@Jonathan Edwards -
I agree it's one of the more perplexing disease associations in ME. It makes a good deal more sense with POTS, where problems with collagen structure could create vasculature weakness resulting in venous pooling, which might make one more susceptible to ME (i.e. a compounded effect of weak collagen and poor autonomic function). It could be that ME occurs to varying degrees after infections in many people, but compensatory mechanisms are sufficient so that it remains subclinical. This fits with general heterogeneity of disease severity in ME, which ranges from very mild / annoying to debilitating.
Dr. Edwards, can you think of any immune mechanism by which collagen could be degraded, resulting in joint loosening? I know you have vast experience with RA in particular. An overactive immune system does have the potential, sometimes, to produce elevated levels of matrix metalloproteinases, many of which can degrade collagen. Does this collagen degradation itself not have a clinically significant effect, or does it just not manifest as joint laxity (and is it possible that erosive bone damage and joint stiffness in RA make it so you can't see laxity anyways)? Have you ever seen joint laxity coexist with RA, and if so, did the RA alter it in any way, either increasing or reducing it?
I suspect you are already aware that in RA, they sometimes now test 14-3-3 eta levels, which correlate with disease severity in RA. Generally, 14-3-3 activates MAPK family proteins (ERK1/2, c-jun) resulting in increased transcription of IL1 and IL6 - the latter of which, in particular, should increase CRP. 14-3-3 eta also induces MMP-1, which is a collagenase, and several other MMP's as well. I know we're now discussing a different disease entirely, but curious if cartilage degradation by activated immune cells could play a role in joint laxity (even though, we'd then have to explain the lack of CRP elevation in these patients - as far as I know, and I could be wrong, there is no general elevation of CRP in hypermobility syndromes).
Clearly ME is not responsible for all cases of "type 3" hypermobility, nor is the converse true (I'm ME w/o EDS, and I know people who are EDS w/o ME). I'm actually pretty inflexible, and not because of pain - I'm just not that bendy. My sister because pretty flexible but that's after a lot of yoga (can put palms flat on floor, etc. - but still wouldn't have a very high beighton score, as arms/legs don't bend past 180, fingers don't bend to arm, etc.) I agree with you in general that type 3 is a hodgepodge.
I read once that men tend to have less EDS because musculature compensates better, and when they have it, it can be later onset. I wonder if something similar is in play for ballet dancers - as long as they stay in peak condition, the strain is born by muscles rather than joints (at least partially).
I'm not sure how much all of this makes sense, and it's just a loose theory that formed in my head last night - there could be more holes than in a block of swiss cheese - but it seemed interesting. It does seem, based on other posters, that the EDS precedes the ME, often by many decades, and that the EDS is usually lifelong, whereas the ME is not. That would argue against any causative role for ME in producing EDS, and suggest rather that EDS may create a predisposition to ME - but I don't know why. Alternatively there is a common risk factor for both, and they manifest differently or at different times.
Does anyone out there have genetically diagnosed non-type 3 EDS and also have ME? Or Type 3 genetically confirmed to be tied to Tenascin-X?