Why Small Wins Matter More Than Miracle Cures in EDS and HSD: The MENS-PMMS Method™ with Dr. Dacre Knight

[01:01] Dr. Linda Bluestein: Welcome back to Bendy Bodies. I'm joined today again by my friend, colleague, and recurring co-host, Dr. Dacre Knight, Medical Director of the UVA Health EDS and Hypermobility Disorder Center. Through our ongoing partnership with UVA Health, we're bringing you practical, evidence-informed strategies to help people with hypermobility and connective tissue disorders live better. Today we're wrapping up our MENS-PMMS series by covering the final four components and sharing some of our favorite treatment pearls and clinical insights for each one of these last four letters. These are the approaches we find most successful and recommend again and again because they make such a meaningful difference in real life. This podcast is for educational purposes only and is not a substitute for personalized medical advice. Stay to the end for hypermobility hacks. Here we go.
[01:49] Well, I am so excited to be back with Dr. Knight, and today we're going to be discussing the last four parts of my Treatment Algorithm, the MENS-PMMS Method™, and we're going to start with P for psychosocial. I know, Dr. Knight, that it can be very challenging to approach this part of the algorithm because a lot of people think, "Oh, you must be saying that it's in my head," or making some assumptions when we start talking about the psychosocial aspects of pain and other symptoms. How do you approach this with your patients?

[02:25] Dacre Knight: Well, it's a lot, and thank you, Dr. Bluestein, for the question. And so glad to be back again with you. There are so many factors and modalities and different approaches that we can take. But I would say that what has been, in my experience, really the most impactful is that it's not really one major breakthrough, or just one specific miracle. It's really just stacking all of these things together. So a continuous run of small wins across all of those domains that you mentioned.
[03:03] If I had to rank them, I'd say that the psychosocial factors, when ordered correctly and when done appropriately, and the nervous system regulation are often the foundation — the most important foundation — and then the modalities and things like that we build on from there. So it's a combination of all of it.

[03:22] Dr. Linda Bluestein: I had a physical therapist once explain this to me when I was not doing well. She said that we had to really work on nervous system safety and a number of these other things. And she said, "It's physiologic, though — it's not psychiatric." And I say that to people a lot because I think people don't often realize how the mind and body are connected in physiologic ways. I think if we educate people about that, it's really, really helpful.
[03:46] I don't know why we feel like if it's psychiatric, it must be our fault and we must have more control over it, because we don't have a lot of control over a lot of the psychiatric things either. But explaining that mind-body connection can really make a big difference. What do you think about that?

[04:08] Dacre Knight: Yeah, I think that really is the key — it's how it's explained, how you address it, and how you're counseling patients. You're not being abruptly dismissive, but you are seeking ways to make these connections, because certainly they are physical and mental and all the rest. We're all psychologically attuned to whatever disorder or condition we're suffering from. So there's no doubt that there are pieces of it that draw in all of those mechanisms, but how you present it and how we discuss it with patients is of a critical nature.

[04:46] Dr. Linda Bluestein: I don't know about you, but I have had some really remarkable cases of just incredible transformations through programs that address nervous system safety, whether it be something like DNRS, Primal Trust, the Gupta program — there are a lot of different options out there now. Have you seen that as well? We know that mast cells do respond to psychological stress, so it makes sense that stress can impact our symptoms so greatly. That's why gaslighting is so bad — it can just make the stress so much worse. People come to us for help, and if they're not believed and not validated, it can just exacerbate their symptoms. But have you seen it work the other way, where people have done some of these modalities and it's really helped their symptoms quite significantly?

[05:32] Dacre Knight: Absolutely. And I think you addressed it correctly — these things can be a compounding problem, but if they are done correctly, they can be a compounding benefit. I just had a patient yesterday describing the stress she was experiencing and how it was disrupting her sleep. She was getting two to three hours of sleep per night for a period of days. All of those things were just adding into symptoms of fatigue and deconditioning and then more muscle pain and all of the joint issues that came with it.
[06:02] And when it came around to, again, just a small win — she had adjusted some of the things that were causing her a lot of stress in her life, and she was able to get more sleep. Just all of it compounding thereafter. It may not even be just sleep that someone is having issues with. It may be work-related, family-related stress, or whatever. But all of those things — it's why we place importance on all of the psychosocial aspects, as I mentioned from the beginning.

[06:39] Dr. Linda Bluestein: Yeah. Whether it's those programs I just mentioned, CBT, DBT — dialectical behavioral therapy — there are so many different options. There's another one called EAET. Have you heard about this? I know there are some studies looking at that in fibromyalgia. In fact, I think it might even have been Mayo Clinic researching that and finding that a lot of people who have these conditions — I should say a lot of people who have either chronic pain, persistent pain, or other conditions — a lot of us, and I'm going to put myself in this same category, have difficulty expressing our needs. Sometimes our body starts speaking for us — we start getting worse and worse symptoms when part of what's needed is to express what we need from our family members.
[07:22] So I think that's another important part of it. It's not just the safety of your nervous system, but it's also working with your support team and being able to express yourself effectively. What are you feeling? What do you need from other people? And how can you get to a better place emotionally?

[07:42] Dacre Knight: Yeah, and that's something I know a lot of patients experience — finding the right people to guide them there. Whatever therapy it may be, the EAET is interesting. The acronym stands for Emotional Awareness and Expression Therapy. And it's been—

[08:01] Dr. Linda Bluestein: I'm glad you could remember it.

