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From the Department of Psychology, DePaul University, Chicago, IL.
Address reprint requests to: Leonard Jason, PhD, Department of Psychology, DePaul University, 2219 N. Kenmore Ave., Chicago, IL 60614. Email: ljason{at}wppost.depaul.edu
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ABSTRACT |
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 TOP ABSTRACT INTRODUCTIONMETHODSRESULTSDISCUSSIONACKNOWLEDGMENTSREFERENCES |
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METHODS: A random sample of 18,675 residents in Chicago, Illinois, was first interviewed by telephone. A control group and a group of individuals with chronic fatigue accompanied by at least four minor symptoms associated with CFS received medical and psychiatric examinations.
RESULTS: Of the 32 individuals with CFS, 40.6% met criteria for MCS and 15.6% met criteria for FM. Individuals with MCS or more than one diagnosis reported more physical fatigue than those with no diagnosis. Individuals with more than one diagnosis also reported greater mental fatigue and were less likely to be working than those with no diagnosis. Individuals with CFS, MCS, FM, or more than one diagnosis reported greater disability than those with no diagnosis.
CONCLUSIONS: Rates of coexisting disorders were lower than those reported in prior studies. Discrepancies may be in part attributable to differences in sampling procedures. People with CFS, MCS, or FM endure significant disability in terms of physical, occupational, and social functioning, and those with more than one of these diagnoses also report greater severity of physical and mental fatigue. The findings illustrate differences among the illness groups in the range of functional impairment experienced.
Key Words: chronic fatigue syndrome • fibromyalgia • multiple chemical sensitivities.
Abbreviations: ANCOVA = analysis of covariance; ANOVA = analysis of variance; CF = chronic fatigue; CFS = chronic fatigue syndrome; DSM-IV = Diagnostic and Statistical Manual of Mental Disorders, fourth edition; FM = fibromyalgia; ICF = idiopathic chronic fatigue; MANCOVA = multivariate analysis of covariance; MCS = multiple chemical sensitivities; SCID = Structured Clinical Interview for DSM-IV.
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INTRODUCTION |
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TOPABSTRACTINTRODUCTIONMETHODSRESULTSDISCUSSIONACKNOWLEDGMENTSREFERENCES |
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Many of the symptoms associated with CFS are also characteristic of other poorly understood illness conditions, including FM and MCS. In the absence of definitive diagnostic markers or laboratory tests to distinguish these conditions, clinical diagnosis is largely based on self-reported symptoms and behavioral criteria. Several previous studies have suggested that CFS and FM have many similarities (6-8). It has been estimated that 20% to 70% of patients with FM meet the criteria for CFS and that about 35% to 75% of patients with CFS also have FM (9-11). The considerable overlap of symptoms experienced by people with CFS and people with FM has led some researchers to question whether diagnostic criteria for CFS and FM are able to adequately distinguish between the two disorders or whether they are the same illness (10). In a multigroup study (9), patients with CFS, FM, and MCS were compared on the basis of symptom criteria. In this study, 70% of patients with FM met criteria for CFS. No significant differences were found in the prevalence of symptoms between patients with CFS and those with FM, except for painful lymph nodes, which were significantly more frequent in the FM group (67%) than in the CFS group (27%). In a comparison of patients with FM and patients with CFS, Schaefer (12) found that women with CFS reported significantly more trouble staying asleep than women with FM. Another characteristic distinguishing CFS and FM was found in a comparison study conducted by Evengard et al. (13), who observed that the majority of patients with FM had elevated levels of substance P in the cerebrospinal fluid but that patients with CFS did not have elevated levels of this substance. In a subsequent comparative study of CF, CFS, and FM (14), patients diagnosed with both CFS and FM were substantially more disabled than patients with either condition alone.
