Linking Mast Cell Activation, Autoimmunity, and EDS with Kara Wada, MD

Dr. Linda Bluestein: [00:00:00] Welcome back, Every Bendy Body, to the Bendy Bodies with the Hypermobility MD podcast with your host and founder, Dr. Linda Blustein, the Hypermobility MD. I am so excited about this conversation today with Dr. Kara Wada. The immune system is being discussed everywhere nowadays with connective tissue disorders and how these might be interplaying with each other.

We just had this pre print that came out about the calocrine. family of genes and how these might be more prominent in people with hypermobile EDS, and now we just had another paper that came out about joint hypermobility, autonomic dysfunction, gastrointestinal dysfunction, and autoimmune markers and In this group of patients with unexplained gastrointestinal symptoms, they actually found postural symptoms in 77 percent of the people.

They actually found [00:01:00] autoimmune or auto inflammatory disorders in 70 percent of these people. And they found that 31 percent of the patients with Uh, those markers had CRP elevations, so signs of inflammation. And last but not least of the points that I want to point out from this paper, which of course I will be discussing, I'm sure, with one of the authors, because this is a really important paper later on this season.

Um, Uh, A lot of these patients, the ones that had joint hypermobility and hypermobility spectrum disorders, they were more likely to have autoimmune markers along with more severe autonomic and gastro intestinal symptom scores. So we saw 43 percent versus 15%. So there's so much happening in the space of the immune system and how it relates to connective tissue disorders.

So this is going to be a great conversation with Dr. Kara Wada today. Dr. Wada is a physician who is quadruple board certified in pediatric and adult allergy, immunology, and lifestyle medicine. She is also a [00:02:00] Sjogren's patient and a life coach. She has her own podcast called Becoming Immune Confident, and I was on her podcast as a guest a while back.

She shares on her podcast her recipe for success, combining an anti inflammatory lifestyle, trusting therapeutic relationships, modern medicine, and how she uses the mind to harness her body's ability to heal. This is going to be a great conversation, so be sure to stick around to the very end so you don't miss any of our special hypermobility hacks.

As always, this is for educational purposes only and is not a substitute for personalized medical advice. So let's jump into this exciting conversation about the immune system and connective tissue disorders. I am so excited to talk with Dr. Wada today. The immune system is so important in all of the hypermobility conditions.

So let's just launch right into the questions. How did you come up with the name Crunchy Allergist?

Dr. Kara Wada: So my nickname as the [00:03:00] Crunchy Allergist really stemmed out of my final project as an allergy immunology fellow. At the end of each year and at the culmination of our fellowship training, we are expected to put together an original presentation for our entire department.

And something I've always been really interested in is what type of evidence do we have to support some of those more natural or home remedy type approaches to taking care of our allergies in our immune system. And so I spent that year, you know, collating all of the research that was out there and putting that into a presentation.

So one of my colleagues, um, who is also pretty active on social media, Dr. Dave Stukas was like, well, goodness, you're kind of like the crunchy allergist. And so that stuck and here we are, oh goodness, not almost 10 years later. Um, and [00:04:00] Still, still holds true. I like using kind of those naturally minded, but also scientifically grounded approaches to care.

Dr. Linda Bluestein: Yeah, and I think that's so important now because of course people are getting bombarded with information, right? And it's so hard to know what's, what's good information, what's not good information. But those holistic things can be so valuable and can be so important, but getting that from someone who is a physician, who has the knowledge.

The medical background and, um, and the training to really advise them on that. I love that. Um, I want to jump right into allergy specifically, because of course, uh, when people have joint hypermobility, they're more likely to have mass cell activation syndrome, they're more likely to have dysautonomia, or more specifically, they may have POTS.

Um, but oftentimes people say, well, what's the difference though between allergy and mass cell activation syndrome? So if you could maybe start by telling us, uh, your thoughts about that.

Dr. Kara Wada: Absolutely. So, allergy is a way that our body can make memory to certain [00:05:00] things in the environment that we have seen, primarily proteins, and those can come from pollen, like our trees or grasses or weeds, can come from molds, can come from our pets and dust mites, also can come from foods, um, and it's our body's ability then to recognize those substances.

And to create an immune system memory. And that memory is encoded with an allergy type flavor. So it's in the form of something called an IgE antibody. So our body sees these proteins. For whatever reason, the immune system has that coded as, Ooh, this is a danger signal, we better remember this. And then it creates, um, as those T cells and B cells talk to one another, creates a lasting memory where those B cells and plasma cells then create this protein called an IgE antibody.

Those antibodies are then expressed or kind of housed on the outside of a couple of types of allergy cells, those mast [00:06:00] cells that you referred to, and also basophils, which are in the bloodstream and pretty close to mast cells. Um, they're essentially kind of the bloodstream equivalent. Um, and it's just one way that those mast cells or those basophils can be activated or turned on to release all of those chemicals then that create the signs and symptoms of an allergic reaction.

So just one way that our, those cells can be turned on. We know that with mast cell activation syndrome, that there are lots of other reasons and ways that those mast cells, um, additionally can be turned on. Um, and it's actually not too uncommon for me to see someone with, you know, pretty significant allergy symptoms and they may or may not know about mast cell activation, but their allergy testing may be completely normal.

So then we're thinking, Hmm, what are some other reasons that these, these immune cells may be getting turned on [00:07:00] and triggered? And that's where. that piece of mast cell activation starts coming into frame of like, Oh, could this be what's going on as well?