[08:03] Dacre Knight: Yeah. It's been highly effective for a lot of those chronic pain conditions you mentioned — what's described as the neuroplastic or nociplastic pain conditions, fibromyalgia. And we see a lot of that in patients with EDS and HSD. You're right, they've done some of those studies at Mayo Clinic. But even finding those resources can be difficult because it does require in-person care, and those specialists are not everywhere — not in every city or community.
[08:34] Another one would be EMDR, or trauma-informed therapy, for those patients who have a history of trauma that is exacerbating some of their symptoms. So there are lots of different modalities, and that's just part of the discussion working with your healthcare professional — understanding which types of therapies and modalities may be most suitable to you or accessible in your area.

[08:57] Dr. Linda Bluestein: And speaking of in-person, are you familiar with Dr. Beth Darnall out of Stanford and her program Empowered Relief? Have you seen anybody trying that? Do you know anybody who's certified to teach those classes?

[09:12] Dacre Knight: I'm very glad you asked, because we're standing up an Empowered Relief program at the University of Virginia as we speak.

[09:18] Dr. Linda Bluestein: That's so exciting!

[09:20] Dacre Knight: It is. Beth has done some fantastic work at Stanford in making this available to anyone who, like you said, is able to get the training and become a certified provider for it. Anyone in allied health can do it if they take the time to go through it. And the data has been very robust for good response from that. So we're excited to get it enrolled for our patients here, and they'll be able to do it virtually. I will definitely have more feedback for you once it's up and running, which should be just a matter of weeks.

[09:58] Dr. Linda Bluestein: That's really exciting. I got to meet her in person for the first time last month — very recently — at the American Academy of Oral Facial Pain Conference, where she and I were both speaking. I think she's really doing great work, and we will also link in the show notes the podcast episode I did with her, which was quite some time ago now, but I had a great conversation with her.

[10:22] Dacre Knight: Likewise. I had met her at a Canadian Pain Society meeting a year or two ago. She was telling me about this Empowered Relief program then, so we're excited to get it involved for our patients as soon as we could.

[10:37] Dr. Linda Bluestein: I'm so glad that you're doing that at UVA. Are there other psychosocial interventions that you feel consistently improve outcomes that we haven't already mentioned?

[10:47] Dacre Knight: There are. And it really does depend on the situation — conditions can be quite severe. I would say one of the most underappreciated factors is loss of trust. So many patients who have been coming into our center have spent years being dismissed, misdiagnosed, and told nothing is wrong. And that changes how they interact with healthcare overall and how they interpret their symptoms.
[11:27] So as far as what we can do for the psychosocial aspects, we first have to get it right that symptoms are not imagined. The brain, body, emotions, relationships, life experiences — all the things we're talking about — they're all connected. Physical illness, as we know with EDS and HSD, can place the nervous system in what feels like a consistent state of threat, and that threat response amplifies the symptoms.
[12:00] So we really just start from the bare minimum: validation. Validation is certainly very therapeutic, and it's really the first meaningful intervention. Thereafter, we have to peel away the layers of years of misdiagnosis and misunderstanding, and then reapply the education and understanding of these conditions. And then if more psychological support is needed, we partner patients with one of our clinical psychologists one-on-one. If it's something that still needs to be addressed but we can do it across multiple patients, then we can potentially do that in a group setting. That's also an effective way of broadcasting the skills and tools and techniques of a clinical psychologist to more than one person — it's more feasible and accessible. But there are certainly some cases that require one-on-one evaluation and treatment.

[12:57] Dr. Linda Bluestein: I love what you said about validation, because that's free, right? They've already paid for the appointment. The validation part is something that we as clinicians can do — it doesn't cost anything extra. Just saying, "I believe you and I hear you." I think that might be our most underrated psychosocial treatment pearl.

[13:15] Dacre Knight: Yeah, step number one. And it really is therapeutic. It's something that patients need to hear and have not heard. And once they hear it and understand that validation is there, then they can have much more meaningful interventions ahead.

[13:41] Dr. Linda Bluestein: Yeah. It can lower the anxiety, and like you said, nervous system safety can improve, and then you can start to do some of the other work. It can be really hard to get a pill — and we're going to go into medications and supplements a little bit later — but it can be hard to get those things to work if your nervous system is just on overdrive and you're in a constant sympathetic state.

[14:03] Dacre Knight: Totally. Yeah. You really just have to reset and start anew. And that's where the validation begins.

[14:12] Dr. Linda Bluestein: Okay. Let's move on to the next letter, which is M for modalities. It's very intentional that of the three Ms, movement was first — which we talked about in a previous episode, and we will link that episode. Oh, and I do want to mention very quickly, before we move on to modalities and the last M, which is medications, that we will also link in the show notes the Dr. Halvorson episode, because that was a really good conversation about medical trauma — he's done a lot of research on that topic. We'll link that episode as well, and also Dr. Caitlin Tuza's episode. Okay.
[14:52] So if you have a brand new patient with EDS or HSD, POTS, MCAS, et cetera, what non-pharmacologic modalities are most likely to make your shortlist?

