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Dysautonomia in Hypermobility Syndromes


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Dysautonomia is the medical term given to a disorder of the Autonomic Nervous System (ANS). The ANS is responsible for the parasympathetic and sympathetic nervous systems. Their function is to control the bodily functions we do not consciously need to think about including breathing, digestion, blood pressure and temperature regulation, and kidney and sexual function. People living with different forms of dysautonomia can display a wide variety of symptoms including dizziness, fainting, palpitations, disturbed bladder function, and bowel dysmotility sometimes leading to malnutrition.


Although often misdiagnosed, dysautonomia isn’t a rare disease. It has been estimated that over 70 million people worldwide live with some form of dysautonomia.

Dysautonomia (also referred to as autonomic dysfunction) occurs in many different forms and subtypes varying in their severity and onset, ease of management and reversibility. These include some of the following:


Neurocardiogenic Syncope is also known as vasovagal syncope. It’s the most common form of autonomic dysfunction and referred to in lay terms as a “faint”. A faint is caused by a sudden reversible decrease in flow of blood to the brain. Triggers can include stressful situations, a warm environment, prolonged standing, and low fluid intake.


Postural Tachycardia Syndrome (PoTS) is prevalent in five times as many women as men and is more closely associated with Ehlers Danlos Syndrome (EDS). It is characterised by fatigue, exercise intolerance, dizziness, palpitations, chest pain, shortness of breath and a persistent increased heart rate (30 beats per minute in adults) within 10 minutes of standing. In a small percentage of sufferers this will result in fainting. The symptoms of PoTS vary widely in severity but for one in four people the impact causes significant limitations that prevent them from being able to work and undertake normal daily activities.


Orthostatic Hypotension (OH) consists of a drop in blood pressure of at least 20mmHg and/or a drop in diastolic blood pressure of 10mmHg or more.


Orthostatic intolerance is a common symptom of dysautonomia. It is defined as symptoms that develop in the upright position that are relieved or prevented by lying down. Orthostatic intolerance is a feature of the three conditions described above. However, some patients can develop non-specific orthostatic intolerance. They have symptoms on standing that improve on lying flat, but do not test positive for PoTS, OH or vasovagal syncope.

THE LINK BETWEEN DYSAUTONOMIA AND HYPERMOBILITY


A connection between dysautonomia and hypermobile Ehlers Danlos Syndrome (hEDS) or Hypermobility Spectrum Disorder (HSD) has been observed, but there have been no large studies on populations of affected patients. Furthermore, it is unclear whether dysautonomia is more common in people with other hypermobility syndromes compared to the general population, and more research is needed in this area. Proposed mechanisms include connective tissue abnormalities in blood vessels or other tissues, damaged nerves, elevated catecholamines (e.g., adrenaline) or histamine levels, medication, and autoimmunity. De Wandele et al performed a controlled study on 39 females and concluded that dysautonomia with cardiovascular and sudomotor dysfunction are present in hEDS and noted that neuropathy, connective tissue laxity and medication play a role in its development.1 Hakim et al, concurred that there may be a link between dysautonomia in patients with hEDS that manifests in cardiovascular autonomic dysfunction, inadequate cerebral perfusion and heightened adrenergic tone leading to conditions including PoTS, but currently felt that the gathered evidence is only based on detailed personal and family history of symptoms, circumstances, and patient’s complaints once other diseases have been excluded.2 Medications required by patients with hEDS/HSD could also be a contributing factor to the symptoms of dysautonomia.


The prevalence of dysautonomia in patients with HEDS/HSD remains unknown despite clinical associations, in part due to lack of research. It reminds us of the “chicken and egg” conundrum; which came first? Evidence from online questionnaires suggests that approximately 26-50% of people with some form of dysautonomia have been previously diagnosed with hEDS/HSD.3

IMPACT OF DYSAUTONOMIA

Dysautonomia contributes to the impact on quality of life and health in patients suffering from hEDS/HSD. There is a growing understanding of how hEDS related physical and physiological pathology contributes to the development of these conditions.1 An inability to remain upright (due to either an abnormal heart rate increase, blood pressure fall, or both), the fatigue that accompanies standing and the energy it takes to perform this manoeuvre is difficult to understand unless it has been experienced. Many authors and patients have likened it to “running a marathon” just to be able to stand. It becomes increasingly debilitating for individuals to complete the simplest of tasks.


Dysautonomia isn’t limited to heart rate and blood pressure abnormalities but is multi-systemic. Patients have issues controlling their temperature, and ability to sweat appropriately. Frequent urination and visual field disturbances are other problems not always recognised and associated with hEDS/HSD. Constant nausea can contribute to a lack of appetite but could also be a symptom of gastrointestinal problems, most commonly gastroparesis in those with hEDS/HSD. General weakness, a disrupted sleep pattern and breathing difficulties facilitate fatigue and intolerance to exercise. Concentration and memory problems can affect an individual’s ability to work or study. For a syndrome referred to as an invisible illness the complications are vast.

MANAGEMENT OF DYSAUTONOMIA


White man in pyjamas, sat on a bed, with a headache and a glass of water

Unfortunately, dysautonomia is often not curable but many successful management strategies have been developed consisting of both non-pharmacological and pharmacological programmes. Non-pharmacological treatments include education to manage the environment, pacing, reducing exposure to triggers, and maintaining a good fitness and hydration level (including increased salt intake). Suggested exercise consists of mostly recumbent activities including Pilates and swimming, to be increased slowly.


