EDS and ME - is there a connection? hEDS

I am sorry that you feel you need to use words like lying @Bluesky. My intention here is simply to be very honest. Dr Grahame was never a rival of mine. He was a dear friend who did more than anyone else to secure my consultant position and professorship. I owe him an awful lot. But I owe patients my honesty more than that.

 

daughter - Ashley
https://twitter.com/user/status/859510189531078656

 

thanks tis a name in uk for both sexes.

interesting that they are runing atp profiles on both.

another area of research mito function that edwards does not see as evidenc for pem.

thanks for clarifying but i doubt i will stay on this forum because of jonathon edwards.

 

This thread is extremely timely for me, since I received virtually no response to this thread:

https://www.s4me.info/threads/referral-to-inherited-metabolic-disorders-clinic.1941/#post-34006

At the time, I wondered if @Jonathan Edwards "expert" views essentially shut down the thread before it even got started, if I was way off base in my understanding that there may be a link between ME, EDS, POTS and MCAD, or if my question merely caught few members' attention. Now I know I'm not the only one to have questioned the worth of information about EDS from the 1970's. After all, hasn't medicine moved well beyond the 1970's regarding many illnesses?

As mentioned in my earlier post, I have been referred to a genetic clinic for evaluation of suspected Ehlers-Danlos Syndrome. The referring physician is a recently graduated internal medicine specialist -- the most thorough doctor I have encountered in my 30 years with ME. After realizing the complexity of my many medical issues she extended the length of my first appointment -- spending a total of 2 1/2 hours with me. The medical report she produced was pages long. So, it seems things have progressed in the minds of at least a few physicians regarding previously unknown and misunderstood illnesses and conditions.

I'm still in my post-Christmas crash, but will attempt to slowly read the above responses before my appointment in a few days. Nevertheless, if anyone would be willing to provide a list of links to information I could take to my consultation, I would appreciate it.

Many thanks, everyone, for the education and support . . . and especially to @Mij without whose "heads-up" I may not have found this thread.

 

As someone who has been diagnosed by a medical geneticist with hEDS/EDS3 (as it was known when I was diagnosed), and who has spent much of my life in braces, on crutches, in physical therapy, and became completely disabled with ME/CFS after surgery to stabilize unstable joints after hundreds of injuries over my life due to hypermobility, I think @Jonathan Edwards has made a very valid critique of the state of hEDS research that those in the field would do well to listen to. Indeed, when he first made these points over at PR a few years ago on an EDS thread, it was one of those "so I'm not crazy; the emperor really might be naked!" moments for me.

There are only a few hundred studies on EDS — which may sound like a lot until you realize MS has over a hundred thousand. And most of those EDS studies on PubMed have NO biological data involved but are clinical observations or studies of questionnaires, prone to all the problems Dr. Edwards has detailed. Don't get me wrong. Medicine has to start somewhere and it begins with clinical observation. BUT clinical observation is NOT established fact. It's just a story some doctor is telling to make up for the void where biological data should be.

Look, we humans like narrative. We have a very hard time dealing with narrative lacuna. And those stories make a hard life a bit easier. Being able to tell the phlebotomist that I have fragile skin because of a supposed genetic defect in my collagen means she treats me a lot nicer when I ask for coban instead tape after a blood draw. And the EDS diagnosis gives my primary care provider some diagnostic flexibility with insurance companies when it comes to things like physical therapy or a wheelchair. These are not small things. I understand why having these stories matters to patients, and why they can feel so threatened when the story is threatened.

But I'm under no illusions about how valid that story is. If hEDS is supposed to be a genetic mutation at conception that supposedly affected the structure of my connective tissue, why did I only start injuring like crazy when I hit puberty? Estrogen maybe? Who knows? Where's the biological evidence to explain it? The only hEDS "symptoms" I had prior to puberty were flexibility and problems with gut motility (my mother still complains about the problems I gave her trying to feed me as a baby). Also when I hit puberty, I started dealing with IBS, fatigue, sore throats, and days that felt like I had the flu. Was it related? Was it pediatric ME/CFS in addition to hEDS? Fibromyalgia? Did the injuries from hypermobility trigger ME/CFS and/or FMS? Who knows? And frankly, even if we had a blood test today, we couldn't go back and give it to my 10-year old self so we'll really never know. And I'm okay with that. But I'm not okay with mere clinical checklists that have more in common with astrological charts than hard, objective biological markers. Those biological markers do not exist for hEDS; there are only clinical observations. Just because something seems to fit with your experience or the doctor's experience does not necessarily make it true. And just because there's a paper on PubMed does not make it true. It also does not negate the reality of your symptoms. It simply means the story to explain why may not be the right one.

