Below is the text of the booklet "The Facts About Chronic Fatigue Syndrome" published in August 1994 by the U.S. Centers for Disease Control and Prevention (CDC). An earlier draft of this text was scanned into an electronic file by Chuck Moss, and that was revised by Maryka Ford and Roger Burns to yield the current file. ------------------------------------------
Chronic fatigue syndrome, or CFS, is a debilitating disorder characterized by profound tiredness or fatigue. Patients with CFS may become exhausted with only light physical exertion. They often must function at a level of activity substantially lower than their capacity prior to the onset of illness. In addition to these key defining characteristics, patients generally report various nonspecific symptoms, including weakness, muscle aches and pains, excessive sleep, malaise, fever, sore throat, tender lymph nodes, impaired memory and/or mental concentration, insomnia, and depression. CFS can persist for years.
The cause of CFS has not been identified and no specific diagnostic tests are available. Moreover, incapacitating fatigue can be associated with a wide range of well-defined illnesses, such as cancer, depression, autoimmune diseases, hormonal disorders, and subacute infections. Since many of these disorders are treatable, other causes of fatigue must be ruled out before a diagnosis of CFS can be made. Although it can be diagnosed only through this process of elimination, CFS is a genuine clinical condition whose cause and treatment are the focus of intense research.
Reports about CFS have been presented at scientific meetings and published in peer-reviewed research journals. However, the body of information is still small, and many findings are preliminary. Finally, unsubstantiated anecdotal information about CFS has confused some patients and physicians regarding what is speculation and what is scientific fact.
The purpose of this brochure is to provide answers to the most commonly asked questions about CFS and to clarify areas that are often misunderstood.
Why is this illness called chronic fatigue syndrome?
A number of names have been proposed over the years to describe clinical features similar to the syndrome we now call CFS. These names include chronic Epstein-Barr virus disease, chronic fatigue immune dysfunction syndrome, epidemic neuromyasthenia, and myalgic encephalomyelitis. The term "chronic fatigue syndrome" was agreed upon in 1988 by a group of experts studying the illness. The group unanimously selected chronic fatigue syndrome because they believed the use of a more specific name would be misleading, given the current knowledge about the disease, and would apply only to some symptoms and patients. For example, no characteristic profile of immune dysfunction has been identified that defines chronic fatigue syndrome, and most patients do not have encephalomyelitis (inflammation of the brain and spinal cord).
If my symptoms do not fit the published case definition of CFS does that mean I do not have CFS?
The case definition published in 1988 (Holmes et al, Ann Intern Med 108:387-9) was produced by medical and public health experts at a meeting sponsored by the Centers for Disease Control (CDC)(Appendix A). The case definition was deliberately designed to define a narrow group of patients for research purposes. Scientists working on CFS need to study patients who have the same, carefully defined illness characteristics. Only by studying relatively homogenous groups of patients are researchers likely to identify a causative agent, physiologic abnormality, or laboratory marker for CFS. This research definition was not designed to be used in the clinical diagnosis of CFS.
How many people in the United States have CFS?
On the basis of results from the first 3 years of its ongoing physician referral-based surveillance study, CDC estimates the minimum prevalence rate of CFS in the United States at 4 to 10 cases per 100,000 adults 18 years of age or older (adjusted for age, sex, and race). Although some media reports have indicated that more than 5 million persons in the United States have CFS, these estimates are not supported by scientific studies.
Who gets CFS?
In the United States, the majority of diagnosed cases of CFS occur in women, most of whom are white. In the CDC's surveillance study, approximately 80% of the cases identified were in women. Most patients are 25 to 45 years old. However, CFS has been diagnosed in a wide range of age groups, including adolescents, and in persons of different races. How frequently CFS occurs among various demographic groups is uncertain but being investigated. Diagnosis of CFS among some groups may reflect differences in culture and factors such as access to medical care. Carefully designed surveillance studies of CFS must be performed before a clear picture of its distribution in the population emerges.
What types of cognitive dysfunction are associated with CFS?
CFS patients commonly report one or more symptoms of cognitive dysfunction, including confusion, difficulty concentrating, impaired thinking, and forgetfulness. Patients often regard these symptoms among the most debilitating features of CFS.
Are there any long-term health problems associated with having CFS?
No scientific evidence exists for any long-term risks associated with CFS. There are anecdotal reports of increased rates of cancer, multiple sclerosis, and other illnesses among CFS patients, but none of these claims have been scientifically established. Unlike immune deficiency diseases, such as AIDS, CFS is not associated with opportunistic infections. Unsubstantiated claims have been made that CFS patients are more prone to suicide, but there are no data to indicate that the suicide rate among CFS patients is higher than that for the general population.