Dr. Linda Bluestein: So could a person have allergy and not mast cell activation syndrome or mast cell activation syndrome and not allergy or both?

Absolutely.

Dr. Kara Wada: It's like the, I go back to middle school English class when we had to use those Venn diagrams, right? Those exercise, we go into what's the same, what's different. And so there is a varying amounts of overlap between those conditions.

Dr. Linda Bluestein: Okay. Okay. And another term I think that gets so confusing for people and you know, I'm an anesthesiologist so, and, and we talked on your show, which was so much fun.

Um, and you know, as an anesthesiologist, my understanding of anaphylaxis was completely different of my understanding of anaphylaxis now. And of course that word gets thrown around and I would love to hear you describe like what is anaphylaxis?

Dr. Kara Wada: Uh, so anaphylaxis is caused [00:08:00] by. A significant number of those mast cells getting triggered at one time, and what will happen as a result of that is that in how we clinically diagnose that is the patient is having symptoms that are affecting more than one system in their body.

So someone just has hives or swelling, that's one, it's kind of affecting their skin. If, though, they have hives and swelling, less changes where their blood pressure drops. or perfused vomiting, or they have trouble with wheezing, you know, any combination of these, that is when that label of anaphylaxis comes into play.

The other little caveat, kind of the asterisk, and the diagnostic criteria is, you know, if someone has cardiovascular collapse, they've passed out, their heart has stopped, like, you don't need more than one organ system for that to count, um, especially, you know, in the context of knowing that there was an allergic trigger for that, um, for that very unfortunate event.[00:09:00]

Dr. Linda Bluestein: Mm hmm. Okay. Okay. Great. So it takes, it takes the two systems. It does not have to have the airway edema and that feature that I always thought of that you had to have that in order to meet the definition of anaphylaxis. Interesting.

Dr. Kara Wada: Okay. And I think one other misperception that comes into play is that the skin has to be involved.

20 percent of cases of anaphylaxis. food allergy in the operating room, you know, bee sting, maybe with completely without any skin findings or swelling at all. And this is actually the situation that we need to be, especially as physicians, more attuned to, because these are the situations that more often have a delay in diagnosis.

Um, and then, you know, with a delay in treatment, the increased risk of really severe downstream consequences of, you know, maybe not being treated quick enough, um, or adequately enough.

Dr. Linda Bluestein: Getting back to mast cell activation syndrome for a second, um, there's [00:10:00] primary, right? Primary mast cell activation syndrome, secondary mast cell activation syndrome.

And when it's secondary, meaning secondary to something else, it could be secondary to an immune deficiency, right? That's, like, not an uncommon situation for mass cell activation syndrome. I feel like there's so much confusion though between immune deficiency and autoimmunity. Um, so can we first talk about immune deficiency and why for this population, that's so important for people to be aware of?

Dr. Kara Wada: Yeah, primary immune deficiency and secondary immune deficiency are much more common than I think we realize. And we know that and recognize that there is a really long gap between when looking back patients start having symptoms and when they're diagnosed. So I think the most recent statistic for common variable immune deficiency, which is one of the more common types, um, is about seven years between onset of symptoms and diagnosis.

So in an immune deficiency, the immune system has a harder [00:11:00] time Either, one, recognizing that there is an infection going on, two, creating memory to say, oh, goodness, we've seen this infection before. We know what to do. So, it might be a little bit like, you know, starting from scratch every time you get the cold, a common cold, as opposed to having, you know, some memory to that or even memory from your vaccines, um, and being able to recognize and respond more appropriately.

The other thing that will happen if you are, have a low immune system or an immune deficiency, you have an infection, the immune system isn't necessarily able to respond as robustly or, you know, as strongly as it should. And so that infection may become more severe, it may damage more tissue. Um, and there's a, you know, when we think about Bacterial infection, you know, our mind kind of sometimes goes to, um, like an [00:12:00] abscess or pneumonia where there's maybe pus involved.

Sounds gross, but this is what happens. There's, you know, and there's that tissue damage related to that. The immune system not only is trying to fight off those bacteria to make memory to those bacteria, it's also responsible for the cleanup process and the repair process afterwards too. The reason I mention that is because it's not uncommon for me to see in clinic patients who have immune deficiencies and also have autoimmunity, which is an overreaction of the immune system where the immune system is saying, Recognizing some of our own parts and pieces, or as my kids say, their bits and bobs, um, as a danger signal and saying, oh, you know, creating inflammation and chronic inflammation in particular areas.

And what is thought to happen is, if the immune system is not able to clean up after, An infection or another [00:13:00] inflammatory kind of insult, but that opens the door for the immune system to misrecognize our own parts and pieces as a danger signal, um, inappropriately so. And so for many of these prime, immune deficiencies, you also will see an increased risk of.

autoimmunity and sometimes allergies too, um, that go along with them. So if anyone out there is, you know, having situations where they get recurrent sinus infections, they're an adult and they're getting your infections more than once in a, you know, great long while. If you are an adult and you've had more than one true pneumonia, these are things that, as an immunologist, my mind is, you know, clued in.

We need to start thinking about checking some labs, um, and evaluating for your immune system's ability to, to recognize and to create memory to these infections through, typically through some [00:14:00] blood work.

Dr. Linda Bluestein: When would you work someone up for autoimmunity?

Dr. Kara Wada: So, typically with autoimmunity, we are going to, um, think about that in situations where someone has ongoing or chronic inflammation, um, and oftentimes we are able to center in on this a little bit better when it is affecting a particular organ system.

