Chronic fatigue syndrome: identification of distinct subgroups on the basis of allergy and psychologic variables

Abstract:

BACKGROUND: We investigated a role for allergic inflammation and psychologic parameters in the development of chronic fatigue syndrome (CFS).

METHODS: The design was a comparison between subjects with CFS and age- and sex-matched control cohorts. Studies were performed on CFS subjects (n = 18) and control cohorts consisting of normal subjects (n = 11), allergic subjects (n = 14), and individuals with primary depression (n = 12). We quantified cytokines at baseline as cell-associated immunoreactive peptides and as transcripts evaluated by means of semiquantitative RNA-based polymerase chain reactions. Psychologic evaluations included administration of the Diagnostic Interview Schedule, the Structured Clinical Interview, and the Symptom Checklist 90-Revised.

RESULTS: Increases in tumor necrosis factor (TNF)-alpha were identified in individual subjects with CFS (50.1 +/- 14.4 pg TNF-alpha per 10(7) peripheral blood mononuclear cells [PBMCs]; mean +/- SEM) and allergic subjects (41.6 +/- 7.6) in comparison with normal subjects (13.1 +/- 8.8) (P < .01 and P < .05, respectively). Similar trends were observed for interferon (IFN)-alpha in allergic subjects (3.0 +/- 1.7 pg/10(7) PBMCs) and subjects with CFS (6.4 +/- 3.4) compared with normal subjects (1.9 +/- 1.4). A significant increase (P < .05) in TNF-alpha transcripts was demonstrated between subjects with CFS and depressed subjects. In contrast to these proinflammatory cytokines, both subjects with CFS (2.6 +/- 1.8 pg/10(7) PBMCs) and allergic subjects (3.4 +/- 2.8) were associated with a statistically significant (P < .01) decrease in IL-10 concentrations compared with normal subjects (60.2 +/- 18.2). As shown in other studies, most of our subjects with CFS were allergic (15 of 18) and therefore presumably demonstrated cytokine gene activation on that basis. The seasonal exacerbation of allergy was associated with a further increase in cellular IFN-alpha (from 2.1 +/- 1.2 to 14.2 +/- 4.5 pg/107 PBMCs; P < .05) but no further modulation of TNF-alpha or IL-10. Similarly, self-reported exacerbations of CFS were associated with a further increase in IFN-alpha (from 2.5 +/- 1.0 to 21.9 +/- 7.8; P < .05) and occurred at times of seasonal exposures to allergens. This linkage does not permit making any definitive conclusions regarding a causative influence of either seasonal allergies or the increase in cellular IFN-alpha with the increase in CFS symptoms. The close association between atopy and CFS led us to speculate that CFS may arise from an abnormal psychologic response to the disordered expression of these proinflammatory and antiinflammatory cytokines. Psychologic variables were predictive of immune status within the CFS sample (65.9% of the variance in immune status; F (3,10) = 6.44, P < .05). Specifically, the absence of a personality disorder but greater endorsement of global psychiatric symptoms was predictive of immune activation.

CONCLUSIONS: Most of our subjects with CFS were allergic, and the CFS and allergy cohorts were similar in terms of their immune status. However, the CFS subjects could be discriminated by the distinct psychologic profiles among subjects with and without immune activation. We propose that in at least a large subgroup of subjects with CFS who had allergies, the concomitant influences of immune activation brought on by allergic inflammation in an individual with the appropriate psychologic profile may interact to produce the symptoms of CFS. In a psychologically predisposed individual, symptoms associated with allergic inflammation are recognized as illness.

