Elsevier

The Lancet

Volume 367, Issue 9507, 28 January–3 February 2006, Pages 346-355
The Lancet

Review
Chronic fatigue syndrome

https://doi.org/10.1016/S0140-6736(06)68073-2Get rights and content

Summary

During the past two decades, there has been heated debate about chronic fatigue syndrome (CFS) among researchers, practitioners, and patients. Few illnesses have been discussed so extensively. The existence of the disorder has been questioned, its underlying pathophysiology debated, and an effective treatment opposed; patients' organisations have participated in scientific discussions. In this review, we look back on several controversies over CFS with respect to its definition, diagnosis, pathophysiology, and treatment. We review issues of epidemiology and clinical manifestations, focusing on the scientific status of CFS. Modern neuroscience and genetics research offer interesting findings for new hypotheses on the aetiology and pathogenesis of the illness. We also discuss promising future issues, such as psychopathophysiology and mechanisms of improvement, and suggest multidisciplinary prospective studies of CFS and fatigue in the general population. These studies should pay particular attention to similarities to and differences from functional somatic syndromes and other fatiguing conditions.

Section snippets

Definitions

The first studies of CFS were limited by the lack of proper diagnostic features and definitions. From 1988 onwards, several case definitions of CFS were developed.10, 11, 12 In 1994, a consensus was reached on a revised case definition from the US Centers for Disease Control and Prevention13 (panel). The importance of criteria on non-specific accompanying symptoms has been questioned, since the number of additional symptoms depends strongly on the assessment method used and no differences have

Epidemiology and prognosis

The difficulties with definition have affected the results of epidemiological studies. Prevalence varies widely. For this reason, only studies using the 1994 case definition of the Centers for Disease Control and Prevention have been reviewed. Two US community-based CFS studies found prevalences among adults of 0·23% and 0·42%; the rates were higher in women, members of minority groups, and people with lower educational attainment and occupational status.22, 23 A prospective primary-care study

Clinical manifestations

The main complaint of patients with CFS is persistent severe fatigue, but most have many concomitant symptoms and, in some, complaints of pain and cognitive dysfunction are just as prominent as the fatigue. Unprompted, patients mention an average of eight complaints and report symptoms of myalgia, impaired memory or concentration, gastrointestinal problems, headaches, and pain in muscles or several joints.30 Dizziness, nausea, anorexia, and night sweats are also reported.31 Many patients,

Aetiology

Many studies have investigated the aetiology and pathogenesis of CFS. More than half of the CFS studies between 1980 and 1995 concentrated on the physical aetiology of CFS, with a slight shift towards psychological and psychiatric research in the next few years.40 Many somatic and psychosocial hypotheses on the aetiology of CFS have been explored. Explanations for CFS were sought in viral infections, immune dysfunction, neuroendocrine responses, dysfunction of the central nervous system, muscle

Pathophysiology

The nature of the underlying pathophysiology of CFS remains unclear. Many biological mechanisms have been hypothesised. Abnormalities in the central nervous system and immune system have been extensively studied. Evidence of discrete neuroendocrine abnormalities has been found. Neuroendocrine challenge tests have found a lower than normal cortisol response to increased corticotropin concentrations and upregulation of the serotonergic system. Studies of neuroendocrine function in patients with

Diagnosis and management

Guidelines for clinical management of CFS have received much less attention than those for its definition. Although CFS protocols have been developed,9, 20 clinicians still express difficulty in diagnosing the disorder. Apart from having to cope with the definition difficulties, they also have to deal with patients who can present their complaints of severe fatigue in different ways. Some patients simply wonder what is going on, whereas others diagnose CFS/ME themselves, which can lead to

Treatment

Systematic reviews have investigated the effectiveness of several CFS treatments.99, 100, 101 CBT and graded exercise therapy (GET) are the only interventions found to be beneficial. The subtle changes found in the hypothalamopituitary-adrenal axis have led to two randomised controlled trials, on the basis of which the researchers have not concluded that steroids are the treatment of choice.102, 103 For immunological interventions such as immunoglobulin, the evidence has been inconclusive.

The future

Although adherents of biopsychosocial and pathological CFS models have made steps towards agreement on definition and diagnosis,131 some of the patients' organisations seem to share the opinion that the success of CBT confirms the bias that CFS has a psychogenic cause. This argument reinforces the old model in which diseases or complaints are considered as either somatic or psychiatric in origin. In modern medicine, the biopsychosocial approach should guarantee that both facets are attended to.

Search strategy and selection criteria

We searched the Cochrane Database of Systematic Reviews (Cochrane Reviews) and the Cochrane Database of Methodology Reviews (Methodology Reviews) up to April, 2005, and MEDLINE, PubMed, and PsycInfo from 1988 to the present. The keywords we used were “chronic fatigue syndrome” and “myalgic encephalomyelitis” in relation to epidemiology, aetiology, pathophysiology, diagnosis, definition, prognosis, prevention, and genetics. For the history of chronic fatigue syndrome, we searched the

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