The most recent case definition of MCS describes it as a chronic condition with reproducible symptoms involving multiple organ systems whose symptoms are produced by low levels of exposure to multiple, chemically unrelated substances and improve or resolve when the chemical agents are removed (15). Self-reported high levels of reactivity to chemical exposure have also been found in patients with CFS in comparison to healthy control subjects (16). In a sample of 33 Gulf War veterans with CFS, 42% had concurrent MCS, and 6% had concurrent FM (17). In addition, Buchwald and Garrity (9) found that 30% of participants with MCS met criteria for CFS. Donnay and Ziem (18) studied a sample of 100 patients with MCS and found that 88% met criteria for CFS and 49% met criteria for FM.
Most studies involving CFS, FM, and MCS samples have been collected from physician-identified or medical facility populations (1). The study reported here was a community-based study that involved first contacting a random sample of 18,675 respondents in Chicago, Illinois, by telephone. Those with CF accompanied by at least four other minor symptoms associated with CFS (2) and a control group were given medical and psychiatric examinations. A certain proportion of patients from this sample were then diagnosed with CFS (1), FM (19), and/or MCS (15). The intent of the study was to address important issues involving the interrelationships among CFS, FM, and MCS; measures of psychiatric comorbidity; and measures of functional status within a community-based sample of chronically fatigued individuals unbiased by help-seeking behavior.
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METHODS |
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TOPABSTRACTINTRODUCTIONMETHODSRESULTSDISCUSSIONACKNOWLEDGMENTSREFERENCES |
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Sample
Procedures developed by Kish (22) were used to select one adult from each household. Birth dates for each adult were gathered, and the person with the most recent birthday was selected to be interviewed. We screened a random sample of adults (aged 18 years or older) between September 1995 and May 1997. A stratified random sample of several neighborhoods in Chicago, which were located 10 to 15 minutes from the site of the medical examinations, was used (see Ref. 20 for more detail).
Procedures
During stage 1, we called 28,673 residential/working telephone numbers and were able to complete the interview for 18,675 households (65.1% completion rate). If interviewees reported during the stage 1 interview that they had been suffering from severe fatigue, extreme tiredness, or exhaustion that had been present for a period of 6 months or longer, they were asked additional questions to assess more specific dimensions of their fatigue, including a series of questions assessing a number of symptoms commonly experienced by people with CFS.
Individuals who indicated that they had been suffering from severe fatigue, extreme tiredness, or exhaustion that had been present for a period of 6 months or longer were defined as having CF. The stage 1 screen revealed that of the 18,675 interviewees, 780 (4.2%) had CF. Of these, 408 had CF and four or more minor symptoms, such as sore throat or muscle pain (2), and they were defined as having CFS-like symptoms.
Those in the CFS-like group (screened positives) and a control sample of individuals who did not have symptoms of CFS (screened negatives) were invited to participate in stages 2 and 3. Individuals agreeing to participate in stage 2 completed the psychiatric interview (SCID) by telephone, and in stage 3 they underwent a medical examination. Of the 408 individuals identified in stage 1 with CFS-like symptoms, 166 completed both stages 2 and 3. There were no significant differences in sociodemographic or fatigue scores between the 166 participants with CFS-like symptoms who completed stages 2 and 3 and the 242 participants with CFS-like symptoms who did not. The control group was composed of individuals selected randomly from the 18,260 persons called during stage 1 who did not have CFS-like symptoms. Among the 199 control subjects randomly selected for evaluation after stage 1, the physician review team reviewed data on 47 individuals after medical and psychiatric evaluation. There were no significant differences in sociodemographic or fatigue scores between the 47 control subjects who completed stages 2 and 3 and the 152 who did not (21).
Measures
Screening Questionnaire.
The stage 1 screening questionnaire assessed interviewees’ sociodemographic characteristics and preliminary classification into screened-positive (CFS-like symptoms) and screened-negative groups. This screening questionnaire has been found to have adequate reliability (23). Basic demographic data included age, ethnicity, socioeconomic status, marital status, and gender.
Fatigue.
The Fatigue Scale was originally used in a hospital-based case control study (24) and was further refined by Chalder et al. (25). Despite its brevity, the scale has been found to be reliable and valid, and it has good face validity and reasonable discriminant validity. The 11-item scale has responses rated on a four-option continuum; the total score ranges from 0 to 33 (with a higher score signifying greater fatigue).
