Chronic tiredness and idiopathic chronic fatigue–a connection?

Abstract:

Evidence is adduced to support the proposal that pathological fatigue is a consequence of impaired capillary blood flow resulting in inadequate oxygen delivery, which is in accordance with physiological concepts of fatigue. Case reports are presented.

Comment in: Chronic fatigue syndrome. [N J Med. 1992]

 

Source: Simpson LO. Chronic tiredness and idiopathic chronic fatigue–a connection? N J Med. 1992 Mar;89(3):211-6. http://www.ncbi.nlm.nih.gov/pubmed/1574202

 

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

 

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/

 

Depression and somatization in the chronic fatigue syndrome

Abstract:

PURPOSE: To report the prevalence, clinical features, and diagnostic associations of the proposed chronic fatigue syndrome (CFS) in a cohort of patients with chronic fatigue and to assess the usefulness of a structured psychiatric interview for detecting previously unrecognized psychiatric morbidity in patients with CFS.

PATIENTS AND METHODS: A consecutive sample of 200 adult patients with a chief complaint of chronic fatigue was prospectively evaluated in a referral-based clinic within a university general medicine practice. All patients received a thorough medical history, physical examination, diagnostic laboratory testing, and portions of the Diagnostic Interview Schedule, version III-A. The criteria for CFS were applied, and patients with CFS were compared with matched control subjects from the inception cohort.

RESULTS: The 60 patients with CFS had similar likelihoods of current psychiatric disorders (78% versus 82%), active mood disorders (73% versus 77%), and preexisting psychiatric disorders (42% versus 43%) when compared with fatigued control subjects. Patients with CFS were more likely to have somatization disorder (p less than 0.001) and to attribute their illness to a physical cause (p less than 0.005) than fatigued controls. Patients with CFS also displayed functional symptoms, often lifelong, which are not part of the case definition of CFS. Depressive features in patients with CFS were similar to those of control subjects, but a trend toward suicidal behavior was noted.

CONCLUSIONS: Patients with CFS have a high prevalence of unrecognized, current psychiatric disorders, which often predate their fatigue syndrome. Assessment of patients with CFS should include a structured psychiatric evaluation.

 

Comment in:

Chronic fatigue syndrome and psychiatric disorders. [Am J Med. 1992]

Chronic fatigue syndrome (CFS) and psychiatric disorders. [Am J Med. 1994]

 

Source: Lane TJ, Manu P, Matthews DA. Depression and somatization in the chronic fatigue syndrome. Am J Med. 1991 Oct;91(4):335-44. http://www.ncbi.nlm.nih.gov/pubmed/1951377

 

Chronic fatigue in adolescents

Abstract:

Nine female and 6 male adolescents (mean age 14.5 +/- 1.7 [SD] years) were evaluated for chronic fatigue associated with at least three additional symptoms present for 18.4 +/- 8.4 months. Eleven subjects experienced the onset of symptoms with an acute illness (seven Monospot-positive). Medical history, physical examination, and laboratory testing yielded little helpful information. Serologic testing for Coxsackie B viruses 1 through 6, cytomegalovirus, Epstein-Barr virus, human herpesvirus 6, and Toxoplasma gondii in subjects and healthy controls provided little evidence for an infectious cause of persistent fatigue.

Children’s Depression Inventory scores and psychiatric interviews with the Schedule for Affective Disorders and Schizophrenia-Children’s Version (K-SADS) identified five subjects with major depression. On the K-SADS, the 10 fatigued subjects without major depression endorsed many secondary symptoms of depression but were less likely than depressed psychiatric clinic patients to endorse primary symptoms such as depressed mood, guilt, and suicidality. At telephone follow-up 13 to 32 months after intake, 4 subjects were completely well, 4 markedly improved, and 7 unimproved or worse.

Further research is necessary to determine whether chronic fatigue in adolescents is prodromal depression, a discrete psychosomatic condition, or an infectious or immunologic disorder that mimics depression.

Comment in:

Chronic fatigue in children: illness or disease? [Pediatrics. 1993]

Chronic fatigue immune dysfunction syndrome: an epidemic? [Pediatrics. 1992]

Chronic fatigue immune dysfunction syndrome: an epidemic? [Pediatrics. 1992]

Chronic fatigue immune dysfunction syndrome: an epidemic? [Pediatrics. 1992]

 

Source: Smith MS, Mitchell J, Corey L, Gold D, McCauley EA, Glover D, Tenover FC. Chronic fatigue in adolescents. Pediatrics. 1991 Aug;88(2):195-202. http://www.ncbi.nlm.nih.gov/pubmed/1861915

 

Psychiatric illness in patients with chronic fatigue and those with rheumatoid arthritis

Abstract

OBJECTIVES: To identify psychiatric differences between patients with chronic fatigue and those with rheumatoid arthritis and to investigate whether patients meeting Centers for Disease Control (CDC) criteria for chronic fatigue syndrome (CFS) can be differentiated from patients with chronic fatigue on measures of disability and psychosocial distress.

DESIGN: Cross-sectional study comparing 98 patients with chronic fatigue with 31 patients with rheumatoid arthritis on structured psychiatric interviews and patient questionnaires. Nineteen patients meeting CDC criteria for CFS were compared with 79 patients with chronic fatigue not meeting CDC criteria on questionnaires measuring disability and psychosocial distress.

SETTING: Consecutive patients with chronic fatigue were selected from a chronic fatigue clinic at the University of Washington, and 31 consecutive patients with rheumatoid arthritis were sampled from a private rheumatology practice.

