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The revised case definition of chronic fatigue syndrome

Centers for Disease Control and Prevention
National Center for Infectious Diseases
Atlanta, Georgia
March, 1995

(condensed from Fukuda, et al. Ann Intern Med 1994; 121:953-9.)

Summary of the underlying philosophy for revising the case definition.

The 1988 chronic fatigue syndrome working case definition (Holmes, et al. Ann Intern Med 1988;108:387-9) did not effectively distinguish CFS from other types of unexplained fatigue. For this reason, it was decided during a 1993 meeting of CFS investigators to develop a logical revision of that definition. The core of the revised CFS case definition is a set of uniformly applicable guidelines for the clinical and research evaluation of CFS and the other forms of fatigue.

In the revised definition, a consensus viewpoint of many of the leading CFS researchers and clinicians (including input from patient group representatives), chronic fatigue syndrome is treated as a subset of chronic fatigue, a broader category defined as unexplained fatigue of 6 months or longer. Chronic fatigue, in turn, is treated as a subset of prolonged fatigue, which is defined as fatigue lasting 1 or more months. The expectation is that scientists will devise epidemiologic studies of populations with prolonged fatigue and chronic fatigue, and search within those populations for illness patterns consistent with CFS.

Guidelines for the evaluation and study of CFS

A thorough medical history, physical examination, mental status examination, and laboratory tests (see diagram) must be conducted to identify underlying or contributing conditions that require treatment. Diagnosis or classification cannot be made without such an evaluation. Clinically evaluated, unexplained chronic fatigue cases can be classified as CFS if the patient meets both the following criteria:

1. Clinically evaluated, unexplained persistent or relapsing chronic fatigue that is of new or definite onset (i.e., not lifelong), is not the result of ongoing exertion, is not substantially alleviated by rest, and results in substantial reduction in previous levels of occupational, educational, social, or personal activities.

2. The concurrent occurrence of four or more of the following symptoms: substantial impairment in short-term memory or concentration; sore throat; tender lymph nodes; muscle pain; multijoint pain without swelling or redness; headaches of a new type, pattern, or severity; unrefreshing sleep; and postexertional malaise lasting more than 24 hours. These symptoms must have persisted or recurred during 6 or more consecutive months of illness and must not have predated the fatigue.

Conditions that exclude a diagnosis of CFS:
1. Any active medical condition that may explain the presence of chronic fatigue, such as untreated hypothyroidism, sleep apnea and narcolepsy, and iatrogenic conditions such as side effects of medication.

2. Some diagnosable illnesses may relapse or may not have completely resolved during treatment. If the persistence of such a condition could explain the presence of chronic fatigue, and if it cannot be clearly established that the original condition has completely resolved with treatment, then such patients should not be classified as having CFS. Examples of illnesses that can have these characteristics include some types of malignancies and chronic cases of hepatitis B or C virus infection.

3. Any past or current diagnosis of a major depressive disorder with psychotic or melancholic features; bipolar affective disorders; schizophrenia of any subtype; delusional disorders of any subtype; dementias of any subtype; anorexia nervosa; or bulemia nervosa.

4. Alcohol or other substance abuse that occurred within 2 years of the onset of chronic fatigue and any time afterwards.

5. Severe obesity as defined by a body mass index [body mass index = weight in kilograms (height in meters)2] equal to or greater than 45.

Clinical Evaluation and Classification of Chronic Fatigue

Any unexplained abnormality detected on examination or other testing that strongly suggests an exclusionary condition must be resolved before attempting further classification.

Conditions that do not exclude a diagnosis of CFS

1. Any condition defined primarily by symptoms that cannot be confirmed by diagnostic laboratory tests, including fibromyalgia, anxiety disorders, somatoform disorders, nonpsychotic or melancholic depression, neurasthenia, and multiple chemical sensitivity disorder.

2. Any condition under specific treatment sufficient to alleviate all symptoms related to that condition and for which the adequacy of treatment has been documented. Such conditions include hypothyroidism for which the adequacy of replacement hormone has been verified by normal thyroid- stimulating hormone levels, or asthma in which the adequacy of treatment has been determined by pulmonary function and other testing.

3. Any condition, such as Lyme disease or syphillis, that was treated with definitive therapy before development of chronic symptoms.

4. Any isolated and unexplained physical examination finding, or laboratory or imaging test abnormality that is insufficient to strongly suggest the existence of an exclusionary condition. Such conditions include an elevated antinuclear antibody titer that is inadequate, without additional laboratory or clinical evudence, to strongly support a diagnosis of a discrete connective tissue disorder.

A note on the use of laboratory tests in the diagnosis of CFS

As indicated in the diagram, a minimum battery of laboratory screening tests should be performed. Routinely performing other screening tests for all patients has no known value. However, further tests may be indicated on an individual basis to confirm or exclude another diagnosis, such as multiple sclerosis. In these cases, additional tests should be done according to accepted clinical standards.

The use of tests to diagnose CFS (as opposed to excluding other diagnostic possibilities) should be done only in the setting of protocol-based research. The fact that such tests are investigational and do not aid in diagnosis or management of the illness should be explained to the patient.

In clinical practice, no tests can be recommended for the specific purpose of diagnosing CFS. Tests should be directed toward confirming or excluding other possible clinical conditions. Examples of specific tests that do not confirm or exclude the diagnosis of CFS include serologic tests for Epstein-Barr virus, enteroviruses, retroviruses, human herpesvirus 6, and Candida albicans; tests of immunologic function, including cell population and function studies; and imaging studies, including magnetic resonance imaging scans and radionuclide scans (such as single-photon emission computed tomography and positron emission tomography).


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