Um, A little easier sometimes than when it's the whole body. Um, so, you know, you think about someone who maybe has inflammatory bowel disease. It's something like Crohn's or, um, ulcerative colitis. You know, that is something that you can kind of zone in on because they're primarily going to be, um, complaining of signs and symptoms related to that.

Chronic diarrhea, blood in the stool, um, You know, stomach pain and having to go to the bathroom that's waking them up from sleep, weight loss and fever, um, you know, some [00:15:00] really significant signs and symptoms of inflammation. Other times, joint stiffness, um, especially in the morning is one thing that really clues us in to think, Ooh, could this be an inflammatory arthritis or connective tissue issue?

Um, you know, I think part of it really is listening to the patient, hearing their story, and looking, um, and listening for those signs and symptoms of inflammation, which redness. Swelling, stiffness, pain, um, fever, um, and I also listen for, again, that, that difficulty with I get a cold and it just takes me forever to get over it.

You know, that's another situation where I'm just thinking, hmm, is there some chronic inflammation that is really making it challenging for this person to.

Dr. Linda Bluestein: Just recently, this big preprint came out out of MUSC and they talked about the calocrine genes and now there's all this talk [00:16:00] about the complement system and you know, so those of us that went to medical school, some of these things are a little more distant in our minds and the ones that didn't are like trying to sort out, wait, what's the complement system?

What's, you know, how does this play a role with the immune system? What should we know about that?

Dr. Kara Wada: Interestingly, so I have not had a chance to pick it up and read the paper quite yet, but I have certainly followed some of the same people have seen this exciting headline. And I find it really interesting because one of the conditions I care about and care for in the clinic, um, with some regularity, it's a rare condition, but I, because I work at a university see, you know, um, some of these rare conditions a little more often as a result of that hereditary angioedema, which is a condition where folks will have a deficiency in a particular enzyme or protein that, um, makes them at greater risk of having swelling episodes.

So swelling of their lips, their voice [00:17:00] box, their gut. And this is related to kind of these overlapping cascades, um, complement, um, calicrinib and bradykinib. One of the medications that we use in our, you know, in our, kind of, we have available to treat Um, is directly related to calocrinone and decreasing, you know, that activity.

And so it just has me kind of wondering, okay, one, would there be any role for this med or the research from that medication to, will that provide some additional insight into what we're learning about hypermobile Ehlers Danlos? Um, and we're, we're going to kind of use that moving forward, um, in hopefully gaining some better understanding to the pathophysiology of where this connective tissue meets inflammation, um, and [00:18:00] shining some more light on that because the reality is that within especially academic allergy immunology.

Practices. Um, many folks are still very much within that consensus one box. And I think sometimes reluctant to accept this, um, this association that you and I see all the time between hypermobility and immune system, uh, misbehaving as I love to refer to it as. Um, and, and I think it's another piece in the puzzle that is going to shed light, give us a better idea and vision of what's going on.

Um, and hopefully convince some of those, um, holdout colleagues, um, with that evidence that, you know, what we're seeing is the reality.

Dr. Linda Bluestein: Yeah. And, and I'm so glad you brought up about consensus one, cause I was one of the authors of the co author, you know, played a minor role in consensus too. And it's like, [00:19:00] uh, so many people do not have a positive trip days and it's like so frustrating of course, for them as patients to be.

You know, not just denied a diagnosis, but to be denied care or, you know, suggestions or anything, which is why I was so excited after you interviewed me for your podcast. I was like, I can't wait to talk to you here and, you know, get your take on these things because I think that's the thing that surprised me the most in working with this population is how much low hanging fruit there actually is and how much we actually can help people, which is of course really exciting.

How do you handle the whole triptase situation?

Dr. Kara Wada: So typically I will check it, um, in part because if it is elevated, That just takes me down a different little, you know, pathway of other things I want to consider. Um, and also, if it's not elevated, okay, let's keep moving on. Let's, you know, let's check your urine studies.

If those aren't elevated still, let's continue to work [00:20:00] on, you know, what are Our goals together as physician and patient are, um, whether, you know, that's to decrease itching, to improve digestion, like, um, to feel more comfortable and confident navigating the outside world, um, staying in, in, in work. Um, when a tryptase is elevated, some things that I want to be thinking about, one, could this be mastocytosis?

So mastocytosis is, Um, essentially, in 95 percent of cases caused by a mutation in the KIT gene, which results in mast cells behaving differently. You'll see typically an increase in number, um, and a change in how they look under the microscope in the bone marrow, the gut, or other tissues. And the reason it's important to recognize and identify these [00:21:00] patients is, especially if they have pretty significant symptom burden, there are specific targeted treatments, um, that are available and or some that are in trial that can be quite helpful.

So, don't want to, you know, miss that. There also, I think, is an increased recognition for, um, you know, hereditary alpha tryptasemia wasn't something that was like, uh, I think it was just one little mention during maybe my, maybe one little mention during my fellowship training. Now in the last, you know, five to eight years really had an increased awareness and understanding that this little, you know, quirk in, in some folks having additional genes of copies of the gene that creates tryptase affect up to 6 percent of the population.

So this is just, you know, other helpful tools and, um, a simple mouth swab testing to get screened for that condition, where it may provide some insight of like, Oh, that's why I'm [00:22:00] so much like my mom, we have the same genes, literally, um, that, you know, that, that have this, and not everyone is symptomatic with this condition, but for those that are, this provides some additional insight as like, Oh, well, maybe this is why I have more of these symptoms.

