Orthostatic intolerance and fatigue in the hypermobility type of Ehlers-Danlos Syndrome

Rheumatology (Oxford). 2016 Aug;55(8):1412-20. doi: 10.1093/rheumatology/kew032. Epub 2016 Apr 18.


Objective: To investigate whether orthostatic intolerance (OI) is a significant predictor for fatigue in Ehlers-Danlos Syndrome, hypermobility type (EDS-HT).

Methods: Eighty patients with EDS-HT and 52 controls participated in the first part of the study, which consisted of questionnaires. Fatigue was evaluated using the Checklist Individual Strength (CIS). As possible fatigue determinants OI [Autonomic Symptom Profile (ASP)], habitual physical activity (Baecke), affective distress [Hospital Anxiety and Depression Scale (HADS)], pain (SF36), medication use and generalized hypermobility (5-point score of Grahame and Hakim regarding generalized joint hypermobility) were studied. Next, a 20 min head-up tilt (70°) was performed in a subsample of 39 patients and 35 controls, while beat-to-beat heart rate and blood pressure were monitored (Holter, Finometer Pro). Before and after tilt, fatigue severity was assessed using a numeric rating scale.

Results: Patients scored significantly higher on the CIS [total score: EDS: 98.2 (18.63) vs controls: 45.8 (16.62), P < 0.001] and on the OI domain of the ASP [EDS: 22.78 (7.16) vs controls: 6.5 (7.78)]. OI was prevalent in EDS-HT (EDS: 74.4%, controls: 34.3%, P = 0.001), and frequently expressed as postural orthostatic tachycardia (41.0% of the EDS group). Patients responded to tilt with a higher heart rate and lower total peripheral resistance (p < 0.001; p = 0.032). This altered response correlated with fatigue in daily life (CIS). In the EDS-HT group, tilt provoked significantly more fatigue [numeric rating scale increase: EDS: +3.1 (1.90), controls: +0.5 (1.24), P < 0.001]. Furthermore, the factors OI, pain, affective distress, decreased physical activity and sedative use explained 47.7% of the variance in fatigue severity.

Conclusion: OI is an important determinant of fatigue in EDS-HT.

Keywords: Ehlers-Danlos syndrome; cardiovascular dysautonomia; fatigue; head-up tilt; hypermobility; orthostatic intolerance.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Case-Control Studies
  • Ehlers-Danlos Syndrome / complications*
  • Exercise / physiology
  • Fatigue / etiology*
  • Female
  • Head-Down Tilt
  • Humans
  • Male
  • Middle Aged
  • Orthostatic Intolerance / etiology*
  • Pain / etiology
  • Stress, Psychological / etiology
  • Surveys and Questionnaires
  • Young Adult

Supplementary concepts

  • Ehlers-Danlos syndrome type 3