The chronic fatigue syndrome: a comprehensive approach to its definition and study. International Chronic Fatigue Syndrome Study Group

Abstract:

The complexities of the chronic fatigue syndrome and the methodologic problems associated with its study indicate the need for a comprehensive, systematic, and integrated approach to the evaluation, classification, and study of persons with this condition and other fatiguing illnesses. We propose a conceptual framework and a set of guidelines that provide such an approach. Our guidelines include recommendations for the clinical evaluation of fatigued persons, a revised case definition of the chronic fatigue syndrome, and a strategy for subgrouping fatigued persons in formal investigations.

Comment in:

The chronic fatigue syndrome. [Ann Intern Med. 1995]

The chronic fatigue syndrome. [Ann Intern Med. 1995]

The chronic fatigue syndrome. [Ann Intern Med. 1995]

The chronic fatigue syndrome. [Ann Intern Med. 1995]

 

Source: Fukuda K, Straus SE, Hickie I, Sharpe MC, Dobbins JG, Komaroff A. The chronic fatigue syndrome: a comprehensive approach to its definition and study. International Chronic Fatigue Syndrome Study Group. Ann Intern Med. 1994 Dec 15;121(12):953-9. http://www.ncbi.nlm.nih.gov/pubmed/7978722

 

Chronic fatigue syndrome and fibromyalgia

Comment on: Population study of tender point counts and pain as evidence of fibromyalgia. [BMJ. 1994]

 

EDITOR,-The relation between muscle pain, tender points, the chronic fatigue syndrome, and fibromyalgia are complex, and simplistic answers are inappropriate. In their paper Peter Croft and colleagues extrapolate their results to make two statements that I believe to be incorrect.’

My conclusions are based on 100 consecutive patients seen at Raigmore Hospital NHS Trust, who fulfilled precise definitions of the chronic fatigue syndrome 2 or fibromyalgia.3 The importance of this definition of the syndrome is that it has the same three month cut off for length of illness as fibromyalgia.3 Of the 100 patients, 99 (74 women, 25 men) had the chronic fatigue syndrome and one (a woman) had fibromyalgia. Of the patients with the chronic fatigue syndrome, 63 had muscle pain and 28 had tender points on examination, 23 had both, and five had no muscle pain but tender points. These results do not support the authors’ statement that the reason why fibromyalgia is not more common in Britain has been the acceptability of the chronic fatigue syndrome as an alternative diagnosis.

The authors also say that it is “inappropriate to define an entity as fibromyalgia.” As a clinical virologist, I strongly disagree with this as the distribution and number of tender points in fibromyalgia are different from those in the chronic fatigue syndrome, and the management of the two conditions is different.4 Patients with the syndrome should be advised not to increase their activities gradually until they feel 80% of normal,5 whereas patients with fibromyalgia may benefit from a regimen of increasing activity.4

You can read the rest of this comment here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2541601/pdf/bmj00468-0067b.pdf

 

Source: Ho-Yen DO. BMJ. Chronic fatigue syndrome and fibromyalgia. 1994 Dec 3;309(6967):1515. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2541601/

 

Immunological abnormalities in patients with chronic fatigue syndrome

Abstract:

Between January 1991 and January 1993, 265 patients who fulfilled the CDC criteria of the working case definition of Chronic Fatigue Syndrome (CFS) have been observed at our Institution and submitted for clinical and laboratory evaluation.

One hundred and sixty-three patients were females and 102 males, the median age was 35 years (range 4-55 years); all patients reported profound and prolonged fatigue, lasting for a median of 3 years (range 6 months-10 years), preceded or accompanied at appearance by fever in 185 cases, and neuropsychologic problems including inability to concentrate, difficulty in thinking, confusion, irritability, forgetfulness, and depression. The fatigue was so severe that it required 102 patients to stop their working activities for a period of time ranging from 3 months to 2 years (range 7 months).

In 40 consecutive patients a comprehensive immunologic testing by single and two-colour flow cytometry was performed and results compared with a group of 35 healthy, age- and sex-matched controls. Whilst no significant differences were found in the absolute numbers of circulating total T cells (CD3+) and of total helper/inducer (CD4+) or suppressor/cytotoxic (CD8+) T cells, an evident reduction in CD3-/CD16+ and CD57+/CD56+ NK lymphocytes along with an expansion of the CD8+/CD56+ and CD16-/CD56+ NK subsets, were found in the CFS group.

In addition, CD56+ NK cells from CFS subjects were found to express an increased amount of cell adhesion molecules (CD11b, CD11c, CD54) and activation antigens (CD38). Both the percentage and absolute numbers of CD4+ T cells bearing the CD45RA antigen appeared significantly reduced in CFS patients, and CD4+ T lymphocytes from CFS subjects displayed an increased expression of the intercellular adhesion molecule-1 (ICAM-1/CD54).

