SIBO and Hypermobility Syndromes with Dr Alena Guggenheim - Part 1

Dr Nirala Jacobi:

If you're struggling with chronic SIBO and you're looking for your underlying cause and just can't seem to find it because let's face it, it can be complicated, this episode might be for you. Because I am talking with Dr. Alena Guggenheim, an expert in hypermobility disorders. Hypermobility disorders such as Ehlers-Danlos syndrome can be associated with relapsing SIBO and are not uncommon in the general population. Dr. Alena Guggenheim is a naturopathic physician and she works as an assistant professor at the Oregon Health and Science University where she specializes in the care of children and adults with chronic pain and joint hypermobility disorders.

Welcome to the podcast, Dr. Guggenheim. It has truly been years in the making and waiting that I get you onto the SIBO Doctor Podcast. So thank you so much for taking your Saturday afternoon to talk to me and to talk to our listeners about the very important EDS or Ehlers-Danlos syndrome, and how it connects or relates to irritable bowel syndrome, SIBO, and gut issues in general. And yeah, we've known about this for a while in the SIBO community, so it's just so wonderful to have your expertise on the podcast. Welcome.

Alena Guggenheim:

Thank you for inviting me. I feel like there's all these little inroads and cracks that we can kind of start to see how important connective tissue is. And I think more and more the patients with chronic recalcitrant GI issues were starting to recognize more in those cases that we're unsure why they're not getting better, what are we missing? And we kind of start to think about the bigger context, which is literally what's making up the human being that has the problem as being important. Because I think, well, first of all, if you go into PubMed and you put Ehlers-Danlos in the search term, you'll see and you can look at it by year, it's like nothing, nothing, nothing. Bam. And every year, the number of published studies is growing exponentially.

When I first started to get interested in hypermobile connective tissue disorders, primarily that first touch with a provider that would finally kind of start to put it together, that maybe connective tissue was part of the problem, was usually in orthopedics, an orthopedic clinic, sometimes with a physical therapist, sometimes with a chiropractor. But it was really being found and finally started to be acknowledged or questioned really from that musculoskeletal perspective, the patient who was going in for their third shoulder stabilization surgery or something like that. But that's shifting and that's changing, and I think this is the perfect place to be talking about gut health and SIBO and IBS is the perfect place to be starting to have that little crack that you can peer in and be like, gosh, what's happening behind the curtain? What's happening in the bigger context of this patient? So this is the perfect place.

Nirala Jacobi:

And because of your work in this field and your presentations at the various SIBO symposiums, I do feel like we have had a leg up on understanding and perhaps helping people to get diagnosed earlier. Because we do see these patients that have these relapsing SIBO situations, and without understanding anything about connective tissue, I don't think I would've put those pieces together. So I do want to thank you for your contributions to this field. So let's kind of dive in. Let's begin with getting a good sense of what are we actually talking about with hypermobile EDS? I know there are lots of different or several different subtypes, but what is EDS? And then we can go into the different presentations or symptom pictures that we can expect with EDS.

Alena Guggenheim:

Great. We'll kind of start with the basics here. So I think one of the challenges is that the nomenclature and the diagnostic criteria, it seems to be kind of in a constant flux really since the '90s. So providers, depending on when they trained, if they got exposure to it, it could have been two whole diagnostic nomenclatures ago. So the most recent rework happened in 2017, and they took the subtypes that were previously seven, they expanded it to 13 different types. The majority of those 13 subtypes are quite rare. We're talking one in a million, one in 500,000, sometimes even less than that. There's a few subtypes that they've identified in three individuals. So the buy in a way, the most common subtype is what got renamed the hypermobile EDS. Previously it was referred to as EDS Type 3. Then it went through a rework and it was EDS hypermobile type.

Now we have semi-officially, probably going to change, who knows, this year, I don't know, to hEDS, hypermobile EDS. And the diagnostic criteria actually made it a little bit harder to get diagnosed. So they wanted people to be hitting a threshold of a certain number of abnormal connective tissue findings. So it's not just about having hypermobile joints, it's about having this wider, I call it... I joke with my patients, I said, "I'm going to go on a connective tissue hunt, and we're looking for multiple signs that you're made out of a different brand of clay." It's not just being bendy. So we're looking at the palate, and we're looking at the skin and scars and the feet and really the anthropomorphic measurements or arm span or something that you might put on it an echo.

