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Keywords:

  • chronic fatigue;
  • chronic fatigue syndrome;
  • demographic data

Abstract

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. METHODS
  5. RESULTS
  6. DISCUSSION
  7. ACKNOWLEDGMENTS
  8. REFERENCES

Abstract Background data were collected from patients presenting with fatigue at the clinic of infectious diseases at Huddinge University Hospital, Stockholm. The main purpose was to look for differences as to demographic and functional status for patients fulfilling criteria for chronic fatigue syndrome (CFS) and chronic fatigue (CF). A cross-sectional questionnaire survey was performed using a variety of instruments. A thorough medical investigation was performed. No difference was found as to social situation, occupation and illness attributions for patients in the two categories. Patients with CFS reported in general a higher degree of ‘sickness’ with more self-reported somatic symptoms, more self-reported functional impairment and more absence from work. A higher degree of psychiatric comorbidity was observed in CF than in CFS patients. A majority of CFS patients (80%) had an acute infectious onset compared to 43% in the CF group. Presently used criteria might, according to findings presented here, define two different patient categories in a population characterized by severe, prolonged fatigue. Because CFS patients (compared to patients with CF) have more somatic symptoms, more often report an infectious, sudden onset and have less psychiatric comorbidity, and CF patients seem to have more of an emotional, burn-out-like component one could speculate about the existence of different pathogenetic backgrounds behind the two diagnoses.


INTRODUCTION

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. METHODS
  5. RESULTS
  6. DISCUSSION
  7. ACKNOWLEDGMENTS
  8. REFERENCES

Chronic fatigue syndrome (CFS) is an illness characterized by unexplained severe, disabling fatigue persisting for more than 6 months. The fatigue is accompanied by various self-reported symptoms such as myalgia, migratory arthralgia, post-exertion malaise, painful lymph nodes, recurrent sore throat, headache, sleep disturbances and impairment of neurocognitive functions. An international research case definition according to the Center of Disease Control (CDC), Atlanta, USA was accepted in 19881 and modified in 1994.2 If less than four of the criteria are fulfillled (and other medical explanations excluded) the condition is named chronic fatigue (CF). The cause(s) and the pathogenesis of CFS are as yet unknown3,4 but the central nervous system appears to be affected. Recent findings point at disturbances of the hypothalamic–pituitary–adrenal axis.5 The role of stress is not yet elucidated but psychosocial factors have been shown to have an influence on the onset and the severity of symptoms.6,7 Social factors of possible influence such as social class and gender have been studied in population-based studies showing no difference as to class8–10 but with a predominance of women.11 In the present study we wanted mainly to investigate if, in a consecutive patient population at a specialist clinic, there are differences as to demographic structure and functional status of patients fulfilling CFS criteria and for those who do not.

METHODS

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. METHODS
  5. RESULTS
  6. DISCUSSION
  7. ACKNOWLEDGMENTS
  8. REFERENCES

Patients

Due to an increasing number of referrals of patients with fatigue as a major complaint to the clinic of infectious diseases at Huddinge University Hospital in Stockholm, a special policlinic was started in 1992.

A total of 640 patients was investigated at the outpatient clinic between September 1992 and April 1998.

Patients were referred mainly from the county of Stockholm. For the diagnosis of CFS the criteria of the CDC definition from 19942 was used. Patients were diagnosed with CFS if they had had a fatigue lasting more than 6 months and fulfilled four or more of the eight criteria (neurocognitive dysfuntion, recurrent sore throat, tender lymph nodes, mild muscle ache, arthralgia, headache, unrefreshing sleep and worsening of symptoms by physical activity). Patients before 1994 were reclassified according to the criteria from 1994.

