Definition of the chronic fatigue syndrome and its issues

Abstract:

This article reviewed Definition of CFS proposed by CDC 1988. There are several issues in Definition for CFS of CDC. It is presented that other chronic clinical conditions have been satisfactorily excluded, including preexisting psychiatric diseases in (2) of major criteria.

However, fibromyalgia can not be excluded from the fifth symptom of minor criteria, myalgia, and also depression from the ninth symptom.

It is practically difficult to define impairment of average daily activity below 50% of the patient’s premorbid activity level for a period of at least 6 months, as shown in (1) of major criteria, and it is not adapted for a first visit patient.

Definition for CFS of CDC has been discussed on EBV infection, but not written on postviral fatigue syndrome and myalgic encephalomyelitis. Especially whether epidemic type of CFS is present or not was not discussed. Diagnostic criteria of CFS is necessary for clinical practice.

 

Source: Hashimoto N. Definition of the chronic fatigue syndrome and its issues. Nihon Rinsho. 1992 Nov;50(11):2591-9. [Article in Japanese] http://www.ncbi.nlm.nih.gov/pubmed/1287235

 

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

 

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

 

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

 

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

 

Frequent double infection with Epstein-Barr virus and human herpesvirus-6 in patients with acute infectious mononucleosis

Abstract:

Clinical infectious mononucleosis (IM) represents a benign self-limited form of lymphoproliferative disease which is usually caused by infection with Epstein-Barr virus (EBV). Microscopic characteristics of this lymphoproliferative disorder, however, are not ultimately specific for EBV infection, but can also be seen in infections with other lymphotropic viruses, especially of the herpesvirus family.

Human herpesvirus-6 (HHV-6) infection can apparently be associated with a number of diseases also seen in EBV infection. Also, postinfectious chronic fatigue syndrome (PICFS) which may follow IM is in more than 60% of the cases accompanied by persistent active HHV-6 infection.

We thus screened serologically 215 cases of acute IM for evidence for infection with EBV, HHV-6 and CMN. Patients were tentatively grouped into those having primary infection or reactivated (probably non-primary) infections. Cases were followed for two years to monitor changes in titers.

Of all 215 cases, 211 (98.1%) were positive for EBV, 137 (63.7%) for primary infections, 21 (9.8%) for reactivated infection, and 53 (24.6%) for latent EBV. Thirty-three (15.3%) cases had primary HHV-6 infection, 63 (29.3%) active or reactivated HHV-6 infection, and 71 (33.9%) latent HHV-6. Double active EBV and HHV-6 infection, including primary and reactivated infections, amounted to 89 (39.5%) cases. Cytomegalovirus (CMV) antibody titers were found in 81 (37%) cases, 48 (22.3%) of which indicated latent infection and 33 (15.3%) active infection. Only two cases had evidence of active CMV infection alone, 1 cases of active CMV and HHV-6 infection. Serologic titers in 12 (5.6%) cases indicated combined active infection with CMV, EBV and HHV-6.

(ABSTRACT TRUNCATED AT 250 WORDS)

 

Source: Bertram G, Dreiner N, Krueger GR, Ramon A, Ablashi DV, Salahuddin SZ, Balachandram N. Frequent double infection with Epstein-Barr virus and human herpesvirus-6 in patients with acute infectious mononucleosis. In Vivo. 1991 May-Jun;5(3):271-9. http://www.ncbi.nlm.nih.gov/pubmed/1654150

 

Enteroviral RNA sequences detected by polymerase chain reaction in muscle of patients with postviral fatigue syndrome

Abstract:

OBJECTIVE: To determine the presence of enteroviral sequences in muscle of patients with the postviral fatigue syndrome.

DESIGN: Detection of sequences with the polymerase chain reaction in a well defined group of patients with the syndrome and controls over the same period.

SETTING: Institute of Neurological Sciences, Glasgow.

SUBJECTS: 60 consecutive patients admitted to the institute with the postviral fatigue syndrome who had undergone extensive investigation to exclude other conditions. 41 controls from the same catchment area without evidence of fatigue, all undergoing routine surgery.

MAIN OUTCOME MEASURES: Routine investigations, serological screen for antibodies to a range of viruses, and presence of enteroviral RNA sequences in muscle biopsy specimens.