And it's basically this list of 12 things. And patients need to have five out of those 12 little check marks of things other than being bendy, combined with either a first degree relative or chronic pain or chronic joint instability. And sometimes patients can feel frustrated because they're like, gosh, I'm a nine out of nine on the Beighton score. I have really bad pain. I've had lots of joint instability and I've got these four signs. So now I don't have EDS. And currently we call that a hypermobility spectrum disorder. And what I really try to stress with people, and this has been validated in multiple studies at this point, that whether somebody meets hypermobile EDS or they meet hypermobile spectrum disorder, that sort of arbitrary line in the sand of having four versus five signs of abnormal connective tissue, it just doesn't predict how much symptoms they're going to be carrying with them either from a musculoskeletal perspective or their SIBO or their headache.

We see lots of headache disorders in this population. We see a lot of GI disorders, we see a lot of psychological symptoms. And whenever I bring up the overlap with psychological symptoms in this population, I always have to do a hard stuff and say if somebody has had experiences in their body that are unpleasant, is a polite way of putting it, all the way to really quite miserable and debilitating, but they look really normal and healthy on the outside, and they are kind of perpetually labeled a hypochondriac or they're labeled a symptom extender or they have amplified pain, and they start to hit more closed doors in their medical care journey, I think that that has big psychological impacts. If you know that there's things wrong and you're not going to get care for them, having anxiety about your health is actually pretty... That's an in appropriate outcome to not having your medical needs met.

There's also the straight up physiology of these things. I think we've shown pretty well that like IBS and SIBO are not psychological disorders, which is great, but we thought that, and many providers still think that, that these are a psychological problem. And if you just get a good therapist and do cognitive behavioral therapy, your IBS will go away. But we know it's so much more complicated than that. We've got obviously the biome, we've got the gut associated lymph tissue. We start sprinkling some mast cells de granulating, we start looking at the neuropsychiatric symptoms of mast cell activation, which we see a lot more in this population. And then to me, it's sort of when you start to look at the biochemistry of the inflammatory storm that these bodies get hung out to dry in, yeah, they're going to have a lot of psychological symptoms.

So I always just stop because so often the people that are experiencing the health consequences of hypermobility have been told for a really long time it's in their head. And I try to validate the psychological symptom that they're having as very much linked to the biology, and also linked often to what we could term medical trauma. And I think even outside of the EDS hypermobile patients, even patients it's a small thing just with SIBO or just with really bad IBS, they can experience that too, that form of medical trauma that happens when people don't understand your symptoms. So they relegate you to the psychological.

Nirala Jacobi:

I think particularly with Ehlers-Danlos, it seems like people, the length of time before they really get a diagnosis is years and years in the making. So just to kind of recap for those people who are listening who are maybe a bit unfamiliar with this hypermobility and with connective tissue disorders, we're really talking about a situation where people are symptomatic because there are parts of the connective tissue that are failing due to a genetic issue. And we will elucidate that a little bit because I think since 2017 this new criteria, did they remove this aspect of looking for a genetic cause?

Alena Guggenheim:

Great question. And I realized that I did a pretty poor job of actually answering your question, which is what is this actually genetically? I just sailed right over that, so I apologize. So first of all, here's what it's not. It's not a collagen deficiency. Sometimes that's how it'll get framed within somebody trying to provide a simplified explanation where it's just like, oh, it's a collagen deficiency. It's not truly a collagen deficiency, especially not the hypermobile type. I promise I'll pick up that thread in a second. So some of the subtypes like classical EDS, vascular EDS, they're linked to a specific collagen gene. And it's not necessarily that the gene isn't making enough collagen, it's that the collagen that gets made is like limpier.

So if there's more of a type of collagen in the lining of a blood vessel versus a type of collagen that's in the skin, then you're going to be seeing for classical EDS, we see a lot of skin stretchiness, really stretchy skin. I have a patient with classical EDS who can take their neck skin and pull it out and tuck it over their chin. So very stretchy skin, very like atrophic scars. So the scars kind of go concave and kind of wrinkle onto themselves. And that's because of the type of collagen that gets [inaudible 00:15:48] is abnormal. It's not technically a deficiency. Hypermobile type, there's some very exciting things on the horizon. I can say we are pretty darn sure it's not a collagen gene. And there's been two large studies that have been happening simultaneously. One has been called the HEDGE study, the other one has been run out of the Norris Lab at the Medical University of South Carolina.

