Mast Cells and How They Affect Allergies
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Mast Cells: How They Affect Vaccine, Drug and Food Allergies
Welcome to The Smartest Doctor in the Room. I’m your host, Dr. Dean Mitchell. Today’s podcast is going to be on mast cells and how they affect vaccines, drugs, food allergies, a lot of things, and possibly this new mast cell activation syndrome.
You know, it just so happens, today’s guest and myself are both specialists in allergy immunology. You know, as my listeners know I do a whole range of things, but when it hits home, I really get very excited. And today, we’re gonna have a very in-depth conversation on how mast cells, an underappreciated cell is so important in allergic reactions to vaccines. And we’re gonna talk a little bit about the COVID vaccination program, drugs, and foods and we’re gonna hopefully discuss a newly described syndrome, which I get a lot of calls now from patients about something called about mast cell activation syndrome, which I think maybe tied to a lot of these conditions together.
I’m sure a lot of you have heard about B-Cells and T-Cells and their importance to the immune system. That’s something that the AIDS epidemic really brought out when I trained in the 1990s and was what they called the adaptive immune system. I don’t want to get too technical, but that’s like your super-smart memory immune system. But, there’s another part of the immune system called the innate or we call primitive immune system, which doesn’t have memory and I think, for a long time ’cause I teach this at the medical school were overlooked and mast cells are considered a part of that.
My guest today, Dr. Mariana Castells is internationally known as an allergy immunology specialist at Harvard Medical School, where she is the director of both the drug hypersensitivity and desensitization center. She’s also the head of the Mastocytosis Center. So, she’s what you call a triple threat in our profession. She’s a top researcher, she’s a well-known clinician, especially with her drug desensitization clinic and she’s really a highly regarded teacher and the last thing, which I have to mention, there’s barely a month that goes by when I’m reading my journals, the allergy journals, the New England Journal, that she’s not in one of these journals, so she’s very current. So, it’s my great pleasure to welcome Dr. Mariana Castells to the podcast.
Dr. Mariana Castells:
Thank you so much. I’m delighted to be here. And actually, I have to say something that I’m so glad that you bringing the mast cells to the forefront. They have been the forgotten children of our immune system. So, I’m totally grateful that you’re thinking about them, that you’re thinking they’re important, that you’re thinking that people need to know more about the mast cells.
I trained in Barcelona, my hometown and I did my medical career over there. To make it, you know, in a nutshell, he had, uh, this conundrum of a little girl who, uh, was, uh, have asthma, have tremendous anaphylactic events, who had hives all the time and nobody was able to figure out what was happening. So, he said, “Hey Mariana, this is your turn. You know, you’re a first-year fellow, just find that out,” and it’s like, “Wait a second. How can I do this?” And then he told me, “You have to be a detective,” and I said, “All right, okay. Okay. Okay.”
So, I had a diary of the girl. What her… what was he… she doing, what was she eating, where was she. So, when she was going through a field in the summer, she was wheezing through those fields in Spain, in, in the north part of Spain. Those fields have potatoes. And then when she was eating, she ate some of the foods that had potato starch. So, I started to put something together, 100 ingredients and everyone of them seem to be kinda relating to potato. So, I asked my boss, “Do you actually think she could be actually allergic to potatoes?” and I said, “That does not exist. Nobody’s allergic to potatoes.”
You know, nobody’s allergic to potatoes. And that, that’s kinda what I really like when people challenge me -… so, that doesn’t exist, it cannot be done. I said, “Okay, let’s, let’s look at it.” You know, that’s the way I was built, my genetics. And so, I actually started to do that for, you know, a very long story short, I discovered that potato is allergenic, it has low molecular allergens and I actually published that in the, for the first time in the Journal of Allergy and Clinical Immunology.
And that attracted a lot of, uh, attention. So it’s mashed potatoes and the peel of the potatoes and the flower of the potatoes and I was able to cross see that the serum of the girl had something.
That light up. But, the most interesting part was the following. So her… I, I said, how can I prove that this is true actually? So, I got the serum of the girl and I put it in the mother’s arm.
I asked the mother, “Eat potatoes,” and it lights up like Christmas trees.
Dr. Dean Mitchell:
Wow. That was old… You could get away with that back in the day, right?
Dr. Mariana Castells:
Yes, yes.
Dr. Dean Mitchell:
Before HIV and Hepatitis.
Dr. Mariana Castells:
1987.
Dr. Dean Mitchell:
But, that was the classic way. You know, I trained at the Cooke Institute in New York. Dr. Cooke, who sort of originated allergy in this country. Something… we’re gonna get into this passive transfer, where exactly what you just described was how they basically knew there was some type of factor, which we later learned was an IgE that triggers allergies. Oh, that’s fascinating.
Dr. Mariana Castells:
For me, what was really fascinating, not only was discovering what made it, but how could she be so sick, you know, from wheezing, uh, losing her blood pressure from passing out and the cells that I discovered behind that were the mast cells.
Dr. Dean Mitchell:
Yeah.
Dr. Mariana Castells:
So, mast cells have those powerful mediators that can do anything and everything from an itch to actually kill you. So, so, that actually open, you know, my fascination to those cells. They are the most ancient cells of our immune system.
Dr. Dean Mitchell:
Right.
Dr. Mariana Castells:
And, and I decided to just go and pursue, at, at that time, I had finished my fellowship, uh, but I pursued a PhD in the field of, uh, mast cell biology.
Dr. Dean Mitchell:
Is that in Spain also or you came to the United States for that?
Dr. Mariana Castells:
I came to the United States, Larry Schwartz, uh, was my mentor and I did that by discovering the Tryptase, you know, the major product of the mast cells is in the nose when you sneeze it’s in the blood when you have anaphylaxis, it’s in your lungs when, uh, there’s a wheezing and that led to my career in the United States.
Dr. Dean Mitchell:
Oh, wow. What a great story. That, that was even better than I thought. So, we’re gonna move on, and again, we’re gonna probably get really in-depth in a lot of things, but I always wanna make sure that the listeners are enjoying this as much as I am. So, mast cells as you were pointing out, I think, they were really a very overlooked cells and I’ll explain to the listeners as what we mean by that. You know, in the field of allergy, I would say, up to the 1950s, ’cause again I trained at an institute where there were a lot of doctors who were very prominent in allergy in New York, in the 1950s, uh, at my institute. You know, they used to always tell me that, you know, our specialty never got any respect. And one of the reasons was, it was sort of considered a fringe, you know, a voodoo, we don’t know what those guys are doing.
I mean, even at the Cooke Institute and I tell patients, they laugh at these stories. People used to bring in their vacuum bags of dust and at the Cooke Institute, they used to take it, dilute it, spin it, do stuff with it, and inject it back into the patients. And u- understandably, our colleagues in the other field of medicine thought this was crazy. And then, in 1967, the doctors Ishikawa, I’m saying this correctly at National Jewish and a Dr. Johansson in Sweden discovered that there was this immune globulin called, Immunoglobulin E for short, which was this mysterious factor that, uh, essentially allergists have been looking for, for years that explained why people develop allergies.
What is the mast cell and why should we be concerned about it?
So, for a long time, I think, in our specialty, there was understandably tremendous amount of attention given to the IgE and everything that influences it and obviously we know that mast cells are one of the cells that have these receptors for IgE, but in that process, we forgot to look at, I quote, “the histology” that it’s actually these cells that are very, very important. So, I wanted to ask you what you think, I mean, obviously, you’re fascinated with mast cells. I’ve heard, I’ve had another podcast where somebody described them as patrol cells. What do you think their role is? I mean, again also, that was why I think, they were ignored because people always thought, “Oh, it’s the allergy cell.” But, people aren’t just born with an allergy cell. A cell has to have a function, right? and the same way histamine. So, what’s your take on all these years of researching this? What is the mast cell and why should we be concerned about it?
Dr. Mariana Castells:
Yes. My fascination led me to work with the people who actually have been like Rick Stevens, Frank Austin, you know, the people who actually have further understanding. But, in that sense, mast cells have been the more primitive cells of the immune system and you know, who are millions of years separated from humans have, have mast cells.
And the reason is that, uh, you know, when we were primitives in our grand… grandmother Lucy was in the woods, the mast cells used to protect us against parasites, against scorpions, against venoms, against bee sting. So, all of that, the mast cells have inside them, you know, b… the granules, they release-
You’ll probably, we will talk about, you know, histamine mediators, all those things. And, the important thing about the mast cells in humans is where are they located. So, the mast cells are located everywhere. The whole skin has mast cells-
Dr. Dean Mitchell:
Right. I think even allergists, honestly, I mean, you’re obviously a super research in this area, but I think, even in my career early on didn’t appreciate that. I mean, it was like, okay, mast cells are in the lungs, they’re in the nose, the skin, quote, “the allergy areas”, but to think about it in the brain or in the gynecological areas, this was eye-opening to me, right?