Finally, the total numbers of circulating (CD19+) B lymphocytes, were significantly higher in CFS cases than in controls, and in 11 out of 30 CFS patients the increase in circulating B cells was sustained by the expansion of the CD5+/CD19+ subset of B lymphocytes.

We conclude that CFS is a syndrome not previously described in Italy, with already known clinical characteristics and appears to be associated with several immunologic abnormalities, including those reported previously in cohort of patients from different countries. We also show for the first time that CD56- NK cell subsets from CFS patients display an abnormally increased expression of cell adhesion molecules and activation markers.

 

Source: Tirelli U, Marotta G, Improta S, Pinto A. Immunological abnormalities in patients with chronic fatigue syndrome. Scand J Immunol. 1994 Dec;40(6):601-8. http://www.ncbi.nlm.nih.gov/pubmed/7997849

 

Sympathetic overactivity in subjects complaining of unexplained fatigue

Abstract:

Theoretical and practical considerations suggest that in subjects complaining of fatigue, in the absence of evident organ dysfunction, an alteration in the autonomic nervous system might be present as a functional correlate.

Autoregressive spectral analysis of R-R interval variability from a surface ECG, was used in healthy control subjects (n = 24, age 45 +/- 4 years) and in subjects complaining of unexplained fatigue (n = 53, age 46 +/- 9 years) to obtain quantitative indices of the state of the sympathovagal balance, both at rest and during a mental stimulus (mental arithmetic), capable of enhancing sympathetic drive. Sympathetic and vagal modulations were inferred from the normalized powers of the low frequency and high frequency spectral components respectively.

We observed in patients, at rest, a prevailing low frequency component of R-R variability (patients low frequency = 73 +/- 11, control subjects 51 +/- 10 normalized units, P < 0.05). The responsiveness to mental arithmetic was reduced in patients as compared with controls. Systolic blood pressure variability did not differ. This suggested a selective imbalance in autonomic control of the sinoatrial node, characterized by sympathetic predominance as well as by vagal withdrawal, at rest.

The possibility of discriminating patients from control subjects on the basis of simple non-invasive functional markers might provide a better understanding of the mechanisms, clinical evolution and outcome of conditions such as the chronic fatigue syndrome, which lack ordinary evidence of disease, but comprise, as physiopathological correlate, a quantitative alteration of autonomic control.

 

Source: Pagani M, Lucini D, Mela GS, Langewitz W, Malliani A. Sympathetic overactivity in subjects complaining of unexplained fatigue. Clin Sci (Lond). 1994 Dec;87(6):655-61. http://www.ncbi.nlm.nih.gov/pubmed/7874856

 

Chronic fatigue syndrome: a review and practical guide

Abstract:

Diagnosis and management of chronic fatigue syndrome (CFS) is a difficult challenge for nurse practitioners. The syndrome is widespread, poorly-defined, and problematic. Despite extensive etiologic research, no cause has been identified. Each case should be carefully evaluated for possible organic, psychiatric, and other factors reported as potential causes. Clinical manifestations, possible causes, and options for management are reviewed.

 

Source: Fox DS. Chronic fatigue syndrome: a review and practical guide. J Am Acad Nurse Pract. 1994 Dec;6(12):565-70. http://www.ncbi.nlm.nih.gov/pubmed/7848743

 

Chronic fatigue syndrome–a controlled cross-sectional study

Abstract:

Twenty-one patients fulfilling the Center for Disease Control criteria for chronic fatigue syndrome (CFS) were examined in a controlled study. Viral antibodies and tests evaluating the immune system were investigated in the patients and in a control group of 21 sex- and age-matched individuals.

Production in vitro of the predominantly T-cell-derived cytokines interleukin-2 and interferon-gamma was significantly higher in patients with CFS compared the control group. Furthermore, the serum concentrations of IgA and IgE were significantly lower in patients with CFS; however, the values were within the normal reference range.

All other variables were similar in the two groups. This study does not suggest a clearly disordered immune system or a chronic viral infection as a major pathogenetic factor in CFS. Longitudinal studies of immunological and virological parameters in CFS are warranted as are studies on patients that are severely handicapped.

Comment in: [Chronic fatigue syndrome and angiotensin-converting enzyme]. [Ugeskr Laeger. 1995]

 

Source: Rasmussen AK, Nielsen H, Andersen V, Barington T, Bendtzen K, Hansen MB, Nielsen L, Pedersen BK, Wiik A. Chronic fatigue syndrome–a controlled cross-sectional study. Ugeskr Laeger. 1994 Nov 14;156(46):6836-40. [Article in Danish] http://www.ncbi.nlm.nih.gov/pubmed/7839498

 

Chronic fatigue syndrome–a defined unity?

