Chronic fatigue syndrome

Alternative names 
CFS; Fatigue - chronic

Chronic fatigue syndrome is a condition of prolonged and severe tiredness or weariness (fatigue) that is not relieved by rest and is not directly caused by other conditions. To be diagnosed with chronic fatigue syndrome, the tiredness must be severe enough to decrease ability to participate in ordinary activities by 50%.

Causes, incidence, and risk factors

The exact cause of chronic fatigue syndrome (CFS) is unknown. Some researchers suspect it may be caused by a virus, such as Epstein-Barr virus or human herpes virus-6 (HHV-6). However, no distinct viral cause has been identified.

Recent studies have shown that chronic fatigue syndrome may be caused by inflammation of pathways in the nervous system, and that this inflammation may be some sort of immune response or autoimmune process. CFS may occur when a viral illness is complicated by an inadequate or dysfunctional immune response. Other factors such as age, prior illness, stress, environment, or genetic disposition may also play a role. CFS most commonly occurs in women ages 30 to 50.

The Centers for Disease Control (CDC) describes CFS as a distinct disorder with specific symptoms and physical signs, based on the exclusion of other possible causes. The number of patients with CFS is unknown.


Symptoms of CFS are similar to those of most common viral infections (muscle aches, headache, and fatigue), often developing within a few hours or days and lasting for 6 months or more.

Main symptoms:

  • Fatigue or tiredness, never experienced to this extent before (new onset), lasting at least 6 months and not relieved by bed rest  
  • Fatigue that is severe enough to restrict activity (serious fatigue develops with less than one-half of the exertion compared to before the illness)

Other symptoms:

  • Fatigue lasting more than 24 hours after an amount of exercise that would normally be easily tolerated  
  • Mild fever (101 degrees F or less)  
  • Sore throat  
  • Lymph node tenderness in the neck or armpit  
  • Muscle weakness, all over or multiple locations, not explained by any known disorder  
  • Muscle aches (myalgias)  
  • Feeling unrefreshed after sleeping an adequate amount of time  
  • Headaches, different from previous headaches in quality, severity, or pattern  
  • Joint pain, often moving from joint to joint (migratory arthralgias), without joint swelling or redness  
  • Forgetfulness or other similar symptoms including difficulty concentrating, confusion, or irritability

Signs and tests

Physical examination may confirm the fever, lymph node tenderness, lymph node swelling, or other symptoms. The throat may appear red without drainage or pus.

The health care provider can presume a diagnosis of chronic fatigue syndrome (CFS) only after ruling out all other known possible causes of fatigue, such as:

  • Infections  
  • Immune or autoimmune disorders  
  • Tumors.  
  • Muscle or nerve diseases (such as multiple sclerosis)  
  • Endocrine diseases (such as hypothyroidism)  
  • Psychiatric or psychological illnesses, particularly depression (since CFS itself may be associated with depression, a diagnosis of depression does not rule out CFS but fatigue related to depression alone must be ruled out for CFS to be diagnosed)  
  • Drug dependence  
  • Other illnesses (such as heart, kidney, liver diseases)

A diagnosis of CFS must include:

  • Extreme, prolonged fatigue  
  • Absence of other causes of chronic fatigue (excluding depression)  
  • At least 4 of the other symptoms listed

There are no specific tests to confirm the diagnosis of CFS, though a variety of tests are usually done to exclude other possible causes of the symptoms.

There are some typical findings on tests that, while not specific enough to diagnose CFS, are seen consistently in people who are eventually diagnosed with the disorder. These include:

  • Higher levels of specific white blood cells (CD4 T cells) compared to other types of white blood cells (CD8 T cells)  
  • Brain MRI showing swelling in the brain or destruction of part of the nerve cells (demyelination)  
  • Specific white blood cells (lymphocytes) containing active forms of EBV or HHV-6


There is currently no treatment that has been proven to be effective in curing CFS Instead, the symptoms are treated. Many people with CFS experience depression and other psychological problems that may improve with treatment.

Some of the proposed treatments include:

  • Antiviral drugs (such as acyclovir)  
  • Drugs to fight “hidden” yeast infections (such as nystatin)  
  • Medications to treat depression (antidepressant drugs)  
  • Medications to treat anxiety (antianxiety drugs)  
  • Medications to reduce pain, discomfort, and fever

Some medications can cause adverse reactions or side effects that are worse than the original symptoms of chronic fatigue syndrome.

Patients with CFS are encouraged to maintain active social lives, and mild physical exercise may also be helpful.

Expectations (prognosis)
The long-term outlook for patients with CFS is variable and difficult to predict at the initial onset. Some patients have been reported to completely recover after six months to a year. Others may take longer for a complete recovery.

Some patients report never returning to their pre-illness state. Most studies report that patients treated in an extensive rehabilitation program have a better prognosis of improving significantly than those patients who don’t seek treatment.


  • Social isolation caused by fatigue  
  • Lifestyle restrictions (some people are so fatigued that they are essentially disabled during the course of the illness)  
  • Depression (related both to symptoms and lack of diagnosis)  
  • Side effects and adverse reactions to medication treatments

Calling your health care provider
Call for an appointment with your health care provider if you experience persistent, severe fatigue, with or without other symptoms of this disorder. Other more serious disorders can cause similar symptoms and should be excluded. More information on CFS is available from the Centers for Disease Control and Prevention and the CFIDS Association of America.

Johns Hopkins patient information

Last revised: December 2, 2012
by Arthur A. Poghosian, M.D.

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