Date sent:      	Thu, 8 Aug 2002 

Cluster analysis to define typology of CFS (part 2)


With respect to disability, Cluster 1 participants demonstrated
significantly lowest levels of disability in terms of limitations in
physical activities such as self-care, walking, climbing stairs,
bending, lifting, and exercising, as compared with Cluster 2 and
Cluster 3 participants. With respect to limitations in work and
other daily activities (including accomplishing less than wanted,
limitations in the kind of activities performed, and difficulty in
performing activities), Cluster 1 participants also exhibited
significantly lower levels of disability than individuals in Cluster
3.In addition to findings regarding limitations in physical
functioning, Cluster 1 participants demonstrated significantly
lowest levels of disability resulting from bodily pain as compared
with participants in Cluster 2 and Cluster 3.As compared with
individuals in Cluster 2 and Cluster 3, Cluster 1 participants also
demonstrated significantly lowest limitations in normal social
activities. In summary, characteristics of Cluster 1 describe a
subgroup of individuals with CFS with moderate lack of energy,
low post-exertional fatigue, moderate cognitive problems,
moderate fatigue following rest, and lowest levels of disability
related to physical and social functioning.


Cluster 2 -High Post-Exertional Fatigue, Alleviated by Rest

Of the 45 participants classified into Cluster 2,eight
(17.8%) were diagnosed with CFS, eight (17.8%) were
diagnosed with ICF,11 (24.4%) were diagnosed with
medically-explained chronic fatigue, and 18 (40.0%) were
diagnosed with psychiatrically-explained chronic fatigue. Cluster
2 was characterized by factor scale scores more consistent with
those reported by individuals with CFS in our sample, and by
those with medically-explained chronic fatigue, than by those
with ICF or psychiatrically-explained chronic fatigue (Refer to
Table I). As evidenced in Table III, the most unique aspect of
Cluster 2 was that it was characterized by significantly highest
scores on the Physical Exertion factor scale, reflecting most
severe fatigue following exertion, and significantly lowest scores
on the Fatigue and Rest factor scale, suggesting that rest is
most restorative for individuals in this cluster. Therefore, this
cluster was labeled, High Post-exertional fatigue, Alleviated by
Rest. Cluster 2 scores on the Lack of Energy factor scale
reflected moderate symptom severity that was significantly lower
than that of Cluster 3 individuals and directionally lower than that
of Cluster 1 participants. Cluster 2 scores on the Cognitive
Problems factor scale also reflected moderate symptom severity
that was directionally higher than Cluster 1 scores and
directionally lower than Cluster 3 scores.

With respect to disability, Cluster 2 participants demonstrated
significantly higher levels of disability with respect to limitations
in physical activities such as self-care, walking, climbing stairs,
bending, lifting, and exercising as compared with Cluster 1
participants. In addition, Cluster 2 participants demonstrated
significantly higher levels of disability resulting from bodily pain
as compared with participants in Cluster 1 and Cluster 3. As
compared with Cluster 1 participants, Cluster 2 participants also
demonstrated significantly higher limitations in normal social
activities. In summary, characteristics of Cluster 2 describe a
subgroup of individuals with CFS with moderate lack of energy,
most severe post-exertional fatigue, moderately severe
cognitive problems, and least severe fatigue following rest in
comparison to Clusters 1 and 3. In comparison to Cluster 1,
Cluster 2 was also characterized by significantly higher levels
of disability related to physical and social functioning.


Cluster 3 -High Post-exertional Fatigue -Not Alleviated by Rest

Of the 85 participants classified into Cluster 3,22 (25.9%) had
CFS,20 (23.5%) had ICF, 20 (23.5%) had medically-explained
chronic fatigue, and 23 (27.1%) had psychiatrically-explained
chronic fatigue. Cluster 3 was characterized by factor scale
scores that were most consistent with those reported by
individuals with CFS in our sample and by those with
medically-explained chronic fatigue than by those with ICF or
psychiatrically-explained chronic fatigue (Refer to Table I). As
evidenced in Table III, the most unique aspect of Cluster 3 was
that it was characterized by significantly highest scores on the
Lack of Energy, Cognitive Problems, and Fatigue and Rest
factor scales, reflecting severe lack of energy, severe cognitive
problems, and severe fatigue that does not improve with rest.
Fatigue following exertion was also severe among Cluster 3
participants. In relation to the other clusters, fatigue following
exertion was significantly higher than that of Cluster 1
participants, but significantly lower than that reported by Cluster
2 participants.

