U.S. Case Definition of Chronic Fatigue Syndrome: Diagnostic and
Theoretical Issues

J Chron Fatigue Syndrome 
Vol. 5, No. 3/4, 1999, pp. 3-33.

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EPIDEMIOLOGY

U.S. Case Definition of Chronic Fatigue Syndrome: Diagnostic and
Theoretical Issues

Leonard A. Jason
Caroline P. King
Judith A. Richman
Renee R. Taylor
Susan R. Torres
Sharon Song


Leonard A. Jason and Caroline P. King are affiliated with DePaul
University.
Judith A. Richman is affiliated with the University of Illinois at
Chicago.
Renee R. Taylor, Susan R. Torres and Sharon Song are affiliated with
DePaul University.
Address correspondence to: Leonard Jason, PhD, Department of
Psychology, DePaul University, 2219 N. Kenmore Avenue, Chicago, IL
60614.
The authors appreciate the financial support provided by NIAD grant # Al
36295. The authors would like to express their appreciation to Erin
Frankenberry, Susan Klein, and Guy Fricano for their constructive advice.

Journal of Chronic Fatigue Syndrome, Vol. 5 (3/4) 1999
© 1999 by The Haworth Press, Inc. All rights reserved.


SUMMARY. In 1994, researchers from the U.S. Centers for Disease
Control and Prevention developed a revised case definition of chronic
fatigue syndrome (CFS) (1), a complex illness characterized by
debilitating fatigue and a number of accompanying flu-like symptoms.
Although Fukuda and associates intended to resolve complexities
surrounding the classification of individuals with CFS stemming from
previous definitional criteria (1), significant problems with the revised
criteria endure. This article highlights reliability issues and other
conceptual and operational difficulties inherent in the current U.S.
definition of CFS (1). We employ case studies derived from a
community-based epidemiological study of chronic fatigue syndrome (2) to
illustrate examples of the potential for misclassification of individuals
with CFS using the current U.S. criteria (1). Moreover, we suggest
alternative approaches to classification and ways to operationalize
specific concepts embedded in the current U.S. criteria (1).

KEYWORDS. Epidemiology, fatigue

[Note:  Figures 1 and 2 referred to within this article may be viewed at:
http://www.co-cure.org/private/v5n3/figures.htm .]

_________________________________________________

Historically, many chronic illnesses have been difficult to define,
particularly when the exact causal agents of the illness are not
known, physical signs and symptoms are nonspecific or variable, and
diagnostic laboratory tests arc not applicable, unavailable, or have
poor specificity and sensitivity (3). With chronic illnesses of this
nature, standard case definitions have had to be developed through the
consensus of expert committees (e.g., carpal tunnel syndrome, rheumatoid
arthritis, systemic lupus erythematosus, and various psychiatric
disorders) (3,4). Chronic fatigue syndrome (CFS) is one of these difficult
illnesses to define, and despite years of research, it remains a poorly
understood and controversial syndrome (5). Even the classification of CFS
has been controversial, and this might reflect the fact that some
researchers consider CFS a medical-neurological illness, whereas others
consider it a psychiatric disorder (6).

One factor that has confounded research on CFS is the lack of
consensus among health care professionals regarding the interpretation and
application of the diagnostic criteria for CFS. Criteria need to possess
adequate sensitivity, identifying all those with CFS, and adequate
specificity, distinguishing those who have other medical or immunological
disorders from those who have CFS. Attempts to specify the diagnostic
criteria for this syndrome have sparked considerable debate and
controversy (6,7). Since its emergence as a new disease category in the
1980s, four definitions of CFS have been proposed, but none have been
derived empirically (8). Perhaps as a result, clinicians and health care
professionals working with chronically fatigued clients have noted a
number of difficulties with each of these case definitions. One study that
compared the original U.S. case definition (9) and the British and
Australian case definitions (10,11) found major differences in criteria
between each of the three case definitions. Tiersky and associates (12)
have produced data indicating that the 1988 and 1994 U.S. CFS case
definition criteria (9,1) identify distinct patient groups. These
differences substantially affected the number of patients meeting the
criteria of each definition (13).

Subtle changes in the wording, interpretation, and application of the
diagnostic criteria used to identify people with CFS can critically
influence prevalence rates and change the characteristics of the samples
being defined. Several recent CFS community-based prevalence studies using
the current U.S. criteria (1) produced prevalence estimates that differ by
a factor of 10, thus suggesting that these investigators might be
identifying different samples of people with CFS (14-16). Unclear criteria
might be responsible for these discrepant rates. The present paper will
focus specifically on the practical and theoretical issues in using the
current U.S. case definition (1), as it is the most commonly used criteria
for diagnosing CFS.


CURRENT U.S. CASE DEFINITION OF CFS

The current U.S. definition (1) requires that the following major
criteria he met for the diagnosis of CFS to be made: (A) six or more
months of persistent or relapsing chronic fatigue of new or definite
onset that is neither the result of ongoing exertion nor alleviated by
rest, and results in substantial reductions in previous levels of
occupational, educational, social, or personal activities; and (B) the
concurrent occurrence of four or more of eight minor symptoms that persist
or reoccur during six or more months of the illness and do not predate the
fatigue.

The current U.S. case definition (1) stipulates that a diagnosis of
CFS should not be made if other conditions that explain chronic
fatigue are present. For example, the following conditions exclude the
diagnosis of CFS: past or current major depression with melancholic or
psychotic features, anorexia nervosa or bulimia, and alcohol or substance
abuse within two years before the onset of CFS, or at anytime afterward.


CLASSIFICATION ISSUES

Several investigators have tried to validate or confirm approaches for the
classification of fatigue using statistical methods (17,18), or by
attempting to distinguish psychological from physical fatigue (19). Others
have tried to clinically confirm the CFS criteria established by the CDC
(20). Nisenbaum and associates (21) found that three correlated factors
(fatigue-mood-cognition symptoms, flu-type symptoms, and visual impairment
symptoms) explained a set of additional correlations between fatigue
lasting for six or more months and 14 interrelated symptoms. No factor
explained the correlations among fatigue lasting for one to five months
and other symptoms. Findings like these are of great interest because they
indicate that only fatigue lasting six or more months (with selected
symptoms) overlaps with published criteria to define CFS.

Disagreement continues about which minor symptoms should be included
within the CFS case definition. For example, Komaroff and associates
(20) compared patients meeting the major criteria of the original U.S. CFS
case definition (9) with healthy controls and groups with multiple
sclerosis and depression. They concluded that eliminating muscle weakness,
arthralgias, and sleep disturbance, and adding anorexia and nausea would
strengthen the case definition. Hartz and associates (22) examined persons
with CFS and compared them to those with other fatigue-related conditions
and those with no symptoms of fatigue. They concluded that persons with
fatigue could be classified by the degree to which they match the case
definition of CFS (1). They also suggested including criteria such as
frequent fever and chills, muscle weakness and sensitivity to alcohol.
Others have provided experimental evidence for the importance of the CFS
criteria (23). While considerable discussion has occurred concerning
designating which symptoms should be included in the case definition, less
attention has been devoted to issues of reliability.


