When POTS Is Only Part of the Picture | Dr. Alexis Cutchins

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If you're talking to a doctor and you're telling them about something you're interested in learning more about yourself and they tell you to stop googling your symptoms, then you have to find another doctor.

Yeah, two key components. They have to care.

Yeah.

And they have to want to learn.

Yeah.

Hi, I'm Dr. Jason Siefferman and welcome to Care Beyond the Pain. In each episode, I will sit down with a provider, a person with pain, or supporter to explore their experience and share their perspective on the pain journey. Together, we will navigate care beyond the pain.

Hi, I'm Alexis Kutchins. I'm a cardiologist. I specialize in taking care of patients with POTS and mast cell activation syndrome, vascular compression disorders, and hypermobility spectrum disorders.

Can we start with that? Cuz that that's an area of overlap that we both share.

Sure.

How did you get into the subspecialty of hypermobility?

I think that I found it from, you know, it was a process after taking care of lots and lots of patients with POTS. I realized that they all had this underlying connective tissue component and so I started learning more about about hypermobility, about EDS, about, um, you know, underlying connective tissue disorders, lipedema, and how they, um, contribute to POTS.

Hm.

So that's kind of it was a segue from POTS to hypermobility.

And then it just naturally grew from there?

Yeah, I um, I I spend a lot of time, you know, taking care of MCAS and autonomic dysfunction or POTS symptoms. And, you know, I think that without a knowledge of connective tissue and kind of the underlying joint abnormalities, pain syndromes, um, vascular issues, you can't really do that completely.

Yes, so that that speaks to one of the biggest challenges with these chronic conditions is getting a diagnosis. And and to understand what's happening, you really have to have a breadth of knowledge. So, can you tell us a little bit about what kinds of complaints patients come in with and and how you piece those together to arrive at diagnosis?

Sure. So, usually patients are coming to see me for POTS, which is tachycardia, palpitations, dizziness, um passing out, syncope. Uh patients will come see me for shortness of breath, exercise intolerance, weakness, fatigue. These are all kind of like cardiovascular manifestations of POTS. Um but usually when I first see them, I'm asking them a lot of other questions like, "Tell me about your headaches." And tell me about, you know, what kind of headaches you have and when do you have headaches and what triggers your headaches?

And I go into depth in, you know, on that pain journey. Then I'll ask them about nausea, vomiting, GI symptoms, you know, in that whole system. And then I often ask about pelvic pain, back pain, leg pain, leg symptoms, um menstrual symptoms. And so, I get this kind of overview of the entire the entire symptom scope, not just their tachycardia and their and their dizziness.

Yeah.

Um and so, once I've gotten those questions answered, I can kind of hone in on uh what I need to diagnose in that patient. So, it might be uh nothing. I mean, they might just have dizziness and that's it. They maybe they don't have any other symptoms. It's rare, but usually, you know, there's something else. And so, if they have a lot of um leg symptoms and pelvic pain, then I go down the route of looking for pelvic venous disease or iliac vein compression and pelvic venous congestion.

If they have a lot of um nausea and vomiting, then I think about abdominal vascular compression syndromes and other things or maybe mast cell activation syndrome. So, it's a lot of history taking and kind of listening to what the symptoms are exactly because there's nuances to all of these. And then kind of tweezing out what those symptoms are and then going after a diagnostic test like an ultrasound or a CAT scan or a MRI.

And what is it about our medical system in mass that you think has failed a lot of these patients?

I think that uh these patients are quite complicated. They take a lot of time. They have a lot going on. I think most people who are seeing these patients for the first time don't think about the global picture. They're thinking about their one organ system that they take care of. For instance, cardiology, they're thinking about the high heart rate. What can I do about the high heart rate so that there's no longer a high heart rate so the patient feels better.

But the reality is that the high heart rate can be a result of many things. It could be a result of chronic pain. It could be a result of mass cell activation. It could be a result of lack of blood return to the heart because of pelvic venous congestion. And so if you're not thinking about all of these different aspects, then the patient is is not going to get complete care. In the medical system as it is, we don't have tons of time to do the deep dive into all of these symptoms, right?

So we're not um you know, we're constrained by a certain amount of, you know, time slot that we're given to, you know, directly target one thing. And so uh it doesn't allow us to kind of explore all of these underlying conditions.

Yeah.

And um and I wish we had a system that did, you know, but unfortunately, it sort of takes people coming out of those systems that can take more time to really understand the global problem. Also, I think that we're not taught enough in medical school about all the symptoms that patients with hypermobility and EDS have and how they all interconnect and how a patient can have, you know, an overarching theme of one underlying condition, which may be connective tissue, mass cell activation. And that encompasses many, many different systems and symptoms, right?

And we're just not the I mean, we're barely taught about connective tissue disorders, let alone mass cell activation syndrome, POTS, like vascular compression syndromes, right? And so there's just not there's not a huge scope of knowledge.

Right.

And uh you're right. Our health care system is fairly siloed.

Yeah.

People know what they know, they stick in their scope.

Yeah.

And it's reinforced through standards of care and practice and malpractice and all of these great standards that we get to work with. And especially in academic centers, I mean I think one thing most people don't understand is that especially within academic centers, providers are siloed.