What is the prognosis for CFS -- will I get better?
Very little is known about the clinical course of CFS. It is among the most important areas of CFS research by both CDC and National Institutes of Health (NIH). The course of this illness differs widely among patients. Some patients recover completely with time, while others seem to grow progessively worse. Often, the illness follows a cyclical course, alternating bewteen periods of illness and relatively good health. Some patients improve to a certain extent but never fully recover.
Is CFS contagious?
There are no published data indicating that CFS is communicable through either casual or intimate contact. Studies of groups of CFS patients and their contacts have shown no evidence of person-to-person transmission of the illness. Several cluster outbreaks of unexplained fatigue reported to CDC in recent years are being investigated. Furthermore, reports that pets are involved in the transmission of CFS, or that they can contract the disorder, are unsubstantiated.
Is it safe for me to become pregnant if I have CFS?
Some physicians have informally noted that the symptoms associated with CFS appear to recede during pregnancy. No controlled studies of CFS and pregnancy have been done.
How is CFS treated?
Without knowing the cause of CFS, it is difficult to identify effective treatments. Medications prescribed for CFS usually are intended to provide symptomatic relief and not a cure. However, a number of unproven and potentially dangerous treatments and diagnostic tests have been given to CFS patients at exorbitant cost. Some of the more common remedies and prescription medicines provided to CFS patients are listed in Appendix B.
Are there certain medications I should avoid?
In most circumstances, patients should trust the advice of their physician. However, certain treatments, such as cyclophosphamide, azathioprene, methotrexate, and hydrogen peroxide injection, are potentially life-threatening, wholly unproven to relieve the symptoms of CFS, and should be avoided. If in doubt, call your local medical society, university medical school, or another physician.
Is a particular dietary or vitamin supplement regimen recommended for people with CFS?
There are no studies to suggest that dietary or vitamin supplements relieve the symptoms of or cure CFS. A list of dietary supplements and vitamins commonly used by CFS patients is included in Appendix B.
Does exercise relieve symptoms or make them worse?
Exercise, as well as other physically and mentally challenging activities, can exacerbate fatigue and other symptoms associated with CFS. Patients report that the effects of exercise may not be felt until 1 or 2 days after the activity. Studies are under way to determine the cause and to characterize the nature of this phenomenom. It is clear, however, that lack of exercise leads to deconditioning. Therefore, a regular regimen of moderate exercise, determined by individual tolerance, is generally recommended.
Can I continue to work if I have CFS (or, can my child with CFS continue to attend school)?
CFS patients may experience a variety of potentially debilitating conditions, including fatigue, arthralgia/myalgia, and difficulty concentrating, that can affect their performance on the job or in school. There is no evidence, however, that CFS can be spread from person to person. Therefore, if you feel well enough to continue working, there is no reason not to.
Is it safe for me to donate blood if I have been diagnosed with CFS?
Since the cause of CFS is unknown, and since it may represent a general set of symptoms caused by a variety of factors, there is currently no formal policy or recommendation concerning donation of biological products, such as blood, by CFS patients. There are no cases of persons who acquired CFS after blood transfusion. In general, however, persons who are not in good health, including those with CFS, are discouraged from donating blood and blood products. If you suspect you have CFS or a similar condition, inform officals at the blood collection center that you have CFS. The blood bank may have specific regulations concerning CFS or comparable illnesses.
What causes CFS?
The cause of CFS has not been identified, but there are several theories. Numerous well-characterized viruses are known to cause severe fatigue during acute infection. While some viruses, such as Epstein-Barr virus (EBV), occasionally establish a chronic active infection that results in persistent fatigue, no single virus has been firmly associated with CFS. One hypothesis is that a virus, stress, or other transient traumatic condition may chronically activate the immune system. According to this hypothesis, the immune system, which ordinarily gears down after an infection has been eliminated, remains activated after the initiating infection has passed. The result is that unusually high concentrations of immune activating factors, some of which are known to cause fatigue at high doses, persist in the bloodstream. Other theories involve proposed disturbances in the hormonal (endocrine) system, and some fatigue may be induced by psychological conditions. Another possibility is that a single causative agent, as yet unidentified, causes CFS.
Is CFS caused by an uncharacterized human retrovirus?
