Cell-mediated immunity in patients with chronic fatigue syndrome, healthy control subjects and patients with major depression

Abstract:

The chronic fatigue syndrome (CFS) is characterized by severe persistent fatigue and neuropsychiatric symptoms. It has been proposed that the abnormalities in cell-mediated immunity which have been documented in patients with CFS may be attributable to a clinical depression, prevalent in patients with this disorder.

Cell-mediated immune status was evaluated in patients with carefully defined CFS and compared with that of matched subjects with major depression (non-melancholic, non-psychotic) as well as healthy control subjects.

Patients with CFS demonstrated impaired lymphocyte responses to phytohaemagglutinin (PHA) stimulation, and reduced or absent delayed-type hypersensitivity (DTH) skin responses when compared either with subjects with major depression or with healthy control subjects (P less than 0.05 for each analysis).

Although depression is common in patients with CFS, the disturbances of cell-mediated immunity in this disorder differ in prevalence and magnitude from those associated with major depression. These observations strengthen the likelihood of a direct relationship between abnormal cell-mediated immunity and the etiology of CFS.

 

Source: Lloyd A, Hickie I, Hickie C, Dwyer J, Wakefield D. Cell-mediated immunity in patients with chronic fatigue syndrome, healthy control subjects and patients with major depression. Clin Exp Immunol. 1992 Jan;87(1):76-9. http://www.ncbi.nlm.nih.gov/pubmed/1733640

Note : You can read the full article here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1554231/

 

Hypothesis: cytokines may be activated to cause depressive illness and chronic fatigue syndrome

Abstract:

Abnormalities in the regulation of the hypothalamo-pituitary-adrenal (HPA) axis are a well recognised feature of endogenous depression. The mechanism underlying this phenomenon remains obscure although there is strong evidence suggesting excessive CRH activity at the level of the hypothalamus.

We propose a novel hypothesis in which we suggest that the aetiological antecent to CRH hyperactivity is cytokine activation in the brain. It is now well established both that interleukins -1 and -6 are produced in a number of central loci and that cytokines are potent stimulators of the HPA axis.

Hence, we suggest that activation of IL-1 and IL-6 by specific mechanisms (such as neurotropic viral infection) in combination with the consequent CRH-41 stimulation, may (via their known biological effects) underly many of the features found in major depression and other related disorders, particularly where chronic fatigue is a prominent part of the symptom complex.

This theory has considerable heuristic value and suggests a number of experimental stratagems which may employed in order to confirm or reject it.

 

Source: Ur E, White PD, Grossman A. Hypothesis: cytokines may be activated to cause depressive illness and chronic fatigue syndrome. Eur Arch Psychiatry Clin Neurosci. 1992;241(5):317-22. http://www.ncbi.nlm.nih.gov/pubmed/1606197

 

Immune responsiveness in chronic fatigue syndrome

Comment on: Immune responsiveness in chronic fatigue syndrome. [Postgrad Med J. 1991]

 

Sir, The paper by Milton and colleagues (1) challenges the hypothesis that patients with postviral fatigue syndrome (myalgic encephalomyelitis) have a persisting viral infection along with consequent immune dysregulation. The protocol employed in the study suggests that their conclusions may not be valid.

Firstly, the 31 patients were selected from a group attending a ‘muscle clinic’ who complained of ‘unexplained chronic fatigue’. Of these only 15 had a clear history of a precipitating viral illness – a key diagnostic feature of postviral fatigue syndrome. Secondly, although other research groups have also demonstrated that raised levels of Coxsackie B virus IgG and IgM antibodies are not diagnostic of the syndrome, (2) these findings cannot be used to exclude the possibility of persisting viral infection within either muscle or the central nervous system.

As far as muscle is concerned, Gow and colleagues( 3) have recently detected enteroviral RNA sequences in muscle biopsies of 53% of patients with a well-defined postviral fatigue syndrome compared to 15% in a control group, and Archard et al. (4) have shown that this persisting enterovirus is poorly replicating.

Demonstrating the presence of persisting virus within the central nervous system is obviously far more difficult without autopsy material. However, Daugherty et al. (5) in America have published the results of MRI scans and cognitive function tests on 20 patients (with age and sex matched healthy controls) showing abnormalities consistent with an organic brain syndrome similar to that seen in patients who are positive for human immunodeficiency virus.

You can read the rest of this letter here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2399327/pdf/postmedj00061-0069a.pdf

 

Source: Shepherd C. Immune responsiveness in chronic fatigue syndrome. Postgrad Med J. 1992 Jan;68(795):66-7. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2399327/

 

Conversation piece

Dr E.G. Dowsett is Honorary Consultant Microbiologist, Basildon and Thurrock Health Authority and is the President of the Myalgic Encephalomyelitis Society.