Procedure

Postal questionnaires covering detailed past and current medical history, fatigue, self-reported complaints, daily functioning and social and cognitive aspects were sent to patients before their first visit to the CFS clinic. During the first visit at the clinic the patients answered questionnaires assessing psychological well-being and coping and had a complete physical examination. When indicated, additional tests or referrals were performed. The patients were classified according to the 1994 criteria and recommendations for clinical evaluation of patients with chronic unexplained fatigue were followed. Fibromyalgia (FM) was diagnosed according to international criteria.12 Thus, the following five classification groups could be identified and compared: (i) patients meeting the CFS criteria; (ii) patients with unexplained CF not fulfilling the CFS criteria; (iii) patients meeting the FM; (iv) patients meeting both the CFS and FM criteria; and (v) patients diagnosed with other causes of chronic fatigue. A database, using Microsoft access, was constructed to process the information received.

Questionnaires

Background data were collected with a self-constructed questionnaire consisting of questions on demographic facts, previous health status, medication, exercise, patient's own attribution etc.

NEPO

The NEPO is a self-constructed questionnaire aimed at measuring the amount of symptoms during the previous 14 days. Ninety-six different symptoms are listed and the response alternatives are ‘none’, ‘mild’ or ‘severe’. In the analysis ‘none’ and ‘mild’ were coded as 0 and ‘severe’ as 1. The scores range between 0 and 96. Subscales were derived on a commonsense basis and correlated highly with the other methods of measuring symptoms.

Comprehensive Psychopathological Rating Scale

Psychiatric symptoms were measured by a self-rating scale for affective syndromes based on the Comprehensive Psychopathological Rating Scale (CPRS-S-A). The validity and reliability of the CPRS-S-A have been well established.13 The test consists of 19 items covering depression, anxiety and obsessional symptoms. Higher scores indicate more symptoms. Maximum scores on each subscale are, respectively, 27, 27 and 24 points. The patients were asked to rate their own condition during the previous 3 days.

Sense of coherence

Sense of coherence (SOC) was measured by Antonovsky's self-rating scale.14 Twenty-nine questions cover three dimensions: (i) comprehensibility; (ii) manageability; and (iii) meaningfulness. The 29 items are graded on a 7-grade scale, which gives a range of 29–203 points. Scores between 140 and 160 indicate good sense of coherence and a good ability to cope. The mean score in five Swedish health survey studies (non-clinical groups) was 151.15

Fibromyalgia Impact Queationnaire

The Fibromyalgia Impact Questionnaire (FIQ) is a 21-item self-report questionnaire that measures health status mainly in those areas that are influenced by FM, and has shown high internal consistency and validity.16,17 The items are standardized on a scale ranging from 0 to 10 with 10 indicating greater impairment. The first 11 items correspond to physical function.

Wessley's Fatigue Questionnaire

The older version of Wessley's Fatigue Questionnaire (WESS) is a 14-item self-report scale that measures physical (8 items) and mental fatigue (6 items).18 The scale has been shown to be reliable and valid. Using the Likert scoring system, the scores range from 0 to 42 (physical, 0–24; mental, 0–18).

Statistical analyses

All of the subjects did not receive all questionnaires and all did not complete them. Thus the number of subjects analyzed differ between questions. However, because there were normal distributions of test scores on the different tests it was possible to use anova in the analysis.

First the comparability of the CF and CFS groups was established by analysing demographic and questionnaire variables by means of χ2 tests. Second, anovas were made for the comparison of the CFS and CF groups, showing the effects of excluding patients with psychiatric comorbidity. Finally, 2 × 2 (sex × duration) analyses of variance with age as a covariate (ancova) were performed comparing mean responses on the various tests, within the CFS and CF groups separately. Illness-duration subsets were divided into the groups of 0–5 years and >5 years. Because the distributions were slightly skewed, the subjects were classified into three groups, scoring low, medium or high on the different tests and then also analyzed by the non-parametric χ2 test.

All statistical analyses were made using spss 8.0.

RESULTS

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. METHODS
  5. RESULTS
  6. DISCUSSION
  7. ACKNOWLEDGMENTS
  8. REFERENCES

Descriptive data

A total of 640 consecutive patients, 442 women (69%) and 198 men (31%), mean age 41 years (range: 10–65 years), were classified and included in the present study. Two hundred and sixty-nine patients (42%) fulfilled the CFS criteria and 216 (34%) were diagnosed as having CF.

