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Fukuda Criteria - Annals Of Internal Medicine:Vol.121; #12 Dec15; 1994 pg 953-959

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The Chronic Fatigue Syndrome

Guidelines for the Clinical Evaluation and Study of the Chronic Fatigue Syndrome and Other Illnesses Associated with Unexplained Chronic Fatigue

Definition and Clinical Evaluation of
Prolonged Fatigue and Chronic Fatigue

Prolonged fatigue is defined as self-reported, persistent fatigue lasting I month or longer. Chronic fatigue is defined as self-reported persistent or relapsing fatigue lasting 6 or more consecutive months.

The presence of prolonged or chronic fatigue requires c1inical evaluation to identify underlying or contributing conditions that require treatment further diagnosis or classification of chronic fatigue cases cannot be made without such an evaluation. The following items should be included in the clinical evaluation.

1. A thorough history that covers medical and psychosocial circumstances at the onset of fatigue; depression or other psychiatric disorders; episodes of medically unexplained symptoms; a1coh01 or other substance abuse, and current use of prescription and over-the-counter medications and food supplements

2. A mental status examination to identify abnormalities in mood. Intellectual function, memory, and personality. Particular attention should be directed toward current symptoms of depression or anxiety, self-destructive thoughts, and observable signs such as psychomotor retardation Evidence of a psychiatric or neurologic disorder requires that an appropriate psychiatric, psychological, or neurologic evaluation be done.

3. A thorough physical examination.

4. A minimum battery of laboratory screening tests including complete blood count with leukocyte differential; erythrocyte sedimentation rate; serum levels of alanine aminotransferase, total protein, albumin, globulin, alkaline phosphatase, calcium, phosphorus, glucose, blood urea nitrogen, electrolytes, and creatinine; determination of thyroid-stimulating hormone; and urinalysis.

Routinely doing other screening tests for all patients has no known value (20, 30) 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 or procedures should be done according to accepted clinical standards. In these cases, the use of tests to diagnose the chronic fatigue syndrome (rather than to exclude 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 should be explained to the patient

In clinical practice, no additional tests, including laboratory tests and neuro imaging studies, can be recommended for the specific purpose of diagnosing the chronic fatigue syndrome. Tests should be directed toward confirming or excluding other etiologic possibilities. Examples of specific tests that do not confirm or exclude the diagnosis of the chronic fatigue syndrome include serologic tests for Epstein-Barr virus, retroviruses, human herpesvirus 6, enteroviruses, 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) of the head.

Conditions That Explain Chronic Fatigue

The following conditions exclude a patient from the diagnosis of unexplained chronic fatigue

I. Any active medical condition that may explain the presence of chronic fatigue (3 I), such as untreated hypothyroidism, sleep apnea, and narcolepsy, and iatrogenic conditions such as side effects of medication.

2. Any previously diagnosed medical condition whose resolution has not been documented beyond reasonable clinical doubt and whose continued activity may explain the chronic fatiguing illness. Such conditions may include previously treated malignancies and unresolved 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: dementia as of any subtype; anorexia nervosa, or bulimia nervosa.

4. Alcohol or other substance abuse within 2 years before the onset of the chronic fatigue and at any time afterward.

5. Severe obesity (32,33) as defined by a body mass index [body mass index= weight in kilograms/(height in meters)2] equal to or greater than 45. Any unexplained physical examination finding or laboratory or imaging test abnormality that strongly 5_;ggests the !"presence of an exclusionary condition must be resolved before further classification.

Conditions That Do Not Adequately Explain Chronic Fatigue

The following conditions do not exclude a patient from the diagnosis of unexplained chronic fatigue.

I. Any condition defined primarily by symptoms that cannot be confirmed by diagnostic laboratory tests, including Fibromyalgia, anxiety disorders, somatoform disorders. nonpsychotic or nonmelancholic 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 tlll1ction and other testing.

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

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 to strongly support a diagnosis of a discrete connective tissue disorder without other laboratory or clinical evidence.


The following are the other members of the International Chronic Fatigue Syndrome Study Group
National Institutes of Health, Bethesda,Maryland:
Ann Schluederberg, ScD; University of Colorado, Denver, Colorado:
James F. Jones, MD; Prince Henry Hospital and University of New South Wales, Sydney, Australia:
Andrew R. Lloyd, MD, FRACP; King's CoI1ege School of Medicine and Dentistry, London, United Kingdom:
Simon Wessely, MRCP, _1RC Psych; Polyclinic Medical Center and Pennsylvania State CoI1ege of Medicine, Harrisburg, Pennsylvania:
Nelson M. Gantz, MD; Texas A & M University Health Science Center and Scott & White Memorial Hospital, Temple, Texas:
Gary P. Holmes, MD; University of Washington Medical Center, Seattle, Washington:
Dedra Buchwald, MD; University of Toronto, Toronto, Canada:
Susan Abbey, MD, FRCP(C); University of California, San Francisco, San Francisco, California, and Aha Bates Hospital, Berkeley, California:
Jonathan Rest, MD; University of California, San Francisco, San Francisco, California:
Jay A. Levy, MD; Food and Drug Administration, Rockville, Maryland:
Heidi Jolson, MD, MPH; Lake Tahoe Medical Center, Incline Village, Nevada:
Daniel L. Peterson, MD; University Hospital Nijmegen, Nijmegen, the Netherlands:
JanH.M.M. Vercoulen, Pill; Centro Regionale di Riferminento Oncologico, Aviano, Italy:
Umberto Tirelli, MD; Karolinska Institute at Huddinge University Hospital, Stockholm, Sweden:
Birgitta Evengard, MD; New Jersey Medical School, Newark, New Jersey:
Benjamin H. Nate1son, MD; Centers for Disease Control and Prevention, Atlanta, Georgia:
Lea Steele, Michele Reyes, and William C.Reeves, MD.


The authors thank Carla Arpino, Judy Basso, Lyria Boast, Janet K. Dale, Karen Ezrine, Marya Grambs, K. Kimberly Kenney, Teruo Kitani, David Klonoff, Dorothy Knight, Gerhard R.F. Krueger, Hirohiko Kuratsune, Gudrun Lindh, Lars Lindquist, Lisa Livens, Alison Mawle, David McCluskey, John O'Connor, Orvalene Prewitt, Bonnie Randall, Karen B. Schmaling, Scott Schmid, John Stewart, Lars Wahlstrom, Denis Wakefield, and Andrew Wilson.

Requests for Reprints
Keiji Fukuda, MD, lVIPH, Mailstop A 15, Division of Viral and Rickettsial Diseases, National Center for Infectious Diseases Centers for Disease Control and Prevention, 1600 Clifton Road, Atlanta, GA 30333

Current Author Addresses:

Drs. Fukuda and Dobbins: Mailstop A I _Division of Viral and Rickettsial Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, 1600 Clifton Road, Atlanta, GA 30333.

Dr Straus: Clinical Center Room II N228, Laboratory of Clinical Investigation, National Institutes of Health, 9000 Rockville Pike. Bethesda, MD 20892.

Dr. Hickie: School of Psychiatry and Department of Infectious Diseases and Immunology, Prince Henry Hospital, University of New South Wales, Little Bay, NSW, 2036, Australia

Dr Sharpe: University of Oxford, Department of Psychiatry, Warneford Hospital, Oxford OX3 7JX. United Kingdom.

Dr.Komaroff: Division of General Medicine, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115

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