There's yeah, there's a fear of stepping outside of your little box.

Yeah, there's a lot of oversight.

Oversight.

Right.

And so that can be very limiting and and for a provider to start to learn, for a doctor to start to learn about the expanses of a condition beyond their scope. A lot of these symptoms are pretty vague, pretty nebulous.

Yeah.

They're hard to pin down. They cross body symptoms.

Yeah.

Body systems. So I mean very much like pain, which is why I think we get along so well is because I I have to approach pain the same way you approach a lot of these cardiac type complaints.

Right.

Because we really have to understand what's going on with all in the body to start to tease out what might be going wrong that's causing some of these things.

Yeah.

And to be honest, when I first heard that a cardiologist was treating POTS, my first thought was, well, that's not a heart problem. That's not a cardiology problem.

I'm like, how did this person get into this field? I want to know what, right?

Yeah.

And and so it's wonderful how you've taken this journey to really extend the scope of your understanding so that you can adequately treat all of these patients.

People come to cardiologists with symptoms that end up being attributed to POTS, right? Like my heart's racing all the time, I don't know what to do about it. Like I feel dizzy every time I stand up. These are things that that cardiologists treat. We want to make sure your heart's structurally normal. We want to make sure you're not having ischemia, that your coronary arteries all open, you know, that your heart's pumping normally, you don't have valvular heart disease. Like cardiologists love these symptoms.

But once we've ruled all those things out,

Yeah.

then the cardiologist is like, well, you don't have anything wrong with your heart, which is true. With POTS, you really often don't have anything wrong with your heart.

[snorts]

It's it's a it's a problem that manifests as cardiac symptoms, but problems are everywhere else. And so, that's the last thing cardiologists want to

take care of, um except, you know, I just happen to kind of enjoy figuring things out and, you know, being curious about stuff. I I think I like taking care of the patients that don't have an answer,

Mhm.

you know, it just keeps things interesting for me. And so, and as you do it more and more, you you develop a knowledge of patterns and you see, you know, you see patients over and over and over again and you realize that they're all very similar.

Yes.

I mean, they're different, but

They're constellations.

Yeah, there are patterns that exist that you can pick up.

Yeah.

And these are patterns that

[clears throat]

are acknowledged by seeing a lot of patients, right? Like those patterns develop when you've seen a high volume, which is what I've done. And so, just listening and and hearing people's stories, you can kind of develop these patterns in your mind and then it's easier to figure out what's going on with each one, right? But yeah, I think it was a little circuitous the way, you know, I developed this expertise, but at the same time I think the cardiologist is kind of the person who's getting these patients to begin with.

And so, why not? Yeah.

Can we jump into treatment a little bit?

Sure.

Because you do cover the full breadth of of a lot of these autonomic symptoms. Where do you start with patients?

So, I usually do some, you know, diagnostic blood work and, you know, imaging, right? And once I've done that, I um or ordered that, I usually start with the patient's most significant symptom. So, you know, if they're having a lot of fatigue, I kind of I target that. Maybe I should target the mast cells a little bit more or I'm looking for mast cell activation syndrome in that population. If they're coming in with um like tachycardia and really like a very high heart rate when they stand, then I'm going to give them something for that.

Um I you know, across the board tell patients for POTS at least to increase sodium, increase water intake, and use compression. This is pretty standard of care and most of the patients that come to me have already been told this before and have already tried this. So, when I say I start with like a beta-blocker or a funny channel blocker like Ivabradine, it's because the patient's already come in kind of teed up with trying all of the non-medical interventions, right? So, um so I do try some medications, you know, there are medications that lower heart rate like I said, beta-blockers, Ivabradine, calcium channel blockers.

There are medications that increase blood pressure, which also help. As you increase blood pressure, you lower heart rate. So, that's like your fludrocortisone, midodrine, you know, desmopressin helps with volume volume expansion. So, um I take the approach of kind of getting the heart a little bit stabilized. Um I have patients who told me who have told me that their mast cell symptoms got better once they were no longer tachycardic. You can have this feedback loop of like high heart rate triggering mast cells and then the mast cells are degranulating and causing more high heart rate and there's this, you know, system.

And so, if you can slow things down a little bit and just get everything a little calmer, sometimes other things calm down as well.

How do you tease out the chicken or egg in that scenario?

It's you know, I think the chicken I think the egg or the chicken. I don't know

That's the problem.

which which one it is, but I do think that MCAS is kind of at the root of a lot of pots. I think of pots as more of a symptom

Mhm.

of um venous disease and MCAS combined and that is a result of underlying connective tissue disorders.

Mhm. I I think of pots as dysautonomia.

Yeah.

And that has a lot of presentations.

Yeah, so I think dysautonomia is driven by MCAS. Like patients come to tell me come tell me that they are sweating excessively or they have weird heat and cold intolerance and if I start treating their mast cell activation syndrome, that improves.

And and the tachycardia gets better, too?

Yeah.

So, then the mast cell was causing the tachycardia. But for others, I'm guessing not the same patients, when you treat the tachycardia, then the mast cell gets better?

