A population-based study of the clinical course of chronic fatigue syndrome

Abstract:

BACKGROUND: Chronic fatigue syndrome (CFS) presents a challenge for patients, health care providers, and health insurance groups because of its incapacitating nature, unknown cause, and poorly understood prognosis. We conducted a longitudinal population-based study to characterize the clinical course of CFS.

METHODS: Sixty-five CFS subjects were identified from a random-digit-dialing survey of Wichita, Kansas residents and followed for up to 3 years. We evaluated changes in CFS classification (partial or total remission, alternative medical or psychiatric diagnoses), CFS case-defining criteria, wellness scores, hours of activities and sleep, and treatments used to reduce fatigue. Associations between risk factors and outcomes were determined by use of logistic regression and generalized estimating equations models.

RESULTS: Only 20%-33% of the subjects were classified as having CFS at follow-up, 56.9% ever experienced partial or total remission, 10% sustained total remission, and 23.1% received alternative diagnoses, of which 20% were sleep disorders. Higher fatigue severity scores and total number of symptoms were negatively associated with ever remitting. Duration of illness < or = 2 years was positively associated with sustained remission. Unrefreshing sleep persisted in at least 79% of the subjects across all periods but, as with most of the CFS symptoms, tended to be less frequent over time. The number of activities affected by fatigue decreased over time, while wellness scores increased. At any follow-up, more than 35% of subjects reporting reduced fatigue used complementary and alternative medicine therapies, and of those subjects, at least 50% thought these therapies were responsible for reducing their fatigue.

CONCLUSIONS: The clinical course of CFS was characterized by an intermittent pattern of relapse and remission. Remission rates documented by our population-based study were similar to those reported in clinical studies. Shorter illness duration was a significant predictor of sustained remission, and thus early detection of CFS is of utmost importance. The persistence of sleep complaints and identification of sleep disorders suggest that CFS subjects be evaluated for sleep disturbances, which could be treated.

Comment in: Chronic fatigue and chronic fatigue syndrome in the general population. [Health Qual Life Outcomes. 2003]

 

Source: Nisenbaum R, Jones JF, Unger ER, Reyes M, Reeves WC. A population-based study of the clinical course of chronic fatigue syndrome. Health Qual Life Outcomes. 2003 Oct 3;1:49. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC269990/ (Full article)

 

Functional status of persons with chronic fatigue syndrome in the Wichita, Kansas, population

Abstract:

BACKGROUND: Scant research has adequately addressed the impact of chronic fatigue syndrome on patients’ daily activities and quality of life. Enumerating specific problems related to quality of life in chronic fatigue syndrome patients can help us to better understand and manage this illness. This study addresses issues of functional status in persons with chronic fatigue syndrome and other fatiguing illnesses in a population based sample, which can be generalized to all persons with chronic fatigue.

METHODS: We conducted a random telephone survey in Wichita, Kansas to identify persons with chronic fatigue syndrome and other fatiguing illnesses. Respondents reporting severe fatigue of at least 1 month’s duration and randomly selected non-fatigued respondents were asked to participate in a detailed telephone interview. Participants were asked about symptoms, medical and psychiatric illnesses, and about physical, social, and recreational functioning. Those meeting the 1994 chronic fatigue syndrome case definition, as determined on the basis of their telephone responses, were invited for clinical evaluation to confirm a diagnosis of chronic fatigue syndrome. For this analysis, we evaluated unemployment due to fatigue, number of hours per week spent on work, chores, and other activities (currently and prior to the onset of fatigue), and energy level.

RESULTS: There was no difference between persons with chronic fatigue syndrome and persons with a chronic fatigue syndrome-like illness that could be explained by a medical or psychiatric condition for any of the outcomes we measured except for unemployment due to fatigue (15% vs. 40%, P <.01). Persons with chronic fatigue syndrome and other fatiguing illnesses had substantially less energy and spent less time on hobbies, schooling, or volunteer work than did non-fatigued controls (P <.01).

CONCLUSIONS: Persons with chronic fatigue syndrome are as impaired as persons whose fatigue could be explained by a medical or psychiatric condition, and they have less energy than non-fatigued controls.

