Chronic Fatigue Syndrome: A Working Case DefinitionHolmes et al 1988
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A case of the chronic fatigue syndrome must fulfill major criteria 1 and 2, and the following minor criteria: 6 or more of the 11 symptom criteria and 2 or more of the 3 physical criteria; or 8 or more of the 11 symptom criteria.MAJOR CRITERIA
1. New onset of persistent or relapsing, debilitating fatigue or easy fatigability in a person who has no previous history of similar symptoms, that does not resolve with bedrest, and that is severe enough to reduce or impair average daily activity below 50% of the patient's premorbid activity level for a period of at least 6 months.
2. Other clinical conditions that may produce similar symptoms must be excluded by thorough evaluation, based on history, physical examination, and appropriate laboratory findings. These conditions include malignancy; autoimmune disease; localized infection (such as occult abscess); chronic or subacute bacterial disease (such as endocarditis, Lyme disease, or tuberculosis), fungal disease (such as histoplasmosis, blastomycosis, or coccidioidomycosis), and parasitic disease (such as toxoplasmosis, amebiasis, giardiasis, or helminthic infestation); disease related to human immunodeficiency virus (HIV) infection; chronic psychiatric disease, either newly diagnosed or by history (such as endogenous depression; hysterical personality disorder; anxiety neurosis; schizophrenia; or chronic use of major tranquilizers, lithium, or antidepressive medications); chronic inflammatory disease (such as sarcoidosis, Wegener granulomatosis, or chronic hepatitis); neuromuscular disease (such as multiple sclerosis or myasthenia gravis); endocrine disease (such as hypothyroidism, Addison disease, Cushing syndrome, or diabetes mellitus); drug dependency or abuse (such as alcohol, controlled prescription drugs, or illicit drugs); side effects of a chronic medication or other toxic agent (such as a chemical solvent, pesticide, or heavy metal); or other known or defined chronic pulmonary, cardiac, gastrointestinal, hepatic, renal, or hematologic disease.
Specific laboratory tests or clinical measurements are not required to satisfy the definition of the chronic fatigue syndrome, but the recommended evaluation includes serial weight measurements (weight change of more than 10% in the absence of dieting suggests other diagnoses); serial morning and afternoon temperature measurements; complete blood count and differential; serum electrolytes; glucose; creatinine, blood urea nitrogen; calcium, phosphorus; total bilirubin, alkaline phosphatase, serum aspartate aminotransferase, serum alanine aminotransferase; creatine phosphokinase or aldolase; urinalysis; posteroanterior and lateral chest roentgenograms; detailed personal and family psychiatric history; erythrocyte sedimentation rate; antinuclear antibody; thyroid-stimulating hormone level; HIV antibody measurement; and intermediate-strength purified protein derivative (PPD) skin test with controls.
If any of the results from these tests are abnormal, the physician should search for other conditions that may cause such a result. If no such conditions are detected by a reasonable evaluation, this criterion is satisfied.MINOR CRITERIA
To fulfill a symptom criterion, a symptom must have begun at or after the time of onset of increased fatigability, and must have persisted or recurred over a period of at least 6 months (individual symptoms may or may not have occurred simultaneously). Symptoms include:
1. Mild fever - oral temperature between 37.5 degrees C and 38.6 degreesC, if measured by the patient - or chills. (Note: oral temperatures of greater than 38.6 degrees C are less compatible with chronic fatigue syndrome and should prompt studies for other causes of illness.)
2. Sore throat.
3. Painful lymph nodes in the anterior or posterior cervical or axillary distribution.
4. Unexplained generalized muscle weakness.
5. Muscle discomfort or myalgia.
6. Prolonged (24 hours or greater) generalized fatigue after levels of exercise that would have been easily tolerated in the patient's premorbid state.
7. Generalized headaches (of a type, severity, or pattern that is different from headaches the patient may have had in the premorbid state).
8. Migratory arthralgia without joint swelling or redness.
9. Neuropsychologic complaints (one or more of the following: photophobia, transient visual scotomata, forgetfulness, excessive irritability, confusion, difficulty thinking, inability to concentrate, depression).
10. Sleep disturbance (hypersomnia or insomnia).
11. Description of the main symptom complex as initially developing over a few hours to a few days (this is not a true symptom, but may be considered as equivalent to the above symptoms in meeting the requirements of the case definition).Physical Criteria
Physical criteria must be documented by a physician on at least two occasions, at least 1 month apart.
1. Low-grade fever - oral temperature between 37.6° C and 38.6° C, or rectal temperature between 37.8° C and 38.8° C. (See note under Symptom Criterion 1.)
2. Nonexudative pharyngitis.
3. Palpable or tender anterior or posterior cervical or axillary lymph nodes. (Note: lymph nodes greater than 2 cm in diameter suggest other causes. Further evaluation is warranted.)
ACKNOWLEDGMENTS: The authors thank Mrs. Josephine M. Lister for manuscript preparation.
Requests for reprints should be addressed to Gary P. Holmes, M.D.; Division of Viral Diseases, Center for Infectious Diseases, Centers for Disease Control; Atlanta, GA 30333.
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