The problem is if we get too attached to these stories, it impedes the hell out of science. We can't ask the right questions or gather the data we actually need. It's precisely what the BPSers have done with their story about aberrant illness beliefs and deconditioning to explain ME/CFS. And it's a nice, neat story, which is why clinicians like it so much even if patients find out the hard way it's complete bullshit. You can have good intentions and still just be spinning stories. Asking if the stories doctors are telling are backed up with any biological data is not the same as saying patients are making up stories. Your symptoms are very real. It's the explanation your doctor is giving you to explain why you're having those symptoms that may not be.

 

I would like to remind everybody here of our forum rule #1

Let's keep things civil people, even if you disagree with each other.

 

I think I'm starting with the assumption that almost any sort of 'strain' could be a risk factor for ME/CFS. We don't know what it is that leads on to ME/CFS, or why it seems to be that certain viruses can trigger it in some people but not others. [edit: I'd actually include 'biopsychosocial' strains in there too, although the evidence of the importance of psychosocial factors often seems weak or overstated].

There are things like people suffering from lots of dislocations and subluxing, and that is likely to be bad in itself, and could lead to sustained problems with minor damage which may leave one at greater risk of other things. People report bruising easily. I can imagine how joint laxity could mean it was more effort to hold positions, etc, and that these sorts of minor issues could lead to mild problems with fatigue, but also provide an additional strain which may place them at greater risk of developing other problems. Also, the idea that these people have a tendency to more stretchy tissue, which would lead to problem with PoTS as blood pushes outward slightly on standing, seems plausible.

There is a danger that Grahame is just being referred patients who happen to fulfil a criteria he has created, but from the perspective of watching ME/CFS patients going on to be examined because of their hypermobility, my hunch is that there is also a pattern of shared features amongst these patients that is more than chance.

There has been conflicting results for ME/CFS and an association with PoTS too, so I'm less sure of a link there (beyond a secondary one related to deconditioning) than you seem to be. So much about these things still seems uncertain.

With a lot of these things like this (ME/CFS & HMS, etc), when there is not a really solid abnormality to focus on it can be hard to chip away and the cause of ill-health. I don't think that they have a good understanding of the cause of disability for people with hEDS (particularly the more seriously affected), but I also think that their probably is some meaningful syndrome in there (while recognising that the evidence for this is far from clear).

It's possible I'm being affected by the fact that ME/CFS patients who end up with an HMS diagnosis often find this politically and practically useful. I don't think so, although I do think that this is something which means I'm less likely to prioritise examining all the evidence here.

Doing the sort of rigorous population based study needed to provide clear evidence of an association between these HMS features would be really expensive, wouldn't it? I don't think a questionnaire based approach would be likely to work out very well. I'm not sure I see an easy way of assessing whether HMS is a valid syndrome or not (but as I say, I've not taken the time to look at all the evidence in this area, and much of what I have seen appears to have problems which make it difficult to interpret).

 

Just my experience in my family: First ME, and then one issue after the other appeared.

 

I'll say it again: Your symptoms are very real. It's the explanation your doctor is giving you to explain why you're having those symptoms that may not be

 

That's really not what he's been saying. If it turned out that those with EDS III had a cause of their symptoms that was significantly unrelated to tissue laxity then that wouldn't make their symptoms any less real, or their concern about them any less justified.

 

Mine was the opposite; first multiple fractures, soft tissue injuries, dislocations, then ME/CFS-like symptoms.

