EDS, hypermobility, and the link, if any, to ME/CFS

I have been sent a very helpful presentation on this from a paediatric rheumatologist. It looks as if maybe people do know and probably there is no link. Some people have been doing the necessary homework. I will post more when I have had a proper look.

 

If there is no real evidence that hypermobility EDS is a valid diagnosis, which I accept there doesn't appear to be, I can't help wondering why charities and some doctors are allowed to promote so much misinformation about it?

 

I think I agree but I want to take things one step at a time. It looks as if one or two other people are already treading that road so hopefully we can make some sense of it all.

 

What if there are some risk factors common to both ME and EDS, even though some people might never suffer from either?

This is pure conjecture here, bearing in mind I am neither scientist nor medically trained.

What if there are some predisposing factors unique to ME, other predisposing factors unique to EDS, and maybe some predisposing factors common to both ME and EDS? If - and I really do mean if - there is some correlation between EDS and ME, could it be that it is not about people having both EDS and ME, but about having some risk factor(s) common to both? If we understood the risk factors much better, might a correlation between the risk factors then become clearer?

 

@Barry

I am seeing a geneticist on Fri and the referring Prof suggested my illnesses including ME, hypermobility +others may be part of a syndrome, and EDS was mentioned.
It sounded as if he saw EDS as the syndrome and the other illnesses as part of this overarching umbrella, but that may not be entirely correct. I was surprised to be referred.
We will see. I do not want any more diagnoses unless the illness can be easily cured.

My diagnoses have truly been getting more in number and complicated and I am starting to feel nervous about Friday.
To be fair, I was reasonably healthy until mid / late 60s, apart from PMS which is an awful illness but was successfully treated, hip replacement for osteoarthritis, then ME diagnosis. It would be strange if I were diagnosed with EDS at 72. The hypermobility has never impacted my life; to be accurate I had a mitral valve prolapse diagnosed 3 years ago. I do have degenerative joint changes appropriate to my age.

Thank you for the information @Jonathan Edwards. I heard the Prof talking to his students about a dominant disorder but cannot remember more than that because there was a lot to absorb and he was speaking to his junior doctors. He did change his diagnosis for the condition for which I see him from a secondary to primary disorder so it seems I have had it from birth, despite it not being apparent until recently. I hope the geneticist can throw some light on all this.

For anyone still reading, I think I will start a thread tomorrow for anyone who has seen a geneticist. I am not sure what to expect and would welcome any experience and advice.

 

@Binkie4 Since you are seeing a geneticist and have had a MVP this might be an interesting read for you.

Paper : Genetics of mitral valve prolapse and its clinical impact
https://www.escardio.org/Journals/E...mitral-valve-prolapse-and-its-clinical-impact

@Jonathan Edwards FYI Also some info on connective tissues genes listed in EDS - some are autosomal dominant and others autosomal recessive

 

Thank you @wigglethemouse . Certainly to be read tomorrow.

 

I am not sure what you mean about it not being about people having both EDS and ME because be definition that is what an association is about, but hopefully that will come out in the wash.

The assumption currently made, which I think is robust, is that EDS only has one risk factor - the presence of a mutant allele on a collagen or related gene. The range of features may be different in different individuals with a particular mutation but it is still EDS.

All the known mutant alleles are dominant, except for I think just one that is X-linked recessive. X-linked recessive genes actually behave as if dominant in men and when scarce, like these, virtually never affect women.

The problem with the current definition of hEDS is that it is too ill-defined. We know it is too ill-defined because estimates of prevalence range from 1/25 to <1/5000. That is to say that some 'experts' think there are 200 times as many cases as others do. That is not a useful definition. Nevertheless, if this is really a form of 'EDS' the assumption remains the same that risk is entirely dependent on one or more connective tissue gene mutations.

So if there are common risk factors for EDS and ME they can only be the EDS gene mutations, because they are the only ones for EDS. That effectively makes ME a complication of EDS in those cases - a secondary condition - at least in some sense.

 

What worries me is that as far as I can see nobody mentioned people with EDS having fatigue until the paper by Rowe and colleagues came out in 1999. None of the patients I remember from 1979 with hypermobility had fatigue problems of any significance, or OI.

Moreover, in the 1999 paper they suggest that fatigue might occur in EDS because of blood pooling in stretchy blood vessels. But I cannot see how that would produce symptoms of ME. As people here keep saying, ME is not really about fatigue. The symptoms are much more than that and they do not go away when sitting or lying.

There are bound to be a few people with ME who have narrowly defined EDS. There will also be 200 times as many people with ME with broadly defined hEDS. But so far I can see no epidemiological evidence for an association beyond chance. Rowe does not even attempt to assess the denominator for his 11 cases (i.e. the total number in the clinic from which they are drawn) beyond saying maybe 100. He says his observations are not reliable evidence for estimating prevalence. As far as I am aware nobody has made a formal analysis of prevalence of EDS (by various definitions) within an unselected ME cohort. The only preliminary information I have at present is that EDS does not turn up at all.

