Chronic Fatigue Syndrome

Aka: Chronic Fatigue Syndrome, Chronic Fatigue Immune Deficiency Syndrome, Myalgic Encephalomyelitis, Systemic Exertional Intolerance Disease

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II. Epidemiology

  1. Prevalence may be as high 0.8% to 2.2% in U.S. (or as low as 37 in 100,000)
    1. Fatigue is common complaint (20% of all patients)
    2. Higher Incidence may be in age 20-50 year old women
    3. Case reports include children as young as age 5 years
  2. Outbreaks have been known to occur for centuries
    1. Los Angeles County Hospital (1934)
    2. Akureyri, Iceland (1948)
    3. Royal Free Hospital, London (1955)
    4. Punta Gorda, Florida (1945)
    5. Incline Village, Nevada (1985)
  3. Gender
    1. More common in women (3-4 fold)
  4. Age
    1. Bimodal peaks in teen years and 30-40 years old
    2. Age range extends into older adults (70 to 80 years old)

III. Causes

  1. Idiopathic, likely multifactorial
  2. Genetic predisposition in some patients
  3. Childhood Trauma increases chronic Fatigue risk 6 fold
    1. Heim (2009) Arch Gen Psychiatry 66(1):72-80 [PubMed]
  4. Various viruses have been implicated (with possible chronic immune activation)
    1. COVID-19
    2. Epstein Barr Virus (Mononucleosis)
      1. EBV titers no higher than in healthy controls
      2. Linde (1992) J Infect Dis 165:994-1000 [PubMed]
    3. Mycoplasma pneumoniae
    4. Coxsackie virus
    5. Human Herpes Virus 6
    6. Cytomegalovirus
    7. Measles
    8. HTLV-II

IV. Precautions

  1. Chronic Fatigue Syndrome is a clinical, organic condition and is debilitating
  2. Chronic Fatigue Syndrome is not a psychological condition or condition of Malingering or Somatization

V. Pathophysiology

  1. Energy Metabolism abnormalities in neurologic and Immune Systems
    1. Impaired ATP generation and utilization
  2. Inflammatory response
    1. T-Cell Activation
    2. Cytokine release
      1. Related to alpha-intrusion sleep disorder

VI. Symptoms

  1. See Fatigue

VII. Diagnosis

  1. See Chronic Fatigue Diagnosis

VIII. Differential Diagnosis

  1. See Fatigue Causes
  2. See Fatigue Red Flags

IX. Labs (based on other likely possible Fatigue Causes)

  1. See Fatigue Diagnostic Testing

X. Course

  1. Most patients partially recover within 2 years
  2. All Chronic Fatigue patients are prone to relapse
  3. Level of Disability varies
    1. Up to 25% of patients are able to work
    2. Homebound or bedbound in 10 to 25%

XI. Management

  1. Understanding physician with regularly scheduled visits
    1. Listen
    2. Counsel
    3. Empathy
    4. Validation
  2. General Measures
    1. Minimize symptoms and maximize function
    2. Consider support group
    3. Avoid Alcohol and substance use
  3. Specific treatment approaches
    1. See Orthostatic Hypotension
    2. See Major Depression Management
    3. See Insomnia
    4. Brain fog
      1. Cognitive pacing
      2. Employ memory aids
    5. Postexertional Malaise
      1. Follow "Stop, Rest, Pace" to avoid postexertional malaise
      2. Assistive Device (e.g. shower chair, walker)
      3. Handicapped parking card
      4. Symptom journal
      5. Work and school accommodations
    6. Pain
      1. See Chronic Pain Management
      2. NSAIDS
      3. Selective Serotonin Reuptake Inhibitors (SSRI)
      4. Duloxetine (Cymbalta)
      5. Tricyclic Antidepressants
        1. Amitriptyline 10 to 25 mg orally at bedtime and increase as tolerated
  4. Previously recommended measures that have fallen out of favor
    1. Cognitive behavior therapy
      1. Identify unhealthy coping mechanisms
    2. Graded Aerobic Exercise
      1. Originally recommended, but later found to be harmful, worsening postexertional malaise
      2. Larun (2019) Cochrane Database Syst Rev 10(10):CD003200 8. +PMID: 31577366 [PubMed]
    3. Avoid empiric therapies which are not yet supported by good evidence
      1. Nicotinamide-adenine dinucleotide (NADH)
      2. Hydrocortisone 5-10 mg PO qd

XII. Resources

  1. CDC: Chronic Fatigue Syndrome
    1. https://www.cdc.gov/me-cfs/

XIII. References

  1. Gantz in Noble (2001) Primary Care Medicine, p. 1325
  2. Craig (2002) Am Fam Physician 65(6):1083-95 [PubMed]
  3. Fulcher (1997) BMJ, 314:1647-52 [PubMed]
  4. Latimer (2023) Am Fam Physician 108(1): 58-69 [PubMed]
  5. Morrison (2001) Obstet Gynecol Clin North Am 28:225-40 [PubMed]
  6. Yancey (2012) Am Fam Physician 86(8): 741-6 [PubMed]

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Related Studies

Ontology: Chronic Fatigue Syndrome (C0015674)

Definition (MEDLINEPLUS)

Chronic fatigue syndrome (CFS) is a disorder that causes extreme fatigue. This fatigue is not the kind of tired feeling that goes away after you rest. Instead, it lasts a long time and limits your ability to do ordinary daily activities.