The Norris Lab has made some discovery about what is the genetic underpinning of hypermobile EDS/hypermobile spectrum disorder. And we don't know what it is yet. So I have all sorts of ideas ahead. Is it going to be somewhere more an immune gene? That's kind of one thing I've really wondered. Is this going to be more a gene that is something actually more like that tends to run these ES bodies kind of hot and inflamed? And that's having a deleterious effect on the connective tissue that's actually showing up as hypermobility. I don't know because it hasn't been published yet. It is under review by a major journal as we speak, and they're not allowed to say what their discovery is until it's been accepted for publication. So I am pretty sure it's not a college and gene.

It's probably going to be something more global that has all of these... Because like hypermobile EDS, hypermobile spectrum, it has all these little octopus tentacles in all these other places in the body in ways that we don't necessarily see with the other subtypes. Which when we start to think about the genetics of it, I do really wonder. I mean, one of the theories, and I'm going to be super clear, this is a super a theory. And I might eat my words next week when this all gets published, but we do see a large overlap with mast cell activation. And as you've probably had, I think you've had some great people on talking about mast cell, and so I'm not saying anything brand new. It's a really hard disorder to diagnose. So I think it's very hard to truly know what the prevalence of MCAS is in this population. I think it's really hard to know the prevalence of MCAS in the general population, and that makes it really hard.

So I can kind of estimate, I make all sorts of estimations in my brain sometimes I think they're probably really wrong, but I kind of go with it. I would say probably 5% of my hypermobile cohort, and I probably have about four to 5,000 hypermobile spectrum patients that I've worked with, have severe MCAS, like recurrent anaphylaxis, angioedema, really needing many interventions to really give them, not even necessarily a quality of life, but to keep them alive. That's a relatively small percent. And then there's kind of the patients really that are the bulk of the patients that have recurrent flushing and hives and tachycardia and diarrhea and vomiting and multiple chemical sensitivity and respiratory allergy kind of stuff.

And just really interstitial cystitis and they're just kind of inflamed everywhere and it has a little allergic flavor to it. That's a lot of my patients. And honestly, it's probably, I'm guessing probably 10% of my patients that I really don't think mast cells are a big part of the problem. I could be wrong about all of that, but suffice it to say, a lot of mobile patients have mast cell. Whether we're going to call it mast cell activation syndrome or what's the new-

Nirala Jacobi:

Mediator release syndrome?

Alena Guggenheim:

Yes, like mediator release syndrome, inappropriate mast cell degranulation syndrome or whatever we want to call it. I'm guessing like 90% of the patients. But when we really drill down into those mediators, there's collagenesis, there's elastases, there's all these little connective tissue digesting enzymes literally present in the mast cells. And mast cells are so unique as an immune cell because they're not circulating, they're embedded in the tissue, which is where we see the problems in these patients, right? They're actually sitting in the fascia, periadjacent to our tendon, they're sitting in the skin, they're all through the gut, they're embedded in the tissue all over the place.

Nirala Jacobi:

So you think it is tied always to MCAS to some extent, or some sort of mast cell involvement is what you typically see. And I mean, let's just also kind of frame it in how the prevalence of hypermobile EDS is, I think you mentioned at some point, it's on par with Celiac disease or so it's one to 3% of the population or something like that, which is not a small number of people, is that...

Alena Guggenheim:

It's not a small number.

Nirala Jacobi:

So it's actually really prevalent and it has these multisystem or it affects multisystems in the body. And so it's good to clarify some of that because people tend to get lost a little bit if we get too technical without clarifying what we're really talking about. So first of all, before we move into the sort of this... What are people coming in with mostly that helps them to get a diagnosis? I'd also like to talk a bit about... Because people that are saying, "Okay, yes, I'm hyper..." What is actually hypermobile? Maybe we can just mention the Beighton score that kind of... Let's clarify, lay the land a little bit for us so that we can move forward in talking about where do people need to go to get proper help for this?

