Beyond Bones - relevance of variants of connective tissue (Hypermobility) to Fibromyalgia, ME/CFS - Eccles et al Feb 2020

BEYOND BONES - THE RELEVANCE OF VARIANTS OF CONNECTIVE TISSUE (HYPERMOBILITY) TO FIBROMYALGIA, ME/CFS AND CONTROVERSIES SURROUNDING DIAGNOSTIC CLASSIFICATION: AN OBSERVATIONAL STUDY

This article is a preprint and has not been peer-reviewed [what does this mean?]. It reports new medical research that has yet to be evaluated and so should not be used to guide clinical practice.

https://www.medrxiv.org/content/10.1101/2020.02.21.20025072v1

 

Given the nonsense that the NHS uses internally over those diagnoses, I would not put any trust whatsoever in what this setting can produce, unfortunately. The study doesn't appear particularly bad, but at some point incompetence catches up to you and destroys credibility far too much to take anything from an ideological playground as being relevant.

Funding:

 

I wonder what on earth 'beyond bones' is supposed to mean. No way would a serious scientific study start with that. It is the sort of catchy title you might give an invited editorial.

Why put it up on Medrxiv?

 

I) Prevalence of hypermobility
The most notable result seems to be that they found that 80% of patients met Brighton Criteria for joint hypermobility syndrome. That seems very high and makes me wonder if there was a significant selection bias. The paper reads:

"Patients were recruited by advertisement from local support organisations for Fibromyalgia and ME/CFS, local rheumatology clinics and via social media and bulletin boards."​

Would be good to know how the advertisement looked like. Did it, for example, mention hypermobility or hEDS?

It seems a bit strange that the authors do not mention exclusions of the patients they examined. Usually, if you recruit patients suspected of having ME/CFS and do the required clinical examination, you'll find patients who have similar symptom but actually have another condition that can explain the results. Here it seems that 97% who responded to the advertisements turned out to have ME/CFS according to the Fukuda criteria and 94% according to the Canadian Consensus Criteria. That seems quite high.

I also don't think that the assessment of hypermobility was done by researchers/clinicians who were blinded to ME/CFS status - perhaps this could have inflated the prevalence figures of hypermobility a bit as well.

II) Symptomatic hypermobility
The authors say that "It is important to note the high rates of mis/underdiagnosis of symptomatic hypermobility in this group." But how do we know that the hypermobility is symptomatic if ME/CFS patients have symptoms anyway? If 37.5% of healthy controls met Brighton Criteria for joint hypermobility than perhaps a lot of ME/CFS patients who met the criteria don't experience any disabling symptoms as a result of it as well.

One way to know more is to look at correlations between ME/CFS symptoms and hypermobility indicators, but the authors note that:

"Across all participants there were no associations between current (i.e. present) Beighton score and baseline pain, fatigue and interoceptive questionnaires."
​

They then go on to focus on Historical Beighton scores (i.e ever being able to perform the relevant manoeuvre) where there were some correlations, but this seems less relevant than the current Beighton score.

The authors also mention that:

"Endorsing both major criteria of Brighton Criteria was significantly associated with fulfilling Canadian criteria for ME"​

I'm no expert in this but from quickly googling the Brighton criteria it seems that "Arthralgia for longer than 3 months in 4 or more joints" is one of the two major criteria, so no surprise that this predicts ME/CFS/FM status. After al, criteria for healthy controls included having a score no more than 3/10 on a pain visual analogue scale. Except for easy bruising, no other minor Brighton criteria (dislocation, skin hyperextensibility of skin etc.) were significantly predictive of ME/CFS.


III) hEDS prevalence
The prevalence of hEDS was also determined and reported as follows:

The authors didn't report a significance test for this presumably because their sample size was too small. They write: "Our control group is too small to make more than anecdotal statements regarding hEDS prevalence." They did note that "A diagnosis of hEDS did not predict presence of Fibromaylgia and or/ME/CFS, nor did individual elements of the diagnostic criteria."

 

Just remember that the main author of this preprint was talking about their results on Twitter a couple of months ago:
https://twitter.com/user/status/1209120124982243328

 

The first author Dr Jessica Eccles has been quite helpful in clarifying some things on Twitter:

https://twitter.com/user/status/1232362095196413954


https://twitter.com/user/status/1232369102154539010


https://twitter.com/user/status/1232686032887435265


https://twitter.com/user/status/1232706104506929155

 

I am afraid it sounds very much like Bendyourdata of the type normally associated with the Brighton criteria.

 

For what it’s worth:
I satisfy all ME, ME/CFS and CFS criteria. I tend to have nearly every symptom listed that a man can have.
But I’ve never had any hypermobilty in any joints. In fact, things went in the opposite direction despite being quite active in the early years and spending a lot of time doing stretching.

 

Me too Dolphin, but it is interesting that three of the members of our local ME support group, who each have had a diagnosis of ME for many many years, have recently been diagnosed with EDS: a new member also shares some of their characteristics.

 

Me too. I don't believe I have EDS but looking at the chart in post #7 above I am surprised at the number of things I would say yes to. Despite the fact I consider myself to be quite a "stiff" person. I especially noticed this in yoga class where there were other women of a similar age.

2 of my siblings tick a lot of those boxes and I was always envious of how flexible they were. A couple of their offspring have been officially diagnosed with hypermobility.

Maybe a link, maybe not. There are other autoimmune disorders in the family that are just as likely to be connected as this is to ME.

 

In contrast to this poorly structured little study there are some big population based studies now indicating that hypermobility has little or no relation to ME/CFS or chronic pain syndromes. It may be worth noting that Dr Eccles is a psychiatrist specialising in mind-body interaction and the BPS people had a major input into floating the idea that there was a link, based again on poorly conducted studies. This is the bio bit of BPS for them.

 

I can't remember if I read it or imagined it, but I thought that lax and deconditioned muscles could give hypermobility. Despite being unable to do very much I was able to touch the floor with my hands with ease. I stopped doing it because I decided it was more a sign of damaged muscle than fitness or ability.

I have no idea where this notion came from or if it is true.

 

Muscle condition/deconditioning is quite different to flexibility. Stretching less should lead to less flexibility, though joint laxity is another story.

I have neither joint flexibility, nor joint laxity and the idea that I could ever touch the floor with the palms of my hands is well, a fantasy at best.

edit- without bending my knees, dear smarty-pants!

 

It's quite easy to do, the trick is to bend your knees.

 

Generally speaking not. But the Beighton manoeuvres for hypermobility are a mixed bag that probably test a combination of e.g. ligamentous length, ligamentous elasticity, bone congruity, and musculotendinous length. I am pretty sure that Carter and Beighton had no real idea why they were choosing the 9 points they did. It is all a mess and almost certainly of no real interest.
I suspect that muscle bulk does not get in the way of any of the Beighton manoeuvres. Ballet dancers who can put their hands flat on the floor usually have highly developed musculature. Elbow flexion may be limited by a large biceps/brachialis complex but flexion is not used to judge mobility.

 

Now published. Open access, https://www.rcpjournals.org/content/clinmedicine/21/1/53