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Chronic fatigue syndrome

Description

An in-depth report on the causes, diagnosis, and treatment of chronic fatigue syndrome.

Diagnosis

It is very difficult to diagnose chronic fatigue syndrome. Even experts do not have a clear definition of what chronic fatigue actually is or what mechanisms in the brain or nervous system are responsible for it. The best diagnostic approach is to determine if the patient matches the criteria for CFS and to rule out other possible causes of symptoms.

Criteria for Chronic Fatigue Syndrome The Centers for Disease Control define CFS as a distinct disorder with specific symptoms and physical signs after eliminating other identifiable causes of these symptoms and signs. 1. Four or more of the following symptoms must have been present for longer than 6 months: Short-term memory loss or a severe inability to concentrate that affects work, school, or other normal activities Sore throat Swollen lymph nodes in the neck or armpits Muscle pain Pain in a number of joints without redness or swelling Intense or changing patterns of headaches Unrefreshing sleep After any exertion, weariness that lasts for more than a day 2. The fatigue must be severe as indicated by the following: Sleep or rest does not relieve it. The fatigue is not the result of excessive work or exercise. The fatigue substantially impairs a person's ability to function normally at home, at work, and in social occasions. Even mild exercise often makes the symptoms, especially fatigue, much worse. 3. The fatigue must be a new, not lifelong, condition with a definite time of onset. Often, the condition first appears as a viral upper respiratory tract infection marked by some combination of fever, headache, muscle aches, sore throat, earache, congestion, runny nose, cough, diarrhea, and fatigue. Typically, the initial illness is no more severe than any cold or flu. 4. The symptoms must persist. In ordinary infections, symptoms go away after a few days, but in CFS, fatigue and other symptoms recur or continue for months to years. Many patients experience symptoms as recurring bouts of flu-like illness, with each attack lasting from hours to weeks. Note: Other symptoms reported with CFS but not part of the criteria include intolerance to alcohol, irritable bowel syndrome, dry eyes and mouth, impaired circulation in the hands and feet, visual disturbances, and painful menstrual periods in women.

Personal and Medical History

A doctor should first take a careful personal and family medical history, which may include a psychological profile, as well as perform a thorough physical examination. Patients should be prepared to answer questions such as:

• When did the fatigue first begin?
• Does anything make it worse or better?
• Is it better at certain times of the day?
• Does physical activity make it worse?
• Are there any other symptoms?
• Has anyone else in the family ever complained of fatigue?
• Is your personal and professional life stressful?

The doctor may also ask about any changes in weight or request a patient to monitor morning and afternoon body temperatures. The patient should report any drugs being taken, including vitamins and over-the-counter or herbal medications.

Laboratory Tests

Inexpensive tests, including thyroid and liver function tests, blood count, and sedimentation rate, are typically recommended to rule out specific conditions that can cause persistent fatigue. No blood, urine, or other laboratory test can specifically diagnose CFS. If any test is abnormal, it is not useful for diagnosing CFS specifically, and the doctor should look for other causes of these abnormalities.

That being said, research published in 2005 found that certain components in urine were unique in people with CFS, and may someday be considered biomarkers of the disease. Additionally, antibodies to Epstein-Barr virus and increased levels of isoprostanes, markers of oxidative stress, have been found in the blood of people with CFS.

Exercise Tests

Some experts recommend exercise tests. In general, CFS patients cannot exercise to the capacity of their peers. A 2003 study found that exercise capacity varied widely among patients who met the AMA guidelines for chronic fatigue syndrome. Therefore, exercise tests may help determine the severity of the condition. Some studies suggest that CFS patients have higher-than-normal ratings of perceived exertion (RPE), which describes the effort attributed to exercise. In a 2003 study, however, the perceptions of how hard they were exercising did not differ between CFS patients and their non-CFS peers. Interestingly, a 2005 Dutch study found the volume of gray matter in the brain to be markedly reduced in people with CFS. Such brain shrinkage has been linked to lower rates of physical activity in people with CFS.

Tilt Test for Neurally Mediated Hypotension

Simply measuring blood pressure will not identify CFS patients in whom the syndrome might be caused by neurally mediated hypotension (an abnormal drop in blood pressure). A tilt test, whereby the person lies on a table tilted upright at a 70-degree angle for a prolonged period, may confirm CFS caused by neurally mediated hypotension if the patient feels lightheaded, sick, and faint after several minutes.