With respect to disability, Cluster 3 participants demonstrated
significantly higher levels of disability with respect to limitations
in physical activities such as self-care, walking, climbing stairs,
bending, lifting, and exercising as compared with Cluster 1
participants, and directionally higher levels as compared with
Cluster 2 participants. With respect to limitations in work and
other daily activities (including accomplishing less than wanted,
limitations in the kind of activities performed, and difficulty in
performing activities), Cluster 3 participants also exhibited
significantly higher levels of disability than individuals in Cluster
1, and directionally higher levels than individuals in Cluster 2.In
addition to findings regarding limitations in physical functioning,
Cluster 3 participants demonstrated significantly higher levels of
disability resulting from bodily pain than Cluster 1 participants,
and directionally higher levels than Cluster 2 participants. Cluster
3 participants also demonstrated significantly higher limitations
in normal social activities than Cluster 1 participants, and
directionally higher limitations than Cluster 2 participants. In
summary, characteristics of Cluster 3 describe a subgroup of
individuals with CFS with severe lack of energy, severe
post-exertional fatigue, severe cognitive problems, severe
fatigue following rest, and most severe levels of disability with
respect to physical and social functioning.


DISCUSSION

The present sample was randomly selected from a stratified,
community-based population of households within several
Chicago neighborhoods. Participants were provided full
psychiatric examination, full medical evaluation, and
independent case review to accurately classify them into
diagnostic subgroups. Most CFS epidemiologic studies have
utilized patients recruited from primary or tertiary care medical
settings, and/or have not included full psychiatric, medical, and
case review evaluation in their methodology. As a result, these
prior samples may not accurately represent individuals with
chronic fatigue and CFS within the general population. Findings
from the present study highlight important symptom-related
differences between medically-diagnosed subgroups of
individuals with chronic fatigue. Results also define clusters that
reflect unique symptom patterns among these individuals.

In a prior study of 780 individuals with self-reported chronic
fatigue within our community-based sample, four dimensions of
fatigue were defined through factor analysis (Jason et al.,2001).
These included: Lack of Energy (measuring fatigue intensity,
energy, weakness, and tiredness); Physical Exertion (measuring
severity of fatigue and symptomatology following exertion);
Cognitive Problems (measuring difficulties with memory,
concentration, and information processing); and Fatigue and
Rest (measuring whether fatigue improves with rest or
sleep). One limitation of the Jason et al. (2001) study was that
self-report of fatigue-related symptoms were not corroborated
with physiological findings.

In the present study, the sample was analyzed according to four
diagnosed chronic fatigue subgroups: CFS, ICF, medically-
explained chronic fatigue, and psychiatrically- explained chronic
fatigue (the chronic fatigue-explained group was split into
medically-explained chronic fatigue and psychiatrically-
explained chronic fatigue). Significant differences between the
groups emerged on only one of the four factor scales, Physical
Exertion. The CFS group had significantly more severe
post-exertional fatigue than the ICF group, and the medically-
explained chronic fatigue group had significantly more severe
post-exertional fatigue than both the idiopathic chronic fatigue
group and the psychiatrically-explained chronic fatigue group.
Directional findings revealed that the medically-explained
chronic fatigue group had the highest level of post-exertional
fatigue of all four groups, with the CFS group having a similarly
high level of post-exertional fatigue. Findings for comparable
levels of post-exertional fatigue severity among the CFS and
medically-explained chronic fatigue groups suggest that
post-exertional fatigue represents a key symptom that
differentiates individuals with CFS and other medical
explanations for chronic fatigue from those with idiopathic and
psychiatrically-explained types of chronic fatigue.

Findings from the cluster analysis supported a typology of CFS
characterized by distinct clusters of individuals. Cluster 1, Low
Post-exertional Fatigue, contained only one participant with CFS
and was characterized by moderate symptomatology on all four
factor scales and lowest levels of disability related to physical
and social functioning. Cluster 1 symptomatology was more
consistent with ICF and psychiatrically-explained chronic fatigue
groups than with the CFS or medically-explained chronic fatigue
groups. Cluster 2, High Post-exertional Fatigue, Alleviated by
Rest, contained a small proportion of individuals with CFS
(25.8%), and was characterized by moderate, but least severe
lack of energy, most severe post-exertional fatigue, moderate
cognitive problems, fatigue that was most positively responsive
to rest, and moderate levels of physical and social disability.
Factor scale scores of Cluster 2 participants were more similar
to those of the CFS and medically-explained chronic fatigue
groups than to those of the ICF or psychiatrically-explained
chronic fatigue groups. Cluster 3,CFS,Not Alleviated by Rest,
contained the highest proportion of participants with CFS
(71.0%) and was characterized by most severe lack of energy
and cognitive problems, second highest post-exertional
fatigue,most severe fatigue in relation to rest,and highest levels
of disability related to physical and social functioning. Factor
scale scores of Cluster 3 participants were most similar to those
of the CFS and medically-explained chronic fatigue groups than
to those of the ICF or psychiatrically-explained chronic fatigue
groups.

