Unmasking MCAS, The Gut-Brain Connection and Its Impact on Sjogren's
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Speaker: Hi everyone and welcome to the Becoming Immune Confident podcast. I'm your host, Dr. Kara Wada, and today we're diving deep into a session from the
2024 Virtual Sjogren's Summit that took place this past July, we're going to talk all about Mast Cell Activation Syndrome, also known as MCAS,
and its potential impact and role for those of us living with Sjogren's.
This topic is close to my heart as both an allergist-immunologist and someone who lives with Sjogren's, and on occasion has had her own mast cells go rogue. While the research on the direct link between mast cell disorders and Sjogren's is still in its early stages, I've observed intriguing connections in my own clinical practice.
In this episode, we'll explore what mast cells are, how they can misbehave, and the possible overlaps between mast cell activation syndrome and Sjogren's. Get ready to unmask the mysteries of MCAS and gain a deeper understanding of how it might be playing a role in your Sjogren's journey. Let's get started.
Introduction to Mast Cell Activation and Sjogren's
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Kara Wada, MD: Hello, hello, and welcome back to this session: Unmasking MCAS, The Gut-Brain Connection and its Impact on Sjogren's. Hi, it's Dr. Kara again. And when Cristina brought this idea to my attention talking about mast cell activation and Sjogren's, I had to sit and pause for a second, in part because, you know, one of my suspicions, clinically, when I'm seeing patients in the office is, is really seeing and thinking about these two entities in the same circles of people.
But when I went to do a literature, like do some research, has anyone actually studied a connection between Sjogren's and mast cell issues that research hasn't really been done yet? So I was a little hesitant, but I think I'm going to really help tell the story about what mast cells are, what is mast cell activation, what could be this connection between MCAS or Mast Cell Activation and Sjogren's, and how I'm thinking about things in my clinical role as an allergy immunology physician.
Understanding Mast Cells
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Kara Wada, MD: So when we think about this condition, we have to talk about first and foremost, what's a mast cell? So again, I'm going to share my screen. We're going to pull up, some slides for the visual.
let's dig in. So what is a mast cell? Why should we care about these cells? How do they misbehave? And what can we do about it? Let's hop in.
So a mast cell is an immune system cell. It's a white blood cell. And we lovingly refer to these cells as quote unquote "allergy cells". But the reality is that these cells actually developed 500 million years ago. That predates all of humanity, right?
So these white blood cells are actually found not only in humans, but also in frogs and lizards and even some animals that don't even have a backbone. So they are really old type of immune system cell. They are known and somewhat unique in their ability to express a certain type of protein called IgE antibody protein, along with another type of closely related white blood cell called basophils.
These are essentially the blood version of mast cells, and we'll, I'll explain a little bit more. But mast cells are found primarily in our connective tissue and the lining of our body, of our epithelial type lining. So, um, you know, kind of in that space under the epithelium of our airways, our gut, and our skin.
Kara Wada, MD: And really their role over all of humanity has been to primarily protect us from parasite infections. Parasites, you know, when we think of the typical parasite, nice little case study, is an intestinal worm. I mean, thank goodness we don't really deal with those. Despite what TikTok says, we don't really deal with those in modern society, but we still have the machinery to help us, you know, have a fair fight against those infections.
So when we think about these mast cells and where do they come from? So when we think about types of white blood cells, all white blood cells start from what's called a stem cell. And then that stem cell has the ability to become any type of white blood cell. Um, but you know, it can kind of take two paths, one of two paths.
It can become what's called a lymphoid cell or a lymphocyte type cell, which include our natural killers, our T cells, our B cells and our plasma cells. These are primarily the T & B, and plasma cells are the part of our immune system that help us create memory. Memory to the things that we've fought off, so we're not reinventing the wheel every time we get sick.
When we go down this other path, the myeloid side, those include our platelets, our red blood cells, mast cells, which we're going to talk about, and some other cells that don't necessarily have memory, but also can evolve in their ability to sense safe, not safe over time. So basophils, neutrophils, eosinophils, and then monocytes, which also become macrophages and microglial cells, which are really under a lot of intense research and discussion for their role in neuroinflammation.