Um, that may, um, or may not look like mast cell activation. So, you know, I think And that's the ways that I find Triptase helpful. I also don't let a negative Triptase, you know, I don't throw that out, the baby out with the bathwater. Yeah.

Dr. Linda Bluestein: Yeah, for sure. And then I tell people if I, if, if we check the Triptase and it's normal, it's negative that to me, that doesn't mean anything other than, yeah, it's helpful for ruling out mastocytosis.

We're going to take a quick break and then we are going to come back and talk about mast cell activation syndrome treatment. We'll So we'll be right back.

This episode of the Bendy Bodies podcast is brought to you by EDS Guardians, paying it forward in [00:23:00] the Ehlers Danlos Syndrome community, patient to patient for the common good. I am proud to serve on the inaugural board of directors for EDS Guardians, a small charity with a big mission and a big heart.

Now seeking donors, volunteers, and partners. Patient advocacy and support programs available now. Travel grants launching in 2025. Learn more, shop for a cause at their swag store, and join the revolution at edsguardians. org. And we're back, and I'm so excited to talk, of course, about mast cell activation syndrome treatments.

But I first want to go back to inflammation, because I know that so many people, like when you were talking about inflammation before, they're like, wait, that's me. I feel like that's. Totally me, even though my CRP is normal, my C reactive protein, my C reactive protein, my CRP is normal. Um, my ESR or sedimentation rate might be normal and we don't have, we have, we can do like the 17 different cytokine panel, right?

The Mayo Clinic cytokine panel, but we don't have great, great tests for that, I, [00:24:00] I don't think quite yet. Um, can you explain a little bit more about the role that inflammation plays in, in, in in these conditions. I think that's really important.

Dr. Kara Wada: Absolutely. So, you know, I think inflammation has become one of these key words that we're all honing in on and has become a bit of the boogeyman, um, especially knowing that chronic inflammation is really at the root of all of the diseases that really affect us in our, you know, in modern living.

But at its core, inflammation is our body's natural and necessary response to infection and to injury. It is our body's ability to recognize and repair, um, to, you know, get everything back to that really happy place of homeostasis that, that, you know, think of it as, you know, that Goldilocks of everything being perfect.

Um, always in a little bit of flux, but in that, that nice spot. [00:25:00] When inflammation, though, sticks around like an unwelcome houseguest and becomes chronic in allergies, in autoimmunity, um, in cancer, that is when it becomes problematic and you know, that is kind of the, the bad inflammation that we talk about when we are thinking about autoimmune or auto inflammatory conditions.

The distinction between those being, are there signs of immune system memory, um, or is it maybe parts of our immune system that don't necessarily capture memory, but are likely epigenetic changes that have resulted in parts of our immune system, um, remaining on or more active than normal.

Dr. Linda Bluestein: Okay. And I'm so glad you brought up the word epigenetic.

So that's basic. Well, I should let you, if you would elaborate about epigenetic, cause you're probably gonna do a better explanation than, than I am.

Dr. Kara Wada: Um, so I think of epigenetic changes as [00:26:00] essentially the on and off switches determining if our genes or, you know, our, the things we've inherited are expressed or non expressed.

Um, and maybe more, a better analogy than a light switch sometimes is a dimmer switch, um, because it's not always on or off, but it may be kind of subtle adjustments as to, you know, how much of a protein is expressed or not expressed too.

Dr. Linda Bluestein: That leads into my next question slash thought. What about the role of hormones?

How do hormones play into all of this?

Dr. Kara Wada: Oh, goodness. Thank you How do we count the ways? We know there's this rule of thumb, um, with, with pregnancy, for instance, that we learn to, to tell our patients, um, and it seems to hold true in allergic conditions and in autoimmune conditions, you know, broad brush strokes, but about one third of patients will get better with those hormone changes associated with [00:27:00] pregnancy.

One third of patients, their underlying inflammatory condition will stay the same. And one third of patients, it will get worse. Um, whether it's chronic hives or asthma or lupus, you know, you kind of see these broad brush strokes. So we've known for, you know, a long time with data from pregnancy, but also looking at data, you know, surrounding puberty, maybe a little less data around menopause because who wants to study menopause?

I say that facetiously, of course. Um, right, right, right. But that, you know, especially estrogen and testosterone, progesterone, these all have, you know, significant impact on, um, our tissues. We know with tissue laxity, you know, pregnancy to carry a pregnancy, I'll defer more to you on, on those aspects. Um, but then also on our immune system functioning as well.

Um, and there, you know, there are, like I [00:28:00] said, some, there's variability between patients even with the same condition that some of these, you know, shifts, um, can affect us differently.

Dr. Linda Bluestein: Okay. And we talked about dysautonomia or dysfunction of the autonomic nervous system kind of at the, at the very beginning.

And of course, a lot of people that have Ehlers Danlos syndromes or hypermobility spectrum disorders or mass cell activation syndrome, they very commonly will have some dysfunction of their autonomic nervous system. And sometimes they do meet the criteria for POTS or postural orthostatic tachycardia syndrome.

How Is the autonomic nervous system connected to the immune system, which I know that's like a huge topic. That could be a huge conversation just right there.

Dr. Kara Wada: I'm going to throw one more condition in the mix that's near and dear to my heart, which is Sjogren's disease, which is one of the number one autoimmune causes of POTS and in dysautonomia.