It can. Yeah. But there's also um the tachycardia that exists from venous pooling, which is not a dysautonomia, it's a normal response of the autonomic nervous system to a a drop in blood volume.

Mhm.

[clears throat]

Your body is compensating by increasing the heart rate to try to get more blood flow to the brain. And so, if you're pooling blood in your pelvis and your lower extremities, then that's going to make you have POTS symptoms. And so, that is also something that needs to be targeted either with compression or with volume expansion or with, you know, more aggressive treatments of pelvic venous disease like stenting the iliac vein or treating the lower extremity veins with GSV ablations, you know, that kind of thing.

So, really understanding what's driving the POTS.

Yeah.

Yeah, and it can be multifactorial, for sure.

Of course. Like we see patients with craniocervical instability causing POTS quite frequently.

Yeah.

Uh and of course, they may also have mast cell activation syndrome and venous compression.

Right. And the CCI can can trigger the mast cell and, you know, vice versa. The degranulated mast cells can cause worsening instability.

What can't trigger mast cell?

I know. I I think everything does.

Going outside triggers mast cell.

Yeah. Yeah.

You know, temperature fluctuations,

Yeah.

mood changes,

Yeah, barometric pressure shifts, yeah. The whole thing. Stress. Yeah, of course.

We're really getting into the nuts and bolts of these diagnostics, which [clears throat] I was I thought it was going to be more about you, but well, talk about the mast cell a little bit. How do you think of mast cell? Like in in terms of how it comes to be. And maybe I can explain how I think of it and then you can elaborate on that.

Yeah, tell me what you think.

So, you know, we learn about primary mast cell activation syndromes, which are generally diagnosed in kids who have, you know, anaphylactic reactions uh to multiple things. They carry on EpiPens their whole lives. But then after COVID, especially, we started seeing a lot more mast cell activation syndromes that weren't quite that severe in adults.

Mhm.

And of course, we had patients before COVID that had these symptoms, but it was much more prevalent afterwards. Uh and so, I've generally come to think of it as being a secondary process either due to a primary autoimmune condition cuz we'll see it in a lot of patients with Sjogren's, psoriasis, RA, um some post-infectious state like Lyme, Epstein-Barr, or COVID, or a primary immunodeficiency. We see lots of patients with primary immunodeficiencies that might actually be pretty mild and don't declare themselves as immunodeficiencies until you ask and they say, "Yeah, I have recurrent ear infections as a kid."

Right.

And then they have some mast cell activation syndrome which I think of as almost a rebalancing of the immune system almost like with the coagulation pathways. When one part's not working another part becomes hyperactive.

Yeah.

Um how do you think of mast cells?

Yeah, so maybe it's I agree with all of that. I think it's it's intimately involved with, you know, our immune systems and our allergic responses and, you know, and it could be triggered by viruses, can be triggered by, um you know, many things. I think that there is a primary component to mast cell activation syndrome. Most of the people who have mast like these new allergies post-COVID infection, let's say, had some sort of allergy as a child and were in some sort of allergic or had childhood, you know, recurrent infections or there was something else there.

And um and so I think it could be aggravated this primary process can be aggravated by in many things and and can blow up in a way that hadn't been before.

A sensitizing factor.

Yeah. Yeah, and so there's still something there that's making those mast cells in in the body of someone who has mast cell activation syndrome go haywire.

Mhm.

And I think that's the underlying connective tissue disorder and the the alignment of collagen in the cells. Which there is this really great um kind of review paper on, you know, the their someone's theory about why MCAS and EDS kind of coexist and the thought process is that the the way that collagen is lining up in the mast cell is is very disordered in patients with EDS. It's kind of like like broke like spaghetti that you like drop on the floor versus um in a normal cell where it's highly organized and very much like a fence post.

And so in those cells that have that that significant organization, the the granules, the vesicles that are inside the mast cell are not going to be as easily triggered to explode.

Interesting. So it's like

But then the ones that are like in this matrix that's kind of loosey-goosey and isn't really organized, they could be a little bit more easily triggered.

Interesting.

And so um I think that this is very real because I think that you know, I think that mast cell activation syndrome drives a lot of complex chronic illness and chronic fatigue, long whatever you name it, Lyme, COVID, EBV, CMV, you know, um and and those patients who develop those things, like long COVID, chronic Lyme, etc. have a predisposition for the syndromes. It's not everyone who contracts COVID.

Of course.

So if we look at all comers who get COVID infection, we're not seeing long COVID in every single one of

Of course.

So what's different about the ones that are getting long COVID? I think they have mitochondrial connective tissue disorder that is predisposed predisposed in their mast cells to not be as structurally sound. And that's what's, you know, making that happen. Now, these patients also have immune dysregulation and that we see in EDS patients. We already have we have some emerging data about, you know, immune deficiencies in patients with EDS.

Yes.

And so uh there's a huge overlap there. And then the autoimmune is kind of this hyperactive immune system, also seen in patients with EDS.

Yes.

And then there's the component [clears throat] of MCAS that drives this like pseudo autoimmune state. Right? And so MCAS can be the primary driver of sort of a a diagnosis of autoimmune disease that may not actually be

Yeah, we see lots of joint involvement, soft tissue inflammation.

Yeah, in something like primary autoimmune.