[15:04] Dacre Knight: That's surely something that can be an issue — you get a sense that you've done everything and there's nothing left. But I will say that among these modalities, there are different combinations that can be used, different timing, different situations. And really it's almost an infinite number of possibilities of how these modalities can be applied. So I take the time to go through that with patients.
[15:31] It does start with easing into it, because these patients feel exasperated — they've had years of misdiagnosis and misunderstanding, and so the response is, "I've tried this, it doesn't work." And again, as I was alluding to earlier, it's not one miracle treatment that I've seen the most benefit from. It is a combination of all these small wins, and maybe a combination of modalities, but learning when to apply them correctly.
[15:59] So that's a roundabout way of answering your question — let me get to the point. The modalities I go through are generally ones that I've had experience using with patients, that patients have reported benefit from, and that are also the safest and relatively inexpensive and attainable. Things like heat therapy for one — probably the easiest. Heating pads, warm baths. Those are very common because very often patients say, "Oh yeah, I love a warm bath, I'm doing it every day, I can't go anywhere." And many times a patient will pull a heating pad out of a bag right next to them.
So those are easy, attainable, and you can travel with them. Other things would be massage, acupuncture, and there are different types of each — acupressure, dry needling, craniosacral therapy, TENS units, KT taping, vagal nerve stimulation, and topical medications. I know we'll get into medications separately, but those modalities, in different settings and situations, can be really effective in combination.

[17:28] Dr. Linda Bluestein: A lot of these things can really make a difference if we set our expectations correctly. If we expect them to take away 100% of our pain and get us our life back, that's less likely to be achievable. But if we think about the 10% rule — which was originally taught to me by Dr. Pradeep Chopra, our colleague — if you get 10% benefit from five different things, now you've gotten 50% improvement. It can really make a big difference.

[18:00] Dacre Knight: Yep. It's all about the small wins.

[18:02] Dr. Linda Bluestein: Yeah. It's all about the small wins for sure. Do you think there are particular modalities that are especially underutilized?

[18:10] Dacre Knight: I would say yes. Heat, like you just demonstrated for us — those are very good and as long as you're not burning yourself, they're very effective. I wouldn't say they're overutilized. But underutilized — yeah, a couple come to mind.
[18:42] Acupuncture, acupressure, dry needling — I would say those are underutilized. Physical therapists do the dry needling; acupuncturists do acupuncture, based on Eastern medicine, the meridians and so on. Dry needling is dependent on the physical therapist's own education, and not every physical therapist is trained in it. So I would say that's underutilized.
[19:10] TENS units too — those are pretty well underutilized. You can order them online. They're low risk and inexpensive. With acupuncture and dry needling you have to go somewhere and it can be more time-consuming, but TENS units you can do on your own. I would put those on the list of being underutilized as well.

[19:32] Dr. Linda Bluestein: Yeah, it's amazing. When I was at my worst — I'm chuckling because my insurance covered my TENS unit, but it was this huge honking thing. You had to get it through one specific company, and you had to get all the pads and patches and they had a belt for the low back and all these different things. Now you can just go on Amazon and order a TENS unit. You can also order a clip to put on your ear to activate the vagus nerve. So there's a lot, like you said, that you can do on your own.
[20:03] And sometimes the TENS unit, by just really getting those muscles to activate, finally gets them to relax — sometimes they're kind of in that constant contracted state. I'm glad you mentioned dry needling too. I'll link the episode with Dr. Mandy Blackman, because we did an episode on that. In the right setting, dry needling can really help turn off those muscles, and it can also actually benefit the autonomic nervous system as well — there can be some really significant changes. And I'm glad you mentioned acupressure, because that's something people can do on themselves.

[20:39] Dacre Knight: And we actually have a dry needling course coming to the University of Virginia later this fall from Jan Demmerholt, who's probably the preeminent dry needling teacher in the country right now. And yeah, it's all of those things you mentioned — if we can get to the point where you're seeing someone, whether it's massage therapy or dry needling or acupuncture, and then you can do some things on your own at home, that's ideal. Whether it's TENS units or acupressure, that's where we want to get, because those are most accessible.

[21:16] Dr. Linda Bluestein: Are you saying that they're coming to UVA specifically to teach dry needling for the UVA EDS and Hypermobility Disorders Center?

[21:27] Dacre Knight: That's right. Yeah. We'll have physical therapists from the area join in and learn, so we can have a referral base for all of those in the region who will be able to perform those services.

[21:39] Dr. Linda Bluestein: That's great. Knowing how to apply those things in this particular population is really essential. So it's wonderful that you're doing that.

[21:48] Dacre Knight: Exactly.

[21:49] Dr. Linda Bluestein: What about braces? How do you determine when a brace is helping versus when it's becoming a crutch?

[21:55] Dacre Knight: Oh, this is a good question. Bracing can certainly help someone function better and gradually build strength, and that's what we want it to do. So if function declines whenever the brace comes off, then obviously we need to rethink the strategy. When we are doing bracing, we can't just give it away frivolously and say, "Here's your brace, there you go." We do have to follow up and assess the patient, whether in a clinical exam or with follow-up physical therapy visits. We have to recognize that there is a continuum of benefit that may be seen when bracing is used.

[22:35] Dr. Linda Bluestein: And I think the distinction between rigid bracing versus something that is more soft is important. I currently have a brace on my ankle — it's actually, I want to say Apollo Neuro, but that's what you wear on your wrist. Apolla Shocks. I have a cuboid bone in my foot that's currently very unhappy and keeps coming out of place, so I'm wearing these Apolla Shocks, which are really great — they're actually socks, not like an ankle brace, but very supportive. They give me nice compression and are working way better than any of my ankle braces. So I think we need to think about whether something is holding the joint rigidly and therefore potentially weakening the muscles, or whether it's providing compression and helping with inflammation, with proprioception, and things like that. There are a lot of tools out there that can be really helpful.

[23:34] Dacre Knight: And there seem to be more tools every day. I've just learned from you about this one, so thank you, Dr. Bluestein. That's excellent. And that's what we want to have available for our patients too.