Dr. Mariana Castells:
So, so it’s actually there are mast cells everywhere. Like you said, in the connective tissue, in the skin in the mucosal membrane of the gastrointestinal tract, they are very important there, from the mouth to the tongue to the esophagus. So, mast cells are located everywhere. Depending on where they are located, they have different functions and then they have different mediators. And so, you know the mast cells in the lung are more kinda simple mast cells like in the alveolar, the breathing tubes, that the mast cells in the skin are bigger, they have more granules and they have more powerful mediators. So, what we call, uh, mast cell heterogeneity has just been unfolding in the last three or four years. Not mast cells are created equal and they are everywhere.
Dr. Dean Mitchell:
Yeah. That’s a really important point and I’m gonna ask you something now again. It’s mechanism-wise, but again I think, for my listeners, I’m gonna try to make it really relatable. You know, I had a professor when I did some of my training at Columbia Presbyterian in New York, and he was really an interesting guy. He was actually one of the few board-certified allergist and dermatologists in the country. You know, because back in the day, uh, people can do multiple training, get certified, but he was just a very charismatic, interesting guy and his big mantra was, “You can’t be allergic to something first time, for example when you eat it.” So, a lot like… ’cause you know, it is perplexing to patients like, “I’ve had shrimp a 100 times, why now did I break out in a rash?”
And I, I always thought about that a lot and explain it to patients, but there is a little bit of a nuance to that because with the mast cells, it does make sense, you know, obviously the, the classic picture of mast cells with the IgE like, looks like the Y shape receptors on them has to have a certain amount of coding before they bind and release the histamine. But, yet we do know people have allergic reactions and we’ll get into this, the first time have come, come from a vaccine. So, what do you see as the, how to differentiate these mast cells being activated by an allergic… like an IgE mechanism versus maybe I guess a compliment. Is that the other… Why would they just start to release… I mean, I know, for example, strawberries and Codine, those are what they call mast cell direct releaser. That you don’t have to, you know, it’s quantitative, it doesn’t have to be repeated, it could just happen on one time. So, I, I know I’m talking a lot, but I’d rather hear what, what you, how you see it.
Dr. Mariana Castells:
Yeah. So, so I think that you’re absolutely right. That, uh, most of the time we have understood mast cells as cells that are reactive when they have been re-exposed many times to Penicillin to, a cat, to pollen they have to withstand you know, three times you were exposed to the pollen then you can react. But, the mast cells as I was mentioning in the last four or five years have been found to have a lot more receptors. So, so what you’re talking about that IgE is that, the mast cell has a receptor for that IgE and then the receptors touch each other, we call cross-linking and then they release the bridging and, and mediators. But, there are many more receptors on the mast cells and for example, their one receptor that is called a kinda fancy name, MRGPRX2 that has been discovered just in the last, you know, five years and that receptor makes people react to, uh, medications like antibiotics, for example, and are called Quinolone, Ciprofloxacin, Levofloxacin and then also, uh, reacts, uh, people who react to general anesthesia, Atracurium, Rocuronium. And they go through those receptors that are called G coupled proteins, so they don’t need to have an IgE on it. So, some people have those receptors more expressed or, or more available and then, boom, they react the first time.
Dr. Dean Mitchell:
That, that is so important, what you’re bringing out. And, and again for the listeners, because I know this is so frustrating for them, it’s frustrating for their doctors because you know, and I’m sure you’ve seen a lot of these cases.
Dr. Mariana Castells:
Right, so one avenue is like with penicillin and I wrote a piece for the New England. So you have to be kinda exposed, you know, several times and then there is also familial transmission. So you… we think that there might be also some genetics involved in that.
And then-.. and we haven’t yet uncovered, you know, the kind of the genetic determinants of that but then, on the other hand, we have discovered more and more, that for example mast cells have receptors for, uh, light, they have receptors for stress.
Dr. Dean Mitchell:
I’m so glad you brought that up. I have this paper right here from somebody in your state (laughs). Theoris, uh, Theoradyce.
Dr. Mariana Castells:
Yes.
Dr. Dean Mitchell:
It’s hard to say his name. Must be Greek or something.
Dr. Mariana Castells:
We call him Theo.
Dr. Dean Mitchell:
Theo. Call him Theo, Dr. Theo. I mean, he wrote an article that was about the impact of psychological stress on mast cells and really delineates the mechanisms and again, ’cause patients are frustrated. They’re like, “Oh, my God, like, why is this happening? I didn’t eat anything that I’m usually allergic to. I didn’t do this.”
Dr. Dean Mitchell:
And I’m like the question obviously you ask them very carefully and sensitively, you know, “Have you been under a lot of stress?” and they go, “Well, yeah. What does that matter?” But it does matter.
Dr. Mariana Castells:
Yeah, there is like, uh, we are also unfolding connection between the- uh, mast cells at the nerve endings.
Dr. Dean Mitchell:
Right.
Dr. Mariana Castells:
So tha- those connections, so those intra connectivity between mast cells and a lot of the other cells in the body and that’s what makes the symptoms, you know, very important. So one thing that I wanna say is that it’s hard to make a diagnosis of a mast cell activation disorder.
Dr. Dean Mitchell:
We’re gonna get to that, yeah. Mm-hmm (affirmative).
Dr. Mariana Castells:
Because mast cells mimic everything and anything. You know?
Dr. Dean Mitchell:
Right. Well that’s what… That’s also what really frustrates doctors. You know, when you look at the lists, a lot of these published papers of what the symptoms could be, the doctors throw their hands up and I’m finding it more and more fascinating, cause and again two patients are doing their due diligence these days.
Dr. Dean Mitchell:
I mean, Google’s become their-
Dr. Mariana Castells:
Yeah.
Dr. Dean Mitchell:
… new medical library. And, uh, you know, and we’re gonna get to that because again, I wanna try to help them but I’d like to transition to a disorder which is rare but is very well defined and I think we need it as the backdrop to that is mastocytosis which I know you’ve done a lot of work on.
Dr. Mariana Castells:
Yes.
Dr. Dean Mitchell:
So I have a list here but I- I like to, you know, I find it fascinating but what would you say is the most common clinical symptoms, like with mastocytosis? And so actually, I’ll tell you one other funny thing too.
Dr. Dean Mitchell:
One of my mentors here in New York at Columbia had spoken to a decade or two ago because, uh, one of the former supermen from TV had mastocytosis. What do you usually find because a- again, you know, some… there are certain symptoms that are… would really surprise people?
Dr. Mariana Castells:
Right, right, right. So I have to say that mastocytosis, you know when I started to do that [inadible 00:18:06] with my mentor like in the early ’90s brought, you know, 40 charts to my table. I was a first year fellow. And he say, “Hey, Marian. Are you gonna take care of those patients?”
Dr. Mariana Castells:
And I said, “What do they have?” and he said, “Mastocytosis.” And I said, “What is that?” And, so then, uh, I learn… and but one of the things that he told me, he says, “You know, the first time they have a symptom and the time where they have a diagnosis spans about 10 years-
Dr. Dean Mitchell:
Wow.
Dr. Mariana Castells:
… so I need you to shorten that time.”
Dr. Dean Mitchell:
Right.
Dr. Mariana Castells:
And so I publish in the New England Journal Magazine about six years ago about a case of mastocytosis from- from a marathon runner and the span of time was nine years. We haven’t made any progress. We haven’t made any progress.
Dr. Dean Mitchell:
That’s tough. Yeah.
Dr. Mariana Castells:
But we- but we know a lot more. So essentially, people can have symptoms that are non-specific. So essentially that is what happens. People feel like flushing, feeling bad diarrhea, feeling all those symptoms.
Dr. Dean Mitchell:
Right.
Dr. Mariana Castells:
And the things that actually is at the core now of this is that there’s a cheap test that’s called tryptase.
Dr. Dean Mitchell:
Yes.
Dr. Mariana Castells:
Very cheap test, you know? It’s-
Dr. Dean Mitchell:
And these have been underappreciated because I think a- as you mentioned-
Dr. Mariana Castells:
… Totally.
Dr. Dean Mitchell:
… And other people that, like, a lot of times they’re saying now even any patient that’s had a venom anaphylaxis maybe any patient that’s had anaphylaxis, maybe they should be screened, right? Because they may be more prone.
Dr. Mariana Castells:
True. This should be the front of every [crosstalk 00:19:24]
Dr. Dean Mitchell:
It used to be a very hard test to get though. I remember we used to have s- send it to Larry Schwartz in, uh-
Dr. Mariana Castells:
Right.