Correct. And not not a destructive inflammatory process, just inflammatory.

Right. And so it's So and and that's very real, too, but treating the end cast seems to help you know, with those symptoms.

So So with mast cell treatment, I mean, generally the primary approach is just lots of antihistamines, cromolyn, maybe Xolair, Dupixent.

Right. Yeah. Yeah.

is there any way of actually treating the primary mast cell process?

You know, that's you know, an interesting question, and I think we're still learning, right? But I think there are a lot of things that you can do that aren't just antihistamines. So the problem with antihistamines is that they just block histamine receptors.

Yeah.

So and there's thousands of mediators, hundreds of mediators coming out of the mast cell that are not histamine.

Yes.

And so we're trying to also stabilize the mast cell. Um so when you think about a primary dysfunction of the mast cell being this this like you know, disordered interstitium or not interstitium, but this disordered kind of cellular matrix. Um the things that keep that that tighter um are, you know, like lowering things like matrix metalloproteinases and, you know, other enzymes that kind of destruct that structure. So there are medications that do that like metformin, doxycycline, exactly.

Interesting.

And so there are some medic- If you want to get to the root of the problem, you know, then you could hypothesize that giving medications like that are actually stabilizing mast cells, which they do. Both of them have data for mast cell stabilization.

Interesting.

And so that's kind of like more of a root cause approach.

Yeah.

Um but then there's others like NSAIDs stabilize mast cells, aspirin, Celebrex, you know, that kind of stuff. Um and then you've got your GLP-1s that uh do great things for anti-inflammatory, stabilize mast cell stabilization.

how?

Well, there's GLP-1 receptors on the mast cells. And so, they target the mast cells directly, but then they also target indirectly inflammation that's caused by insulin resistance and glucose intolerance and fluctuations in blood sugar. And so, they're going to help, you know, quite quiet down that inflammatory response at the same time.

Mhm.

But, they definitely do something to stabilize the mast cell, and I think it's it's an interaction with the GLP-1 receptor on the cell itself.

Interesting.

Yeah. Theoretically. So, there's there's a lot of different things. There's I think that the Xolair, Dupixent, Rapcedo kind of biologic area is fascinating, and um I think they're useful, but not necessary in everyone, and there's a lot of ways to kind of treat MCAS before you get there.

And they're not useful in everyone.

They're not. Sometimes they don't work. Yeah. And so, or sometimes they just work partially, and you have to kind of pick up the the rest of it with other stuff.

Mhm.

Yeah.

Uh can we talk about low-dose naltrexone a little bit?

Sure.

What's your approach?

I love low-dose naltrexone for pain and for fatigue. Um I use it often. I prescribed it today for a patient who um I'm hoping it'll help her. But, uh I I start I mean, my approach is I start at 0.5 mg. I tell patients to take 0.5 mg in the morning daily for 2 weeks. If they have no improvement in symptoms whatsoever, then they go up to 1 mg daily for 2 weeks. If they have no improvement in symptoms, then they go up again.

And we do a a 2-week trial at each dose, but until I tell them stop at 4.5 mg. Um I like this approach because some of my patients have a really good response at let's say 1.5 mg, and some of them need 4 mg. Some of them find that 0.5 is too much, and we need to half that or even go lower. So, there's a huge spectrum of response to low-dose naltrexone, and so, usually, I think, you know, some people say you have to be on it for 3 months before you're going to see a benefit.

I I I don't see that in my population of patients. I tell them if you haven't had any benefit in 2 weeks, then we're going to go up to the next dose. Usually they'll see a benefit once they hit the therapeutic dose, they get the benefit and then we stay at that dose for 3 months. You know, and see if there's more improvement or if you have a you know, if you increase your benefit from it. And and then we could try going up again, but often times I'll go up higher and then the effect wears off or they don't have the same effect.

So you want to make sure you hit that therapeutic window. I have a fraction of patients who get better with each incremental dose. But I don't find that that's that common. I find there's usually like one dose for each patient. I don't know how do you What do you think? Is that crazy? Am I Am I totally off base?

I think [clears throat] I think this is like a lot of other medications where there's a Goldilocks dose and you just have to find it. But knowing where that is for each patient is difficult and it takes time to find.

Right.

Uh you know, the GLP's can be like that too a little bit. I'm I'm curious for those patients who are hyper reactive or hyper responsive, uh you know, it happens with the GLP 2's even at a very low dose like half a milligram, they can't tolerate it. What do you think's happening physiologically?

[sighs and gasps]

It's a good question. You know, I have some I have these very very hyper reactors, right? They they require infinitesimal small doses of every medication and when that exists, when I'm starting a GLP 1, I'll start at literally the lowest possible dose I can get in them. Um I think that there are differences in metabolism in these patients in this population. Some of them are like normal standard metabolizers. And and this could be for for several different drug types, right?