With respect to CFS, findings suggest that a majority of
individuals with moderate to severe symptoms can be accurately
classified into two important subgroups: one distinguished by
severe post-exertional fatigue, and fatigue that is alleviated by
rest; and one distinguished by severe overall symptomatology,
severe post-exertional fatigue, and fatigue that is not alleviated
by rest. The later subgroup, Cluster 3, contained the largest
proportion of individuals with CFS. This cluster appears to
characterize a majority of individuals with CFS who report
severe fatigue following exertion, symptomatology that is not
alleviated by rest, and severe limitations in physical, social, and
occupational functioning. The first subgroup, Cluster 2,
contained a smaller proportion of individuals with CFS and
appeared to represent a subgroup of individuals who also report
severe fatigue following exertion, but find that rest alleviates
some of their symptoms. Given that this subgroup reported less
interference with physical, social, and occupational functioning
than the Cluster 3 subgroup, characteristics of Cluster 2 appear
to define a somewhat higher functioning subgroup of individuals
with CFS; a subgroup that may be able to manage their activity
levels and energy expenditures sufficiently well so as to reap
positive benefits from rest and experience fewer limitations in
functioning. This hypothesis is consistent with the principles of
the envelope theory (Jason et al.,1999b), which point to
improved functional capacity when individuals with CFS pace
their activity according to their available energy resources and
maintain a consistent level of activity over time. Individuals in
both Clusters 2 and 3 were also more likely to be of low
socioeconomic status than individuals in the first cluster, whose
symptomatology was least consistent with that of CFS. It is
possible that the experiences of more severe symptomatology
and greater limitations in functioning among individuals in
Clusters 2 and 3 were associated with decreased ability in
achieving higher socioeconomic status.

The distinguishing characteristics of Clusters 2 and 3 provide
empirical support for key aspects of CFS case definitions in the
United States,Great Britain, and Australia (Dowsett et al.,1994;
Fukuda et al.,1994, Lloyd et al.,1990), pointing to some
consistency in prior attempts to define central characteristics of
this syndrome, and highlighting potential questions about the
designation of criteria as major (mandatory for a diagnosis) or
minor (optional counting toward a diagnosis).

One key characteristic that distinguished Clusters 2 and 3
(containing almost all participants with CFS) from Cluster 1
(containing only one CFS participant), was markedly high
severity of post-exertional fatigue. This symptom has been
designated as a major criteria for the London definition of
myalgic encephalomyelitis (CFS) (Dowsett et al.,1994), but as
one of the minor criteria for the US definition of CFS (Fukuda et
al.,1994). Results from the present investigation highlight the
relative importance of this symptom as a diagnostic marker for
CFS and point to the potential utility in designating
post-exertional fatigue as a major criteria for CFS in future
attempts to define this syndrome.

A second key characteristic, fatigue in relation to rest,
distinguished individuals in Cluster 2 from those in Cluster
3.While individuals with CFS were contained in both clusters,
those in Cluster 3 differed most significantly from those in
Cluster 2 with respect to whether their fatigue was alleviated by
rest. One of the major criteria for the current US definition of
CFS (Fukuda et al.,1994) requires that fatigue is not
substantially alleviated by rest in order for an individual to
receive a diagnosis. Findings from the present investigation
suggest that this criteria may be more accurately designated as
one of the minor criteria for CFS so that it does not artificially
exclude those with CFS who may experience some symptom
relief with rest.

A third result deserving of attention involves the finding for more
severe cognitive problems in Clusters 2 and 3 as compared with
Cluster 1.This finding highlights the importance of cognitive
problems to the experience of CFS, and supports the
designation of cognitive problems as a major criteria for CFS in
the London (Dowsett et al., 1994) and Australian (Lloyd et al.,
1990) criteria. Future attempts to define CFS should consider
designating cognitive problems as one of the major diagnostic
criteria.

A fourth issue regards the prominence and severity of fatigue.
Although lack of energy was significantly more severe among
individuals in Cluster 3 as compared with Cluster 2, the level of
fatigue experienced by individuals in both clusters was
moderate to severe. Moreover, level of fatigue severity among
individuals in Cluster 1 was comparable to and only slightly
higher than that of individuals in Cluster 2. Taken together, these
findings suggest that fatigue severity, while fundamental to a
CFS diagnosis, does not present an adequate means of
differentiating individuals with CFS from individuals with less
severe conditions, such as ICF or psychiatrically-explained
chronic fatigue.

In summary, findings from the present investigation are unique in
that they highlight the role of symptom severity and patterning in
characterizing various subgroups of individuals with chronic
fatigue and CFS. They not only lend support to prior evidence
demonstrating the empirical validity of some of the symptoms
included in current case definitions of CFS (Lloyd et al.,1990;
Dowsett et al., 1994; Fukuda et al.,1994), but they also
underscore the importance of post-exertional fatigue and fatigue
in relation to rest in differentiating subgroups of individuals with
chronic fatigue and CFS. These results can inform future
research involving empirical modification of the current case
criteria for CFS as well as facilitate efforts to more accurately
evaluate and treat individuals with this disorder.


Acknowledgement
Financial support for this study was provided by NIAID Grant
Number AI36295.


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