One report in the scientific literature described possible retrovirus DNA sequences in lymphocytes from CFS patients that were not present in healthy persons. Despite intensive efforts, several laboratories could not confirm the results of this study. Anecdotal reports that CFS is caused by a human spuma virus are unsubstantiated. In addition, CFS does not have any relationship to a recently reported rare disease, human immunodeficiency virus (HIV)-negative AIDS. There is also no evidence to suggest that CFS is caused by HIV 1, the virus that causes AIDS. Reduced CD4 counts are rarely observed in CFS patients. There is no evidence of life-threatening or clinically noteworthy compromise of the immune system in CFS patients. Retrovirus involvement in CFS is unlikely, although it continues to be investigated.
Does human herpesvirus type 6 (HHV-6) cause CFS?
HHV-6 is an extremely common herpesvirus infection that causes roseola in children and infects at least 95% of persons older than 1 year. Like all herpesviruses, HHV-6 normally remains latent within infected persons but can be reactivated periodically. Some studies have reported inconclusive evidence of HHV-6 reactivation in CFS patients; others have found no correlation between HHV-6 infection and CFS. However, since it is virtually ubiquitous in the general population, HHV-6 infection cannot be used to diagnose CFS.
Do enteroviruses cause CFS?
Like herpesviruses, some enteroviruses are known to cause severe fatigue and muscle weakness. Enteroviruses have been studied by several groups for their involvement in CFS. As with other potential viral causes, no strong associations can be made between recent infection by enteroviruses and CFS.
Can CFS be diagnosed by laboratory tests?
No diagnostic test exists for CFS. Currently, laboratory tests are useful solely to rule out other causes of fatigue. The same is true of serologic tests for certain viruses. Numerous scientific reports have documented immunologic differences between groups of CFS patients and healthy controls, but differences are not observed consistently, and test results between individual patients and controls overlap considerably. In other words, the test values for a randomly chosen CFS patient and those for a randomly chosen healthy person may both fall into the normal range for any of these tests.
How is CFS diagnosed?
CFS is currently diagnosed by a history of illness suggestive of CFS, and through the systematic exclusion of other possible causes. A patient must first have profound fatigue for a minimum of 6 months. To complete the diagnosis, a physician must rule out the many clinically defined (and often treatable) causes of chronic fatigue by using a panel of routine diagnostic tests. Consult Appendix A for specific examples of illnesses that may cause severe fatigue.
Are there CFS specialists who are more qualified than physicians in general practice to diagnose this illness?
As with any illness, some physicians are more familiar with CFS than others but any licensed physician should be able to diagnose CFS. Persons who suspect they might have CFS should seek a doctor with whom they have a comfortable rapport, and who has knowledge of or is open to learning about CFS. Call the nearest university-based medical center if you have difficulty locating a physician who is familiar with the syndrome.
Can CFS be diagnosed by using extremely sensitive molecular tests to demonstrate the presence of retrovirus-like DNA sequences?
No. One published report has been erroneously interpreted to indicate that CFS can be diagnosed by using the polymerase chain reaction method to detect human T-cell lymphotrophic virus type II (HTLV-II)-like DNA sequences in the Iymphocytes of patients. However, more recent studies do not support this view. As such, this expensive research test is not useful in the diagnosis of CFS (see Possible Causes of CFS).
Should diagnostic imaging techniques, such as MRI, PET scan, and SPECT scan, be used in the diagnosis of CFS?
Several reports in the peer-reviewed clinical literature have described CFS patients with recognizable abnormalities seen in MRI or SPECT scans of the brain. However, these preliminary reports have not been confirmed by definitive follow-up studies and did not identify abnormalities in all CFS patients. Since the importance of these early reports is not known, these costly procedures are not appropriate for the clinical diagnosis of CFS.
CFS patients have been shown to have increased antibody levels (i.e., elevated titers) to various infectious agents, including EBV, cytomegalovirus, HHV-6, rubella, enteroviruses, and Borrelia. Does this observation indicate that CFS can be triggered by the reactivation of latent infections?
Some viruses, most notably the herpesviruses, can establish a state of prolonged dormancy, known as a latent infection, within their host. Such viruses normally reactivate periodically and consequently restimulate the immune system. Published studies have reported elevated titers to a number of these agents among CFS patients compared with controls. However, test values between individual patients and controls broadly overlap, indicating that such tests cannot be used to diagnose CFS. Early studies concluded that there was an association between high levels of serum antibody to EBV (which is known to cause fatigue) and CFS. However, more recent studies have shown that elevated EBV titers are not correlated with CFS. Rubella, enteroviruses, and Borrelia cannot produce a latent infection, but they can persist for prolonged periods in an infected person. Finally, because persons within a given population exhibit a broad range of titers to viruses that establish latent infections, "elevated titer" is difficult to define.
