Gut Check: Hypermobility and Gastric Disorders with Dr Dacre Knight
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Welcome to Gut Check, a podcast from the Gastroenterology Learning Network. My name is Brian Lacy. I'm a professor of medicine at the Mayo Clinic in Jacksonville, Florida, and I am absolutely delighted to be speaking today with Dr. Dacre Knight, associate professor of medicine and medical director of the Mayo Clinic EDS clinic. Dr. Knight is an expert in Ehlers-Danlos syndrome, which we’ll abbreviate as EDS today, and he's also an expert in hypermobility syndromes and runs a very large referral practice that evaluates and treats patients with these complicated disorders.
So Dr. Knight, welcome. Let's begin very simply by making sure that we are using the correct terminology because this field has undergone significant changes in the past 2 decades. Is the correct term now hypermobility spectrum disorder, abbreviated HSD? And does this include all of the distinct EDS subtypes?
Dr Knight:
Yeah. Well, thank you Brian, and thank you for having me here today. It's a real pleasure. Yeah, I think this is good place to start as any because it is very complex and so we are certainly hearing about these things more and more, so getting the term straight I think is a natural starting point. So Ehlers-Danlos syndromes cover a fairly large group of heritable connective tissue disorders. There are 13 named types of EDS now of the recent reclassification in 2017. We have now a group 2 that is more broad, encompassing what we call hypermobility spectrum disorders, HSD. So we have EDS and HSD. We might get into the details here today about the management similarities and differences. But yeah, when we're talking about terms of EDS and HSD, that's how we describe them to begin with.
Dr Lacy:
So this is great, and then I'm going to have you clarify things even a little bit more because I may be a bit confused. And when we speak of EDS, as you already mentioned, there are 13 subtypes and could you clarify, is it type 2 or is it type 3, that's the hypermobile subtype, which is sometimes also called the hypermobile variant EDS syndrome. Right?
Dr Knight:
Right. Yeah, exactly. And that is the one that certainly draws more of the attention in recent years because it is what seems has the highest prevalence of all of them. And this was yes, previously described as type 3 and in some of the former classification systems. So now it's just simply these are just named subtypes now. So HEDS or hypermobile Ehlers-Danlos syndrome, hypermobile EDS is how we describe those. Yeah, so that's what we would call it as what was previously type 3.
Dr Lacy:
Okay, great. So we'll use that term of hypermobile EDS. That's perfect for our audience. And before we delve into the pathophysiology and diagnosis of these disorders, I want to understand a little bit more about the scope of the problem. How common are these hypermobility disorders?
Dr Knight:
Well, I wish we really had better data to tell us specifically, but as you can imagine, there's a lot of conditions are hard to really get accurate prevalence of, there are so many likely undiagnosed individuals out there. But we know for some of the rare types of Ehlers-Danlos syndrome, so let's say like the vascular type of EDS, those are much more rare. We're talking about 1 in 100,000 people. On the more common end would be the classic EDS and the most common, the hypermobile type of EDS, and we think that's around at least 1 in 5,000. What's interesting though is that it gets folded in together, as I mentioned previously with the hypermobility spectrum disorders, which are even at a higher prevalence than that, and we think that's closer to about 1 in 500 people.
Dr Lacy:
Wow, that's really helpful information and certainly a lot more prevalent than I think many patients and many providers believe. So this is great to set the stage. And so how do we broadly characterize these disorders? Is it simply just having one or more joints that are hypermobile or do patients need to have other symptoms as well? So as an example in the GI clinic, should I be asking all of my patients about unexplained bruising or poor wound healing as an example?
Dr Knight:
Yeah, this is another great question, Brian. And I think we all wish that we had all the time in the world to go through and screen for any possible condition that many of our complex patients have, because I think we would find that many organ systems are affected right across the board. And so other characteristic features, and I think we can kind of break it down in what's of interest maybe to some of your listeners and other clinicians out there if they're seeing patients in their practice and GI practice and such. So yeah, joint hypermobility is generally one of the cardinal features combined with chronic unresolved pain. Those are most commonly the historically presenting features. So it may be just chronic unresolved pain at first. And then you ask a couple of questions here and there realize that, oh yes, they are hypermobile. And usually when we have patients referred to our practice is actually, as you can imagine, with a roundabout way of patients being seen by physical therapy or orthopedist first because they notice the hypermobility and then they've already been assessing them for the pain.