Dr. Dean Mitchell:
… Virginia. But now the major labs are all doing it, right?
Dr. Mariana Castells:
Blood count, you know, a CBC is actually more expensive than a Tryptase level.
Dr. Dean Mitchell:
Really?
Dr. Mariana Castells:
So- so getting screened for Tryptase is the first thing about mastocytosis and people who have mastocytosis have more mast cells in their body.
Dr. Dean Mitchell:
Okay.
Dr. Mariana Castells:
But it’s not that they’re more active; they just have more mast cells.
Dr. Dean Mitchell:
Right. Yes, that’s a big distinction, right.
Dr. Mariana Castells:
Right. And then a rash is the first symptom, so.
Dr. Dean Mitchell:
Well, let me- let me… I wanna ask you two things that you published in a paper that I have here which I- I thought also was super, super important. It was actually about mast activation but it really probably could apply to… it obviously does apply to mastocytosis because I- I think people don’t appreciate the GI symptoms and a lot of cases like hereditary angioedema which is another condition we see.
Dr. Dean Mitchell:
Sometimes that’s the first presentation. You know, ’cause again, you always think you know, it’s got to be an allergic kinda presentation but when patients, they have, like you mentioned diarrhea or bloating or ulcers, things like that nature, first they wouldn’t start to think about it as mastocytosis obviously.
Dr. Mariana Castells:
Right.
Dr. Dean Mitchell:
When you look at the history because you’ve took… obviously taken care of probably maybe more patients in the United States than anybody with this, do you find the GI is very prominent and that usually is-
Dr. Mariana Castells:
Yeah. So- so the secret for the mastocytosis is the two- two warning organ systems.
Dr. Dean Mitchell:
Okay.
Dr. Mariana Castells:
So- so essentially, one of the major expressions of mastocytosis is having abdominal bloating, pain, diarrhea but again it has to be paired with some other symptom. So because the mast cells, you know, are everywhere.
Dr. Dean Mitchell:
Right, they’re not just so isolated. Yeah.
Dr. Mariana Castells:
Exactly. So having diarrhea is probably Crones or is-
Dr. Dean Mitchell:
Mm-hmm (affirmative).
Dr. Mariana Castells:
… uh, irritable bowel syndrome. So other disease but diarrhea with flushing.
Dr. Dean Mitchell:
Yes. Right.
Dr. Mariana Castells:
Diarrhea with some other… So- so again the secret of, uh, making a good diagnosis is thinking about always like two organ systems.
Dr. Dean Mitchell:
I like that. And I’m gonna challenge you on something else too. Now this is kind of funny because I’ve been giving a lot of thought to this. My first day 30 years ago, so in the clinic [inaudible 00:21:15] hospital in New York, before they would let you do skin tests, they say look, check for dermatographia and for listeners that’s where we stroke the skin and we look to see if it hives up immediately.
Dr. Dean Mitchell:
Like, you know, the patients notice when they say by accident stroke their skin too hard with something and it weals up and I always say dermatographia, means I can write your name on your back. And I wanna ask you this but we were taught that dermatographia is in 5% of the general population. But as you published that’s in 90% of the patients that have this mast cell mastocytosis or mast cell activation which we’ll get to.
Dr. Dean Mitchell:
So do you think that’s actually also a good crude test to just get your, uh… ’cause I’ve been, you know, telling patients, like, you know to help confirm a long with Tryptase or even to think about ordering Tryptase level. What- what’s your thoughts on that?
Dr. Mariana Castells:
So dermatographism, yeah, like you said is like scratching the skin and being able to write your name there and it’s like creating what we call a real end flare and that is due to the release of histamine and some other potential leukotrienes and Patagonian there. And it’s much more often seen in patients with chronic [Phonetic 00:22:20] carrier and in other- other diseases.
Dr. Mariana Castells:
So a dermatographism that is very exacerbated. So it happens every single day, it happens all the time and that bothers the quality of life I think is a good sign that maybe and- and [crosstalk 00:22:35].
Dr. Dean Mitchell:
The mast cells are activated or excessive?
Dr. Mariana Castells:
All the time. And- and then associated with some flushing also.
Dr. Dean Mitchell:
Yeah.
Dr. Mariana Castells:
Like, uh, spontaneous flushing, not… ’cause dermatographia is like a physical part. You have to touch it. But then associated with flushing can be a telltale sign that there is more activation at the mast cells definitely.
Dr. Dean Mitchell:
Yeah. It’s interesting ’cause maybe [inaudible 00:22:54] a lot of the [inaudible 00:22:55] carrier symptoms especially the physical ones.
Dr. Mariana Castells:
Mm-hmm (affirmative).
Dr. Dean Mitchell:
These all might be mast cell related diseases. Uh, let me just say ’cause I wanna finish up on the mastocytosis ’cause they said it’s a very well described but rare condition. So you normally would look at a CM Tryptase level, you would then also [inaudible 00:23:08] the blood if that was elevated, would you look at what’s called the C Kit mutation in the blood?
Dr. Mariana Castells:
Right. So for somebody who has like symptoms of, you know, abdominal bloating, some diarrhea-
Dr. Dean Mitchell:
Mm-hmm (affirmative).
Dr. Mariana Castells:
… flushing, and then episodes of kinda feeling very dizzy and then almost losing it, like we call it syncope.
Dr. Dean Mitchell:
Right.
Dr. Mariana Castells:
Or anaphylaxes in that- in that person, we would actually look at the tryptase level and then we will do something that’s called a kit mutation and the kit mutation is the presence of the kit is also on the mast cells and is the cause of the mastocytosis. There’s a mutation and the telltale mutation is called the Dias David 816 Vs Vector. So it’s a specific mutation.
Dr. Mariana Castells:
And we can actually, without doing a bone marrow, we can have that mutation done.
Dr. Dean Mitchell:
That’s what I wanted to ask you because back in the day it seemed like they were referred to a hematologist for bone marrow. So now that could be done in the blood.
Dr. Mariana Castells:
In the- in the peripheral blood. And i- and if it’s positive, you know, then we can… I mean, we had a- we had a woman who, uh, was starting to react to allergy shots and then she was having the sync able opposites pretty severe. Eventually we stopped that and then she started to have abdominal bloating and then diarrhea and then she was losing it at home. Young woman and her tryptase was very mildly elevated because if you look at the WHO criteria, it has to be 20 but her tryptase was 12.
Dr. Mariana Castells:
So we said, you know, we did a peripheral blood mutation. It was positive.
Dr. Dean Mitchell:
Really? Oh, so you really went that extra step. Yeah.
Dr. Mariana Castells:
I went an extra step and then we did a bone marrow biopsy and she has systemic mastocytosis. And why- why is that so important? Because now she’s protected. Every time she goes to have surgery, she can have her antihistamine. She carries an epipen. And those mast cells that are, um, mutated react to specific and non-specific things.
Dr. Dean Mitchell:
Mm-hmm (affirmative).
Dr. Mariana Castells:
So again, people who have mastocytosis can also have, like, food allergies. They can also have environmental allergies.
Dr. Dean Mitchell:
Right, right. So they get lo- they get looked at. I had a patient that came to me who was getting repeated severe local reactions to allergy injections from another doctor ’cause I only do sublingual and I think she had an anaphylactic episode too and then finally really one… you know, she had switched doctors and one of the doctors before she got started said hey before we give you anymore shots. She was really smart, she said let’s get a tryptase level and sure enough it was elevated and, uh, I actually was able to treat her with sublingual.
Dr. Mariana Castells:
So I think let me- let me just [crosstalk 00:25:20].
Dr. Dean Mitchell:
Yeah, sure.
Dr. Mariana Castells:
The- the patient that I published in the New England, we published in the New England, uh, nobody had actually undressed that patient. So the telltale of mastocytosis is looking for what we call urticaria pig-mentosa.
Dr. Dean Mitchell:
Yeah.
Dr. Mariana Castells:
So when somebody has all those symptoms. Say you know, undress. So when he came to my office I said okay, undress yourself. I wanna see the whole body, your whole skin. He said to me but you are an allergist.
Dr. Dean Mitchell:
(Laughing).
Dr. Mariana Castells:
Undress for you-
Dr. Dean Mitchell:
You’re not a gynecologist or a urologist, okay.
Dr. Mariana Castells:
Uh, or a dermatologist, you know, or even a dermatologist. No, no, I said we need to. So that’s kind of the other thing you know, the- the drugs that are already helping with [inaudible 00:25:55] that don’t go away those are other telltale signs.