Alena Guggenheim:

That's a really hard question, but I'll take on the easy question first, which is like, what is hypermobility? Well, Dr. Beighton, gosh, I believe in the '70s is when Dr. Beighton put together the Beighton score. I was going to say a love-hate, but I'm going to call it a like-dislike. I have a like-dislike relationship with the Beighton score because it essentially picked easy to define joints. So it is a nine-point score. You get one point for being able to push palms flat on the floor without bending your knees. So that's one point. You get a point for each side that you can bend the thumb forward and touch the dorsal side of the forearm.

Sometimes, and this is hard, because I know we're primarily auditory, not visual, but sometimes people want to go bend their thumbs back. But it's not wrist extension, it's wrist inflection, thumb touching the forearm, and you get a point for each side. And then you get a point for having the wrist and neutral and the pinky going into extension past 90 degrees. So you get a point for each pinky. Then you can get kind of fancy and pull out a inclinometer or a goniometer, and you measure the elbows, you get a point for each elbow that's 10 degrees or more hyperextended. And same thing with a little goniometer slash or an inclinometer measure the knees in standing 10 degrees or more hypermobile. You get a point for each of them.

Now, I can say a lot, I have a number of people who technically have a normal Beighton score. Maybe their Beighton score is a three or a four. And there's kind of a different definition of what's abnormal based on age categories, which I can share if you think that people want to be taking that kind of frantic notes. But for instance, I have a patient with a normal more than one Beighton score who can take both their legs and put them behind their head and can jump rope through their arms with their shoulders fully subluxating and can actually just go around in full circles holding on to their fingers. So there are a number of joints that are not included in the Beighton score that honestly are just really hard to quantify. Like quantifying hip mobility, shoulder mobility, ankle mobility, those are much harder from the provider level to be able to assess. So they're essentially not included.

Nirala Jacobi:

And I will put a link to the Beighton score in the show notes, just for those of you listening. And I often find it's a good starting point to have a conversation and for patients to start exploring this potential contribution to their chronic health issues.

Alena Guggenheim:

There is an even easier place to start, which is there is a validated five question that is about 85% sensitive for picking up a hypermobile spectrum disorder. So for instance, when I started working at the academic pain center that I work, the provider that specialized in fibromyalgia, she just started including these five questions and all of her new patient visits were the fibromyalgia population. Not surprisingly, a lot of them were popping up positive and she would not have necessarily thought to even do a Beighton and score. It would actually be a really interesting study to do, is to kind of take all the referrals into a academic pain center and screen them with these five questions in a Beighton score.

So here are the five questions. They're kind of silly and kind of dorky, but here you go. Can you now or could you ever place your hands flat on the floor without bending your knees? Can you now or could you ever touch your thumbs to your forearms? As a child or teenager, did you amuse your friends by contorting your body or could you do the splits? And fourth question is... Hold on, I'm going to come back to the fourth question. The fifth question is do you consider yourself double jointed? And then the fourth question is, have you ever had a knee or shoulder dislocate more than once? So if somebody answers two or more on those five questions, which could just be included in your intake paperwork, that's about 85% sensitive for picking up a hypermobile disorder.

Nirala Jacobi:

And do they need further diagnosis? Because it sounds like from what we discussed so far that it is more or less a clinical diagnosis. You have to fit two out of five criteria or something like that.

Alena Guggenheim:

Yeah. You have to fit three of three criteria. And we can put a link to that in the show notes too, because the Ehlers-Danlos society has it in a really nice one-pager that providers can just print it, actually handwrite on it, and then scan it into the patient's chart. Or I kind of took the criteria and I just turned it into a dot phrase, but we can definitely put a link to that in the show notes. The five questionnaires are also really helpful for older patients. So EDS through the timeline is kind of these super bendy wendy kids, usually kind of tired and achy teenagers, and through their 20s and 30s, we're seeing for somebody that's really predominant in the musculoskeletal realm, which I'll say... I'll come back, I'll put a bookmark on that one too, because sometimes the musculoskeletal system is relatively mild symptom severity. And sometimes the musculoskeletal system is the predominant area.