 

Source: Borish L, Schmaling K, DiClementi JD, Streib J, Negri J, Jones JF. Chronic fatigue syndrome: identification of distinct subgroups on the basis of allergy and psychologic variables. J Allergy Clin Immunol. 1998 Aug;102(2):222-30. http://www.ncbi.nlm.nih.gov/pubmed/9723665

 

Treating chronic fatigue with exercise. Exercise, and rest, should be tailored to individual needs

Comment on: Putting the rest cure to rest–again. BMJ. 1998

 

 

Editor – While I welcome Sharpe and Wessely’s reminder about the dangers of bed rest,1 I am concerned about the blanket advice regarding activity levels for patients with chronic fatigue. Chronic fatigue syndrome is now generally acknowledged to be a heterogeneous condition, not a single entity with a single cause. Accordingly, what may suit one person may be totally inappropriate for another. As research has shown, most patients with chronic fatigue syndrome remain ambulant, spend relatively few daytime hours resting, are no more inactive than people with mild multiple sclerosis, and tend to perform at or near their activity ceiling.2 What these patients need is not a strict programme in which rest is allowed according to a predetermined plan but a flexible approach that does not ignore current energy levels or make people feel guilty if they increase rest periods when they consider this to be right for them.

From a theoretical perspective, inactivity may well be an important factor in chronic fatigue syndrome, but I note that Sharpe and Wessely did not provide a single reference to back their claim that many patients simply “go home and rest,” let alone that most resort to “excessive rest.” Does this mean that the theory that “excessive inactivity” perpetuates chronic fatigue syndrome is based largely on anecdotal reports and articles in magazines? Moreover, in this age of evidence based medicine, discussions of a treatment should mention the negative reports of its efficacy as well as the positive.3,4

You can read the rest of this comment here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1113801/

 

Source: Goudsmit E. Treating chronic fatigue with exercise. Exercise, and rest, should be tailored to individual needs. BMJ. 1998 Aug 29;317(7158):599; author reply 600. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1113801/

 

Sleep abnormalities demonstrated by home polysomnography in teenagers with chronic fatigue syndrome

Abstract:

To provide objective information about sleep physiology in young people with chronic fatigue syndrome (CFS), home polysomnography (PSG) was performed on 18 teenagers, aged 11-17 years, in whom CFS had been diagnosed according to internationally accepted criteria. The results were compared with those for healthy controls matched individually for gender and age.

Compared with controls, CFS subjects showed significantly higher levels of sleep disruption by both brief and longer awakenings. Disruption of sleep in this way could at least contribute to the daytime symptoms of young people with CFS. The underlying cause of the disruption needs to be considered in each individual case.

Further research is required to clarify the relative contribution of this neurobiological aspect of CFS in young people.

 

Source: Stores G, Fry A, Crawford C. Sleep abnormalities demonstrated by home polysomnography in teenagers with chronic fatigue syndrome. J Psychosom Res. 1998 Jul;45(1):85-91. http://www.ncbi.nlm.nih.gov/pubmed/9720858

 

Illness beliefs and treatment outcome in chronic fatigue syndrome

Abstract:

Longitudinal studies have shown that physical illness attributions are associated with poor prognosis in chronic fatigue syndrome (CFS). Speculation exists over whether such attributions influence treatment outcome. This study reports the effect of illness beliefs on outcome in a randomized controlled trial of cognitive-behavior therapy versus relaxation.

Causal attributions and beliefs about exercise, activity, and rest were recorded before and after treatment in 60 CFS patients recruited to the trial. Physical illness attributions were widespread, did not change with treatment, and were not associated with poor outcome in either the cognitive-behavior therapy group or the control group.

Beliefs about avoidance of exercise and activity changed in the cognitive behavior therapy group, but not in the control group. This change was associated with improved outcome. These findings suggest that physical illness attributions are less important in determining outcome (at least in treatment studies) than has been previously thought. In this study, good outcome is associated with change in avoidance behavior, and related beliefs, rather than causal attributions.

 

Source: Deale A, Chalder T, Wessely S. Illness beliefs and treatment outcome in chronic fatigue syndrome. J Psychosom Res. 1998 Jul;45(1):77-83. http://www.ncbi.nlm.nih.gov/pubmed/9720857

 

Longitudinal changes associated with improvement in chronic fatigue patients

Abstract:

Tertiary care patients with chronic fatigue were followed for 2.5 years to determine if changes in physical and psychological status were associated with improvements in chronic fatigue, physical functioning, and return to work.