Dr. Dean Mitchell:
Well that’s also your European training and I wanna tell you why. It’s really funny ’cause I trained in Israel and they all used to tell me a very funny story because one of the doctors there in Israel was training at- at one of the Harvard hospitals, his fellowship and, uh, you know it was, uh, I guess it was back in the ’80s, whatever and you know all the technology was coming out and they sent him to go see a patient and he went there with a couple of the other fellows. Not the older doctor but the… you know, the… not the attendee but the fellows.
Dr. Dean Mitchell:
And he goes to the bedside and he’s putting his hand, you know, checking where the chest wall is and listening very carefully auscultation and the other American cardiology fellows are looking and like, “What are you doing?” And he goes, “We’re gonna do an eco in a few minutes, we don’t really need to do this,” you know?
Dr. Mariana Castells:
(Laughs).
Dr. Dean Mitchell:
And you- you really think how- how much has picked up by still physically examining the patient.
Dr. Mariana Castells:
How important? How important is that? How important? And I guess that this guy had been seen by nine doctors when I asked him to address and he had typh-
Dr. Dean Mitchell:
Oh, he had the lesions, yeah.
Dr. Mariana Castells:
Oh, yes. He had urticaria pig- mentosa limited to his upper thighs but you know, if you don’t take the pants down you don’t actually see that.
Dr. Dean Mitchell:
Yeah. That’s a good point (laughing).
Dr. Mariana Castells:
I have a quick plug also, you know for myocytolysis, men that react to haemolacria bee stings and then pass out, are very likely to have mastocytosis. So, this is something that- that we have discovered uh-
Dr. Dean Mitchell:
Mm-hmm (affirmative)
Dr. Mariana Castells:
Uh- a sub-class of mastocytosis so men of all ages who pass out after a bee sting, a wasp, that is potentially like 30% of them are going to have like what we call a [Phonetic 00:27:27] muscle disorder and systemic muscle cytosis. And, that’s very important because those events are almost you know [crosstalk 00:27:33].
Dr. Dean Mitchell:
Yeah, you know its interesting you said that too because again one- somebody also who trained me also said something very interesting like when I was an internal medicine resident in New york. And, our hospital was right near central park. And, at sometimes, you know in the summer, a pati- you would have a young patient come in and they were hypotensive.You know and there was obviously-
Dr. Mariana Castells:
Yeah.
Dr. Dean Mitchell:
[inadible 00:27:53] Something terrible was going on and of course everybody is getting ready to shock them, and, you know whatever. And, up came one of my very good attending said, “be very careful, look at the body very carefully check for any insect [crosstalk 00:28:06].” You know me, cause again like you know what kids [inaudible 00:28:08] working or stung in the park here in the middle of New York city, but there is a park there, and where there is a park there’s bees and wasps and everything. And, you don’t treat that right way you know obviously-
Dr. Mariana Castells:
Well and- and to- to ah- follow up on that, EpiPen [inaudible 00:28:25] that really is the important thing and from this you know if [inaudible 00:13;32] so people who have had those episodes, they really need to talk through their allergies to their primary care physician, to the pediatrician.
Dr. Mariana Castells:
Am I a candidate for carrying you know [inaudible 00;00:13:45] because what happens is when those events happen, the one in the central park we are not there, the doctors, we are not there the patient is by itself. They really need to be able-
Dr. Dean Mitchell:
100%.
Dr. Mariana Castells:
To be educated and then uh- instruct themselves and know what to expect from that so there [inaudible 00:28:59] a key critical I mean learning you know from mast cells and know how powerful they are and they can actually wipe out blood pressure in minutes. So somebody who is really really healthy can become you know almost like [crosstalk 00:29:12]
Dr. Dean Mitchell:
Right, here you take a perfectly healthy person who is now like an older person who has got heart failure.
Dr. Mariana Castells:
Exactly.
Dr. Dean Mitchell:
This is a young person in the prime of their life and all of a sudden they are tendering for survival.
Dr. Mariana Castells:
And I remember you know in Virginia the first time I was in the emergency room with Larry Schwartz, this guy comes, very chubby two coronaries and he had been stung by 20 bees. And, he is like chocking he is sweating.
Dr. Dean Mitchell:
Mh-hmm (affirmative)
Dr. Mariana Castells:
And we cannot incubate. And, somebody is like, “We cannot give an EpiPen to somebody who is cardiac” and I say, “we are going to give two EpiPen”.And we give and he had a little blip in his ST. That’s it but [crosstalk 00:29:46].
Dr. Dean Mitchell:
That’s a great point. You know it’s so interesting you say that to- I love when you bring up certain things you know one most disappointing things to me is that so often when I have seen patients after they you know when there is anew patient after they have been to the
Dr. Dean Mitchell:
… emergency room, so few are given epinephrine for allergic reactions.
Dr. Mariana Castells:
What? How?
Dr. Dean Mitchell:
I think they’re- I don’t know if the staff is nervous that they’ll- gonna get an arrhythmia… I mean even young patients, they- it’s always Benadryl, putting them on steroids, and I’m like, this person needed an Epi-pen yesterday, you know?
Dr. Mariana Castells:
Right, right. Yeah, right now. So I go to the emergency room when I was a fellow with Dr. [Shefferd 00:30:19], my other mentor, and I see somebody wheezing, covered in hives, and- and there’s a drip, like, with Benadryl and steroids. And I said, “How many epis-
Dr. Dean Mitchell:
Yeah.
Dr. Mariana Castells:
… have you given to this patient?” And they said, “Oh, epi? No, no, no.” And they have given a Benadryl and steroids. There’s no indication in anaphylaxis for Benadryl or steroids.
Dr. Dean Mitchell:
Just so- you probably know, [inaudible 00:30:38] anyway, so the epinephrin really stabilizes the mast cell from secreting more of the- these mediators that are so dangerous, you know.
Dr. Mariana Castells:
Totally, totally, totally.
Dr. Dean Mitchell:
Let me ask you too, when we finish up on mastocytosis, ’cause this is a- this a- an amazing lecture for me. Um, what do you do as far as treatment? You- do you target the organ? There’s no really definitive underlining like kinase inhibitors or something for this at this point. Or is there?
Dr. Mariana Castells:
No, no, no, there is- there is-
Dr. Dean Mitchell:
Oh there is? Okay.
Dr. Mariana Castells:
There is. Actually, we have really good-
Dr. Dean Mitchell:
Oh, is this new?
Dr. Mariana Castells:
… news. So the first-
Dr. Dean Mitchell:
I mean I remember, you know- okay. You-
Dr. Mariana Castells:
Yes. It’s fli- it’s new. So the first block is for the TMS, The Mastocytosis Society, and anybody who has mastocytosis so- should go on the website because, you know, I am on the board of medical, uh, uh, uh surveyors, and- and- and that’s- that is really a good place for filtering information, you know? Because you go and- and say, Dr. Google doesn’t help. You really need to have filtered information.
Dr. Dean Mitchell:
Yeah.
Dr. Mariana Castells:
So for people who have mastocytosis, I would like them to go to the TMS and to the Centers of Excellence. And so now, you know, starting, uh… We- there- there is one thing, you know, when I actually started to do mastocytosis doctorate, Austin told me, “You know, uh, they live 40 years. The life expectancy with y- indoline count-
Dr. Dean Mitchell:
Really?
Dr. Mariana Castells:
Uh, indoline systemic mastocytosis is a disease like rheumatoid arthritis, or even diabetes, or… uh, so you can live, you know, 40 years, 50 years with that.
Dr. Dean Mitchell:
Yeah.
Dr. Mariana Castells:
So treat the symptoms.” So I started to do that. And for 20 years I did that. But you know patient came- came back to me and said, Dr. [Kesel 00:31:59], you know, I really don’t go out too much of my house because I d- I never know when I’m gonna have diarrhea. And- and- and people were coming back to me and says, “You know, I passed out and I was not expected to pass out.”
Dr. Mariana Castells:
So we started to think about that, and I used something that’s called Omalizumab, anti-Ig-
Dr. Dean Mitchell:
Mm-hmm (affirmative).
Dr. Mariana Castells:
… for those patients. And we have already published that, and it really works. But in the last five years, I’ve been pushing abroad for companies that have what we call tyrosine kinase inhibitors. And for the first time in the last few years, we have clinical trials now with one of them, it’s a tyrosine kinase inhibitor, that blocks the kit, and that kit mutated. And- and that- that is a clinical trial that is now multi-center.
Dr. Dean Mitchell:
So it’s not available yet but it’s- it’s on it’s way.
Dr. Mariana Castells:
It is totally, and the patients who have mastocytosis can jump on those clinical trials. They- they are open. I have two clinical trials now at the Brigham, and they’re- there’s multi-center, there’s many, many other centers that do mastocytosis where the patients can jump into those clinical trials.
