Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (CFS)
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- A complex physical illness characterized by a new or definitive onset of debilitating fatigue that persists for >6 months and significantly reduces a person’s ability to perform usual activities. Key features include:
- Impaired memory or concentration
- Joint and muscle pain
- Unrefreshing sleep
- Postexertional malaise
- Orthostatic intolerance (i.e., dizziness and light-headedness when standing up)
- Synonyms: myalgic encephalomyelitis, chronic Epstein-Barr virus syndrome, postviral fatigue syndrome, chronic fatigue immune dysfunction, and systemic exertion intolerance disease (1)
- Fatigue is not relieved by rest and results in >50% reduction in previous activities (occupational, educational, social, and personal).
- Other potential medical causes must be ruled out (2).
- Usually sporadic or isolated cases, although cluster outbreaks have occurred in different parts of the world—Iceland (1948); London, England (1955); New Zealand (1984); and the United States (1984 and 1985)
- Onset usually from age 30 to 50 years; can affect all ages (1)[B]
- Females affected 3 to 4 times more than male
- Estimated annual cost from loss of productivity and medical bills ranges from $17 to 24 billion in the United States.
Etiology and Pathophysiology
- Unknown and likely multifactorial
- Possible interaction between genetic predisposition, environmental factors, an initiating stressor, and perpetuating factors
- A recent theory attributes possible neuroendocrine immunologic and biochemical effects in CFS to dysbiosis of the gut microbiome.
- Physiologic or environmental stressors are potential precipitants.
- Many patients with chronic fatigue recall significant stressors (e.g., major medical procedure, loss of a loved one, loss of employment) in months before symptom onset.
- History of childhood trauma is common.
- Systems hypothesized to contribute include:
- Neuroendocrine (e.g., diminished cortisol response to increased corticotropin concentrations)
- Immune (e.g., increased C-reactive protein and β2-microglobulin)
- Neuromuscular (e.g., dysfunction of oxidative metabolism)
- Autonomic (orthostatic hypotension)
- Serotonergic (e.g., hyperserotonergic mechanisms or upregulation of serotonin receptors)
Higher concordance among monozygotic twins compared with dizygotic twins
Possible predisposing factors:
- Personality characteristics (neuroticism and introversion)
- Childhood inactivity or overactivity
- Inactivity in adulthood after infectious mononucleosis
- Familial predisposition
- Comorbid depression or anxiety
- Long-standing medical conditions in childhood
- Childhood trauma (emotional, physical, sexual abuse)
- Prolonged idiopathic chronic fatigue
- Postinfectious fatigue and CFS have been noted to follow mononucleosis, Ross River virus, Coxiella burnetii, herpes zoster, Q fever, and Giardia lamblia.
- Due to concern for possible infectious etiology, CFS patients excluded from donating blood by the American Red Cross in 2010
Commonly Associated Conditions
Common comorbidities include:
- Fibromyalgia (more common in women)
- Irritable bowel syndrome
- Gynecologic conditions (pelvic pain, endometriosis) and GYN surgeries (hysterectomy, oophorectomy) (2)
- Anxiety disorders
- Major depression
- Posttraumatic stress disorder (including physical and/or past sexual abuse)
- Domestic violence
- Attention deficit hyperactivity disorder (ADHD)
- Postural orthostatic tachycardia syndrome (POTS)
- Sleep disorders, including OSA
- Reduced left ventricular size and mass