Cytokines in parvovirus B19 infection as an aid to understanding chronic fatigue syndrome

Abstract:

Human parvovirus B19 infection has been associated with various clinical manifestations of a rheumatic nature such as arthritis, fatigue, and chronic fatigue syndrome (CFS), which can persist for years after the acute phase.

The authors have demonstrated recently that acute B19 infection is accompanied by raised circulating levels of IL-1b, IL-6, TNF-a, and IFN-g and that raised circulating levels of TNF-a and IFN-g persist and are accompanied by MCP-1 in those patients who develop CFS.

A resolution of clinical symptoms and cytokine dysregulation after intravenous immunoglobulin (IVIG) therapy, which is the only specific treatment for parvovirus B19 infection, also has been reported. Although CFS may be caused by various microbial and other triggers, that triggered by B19 virus is clinically indistinguishable from idiopathic CFS and exhibits similar cytokine abnormalities and may represent an accessible model for the study of CFS.

 

Source: Kerr JR, Tyrrell DA. Cytokines in parvovirus B19 infection as an aid to understanding chronic fatigue syndrome. Curr Pain Headache Rep. 2003 Oct;7(5):333-41. http://www.ncbi.nlm.nih.gov/pubmed/12946285

 

Distinguishing patients with chronic fatigue from those with chronic fatigue syndrome: a diagnostic study in UK primary care

Abstract:

BACKGROUND: Chronic fatigue syndrome (CFS) has been defined, but many more patients consult in primary care with chronic fatigue that does not meet the criteria for CFS. General practitioners (GPs) do not generally use the CFS diagnosis, and have some doubt about the validity of CFS as an illness.

AIM: To describe the proportion of patients consulting their GP for fatigue that met the criteria for CFS, and to describe the social, psychological, and physical differences between patients with CFS and those with non-CFS chronic fatigue in primary care.

DESIGN OF STUDY: Baseline data from a trial of complex interventions for fatigue in primary care.

SETTING: Twenty-two general practices located in London and the South Thames region of the United Kingdom recruited patients to the study between 1999 and 2001.

METHOD: One hundred and forty-one patients who presented to their GP with unexplained fatigue lasting six months or more as a main symptom were recruited, and the Centers for Disease Control (CDC) case definition was applied to classify CFS.

RESULTS: Approximately two-thirds (69%) of patients had chronic fatigue and not CFS. The duration of fatigue (32 months) and perceived control over fatigue were similar between groups; however, fatigue, functioning, associated symptoms, and psychological distress were more severe in the patients in the CFS group, who also consulted their GP significantly more frequently, were twice as likely to be depressed, and more than twice as likely to be unemployed. About half (CFS = 50%; chronic fatigue = 55%) in each group attributed their fatigue to mainly psychological causes.

CONCLUSIONS: In primary care, CFS is a more severe illness than chronic fatigue, but non-CFS chronic fatigue is associated with significant fatigue and is reported at least twice as often. That half of patients, irrespective of CFS status, attribute their fatigue to psychological causes, more than is observed in secondary care, indicates an openness to the psychological therapies provided in that setting. More evidence on the natural history of chronic fatigue and CFS in primary care is required, as are trials of complex interventions. The results may help determine the usefulness of differentiating between chronic fatigue and CFS.

 

Source: Darbishire L, Ridsdale L, Seed PT. Distinguishing patients with chronic fatigue from those with chronic fatigue syndrome: a diagnostic study in UK primary care. Br J Gen Pract. 2003 Jun;53(491):441-5. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1314617/ (Full article)

 

The radicalized self: the impact on the self of the contested nature of the diagnosis of chronic fatigue syndrome

Abstract:

Chronic fatigue syndrome (CFS) is a relatively new disease that is difficult to diagnose. It is also a contested disease immersed in dispute about whether it is a physical or psychiatric reality. Sufferers often claim to experience not only the physical challenges of the disease, and these can be extensive, but also, initially, the anomie of suffering from a condition whose very reality is debated both in the medical and in the wider communities.

Theories of self in illness emphasize how people who are diagnosed as chronically ill work hard as they seek to maintain previous, or to develop supernormal, selves. Such goals are cast in a critical light by Foucault’s notion of the technologies of self in the context of circulating neo-liberal discourses. As people with CFS, lacking an uncontested medical diagnosis, search for meaningful self-identities, they resist previously available discourses to take up an alternative discourse, one that we call radicalized selves.

