Connective Tissue Disorder

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Research: Is Chronic Fatigue Syndrome a Connective Tissue Disorder?

Source: PEDIATRICS Vol. 115 No. 4 April 2005, pp. e415-e422

(doi:10.1542/peds.2004-1515)

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, M.L. Bots, PhD,

MD, 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 Julius Center

for Health Sciences and Primary Care, University Medical Center

Utrecht, Utrecht, Netherlands

ABSTRACT

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.