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Chronic
fatigue syndrome is defined as long-standing, severe, disabling
fatigue without demonstrable muscle weakness. Underlying disorders
that could explain the fatigue are absent. Depression, anxiety,
and other psychologic diagnoses are typically absent. Treatment is
rest and psychologic support, often including antidepressants.
This definition of chronic fatigue syndrome (CFS) has several variants, and heterogeneity among patients who meet the criteria of this definition is considerable. Prevalence is impossible to state precisely; it varies from 7 to 38/100,000 people. Prevalence may vary because of differences in diagnostic evaluation, physician-patient attitudes, social acceptability, risk of exposure to an infectious or toxic agent, or definition and case finding. CFS occurs slightly more often in females. In office-based studies, prevalence is highest among whites. However, community surveys indicate a higher prevalence among blacks, Hispanics, and American Indians than among whites.
Etiology
and Pathophysiology
Etiology is controversial, and the precise cause remains unknown. Psychologic factors may be the cause in an unknown percentage of cases; however, CFS seems to be distinct from typical depression, anxiety, or other psychologic disorders. A chronic viral infection has been proposed as a cause because many patients relate onset of CFS to an event similar to influenza or mononucleosis. Epstein-Barr virus has also been proposed as a cause, but immunologic markers of exposure do not appear to be sensitive or specific. Other possible but unproven viral causes include enteroviruses, human herpesvirus 6, and human T-cell lymphotropic virus. Allergic reactions have also been proposed; about 65% of patients report previous allergies, and the rate of cutaneous reactivity to inhalants or foods is 25 to 50% higher in this group than in the general population.
Various immunologic abnormalities have been reported; they include low levels of IgG, decreased lymphocytic proliferation, low interferon-γ levels in response to mitogens, and poor cytotoxicity of natural killer cells. Some patients have abnormal IgG, with circulating autoantibodies and immune complexes. Many other immunologic abnormalities have been studied; none provides adequate sensitivity and specificity for defining the syndrome. Additionally, no consistent or readily reproducible pattern of immunologic abnormalities has been identified.
Other proposed mechanisms include neuroendocrine abnormalities, abnormal levels of neurotransmitters, inadequate cerebral circulation, and elevated levels of ACE.
Data indicate that relatives of patients with CFS have an increased risk of developing the syndrome, suggesting a familial or genetic component.
Symptoms,
Signs, and Diagnosis
Onset is usually abrupt, and many patients report an initial viral-like illness with swollen lymph nodes, extreme fatigue, fever, and upper respiratory symptoms. The main symptom is severe fatigue (usually for ≥ 6 mo) that interferes with daily activities (see Table 1: Syndromes of Uncertain Origin: Diagnostic Criteria for Chronic Fatigue Syndrome for other symptoms).
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Table 1
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Diagnostic
Criteria for Chronic Fatigue Syndrome
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Unexplained, persistent, or relapsing chronic fatigue that is new or has a definite onset; that is not due to ongoing exertion; that is not substantially alleviated by rest; and that substantially reduces occupational, educational, social, or personal activities
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At least 4 of the following for ≥6 mo*:
Impaired short-term memory (self-reported) severe enough to substantially reduce occupational, educational, social, or personal activities
Tender, enlarged, painful cervical or axillary lymph nodes
Abdominal pain
Multijoint pain without joint swelling or tenderness (arthralgia)
Headaches that are new in type, pattern, or severity
Postexertional malaise lasting >24 h
Cognitive difficulties (especially with concentrating and sleeping)
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*Must not predate the fatigue.
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Data from the Centers for Disease Control and Prevention, the National Institutes of Health, and the International Chronic Fatigue Study Group.
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Usually, no signs of muscle weakness, arthritis, neuropathy, or organomegaly are present. However, some definitions require the presence of low-grade fever, nonexudative pharyngitis, or palpable or tender lymph nodes.
Because the cause is unknown, diagnosis is by clinical criteria (see Table 1: Syndromes of Uncertain Origin: Diagnostic Criteria for Chronic Fatigue Syndrome). Further evaluation aims to exclude treatable disorders. A reasonable assessment includes CBC and measurement of electrolytes, ESR, and thyroid-stimulating hormone. In some cases, chest x-ray and tests for antinuclear antibody, rheumatoid factor, hepatitis, and HIV should be added. Other viral antibody and other expensive tests are unlikely to shed light on the diagnosis or cause. Obvious depression or severe anxiety excludes the diagnosis of CFS.
Treatment
Nonsedating antidepressants are commonly prescribed, although their value is undetermined. Antiviral treatments with acyclovir and amantadine do not appear effective. Studies of immunologic treatments, including high-dose immune globulins, dialyzable WBC extract, amphigen, interferons, isoprinosine, and corticosteroids, have been inconclusive and mostly disappointing. Dietary supplements and high-dose vitamins are commonly used, but their usefulness has not been substantiated. Psychologic intervention (eg, individual or group therapy) may help some patients. Formal, structured physical rehabilitation programs may help. Persistent or prolonged rest should be firmly discouraged because it can worsen deconditioning and promote progressive frailty.
Last full review/revision November 2005
Content last modified November 2005
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