Description

• A condition characterized by (1) profound mental and physical exhaustion, (2) with at least 6 months presence of multiple systemic and neuropsychiatric symptoms, and (3) at least 4 of 8 associated conditions are required per CDC definition:
  • Impaired memory
  • Sore throat
  • Tender lymph nodes
  • Persistent muscle or joint pain
  • New headaches
  • Nonrefreshing sleep
  • Postexertional malaise
• Must have a new or definite onset (not lifelong). 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.
• Exclusions:
  • Patients are excluded from chronic fatigue syndrome (CFS) definition until 2 years after resolution of substance/alcohol abuse, 5 years after resolution of anorexia nervosa or bulimia, and if they have BMI ≥45.

Epidemiology

• Predominant age: 20–50 years
• Predominant sex: Male < Female
• All socioeconomic groups
• Various, and at times contradictory, associations between ethnicity and incidence have been reported. Higher rates found in ethnic minorities (Native Americans and African Americans) compared with white populations, based on a population study. Service-based studies (tertiary care) have reported higher rates among whites, or no association between incidence and ethnicity (1).

Prevalence
Estimates vary widely and depend on case definition and population studied, but a reasonable estimate using a strict case definition is 100 cases per 100,000 population. Community-based studies have reported prevalence rates of 0.23% and 0.42%.

Risk Factors

Possible predisposing factors include (2,3):

• Personality characteristics (neuroticism and introversion)
• Lifestyle:
  • Childhood inactivity or overactivity
  • Inactivity in adulthood after infectious mononucleosis
  • Familial predisposition
  • Comorbid mood disorders of depression and anxiety
• Long-standing medical conditions in childhood
• Childhood trauma (emotional, physical, sexual abuse)
• Prolonged idiopathic chronic fatigue (4)

Genetics
Higher concordance among monozygotic twins compared with dizygotic twins

Etiology

• Unknown and likely multifactorial:
  • Possible interaction between genetic predisposition, environmental factors, an initiating stressor, and perpetuating factors
• Physiologic or environmental stressor could be precipitant.
• Many patients with chronic fatigue recall significant stressors (e.g., major medical procedure, loss of a loved one, loss of employment) in months before symptoms began.
• Systems hypothesized to contribute to physiology include:
  • Neuroendocrine (e.g., diminished cortisol response to increased corticotropin concentrations)
  • Immune (e.g., increased C-reactive protein and beta-2 microglobulin) (5)
  • Neuromuscular (e.g., dysfunction of oxidative metabolism) (5)
  • Autonomic (orthostatic hypotension is reported in a proportion of CFS sufferers)
• Serotonergic (e.g., hyperserotonergic mechanisms or upregulation of serotonin receptors)

Commonly Associated Conditions

Common comorbidities include:

• Fibromyalgia (more common in women)
• Irritable bowel syndrome
• Temporomandibular joint disorder
• Anxiety disorders
• Major depression
• Posttraumatic stress disorder (including physical and/or sexual past abuse)
• Domestic violence