Dr. Dean Mitchell:
Mm-hmm (affirmative).
Dr. Mariana Castells:
And actually, you know, the clinical trials are so fabulous that the- it- they can actually even clear part of their skin legions.
Dr. Dean Mitchell:
Really? Wow.
Dr. Mariana Castells:
So- so we are actually working towards children, because on thing we haven’t talked about is that, you know, kids who have early keratin [mitosine 00:33:10] cutaneous mastocytosis, by puberty, most of the kids are cured.
Dr. Dean Mitchell:
Why do you think that is, anyway? Do you have any thoughts on that? Like why- why does that happen? I mean there’s very few things in life, I mean, that just kind of disappear.
Dr. Mariana Castells:
Well, it- it would be a- take a longer conversation, but the origin of the skin mast cells is different than the origin of the other mast cells, so there is two waves of mast cells. And so I… and the puberty, you know, the regulatory sites for those mast cells, uh, e- estrogen, progesterone, and testosterone. So you can actually eliminate the clone. So we’re working very actively on that.
Dr. Dean Mitchell:
That’s really fascinating, that’s great to know for- for people listening. Let’s move on to something- to the- I guess the- the cousin of mastocytosis, mast cell activation syndrome. Which, again, as I said, 10 years ago was so more- nobody had ever even heard of this. For quite a while, a lot of doctors said, “Oh, this is just another diagnosis made up by the functional medicine community, you know, to- to- you know, to kind of- kind of diagnosis that ever- the crazy patients, the ones that have brain fog, headaches, whatever… you know, kind that I see for a lot of different reasons who, you know, really suffering and have legitimate symptoms.
Dr. Dean Mitchell:
So how do you… I know you published on this a little, too, how do you go about assessing these patients and differentiating them from the mastocytosis like that hematologic disorder, and versus the people that are just- whether it- maybe don’t have this. So what is- what is your core things that you use?
Dr. Mariana Castells:
Right. So in 1991, they made- you know, or… I did not, but, uh, all the people who are doing mastocytosis in the world, from Peter Valant, Dean Metcalfe, Frank Austen, Lawrence Schwartz, everybody, met there, and they made the- what we call the WHO criteria, the World Health Organization criteria for mastocytosis. And they actually made a provision, and they said at that time, 1991, they said, “There might be patients who have symptoms of mastocytosis, and we can define them now, that do not have the mutation, and do not have a bone marrow that has a mast cell aggregate because that meets… And they don’t express what we call CD25, which is like the adhering mast cells. And those patients, in the future, will need to be studied.” And that was 1991.
Dr. Mariana Castells:
So at that time, the- we recognized as- as a community that there are patients who present with flushing, with itching, with abdominal bloating, with, uh, brain fog, uh, with, uh, wheezing, with syncopal episodes-
Dr. Dean Mitchell:
Man.
Dr. Mariana Castells:
… or pre- uh, who- who’s quality of life is not good, who might actually respond well somehow, and we can talk about what is the management of those patients. But when we look at their tryptase levels, their tryptase might not be elevated to 20, which is the cutoff, and when we look at their bone marrow biopsy, they may not have a mast cell aggregate. So they don’t conform to the, uh, WHO criteria.
Dr. Mariana Castells:
So that’s kind of backing that. Now, coming now towards here, uh, we have actually several things. One is that- what we call the- a non-clonal mast cell activation syndrome, is a collection of patients who present the symptoms that we just taught, in which we measure three things. We measure the urine mediators, so, like, uh, n methylhistamine and prostaglandins.
Dr. Dean Mitchell:
So let me ask you something about that, so but do- so you do find that to be helpful? The- the-
Dr. Mariana Castells:
Very helpful.
Dr. Dean Mitchell:
And that- that was that- that’s a 24 hour urine? You need, like, pans-
Dr. Mariana Castells:
Yes. And we- and- and the Mayo Clinic is actually doing now without the- the 24 hours. So in spot [crosstalk 00:36:24].
Dr. Dean Mitchell:
Really?
Dr. Mariana Castells:
Yes.
Dr. Dean Mitchell:
Wow.
Dr. Mariana Castells:
So we started-
Dr. Dean Mitchell:
Now, do they need to, let’s say, um, be off antihistamines, or any- it doesn’t really matter?
Dr. Mariana Castells:
They don’t- they don- it doesn’t matter because, you know, the antihistamines bind to the histamine receptor. It doesn’t bind to histamine.
Dr. Dean Mitchell:
Okay.
Dr. Mariana Castells:
They can continue to do that on antihistamines. Uh, and we measure those mediators in the urine, and then we measure the mediators in the [crosstalk 00:36:45].
Dr. Dean Mitchell:
Do you find that sometimes those are elevated where the tryptase is, like you said, somewhere still in- in- in a normal range? I mean…
Dr. Mariana Castells:
Normal range. Absolutely.
Dr. Dean Mitchell:
You do both of them? The PG… I’m sorry, the- was it the PGD2 and the n methyl-
Dr. Mariana Castells:
Yes.
Dr. Dean Mitchell:
Was it n methylhistam-
Dr. Mariana Castells:
N methylhistamine. So we measure those mediators in the urine, and we found them elevated. And more importantly, we actually allow them to measure that when they are not feeling well. So sometimes-
Dr. Dean Mitchell:
Mm-hmm (affirmative).
Dr. Mariana Castells:
… you know, the- the mast cell activation syndrome is a disease where, you know, there are good days and bad days. And so we actually ask, “Okay, when you have your bad day, just go ahead and then measure your mediators.”
Dr. Dean Mitchell:
Good point.
Dr. Mariana Castells:
And I have had patients, you know, who I have carried for about a year. And at the beginning, I could find that baseline, everything is normal, and when they have-
Dr. Dean Mitchell:
Yeah.
Dr. Mariana Castells:
… their bad days, like six [inaudible 00:37:28] after that, we have been able to measure, and it’s been elevated. And why is that so important? Because then we can do targeted therapy.
Dr. Dean Mitchell:
That’s what I wanted t- yeah. That was what- that was what I wanted to get to next. You know, before we get to [inaudible 00:37:39] there… I just want to clarify one other thing, too, for the listeners and… So, uh, again, clinically to make the diagnose- and again, when I was looking at one of your papers which I thought was really excellent to explain… it’s like, so about 90% of these patients have abdominal pain, which, again, as I said, w- might get overlooked. They would be looking for other GI issues like small bacterial overgrowth, or you know gastritis, things like that.
Dr. Dean Mitchell:
90% of them, you’ve mentioned, had dermatographia, you know, where they stroke the skin, or some type of flushing. And this I found very interesting, too. 72%, again and you surveyed, had medication reactions. So that’s-
Dr. Mariana Castells:
Yeah.
Dr. Dean Mitchell:
… like another alert. Now, when you have people… penicillin, when it starts telling you two or three medications, that should set off the light bulb, something’s going on here.
Dr. Mariana Castells:
And there is a confounding factor. If you look at that paper, I think it’s the Hamilton paper. Uh, the, uh, this paper, uh, says, that, uh, you know, over 80% of those patients are females.
Dr. Dean Mitchell:
Yes. Yeah, I hate that rate. Yeah.
Dr. Mariana Castells:
And that- and that is- and- and that… No, no. That’s a very interesting thing. And then also because- because there is also in the drug allergy, which is my second field of expertise, we also find that there is more females than males. So- so again, why is that… Is it females because they’re exposed to, you know, ups and downs-
Dr. Dean Mitchell:
In the hormones?
Dr. Mariana Castells:
… in- in hormones? They’re recognized non-fr- from non-self in a different way… So there’s a lot of i- interesting things now, and the NIH is very interesting in studying, you know, personalizing that to the females. And- and- and underst- further understanding inflam- what you call the inflammasome. Are we more inflamed because we go up and down, up and down-
Dr. Dean Mitchell:
Yeah.
Dr. Mariana Castells:
… all the time?
Dr. Dean Mitchell:
But a shout out to women, though, you know, the one- the one thing I do say- I always say they’re the, uh… you know, and my- my patients laugh, I always say they’re the stronger sex because of course when they give childbirth… But it- obviously COVID’s proving that, too. Women are definitely doing better than men. (Laughs) you know what I mean?
Dr. Mariana Castells:
Yeah, for- for something as- for some things it- it would work-
Dr. Dean Mitchell:
Yeah.
Dr. Mariana Castells:
… for some other things, it doesn’t, you know? There is a lot more woman who has drug allergies, and there’s a lot more woman who have this mast cell activation, you know, syndrome.