But then by the time they're 55, 60, they've maybe had a lot of tendinosis and things have really stiffened up and they're having early osteoarthritis that's limiting their range of motion. They had a lot of tendonitis in the past. Now it's all tendinosis and things aren't moving as well. So in somebody over 50, you can actually add to their Beighton score based on their response to those five questions because they really might be quite stiff by the time you see them. And that's why they kind of add those questions in about, did you contort your body and do the splits when you were a kid? And you just wouldn't think to ask that, right? Hey, were you like a gymnast when you were a kid? Did you do ballet and have no trouble with the flexibility portion of it? Those just aren't like the normal standard medical history questions we ask.

Nirala Jacobi:

So it's more and more evident that it's this very elusive condition that we don't yet know what actually the actual damage is or the damage that's being caused by what? Is it the immune system? Is it connective tissue somehow? Is it-

Alena Guggenheim:

How much of it is the nervous system.

Nirala Jacobi:

The neuroimmunology of it. What are we actually dealing then? It's like a clinical diagnosis, which means there isn't a blood test for it that can tell you whether or not you have it. And plus all kinds of different systems are involved. So I understand how difficult it is for people to actually get a proper diagnosis. Now, let's kind of... Well, you've just already answered that because connective tissue is in every compartment of our body, basically, and it's everywhere, so we are going to see systems in a lot of different areas of the body. But let's talk about how it affects the digestive tract because it is so relevant to obviously the SIBO Doctor Podcast as to these people that are on this merry-go-round of treatment for SIBO, when really, what can we do to improve their relapse frequency?

Alena Guggenheim:

Great. So I promise I'm going to get there in about two sentences, which is there's these really cool movement in medicine to create these concepts around a spidergram. Have you seen a spidergram before?

Nirala Jacobi:

I think I have, yeah.

Alena Guggenheim:

Yeah. So basically, you kind of look at these points around a center, and there's body systems, so GI, neurological, musculoskeletal, neuropsychiatric, urogenital, skin. And then you can essentially get a symptom severity for each of those categories. So maybe somebody's nine out of 10 on the musculoskeletal. They've had 15 orthopedic surgeries and pain is their primary complaint, and their GI is relatively okay. Every once in a while I do a history and I'm like, "Let's talk about your GI." And they're like, "Oh, everything's fine." And I'm like, "What? Okay, okay, I will take it." And then sometimes the musculoskeletal stuff is relatively mild, but GI is really the category that is most prominent.

And then you can draw a little spidergram around that center point, and they're kind of fun to just conceptualize what your individual patient or what you are experiencing and trying to just have a better way of understanding complex chronic illness that's affecting all these body systems at once. Now, my casual observation is that the patients who score very high on the GI axis tend to be globally my most impacted and disabled folks, which seems almost too simple to say. I think the providers listening to this podcast, the patients listening to this podcast, have that understanding, right, if your GI tract isn't happy, nothing in our treatment plan is going to work. Because it impacts being able to put hydration into the body, it impacts being able to put nutrients in, absorb those nutrients.

And those are the fundamental pieces. You need water, you need food, you need air. And two of those are coming from your... You're dependent on your GI tract working for those basic ingredients of life. So the patients of mine with the really severe GI symptoms and the recalcitrant recurrent SIBO, it just has all of these domino effects on everything. And I think we can sit here and scratch our heads and wonder where did it all go wrong? Is it the nervous system that is having... We haven't exactly started talking about dysautonomia yet, but this is a good place to start weaving that piece in, that the autonomic nerves may be actually changing the neurological function of the GI tract. And then the bugs are changing, and then the immune system is responding, and the mast cells are de granulating next to the nerves, and then the nerves are slowing down even more.

And oh, crap, now we have methane and that's going to freeze everything up. And we can kind of intellectualize about it and wonder where did it all go wrong? Where was the first place? And I think that's thinking about it the wrong way, because it feels like an infinity problem. You can kind of hop into it anywhere. And I don't know that we're always going to understand where the emanating first place of the problem is. Then it's all happening within, for the hypermobile folks, it's happening within the context of the actual connective tissue of the GI tract being impacted, like the actual material that the guts are made of. And then the bugs have become imbalanced, and the system is maybe freezing in some places and puts it on eject and other places.