So, you know, big area of interest for those of us with Sjogren's knowing that that can cause, um, issues with small fiber neuropathy, right, and brain fog and, um, these sorts of things. All right.
Mast Cells and Allergic Reactions
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Kara Wada, MD: So when we think about mast cells, why are they called allergy cells? Well, when we think about what types of symptoms we experience in modern life, when these cells become activated or they get turned on, we develop symptoms that we understand as signs and symptoms of an allergic reaction: itchy, watery eyes, runny nose, coughing, wheezing, hives, abdominal cramps, diarrhea, nausea, vomiting, itching, flushing, passing out, high blood pressure. Some other symptoms that can occur that we don't talk as much about, fatigue, malaise, just feeling icky, weight loss, aches, pains can also be a part of it as well.
So we go back to thinking about these mast cells and their purpose. Tiny itty bitty little white blood cells and this big bad intestinal worm. It's like David and Goliath. These cells are not able to act like Pac Man and gobble up a worm like a typical white blood cell would do with a bacteria.
Because the white blood cell is bigger than the bacteria, right? Instead, these cells have pre formed packets of these granules, that if they are released, they are what are responsible for the development of these symptoms. And it's through those symptoms and the, you know, the release of those, uh, different chemical mediators, that our body would have fought off those parasite type infections. So if you think about if you have an intestinal worm and your body causes you to have intense cramping and diarrhea, that might do a pretty good job to help you pass those worms, right? Or if you had something under your skin and it triggered itching and swelling and you start scratching, that you may then scratch out whatever was there.
So you kind of have a better idea of how these cells evolved and how, you know, through evolution that these, you know, would have been protective, in the right scenario. Now, a little less helpful. So, um, we have a little bit of a busy slide, but this is just a slide that is saying there are a couple of types of mast cells, and the mast cells that are in our gut versus the ones in our skin have different types of these chemical mediators and different types of, you know, packets, different types of receptors that can turn on the ability to release these packets of, um, of essentially information chemicals that turn on other types of inflammation and they can behave differently. I want you also just to take note about how different these types of receptors are.
So there's, you know, different kind of cartoons of, um, essentially what would be like a lock and key on the surface of these cells. They have fancy names like TLR, and Integrin, and P2X7, and MRGPRX2, LCAM, some funky names, right? But on the surface as well, if you are someone who is an allergic person, your body can express allergic antibody protein.
So these IgE antibodies would also be on the surface of these cells as another type of receptor in the case of folks who are allergic. But I think it's important to realize that in addition to those allergic proteins, there's a whole bunch of other proteins that are present too. And they all function a little differently in the types of chemical mediators they're going to release. And those mediators are going to stimulate all sorts of, you know, different nuanced, um, responses of our immune system.
So why should we care? You know, as we talked about in my session on the epithelial barrier, we continue to evolve as humans. So the fact that we're continuing to see changes in how these cells respond to that change in our environment, doesn't surprise me in the, in, in the least. You know, we think about allergies over, you know, a quarter of people suffer from allergies.
And, and in my prior talk, too, talked about how autoimmune disease, this old data, 5 to 8%. Well, we know that 1 percent of the population's estimated to have Sjogren's disease. So certainly this is a far underestimate, underestimate of, you know, what the reality is. And as I've talked before, you know, this condition, Eosinophilic Esophagitis, EOE, it wasn't a thing when I was born 40 years ago and now it's no longer a rare disease.
It's fairly common. And why do I go back to that one? Well, eosinophils are also allergy white blood cells. They're pretty, you know, they're kind of in that same ballpark of how and what they were responding to back in our, you know, our prehistoric times. So I'm not surprised that we are continuing to see an evolution in how our mast cells are misbehaving.
We've already seen our eosinophils are doing it in different ways, you know, over the last several decades.
Mast Cell Disorders and Misbehaviors
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Kara Wada, MD: So we think about this spectrum of how our mast cells can misbehave. You know, we look at this entire entity of mast cells and how they can go awry. There are subgroups. So there are certain people that we know, they have a genetic mutation in their mast cells that result in a condition called *mastocytosis*.