Dr. Dean Mitchell:
Let me ask you one other thing, too, just be- before we get into how to treat this because I know the- again, a lot of listeners really want this. But a- again, something I think I started to learn the last year, too, was that sometimes also when you have this borderline elevated tryptase level you may actually have this genetic condition called alpha-
Dr. Mariana Castells:
Exactly.
Dr. Dean Mitchell:
… hereditary tryptasemia, which is actually a lot more common than than we thought.
Dr. Mariana Castells:
Than we thought. It’s called Hereditary alpha tryptasemia, HAT for short. So this is- this was discovered by, uh, Dr. Joshua Miller-
Dr. Dean Mitchell:
Yeah. He’s NIH. Yeah.
Dr. Mariana Castells:
… and- and Jonathan Lyons at the NIH in 2016. It was published very, uh, prominently in nature genetics, and they found that people who presented, uh, you know, with symptoms, uh, of flushing, of-
Dr. Dean Mitchell:
Mm-hmm (affirmative).
Dr. Mariana Castells:
… itching, and… But they also had other symptoms like puss-like symptoms, maybe, uh, [inaudible 00:40:10] symptoms, they had duplication or triplication of the TPSAB1, uh, which is the tryptase-s genetic marker. They also sampled the general, uh, public, and they saw that this- the mutation is very common.
Dr. Dean Mitchell:
Mm-hmm (affirmative).
Dr. Mariana Castells:
So, uh, 4% to 6%, and that’s been replicated in- in the UK, and some other studies. Have it but they don’t have any symptoms. So having it, you know, having it is not sufficient. So the majority of the people who have it don’t have symptoms, so we need kind of a two hit thing.
Dr. Dean Mitchell:
There was a paper that said, though, the reason they like to check for that. Let’s say somebody has a borderline elevated tryptase level before going to a bone marrow. But you’re saying you don’t have to do a bone marrow anyway now? You could do the C- you could do it thought the blood? So could we avoid that?
Dr. Mariana Castells:
Yeah.
Dr. Dean Mitchell:
I mean I- you know, patients don’t look forward to the bone marrow. (Laughs)
Dr. Mariana Castells:
Exactly. So if we have somebody who has, like, a tryptase between 11.4, which is a [inaudible 00:40:59] and 20, which is the- kind of the mastocytosis, in- in all that gray area, we do- we do the KIT mutation-
Dr. Dean Mitchell:
Yeah.
Dr. Mariana Castells:
… the one that I mentioned.
Dr. Dean Mitchell:
Mm-hmm (affirmative).
Dr. Mariana Castells:
To rule out mastocytosis. And then we do the gene- something that’s called, “Gene by Gene.” So genotyping for hereditary alpha-tryptasemia.
Dr. Dean Mitchell:
Okay.
Dr. Mariana Castells:
So the HAT. And we do those two tests. And- and the- those two tests can be done by swabbing the cheek. So we don’t really need to do a blood test.
Dr. Dean Mitchell:
For which one? For the g- oh, for the genetic one?
Dr. Mariana Castells:
For the HAT.
Dr. Dean Mitchell:
Interesting, interesting. Does that- does that go to a che- to, like, a… There was a lab that did it.
Dr. Mariana Castells:
Called Gene by Gene.
Dr. Dean Mitchell:
Oh, Gene by Gene.
Dr. Mariana Castells:
Yes. And I don’t have stakes on the lab, so (Laughs).
Dr. Dean Mitchell:
Nice.
Dr. Mariana Castells:
I’m not doing a plug for them.
Dr. Dean Mitchell:
No, it’s great to know.
Dr. Mariana Castells:
But- but it’s the only on that we have.
Dr. Dean Mitchell:
No, I- I love d- I love doing when the- obviously, when it has to come up with celiac and I think it’s obviously that- that is an area where genetic testing is gonna be awesome. Let me ask you- w- and then w- because there’s another area I want to go onto, but… So, in treating these patients, uh, uh, I’m gonna- I’m gonna do, like, a little bit of a shot gun thing. Gastrocrom. Uh, d- Cromy- sodium cromolyn-
Dr. Mariana Castells:
Yes.
Dr. Dean Mitchell:
… you know, which is, again, hard to get sometimes, you know, it’s a liquid, you gotta drink it. You find it effective. Is it good for GI symptoms with th- mast cell activation, you know, and- or even-
Dr. Mariana Castells:
W- and so we start from the beginning. We do H1, H2. H1 H2 antihistamines are kind of the first line. The second line would be a leukotriene blockade. Something like-
Dr. Dean Mitchell:
Okay.
Dr. Mariana Castells:
… montelukasts, Accolate, zileuton. The third thing would be prostaglandin blockade also-
Dr. Dean Mitchell:
Really?
Dr. Mariana Castells:
… and we use aspirin for that.
Dr. Dean Mitchell:
Oh wow.
Dr. Mariana Castells:
So those are the three. So we kind of target their- their mast cell mediators from the histamine to the leukotriene to the prostaglandins. And then we use what we call mast cell stabilizers which would be, uh, sodium cromolyn, and then Ketotifen, which is like a- a mast cell stabilizer and an antihistamine. So those two are extremely helpful.
Dr. Mariana Castells:
And- and the sodium cromolyn, you know, can be used from 100 milligrams daily, to 800 milligrams daily. So it’s, like, two vials four times a day, or one vial once a day.
Dr. Dean Mitchell:
When would you use that? Would you use it if they’re having a lot of GI or- or just in general?
Dr. Mariana Castells:
Uh, so that’s a really good questions. So the, uh, yeah, the sodium cromolyn has shown, you know, in questionnaires, to actually help with gastrointestinal symptoms, with skin symptoms-
Dr. Dean Mitchell:
Really?
Dr. Mariana Castells:
… and with brain symptoms.
Dr. Dean Mitchell:
So it does help with the skin?
Dr. Mariana Castells:
So it does skin and then brain symptoms. So it stabilizes the mast cell across-
Dr. Dean Mitchell:
And would they need to do this before meals? I mean, it’s impor- so it doesn’t get… Yeah. Mm-hmm (affirmative).
Dr. Mariana Castells:
Yes. Yes. 15 minutes. For better absorption. Not- not for anything else.
Dr. Dean Mitchell:
Right.
Dr. Mariana Castells:
Just for better absorption. And then- and then we go, uh, mast cell stabilizer, and then- and then for people who do have, like, what was an anaphylactic event, we have been starting to use, uh, as chronic idiopathic urticaria, the Omalizumab, the anti-IgE.
Dr. Dean Mitchell:
Mm-hmm (affirmative).
Dr. Mariana Castells:
The- the Xolair thing. So… And we have a paper by Dr. Giannetti, my associate in the Mastocytosis Center, the co-director now, uh, where it’s been extremely helpful. So it has stabilized, you know, most of the people, uh, without-
Dr. Dean Mitchell:
What do you think about dissen- the classic desensitization? I do a lot of sublingual, which I found to be very mo- it works very smoothly. We don’t get anaphylactic reactions, I’ve done this for over 30 years. And actually I’m doing it with the foods now, which I’m really excited about.
Dr. Mariana Castells:
Yeah.
Dr. Dean Mitchell:
I’m sure you- because you know-
Dr. Mariana Castells:
Yeah, that works.
Dr. Dean Mitchell:
… Edward Kim, you know, a- a friend of mine, a colleague, you know, has done a lot of great work with peanut. But- so what do you think about desensitization as a… And obviously that’s your center, but… As a way of stabilizing the mast cell? Would that be… Let’s say… because someone says, “Oh, I’m terrible in the spring.” Or, you know, there is some foods that are causing-
Dr. Mariana Castells:
Oh, definitely.
Dr. Dean Mitchell:
… So you- it could hopefully shift that immune response to a more stabilized-
Dr. Mariana Castells:
Right. So we actually would, uh, like to, uh, stabilize all the patients through their Ig reactions. So if somebody has a food allergy, we say either you don’t eat it, or you get desensitized. If they have allergies, which 20% of the patients with mastocytosis will have allergies like in the general population. We said, uh, you know, allergy, uh, treatment, immunotherapy, vaccinations, whatever sort of that. And that tremendously helped stabilize the mast cell. So that- that is very helpful.
Dr. Dean Mitchell:
Okay. I’m gonna ask you about a little bit of holistic stuff, too, here, because the patients like to ask, and I find it interesting. They say vitamin C, they say quercetin, do- do you find, uh, there’s any merit to some of those? Helping to stabilize the mast cells?
Dr. Mariana Castells:
Uh, so, what I say is like one size doesn’t fit all. So, uh, because we- we cannot know-
Dr. Dean Mitchell:
It can’t hurt.
