An Overview of Chronic Fatigue Syndrome

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Chronic fatigue syndrome is a condition involving deep fatigue, unrefreshing sleep, and a worsening of symptoms after exertion. Its exact cause is unknown, but it is believed that a combination of genetic predisposition and environmental factors bring it about. With no simple test to identify it available, diagnosis is based on the symptoms and exclusion of other causes. Treatment is aimed at modifying your lifestyle and relieving symptoms with medications and therapies. The condition is also known as myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) or systemic exertion intolerance disease (SEID).


Every person with chronic fatigue syndrome has his or her own unique set of symptoms, the intensity of which can vary. The symptoms that are required for the diagnosis of ME/CFS are fatigue, post-exertional malaise, and sleep problems. In addition, either cognitive impairment (brain fog) or a worsening of symptoms while you are upright (orthostatic intolerance) must be noted.

The fatigue and drop in activity level must be present for at least six months. The characteristics of the fatigue must include that it is not relieved by sleep or rest, it isn't the result of strenuous exertion, and it significantly lowers your ability to function normally in most situations. Your symptoms may worsen for 24 hours to days or even weeks after physical or mental exertion.

Other common symptoms include:

  • Sudden and distinct onset, especially following a flu-like illness
  • Pain, including muscle aches, joint aches, or headaches
  • Flu-like symptoms that may include a sore throat, swollen lymph glands, or low-grade fever
  • Sensitivities and intolerances to heat, cold, noise, light, or alcohol

There can be many additional symptoms including anxiety or a sensation of irregular heartbeat. Common overlapping conditions include depression, irritable bowel syndrome, tinnitus, premenstrual syndrome, and endometriosis.


Researchers don't yet know the exact cause of chronic fatigue syndrome, but many experts now believe it may be triggered by genetic mutations combined with exposure to certain viruses or toxins. Many more women than men are diagnosed with ME/CFS, which may be explained if an underlying cause is ever determined.

Several viruses and other infectious agents have been investigated for links to this condition. Some of them have been proven to not be related, while others have a less certain relationship. Some doctors and researchers believe a handful of pathogens—including Epstein-Barr virus, HHV-6, Lyme disease, and enterovirus—do play a role in some cases.

Disruption or dysregulation of the sympathetic nervous system and the hormones involved in the hypothalamic-pituitary-adrenal (HPA) axis may be involved. The HPA axis controls your response to stress, regulates sleep, and is involved in mood disorders such as depression.

Irregularities have been seen in the immune systems of people with ME/CFS, although there is no consistent pattern. In some, the immune system may be chronically active. In others, some of the cells are abnormally active or low-functioning. However, true immune deficiency is not a feature of ME/CFS.


The diagnostic process for ME/CFS can be long and complicated. ME/CFS is a diagnosis of exclusion, which means that other conditions with similar symptoms must be ruled out before your doctor can diagnose it.

There is no blood test, scan, or anything else that can be used as a diagnostic marker. The disease is therefore diagnosed based on symptoms and the lack of another explanation. Other conditions that are considered include chronic infections, sleep disorders, autoimmune disorders, heart disease, hypothyroidism, and clinical depression. Some of these conditions may occur as overlapping conditions with ME/CFS.

Chronic Fatigue vs. Fibromyalgia

Many people with chronic fatigue syndrome fit the criteria for fibromyalgia syndrome (FMS), and vice versa. There is ongoing confusion as to whether these are different conditions or variations of the same disorder. Both lack a definitive cause or a test that can be used to diagnose them, and both are only defined by their symptoms.

The common symptoms of both conditions include fatigue, chronic widespread pain, unrefreshing sleep, cognitive impairment, and dizziness and impaired coordination. The difference is the ME/CFS has a primary symptom of fatigue while fibromyalgia has a primary symptom of pain. ME/CFS is also more likely to be tied to flu-like symptoms. 

While both may involve pain, FMS is linked to several pain conditions and sleep disorders that do not appear to be linked to ME/CFS. A tender point examination and questionnaire can help differentiate FMS, while ME/CFS relies on excluding any other condition that could be producing the symptoms.

The treatment of the two conditions changed in 2007 with the FDA approval of Lyrica (pregabalin) for fibromyalgia. It is an anti-seizure medication used for nerve pain. The FDA also approved the use of the antidepressants Cymbalta (duloxetine) and Savella (milnacipran) for FMS. These antidepressants may also be prescribed for ME/CFS, but as a treatment for overlapping depression rather than as a therapy for the condition itself.


There are no specific FDA-approved drugs or common regimens for treating ME/CFS. The treatment is geared to the individual to relieve symptoms and improve quality of life.

Lifestyle changes are used to manage the symptoms of fatigue, post-exertional malaise, sleep problems, and brain fog. Because ME/CFS can be an extremely stressful condition and worsen with stress, some people benefit from counseling, support groups, and stress-reduction techniques.

A typical treatment regimen can include over-the-counter or prescription medications to help with specific symptoms, supplements, other complementary or alternative therapies, and emotional support. Some doctors prefer cognitive behavioral therapy and exercise that gradually increases in difficulty, but this approach is extremely controversial due to post-exertional malaise. Some medical practitioners recommend dietary changes, yoga, and acupuncture.

Most people with this disease need to experiment with multiple treatment options before they find a successful regimen.

A Word From Verywell

ME/CFS is a difficult condition to live with. However, in time, you can find treatments and learn coping strategies that help you live a full life. Hope is on the horizon—researchers are getting closer to understanding what's going on in your body as well as how to better diagnose and treat it. Keep advocating for yourself and be sure you are working with a doctor who is as dedicated to helping you feel better as you are.

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