Dysautonomia in the Ehlers–Danlos syndromes and hypermobility spectrum disorders—With a focus on the postural tachycardia syndrome

Abstract

Dysautonomia (autonomic dysfunction) occurs in the Ehlers-Danlos syndromes (EDS) and hypermobility spectrum disorders (HSD). Symptoms include palpitations, dizziness, presyncope, and syncope, especially when standing upright. Symptoms of orthostatic intolerance are usually relieved by sitting or lying and may be exacerbated by stimuli in daily life that cause vasodilatation, such as food ingestion, exertion, and heat. Neurocardiovascular dysautonomia may result in postural tachycardia syndrome (PoTS), a major cause of orthostatic intolerance. It is defined by a rise in heart rate of >30 beats per minute (bpm) in adults and >40 bpm in teenagers while upright, without a fall in blood pressure (BP; orthostatic hypotension). In some, it can be compounded by the presence of low BP. For many, there is delay in clinicians recognizing the nature of the symptoms, and recognizing EDS or HSD, leading to delays in treatment. The onset of PoTS may be linked to an event such as infection, trauma, surgery, or stress. Gastrointestinal and urinary bladder involvement may occur, along with thermoregulatory dysfunction. In some, the mast cell activation syndrome may be contributary, especially if it causes vasodilatation. This paper reviews neurocardiovascular dysautonomia with an emphasis on PoTS, its characteristics, associations, pathophysiology, investigation, and treatment.

Looking back and beyond the 2017 diagnostic criteria for hypermobile Ehlers‐Danlos syndrome: A retrospective cross‐sectional study from an Italian reference center

“…Regarding other comorbidities such as chronic fatigue, dysautonomia (e.g., orthostatic intolerance, POTS), psychological distress (e.g., anxiety, sleep disturbances, impaired memory/concentration, depression), functional gastrointestinal and bladder disorders, and allergic/atopic features, we found that, with a few exceptions, the presence of individual comorbid features was no more or less frequent in hEDS and HSD, in line with other reports (Brock et al, 2021; Celletti et al, 2020; Hakim et al, 2021; Lam et al, 2021; Mathias et al, 2021; McGillis et al, 2020; Ruiz Maya et al, 2021; Wasim et al, 2019). In addition, many of these comorbidities are also frequently observed in other EDS forms, such as classical and vascular EDS, as well as rarer types (Malfait et al, 2020; Ritelli, Rovati, et al, 2020; Ritelli, Venturini, et al, 2020), and in other chronic pain and fatigue conditions (Hakim et al, 2021).…”

“…Dysautonomia is also common and can impact pain and fatigue levels. Autonomic dysfunction may underlie both musculoskeletal pain and fatigue (Mathias et al, 2021; Ruiz Maya et al, 2021). Psychiatric and psychological comorbidities like depression and anxiety also frequently co‐occur and can worsen physical symptoms (Baeza‐Velasco et al, 2021; Bulbena‐Cabré et al, 2021).…”

“…However, shortly after the updated diagnostic criteria were introduced, several authors raised concerns about their limits, since they neither effectively recognize the more severely affected patients nor account for the numerous extra‐musculoskeletal manifestations of hEDS (Aubry‐Rozier et al, 2021; Castori, 2021; Copetti et al, 2019; Hakim, 2019; Hakim et al, 2021; Martinez et al, 2021; Morlino et al, 2019; Williams, 2019; Yew et al, 2021). These associated conditions are nowadays recognized, with varying levels of evidence, as JHM‐associated comorbidities and include chronic fatigue, pelvic floor problems, bladder dysfunction, various dysautonomic features (e.g., orthostatic decompensation, unstable cardiac rhythms and rates, postural orthostatic tachycardia syndrome [POTS], and gastrointestinal dysfunction), neurological involvement, behavioral disturbances, psychological distress, and immune system alterations such as mast cell disorders (Atwell et al, 2021; Brock et al, 2021; Castori et al, 2017; Celletti et al, 2020; Fernandez et al, 2022; Lam et al, 2021; Malfait et al, 2017; Malfait et al, 2020; Mathias et al, 2021; Pietri‐Toro et al, 2023; Rashed et al, 2022; Ruiz Maya et al, 2021; Thwaites et al, 2022; Tinkle et al, 2017; Vermeulen et al, 2022; Wasim et al, 2019). These comorbidities are common not only in hEDS but also in HSD, although their exact incidence has not been extensively documented thus far.…”

The adapted Autonomic Profile (aAP) home-based test for the evaluation of neuro-cardiovascular autonomic dysfunction

“…It was based on experience over three decades and on information in the two autonomic departments that he developed and directed (at St Mary's Hospital/Imperial College London and the Autonomic Unit at Queen Square, University College London). Pre-pandemic evaluation utilised ambulatory and programmed BP/HR recorders (as used in hypertension assessment), with additional measurements while lying and standing, and to food and physical exertion [13,14]. This became challenging during the pandemic as the patients needed to travel to the centre to collect the recorders and there was uncertainty about equipment sterilising procedures to avoid virus transmission.…”

The α2A-adrenergic receptor (ADRA2A) modulates susceptibility to Raynaud’s syndrome

“…The targets of the autonomic nervous system include body temperature, heart rate, respiration, bowel movements and digestion, sexual arousal, endocrine function, blood pressure regulation and vascular tone. However, when the autonomic nervous system malfunctions, it can lead to symptoms and diseases of dysautonomia, affecting many different functions of the autonomic nervous system including vascular tone and blood pressure as seen with Raynaud’s syndrome (RS) 1 .…”