This paper raises questions about the constraints and liberties, power and powerlessness associated with a clear and undisputed medical diagnosis. It suggests a model of the self in chronic illness that considers not only changes in body and biography but also the availability of an uncontested diagnosis.

 

Source: Clarke JN, James S. The radicalized self: the impact on the self of the contested nature of the diagnosis of chronic fatigue syndrome. Soc Sci Med. 2003 Oct;57(8):1387-95. http://www.ncbi.nlm.nih.gov/pubmed/12927469

 

Abnormal impedance cardiography predicts symptom severity in chronic fatigue syndrome

Abstract:

BACKGROUND: Findings indicative of a problem with circulation have been reported in patients with chronic fatigue syndrome (CFS). We examined this possibility by measuring the patient’s cardiac output and assessing its relation to presenting symptoms.

METHODS: Impedance cardiography and symptom data were collected from 38 patients with CFS grouped into cases with severe (n = 18) and less severe (n = 20) illness and compared with those from 27 matched, sedentary control subjects.

RESULTS: The patients with severe CFS had significantly lower stroke volume and cardiac output than the controls and less ill patients. Postexertional fatigue and flu-like symptoms of infection differentiated the patients with severe CFS from those with less severe CFS (88.5% concordance) and were predictive (R2 = 0.46, P < 0.0002) of lower cardiac output. In contrast, neuropsychiatric symptoms showed no specific association with cardiac output.

CONCLUSIONS: These results provide a preliminary indication of reduced circulation in patients with severe CFS. Further research is needed to confirm this finding and to define its clinical implications and pathogenetic mechanisms.

 

Source: Peckerman A, LaManca JJ, Dahl KA, Chemitiganti R, Qureishi B, Natelson BH. Abnormal impedance cardiography predicts symptom severity in chronic fatigue syndrome. Am J Med Sci. 2003 Aug;326(2):55-60. http://www.ncbi.nlm.nih.gov/pubmed/12920435

 

Modification of the functional capacity of sarcoplasmic reticulum membranes in patients suffering from chronic fatigue syndrome

Abstract:

In chronic fatigue syndrome, several reported alterations may be related to specific oxidative modifications in muscle. Since sarcoplasmic reticulum membranes are the basic structures involved in excitation-contraction coupling and the thiol groups of Ca(2+) channels of SR terminal cisternae are specific targets for reactive oxygen species, it is possible that excitation-contraction coupling is involved in this pathology.

We investigated the possibility that abnormalities in this compartment are involved in the pathogenesis of chronic fatigue syndrome and consequently responsible for characteristic fatigue. The data presented here support this hypothesis and indicate that the sarcolemmal conduction system and some aspects of Ca(2+) transport are negatively influenced in chronic fatigue syndrome.

In fact, both deregulation of pump activities (Na(+)/K(+) and Ca(2+)-ATPase) and alteration in the opening status of ryanodine channels may result from increased membrane fluidity involving sarcoplasmic reticulum membranes.

 

Source: Fulle S, Belia S, Vecchiet J, Morabito C, Vecchiet L, Fanò G. Modification of the functional capacity of sarcoplasmic reticulum membranes in patients suffering from chronic fatigue syndrome. Neuromuscul Disord. 2003 Aug;13(6):479-84. http://www.ncbi.nlm.nih.gov/pubmed/12899875

 

Complement activation in a model of chronic fatigue syndrome

Abstract:

BACKGROUND: A need exists to identify biological markers in chronic fatigue syndrome (CFS).

OBJECTIVE: To use an exercise and/or allergen challenge to induce the symptoms of CFS and to identify a biological marker that correlates with these symptoms.

METHODS: Patients with CFS (n = 32) and age-matched, normal control patients (n = 29) exercised for 20 minutes on a stationary bike at 70% of their predicted max work load (Watts). Patients from each group with positive skin test results were also challenged with intranasally administered relevant allergens. Symptoms were recorded for 2 weeks before and 1 week after each challenge, using 3 different instruments. Blood samples were taken before, and 0, 1, 6, and 24 hours after challenges. Levels of complement split products, cell-associated cytokines, and eosinophilic cationic protein were measured. Mean preexercise and postexercise symptom scores were evaluated for each group.