Dr. Mariana Castells:
… uh, f-
Dr. Mariana Castells:
… uh, it cannot hurt, but because we don’t know our genetics, you know, we, we don’t really know our receptors. So, I always say, somebody comes and says, “I, I would like to try [inaudible 00:45:08].” I say, “Just try it for three months.” So, don’t do it for longer-
Dr. Dean Mitchell:
Right.
Dr. Mariana Castells:
… if it doesn’t help but, but trying doesn’t hurt.
Dr. Dean Mitchell:
Yeah.
Dr. Mariana Castells:
Uh, and I totally agree with, we know less than we would like to know in terms of the patient’s genetics.
Dr. Dean Mitchell:
You wanna know one of the little secret, which you probably know, but I, I find this fascinating, ’cause I learned this many years ago from an allergist, that was very unusual, in Buffalo, Doris Rapp. Back in the day, she used to treat food allergy patients with, um, essentially sodium bicarbonate, okay? And, uh, she called Alka-Seltzer Gold because it didn’t have Aspirin in it. So, I, you know, I remember I, I actually went up to visit her myself once with my wife to, she was a physician, to see what she was doing in allergy. It, it was just fascinating, you know?
Dr. Dean Mitchell:
And then, I saw a paper from Japan, again, maybe about 20 years ago, this was really interesting. There was a patient that had exercise, wheat induced exercise anaphylaxis, you know, if he ate wheat he was okay, but if he ate wheat and then he went, you know, the exercise-
Dr. Mariana Castells:
Yep.
Dr. Dean Mitchell:
… he went into anaphylaxis. You’re familiar with that, you know Dr. uh, who is it? It was the ex-
Dr. Mariana Castells:
Sheffer.
Dr. Dean Mitchell:
Sheffer. He’s the expert on that. But anyway, in the study in Japan, there was a case study they g- I don’t know why they thought of doing this, they gave him a very high load of sodium bicarbonate. I think like two grams or something, and he didn’t develop any symp- you know, pro- prophylactically, and beforehand-
Dr. Mariana Castells:
Uh-huh (affirmative).
Dr. Dean Mitchell:
… he didn’t develop any symptoms. So, I started thinking about what Dr. Rapp said, and then this. What I was recommending for a long time to patients, especially the ones that had food allergies, like, they, they would go to a wedding, a bar mitzvah or someplace where they didn’t know where the, what was gonna be in the food. I said, you know, “Take two sodium bicarbonate before.”
Dr. Mariana Castells:
Yeah.
Dr. Dean Mitchell:
And, as you know, it changes the PH, which again, it’s chemistry. It affects the mast cell releases. And then, recently I saw a paper where on the Parizol, does some- something also as proton hump, pump inhibitors, somehow affect the mast cell. So, what do you think about that? I don’t know if you’ve tried or either you think it’s interesting [inaudible 00:46:53]?
Dr. Mariana Castells:
No, you know, in terms of what I, I’ve been fascinated by the, um, the food trigger exercising induced anaphylaxis and we’ve published with Dr. Sheffer, so you could actually sit in a chair, watch TV and eat wheat but if you actually eat wheat and then go run then, then you have your anaphylactic event. And, essentially is, is also the, the two hit. So, the antigen per se is not sufficient, you need to change something in the body.
Dr. Dean Mitchell:
Yeah.
Dr. Mariana Castells:
And, that, and it had been said that, you know, the, uh, TTA, transglutaminase was the enzyme that needed to be changed, and you, and people release that enzyme during exercise, and that’s why it changes the acratopes. But, the PH also does the same thing. So, if you change that in one way or another, the absorption of the allergens is different, and the acratopes or the pieces that are allergenic, do change. So again, I don’t do that myself, but I think there’s a lot of research that needs go into that because it’s really important.
Dr. Dean Mitchell:
It’s easy to do. I, I’ve even, and, like, Dr. Rapp used to recommend, even while patients were having a reaction. I mean, obviously if you need epinephrine you’re gonna, you have to use that but it’s just so fascinating to get it another way. And we, again, we started to realize, and I’m actually hopefully gonna to talk to Dr. Fasano again in a few weeks, we, he has a new book coming out called Gut Feelings, I mean, just how important the gut is to the whole immune system.
Dr. Mariana Castells:
Absolutely. But, the thi- the good thing, the good thing about that, uh, the, the things that we need is controlled studies. We really need to do that-
Dr. Dean Mitchell:
Sure.
Dr. Mariana Castells:
… in a way that we know that it’s, it’s just not, you know, a placebo effect that it’s really, because people, I mean, and, and myself included, we think, “Oh, okay, this is gonna help me.” And, it really, you know, placebo effect can be up to 30%, so we need controlled studies and that would be really important.
Dr. Dean Mitchell:
I know your time is so valuable, I think I’m gonna finish up on one last little area, which is not such a little area, and it’s vaccine allergy. It’s not something we’ve thought about a lot before and I also have a paper that you just published with Dr. Phillips about maintaining safety with SARS-CoV-2. Now, I fortunately had my second shot, thank god I did fine but I don’t really have allergies, but it is scary, you know. Uh, ’cause you mentioned in the paper, obviously we’re having this mass inoculations going on now, and, and typically an allergic reaction to a vaccine is one in a million, so not too high. You know, reports now from the new Moderna and Pfizer vaccines, I believe, is about 11 cases per million which is considerably high, it’s 10 times higher.
Dr. Mariana Castells:
So, so, essentially I agree with you that this is kinda new, I mean, th- th- there’s this new vaccine. I had my Moderna vaccine, second shot, like, two weeks ago. I just felt under the weather for a couple days.
Dr. Dean Mitchell:
Yeah, oh yeah. You, you feel awful. Yeah, just to warn everybody, but it, but it gets better the next day, you know? (laughs) But, it’s awful.
Dr. Mariana Castells:
Ex- Exactly, and it’s, it’s better. We looked at, uh, you know, all the Moderna and Pfizer anaphylactic events. So, essentially it, it, it is approximately one to two over 100,000, which is higher than other vaccines.
Dr. Dean Mitchell:
Right.
Dr. Mariana Castells:
But, i- i- but essentially, everybody who has had a hypersensitivity or an anaphylactic reaction, with one or two EpiPens, they have been out of the woods completely and very quickly and fast.
Dr. Dean Mitchell:
That’s good.
Dr. Mariana Castells:
So, the treatment- yeah. And, we’re worried about that.
Dr. Dean Mitchell:
You know, but you know what’s scar- but I will say this is what’s scary, ’cause I don’t know where, y- you probably got your vaccine at the hospital I assume, you know, I actually had to go, the second place was, uh, at like a, the, the raceway track here in Long Island. They, and it was really, it was like being in line at a concert, you know? (laughs) You’re just winding through. And, all I remember kept saying to myself, first of all, I brought along my own EpiPens, really probably not so much for myself, but if s- you know, being the allergist on call in case somebody else needed it there, uh, it’s a little worrisome. I mean, there’s this mass thing going on and god forbid there are one or two people going down-
Dr. Mariana Castells:
Right.
Dr. Dean Mitchell:
… uh, uh, it’s-
Dr. Mariana Castells:
And so, and so, we have, we have made some recommendations for people who actually had severe food allergies, uh, drug allergies, who actually carry an EpiPen, we recommend that they actually carry their un- unexpired EpiPen to the site.
Dr. Dean Mitchell:
Absolutely.
Dr. Mariana Castells:
And then, they are monitored for 30 minutes instead of 15 minutes. And then, the real allergic people, we ask them to get, you know, an antihistamine, you know, their favorite antihistamine 15 minutes before-
Dr. Dean Mitchell:
Oh, Okay.
Dr. Mariana Castells:
… 30 minutes, so for really severely allergic people, you know, people who have reacted to foods. And then, and the, the other thing that’s really important is that the polyethylene glycol and the polysorbate-
Dr. Dean Mitchell:
You know, back in, in, back in the day and, uh, was it Dr. Kelso out in San Diego was always, you know-
Dr. Mariana Castells:
Yes.
Dr. Dean Mitchell:
… he was, like, a big expert on this but, you know, they, okay, so we’re looking at the inactive ingredients, but do you think it’s the inactive ingredients, or again, is it sort of this mast cell compliment mediate, something else, mechanism, you know? Especially when it’s on the first dose.
Dr. Mariana Castells:
Right.
Dr. Dean Mitchell:
‘Cause it looks like it’s on the first dose with some of these patients.
Dr. Mariana Castells:
Right. And, most of the patients have never been exposed to, you know, something like a polyethylene glycol or, uh, but there are actually also other patients who have actually been exposed to like MiraLAX, you know-
Dr. Dean Mitchell:
Yeah.
