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INTRODUCTION

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a chronic complex illness with multisystem manifestations and long-term impact on functional impairment comparable to multiple sclerosis, rheumatoid arthritis, and congestive heart failure. The hallmark of ME/CFS is persistent and unexplained fatigue resulting in significant impairment in daily functioning along with worsening symptoms following physical or mental exertion that would have been tolerated before illness (post-exertional malaise). Besides intense fatigue, many patients report concomitant symptoms such as pain, cognitive dysfunction, and unrefreshing sleep. Additional symptoms can include headache, sore throat, tender lymph nodes, muscle aches, joint aches, feverishness, difficulty sleeping, psychiatric problems, allergies, and abdominal cramps.

The condition has been known by many names and debate about the name and case definition continues. The composite name ME/CFS was adopted by the U.S. Department of Health and Human Services in recognition of the limitations of either ME (absence of definitive inflammation in brain and spinal cord) or CFS (trivializes an often devastating illness through confusion with fatigue that everyone experiences). An alternative name, systemic exertion intolerance disease (SEID), proposed by the 2015 Institute of Medicine (IOM, now the National Academy of Medicine) committee reviewing ME/CFS, has not gained acceptance.

EPIDEMIOLOGY

Determining how frequently ME/CFS occurs and characteristics of those affected has been complicated by variability in study design and application of case definitions. In the absence of a simple diagnostic test, evaluation by an experienced clinician is required for case identification. Clinic-based studies most accurately identify patients with ME/CFS but overrepresent higher socioeconomic groups with access to ME/CFS clinics. Population-based surveys that included a clinical evaluation estimated a prevalence of 0.2–0.7%, suggesting ≥1 million Americans have ME/CFS. However, these surveys found that ≥80% of those meeting criteria for ME/CFS had not been diagnosed by a health care provider. ME/CFS is three to four times more common in women than men. The highest prevalence of illness is among those 40–50 years of age, but the age range is broad and includes children and adolescents. Persons of all race and ethnicities are affected, and there is some evidence that socioeconomically disadvantaged groups are at increased risk.

RISK FACTORS AND PATHOPHYSIOLOGY

A wide variety of infectious agents have been reported to be associated with a postinfectious fatiguing illness resembling ME/CFS. These include both viral and nonviral pathogens, such as Epstein-Barr virus, Ross River virus, Coxiella burnetti (Q fever), Ebola virus, SARS-CoV-1, and Giardia. While recovery from these infections is the rule, approximately 10% of those infected remain ill for ≥6 months. Most recently, published reports suggest that SARS-CoV-2 infection is also associated with prolonged fatiguing illness. Host and pathogen factors associated with recovery versus persistent disease remain elusive. In addition to infectious insults, a variety of stressors, including physical trauma, adverse events, and allostatic load (or “wear and tear” on the body) have been found to be associated with ...

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