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 whether the patient matches the criteria for CFS and to rule out other possible causes of symptoms.
In May 2006, the Centers for Disease Control and Prevention (CDC) released a revised definition for Chronic Fatigue Syndrome based on a consensus of many of the leading CFS researchers and doctors (including input from patient group representatives). In the revised definition, chronic fatigue syndrome is considered a subset of chronic fatigue, a broader category defined as unexplained fatigue that lasts for 6 months or longer. Chronic fatigue is considered a subset of prolonged fatigue, which is defined as fatigue that lasts for 1 month or more.
Unexplained chronic fatigue can be classified as CFS if the patient meets the following criteria:
Any other abnormality found during an exam or other tests that could explain CFS symptoms must be resolved before further attempting to classify the condition.
In 2007, the National Institute for Health and Clinical Excellence (NICE) released new guidelines for the diagnosis and management of CFS in adults and children. According to these guidelines, CFS may be diagnosed if the person has disabling fatigue that starts suddenly, lasts a long time, keeps coming back, and can't be explained by another condition.
People with CFS also can have the following symptoms:
After ruling out other possible causes, the doctor should consider a diagnosis of CFS if symptoms have lasted for 4 months in adults or 3 months in children. Children should be diagnosed by a pediatrician.
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:
The doctor may also ask about any changes in weight, or request that a patient monitor his or her morning and afternoon body temperatures. Patients should report any drugs they are taking, including vitamins and over-the-counter or herbal medications.
Standard tests are typically recommended to rule out specific conditions that can cause persistent fatigue. These tests include:
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 said, research has found that certain components in urine are unique in people with CFS, and may someday be considered biomarkers of the disease. Additionally, antibodies to Epstein-Barr virus, increased levels of isoprostanes, and decreased levels of alpha-tocopherol (vitamin E) -- markers of oxidative stress -- have been found in the blood of people with CFS.
Among the many other common conditions that can lead to feelings of temporary exhaustion are the following:
In most of these cases, fatigue can be relieved with adequate rest. It is important to note that longstanding fatigue can be a sign 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 the conditions have been previously treated, because they may not have completely resolved or they 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 fatigue that lasts for many months. Blood tests will indicate the Epstein-Barr virus (EBV), which causes mononucleosis.
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. Most of these conditions can be confirmed with laboratory or x-ray/radiologic findings. However, some autoimmune diseases may evolve slowly. Even if a diagnosis of chronic fatigue syndrome is considered, doctors should keep track of any changes in symptoms over time to rule out these serious illnesses.
Post-Lyme Disease Syndrome. Rarely, patients treated for Lyme disease continue to have nonspecific symptoms, which can last for years after antibiotic treatment and that resemble symptoms of chronic fatigue syndrome.
Depression and Severe Mental Disorders. The Centers for Disease Control (CDC), which established the definitions for chronic fatigue syndrome, recognizes depression as one of the symptoms of CFS. In one study, 36% of CFS patients were depressed. Depression in these patients was associated with lower self-esteem and an increased likelihood of suicidal thoughts. However, according to the CDC, anyone with a history of major depression or other severe psychiatric disorders, including bipolar disorder and schizophrenia, does not meet the criteria for chronic fatigue syndrome.
Symptoms of major depression include the following:
Major depression is likely if a person has several of these symptoms and no physical symptoms (such as sore throat, aches and pains, or fever). The longer fatigue has continued without physical symptoms, the more likely that the diagnosis is depression.
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 2 years. The symptoms of dysthymia have been described as a "veil of sadness" that covers most activities.
Patients with depression generally perceive their illnesses differently than people with CFS:
Many previously healthy patients with CFS 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. These situations can contribute to, and even cause emotional disorders in susceptible individuals, which can worsen CFS.
Sleep Disturbances. Certain sleep disorders may cause persistent fatigue and can be confused with CFS:
Researchers have found that people with CFS have altered amounts of slow wave sleep, which could indicate a problem with sleep regulation. Non-restorative sleep and nighttime restlessness are the most common complaints of people with CFS.
Conditions that Cause Joint Pain, Muscle Aches, or Both. A number of illnesses cause one or more CFS symptoms, including arthritic symptoms, fever, and fatigue.
Severe Obesity. People who are severely obese often have symptoms of chronic fatigue because of the stress imposed by their weight. People who are obese are also at higher 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:
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.
Blockmans D, Persoons P, Van Houdenhove B, Bobbaers H. Does methylphenidate reduce the symptoms of chronic fatigue syndrome? Am J Med. 2006;119:e23-30.
Fuller-Thomson E, Nimigon J. Factors associated with depression among individuals with chronic fatigue syndrome: findings from a nationally representative survey. Fam Pract. 2008;25:414-422.
Goldman L, Ausiello D. Cecil Medicine. 23rd ed. Philadelphia, Pa: Saunders Elsevier, 2007.
Haig-Ferguson A, Tucker P, Eaton N, Hunt L, Crawley E. Memory and attention problems in children with CFS/ME. Arch Dis Child. 2008 Nov 11 [Epub ahead of print].
Hampton T. Researchers find genetic clues to chronic fatigue syndrome. JAMA. 2006;295(21):2466-2467.
Kerr JR. Gene profiling of patients with chronic fatigue syndrome/myalgic encephalomyelitis. Curr Rheumatol Rep. 2008;10:482-491.
Knoop H, Stulemeijer M, de Jong LW, Fiselier TJ, Bleijenberg G. Efficacy of cognitive behavioral therapy for adolescents with chronic fatigue syndrome: long-term follow-up of a randomized, controlled trial. Pediatrics. 2008;121:e619-e625.
National Institute for Health and Clinical Excellence. Chronic fatigue syndrome/myalgic encephalomyelitis (or encephalopathy): diagnosis and management of CFS/ME in adults and children. August 2007.
Price JR, Mitchell E, Tidy E, Hunot V. Cognitive behaviour therapy for chronic fatigue syndrome in adults. Cochrane Database Syst Rev. July 2008(3):CD001027.
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