Chronic fatigue syndrome–study of 51 cases treated at the Second Tokyo National Hospital

Abstract:

Fifty-one patients with chronic fatigue syndrome (CFS) were studied. Tender points, which are a characteristic clinical feature of fibromyalgia, were found in all but two of the patients at 11.4 points (mean) per patient. IgG antibody titers to EB virus viral capsid antigen were more elevated in the CFS patient group compared to that of the control (p < 0.0015). IgG antibody titers to HHV-6 were not higher in the patient group. NK cell activity was not more decreased in the patient group, whereas, the mean number of NK cells was lower (p < 0.005) in the patient group, when CD57 was used as the NK cell marker. Viral infections and/or disorders in cellular immunity may be important factors in the pathogenesis of CFS.

 

Source: Nishikai M. Chronic fatigue syndrome–study of 51 cases treated at the Second Tokyo National Hospital. Nihon Rinsho. 1992 Nov;50(11):2641-7. [Article in Japanese] http://www.ncbi.nlm.nih.gov/pubmed/1337560

 

Viral infection and its causative role for chronic fatigue syndrome

Abstract:

Patients with chronic fatigue syndrome (CFS), of unknown etiology, have been increasingly reported. This syndrome is characterized by debilitating fatigue, lymphadenopathy, and fever. Herein, I focus on and review this syndrome from the view point of the causative role of viral infection. Since the symptoms of CFS are similar to those of chronic infectious mononucleosis (CIM) or chronic Epstein-Barr virus infection (CEBV), the role of EBV has been intensively studied. The etiological relationship between EBV and CFS, however, is questioned, like other lymphotropic viruses, including human retroviruses, adenoviruses and human herpesvirus 6. Additionally, severe chronic active EBV infection syndrome (SCAEBV) is also discussed in this review because symptoms of this disorder are similar to those of CFS but more severe in degree. Currently, the cause(s) and treatment of CFS are enigmatic and require further research and multidisciplinary study.

 

Source: Okano M. Viral infection and its causative role for chronic fatigue syndrome. Nihon Rinsho. 1992 Nov;50(11):2617-24. [Article in Japanese] http://www.ncbi.nlm.nih.gov/pubmed/1337559

 

Chronic fatigue syndrome and virus infection: human herpesvirus 6 (HHV-6) infection

Abstract:

Chronic fatigue syndrome (CFS) is newly-recognized disease characterized by chronic and debilitating fatigue. It has been suggested that viral infection may be involved in this syndrome from the results of clinical examination, including increased activity of 2′,5′-synthetase in leukocytes of patients. The following viruses have been reported as etiologic agents of this disease. First, many studies have found elevated levels of IgG to viral capsid antigen and early antigens to Epstein-Barr virus (EBV), but low titer or absence of antibody to EBV-associated nuclear antigen. Second, the enteroviruses have also been implicated as possible causative agent of CFS, because virus could be isolated from patients. Recently it was also reported that antibodies to human T-lymphotropic virus (HTLV) and HTLV type II (HTLV-II) gag sequence were detectable in patients. Finally several reports state that human herpesvirus 6 (HHV-6) could be isolated from CFS patients in the high frequency. In conclusion, it is still early to identify the etiologic agent from these reports, and more effort is needed.

 

Source: Yamanishi K. [Chronic fatigue syndrome and virus infection: human herpesvirus 6 (HHV-6) infection]. Nihon Rinsho. 1992 Nov;50(11):2612-6. [Article in Japanese] http://www.ncbi.nlm.nih.gov/pubmed/1337558

 

Chronic fatigue immune dysfunction syndrome

Abstract:

Chronic fatigue syndrome (CFS) is characterized by unexplained, debilitating fatigue or easy fatigability lasting longer than six months. While a viral basis of infection is proposed to be the cause of CFS, other viral infections do not generally persist after several weeks.

Immunological disorders, including abnormal functions and distributions of T lymphocytes, B lymphocytes, natural killer (NK) cells, and monocyte/macrophages, are described in CFS. NK cells are known to play an important role in host resistance against viral infection as well as in the regulation of the immune systems.

Restoration of NK activity resulted in recovery from CFS. Taken together, immunological abnormalities, especially dysfunction of NK cells, may be involved in CFS.

