Myth of the chronic fatigue syndrome

THE CHRONIC FATIGUE SYNDROME is a symptom complex characterized by fatigue, myalgias, arthralgias, neurologic symptoms-headaches, paresthesias, dizziness-lymph node swelling or tenderness, cognitive dysfunction, sleep disorders, and depression. The symptoms are similar to those seen in inflammatory illnesses and can be induced by the systemic administration of interferon beta. Severe fatigue is a perplexing and constant complaint in many patients with multiple sclerosis. This indicates that the perception of energy level has a sensitive physiologic basis that is dependent on the homeostasis of other body systems.

The chronic fatigue syndrome has gained popularity among the lay public and has stimulated considerable scientific debate about its existence. Many investigators and practitioners have attributed the disorder to chronic depression. Difficulty arises from the diverse symptoms associated with fatigue states; fatigue is a prominent feature of many systemic, neurologic, and psychiatric disorders. Also, fatigue is a subjective complaint without a quantifiable measure. This interweaving of many symptoms and diagnoses with disabling fatigue makes it difficult to compare patient groups. Terms applied to disorders that probably represent chronic fatigue syndrome are chronic infectious mononucleosis, myalgic encephalomyelitis, idiopathic chronic fatigue and myalgia syndrome, epidemic neuromyasthenia, postviral fatigue syndrome, and fibrositis-fibromyalgia.

You can read the rest of this article here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1002920/pdf/westjmed00095-0070a.pdf

 

Source: Murray RS. Myth of the chronic fatigue syndrome. West J Med. 1991 Jul;155(1):68. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1002920/

 

Altered cytokine release in peripheral blood mononuclear cell cultures from patients with the chronic fatigue syndrome

Abstract:

Chronic fatigue syndrome (CFS) is an idiopathic illness associated with a variety of immunologic abnormalities. To investigate potential pathogenetic mechanisms, we evaluated serum levels and peripheral blood mononuclear cell (PBMC) production of selected cytokines and immunoglobulins.

Serum bioactive transforming growth factor beta (TGF-beta) levels were higher (P less than 0.01) in patients with CFS (290 +/- 46 pg/mL) than in control subjects (104 +/- 18 pg/mL), but levels of other cytokines tested were not different. Lipopolysaccharide-stimulated release of interleukin 1 beta (IL-1 beta), IL-6, and tumor necrosis factor-alpha was increased (P less than 0.05) in PBMC cultures from patients with CFS versus control subjects; enhanced (P less than 0.01) IL-6 release to phytohemagglutinin was also observed.

In contrast, TGF-beta release in response to lipopolysaccharide was depressed (P less than 0.01) in PBMC cultures derived from patients with CFS. No differences in IL-2 and IL-4 or immunoglobulin production were observed.

The enhanced release of inflammatory cytokines by stimulated PBMC from patients with CFS suggests that these cells are primed for an increased response to immune stimuli. These data also suggest an association between abnormal regulation of TGF-beta production in vivo and in vitro with the immunologic consequence of CFS.

 

Source: Chao CC1, Janoff EN, Hu SX, Thomas K, Gallagher M, Tsang M, Peterson PK. Altered cytokine release in peripheral blood mononuclear cell cultures from patients with the chronic fatigue syndrome. Cytokine. 1991 Jul;3(4):292-8. http://www.ncbi.nlm.nih.gov/pubmed/1873478

 

Antibodies to Epstein-Barr virus in patients with chronic fatigue

Abstract:

To clarify the role of Epstein-Barr virus (EBV) infection and the value of EBV antibody testing in evaluating patients with chronic fatigue, we studied 200 consecutive patients with chronic fatigue (mean duration, 9 years).

Complete EBV serologic panels were obtained for 154 patients, 35 (23%) of whom met serologic or clinical criteria for chronic or reactivated EBV infection. We compared these patients with chronic EBV infection (CEBV cases) to 35 age- and sex-matched patients who were selected from the same cohort of fatigued patients but who did not meet the criteria (CEBV control subjects).

We found few differences between groups in demographic characteristics, clinical features, and symptoms; CEBV cases were more likely to meet criteria for the proposed chronic fatigue syndrome (14% vs 0%), and to report that they suffered from an influenza-like illness at the onset of their fatigue syndrome (34% vs 12%), that they lost their job because of their fatigue (37% vs 11%), and that their fatigue was improved by recreational activity (26% vs 3%).

Physical examination and laboratory testing showed few abnormalities in either group. Psychiatric morbidity was common in both groups, including mood disorders (63% of CEBV cases vs 54% of CEBV controls), anxiety (11% vs 9%) and somatization disorder (9% in each group).

We conclude that EBV serologic patterns have little clinical usefulness in evaluating patients with chronic fatigue.