Dr. Mariana Castells:
… has polyethylene glycol. And, a lot of people have been exposed to MiraLAX that have not reacted to the vaccines. So, again, we really don’t know how the vaccine induce those reactions, and the NIH is actually promoting a study to understand the mechanisms of those reactions. My take on that is that, people, like you said, who have EpiPens, need to bring their there, need to be monitored for a little bit longer, and they need to take, you know, their antihistamine, their favorite antihistamine 30 minutes. And, and then, and then, the benefits of being vaccinated versus not being vaccinated are tremendous. I mean-
Dr. Dean Mitchell:
But, would you say to a person that’s had a god forbid an anaphylactic reaction to the first one, that to not get the second one, I mean, at this point?
Dr. Mariana Castells:
Uh, f- if they had a, a true anaphylactic reaction, like I said, with a tryptase elevation, then potentially waiting for the second wave of vaccines, which will not contain the polyethylene glycol we can contain. But, but, we have a, a really, really minu- minuscule amount of those people-
Dr. Dean Mitchell:
Yeah.
Dr. Mariana Castells:
… you know, it’s like a, a handful, maybe 10 people for Moderna or 12 for Pfizer, that have truly an anaphylactin on that. So, definitely, uh, if they have an anaphylaxe we, kinda, wait for the next wave. Now, the, the good news is that, uh, we have been following some of those with antibodies. So, you know, Duane Wesemann-
Dr. Dean Mitchell:
Right, right.
Dr. Mariana Castells:
… a, a, a res- a B cell researcher and they have found that with the Moderna, for example, I have a, a patient of mine is the first guy who anaphylaxed on Moderna here at the BMD, uh, BMC in Boston. And, uh, he has really strong antibody titers to the spike protein.
Dr. Dean Mitchell:
Wow.
Dr. Mariana Castells:
Uh, and, and, and so, so, again, with one dose, might actually be, be sufficient.
Dr. Dean Mitchell:
Yeah, that, that, that is right, that is the promising thing, obviously, so. Wow, we have covered so much, I have learned a ton. I hope our listeners appreciate, I’ve been telling my patients for weeks now, that I was getting the chance to interview you and, uh, I’m just so glad this came up. So, Dr. Castells, I wanted to thank you so much for taking the time out of your busy schedule, to teach us all about mast cells and why they’re so important.
Dr. Mariana Castells:
Thank you so much. No, I wanted to finish on a, kinda, a, an interesting note from my research. So, the, the reason I got interested in desensitizing people, so my other life is to take people who have had an anaphylactic reaction, [inaudible 00:53:29] to them, you gonna be able to use that medication. And, the reason I, we say that, is because they have cancer and they want a chemotherapy-
Dr. Dean Mitchell:
Right.
Dr. Mariana Castells:
… that’s th- what we call The First Line Therapy, so we desensitize about 900 cases per year at the Dana-Farber now in the desensitization, uh, center, that I have created, and now the next generations, they are actually coming to do that. And, my dream is that every center, that cancer center, will have, you know, an allergist or two, that would do desensitization for those people. But then, people also who have chronic inflammatory diseases, that have a monoclonal or something that really helps them, w- we also want that quality of life, and that’s what we really want.
Dr. Mariana Castells:
And, and, the reason I got so interested and I thought this, this was not like a, a, kinda, a, a moment of, “Okay, we can do this and not based on-” it’s because when I was a [inaudible 00:54:16] with Dr. Austin, I discovered that mast cells have inhibitor receptors. So, essentially, mast cells are cells that are ready to explode, to give, you know-
Dr. Dean Mitchell:
Hmm, Hmm. (affirmative)
Dr. Mariana Castells:
… true case histamine rece- but they actually have inhibitor receptors that will walk them into the mode where they don’t react. And, all the desensitization protocols that we have been able to produce, are such that will lock the mast cells into an inhibitory mode. And, I would like, you know, all the, you know, the people who actually listen to that, you know, the modern allergies and, and all the, the new, uh, cani- emil- clinical ML, sh- should think about inhibitory mechanisms a little bit like the immunotherapy for cancer, you know. You, kinda, awaken cells that are dormant, like the T cells that can now attack the cancer, this is the other way around. The mast cells are ready to attack, we shut them down.
Dr. Dean Mitchell:
Yeah. I am so glad you brought that up. I actually had this on my list, I just didn’t know if we were gonna have time but I think it is so important. There are people that are truly suffering, that need help, you know, with certain medications and they have these, you know, apparent allergic reactions. You are really one of the only people I know in the country, that has such a center and, you know, sometimes I’m lucky I’m in New York, they can go up to see you, uh, I’ve referred people. And, yeah, it would be, it would be tremendous, especially in New York and other cities. You know, unfortunately, we know what’s going in allergy, with the fellowships, kind of, shrinking and the whole field really in flux, I think it’s such an important expertise. I hope you’ll do a course, maybe I’ll come up and do some training with you and, uh-
Dr. Mariana Castells:
(laughs)
Dr. Dean Mitchell:
… and other people in New York because this does come and it’s very frustrating for patients. But, yes, your center is really world class, no question.
Dr. Mariana Castells:
Well, you know, as allergists and clinical immunologists, we can reach to all the other specialists.
Dr. Dean Mitchell:
That’s right.
Dr. Mariana Castells:
And, and that’s what I think is really important, that a, a multidisciplinary approach. In medicine, we h- we have the tendency to have silos but my tendency’s the other way around, maybe, you know, because I, I was brought in a place where you, you speak different languages but you actually have to communicate.
Dr. Dean Mitchell:
Yeah.
Dr. Mariana Castells:
And, and for me, that’s what, the only thing that works.
Dr. Dean Mitchell:
That’s beautiful, you know, and I’ll, I’ll end with a really funny story too. The, the head of my fellowship program, Dr. Greco, he was actually very well known because he was a head AIDS researcher, he was pulmonar- he’s board certified in four different specialties, but he used to sit there sometimes and, like, moan a little bit, he goes, “You know, the problem with our specialty in allergies is, we don’t have an organ, you know what I mean? It’s, like, you know, you’re a pulmonologist, you have the lung, you know. You’re a cardiologist-” And, I remember him saying to him, “Yeah, that’s not good.”
Dr. Dean Mitchell:
But then, you know, over the years, to me, like you being a detective, that’s what I love about our specialty. I’m not held to any one organ, we, you know, we have to deal with this whole body and be really good detectives, and help our patients.
Dr. Mariana Castells:
I was gonna say, we don’t have an organ, we have the language.
Dr. Dean Mitchell:
Yes.
Dr. Mariana Castells:
We have the language-
Dr. Dean Mitchell:
Yes, that’s most important.
Dr. Mariana Castells:
… to communicate. And, that’s the most important thing, we can actually teach every one of the specialties, your reactions to the medications are not-
Dr. Dean Mitchell:
Right.
Dr. Mariana Castells:
… toxic, you’re actually, those are immune reactions, the patient can go back to the medication. That was my first teaching to oncologists. Oncologists, you know, don’t even look at allergies, until now, and now they look at it as, is, like, “Oh, my gosh. This is not a toxic effect of chemotherapy.” “No, this is an immunological effect, it’s likely IGE, the patient can go back, the patient can be desensitized.” So, we have a universal language and I think that’s, uh, really, really important for the next generations. We have a specialty that is thriving and should thrive because we can help everybody, starting from the patients.
Dr. Dean Mitchell:
Well, you’re an amazing role model and, uh, inspire all of us, you know, as, uh, allergy doctors. So, again, thank you so much for your time.
Dr. Mariana Castells:
Thank you, Dr. Mitchell, that was a pleasure to have you and be able to, you know, to talk a little bit about, you know, the passions that I have in life, you know, from many, many years. Thank you, thank you so much.
Dr. Dean Mitchell:
My pleasure, my pleasure. Thank you so much.
Dr. Mariana Castells:
Bye bye.
About the Author – Dr. Dean Mitchell, M.D.
Dr. Dean Mitchell M.D. is a Board-Certified and Immunologist based out of NYC. He graduated from the Sackler School of Medicine and completed training at the Robert Cooke Allergy Institute in New York City. He is also a Professor of Clinical Immunology at Touro College of Osteopathic Medicine, a fellow of the American Academy of Allergy, Asthma and Immunology, and the author of Allergy and Asthma Solution: The Ultimate Program for Reversing Your Symptoms One Drop at a Time. Dr. Dean Mitchell, M.D. has also been featured in The New York Times, The Huffington Post, Fitness Magazine, Dr. Oz, and News NY 1. Dr. Mitchell also hosts the podcast The Smartest Doctor in the Room – a combination of a lively, personal, and in-depth interview with top healthcare specialists.