The main symptom of CFS is severe fatigue that lasts for 6 months or more. You also have at least four of these other symptoms:

  • Feeling unwell for more than 24 hours after physical activity
  • Muscle pain
  • Memory problems
  • Headaches
  • Pain in multiple joints
  • Sleep problems
  • Sore throat
  • Tender lymph nodes

CFS is hard to diagnose. There are no tests for it, and other illnesses can cause similar symptoms. Your doctor has to rule out other diseases before making a diagnosis of CFS.

No one knows what causes CFS. It is most common in women in their 40s and 50s, but anyone can have it. It can last for years. There is no cure for CFS, so the goal of treatment is to improve symptoms. Medicine may treat pain, sleep disorders, and other problems. Lifestyle changes, coping techniques, and a special, gradual exercise program can also help.

Centers for Disease Control and Prevention
Definition (NCI_NCI-GLOSS) A condition lasting for more than 6 months in which a person feels tired most of the time and may have trouble concentrating and carrying out daily activities. Other symptoms include sore throat, fever, muscle weakness, headache, and joint pain.
Definition (NCI) A syndrome of unknown etiology. Chronic fatigue syndrome (CFS) is a clinical diagnosis characterized by an unexplained persistent or relapsing chronic fatigue that is of at least six months' duration, is not the result of ongoing exertion, is not substantially alleviated by rest, and results in substantial reduction of previous levels of occupational, educational, social, or personal activities. Common concurrent symptoms of at least six months duration include impairment of memory or concentration, diffuse pain, sore throat, tender lymph nodes, headaches of a new type, pattern, or severity, and nonrestorative sleep. The etiology of CFS may be viral or immunologic. Neurasthenia and fibromyalgia may represent related disorders. Also known as myalgic encephalomyelitis.
Definition (MSH) A syndrome characterized by persistent or recurrent fatigue, diffuse musculoskeletal pain, sleep disturbances, and subjective cognitive impairment of 6 months duration or longer. Symptoms are not caused by ongoing exertion; are not relieved by rest; and result in a substantial reduction of previous levels of occupational, educational, social, or personal activities. Minor alterations of immune, neuroendocrine, and autonomic function may be associated with this syndrome. There is also considerable overlap between this condition and FIBROMYALGIA. (From Semin Neurol 1998;18(2):237-42; Ann Intern Med 1994 Dec 15;121(12): 953-9)
Definition (PSY) Syndrome thought to be caused by a viral organism resulting in chronic fatigue, fever, pain, sore throat, and, in some cases, depression.
Definition (CSP) distinctive syndrome characterized by chronic fatigue, mild fever, lymphadenopathy, headache, myalgia, arthralgia, depression, and memory loss; candidate etiologic agents include Epstein-Barr and other herpesviruses.
Concepts Disease or Syndrome (T047)
MSH D015673
ICD9 780.71
ICD10 G93.3 , R53.82
SnomedCT 52702003, 247372003, 267684004, 154989001, 193054000, 192735003, 267683005, 271798008, 154991009, 155062000, 51771007
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Portuguese SINDROME DE FADIGA POS-VIRAL, Encefalomielite miálgica, Doença de Royal Free, Síndrome de fadiga pós-vírica, Síndrome de fadiga pós-vírica NE, Síndrome de fadiga crónica, Síndrome de fatiga pós-viral, Encefalomielite Miálgica, Síndrome de Fadiga Crônica, Síndrome de Fadiga Pós-Viral, Síndrome Semelhante à Mononucleose Infecciosa Crônica
