linked together and it's okay to go get help before things are crazy bad. Part of it is physician education, medical profession education. As you mentioned with the heart attack, there are protocols you could go through to try to find the MCAS or the MCAD, but they're not necessarily being applied. And then there's having that education of what to do with the diagnosis once you have it. Is that fair to say? Because I know we have a lot of people say to us, how do I get a diagnosis? I feel these things — how do I get a diagnosis?

[30:13] Anne Maitland, MD, PhD: Literally. I think there are plenty of sources out there. First of all, the Mast Cell Society has a very concise assessment. There are several books out there. I'm going to give a shout out to Amber Walker, who just came out with The Trifecta Passport — a very concise explanation as well. I will also acknowledge Diana Jovine — God bless her — for going up to all of us who were on the lecture circuit, not necessarily the frontline of allopathic medicine, but going to a lot of patient organization meetings, and saying, this is what we're seeing. She herded us like cats and got all of us to volunteer our chapters for a book, because we are so overwhelmed by what's going on with so many people, both children and adults.
[31:20] Because the longer this goes on, the longer it goes on. You start acquiring other injuries. Other organ systems become involved because that stress factor never stands down. And when the stress factor never stands down, more chemicals get kicked out, more collateral damage from the chemicals, and it keeps passing forward.
[31:41] So we wanted to make efforts to educate patients, because honestly, most patients probably have more knowledge on how to buy a used car than on how to identify a practitioner who can help them. We also want to educate our colleagues, especially in primary care, because that's supposed to be your guide — not necessarily your gatekeeper — the person who steers you. And the first thing that practitioner has to admit is: I don't know about this, but this is who I think you can go to who might be able to take that baton and take you further.
[32:23] And that's how I started — I trained in institutions that had in-house allergy immunology practitioners, and I didn't learn about mast cells until I met a little boy who was the eleventh allergy immunology specialist that he had met. And he was four years old. Asthma, anaphylaxis, joint pain, couldn't go to school, sensitive to changes. The whole family was down to about eight foods.
[32:59] And here's the thing: people have a tendency to focus on what they eat. I get that you have more control supposedly over what you eat than over the air that you breathe. But you swallow one to two times per minute. You breathe 18 times per minute. And your skin is always exposed to the environment. All of those organ systems have to assess what's coming in — is it healthy for you or not? And if they think it's not, and that danger signal goes out, the skin, respiratory tract, gastrointestinal tract, brain, joints, and bladder are all going to take a hit. It just goes on and on until somebody says enough. And people really decline. They use up all their social capital. The practitioners are frustrated. Some patients frankly get fired from their practices — which is a real thing. And I'm not saying I know all of it, but again, most patients come to my office — I think they'd rather be at a concert, well, before COVID — than spending money on doctors and tests that don't give any answers.
[34:18] And I have to tell you, this is an old story. Now it's EDS, POTS, and MCAD. Ten years ago it was fibromyalgia. Before that it was gluten. And Francis Peabody talked about this — the woman deemed "nothing's the matter with her" back in 1927, to the Harvard community. He said, quote unquote, she suffered at the hands of many practitioners before she showed up at that Boston hospital, which then said, we have all the scientific advancements and we're going to figure out what's going on. And lo and behold, all of their testing was normal. And they said, there's nothing wrong with her, and kicked her out. That was 100 years ago. And I'm thinking, what kind of tools did you have 100 years ago that you could be so arrogant?
[35:14] So it's education of the patient so they can be a better consumer — because that's exactly what you are in this healthcare system. Education of the practitioners: you don't know about this, here's what you need to look for. Asthma, which in my opinion is a mast cell disorder of the lungs, is common — 10% of the population. 70% of them are undertreated and underdiagnosed because we don't screen for asthma until you have an attack. And typically nobody likes to venture outside of their little corner of the sandbox. Pulmonologists don't want to talk about the nose and sinuses, and they certainly don't want to talk about the skin. Dermatologists — ah, you've got to go. So you end up going to all these different practitioners and nobody is looking at the level of the forest.
Even in allergy immunology and hematology oncology — hematology oncology has a tendency to focus on the cancer. I'm like, I'm trying to make sure you don't get there. Allergists are saying the tryptase is normal. And I'm like, well, people who have peanut-induced anaphylaxis, their tryptase never goes up. So what does that mean? Our testing is insufficient.
[36:40] And if you've ever collected urine for 24 hours, had to put it in your refrigerator — which a lot of people are not very happy about — and then taken it to the lab where the person lets it sit on the counter and doesn't process it properly — we have to come up with, just like we had to come up with a rapid test for COVID, a rapid test for mast cell disorders. And it has to involve different types of testing. Just like heart attacks — before, we would only look at CK creatine kinase. But then they added troponins, and more after that. We need to do the same thing for mast cells.
[37:20] Because here's the thing: one out of two of us has a chronic disorder. It's just a question of how well controlled it is or isn't. Given the prevalence of insults to our respiratory tract, skin, and gastrointestinal tract, nearly one out of two of us more than likely has a mast cell disorder. And mast cell activation syndrome, by definition, is in many ways a low-grade anaphylaxis — because basically you're having reactions across two or more organ systems. And anaphylaxis is a grading system, just like earthquakes. You can have a 1.2 where you just have hives, or you can have a 5.6 where you should have called 911 ten minutes ago.
So there are ways we need to improve the education of both the primary care, the specialists, and the patient population — so they know, like when you're trying to buy a car, what kind do I need, what kind of gas mileage, how much do I want to spend. And here's the thing: once you get a working diagnosis, first of all, it's a relief, because so many people have been told this is just in their heads — which, in my mind, and what Francis Peabody called it 100 years ago, is a medical failure. You failed to pursue the truth.
[39:14] So most people are just relieved when they come into my office and I say yes. And by the way, you're sitting in a W. And they look at me like, wait a minute, you're an allergist? And I get the same look I got when I presented a similar abstract at the American Academy of Allergy, Asthma, and Immunology back in 2013. They're like, fellow allergist, you're telling me you have to bend people to figure out whether or not their mast cells are misbehaving?

