Chronic Fatigue Syndrome - Harvard Health

What is myalgic encephalomyelitis/chronic fatigue syndrome?

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complicated illness characterized by at least six months of extreme fatigue that is not relieved by rest, and a group of additional symptoms that also are constant for at least six months. In many people with ME/CFS, the disorder begins suddenly, often following a flulike infection or an episode of physical trauma such as surgery. Less often, ME/CFS develops gradually. The illness lasts for many months or years, and only a small percentage of people recover full health.

Many people feel tired a lot of the time, and many seek help from their doctors. Most people who experience chronic (long-lasting) fatigue are not suffering from ME/CFS. Depression and overwork are much more common causes of chronic fatigue.

The exact cause of ME/CFS remains a mystery. The illness can follow a number of common infectious illnesses, such as Lyme disease or infectious mononucleosis, but not all cases are tied to infections.

When patients with ME/CFS are compared to people of the same age, gender, and socioeconomic background who do not have ME/CFS, testing reveals underlying abnormalities involving the brain, immune system, energy metabolism, blood vessels, and bacteria in the gut.

With regard to the brain, testing has found that people with ME/CFS have abnormalities in the hypothalamus (a part of the brain that regulates hormones and vital functions) and the pituitary gland. They also have abnormalities in the part of the nervous system called the autonomic nervous system, which controls blood pressure, heart rate, body temperature, and other vital body functions. For example, many patients with ME/CFS have an unusually high heart rate and low blood pressure when they have been standing for a while.

Several parts of the immune system remain activated for long periods in people with ME/CFS. There is growing evidence that some patients with ME/CFS have an autoimmune condition: their immune system is attacking particular tissues in the body.

Patients with ME/CFS have defects in the ability of cells in their bodies to make energy. Abnormalities of the lining of blood vessels, and of how blood vessels function, also have been identified. Finally, there are differences in the bacteria that live in the gut and create low-level but ongoing inflammation in the gut wall.

Many of the abnormalities of the immune system, energy metabolism, and the nervous system seem to come and go. Furthermore, not all of the abnormalities affect every patient with ME/CFS.

Finally, there is a genetic component to the illness. Studies indicate that certain genes are built differently — genes that affect brain function, the immune system, and energy metabolism.

In the United States alone, ME/CFS is estimated to affect up to 3.1 million people, and generates direct and indirect expenses of approximately $36 billion to $51 billion annually, according to the U.S. National Academy of Medicine (NAM) and the Centers for Disease Control and Prevention (CDC). Women are affected about two to three times as often as men. Although the illness is most common in people 25 to 45 years old, ME/CFS can attack people of all age groups, including children. The condition also is found in people of all racial, ethnic, and economic backgrounds. It appears to be more common in African Americans and Latinos, and in people in lower socioeconomic groups. It appears to be less common in Asian Americans.

Although most cases of ME/CFS do not occur during epidemics, at least 30 outbreaks of ME/CFS have been reported, during which many people in the same area suddenly developed the illness at the same time. However, health experts have failed to identify a cause for their ME/CFS symptoms.

A condition very similar to ME/CFS has developed in some people infected with the SARS Co-V2 virus that causes COVID-19: a persistent, debilitating illness that has lasted for several years, called long COVID. Not only are the symptoms of ME/CFS and long COVID similar, but they also appear to share many similar underlying physical abnormalities.

Symptoms of ME/CFS

The most prominent symptom of ME/CFS is an unexplained feeling of fatigue, which is not relieved by rest. However, many other medical conditions cause marked fatigue.

To better identify people with ME/CFS, diagnostic criteria should include these four types of symptoms:

a substantial reduction or impairment in the ability to engage in pre-illness levels of occupational, educational, social, or personal activities for longer than six months
post-exertional malaise (PEM), which is a worsening of symptoms following physical, mental, or emotional exertion that would not have caused a problem before the illness. PEM can last a couple of days to more than a week following the bout of exertion.
unrefreshing sleep that leaves a person not feeling better, or perhaps even feeling worse after a full night’s sleep, and no other reason for poor sleep quality
one or both of these neurological symptoms:
- cognitive impairment, such as problems with thinking, memory, attention, organization skills, and information processing. These symptoms are often made worse after physical exertion, prolonged standing, or mental tasks.
- orthostatic intolerance, which is a worsening of symptoms upon assuming and maintaining upright posture. This can include lightheadedness, fainting, increased fatigue, cognitive worsening, headaches, or nausea with standing and often some relief with lying down.