Comment in: Chronic fatigue and chronic fatigue syndrome in the general population. [Health Qual Life Outcomes. 2003]

 

Source: Solomon L, Nisenbaum R, Reyes M, Papanicolaou DA, Reeves WC. Functional status of persons with chronic fatigue syndrome in the Wichita, Kansas, population. Health Qual Life Outcomes. 2003 Oct 3;1:48. http://www.ncbi.nlm.nih.gov/pubmed/14577835

 

Prevalence and incidence of chronic fatigue syndrome in Wichita, Kansas

Abstract:

BACKGROUND: Chronic fatigue syndrome (CFS) is a debilitating illness with no known cause or effective therapy. Population-based epidemiologic data on CFS prevalence and incidence are critical to put CFS in a realistic context for public health officials and others responsible for allocating resources and for practicing physicians when examining and caring for patients.

METHODS: We conducted a random digit-dialing survey and clinical examination to estimate the prevalence of CFS in the general population of Wichita, Kan, and a 1-year follow-up telephone interview and clinical examination to estimate the incidence of CFS. The survey included 33 997 households representing 90 316 residents. This report focuses on 7162 respondents aged 18 to 69 years. Fatigued (n = 3528) and randomly selected nonfatigued (n = 3634) respondents completed telephone questionnaires concerning fatigue, other symptoms, and medical history. The clinical examination included the Diagnostic Interview Schedule for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, laboratory testing, and a physical examination.

RESULTS: The overall weighted point prevalence of CFS, adjusted for nonresponse, was 235 per 100,000 persons (95% confidence interval, 142-327 per 100,000 persons). The prevalence of CFS was higher among women, 373 per 100,000 persons (95% confidence interval, 210-536 per 100,000 persons), than among men, 83 per 100,000 persons (95% confidence interval, 15-150 per 100,000 persons). Among subjects nonfatigued and fatigued for less than 6 months, the 1-year incidence of CFS was 180 per 100,000 persons (95% confidence interval, 0-466 per 100,000 persons).

CONCLUSIONS: Chronic fatigue syndrome constitutes a major public health problem. Longitudinal follow-up of this cohort will be used to further evaluate the natural history of this illness.

 

Source: Reyes M, Nisenbaum R, Hoaglin DC, Unger ER, Emmons C, Randall B, Stewart JA, Abbey S, Jones JF, Gantz N, Minden S, Reeves WC. Prevalence and incidence of chronic fatigue syndrome in Wichita, Kansas. Arch Intern Med. 2003 Jul 14;163(13):1530-6. http://www.ncbi.nlm.nih.gov/pubmed/12860574

 

Utility of the blood for gene expression profiling and biomarker discovery in chronic fatigue syndrome

Abstract:

Chronic fatigue syndrome (CFS) is a debilitating illness lacking consistent anatomic lesions and eluding conventional laboratory diagnosis. Demonstration of the utility of the blood for gene expression profiling and biomarker discovery would have implications into the pathophysiology of CFS. The objective of this study was to determine if gene expression profiles of peripheral blood mononuclear cells (PMBCs) could distinguish between subjects with CFS and healthy controls.

Total RNA from PBMCs of five CFS cases and seventeen controls was labeled and hybridized to 1764 genes on filter arrays. Gene intensity values were analyzed by various classification algorithms and nonparametric statistical methods. The classification algorithms grouped the majority of the CFS cases together, and distinguished them from the healthy controls.

Eight genes were differentially expressed in both an age-matched case-control analysis and when comparing all CFS cases to all controls. Several of the differentially expressed genes are associated with immunologic functions (e.g., CMRF35 antigen, IL-8, HD protein) and implicate immune dysfunction in the pathophysiology of CFS. These results successfully demonstrate the utility of the blood for gene expression profiling to distinguish subjects with CFS from healthy controls and for identifying genes that could serve as CFS biomarkers.

 

Source: Vernon SD, Unger ER, Dimulescu IM, Rajeevan M, Reeves WC. Utility of the blood for gene expression profiling and biomarker discovery in chronic fatigue syndrome. Dis Markers. 2002;18(4):193-9. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3851413/ (Full article)

 

Analysis of 16S rRNA gene sequences and circulating cell-free DNA from plasma of chronic fatigue syndrome and non-fatigued subjects

Abstract:

BACKGROUND: The association of an infectious agent with chronic fatigue syndrome (CFS) has been difficult and is further complicated by the lack of a known lesion or diseased tissue. Cell-free plasma DNA could serve as a sentinel of infection and disease occurring throughout the body. This type of systemic sample coupled with broad-range amplification of bacterial sequences was used to determine whether a bacterial pathogen was associated with CFS. Plasma DNA from 34 CFS and 55 non-fatigued subjects was assessed to determine plasma DNA concentration and the presence of bacterial 16S ribosomal DNA (rDNA) sequences.