Um, When we think about, you know, where, where this malfunction is going on, I [00:29:00] always, at least, you know, from my point of view, like to think back to what are, what's going on with the mast cells, um, because they are physically located, one, in our connective tissues, but also two, right nearby, if not touching those small fiber nerves that are responsible for much of our autonomic.

nervous system function. Um, this was the hot topic, uh, not specifically dysautonomia, but this interface between mast cells and the nervous system, and frankly, the immune system and the nervous system at our American College of Allergy, Asthma, and Immunology meeting this past spring. And I think a hot topic for ongoing discussion, um, in research surrounding, you know, these two systems that.

Frankly, for a long time, much of medicine is kind of siloed. Um, I know at least at our institution, the neurologists are kind of over in their institute. We're kind [00:30:00] of over with the ear, nose, and throat docs doing our thing. Uh, the rheumatologists are over in a different area. And so, you know, bringing together some of these disciplines, I think, is really necessary to, to better understand how, you know, mast cells are playing a role, how the macrophages, in particular, microglial cells, which are central nervous system's um, equivalent of macrophages, how those may be playing a role.

We know that those cells in particular can be both, um, to, to name one of my favorite books, they can be both angels and assassins, um, both calming inflammation and promoting inflammation within, um, within the central nervous system and, and elsewhere too. And I know talking, um, you know, with the folks from Dysautonomia International, um, in, in particular, Lauren Stiles, who I swear she should have, uh, an honorary medical degree, um, but, [00:31:00] you know, some additional research honing in on the ganglia, so these, um, little essentially like transformer boxes, um, um, outside of our brain, but that, you know, are these, um, areas that are really hard to, to assess clinically.

Like, we don't have good studies to look at them on imaging or to necessarily test them. Um, but, you know, that's an area of focus that I think has come into The discussion of where some of this inflammation may be occurring as well.

Dr. Linda Bluestein: Yeah. And that's such an important point because you and I both know that so often the frustration that patients experience is that they go in for an evaluation and nothing shows up, right?

Like all their labs are normal, their imaging is normal, but they know that they don't feel good. And then oftentimes what ends up happening is, is that. The doctor gets the sense from the person, oh, you want to be sick. I literally had a doctor say that to me. I had a rheumatologist say that to me. Oh, you [00:32:00] want to have a rheumatologic condition?

Like, no, I don't want to have a rheumatologic condition, but I don't feel good. I know something's wrong. I've got so many problems and, you know, and nothing shows up. So it's, that's challenging.

Dr. Kara Wada: I always go back to that little meme slash comic with the high five of your labs are normal. And then the poor patient is drowning.

It's just, it is such an accurate reflection of that situation that I, I, I swear I hear from probably 95 percent of patients who are coming in with, you know, this constellation of symptoms.

Dr. Linda Bluestein: Definitely. Okay. So in terms of, um, you were mentioning something about like autoimmunity and epigenetic, or we were talking about epigenetics.

So are autoimmune conditions increasing? We know that obviously we have a lot of things in our environment that we were not exposed to before. What's happening in that, in that space?

Dr. Kara Wada: Yeah. So one of [00:33:00] the really big paradigm shifts that has occurred over my career, which I, I've continue to nerd out about is, you know, this change from when I went through medical school, the idea was, oh, we are seeing more allergies.

We're seeing more autoimmune disease because we're cleaner. We have antibiotics, we have hand sanitizer, moms are vacuuming more. That's the problem. And the reality is that a little bit of that's probably playing a role, but there is this overarching hypothesis that's really come to the forefront called the epithelial barrier hypothesis, which goodness, it's a mouthful.

But what it's really explaining is that, you know, our bodies have Ways of interacting with our outside world, and that's through our skin, our gut, and our airway. And at these interfaces, we have, have these barriers, these epithelial barriers, that's the name of the, the types of cells or tissue. And those barriers [00:34:00] are supposed to be somewhat permeable.

We want to absorb oxygen. We want to absorb nutrients, right? Um, to be able to process vitamin D through our skin. Um, but there also should be an element of selectivity. Should have some bouncers there that are doing a good job of kind of keeping the bad stuff out. And unfortunately, there are a lot of things that come into play in our everyday modern existence.

They essentially put more chinks in our armor and leave us with those barriers being a little more leaky or permeable than it ought to be. And what happens when that barrier is more permeable is you also see a change in the microbes that live in us and on us. You see typically a loss in the amount of diversity.

You see a change in the types of microbes and or the behavior. So on the skin, for instance, you might normally see staph [00:35:00] epidermidis. If in the case of eczema, more often you may see staph aureus and that staph aureus may also be producing toxin, which happens to make the skin more leaky. And what will happen is, you know, some of these microbial microbes themselves, or their products, and other things we're exposed to in the environment, find their way, not on the outside, but on the inside, um, and in contact with then our immune system.

So our immune system then gets turned on. And we can see then the, you know, the propagation of inflammation of various kinds, you know, and types and flavors of inflammation that then, um, you'll see downstream effects from. So, you know, one of the main examples we see in, in allergy, for instance, is eczema.

In little babies who have significant eczema, we see a marked increased risk of development of food allergy. The thought [00:36:00] being that the immune system is seeing food through the skin, through that leaky barrier, before it's able to get tolerance and build tolerance through the gut. And so, you know, that that change in how the immune system is exposed and kind of trained is different.

And so then you see a difference in how it might respond in, you know, given susceptible person. We'll also see that crosstalk between exposure to air pollution, developing eczema, putting us at increased risk for various autoimmune diseases, changes, you know, in the gut microbiome, increasing our risk of psoriatic arthritis, MS, um, so there's crosstalk between, you know, these leaky barriers in one spot may create a problem elsewhere in the body.