So those are the first starting points. How do you get an assessment on hypermobility? There is a tool that has been validated and is used quite widely now, which we call the 5-point questionnaire, which was developed by Dr. Graham and Dr. Hakeem, and to get an assessment on the degree of hypermobility. So 5 pretty straightforward questions you can ask patients. So if you have ever in your life ever been able to put your hands flat on the ground knees fully straight? Have you ever been able to do splits? Have you ever had any dislocations, like repeated dislocations like joint or kneecap dislocations? Have you ever been able to touch your thumb to your arm? And the fifth one, were you ever considered double jointed? So 5 areas kind of give you a good idea. If you've had at least 2 of those, then we would say yeah, there's some likely some validated hypermobility present.
Dr Lacy:
Wow, super helpful. Great clinical pearl. These, this 5-point questionnaire with at least 2 questions, meaning some significance and certainly that's something we could all use in clinic. Remind me though, because this field is changing, that the Beighton score is an important part of the diagnostic criteria. Is that still correct? Does this still really, is it being used in clinic to assess joint hypermobility and how is that score generated?
Dr Knight:
That's exactly right, Brian. So that would be the next sequence of the evaluation. So we kind of get a general scope of the problem. Yeah, patient has pain, they've got hypermobility. Next step being yes, we could do some 5-point questionnaire to get an assessment on the degree of hypermobility. Is there something really of significance there? And then yes, the Beighton test is next as part of the formal evaluation. So it's now 1 of 3 criteria that are used to fulfill a diagnosis of hypermobile EDS. So the Beighton score is 9 different areas in the body, and it does take some time to know how you do it correctly. I mean, you could just look these things up online and see pretty straightforward, but we're looking at 9 different areas. So it starts with the upper extremities first. So the thumbs on both sides, the thumbs, so you, it's hard to describe it just by telling someone. If you see a picture of it, it's pretty straightforward, but you're essentially, it's laxity of the wrist, so you're just bending the wrist to a point where the thumb could touch the arm. And then the pinkies would be hyperextending where you'd see less than a 90-degree angle to the back of the hand or more than 90 degrees at the front of the pinky. And then the elbows and knees hyperextending beyond 10 degrees, and there's 1 point for each of those joints. So that would be a total of 8. And then the ninth score is again, finally the hands flat on the ground with the knees fully locked back, bending over at the torso.
Dr Lacy:
Alright, that's wonderful. So now I think we all have a better understanding of what the Beighton score is and how you generate that score using these different criteria. Moving on just a little bit is my understanding is that the hypermobile variant does not currently have an identifiable underlying genetic basis or a specific pathophysiology. And is that maybe why this is such a controversial area? Because we know that in contrast with some other EDS subtypes, there is a known genetic cause maybe a change in coding of collagen or enzymes that play a role in the generation of the extracellular matrix. Is that correct?
Dr Knight:
Absolutely. So then you can imagine that this is why there is such a great emphasis in our research interests and the goals, and we're collaborating with Ehlers-Danlos Society and trying to uncover whether it is a gene, single gene, multiple genes. And likely the more time that has gone by is more and more likely it is not monogenetic, it is likely polygenic. So multiple genes involved, or maybe there are other biomarkers that we can come to identify. There's a team led by Dr Marina Colombi in Italy that has made some great strides here and uncovering some mechanisms of biomarker identification, which we are actually just pleased to share that our application for the discovery lab with Mayo Rochester colleagues was awarded to replicate some of those studies for our patients with questionable diagnosis of HEDS. But yeah, so the mystery about the molecular causes of HEDS still being elusive is yes, it's very difficult for other clinicians to understand, get more awareness in the medical community of the depth and the significance of this problem that's out there.
Dr Lacy:
I think that most clinicians, they're looking for a simple biomarker or simple test that can make that diagnosis. But it sounds like right now it's thinking about it, understanding the prevalence, asking some great clinical questions, and then maybe using the 5-point questionnaire and the Beighton's criteria to really get that diagnosis.
Dr Knight:
That's it.
Dr Lacy:
So Dacre, focusing a little bit more on the hypermobile variant, which is probably the type of hypermobility spectrum disorder, most commonly encountered by gastroenterologists and probably even in primary care too. Who is the typical patient? Is this a younger patient or an older patient? Is it a man or a woman? Are there differences based on ethnicity or race?
Dr Knight:
I should say this is another interesting area of research too because we do see that there are some groups that seem to be affected more and diagnosed much more than others, and we don't really know why that is. We think that there are some mechanisms that are driving it, but for example, just to describe it, as you asked, over 90% of our patients who are diagnosed are women. And among those we see an age range, average age of about 39 years. And so we know that there may be some age differences. And going back to the Beighton score, so just kind of ran through quickly of what are the features we're looking for, but the score itself, as you can imagine, is obviously important. So what is the score? So it's a higher cutoff for children who are more naturally hypermobile and it goes down to around 5. A score of five would be what's the distinction after the age of puberty. And then it goes down further after the age of 50. It's sort of arbitrary by that age, but at that age we'd say a cutoff of 4 would be significant.