RESULTS: DNA was isolated from 81 (91%) of 89 plasma samples. The 55 non-fatigued subjects had higher plasma DNA concentrations than those with CFS (average 151 versus 91 ng) and more CFS subjects (6/34, 18%) had no detectable plasma DNA than non-fatigued subjects (2/55, 4%), but these differences were not significant. Bacterial sequences were detected in 23 (26%) of 89. Only 4 (14%) CFS subjects had 16S rDNA sequences amplified from plasma compared with 17 (32%) of the non-fatigued (P = 0.03). All but 1 of the 23 16S rDNA amplicon-positive subjects had five or more unique sequences present.

CONCLUSIONS: CFS subjects had slightly lower concentrations or no detectable plasma DNA than non-fatigued subjects. There was a diverse array of 16S rDNA sequences in plasma DNA from both CFS and non-fatigued subjects. There were no unique, previously uncharacterized or predominant 16S rDNA sequences in either CFS or non-fatigued subjects.

 

Source: Vernon SD, Shukla SK, Conradt J, Unger ER, Reeves WC. Analysis of 16S rRNA gene sequences and circulating cell-free DNA from plasma of chronic fatigue syndrome and non-fatigued subjects. BMC Microbiol. 2002 Dec 23;2:39. Epub 2002 Dec 23. http://www.ncbi.nlm.nih.gov/pubmed/12498618

 

Longitudinal analysis of symptoms reported by patients with chronic fatigue syndrome

Abstract:

PURPOSE: To determine the effect of chronic fatigue syndrome (CFS) illness duration and onset type on the likelihood of reporting a symptom during successive follow-up periods.

METHODS: In 1997, a two-phase RDD survey in Wichita, Kansas, was conducted to estimate the prevalence of CFS. Phase I identified 56,154 respondents 18-69 years of age and screened for severe fatigue, extreme tiredness or exhaustion lasting for 1 month or longer. In phase II an equal number of fatigued (n = 7,176) and randomly selected non-fatigued subjects were asked about 8 CFS and 13 non-CFS symptoms, as well as the presence of specific medical and psychiatric conditions. Eligible respondents were clinically evaluated to establish CFS diagnosis. Phase II respondents were re-contacted at 12- (n = 4,331) and 24-months (n = 4,266) for additional follow-up and diagnosis. In this study we considered symptoms reported as being present most of the time during each successive observation period. Generalized estimating equations were used to model symptoms over time and to address study questions. Such a model accounts for correlations among repeated symptoms for each subject. We used an auto-regressive structure for the correlation matrix, assuming the correlations between each pair of repeated symptoms should decrease as the time between symptoms increased.

RESULTS: There were 74 CFS patients who had been ill for 1 to 20 years (median = 6.3 years). Among these, 46 reported gradual and 28 reported sudden onset. Symptoms fluctuated over the course of illness. However, only stomach pain (non-CFS symptom) was more likely to be reported as duration of illness increased (p < 0.05). There was no association between onset type and the likelihood of reporting a symptom during an interview, except that chills and severe headaches were more likely to be reported by sudden cases.

CONCLUSIONS: The likelihood of expressing CFS and non-CFS symptom “most of the time” is the same across years of illness. More analyses are warranted to consider expression of symptoms for >/=6 months and severe symptoms.

 

Source: Nisenbaum R, Jones A, Jones J, Reeves W. Longitudinal analysis of symptoms reported by patients with chronic fatigue syndrome. Ann Epidemiol. 2000 Oct 1;10(7):458. http://www.ncbi.nlm.nih.gov/pubmed/11018368

 

Human herpesviruses 6 and 7 in chronic fatigue syndrome: a case-control study

Abstract:

We conducted this study to determine whether infection with human herpesvirus (HHV) 6A, HHV-6B, or HHV-7 differed between patients with chronic fatigue syndrome and control subjects. We recruited 26 patients and 52 nonfatigued matched control subjects from Atlanta.

