Published online April 1, 2005
PEDIATRICS Vol. 115 No. 4 April 2005, pp. e415-e422 (doi:10.1542/peds.2004-1515)
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ELECTRONIC ARTICLE

Is Chronic Fatigue Syndrome a Connective Tissue Disorder? A Cross-Sectional Study in Adolescents

E.M. van de Putte, MD*, C.S.P.M. Uiterwaal, PhD, MD{ddagger}, M.L. Bots, PhD, MD{ddagger}, W. Kuis, PhD, MD*, J.L.L. Kimpen, PhD, MD* and R.H.H. Engelbert, PhD§

* Departments of Pediatrics
§ Pediatric Physical Therapy and Pediatric Exercise Physiology, Wilhelmina Children’s Hospital
{ddagger} Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, Netherlands

Objectives. To investigate whether constitutional laxity of the connective tissues is more frequently present in adolescents with chronic fatigue syndrome (CFS) than in healthy controls. Increased joint hypermobility in patients with CFS has been previously described, as has lower blood pressure in fatigued individuals, which raises the question of whether constitutional laxity is a possible biological predisposing factor for CFS.

Design. Cross-sectional study.

Participants. Thirty-two adolescents with CFS (according to the criteria of the Centers for Disease Control and Prevention) referred to a tertiary hospital and 167 healthy controls.

Methods. The 32 adolescents with CFS were examined extensively regarding collagen-related parameters: joint mobility, blood pressure, arterial stiffness and arterial wall thickness, skin extensibility, and degradation products of collagen metabolism. Possible confounding factors (age, gender, height, weight, physical activity, muscle strength, diet, alcohol consumption, and cigarette smoking) were also measured. The results were compared with findings in 167 healthy adolescents who underwent the same examinations.

Results. Joint mobility, Beighton score, and collagen biochemistry, all indicators of connective tissue abnormality, were equal for both groups. Systolic blood pressure, however, was remarkably lower in patients with CFS (117.3 vs. 129.7 mm Hg; adjusted difference: –13.5 mm Hg; 95% confidence interval [CI]: –19.1, –7.0). Skin extensibility was higher in adolescents with CFS (mean z score: 0.5 vs. 0.1 SD; adjusted difference: 0.3 SD; 95% CI: 0.1, 0.5). Arterial stiffness, expressed as common carotid distension, was lower in adolescents with CFS, indicating stiffer arteries (670 vs 820 µm; adjusted difference: –110 µm; 95% CI: –220, –10). All analyses were adjusted for age, gender, body mass index, and physical activity. Additionally, arterial stiffness was adjusted for lumen diameter and pulse pressure.

Conclusions. These findings do not consistently point in the same direction of an abnormality in connective tissue. Patients with CFS did have lower blood pressure and more extensible skin but lacked the most important parameter indicating constitutional laxity, ie, joint hypermobility. Moreover, the collagen metabolism measured by crosslinks and hydroxyproline in urine, mainly reflecting bone resorption, was not different. The unexpected finding of stiffer arteries in patients with CFS warrants additional investigation.


Key Words: chronic fatigue syndrome • connective tissue disease • cardiovascular factors • autonomic nervous system

Abbreviations: CFS, chronic fatigue syndrome • EDS, Ehlers-Danlos syndrome • HP, hydroxylysylpyridinoline • LP, lysylpyridinoline • CDC, Centers for Disease Control and Prevention • CIMT, carotid intimal-medial thickness • Hyp, hydroxyproline • CIS-20, Checklist Individual Strength-20 • CI, confidence interval


Accepted Nov 9, 2004.


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