Results indicated that improvement in psychological symptoms, DSM-III-R disorders, physical examination signs, and changes in whether the patient continued to meet criteria for chronic fatigue syndrome (CFS) were associated with recovery from fatigue, improved functioning, and return to work.

Patients who never met CFS criteria or only met criteria at the initial assessment, reported improved physical functioning.

Patients whose psychiatric disorders and physical examination signs were still present at a mean follow-up time of 2.5 years were more likely to have persistent fatigue and work disability.

Loss of physical examination signs was a significant independent predictor of improved functioning and return to work. These results suggest that psychiatric status, as well as physical status, are associated with recovery from chronic fatigue.

 

Source: Russo J, Katon W, Clark M, Kith P, Sintay M, Buchwald D. Longitudinal changes associated with improvement in chronic fatigue patients. J Psychosom Res. 1998 Jul;45(1):67-76. http://www.ncbi.nlm.nih.gov/pubmed/9720856

 

Coping and adaptive outcome in chronic fatigue syndrome: importance of illness cognitions

Abstract:

In this study, the relations between illness representations, coping behavior, and adaptive outcomes in chronic fatigue syndrome (CFS) patients (N=98) were examined. Following Leventhal’s self-regulation model, it was hypothesized that illness representations would be directly related to coping and, via coping, to adaptive outcome.

The results showed patients who considered their illness to be a serious condition, who believed that they had no control over their illness, who saw little possibility for cure, and who believed their illness to have serious consequences to cope with their illness in a passive way, report higher levels of impairment in physical and social functioning and report greater problems in mental health and vitality.

A series of regression analyses showed illness representations to be stronger predictors of adaptive outcome than coping scores. The implications of these findings for the treatment of CFS patients are discussed.

 

Source: Heijmans MJ. Coping and adaptive outcome in chronic fatigue syndrome: importance of illness cognitions. J Psychosom Res. 1998 Jul;45(1):39-51. http://www.ncbi.nlm.nih.gov/pubmed/9720854

 

Three cases of dermatomyositis erroneously diagnosed as “chronic fatigue syndrome”

Abstract:

The authors report three cases of dermatomyositis, which ha been erroneously diagnosed as “chronic fatigue syndrome” due to the presence of elevated titers of serum anti-Epstein Barr antibodies.

 

Source: Fiore G, Giacovazzo F, Giacovazzo M. Three cases of dermatomyositis erroneously diagnosed as “chronic fatigue syndrome”. Eur Rev Med Pharmacol Sci. 1997 Nov-Dec;1(6):193-5. http://www.ncbi.nlm.nih.gov/pubmed/9718854

 

The low dose ACTH test in chronic fatigue syndrome and in health

Abstract:

OBJECTIVE: A number of dynamic tests of the hypothalamic-pituitary-adrenal axis provide evidence for a mild central adrenal insufficiency inchronic fatigue syndrome (CFS). The 1 microgram adrenocorticotropin (ACTH) test has been proposed to be more sensitive than the standard 250 micrograms ACTH test in the detection of subtle pituitary-adrenal hypofunctioning. We aimed to establish whether the 1 microgram ACTH test would support such a dysregulation in CFS, and also, given the relative novelty of this test in clinical practice and the uncertainty with regard to appropriate cut-off values for normality, to compare our healthy volunteer data with those of previous studies.

PATIENTS AND DESIGN: Twenty subjects with CFS, diagnosed according to Centres for Disease Control and Prevention criteria, were compared with 20 healthy volunteer subjects. All participants underwent a 1 microgram ACTH test beginning at 1400 h. Plasma samples for cortisol estimation were drawn at 0, +30 and +40 min.

RESULTS: Baseline cortisol values did not differ between CFS patients and healthy subjects. The delta cortisol (maximum increment from baseline) value was significantly lower in the CFS than the volunteer group (P < 0.05). Comparison of the +30 min cortisol values revealed no significant differences. Using an incremental cortisol of > 250 nmol/l as an arbitrary cutoff point, two (10%) of the healthy subjects and nine (45%) of the CFS subjects failed the test on this basis (chi 2 = 4.3, df = 38, P < 0.05).