For the total group of attending patients the median duration of illness at diagnosis was 3.0 years (range: 0.5–50 years). At the onset of illness, 58% were married or cohabited. Thirty percent of the population in Stockholm is married.19 Eighty-one percent reported that they were working or studying and there were no differences in socioeconomic status compared to the population in Stockholm. The number of patients on any amount of sick leave at onset was 1% and at the time of their first visit to the clinic it was 23%. Twenty-eight percent reported exposure to stress at onset. Medical comorbidity was noted in 22% and psychiatric comorbidity in 13%. Past psychiatric history, defined as having been treated by a professional psychologist/psychiatrist, was reported in 12%. Fifty-four percent of all patients reported an acute onset of illness.

The different groups are presented in Table 1. This evaluation focuses on the comparison between CFS and CF patients as well as gender differences.

Table 1. . Classification of subjects
Diagnosisn%Women %Men %Psychiatric comorbidity%
  • Psychiatric comorbidity (patients classified as ‘suffering from stress’ were not regarded as having psychiatric comorbidity).

  • Determined by doctor.

  • 2 between CFS and CF, P < 0.01.

  • CFS, chronic fatigue syndrome; CF, chronic fatigue.

CFS269427030 7*
CF21634594116*
FMS 44 791 9 9
CFS/FMS 39 695 5 5
Others 7211693135

Sixty-nine percent of patients fulfilling criteria for CFS were women. For CF patients the female dominance was less marked. There were significantly more patients with psychiatric comorbidity in the CF group.

There were no differences in socioeconomic and marital status between the CFS and the CF -group (Table 2). The mean age at first visit was 39 years for women and 38 years for men in the CFS group and 41 and 40 years, respectively, in the CF group. The mean age at the time of diagnosis for CFS patients was 38 years.

Table 2. . Demographic data on patients with CFS and CF
VariableCFSCF
n (W/M)Women %Men %PTotal %n (W/M)Women %Men %PTotal %P††
  1. χ2 significance between the sexes in the CFS group; χ2 significance between the sexes in the CF group; ††χ2 significance between the totals of the CFS and CF group, corrected for gender; ‡‡χ2 significance between the men in the two groups; *P < 0.01.

  2. CFS, chronic fatigue syndrome; CF, chronic fatigue.

Age187/82    128/88     
 Mean 3938 39 4140 40 
 Range 10–6518–59 10–65 20–6817–64 17–64 
Marital status143/62    75/52     
 Single 3147 40 4335 39 
 Married/living together 6350 56 5154 52 
 Living apart  6 3  5  712  9 
Occupation at onset162/68    77/53     
 Blue collar 2431 28 1615 15 
 White collar 4944 47 5842 50 
 Student  815 11 1017 14 
 Unemployment  3  1  1 4  3 
 Sick leave  2  1   
Occupation at first visit159/66    79/56     
 Blue collar 1415 15  618 12 
 White collar 3441 38 4238 40 
 Student  7 9  8  8 9 8 
 Unemployment  812 10 17 4 10 
 Sick leave 2617 21 1814 16 
Has any time been on sick leave because of fatigue159/667668 7174/567246‡‡*59*

More men with CFS had been on sick leave than men with CF.

Infections

More CFS patients (46% compared to 34% of CF patients) attributed the cause to infection. More patients with CF believed stress was a starter (24% compared to 16%) and more CF patients believed several factors were involved. There were no gender differences in the answers to the question of attribution.

Significant differences between the groups were found mainly with regard to history of illness (Table 3).

Table 3. . Descriptive data on illness history in patients with CFS and CF
VariableCFSCF
n (W/M)Women %Men %PTotal %n (W/M)Women %Men %pTotal %P††
  1. χ2 significance between the sexes in the CFS group; χ2 significance between the sexes in the CF group; ††χ2 significance between the totals of the CFS and CF group, corrected for gender; *P < 0.05; ***P < 0.001.