So you have your hyper metabolizers, but for one group of meds and then they slow metabolize another group of meds and then you've got the ones that just hyper metabolize everything and everything wears off after 2 days. And then you have the ones that don't metabolize anything and it's lingering their systems forever or they they're very sensitive to the smallest dose and and I don't I think there's a genetic component to it. Um I I don't know if I could name

Mhm.

what's going on pathophysiologically with them.

curious if you thought there was a mast cell reaction or anything to the Like we see it with cromolyn, right? So whenever I prescribe cromolyn, I I have patients start at a very low dose to sip throughout the day and I warn them in advance they might react. If they do, that actually means you need it. Uh but we need to load you up with more antihistamines and slowly introduce that dose and let you gradually build it up.

Yeah, so that in in initiating MCAS targeted drugs, which I guess you could say a GLP-1 would be one of those. Although usually they were you know the reaction I'm seeing from a GLP-1 is going to be like a gastroparesis, constipation kind of symptom. So it's like literally they're they're hyperreacting to that medicine.

Yeah.

So we start we do the same thing with cromolyn. We start at 25 mg taken throughout the day for the first four first days and then we slowly titrate it up. Um and usually that flare in symptoms goes away after 4 days and then they can bump it up again and then they flare again and then they bump it up again and as they've gotten more cromolyn on board, they can make take bigger steps

Yeah.

to increase the dose. Um and so and that happens with other mast cell targeted medications. So like ketotifen will make you tired before it helps with the fatigue.

Mhm.

Um I've seen this with Pepcid where it can give you reflux and you have to kind of push through the reflux before it helps with other systemic symptoms.

Yes.

And so um it's not all mast cell targeted therapies, but there are some that definitely have that weird hiccup. But I don't I don't see that with the GLP-1s. I don't see this like push through and it's going to get better effect. I usually just continue to lower the dose.

Yeah, no, no, I'm the same.

until they can tolerate it at all.

Yeah.

And then you know, we see what happens.

Yeah, I explain that the mast cells are bratty. They don't want to be subdued.

Yeah, no. Yeah, they they are very finicky and difficult to treat, for sure.

And can you speak about some of the other conditions you you see and treat?

Yeah. Uh where do you want me to start? Pelvic venous disease?

Uh yeah, let's talk about it.

So, um I you know, in the my population of POTS patients, I was seeing lots of venous insufficiency and lower extremity venous disease. Um I think it is stemming from the abnormality in connective tissue and how closely that relates to the veins themselves, cuz the veins are primarily built of collagen and elastin and they don't have a lot of smooth muscle versus the arteries, which are smooth muscle-based and so they don't really have this shift that occurs when you have a damage to the collagen and elastin fibers.

So, um the treating the veins was helping, doing GSV ablations was helping my patients, but um some of them weren't getting a good result from that, so I started looking at the pelvic veins. And um this is work that was being done by Steve Smith and Peter Rowe, who are in the space, who are you know, great. Um so I kind of like took off of their ideas and started looking for iliac vein compression in my patients and asking about pelvic pain. So, as you know, these patients have a lot of pelvic pain and um they could have endometriosis, they can have fibroids, they can have

causes.

So many things, right? Um and one of the causes of their pelvic pain is in fact congestion of the pelvis pelvic veins, right? So, um compression of the left iliac vein we see in about 80% of our patients with POTS. And um I believe that opening up that iliac vein helps with venous return, helps decongest the pelvis, there's more blood flow back to the heart, which means there's more blood flow to the brain and you have fewer POTS symptoms. You also have improvement in pelvic pain or pain with intercourse, low back pain that is orthostatic in nature, all of these things improve when you fix the pelvic congestion.

So, we look for that in all of our pretty much all of our patients because when I ask about pelvic pain, they say yes. I mean, I'm not looking for it in someone who has no symptoms whatsoever of pelvic venous disease, but most of them have it. Right.

And we will see the May-Thurner without pelvic pain.

Yeah.

Uh but the the question I have is how do we know which ones need to be treated? Because we've sent plenty of patients with iliac vein compression for stenting, and they didn't get any better.

Yeah. Um I think that they do get better. I think they they that you have to ask the right questions, and you have to make sure all of their venous disease is treated. So, they have if they have concomitant nutcracker left renal vein compression, and that is still there, then they're going to continue to have orthostatic intolerance. If they have um lower extremity venous disease that has not been treated, then they're going to continue to pool in their legs, and they're not going to have complete revascularization or improved flow back to the heart.

So, you can stent the iliac vein and not have POTS symptoms improve. Usually, pelvic pain improves to a certain extent. There's some symptom that gets better, low back pain. For instance, I had a patient who was sent for an iliac vein stent. She came back to see me, and she said she felt no different. I was like, "Wow, that's interesting." And I looked at her imaging, and she had all of these paraspinal collaterals. I was like, "Did you have back pain?

It looks like from your imaging that you would have had back pain." She's like, "Oh, yeah, I had horrible back pain." I was like, "Well, is that gone?" She's like, "Yeah, though." "That's gone."

Okay, well, that's great. And then I was like, "Well, what what hasn't gotten better? You said you feel the same." She's like, "My fatigue is exactly the same."

Yeah.

I was like, "Okay, well, um tell me about what you're doing. You know, like, what are you doing now that you're out of this procedure, and you don't have back pain anymore, and you know, what's your day like? How is it compared to what it was before?" She's like, "Well, I'm exercising every day for an hour." I was like, "Wow. Were you doing that before you got the iliac vein stent?" She's like, "Oh, no, not at all." I was like, "Okay, well."