[23:45] Dr. Linda Bluestein: Yeah, I'll put a link in the show notes about that too. They were designed originally for dancers because they have a little bit of padding under the toes — a lot of dancers are performing barefoot, or at least not wearing shoes with any padding. Even ballet shoes don't have any padding under the ball of the foot. So we can end up with a lot of pain in that part of the foot. The idea with these was to give at least a little padding there, but the compression around the ankle is really, really nice. I'm particularly wearing the ones that are a little bit looser around the toes — the first pair I had was kind of tight around the toes, and I'm old enough that I have some arthritis in my toes, starting to get overlapping toes and things like that. So this was a really great option for me.

[24:32] Dacre Knight: That's brilliant. Yeah, that makes great sense.

[24:35] Dr. Linda Bluestein: Is there a particular modality that you recommend quite frequently that clinicians are not really talking about?

[24:44] Dacre Knight: I would say yes. Maybe in the same category of underutilized. I've actually learned from my colleague here, Dr. Ina Stevens, who's been practicing integrative medicine for a while, and how she educates patients on diaphragmatic breathing and breathing exercises. That's been a core part of our treatment and discussions and use of different modalities, and I don't think it gets a lot of attention outside of here.
[25:21] Usually it takes one clinician to start ascribing to it, find the benefit for their patients, and then share that knowledge — as Dr. Stevens did with me. And then finding the benefit for my own patients. But unless you have those connections and those experiences, it may be underutilized. I think that's how it is for most community physicians who are treating EDS and HSD patients. It has profound benefits. There's good training material on how it's done, and when it comes to nervous system regulation, this is really a huge benefit.

[26:05] Dr. Linda Bluestein: I'm so glad you brought that up, because that's free and always accessible. Our breath is always there — you don't have to look around and say, "Oh darn it, I don't have my, whatever, pick a modality of your choice." You don't have to say, "Oh darn it, I have to pack that in my suitcase." Diaphragmatic breathing is something that you can, at least in theory, access at any point in time. And that's really important.
[26:31] I actually had a psychologist once tell me she gave me an F-minus in breathing.

Dacre Knight: Okay.

[26:36] Dr. Linda Bluestein: She pointed out that I was breathing really shallowly. And there's data on this — I actually went to the Mayo Clinic three-day pain program with a family member a number of years ago, and they were talking about diaphragmatic breathing and the data on breathing in people with persistent pain. Isn't there a lot of data showing that when we're in pain, we breathe really shallowly, and that is probably not helping us?

[27:06] Dacre Knight: No, it's just triggering our sympathetic response and our stress response. And we were just talking about stress making things worse. We can actually do the opposite — we can decrease the stress response with correct breathing maneuvers. And that's fantastic, because just like we're talking about, the most accessible things are really the ones we want to tune into the most.

[27:29] Dr. Linda Bluestein: And speaking of UVA and the amazing Dr. Ina Stevens — before we go to the break, would you be able to share with us, I believe you have some openings right now. By the time this airs, maybe you'll have different openings at the UVA EDS and Hypermobility Disorders Center. But can you share with people how they might be able to find out what openings there are and what you might be looking for as you're building your team and expanding the center?

[27:58] Dacre Knight: Well, thank you for asking first. And it really is a consequence, perhaps, of the good work you're doing here, Dr. Bluestein, because we're getting so many more patients who want to come see us. That's great — we want to be of service to patients — but it just means we need to continue to rise to meet this need. Our waitlist continues to grow, and we have to expand our center as well to meet that.
[28:27] We've recently hired a nutritionist, genetic counselor, and more physical therapists and occupational therapists. I think the recent openings still are for advanced practice providers — so nurse practitioner or physician assistant — and an occupational therapist. Eventually we do want to incorporate healthcare professionals in some of the things we're talking about too, so mind-body therapists and licensed health and wellness coaches, who have been very effective in the care of our patients.
[29:14] Those positions will be available on LinkedIn and on our Ehlers-Danlos Center website at UVA Health. Just Google "Ehlers-Danlos at University of Virginia" and you'll see the page where those positions will be posted. Thank you for asking, because we want to continue to grow and continue to meet patients' needs.

[29:22] Dr. Linda Bluestein: Most definitely. I think a lot of people are already aware of the waiting list. And you — the listener — can help shorten the waitlist by spreading the word about these openings and directing people to the LinkedIn page and the links in this podcast. People can help the community by helping build the center. Okay, great.

[29:48] Dacre Knight: Yeah, help everyone.

[29:50] Dr. Linda Bluestein: Yes. Okay, we're going to take a quick break, and when we come back, we are going to talk about our favorite pearls about medications and supplements.
[30:45] We are back with Dr. Knight to discuss the last two letters of my treatment algorithm — M and S for medications and supplements. A lot of people have tried many different medications, so this can be really tricky. Oftentimes people are very sensitive to medications or they've failed a lot of different treatments. How has that reality shaped your prescribing philosophy?

[31:16] Dacre Knight: With anything related to EDS and hypermobility disorders, there is certainly a learning curve. We all started from nothing when going into this field, and it's been quite a steep curve. But with medications as well — a lot of the medications I had turned to as a general internal medicine physician were very effective across a broad range of conditions: everything from diabetes to hypertension to many other chronic diseases. In some ways we're reapplying these medications for different conditions but looking at some similar effects — beta blockers in POTS, for example.
[32:00] The prescribing philosophy stays the same: we always start low and go slow, and really try to only change one medication at a time, because otherwise if we're changing multiple things at once, we don't really know what is doing what. That's a critical directive.
[32:21] I'd also say that there are certainly medication sensitivity issues that come up in our EDS and HSD population more so than I would have seen in my general population in previous years as an internist. This brings into play the field of pharmacogenomics, and sometimes there are indications for pharmacogenomic testing when it's related to medication sensitivity or resistance. All of it is really just trying to bring better outcomes and more effective use of medications. Starting low, going slow, only changing one medication at a time, being cognizant of the possibility of medication resistance or sensitivities — and then reaching the best results with all of those things.

