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 whether the patient matches the criteria for CFS and to rule out other possible causes of symptoms.

Criteria for Chronic Fatigue Syndrome

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:

1. Unexplained persistent or relapsing chronic fatigue that is either new or that started at a definite period of time; is not the result of ongoing exertion; is not substantially relieved by rest; and significantly reduces activities such as work, education, and social life.
2. Also, four or more of the following symptoms, which must have continued or recurred during 6 or more consecutive months of illness and must not have started before the fatigue:
   • Significant impairment in short-term memory or concentration
   • Sore throat
   • Tender lymph nodes
   • Muscle pain
   • Joint pain without swelling or redness
   • Headaches of a new type, pattern, or severity
   • Unrefreshing sleep
   • Malaise that lasts for more than 24 hours after exertion

Conditions that Can Rule Out a CFS Diagnosis

1. Any active medical condition that may explain the presence of chronic fatigue, such as:
   • Untreated hypothyroidism (underactive thyroid gland)
   • Sleep apnea and narcolepsy (common sleep disorders)
   • Side effects of medication
2. An illness (such as cancer, or hepatitis B or C virus infection) that relapsed or did not completely get better during treatment, that could explain the presence of chronic fatigue.
3. A past or current major depressive disorder, such as:
   • Bipolar affective disorder
   • Schizophrenia
   • Delusional disorder
   • Dementia
   • Anorexia nervosa or bulimia nervosa
4. Alcohol or other substance abuse that occurs within 2 years of the onset of chronic fatigue and at any time afterward.
5. Severe obesity, as defined by a body mass index (BMI) equal to or greater than 45. (Note: Body mass index values vary considerably among different age groups and populations. No "normal" or "average" range of values can be suggested. The range of 45 BMI or higher was selected because it falls within the range of severe obesity.)

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:

• Difficulty thinking, concentrating, remembering, finding the right words, planning, and organizing
• Difficulty sleeping
• Dizziness or nausea
• General malaise or flu-like symptoms
• Headaches
• Muscle or joint pain in many areas of the body without inflammation
• Painful lymph nodes without disease
• Fast heartbeat (palpitations) without heart problems
• Sore throat
• Worsening of symptoms with physical exertion

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.

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 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.

Laboratory Tests

Standard tests are typically recommended to rule out specific conditions that can cause persistent fatigue. These tests include:

• Blood count
• Blood tests for gluten sensitivity
• C-reactive protein
• Creatine kinase
• Erythrocyte sedimentation rate or plasma viscosity
• Liver function
• Random blood sugar (glucose)
• Serum calcium
• Serum creatinine
• Serum ferritin levels (only in children)
• Thyroid function
• Urea and electrolytes
• Urine test for protein, blood, and glucose

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.

Identifying Other Causes of 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 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:

• A depressed mood every day
• Significant weight gain or loss (10% or more of an individual's usual 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 make decisions
• Suicidal thoughts
• Loss of interest and enjoyment

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:

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

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:

• Sleep apnea is a common disorder that can cause daytime fatigue without the patient being aware of the problem. Apnea is actually a breathing disorder that is 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.

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:

• Hepatitis
• Anemia
• Hemochromatosis (a hereditary disease caused by iron overload)
• Various forms of cancer
• Neuromuscular diseases (such as myasthenia gravis)
• Hypothyroidism
• 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.