MAIN RESULTS: Patients with chronic fatigue had a significantly higher prevalence of lifetime major depression and somatization disorder than did patients with rheumatoid arthritis. Patients with chronic fatigue also had a significantly higher prevalence of current and lifetime psychiatric diagnoses. Only 19 of 98 patients with chronic fatigue met CDC criteria for CFS. Patients meeting CDC criteria for CFS could not be differentiated from the larger group of patients with chronic fatigue on any study variable.

CONCLUSIONS: Patients with chronic fatigue have a significantly higher burden of psychiatric illness than do patients with rheumatoid arthritis. The psychiatric illness preceded the development of chronic fatigue in over half the patients. Centers for Disease Control criteria for CFS did not select a subset of chronic fatigue patients who could be differentiated on disability or psychosocial parameters from patients with chronic fatigue who did not meet CDC criteria.

Comment in The trouble with chronic fatigue. [J Gen Intern Med. 1991]

 

Source: Katon WJ, Buchwald DS, Simon GE, Russo JE, Mease PJ. Psychiatric illness in patients with chronic fatigue and those with rheumatoid arthritis. J Gen Intern Med. 1991 Jul-Aug;6(4):277-85. http://www.ncbi.nlm.nih.gov/pubmed/1890495

 

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

 

Chronic fatigue in children: clinical features, Epstein-Barr virus and human herpesvirus 6 serology and long term follow-up

Abstract:

During a 2-year period, 23 patients (14 girls, 9 boys) with chronic fatigue were referred to the Pediatric Infectious Disease Clinic of a tertiary care center, representing 19% of all out-patients seen in that clinic during that time. The median age was 14 years and the median duration of symptoms before referral was 6 months; 65% had missed at least 2 weeks of school and 30% required a home tutor.

There were few positive physical findings and no elevation of white blood cell count (median, 7000/mm3) or erythrocyte sedimentation rate (median, 5 mm/hour). Twenty-five percent had no evidence of Epstein-Barr virus infection, 15% had current or recent infection and 60% had past infection; 33% of the latter had detectable antibody to early antigen but the titers were low. Human herpesvirus 6 titers in 8 patients were similar to those in age- and sex-matched controls.

Of 17 patients contacted after a median of 26 months, 76% reported definite improvement, although 38% of these still experienced occasional symptoms. In this referral population chronic fatigue was a common presenting complaint, was associated with marked degrees of dysfunction and bore no relationship to Epstein-Barr virus or human herpesvirus 6 infection. In most children the disorder was self-limited, although a minority were persistently or severely affected.

 

Source: Marshall GS, Gesser RM, Yamanishi K, Starr SE. Chronic fatigue in children: clinical features, Epstein-Barr virus and human herpesvirus 6 serology and long term follow-up. Pediatr Infect Dis J. 1991 Apr;10(4):287-90. http://www.ncbi.nlm.nih.gov/pubmed/1648198

 

Clinical and laboratory findings in the Paul-Bunnell negative glandular fever-fatigue syndrome

Abstract:

Forty-one patients with recurrent fatigue were studied for evidence of symptom clustering, abnormal laboratory findings and infection with novel viruses. Symptom enquiry and investigations were repeated 4 months later.

Four patients were found to have diseases compatible with their symptoms. In those remaining, an initial acute onset of symptoms was associated with an intermittent course, tender glands and a raised number of T suppressor lymphocytes. Raised numbers of T suppressor lymphocytes at follow-up correlated with resolution of symptoms. Antibodies to human herpesvirus 6 (HHV-6) were found in 75% of the patients as compared to 53% of a control group and more patients than controls were strongly seropositive.

Some patients with chronic fatigue have a pattern of illness which suggests glandular fever, although acute infection with Epstein-Barr virus (EBV) is not demonstrated. Primary or reactivation infection with HHV-6 may have a role in this syndrome.

 

Source:  Read R, Larson E, Harvey J, Edwards A, Thomson B, Briggs M, Fox J. Clinical and laboratory findings in the Paul-Bunnell negative glandular fever-fatigue syndrome. J Infect. 1990 Sep;21(2):157-65. http://www.ncbi.nlm.nih.gov/pubmed/2172387

 

Chronic fatigue. A prospective clinical and virologic study

Abstract:

To evaluate the clinical and virologic course of patients with chronic fatigue who had elevated Epstein-Barr virus (EBV) titers, we prospectively followed up 26 patients with serial cultures for EBV in blood and saliva and serial EBV serologic and clinical and psychiatric evaluations, and we compared these results with those for healthy controls.

The frequency of isolating EBV in blood or demonstrating EBV infection by in situ hybridization in blood lymphocytes or in saliva was similar in patients and controls. The prevalence and titers of antibody to human herpesvirus type 6 were also similar in the two populations. Patients with chronic fatigue did demonstrate higher in vitro natural killer activity and lower in vitro interleukin 2 production than controls, and patients had a high frequency of DSM-III depressive illness. Over 50% of patients with chronic fatigue improved over the course of follow-up. Improvement was not associated with any discernible change in titers of EBV proteins.

No evidence of ongoing EBV infection with either transforming or nontransforming strains was demonstrated in this population of patients with chronic fatigue. Clinically, most patients gradually improve over time.

 

Source: Gold D, Bowden R, Sixbey J, Riggs R, Katon WJ, Ashley R, Obrigewitch RM, Corey L. Chronic fatigue. A prospective clinical and virologic study. JAMA. 1990 Jul 4;264(1):48-53. http://www.ncbi.nlm.nih.gov/pubmed/2162397