To me, if there is a link between hEDS (which is what I think you meant instead of HMS?), it's probably this. You get injured, if you get so repeatedly or bad enough or need surgery, or whatever, it triggers whatever biological process causes ME/CFS. But it gets complicated because there's so much overlap with FMS. And the injury/trigger theory would fit with central sensitization (if that is what's causing FMS, that is). So, is it connected to FMS or ME/CFS? And have we even definitively established that FMS and ME/CFS are separate disorders? Most people think they are but I don't think the evidence can say that with any certainty.

 

Ditto.

 

@MsUnderstood

I see that you have posted, and many others, but have not yet read the posts. I think your post and others need reading carefully which I will do after a stress test tomorrow.

I had to stop taking betablockers for the test so HR is high and I am trying to ensure I can complete the test with the least pem

 

Or, let me put this another way. Your symptoms -- and all of those diagnosed with hEDS -- are almost certainly based on a biological problem. It's simply that the diagnostic criteria used to explain that biological problem have almost no biological basis.

I don't know if that helps?

 

sorry this quote looks too out of context now, and too unwell to go back and retrieve the full quote, but it was in relation to MCAS.

The fact that nobody in the research community talks about it is what is so worrying when so many of us have this issue. I know when i asked Ron Davis was aware of a connection, but so far there is not much coming out of the M.E research community about it. From the other side of things Dr Afrin, who is the leading expert on Mast cell activation diseases/syndrome does discuss 'CFS' and notes the co morbid nature or possible misdiagnosis of CFS with MCAS.

If you are not aware at all of the condition and wish to know more i am happy to provide research papers and articles. Adding MCAS to severe M.E has literally added a whole new level of hell to my and others lives, which makes it impossible to even lead a semblance of a normal life.

If you look over at PR on the dedicated mast cell sub forum you can get a small snapshot of how many PWME have this co morbid condition.

Its been interesting having the hEDS discussion here and listening with as rational an ear as possible and i feel like i am learning all the time. I had been on the point of making an appointment with Dr Hakim, but perhaps it is not a wise use of my precious energy and resources to pursue this current issue and im now leaning towards putting my energy into other areas, OI testing being the most pressing (i inadvertently earlier referred to OI as POTS - i do this all the time by mistake.

 

I think if there is any causal link between an EDS subtype and ME/CFS it would have to be that the congenital laxity of tissues leads to susceptibility to ME/CFS. An illness like ME/CFS starting in adolescence or adult life cannot cause an EDS syndrome. Joint laxity developing later in life is a completely different problem, related to arthritis.

Hypermobility causing injuries and dislocations is actually quite uncommon and a tiny proportion of people with hypermobility. I have seen some striking cases but probably no more than a dozen over forty years in general rheumatology. In contrast I looked after 500 people with RA. RA prevalence is about 0.5%. I think 0.2% is a fair estimate for ME/CFS. Maybe people with lax joints chiefly go to orthopaedic surgeons but my impression is that congenital laxity severe enough to actually cause pain is not common.

Without injuries and dislocations lax joints are not generally a problem. Many ballet dancers owe their skills to being hypermobile and although they do get injuries they are not out of proportion to the extreme activities they undergo. (My wife and a friend know the dancers of the Royal Ballet School well and follow them through to performance artist status.) None of them as far as I know has orthostatic intolerance.

Another point is that in the striking cases of joint laxity I have seen the problem tended to be a problem for one particular class of joint. I remember a young girl with extreme knee collateral laxity who could not walk effectively without deep wedges on her shoes. But other joints seemed OK. I remember cases of recurrent shoulder dislocation but again other joints did not seem a major problem. No doubt there are a small number of people with severe laxity of multiple joints but they must be rare. I am talking about the sort of laxity that would be obvious if the person was a shop assistant taking money or a nurse doing duties, or a lecturer showing slides etc. Although established ankylosing spondylitis has a prevalence of about 0.1-0.2% I notice people with the condition about every three months in the street, because it alters the way they move.

If the prevalence of ME is 0.2% and 10% of that is secondary to marked joint laxity then I guess it would be possible that 1 in 5000 children have lax enough joints to end up with an ME like illness. But what puzzles me there is that this level of laxity is obvious to everyone. These people need callipers or heel wedges or were able to do amazing contortions as children. The Beighton score is irrelevant here because it is a test of mild laxity and lots of people score highly. You do not need to do a Beighton score on someone with three episodes of patellar dislocation.