  2. CF, chronic fatigue; CFS, chronic fatigue syndrome.

Acute infectious onset183/797585 80128/864540 43***
Sudden onset177/787674 75124/843837 37***
Patients’ attribution 47/17     35/18     
 Infection 4547 46 3433 34 
 Stress 1912 16 3111 24 
 Amalgam 11 6 8  6 6  5 
 Several 1112 11 1717 17 
 Others 1524 19 1133 20 
Duration of illness (years)181/80   120/83      
 0–5 8065*73 7368 70 
 >5 2035 27 2732 30 
  Median, years 2,03,2 2,5 3,03,0 3,0 
  Range 0–230–15 0–23 0–230–25 0–25 
No. doctors visited154/65     70/54     
 1–5 7155*63 7772 75 
 >5 2945 37 2328 25 
Allergy160/655642 49 79/554935 42 
Psychiatric treatment before onset159/6813 6 10 81/5519 9 14 
Psychiatric treatment after onset157/694029 34 80/564543 44*

A majority of patients in the CFS group (80%) had an acute infectious and sudden onset, which was not the case in the CF group (43%). No gender difference was found.

Patients who had an acute infectious onset did not differ in any respect from those with a gradual onset. Those who had been on sick leave for more than 10 years more often lived alone, had had more sick leave and had visited more doctors than other patients. Some patients reported that they exercised extensively before onset. These patients had a tendency to report more symptoms at onset but did not differ in any other way from the others.

Approximately half of the patients in both groups reported having an allergy. Fourteen percent of all patients had had psychiatric treatment before onset while after onset significantly more of the CF patients had had psychiatric treatment. No gender difference was found.

Family history

Reumatism was significantly more common in the families of the CFS patients. Apart from this there were no differences in occurrence of diseases (Table 3). Allergy was reported in approximately 50% of the families and migraine by 40%. Long-term fatigue was quite common: 15% in CFS families and 23% in CF families; and long-term pain was reported in 27% of the families of CFS patients compared to 22% of CF families. It was rare to have a partner with pain.

Gender differences

We found some significant gender differences within the CFS group: women had more children (data not shown), exercised less before onset and reported less contact with solvents at onset than men. Women more often worked with service and health care (P < 0.001; data not shown). Men had a longer history of illness compared to women when diagnosed (P < 0.05) and had visited more doctors. Eighty-nine percent of the men exercised before onset compared to 60% of men in the general population of Stockholm. A group of patients had exercised extensively (more than five times per week). The number of patients responding, however, was low (data not shown). Men with CF had not been on sick leave to the same extent as women with CF or as patients in the CFS group (men and women). In the CFS group women slept longer than men (P < 0.001), less significantly so in the CF group (P < 0.05). Also, women with CFS felt more depressed than men. This was also found in the CF group.

Psychiatric symptoms

A comparison was made between patients with and without psychiatric comorbidity within the classification groups (CFS and CF; Table 4). In the analysis of the whole group no difference was found as to degree of depression but when the group of patients with psychiatric comorbidity was excluded the CF patients differed from the CFS patients, the former group having a higer mean depression score.

Table 4. Comparison by one-way anova between CFS and CF patients with and without psychiatric comorbidity (as defined by the doctor) on various test results
QuestionnairePsychiatric comorbidity excludedPsychiatric comorbidity onlyTotal
nCFS M (SD)CF M (SD)PnCFS M (SD)CF M (SD)PnCFS M (SD)CF M (SD)P
  • *

    P < 0.05;

  • **

    P < 0.01;

  • ***

    P < 0.001.

  • CF, chronic fatigue; CFS, chronic fatigue syndrome; NEPO, questionnaire measuring amount of symptoms in previous 14 days; CPRS-S-A, Comprehensive Psychopathological Rating Scale (self-rating for affective symptoms); SOC, sense of coherence, FIQ, Fibromyalgia Impact Questionnaire.