RESULTS: Exercise challenge induced significant increases of the complement split product C4a, but not C3a or C5a, at 6 hours after exercise only in the CFS group (P <.01), regardless of allergy status. Mean symptom scores were significantly increased after exercise through the use of a daily diary (P <.03) and a weekly diary (P <.01) for the CFS group only. Mean scores for the Multidimensional Fatigue Inventory categories “reduced activity” and “mental fatigue” were significantly increased in the CFS group only (P <.04 and P <.02, respectively).

CONCLUSIONS: Exercise challenge may be a valuable tool in the development of diagnostic criteria and tests for CFS. Establishment of a role for complement activation products as markers or participants in production of illness require further study.

 

Source: Sorensen B, Streib JE, Strand M, Make B, Giclas PC, Fleshner M, Jones JF. Complement activation in a model of chronic fatigue syndrome. J Allergy Clin Immunol. 2003 Aug;112(2):397-403. http://www.ncbi.nlm.nih.gov/pubmed/12897748

 

Enhanced glucocorticoid sensitivity in patients with chronic fatigue syndrome

Abstract:

OBJECTIVE: Alterations of the immune-neuroendocrine interplay have been described in chronic fatigue syndrome (CFS). Employing a recently developed method, the study set out to investigate whether patients with CFS have an altered sensitivity to glucocorticoids (GCs) when under stress.

METHODS: A total of 21 CFS patients and 20 healthy age- and gender-matched controls underwent a standardized psychosocial stress test (Trier Social Stress Test, TSST). Salivary and plasma cortisol levels were measured repeatedly following exposure to the stressor. GC sensitivity was assessed in vitro by dexamethasone inhibition of lipopolysaccharide-stimulated production of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNC-α).

RESULTS: Cortisol responses following the TSST did not differ significantly between CFS patients and healthy controls. GC sensitivity differed significantly between CFS patients and healthy controls, with CFS patients showing a greater sensitivity towards GCs (TNF-α: F 1/39 = 7.32, P = 0.01; IL-6: F 1/39 = 9.73, P = 0.004).

CONCLUSION: Consistent with recent evidence, CFS patients are characterized by an enhanced sensitivity to glucocorticoids. The implications for secondary processes, such as the regulatory influence of glucocorticoids on immune processes, are discussed.

 

Source: Gaab J, Rohleder N, Heitz V, Schad T, Engert V, Schürmeyer TH, Ehlert U. Enhanced glucocorticoid sensitivity in patients with chronic fatigue syndrome. Acta Neuropsychiatr. 2003 Aug;15(4):184-91. doi: 10.1034/j.1601-5215.2003.00033.x. http://www.ncbi.nlm.nih.gov/pubmed/26983566

 

Multiple co-infections (Mycoplasma, Chlamydia, human herpes virus-6) in blood of chronic fatigue syndrome patients: association with signs and symptoms

Abstract:

Previously we and others found that a majority of chronic fatigue syndrome (CFS) patients showed evidence of systemic mycoplasmal infections, and their blood tested positive using a polymerase chain reaction assay for at least one of the four following Mycoplasma species: M. fermentans, M. hominis, M. pneumoniae or M. penetrans.

Consistent with previous results, patients in the current study (n=200) showed a high prevalence (overall 52%) of mycoplasmal infections. Using forensic polymerase chain reaction we also examined whether these same patients showed evidence of infections with Chlamydia pneumoniae (overall 7.5% positive) and/or active human herpes virus-6 (HHV-6, overall 30.5% positive).

Since the presence of one or more infections may predispose patients to other infections, we examined the prevalence of C. pneumoniae and HHV-6 active infections in mycoplasma-positive and -negative patients. Unexpectedly, we found that the incidence of C. pneumoniae or HHV-6 was similar in Mycoplasma-positive and -negative patients, and the converse was also found in active HHV-6-positive and -negative patients. Control subjects (n=100) had low rates of mycoplasmal (6%), active HHV-6 (9%) or chlamydial (1%) infections, and there were no co-infections in control subjects. Differences in bacterial and/or viral infections in CFS patients compared to control subjects were significant.