[33:23] Dr. Linda Bluestein: Before we go on to specific medications, I have a few follow-ups. I totally agree with everything you said. First question: do you have a specific guideline for that "one change at a time" approach? We all probably have this slightly different, and it may vary by the patient, but do you have a certain number of days you tell people — three to five days, seven to ten days, two weeks?

[33:51] Dacre Knight: That's a great question. The simplest response is that it varies by the medication mechanism itself — the drug half-life, which is how long it takes to metabolize at least 50% of the drug. We use that to understand how long the drug will be in the system, and therefore what the likely response time and discontinuation response time will be.
[34:24] Now, the science behind drug metabolism and half-life is very good — fairly accurate within hours. But there are so many other things going on in a patient's life: all the other treatments and modalities, the stress, the sleep issues, all the psychosocial things we talked about. So I usually at least double the sort of prescribed half-life indication when stopping and starting. If a medication has a half-life of a day or less, I would give it at least a few days on the generous side before saying whether it is or isn't working.
[35:16] For some of the mast cell activation treatments, because there can be much longer half-lives when we're talking about antihistamines and other classes, I may even give it up to a couple of weeks before making a determination. That's also considering the urgency and nature of the condition — if symptoms are very severe and we need to be more on point with timing, we may move a bit faster. But there are so many things going on in the human body and in the homeostasis of someone living with EDS and HSD that it's hard to have a hard and fast rule. I generally just err on the side of giving it more time than what the specific pharmacokinetics of the drug would suggest.

[36:13] Dr. Linda Bluestein: Are there certain drugs — I'm thinking of low-dose naltrexone, for example — where you might say, let's give it a longer period before we say this is not working? I generally ask people to give low-dose naltrexone about a six-month trial. Do you do that, or do you handle it differently?

[36:33] Dacre Knight: Yeah, I would agree with you. That's an appropriate approach. And there are some other mast cell activation medications, like cromolyn sodium for example, that you end up titrating quite a bit — you go up, then you go down, and you may go up again. The half-life of low-dose naltrexone, I believe, is less than a day — I don't know exactly off the top of my head — but the biological impact, which is what I think you're describing, is longer. Certainly weeks and months. So we want to give it that kind of full course of monitoring.

[37:27] Dr. Linda Bluestein: Yeah. So with LDN, even though the half-life is hours, we want to give it plenty of time so we can see what the effect is on the glial cells and on endogenous opioids.
[37:37] Let's talk a little more about pharmacogenomics. I'm a lot older than you are — when I went through my training, there was no pharmacogenomics. Sometimes I see what I think might be some overreliance on that data. I think it could be very helpful, but I really urge people to use it as a guideline more than an absolute, because I don't think we have enough robust data yet. Do you agree, or do you think it's highly accurate?

[38:10] Dacre Knight: I definitely agree. The way I've utilized pharmacogenomic testing is directly in line with a pharmacist. Yes, we can look at the genomics to predict how someone's unique DNA will affect their response to a specific medication or class of medication — it helps narrow us down from a one-size-fits-all approach. It allows us to prescribe the right drug at the right dose based on someone's genetic blueprint.
[38:56] But if we take it too narrowly, we don't account for the other factors involved with DNA and genetic mechanisms of disease and therefore response to medications. That's why I would enlist the help of a pharmacist when thinking about these things. And if a class of medication looks like it's not going to work but there are no other classes available, we may still need to do some dose adjustments rather than saying your unique DNA characteristic means you'll have nil response — because there's nothing else to try. We have to take all of those things into consideration. It's just another tool among many at our disposal, and we put it all together.

[40:10] Dr. Linda Bluestein: And that's what I tell people about fluoroquinolones, too. It's not that we never take them — if you have allergies to different antibiotics and you have an infection that's sensitive to fluoroquinolones but not a lot of other things, you always have to take into consideration the entire clinical picture.
[40:34] What about deprescribing? I see a lot of people who are on a lot of medications and supplements, and sometimes I look at their medication list and think, "Oh my gosh, maybe the fact that you're on three or four different antidepressants at these doses is actually making your symptoms worse, not better." I wish we were taught more about deprescribing in medical school. Is that something you find yourself doing with this patient population?

[41:08] Dacre Knight: Definitely. There is certainly a lot of trial and error when we're talking about all of these modalities and medications. There may definitely be medications we have to move away from — either they're ineffective or the side effects are too severe. That's why we start low and go slow, so we can monitor for any adverse response and make quicker adjustments before they become so profound that someone's blood pressure bottoms out and they end up in the hospital, or something else untoward happens.
[41:56] Deprescribing is just as important as prescribing. We again have to think about half-life and duration of biological effects when deprescribing, because that matters when we're starting a new medication — how long is the other medication actually out of the system before we add something similar or on top of it that may make side effects worse? Some antidepressants require a taper over a range of weeks if not longer. So going down on the dosage — depending on the half-life and the situation — is critical in the nature of deprescribing.

[42:45] Dr. Linda Bluestein: I'm glad you mentioned the taper, because that is so important. With a lot of those antidepressants, even if you taper slowly, it can be pretty rough. So what medications have most changed your practice?

