Dysautonomia and its underlying mechanisms in the hypermobility type of Ehlers-Danlos syndrome

Semin Arthritis Rheum. 2014 Aug;44(1):93-100. doi: 10.1016/j.semarthrit.2013.12.006. Epub 2013 Dec 30.


Objectives: Many non-musculoskeletal complaints in EDS-HT may be related to dysautonomia. This study therefore aims to investigate whether dysautonomia is present and to explore the underlying mechanisms.

Methods: A total of 39 females with EDS-HT and 35 age-matched controls underwent autonomic function testing. Resting autonomic tone was assessed using heart rate variability (frequency domain) and baroreflex sensitivity analysis (cross correlation). Autonomic reactivity was assessed using the Autonomic Reflex Screen test battery. Factors suspected to contribute to dysautonomia, e.g., neuropathy, medication use, decreased physical activity, depression, pain-induced sympathetic arousal, and connective tissue laxity, were quantified using validated questionnaires, the Beighton score, and measurement of skin extensibility.

Results: The EDS-HT group showed autonomic deregulation with increased sympathetic activity at rest and reduced sympathetic reactivity to stimuli. Increased resting activity was indicated by a higher LF/HF ratio compared to controls (1.7 ± 1.23 vs 0.9 ± 0.75, p = 0.002); decreased reactivity by a greater BP fall during valsalva (-19 ± 12 vs -8 ± 10, p < 0.001), and a smaller initial diastolic BP increase during tilt (7% vs 14%, p = 0.032). Orthostatic intolerance was significantly more prevalent in EDS-HT than controls (74% vs 34%) and was most frequently expressed as postural orthostatic tachycardia. Lowered QSART responses suggest that sympathetic neurogenic dysfunction is common in patients (p < 0.013), which may explain the dysautonomia in EDS-HT. Further, connective tissue laxity and vasoactive medication use were identified as important factors in aggravating dysautonomia (p < 0.035).

Conclusion: Dysautonomia consisting of cardiovascular and sudomotor dysfunction is present in EDS-HT. Neuropathy, connective tissue laxity, and vasoactive medication probably play a role in its development.

Keywords: Autonomic dysfunction; Ehlers–Danlos syndrome; Hypermobility; Orthostatic intolerance.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Blood Pressure / physiology*
  • Ehlers-Danlos Syndrome / complications*
  • Ehlers-Danlos Syndrome / physiopathology
  • Female
  • Heart Rate / physiology*
  • Humans
  • Middle Aged
  • Primary Dysautonomias / complications*
  • Primary Dysautonomias / physiopathology
  • Surveys and Questionnaires