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

 

Chronic fatigue syndrome in Minnesota

Abstract:

Chronic fatigue syndrome (CFS), an illness characterized by debilitating fatigue and a number of associated symptoms, was identified in 135 patients using the case definition provided in 1988. The demographic features of these patients, 97% of whom resided in Minnesota, were similar to those reported elsewhere.

About three-fourths of the cases occurred between 1984 and 1989, and in 123 (91.1%), the illness began with what appeared to be an acute infection. Patients had been ill for an average of 4.3 years before enrollment in the study.

Fatigue was their most troublesome symptom, although a majority of the patients rated most of the general symptoms and neuropsychological complaints associated with CFS as moderate or severe. Follow-up data obtained on 62 patients one year after initial evaluation revealed that none had completely recovered. However, about 40% reported some improvement in each of the CFS symptoms.

 

Source: Peterson PK, Schenck CH, Sherman R. Chronic fatigue syndrome in Minnesota. Minn Med. 1991 May;74(5):21-6. http://www.ncbi.nlm.nih.gov/pubmed/1861659

 

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

 

Human herpesvirus-6 (HHV-6) (short review)

Abstract:

Human Herpesvirus-6 is the etiological agent of Roseola infantum and approximately 12% of heterophile antibody negative infectious mononucleosis. HHV-6 is T-lymphotropic, and readily infects and lyses CD4+ cells. The prevalence rate of HHV-6 in the general population is about 80% (as measured by IFA) with an IgG antibody titer of 1:80. A lower prevalence, however, is observed in some countries.

HHV-6 is reactivated in various malignant and non-malignant diseases as well as in Chronic Fatigue Syndrome and transplant patients. Furthermore, elevated antibody titers were also observed in lymphoproliferative disorders, auto-immune diseases and HIV-1 positive AIDS patients. There appears to be some strain variability in HHV-6 isolates.

The GS isolates of HHV-6 (prototype) was resistant to Acyclovir, Gancyclovir, but its replication was inhibited by Phosphonoacetic acid and Phosphoformic acid. HHV-7 isolated from healthy individuals showed, by restriction analysis, that 6 out of 11 probes derived from two strains of HHV-6, cross-hybridized with DNA fragments, derived from HHV-7.

 

Source: Ablashi DV, Salahuddin SZ, Josephs SF, Balachandran N, Krueger GR, Gallo RC. Human herpesvirus-6 (HHV-6) (short review). In Vivo. 1991 May-Jun;5(3):193-9. http://www.ncbi.nlm.nih.gov/pubmed/1654146

 

Fibromyalgia, chronic fatigue syndrome, and myofascial pain syndrome

Abstract:

There continues to be an emerging body of literature related to fibromyalgia and the related conditions chronic fatigue syndrome and myofascial pain.

During the past year, the most notable contributions included a large multicenter study providing new diagnostic criteria for the classification of fibromyalgia and clinical studies describing the overlap of fibromyalgia, chronic fatigue syndrome, and myofascial pain.

Pathophysiologic studies were often preliminary and uncontrolled but the focus of these studies on abnormal nociception, neurohormones, and muscle metabolism provides an exciting hypothesis to unify pain, fatigue, and sleep disturbances, the primary symptoms of fibromyalgia. Unfortunately, new therapeutic trials were neither innovative nor especially encouraging.

 

Source: Goldenberg DL. Fibromyalgia, chronic fatigue syndrome, and myofascial pain syndrome. Curr Opin Rheumatol. 1991 Apr;3(2):247-58. http://www.ncbi.nlm.nih.gov/pubmed/2064904

 

Panic disorder among patients with chronic fatigue

Abstract:

Among 200 adults with a chief complaint of chronic fatigue evaluated in an internal medicine practice, currently active panic disorder was diagnosed in 26 patients (13%), a frequency tenfold greater than that in the general population. Panic disorder preceded or was coincidental with the onset of chronic fatigue in 21 of these patients.

In comparison with the rest of the study cohort, significantly more patients with panic disorder had a history of severe depression, including persistent thoughts of death or suicide. Moreover, more patients with panic disorder showed a lifetime tendency to have physical symptoms that remained unexplained after medical evaluation.

Our findings suggest that treatable panic disorder is an important contributor not only to major depression and somatization, but also to the etiology and clinical presentation of chronic fatigue in patients in an outpatient practice.

 

Source: Manu P, Matthews DA, Lane TJ. Panic disorder among patients with chronic fatigue. South Med J. 1991 Apr;84(4):451-6. http://www.ncbi.nlm.nih.gov/pubmed/2014428