Ruling Out Chronic Fatigue Syndrome

Among the many other common conditions that can lead to feelings of temporary exhaustion are the following:

• Depression
• Infections
• Pregnancy
• Extreme exercise
• Excessive stress

In most of these cases, fatigue can be relieved with adequate rest. It is important to note that longstanding fatigue can be the harbinger of a serious medical or psychological problem. A number of more serious conditions may cause persistent fatigue and other symptoms of CFS and should be ruled out. Patients and doctors should not overlook these diseases, even if they have been previously treated, because they may not have completely resolved or may cause residual fatigue. Doctors can usually distinguish these diseases from CFS after a clinical evaluation and laboratory testing.

Infectious Mononucleosis and Epstein-Barr Virus. Infectious mononucleosis is marked by fatigue and swollen glands. It primarily affects adolescents and young adults. Some patients may have lingering fatigue that lasts for many months and blood tests that indicate a persistence of the Epstein-Barr virus (EBV), which causes mononucleosis.

In some people with CFS, there may be no direct link to Epstein-Barr virus. Many healthy persons without CFS have the same signs of low-level EBV infection, and, conversely, many patients with CFS show no signs of EBV infection. In others, however, the virus may play a role. Research published in 2005 shed new light on ways in which latent Epstein-Barr virus may cause immune problems and CFS-like symptoms.

Autoimmune Diseases. Some diseases, including systemic lupus erythematosus, multiple sclerosis, and rheumatoid arthritis, are caused by autoimmunity , a condition in which the person's immune system attacks the body's own tissues. The early symptoms of these conditions may mimic some of those that appear in CFS, such as muscle and joint pain and fatigue. These diseases, like CFS, also occur more often in women than in men. Autoimmune diseases evolve slowly, and even if a diagnosis of chronic fatigue syndrome is considered, doctors should keep track of any changes in symptoms over time in order to rule out these serious illnesses. It should also be noted that some experts are concerned that many patients who actually have CFS will be mistakenly diagnosed with these diseases, particularly multiple sclerosis, and subjected to unnecessary treatments.

Post-Lyme Syndrome. A delayed response or recurrence of previously treated Lyme disease (called post-Lyme syndrome) may be mistaken for chronic fatigue syndrome in people who live in areas where there are outbreaks. Although the two disorders are similar, one study found that CFS patients reported more flu-like syndromes and those with post-Lyme disease performed significantly worse on tests of mental functioning and motor control. If CFS patients are mistakenly diagnosed and treated for Lyme disease, they may take prolonged courses of antibiotics that can have serious side effects, ultimately doing more harm than good.

Psychosis and Severe Mental Disorders. The Centers for Disease Control (CDC), which set up the definitions in the US for research in chronic fatigue syndrome, recognize depression as one of the symptoms of CFS. However, the CDC rules out chronic fatigue syndrome as a diagnosis for anyone with a history of major depression or other severe psychiatric disorders, including bipolar disorder and schizophrenia. Depression or anxiety not associated with a psychosis or severe mental illness does no t rule out CFS.

Symptoms of major depression include the following:

• A depressed mood every day
• Significant weight gain or loss (10% or more of an individual's typical body weight)
• Insomnia or excessive sleeping
• Restlessness or a sense of being slowed down
• Low energy every day
• Worthless or inappropriately guilty feelings
• An inability to concentrate or to make decisions
• Suicidal thoughts

Major depression is likely to be the responsible condition in the presence of several of these symptoms and if there are no physical symptoms (such as sore throat, aches and pains, or fever). And the longer fatigue has continued without such physical symptoms, the more likely that the diagnosis is depression.

Of note, a persistent form of minor depression called dysthymia may be more difficult to differentiate from CFS and may actually account for a subset of CFS cases. Dysthymia is characterized by many of the same symptoms that occur in major depression but they are less intense and last much longer, at least two years. The symptoms of dysthymia have been described as a "veil of sadness" that covers most activities.

A 2001 study suggested that patients with depression and those with CFS differ in how they perceive their illnesses:

• Patients with depression had significantly lower self-esteem, more thought distortions (for instance, focusing on the negative or personalizing their situations), and believed their conditions stemmed from psychological factors.
• CFS patients, even those with concurrent depression or dysthymia, tended to identify medical causes as the source of their problems and to focus on physical symptoms.