ISSUES REGARDING RELIABILITY

In all health-related disciplines, the reliable diagnosis of clinical
conditions is clearly a matter of importance (24). Derived from the field
of medicine, clinical diagnosis historically has been closely linked to
medical conceptions of disease entities in which the key to diagnosis is
the identification of specific pathologic conditions that may account for
the presenting symptoms (24). As a result, the diagnostic process is
inherently bound by the limits of medical knowledge and by the accuracy of
diagnostic measures. When available diagnostic tests are negative and
there are no alternative physiological explanations, clinicians sometimes
presume the source of the individual's symptoms to be psychological in
nature, particularly when the patient is a woman (25). Furthermore, if the
diagnostic category lacks precision and covers a moderate variety of
behaviors, reliability of diagnosis is likely to be decreased. Because of
the profound influence of the medical model on diagnosis, and the close
ties between diagnosis and treatment prescriptions, diagnostic accuracy is
of keen importance (24).

Low reliability of routine diagnostic procedures is a crucial problem in
psychiatry and medicine, affecting both clinical work and research efforts
to improve the management, treatment, and care of patients (26). The
greatest source of disagreement among clinicians is criterion
variance-differences in the formal inclusion and exclusion criteria used
to classify patients' data into diagnostic categories. Criterion variance
is likely to occur when explicit criteria do not exist for diagnostic
categories (27). In considering issues of criterion variance for CFS, it
is important to recognize that CFS is a syndrome rather than a disease. As
such, clinical diagnosis of this condition can be expected to vary
depending upon the selection and interpretation of diagnostic criteria.

Criterion variance has significant implications with respect to the
reliability of both clinical practice and research (28). Clinically,
if a specific treatment is indicated for a given disorder, an
incorrect diagnosis can have serious consequences, including improper
treatment leading to other illnesses or death (24). In other cases,
incorrect diagnosis may lead to social stigmatization or even
inappropriate institutionalization (29). Within the realm of research, if
there is limited reliability of the diagnostic groups studied, the results
of any study using such diagnostic categories are likely to be unreliable
and/or invalid (24,26). Issues concerning reliability of clinical
diagnosis are therefore complex, and have important research and practical
implications.

With respect to CFS, issues concerning reliability are equally
complex, with similarly important clinical and research implications. Due
to the lack of sufficient objective clinical signs or laboratory
diagnostic markers, the current case definition for CFS is largely
dependent upon subjective factors and patient self-report (1). Symptoms of
sore throat, or lymph node pain can only he infrequently confirmed by a
physician, and other symptomatic criteria are even more difficult to
confirm because of their ambiguous nature (e.g., difficulty concentrating)
(3). Efforts to develop objective clinical means of distinguishing
patients with CFS from those with other illnesses are therefore greatly
needed.

In response to this need, Lapp and Cheney developed a clinical case
definition for practitioners modeled after the current CDC case
definition (30). Although their clinical criteria (30) closely
resemble the CDC research definition (1), two distinctions include
Lapp and Cheney's elevation of neurocognitive dysfunction to the major
criteria, and their description of both major and minor criteria in more
detail than originally proposed by the CDC definition. Lapp and Cheney
also included subcategorization systems focusing on important variables of
illness onset and severity (30). We argue that precise criteria for
identifying key symptoms of CFS similar to these are essential for
adequate reliabilities to be obtained.


SAMPLE FOR THE QUALITATIVE ANALYSES

In the sections below, we address problems of reliability with the
Fukuda et al. definition of CFS (1) utilizing case studies derived
from a community-based epidemiological study of CFS (2) and case
studies obtained from previous clinical research studies conducted by the
DePaul University research team over the past seven years (3 1-33). The
community-based epidemiological study was carried out in three stages.
Stage I entailed a cross-sectional telephone survey of a random sample of
28,673 adults (18 years and older). This initial screening entailed a
stratified random sample of households in ethnically diverse neighborhoods
of Chicago. Stage II involved a structured psychiatric assessment, and
Stage III involved a medical exam and structured medical history by a
physician with expertise in the diagnosis of CFS. These data, plus medical
records, were provided to physicians who independently reviewed all data
on each participant completing stages I through III in order to make a
diagnosis of CFS.

This paper utilized a multidisciplinary case study team, which
reviewed the data collected on all participants who completed Stages I
through III in the epidemiology study, as well as the ratings by the
physician reviewers. The multi-disciplinary team consisted of PhD-level
professionals from the fields of psychology, sociology and epidemiology,
as well as graduate students from a clinical psychology doctoral program.
All members of the case study review team had expertise in the assessment
and diagnosis of CFS.

After each participant's case history and data were presented, the
team discussed discrepancies among the physicians' diagnostic ratings and
assessed apparent sources of the discrepancies (i.e., diagnostic criterion
in question). In addition, the team also noted when physicians might have
inappropriately applied the criteria and either erroneously diagnosed a
participant with CFS or erroneously excluded a participant from the
diagnosis of CFS. A list of difficulties with the clinical application of
the Fukuda CT al. criteria (1) were generated from these meetings and are
presented below along with case studies to illustrate these issues.


PROBLEMS INVOLVING THE CURRENT U.S. CASE DEFINITION:
OVER-INCLUSIVENESS

Although the current U.S. definition (1) requires fewer minor symptoms in
comparison to the original U.S. definition by Holmes and colleagues (9),
the current definition has been criticized by some CFS researchers as
being too broad (8). According to Fukuda, the new definition of CFS might
not exclude people who have purely psychosocial stress, or many
psychiatric reasons for their fatigue (Fukuda, Personal communication,
August 30, 1995). As a result, individuals with purely psychiatric
disorders and psychological explanations for their fatigue might be
included within the CFS rubric. While it is possible for some individuals
with CFS to have psychiatric problems before or after the onset of CFS, or
even both, the inclusion of individuals with purely psychiatric disorders
may seriously complicate the interpretation of epidemiological and
treatment studies (8).

For example, under the new and broader U.S. definition of CFS (1),
there is the potential for the subtle distinction between fatigue
produced by primary depression versus fatigue produced by CFS to be
discounted. The main problem is that there is considerable overlap
between the symptoms for major depression and the minor symptom
criteria for CFS. Chronic fatigue, unrefreshing sleep, joint pain,
muscle pain, and impaired concentration are common symptoms of both
major depression and CFS (20). Because major depression is not an
exclusionary condition, it is possible for patients with major
depression as a primary disorder to be misdiagnosed as having CFS.