Many people with ME/CFS also experience additional symptoms, including:

muscle pain
pain in the joints without swelling or redness
headaches of a new type, pattern, or severity
swollen or tender lymph nodes in the neck or armpit
a sore throat that is frequent or recurring
sensitivity to light and sound
nausea
allergies or sensitivities to foods, odors, chemicals, or medications.

Diagnosing ME/CFS

Although there is a lot of evidence that ME/CFS is caused by a physical problem involving the brain, immune system, energy metabolism, blood vessels, and the bacteria in the gut, there is no laboratory test or procedure to confirm the diagnosis. Today, the diagnosis of ME/CFS is based on the presence of the four major symptoms noted above.

Your doctor will also want to consider other possible reasons for your symptoms, such as:

hypothyroidism (underactive thyroid gland)
adrenal insufficiency (underactive adrenal gland)
heart disorders
sleep apnea or narcolepsy
side effects of medications
chronic hepatitis
kidney disease.

Your doctor will examine you and likely order some basic blood tests such as a red blood cell count (hematocrit), white blood cell count and differential white blood cell count, thyroid, kidney, and liver tests. Additional, more specialized testing may be needed, including testing of your autonomic nervous system.

Expected duration of ME/CFS

To be diagnosed as ME/CFS, symptoms must last for at least six months. Unfortunately, in many people, symptoms persist for years. Symptoms tend to be worse in the first one to two years, and level of functioning gradually improves over time. However, only a small percentage of people recover to full health.

Preventing ME/CFS

There are no specific actions a person can take to prevent ME/CFS.

Treating ME/CFS

There is no FDA-proven treatment for ME/CFS. However, clinician acknowledgement of the patient’s condition as ME/CFS and symptom-guided approaches can improve quality of life.

In general, doctors use a combination of the following:

Lifestyle changes: Patients are often initially encouraged to slow down, minimize physical exertion, and try to avoid psychological stress. They learn to save their energy for essential activities at home or work and to cut back on less important activities.
Pacing of physical activities: Patients must first recognize the level of physical exertion that will trigger post-exertional malaise (PEM) symptoms and avoid reaching that level. With the help of a physical therapist or personal trainer experienced with ME/CFS, they then can begin an exercise program. But it must be paced to avoid PEM symptoms. Once there is comfort with what activities can be done and for how long, a program to help prevent deconditioning can be constructed.
Pacing of cognitive activities: Similar to the goals for physical pacing, patients need to initially try to avoid stressful, intense, or prolonged mental tasks, especially those with tight deadlines. Adaptations to work or school obligations are often required.
Addressing symptoms related to orthostatic intolerance: Staying well hydrated, adding salt, wearing compression stockings, and avoiding prolonged standing can help prevent lightheadedness and extreme fatigue.
Improving sleep quality: This starts with sleep hygiene. Your doctor may suggest low-dose trazadone or a tricyclic antidepressant before bed.
Treating existing pain: Aspirin, acetaminophen (Tylenol), or nonsteroidal anti-inflammatory drugs (NSAIDs) are used to treat headaches, muscle pain, and joint pain. Antidepressant medications also may help to reduce chronic pain.

When to call a professional

Call your doctor if you have symptoms of ME/CFS, especially if extreme fatigue prevents you from fully participating in activities at home, work, or school.

Prognosis

People with ME/CFS usually experience their most severe symptoms in the first one to two years of illness. After that time, a small number of people recover totally, and others slowly improve their ability to function but do not recover fully. Unfortunately, a small number become totally incapacitated. For most people there is gradual improvement, although they usually cannot achieve the same activity level that they were capable of before becoming ill. Recovery tends to be less likely among people who: