The exact cause of ME/CFS is unknown. It may have more than one cause. For example, two or more possible causes may work together to trigger the illness.

Researchers are looking into these possible causes:

• Infection -- About 1 out of 10 people who develop certain infections, such as Epstein-Barr virus and Q fever, go on to develop ME/CFS. Other infections have also been studied, but not one cause has been found.
• Immune system changes -- ME/CFS may be triggered by changes in the way a person's immune system responds to stress or illness.
• Mental or physical stress -- Many people with ME/CFS have been under serious mental or physical stress before becoming ill.
• Energy production -- The way that cells within the body get energy is different in people with ME/CFS than in people without the condition. It's unclear how this is linked to developing the illness.
• Long COVID or Post-acute sequelae of SARS CoV-2 infection (PASC) -- Some people who have been infected with the COVID-19 virus continue to have symptoms weeks or months later. This is called long COVID. Because symptoms such as extreme fatigue, difficulty concentrating, dizziness, and sleep problems are similar to ME/CFS, researchers are looking into a possible connection between the two conditions.

Genetics or environmental factors may also play a role in the development of ME/CFS:

• Anyone can get ME/CFS.
• While most common in people between 40 and 60 years old, the illness affects children, adolescents, and adults of all ages.
• Among adults, women are affected more often than men.
• White people are diagnosed more than other races and ethnicities. But many people with ME/CFS have not been diagnosed, particularly among minorities.

There are three main, or "core," symptoms in people with ME/CFS:

• Profound fatigue
• Worsening symptoms after physical or mental activity
• Sleep problems

People with ME/CFS have persistent and profound fatigue and are unable to do activities they were able to do before the illness. This extreme fatigue is:

• New
• Lasts at least 6 months
• Not due to unusual or intense activity
• Not relieved by sleep or bed rest
• Severe enough to keep you from participating in certain activities

ME/CFS symptoms can become worse after physical or mental activity. This is called post-exertional malaise (PEM), also known as a crash, relapse, or collapse.

• For example, you may experience a crash after shopping at the grocery store and need to take a nap before driving home. Or you may need someone to come pick you up.
• There is no way to predict what will cause a crash or know how long it will take to recover. It can take days, weeks, or longer to recover.

Sleep issues may include problems falling or staying asleep. A full-night's rest does not relieve fatigue and other symptoms.

People with ME/CFS also often experience at least one of the two following symptoms:

• Forgetfulness, concentration problems, problems following details (also called "brain fog")
• Worsening symptoms when standing or sitting upright. This is called orthostatic intolerance. You may feel dizzy, lightheaded, or faint when standing or sitting up. You also may have vision changes or see spots.

Other common symptoms include:

• Joint pain without swelling or redness, muscle aches, muscle weakness all over, or headaches that differ from those you have had in the past
• Sore throat, sore lymph nodes in the neck or under the arms, chills and night sweats
• Digestive problems, such as irritable bowel syndrome
• Allergies
• Sensitivity to noise, food, odors, or chemicals

The Centers for Disease Control (CDC) describes ME/CFS as a distinct disorder with specific symptoms and physical signs. Diagnosis is based on ruling out other possible causes.

Your health care provider will try to rule out other possible causes of fatigue, including:

• Drug dependence
• Immune or autoimmune disorders
• Infections
• Muscle or nerve diseases (such as multiple sclerosis)
• Endocrine diseases (such as hypothyroidism)
• Other illnesses (such as heart, kidney, or liver diseases)
• Psychiatric or psychological illnesses, particularly depression
• Tumors

A diagnosis of ME/CFS must include:

• Absence of other causes of long-term (chronic) fatigue
• At least four ME/CFS-specific symptoms
• Extreme, long-term fatigue

There are no specific tests to confirm the diagnosis of ME/CFS. However, there have been reports of people with ME/CFS having abnormal results on the following tests:

• Brain MRI
• White blood cell count

There is currently no cure for ME/CFS. The goal of treatment is to relieve symptoms.

Treatment includes a combination of the following:

• Sleep management techniques
• Medicines to reduce pain, discomfort, and fever
• Medicines to treat anxiety (anti-anxiety drugs)
• Medicines to treat depression (antidepressant drugs)
• Healthy diet

Some drugs can cause reactions or side effects that are worse than the original symptoms of the disease.

People with ME/CFS are encouraged to maintain an active social life. Mild physical exercise may also be helpful. Your health care team will help you figure out how much activity you can do, and how to slowly increase your activity. Tips include:

• Avoid doing too much on days when you feel tired
• Balance your time between activity, rest, and sleep
• Break big tasks into smaller, more manageable ones
• Spread out your more challenging tasks throughout the week

Relaxation and stress-reduction techniques can help manage chronic (long-term) pain and fatigue. They are not used as the primary treatment for ME/CFS. Relaxation techniques include:

• Biofeedback
• Deep breathing exercises
• Hypnosis
• Massage therapy
• Meditation
• Muscle relaxation techniques
• Yoga

It also may be helpful to work with a therapist to help you deal with your feelings and the impact of the illness on your life.

Newer medicine approaches are being researched.

Some people may benefit from taking part in an ME/CFS support group.

The long-term outlook for people with ME/CFS varies. It is hard to predict at the time that symptoms first start. Some people completely recover after 6 months to a year.

About 1 in 4 people with ME/CFS are so severely disabled that they can't get out of bed or leave their home. Symptoms can come and go in cycles, and even when people feel better, they may experience a relapse triggered by exertion or an unknown cause.

Some people never feel like they did before they developed ME/CFS. Studies suggest that you are more likely to get better if you receive extensive rehabilitation.

Complications may include:

• Depression
• Inability to take part in work and social activities, which can lead to isolation
• Side effects from medicines or treatments

Call your provider if you have severe fatigue, with or without other symptoms of this disorder. Other more serious disorders can cause similar symptoms and should be ruled out.

If you or someone you know is thinking about suicide, call or text 988 or chat 988lifeline.org. You can also call 1-800-273-8255 (1-800-273-TALK). The 988 Suicide and Crisis Lifeline provides free and confidential support 24/7, anytime day or night.

You can also call 911 or the local emergency number or go to the hospital emergency room. DO NOT delay.

If someone you know has attempted suicide, call 911 or the local emergency number right away. DO NOT leave the person alone, even after you have called for help.

CFS; Fatigue - chronic; Immune dysfunction syndrome; Myalgic encephalomyelitis (ME); Myalgic encephalopathy chronic fatigue syndrome (ME-CFS); Systemic exertion intolerance disease (SEID)

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Smith ME, Haney E, McDonagh M, et al. Treatment of myalgic encephalomyelitis/chronic fatigue syndrome: a systematic review for a National Institutes of Health Pathways to Prevention Workshop. Ann Intern Med. 2015;162(12):841-850. PMID: 26075755 pubmed.ncbi.nlm.nih.gov/26075755/.

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Updated by: Neil J. Gonter, MD, Assistant Professor of Medicine, Columbia University, New York, NY, and private practice specializing in Rheumatology at Rheumatology Associates of North Jersey, Teaneck, NJ. Review provided by VeriMed Healthcare Network. Also reviewed by David C. Dugdale, MD, Medical Director, Brenda Conaway, Editorial Director, and the A.D.A.M. Editorial team.