 

DR P.D. WELSBY: I, and indeed many general physicians, are often asked to see patients whose main complaint is ‘tiredness all the time (TATT)’. From my previous experience also of general practice it seems that there is a wide continuous spectrum of debility ranging from a few days or weeks, but sometimes, distressingly, lasting for years. Such illnesses may or may not follow symptoms of an infection. Does the Myalgic Encephalomyelitis (ME) Society differentiate between post-viral debility, postinfectious (often an undefined infection) fatigue syndrome, chronic fatigue syndrome and ME? If so, how, and should it make any difference to medical management?

DR E.G. DOWSETT: One of the most striking features of ME is that the patient is not tired all the time! Extreme and sudden variability of energy levels both within and between episodes of illness differentiate this syndrome from other diseases associated with fatigue. One can only deplore the current fashion in the United States as well as the United Kingdom to redefine and rename a disability which has been clearly described in the literature for at least 100 years.’ There is nothing to be said in favour of the American acronym CFIDS (chronic fatigue immune deficiency syndrome) with its connotation of a primary immune dysfunction. The term ‘chronic fatigue syndrome’ recently adopted in this country also is nonspecific and non-descriptive because most of the definition is based on a vast number of exclusions (some of which, for example, endocrine disturbance, are actually found in ME). ‘Post-viral fatigue syndrome’, another British name, describes one essential feature (the association of the illness with viral infection) but gives the impression that the infection was antecedent rather than, as we now know, persistent. I prefer to use the more specific term ‘myalgic encephalomyelitis’ as it emphasizes the essential encephalitic component of the illness, the muscle pain, and the close clinical and epidemiological similarity to poliomyelitis.

You can read the rest of this interview here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2399326/pdf/postmedj00061-0066.pdf

 

Source: E. G. Dowsett. Conversation piece. Interview by P. D. Welsby.Postgrad Med J. 1992 Jan; 68(795): 63–65. PMCID: PMC2399326 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2399326/

 

Chronic fatigue syndrome

Comment on: Chronic fatigue syndrome. [J Neurol Neurosurg Psychiatry. 1991]

 

As neurologists in a country where the chronic fatigue syndrome (CFS) has almost no recognized official existence, we often feel bewildered by the papers on the subject we read in the Anglo-Saxon literature. We wonder whether the clinical experience of some of their authors is so different from ours that they do not consider that their approach may result in a disservice to their patients. The JNNP has followed a sensitive line culminating in Wessely’s excellent editorial. We still, however, feel that his kid-glove handling of the subject reflects the controversy that surrounds it in the UK.

Avoiding the futile organic versus functional debate, in our neurology department we refer to many of the problems we see in our practice as the “chronic vigilance syndromes”: specific patterns of enhanced attention centred on particular bodily structures and functions. Naturally, the commonest in a neurologist’s outpatient clinic are the “cephalic vigilance syndromes” in their two main forms: the painful, with its several varieties of chronic headaches, and the operational one with its subjective unsteadiness, concentration problems and various odd turns. “Thoracic vigilance” patients are often referred to cardiologists or pneumologists but a fair number also come to us, especially if they have hyperventilation symptoms such as dizziness and paraesthesiae. Among the different types of patients with fatigue we are also familiar with the occasional “neuro-muscular vigilance” patient whose symptoms parallel your CFS cases. We have the noncontrolled impression that in our environment such patients often have a premorbid preoccupation with their locomotor system.

You can read the rest of this comment here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC488951/pdf/jnnpsyc00486-0096a.pdf

 

Source: Digon A, Goicoechea A, Moraza MJ. Chronic fatigue syndrome. J Neurol Neurosurg Psychiatry. 1992 Jan;55(1):85. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC488951/

 

Chronic fatigue syndrome and women: can therapy help?

Abstract:

This article presents current research on chronic fatigue syndrome, which currently afflicts mostly females between the ages of 25 and 55. Because depression is a common symptom of chronic fatigue syndrome, mental health practitioners are often involved with the victims and must formulate an appropriate treatment strategy that considers the physiological, intrapsychic, interpersonal, and environmental aspects of the client. This article includes case material focusing on a woman who was medically diagnosed with the Epstein-Barr virus and was in psychotherapy with the author. The difficulty of managing the interplay of the real health problems and the emotional issues presented by the client is highlighted.

Comment in:

“Chronic fatigue syndrome and women: can therapy help?”. [Soc Work. 1992]

“Chronic fatigue syndrome and women: can therapy help?”. [Soc Work. 1992]

“Chronic fatigue syndrome and women: can therapy help?”. [Soc Work. 1992]

Source: Burke SG. Chronic fatigue syndrome and women: can therapy help? Soc Work. 1992 Jan;37(1):35-9.  http://www.ncbi.nlm.nih.gov/pubmed/1542805

 

Alleged link between hepatitis B vaccine and chronic fatigue syndrome

In 1989, 3456 cases of hepatitis B were reported in Canada. It is generally accepted that the true incidence of the disease is about 10 times the reported incidence.

