Chronic fatigue syndrome (CFS) is the most common name used to specify a medical disorder or group of disorders  generally defined by persistent fatigue accompanied by other specific symptoms for a minimum of six months, not due to ongoing exertion, not substantially relieved by rest, nor caused by other medical conditions.


The disorder may also be referred to as myalgic encephalomyelitis (ME), post-viral fatigue syndrome (PVFS), or several other terms. Although classified by the World Health Organization under Diseases of the nervous system, the etiology (cause or origin) of CFS is unknown, and multiple psychological and physiological factors may contribute to the development and maintenance of symptoms.There is no diagnostic laboratory test or biomarker for CFS.


A great deal of debate has surrounded the issue of how best to define CFS. In an effort to resolve these issues, an international panel of CFS research experts convened in 1994 to draft a definition of CFS that would be useful both to researchers studying the illness and to clinicians diagnosing it.


In essence, in order to receive a diagnosis of chronic fatigue syndrome, a patient must satisfy two criteria:

  1. Have severe chronic fatigue of six months or longer duration with other known medical conditions excluded by clinical diagnosis; and
  2. Concurrently have four or more of the following symptoms: substantial impairment in short-term memory or concentration; sore throat; tender lymph nodes; muscle pain; multi-joint pain without swelling or redness; headaches of a new type, pattern or severity; unrefreshing sleep; and post-exertional malaise lasting more than 24 hours.


The symptoms must have persisted or recurred during six or more consecutive months of illness and must not have predated the fatigue.


A number of illnesses have been described that have a similar spectrum of symptoms to CFS. These include fibromyalgia syndrome, myalgic encephalomyelitis, neurasthenia, multiple chemical sensitivities, and chronic mononucleosis. Although these illnesses may present with a primary symptom other than fatigue, chronic fatigue is commonly associated with all of them.


Other Conditions That May Cause Similar Symptoms


In addition, there are a large number of clinically defined, frequently treatable illnesses that can result in fatigue. Diagnosis of any of these conditions would exclude a definition of CFS unless the condition has been treated sufficiently and no longer explains the fatigue and other symptoms.


These include hypothyroidismsleep apnea and narcolepsy, major depressive disorders, chronic mononucleosis, bipolar affective disordersschizophrenia, eating disorders, cancer, autoimmune disease, hormonal disorders*, subacute infections, obesity, alcohol or substance abuse, and reactions to prescribed medications.


Other Commonly Observed Symptoms in CFS


In addition to the eight primary defining symptoms of CFS, a number of other symptoms have been reported by some CFS patients. The frequencies of occurrence of these symptoms vary from 20% to 50% among CFS patients.


They include abdominal pain, alcohol intolerance, bloating, chest pain, chronic cough, diarrhea, dizziness, dry eyes or mouth, earaches, irregular heartbeat, jaw pain, morning stiffness, nausea, night sweats, psychological problems (depression, irritability, anxiety, panic attacks), shortness of breath, skin sensations, tingling sensations, and weight loss.


Theories abound about the causes of chronic fatigue syndrome. No primary cause has been found that explains all cases of CFS, and no blood tests or brain scans can definitively diagnose the condition.


Convergence of Factors.


A number of experts believe that CFS develops from a convergence of conditions that may include the following:


  • Genetic factors.
  • Brain abnormalities.
  • A hyper-reactive immune system.
  • Viral or other infectious agents.
  • Psychiatric or emotional conditions.


For example, most patients report some moderate-to-serious physical illness (such as a chronic viral infection) or emotional event (like an episode of depression) before CFS. Some experts theorize that such events, alone or in combination, may interact with certain neurologic and genetic abnormalities to trigger CFS.


Still, it is not clear what sequence of events actually leads to the fatigue and other prominent symptoms of this disorder. Nor is there any specific brain or nervous system problem that experts can point to with assurance.


Genetic Defects


CFS has been linked with genes involved in the hypothalamic-pituitary-adrenal axis and the sympathetic nervous system. These genes control response to trauma, injury, and other stressful events. Nevertheless, researchers have been unable to determine how the genetic variations influence symptoms.


A number of studies have found alterations in genes involved with immune function, communication between cells, and transfer of energy to cells.


Researchers have identified many different genes in patients with CFS related to blood disease, immune system function, and infection. However, no clear pattern has been found.


Central Nervous System and Hormone Abnormalities


Abnormal levels of certain chemicals regulated in the brain system known as the hypothalamus-pituitary-adrenal (HPA) axis have been proposed as a cause of CFS. This system controls important functions, including sleep, stress response, and depression.


