In the spring of 2017, a large group of papers were published in the American Journal of Medical Genetics summarizing the state of knowledge of the connective tissue disorders known as Ehlers-Danlos Syndrome (EDS) and proposed changes in how one of those conditions, specifically Hypermobile EDS (hEDS), is defined [1, 2].
hEDS (formerly known as EDS, Hypermobile Type, or EDS Type III) is the most common type of EDS. While there are currently no good estimates, it is clearly not a rare disorder (“rare” meaning < 1:2,000 people) and it comprises the vast majority of the EDS population.
The new nosological changes are in and of themselves somewhat confusing, and I’m going to attempt to explain them so that the lay community can understand them better. However, more confusing is the fact that many individuals will still have diagnoses that are now obsolete and overlap several diagnostic categories, requiring re-assessment to determine which label is currently most appropriate.
Specifically, Joint Hypermobility Syndrome (JHS) is no longer in use. However, the new diagnostic substitute depends on whether the condition is “benign” (i.e., doesn’t involve musculoskeletal pain/instability). Individuals with “non-benign” forms of JHS will now receive the label, Generalized Hypermobility Spectrum Disorder (G-HSD). People whose primary symptom is generalized joint hypermobility (GJH) (Beighton ≥5 for adults under age 50) and don’t have chronic pain/instability will receive the diagnosis of Asymptomatic Generalized Joint Hypermobility (A-GJH). Obviously, this latter diagnosis can change with age, requiring occasional reassessments.
The criteria for hEDS have also become stricter, placing greater emphasis on collagen deficiency in organ systems in addition to that of the musculoskeletal (e.g., skin, prolapsed organs, heart defects, etc.). This means that many individuals who have diagnoses of EDS, Hypermobile Type or Type III, may no longer make cutoff for the new hEDS definition but would instead be grouped under G-HSD.
While these changes have certainly rattled and confused the hEDS/JHS community, the new nosology also expands the range of diagnoses that can be made, which may ultimately help us in acknowledging a wider range of affected people. Whether or not this new diagnostic scheme remains in longterm use or will continue to change as more research comes to light remains to be seen.
Since the relationship of hEDS, Hypermobility Spectrum Disorders, and generalized joint hypermobility behaves like a complex spectrum condition in that diagnosis can change with age and a range of these diagnoses occur within the same families, I suspect some day these conditions will all be subsumed under a larger umbrella diagnosis that includes the rare severe conditions at one end (Classical EDS, Vascular EDS, etc.), the severe but more common hEDS, followed by the HSDs, and finally benign hypermobility at the other end. Given that conditions such as Postural Orthostatic Tachycardia Syndrome (POTS) and Mast Cell Activation Syndrome (MCAS) occur in conjunction with vascular EDS, classical EDS, hEDS, and other HSDs suggests these conditions do indeed share a strong relationship with one another, despite the EDS diagnostic cutoff, which may ultimately turn out to be arbitrary.
Figure borrowed from Castori et al. (2017) illustrating the proposed spectrum of hypermobility.
According to new nosology, those with hypermobility but who do not meet cutoff for hEDS will be placed into one of two main categories: Hypermobility Spectrum Disorder (HSD) and asymptomatic joint hypermobility.
HSDs are composed of the following diagnoses:
- Generalized Hypermobility Spectrum Disorder (G-HSD) – Generalized joint hypermobility plus musculoskeletal pain and/or instability. This replaces the previous diagnosis of “non-benign” JHS.
- Peripheral Hypermobility Spectrum Disorder (P-HSD) – Joint hypermobility in the peripheral joints (hands, feet) plus pain and/or instability.
- Localized Hypermobility Spectrum Disorder (L-HSD) – Joint hypermobility limited to single joints or body parts plus pain and/or instability.
- Historical Hypermobility Spectrum Disorder (H-HSD) – A history of joint hypermobility plus current pain and/or instability.
Meanwhile, “benign” forms of joint hypermobility include:
- Asymptomatic Generalized Joint Hypermobility (A-GJH) – Generalized joint hypermobility without pain or instability. May change with age. Replaces previous diagnosis of “benign” JHS.
- Asymptomatic Peripheral Joint Hypermobility (A-PJH) – Peripheral joint hypermobility without pain or instability.
- Asymptomatic Localized Joint Hypermobility (A-LJH) – Joint hypermobility limited to single joints or body parts, without pain or instability.
So to summarize:
- There is now recognition of a spectrum of joint hypermobility, acknowledging the existence of conditions that don’t include current generalized joint hypermobility but a history of the same or fewer affected joints. In addition, these conditions are divided according to the presence of a “disorder,” referring to the occurrence of musculoskeletal pain/instability. When this type of impairment is present, a Hypermobility Spectrum Disorder diagnosis is given. When the hypermobility appears benign and a “disorder” is not currently present, an asymptomatic joint hypermobility diagnosis is used. These latter diagnoses may change with age.