Johnson and associates (34) suggest that, while many people with CFS
also have secondary depression, the type of depressive symptoms they
report are qualitatively different from those reported by people with
clinical depression. Using the Beck Depression Inventory (BDI) (35),
Johnson and associates (34) categorized individual BDI items into four
clusters: mood, self-reproach, somatic, and vegetative. In comparison to
people diagnosed with clinical depression, Johnson and colleagues (34)
found qualitative differences in the nature of the items endorsed on the
BDI by people with CFS and people with clinical depression. The BDI scores
of people with CFS were comprised mainly of items concerning physical
complaints and somatic symptoms of fatigue. Participants with CFS reported
cardinal depressive symptoms of disturbed mood and self-reproach less
frequently than participants with depression. Taken together, these
findings suggest that while depressive symptoms are common in samples of
people with CFS and depression, the types of items involved are
qualitatively different. The following case study illustrates this issue.

Case 1 is a 28-year-old African-American female with a six-year
history of fatigue, which began after the birth of her child. She
described a sudden onset of her fatigue, and added that it gradually
became worse over time. Overall, she estimated that the fatigue
reduced her ability to do things by 80%, and she reported symptoms of both
physical and mental fatigue. In addition, she reported symptoms of
insomnia, sore throat, headache, and impaired memory and concentration.
Her medical history and examination revealed no significant medical
exclusionary findings. The examining physician did obtain a significant
history of past and current depression. On the psychiatric interview, she
received the diagnosis of major depression without melancholic features.
She reported sadness, indecisiveness, suicidal thoughts, low self-esteem,
weight loss, and early morning awakenings.

Case 1's symptomatology could meet the U.S. criteria for CFS (1). Her
diagnosis of major depression is not exclusionary in and of itself.
However, a careful assessment of her depressive symptomatology strongly
suggests that her primary problem is that of depression with secondary
fatigue. In fact, she herself stated that her primary problem was
depression and that the depression was causing her to feel tired and
unable to perform tasks. In addition, she did not suffer from exercise
intolerance. She reported physical exercise had no effect on her sense of
tiredness. Additional evidence supporting the diagnosis of primary
depression is the presence of suicidal ideation and self-reproach,
symptoms that are less common in people with CFS (34).

What Is Persistent or Relapsing Chronic Fatigue?

Self-report is unavoidable for some variables such as fatigue, which
is a complex psychological state that cannot be measured otherwise.
This is clearly not the case for symptoms for which objective
measurements are available and constitute the gold standard. Activity
levels might provide indication of the fatigue state of an individual,
particularly when individuals with CFS engage in significantly less
activity than healthy controls. Tryon (36) reviews instruments for
measuring activity level. Tryon and Williams (37) describe a computerized
actigraph capable of recording intensity of activity every minute of the
day and night for 22 consecutive days. This technology for obtaining
objective longitudinal activity measurements within an individual's
natural environment can and should be used to further examine the
construct of fatigue.

A recent study illustrates the use of actigraph data in assessing
activity levels in CFS (31). A healthy control participant had regular
spiking of activity units, with high levels of variability in activity
during the day and low levels at night (see Figure 1). In contrast,
participants with CFS did not exhibit the high spiking of units of
activity that occurred for the control participant, and they demonstrated
less clearly defined patterns of high variability during the day and low
variability at night (see Figure 2 for data on one participant with CFS).
Given these findings for clear patterning differences, it is possible that
the actigraph might be a useful tool to measure daily patterning of
activity, and help differentiate the activity of those with chronic
fatigue versus those whose activity might be explained by mild, occasional
states of fatigue (38).

The issue of extent of self-perceived fatigue is of critical
importance in deciding whether a person has "persistent and relapsing
chronic fatigue." Using standardized instruments to assess fatigue (28)
and deciding on cut-off points for persistent fatigue would improve
efforts at reliably assessing this symptom. The Fatigue Severity Scale
(39) is a reliable and easy-to-use measure that assesses fatigue. Patients
with CFS have been found to score significantly higher on this measure
than patients with multiple sclerosis or depression (39).


CFS Onset

The diagnosis of CFS is greatly complicated by the vague wording of
the major criteria and the absence of clinical guidelines for health
care professionals to follow. The first major criterion specified by
the U.S. case definition requires the presence of persistent or
relapsing chronic fatigue that is of "a new or definite onset" (1).
However, this criterion does not specify what should be considered the
clinical marker of onset-the onset of the fatigue itself, or the onset of
the first symptom that eventually developed into the fatigue syndrome
(e.g., a sore throat that later developed into a flu, which eventually
produced chronic fatigue). One of our participants gradually developed
fatigue at age 20, but did not develop the accompanying four minor
symptoms until age 26. Thus, it was unclear whether this patient's CFS
would be considered of "new or definite" onset. We believe that the case
definition should be modified to include explicit guidelines for scoring
this criterion to improve diagnostic reliability. It would also he useful
to assess whether or not the onset was associated with an infectious
illness (23). The following case study is presented to illustrate
difficulties related to the onset criterion.


Case 2 is a 32-year-old male with a history of over 15 years of
chronic fatigue. Fatigue onset occurred gradually during adolescence
and it became worse in recent years. Case 2 reported both mental and
physical fatigue, producing substantial reductions in his ability to
do things. He also reported symptoms of post-exertIonal malaise,
unrefreshing sleep, sore throats, and lymph node pain. The psychiatric
interview and medical history and examination did not reveal exclusionary
medical or psychiatric diagnoses.

Case 2 clearly exhibits many of the required symptoms of CFS. However,
because fatigue onset occurred in adolescence, this participant's fatigue
would be rated as lifelong and he would be excluded from a CFS diagnosis
by the research case definition (1). We believe the onset criterion should
be expanded into categories to allow for the inclusion of people whose
illness onset does not fit neatly into a discrete period of time
characterized as "new or definite." Rather than excluding such individuals
from the diagnosis of CFS, we suggest that they be subclassified into the
following categories: (A) sudden (onset of fatigue symptoms within 24
hours; 1 week; 1 month); (B) gradual (onset of fatigue symptoms 2-6
months; 7-12 months; 1-2 years, greater than 2 years, but did not begin
during childhood or adolescence); or (C) lifetime (onset during childhood
or adolescence). Albeit a minority, there are individuals with CFS who
report a lifetime onset of CFS (40). Many others report a gradual onset of
symptoms.

Ongoing Exertion

The major criteria also stipulate that fatigue must not result from
ongoing exertion nor be alleviated by rest (1). The term "ongoing
exertion" is relative, and it is not clear how "ongoing" should be
operationalized. For example, if a person reported feeling fatigued
after only 20 minutes of either moderate mental or physical activity,
would the fatigue he considered the result of "ongoing exertion"? Some
individuals with CFS report becoming severely fatigued after ongoing
exertion involving small amounts of effort. Should such individuals be
excluded from a diagnosis of CFS? The difficulty with this criterion
concerns the relative nature and experience of ongoing exertion.
Individuals differ in their tolerance of levels of activity and in their
definition of over-exertion.