Do CFS patients have lower-than-normal numbers of natural killer cells or natural killer cells with impaired function?
Some investigators have reported lower numbers of natural killer cells or lower levels of natural killer cell activity in CFS patients than in controls. Others have been unable to observe any natural killer cell abnormalities among CFS patients. No study of natural killer cells in CFS patients has ever defined an abnormality that consistently identifies the patients. As with other experimental assays, measured levels of natural killer activity varied greatly among patients and controls, and individual test results overlapped considerably; thus no clearly abnormal values separated all (or most) cases from all (or most) controls.
Are T-cell activation markers present on a higher number of immune cells in CFS patients?
One study showed that the CD8 T-cell subpopulation contained an increased number of cells expressing the activation markers CD38 and HLA-DR in a subset of CFS patients who were very ill. This finding was true for a large proportion of CFS patients (90%), but only a small fraction of healthy controls (10%). However, similar shifts in the expression of activation markers have been observed for various acute viral infections and would be expected of any active infection. The usefulness of activation markers in diagnosing CFS remains to be established.
Could elevated levels of serum cytokines indicate CFS?
One of the more intriguing theories about the cause of CFS is that one of a number of possible "triggering events" results in a chronic activation of the immune system in these patients. If this theory is correct, one or more serum cytokine levels of CFS patients may be more elevated than those of healthy controls. Such results have been reported anecdotally for interleukin-1, for example, but no characteristic pattern of serum cytokines has been established.
If I have allergies, am I more prone to get CFS?
Several studies have demonstrated that some, but by no means all, CFS patients have a history of allergies. Allergy could be one predisposing factor for CFS, but it cannot be the only one, since not all CFS patients have allergies.
The case definition of CFS for research purposes, from Holmes et al, Ann Intern Med (1988) 108:387-9.
A case of chronic fatigue syndrome must fulfill both major criteria listed below, and the following minor criteria: 6 or more of the 11 symptom criteria and two or more of the three physical criteria; or eight or more of the 11 symptom criteria.
Major Criteria
Minor Criteria
Symptom Criteria
For inclusion in the definition of a case, a symptom must have begun at or after onset of fatigue, and must have persisted for at least 6 months (individual symptoms may or may not have occurred simultaneously):
Physical Criteria
Medications, herbal preparations, and miscellaneous treatments which have been used against CFS
Vitamins, coenzymes, and minerals
________________________________________________________________
Treatment Name Value in Side effects associated
treating with the use of this treatment
CFS*
----------------------------------------------------------------
Coenzyme Q-10 F harmful effects unknown
Vitamin B-12 X harmful effects unknown
Vitamin C X long term use at high dose
may cause development
of kidney stones
Vitamin A X high doses of this vitamin
can cause a wide variety
of clinical symptoms
including permanent liver
damage
Selenium X compounds of this
element may cause
gastrointestinal
disturbances and some
are carcinogenic
Germanium X harmful effects unknown
Zinc X harmful effects unknown
Iron X high doses of iron salts
may be toxic
Adenosine F harmful effects unknown
monophosphate
L-tryptophan F contaminated lots have
been implicated in
triggering eosinophilia-
myalgia syndrome
Magnesium sulfate X harmful effects unknown
----------------------------------------------------------------
*X = no proven utility for CFS; F = no known clinical value
Herbal Preparations
________________________________________________________________
Treatment Name Value in Side effects associated
treating with the use of this treatment
CFS*
----------------------------------------------------------------
Astralagus X harmful effects unknown
Echinacea X harmful effects unknown
Garlic X harmful effects unknown
Ginseng X moderate use considered
safe but allergic reactions
have been reported. High
doses may cause a
variety of adverse
symptoms
Gingko biloba F harmful effects unknown
Comfrey X contains tannin and
lasiocarpine both of which
are considered
carcinogenic. Alkaloids in
comfrey may result in liver
damage
Primrose oil C harmful effects unknown
Shitake mushroom F harmful effects unknown
extract
Borage seed oil F harmful effects unknown
Quercetin X harmful effects unknown
Bromolain X "therapeutic doses" may
cause nausea vomiting
diarrhea skin rash and
menorrhagia
-----------------------------------------------------------------
*X = no proven utility for CFS; F = no known clinical value; C =
conflicting findings in clinical trials
Analgesics
