812
Chronic Fatigue Syndrome David C. Klonoff
From the DepartmentofMedicine, University ofCalifornia at San Francisco, San Francisco, California
"Spontaneous fatigue betokens disease"
-r-Hippocrates [l J The symptoms of chronic fatigue syndrome (CFS) occur out of proportion to currently identifiable pathology. This disparity now challenges the medical community. A review of the literature on CFS is hampered by three obstacles that impede the comparison or combination ofdata from different series. First, the same criteria for defining CFS have not been uniformly applied to patients in different series and no laboratory test exists for confirming the diagnosis of CFS. Second, CFS researchers possess inadequate objective tools to assess severity of illness, functional limitation, and response to therapy. Third, many assertions derived from CFS research are undermined by poor scientific technique, such as deficient control or placebo comparisons. The cause or causes of CFS are unknown. This article reviews the definition, risk factors, organ system involvement, diagnosis, and proper treatment of CFS.
Definition History CFS is a new name for a centuries' old disorder characterized by chronic fatigue and multiple somatic symptoms. Syndromes resembling CFS in the eighteenth, nineteenth, and early twentieth centuries were known as febricula, neurasthenia, and DaCosta's syndrome, respectively [2J. In the 1920s through 1950s, many such cases were attributed to chronic brucellosis [3]. In the 1960s and 1970s, the disorder was attributed to hypoglycemia, and in the early 1980s to candidiasis and environmental illness, also known as "twentieth century disease" [2, 4]. In the mid-l 980s, four reports described a syndrome consisting of fatigue, multiple somatic
Received 28 January 1992; revised 7 May 1992. Reprints or correspondence: Dr. David C. Klonoff 1870 El Camino Real, Suite 200, Burlingame, California 940 IO. Clinical Infectious Diseases
1992;15:812-23
© 1992 by The University of Chicago. All rights reserved.
1058-4838/92/1505-0009$02.00
complaints, and elevated antibody titers to Epstein-Barr viral antigens [5-8]. Many chronically fatigued patients were subsequently diagnosed as having chronic Epstein-Barr virus (EBV) disease, chronic EBV syndrome, or chronic mononucleosis [9]. In 1987, these three terms were replaced by a new name, the chronic fatigue syndrome [10]. Epidemics of CFS, reported since the 1930s, have variously named the disorder Iceland disease, Akureyri disease, epidemic neuromyasthenia, Royal Free disease, and benign myalgic encephalomyelitis [9, 11]. In the British Commonwealth, CFS is now sometimes known as myalgic encephalomyelitis.
Centers for Disease Control's Case Definition In 1987, the Division of Viral Diseases of the Centers for Disease Control (CDC; Atlanta) called a meeting for investigators and clinicians to develop a consensus on the features of the chronic EBV syndrome. The group doubted that EBV infection and the symptom complex known as chronic EBV syndrome were causally related. Chronic EBV syndrome was renamed the chronic fatigue syndrome and a case definition of this syndrome was devised (table 1) [10]. The definition was based on signs and symptoms only because no diagnostic tests exist for CFS. The definition was designed for research purposes and was made intentionally restrictive, emphasizing specificity over sensitivity, so that research studies could best detect associations between risk factors or laboratory abnormalities and CFS itself. The group recognized that "persons who may have less severe forms ofthe syndrome or who have less characteristic clinical features may be excluded by the new definition" [10]. Similar criteria have subsequently been proposed in New Zealand in 1987 [12], in Australia in 1988 [13], in the United States in 1988 [14], and in Britain in 1990 [15, 16]. At a workshop of the National Institute of Allergy and Infectious Diseases (NIAID)/National Institute of Mental Health (NIMH) in 1991, the CFS case definition was modified by excluding specific psychiatric diagnoses and types of postinfectious fatigue and by including selected confounding diagnoses that overlap with CFS (table 2) [17). Researchers
Downloaded from http://cid.oxfordjournals.org/ at University of Iowa Libraries/Serials Acquisitions on May 31, 2015
Chronic fatigue syndrome (CFS) is definedby symptoms and diagnosedwithout any objective diagnostic tests. Risk factors for developing CFS may include infection, psychiatric disorders, and allergies. Modest dysfunction of multiple organ systems, including the immune, central nervous, endocrine, and muscular systems, have been identified in cases of CFS. Symptoms of various organic, psychiatric, and poorly understood disorders overlap those of CFS. There is no known cure for CFS; however, exercise,counseling, and medications may provide symptomatic relief.
CIO 1992; 15 (November)
Chronic Fatigue Syndrome
Table 1. Centers for Disease Control's case definition of the chronic fatigue syndrome (CFS). A case of CFS must fulfill both major criteria as well as either eight symptom criteria or six symptom criteria plus two physical criteria.