Some participants in our sample were working two jobs, had little time for
rest, and their fatigue clearly seemed to result from ongoing exertion.
Working a full-time job and taking care of children is an example of the
type of exertion that can cause extreme, albeit "normal," fatigue. If
these individuals cut back on their over-exerted lifestyles, their fatigue
would quickly dissipate. Engaging in usual amounts of activity would not
result in fatigue. These individuals did not have CFS, as their fatigue
was clearly due to over-exertion. However, there were participants with
CFS who worked sedentary part-time jobs, were responsible for childcare
tasks, and had no energy for any other tasks. These individuals reported
chronic or relapsing fatigue and at lease four minor symptoms (1). These
individuals had minimal energy resources that were constantly being tapped
by their responsibilities, and ongoing exertion exacerbated their
conditions. The following case study illustrates the relative nature of
the term, "ongoing exertion."

Case 3 is a 46-year-old married, Caucasian woman who is currently
self-employed as a real estate agent working 30-40 hours a week. She
is responsible for her four children ages 6, 7, 11, and 12. Before she
became ill she worked 60 to 70 hours a week, and described her premorbid
lifestyle as also being extremely active and busy. The onset of her
fatigue was sudden, and it was accompanied by weakness, lymph node pain,
muscle pain, joint pain, post-exertional malaise, impaired memory and
concentration, and new headaches. She described the course of her illness
as relapsing, with periods of feeling better.

On the surface, Case 3's current self-reported levels of activity do
not appear to match the activity profile of a person with CFS. Her
current 30-to 40-hour work week, childcare responsibilities, and
active lifestyle and are misleading. Some might argue that ongoing
exertion is causing her fatigue. However, upon closer examination, her
physical symptomatology does match the classic profile of a person with
CFS (1). Despite her ability to work full-time and take care of her
children, she reported that these responsibilities affect her overall
health and cause frequent relapses. She reported that she feels fatigued
constantly and has no energy left for anything else. The critical factor
in this case is evaluating this participant's pre-morbid lifestyle. In so
doing, one observes that she has experienced a 50% decrease in activity.
In contrast to her pre-morbid lifestyle, this participant now works out of
her home, limits all physical activity, and screens her phone calls. On
some occasions she is so ill she cannot work at all. Thus, clinicians must
recognize that activity level is relative. When assessing CFS, current
lifestyle and activity level must be contrasted with pre-morbid lifestyle
and activity level. If current lifestyle and activity levels are not
compared to pre-morbid lifestyle and activity levels, a person may not
appear to meet one of the major diagnostic criteria for CFS.

The issue of ongoing exertion is also illustrated by recent reports
from Olympic athletes. Speed skater, Amy Peterson, won silver and
bronze metals at the 1992 and 1994 Winter Olympics. After the 1994-95
season, she became ill with mononucleosis. By the end of the 1995-96
season, she was diagnosed with CFS (41). For two years, she fought the
fatigue and trained inconsistently. During this time, she cut back on all
activities other than skating, including college courses and a part-time
job. She spent some days in bed; on other days she cut back on her
training. By the summer of 1997, she joined a team to compete for the next
Olympics and won all of her races in the U.S. trials in January of 1998.
Her success led to an article on her fight with CFS in USA Today magazine
(41). Some have questioned whether Amy really had CFS because she was
still able to train and race. We argue that the illness affects people in
different ways. Some with CFS are bed-ridden for long periods of time,
while others like Amy are not able to get out of bed on some days, but can
engage in exercise on other days.

Two other world class athletes with CFS are Michelle Akers, a star of the
U.S. Women's Olympic soccer team, and Peter Marshall, a British World Cup
soccer player (42). Michelle and Gary also had CFS and made comebacks
after absences from soccer. These athletes had the major and minor
symptoms of CFS. The question is whether one could argue that, because
each was pushing themselves in competitive training and sports, their
fatigue might have been due to ongoing exertion. However, exertion and
training did not negatively affect them before they acquired CFS. These
athletes need to be considered among the higher functioning people with
CFS, and more will be provided about this sub-classification in a later
section.

The key diagnostic issue is what occurs when either of these Olympic
athletes, or an overextended parent, reduce their activity levels to
their premorbid, usual patterns of work and family life, and severe
symptoms persist. If so, it is more likely that they have CFS rather
than fatigue due to ongoing exertion. If minimal activity is all that can
be tolerated before extreme fatigue is experienced, and the individual's
level of available energy is extremely depleted, then minimal ongoing
exertion can cause fatigue, and such fatigue should not be exclusionary.


Alleviated by Rest

A third problem with the major criteria is the requirement that the
fatigue is not substantially alleviated by rest (1). Informally known as
the "fifty-percent solution" (43), or the "envelope theory" (33), some
people with CFS have found that by keeping their expended energy levels
within the envelope of perceived energy levels, they can prevent severe
levels of fatigue and possibly future relapses. Thus, by not over-exerting
themselves and using more energy than they perceive themselves to have,
persons with CFS can avoid the set backs and relapses that commonly occur
in response to over-exertion. This raises the question of whether the
restriction of one's physical activity to manageable levels of fatigue
qualifies the fatigue as being substantially alleviated by rest. It is
possible that some health care professionals may classify the fatigue
experienced by these individuals as being substantially alleviated by
rest, while other health care professionals may not. The following case
study (33) is presented to illustrate this issue.

Case 4 was diagnosed with CFS six years prior to participation in the
study, and had no prior history of any psychiatric disorder. The onset of
CFS for this individual was sudden, and was marked by the presence of a
viral infection. A 100-point scale was used to rate his levels of fatigue
(0 = no fatigue, 50 = moderate fatigue, 100 = extreme fatigue), perceived
energy (0 = no energy, 100 = abundant energy similar to his condition when
he was completely well), and expended energy (0 = no energy, 100 =
abundant energy). During the first month of data collection, his levels of
expended energy (M = 39%) greatly exceeded his levels of perceived energy
(M = 24%). As a result, the degree of fatigue (M = 35%) he experienced
remained consistently high. Over the next months, the participant made
efforts to keep his expended energy close to his perceived energy.
Gradually, he was able to increase perceived and expended energy, with
perceived and expended energy remaining relatively well matched. When this
occurred, levels of fatigue (M = 13%) were considerably lower than the
levels of perceived energy (M = 49%) and expended energy (M = 55%).

The above case study demonstrates the critical relationship between
expended energy, perceived energy, and fatigue for patients with CFS. The
data collected on this participant demonstrates the extreme levels of
fatigued experienced by the participant when he greatly exceeded his
levels of perceived energy. In addition to exacerbating levels of fatigue,
this over-exertion also appeared to deplete the participant's energy
resources. However, during the study, he began to contain his levels of
expended energy on a daily basis such that his levels of expended energy
were relatively close to his levels of perceived energy. As a result, the
participant's fatigue levels remained low and his levels of perceived
energy gradually increased.

