Is joint hypermobility linked to self-reported non-recovery from COVID-19? Case–control evidence ... , 2024, Eccles et al

Off the top of my head —

• Beta-adrenergic receptor auto-antibodies
• Something messing up acetylcholine or its receptors
• Something messing up nitric oxide generation
• Impaired endothelial generation of ATP, leading to reduced NO generation and availability to vascular smooth muscle cells
• Damage / impairment of the vasa vasorum (the small blood vessels in the wall of the capacitance vessels themselves), possibly by microclots

 

Thanks, seems like a good list. You'd think these hypothesis wouldn't be that hard to test, I guess it just takes money, time and some rigorous trial protocols that have been lacking. Doesn't seem like immune modulating drugs, mestinon, or nicotine has been that effective.

Also I meant to say blood pooling not blood blood .

 

In the teensy NIH study (Walitt et al. 2024), there was no difference in Beighton scores between pwME and healthy volunteers. It’s in Supplementary Data file 5:

Characteristic HV (n=21) ME/CFS (n=17) p-value

Beighton Score [mean (SD)] 0.6 (1.0) 1.4 (2.2) 0.1

The Mudie et al. study in ME/CFS suggests to me that there is no connection between hypermobility and ME/CFS, but that people with EDS and ME/CFS may be more severely affected than people with ME/CFS but not EDS, and that could be worth looking at in better studies. (All self-reported in Mudie et al.) https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2024.1324879/full#h4

This is Mudie et al's table 3 of people with ME/CFS and with or without hypermobility, but not EDS:


And this is table 2 from Mudie et al:


There is no table in Mudie et al comparing those with and without EDS. I think in table 1 (not shown in this post), which compares those with and without hypermobility, the few statistically significant differences are likely attributable to the higher rate of EDS in those with hypermobility.

 

If I remember rightly there is no evidence for any of the patients in the Mudie study actually having EDS. I think it was just that someone had told them they had - which is hopelessly inadequate since so many 'ME physicians" diagnose EDS on anyone with loose joints.

It is also extremely difficult to compare severity on reports of symptoms. To have any biological value one would need objective evidence of a difference in disability using altimetry or whatever.

 

Agree on both counts.

I haven't seen a methodologically sound study that suggests a link between ME/CFS and either hypermobility or EDS, however either is defined.

I think it's also possible that physicians are more likely to diagnose EDS when someone's ME/CFS is severe. And/or that people with severe ME/CFS see more physicians in their search for help and so are more likely to end up in the office of a physician who thinks there's a link.

Would it be possible to do a study of pwME/CFS and pwEDS where a physician is blinded to whether people have ME/CFS or not and has to do a physical exam only to establish if certain features of EDS that are not part of ME/CFS are present, like velvety skin or wide scars and take a history only of things like of organ tearing, whether symptoms started with an infection or not?

 

'Velvety skin' is such a subjective thing you can diagnose it in almost anyone. People with true EDS with skin changes have visibly abnormal patches of redundant skin or scars. But those who have skin changes are not hEDS, they are genuine monogenic EDS cases and probably mostly have identifiable gene defects.

I have not come across anyone with ME with a known EDS gene defect. By chance there will be a few - maybe 100 people in the UK with both. There might well be one or two on this forum, but there will also be people with all sorts of other uncommon diseases by chance.

I would hope that the DecodeME GWAS study will confirm the absence of any findings of a link to EDS genes that seemed to be the conclusion of the preliminary look see in the Leeds Biobank on about 2,000 cases.

 

It seems plausible. When people have naturally flexible connective tissue, low body weight and can't use their muscles much, it probably exaggerates joint discomfort and subluxations. By the time my mam was 90, thin and frail, the head of her right femur would barely stay put—but she had bendy joints and hip dysplasia, not EDS.

I have EDS on my medical record because I spent decades needing my right hip shoved back into place, but if it's ever X-rayed, it probably looks like my mam's (and my aunt's, sister's, and several cousins'). Some of us have right shoulder blades so winged they look a bit like they belong to people with FSHD, but it's just another skeletal quirk. It makes me wonder how many of those who diagnose EDS actually look at the joints themselves.

 

It's not completely beyond the realm of possibility that there's a shared risk moving the ME vulnerability needle. From Genetic overview of postaxial polydactyly: Updated classification (2023, Clinical Genetics) —

GeneCards links for those is —

ZNF141
GLI3
IQCE
GLI1
FAM92A1
KIAA0825
DACH1

FAM92A1 is aka CIBAR1 —

I haven't come across polydactyly ever highlighted in ME patient histories though, so I very much doubt there'd be anything there. Perhaps there's a rare mutation that allows polydactyly and non-lethal mitochondrial impairments?

 

Oh that wasn't what I intended! What I was pondering was whether a study could be done that would control for diagnostic preferences, by not allowing the assessor to know whether the participant had a diagnosis of ME/CFS or EDS, and getting them to just work through a carefully honed checklist of physical signs and possibly a couple of history items. The purpose would be to see whether pwME really do have more signs of EDS than the general population - and so would need to include participants from the general population too, which I didn't explicitly say.

Mr Evergreen tells me that I switch topics with no warning, and I think that's what I did in my post, oops.