[42:59] Dacre Knight: Those that have really been novel. Low-dose naltrexone — this has been around for a while, but the targeted use of it and the benefit of it has gotten a lot of attention recently, and for good reason. It's been very helpful for many patients and has a very good safety profile.
A newer one that's been getting attention related to POTS is ivabradine, and I've seen a lot of benefit for patients with that. Some of the newer migraine-targeted therapies too — there's been a real upswing in a variety of migraine headache medications and therapies that patients describe as life-changing.
And then for mast cell activation, those that have been around for a while have been tried and true — the second-generation antihistamines, if patients are able to see some benefit from them, like the non-sedating cetirizine, Allegra, Claritin. Beta blockers for POTS symptoms as well.
[44:25] When we get into the discussion about EDS and hypermobility disorders, medication is very difficult because of the chronic nature of the pain — this is why many of the pain medications, the Tylenol and Advil, are not really our best friends. They can be necessary and useful in certain situations, but the ongoing nature of hypermobility can make it very difficult to find the one medication that really makes the difference.

[44:55] Dr. Linda Bluestein: And we know that there are no on-label treatments for hypermobile EDS and HSD. So all of the treatments we use are quote, off-label. I've discussed what that means in another podcast — without taking too much time here, it just means we're repurposing the medication for a different indication than what it was originally approved for. That's not a bad thing, we do it all the time, but it's something to be aware of.
[45:21] When it comes to POTS — postural orthostatic tachycardia syndrome — do you have favorite medications? For example, do you use pyridostigmine, Midodrine? You mentioned ivabradine, which does help with heart rate. What about fludrocortisone? Are those things you prescribe often?

[45:37] Dacre Knight: They are, some more than others. It's interesting — different clinicians have got their go-to as well. I have a colleague in Atlanta, Howard Snapper, who really favors desmopressin. Dr. Alan Posinki really favors propranolol, the beta blocker. And yes, if patients come to me who are already on Midodrine and it's helpful — particularly in cases where they've had a lot of hypotension and issues with low blood pressure. So it ranges depending on the situation.
[46:17] I mentioned ivabradine, and yes, Florinef — fludrocortisone — can also be useful in the right setting. The ones I turn to most often would be the beta blockers, at least to get things started. And I'm learning a lot from Dr. Snapper about the application of desmopressin, and of course Midodrine and pyridostigmine as well — there's certainly potential benefit there.

[46:52] Dr. Linda Bluestein: I heard on a long COVID webinar once someone talking about "treatment roulette." And I think it's important to point out that as much as Dr. Knight knows, and as much as I know about this patient population and these conditions, unfortunately we don't really have great indicators yet for what medication is going to be most successful for a given patient. So it does require trial and error, which is frustrating for everyone involved.
[47:22] Do you see certain prescribing mistakes that come up more commonly that you want people to be aware of? We know a lot of clinicians listen to this podcast.

[47:35] Dacre Knight: We touched on it earlier — one of the most common problems is polypharmacy. We talked about deprescribing and the importance of deprescribing — it's to avoid just racking on more and more medications as more and more problems arise, and then trying to find a solution with a drug and ending up chasing our tail, or at worst shooting ourselves in the foot. We end up adding medications to treat side effects of other medications.
[48:11] I understand the extreme version of it, and I've also seen this happen: patients say, "All right, I'm just stopping everything," and they just stop everything abruptly. We don't want that either. Let's find the intelligent way through this — to remove medications that may be causing side effects, and any other medications being used to treat those side effects.
[48:44] Polypharmacy is really all too common in our patients because there are so many conditions and symptoms they suffer from — everything from migraines to stomach issues to pain issues. It's not to say these medications are not necessary; there are certainly cases where someone can, yes — we've talked about Hickam's dictum — everyone can have as many problems as they want, and those problems may need treatment. But we also have to think about how these medications may interact with each other.

[49:18] Dr. Linda Bluestein: Let's move on to supplements, because we're running out of time, and I feel like we could have taken this entire episode to talk about just medications and supplements — maybe we'll do that at a future time. Lots of patients, as I'm sure you've seen, spend many thousands of dollars on supplements. How do you think supplements fit into an evidence-informed treatment plan?

[49:42] Dacre Knight: I will say first — they fit into a capitalist market, that's for sure, because there are lots of people who want to make money selling you supplements. Buyer beware, to begin with, and obviously consult with your physician. Very often physicians are not consulted about supplement use and intake. I'm very grateful when patients do bring it up, but most often patients have already just started, and they say, "This is what I'm taking." And I say, "All right, let's spend some time going through them," because they are important.
[50:21] Supplements can be fine and can certainly be a solution, but they should solve a problem — not just create a collection of supplements and extra financial burden, because they add up very quickly. If it's a nutritional or vitamin deficiency, I work on correcting those deficiencies using the simplest regimen possible rather than multivitamins and things like that, which get more expensive. We target the specific deficiencies and work through it from there.

[51:12] Dr. Linda Bluestein: I had a patient the other day who is on a carnivore diet and was actually diagnosed by her PCP with scurvy — her vitamin C level was that low, which of course is going to hurt your connective tissue. So you're absolutely right — while we have to be careful about overprescribing and overutilizing supplements, there are true deficiencies. And we had a great conversation, you and I, with Dr. Gregory Plotnikoff about vitamin D — I want people to check that episode out too.
[51:43] At the same time, we need to be very cognizant of what things need to be corrected and what's the best way to correct them. And are there ways to evaluate what's actually needed? Unfortunately for some things like magnesium, we don't have good tests, but for vitamin D we do. And there are other supplements with no test at all — but if it's safe, we can consider doing a trial. For example, palmitoylethanolamide, abbreviated as PEA, can be very helpful for pain, inflammation, central sensitization, and stabilizing mast cells. But we need to be very thoughtful about what we're using and very aware of the capitalist element — there's almost no limit to the number of options, especially when you start looking at peptides and the direct-to-consumer labs being marketed to people. A lot of this I think is overhyped.
[52:45] Are there certain supplements in particular that you think are overhyped?