What this suggests is that some individuals with CFS are able to
reduce their overall fatigue levels by staying within their energy
envelope. This does not mean that they do not have CFS. Rather it
means that these individuals have learned to control these symptoms by
reducing episodes where they were doing much more than their limited
energy might allow. Therefore, rather than excluding those whose fatigue
is reduced or eliminated by rest, it might be useful to consider the
overall level of energy an individual has. Some individuals will have high
levels of fatigue, which are always constant and not alleviated by rest
(32). Other individuals with CFS will have minimal-to-moderate fatigue at
times, and rest can he restorative to them. What is critical is that they
still have severe restrictions in lifestyle, and it is this issue that we
consider next.


What Are Substantial Reductions?

A key issue concerning the Fukuda et al. (1) major diagnostic criteria is
the measurement of substantial reductions in activity levels. The case
definition requires "the presence of persistent or relapsing chronic
fatigue that . . . results in substantial reductions in previous levels of
occupational, educational, social, or personal activities" (1, p.956).
However, no guidelines have been provided to evaluate or quantify
"substantial reductions" in activity level or energy level. As a
consequence, evaluators must use their own opinion and clinical judgment
to determine whether a substantial reduction has occurred. This judgment
call is likely to vary, thereby decreasing diagnostic reliability. The
following case study illustrates the subtleties and subsequent
difficulties associated with the "substantial reduction" criterion.

Case 5 is a 38-year-old African-American woman who is currently
employed full-time as a nurse's aid working the night shift. The onset of
her illness was slowly progressing, and accompanied by weakness, fatigue,
muscle pain, joint pain, and extreme sleepiness. The participant reported
that the fatigue is not due to ongoing exertion, nor is it due to chronic
sleep deprivation. She also reported short-term memory and concentration
difficulties, myalgias, unrefreshing sleep, and post-exertional malaise.
The participant denied sore throats, lymph node pain, or headaches.

Although this participant meets the criteria for the U.S. case
definition of CFS, some might question this diagnosis because she is
able to work full-time. However, despite her ability to hold a
full-time job, she has had to sacrifice her social and personal
activities. The Medical Outcome Survey Short Form (MOS SF-36) (44), a
measurement of disability, revealed a number of limitations in her daily
living. Her health has significantly limited her ability to engage in
activities such as lifting or carrying groceries, climbing several flights
of stairs, and walking several blocks. This is a clear indicator that she
has had a major decrease in her pre-morbid activities. Her case
demonstrates the importance of carefully assessing the criterion of
"substantial reductions." Standardized activity inventories with cut-off
scores, like the MOS SF-36 (44), are needed to improve the reliability of
this criterion. Health care professionals must be careful to assess all
areas of functioning listed under this criterion (i.e., occupational,
educational, social, or personal activities), and not just focus on degree
of occupational functioning. For some individuals with CFS, it is possible
to work full-time during certain phases of the illness at the expense of
social or personal activities.

In addition to including criteria to determine the meaning of
substantial reductions in activity, associated criteria are needed to
assess issues of illness severity and remission states. Borrowing from
Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition
(DSM-IV) (45) terminology and the CFS clinical case definition developed
by Lapp and Cheney (30), patients' severity of symptoms might be
classified as follows: (A) minimal (just enough symptoms to meet the
diagnosis, particularly occurring with exertion, usually able to work);
(B) mild (few symptoms in excess of those in the diagnosis, occurring even
at rest, may he able to work); (C) moderate (many symptoms in excess of
those in the diagnosis, moderate symptoms at rest that become severe with
effort, unable to work); (D) severe (often housebound or bedbound); (E) in
partial remission (full criteria for the syndrome were previously met, but
currently only a few symptoms remain with effort, able to work); and (F)
in full remission (no longer any symptoms, even with effort, able to
work).

Predating Minor Symptoms

A general difficulty with the minor symptom criteria of the case
definition is the specification that the four or more minor symptoms
must not predate the fatigue (1). Clarification is needed as to what
exactly "predating" the fatigue means. If a patient had only four
minor symptoms, and one of the symptoms (e.g., sore throat) began
three months before the overwhelming fatigue, the definition suggests that
this individual would be excluded from the diagnosis of CFS. Some
individuals who develop CFS experience a prodromal phase, in which
symptoms begin to appear in the year prior to the onset of fatigue. It is
therefore unclear why such symptoms would not be counted as minor
symptoms. This lack of precision in the definition is likely to lead to
problems in interrater reliability, as well as to misdiagnoses of patients
who have CFS. The following case study illustrates potential difficulties
with the stipulation of the U.S. case definition that the four minor
symptoms must not predate the fatigue (1).

Case 6, a 28-year-old Latino man, is currently employed full-time as a
sales representative and delivery person for a uniform company. On
physical examination, he attributed his fatigue equally to mental and
physical factors and reported that his ability to perform has decreased by
about 50%. Rest does not alleviate the fatigue, and the fatigue produces a
substantial reduction in personal and social activities. In addition, he
reported myalgias, headaches, non-restorative sleep, and difficulty
concentrating. He noted that these symptoms have become worse since the
onset of fatigue. He also reported that the onset of his muscle pain
pre-dated the onset of his fatigue problem.

Case 6 reports four minor symptoms, but one of them predated the
occurrence of the fatigue. Because the symptom of muscle pain predated the
fatigue, it does not count toward fulfilling the criterion of four minor
symptoms according to the U.S. case definition (1). This case illustrates
the potential for some people who likely have CFS to be excluded from the
Fukuda et al. (1) definition.


Definitions of Minor Criteria

A second general problem with the minor symptom criteria is the lack
of operational definitions and scoring criteria for the eight symptoms
specified by the U.S. case definition (difficulties with memory and
concentration; sore throat; lymph node pain; muscle pain; joint pain;
headache; unrefreshing sleep; and post-exertional malaise) (1). For
example, the definition of unrefreshing sleep leaves room for a variety of
interpretations. One person might define unrefreshing sleep as regularly
staying up late several times a week and feeling exhausted in the morning.
Another person might not think they have unrefreshing sleep because they
are able to sleep well enough once a week hut have nonrestorative sleep on
the other days. Research findings indicate that fatigue is associated with
any disturbance in sleep (e.g., too much steep, sleep at the wrong time,
and fragmented sleep) (6). Patients with CFS often report unrefreshing,
disturbed, or poor quality sleep (6). If a fatigued person reports extreme
difficulties falling asleep, maintaining sleep, or waking up early, and
still reports that sleep, when obtained, is restorative, it would seem
inaccurate to claim that this individual is asymptomatic in the area of
sleep hygiene. Komaroff and associates (20) found that 98% of a
chronically fatigued group had sleep disturbances, but only 89% reported
awakening unrested. Thus, without a concrete operational definition,
unrefreshing sleep can be subject to different interpretations by
respondents.

