The Presentation of ME/CFS Is Not Influenced by the Presence or Absence of Joint Hypermobility, 2021, Vogel, Rowe et al

Objective
To examine demographic and clinical characteristics of individuals with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) with and without joint hypermobility We hypothesized that JH+ patients would have an earlier onset of ME/CFS symptoms as well as increased severity, greater number of co-morbid conditions, and lower health related quality of life.

Study design
From an observational cohort study of 55 individuals meeting the Fukuda criteria for ME/CFS, we compared groups using a Beighton score cut-off of 4 or higher to indicate JH. Chart data were collected to examine the age and type of onset of ME/CFS, and the presence of comorbid conditions. The impact on quality of life was assessed through questionnaires that included the Peds QL, Functional Disability Inventory, Peds QL Multidimensional Fatigue Scale, and Anxiety Subscale of the Symptom Checklist 90.

Results
There was no significant difference between groups in mean (SD) age at onset of ME/CFS (13.3 [3.3] years vs 13.3 [2.3] years; P = .92), sex, frequency, and severity of ME/CFS symptoms, orthostatic intolerance symptoms, or comorbid conditions. There was no significant difference between groups in measures of health-related quality of life using a Beighton score cut-off of 4 or a cut-off of 5 to define joint hypermobility.

Conclusions
Despite being a risk factor for the development of ME/CFS, JH as defined in this study was not associated with other clinical characteristics of the illness.

Paywall, https://www.jpeds.com/article/S0022-3476(21)00887-8/fulltext

 

So it looks as if when hyper mobility and ME/CFS occur together they don't have much to do with each other.

All Rowe now has to do is a proper population study to check his continued assumption that hypermobility is a 'risk factor' for ME/CFS. I bet it isn't.

A Beighton score of 4 in a young woman is very normal. It's time Beighton was assigned to history.

 

I do not understand why, in 2021, this uses Fukuda.

 

27 patients in each group is small so that the study was only powered to detect large effects. There was also a loss of power because they dichotomized the Beighton scale. They could have also used regression and report correlations between the Beighton scale and other measures of disability.

 

The paper writes:

"The paradox of how JH is a risk factor for developing ME/CFS but does not appear to change the mode of onset or manifestations of the illness requires explanation."
​

I haven't seen any evidence that JH is a risk factor for developing ME/CFS...

 

I think the limited evidence comes from inadequately controlled studies from Rowe and from Knoop.

 

I was thinking that even if JH was more prevalent in ME/CFS patients than controls, it still might not mean that it is a risk factor (which to me suggests evidence from longitudinal studies).

Is JH something that is set at birth or can it be influenced?

 

JH evolves during childhood but is probably largely genetically programmed. It can probably be modified by stretching activities during childhood - maybe in ballet dancers - although I am not sure there is evidence on this. By the age of 18 nearly all ligament insertions have ceased growing and as far as I know all that happen thereafter is getting stiffer from bone overgrowth with age (or ank. spond.) or neurological disease limiting muscle range such as spasticity. Mobility gradually decreases with age too.

So JH is set before most people get ME/CFS although some will still be growing.

It is conceivable that there are non-causal associations involved - maybe people with JH go out more and get more viral infections, as an implausible example.

 

Ditto.

 

Yes, it looks like a bit of a stretch to me.

 

Is this simply a matter of checking prevalence of JH in the general population, versus prevalence among those newly diagnosed with ME/CFS? Or is it more subtle than that?

 

Are they just using JH as a proxy for EDS ? It would be unsurprising if some EDS cases were swept up by ME/CFS diagnostic criteria but they aren't going to find statistical evidence in small studies.

 

It is more subtle in that you want to make sure that the ascertainment of a diagnosis of ME/CFS and of JH is not coloured by beliefs about JH and ME.

There are some population studies in children that tend to suggest that JH isn't associated with anything much to do with ME. There is the ME Biobank cohort I am told that they found no increase in JH.

 

NO I think they are just looking at joint hypermobility per se. The problem is that some fringe physicians are now conflating that with what used to be called EDS III and is now called hEDS, which as far as I can see isn't really a form of EDS anyway. There is very little evidence for monogenic dominant or sex-linked recessive (i.e. 'EDS') hypermobility syndromes.

 

Why isn't it a form of EDS? I know dx cannot be genetically confirmed. What, if anything, is it?

 

EDS is defined as a cluster of monogenic disorders where connective tissues are abnormal because of a defect in a single collagen or related gene. In that respect it is akin to haemophilia or Marfan's or sickle cell disease or a wide range of other gene defects.

EDS III was posited as a subgroup of EDS with predominantly musculoskeletal features rather than internal organ features. But when the individual genes for other forms of EDS were identified few if any single gene defects were found for 'EDS III'. EDS III was always a clinical diagnosis and rather vague because joint laxity is common as a polygenic state and it was never clear how that would be differentiated from EDS III.

I believe that there are a few cases of monogenic defects that would fit the original idea of EDS III. However, both in the 1970s, when I first got involved in this, and since, now with 'hEDS' the category has more often than not been used simply as a rag-bag name for hypermobility. It has also been claimed to be multi system but the whole point of the EDS III category was that it was not - multi system EDS came under other categories.

The time has probably come to abandon the EDS name, since we now have a group of distinct monogenic disorders with known genes. There may be a few cases of monogenic disorders where the genes are not known but the great majority of people who got called EDS III should never have been in the category.