Serum samples were tested by enzyme immunoassay for seroreactivity to HHV-6, and all were seropositive. Lymphocyte specimens were cocultivated with cord blood lymphocytes and assayed for HHV-6 and HHV-7; neither virus was isolated. Finally, lymphocytes were tested by use of 3 polymerase chain reaction methods for HHV-6A, HHV-6B, and HHV-7 DNA. HHV-6A or HHV-6B DNA was detected in 17 (22.4%) of 76 samples, and there were no significant differences (by matched analyses) between patients (3 [11.5%] of 26) and control subjects (14 [28%] of 50).

HHV-7 DNA was detected in 14 subjects, and although control subjects (12 [24%]) were more likely than patients (2 [7.7%]) to be positive, the difference was not statistically significant. We found no evidence that active or latent infection with HHV-6A, HHV-6B, HHV-7, or any combination these 3 HHVs is associated with chronic fatigue syndrome.

 

Source: Reeves WC, Stamey FR, Black JB, Mawle AC, Stewart JA, Pellett PE. Human herpesviruses 6 and 7 in chronic fatigue syndrome: a case-control study. Clin Infect Dis. 2000 Jul;31(1):48-52. Epub 2000 Jul 24. http://www.ncbi.nlm.nih.gov/pubmed/10913395

 

The epidemiology of chronic fatigue in San Francisco

Abstract:

Despite considerable research on chronic fatigue syndrome (CFS) and conditions associated with unexplained chronic fatigue (CF), little is known about their prevalence and demographic distribution in the population. The present study describes the epidemiology and characteristics of self-reported CF and related conditions in a diverse urban community.

The study used a cross-sectional telephone screening survey of households in San Francisco, followed by interviews with fatigued and nonfatigued residents. Respondents who appeared to meet case definition criteria for CFS, based on self-reported fatigue characteristics, symptoms, and medical history, were classified as CFS-like cases. Subjects who reported idiopathic chronic fatigue (ICF) that did not meet CFS criteria were classified as ICF-like cases.

Screening interviews were completed for 8,004 households, providing fatigue and demographic information for 16,970 residents. Unexplained CF was extremely rare among household residents <18 years of age, but was reported by 2% of adult respondents. A total of 33 adults (0.2% of the study population) were classified as CFS-like cases and 259 (1.8%) as ICF-like cases. Neither condition clustered within households.

CFS- and ICF-like illnesses were most prevalent among women and persons with annual household incomes below $40,000, and least prevalent among Asians. The prevalence of CFS-like illness was elevated among African Americans, Native Americans, and persons engaged in clerical occupations. Although CFS-like cases were more severely ill than those with ICF-like illness, a similar symptom pattern was observed in both groups.

In conclusion, conditions associated with unexplained CF occur in all sociodemographic groups but appear to be most prevalent among women, persons with lower income, and some racial minorities.

 

Source: Steele L, Dobbins JG, Fukuda K, Reyes M, Randall B, Koppelman M, Reeves WC. The epidemiology of chronic fatigue in San Francisco. Am J Med. 1998 Sep 28;105(3A):83S-90S. http://www.ncbi.nlm.nih.gov/pubmed/9790487

 

Factor analysis of unexplained severe fatigue and interrelated symptoms: overlap with criteria for chronic fatigue syndrome

Abstract:

The objective of this study was to identify factors explaining the correlations among unexplained severe fatigue of different durations (1-5 months or > or =6 months) and symptoms reported as being significant health problems during a preceding 4-week period.

Between June and December of 1994, a cross-sectional, random digit dialing telephone survey was conducted among residents of San Francisco, California. All subjects who reported having severe fatigue lasting for > or =1 month and a random sample of nonfatigued subjects were asked to participate in a detailed telephone interview. Data from 1,510 individuals aged 18-60 years who did not have medical or psychiatric conditions that could explain their severe fatigue were analyzed.

Common factor analyses identified three correlated factors (defined as “fatigue-mood-cognition” symptoms, “flu-type” symptoms, and “visual impairment”) that explained the correlations among fatigue lasting for > or =6 months and 14 interrelated symptoms. No factor explained the correlations among fatigue lasting for 1-5 months and other symptoms.

The combination of fatigue of > or =6 months’ duration and selected symptoms overlaps with published criteria used to define cases of chronic fatigue syndrome (CFS). Although symptoms described in this study were reported as appearing within the preceding month, and CFS symptoms must have been present for the previous 6 months, these results provide empirical support for the interrelations among unexplained fatigue of > or =6 months’ duration and symptoms included in the CFS case definition.