- Joint Hypermobility Syndrome is now an obsolete diagnosis. “Benign” JHS is now known as Asymptomatic Generalized Joint Hypermobility, while “non-benign” JHS is referred to as Generalized Hypermobility Spectrum Disorder.
- The name for Ehlers-Danlos Syndrome, Hypermobile Type or Type III, has now changed to Hypermobile Ehlers-Danlos Syndrome. The criteria for hEDS have also tightened to place greater emphasis on organ systems besides musculoskeletal, such as skin, heart, etc. For this reason, a portion of individuals with Hypermobile Type/Type III diagnoses will no longer make cutoff for hEDS and would instead receive diagnoses of Generalized Hypermobility Spectrum Disorder if re-assessed.
Well, I hope this explanation has been helpful and clears up some of the confusion. Admittedly, some of the changes in nosology have proven mind-boggling for patients and doctors alike. However, the fact that there is now recognition of a broader spectrum of conditions is promising. While I don’t think the division between EDS, HSDs, and asymptomatic joint hypermobility will remain as it’s currently written, this is another step forward in the recognition of these conditions as a single, potentially related spectrum.
For now, definitions have tightened, which I know many are not happy about. But as with most diagnostic arguments in medicine concerning complex conditions, the pendulum will undoubtedly swing the other way again in future. Hopefully sooner rather than later.
Is there a reason known for which EDS co-occurs more often with ASD? I myself know a number of autistic people having both.
There’s no published research available that gives stats on how common ASD is in the different forms of EDS. However, from our initial survey studies, I have seen ASD reported in association with many different types of EDS (hEDS, classical, vEDS). Of course, the hEDS/ASD combo will be more common because there are such huge numbers of people with hEDS compared to the other conditions, which are much rarer. In terms of mechanism, that’s still a big unknown. However, with the results of our early research, I’m a proponent for a mechanism that affects both growth and morphology (i.e., a morphogen) but which also regulates activity of the immune system. I suspect the immune component may be a common factor in EDS and autism risk. But that’s currently just speculative.
EDS is widely recognized as a cause of syndromic autism.
I wouldn’t say “widely” recognized per se, even though there’s much in the literature suggesting links and our own studies (currently in the works) support that idea. But from my personal experience, I would be inclined to agree. Although this form is rarely associated with intellectual disability, in contrast to most recognized forms of syndromic autism.
Something that concerns me is the emphasis on hypermobility to the exclusion of skin involvement. Joint hypermobility can change throughout the lifespan, but skin involvement, which is at the core of EDS, doesn’t change and many people don’t realise the implications until they have surgery such as a C-section and then wonder why their incision doesn’t heal properly.
Although skin involvement is mentioned in the new nosology papers, it often gets left out in the further discussions.
It is notable that both Ehlers and Danlos were dermatologists, not rheumatologists.
To a certain extent I definitely agree, especially with regards to the changing phenotype of hypermobility that can occur across a person’s life. The Beighton is a simplistic measurement that, when invented, was not intended for diagnostic purposes. Although I would also hesitate to place greater importance on skin involvement as some people with lighter variations don’t show the extreme effects to the skin as more extreme hEDS or rarer forms of EDS. However, I do agree that any single symptom shouldn’t be given undue importance but it should be a gestalt of symptoms. Also, as some many have argued, hopefully future changes in nosology will also include what are currently considered “secondary” symptoms like immune disorders, autonomic dysfunction, etc., as additional (yet potentially optional) primary symptoms. I know Dr. Graham has alluded to the fact he believes future diagnostic iterations will change to include those as part of the criteria. Again, not as a must-have, but as yet another primary feature that’s highly indicative of EDS/HSD when paired with other symptoms of connective tissue disease. I think the most important part is to establish that there is indeed some kind of connective tissue disease (which can include any number of features, including features of the skin, joint hypermobility, joint pain, myalgia, etc.) and that two or more tissue types are affected, indicating multisystemic effects. I think that’s what the new criteria are trying to get at to some extent, but the features selected are rather limiting and don’t necessarily encompass the range of tissue dysfunction people actually experience.
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Thanks so much for this explanation of the changes for diagnosis! I’m currently in the middle of seeing a specialist who diagnosed me with Joint Hypermobility Syndrome, but sent me home with a couple medical journals and book (Learning to Bend without Breaking) which referred to the disorder as EDS-H. So, although I have a follow up soon and treatments for the two of them aren’t terribly different, I can’t seem to help to get caught up in the name… I will ask him for clarifaction when I see him next, but is it in your experience that Drs are slow to recognize new information? Or is it because he thinks they are one and the same?
I think the practicing medical community can definitely be slow to catch onto changes in nosology, especially when the changes aren’t collected in a manual (e.g., DSM, ICD) and are also complicated (let’s face it, the new criteria ARE complicated, haha). So it’s definitely going to take some years before docs catch up. He may also consider them the same condition, since information has been somewhat fuzzy until recently. But glad you found the blog helpful! 🙂
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