NEPO216/105 17 (10,9) 13 (10,9)***17/31 15 (12,0)  19 (14,7) 237/141 17 (10,9) 14 (12,2)**
Wessley Fatigue Questionnaire98/65    8/17   109/86   
 Physical  18 (5,6) 16 (5,3)   20 (3,5)  19 (3,7)   18 (5,4) 16 (5,2) 
 Mental  12 (4,0) 10 (3,4)**  12 (2,6) 12 (1,9)   12 (3,8) 10 (3,3)**
CPRS-S-A95/64    7/18   105/86   
 Depression  6,9 (4,3)5,6 (3,8)*  5,6 (3,6)11,1 (4,5)** 6,8 (4,2) 6,8 (4,7) 
 Anxiety  7,7 (3,5) 6,3 (3,7)*  6,5 (3,5)  9,4 (4,2)   7,5 (3,5) 7,1 (4,0) 
 Obsession  5,9 (3,9) 4,7 (3,6)0.06 5,3 (3,1)  9,4 (4,4)*  5,9 (3,8) 5,7 (4,3) 
SOC95/65141 (25,2)142 (29,8)  8/18127 (42) 116 (30,5) 106/87139 (27,1)137 (31,6) 
FLQ97/67    8/18   108/88   
 Physical function  4,2 (2,6) 3,4 (2,6)0.06 4,1 (2,8)  3,6 (2,2)   4,2 (2,6)3,4 (2,5)*
 Total  5,6 (1,5) 4,5 (1,8)*** 5,6 (2,0)  5,7 (1,5)   5,5 (1,5)4,8 (1,8)***

The 2 × 2 (sex × duration) analyses of variance with age as a covariate (ancova) showed some main effects, especially for NEPO. Patients with a longer duration of the illness in both groups reported more symptoms (CFS: F1.226 = 6.50, P < 0.02; CF: F1.130 = 7.46, P < 0.01). Men in the CFS group reported less symptoms (F1.226 = 17.35, P < 0.001). No significant differences in the other tests were found and there were no significant interactions. When analysing the data by means of χ2 the same pattern could be seen.

Duration of illness had some effect on coping in the CFS group because those with a duration >5 years in the CFS group had lower scores on SOC (χ2 = 6.1, P < 0.05). In the CFS group 49% of the women and 44% of the men had scores on SOC < 140, indicating a low sense of coherence. Also, 28% and 15%, respectively, had scores >160, indicating an abnormally high sense of coherence. In the CF group 61% of the women and 47% of the men had scores <140 and 29% and 31%, respectively, had scores >160. Thirty-three percent of CFS patients having a duration of illness of <5 years had scores >160, indicating an abnormally high sense of coherence.

However, when the time factor was analyzed in relation to fatigue according to the WESS questionnaire, contradictory results were found. Chronic fatigue patients with longer duration had high scores on fatigue (χ2 = 6.6, P < 0.05), but in the CFS group the opposite was the case, thus patients with longer duration had lower scores on fatigue (χ2 = 10.5, P < 0.01).

DISCUSSION

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. METHODS
  5. RESULTS
  6. DISCUSSION
  7. ACKNOWLEDGMENTS
  8. REFERENCES

The studied population of patients attending a referral polyclinic at Huddinge University Hospital is a biased population and is not representative of CFS occurring in the population. However, when CFS patients are compared with patients not fulfilling the criteria some findings and data on the natural course of the illness differ between the groups. These findings and the gender differences have valuable potentials for understanding the pathogenesis of CFS: whether the cause is biological or a biological consequence of a social structure.

It is of interest to note that patients with CFS or CF did not differ from the population in Stockholm in socioeconomic status.

There were no significant differences between CFS and CF patients as to social situation, occupation and illness attributions. This was confirmed by measurement of the sense of coherence, which measures the comprehension of the situation, the capacity to handle it and the sense of meaningfulness. There was a dominance of white collar workers. Most patients believed an infection was the cause but stress was also mentioned as an important causative agent or component, reflecting an open attitude as to attribution.