So all of those things combined give us reason to believe that yes, there's some groups that may be affected more than others. Are women more naturally more hypermobile? Is there sex differences maybe as having testosterone a benefit, having increased muscle mass? Is that protective for men? We don't know. So that was actually our first research grant that was awarded to understand these sex differences. And we hope that we collaborate with other researchers in other fields, and we know that there's other sex differences in many other conditions too. So we can share that knowledge and learn from those studies too potentially of why we see usually a younger population and mostly women.
Dr Lacy:
So very exciting. And for our listeners, stay tuned. It sounds like we're going to be getting some really important information in the years to come. And so recognizing that for many of our listeners on this podcast, they focus on the GI track, whether as patients or providers. What are some of the most common GI symptoms or disorders reported by patients with a hypermobile variant?
Dr Knight:
Yeah, I was hoping we're going to get into this topic now being a GI podcast, because this is something that's very interesting to me, too, because we do see in our patients, we see the majority of our patients with some GI disturbance. And maybe one day I'll host you on a podcast, Brian, if I ever get to this level of accomplishment as you have. But to understand where this relationship lies is I think is really fascinating.
But to your question, what we see as most may expect is that we see most commonly these disorders of the gut-brain interaction. And I don't know that we've got good understanding of which of those subtypes we see more common than others or if it's really different than what would be seen in the general population because it runs the gamut. And we try to use that to, of course take to the next step of understanding the pathophysiology and mechanisms as we're doing that, we want to give patients the best treatment they can, the best hope of living a high quality of life. So in doing so, the first step is to recognize that they're there. And then by far I would say yes, that is the majority of our patients for one. And as far as the disorders goes, that the disorders, the gut-brain interaction take the cake there.
Dr Lacy:
And so obviously the key question here is, and in your opinion, is there a direct relationship meaning that a hypermobility disorder causes the GI symptoms, or do you think it's just simply an overlap of what now are common disorders, DGBIs, disorders that got brain interaction, and these hypermobility syndrome?
Dr Knight:
And that is the question, and I guess I will do my best to come up with my own ideas, but I should say that they're probably not any better than any other expert gastroenterologist out there because I really don't know, to be honest with you, what is it? And I think that yes, that theories are the questions that come up is there a tissue problem that is obviously what is the focus of our concern for patients with EDS and hypermobility spectrum disorder? Is there a problem that's driving it? And because we see not only the gut issues come up in our patient population, but we do see so many other comorbidities that are maybe not as necessarily as high as the gut disorders, but we do see an increased frequency of things like POTS in our patients compared to the general population, at least, other autonomic disturbances in that category. A very high percentage of patients who meet diagnostic criteria for fibromyalgia, which historically has been the diagnosis patients have been given, incorrectly missing a diagnosis of EDS or HSD, but we still know that it can be comorbid to those. And then migraine headaches and of course, and all the other chronic pains that come with it.
So the natural question is, is there something Occam’s razor style now here that's connecting all of those pieces there? Is it the tissue? And maybe I think that's as good of a theory as any and the aphorism in our field as if you can't connect to the issues think connective tissue. So maybe we will use that as our starting point in our investigation into the GI world here too. So yeah, I think we'd need more answers there.
Dr Lacy:
Absolutely. And I like the way you put all together. So that's a perfect segue to thinking about treatment. So one question that comes up all the time is if a patient has a hypermobility disorder and a GI disorder such as irritable bowel syndrome or functional dyspepsia, do we treat them differently because they have that hypermobility disorder or do we just focus on the predominant symptom and really just focus on that and treat them the same way as somebody who doesn't have a hypermobility disorder?
Dr Knight:
That is one thing that patients do often ask about, and they have a lot of consternation when they come to our Mayo Clinic EDS clinics like, well, we've come to this destination medical center, you guys are the experts, and we have a lot of hesitance of going back in our local community where there's really not much knowledge about it. But the fact is, is that the GI disorders included, a lot of the management is the same as it would be in the general population. Where we have to do our due diligence is to recognize that those problems are there or that there may be a higher likelihood of those problems being present and knowing sort of what things to look out for. And we do also, so for clinicians who may be listening today, we get these questions from other providers who want their patients to be seen by us to make sure that they're okay for surgery or they're okay for this type of treatment.
