Misunderstood illness leaves millions exhausted, with most cases undiagnosed

Chronic fatigue syndrome, formally known as myalgic encephalomyelitis, is a poorly understood illness that leaves millions exhausted and often undiagnosed. In the United States, about 3.3 million people live with the condition, and as many as one in four experience bedbound periods at some point during the illness. Despite its prevalence, many experts say clinicians routinely miss the diagnosis, with past research suggesting only about 15% of affected individuals are correctly identified.

The National Academy of Medicine defines the syndrome as having three core symptoms that last at least six months: severe fatigue that is new and markedly limits daily activities; malaise that worsens after physical or mental effort that previously was well tolerated; and unrefreshing sleep. Some patients also report trouble with thinking and memory, commonly called brain fog, or lightheadedness when standing.

There are no tests to confirm chronic fatigue syndrome. Doctors diagnose it by reviewing symptoms, conducting physical exams and excluding other disorders that can mimic the illness, such as hypothyroidism and depression. The CDC notes that management is tailored to the symptoms that most affect a patient’s quality of life and may involve a combination of lifestyle changes, therapies and medications.

"CFS, fibromyalgia and long COVID are all related conditions with different names," Dr. Jacob Teitelbaum, author of "From Fatigued to Fantastic" — whose research focuses on chronic fatigue syndrome — told Fox News Digital. "What these illnesses have in common is that they are immune disorders, and immune disorders predominantly affect women." He noted that many genes related to immune disorders sit on the X chromosome, suggesting a genetic component.

Experts say there are likely multiple causes and triggers, with energy depletion potentially tied to dysfunction in the hypothalamus, the brain region that regulates sleep, hormones, blood pressure and pulse. The hallmark signs include insomnia despite exhaustion, brain fog and widespread pain. Anything that causes severe energy depletion can trigger the syndrome, including chronic life stressors, nutritional deficiencies, thyroid and stress hormone imbalances, and sleep problems.

Two classic infections have been linked to onset in some patients, and sudden hormonal shifts after pregnancy can also play a role, Teitelbaum cautioned. Head and neck trauma and sudden hormonal changes after pregnancy can trigger chronic fatigue as well.

There aren’t currently any blood tests to uniformly diagnose the syndrome, but Dr. Oh said she is hopeful that will change in the future. Her research team developed an experimental artificial intelligence–based tool, BioMapAI, that has been shown to identify the condition with high accuracy by analyzing stool, blood and other common lab tests, according to early research published in July in the journal Nature Medicine.

Given how differently chronic fatigue syndrome can affect people, there is no universally effective therapy, according to Oh. The CDC recommends that patients work with their doctors to create a management plan based on the symptoms that most affect quality of life. There are no tests to confirm chronic fatigue, so doctors diagnose it by evaluating symptoms and excluding other disorders. Treatments generally include a combination of lifestyle changes, therapies and medications, with patients and their physicians weighing potential benefits and risks.

There are some alternative therapies that have shown promise for some patients. Teitelbaum developed a protocol called SHINE, which focuses on sleep, hormones and hypotension, infections, nutrition and exercise. Some research has shown that this approach can help improve the quality of life for people with CFS and fibromyalgia, though findings are not universal. Others may find benefit from physiotherapy or physical therapy. Those who experience persistent fatigue that hinders their ability to participate in regular activities or impacts their quality of life should speak with a doctor.