In a study on Fibromyalgia, Wolfe and colleagues (46) assessed sleep
disturbance by asking if the patient awakened tired or un-refreshed
"never," "seldom," "often or usually," or "always." "Often or usually" or
"always" were scored as positive and other replies as negative. These
types of scales are improvements over the binary system of asking patients
to indicate whether or not they have unrefreshing sleep, or other minor
symptoms. Operational criteria and standardized guidelines are needed to
improve assessment of this and other minor criterion.


Binary Classification of Minor Symptoms

In the current U.S. definition (1), the eight minor symptoms are
scored using binary classification (i.e., occurrence versus
nonoccurrence), and their presence is pivotal to the diagnosis of CFS.
Despite the importance of these symptoms in defining CFS, current
approaches to charting and assessing symptoms rely on data collected at
only one time point, and only the categorical presence or absence of
symptoms is assessed (32,47,48).

Many patients with CFS have symptoms for extended periods of time, but
because of imprecise wording of the binary symptoms, some individuals with
CFS are not scored as having a symptom when they actually have it. One
minor symptom relevant to this issue is post-exertional malaise lasting
more than 24 hours (1). Some patients do not endorse this item because
they only have post-exertional malaise for two to five hours, or for 10-12
hours. When they are asked if they are severely fatigued after exercise,
they answer affirmatively, but they deny that the post-exertional malaise
lasts more than 24 hours. These patients may have limited all types of
exercise, and thus may rarely experience this symptom. However, if they
exercised, they would be extremely fatigued. This suggests that, for some
patients who do have exercise intolerance, this symptom might not be
counted using the current case definition of CFS. Hartz and associates
(22) used a measure that assessed the number of hours that a patient
remained fatigued after moderate levels of physical activity. This measure
was strongly correlated with the number of CFS symptoms and neurocognitive
symptoms experienced by the patients.

In a recent study (31), data were collected on a healthy non-CFS
control participant. Although this participant did not suffer from any
chronic illnesses, he experienced a number of the CFS definitional
symptoms for six or more months. Using binary classification, the control
participant came close to meeting the Fukuda et at. (1) symptom criteria
for CFS. He reported the presence of fatigue and three minor symptoms.
However, when the participant rated the severity of his symptoms, the
nature of his condition became clear. He rated his one major symptom,
fatigue, and all three of his minor symptoms as being quite mild (5 points
on 100-point scale, with higher scores indicating more severity). Had data
only been collected on binary symptom occurrence and not symptom severity,
his symptom profile would have had many of the characteristics of a person
with CFS, or might have been considered suggestive of serious or chronic
illness.

In contrast, an unemployed, 56-year-old, Caucasian male reported that he
had been suffering from CFS for approximately the last 20 years. He
requires approximately 12 hours of rest per day, and limits his daily
activities to only two or three hours a day. The fatigue levels and other
symptoms in this individual were substantially higher than the control
participant. Had data only been collected on symptom occurrence, these
meaningful differences would have been obscured.


PROBLEMS WITH EXCLUSIONARY CONDITIONS
TO THE CURRENT U.S. CASE DEFINITION

While the over-inclusion of individuals with purely psychiatric
disorders in the CFS population may seriously complicate the
interpretation of epidemiological and treatment studies, the exclusion of
people with particular psychiatric diagnoses identified by the U.S. case
definition (1) is also problematic. This issue is particularly relevant in
cases of melancholic depression, eating disorders, and alcohol and
substance abuse.

Melancholic Depression

The U.S. case definition stipulates that all people with a diagnosis
of past or current melancholic depression are excluded from the
diagnosis of CFS (1). According to the DSM-IV (45), melancholic
depression can be characterized by the presence of either a loss of
pleasure in activities, or a lack of response to pleasurable stimuli
and the presence of at least three of the following symptoms:
inappropriate guilt; significant weight loss; marked psychomotor
agitation or retardation; early morning awakenings; increased feelings of
depression in the morning; and a distinct quality of depressed mood. Given
that a number of these criteria involve somatic symptoms similar to those
experienced by people with CFS, it is possible for a person with CFS to
fulfill criteria for melancholic depression solely by virtue of their CFS
symptomatology. Specifically, depressed mood, weight loss, psychomotor
retardation, and early morning awakening arc symptoms shared by patients
with CFS and melancholic depression. To obtain a diagnosis of melancholic
depression, a patient needs to have these symptoms for only two weeks.
During the course of becoming ill, it is not uncommon for people to have
several weeks or phases of being depressed and lacking pleasure in all
activities. Even if one rebounds from this state after a few weeks, past
history of melancholic depression would exclude a diagnosis of CFS. This
is problematic because such individuals might be excluded from the
diagnosis of CFS. The following case study illustrates this issue.

Case 7 is a 46-year-old Caucasian woman who is presently unemployed.
Overall, she reported a decrease in her ability to do things by about 90%.
She reported symptoms of post-exertional malaise, sore throat, lymph node
pain, headache, difficulty concentrating, non-restorative sleep, and joint
pain. She also reported that she has been suffering from depression since
she became ill. At the time of the evaluation she was taking Zoloft, which
significantly alleviated her depressed mood. She added that her sense of
tiredness is not alleviated by this medication and she feels that the
tiredness is a separate process from any psychological stress and feeling
of depression.

On paper, this participant met DSM-IV criteria for psychiatric
diagnosis of major depression with melancholic features. However, when
specific items of the psychiatric interview were examined, there was an
absence of symptoms of self-reproach (e.g., feelings of worthlessness,
inappropriate guilt and suicidal ideation). Rather, this participant
reported symptoms related to mood and somatic features (e.g., feelings of
depressed mood, fatigue, weight gain, and psychomotor retardation).
Because CFS is associated with many somatic symptoms and some mood-related
symptoms, it is possible that this participant received the diagnosis of
major depression with melancholic features due to symptoms related to CFS.
As a result, she may have been inappropriately excluded from the diagnosis
of CFS. In making diagnostic decisions, care needs to be exercised in
constructing appropriate diagnostic measures, as the type of test used, as
well as how the items are interpreted, have enormous consequences for the
extent of psychiatric comorbidity (49).


Eating Disorders

Another concern with the Fukuda et al. (1) criteria is the exclusion
of individuals with past or present anorexia nervosa and/or bulimia
nervosa. According to the DSM-IV (45), anorexia nervosa is
characterized by refusal to maintain a minimally normal body weight,
intense fear of gaining weight, and a significant disturbance in the
perception of body shape or size. Bulimia nervosa is characterized by the
presence of binge eating and inappropriate compensatory methods to prevent
weight gain (45). While the rationale to exclude individuals with active
eating disorders is understandable (i.e., fatigue is caused by extreme
restriction of nutritional intake or compensatory behavior), it is not
clear why individuals with past eating disorders that did not result in
permanent organic damage (e.g., heart condition) should he excluded,
particularly if the disorder was resolved several years prior to the onset
of chronic fatigue. This concern is illustrated by the following case
study.


Case 8 experienced an onset of anorexia nervosa 20 years ago. It
resolved 15 years ago. For the past eight years, this participant has been
disabled with chronic fatigue and five minor CFS symptoms. Although she
previously worked as a nurse, she is currently receiving disability for
CFS.


