BMJ No. 7061 Volume 313 Saturday 5 October 1996
The term chronic fatigue syndrome is relatively new. It first appeared in the 1988 proposal by the United States Centers for Disease Control(2) to formalise a working case definition for symptoms that had been variously named and attributed to numerous causes for over two centuries. Through field testing, the case definition was revised and simplified in 1994.(3) In essence, it classifies a constellation of prolonged and debilitating symptoms as worthy of medical attention and study (see box). Related case criteria were developed by consensus at Oxford in 1991.(4) Neither the American nor the Oxford criteria assume the syndrome to be a single nosological entity. As the royal colleges' report concludes, the term chronic fatigue syndrome is appropriate because it carries none of the inaccurate aetiological implications of the alternative acronyms - myalgic encephalomyelitis, chronic fatigue syndrome, and immune dysfunction syndrome.
The new report reviews the epidemiology of chronic fatigue syndrome. It notes that chronic fatigue syndrome describes only the minority of the fifth or so of patients under primary care who present with chronic fatigue. Several perceived socioeconomic correlates of chronic fatigue syndrome that spawned colloquial names for the syndrome, such as "yuppie flu," have been dismissed by proper study. Only its greater prevalence in women has been confirmed, as in related syndromes like fibromyalgia.
There is no credible support for outbreaks or the transmissibility of chronic fatigue syndrome. The report addresses this vexing issue too tangentially, but through its comprehensive review of the data it does pointedly dismiss claims that chronic fatigue syndrome is a chronic viral infection. In the United States, the viral hypothesis of chronic fatigue syndrome has been a moving target, with new herpes viruses and putative retroviruses displacing in turn the association with chronic fatigue originally noted for Epstein-Barr virus.
In Britain, the pre-eminence of a neuromuscular hypothesis of chronic fatigue syndrome sustained a preoccupation with enteroviruses as aetiologic factors for two decades; the weight of evidence stands largely against this now. The report does note that one blinded study,(5) in which enteroviral sequences were detected more often in sera from patients than from healthy controls, still awaits repetition. Our own blinded study using polymerase chain reaction found no enteroviral RNA in sera or other specimens from patients or control subjects (H Rotbart et al, unpublished observations).
Although the persistence of known microbes does not explain chronic fatigue syndrome, the report nicely summarises recent British studies which confirm that acute infections can precipitate the syndrome.(6)(7) The mechanism is not known, but the cumulative data over several decades show that fatigue from an acute infection (or other acute stresses perhaps) can be sustained in certain predisposed individuals.(8)
Studies purporting to demonstrate immunological abnormalities in patients with chronic fatigue syndrome are justifiably criticised in the report for inconsistency, lack of standardisation of the laboratory methodologies, and nonspecificity of findings.(9) The report is more charitable towards recent neuroendocrine data, possibly because these are too preliminary to be either accepted or dismissed. The existing data suggest subtle abnormalities in the hypothalamic-pituitary-adrenal axis.(10) It will prove difficult to implement the report's recommendation that patients be assessed and managed using a biopsychosocial approach-that is, one which stresses the complex interplay of social, behavioural, and emotional factors in the presentation and perpetuation of symptoms. The report declares that, over multiple sessions, a trusting and non-authoritarian physician can engage a patient in a constructive therapeutic alliance in which there is a thoughtful application of a few key laboratory tests, administration of a few symptomatic medications, encouragement of very graded exercise, and progressive re-entry into school or work.
The report acknowledges "a number of difficulties in achieving this in practice," such as the resistance of some patients to psychosocial assessment and management. There are also important limitations for primary care physicians wishing to employ this approach. Few will have been properly trained, and few primary care settings are structured to facilitate the multidisciplinary collaborations necessary for a formal biopsychosocial intervention. In addition, increasing emphasis on cost containment by the NHS and by the United States' burgeoning managed care industry creates financial disincentives to such intensive regimens.
A more practical recommendation might be to study whether key elements of the biopsychosocial approach can be efficiently and effectively incorporated into the traditional health care environment. Here the report is resolute, as it should be: advances in the management of chronic fatigue syndrome must be based on careful research. Three well chosen areas of research are proposed: the neurobiology of fatigue, controlled therapeutic trials, and the assessment and management of children and adolescents.
STEPHEN E STRAUS
Chief
Laboratory of Clinical Investigation,
National Institute of Allergy and Infectious Diseases,
Bethesda, MA 20892,
USA
REFERENCES
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9 Strober W. Immunological function in chronic fatigue syndrome. In: Straus S, ed. Chronic fangue syndrome. New York; Mark Dekker, 1994; 207-40, 1961.
10 Demitrack M A, Dale J K, Straus S E, Laue L, Listwak S J, Kruesi M J P, et al. Evidence for impaired activation of the hypothalamic-pituitaty-adrenal axis In patients with chronic fatigue syndrome. J Clin Endocrinol Metab 1991;73;1-10.