TL: Chronic Fatigue Syndrome by CDC Original Source Centers for Disease Control and Prevention Original Date: March 9, 1995 Copyright Restrictions: Copyable with attribution ``````````````````````````````````````````````````````````````````````````` CENTERS FOR DISEASE CONTROL AND PREVENTION Last Rev'd: March 9, 1995 CHRONIC FATIGUE SYNDROME ``````````````````````````````````````````````````````````````````````````` The Centers for Disease Control and Prevention is actively engaged in Chronic Fatigue Syndrome research. This document reflects current and reliable information. At this time CDC is not equipped to handle counseling, but suggests that you call your nearest support group. GENERAL DESCRIPTION Chronic Fatigue Syndrome, or CFS, is characterized by persistent and debilitating fatigue and additional nonspecific symptoms such as sore throat, headache, tender muscles, joint pains, difficulty thinking and loss of short term memory. On physical examination, patients may have nonspecific findings such as low grade fever and redness in the throat, but frequently no abnormalities are found. No laboratory test or panel of tests is available to diagnose CFS, so the diagnosis is made solely on clinical grounds. The cause of CFS is unknown. In some individuals, CFS appears to develop after an acute illness like influenza or infectious monucleosis, both of which usually resolve within a few months, or after periods of unusual stress. In other persons, however, CFS appears to develop gradually with no precipitating event. Symptoms are usually most severe early in the course of illness. Later in the illness, periods of partial improvement may be followed by relapses or recovery. While some patients have recovered after several months of illness, others have remained ill for many years. The average duration and full clinical picture of CFS over time is unknown. The degree to which CFS patients are disabled varies widely. Some patients continue to function at home and at work, although at a reduced level of activity, while others become severely disabled and cannot perform many of the routine activities of daily living. CFS affects females and males, and adolescents as well as adults. Most reported cases, however, have occurred in young to middle aged adults with females diagnosed more frequently than males. It is unclear to what extent these demographic characteristics reflect biases among reported cases. CFS does not appear to be directly transmissible from person to person, and there is no justification for CFS patients to be isolated. No deaths from CFS have been reported. Epidemiologic studies of CFS have not documented clear and consistent risk factors. The total number of persons with CFS in the United States is unknown. CDC has conducted surveillance for CFS in four cities across the United States since 1989. Preliminary analysis of the first three years of data indicates that in these sites, two to 7 adults out of 100,000 have CFS. These figures, or prevalence rates, are based upon persons who meet all of the criteria in the CFS research case definition, which was published in the Annals of Internal Medicine in 1988. Because this case definition was deliberately designed to be restrictive for purposes of research, these prevalence rates probably represent low estimates. They should not be used to estimate the overall number of CFS patients in the rest of the United States because the cities chosen for CFS surveillance were not selected randomly. CASE DEFINITION OF CFS In 1987, a panel of experts met at CDC in order to define chronic fatigue syndrome for research purposes. The criteria chosen to define CFS cases were deliberately selected to be restrictive in order to facilitate research. The goal of the case definition was to identify CFS patients who were relatively similar in terms of their illness. The case definition was not designed to diagnose all persons with CFS or to process CFS associated disability claims. This research case definition, which was published in March 1988 in the Annals of Internal Medicine, essentially requires: 1) the presence of new and debilitating persistent or relapsing fatigue for at least 6 months, and 2) the exclusion, by medical examination and laboratory testing, of other clinical conditions (including psychiatric disorders) that may also cause prolonged fatigue, and 3) the presence of a combination of 8 or more symptom and physical sign criteria during 6 or more months of illness. The symptom criteria are mild fever, sore throat, painful lymph nodes, generalized muscle weakness, muscle aches, prolonged fatigue following exercise, generalized headaches, joint pains, various nervous system complaints, sleep alterations, and development of the symptom complex over a few hours to a few days. The physical examination criteria are low grade fever, an inflamed pharynx without pus, and enlarged lymph nodes. DIAGNOSTIC EVALUATION Severe persistent