She's like, "I just felt like I could go back to doing what I was doing before I got sick." I was like, "Well, that's not going to work because you have post-exertional malaise, and you have not You have to recondition. And you can't just hop back into exercising for an hour a day when for 3 years you've not been exercising." That's impressive. So, she came to see me, and she said she felt no different, but clearly she had major benefits from this procedure.

And so, I think that sometimes people are hoping that they're going to be cured, and they're not. And I'm not promising a cure to anyone. Um I think it's one factor in many, many factors

Yes, yes, yes.

of getting better. And I think these patients, a lot of the time, not only have real vein compression or or lower extremity venous disease, but they have jugular venous compression, and they have CCI, and they have increased intracranial pressure, and sometimes those things get better with decompression of the pelvis, but sometimes they don't, and you have to go after other areas, right? Or their mast cell activation syndrome is isn't completely treated.

Whatever.

And so, I think it's a it's good stepping stone stone, and in some people it's like a major change. I think those are the people who really have their mast cell activation syndrome treatment dialed in. They've been treated for their POTS. They've been getting better. And then you stent their iliac vein, and they're like, "Oh,

Yeah.

now I feel great."

What you're describing is a complexity that we see in pain as well. And of course, in patients with hypermobility, there's not just one system that's having issues. Multiple systems that are having issues. They often overlap. They feed into each other. And if if a patient has three things causing eight out of 10 discomfort, and you take one away, they still have two things causing eight out of 10

of 10 discomfort. Yeah, exactly.

So, it it

You have to check the leg.

Yeah. And sort of framing it that way, understanding that that way you described, uh you know, the venous congestion, just stenting the the May-Thurner is not enough. You then have to go and ablate the veins and do all the other work around it. And if there's any other compression, you also have to That's how I think about musculoskeletal issues, right? So, when I see a hypermobile patient, and they have CCI, I I can't just start by treating the CCI, right?

I have to get their shoulders stable. Then I have to fix the neck, get the neck more stable, and then we can go up to the CCI.

Yeah.

Because without that foundation, all of these things are pulling on the CCI, which is part of the reason why it's a problem in the first place. So, if we don't correct the foundation, it's hard to get some durable relief.

I think that what's harder about the venous compression syndromes is where do you start, and what do you do first, right?

You can't see it so easily.

Yeah, it's hard to know what is the major contributor, or what, you know, what's going to be that ultimate fix that ends up, you know,

Yeah.

creating a level of improvement that is tangible.

And if it's the nutcracker, most people don't want to do that.

If the nutcracker is hard to treat, yeah, you have to have major surgery for it. So, I I like to avoid it at at all costs.

Of course.

And so, if we can avoid it, you know, we do. Um there are other things we can go after first, right?

Right.

And then and then you get to a point where it's like, well, I guess we have to do the nutcracker.

No, it's the same approach for a lot of things, right? Uh it it's hard to prove that some things are causing pain. Like, even we do splanchnic blocks, right? Or a renal hyper block. It doesn't really prove that the nutcracker is the source of the pain.

Yeah.

So, it's hard to convincingly say we should do that.

Yeah.

You know, I mean, I have a lot of young patients who have iliac vein compression, and I can't tell them in advance of getting the stent if it will help their pain or not. And they don't necessarily want to commit to a stent, the surgeon doesn't necessarily want to commit to a stent, and they're looking at me for an answer.

I know.

And so, my approach is, you know, let's look at everything else that can be explaining that that pelvic pain. If we've taken everything else off the table that we can reasonably take off the table,

Right.

it'll make it easier to decide.

Yeah. I think that's reasonable. Well, I have a question about um your, you know, prolotherapy, and kind of where you're segueing into other other injections.

Sure.

Like, what's what are your where are we at?

How how do we line things up?

Yeah.

So,

[clears throat]

when we see a patient with a hypermobile joint, my first question is is there some underlying inflammatory process that we might upset by using regenerative medicine?

Mhm.

So, if there's an uncontrolled or unidentified autoimmune process or mast cell activation syndrome, they will either flare or not respond.

Mhm.

Uh and the non-responders are often more difficult to identify and we can go off on a tangent about, you know, seronegative inflammatory conditions like seronegative Sjogren's, seronegative RA can be really difficult to diagnose in young hypermobile patients because the disease process hasn't declared itself with joint destruction yet.

Yeah.

But yet the body is constantly attacking its own collagen. Uh so, I I may do an injection like prolotherapy or PRP to stimulate new collagen production, but it's almost like that fresh newly produced collagen is just a feast for their immune system and they get no benefit from

Mhm.

prolotherapy. And I it took me a while to recognize this, right? Because I would be treating these patients, they wouldn't respond to treatment, we would escalate, um and nothing was working, but then eventually the autoimmune process declared itself. They would have an inflamed TMJ or something would get them to the rheumatologist, they'd get diagnosed, they'd get on hydroxychloroquine or some treatment for an autoimmune process, and then they would be feeling better except the hypermobility persisted. So, we would re-trial the prolotherapy and then they would respond.

Mhm.

