Severity classes in adults with hypermobile Ehlers-Danlos syndrome/hypermobility spectrum disorders: a pilot study ..., 2019, Copetti et al.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3489993/

 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4016972/
"Each of these five clusters of clinical characteristics (cutaneous, connective tissue, GI, atopic, neuropsychiatric) were independently and significantly associated with elevated tryptase."

 

These are based on in vitro studies. As I pointed out, in vivo, enzymes are balanced by inhibitors. Unfortunately, a lot of researchers will extrapolate from in vitro findings ignoring the in vivo situation.

There is no doubt that fibrosis can occur following chronic asthma, which involves mast cells. However, in the equivalent situation in joint tissue where fibrosis follows inflammation it became clear in the 1980s that the problem cannot simply be put down to enzyme activity. Cell death is likely to be an essential element before remodelling occurs.

And again, I would emphasise the need to consider the location. Fibrosis occurs in the lung following severe chronic inflammation at that site. As far as I know nobody with 'MCAS' and probably nobody with mastocytosis has been found to have inflammation in the upper cervical ligaments and nowhere else. If it was happening elsewhere then it would be laconically evident.

Blaming mast cells for CCI is a bit like saying that if you fill up a car with petrol you are likely to get a clean windscreen because petrol is a good cleaning agent. It is as disconnected as that.

 

This paper shows that if you set up an experimental system that causes tissue damage you need mast cells to be functioning. That applies to the arthritis situation as well. The car does not go at all without the petrol. But that does not lead to the conclusion that mast cell enzymes on their own can cause tissue degradation.

Remember that all these papers are written by people marketing a particular idea in order to get grants. Overinterpretation is the name of the game.

 

But in that paper there is hardly any mention of what these 'connective tissue' problems are except for musculoskeletal pain. I get the impression that this group have joined the MCAS/POTS/EDS bandwagon and are chucking it all in to press their case.

You will always find a handful of papers pushing an idea, especially if it has become a popular meme. The important thing is the despite at least ten years of this one floating around there is essentially no evidence for ligamentous laxity occurring as a result of mast cell activity.