Even though this participant exhibits all the classic CFS symptoms,
because she had anorexia nervosa 20 years ago, she was excluded from a CFS
diagnosis under the Fukuda et al. criteria (1). In our work, we have also
noticed a tendency for physicians to exclude people diagnosed with binge
eating disorder. Binge eating disorder is not listed as an exclusionary
psychiatric diagnosis by Fukuda and associates (1), and therefore should
not be treated as such by health care professionals. Given that those
suffering from binge eating do not engage in any compensatory behavior
(e.g., fasting, use of laxatives, purging, or vigorous exercising) that
might cause fatigue, there is no explicit rationale for excluding people
with binge eating disorder from the diagnosis of CFS.


Alcohol and Substance Abuse

Another exclusionary condition is the requirement that all patients
with a history of alcohol or substance abuse within two years before
the onset of CFS, or anytime afterward, are excluded from the
diagnosis of CFS. According to the DSM-IV, substance abuse is
essentially characterized by "a maladaptive pattern of substance use
manifested by recurrent and significant adverse consequences related
to the repeated use of substances (45, p. 182)." For example, a person may
repeatedly fail to fulfill major role obligations, place themselves in
hazardous situations, incur multiple legal problems, or experience
recurrent social or interpersonal problems. A diagnosis of substance abuse
should not be given unless one or more of these four problems occur in a
12-month period. We have noted that physicians sometimes diagnose
individuals with substance abuse solely on the reported use of substances.
Many individuals regularly use alcohol or other substances, but the use
does not cause any of the problems noted above. Use of a standardized
psychiatric questionnaire is essential to reduce this diagnostic error.

Our second concern is the exclusion of all individuals with a history of
alcohol or substance abuse occurring anytime after the onset of CFS. We
have noticed that with some individuals, the use of alcohol or other
substances is secondary to the onset of fatigue as a form of
self-medication or coping to deal with the dysphoric emotions and physical
pain commonly associated with disabling medical illness. In such cases,
the alcohol or substance abuse are less likely to be etiological factors
contributing to or responsible for the chronic fatigue. Rather, the
alcohol or substance abuse may be a consequence of living with chronic
pain and, perhaps, the inability to obtain sufficient pain medications.


DISCUSSION

This paper contends that the reliability of current CFS criteria (1)
might be improved. To accomplish this important task, it is relevant
to examine the significant improvements that have been made in the
reliability of clinical diagnoses in the fields of psychology and
psychiatry over the past 50 years. In the 1950s, researchers in the
field of diagnostic reliability recognized that one of the key factors
contributing to the problem of low interrater reliability in psychiatric
diagnosis was the inability of two or more examiners to write down and
agree in advance what symptoms or other behaviors had to he present before
a specific diagnosis could be made (50). This is not unlike the current
state of affairs of the diagnostic criteria for CFS. Because a diagnosis
or classification can be no more accurate than the classifier's knowledge
and understanding of what he or she is classifying, it was determined that
the first step to improving diagnostic reliability was the development of
operationally explicit and objectively denotable criteria (50,51).

By the 1970s, researchers in the field of diagnostics also recognized that
the provision of operationally explicit, objectively denotable criteria
was not enough to ensure that clinicians will know how to elicit the
necessary information from a clinical interview to permit them to apply it
to the reliable criteria (52). These concerns led to the development of a
series of structured interview schedules (24,50). The benefit of
structured interview schedules is that they ensure that clinicians in the
same or different settings conduct clinical interviews using standardized
questions that maximize the accuracy of clinical diagnosis (52). Thus,
structured interview schedules serve to remove unreliability introduced by
differences in the way clinicians elicit clinical information. Together,
the provision of operationally explicit, objectively denotable criteria
and standardized interviews were found to significantly improve the
reliability of clinical diagnosis for a number of psychological and
psychiatric conditions (26). It is possible that similar strategies might
be used to enhance the reliability of CFS criteria.

Diagnostic and epidemiological research requires diagnostic categories
that are both reliable and valid (53). The criteria used in different case
definitions must be clearly operationalized. Field tests must be conducted
to determine the reliability and validity of these nosologies. In the
determination of psychiatric diagnosis, considerable improvements were
made to the DSM-IV (45) when committees were appointed to make
recommendations concerning different features of the overall diagnostic
system (26). These recommendations were implemented in nationwide field
trials to establish diagnostic reliability. This approach might be used to
bring greater precision to the case definition of CFS, which is based on a
single consensus panel of CFS researchers.

A recent study by Zheng and associates (54) illustrates some of the
benefits to the approach advocated above. In their community-based
study of the prevalence of neurasthenia among Chinese-Americans, they used
well-defined, operational ized diagnostic criteria and structured
interviews. They found neurasthenia to be more common than any other
discrete mental disorder as defined by the Diagnostic and Statistical
Manual of Menial Disorders, Third Edition, Revised (DSM III-R) (55),
occurring in 4.98% of their sample. Seventy-eight percent of these
individuals were distinctly separate from any other DSM-III R psychiatric
category when current symptom profiles were considered.

Another classic study identified ways to establish criteria for the
classification of Fibromyalgia (46). Wolfe and associates (46) studied 558
consecutive patients, 293 patients with Fibromyalgia and 265 control
patients. They found that the combination of widespread pain and mild or
greater tenderness in 11 or more of 18 tender point sites yielded a
sensitivity of 88.4% and a specificity of 8 1.1%. While sleep
disturbances, fatigue, and stiffness were central symptoms of
Fibromyalgia, with each present in more than 75% of patients, only 56% of
patients had all three symptoms. Moreover, the simultaneous presence of
these three symptoms was not required for a diagnosis of Fibromyalgia.
This study used standardized questionnaires to obtain historical
information, collecting data free from interviewer-introduced bias (the
examiners were not aware of the diagnosis or physical findings of the
examination).

The current CFS case definition was crafted for use as research
criteria, not as a clinical case definition (1). An attempt was made
to identify homogeneous groups of patients who would not have
alternative explanations for their fatigue. However, these criteria
are difficult to apply in clinical practice (30). Manu and Pollack
(56) found that a sizable number of patients (37.5%) clinically
diagnosed with CFS did not meet the research case definition of CFS
(1). Many practitioners may already be implicitly employing a broader
clinical case definition rather than the research case definition. Without
sacrificing reliability, it would be useful to develop a broader clinical
case definition that would enable more individuals to receive an accurate
diagnosis of CFS.

DSM-IV (45) has been criticized for diagnosing individuals as having
distinct diagnostic entities rather than locating individuals on a
continuity of functioning in various domains (26). Similar
controversies will occur in considering diagnostic criteria for CFS
(6). It is possible that the advantages of both systems could be used by
employing qualitative scales to tap distinct symptoms comprising
diagnostic entities. Other considerations that have been dealt with by
diagnosticians who developed the DSM-IV criteria (45) include the need to
incorporate culture and ethnicity into conceptualizations to insure that
labels are not inappropriately used to create illness (57). Such issues
might need to be addressed in developing criteria for CFS.

