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1988 CFS Criteria Holmes et al

Chronic Fatigue Syndrome: A Working Case Definition

Go TO :- The 1988 CDC  Holmes et al., CFS Symptoms - Definition

Bron: Ann Intern Med. 1988; 108:387-389.

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GARY P. HOLMES, M.D.; JONATHAN E. KAPLAN, M.D.; NELSON M. GANTZ, M.D.; ANTHONY L. KOMAROFF, M.D.; LAWRENCE B. SCHONBERGER, M.D.; STEPHEN E. STRAUS, M.D.; JAMES F. JONES, M.D.; RICHARD E. DUBOIS, M.D.; CHARLOTTE CUNNINGHAM-RUNDLES, M.D.; SAVITA PAHWA, M.D.; GIOVANNA TOSATO, M.D.; LEONARD S. ZEGANS, M.D.; DAVID T. PURTILO, IVI.D.; NATHANIEL BROWN, M.D.; ROBERT T. SCHOOLEY, M.D.; and IRENA BRUS, M.D.; Atlanta, Georgia; Worcester and Boston, Massachusetts; Bethesda, Maryland; Denver, Colorado; New York and Manhasset, New York; San Francisco, California; and Omaha, Nebraska

From the Division of Viral Diseases, Centers for Disease Control, Atlanta, Georgia; Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts; Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts; Laboratory of Clinical Investigation, National Institutes of Health, Bethesda, Maryland; Department of Pediatrics, National Jewish Center for Immunology and Respiratory Medicine, Denver. Colorado; Atlanta Medical Associates, Atlanta, Georgia; Department of Medicine, Mount Sinai Medical Center, New York, New York; Department of Pediatrics, North Shore University Hospital, Manhasset, New York; Division of Biochemistry and Biophysics, Food and Drug Administration, Bethesda, Maryland; Department of Psychiatry, University of San Francisco School of Medicine, San Francisco, California; Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, Nebraska; Department of Medicine, Massachusetts General Hospital. Boston, Massachusetts; and Department of Medicine, Beth Israel Medical Center, New York, New York. Annals of Internal Medicine. 1988; 108:387-389,

The chronic Epstein-Barr virus syndrome is a poorly defined symptom complex characterized primarily by chronic or recurrent debilitating fatigue and various combinations of other symptoms, including sore throat, lymph node pain and tenderness, headache, myalgia, and arthralgias. Although the syndrome has received recent attention, and has been diagnosed in many patients, the chronic Epstein-Barr virus syndrome has not been defined consistently. Despite the name of the syndrome, both the diagnostic value of Epstein-Barr virus serologic tests and the proposed causal relationship between Epstein-Barr virus infection and patients who have been diagnosed with the chronic Epstein-Barr virus syndrome remain doubtful. We propose a new name for the chronic Epstein-Barr virus syndrome - the chronic fatigue syndrome - that more accurately describes this symptom complex as a syndrome of unknown cause characterized primarily by chronic fatigue. We also present a working definition for the chronic fatigue syndrome designed to improve the comparability and reproducibility of clinical research and epidemiologic studies, and to provide a rational basis for evaluating patients who have chronic fatigue of undetermined cause.

THE CHRONIC EPSTEIN-BARR virus syndrome, also known as chronic mononucleosis or chronic mononucleosis-like syndrome, is a syndrome of unknown cause that has been the subject of interest in both medical and popular literature, particularly since 1985. As it was described (1-4) in four groups of patients, the syndrome consists of a combination of non-specific symptoms - severe fatigue, weakness, malaise, subjective fever, sore throat, painful lymph nodes, decreased memory, confusion, depression, decreased ability to concentrate on tasks, and various other complaints - with a remarkable absence of objective physical or laboratory abnormalities. The syndrome was linked in these and other reports to Epstein-Barr virus, because many, but not all, of the 'patients had Epstein-Barr virus antibody profiles that suggested reactivation of latent infection.

Reference laboratories soon began to advertise Epstein-Barr virus serologic tests for use in the diagnosis of the chronic Epstein-Barr virus syndrome (5). Although reliable data are not available, indications are that the syndrome has been diagnosed commonly by physicians, often on the basis of poorly defined diagnostic criteria. Since late 1985, the Division of Viral Diseases, Centers for Disease Control, has responded to several thousand telephone and mail requests for information about the chronic Epstein-Barr virus syndrome, both from physicians and from patients in whom the syndrome has been diagnosed. Judging from the inquiries received, many physicians appear to have based their diagnoses on little more than the presence of detectable serum Epstein-Barr virus antibody titers.

More recent studies (6, 7) have cast doubt on the diagnostic value of positive Epstein-Barr virus serologic results and on the proposed relationship between Epstein-Barr virus infection and patients who have been diagnosed with the chronic Epstein-Barr virus syndrome. Although some statistically significant associations between positive Epstein-Barr virus serologic tests and illnesses diagnosed as the chronic Epstein-Barr virus syndrome were identified in one study using age-, sex-, and race-matched controls (6), the serologic associations between the syndrome and cytomegalovirus, herpes simplex virus types 1 and 2, and measles virus were as strong as or stronger than the association with Epstein- Barr virus. Epstein-Barr virus serologic results in this study were also found to be poorly reproducible, both within and among laboratories, leading to the conclusion that the results of these tests are not directly comparable unless they have been done in parallel.

With the apparent lack of correlation between serum Epstein-Barr virus titers and the presence of chronic fatigue symptoms, it is premature to focus research and diagnostic efforts on Epstein-Barr virus alone. Many public health officials and clinicians are concerned that a diagnosis of the chronic Epstein-Barr virus syndrome may not be appropriate for persons with chronic fatigue who have positive Epstein-Barr virus serologic tests, and that definable occult diseases may actually be the cause of symptoms such as fatigue, weakness, and fever. It is also inappropriate to use a name for the syndrome that implies a specific causal agent. We, therefore, propose a new name - the chronic fatigue syndrome -that describes the most striking clinical characteristic of the chronic Epstein-Barr virus syndrome without implying a causal relationship with Epstein-Barr virus.

Because of the non-specific nature of the symptoms and the lack of a diagnostic test, researchers have had difficulty devising a case definition for the chronic Epstein-Barr virus syndrome. When definitions have been described, they have differed greatly among the various published studies, making direct comparisons of the study results difficult. We have organized an informal working group of public health epidemiologists, academic researchers, and clinicians, to develop a consensus on the salient clinical characteristics of the chronic Epstein-Barr virus syndrome and to devise a definition for the chronic fatigue syndrome that will be the basis for conducting future epidemiologic and clinical studies. Because the syndrome has no diagnostic test, the definition at present is based on signs and symptoms only. This definition is intentionally restrictive, to maximize the chances that research studies will detect significant associations if such associations truly exist. It identifies persons whose illnesses are most compatible with a possibly unique clinical entity; persons who may have less severe forms of the syndrome or who have less characteristic clinical features may be excluded by the new definition.

The chronic fatigue syndrome is currently an operational concept designed for research purposes that physicians must recognize not necessarily as a single disease but as a syndrome - a complex of potentially related symptoms that tend to occur together - that may have several causes. Periodic reconsideration of conditions such as those listed under major criteria, part 2, should be standard practice in the long-term follow-up of these patients.

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