Date sent:      	Wed, 17 Apr 

Possible Triggers and Mode of Onset of Chronic Fatigue Syndrome

J of Chronic Fatigue Syndrome, Vol. 10(2) 2002, pp. 3-18

P. De Becker, PhD; N. McGregor, PhD; K. De Meirleir, MD, PhD

P. De Becker, VUB, Vakgroep Interne Geneeskunde, KRO gebouw
niv.-1, Laarbeeklaan 101, 1090 Brussels, Belgium.
N. McGregor, Collaborative Pain Research Unit, Department of Biological
Sciences, Faculty of Science, University of Newcastle, Callaghan, New South
Wales, Australia.
K. De Meirleir, VUB, Vakgroep Interne Geneeskunde, KRO gebouw niv.-I,
Laarbeeklaan 101, 1090 Brussels, Belgium.
Address correspondence to: P. De Becker, AZ-VUB, KRO gebouw niv-1, Dienst
Sportgeneeskunde, Laarbeeklaan 101, 1090 Brussels, Belgium (E-mail:
mailto:pdbeck@minf.vub.ac.be ).


ABSTRACT.
To identify the possible triggering events of CFS, we collected data on
1546 CFS patients and 309 excluded fatigued patients. Using extensive
present and past medical history and lab reports as close as possible to
the date of onset, an attempt was made to identify the agents that could
play a role in the disease process.

Significant differences were found between the events at onset, between the
Fukuda or Holmes definitions and a sudden as distinct from a gradual onset.
We further found a series of subgroups of events that occurred at onset of
CFS. Each of these onset event clusters was associated with an infectious
event, blood transfusion or hepatitis B vaccination. In a large percentage
of our study group an infectious event was combined with a non-infectious
event. In summary, we can conclude that a number of different stressors and
consequent immunological and neuroendocrinological changes can contribute
to the onset of CFS.

KEYWORDS. Chronic fatigue syndrome, etiology, onset, infectious agents,
triggering events


INTRODUCTION

CFS is diagnosed using a clinical case definition established in 1988 (1)
and revised in 1994 (2). The major distinguishing symptom is debilitating
fatigue of more than 6 month's duration associated with a marked decrease
in daily activity, that cannot be attributed to any known medical cause,
and a constellation of other non-specific symptoms.

Over the years, a large number of studies have been conducted to unravel
the pathogenesis of CFS. CFS has been attributed to a variety of infectious
agents, including Epstein-Barr virus (EBV), human herpesvirus 6 (HHV-6),
Cytomegalovirus, enteroviruses, retroviruses, stealth viruses, Borna virus
and Ross River virus (3-13). However, the results of these studies are not
consistent (14-19). Many of these viruses (EBV and HHV-6) are endemic
within human beings with infections occurring early in life (4).

Therefore, new primary infection by these viruses is unlikely. Most
evidence points to a reactivation of these endemic viruses, rather than
primary infection (14,16,20.)

Not being able to identify a viral agent does not mean per se that a new
viral infection did not take place. Levy proposed a "hit and run" effect,
whereby, a virus might infect the host, cause immune abnormalities leading
to CFS, and then be eliminated, leaving the immune system in an activated
state (20). Alternate hypotheses suggest that bacterial stealth infections,
including Brucella species (12), Mycoplasma species (21,22) and Chlamydia
pneumoniae (23) may be important in patient morbidity. Thus, although it is
clear that no single etiologic agent can be unequivocally associated with
most cases of CFS, a number of infections do seem to precede the
development of CFS.

Studies investigating the precipitating factors for CFS revealed a high
percentage of patients who attributed their disorder to some kind of
infectious agent. Salit reported that 72% of CFS patients reported an
apparently infectious illness associated with the development of CFS (24).
Earlier studies also reported a similar percentage of viral illnesses
preceding the onset of CFS (13,25-28). Alternatively, other investigators
have suggested that non-infectious factors may also play a role in the
etiopathogenesis of CFS. In the three months to a year preceding CFS,
stressful and negative life events took place very commonly in patients who
later developed CFS (24,29). It is clear that there is no consensus among
researchers and clinicians regarding the onset of CFS and there is a high
degree of heterogeneity in the results.

As CFS is a defined condition with a definitive or sudden onset, it should
be possible to trace the factors that may have been precipitants (24,30).
In this study, we examined a large group of CFS patients and explored the
events prior to the development of CFS. No attempt was made to identify any
specific pathogen. In this descriptive study we report the various modes of
onset in a large Belgian study population.

© 2002 by The Haworth Press, Inc. All rights reserved.

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