Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (CFS)

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (CFS) is a topic covered in the 5-Minute Clinical Consult.

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Basics

Description

  • A chronic and 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 pre-illness activities. Key features include (1):
    • Impaired memory or concentration
    • Joint and muscle pain
    • Unrefreshing sleep
    • Post-exertional malaise (PEM)
    • Orthostatic intolerance (i.e., dizziness and light-headedness when standing up)
  • Synonyms: myalgic encephalomyelitis (ME), 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 pre-illness activities (occupational, educational, social, and personal).
  • Other potential medical causes must be ruled out.

Epidemiology

  • Usually seen as sporadic or in isolated cases, although cluster outbreaks in school-age children have occurred around the world: Iceland (1948); London, England (1955); New Zealand (1984); and the United States (1984 and 1985).
  • Can affect all ages; incidence peaks at 10–19 years and 30–39 years (1)
  • More female than male adults are affected
  • Estimated annual cost (direct and indirect) $17–24 billion

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; as extrapolated from the US population (2017) an estimated 1.7 to 3.38 million patients may suffer from ME or CFS.

Etiology and Pathophysiology

Cause is unknown and most likely multifactorial—a combination of genetics, initiating stressors, and perpetuating factor(s):

  • 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 include:
    • Delay in diagnosis and consequently disease management
    • Overexertion
    • Stress
    • Inadequate sleep
    • Co-morbid conditions, such as orthostatic intolerance
  • Hypothesized contributing systems and factors include:
    • Cellular metabolism (e.g., reduced oxidative phosphorylation and mitochondrial function)
    • Neuroendocrine system (e.g., diminished cortisol response to increased corticotropin concentrations)
    • Immune system (e.g., increased pro-inflammatory cytokines, C-reactive protein, and β2-microglobulin)
    • Muscular system (e.g., reduced glucose and oxygen uptake)
    • Autonomic system (e.g., orthostatic hypotension)
    • Serotonergic system (e.g., hyperserotonergic mechanisms or upregulation of serotonin receptors)
    • Gastrointestinal system (e.g., increased wall permeability, altered gut microbiota, IBS co-morbidity)
Genetics
  • Higher concordance in monozygotic twins than dizygotic twins
  • Genetic polymorphisms in several neuroimmunoendocrine-related genes have been reported and may contribute to the risk of developing disease (2)
  • Due to the historical occurrence of ME/CFS outbreaks, there may be a common predisposing genetic mutation that is hidden by the rare combination of trigger events required to induce a disease phenotype.

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)
  • Irritable bowel syndrome (IBS)
  • Gynecologic conditions (pelvic pain, endometriosis) and surgeries (hysterectomy, oophorectomy)
  • Anxiety disorders and/or major depressive disorders
  • Post-traumatic 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

-- To view the remaining sections of this topic, please or --

Basics

Description

  • A chronic and 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 pre-illness activities. Key features include (1):
    • Impaired memory or concentration
    • Joint and muscle pain
    • Unrefreshing sleep
    • Post-exertional malaise (PEM)
    • Orthostatic intolerance (i.e., dizziness and light-headedness when standing up)
  • Synonyms: myalgic encephalomyelitis (ME), 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 pre-illness activities (occupational, educational, social, and personal).
  • Other potential medical causes must be ruled out.

Epidemiology

  • Usually seen as sporadic or in isolated cases, although cluster outbreaks in school-age children have occurred around the world: Iceland (1948); London, England (1955); New Zealand (1984); and the United States (1984 and 1985).
  • Can affect all ages; incidence peaks at 10–19 years and 30–39 years (1)
  • More female than male adults are affected
  • Estimated annual cost (direct and indirect) $17–24 billion

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; as extrapolated from the US population (2017) an estimated 1.7 to 3.38 million patients may suffer from ME or CFS.

Etiology and Pathophysiology

Cause is unknown and most likely multifactorial—a combination of genetics, initiating stressors, and perpetuating factor(s):

  • 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 include:
    • Delay in diagnosis and consequently disease management
    • Overexertion
    • Stress
    • Inadequate sleep
    • Co-morbid conditions, such as orthostatic intolerance
  • Hypothesized contributing systems and factors include:
    • Cellular metabolism (e.g., reduced oxidative phosphorylation and mitochondrial function)
    • Neuroendocrine system (e.g., diminished cortisol response to increased corticotropin concentrations)
    • Immune system (e.g., increased pro-inflammatory cytokines, C-reactive protein, and β2-microglobulin)
    • Muscular system (e.g., reduced glucose and oxygen uptake)
    • Autonomic system (e.g., orthostatic hypotension)
    • Serotonergic system (e.g., hyperserotonergic mechanisms or upregulation of serotonin receptors)
    • Gastrointestinal system (e.g., increased wall permeability, altered gut microbiota, IBS co-morbidity)
Genetics
  • Higher concordance in monozygotic twins than dizygotic twins
  • Genetic polymorphisms in several neuroimmunoendocrine-related genes have been reported and may contribute to the risk of developing disease (2)
  • Due to the historical occurrence of ME/CFS outbreaks, there may be a common predisposing genetic mutation that is hidden by the rare combination of trigger events required to induce a disease phenotype.

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)
  • Irritable bowel syndrome (IBS)
  • Gynecologic conditions (pelvic pain, endometriosis) and surgeries (hysterectomy, oophorectomy)
  • Anxiety disorders and/or major depressive disorders
  • Post-traumatic 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

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