[39:51] Dr. Linda Bluestein: And I'm like, that's exactly what I'm telling you. Wow, that is so much fabulous information and so much to unpack. One of the things that is so challenging for people to understand is the relationship between hypermobility and connective tissue disorders — because obviously those are not the same, but they're related — and then understanding the relationship between those and mast cell activation, and between mast cell and pain, because we know that mast cell activation or mast cell disorders are also related to painful syndromes and can contribute to pain. Can you explain a little bit about that?

[40:31] Anne Maitland, MD, PhD: Mast cells were originally identified not in humans but in tadpoles in the 1860s. Then Paul Ehrlich — who was one of the founding fathers of immunohistochemistry and also considered one of the founding fathers of translational medicine — identified mast cells in every part of the connective tissue in human beings. And so if you were to stain the connective tissue for mast cells — as we do for people we're trying to assess for a clonal mast cell disorder like mastocytosis, systemic mastocytosis, or monoclonal mast cell activation syndrome — which is a lot of terms to say: are your mast cells misbehaving because something is broken within some of them? As opposed to what most people have, which I consider non-clonal or secondary mast cell activation syndrome, meaning the mast cells are being good police officers and repair persons, they're just getting bad orders.
[41:36] So if you were to do a special stain for mast cells — and by the way, this is really important: mast cells are tissue-based. There are fewer than 1,000 circulating in the blood for you to pick up. So if you're going to look for them — just like if somebody's having a heart problem, you want to look at the heart. The blood can give some good collateral information, but you really want to look at where the problem is.
[42:07] If you were to take a piece of skin or a piece of gut — as they normally do when they do an endoscopy or colonoscopy — and stain for mast cells and stain for nerves, you'll find that they sit right next to each other, embedded in the connective tissue. And the job of the mast cell and the nerves is to act as an early warning system and early response team. That's where that trifecta, that triad, that I'm talking about comes in.
[42:37] You have the epithelial barrier. An average adult has 75 square feet of territory that's always exposed to the environment — whether you're talking about the skin, the 25 feet of gastrointestinal tract from what you swallow, from the tip of your nose to the base of your lungs, and the urogenital tract. They all have different connective tissue and epithelial lining, but it is all connective tissue. Right below the surface area, you have the mast cells and the nerves. And they talk all the time. They're like SEAL Team Six. That's what you want, because that epithelial lining has to deal with — within just a centimeter or so — ten times the amount of foreign entities than you have cells in your body. Talk about having gorillas at the gate.
[43:40] And here's the thing: what do our bodies need to do? We need to bring in oxygen, we need to bring in nutrients, and we need to get rid of waste products, which means we have ports of entry and exit. Who do you think is guarding those? And who do you think is supposed to respond if somebody is trying to get in when they shouldn't?
[44:01] This is a very old theory, and I was first introduced to it by Polly Matzinger, who has a wonderful story I would recommend reading in the New York Times. I first met her when I was a lab technician. She gave a lecture back in 1987 talking about the Danger Theory. At that point in time, one of the major tenets of trying to understand how the immune system turns on and turns off was tolerance. The argument was: we're just born with all the cells that recognize us, so those cells and proteins won't attack us — they'll only go after what's not us. But then how do you explain pregnancy? Or how do you explain going into a new country and trying a new food? She said: it is tissue injury that tells the immune system and the nervous system something's wrong.
[45:13] And what piqued my interest was one of the papers that she wrote where the lead author was her dog. And talk about her beginnings — she was a waitress at a diner next to Scripps in California. She was listening to the scientists talk, and she asked a really good question. They said, you need to go to graduate school. And now where is she? She's at the National Institutes of Health.