[52:55] Dacre Knight: That's a good question. Yes — those that give the impression they're going to cure everything. That may sound plausible if it's something that helps sleep and sleep improves everything else, but to label it as such and market it that way — I would be wary of what's actually in it. They might just throw in a whole bunch of different things: "This does X, Y, and Z, this does whatever else." And those added ingredients at excessive levels may not be very good for you. So anything marketed in that fashion is concerning.
[53:51] Otherwise, magnesium and vitamin D, yes — of course. Iron is another one we pick up when patients have low iron levels that need to be supplemented. Omega-3 fatty acids and so forth. But be wary of those that make far-reaching claims.

[54:19] Dr. Linda Bluestein: Right. If anybody uses the word "cure" in association with any condition, that should raise a yellow flag at the very least, and possibly a red flag, because in medicine we have cures for very few things.

[54:36] Dacre Knight: Exactly.

[54:36] Dr. Linda Bluestein: Much less in this space.

[54:38] Dacre Knight: Right. Much less something that's not FDA approved — just on the supplement market.

[54:45] Dr. Linda Bluestein: Yep. So let's move on from that. In the last couple of minutes, let's talk about lessons you've learned that you want to share with clinicians. You've spent years building some of the country's best connective tissue disorder programs. Looking back, what do you do differently now than you did five or ten years ago?

[55:06] Dacre Knight: It's striking to me how fast these things go by. Whether it's hosting podcasts or doing research or hiring or training and educating others, the time just goes by so fast. But there are certainly things we've learned along the way.
[55:34] I have personally learned that — taking this episode as an example, talking about medications, supplements, modalities, and psychosocial things — it really is a waste of time looking for one single answer. What is the one single thing? This gets batted around between POTS and mast cell and hypermobility — we're talking about biological mechanisms and single gene mutations and final common pathways. There's a lot of time and a lot of value in that research. But there's also a lot of time wasted where we could really be focusing the energy on here and now. How many patients are out there who need help that otherwise don't have any? Let's focus on attending to those. We can be building the research models and doing the experiments to move the science forward in the interim, but let's get patients cared for. Let's get this information to other providers so they can care for patients better. So it's really about building this full comprehensive framework across this health system — across the country, really — for patients to be attended to better.

[56:41] Dr. Linda Bluestein: And what do you think separates clinicians who become excellent at caring for these patients from those who struggle?

[56:57] Dacre Knight: We use the cliché of "thinking outside the box" a lot, but I really ascribe to that, because these disorders affect far more than just joints. They influence every organ system and every aspect of someone's life — not just the tissue itself, but the psychosocial effects we were talking about earlier, their work-life balance, their relationships.
[57:27] And it may not be out-of-the-box thinking in the traditional sense, but at least having that generalist view, incorporating integrative medicine approaches, functional medicine approaches, all of those other modalities. We have to look broadly at what these conditions affect, and therefore what we can use to treat them. I would say that's what separates the good clinicians from the rest — they are thinking broadly.

[58:02] Dr. Linda Bluestein: If listeners remember just one thing from today's discussion, what do you want that to be?

[58:09] Dacre Knight: Well, we've certainly gone through a lot, and I hope it hasn't been too confusing — because sometimes it gets very confusing to me quickly too, when we talk about all these things we can try. I'm also learning so much as I go through this. I've learned a lot from you even just from this episode, Dr. Bluestein. So thank you.
[58:27] I would say, if there is one thing to take away: the whole process of treatment and recovery is, as I alluded to earlier, not just one specific miracle treatment, not one missing piece. I think that's what a lot of people are looking for — that one specific thing. And I know I sound like I'm repeating myself talking about small wins, but it's really about understanding all of those small wins along the way, understanding the whole person, and recognizing all of those meaningful gains that can benefit that person. When we do that consistently, patients improve far more than anyone thought possible. If we're looking for all of those areas of improvement rather than one specific thing, it's really tremendous how much improvement I can see in someone's trajectory.

[59:27] Dr. Linda Bluestein: I think oftentimes it's easy to realize when you're getting worse, but not easy to recognize when you're getting better. I was texting with a friend of mine the other day who was there for me when I was at my worst. It was my birthday, so he had texted me to wish me a happy birthday. And somewhere along the way, he wrote, "Wait — you're not in pain every day anymore?" And I wrote back, "Actually, now that you mention it, no." He hadn't talked to me for a while, so in his mind he was thinking of me as I was. And this conversation really made me realize how incredible that improvement is, because we just adapt — we adapt to whatever's going on, whether it's worse or better, and it's very easy to focus on what we would still like to be better.

[1:00:29] Dacre Knight: And I think you hit it right on the head — we may not just focus on symptoms alone. We may focus on function and quality of life and joy of living. What are patients engaged in? Are they engaging with their friends and family in the way they want to? Are they able to participate in hobbies they previously enjoyed? That's the core of it — we want patients to be able to do the things that they want to do.