Dr. Linda Bluestein: It is amazing how connected things are. Yet, like you said earlier, how we were taught that there's these separate systems and that we're not really taught how they, how they talk to each other. So yeah, super, super fascinating. [00:37:00] Um, and getting back to mast cell activation syndrome, because I know a lot of people are going to want to know this.

You know, we all probably treat Mast Cell Activation Syndrome a little bit differently, um, you know, but there's going to be for sure some like common threads or some things that people can do on their own, right, that they don't necessarily, we're going to talk about what people should do if they don't have someone like you on their team because I'm sure everyone listening to this now is like, Oh my gosh, how do I get an appointment with Dr.

Wada? And we'll of course talk about where they can find you. What kind of treatments do you find most effective in Mast Cell Activation Syndrome? Um,

Dr. Kara Wada: So it depends when someone has found me, you know, sometimes early in the game, we're able to, you know, work on some of those low hanging fruit that you mentioned, working with some of the, I call the front door and the back door of those mast cells, the H1 and H2 blockers.

And sometimes that takes a significant amount of trial and error, you know, trying the different types that are out there. [00:38:00] Some people do best with fexofenadine. Others get really, really sleepy with cetirizine. So then maybe we try loratadine or desloratadine. Maybe we'll try the children's version because, you know, they just need a little bit.

There's a, you know, a lot of kind of trial and error and nuance. Um, additionally, you know, certain patients, I'm always a little bit surprised, but pleasantly surprised when famotidine, which is common H2 blocker, um, for some folks that just seems to be extra helpful and in others, not so much. So usually we'll work through H1, H2.

We'll talk about maybe trying a leukotriene based blocker, typically Montelukast. talking through some of the pros and cons. It does have a black box warning due to concerns, rare side effect of mood changes, but I think really important to have that shared decision making with the patient. Um, and then, um, after that, we're [00:39:00] usually, you know, also talking a little bit about lifestyle and nutrition.

What are some antioxidants that we can easily add in, um, that may be helpful? Quercetin, vitamin C, Mediolin, you know, some of these. have a pretty good safety profile. I think one of the big Um, struggles that sometimes comes up, and absolutely understandably so, is that patients with mast cell often may have trouble with excipients, which are the, the extra things within a medication, extra ingredients, the fillers, um, binders, those sorts of things.

So trying to parse out if we think that's an issue, um, is, is a challenge. And also then, you know, in someone who is highly reactive, Um, deciding at what point we feel comfortable, um, maybe trying some medications that are injection based. [00:40:00] So, if I have a patient, for instance, who has more run in the mill chronic hives and swelling or chronic urticaria, Zolair omeluzumab is a game changer.

It is an antibody based medication that essentially lowers the ability for those IgE antibodies to bind to the outside of mast cells, overall decreases the amount of IgE in the body. It's helpful for those who have hives, even hives that are unrelated to allergy, which we're still trying to really totally understand.

We don't totally understand why that fully works, but it does work really well. But if I have a patient who is very reactive to medications in general, often the idea of using a medication that's injected once a month, that's going to be in their system for four weeks. That's a big ask. And that's, you know, that's usually a lot of, [00:41:00] um, and from my standpoint too, kind of this discussion of like, ooh, how do we feel about this?

You know, is, is the juice worth the squeeze? Is, is the risk benefit, um, there? And are there ways that we might try to do a test dose? Uh, to see if someone tolerates it okay as well. Um, I also have added low dose naltrexone to my, my toolbox. It's kind of still relatively, you know, I have probably a couple dozen patients on it, but I've really been happy.

Patients have been happy, so I've been happy. Um, with, um, how they've responded to that, and then also thinking about some other medications that are available and approved outside the U. S., um, little more challenging to get here are things like ketotifin, um, which can be compounded. And then, um, I have to say, uh, gastrocrom and cromalin, um, also has been a game changer.

I certainly have some patients where It doesn't seem to be a [00:42:00] great fit, but, um, goodness, this, we've had some issues with patients getting it, there's been some shortages, and, um, that's really frustrating because for those that it works, it's like, oh, we want to keep that. Keep that available to them.

Dr. Linda Bluestein: And it's such an old drug.

I was prescribed Cromeland when I was a teenager, you know, and so that was a long time ago. So it's so frustrating when we have these generic drugs that have been around forever that we, that we can't get. So yeah, yeah, it's, it's, it's really, really crazy.

Dr. Kara Wada: And where the price point is so high too. Yes.

Dr. Linda Bluestein: Yeah.

Even though it's generic, right? It's yeah. No, that is an excellent point. Um, so there's going to be people listening to this that just are like, wow, this is a great wealth of information, but they're still frustrated because they don't have their own health advocate and they're dealing with a complex condition that's, you know, so misunderstood.

Are there some key steps that they can do?

Dr. Kara Wada: First and foremost, I think learning how to best communicate [00:43:00] your story can be really helpful in, in feeling more confident and advocating for yourself. Um, the reality is that our medical system, at least here in the U. S., is frankly, A dumpster fire in many ways.

Like it's really broken for, not obviously for, for patients. I, um, I too suffer from an autoimmune disease. I have some, um, some dysautonomia as well. Like, and I think it's that experience on the patient side of things that has only made me that more acutely aware of one, the privilege I have, um, absolutely.

And two, you know, okay, how can we maybe. come together and how can I help, um, patients understand from, you know, step in the doctor's shoes just for like 30 seconds so that they can understand how to better communicate to someone who maybe as a physician hasn't been in your shoes. Um, [00:44:00] so I think taking some time before a visit to kind of come to this, you know, place, okay, what, what are, what's my goal for this What do I need to communicate to the doctor, um, or other healthcare professional?