They tend to secrete higher levels of tryptase, one of those chemical mediators, which we can measure on blood testing. And if you were to do a bone marrow biopsy or a certain, maybe a biopsy of the intestines. You may then see not only an excess number of mast cells there, but they also may look funny under the microscope and they're behaving differently too.
So that's one particular type of mast cell disorder.
There are some folks who are just plain old allergic. Their mast cells are behaving how they should, it's just maybe we shouldn't have made an allergic memory to the pollen outside, right? That's not super helpful, um, but it's recognizing that pollen, those mast cells are triggering, we're having itching, sneezing, runny nose, asthma, so on and so forth. There also are some folks who we don't quite understand. But just randomly have anaphylaxis. This is the IA, Idiopathic Anaphylaxis. We know anaphylaxis is a whole body systemic type response where we have a significant number of mast cells that are activated at one time and create symptoms of allergy in more than one part of our body.
So you have itching, sneezing, wheezing, and throwing up. You may have hives and throwing up. You may just pass out. You don't need more than one body system. If you like go into cardiopulmonary arrest, that, that counts if it, if there was an allergic trigger.
We can see anaphylaxis and allergic disorders. Certainly see it fairly often with food allergy, see it with mastocytosis, and there are some people for whatever reason that they have something called idiopathic anaphylaxis. Portion of those people may also have mast cell activation syndrome, where their mast cells, for whatever reason, are a little more irritable.
And they are, you know, always on this, you know, safe, not safe kind of continuum. They're more likely to see the world as unsafe, even if it's actually probably safe. There is a lot of controversy though, about how we figure out who specifically fits under this mast cell activation umbrella. And there are two sets of criteria: consensus one and consensus two. And so if you unfortunately are someone who suffers from mast cell, you may have been stuck somewhere between, you know, this, this ongoing professional debate between what exactly is going on. And, and I apologize, it's really unfortunate, but it's the reality. It's where we are.
So when I see a patient in the clinic, if they're worried about mast cell disorders, I'm also thinking about what could look like mast cell, and what might overlap with mast cell. And I will say Sjogren's ends up on both of these lists. And why? So these mast cells we talked about, they are located in the tissue, typically in the connective tissue. Sjogren's is a connective tissue disease disorder. They also are found in very close proximity to those small fiber nerves. Those same small fiber nerves that tend to be affected in Sjogren's. There is a lot of discussion and still debate about, kind of this role in this interplay between mast cell activation and dysautonomia.
Sjogren's is the number one cause of, number one autoimmune cause of POTS, the primary, and most prevalent type of dysautonomia. So there's a lot of things that are kind of interwoven here in the physiology in what's going on.
When I'm also thinking, you know, about I said mast, you know, what could mimic, but what also could be adjacent to mast cell.
So dysautonomia and POTS, hypermobility, dysbiosis and SIBO, which we see more often again in Sjogren's. I'm also thinking, okay, is this mast cell activation or does this patient and or does this patient have trouble digesting histamine? Histamine intolerance, kind of like lactose intolerance, but with histamine. Histamine is naturally found in foods to varying levels, kind of like lactoses and dairy products. Some folks have a harder time digesting that, breaking that down. Similar with salicylates, it's not just in aspirin, also found naturally in foods, FODMAPs, types of carbohydrates that can be fermented in our gut.
Also a condition about 6 percent of the population has where they have extra copies of the gene that makes tryptase, Alpha Hereditary Tryptasemia. These folks may have, not all, some are totally asymptomatic, but some may have more symptoms. Certainly, some folks have chronic hives and chronic swelling conditions, bread and butter of my clinical practice.
Alpha-gal, it's an allergy to mammal-based meat, cow, pig, lamb, deer, elk, bison, anything that we would eat that has four legs, we can become allergic to through a tick bite, um, from the Lone Star tick. And although that has been geographically somewhat limited as we've seen climate evolve and climates, weather patterns change, those ticks are moving.
So even in my area of Central Ohio, wasn't a thing when I finished training seven years later, seeing more and more patients, with that condition.
