Hypermobile Ehlers-Danlos Syndrome (hEDS) and Hypermobility Spectrum Disorder (HSD)— Assessing Criteria and Their Modification in Clinical Practice.
Principal Investigators: Dr. Alan Hakim and Dr. Clair Francomano
On behalf of the hEDS/HSD Working Group of the International Consortium on the Ehlers-Danlos Syndromes and Hypermobility Spectrum Disorders.
Investigators: Fraser Burling (NZ), Marco Castori (IT), Helen Cohen (UK), Patricia Grether (MX), Christina Laukaitis (USA), Fransiska Malfait (BE), Nimish Mittal (CA), and Louise Tofts (AU).
The hEDS/HSD Working Group of the International Consortium (IC) on the Ehlers-Danlos Syndromes (EDS) and Hypermobility Spectrum Disorders (HSD) is pleased to announce the start of a study to review the criteria for the diagnosis of hypermobile EDS and HSD.
The study is funded by a generous private donation to The Ehlers-Danlos Society. The study has received IRB (ethical board) approval from Indiana University, USA, and will also gain ethical approval for all the sites involved around the world which include the USA, Canada, Mexico, UK, Belgium, Italy, Australia, and New Zealand.
Statistical support is being provided through Penn State, USA.
The Ehlers-Danlos Society will manage the administrative support needed for the study.
Who is the hEDS/HSD Working Group of the International Consortium on the Ehlers-Danlos Syndromes and Hypermobility Spectrum Disorders?
The International Consortium (IC) was created in 2014 by what was then Ehlers-Danlos National Foundation (EDNF) and The Ehlers-Danlos Support UK (EDS UK). The IC is an independent working group of medical professionals and experts.
The members of the group are listed here.
In addition, their work towards this study was supported by Prof. Byers, Prof. Malfait, and Dr. Francomano as members of the IC Steering Committee, and Dr. Hakim who since 2018 has been a member of the Steering Committee and Chair of the hEDS/HSD Working Group.
Why is the study being done?
There has been a growing commentary internationally from clinicians, organizations, institutions, and the community about whether the 2017 International Criteria for hEDS need modifying to be more inclusive of other signs and symptoms and comorbid conditions.
In addition, many ask the question, “Is there a meaningful difference between hEDS and HSD, and in what ways?” Recent studies are starting to show that in several ways people with HSD have the same type and severity of associated comorbid conditions as those with hEDS.
Another question is, how should the criteria be adapted for children and adolescents?
Over 2018-21, the hEDS/HSD working group of the IC identified several major themes from these discussions after reviewing surveys of opinions and comments from stakeholders, expert clinical opinion, audits of data from clinics, and all the latest published literature.
The following broad questions were identified and will be explored in the study:
- Should more joints be tested for hypermobility? Are the Beighton score and the 5-part questionnaire enough when looking for generalized joint hypermobility? Would the inclusion of other joints not in the Beighton score improve the screening for generalized joint hypermobility?
- Are all the signs and symptoms in the current criteria the right ones? Should some be removed? Should others be added? Should certain ones carry more importance than others? Should they be clustered into groups rather than considered individually?
- Is the current structure of the hEDS criteria the right one? Are there other, better ways of structuring the criteria that include the different ways a diagnosis of hEDS might be made?
- What are the key signs or “red flags” that should be included in the criteria that should alert the clinician that there may be another diagnosis, such as a rarer type of EDS?
- Now that more is known about associated conditions such as postural orthostatic tachycardia syndrome (PoTS) and slow gut transit, is there evidence that these conditions should be included in an updated version of the criteria?
- Is there a stronger association with comorbid conditions in hEDS or HSD compared to other chronic pain conditions? Also, is it possible to tell hEDS apart from HSD by any of the comorbid conditions? Does the inclusion of comorbid conditions improve the sensitivity and specificity (the likelihood of making a correct diagnosis) of the criteria?
What will the study examine?
Following several IC hEDS/HSD Working Group discussions, consideration of stakeholder opinions, audits of clinic data, and a full review of the literature, the group identified many aspects that will be examined in the study.
The study will look at each participant’s:
- age, gender, race, and all their medical diagnoses;
- joints — which are hypermobile and/or unstable (subluxations and dislocations);
- types of musculoskeletal and neuropathic pain and which areas of the body are affected;
- family history, and any genetic testing;
- body shape for marfanoid features;
- history of fractures;
- skin for the many different signs found in EDS;
- eyes, teeth and gums, heart, abdominal wall (hernias), and pelvic organs and pelvic floor;
- history/diagnosis of any of many comorbid concerns — twenty-six concerns are being explored with the opportunity for the researcher to add other concerns if not included in the list; and
- signs and symptoms that are “red flags” for a possible other diagnosis.
The study data will be explored statistically to look at the following things:
- How strong is the association between each one of the various signs, symptoms, and comorbid conditions with hEDS compared to HSD, with hEDS compared to other non-hypermobile pain conditions, and with HSD compared to other non-hypermobile pain conditions?
- Which of these signs, symptoms, and comorbid conditions separates hEDS from HSD because of a stronger association in one compared to the other? And which ones separate hEDS or HSD from other non-hypermobile pain conditions?
- Using the above information, can different criteria structures be designed and tested to see if they are better than the current criteria at identifying hEDS vs. HSD vs. other chronic pain conditions?
- Through stakeholder engagement and testing in practice, do any of these revised criteria models make clinical sense and which one should be published as a recommended revision of the 2017 International criteria for hEDS and HSD?
In addition, the researchers are aware of the work being undertaken to identify genetic markers for hEDS. There will be the possibility to set up a study extension to look at genetic markers in those participating in this study and use that information in the criteria revision.
Can I take part in the study?
The study will recruit participants among individuals who have been referred for assessment and management of their pain disorder and are attending an outpatient clinic appointment at one of the study sites over the period 2022-23.
Attendance at the clinic will be through the normal referral process for that service. It will not be possible to apply to join the study or attend the clinic only for the purpose of taking part in the study.
Individuals attending the clinic will be approached by their clinic team, invited to take part, and provided with the information needed to consent and be part of the study.
When will the study results be published?
Recruitment of study participants will take place from April 2022 to September 2023. The study may close to recruitment earlier if the required number of participants is reached sooner.
Analysis and review of the data will take place after closing the study and is likely to be ready for presentation to stakeholder groups (which includes the patient community) in early 2024.
It is anticipated that conclusions and any recommendations will be published in mid to late 2024.