A number of patients who are diagnosed with CFS report having felt depressed before the onset of chronic fatigue. Many other CFS patients, however, felt alert and mentally sound before the onset of CFS symptoms. Many of these previously healthy patients become depressed and anxious because they feel so exhausted all the time. CFS may also lead to highly stressful socioeconomic situations, such as social isolation and poverty, that can contribute to and even cause emotional disorders in susceptible individuals, which in turn can worsen CFS.

Sleep Disturbances. Certain sleep disorders may cause persistent fatigue and be confused with CFS:

• Sleep apnea is a common disorder that can cause daytime fatigue without the patient being aware of the problem. This is actually a breathing disorder often marked by loud snoring and thrashing in bed. A person may not realize the problem exists unless it is brought to his or her attention by a sleeping partner or observer.
• Narcolepsy is a peculiar and rare disorder in which a person suddenly falls asleep without any previous signs of fatigue.
• Other sleep disorders that cause daytime fatigue include insomnia and restless legs syndrome.

In addition, many patients with CFS suffer from sleep problems. A 2004 study found that over 80 percent of CFS patients experienced at least one type of sleep disorder. Non-restorative sleep and nighttime restlessness were the most common complaints.

Conditions that Cause Joint Pain, Muscle Aches, or Both. A number of illnesses cause one or more of CFS symptoms including arthritic symptoms, fever, and fatigue.

Other Diseases that Cause Joint Pain, Muscle Aches, or Both
Disease	Specific Subtypes
Osteoarthritis
Rheumatic Autoimmune Diseases	Rheumatoid arthritis, systemic vasculitis, systemic lupus erythematosus, scleroderma, Still's disease (also called juvenile rheumatoid arthritis), Behcet's disease
Infectious Arthritis	Lyme disease, septic arthritis, bacterial endocarditis, mycobacterial and fungal arthritis, viral arthritis
Postinfectious or Reactive Arthritis	Reiter syndrome (a disorder characterized by arthritis and inflammation in the eye and urinary tract), rheumatic fever, inflammatory bowel disease
Crystal Induced Arthritis	Gout and pseudogout
Fibromyalgia	Having fibromyalgia does not necessarily rule out accompanying CFS
Other Diseases	Hepatitis C, familial Mediterranean fever, cancers, AIDS, leukemia, bunions, Whipple's disease, dermatomyositis, Henoch-Schonlein purpura, Kawasaki's disease, erythema nodosum, erythema multiforme, pyoderma gangrenosum, pustular psoriasis

Severe Obesity. People who are severely obese often have symptoms of chronic fatigue because of the stress imposed by the weight. People who are obese are also at particular risk for sleep apnea, which can confuse the diagnosis.

Other Medical Conditions that Usually Rule Out CFS. Many diseases, both benign and serious, can fully explain prolonged or chronic fatigue, including hepatitis, anemia, hemochromatosis (a hereditary disease caused by iron overload) infections, various forms of cancer, neuromuscular diseases (such as myasthenia gravis), hypothyroidism, and diabetes.

Drugs and Alcohol. Fatigue is a side effect of many prescription and over-the-counter medications, such as antihistamines. In addition, dependency on or abuse of alcohol or illicit drugs may manifest as chronic fatigue. Medications should be considered as a possible cause of fatigue if an individual has recently started, stopped, or changed medicines. Withdrawal from caffeine can produce depression, fatigue, and headache.

Conditions That Do Not Rule Out Chronic Fatigue Syndrome

Many diagnosable conditions cause symptoms similar to CFS, but they can overlap. As such, their presence does not necessarily rule CFS out as a co-disorder. In fact, CFS patients appear to be at high risk for developing depression and additional health problems, particularly those with similar symptoms (for example, fibromyalgia, irritable bowel syndrome, chronic pelvic pain, chemical sensitivities, and temporomandibular disorder).

Some tests may be positive for one or more of these diseases. However, if the results are ambiguous or weak or if they have been treated successfully, CFS should not be ruled out if the patient still also meets the criteria for it.

• Review Date: 1/4/2007
• Reviewed By: Harvey Simon, MD, Editor-in-Chief, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital

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