Thinking about other like less well understood, you know, MCAS and multiple chemical sensitivity. I think we'll end up finding are more closely related than, than we currently understand.
Then interstitial cystitis, again, something that we'll often see in folks with mast cell, often see in patients who have Sjogren's. So again, some of these overlapping issues going on.
Clinical Approach to Mast Cell Activation
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Kara Wada, MD: So when I'm seeing a patient in the clinic, what am I thinking about?
First and foremost, I need time to really get a thorough history and physical exam. It's actually why I've put together a document, for you to help be able to provide that complete comprehensive history to your healthcare professional because I know not all of you are in Ohio or able to come to Ohio to see me. So we have that available. We'll make sure to link to it below.
But it helps you put your story in a way that your physician, is going to better kind of understand and be able to hopefully make better sense of. I think, you know, part of my role as both a physician and a patient is helping you communicate better with your healthcare team because sometimes we are not talking the same language.
I generally also will check a tryptase level, again to make sure we're not dealing with something like mastocytosis. If it's elevated, that takes us down one path. If it's normal, it takes us down a different path and we may be getting 24 hour collection of urine looking for other mast cell mediators.
At the same time, if I'm hearing signs and symptoms and stories that sound like there might be some component of the mast cells misbehaving, I'm also thinking, what could be driving this?
What could be kind of that underlying root cause that may be going on? What may be some other of those, what we call comorbidities, other conditions that may be going along with. Is there undiagnosed Sjogren's? Is there SIBO? What sorts of things are going on? Is there histamine intolerance?
And we're also thinking about what are some, you know, easy, and or low risk things that we can do, interventions we can take to see helpful, not helpful like doing a little bit of putting ourselves in the driver's seat, being a scientist in our own care, and assessing how some of these interventions, you know, are they helpful, not helpful, and going from there.
Treatment and Management Strategies
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Kara Wada, MD: So what can we do about it? Some of these slides are from a presentation that I gave to my peers and part of it is treating other humans like human beings, trauma-informed, compassionate care. The issue is our medical system, at least in the U. S., is what I can speak to, is not set up for this.
We don't have, unfortunately, the ability to, in most instances, to spend the time necessary. And it's really unfortunately led to a lot of breakdown between physician and patient relationships. I know, um, you all know about that from personal experience, I'm sure, all too well.
But there are some things that we can think about when it comes to, treatments. So we can think about trying some antihistamines. In the case of Sjogren's, we have to do that conscientiously, knowing those medications may increase dryness. We can try things like mast cell stabilizers, cromolyn.
Someone has a history of anaphylactic reactions. They absolutely should be carrying injectable epinephrine. Rarely, but occasionally we need to use corticosteroids. And for those folks who do have known mastocytosis, there are some newer medications called Tyrosine Kinase Inhibitors, which are really helpful, especially in systemic severe cases.
Potential Triggers and Patient Guidance
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Kara Wada, MD: The biggest and most helpful thing I can do is to help walk folks through, what are possible triggers? What are some things to keep an eye and an ear out for? But also realizing that not everything on this trigger warning list that we're going to go through, is necessarily going to trigger them.
Part of what I like to do also is helping people rebuild confidence in their ability to navigate through the world with less fear. Because you can imagine if you are walking through life thinking your allergy cells are going to trigger at any moment, this really can, like take the fun out of life in a lot of ways, because you are always on high alert.
And so helping rebuild that trust in ourself, rebuild that sense of safety in our environment is so critically important.
But some things to think about: changes in temperature, really hot, really cold, sudden temperature changes. Big storm fronts for some people. Stressors. Emotional, physical, like a car accident, a surgery, right? Environmental: wildfires, pollution. You're allergic to cats or dogs, visit a family member that has them, okay? Exercise. The more intense, the more likely to possibly be a problem. So like a HIIT workout or running sprints. More likely to be a problem than just taking a stroll around the block.
Getting too tired, alcohol, other foods and beverages, especially high histamine type foods for some folks.
Medications. One of those receptors I mentioned on that page, there's a specific receptor there that MDMX one that a lot of medications can can trigger mast cells through. So opioids, NSAIDs, certain antibiotics like vancomycin, ciprofloxacin, and levofloxacin. Some local anesthetics and contrast dye for imaging like CAT scans.
