The Ehlers-Danlos Syndromes Toolkit

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.


Key points

The Ehlers-Danlos syndromes received a major overhaul in 2017 and this is what we now know:

  • EDS are heritable connective tissue disorders affecting the quality of collagen in every part of the body.
  • There are now 13 recognised subtypes of EDS, 12 of which are genuinely rare and have the aberrant gene identified.
  • Hypermobile EDS (hEDS) and hypermobility spectrum disorder (HSD) is by far the most common type; these conditions are part of a spectrum and the distinction is hoped to be useful for research, but is otherwise academic.
  • hEDS/HSD is a multi-system disorder which can have a marked impact on health and which may help us to explain apparently mysterious multiple symptoms.
  • Don’t let the changing terminology confuse you. 3.4% of the population have generalised joint hypermobility and chronic widespread pain (a proxy for the now obsolete diagnosis of Joint Hypermobility Syndrome (JHS).
  • Patients who in the past received a diagnosis of JHS (or Benign JHS), EDS-Hypermobility Type or EDS Type III would now be categorised as having hEDS or HSD. New diagnostic criteria for hEDS can be found here.
  • “If you can’t connect the issues, think connective tissues” Non-specific and medically unexplained symptoms are usually real and should not be dismissed. It can be easy to make a big difference to the quality of life of some of your most complex patients with a few simple and inexpensive measures, but the journey starts with recognition.
  • The median time from symptom onset to seeking a GP opinion is 2 years and the median time to diagnosis 10 years1. If we make an early diagnosis and manage the conditions appropriately, there may be potential to reduce long term disability which can occur from EDS.
  • Enquire about family members; these are hereditary disorders of connective tissue so positive family histories are common. Although no gene has yet been identified, hEDS is primarily of autosomal dominant inheritance.
  • Children can present with symptoms of hEDS/HSD, including abdominal symptoms or growing pains. They may also present with neurodevelopmental disorders such as hyperactivity, inattention, dyspraxia, autistic spectrum disorder, sleep and food issues, emotional problems, hypersensitivity and anxiety.
  • A low Beighton score does not exclude hEDS/HSD. Patients stiffen with age so their Beighton score may decrease, although pain may worsen. The extent of multi-system symptoms is not related to the Beighton score.
  • Consider co-existing conditions; In recent years, we have begun to understand more about associated or co-morbid conditions which are frequently found in people with hEDS, including autonomic dysfunction (postural tachycardia syndrome (PoTS) and symptomatic low blood pressure), mast cell activation syndrome (MCAS) and gastrointestinal dysfunction.

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)

When to suspect hEDS

‘If you can’t connect the issues, think connective tissues’

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.

This series of slides gives an overview of hEDS and associated conditions [PPT]

Common patient histories in General Practice

Big ticket (mis)diagnoses

The following diagnoses should prompt you to assess carefully for hEDS/HSD and also MCAS and PoTS/autonomic dysfunction.

  • Joint Hypermobility syndrome

  • Chronic Fatigue syndrome or Myalgic Encephalomyelitis

  • Fibromyalgia or Chronic Pain syndromes

  • IBS and functional dyspepsia

  • Medically Unexplained Symptoms - Hypochondria, Hysteria, Conversion Disorder, Bodily Distress Disorder, Munchausen’s Syndrome

Visual representations of EDS

Diagnosing hEDS in primary care

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:

  • Check the Beighton Score is at least 4 – ‘I used to be able to’ is acceptable

  • Ask about family history of hypermobility and EDS. Bear in mind that relatives may have been misdiagnosed with fibromyalgia, chronic fatigue syndrome (see Big Ticket Misdiagnoses above).

  • Look at the patient’s problem list – current and past – and seek conditions known or believed to be more prevalent in hEDS/HSD. Consider the Just GAPE questions.
    a. Joints and U/other Soft Tissues
    b. Gut
    c. Allergy/atopy/auto-immune
    d. Postural Symptoms
    e. Exhaustion

  • Explain that you are considering whether they might have a problem with their collagen or mast cells or autonomic nervous system. It is common to ask the patient to take a look at evidenced based patient support websites in their own time (see section ‘resources for patients’). Often they will find connections you will not have had chance to cover. Sometimes they return saying that it doesn’t seem to connect.

  • Usually there is relief or elation that at last a healthcare professional is recognising their symptoms as real and understands their relevance. Occasionally there is anger or denial, especially where a patient has experienced prolonged misdiagnosis.