Abstract:

Chronic fatigue syndrome (CFS) is characterized by a sudden onset of an influenza-like illness followed by marked chronic fatigue and abnormal exercise-induced exhaustion. The precise pathogenesis of this disorder is unknown, but viral infection triggering immune imbalance has been suggested. The literature on CFS is reviewed. We find no consistent support for chronic viral infection or immunological dysfunction. The data in the published studies are rather conflicting, and further research in order to identify parameters that differentiate CFS from other disorders is necessary.

Comment in:

[Chronic fatigue syndrome and angiotensin-converting enzyme]. [Ugeskr Laeger. 1995]

[Chronic fatigue syndrome–a psychosocial syndrome?]. [Ugeskr Laeger. 1995]

 

Source: Rasmussen AK, Andersen V, Nielsen H, Wiik A. Chronic fatigue syndrome–a defined unity?Ugeskr Laeger. 1994 Nov 14;156(46):6832-6. [Article in Danish] http://www.ncbi.nlm.nih.gov/pubmed/7839497

 

Chronic fatigue syndrome update. Findings now point to CNS involvement

Abstract:

Neither Epstein-Barr virus nor human herpesvirus 6 appears to play a causative role in chronic fatigue syndrome. The possibility that a novel human retrovirus may be present in patients with the syndrome needs further study. A number of abnormalities found in patients with chronic fatigue syndrome point to central nervous system (CNS) involvement. These include immunologic abnormalities, indications of pituitary and hypothalamic involvement, abnormal basal plasma levels of certain neurotransmitter metabolites, and cerebral perfusion abnormalities. The symptom pattern of chronic fatigue syndrome may eventually be explainable in terms of CNS dysfunction.

 

Source: Bell DS. Chronic fatigue syndrome update. Findings now point to CNS involvement. Postgrad Med. 1994 Nov 1;96(6):73-6, 79-81. http://www.ncbi.nlm.nih.gov/pubmed/7971614

 

Enteroviruses and the chronic fatigue syndrome

Abstract:

The possible role of enteroviral persistence in the etiology of the chronic fatigue syndrome (CFS) was investigated by serological testing, VP-1 antigen testing, and polymerase chain reaction (PCR) analysis of stool specimens as well as by viral cultures of stool–both direct and after acid treatment. No differences between 76 patients with disabling unexplained fatigue and 76 matched controls were found by serological or antigen testing.

Furthermore, no enteroviruses were isolated from any stool culture. Enterovirus was detected by PCR in one stool specimen from a patient with CFS but was not detectable in a second sample obtained from the same patient 3 months later. All stool specimens from controls were PCR-negative. These results argue against the hypothesis that enteroviruses persist in patients with CFS and that their persistence plays a role in the pathogenesis of this syndrome.

 

Source: Swanink CM, Melchers WJ, van der Meer JW, Vercoulen JH, Bleijenberg G, Fennis JF, Galama JM. Enteroviruses and the chronic fatigue syndrome. Clin Infect Dis. 1994 Nov;19(5):860-4. http://www.ncbi.nlm.nih.gov/pubmed/7893870

 

Psychobehavioral and immunological characteristics of adult people with chronic fatigue and patients with chronic fatigue syndrome

Abstract:

The psychobehavioral responses and cellular immune function were investigated in healthy people (control, N = 21), adult people with chronic fatigue (fatigue-non-CFS group, N = 24), and patients with chronic fatigue syndrome (CFS, N = 10).

Based on psychobehavioral responses, the fatigue-non-CFS group had low general activity levels (p < .05) and slightly depressive tendencies (p < .01) compared with the control. They had many life event stresses (p < .05) and sleep disturbances (p < .01), and they could not cope appropriately with stresses.

The fatigue-non-CFS group also showed significantly lower natural killer (NK) cell activity (p < .01) and decreased numbers of CD16+ and CD56+ cells (p < .05). Compared with the fatigue-non-CFS group, patients with CFS had higher degrees of physical fatigue (p < .01) and more life event stresses (p < .05).

They had lower general activity levels and social introversion. They were also in a depressive state. NK cell activity and the numbers of CD16+ and CD56+ cells were significantly reduced in patients with CFS (p < .01).

These findings suggest that adult people with chronic fatigue may be in an intermediate state between the healthy control and patients with CFS in terms of psychobehavioral responses and low NK cell activity. We observed three cases in such an intermediate state in whom CFS subsequently developed.

 

Source: Masuda A, Nozoe SI, Matsuyama T, Tanaka H. Psychobehavioral and immunological characteristics of adult people with chronic fatigue and patients with chronic fatigue syndrome. Psychosom Med. 1994 Nov-Dec;56(6):512-8. http://www.ncbi.nlm.nih.gov/pubmed/7871106