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 preillness activities
• Key features include (1):
  • Impaired memory or concentration
  • Joint and muscle pain, unrefreshing 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, and systemic exertion intolerance disease
• Fatigue is not relieved by rest and results in >50% reduction in preillness activities (occupational, educational, social, and personal).
• Other commonly associated symptoms include heart rate variability; excessive sweating; muscle and joint pain; and light, sound; and chemical sensitivity (2).
• Other causes such as schizophrenia, manic-depressive illness, substance abuse, eating disorder, or proven organic brain disease must be ruled out (3).

Epidemiology

• Can affect all ages; incidence peaks at 10 to 19 years and 30 to 39 years (1).
• Females are twice as likely to be affected (3).
• Up to 70% of patients are unable to return to work, and one quarter remain bedridden or housebound (2).

Prevalence

• Affects all racial and ethnic groups; more prevalent in minority and low socioeconomic groups
• Estimated at 519 to 1,038 diagnosed per 100,000; 1.7 to 3.4 million patients may suffer from ME or CFS.
• Up to 90% of cases may remain undiagnosed (2).

Etiology and Pathophysiology

Cause is unknown and likely multifactorial

• Suspected initiating stressors:
  • Viral, bacterial, or parasitic infection: Epstein-Barr virus (EBV), retroviruses, Lyme disease, Q fever, human herpesvirus type 6, enteroviruses, Ross river virus, Borna disease virus
  • Significant physical or emotional trauma
  • Recent vaccination
  • Overexertion, chronic sleep deprivation
  • Toxin exposure (e.g., organophosphate pesticides) or an atypical adverse reaction to a medication
• Suspected perpetuating factors:
  • Delay in diagnosis
  • Overexertion
  • Stress, inadequate sleep
• Hypothesized contributing systems and factors (4):
  • Cellular metabolism (e.g., reduced oxidative phosphorylation and mitochondrial function)
  • 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 (4).

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 (more common in women)
• 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