The Ehlers-Danlos syndromes (EDS) are heritable connective tissue disorders affecting the quality of collagen in every part of the body. They were once considered to be very rare and only seen by rheumatologists. There are 13 types of Ehlers-Danlos syndrome, most of which are indeed rare. However, the hypermobile type of EDS (and associated hypermobility spectrum disorder) is thought to be common and this toolkit will focus primarily on this type, although many of the clinical signs and symptoms discussed can also appear across the other EDS types. The old diagnosis of Joint Hypermobility syndrome (JHS) is now considered part of the spectrum of Hypermobile EDS.
Hypermobile EDS is now understood as a multi-system disorder which can have a marked impact on health and which may help us to explain apparently mysterious multiple symptoms.
This toolkit sets out the latest thinking in EDS, including the new approaches to diagnosis and treatment set out by the International Consortium on the Ehlers-Danlos syndromes in 2017, as they relate to primary care.
The Ehlers-Danlos syndromes received a major overhaul in 2017 and this is what we now know:
The key role of the GP at this moment in time is in diagnosing hEDS/HSD, validating the patient’s symptoms and co-ordinating care. hEDS/HSD isn’t as rare as you may think.
1Hakim, A. J.Rheumatology, Volume 51, Issue suppl_3, 1 May 2012. iii2 (I11) (Abstract)
There are many ways in which you may begin to suspect a patient has hEDS/HSD. Some general clues which should alert you are (young) patients with multiple, or unusual symptoms and normal basic investigations. Patients may not respond as expected to usual treatments, be they medical, surgical, psychological, or the application of time. More specific complaints are detailed below.
The following diagnoses should prompt you to assess carefully for hEDS/HSD and also MCAS and PoTS/autonomic dysfunction.
There are thirteen subtypes of EDS, most of which are very rare. This section focuses on the hypermobile subtype (hEDS) and the related condition hypermobility spectrum disorder (HSD), where there are features of hEDS but the full criteria are not met. These conditions are not rare. As GPs, we may work with a ‘suspected’ diagnosis for each of these conditions without referring for confirmation. The associated conditions, approach to management and the prognosis are felt to be the same for hEDS and HSD, so there is no clinical necessity to state with certainty which label is applicable.
How should a GP approach the diagnosis and management of a patient with possible EDS/HEDS? There is nothing in the medical literature to help with this task. As an EDS-aware GP, this describes the usual practice. This usually occurs over a number of appointments:
Autonomic dysfunction is an umbrella term used to describe any malfunction of the autonomic nervous system. It’s sometimes referred to as dysautonomia, and can occur in many different medical conditions.
Autonomic dysfunction is commonly associated with EDS, especially the hypermobile type. Patients experience a symptom called orthostatic intolerance – the development of symptoms in the upright position that are usually relieved by lying down. The commonest syndromes of orthostatic intolerance found in hEDS/HSD are orthostatic hypotension, postural tachycardia syndrome (PoTS) and recurrent vasovagal syncope. There is much crossover in the symptoms of these three syndromes, which include presyncope/syncope, palpitations, fatigue, sweating, headache, exercise intolerance, blurring of vision and nausea. Symptoms of all three syndromes are known to be highly debilitating.
Orthostatic hypotension is defined a drop in blood pressure of over 20/10 mmHg when moving from a recumbent to an upright position.
PoTS is defined as:
The diagnoses of POTS, OH and vasovagal syncope are not mutually exclusive in a patient. Physiological treatments for all three conditions are broadly similar and include increased fluids, salt, dietary adjustments, postural manoeuvres to prevent fainting and graduated exercise regimens. Medication can also be of benefit.
Mast cell activation syndrome (MCAS) is an immunological condition. The mast cells inappropriately and excessively release chemical mediators, resulting in a wide range of chronic inflammatory and immune symptoms. This sometimes includes anaphylaxis or near-anaphylaxis attacks. Mast cells form a part of our innate immunity and exist in every part of the body.
MCAS and its relationship to hEDS is a new but frequent topic of discussion amongst patients and clinicians alike. Many patients, particularly in the USA, are being diagnosed with both conditions and there are several observational studies suggesting an overlap. However, the evidence of a definitive link, and research into what that link might be is at a very early stage. Treatment of MCAS is covered in the later section.
Simple introductory explanation of MCAS:
Many hypermobile patients will be managed, at least for the majority of their lives, solely within Primary Care. There may not be much advantage to your patient from seeing a rheumatologist who does not have a special interest in hypermobility, certainly not simply for confirmation of a hEDS or HSD diagnosis. However, there are certain situations where a referral may be advisable.
1) If any hypermobile condition other than hEDS/HSD is suspected, referral is indicated so that formal genetic testing may be considered. This would usually be warranted only if more than one of the following features is seen.
Personal or family history of any of the following should lead to the consideration of Vascular EDS
2) Where a patient has ongoing musculoskeletal symptoms despite adequate analgesia, physiotherapy/OT/podiatry input, referral to rheumatology should be considered. It must be remembered that patients may have more than one musculoskeletal condition co-existing. Some studies have shown a higher prevalence of inflammatory and autoimmune diseases in hEDS
3) For other significant or extra-articular symptoms, you may find that there are local specialists who have interest in patients with hypermobility. For example, gastroenterology referral may be beneficial for patients with gut issues in addition to constitutional symptoms, or intractable constipation with complications. Consideration of referral for chronic pain management may also be warranted.
4) Hypermobile patients with severe and complex problems can be seen at the tertiary referral clinics at UCLH and Stanmore. If you think this service might be appropriate for your patient, they need to be referred by a rheumatologist
Troublesome symptoms can vary wildly between patients as well as over time. It is key to work together to help people develop an effective self-care toolkit, allowing patients some leeway to alter medication doses or use as-required medicines where appropriate. A study on lived experience makes for sobering reading.
New research shows hEDS and HSD 10 times more common than previously thought, The Ehkers-Danlos Support UK
Using a tool such as an assessment wheel can facilitate management of the multiplicity of ongoing medical problems.
Here we will offer a brief overview of management issues in hEDS/HSD, albeit this is difficult with such a complex condition. For more detailed information, please consult the ‘Resources’ section.
There are vibrant online patient communities, including numerous bloggers, Facebook groups and Twitter hashtags, which many patients find very supportive, although care should always be taken with respect to any advice offered on such platforms. It is often very validating to find others with the same life and health experience, especially with a condition which the medical profession does not always treat well.
Please disregard the sections on classification of subtypes of EDS in all papers published prior to March 2017.
Services for patients with ‘Complex EDS’ and the genetics service (for all EDS sub-types other than hEDS) are commissioned centrally by NHS England, National Services Division in Scotland, Welsh Health Specialised Services Committee, and the Health and Social Care Board in Northern Ireland.
We know that patients are high consumers of healthcare, in terms of GP visits, outpatient appointments, inpatient bed days, prescriptions, surgery and physiotherapy, although reported results of such treatments are often disappointing.
An article by Prof R Grahame, world-renowned expert in EDS, setting out the poor current state of care for those with HSDs (written before the new diagnostic criteria)
Lived Experience of Joint Hypermobility syndrome (now termed Hypermobility Spectrum Disorder) including the difficulty and importance of gaining a diagnosis.
This article ‘Joint hypermobility syndrome in childhood. A not so benign multisystem disorder?’ concludes ‘JHS is poorly recognized in children with a long delay in the time to diagnosis. [This] results in poor control of pain and disruption of normal home life, schooling and physical activities. Knowledge of the diagnosis and simple interventions are likely to be highly effective in reducing the morbidity and cost to the health and social services.’