fatigue and other CFS symptoms can be associated with many other illnesses. These illnesses include underlying major depression and anxiety disorders, autoimmune diseases such as systemic lupus erythematosus, malignancies such as ovarian cancer, lymphoma or leukemia, infectious diseases such as endocarditis, hepatitis, syphilis, or AIDS, and a variety of other diseases such as anemia, diabetes, and diseases of the thyroid, heart, lungs, liver, kidneys, gastrointestinal tract, and endocrine system. The exclusion of other possible diseases as a cause of CFS symptoms is the most important part of the diagnostic evaluation. Since many of these diseases can be treated or managed appropriately following diagnosis, and since some of these conditions can be progressive or even fatal if untreated, it is absolutely imperative that a thorough medical evaluation be done before a diagnosis of CFS is made. The role of laboratory and radiologic testing in the diagnostic workup of CFS is to exclude other possible diseases. There are no laboratory tests currently available, including tests for infections, tests for activation of the body's natural defenses against infection, or tests for immune function, that can identify CFS. In particular, tests for Epstein-Barr Virus or EBV, human T-cell lymphotropic virus type-II or HTLV-II, human spumavirus, and immunologic abnormalities should not be used to diagnose CFS. Such tests do not distinguish people with CFS from healthy people and are expensive. Some physicians have reported finding brain abnormalities in CFS patients using radiologic tests such as magnetic resonance imaging, known as MRI scans, or nuclear medicine brain scans such as PET or SPECT scans. The meaning of these findings is unknown. They are not unique to CFS and are not found in all CFS patients. Therefore MRI and nuclear medicine scans, which are very expensive, should not be routinely used to diagnose CFS. These radiologic scans should only be used, when clinically warranted, to exclude the possibility of another brain disease. CDC cannot recommend specific physicians for referral. Our general recommendation is to contact the county medical society, closest university, or a local CFS patient support group for a referral to an internist, infectious disease specialist, or other physician who is knowledgeable about CFS. POSSIBLE CAUSES OF CFS The cause of CFS is unknown. It is also unknown whether or not CFS is a single illness or a group of different illnesses that share common symptoms. A number of theories about the underlying cause or causes of CFS have been proposed. Some theories have focused on possible underlying viral infections, while others have focused on possible underlying immunologic, hormonal, neurologic, and psychological dysfunction. Some of the more prominent theories are discussed in more detail. Possible Viral Causes Epstein-Barr virus or EBV, which is the virus that causes mononucleosis, was widely thought to be responsible for CFS in the 1980s. Later studies, however, indicated that EBV was not the cause of CFS. Most adults have antibody to EBV, and a positive test for EBV, even at a highlevel of antibody, does not diagnose CFS. In addition to EBV, several other viruses have been proposed as possible causes of CFS, including cytomegalovirus, Coxsackie B virus, adenovirus type 1, and human herpesvirus 6 or HHV-6. Although it is possible that viral infections play a role in causing CFS in some patients, none of these viruses has been consistently associated with CFS. More recently, there have been reports suggesting associations between CFS and human retroviruses. These reports, which suggested that CFS may be associated with human spumavirus and viruses like human T-cell lymphotropic virus type-II, received a great deal of attention and generated a great deal of excitement. Since then, however, three published studies have failed to verify an association between CFS and any known human retroviruses. At present there does not appear to be an association between human retroviruses and CFS. The only role for retroviral testing in the diagnosis of CFS should be to exclude the possibility of infection with human immunodeficiency virus or HIV. Possible Immunologic Causes Several subtle immunologic abnormalities have been described in some patients with CFS. Results of immunologic studies as a whole have been confusing, and the results of some published findings are in conflict. Recently a panel of distinguished immunologists and virologists from the National Chronic Fatigue Syndrome Advisory Council issued an official statement regarding immunologic and virologic aspects of chronic fatigue syndrome. In their statement, the following points were made: 1) No test is diagnostic for CFS. 2) There is evidence of immune abnormalities in CFS studies,which suggests a pattern of chronic immune activation. However, similar findings can be found in other chronic disorders such as chronic infections, autoimmune disorders, and allergies. 