Psychiatric Interview.
In stage 2, the SCID (26) was used to assess current and lifetime psychiatric diagnoses as defined on axis I of the DSM-IV (27). The SCID is a valid and reliable semistructured interview guide that approximates a traditional psychiatric interview (28). Trained advanced clinical psychology graduate students with master’s degrees administered the SCID.
Medical Questionnaire.
The Medical Questionnaire is a modified version of the Chronic Fatigue Questionnaire (29). Before the physician examination, the Medical Questionnaire was administered to all participants to assess current and past medical history. This comprehensive instrument assessed symptoms related to CFS as well as other medical and psychiatric symptoms to help rule out exclusionary conditions.
Medical Outcomes Study.
Patients also filled out the MOS 36-Item Short-Form Survey (30), a reliable and valid measure that discriminates between gradations of disability. This instrument encompasses multiple-item scales that assess physical functioning, role limitations, social functioning, bodily pain, general mental health, vitality, and general health perceptions. Nontransformed, scaled scores were computed (30) and are presented herein.
Physician Examination.
A physician conducted a detailed medical examination to rule out exclusionary medical conditions and to detect evidence of diffuse adenopathy, hepatosplenomegaly, synovitis, neuropathy, myopathy, cardiac or pulmonary dysfunction, or any other medical disorder. An 18-tender-point examination was used to test for FM (31). Laboratory tests administered to all participants included a chemistry screen (glucose, calcium, electrolytes, uric acid, liver function parameters, and renal function parameters), complete blood count with differential and platelet counts, T4 and thyroid-stimulating hormone, erythrocyte sedimentation rate, arthritic profile (which included rheumatoid factor and antinuclear antibody), hepatitis B surface antigen, creatine phosphokinase, a human immunodeficiency virus screen, and urinalysis.
Diagnosis.
A team of four physicians and a psychiatrist were responsible for making final diagnoses. Two physicians independently rated each file. If a disagreement occurred, a third physician rated the file.
Each of the 213 participants evaluated in stages 2 and 3 was diagnosed by the physician review team in one of four ways: 1) Individuals evaluated as meeting the current US definitions of CFS (2) were given a final diagnosis of CFS; 2) individuals not meeting full CFS criteria but having unexplained CF and no exclusionary medical conditions detected in evaluation were given a final diagnosis of ICF; 3) individuals with exclusionary medical or psychiatric conditions detected in evaluation were given a final diagnosis of CF-explained; and 4) remaining individuals evaluated as not having CF were given a final diagnosis of no fatigue. Individuals were diagnosed with concurrent FM if they met the current case definition (19). In addition, patients were diagnosed with MCS if they reported on the Medical Questionnaire that they had symptoms of feeling ill from a low level of exposure to two or more listed chemical agents that affected two or more organ systems. This is the most recent definition of MCS (15).
A prior study compared sociodemographic and psychiatric data from individuals diagnosed with CFS, ICF, or CF-explained and control subjects (21). Individuals in the CFS, ICF, CF-explained, and control groups did not differ significantly with respect to racial/ethnic identification, age, and marital status. With respect to gender, significantly higher numbers of women than men were observed in the CFS, ICF, and CF-explained groups than in the control group. In terms of work status, a significantly higher number of individuals in the control group reported working full time compared with individuals in CFS, ICF, and CF-explained groups, who were more likely to be unemployed, on disability, or working part time. With respect to education, individuals in ICF and CF-explained groups exhibited significantly lower levels of educational attainment than individuals in the control group.