 

Source: Matthews DA, Lane TJ, Manu P. Antibodies to Epstein-Barr virus in patients with chronic fatigue. South Med J. 1991 Jul;84(7):832-40. http://www.ncbi.nlm.nih.gov/pubmed/1648795

 

The chronic fatigue syndrome

Abstract:

The chronic fatigue syndrome (CFS) was formally defined in 1988 to describe disabling fatigue of at least 6 months’ duration of uncertain etiology. Reports of CFS have emerged from the United States, Canada, the United Kingdom, Australia, New Zealand, Israel, Spain, and France. The disease primarily affects individuals between 20 and 50 years of age, and there is a preponderance of females.

Although a triggering infectious illness is reported by most patients with CFS, there is no convincing evidence causally linking any currently recognized infectious agent to CFS. Multiple minor immunologic aberrations are frequent but inconsistent and of uncertain significance. There is no consistent evidence for myopathy or physical deconditioning.

Depression is found in approximately 50% of CFS patients, with depression preceding the physical symptoms in half of the cases. No therapy has been proved effective in controlled clinical trials with prolonged follow-up, although antidepressants have not been formally evaluated.

The long-term prognosis of patients with CFS has not been well studied, but CFS appears to be a disease of prolonged duration with considerable morbidity but no mortality. Further research into the pathogenesis and treatment of CFS is necessary.

 

Source: Shafran SD. The chronic fatigue syndrome. Am J Med. 1991 Jun;90(6):730-9. http://www.ncbi.nlm.nih.gov/pubmed/2042689

 

Depression, chronic fatigue syndrome, and the adolescent

Abstract:

To summarize, CFS and depression present very real problems for adolescent patients, their families, and their physicians. The wealth of symptoms presented may signal the presence of any number of psychiatric or physiologic disorders. As part of the evaluation to rule out other maladies, the physician must identify the developmental issues and life stress events with which patients or their families are struggling. Helping patients to accept psychiatric referral to address these issues is indicated if it is thought that they may be contributing to the onset or maintenance of the symptoms. Referral is also indicated if a protracted clinical course evolves and the patient’s normal course of growth and development appears to be in jeopardy.

 

Source: Strickland MC. Depression, chronic fatigue syndrome, and the adolescent. Prim Care. 1991 Jun;18(2):259-70. http://www.ncbi.nlm.nih.gov/pubmed/1876612

 

Immune responsiveness in chronic fatigue syndrome

Abstract:

We have endeavoured to find immunological indications of chronic virus infection in patients with chronic fatigue syndrome (myalgic encephalomyelitis) and to investigate immune responsiveness to viruses in such patients in comparison with normal subjects and patients with muscular dystrophy.

Levels of circulating IgM immune complexes were elevated (above the 95% normal control range) in 10 (17%) of 58 patients with chronic fatigue syndrome, which was not significantly different from the normal controls or from dystrophy controls (by Mann Whitney U test). Levels of IgG complexes were only increased in 10% of patients. Lymphocyte proliferation in response to concanavalin A (Con A), assessed by increase in 3H-thymidine incorporation, did not differ between 14 patients and 18 normal subjects.

The proliferative response to Coxsackie B virus antigen did not differ between chronic fatigue patients and normal subjects when expressed either as an increase in counts or as a stimulation index. Adjustment of the counts in relation to the proliferation response to Con A, as an indication of the overall proliferative response of the cell preparation, did not reveal any hidden difference. IgM antibodies to Coxsackie B viruses were not found in any of 20 patients and in 1 of 20 dystrophy controls.

Significant levels of neutralizing antibodies to Coxsackie B viruses 1-5 were found in 6 out of 19 (32%) patients compared with 4 out of 17 (24%) dystrophy controls, which does not differ from currently expected normal incidence. Antibody titres to other respiratory viruses were also not notably different between the patient and control groups.

In conclusion we can find no evidence for a definable viral aetiology for the chronic fatigue syndrome, neither in terms of a persistent infection nor an altered ability to respond to virus.

Comment in: Immune responsiveness in chronic fatigue syndrome. [Postgrad Med J. 1992]

 

Source: Milton JD, Clements GB, Edwards RH. Immune responsiveness in chronic fatigue syndrome. Postgrad Med J. 1991 Jun;67(788):532-7. http://www.ncbi.nlm.nih.gov/pubmed/1656416

Note: You can read the full article here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2398884/

 

Chronic fatigue syndrome: lack of association with hepatitis C virus infection

Abstract:

Chronic fatigue syndrome (CFS) is a debilitating heterogeneous disorder lacking consistent, objective physical or laboratory abnormalities. Among the hypothetical etiologies for CFS are chronic viral infections. The present controlled seroprevalence study found that, among typical CFS patients, evidence of hepatitis C virus (HCV) infection is uncommon. Only one of 36 patients and none of 14 controls were anti-HCV positive. The positive patient had persistent aminotransferase elevations and prior posttransfusion hepatitis. Thus HCV infection is not a common feature of CFS and should not be routinely sought.

