Orthostatic intolerance and fatigue in the hypermobility type of Ehlers-Danlos syndrome
Abstract
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.
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Cardiovascular autonomic abnormalities have been characterized in JHS/hEDS with a variety of profiles, including postural orthostatic tachycardia syndrome, orthostatic intolerance, and neuromediated hypotension.
“More recently, cardiovascular autonomic abnormalities have been characterized in JHS/ hEDS with a variety of profiles, including postural orthostatic tachycardia syndrome, orthostatic intolerance and neuromediated hypotension [28,29].”
From Severity classes in adults with hypermobile Ehlers–Danlos syndrome/hypermobility spectrum disorders: a pilot study of 105 Italian patients (2019) · cites this paper as [28]
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- Authors
- De Wandele, I., Rombaut, L., De Backer, T., Peersman, W., Da Silva, H., De Mits, S., De Paepe, A., Calders, P., & Malfait, F.
- Affiliations
- Ghent University Hospital (BE)
- Venue
- Rheumatology
- Publisher
- Oxford University Press (OUP)
- Published
- 2016-04-18
- Volume
- 55
- Issue
- 8
- Pages
- 1412-1420
- ISSN
- 1462-0324 (ISSN-L)
- 1462-0332
- OpenAlex
- W2338172465
- Cited by
- 72
- References
- 48
- Citations by year
- 2026: 1 · 2025: 9 · 2024: 5 · 2023: 3 · 2022: 8 · 2021: 26 · 2020: 5 · 2019: 2 · 2018: 5 · 2017: 6 · 2016: 2
- FWCI
- 5.54
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Lara D. Veeken (publishedVersion)
- PubMed (publishedVersion)
- Ghent University Academic Bibliography (Ghent University) (submittedVersion)
- HighWire Press Open Archive (submittedVersion)
- Funders
- Fonds Wetenschappelijk Onderzoek
- Topics
- Health Sciences › Medicine › Surgery › Cardiovascular Syncope and Autonomic Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Connective tissue disorders research
- Health Sciences › Medicine › Psychiatry and Mental health › Fibromyalgia and Chronic Fatigue Syndrome Research
- Keywords
- Ehlers-Danlos syndrome hypermobility type, orthostatic intolerance, fatigue, postural orthostatic tachycardia syndrome, head-up tilt, autonomic dysfunction, generalized joint hypermobility, pain, emotional distress, physical activity, sedative use, predictors of fatigue
- MeSH terms
- Adult, Aged, Ehlers-Danlos Syndrome, Fatigue, Female, Humans, Male, Middle Aged, Pain, Surveys and Questionnaires, Stress, Psychological, Exercise, Case-Control Studies, Head-Down Tilt, Orthostatic Intolerance, Young Adult
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