Statistical Analyses
2 analyses were used to compare the four CF status groups (CFS, ICF, CF-explained, and no fatigue) with the coexisting diagnostic criteria for MCS, FM, MCS, FM, and no diagnosis. In the event of significant overall group differences, individual 2 analyses were then conducted to compare each of the CF status groups (CFS, ICF, CF-explained) and the no fatigue group. Next, 2 analyses were conducted between diagnostic groups (CFS only, MCS only, FM only, more than one diagnosis, and no diagnosis) and all dichotomous variables, including race, gender, work status, marriage status, whether a participant had children, and presence of psychiatric diagnoses. If significant overall group differences were found, then individual 2 analyses were used to assess associations between patient diagnostic groups (CFS only, MCS only, FM only, more than one diagnosis) and the no diagnosis group on the dichotomous variable. A series of one-way ANOVAs were performed for the continuous variables of age, socioeconomic status, psychiatric comorbidity, fatigue severity, and disability. When overall effects were detected, patient groups were compared with the no diagnosis group. To decrease the likelihood of a Type 1 error, Bonferroni adjustments were made.
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RESULTS |
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Fatigue Status
The 213 individuals evaluated by the physician review team were categorized according to their fatigue status. Thirty-two were diagnosed with CFS (as reported above), 45 with ICF, 89 with CF-explained, and 47 with no fatigue (control subjects). Table 1 presents the percentage of individuals with MCS, FM, MCS and FM, and no diagnosis within each of the four categories of fatigue status (CFS, ICF, CF-explained, and no fatigue). 2 analyses revealed a significant overall difference when examining coexisting diagnoses in the CFS, ICF, CF-explained, and no fatigue status groups (2 (9, N = 213) = 29.70, p < .01). Associations between each CF status group and the no fatigue group were then assessed, with individuals in the CFS status group differing significantly from those in the no fatigue group (2 (3, N = 79) = 17.99, p < .01), individuals in the ICF status group differing from those in the no fatigue group (2 (3, N = 92) = 17.69, p < .01), and individuals in the CF-explained group also differing from those in the no fatigue group (2 (3, N = 136) = 20.42, p < .01). Individuals in all three CF status groups (CFS, ICF, and CF-explained) had higher percentages of coexisting MCS and higher percentages of coexisting FM and were much less likely to have no other diagnosis than those in the no fatigue group.
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2 analyses of work status (working vs. not working) comparing individuals with CFS only, MCS only, FM only, more than one diagnosis, and no diagnosis revealed significant differences (2 (1, N = 124) = 8.67, p < .05). Individuals with more than one diagnosis were less likely to be working than those with no diagnosis (33.3% vs. 65.0%, respectively). The possible confounding effects of work status were controlled by using work status as a covariate in all analyses that followed.
Outcome Measures
An ANCOVA was conducted to compare individuals with CFS only, MCS only, FM only, more than one diagnosis, and no diagnosis while controlling for any potential confounding factors associated with work status. No significant differences were found with respect to the total fatigue severity score, which includes mental and physical subscales. Next, a MANCOVA was conducted to compare individuals across the same diagnostic categories in terms of both mental and physical fatigue severity scores while controlling for any potential confounding factors associated with work status. Significant differences were found overall (F(4,208) = 2.92, p < .05). Table 2 presents the means for the fatigue scale scores according to each diagnostic category. Post hoc testing revealed that individuals with MCS or more than one diagnosis demonstrated significantly higher levels of physical fatigue than individuals with no diagnosis, and individuals with more than one diagnosis also demonstrated significantly higher levels of mental fatigue than those with no diagnosis.
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With respect to the number of lifetime psychiatric diagnoses of each individual, an ANCOVA, controlling for the effects of work status, revealed significant differences across the diagnostic categories of CFS only, MCS only, FM only, more than one diagnosis, and no diagnosis (F(4,207) = 10.82, p< .05). Findings are presented in Table 3. Although post hoc testing revealed no significant differences between diagnostic groups, individuals with MCS (mean = 2.5) had a directionally greater number of psychiatric diagnoses than individuals with no medical diagnosis (mean = 1.8). A similar analysis assessing the number of current psychiatric diagnoses of each individual was also conducted, revealing no significant differences between the groups.