CONCLUSIONS: This study provides further evidence for a subtle pituitary-adrenal insufficiency in subjects with chronic fatigue syndrome compared to healthy volunteers. Disparities between our healthy volunteer data and those of other groups using the 1 microgram ACTH test suggest that the test may not be as reliable as previously indicated.

Comment in: The 1microg Synacthen test in chronic fatigue syndrome. [Clin Endocrinol (Oxf). 2000]

 

Source: Scott LV, Medbak S, Dinan TG. The low dose ACTH test in chronic fatigue syndrome and in health. Clin Endocrinol (Oxf). 1998 Jun;48(6):733-7. http://www.ncbi.nlm.nih.gov/pubmed/9713562

 

Chronic fatigue syndrome: an immunological perspective

Abstract:

OBJECTIVE: The aim of this study is to review research examining an immunological basis for chronic fatigue syndrome (CFS) and to discuss how a disturbance in immunity could produce central nervous system (CNS)-mediated symptoms.

METHOD: Data relevant to the hypothesis that abnormal cytokine release plays a role in the pathogenesis of CFS are reviewed as well as recent evidence relating to potential mechanisms by which immune products may enter the brain and produce a disturbance in CNS processes.

RESULTS: Examinations of cytokine levels in patients with CFS have produced inconclusive results. Recent evidence suggests that abnormal release of cytokines within the CNS may cause neural dysfunction by a variety of complex mechanisms.

CONCLUSION: Neuropsychiatric symptoms in patients with CFS may be more closely related to disordered cytokine production by glial cells within the CNS than to circulating cytokines. This possibility is discussed in the context of unresolved issues in the pathogenesis of CFS.

 

Source: Vollmer-Conna U, Lloyd A, Hickie I, Wakefield D. Chronic fatigue syndrome: an immunological perspective. Aust N Z J Psychiatry. 1998 Aug;32(4):523-7. http://www.ncbi.nlm.nih.gov/pubmed/9711366

 

Hormonal influences on stress-induced neutrophil mobilization in health and chronic fatigue syndrome

Abstract:

This investigation tested the hypotheses that women diagnosed with chronic fatigue syndrome (CFS) would exhibit significantly greater systemic indices of exercise-induced leukocyte mobilization and inflammation (neutrophilia, lactoferrin release, complement activation) than controls matched for age, weight, and habitual activity and that responses in the luteal phase of the menstrual cycle would be greater than in the follicular phase.

Subjects stepped up and down on a platform adjusted to the height of the patella for 15 min, paced by metronome. Blood samples were collected under basal conditions (the day before exercise) and following exercise for determination of circulating neutrophils and plasma concentrations of lactoferrin, C3a des arg, and creatine kinase. Complete, 24-hr urine collections were made for determination of cortisol excretion.

For all subjects, circulating neutrophil counts increased 33% (P < 0.0001) and lactoferrin increased 27% (P = 0.0006) after exercise, whereas plasma C3a des arg and creatine kinase did not increase. No indication of an exaggerated or excessive response was observed in the CFS patients compared to the controls.

In healthy women, circulating neutrophil numbers exhibited previously described relationships with physiological variables: basal neutrophil counts correlated with plasma progesterone concentrations (R = 0.726, P = 0.003) and the exercise-induced neutrophilia correlated with both urinary cortisol (R = 0.660, P = 0.007) and plasma creatine kinase (R = 0.523, P = 0.038) concentrations. These relationships were not observed in the CFS patients (R = 0.240, P = 0.370; R = 0.042, P = 0.892; and R = 0.293, P = 0.270; respectively).

These results suggest that normal endocrine influences on the circulating neutrophil pool may be disrupted in patients with CFS.

 

Source: Cannon JG, Angel JB, Abad LW, O’Grady J, Lundgren N, Fagioli L, Komaroff AL. Hormonal influences on stress-induced neutrophil mobilization in health and chronic fatigue syndrome. J Clin Immunol. 1998 Jul;18(4):291-8. http://www.ncbi.nlm.nih.gov/pubmed/9710746