Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (CFS)

BASICS

Chronic, complex illness with new/prolonged, debilitating fatigue (>6 months, moderate/severe at least half the time)
Marked reduction in activity, not explained by another medical condition
Key features: impaired memory/concentration, joint/muscle pain, nonrestorative sleep, postexertional malaise (PEM), orthostatic intolerance
Synonyms: myalgic encephalomyelitis (ME), postviral fatigue syndrome, chronic Epstein-Barr virus syndrome, chronic fatigue immune dysfunction, systemic exertion intolerance disease

Cause unknown, likely multifactorial
Suspected stressors: viral/bacterial/parasitic infection (e.g., EBV, Lyme, HHV6), recent vaccination, overexertion, sleep deprivation, toxins, trauma, adverse medication reaction
Contributing factors:
Cellular metabolism: ↓ oxidative phosphorylation/mitochondrial function (T cells)
Neuroendocrine: ↓ cortisol response
Immune: ↑ cytokines, CRP, β2-microglobulin
Muscular: ↓ oxygen uptake
Autonomic: orthostatic hypotension
Serotonergic: upregulated serotonin receptors
GI: ↑ permeability, altered microbiota, IBS
Genetics: higher concordance in monozygotic twins; polymorphisms in neuroimmunoendocrine genes

Family history
Personality: neuroticism, introversion
Comorbidities: depression, anxiety, childhood trauma, inactivity/overactivity, long-standing medical/mental health issues
Prolonged idiopathic chronic fatigue

Fibromyalgia, IBS, pelvic pain, endometriosis, gynecologic surgery
Anxiety, depression, PTSD, ADHD
POTS, OSA, migraines, TMJ, interstitial cystitis, Hashimoto, Raynaud, allergies
Multiple chemical sensitivities, myofascial pain, reduced LV size/mass, mitral valve prolapse

IOM 2015 Criteria:
Substantial reduction in activity ≥6 months with profound, new fatigue not alleviated by rest
PEM: worsening after exertion
Nonrestorative sleep
At least one: cognitive impairment or orthostatic intolerance

Idiopathic chronic fatigue, depression, anxiety, substance use
Poor sleep hygiene, pregnancy, menopause
Sleep, endocrine, chronic/acute infection, medication, toxin, rheumatologic, inflammatory, neurologic, cardiovascular, malignancy

No specific test; screen to exclude other causes
Initial labs: CBC, CMP, UA, TSH, free T4, ESR/CRP, Mg, Phos, B12, folate, CK, Vit D, iron studies
Follow-up: ANA, RF, TST, salivary cortisol, HIV, RPR, Lyme, TTG IgA, drug screen, age/gender-appropriate cancer screening, EEG/MRI (if CNS symptoms), polysomnography (if sleep disorder suspected)

Symptom control and guided self-management
Address most troublesome symptoms (pain, insomnia)
CBT: not curative, but may improve coping/rehab
GET: gradual increase, only with trained professional; pacing to manage PEM
Multidisciplinary approach

No established drugs for CFS
Symptom-based: nonaddicting sleep aids (hydroxyzine, trazodone, doxepin); agomelatine promising; antivirals, antidepressants, immunoglobulins, steroids, modafinil, methylphenidate, gabapentin, galantamine—no clear benefit
Use lowest effective dose

Acupuncture, massage, chiropractic, PT, stretching, hydrotherapy, yoga, tai chi, qigong, meditation
Hot/cold packs, warm baths, electrical massagers, TENS
Homeopathy/biofeedback: equivocal evidence