Odors, perfumes, scents, fragrance. Again, better off to skip it. Venom- often a sting reaction is one of the ways that we will pick up that someone has a mast cell disorder. They have a sting and they have a really strong anaphylactic reaction. That clues us in as allergists to think about mast cell disorders.
Infections. Saw it with COVID, right? That not uncommon to see folks with development of hives, swelling, and sometimes mast cell activation after COVID infection, but certainly with bacterial and fungal infections too.
We know certain folks- mechanical disruption of the cell membrane. Scratching, irritation, itchy, scratchy clothing, friction, vibration, all those things are triggers for some folks. And unfortunately, sunlight for some people too. I also have one patient who is quite sensitive to water. She's noticed that, she's showered when she's traveled and her skin is much happier than the water at her home. And so we're trying to currently kind of work through what the differences there may be.
Emerging Treatments and Research
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So some other things that may be helpful but are under investigation. I have probably about two dozen patients on low dose naltrexone now, which is a partial blocker of the opioid receptor and helps decrease inflammation at that nervous system, immune system juncture. Also found it helpful for chronic itch. And there are some small studies to say it may be helpful for Sjogren's as well.
Kara Wada, MD: Vagal nerve stimulation, either through exercises, you can do at home. There are some new devices that are out there. And then certain brain retraining type programs that are also centered on our limbic center, that lizard brain I talked about at trying to help increase our safety signals in our body.
Certain folks with histamine intolerance may find some benefit from DAO supplementation. It's an enzyme that helps us break down histamine. The studies on that have been pretty mixed. And then there are certain antioxidants that seem to be helpful anecdotally, quercetin, luteolin, and higher dose vitamin C are some others that come to mind.
So we have a lot still to learn, about mast cell disorders. How these conditions may relate to other autoimmune conditions and this interface between the immune system, the nervous system.
Conclusion and Community Engagement
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Kara Wada, MD: I hope you found this helpful. I'd love to hear your, your stories, your questions. Had you heard about mast cell activation before? Have you tried to talk with your doctor about it? Let's continue this conversation And if we aren't connected already, I would love to continue this conversation also over on Instagram. That's the social media platform I'm most active on @immuneconfidentmd and posting there all about allergies, autoimmunity, Sjogren's, mast cell activation, all with this core of one, realizing it all stems from misbehaving immune system behavior and also working on rebuilding that confidence in ourselves and our ability to take that next best step forward in whatever we need to do for our health and healing journey.
Speaker: I hope you found this helpful. Can't wait to see you again at our next session. That's a wrap on our exploration of mast cell activation syndrome and its possible connections to Sjogren's. I hope you found this information helpful and empowering and that you feel ready or a little bit more ready to take that next step in managing your health. And speaking of taking action, I want to share some exciting news. Based on the incredible feedback from our first round, the Sjogren's Superpowers Activated 28-Day Challenge is back for round two. Here's what one participant, Karen, had to say. "Extremely informative in a very caring and compassionate manner. Dr. Kara and Jennifer share beneficial, practical tools that are easily incorporated into daily living. The bite sized daily topics and lessons were the right amount of time, not overwhelming. This is not a one and done type of course. You'll find yourself using some nugget of knowledge learned each day long after the course completion. Highly recommend."
it is truly inspiring to hear how this challenge is helping people like Karen feel more energized. Reduce pain and even sleep better.
The next round kicks off later this month on October 24th, so if you are ready to experience the benefits for yourself, don't miss out.
Join the wait list now at www.drkarawada.com and snag a special early bird discount if you're on the wait list, you can also find the link in the show notes. Thank you so much for listening to Becoming Immune Confident, and I cannot wait to connect with you again in the next episode.
Kara Wada, MD: Hey there, amazing listeners. Before we wrap up today's episode, I want to take a quick moment to ask for your support. If you're enjoying the content of the Becoming Immune Confident Podcast, we're bringing you week after week, there's a simple, but incredibly impactful way you can show your appreciation.
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