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



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.



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.



OI is an important determinant of fatigue in EDS-HT.
Centre for Medical Genetics, Ghent University Hospital Centre for Medical Genetics, Ghent University Hospital inge.dewandele@ugent.be.
Inge
I
De Wandele
Centre for Medical Genetics, Ghent University Hospital Centre for Medical Genetics, Ghent University Hospital.
Lies
L
Rombaut
Centre for Medical Genetics, Ghent University Hospital.
Tine
T
De Backer
Centre for Medical Genetics, Ghent University Hospital.
Wim
W
Peersman
Centre for Medical Genetics, Ghent University Hospital.
Hellen
H
Da Silva
Centre for Medical Genetics, Ghent University Hospital.
Sophie
S
De Mits
Centre for Medical Genetics, Ghent University Hospital.
Anne
A
De Paepe
Centre for Medical Genetics, Ghent University Hospital.
Patrick
P
Calders
Centre for Medical Genetics, Ghent University Hospital.
Fransiska
F
Malfait
D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D004535:Ehlers-Danlos Syndrome / Q000150:complications*; D015444:Exercise / Q000502:physiology; D005221:Fatigue / Q000209:etiology*; D005260:Female; D018475:Head-Down Tilt; D006801:Humans; D008297:Male; D008875:Middle Aged; D054971:Orthostatic Intolerance / Q000209:etiology*; D010146:Pain / Q000209:etiology; D013315:Stress, Psychological / Q000209:etiology; D011795:Surveys and Questionnaires; D055815:Young Adult
Ehlers-Danlos syndrome; cardiovascular dysautonomia; fatigue; head-up tilt; hypermobility; orthostatic intolerance