Major Criteria 1. New onset of fatigue lasting 6 months reducing activity to
Chronic Fatigue Syndrome David C. Klonoff
From the DepartmentofMedicine, University ofCalifornia at San Francisco, San Francisco, California
"Spontaneous fatigue betokens disease"
-r-Hippocrates [l J The symptoms of chronic fatigue syndrome (CFS) occur out of proportion to currently identifiable pathology. This disparity now challenges the medical community. A review of the literature on CFS is hampered by three obstacles that impede the comparison or combination ofdata from different series. First, the same criteria for defining CFS have not been uniformly applied to patients in different series and no laboratory test exists for confirming the diagnosis of CFS. Second, CFS researchers possess inadequate objective tools to assess severity of illness, functional limitation, and response to therapy. Third, many assertions derived from CFS research are undermined by poor scientific technique, such as deficient control or placebo comparisons. The cause or causes of CFS are unknown. This article reviews the definition, risk factors, organ system involvement, diagnosis, and proper treatment of CFS.
Definition History CFS is a new name for a centuries' old disorder characterized by chronic fatigue and multiple somatic symptoms. Syndromes resembling CFS in the eighteenth, nineteenth, and early twentieth centuries were known as febricula, neurasthenia, and DaCosta's syndrome, respectively [2J. In the 1920s through 1950s, many such cases were attributed to chronic brucellosis [3]. In the 1960s and 1970s, the disorder was attributed to hypoglycemia, and in the early 1980s to candidiasis and environmental illness, also known as "twentieth century disease" [2, 4]. In the mid-l 980s, four reports described a syndrome consisting of fatigue, multiple somatic
Received 28 January 1992; revised 7 May 1992. Reprints or correspondence: Dr. David C. Klonoff 1870 El Camino Real, Suite 200, Burlingame, California 940 IO. Clinical Infectious Diseases
1992;15:812-23
© 1992 by The University of Chicago. All rights reserved.
1058-4838/92/1505-0009$02.00
complaints, and elevated antibody titers to Epstein-Barr viral antigens [5-8]. Many chronically fatigued patients were subsequently diagnosed as having chronic Epstein-Barr virus (EBV) disease, chronic EBV syndrome, or chronic mononucleosis [9]. In 1987, these three terms were replaced by a new name, the chronic fatigue syndrome [10]. Epidemics of CFS, reported since the 1930s, have variously named the disorder Iceland disease, Akureyri disease, epidemic neuromyasthenia, Royal Free disease, and benign myalgic encephalomyelitis [9, 11]. In the British Commonwealth, CFS is now sometimes known as myalgic encephalomyelitis.
Centers for Disease Control's Case Definition In 1987, the Division of Viral Diseases of the Centers for Disease Control (CDC; Atlanta) called a meeting for investigators and clinicians to develop a consensus on the features of the chronic EBV syndrome. The group doubted that EBV infection and the symptom complex known as chronic EBV syndrome were causally related. Chronic EBV syndrome was renamed the chronic fatigue syndrome and a case definition of this syndrome was devised (table 1) [10]. The definition was based on signs and symptoms only because no diagnostic tests exist for CFS. The definition was designed for research purposes and was made intentionally restrictive, emphasizing specificity over sensitivity, so that research studies could best detect associations between risk factors or laboratory abnormalities and CFS itself. The group recognized that "persons who may have less severe forms ofthe syndrome or who have less characteristic clinical features may be excluded by the new definition" [10]. Similar criteria have subsequently been proposed in New Zealand in 1987 [12], in Australia in 1988 [13], in the United States in 1988 [14], and in Britain in 1990 [15, 16]. At a workshop of the National Institute of Allergy and Infectious Diseases (NIAID)/National Institute of Mental Health (NIMH) in 1991, the CFS case definition was modified by excluding specific psychiatric diagnoses and types of postinfectious fatigue and by including selected confounding diagnoses that overlap with CFS (table 2) [17). Researchers
Downloaded from http://cid.oxfordjournals.org/ at University of Iowa Libraries/Serials Acquisitions on May 31, 2015
Chronic fatigue syndrome (CFS) is definedby symptoms and diagnosedwithout any objective diagnostic tests. Risk factors for developing CFS may include infection, psychiatric disorders, and allergies. Modest dysfunction of multiple organ systems, including the immune, central nervous, endocrine, and muscular systems, have been identified in cases of CFS. Symptoms of various organic, psychiatric, and poorly understood disorders overlap those of CFS. There is no known cure for CFS; however, exercise,counseling, and medications may provide symptomatic relief.
CIO 1992; 15 (November)
Chronic Fatigue Syndrome
Table 1. Centers for Disease Control's case definition of the chronic fatigue syndrome (CFS). A case of CFS must fulfill both major criteria as well as either eight symptom criteria or six symptom criteria plus two physical criteria.
Major Criteria 1. New onset of fatigue lasting 6 months reducing activity to