Hepatitis B virus is a major cause of acute and chronic hepatitis, cirrhosis and primary hepatocellular carcinoma. Chronic hepatitis may develop in 10% of infected adults and 90% of infected infants and may progress to cirrhosis and hepatocellular carcinoma. In its acute form hepatitis B is fatal in a small number of cases. The disease is transmitted through sexual contact and infected blood and other body fluids. Carriers frequently show no symptoms until later in life and may therefore infect others unknowingly.

Hepatitis B vaccine has been used in populations that have an established risk of infection with known consequences (e.g., health care workers, male homosexuals and injection drug users).

Recent attention in the Canadian press has focused on the possible association between hepatitis B vaccination and chronic fatigue syndrome (CFS).

You can read the rest of this article here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1488229/pdf/cmaj00290-0039.pdf

 

Source: [No authors listed] Alleged link between hepatitis B vaccine and chronic fatigue syndrome. CMAJ. 1992 Jan 1;146(1):37-8. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1488229/

 

Chronic fatigue syndromes in clinical practice

Abstract:

Chronic fatigue is a common and difficult challenge in clinical practice. The majority of patients with this chief complaint have treatable mood or anxiety disorders, complicated by a tendency toward somatization. A minority of patients suffer from sleep disorders, endocrinologic abnormalities, or chronic inflammatory conditions. Prolonged recovery after viral infections is only rarely the cause of chronic fatigue. Specific pharmacologic interventions and cognitive-behavioral therapy are effective in an environment that is sensitive to the patient’s interpretation of symptoms and avoids unproven medical investigations and therapies.

 

Source: Manu P, Lane TJ, Matthews DA. Chronic fatigue syndromes in clinical practice. Psychother Psychosom. 1992;58(2):60-8. http://www.ncbi.nlm.nih.gov/pubmed/1484921

 

The pathophysiology of chronic fatigue syndrome: confirmations, contradictions, and conjectures

Abstract:

OBJECTIVE: To examine published data regarding patient cohorts with the recently defined chronic fatigue syndrome.

METHOD: Review of thirty-two peer-assessed research publications that included full disclosure of the methodology employed; classification of the findings as confirmed, contradictory, or non-duplicated.

RESULTS: Research studies have confirmed that the majority of patients with the chronic fatigue syndrome: 1) are white middle-aged women, 2) have a high prevalence of current major depression and somatization disorder, 3) have abnormal personality traits, 4) believe that their fatigue has a physical cause, and 5) show mild abnormalities of humoral immunity. Contradictory data have been presented with regard to: 1) the time of onset of depressive disorders, 2) the etiologic role of herpetic and enteroviral infections, 3) the presence of abnormal cellular immunity, and 4) the clinical utility of immunoglobulin therapy. Non-duplicated research has indicated 1) hypothalamic-pituitary-adrenal axis dysfunction, 2) abnormalities on magnetic resonance images of the brain, 3) altered cytokine production, and 4) the possibility of retroviral infection.

CONCLUSIONS: As presently defined, the chronic fatigue syndrome has many of the clinical and biological features associated with depressive and somatoform disorders. A specific etiologic role for infections or immune dysfunction has not been confirmed.

 

Source: Manu P, Lane TJ, Matthews DA. The pathophysiology of chronic fatigue syndrome: confirmations, contradictions, and conjectures. Int J Psychiatry Med. 1992;22(4):397-408. http://www.ncbi.nlm.nih.gov/pubmed/1338059

 

Tired all the time

General practitioners often see a syndrome they call “tired all the time.” How often doctors see it depends on how tiredness is defined and where it is measured. Morrell recorded fatigue as the most important reason for consultation in 24 per 2000 registered patients in one year 1; Jerrett recorded fatigue as a presenting or supporting symptom in 150 per 2000 registered patients.2 Yet patients may not necessarily mention fatigue when they consult. A survey of patients waiting in one surgery found that a tenth reported “substantial fatigue” for a month or more 3; 18-34% of respondents in a community survey reported always feeling tired in the past month 4; and when young women patients were asked to record symptoms in diaries 400 episodes of fatigue were recorded for every one reported to the doctor.5 Clinicians may regard this iceberg as a puzzle, and a blessing. But how should they manage the cases that do present?

Little has been published on tiredness in primary care, with only one prospective study from Britain2 and two retrospective ones from American family practice.67 The results suggest that psychosocial causes are paramount in 40-51% of cases and physical causes in 21-39%.267 The remaining cases are of mixed or undetermined cause. Fatigue presents three times more often in women of childbearing age,2 who often have a working day that is long and difficult to organise, with no boundary between home and work.8 The wise doctor steers between the extremes of trivialising and medicalising such “social” fatigue. If the cause is existential rather than medical counselling may help the patient consider various alternatives and make new choices.

You can read the rest of this article here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1671843/pdf/bmj00157-0008.pdf

 

Source: Ridsdale L. Tired all the time. BMJ. 1991 Dec 14;303(6816):1490-1. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1671843/