And it was just interesting it was the controlling the autoimmune process that actually allowed them to respond. So, the the hypothesis working backwards from that is that their autoimmune process was actually degrading the collagen,

Yeah.

possibly contributing to some of the hypermobility, but definitely preventing healing new collagen from forming. So, anyway, I start by looking, is there a systemic inflammatory process? And if we have, you know, reasonably if there's not, then we'll go ahead and trial prolotherapy.

So, when you say that, are you looking at like CRP, sed rate, or is it more granular than that?

Mostly history based.

Yeah.

So, I'm asking that, you know, do you get joint stiffness? Do you get fatigue? Do you I mean, a lot of these overlap, so it's kind of difficult. Any autoimmune conditions in your family? Uh if there's any suspicion, I'll have them trial a course of an anti-inflammatory for 2 weeks, something like Celecoxib for 2 weeks, just to see if they feel better because generally speaking, hypermobility doesn't cause inflammation, right? It'll cause cranky joint pain, but not inflammatory joint pain.

So, it's generally not responsive to anti-inflammatory. So, if someone has an underlying autoimmune inflammatory condition, they'll generally do well with an NSAID. Um and when I say do well, I mean like 60% global improvement. Things that they weren't thinking about, things that they had acclimated to cuz they've been living with it for years, but oh yeah, I could wake up in the morning I could get out of bed, you know, I didn't my back wasn't stiff in the morning. Things that they had just normalized that they weren't even reporting to me as symptoms got better.

So, I'm looking for things like that. And then on the mast cell side, of course I'm asking, do you get any puffiness in your joints? Do you have certain food intolerances? Do you have multiple allergies? Did you have eczema or allergies as a kid? Do you get hives? Things like that, right? So, we can trial a a prolotherapy injection, and we'll see what happens. So, prolotherapy is dextrose. I generally use 20% dextrose because it will give me the most uh stimulatory effect without causing uh undue pain.

So, at 25% dextrose, that's when you get a neurolytic effect, which has a role. So, if you have an end-stage osteoarthritic joint, uh you know, 25% dextrose can be really helpful for reducing pain sensed in the joint. But, if we're just trying to uh strengthen the ligaments, joint, shrink the capsule a little bit, 20% dextrose is pretty good for that. So, we'll trial that uh usually with lidocaine, and we'll see what happens. Um I explain they'll be sore, stiff, achy for 2 to 4 days.

That's that inflammatory cascade triggering a healing response, and then it takes about 2 weeks to notice if it's going to work or not.

And do you tell them not to take Do they stop their hydroxychloroquine at that time?

What about their Cele- like Celebrex or their NSAIDs?

only thing they would stop would be an anti-inflammatory. Uh if they're on a steroid, generally we wait until that steroid course is over. Uh and if they're on an NSAID, they just they stop the NSAID. If it's someone who's dependent on an NSAID, I mean, that then that probably means there's an underlying autoimmune process, otherwise they wouldn't be on an NSAID in the first place.

Yeah. Or mast cell activation syndrome.

I I'm I might be more of the belief that the NSAID is helping an underlying inflammatory process that's not mast cell based.

Yeah, I don't know.

Exactly.

Uh but absolutely, if they have mast cell and it's not controlled, um and it's only controlled by an NSAID, I would be suspicious that it's maybe secondary mast cell to an autoimmune condition.

Yeah, but I have patients on aspirin daily, for instance, for their MCAS.

Like low dose or full dose?

Both. I mean, I start with 81, but I have some patients up to 350 twice a day or or, you know,

Okay.

And so, 325 twice a day, 650 twice a day, you know, higher doses. And um and that's, you know, helping with their flushing and helping with their um their hives and their like allergic mast cell and their pain and, you know, other but mast cell mediated stuff.

Interesting.

Mhm. So,

I I would double down on the rheumatologic investigation.

Yeah.

before because I we would have to stop the aspirin. If it If it's a baby aspirin, that's fine. But for full dose aspirin, it's it's going to deactivate the inflammatory cascade.

Yeah.

So,

Yeah, you want that active or your therapy is not going to work.

Yeah. Yeah. So, I'll see them back at 2 weeks after the prolotherapy. If they didn't flare, amazing. Great. Do they feel any better? If they do, amazing. But not everyone feels better after the first injection, you know, I'll I'll hold up my hands and like mimic the shoulder joint. And I'm like, if your shoulder's down here and we move it up to here, you're not going to notice much functional improvement, right? We're going to have to get the shoulder up to here until you really appreciate a meaningful change.

Yeah.

But, you know, at least while it was numb, did you feel what some that somewhat better? Because when I when we do the initial injection, I'm pretty much filling the joint with fluid, which gives it pseudo stability, right? I'm filling that dead space in the joint, so it'll feel stable. Especially with the sacroiliac joints in the hips, when they bear weight, they'll feel more stable. They'll feel the alignment shift.

Yeah.

And it'll be meaningful. They're like, "Oh, yeah. That's how it's supposed to feel."

Mhm.