And, um, and then kind of trying to come up with a little bit of a game plan related to that. I think one other little tip I'd put in there is when you call to schedule your appointment, um, with whomever it is, you can ask whoever that scheduling person is, how long is this appointment scheduled for? And that at least might give you a better idea of.

And you could even ask, does this person double book? Where maybe that 15 minute appointment is actually seven and a half minutes. Um, so that you kind of have a better idea. And if you are someone who has a really complex history, maybe share that with the scheduler. Say, Hey, I have a pretty complex history.

Is there any way [00:45:00] to have an appointment slot that maybe would allow for a little extra time? Or if I send my records ahead. Would the doctor maybe take a look at them ahead of time or not? Every office is going to be a little bit different in how they handle those situations, but those are questions that you absolutely have the right and ability to ask.

And I think, you know, sometimes that answer back is also helpful to take note of to see, you know, it's, it's a two way street, right? Certainly there are limitations sometimes within our networks and so on and so forth, but um, really having that trusting therapeutic relationship is so critical, um, especially for those of us that have chronic multi system inflammatory disorders.

So yeah, preparing for your visit, kind of knowing your story, owning your story. And then I think the third and final thing is you have to, [00:46:00] unfortunately, get comfortable with being uncomfortable. Because as I mentioned, the system, we all know, is not made for us. And it's going to require us to sometimes You know, have to advocate more, you know, than we would like and or be kind of a little bit of a pest at times to like check in on things, follow up on things.

Um, it may require us to, uh, have to call and get records and do things that, like, we really shouldn't have to, you know, shouldn't have to do necessarily, but we do. Um, and it requires us sometimes to revisit areas that have been traumatic, um, you know, for, for so many that have experienced trauma. within the medical system, which we know for hypermobile EDS is like pretty much everyone.

Dr. Linda Bluestein: Right. It's, it's extremely common, unfortunately. And I think that those are such great tips and, and [00:47:00] hopefully everyone will, will take those to heart because, you know, it, it is important to advocate for yourself, but also physicians are in such a difficult place nowadays. The system isn't set up for either of us.

It's not set up for, The physicians that are caring for complex patients and it's not set up for complex patients. So we're really, uh, we're struggling.

Dr. Kara Wada: And, you know, one of the areas that I think is on my, on my to do list to focus in on too, is we think about medical education as medical students in resident, well, maybe a little bit more in residency, but as medical students.

We're always asked to answer the question with one answer, um, where, you know, whether it's through a case based learning, you know, environment where we're all talking together about a particular case or it's one of our board examinations where there's one right answer. And the reality is for those of us, the increasing number of us with chronic multi system [00:48:00] conditions, there's more than one right answer.

And that's just not part of the teaching paradigm that at least kind of was how I was taught through medical school. So it's really created, I've kind of had to learn as I go, um, to, you know, accept that, you know, as a, as a physician, I don't have, and especially in my field, I don't have very many quick fixes, occasionally get those runny noses I can fix pretty quickly.

Asthma, I can get out of control. Like those are great quick wins. Um, but off more often than not in, especially in mast cell disorders, I am like putting on my waders and going into that, you know, this, you know, muddy, um, it's the science is muddy. Um, it's challenging because I need to build trust with that patient across from me who has.

So, I think that's a great reason not to trust me as part of the [00:49:00] system. Um, and also, you know, dealing with pressures, which thankfully not too bad where I am, but pressures from administration or, you know, other things to say, oh, see more patients, less time. So

Dr. Linda Bluestein: in terms of lifestyle solutions, because we know that, that those do exist, right?

But speaking of time that you have for a visit, and so some of those are kind of, you know, time consuming, this is a great way to share some of the more cost effective lifestyle solutions that you've discovered. What are some of those that have really made a difference in managing your own autoimmune condition?

Dr. Kara Wada: Yeah. So I think, you know, a few that for me have been game changers. One is I need my sleep. I am someone who needs a good eight hours, sometimes a little more. Occasionally, if I'm like in a good place, I can do a little less. Um, but that's really been a, a non negotiable. It's really rare that I'm going to purposely stay up past [00:50:00] nine o'clock and just

Dr. Linda Bluestein: doing.

Dr. Kara Wada: Um, number two is, um, really honing in on managing my mind. Um, I have always been, you know, a type 2 go getter, or type, sorry, type A go getter. Um, got the to do list a mile long, you know, wanting to make sure I do things to the best of my ability. And if I don't having a lot of that negative self talk, um, you know, coming in after.

So I think learning various tools to help pull me out of that constant fight or flight, um, have been really helpful. Meditation. I try to get at least five or 10 minutes in each morning before I pick up my phone to check other things. Um, I have a pretty regular journaling routine, um, and I've been playing around with some different vagal nerve, you know, stimulation exercises, you know, I'm always [00:51:00] trying out kind of some new things, dabbled in some of the, um, like dynamic neural retraining.

I think there's some really cool tools that are out there that frankly have very little risk aside from the time that we invest in them, um, and have good evidence to say, you know, that evidence specifically for mast cell yet, but in other conditions that may affect our health, we know that they're helpful.

So, and then, um, you know, coming in third and fourth hand in hand, nutrition and movement. Um, as a teen, I was always pretty active on sports teams, although I wasn't. Super athletic. I like to run. Um, and as I had increased back stiffness and pain and having kids and just being life, um, I kind of fell out of those, um, those habits.