RESULTS: 15 (25%) patients and 10 (24.4%) controls had important serological findings. 12 patients had neutralising antibody titres of greater than or equal to 256 to coxsackieviruses B1-5 (six positive for enteroviral RNA sequences, six negative); three were positive for Epstein-Barr virus specific IgM (two positive, one negative). Six controls had similar neutralising antibody titres to coxsackieviruses (all negative); one was positive for Epstein-Barr virus specific IgM (negative); and three had titres of complement fixing antibody greater than or equal to 256 to cytomegalovirus (all negative). Overall, significantly more patients than controls had enteroviral RNA sequences in muscle (32/60, 53% v 6/41, 15%; odds ratio 6.7, 95% confidence interval 2.4 to 18.2). This was not correlated with duration of disease, patient and age, or to raised titres of antibodies to coxsackieviruses B1-5.

CONCLUSIONS: Persistent enteroviral infection of muscle may occur in some patients with postviral fatigue syndrome and may have an aetiological role.

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

 

Source: Gow JW, Behan WM, Clements GB, Woodall C, Riding M, Behan PO. Enteroviral RNA sequences detected by polymerase chain reaction in muscle of patients with postviral fatigue syndrome. BMJ. 1991 Mar 23;302(6778):692-6. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1669122/ (Full article)

 

Chronic fatigue syndrome: I. Epstein-Barr virus immune response and molecular epidemiology

Abstract:

Patients with chronic fatigue syndrome were compared to healthy seropositive control subjects in an open study and a case-control study analyzing spontaneous transformation rates of peripheral blood lymphocytes, EBV viral genome characteristics as determined by DNA restriction fragment polymorphisms, and antibody production by Western blot analysis.

Thirty percent of patients versus 8% of control subjects underwent spontaneous transformation in the two studies. Viral genome patterns were overall similar to one another, with polymorphisms frequently present in BamHI B’, K, H, and Y fragments. Only one line was found with the EBNA-2B genotype.

Nineteen lines were found to contain viral DNA in the linear form suggesting active lytic replication. Western blot studies suggested that ill subjects made antibodies to lytic proteins more frequently than did healthy control subjects. Lack of control of EBV outgrowth in vitro is correlated with antibody evidence of active infection in vivo in some patients with chronic fatigue syndrome.

 

Source: Jones JF, Streib J, Baker S, Herberger M. Chronic fatigue syndrome: I. Epstein-Barr virus immune response and molecular epidemiology. J Med Virol. 1991 Mar;33(3):151-8. http://www.ncbi.nlm.nih.gov/pubmed/1679118

 

Infectious mononucleosis, Epstein-Barr virus, and chronic fatigue syndrome: a prospective case series

Abstract:

Epstein-Barr viral infection, specifically infectious mononucleosis, typically has a more protracted course than other acute viral illnesses. Some recent observers have additionally suggested the possibility that Epstein-Barr virus (EBV) is the etiologic infectious agent in chronic fatigue syndrome, based on the finding of higher proportions of elevated antibodies to the EBV early antigen in some patients complaining of chronic fatigue.

Straus et al reported on 23 patients with chronic fatigue, 83% of whom exhibited persistently elevated antibodies in modest titer to the early antigen. Ten of these patients had never fully recovered from an episode of acute infectious mononucleosis. Other studies had noted similar associations between persistently elevated antibodies to EBV-specific antigens and chronic symptoms in patients who presented with chronic symptoms after mononucleosis.

Three important antigen complexes, demonstrable by immunofluorescence procedures, are expressed in EBV-infected cells. The early antigen is thought to function perhaps in early replication of viral DNA. A late antigenic complex, the viral capsid antigen, may represent, in addition to structural capsid proteins, components of the viral enzymatic machinery for late phases of replication or transformation. The Epstein-Barr nuclear antigen is felt to function in viral transformation of host cells.

 

Source: Fark AR. Infectious mononucleosis, Epstein-Barr virus, and chronic fatigue syndrome: a prospective case series. J Fam Pract. 1991 Feb;32(2):202, 205-6, 209. http://www.ncbi.nlm.nih.gov/pubmed/1846641