 

Source: Uchida A. Chronic fatigue immune dysfunction syndrome. Nihon Rinsho. 1992 Nov;50(11):2625-9. [Article in Japanese] http://www.ncbi.nlm.nih.gov/pubmed/1287238

 

Epstein-Barr virus infection and associated diseases in children. I. Pathogenesis, epidemiology and clinical aspects

Abstract:

Epstein-Barr virus (EBV), an ubiquitous human B lymphotropic virus, is the cause of infectious mononucleosis. Moreover, EBV infection can be followed by lymphoproliferative diseases in patients with inherited and acquired immunodeficiencies.

Primary EBV infection may be a threat to all children after marrow or organ transplantation or those receiving chronic immunosuppressive treatment for various other reasons. The virus has been also implicated in the pathogenesis of different malignant tumours such as Burkitt lymphoma, nasopharyngeal carcinoma, Hodgkin disease and some T-cell lymphomas.

This review focuses on various aspects of virus-host interactions, immune mechanisms of the host, and the still experimental therapeutic approaches in EBV-associated diseases.

 

Source: Schuster V, Kreth HW. Epstein-Barr virus infection and associated diseases in children. I. Pathogenesis, epidemiology and clinical aspects. Eur J Pediatr. 1992 Oct;151(10):718-25. http://www.ncbi.nlm.nih.gov/pubmed/1330572

 

Monospot and VP1 tests in chronic fatigue syndrome and major depression

Abstract:

Thirty-four patients with chronic fatigue syndrome (CFS) were compared with controls with DSM-III-R major depression on the Monospot and VP1 antigen tests.

There was no significant difference in the numbers initially VP1 positive in the groups (11/34 and 7/34 positive in the chronic fatigue and major depression group respectively). Four CFS but no depressed patients were Monospot positive initially. No patient was both Monospot and VP1 positive. Patients positive on the tests were offered a repeat 6 months later. Eight of the 11 VP1 positive patients in the CFS group were retested and four remained positive, but none of the four depressed patients retested remained positive. No patient retested remained Monospot positive.

The Monospot and VP1 tests appear to have little discriminating ability between these groups as screening tests and their predictive validity is unclear.

 

Source: Lynch SP, Seth RV, Main J. Monospot and VP1 tests in chronic fatigue syndrome and major depression. J R Soc Med. 1992 Sep;85(9):537-40. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1293640/ (Full article)

 

Clinical, epidemiologic, and virologic studies in four clusters of the chronic fatigue syndrome

Abstract:

BACKGROUND: The purpose of this study is to provide a case definition of chronic fatigue syndrome in an outbreak occurring in the Nevada-California region to evaluate candidate etiologic agents and observe the natural history of the illness.

METHODS: Patients diagnosed as having chronic fatigue syndrome were studied by repeated interviews, questionnaires, and blood collection over a 3-year period. Serum samples were tested for antibodies to Epstein-Barr virus, human herpesvirus-6, and human T-lymphotropic viruses I and II. Leukocytes from typical cases were also assayed for human T-lymphotropic viruses I and II.

RESULTS: Cases were defined as persons who had: (1) severe persistent fatigue following an acute illness appearing in an individual with no previous physical or psychological symptoms; (2) presenting signs and symptoms of an acute infection; (3) severe and persistent headache and/or myalgias; and (4) abrupt change in cognitive function or the appearance of a new mood disorder. After 3 years of follow-up, almost all study subjects were able to return to pre-illness activity. None of the viruses evaluated–human T-lymphotropic viruses I and II, Epstein-Barr virus, or human herpesvirus-6–could be etiologically linked to these outbreaks.

CONCLUSION: Clinical features of outbreaks of chronic fatigue syndrome differ sufficiently to suggest different etiologic agents. Giardiasis appears to have precipitated one of the four clusters in this study but the cause(s) of the other three outbreaks is as yet uncertain. The overall prognosis ofchronic fatigue syndrome is usually favorable.