[45:51] Dr. Linda Bluestein: That's awesome.

[45:52] Anne Maitland, MD, PhD: Right? Sometimes you need to be from the outside. And in many ways, a lot of people with bendy bodies are on the outside of healthcare looking in. But as a group, we're going to be able to change things. We have to change how we think about things. We have to change how we're dealing with our environment and appreciate that our environment — whether we want to admit to it or not — has completely changed in less than a generation. Whether you're talking climate change, whether you're talking about access to food sources, whether you want to talk about the fact that we spend more than 90% of our time inside of something — a building, a car, a mall — all manufactured.
[46:41] So the air we breathe, and by the way even clothing — think about it. The '70s were the polyester age. And polyester back then was really irritating. So they worked really hard to come up with better fibers. Think about how our food was produced and stored, the clothing we wear. Back then, Ivory soap was 99 and 44/100s pure. Now you need a chemistry degree to understand what's in it.
[47:08] So we are being inundated with substances our bodies have never seen, some of which cause direct injury. We have more microplastic particles in our lungs nowadays than ever. What do you think that stuff is doing? It's causing micro-injury. And here's the thing about mast cells and nerves — they're kind of like ninjas. You've got to light them up to see them. And Linda, you remember the term — because you try to identify people who have pain syndromes out of proportion to their exam, right?

[47:52] Dr. Linda Bluestein: Yes.

[47:53] Anne Maitland, MD, PhD: So going back to that little boy I told you about — listening to their story, and I had more than seven minutes to listen. He came out rashy. God bless the family, they had a pediatrician, old school. He said, look, I don't know what you've got, but I want you to keep breastfeeding, and I want you to limit your diet and try to stay in a wholesome environment. And he was fine for a year. Then the pediatrician retired. A new one on the block came in. Why isn't your kid on milk? And the kid had to get four vaccinations at once. He regressed completely. Kind of like Jesus walked in and then Jesus walked out. They had three years of anaphylaxis, asthma, and gastrointestinal distress. He saw at least 27 or 28 providers before he came to my office.
[48:51] The only reason he came to my office is because I had taken care of a patient with systemic mastocytosis, and his mother had heard something about connective tissue disorders and mastocytosis. And I attended one of the three programs in the country that studied mast cells.

[49:12] Dr. Linda Bluestein: Wow.

[49:13] Anne Maitland, MD, PhD: That's the only reason that I met them. And I just looked at them and thought, you look really long, like sitting a certain way. And she said, yeah, I think we have Ehlers-Danlos. At the time it was called classic type 3. And of course I had to go to the computer — my reference point, Dr. Google — and ask: is there anything out there regarding mast cells? Because I only know two systems that can cause that type of reaction, and that would be nerves and mast cells.
[49:52] As an allergy immunology specialist, I know a little bit about nerves, but I do know there are plenty of non-immune-mediated physical triggers. Think about hives. You have cold-induced hives, vibration-induced hives, solar-induced hives, dermatographism, which is pressure. All these nerve-mast cell related things causing swelling and itch and hives. We also know the same thing for asthma — cold-induced asthma, humidity-induced asthma. All these non-immunologic triggers cause problems in the skin, the gut, and the respiratory tract.
[50:38] I still remember the first patient who came to me with interstitial cystitis saying, I have food allergies. And I said, I'll test you, but that doesn't sound right. And again, this is not about allergens. It's not about me finding a mugshot of IgE that recognizes oranges. It's a chemical issue. When your body is stressed, it's not going to like the chemical, or the temperature, or the humidity. So mast cells and nerves talk to each other all the time in the epithelial layer — the connective tissue exposed to the environment — trying to figure out what's coming in, whether it should be there or not, whether the temperature is right, whether the amount of water is right. It is all about how we are navigating our step-by-step journey in the environment that we're in.

[51:37] Jennifer Milner: It sounds like it's education all around, which I feel like is a huge topic for us everywhere. But it's not just educating physicians and educating the patient — it's also educating the body. Reeducating the mast cells to respond appropriately, reeducating the body to support itself. Education is key all around. This podcast has been hugely educational for me, and helpful. Thank you.