Uh and and that's that's usually the indication that hypermobility is the source of that specific problem. I mean, I can go off on a tangent and you know, if we're diagnosing pelvic pain, pudendal neuralgia, for example. Pudendal neuralgia can be downstream from the hips, it can be downstream from the sacroiliac joints. If hypermobility and of either of those joints is the source of strain on the pudendal nerve, if we fill those joints with fluid, it'll stabilize them. And that will release the tension on the pudendal nerve, so the pudendal neuralgia will go away.

Or at least dramatically lessen. Their sitting tolerance will improve. So, I'll also just fill a joint with fluid diagnostically to determine whether or not hypermobility in that joint is a reason for a downstream problem.

Yeah. Yeah. Makes sense.

So, they come back 2 weeks after the prolotherapy. If they notice some improvement, or if I notice some improvement, or at least they didn't flare, we'll usually do a second injection. And then after that second injection, the vast majority of people notice some improvement. If they don't, and I don't notice anything on my exam, then I'm questioning, is there an autoimmune process that we've been ignoring? Uh and you know, there has to be a couple of data points that point in that direction uh for me to give that due consideration.

Uh otherwise, we go on to platelet-rich plasma, PRP. That's where we blood Draw your blood, spin it down, we get the platelets, we inject them. They stimulate a healing response through a completely different cascade. And some patients that don't respond to prolotherapy do respond well to the the PRP. The way I think about the two in terms of their effects on the joint, the PRP is generally better for healing structures. So, if there's a tear, a labral tear, a meniscal tear, uh tendon rupture, something like that.

Maybe not a full rupture, but a tear. Uh PRP is much better for healing those things. It's not as good for tightening. The dextrose seems to be better at tightening.

Okay.

So, my general approach is to use the dextrose to try to tighten the joint to normalize range of motion. And then if they are still having pain from meniscal tear, labral tear, something like that, then we would use the PRP to heal that. Doing it the opposite direction is what's commonly done in the outside world. Um but if you have a hypermobile hip with a labral tear and you heal the labrum with PRP, it's not going to stay healed because the hypermobile hip is just going to tear it again.

Yeah.

So, I try to fix the stability first.

Yeah, makes sense.

Now, we're actually submitting a proposal for a study to use doxycycline for hypermobility. Um because the benefit you mentioned in term of mechanistically how it works, but then also it's used in other areas of the body like for pneumothorax. And people with hypermobility also get spontaneous pneumothorax, right? So, uh can it also be used in a joint? There's some data to suggest that, you know, it's safe and reasonable. Um so, we are actually getting IRB approval at the moment to start a study where we will begin with the prolotherapy, escalate to the PRP, if that doesn't work then escalate to the doxycycline.

And we'll see where patients find the benefit.

Yeah.

And they'll have options after two rounds of each injection if they want to switch or move on to the next. Um and then the final tool that we have is hyaluronic acid. So, we'll use hyaluronic acid for osteoarthritic joints. You know, it's FDA approved for osteoarthritis of the knee, but I will also use it in sacroiliac joints, hips, shoulders, uh any I'll put it in the TMJs. Basically, any joint where there's significant joint degeneration from an autoimmune inflammatory process, it's very helpful there.

But also just a hypermobile joint. So, if someone has a hypermobile sacroiliac joint and they don't respond to regenerative medicine and they don't want to go for a sacroiliac fixation procedure, right? They don't want surgery to fuse the SI joint, I will try filling it with hyaluronic acid. So, the hyaluronic acid is inert, it doesn't cause any inflammation, it stays there for about 6 months. And if we can put enough volume in the joint to stabilize the joint or at least improve the stability of the joint, it may reduce their symptoms.

I think it's very needed in this population for sure.

Yeah, I'm eager to get the study out there because there's no study looking at regenerative medicine for hypermobility spectrum or EDS, only four joint sprains, post-traumatic things like that.

Yeah, yeah, yeah.

So, if patients want to come work with you, how can they find you?

Um well, they can go to my Instagram Dr. Cutchins at Dr. Cutchins or my website cutchinscvm.com. Uh we are located on 60th Street between Madison and Park and um happy to see people.

Amazing.

Yeah.

And just as a final word, what is your message to all of those patients who have been through the ringer with hundreds of doctors and don't have good answers and they maybe are afraid to go try another one?

You know, I get asked this a lot and it's kind of it's hard to say, you know, you got to keep trying, but I think you do. There are people out there who really care and who really want to help patients. And even if they don't have all the answers and all the knowledge and they're not experts in POTS, hypermobility, MCAS, if they're willing to listen to you, read a paper that you bring to them, uh you know, if you ask them to look into something and they're willing to do that, then that's someone you should stick with and try to work with and try to get, you know, more um more help from.

If you're If you're talking to a doctor and you're telling them about something you're interested in learning more about yourself and they tell you to stop Googling your symptoms, then you have to find another doctor.

Yeah, two key components, they have to care.

Yeah.

And they have to want to learn.

Yeah. Yeah. So, I I think there there plenty of those doctors out there, they're just a little harder to find.

Yeah. All right. Well, thank you so much for joining us.

Thank you. Thank you. Loved it.

Thank you for joining us on another episode of Care Beyond the Pain. The pain journey is rarely a straight line. To learn more about how to navigate it, you may visit our website manhattanpainmedicine.com or read our book Pain Answered found on Amazon. Until next time.