Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (CFS)

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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 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

-- 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 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

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