Any definition of CFS must include important sub-types of patient
groups. An examination of patient characteristics in several empirical
investigations of CFS conducted in England, the US, and Australia suggests
that two subsets of patients can be distinguished by symptom severity,
functional level and psychiatric status (28,58,59). Other investigators
have also argued for the presence of important subgroups of patients
including the presence versus absence of a pre-morbid psychiatric
condition and gradual versus sudden onset of the illness (60). Johnson and
colleagues (61) suggest that there might be two groups of CFS patients,
one with sudden onset, nonpsychiatric and serious cognitive impairments,
and the other with slow onset, psychiatric comorbidity, and mild cognitive
impairment. These groupings are very similar to what Hickie and colleagues
(58) suggested in their classification study.

These studies are of importance because they suggest two distinct
groups of patients with CFS. A diagnostic definition of CFS needs to
be able to capture both groups. If the criteria are biased toward one of
these groups, the samples will not adequately represent the patient
population. It is possible that a higher functioning group of CFS patients
have greater fluctuations in their daily energy levels. Rest might even be
somewhat restorative to these individuals, even though their overall
energy levels are considerably diminished from their pre-morbid levels.
Definitional criteria need to be written so that those with this level of
functioning are not excluded from a CFS diagnosis.

One consequence of such patient heterogeneity is that when patient
groups are combined, it is possible that distinctions between
individuals with different causes of their fatigue, or different
syndromes, are blurred. Conceivably, the lack of consistent laboratory
findings among CFS patients might be due to this effect. A recent study by
Russo and associates (62) found that changes in physical signs were a
significant predictor of recovery even after controlling for changes in
psychiatric diagnosis. For years, investigators have noted many biological
abnormalities among patients with CFS, including over-activated immune
systems (63), biochemical dysregulation in the 2-5A synthetase/RNase L
pathway (64), cardiac dysfunction (65), EEG abnormalities (66),
abnormalities in cerebral white matter (67), decreases in blood flow
throughout the brain (68), and autonomic nervous system dysfunction (69).
Lack of consistency in laboratory findings might be a function of
combining patients into a large heterogeneous group rather than analyzing
them within sub-groups. To complicate matters further, individuals with
CFS experience different phases of the illness. If researchers collapse
the responses of patients in different phases, the findings might he
obscured because patients arc experiencing fundamentally different
processes (70). Their experiences and responses, therefore, may need to be
understood separately rather than combined into an unwieldy and
heterogeneous category.

Many of the CFS minor symptoms are contained within DSM-IV (45)
categories. If a person with CFS specifies a large number of physical
problems caused by this illness, these physical problems might also make
the person eligible for a diagnosis of somatization disorder, depending
upon the accuracy of the diagnostician and/or the diagnostic instrument
used. The Diagnostic Interview Schedule (DIS) (71), a structured
psychiatric instrument designed for use in community surveys (72), has
frequently been used to assess psychiatric comorbidity in CFS samples.
However, this instrument was not designed for use with medically ill
populations. In addition, CFS research groups using the DIS have employed
different decision rules in scoring responses; these decision rules
determine whether research groups view symptoms as resulting from medical
illness or from psychiatric disorders.

Some CFS investigators use a semi-structured clinical interview, the
Structured Clinical Interview for the DSM-IV (SCID) (73) to assess
psychiatric disorders. In contrast to the rigid interview structure of the
DIS, the SCID uses open-ended questions and all potential sources of
information to encourage a thorough description of the problems by the
respondent. Moreover, use of the SCID is limited to highly trained mental
health clinicians. A recent study by Taylor and Jason (49) administered
the DIS and SCID to a sample of people with CFS and found that 50% of the
sample received at least one current Axis-I psychiatric diagnosis when the
DIS was used, whereas 22% received an Axis-I diagnosis when the SCID was
used. These findings suggest that some of the discrepant psychiatric rates
reported in studies might be attributable to the psychiatric instrument
used and to how it was scored. There is a critical need to determine which
instruments are most accurate in assessing symptoms and psychiatric
comorbidity in samples of CFS patients.

Investigators also need to recognize that samples of patients with CFS
might differ substantially due to their source of recruitment. There have
been few truly randomized studies of CFS in the general population, and it
is still unclear what the relative distribution of CFS is across important
socio-demographic groups (racial/ethnic, socioeconomic, and gender) (8).
Population-based community samples, which are unbiased by help-seeking
behaviors or by differential access to the health care system, might
obtain participants who differ from those in tertiary care settings (74).
Most studies describing patients with CFS have largely been recruited from
physician referrals or health maintenance organizations, and these samples
might not be characteristic of the overall population of people with CFS
(8). One community-based study on CFS provides data supportive of this
proposition. Laurie and colleagues (75) identified two new chronic fatigue
cases in their community-based study, and both recovered within a year
(only one had a psychiatric diagnosis), whereas the two more long-standing
cases both had psychiatric diagnoses, and neither recovered eighteen
months later.

Fibromyalgia Syndrome and Multiple Chemical Sensitivity (MCS)
represent additional illnesses of interest where issues of diagnostic
accuracy are concerned. A study by Buchwald and Garrity (76) found that a
majority of both CFS and Fibromyalgia cohorts suffered from MCS, and that
the overlap between individuals with CFS and Fibromyalgia was even higher.
Donnay and Ziem (77) report on the prevalence and overlap of CFS and
Fibromyalgia among 100 patients with MCS. Of the 100 patients with MCS,
88% met the criteria for CFS. The prevalence of CFS was slightly higher
among men (91% vs. 87%). Evaluating the presence of these three illnesses
seems essential, particularly as it is probable that those individuals
with CFS who are most ill have additional diagnoses of Fibromyalgia and/or
MCS.

As presented by Cantwell (53), diagnostic criteria should specify
which diagnostic instrument to use, what informants to use, and how to
rate for presence and severity of the criteria. Future definitions of CFS
should include specific guidelines pertaining to the importance of symptom
severity in the diagnostic procedure. Given the high variability in
symptom severity among persons with CFS, a standardized

procedure for determining whether or not a particular symptom is
severe enough to qualify as one of the four minor CFS symptoms should be
employed. Presently, there are no guidelines for physicians to follow when
determining whether a symptom is severe enough to qualify as meeting the
diagnostic criteria. If CFS is to be diagnosed reliably across health care
professionals, we recommend the establishment of discrete cutoff points.

Without such standardization, symptom variability will remain a
function of the assessment procedure and etiological factors. If
health care professionals are to improve their understanding of the
complexities of this disease and their ability to identify distinct
subtypes of CFS patients, the current U.S. case definition (1) may
need to be revised to clarify the significance of symptom severity in
diagnostic and assessment procedures (8,78).


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