However, in patients with hEDS/HSD (as already recognised) the post-exercise fatigue suffered is often severe and so patients find it difficult to engage in some exercises, leading to a possibility of deconditioning and further deterioration in their condition. Prominent features of hEDS/HSD and other hypermobility syndromes are joint laxity and pain, making some exercises difficult. Patients frequently subluxate and dislocate their joints and so the safety of exercise must be a considered factor. Increasing fluid intake prior to exercise is also suggested. Patients with dysautonomia are often advised to drink at least 2-3 litres of fluids per day and boosting fluids before exercise can be helpful. However, patients with hEDS/HSD can experience gastroparesis making it difficult for their digestive systems to process the increased fluid intake.

In a review by Satish Raj, he recommends that pharmacological therapy is only considered in cases where non-pharmacological approaches have been tried and the response was inadequate and where the patient has moderate to severe impairment of daily functions.4 No drugs have been specifically approved for the use in PoTS, although some drugs are licenced for orthostatic hypotension. The medications used are aimed at increasing blood volume, narrowing blood vessels, and reducing sinus tachycardia whilst upright in PoTS. Depending on a patients’ comorbidities, beta blockers such as bisoprolol and propranolol can be used. Ivabradine is useful as it slows the heart rate without lowering blood pressure. Midodrine and fludrocortisone are most useful in patients who have PoTS accompanied by low blood pressure. The medications have low therapeutic ranges, so it is important to start at lower doses. As with any medication, there may be interactions with other medications already taken by patients with hEDS/HSD, or they may aggravate current symptoms.

The negative impact of cardiovascular symptoms on physical and psycho-social well-being may generate a need for a more holistic evaluation and on-going management and support. A patient’s prognosis remains uncertain with outcomes ranging from resolution of symptoms to a severe long term disability affecting education, employment, and socialisation.

OBTAINING A DIAGNOSIS


Dysautonomia is a complex umbrella term for a wide range of symptoms. It can often be daunting to know where to begin on the road to diagnosis. Unless you are already under a hypermobility specialist, it is advisable to start by discussing your concerns with your General Practitioner and perhaps briefly diarising events and symptoms experienced.

Some charities including PoTS UK provide printable leaflets that can be bought to an appointment to initiate a discussion exploring the possibility of dysautonomia. Patients with hEDS/HSD can also consider undertaking an active stand test at home under supervision, but not to the detriment of their safety, as this could bring on symptoms or fainting. The stand test would require the patient to lie down quietly for some time and record their symptoms, blood pressure and heart rate, then take further recordings immediately upon standing, and at 2 minutes, 5 minutes, and 10 minutes.

FUTURE RESEARCH

To better understand the relationship between dysautonomia in patients with hEDS/HSD, healthcare professionals concur that further targeted research is needed to improve the quality of care and lives of these patients. Without the funding and exposure that many diseases are privy to, it is hard to see how treatments and strategies will develop.

Most recently, Gall et al, conducted an observational case series on PoTS in post-COVID-19 patients. In addition to undergoing other tests, patients were assessed for hypermobility using the Beighton score. All patients met the diagnostic criteria for PoTS, and 7 of the 14 were found to be hypermobile. The investigators felt that the diagnosis of PoTS was linked to COVID-19 rather than a pre-existing autonomic condition. Although it was not reported whether the patients also met the criteria for hEDS/HSD, it raises the possible question as to whether people with hypermobility could be predisposed to developing long COVID and PoTS.5 However, the sample size was extremely small, and more research would be needed in this area to explore this further, especially as there are so many wider factors relating to long COVID that are not yet understood.

Funding for research into a better understanding of dysautonomia has always been limited. Patients with PoTS have historically had poor access to healthcare as Opie and Nuttall so eloquently noted.6 With new initiatives to understand long COVID and new rapidly established multidisciplinary services to support patients, perhaps there is a ray of hope that these developments will benefit the hEDS/HSD community by providing new insights into understanding the mechanisms of dysautonomia, and new skills in recognition and management of dysautonomia by healthcare professionals.

For more detailed information on symptoms and management of autonomic dysfunction, please visit the PoTS UK website: https://www.potsuk.org/ References

  1. De Wandele I, Rombaut L, Leybaert L, Van de Borne P, De Backer T, Malfait F, et al. Dysautonomia and its underlying mechanisms in the hypermobility type of Ehlers-Danlos Syndrome. Semin Arthritis Rheum. 2014;44:93-100.

  2. Hakim A, O’Callaghan C, De Wandele I, Stiles L, Pocinki A, Rowe P. Cardiovascular autonomic dysfunction in Ehlers-Danlos Syndrome-Hypermobile type. Am J Med Genet Part C Semin Med Genet. 2017;175:168-74.

  3. Miller AJ, Stiles L, Sheehan T, Bascom R, Levy HP, Francomano C, et al. Prevalence of Hypermobile Ehlers-Danlos Syndrome in Postural Orthostatic Tachycardia Syndrome. Auton Neurosci. 2020;224:102637.

  4. Raj SR, Fedorowski A, Sheldon RS. Diagnosis and management of postural orthostatic tachycardia syndrome. CMAJ. 2022;194:E378-85.

  5. Gall NP, James S, Kavi L. Observational case series of postural tachycardia syndrome (PoTS) in post-COVID-19 patients. Br J Cardiol. 2022;29:16–20.

  6. Opie M, Nuttal M. Pipedreams, the pandemic and PoTS: is the post-COVID-19 era a turning point for PoTS services? Br J Cardiol. 2022;29:5-7.


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