 

Source: Dale JK, Di Bisceglie AM, Hoofnagle JH, Straus SE. Chronic fatigue syndrome: lack of association with hepatitis C virus infection. J Med Virol. 1991 Jun;34(2):119-21. http://www.ncbi.nlm.nih.gov/pubmed/1653818

 

Postviral fatigue syndrome

Comment on: Postviral fatigue syndrome. [BMJ. 1991]

 

SIR, In his letter Dr Anthony Knudsen comments (1) on the recent paper by Dr J W Gow and colleagues on the postviral fatigue syndrome.(2) Dr Knudsen refers to the fact that the aetiology of the syndrome has not been established and to the dearth of definitive pathological findings. Though he does not directly express an opinion, he mentions “the view held by some that the condition is stress related and of psychological origin.”

The body of opinion that holds that the postviral fatigue syndrome has a physical, organic origin seems often to be criticised because it cannot produce “the evidence.” Yet these critics seem quite sanguine about putting forward the hypothesis that the syndrome is of psychological or psychiatric origin without a hint of an opinion regarding the basis of this hypothesis, far less evidence to support it.

You can read the rest of this comment here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1669836/pdf/bmj00125-0065d.pdf

 

Source: M L Sweeney. Postviral fatigue syndrome. BMJ. 1991 May 11; 302(6785): 1153–1154. PMCID: PMC1669836 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1669836/

 

Postinfectious chronic fatigue syndrome: case history of thirty-five patients in Germany

Abstract:

Thirty-five patients with chronic fatigue syndrome according to the criteria of Holmes were followed for periods of up to eight years. The most frequent symptoms were severe fatigue, arthralgias and myalgias, recurrent oropharyngitis and various psychiatric disorders.

More than half of the patients suffered from neuropathy, lymphadenopathy, gastrointestinal complaints and recurrent low-grade fever. Recurrent or persistent activity of human herpesvirus -6 infection was seen in 73% of the patients and of Epstein-Barr virus in 34.4%. In addition, various other infections were diagnosed at lower frequency.

Initial routine immunologic screening revealed various types of deficiencies, these were yet inconsistent and variable when different patients were compared with each other. Tentative treatments included in immunoglobulins, nonspecific immunostimulation and virostatic drugs. No consistently positive results were obtained with any treatment schedule although immunoglobulins appeared the most efficient measure. In addition, psychologic care of the patients is indicated, since disturbances in the psycho-neuroimmunologic regulation may play a significant role in the pathogenesis of the disease.

 

Source: Hilgers A, Krueger GR, Lembke U, Ramon A. Postinfectious chronic fatigue syndrome: case history of thirty-five patients in Germany. In Vivo. 1991 May-Jun;5(3):201-5. http://www.ncbi.nlm.nih.gov/pubmed/1893076

 

Psychiatric symptoms, personality and ways of coping in chronic fatigue syndrome

Abstract:

This study aimed to investigate the psychological characteristics of chronic fatigue syndrome (CFS: Holmes et al. 1988).

A battery of psychometric instruments comprising the General Health Questionnaire (GHQ), the Beck Depression Inventory (BDI), the Minnesota Multiphasic Personality Inventory (MMPI) and the Lazarus Ways of Coping (WoC) inventory, was administered to a sample of clinically-defined CFS sufferers (N = 58), to a comparison group of chronic pain (CP) patients (N = 81) and to a group of healthy controls matched for sex and age with the CFS sample (N = 104).

Considerable overlap was found between CFS and CP patients at the level of both physical and psychological symptoms. This raises the possibility that CFS sufferers are a sub-population of CP patients. However, while there was some commonality between CFS and CP patients in terms of personality traits, particularly the MMPI ‘neurotic triad’ (hypochondriasis, depression and hysteria),

CFS patients showed more deviant personality traits reflecting raised levels on the first MMPI factor, emotionality. Moreover, results were not consistent with the raised emotionality being a reaction to the illness, but rather were consistent with the hypothesis that emotionality is a predisposing factor for CFS.

The majority of CFS patients fell within four personality types, each characterized by the two highest MMPI scale scores. One type (N = 20) reported a lack of psychological symptoms or emotional disturbance contrary to the overall trend for the CFS sample. This group conformed to the ICD-10 classification of neurasthenia.

 

Source: Blakely AA, Howard RC, Sosich RM, Murdoch JC, Menkes DB, Spears GF. Psychiatric symptoms, personality and ways of coping in chronic fatigue syndrome. Psychol Med. 1991 May;21(2):347-62. http://www.ncbi.nlm.nih.gov/pubmed/1876640