[1:01:00] Dr. Linda Bluestein: Absolutely. Focusing on function is so important. I remember when I was having a lot of problems with my wrist. The pain most of the time wasn't bad — if you asked me a pain number, it'd be like a one or two — but I couldn't open a door. So focusing on function is really essential.
[1:01:17] Do you have a hypermobility hack to share with us to wrap up this episode?

[1:01:24] Dacre Knight: I don't really have anything right offhand, but putting all of these things together — maybe just what you said: improvement itself is a form of treatment, and maybe a form of a cure, even if we're not looking for a cure specifically. Improvement, small gains, small wins — every small win is a hack in itself that we just continue to build on.

[1:01:53] Dr. Linda Bluestein: Love that. I'm writing that down. Okay. And I have a very practical quick hack to add: there are a lot of specialty labs out there, a lot of companies marketing directly to this population. There's kind of a gold rush mentality — a lot of people have figured out that there are many people walking around with possible hypermobility disorders or symptomatic joint hypermobility, and companies are catching on.
[1:02:23] Number one, be aware of that and be cautiously skeptical — put on your detective lens and ask, is this really necessary? Is there really data and science behind this? And also, some of these labs are ones you can get through Quest, LabCorp, or Mayo Clinic. Don't assume that if a lab is being marketed to you, you have to do it through that company.
[1:02:50] And for patients listening right now: you can make life easier for your clinicians if you look up the CPT code and the diagnosis codes that make it more likely to get that lab covered by your insurance. For example, if you want to get an omega-3/omega-6 index, there might be certain diagnosis codes your insurance requires. If you do that homework for your clinician, that can be really helpful. So that's my little hack on top of your hack.
[1:03:23] Okay. Before we go, can you share any special projects you're up to or anything you're especially excited about, and where people can find you?

[1:03:34] Dacre Knight: Certainly our program growth is very exciting. As I said earlier, we're rising to meet the needs of patients on our growing waitlist. One other very exciting thing is that I've been mentoring a colleague at the University of California, San Francisco, to build a budding EDS clinic there — which will really be helpful to patients on the West Coast of the country. Please give her some time to continue building that before everyone inundates her with a massive waitlist. I will continue helping her build it.
[1:04:19] And there have been two MDs who have replaced me at the Mayo Clinic EDS clinic, so I'm always excited to see these programs expand wherever possible across the country. I'm on LinkedIn — I'm not on many social media platforms because I kind of leave the social media to you, Dr. Bluestein — but I am here on the Bendy Bodies Podcast as well.

[1:04:51] Dr. Linda Bluestein: Yes, and we are thrilled that you are. It's a wonderful way for people to learn from you and learn about the incredible work you're doing at UVA. I love that you're doing the Empowered Relief program and the dry needling training — just to circle back to those things. You're doing some incredible work there.
[1:04:59] And I love that you're mentoring someone who is looking to start another EDS center. I do that as well — I offer professional mentorship, and I'm actually mentoring a couple of physicians in other countries, which is really exciting. I think there are so many reasons for people to be hopeful right now. And that's a huge goal of this podcast — to let people know we are there for you, we are really trying to help you. Dr. Knight is such an essential member of this community and a leader in this space. This was such a fantastic conversation. Thank you so much for joining me again, Dr. Knight. I love all the great things that you're doing. I don't know how you do it all — you're in a lot of different places doing a lot of different things — but please keep it up.

[1:05:57] Dacre Knight: Thank you so much, Dr. Bluestein. It's always a pleasure to be here.

[1:06:36] Dr. Linda Bluestein: Thank you for listening to this week's episode of the Bendy Bodies Podcast. If you'd like to go deeper, I share additional education, clinical insights, and resources in my newsletter, the Bendy Bulletin, which you can find on Substack at hypermobilitymd.substack.com. You can also help us spread the word about connective tissue disorders by leaving a review, sharing this episode, or sending it to someone who needs it. These small actions truly make a difference in raising awareness about these conditions that are still widely misunderstood. And don't forget — full video episodes are available every week on YouTube at Bendy Bodies Podcast.
[1:07:10] As many of you know, my passion is helping people better understand and navigate symptomatic joint hypermobility. In addition to my clinical and educational work, I offer one-on-one coaching, professional mentorship for healthcare professionals, and expert witness services. If you'd like to learn more, please visit the services page at hypermobilitymd.com. You can find me, Dr. Linda Bluestein, on Instagram, Facebook, TikTok, X, and LinkedIn, all at hypermobilitymd.
[1:07:36] As part of our collaboration with the UVA Health EDS and Hypermobility Disorders Center, we also want to share a few helpful resources. For questions or appointment inquiries, you can contact them at [email protected]. That's the letter R, [email protected], or call 434-243-8200.
[1:08:01] Our incredible production team is Human Content. You can find them on TikTok and Instagram at Human Content Pods. We love bringing on guests with unique perspectives to share. However, these unscripted discussions do not necessarily reflect my views or opinions. Furthermore, perspectives expressed within Bendy Bodies media, including this podcast, do not reflect the views or opinions held by Human Content Inc. Although we may share healthcare perspectives on this podcast, no statements made on Bendy Bodies should be considered medical advice. Listening to or watching this podcast does not constitute a doctor-patient relationship. Please always consult a qualified healthcare provider regarding your own care. For information about the Bendy Bodies program disclaimer and ethics policy, submission verification and licensing terms, HIPAA release terms, or to get in touch with us, please visit bendybodiespodcast.com. Bendy Bodies Podcast is a Human Content production. Thank you for being a part of our community, and we'll catch you next time on the Bendy Bodies Podcast.