And so really recommitting, I turned 40 this [00:52:00] spring. And so my goal at the beginning of the year was to get strong, but to do that in a way that was fun and that I could stick with for the long term, um, knowing that. Those muscles are going to help provide, you know, some cushion for my joints. Um, help support, um, my, my connective tissues kind of working on those, um, and, uh, and nutrition really focusing in on a plant forward diet.

I'm, um, fortunate that I don't, um, I don't have any issues with histamine intolerance. I know that's something that, you know, might be something that those with mast cell also kind of know or recognize might be triggers Um, other foods that might kind of trigger things. Um, but really at the end of the day, aiming for the least restrictive, um, but also, uh, nutrient dense.

So plant all the variety of the colors, [00:53:00] um, getting some plant proteins in there during the week too. Um, and those healthy fats. Um, really a far cry from, um, low fat sugar replacement, uh, you know, pop tart toaster strudel breakfast, um, that I was raised on.

Dr. Linda Bluestein: Yeah. Yeah. I remember when all that sugar free stuff came out and it's like, Oh, I, even as a teenager, I was like, is this really a good idea?

Yeah. Um, um, Okay, so we always like to finish every episode with a hypermobility hack. And you've already given us so many great hacks and tips and this could be a hack related to the immune system or something that you've learned from your own, you know, conditions or something that your patients have found valuable.

Um, do you have a hack that you can share with us?

Dr. Kara Wada: I don't know so much if it's a hack, but I think a really important lesson that I'm continually Needing to relearn, and I think has been important in many of my patients [00:54:00] too, is learning to listen to our bodies and tune in to what our bodies are telling us.

So much of, you know, medical training is learning to ignore, ignore your hunger, ignore your need to go to the bathroom, ignore your cries for your body to sit down or to sleep. And so I would just say, spend that time reconnecting with who you are, what your body is telling you, because if you listen, it will oftentimes, it will clue you in to what you need.

Love

Dr. Linda Bluestein: that. Boy, I never thought about it that way before, but you're right. I mean, you know, I, now it's like, Oh, I get to go to the bathroom whenever I want. But yeah, for all those years, not being able to go to the bathroom or eat or, you know, so, so that's, uh, those are such great points. Um, so this was such a great conversation.

It was so great to, to chat with you, Dr. Wada. And before you go, could you, Tell [00:55:00] us, um, if you have any special projects that you're working on or any special research that you're doing and also where we can find you.

Dr. Kara Wada: So I have a couple things coming up. Um, this is the third year I'll be hosting the virtual Sjogren's Summit.

So I was diagnosed with Sjogren's disease about five years ago and realized that, goodness, what I learned to answer those multiple choice questions right was not the reality. I learned the reality from my fellow Shogi, um, community. So it's a two day free event where we all come together to learn, to be empowered, um, and, and advocate and grow together.

So if folks want to check that out, it's shogrunssummit. com. And then, um, let's see. Otherwise, uh, the best place to connect is probably either on Instagram or through my website. So I'm an immune confident MD. Um, formerly the Crunchy Allergist, but kind of also evolving and building that confidence [00:56:00] together, both in allergic and autoimmune, um, awareness and education.

And, um, over on my website, I think one resource that would be really helpful for this group would be, um, I took the new patient paperwork that I put together for my new mast cell patients and turned it into a little workbook to help those, one, that are coming to see me in clinic, but also those who may be going to see their own healthcare providers put their story and all their information in one place so that they can print it out and then have that to share their story.

And I think You know, the, the real keys in that at the end are what are your goals and how can I, is there anything I need to know to better take care of you? Um, and those aren't questions that we always remember to ask our patients. We should, um, and so my hope is by having that there, that if they're, you know, if your doc's quickly looking through kind of taking that information and that, [00:57:00] that that most.

I think the most important information will also catch their eyes and their hearts as well. So that's over at drcarawada. com and we'll make sure that's over in the free resources section.

Dr. Linda Bluestein: Okay. I just wanted to make sure that we know exactly where to find that because that sounds like an incredible resource.

So wonderful. Well, thank you so much again, Dr. Wada. It was so great to chat with you. And I know I learned a lot and I'm sure everyone else will as well. So thank you.

Dr. Kara Wada: Thank you so much, Linda. This has been fantastic. and I can't wait till we get to talk again.

Dr. Linda Bluestein: Wow. That conversation with Dr. Wada was so great and I hope you enjoyed it as much as I did.

I'm sure that there were so many insights and just such valuable information that she shared. And I just want to thank you so much for listening to this week's episode of the Bendy Bodies with the Hypermobility MD podcast. Please help us spread the word about joint hypermobility and related conditions by sharing this podcast and [00:58:00] leaving us a review.

This really helps to raise awareness about these complex conditions. You can find me, Dr. Linda Blustein, on so many different social media platforms, Facebook, Instagram, X, and LinkedIn at HypermobilityMD. If you'd like to meet with me one on one, check out the available options on the services page of my website at hypermobilitymd.

com. You can find human content, my producing team, at humancontentpods on TikTok and Instagram. You can also find full video episodes on YouTube at bendybodiespodcast. To learn more about the Bendy Bodies program disclaimer and ethics policy, submission verification and licensing terms and HIPAA release terms, or to reach out with any questions, please visit BendyBodiesPodcast.

com. Bendy Bodies Podcast is a human content production. Thank you so much for being a part of the community and we'll catch you next time on the Bendy Bodies [00:59:00] Podcast.