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Fukuda et al., Criteria - Annals Of Internal Medicine:Vol.121; #12 Dec15; 1994 pg 953-959
    Symptoms Go to :- The 1994 CDC  Fukuda et al., CFS Symptoms

Current CDC   revised   »»CFS Symptoms««
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The Chronic Fatigue Syndrome

A Comprehensive Approach to Its Definition and Study

The complexities of the chronic fatigue syndrome and the methodologic problems associated with its study indicate the need for a comprehensive, systematic, and integrated approach to the evaluation, classification, and study of persons with this condition and other fatiguing illnesses. We propose a conceptual framework and a set of guidelines that provide such an approach. Our guidelines include recommendations for the clinical evaluation of fatigued persons, a revised case definition of the chronic fatigue syndrome, and a strategy for subgrouping fatigued persons in formal investigations

Ann Intern Med : Dec. 15; 1994 Vol. 121; #12: Pgs :953-959.

From the Centers for Disease Control and Prevention. Atlanta, Georgia; the National Institutes of Health. Bethesda, Maryland; Prince Henry Hospital and University of New South Wales, Sydney. Australia: University of Oxford and Warneford Hospital Oxford. United Kingdom; and Brigham and Women's Hospital and Harvard University, Boston, Massachusetts (For current author addresses. see end of text.)

We have developed a conceptual framework and a set of research guidelines for use in studies of the chronic fatigue syndrome. The guidelines cover the clinical and laboratory evaluation of persons with unexplained fatigue; the identification of underlying conditions that may explain the presence of chronic fatigue; revised criteria for defining cases of the chronic fatigue syndrome; and a strategy for dividing the chronic fatigue syndrome and other unexplained cases of chronic fatigue into subgroups.


The chronic fatigue syndrome is a clinically defined condition (1-4) characterized by severe disabling fatigue and a combination of symptoms that prominently features self-reported impairments in concentration and short-term memory, sleep disturbances, and musculoskeletal pain. Diagnosis of the chronic fatigue syndrome can be made only after alternative medical and psychiatric causes of chronic fatiguing illness have been excluded. No pathognomonic signs or diagnostic tests for thiscondition have been validated in scientific studies (5- 7); moreover, no definitive treatments for it exist (8). Recent longitudinal studies suggest that some persons affected by the chronic fatigue syndrome improve with time but that most remain functionally impaired for several years (9, 10).

Issues in Chronic Fatigue Syndrome Research

The central issue in chronic fatigue syndrome research is whether the chronic fatigue syndrome or any subset of it is a pathologically discrete entity, as opposed to a debilitating but nonspecific condition shared by many different entities. Resolution of this issue depends on whether clinical, epidemiologic, and pathophysiologic features convincingly distinguish the chronic fatigue syndrome from other illnesses.

Clarification of the relation between the chronic fatigue syndrome and the neuropsychiatric syndromes is particularly important. The latter disorders are potentially the most important source of confounding in studies of chronic fatigue syndrome. Somatoform disorders, anxiety disorders, major depression, and other symptomatically defined syndromes can manifest severe fatigue and several somatic and psychological symptoms and are diagnosed more frequently in populations affected by chronic fatigue (11-13) and the chronic fatigue syndrome (14,15) than in the general population.

The extent to which the features of the chronic fatigue syndrome are generic features of chronic fatigue and deconditioning due to physical inactivity common to a diverse group of illnesses (16, 17) must also be established.

A Conceptual Framework for Studying the Chronic Fatigue Syndrome

In the United States, 24% of the general adult population has had fatigue lasting 2 weeks or longer; 59% to 64% of these persons report that their fatigue has no medical cause (18, 19). In one study, 24% of patients in primary care clinics reported having had prolonged fatigue (2] month) (20) In many persons with prolonged fatigue, fatigue persists beyond 6 months (defined as chronic fatigue) (2 I, 22)

We propose a conceptual framework (Figure]) to guide the development of studies relevant to the chronic fatigue syndrome. In this framework, in which the chronic fatigue syndrome is considered a subset of pro]onged fatigue (21 month), epidemiologic studies of populations defined by prolonged or chronic fatigue can be used to search for illness patterns consistent with the chronic fatigue svndrome. Such studies, which differ from case control and cohort studies based on predetermined criteria for the chronic fatigue syndrome, will also produce much-needed clinical and laboratory background information.

This framework also clarifies the need to compare populations defined by the chronic fatigue syndrome with several other populations in case-control and cohort studies. The most important comparison populations are those defined by overlapping disorders, by prolonged fatigue, and by forms of chronic fatigue that do not meet criteria for the chronic fatigue syndrome controls drawn exclusively from healthy populations are inadequate to confIrm the specificity of chronic fatigue syndrome-associated abnormalities.

Figure I. A conceptual framework of abnormally fatigued populations, illcluding those with the chronic fatigue syndrome (CFS) and overlapping disorders.

This figure consists of a diagram showing the background as the general population, a circle representing the chronically fatigued subset, a joint subset of overlapping disorders (depression, fibromyalgia), and then within the fatigued group, and intersecting the "overlapping disorders" is a joint circle representing CFS and Idiopathic chronic fatigue

Need for Revised Criteria To Define the Chronic Fatigue Syndrome

The possibility that chronic fatigue syndrome study populations have been selected or defined in substantially different ways has made it difficult to interpret conf1icting laboratory fIndings related to the chronic fatigue syndrome (23). For example, the North American chronic fatigue syndrome working case definition (l) has been inconsistently applied by researchers (24) This case definition is frequently modified in practice because some of the criteria are difficult to interpret or to comply with (25) and because opinions differ about the classification of chronic fatigue cases preceded by a history of psychiatric illnesses (26, 27)

Current criteria for the chronic fatigue syndrome also do not appear to define a distinct group of cases (28; Reyes M, et a1. Unpublished data). For example, participants in the Centers for Disease Control and Prevention (CDC) chronic fatigue syndrome surveillance system (29) who met the chronic fatigue syndrome case definition did not substantially differ by demographic characteristics, symptoms, and other illness features from those who did not meet the definition (except by criteria used to place patients into one of our predetermined surveillance classifIcation categories [Reyes M, et a1. Unpublished data]). These findings indicate that additional subgrouping or stratification of study cases into more homogeneous groups IS necessary for comparative studies.

Need for Clinical Evaluation Standards

Our experience suggests that fatigued persons often receive either inadequate or excessive medical evaluations. In the CDC chronic fatigue syndrome surveillance system, all participants were clinically evaluated by a primary physician before enrollment. Subsequently, 18% were found to have a preexisting medical condition that plausibly accounted for their chronic fatiguing illness (Reyes M, et al. Unpublished data). These medical conditions were identified either from a single battery of routine laboratory tests done on blood specimens obtained at enrollment or trom review of available medical records. We believe that inappropriate tests are often used to diagnose the chronic fatigue syndrome in chronically fatigued persons. This practice should be discouraged.

Need for a Comprehensive and Integrated Approach

The complexities of the chronic fatigue syndrome and the existence of several obstacles to our understanding of it make a comprehensive and integrated approach to the study of the chronic fatigue syndrome and similar illnesses desirable. The purpose of the following proposed guidelines (Figure 2) is to facilitate such an approach.

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Figure 2. Evaluation and classification of unexplained chronic fatigue. ALT = alanine aminotransferase; BUN = blood urea nitrogen; CBC = complete blood count; ESR = erythrocyte sedimentation rate; PO4 = phosphorus; TSH = thyroid-stimulating hormone; UA = urinalysis.

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