Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (CFS)

Description

• A chronic and complex physical illness characterized by a new or definitive onset of debilitating fatigue that persists for >6 months with moderate to severe intensity at least half of the time, which significantly reduces a person’s ability to perform activities, and can’t be fully explained by an underlying medical condition
• Key features include impaired memory or concentration, joint/muscle pain, nonrestorative sleep, postexertional malaise (PEM), orthostatic intolerance.
• Synonyms: myalgic encephalomyelitis (ME)/chronic fatigue syndrome (CFS), chronic Epstein-Barr virus syndrome, postviral fatigue syndrome, chronic fatigue immune dysfunction, systemic exertion intolerance disease

Epidemiology

• Can affect all ages; incidence peaks at 10 to 19 years and 30 to 39 years.
• Females are twice as likely to be affected.

Prevalence

• Affects all racial and ethnic groups; more prevalent in minority and low socioeconomic
• Estimated at 519 to 1,038 diagnosed per 100,000; 1.7 to 3.4 million patients may have ME/CFS.
• Up to 90% of cases may stay undiagnosed (1).

Etiology and Pathophysiology

The cause is unknown and likely multifactorial.

• Suspected initiating stressors:
  • Viral, bacterial, or parasitic infection: Epstein-Barr virus, retroviruses, Lyme disease, Q fever, human herpesvirus type 6 (HHV6), enteroviruses, Ross River virus, Borna disease virus
  • Recent vaccination; overexertion, chronic sleep deprivation; toxin exposure (e.g., organophosphate pesticides) or an atypical adverse reaction to a medication; significant physical or emotional trauma
• Hypothesized contributing factors:
  • Cellular metabolism (e.g., reduced oxidative phosphorylation and mitochondrial function in T cells); neuroendocrine system (e.g., diminished cortisol response to increased corticotropin); immune system (e.g., increased proinflammatory cytokines, C-reactive protein, and β₂-microglobulin); muscular system (e.g., reduced oxygen uptake); autonomic system (e.g., orthostatic hypotension); serotonergic system (e.g., upregulation of serotonin receptors); gastrointestinal system (e.g., increased wall permeability, altered gut microbiota, irritable bowel syndrome [IBS] comorbidity)

Genetics

• Higher concordance in monozygotic twins
• Genetic polymorphisms in several neuroimmunoendocrine-related genes may contribute to developing disease.

Risk Factors

• Family history of ME or CFS
• Personality characteristics (neuroticism and introversion); comorbid depression or anxiety
• Long-standing medical and/or mental health conditions in childhood; childhood inactivity or overactivity; childhood trauma (emotional, physical, or sexual abuse)
• Prolonged idiopathic chronic fatigue

Commonly Associated Conditions

• Fibromyalgia
• IBS
• Gynecologic conditions (pelvic pain, endometriosis) and surgeries (hysterectomy, oophorectomy)
• Anxiety disorders and/or major depressive disorders; posttraumatic stress disorder (PTSD), including physical and/or past sexual abuse; domestic violence; attention deficit hyperactivity disorder (ADHD)
• Postural orthostatic tachycardia syndrome (POTS); sleep disorders, including obstructive sleep apnea (OSA)
• Reduced left ventricular size and mass; prolapsed mitral valve; temporomandibular joint syndrome
• Multiple chemical sensitivities; migraines, myofascial pain syndrome
• Hashimoto thyroiditis, Raynaud phenomenon; interstitial cystitis, sicca syndrome, allergies