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2 analyses using the Mantel-Haenszel test were used to assess these differences while controlling for the effects of work status. Significant overall group differences were found with respect to whether individuals had irritable bowel syndrome at any point in their lives. People with CFS (23.0%), MCS (25.0%), and FM (37.5%) were significantly more likely than those with no diagnosis (5.2%) to have a lifetime history of irritable bowel syndrome. |
DISCUSSION |
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TOPABSTRACTINTRODUCTIONMETHODSRESULTSDISCUSSIONACKNOWLEDGMENTSREFERENCES |
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Prior studies of the prevalence of coexisting CFS and MCS estimate that 42% of people with CFS also have MCS (17) and that 13% to 88% of people with MCS also have CFS (9, 17, 18). The present study found that 40.6% of patients with CFS have coexisting MCS and that 14.4% of patients with MCS have CFS, which are within the range found in these prior studies. In the present study, the rate of CFS coexisting among patients with MCS is lower than the rate of 88% found by Donnay and Ziem (18); this difference may be attributed to the greater degree of disability associated with individuals who seek help from primary or tertiary health care settings or the fact that our sample included only individuals with CF and CFS-like symptoms. In each group of individuals reporting CF (CFS, ICF, and CF-explained), a coexisting diagnosis of MCS was found at a rate of 40.6% to 44.9% across all three groups.
Of the 32 individuals with CFS, only 13 (40.6%) had CFS without any other coexisting illness. Of the 22 individuals with FM, only 8 of these (36.4%) had FM without any other coexisting illness. Of the 90 individuals with MCS, 68 (75.6%) had MCS alone, indicating that MCS is more likely to exist without any other coexisting condition. The higher rate of MCS existing without any other diagnosis is contrary to the findings of Donnay and Ziem (18), who reported that a diagnosis of MCS alone seldom occurred (in only 10% of women and 9% of men). Specifically, Donnay and Ziem (18) found that 88% of the patients with MCS in their study also met criteria for CFS and 49% also met criteria for FM. Of the patients with MCS who also met criteria for FM, nearly 100% also met criteria for CFS.
Sociodemographic differences between diagnostic groups were found with respect to the work status of individuals. A lower percentage of individuals with more than one diagnosis were working as compared with those with no diagnosis. This finding suggests that having more than one diagnosis may be associated with more difficulties in maintaining employment. Factors that contribute to this difficulty include findings that individuals with more than one diagnosis reported significantly more severe physical and mental fatigue and were more disabled than those with no diagnosis.
When the fatigue scale (25) was analyzed across the five diagnostic categories with respect to its mental and physical fatigue subscales, significant differences were found, with individuals with MCS demonstrating significantly greater physical fatigue than individuals with no diagnosis. Individuals with more than one diagnosis demonstrated greater mental fatigue as well as greater physical fatigue than individuals in the no diagnosis group. Because no differences were found between individuals with CFS or FM and those in the no diagnosis group, this finding may indicate that fatigue is a greater component of MCS than of CFS or FM. However, mean scores for individuals with FM actually reflect greater physical and mental fatigue than those reported by individuals with MCS, and the lack of significance may be attributed to a lack of power resulting from the small size of the FM group. Additionally, mean physical and mental fatigue scores of individuals with CFS are very similar to those of individuals with MCS but may also have failed to reach significance because of the small sample size.
When scores on the Medical Outcomes Study SF-36 Health Survey were analyzed across the five diagnostic categories (CFS only, MCS only, FM only, more than one diagnosis, and no diagnosis), significant overall differences were found, indicating that CFS, MCS, FM, or more than one of these fatigue-related illnesses have disabling effects on individuals who suffer from them. This measure reflects the fact that the presence of one or more of these illnesses creates a significant impairment on both physical and psychosocial functioning. However, specific functional impairments differ across each of these illnesses and may reflect some unique characteristics of each illness. Specifically, individuals with CFS demonstrated physical role impairment, more bodily pain, lower vitality, and impaired social functioning compared with those with no diagnosis. Similar to individuals with CFS, individuals with FM also demonstrated more bodily pain and impaired social functioning than those with no diagnosis. However, individuals with FM seemed to demonstrate a wider range of physical impairment than individuals with CFS, as reflected by significantly higher levels of impairment in physical functioning and physical role impairment as compared with control subjects. Individuals with FM did not demonstrate functional impairment related to lower vitality (energy and fatigue) as compared with the no diagnosis group, whereas all of the other diagnostic groups did. Individuals with MCS differ from those with no diagnosis on seven of the Medical Outcomes Study scales (all except role-emotional) and thus demonstrated the widest range of functional impairment. Together these findings illustrate important differences between the diagnostic subgroups with respect to the types and range of functional impairment experienced.