 

Source: Nisenbaum R, Reyes M, Mawle AC, Reeves WC. Factor analysis of unexplained severe fatigue and interrelated symptoms: overlap with criteria for chronic fatigue syndrome. Am J Epidemiol. 1998 Jul 1;148(1):72-7. http://aje.oxfordjournals.org/content/148/1/72.long (Full article)

 

Surveillance for chronic fatigue syndrome–four U.S. cities, September 1989 through August 1993

Abstract:

PROBLEM/CONDITION: Although chronic fatigue syndrome (CFS) has been recognized as a cause of morbidity in the United States, the etiology of CFS is unknown. In addition, information is incomplete concerning the clinical spectrum and prevalence of CFS in the United States.

REPORTING PERIOD COVERED: This report summarizes CFS surveillance data collected in four U.S. cities from September 1989 through August 1993.

DESCRIPTION OF SYSTEM: A physician-based surveillance system for CFS was established in four U.S. metropolitan areas: Atlanta, Georgia; Wichita, Kansas; Grand Rapids, Michigan; and Reno, Nevada. The objectives of this surveillance system were to collect descriptive epidemiologic information from patients who had unexplained chronic fatigue, estimate the prevalence and incidence of CFS in defined populations, and describe the clinical course of CFS. Patients aged > or = 18 years who had had unexplained, debilitating fatigue or chronic unwellness for at least 6 months were referred by their physicians to a designated health professional(s) in their area. Those patients who participated in the surveillance system a) were interviewed by the health professional(s); b) completed a self-administered questionnaire that included their demographic information, medical history, and responses to the Beck Depression Inventory, the Diagnostic Interview Schedule, and the Sickness Impact Profile; c) submitted blood and urine samples for laboratory testing; and d) agreed to a review of their medical records. On the basis of this information, patients were assigned to one of four groups: those whose illnesses met the criteria of the 1988 CFS case definition (Group I); those whose fatigue or symptoms did not meet the criteria for CFS (Group II); those who had had an identifiable psychological disorder before onset of fatigue (Group III); and those who had evidence of other medical conditions that could have caused fatigue (Group IV). Patients assigned to Group III were further evaluated to determine the group to which they would have been assigned had psychological illness not been present, the epidemiologic characteristics of the illness and the frequency of symptoms among patients were evaluated, and the prevalence and incidence of CFS were estimated for each of the areas.

RESULTS: Of the 648 patients referred to the CFS surveillance system, 565 (87%) agreed to participate. Of these, 130 (23%) were assigned to Group I; 99 (18%), Group II; 235 (42%), Group III; and 101 (18%), Group IV. Of the 130 CFS patients, 125 (96%) were white and 111 (85%) were women. The mean age of CFS patients at the onset of illness was 30 years, and the mean duration of illness at the time of the interview was 6.7 years. Most (96%) CFS patients had completed high school, and 38% had graduated from college. The median annual household income/for CFS patients was $40,000. In the four cities, the age-, sex-, and race-adjusted prevalences of CFS for the 4-year surveillance period ranged from 4.0 to 8.7 per 100,000 population. The age-adjusted 4-year prevalences of CFS among white women ranged from 8.8 to 19.5 per 100,000 population.

INTERPRETATION: The results of this surveillance system were similar to those in previously published reports of CFS. Additional studies should be directed toward determining whether the data collected in this surveillance system were subject to selection bias (e.g., education and income levels might have influenced usage of the health-care system, and the populations of these four surveillance sites might not be representative of the U.S. population).

ACTIONS TAKEN: In February 1997, CDC began a large-scale, cross-sectional study at one surveillance site (Wichita) to describe more completely the magnitude and epidemiology of unexplained chronic fatigue and CFS.

 

Source: Reyes M, Gary HE Jr, Dobbins JG, Randall B, Steele L, Fukuda K, Holmes GP, Connell DG, Mawle AC, Schmid DS, Stewart JA, Schonberger LB, Gunn WJ,Reeves WC. Surveillance for chronic fatigue syndrome–four U.S. cities, September 1989 through August 1993. MMWR CDC Surveill Summ. 1997 Feb 21;46(2):1-13. http://www.cdc.gov/mmwr/preview/mmwrhtml/00046433.htm (Full article)