And there's actually been some really fascinating work around this. In fact, maybe I can talk to you about how to put a plugin to get the researcher to come on your podcast from Dr. Laura Pace. And she has actually looked at the prevalence and types of motility disorders in this population. And I don't want to misquote her work because it's probably been six months since I read the exact numbers. So I'm going to give you an approximation. About 80 to 90% have a motility disorder, and it can be too fast in some places and too slow in others. And if it wants to, it can swap. So some patients are going to have gastroparesis, other patients are going to have gastric dumping, and within the same patient, sometimes they might be frozen, sometimes they might be dumping. And that's the effect of a truly disordered autonomic nervous system. Same thing with the small bowel we can see. And Dr. Pace primarily uses smart pill, which is a much more accurate way to evaluate global motility, and it's hard to access for people. I don't know what your access for smart pill is in Australia.

Nirala Jacobi:

Not very good.

Alena Guggenheim:

Yeah. Wait, we have it at my institution, but it's very hard to get covered by insurance. And it's really a shame because we have these really antiquated ways that we evaluate motility, you know, eat your radioactive eggs and toast and take your pictures of your stomach, and now you've evaluated GI. You can do a small bowel follow through with a barium. You can do Sitz markers, and then if you really want to understand what's happening at the very end, you can put your patient through a defecography or an anorectal manometry. But those are all, if you're going to evaluate motility from the top to the bottom, that's one, two, three, four, five. You're looking at five different kind of antiquated technology tests when you could just put a smart pill in and you get the whole thing including pH and where...

Nirala Jacobi:

Yeah, samples along the way and stuff. So motility is obviously, we talk about in regards to SIBO that the dysmotility being and a major aspect of recurrence, frequent recurrence, whether that's due to EDS or not. So it affects the way that motility, or let's say either a per peristaltic wave if we're talking about large intestine, gets propagated through the bowel and in the small bowel as well. And then there are also other aspects of where we see more structural abnormalities potentially in these patients, where we actually see these guts that are very soft and saggy and structural issues depending on positional changes. So standing versus lying, the gut is in a different anatomical position. So this is probably more further down the track. Or in terms of development or aging, I think, I don't know if you see that very strongly initially.

Alena Guggenheim:

I mean, maybe this is going to be too much and you can tell me that this is going too far down a rabbit hole. But even in very young patients, including I've worked with kids pre-puberty that are having nerve compression syndromes in their GI tract, like median arcuate ligament syndrome, where the ligament is that kind of sits up near the diaphragm is actually sitting too low. And then it's actually putting physically, kind of pushing the celiac plexus of nerves and also potentially compressing the celiac artery, which goes to the stomach and the livers and the upper small bowel. And then you're actually either getting a neurogenic... They kind of jokingly call it purple tunnel of the gut, or you're getting actual ischemic pain from changes in blood flow depending on how pronounced that ligament is pushing.

And that also has impacts on motility. So I think before I had the context of this, I thought of when I was... Because I've been doing SIBO a lot longer than I've been like into EDS. And SIBO was actually a big part of what really caught my interest in this population. Why do I have all these SIBO patients that aren't getting better? I've gotten their methane down and I don't understand why we can't get things moving. It's not methane's fault anymore. And then we started to get more of the information around anti-vinculin, but I had these patients who did not have an infectious trigger and didn't look like they had post-infectious IBS subtype, and didn't make any methane, and yet things sat in there, so much GI pain. And then as we do, we just want to try and understand things. So that was a big part of what...

Nirala Jacobi:

Before you were mentioning that motility can go really either way, either too fast, too slow, but in your experience you saw mostly sort of an EMO type or intestinal methane overgrowth in these people?

Alena Guggenheim:

I don't actually know because honestly, every time I look back on myself over time, I'm like, oh gosh, I just didn't know things. What a baby. I was in preschool and I was kind of just trying my best to help people. But I think about that even, and I think all of us should, if we're continuing to learn and try to look at all these unexplanatory of why things go wrong with the body, we should look back on what we were doing three years ago or five years ago, where God, for me, 15 years ago now, and just be like, oh God, I am kind of embarrassed by that. But I was doing the best I knew at the time.

Nirala Jacobi:

That's the evolution of every practitioner.

Alena Guggenheim:

That's the evolution of it. Exactly.

Nirala Jacobi:

That's how it is. And that's why we must never leave this profession because we get better with age.

Alena Guggenheim:

Yes.

Nirala Jacobi:

One would hope.