When psychiatric comorbidity was measured across the five diagnostic categories (CFS only, MCS only, FM only, more than one diagnosis, and no diagnosis), significant overall differences were found with respect to the number of lifetime axis I psychiatric diagnoses of each individual. Analyses of the mean number of psychiatric diagnoses revealed that individuals with either MCS and/or more than one diagnosis were directionally more likely to receive current and lifetime psychiatric diagnoses than individuals with CFS, FM, or no diagnosis (see Table 2). However, because post hoc findings on psychiatric comorbidity were not significant, all of these potential explanations must be interpreted with caution. Notable was the high rate of psychiatric disorders in the entire sample, even among those with no diagnosis of CFS, FM, or MCS. This finding may be attributable to a variety of factors, including 1) an increased likelihood of the occurrence of psychiatric disorder in individuals with CF (34) and with CFS-like illness (R. R. Taylor et al., manuscript submitted); 2) the larger quantity and scope of axis I psychiatric disorders assessed by the SCID in the present study (eg, instruments used in other studies, such as the Diagnostic Interview Schedule (35) and the General Health Questionnaire (36), do not measure adjustment disorders, dissociative disorders, disorders due to a general medical condition, and disorders not otherwise specified); and 3) contextual risk factors associated with urban living, such as increased psychosocial stress and specific neighborhood risk factors (37, 38).
The analyses of specific psychiatric and medical diagnoses can be compared with those of a study conducted by Hudson et al. (10) that looked at a similar group of specific diagnoses in a group of tertiary care patients with FM. The Hudson et al. (10) study, which sampled individuals with FM only without making comparisons to a control group, found that people with FM had high rates of irritable bowel syndrome, major depression, and panic disorder. The FM group in the present study was found to have higher rates of irritable bowel syndrome than the no diagnosis group (37.5% vs. 5.2%, respectively). However, individuals with FM were not found to have significantly higher rates of major depression or panic disorder as compared with those in the no diagnosis group. These differences may be due to the fact that the sample selected in the study conducted by Hudson et al. (10) was selected from a tertiary care center, whereas the sample in the present study was from a random sample of chronically fatigued individuals with CFS-like symptoms.
The focus of the present investigation was only on individuals whose responses to queries suggested that they might meet the criteria for CFS. Thus, large numbers of individuals having FM or MCS were not included in the final sample. Thus, this study pertains to comorbid conditions seen in a community-sample of subjects with CFS-like symptoms. Because of the skewed sample, bidirectional inferences need to be interpreted with caution. This may account for the disparate findings between this study and others.
The present study did find overall differences between our samples of individuals with CFS, MCS, FM, or more than one of these diagnoses with respect to work status, number of lifetime psychiatric diagnoses, severity of fatigue, and disability. Specifically, individuals with MCS reported greater physical fatigue than those with no diagnosis. Individuals with more than one diagnosis also reported greater physical fatigue and mental fatigue than those with no diagnosis. Individuals with CFS only, MCS only, FM only, and more than one diagnosis demonstrated greater disability compared with those with no diagnosis on various Medical Outcomes Study subscales, individuals with FM demonstrated more physical impairment, and individuals with MCS demonstrated more functional impairment than all other illness groups in comparison to control subjects.
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ACKNOWLEDGMENTS |
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TOPABSTRACTINTRODUCTIONMETHODSRESULTSDISCUSSIONACKNOWLEDGMENTSREFERENCES |
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Received for publication October 25, 1999.
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TOPABSTRACTINTRODUCTIONMETHODSRESULTSDISCUSSIONACKNOWLEDGMENTSREFERENCES |
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