A total of 80% of CFS patients reported an acute infectious onset compared to 43% of patients with CF (P < 0.001). This is concordance with earlier reports.20 However, it is to be stressed that these patients are referred to a clinic for infectious diseases and this population is not necessarily representative of cases in the population.

Mean age at first visit was 39 years and the mean time of duration of symptoms since onset was 2.5 years. The diagnosis of CFS was usually made at the special polyclinic: reflecting either a reluctance by other doctors to make the diagnosis or (more likely) that the diagnosis is not well known. This is also in concordance with earlier reports.20

What is clear in this population is that patients with CF had more psychiatric comorbidity. When the subgroup of patients with psychiatric comorbidity was analyzed, significantly more of the CF patients had high scores on the depression scale.

This could reflect the fact that CF patients were undiagnosed before referral to Huddinge University Hospital and had not received proper treatment in primary care.

According to FIQ health status scores, the CF patients have better health (P < 0.001) than CFS and other patients. In general, patients with CFS reported a higher degree of ‘illness’ with more self-reported symptoms and more self-reported functional impairment, which is in concordance with earlier reports.21 Patients with CFS reported a higher prevalence of sick leave (P < 0.01; after adjustment for gender). Men with CFS had been on sick leave more than men with CF.

Thus, it is a clear finding that patients with CFS (irrespective of gender) suffer from more symptoms, more functional disability and have more time away from work than patients with CF.

Some gender differences were found in that men with CFS had felt sick for a longer period and had visited more doctors than women, although they reported less of some symptoms such as fever, headache, difficulties awakening, and depression than the women in the CFS group. Also, men in the CF group reported less symptoms at onset than CF women. This is in accordance with earlier reports that found that women consulted their general practitioner with higher levels of fatigue.22,23 Men tended to report less symptoms overall in the normal population, for example sleep disturbances, fatigue and anxiety.24 Although men reported less symptoms and scored better on SOC than women (data not shown), they had been sick for a longer time and had seen more doctors. This could reflect a traditional gender-based behavior, with a tendency to denial and stoicism among men.

The genetic background can be mirrored in diseases found in several generations. A family history of rheumatism is more common with CFS patients than with CF patients. Otherwise allergy, diabetes, migrain and chronic pain are the most frequently mentioned diagnoses. Whether this influences the onset of the illness in any way cannot be concluded from the present study.

The symptoms at onset were mostly the same ones as those existing at the time of diagnosis on average 2.5 years later, usually at the special polyclinic. These symtoms are the criteria for diagnosis. Thus, if these symptoms exist at onset they are likely to continue. This contradicts a development of symptoms over time, with a CF condition changing into CFS.

However, if the duration exceeded 5 years, CFS patients reported a lower degree of fatigue. This could point at adjustment.

In conclusion, although similar as to the demographic background, in this population differences can be found between CFS and CF patients apart from the number of symptoms. A higher proportion of the CF patients have psychiatric comorbidity. As part of the definition they have less symptoms and are less fatigued but there is no development of symptoms with time. The patients with CFS reported that they had the same symptoms when they fell sick as they did when they were diagnosed, as did the patients with CF. It might be that the two groups, as defined by presently used criteria, represent two different patient categories with different etiological factors. Biological differences as to the cerebral uptake of acetylcarnitine with a reduced uptake in certain cerebral areas in CFS patients compared to healthy controls have been detected.25 It would be of interest also to study CF patients from this aspect.

One may speculate, from the findings reported here, that CF has more of an emotional, burn-out-like component and a better prognosis. It should be of importance to study the long-term prognosis for both groups.

ACKNOWLEDGMENTS

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. METHODS
  5. RESULTS
  6. DISCUSSION
  7. ACKNOWLEDGMENTS
  8. REFERENCES

The present study was financed by the National Board of Health and Welfare, the National Board of Insurance and the Stockholm County.

REFERENCES

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. METHODS
  5. RESULTS
  6. DISCUSSION
  7. ACKNOWLEDGMENTS
  8. REFERENCES
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