Severity and incidence of patients’ signs and symptoms were compared within the above groups. Although there was a tendency for patients with multiple infections to have more severe signs and symptoms (p<0.01), the only significant differences found were in the incidence and severity of certain signs and symptoms in patients with multiple co-infections of any type compared to the other groups (p<0.01). There was no correlation between the type of co-infection and severity of signs and symptoms. The results indicate that a large subset of CFS patients show evidence of bacterial and/or viral infection(s), and these infections may contribute to the severity of signs and symptoms found in these patients.

 

Source: Nicolson GL, Gan R, Haier J. Multiple co-infections (Mycoplasma, Chlamydia, human herpes virus-6) in blood of chronic fatigue syndrome patients: association with signs and symptoms. APMIS. 2003 May;111(5):557-66. http://www.ncbi.nlm.nih.gov/pubmed/12887507

 

Medically unexplained physical symptoms, anxiety, and depression: a meta-analytic review

Abstract:

OBJECTIVE: Our objective was to review and compare, with meta-analytic methods, observational studies on the association of medically unexplained physical symptoms, anxiety, and depression with special emphasis on healthy and organically ill control groups and on different types of symptoms, measures, and illness behavior.

METHODS: A search of MEDLINE and PsycLIT/PsycINFO for abstracts from 1980 to April 2001 was performed; principal investigators in the field were contacted and article reference lists were used to retrieve additional relevant articles. Two hundred forty-four studies were included on the basis of consensus ratings if they fulfilled seven of eight inclusion criteria pertaining to diagnostic accuracy and statistical appropriateness. Five hundred twenty-two studies were deferred or excluded. We focused specifically on the four functional somatic syndromes for which there were sufficient numbers for meta-analytic integration: irritable bowel syndrome (IBS), nonulcer dyspepsia (NUD), fibromyalgia (FM), and chronic fatigue syndrome (CFS). Data were extracted independently by two authors according to a prespecified coding manual with up to 70 parameters per study.

RESULTS: Effect sizes for the association of the four functional somatic syndromes with depression and anxiety were of moderate magnitude but were highly significant statistically when compared with healthy persons and controls with medical disorders of known organic pathology. Moreover, this association was significant whether depression was measured with or without somatic items. Chronic fatigue syndrome is characterized by higher scores of depression, fibromyalgia by lower scores of anxiety than irritable bowel syndrome. Consulting behavior and severity of somatization is related to higher levels of anxiety and depression.

CONCLUSIONS: Meta-analytic integration confirms that the four functional somatic syndromes (IBS, NUD, FM, CFS) are related to (but not fully dependent on) depression and anxiety. At present, there is only limited meta-analytic evidence for the same sort of association for medically unexplained physical symptoms in general. In view of the relative independence from depression and anxiety, classification and treatment of these symptoms and syndromes as “common mental disorders” does not seem fully appropriate.

 

Source: Henningsen P, Zimmermann T, Sattel H. Medically unexplained physical symptoms, anxiety, and depression: a meta-analytic review. Psychosom Med. 2003 Jul-Aug;65(4):528-33. http://www.ncbi.nlm.nih.gov/pubmed/12883101

 

Mycoplasma blood infection in chronic fatigue and fibromyalgia syndromes

Abstract:

Chronic fatigue syndrome (CFS) and fibromyalgia syndrome (FMS) are characterised by a lack of consistent laboratory and clinical abnormalities. Although they are distinguishable as separate syndromes based on established criteria, a great number of patients are diagnosed with both.

In studies using polymerase chain reaction methods, mycoplasma blood infection has been detected in about 50% of patients with CFS and/or FMS, including patients with Gulf War illnesses and symptoms that overlap with one or both syndromes. Such infection is detected in only about 10% of healthy individuals, significantly less than in patients.

Most patients with CFS/FMS who have mycoplasma infection appear to recover and reach their pre-illness state after long-term antibiotic therapy with doxycycline, and the infection can not be detected after recovery. By means of causation and therapy, mycoplasma blood infection may permit a further subclassification of CFS and FMS.

It is not clear whether mycoplasmas are associated with CFS/FMS as causal agents, cofactors, or opportunistic infections in patients with immune disturbances. Whether mycoplasma infection can be detected in about 50% of all patient populations with CFS and/or FMS is yet to be determined.

 

Source: Endresen GK. Mycoplasma blood infection in chronic fatigue and fibromyalgia syndromes. Rheumatol Int. 2003 Sep;23(5):211-5. Epub 2003 Jul 16. http://www.ncbi.nlm.nih.gov/pubmed/12879275