There is also the fact that ME/CFS pretty much by definition appears out of nowhere in someone who previously did not have related symptoms. So it sees that we would have to invoke some sort of neural feedback with 'central sensitisation' or somesuch. But even central sensitisation does not seem to explain delayed PEM. And the level of recurrent injury needed to get this would surely be at a level that would make it obvious to the person and the doctor that this was causing the onset of fatigue.

Maybe I am not seeing this clearly but it doesn't match up to me yet.

 

Very helpful discussion. Thank you @Michelle and @Esther12 for your recent posts which particularly resonated. It's very interesting as I try to make sense of what's going on with my sister with hEDS dx (and other conditions which complicates things), and myself - what is similar and what is different.

 

I saw a link following my specific Rieger syndrome foxc1 Foxo1a(b cell & insulin signalling amongst many other metabolic functions) paper from oxford
I don’t have eds or pots
It says HDGF hepatoma derived growth factor and collagen IV a-3 col4a3 downregulated be foxc1
I probably have a deletion there so presume mine must be unregulated
Would heparin help I wonder

 

I saw the orthopedist(s) routinely growing up but never once went to a rheumatologist until I was almost 30 and referred to one to be evaluated for Fibromyalgia (which seems a far more likely candidate for causing wide-spread pain than hEDS).

It started with one joint: my right ankle in which I had a bimalleolar fracture with ligament tears when I was ten years old. It never really healed properly and I have continued to have various ligament injuries every since. Within a year and a half of the ankle fracture, my right patella began subluxating and just not tracking properly. Within a year of that, my right shoulder started subluxating and then spontaneously reducing. I never told anybody because it always went right back into place, though it would be sore for weeks after. Besides, when I began complaining of pain in my legs a year or so after the ankle fracture, the pediatrician said it was growing pains or that I projecting pain or whatever. My 11 year old self took it to mean that everybody had pain like that and I should quit being such a pussy and just buck up and live with it. It wasn't until I was almost 30 before I began to realize that the pain (which was much worse by then) was not normal.

I've read that estrogen contributes to ligament laxity. Could puberty (all of this started post-puberty) have played a role? Within a year of the ankle fracture, I also began developing ME-like symptoms and was, thus, becoming less active, so assume muscle atrophy may have played some role as well, though I remained active enough that I'm hesitant to say I definitely had ME by that point. Fluge and Mella have spoken of blood flow dysfunction (though, tbh, I'm unclear about what they mean, exactly, by it) and wondered what role that might have if joints aren't getting enough blood. I know all of this is just pure speculation. What we need is some damn lab work already!

While I find the scientific validity of the research being published on hEDS to be poor, I can't deny the very practical benefit of the stories they are telling. When I look back at my adolescence, everybody had a vague sense that something was wrong with me. After the EDS diagnosis, the mother of a friend of mine growing up exclaimed "I knew something was wrong. You were always on crutches and that's just not normal!" In terms of both the injuries and the ME-like symptoms, I routinely missed at least 20 days of school a year. But without some diagnosis, some story to give school officials, I never got any educational support. I went on to study for an academic career that my professors seemed to think I was intellectually capable of but given how much school I routinely missed, was really, looking back, never going to be an option. But without some explanation, I had no idea why or what to do with my life.

From the perspective of the science, these stories muddle everything up. But when it comes to the day to day practicalities of living, what do we do without these stories?

[ETA: I got distracted and meant to finish the paragraph about joint involvement by noting that as the years have passed, I've had joint laxity/dysfunction/subluxations/dislocations in many of my major joints (SI joint, both ankles, hips, various vertebrae and ribs, both shoulders, left elbow, and the index & middle fingers of both hands frankly dislocate so that I have to pop them back into place making it very difficult to, say, cut a steak). I've assumed that's been due to weight gain and muscle atrophy as ME has worsened. Though the finger problems have just been in the last 10 years and surprised me. Physical therapy has been helpful in targeting muscles to strengthen. ME makes exercise a challenge though I seem to have found a good balance of 2-4 rep exercises once or twice a week. Indeed exercise seems a funny word to use given it lasts for about 30 seconds or so. ]