[52:11] Anne Maitland, MD, PhD: So my private practice has now folded into a group called Clinical Paradigms, where it's kind of hard to call Dr. Pisano a nutritionist — she has a PhD in nutritional genomics. I have to tap out after the Krebs cycle, but she has the resources. She has a wonderful person who's a Pilates instructor named Sabrina Foss. And she has a wonderful woman who helps with addressing the emotional and psychological burden — trying to tease out all that has happened along the journey that has put up mental defense mechanisms to having insults happen to you. And she also has nurse nutrition specialists who coach you along the way.
[53:23] If we can get the body to operate more efficiently, if we can bring the mast cells and nerves down to a basal level of activity — where the temperature shouldn't be a problem, or putting my hand out here shouldn't be such a stress — that's the goal. Addressing the cervical spine is honestly important too; there are a lot of structures that go through there, and if it's a problem, you have people who have swallowing difficulties.
[53:52] Which leads me to the third person, Dr. Isabelle Brock, who brings her experience treating EDS and comorbid disorders — she practiced in France for six or seven years and is now here in the U.S. We all talk to each other, just like you have cancer teams and heart failure teams. We now have an EDS, mast cell, neuro combination team going.
[54:23] And I tell people — both children, their caregivers, and patients — you're like a Maserati trying to drive on the streets of New York City. You hit one pothole and that's a $15,000 repair. And then you're going to take it to a GM dealer. I'm not trying to knock GM dealers, but your body is an exquisite biological machine. Individuals that have undiagnosed connective tissue issues, immune dysfunction, and neurological dysfunction who keep on pushing it end up with increased wear and tear. You can pay that price both in your mental and physical health, which are tightly linked.
[55:17] So it's still a learning journey for me. I reach out to Dr. Ruhoy, I reach out to Dr. Bolognese, because we're all looking with a different set of eyes. We have to step outside of our areas of expertise to understand the interconnectedness between the mast cells, the nerves, and the connective tissue.

[55:39] Jennifer Milner: I agree, and we are all about teamwork here. We love having a variety of people who can pour in from different points of view. That's why we are so grateful to you for coming in and sharing your expertise. For people who want to learn more, how can they get in touch with you? Where can they find you out in the internet world?

[55:59] Anne Maitland, MD, PhD: The easiest access is either clinicalparadigms.com, or the Center for Chiari, EDS, and MCAD at Mount Sinai South Nassau in New York.

[56:10] Jennifer Milner: Okay, we will have those in our show notes for you so that you can find those there. We are so grateful, Dr. Maitland, for you coming on and having this conversation with us. You've been listening to Bendy Bodies with the Hypermobility MD, and we've been speaking with Dr. Anne Maitland, MD, PhD, Chair of the Allergy and Immunology Working Group for the International Consortium on EDS and HSD. Dr. Maitland, thank you so much for taking the time to come on the Bendy Bodies Podcast.

[56:50] Anne Maitland, MD, PhD: My pleasure.

[56:52] Jennifer Milner: We are so grateful for the wisdom that you have shared with us today.

[56:56] Anne Maitland, MD, PhD: I appreciate yours. And next time, I hope to hear more about the experiences that you've been on — this journey — because all of us are talking from each side of the bed rail, as you see.

[57:10] Dr. Linda Bluestein: Definitely. It's fascinating. These groups of conditions are so humbling — every day you realize how much you have yet to learn, but also how much we already know and how much we can do for people.

[57:34] Anne Maitland, MD, PhD: Be kind to yourself. Really, be kind to yourself — start there first. And don't give up hope. There are more people working together on all different types of levels. And in many ways, what you're doing now is acting as a beacon — lighting the way for people who just don't have those resources. So I appreciate all that you're doing. And again, thank you for this wonderful invitation.

[58:02] Jennifer Milner: Thank you, and thank you everybody for tuning in today.

[58:08] Anne Maitland, MD, PhD: Bye. Salud.

[58:11] Dr. Linda Bluestein: Thank you for joining us for this episode of Bendy Bodies with the Hypermobility MD, where we explore the intersection of health and hypermobility for dancers and other aesthetic athletes. If you found this information valuable, please share it with a colleague or friend and leave us a review on your favorite podcast player. Remember to subscribe so you won't miss future episodes.
[58:32] If you want to follow us on Instagram, it's @bendy_bodies, and our website is www.bendybodies.org. If you want to follow Bendy Bodies founder and co-host Dr. Bluestein on Instagram, it's @hypermobilitymd, all one word, and her website is www.hypermobilitymd.com. If you want to follow co-host Jennifer Milner on Instagram, it's @Jennifer.Milner, M-I-L-N-E-R, and her website is www.jennifer-milner.com.
[59:09] Thank you for helping us spread the word about hypermobility and associated conditions. We want to hear from you — please email us at [email protected] to share feedback. The thoughts and opinions expressed on this podcast are solely those of the co-hosts and their guests. They do not necessarily represent the views and opinions of any organization. The thoughts and opinions do not constitute medical advice and should not be used in any legal capacity whatsoever. This information is not intended to diagnose, treat, cure, or prevent any disease, as this information is for educational purposes only and is not a substitute for medical advice, diagnosis, or treatment. Please refer to your local qualified health practitioner for all medical concerns. We'll catch you next time on the Bendy Bodies Podcast.