CFS is commonly diagnosed in patients with Ehlers-Danlos syndrome hypermobility type/joint hypermobility syndrome, 2011, Castori et al.

Castori M, Celletti C, Camerota F, Grammatico P. Chronic fatigue syndrome is commonly diagnosed in patients with Ehlers-Danlos syndrome hypermobility type/joint hypermobility syndrome. Clin Exp Rheumatol. 2011;29(3):597-598. https://www.clinexprheumatol.org/article.asp?a=4635

No abstract, this is a letter to the editor of the journal.

Although the authors used the Fukuda criteria, they reported the prevalence of each symptom individually. They also conducted labs & a clinical record review for each patient.

The study included 46 people with both EDS hypermobility type (EDS-HT) and joint hypermobility syndrome (JHS). 80.6% (37) had post-exertional malaise, 82.6% (38) had disabling fatigue for >6 months, and overall 82.6% (38) met the Fukuda criteria. Not a perfect match for ME/CFS criteria due to PEM, but it might give a rough impression of the prevalence of CFS in EDS-HT/JHS.

Unfortunately, no information is given about the control group (n = 95). Per the table of CFS symptom prevalence in both groups, it clearly includes non-healthy subjects: 43% have unrefreshing sleep, 37% have impaired memory/concentration, etc. Though it is sex-matched and arguably age-matched (ranges: 8-58 for patients with EDS-HT/JHS vs 28-45 for controls). A plausible explanation could be that the controls were just recruited from the physical rehab and/or genetics department(s) the authors worked at.

The authors conclude that joint hypermobility, EDS-HT and JHS should be screened for in patients with CFS.

Relevant parts (spacing mine):

Note: the criteria for EDS-HT and JHS predate the stricter 2017 New York criteria for hypermobile EDS (hEDS). If my understanding is correct, some of these patients would meet the 2017 criteria, while those who don't would now be diagnosed with hypermobility spectrum disorder (HSD). Is this correct @Jonathan Edwards?

 

I'm not sure what this tells us, especially with the direction of the association. The authors screened for CFS in EDS-HT/JHS, but they conclude EDS-HT/JHS should be screened for in CFS.

 

I don't think any of these people should be diagnosed with anything related to hypermobility since we have no idea whether that is relevant to any symptoms. The high rates of fatigue are almost certainly a reflection of the way the patients were recruited. It is a self-perpetuating story.

 

I'm confused: do you mean that it is likely these patients presented with fatigue then were diagnosed with EDS-HT/JHS?

I agree the risk of referral bias is important if patients at a ME/CFS clinic are screened for hypermobility, but isn't it more likely that patients at an EDS clinic (as in this study) would have primarily been referred to it for hypermobility symptoms (subluxations etc)?

I also wonder how post-exertional malaise was assessed in this study. If it wasn't through a questionnaire (which doesn't seem to be the case, at least it's not reported), the authors may have given an incomplete explanation of PEM to participants that would have influenced their self-reporting of PEM. 9.4% (9) of the control group reported PEM, though this is consistent with the 8.4% (8) who reported chronic disabling fatigue.

 

It depends on what sort of 'EDS clinic'. Clinics run by geneticists see tiny numbers of people with Mendelian genetic disorders who are mostly referred because of problems in other organ systems. On the other hand 'hypermobility' or now 'hEDS clinics see mostly people who have pain or fatigue and who have gone to a physio who has heard of this 'EDS clinic'. Dr Alan Hakim runs a clinic for hyper mobile people with pain and fatigue. Rodney Grahame (his trainer) used to run one at our unit. I would estimate that less than 1% of people given a diagnosis of EDS would be considered to have EDS by a geneticist.

 

Thank you for your explanation! In the case of this study, the lead author Marco Castori is a member of the medical & scientific board of the Ehlers-Danlos Society and he has published extensively on joint hypermobility and hEDS. So it seems likely that there is an important risk of referral bias to his clinic in Rome, especially if there are few EDS clinics/specialized hospital units in Italy. https://www.ehlers-danlos.com/marco-castori/

Unfortunately for patients, I think the same is happening in France with Prof Claude Hamonet's clinic in Paris. As you know he's a historical figure of EDS here, and he certainly has advocated for medical education on EDS & has helped many patients. But he also seems to stir controversy: some French MDs, even local GPs, have expressed their surprise at the amount of (h?)EDS diagnoses coming from his clinic. They colloquially refer to these diagnoses as "Ellasanté EDS", from the name of his clinic. And they do not consider hEDS to be a valid diagnosis (or at least not one of the EDS) considering the lack of a genetic marker, but instead see it as over-diagnosis/over-medicalization/a wastebasket created by overly specialized doctors.

(As an aside: in March, the French High Authority of Health released their official clinical guidelines on non-vascular EDS. For hEDS, they put a clear emphasis on psychological factors, deconditioning, and avoidance of exercise -- kinesiophobia -- due to a supposed fear of pain & injury.)

 

That sounds right. Perhaps Hamonet is the Grahame of France

I am not quite sure what is implied there. Kinesiophobia is clearly not the cause of a genetic laxity of tissues. Whether or not hEDS is Mendelian one has to assume it is limited to genetic states. Tissues do not get lax secondarily as a rule. So presumably the idea is that kinesiophobia is an important aspect of the clinical problems that 'hEDS' patients have. If it is, it seems to me likely to be the fault of the doctors giving overblown explanations about risk of injury.

I suspect that the Ehlers-Danlos Society has a lot of members who do not in any useful sense have EDS.

 

What do you suggest they get diagnosed with instead of EDS?