And generally speaking, it is okay. I mean, there's not any just direct contraindication to a specific procedure or treatment having a diagnosis of HEDS or HSD. Now, there are other types of EDS, like I mentioned earlier, the vascular type of EDS, which does come at a higher risk of things like gut perforation, rupture, things like that, aneurysms, et cetera. So we may have to weigh in a little bit more closely in those cases, usually past procedures and past surgery inform future surgeries. So even in our HEDS patients where we just could say that, yeah, generally you don't have to have any specific contraindications procedures. If they have had a lot of complications in the past, then yeah, that's when we start saying, okay, well let's try to pay attention to this more closely about wound healing and things like that.
So the gut, I would put that in the same category. So treating the gut disorders, motility disorders and such, there's not anything that we do specifically different for general management of those, but we just have to keep in mind that these are complex patients and it may not only be the gut disorder or the motility problem that they're suffering from. So we kind have to work in a multidisciplinary approach, which does work so well in places like Mayo Clinic.
Dr Lacy:
No, that's perfect. And so just to fine tune that a little bit, I think all providers are trying to be very conscientious and careful and recognizing that the prevalence is much higher than I was aware of for the hypermobility subtype. Are there questions we should focus on for that maybe rare patient, that person with Marfans, and maybe we're going to miss somebody with an enlarging aortic aneurysm, or is that so uncommon and we really don't need to worry about that routinely?
Dr Knight:
Yeah, that is a good question, even for those in my field too, because it's not always clear. We are trying to be the best clinicians we can. We just gather as much information and patient history as we can to help us make those distinctions and kind of raise the alarm bells if there is a more severe subtype of a connective tissue disorder present like Marfans or vascular EDS. So we say in the field of the genetics that family history is the quickest and easiest genetic test that's out there. So you can certainly use some of those types of clues. Any patient, I think where you're getting at, which is good questions, it is any patient with hypermobility and potentially a diagnosis of a hypermobility disorder or HDS, should they be considered for evaluation of things like vascular EDS or Marfan syndrome? The short answer is no, but always to be on the safe side and is even in our practice, if there is any doubt or question, you would just refer them on to the specialist who would be able to help make that distinction for you, or they arrive at our specialty clinic and we can't even just make it based on a clinical judgment or family history, then we will do conductor genetic testing to elucidate that and it's a little bit better.
So that's kind of the general approach. So when in doubt, no reason to seek out the answer with specialty and support from your colleagues.
Dr Lacy:
No, that's wonderful and very reassuring. So Dacre, as we wind down here, what advice can you give to our listeners about how to educate or reassure patients with hypermobility syndrome and specifically the hypermobility variant of EDS?
Dr Knight:
Well, one thing that's reassuring is, you mentioned it too earlier too, Brian, is that we hope to have some things look forward to as far as further discussions and discovery goes. So that's one thing I like to reassure listeners, is that we are doing the work as actively as we can, writing grant applications almost weekly it seems at this point, to try to get the funding to support the research, to make the discoveries so we can have these better answers and better diagnostic tools and treatments for your patients. Because we know that not only the patients are suffering, but providers ourselves, we are suffering because we want to give them the best help and we definitely feel the shortcoming when patients don't get the sense that they're getting all the answers or help that they want, and we feel that we want to be able to give that to them.
So rest assured that is in progress and we hope to be able to share that in the future. In the meantime, yeah, we will continue to do what we can to support each other, share our knowledge that we're gaining here. I'm happy to be here today to share all the experience that I've gained along the way if it is helpful to others because we know that these are challenging situations and we know that we go into this field for the reason that it is a challenge, and we find that as our passion, our drive to meet the challenge and rise to it and help those who are suffering.
Dr Lacy:
Wonderful. This has really been a phenomenal conversation. Thank you so much. Any last thoughts for our listeners?
Dr Knight:
Yeah, my pleasure, Brian. I really enjoyed being here, so I don't have anything specifically just stay tuned. I hope that we have more coming. We're actually in the first stages of drafting our text on hypermobility disorders and Ehlers-Danlos syndrome. So we may like to include a section on gastrointestinal disorders too. So Brian, maybe consider this your formal invitation if you're prepared for that anytime in the future. But yeah, more to come. The future is bright, so I like to keep our heads up.
Dr Lacy:
Wow. I rarely regret making an invitation to an expert, but now I may be questioning, and that's wonderful.
So again, thank you for lending your expertise on this important and controversial topic to our listeners on Apple, Spotify, and other streaming networks. I'm Brian Lacy, a professor of medicine at the Mayo Clinic in Jacksonville, Florida, and you have been listening to Gut Check, a podcast from the Gastroenterology Learning Network. Our guest today was Dr. Dacre Knight from the Mayo Clinic in Jacksonville, Florida. I hope you found this just as enjoyable as I did, and I look forward to having you join us for future Gut Check podcasts. Stay well.