_________________________________________________________________
Treatment Name Value in Examples Side effects associated
treating with the use of this
CFS* treatment
-----------------------------------------------------------------
Nonsteroidal anti- S naproxen abdominal pain/dyspepsia/
inflammatory ibuprofen nausea/vomiting
drug (NSAID) piroxicam /drowsiness/headache/
depression/fatigue/
naproxen may impair some
immune functions
Other S cyclobenza- gastrointestinal
prine bleeding/drowsiness/
dry mouth/dizziness
_________________________________________________________________
*S = useful for relief of symptoms
Acute anxiety
_________________________________________________________________
Treatment Name Value in Examples Side effects associated
treating with the use of this
CFS* treatment
-----------------------------------------------------------------
Benzodiazepines S alprazolam sedation/anterograde
lorazepam amnesia/withdrawal
symptoms
Other S buspirone dizziness/headache/
drowsiness/nausea
________________________________________________________________
*S = useful for relief of symptoms
Hypnotics
________________________________________________________________
Treatment Name Value in Examples Side effects associated
treating with the use of this
CFS* treatment
----------------------------------------------------------------
Benzodiazepines S clonazepam hallucinations/ataxia/
triazolam depression
temazepam
Other S zolpidem dizziness/headache
Other S trazodone drowsiness/headache/
gastrointestinal
bleeding
________________________________________________________________
*S = useful for relief of symptoms
Antidepressants
________________________________________________________________
Treatment Name Value in Examples Side effects associated
treating with the use of this
CFS* treatment
----------------------------------------------------------------
Tricyclic S doxepin dry mouth/drowsiness/
amitriptyline weight gain/
desipramine tachycardia/weakness/
nortriptyline fatigue
Serotonin S fluoxetine headache/tremor/
reuptake sertraline agitation/nervousness
inhibitors paroxetine
Other S bupropion anxiety/agitation/
insomnia/tremor/
anorexia/seizures
________________________________________________________________
*S = useful for relief of symptoms
Additional drug therapies
________________________________________________________________
Treatment Name Value in Examples Side effects associated
treating with the use of this
CFS* treatment
----------------------------------------------------------------
Calcium channel X nimodipine dizziness/
blockers nicardipine hypotension/
cardene headache/nausea
H-2 blockers X ranitidine headache/dizziness/
cimetidine nausea/rashes/
myalgia/impotence/
has been reported to
alter immune function
Immune U cyclophos- destruction of immune
suppressants phamide cells/hair loss/liver
azathioprine damage/kidney damage/
methotrexate toxicity to developing
embryos/ interstitial
pneumonitis
Other X naltrexone insomnia/liver damage
Other X pentoxifylline gastrointestinal
upset/dizziness
________________________________________________________________
*X = no proven utility for CFS; U = use unjustified for CFS
Allergy medications
________________________________________________________________
Treatment Name Value in Examples Side effects associated
treating with the use of this
CFS* treatment
----------------------------------------------------------------
Non-sedating S terfenadine drowsiness/interaction
antihistamines astemizole with erythromycin
loratidine
Antihistamines S diphenhydra- drowsiness
mine
Other S hydroxyzine sedation
________________________________________________________________
*S = Useful for relief of symptoms
Miscellaneous therapies
________________________________________________________________
Treatment Name Value in Side effects associated
treating with the use of this treatment
CFS*
----------------------------------------------------------------
Gamma globulin C harmful effects unknown
Ampligen P harmful effects unknown
Kutapressin X allergic reactions
Hydrogen F this treatment is considered
peroxide injection highly unorthodox and could
initiate a stroke
High colonic F known to promote
enemas intestinal disease
________________________________________________________________
*x = no proven utility for CFS; F = no known clinical value; C =
conflicting findings in clinical trials
Generic and trade names of drugs
used to manage patients with CFS
____________________________________________
Generic name Trade name
--------------------------------------------
Alprazolam Xanax
Amitryptline Elavil, Endep,
Etrafon, Limbitrol,
Triavil
Bupropion Wellbutrin
Buspirone BuSpar
Cimetidine Tagament
Clonazpam Klonopin
Cyclobenzaprine Flexeril
Desipramine Norpramin
Doxepin Adapin, Sinequan
Fluoxetine Prozac
Lorazepam Ativan
Nortriptyline Aventyl, Pamelor
Paroxetine Paxil
Pentoxifylline Trental
Ranitidine Zantac
Sertraline Zoloft
Temazepam Restoril
Trazodone Desyrel
Triazolam Halcion
Zoldipem Ambien
Any comments? Send them to Bill Jackson at cfsdays@yahoo.com
Back to CFS Index Page