  • When suspecting EDS, always consider indications for referral, in particular, clues to rare subtypes (see Referrals section), but this is rarely the case. Whether a patient meets the full hEDS criteria or not has no impact on management.

  • A symptoms-based approach to hEDS/HSD is then indicated. Discuss what issues are affecting the patient the most at present and work from there to build a long-term relationship of mutual learning.

  • At the present time, the coding system does not offer us accurate codes, although an update has been requested. If you are confident of the diagnosis, you may code ‘EDS’. Otherwise, use symptom-based codes and write that you are considering the possibility of hEDS/HSD in free text. 

hEDS/HSD further reading

Emerging major associations

Autonomic Dysfunction (including Orthostatic Hypotension, Postural Tachycardia syndrome and Vasovagal Syncope)

Autonomic dysfunction (sometimes also referred to as dysautonomia) is an umbrella term used to describe any malfunction of the autonomic nervous system, 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

  • a sustained increase in heart rate of 30 beats per minute or more (in the absence of orthostatic hypotension) when moving from recumbent to standing position

  • heart rate increase should be over 40 bpm in those aged 12-19 years

  • heart rate increase must be associated with frequent symptoms of PoTS

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.

Further information

Mast Cell Activation Syndrome (MCAS)

Mast cell activation syndrome (MCAS) is an immunological condition in which mast cells inappropriately and excessively release chemical mediators, resulting in a wide range of chronic inflammatory and immune symptoms, sometimes including anaphylaxis or near-anaphylaxis attacks. Mast cells form a part of our innate immunity and are to be found 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

Review article published by the International Consortium in 2017 on MCAS in EDS

The first significant cohort study of patients with MCAS describes in detail the symptoms and co-existent conditions and should help us to recognise MCAS

Indications for referral in EDS

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.

Clinical signs

  • Skin features - classical (Abnormal scars, very elastic skin) or vascular (translucent skin, skin which tears easily, abnormal bruises - very large or in unusual sites)

  • Unusual facial features (thin lips, prominent eyes, narrow nose) in addition to skin fragility

  • Severe scoliosis

  • Marfanoid body habitus associated with an abnormal echocardiogram or lens dislocation

Personal or family history of any of the following should lead to the consideration of Vascular EDS

  • Vascular events (aneurysms, subarachnoid haemorrhage, recurrent severe post-operative haemorrhage, arterial dissection)

  • recurrent spontaneous pneumothorax

  • bowel perforationuterine rupture

  • v. severe peripartum perineal tear

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

Treatment of hEDS/HSD in primary care

People with hEDS/HSD tend to learn how to manage most of their symptoms without recourse to medical professionals despite the significance of the impact of symptoms

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.

10 Top Tips for Doctors (from a doctor with hEDS) [PDF]

One study found that patients had a mean of 5 different complaints at one point in time

Using a tool such as an assessment wheel can facilitate management of the multiplicity of ongoing medical problems.

Brief overview of management issues in hEDS/HSD


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. 

 

Resources aimed at patients and their carers

Patient charities in the UK

International patient charities

Chronic Pain

Videos

Books

Social media

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.

  • Ehlers-Danlos Support UK has a Facebook group, @EhlersDanlosUK as well as closed local and regional groups for support and specific closed groups for parents, men’s support and partners’ support. You must be a member to join the closed groups but membership is free.
  • HMSA has a Facebook group @TheHMSA
  • Twitter: @ehlersdanlosuk, @HMSACharity, @TheEDSociety, @UKPoTS, @DrEReinhold, @LoveInYourTummy and commonly used hashtags #EDS #hEDS #hypermobility #zebra #MCAS #POTS #dysautonomia #invisiblevisible

Resources for training/education and QI tools

Books

Webinars and videos    

Papers

Please disregard the sections on classification of subtypes of EDS in all papers published prior to March 2017.

Podcasts

Information for commissioners

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.’

How to develop services

Section 7 of this review article covers the requirements of a comprehensive service for patients with EDS

This toolkit has been developed in partnership between the RCGP Clinical Innovation and Research Centre and Ehlers Danlos Support UK led by Emma Reinhold and with contributions from Lisa Jamieson, Lesley Kavi, Kay Julier, Hanadi Kazkaz, Alan Hakim, Nikki Praiba, Gemma Pearce, Philip Bull and Jan Groh.

Please send any feedback or suggestions to circ@rcgp.org.uk

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