3) Among the most frequently identified abnormalities are the following: chronic activation of T-cells, decreased function of natural killer cells, reduction of subsets of CD8 positive suppressor cells, and increased levels of antibody to Epstein-Barr virus early antigen. 4) Other immune abnormalities have been inconsistently reported. These include: failure to respond to skin tests, deficiencies of immunoglobulin subclasses, and abnormal CD4 and CD8 numbers and ratios. Recently researchers at the National Institutes of Health reported finding slightly lower percentages of naive CD4 T-cells circulating in the blood of CFS patients than in controls. The significance of these reported immunologic abnormalities is uncertain, but to keep these reports in perspective, the following points should be kept in mind. While it is possible that immunologic abnormalities may be part of the process that causes CFS, these abnormalities may also represent nonspecific immune changes that occur as part of many chronic diseases. It is clear, however, that severe suppression of the immune system such as that seen in AIDS, does not occur in CFS. The opportunistic infections common to AIDS are not seen in CFS. Possible Psychological Causes The role of psychological factors and psychiatric diseases in causing CFS is highly controversial and particularly difficult to study. It is clear that psychiatric disease, and especially depression, is frequently found in individuals with persistent fatigue and among patients referred for evaluation for CFS. Approximately half of the individuals referred to the CDC's CFS surveillance system have evidence of psychiatric illness, which was present before the start of their CFS symptoms. It is also clear that CFS patients commonly experience depression or anxiety sometime during the course of their illness. These kinds of findings have led some researchers to conclude that CFS is one specific manifestation of underlying psychiatric illness. Other researchers, however, point out that many patients who develop CFS do not have evidence of prior psychiatric disease, and that the depression or anxiety that develops after the start of CFS symptoms may be a part of the CFS disease process or simply a natural reaction to any chronic illness. TREATMENT Treatment for CFS should be initiated only after the possibility of another disease has been excluded as thoroughly as possible. No medication has been shown to be effective for curing CFS in well conducted clinical trials. The current standard of treatment is to treat the symptoms of CFS. Most experts begin by recommending a regimen of adequate rest, balanced diet, and physical conditioning. Moderate exercise is generally helpful to minimize loss of physical conditioning, but patients should take care to avoid over exertion since this can lead to relapses of severe fatigue and other symptoms. Non-steroidal anti-inflammatory medications can be useful for treating headaches, and muscle and joint pains. Since all medications can have side effects, a physician should be consulted for specific recommendations regarding drugs. Among the numerous medications claimed to be effective for treating CFS are a variety of antiviral and immune system modulating drugs, vitamins, and holistic remedies. While some of these treatments may be of benefit to some patients, other treatments are expensive, are of no proven use, and are potentially harmful to the patient. If you are in doubt about a specific therapy, one or more reputable physicians in your area should be consulted. Acyclovir and gamma globulin are two medications that have undergone rigorous clinical testing in CFS patients. Acyclovir, which is usually used to treat herpes infections, was shown to be no more effective than a placebo in treating CFS patients. Gamma globulin, which is composed of antibodies pooled from many individuals, was tested in two trials. One trial conducted in the U.S. showed no benefit. The other trial conducted in Australia showed minimal benefit, but this benefit was lost after the trial ended. Currently, two other medications, cortisol and ampligen are undergoing controlled trials. [NOTE: Ampligen trial was discontinued] FOR FURTHER INFORMATION There are several national and local non-profit support groups for persons with chronic fatigue syndrome. These groups publish periodic newsletters, provide lists of interested physicians, and facilitate contact between affected persons. The CDC does not endorse these organizations or their published information but provides the names and addresses of the two largest national organizations for further information. These are: 1) The National CFS Association, 919 Scott Avenue, Kansas City, KS. 66105. Tel. (913) 321-2278. 2) The CFIDS Association, Community Health Services, P.O. Box 220398, Charlotte, NC. 28222-0398. Tel. (704) 362-2343 .