Comment in: Human herpesvirus type 6 and chronic fatigue syndrome. [Arch Intern Med. 1993]

 

Source: Levine PH, Jacobson S, Pocinki AG, Cheney P, Peterson D, Connelly RR, Weil R, Robinson SM, Ablashi DV, Salahuddin SZ, et al. Clinical, epidemiologic, and virologic studies in four clusters of the chronic fatigue syndrome. Arch Intern Med. 1992 Aug;152(8):1611-6. http://www.ncbi.nlm.nih.gov/pubmed/1323246

 

Sleep, Epstein-Barr virus infection, musculoskeletal pain, and depressive symptoms in chronic fatigue syndrome

Abstract:

Sleep physiology, viral serology and symptoms of 14 patients with chronic fatigue syndrome (CFS) were compared with 12 healthy controls. All patients described unrefreshing sleep and showed a prominent alpha electroencephalographic nonrapid eye movement (7.5-11.0 Hz) sleep anomaly (p less than or equal to 0.001), but had no physiologic daytime sleepiness.

There were no group differences in Epstein-Barr virus (EBV) antibody titers. The patient group had more fibrositis tender points (p less than 0.0001), described more somatic complaints (p less than 0.0001), and more depressive symptoms (p less than 0.0001). Patients with CFS do not show evidence for a specific chronic EBV infection, but show altered sleep physiology, numerous tender points, diffuse pain, and depressive symptoms. These features are similar to those found in fibromyalgia syndrome.

 

Source: Whelton CL, Salit I, Moldofsky H. Sleep, Epstein-Barr virus infection, musculoskeletal pain, and depressive symptoms in chronic fatigue syndrome. J Rheumatol. 1992 Jun;19(6):939-43. http://www.ncbi.nlm.nih.gov/pubmed/1328633

 

Serum levels of lymphokines and soluble cellular receptors in primary Epstein-Barr virus infection and in patients with chronic fatigue syndrome

Abstract:

The immunopathology in primary Epstein-Barr virus (EBV) infections and in chronic fatigue syndrome was studied by examining serum levels of interleukins (IL) and of soluble T cell receptors in serum samples.

Serum samples were from patients during and 6 months after primary EBV-induced infectious mononucleosis and from patients with chronic fatigue syndrome and serologic evidence of EBV reactivation. Markers for T lymphocyte activation (soluble IL-2 and CD8) and for monocyte activation (neopterin) were significantly elevated during acute infectious mononucleosis but not in patients with chronic fatigue syndrome.

Interferon-alpha, IL-1 beta, and IL-6 levels were not significantly increased in any patient group but inferferon-gamma levels were significantly increased during the acute phase of infectious mononucleosis. The levels of IL-1 alpha were significantly higher than in controls both in patients with infectious mononucleosis and in those with chronic fatigue syndrome. In the latter, the lack of most markers for lymphocyte activation found in patients with infectious mononucleosis makes it less likely that EBV reactivation causes symptoms.

 

Source: Linde A, Andersson B, Svenson SB, Ahrne H, Carlsson M, Forsberg P, Hugo H, Karstorp A, Lenkei R, Lindwall A, et al. Serum levels of lymphokines and soluble cellular receptors in primary Epstein-Barr virus infection and in patients with chronic fatigue syndrome. J Infect Dis. 1992 Jun;165(6):994-1000. http://www.ncbi.nlm.nih.gov/pubmed/1316417

 

Studies on the relationship between chronic fatigue syndrome and Epstein-Barr virus in Japan

Abstract:

Among 1,153 consecutive patients, 22 patients (1.9%) who complained of chronic fatigue for a period of over 6 months without detectable causes were studied.

Ten patients (0.86%) satisfied the criteria of chronic fatigue syndrome (CFS) and were classified to be definite cases of CFS. The other patients were classified as probable cases.

In order to clarify the role of Epstein-Barr virus (EBV) as a cause of CFS, we measured various antibodies for EBV. The definite cases had significantly higher titers of early antigen complex (EA)-IgG than both the probable cases and controls.

We proposed the EA-IgG/EBNA ratio as the indicator of activation of EBV and attempted to estimate the degree of fatigue by the EA-IgG/EBNA ratio. The highest ratio value (16.0) of the 22 patients ratios was the most serious case. In general, the ratio correlated with the degree of fatigue. Based on these results, it was concluded that a relationship does exist between CFS and EBV.

 

Source: Kawai K, Kawai A. Studies on the relationship between chronic fatigue syndrome and Epstein-Barr virus in Japan. Intern Med. 1992 Mar;31(3):313-8. http://www.ncbi.nlm.nih.gov/pubmed/1319246

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