Of particular interest to researchers are the following chemicals and other factors controlled by the HPA axis:

  • Changes in Important Neurotransmitters. Some patients with CFS have abnormally high levels of serotonin - a neurotransmitter (chemical messenger in the brain), deficiencies of dopamine - an important neurotransmitter associated with feelings of reward, or imbalances between norepinephrine and dopamine. However, routine clinical testing for such chemical imbalances is cost-prohibitive.
  • Stress Hormone Deficiencies. A number of studies on CFS patients have observed lower levels of cortisol, a stress hormone produced in the adrenal glands. Deficiencies of cortisol have been suggested as the reason why CFS patients have an impaired and weaker response to psychological or physical stresses, such as infection or exercise. However, administering replacement cortisol improves symptoms only in some patients.
  • Disturbed Circadian Rhythms. Evidence suggests that, in certain patients, CFS is a disorder of the sleep-wake cycle, which is regulated by the so-called circadian clock, a nerve cluster in the HPA axis. Some mentally or physically stressful event, such as a viral infection, may disrupt natural circadian rhythms. An inability to reset these rhythms results in a perpetual cycle of sleep disturbances. Medications that improve sleep can be very helpful for certain patients with CFS.


It is still not clear whether any of these changes are causes of chronic fatigue syndrome, or merely findings in some patients.




Because most of the features of CFS resemble those of a lingering viral illness, many researchers have focused on the possibility that a virus or some other infectious agent causes the syndrome in some cases.


Still, not all CFS patients show signs of infection. Although experts have long been divided on whether infections play any role in this disorder, subtypes of viral-related and non-viral CFS may both exist.




The theory that CFS has a viral cause is not based on hard evidence, but on various observations that suggest an association, such as the following:

  • CFS patients may be found to have elevated levels of antibodies to many organisms that cause fatigue and other CFS symptoms. Such organisms include those that cause Lyme disease, candida ("yeast infection"), herpesvirus type 6 (HHV-6), human T cell lymphotropic virus (HTLV), Epstein-Barr, measles, coxsackie B, cytomegalovirus, or parvovirus. Many of these infectious agents are very common, however, and none has emerged as a significant cause of CFS. Well-designed studies of patients who met strict criteria for chronic fatigue syndrome and of patients with chronic fatigue without any known cause have not found an increased incidence of any specific infections.
  • In up to 80% of cases, chronic fatigue syndrome starts suddenly with a flu-like condition. However, there is no evidence that CFS is spread through casual contact, such as shaking hands or coughing, or by intimate sexual contact.
  • In the U.S., there have been reports of cluster outbreaks of CFS occurring within the same household, workplace, and community (but most have not been confirmed by the Centers for Disease Control and Prevention). However, most cases of CFS occur sporadically in individuals, and do not appear to be contagious.


Immune System Abnormalities


CFS has sometimes been referred to as the "chronic fatigue immune dysfunction syndrome". A number of studies have found many irregularities of the immune system. Some components appear to be over-reactive, while others appear to be under-reactive, but no consistent picture has emerged to explain CFS as a disease of the immune system.



Some studies have reported that a majority of CFS patients have allergies to foods, pollen, metals (such as nickel or mercury), or other substances. One theory is that allergens, like viral infections, may trigger a cascade of immune abnormalities leading to CFS. However, most allergic people do not have CFS.


Autoimmune Abnormalities. The risk profile for chronic fatigue syndrome is similar to the risk profiles for a number of autoimmune diseases. Studies are inconsistent, however, in reporting the presence of autoantibodies (antibodies that attack the body's own tissues) in CFS, and the disease is unlikely to be due to autoimmunity.


Low Blood Pressure


Studies have observed that some patients who fit the strict criteria for chronic fatigue syndrome also have symptoms of a condition known as neurally mediated hypotension (NMH). NMH causes a dramatic drop in blood pressure when a person stands up, even for as little as 10 minutes. Its immediate effects can be lightheadedness, nausea, and fainting.


However, studies have reported no higher incidence of NMH in chronic fatigue patients.


Psychological Factors


Psychological, personality, and social factors are strongly associated with chronic fatigue in most patients. The complex relationship between physical and emotional factors has yet to be fully understood, however. Studies have not found any consistent association between emotional or personality disorders and CFS to explain a causal role. Psychological factors, then, are unlikely to be a primary cause of CFS. However, they may play a role in increasing susceptibility to the disorder. In many cases, CFS promotes psychological and social dysfunction.


Since there is no known cure for CFS, treatment is aimed at symptom relief and improved function. A combination of drug and nondrug therapies is usually recommended.


No single therapy exists that helps all CFS patients.


Lifestyle changes, including prevention of overexertion, reduced stress, dietary restrictions, gentle stretching and nutritional supplementation, are frequently recommended in addition to drug therapies used to treat sleep, pain and other specific symptoms.


Carefully supervised physical therapy may also be part of treatment for CFS. However, symptoms can be exacerbated by overly ambitious physical activity. A very moderate approach to exercise and activity management is recommended to avoid overactivity and to prevent deconditioning.


Although health care professionals may hesitate to give patients a diagnosis of CFS for various reasons, it's important to receive an appropriate and accurate diagnosis to guide treatment and further evaluation.


Delays in diagnosis and treatment are thought to be associated with poorer long-term outcomes. For example, CDC's research has shown that those who have CFS for two years or less were more likely to improve. It's not known if early intervention is responsible for this more favorable outcome; however, the longer a person is ill before diagnosis, the more complicated the course of the illness appears to be.

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