 

This paper contains an interesting discussion of the evidence/lack of evidence for hEDS, POTS ,MCAS and the links between them
https://link.springer.com/article/10.1007/s12016-019-08755-8

 

Thanks for posting this Theresa. The paper is interesting although I would recommend skipping directly to the discussion section. The rest are like seperate articles on each of the three conditions, making the paper way too long.

The authors argue that there are very little papers demonstrating a link between these three conditions an the few papers that didn't use validated diagnostic criteria, or older versions that are less strict. The emphasize that "No epidemiological studies were found addressing the coexistence of mast cell activation disorder, hypermobile EDS, or POTS using the current criteria." They also argue that there hasn't been a mechanism identified that could explain a connection between the three illnesses, each which is poorly understood on its own.

They briefly discuss the findings of Lyons et al.who identified a group of patients with a genetic mutation (TPSAB1) linked to tryptase levels that have symptoms characteristic of the three disorders. But according to the authors.

Finally, they argue that all three disorders consist of vague and common symptoms such as fatigue, nausea, hypotension, impaired cognition, headaches, diarrhea etc. (Interestingly exercise intolerance is also mentioned!). Because the link between the three disorders is often repeated on internet groups, they think that patients often believe they have all three disorders, without this necessarily being the case. They argue for applying strict and recent criteria. Their conclusions reads:

 

Moved from this thread:
https://www.s4me.info/threads/we-sh...-patients’-diagnoses-are-invalid.10495/page-6

It may be of interest to look at this letter written by the President of the British Society for Paediatric and Adolescent Rheumatology and the Chair of the Child Protection Standing Committee at the Royal College of Paediatrics and Child Health.

I do not agree with all of their approach but it gives an indication of how concerned UK paediatricians are about the inappropriate use of the hEDS label. I write what I do about hEDS here because I share their concerns. The target of the complaint, Rodney Grahame, is a lifelong friend of mine and the man who first trained me as a specialist. However, I agree with the authors that he has potentially caused a lot of harm.

https://www.rcpch.ac.uk/sites/default/files/2018-08/eds_editorial_response_final_0.pdf

 

Can we be entirely sure that that letter is not refighting old battles? What was the name of the specialist who was struck off for having the temerity to question CPS selected experts on the issue of retinal bleeding? Many thought her questioning of the evidence was entirely reasonable and proper. Mention of that sets alarm bells sounding. Everything would need to be double checked.

EDIT it was Dr Waney Squire. She was reinstated on appeal.

 

I guess it may be what this thread is about, if not explicitly.

I have been trying to get my head around the problem with the diagnosis and I think I have worked out what it really is.

EDS was recognised decades ago as a connective tissue abnormality with a dominant inheritance pattern, giving strong family pedigrees. There are several types and it was established that there are several genes that can be defective. Most defective mutations are Mendelian dominant but a few are X-linked recessive. X-linked recessive mutations behave as if they were dominant, but only in males.

In simple terms this means that EDS runs strongly in families with on average half of the children of an affected person, or half of the sons of a carrier woman, being affected. The other children are normal and there are no in-betweens.

The broadening of the concept of EDS from that of a single disease to a cluster of rare dominant pattern inherited diseases started even before we knew that genes were DNA I suspect. By the 1970s there were several types of EDS defined. EDA III was defined as only producing joint hypermobility (pretty much).

Some time around the 1970s or 1980s people stared saying that joint hypermobility and EDS III are the same thing, because they describe the same presentation - joint hypermobility. But the mistake here is to forget the Mendelian dominant inheritance indicating a single gene mutation. This is not just having a family history, which you will get with polygenic hypermobility - which is like being tall, just the end of a spectrum. Mendelian pedigrees are very specific and are important because they indicate a single gene disorder.

People at the mobile end of the hypermobility spectrum may get just as much trouble from lax joints as people with EDS, and maybe more. However, I suspect very few have a single gene disorder. The problem for the hEDS diagnosis then is that it has no boundaries - just as being tall has no boundaries. That means that there are no 'experts' who can diagnose hEDS better than someone else. It is a matter of arbitrary choice. Criteria can be invented but they have no particular merit.

As indicated by the letter above, the 'experts' in the UK have been using terms like hEDS in a way that looks to be a potential cause of harm. In the past I was right in the middle of that and left the field because I was not happy that patients were being advised helpfully.

 

I don't think the situations are similar.

 

Again:

https://rarediseases.info.nih.gov/diseases/2081/hypermobile-ehlers-danlos-syndrome

 

One thing that non-geneticists may forget is variation in gene expression, which may explain people with low-level (including non-clinical) symptoms.

Alternatively there could be other genes that influence other types of joint laxity, or the variant categories might not be fixed correctly (if you look at a chart for what genes are for which variant, there is some overlap (including for a few people with what's now categorized as hEDS having a gene identified as normally going with the Classical-like variant).

ETA: helpful description of genes here under causes.

 

I withdrew my post because I decided it was not necessary to address a part of the conversation which was not relevant to whether hEDS is a genuine disease or not.

 

What harm do you think it will cause?