Italian Sindrome da affaticamento post-virale, Sindrome da stanchezza cronica, Sindrome da affaticamento post-virale NAS, Malattia Royal Free, Sindrome fibromialgica da affaticamento cronico, Sindome del Royal Free Hospital, Encefalomielite mialgica, Sindrome da fatica postvirale, Sindrome da affaticamento cronico e disfunzione immunitaria, Disordine da affaticamento cronico, Sindrome da infezione cronica mononucleosi-simile, Sindrome da affaticamento cronico
Dutch myalgische encefalomyelitis, postviraal vermoeidheidssyndroom NAO, Royal Free ziekte, postviraal vermoeidheidssyndroom, IJsland; aandoening, benigne; myalgische encefalomyelitis, encefalomyelitis; benigne myalgisch, encefalomyelitis; myalgisch, myalgisch; encefalomyelitis, postviraal; syndroom, moeheid, syndroom; postviraal, moeheid, syndroom; vermoeidheid, chronisch, syndroom; vermoeidheid, postviraal, vermoeidheid; syndroom, chronisch, vermoeidheid; syndroom, postviraal, vermoeidheidssyndroom; na virusinfectie, Vermoeidheidssyndroom na virusinfectie, chronisch vermoeidheidssyndroom, postvirale vermoeidheidssyndroom, Chronische-vermoeidheidsyndroom, Encefalomyelitis, myalgische, ME, Mononucleosisachtig syndroom, infectieus, Myalgische encefalomyelitis, Postviraal vermoeidheidsyndroom, Syndroom, postviraal vermoeidheid-, Vermoeidheidsyndroom, postviraal
French Encéphalomyélite myalgique bénigne, Syndrome de fatigue post-virale, EM, Syndrome de fatigue post-virale SAI, SYNDROME FATIGUE POST-VIRAL, Syndrome de fatigue chronique, Grippe des yuppies, Syndrome de fatigue chronique post-virale, Encéphalomyélite myalgique
German myalgische Enzephalomyelitis, postvirales asthenisches Syndrom NNB, ME, Royal Free-Krankheit, Postvirales Ermuedungssyndrom, chronisches Ermuedungssyndrom, postvirales asthenisches Syndrom, Enzephalomyelitis, myalgische, Royal-Free-Krankheit, Chronisches Ermüdungssyndrom, Chronisches Ermüdungssyndrom und Immundefektsyndrom, Ermüdungssyndrom, chronisches, Ermüdungssyndrom, postvirales, Infektiöse-Mononukleose-ähnliches Syndrom, Postvirales Ermüdungssyndrom
Spanish EM (Encefalomielitis miálgica), Síndrome de fatiga postvírico NEOM, Encefalomielitis miálgica, Enfermedad de Royal Free, Síndrome de fatiga postvírico, síndrome de fatiga crónica, síndrome de fatiga crónica (trastorno), enfermedad de Islandia, enfermedad de Islandia (trastorno), encefalomielitis miálgica benigna, enfermedad de Akureyri, neuromiastenia epidémica, síndrome de agotamiento crónico, síndrome de fatiga postviral (trastorno), síndrome de fatiga postviral, síndrome de fatiga posviral, Síndrome de fatiga crónica, Síndrome de fatiga postviral, Encefalomielitis Miálgica, Síndrome de Fatiga Crónica, Síndrome de Fatiga Postviral, Síndrome Semejante a la Mononucleosis Infecciosa Crónica
Japanese ウイルス感染後疲労症候群ＮＯＳ, ローヤルフリー病, ﾏﾝｾｲﾋﾛｳｼｮｳｺｳｸﾞﾝ, ｷﾝﾂｳｾｲﾉｳｾｷｽﾞｲｴﾝ, ﾛｰﾔﾙﾌﾘｰﾋﾞｮｳ, ｳｲﾙｽｶﾝｾﾝｺﾞﾋﾛｳｼｮｳｺｳｸﾞﾝ, ｳｲﾙｽｶﾝｾﾝｺﾞﾋﾛｳｼｮｳｺｳｸﾞﾝNOS, Royal Free病, 慢性疲労症候群, ウイルス感染後疲労症候群, 慢性伝染性単核球症様症候群, 慢性疲労免疫不全症候群, 筋痛性脳脊髄炎, 伝染性単核球症様症候群-慢性, 疲労症候群-ウイルス感染後, 疲労症候群-慢性, 脳脊髄炎-筋痛性
Swedish Trötthetssyndrom, kroniskt
Czech syndrom chronické únavy, Únavový syndrom po virovém onemocnění NOS, Únavový syndrom po virovém onemocnění, Chronický únavový syndrom, Postvirální únavový syndrom, Myalgická encefalomyelitida, postvirový únavový syndrom, chronický únavový syndrom, myalgická encefalomyelitida, ME/CFS, myalgická encefalitida, CFS
Finnish Krooninen väsymysoireyhtymä
Russian ENTSEFALOMIELIT MIALGICHESKII, USTALOSTI SINDROM KHRONICHESKII, UTOMLENIIA SINDROM KHRONICHESKII, EPSHTEINA-BARRA VIRUSNYI SINDROM KHRONICHESKII, POSTVIRUSNYI UTOMLENIIA SINDROM, UTOMLENIIA SINDROM POSTVIRUSNYI, KHRONICHESKOGO UTOMLENIIA SINDROM, MONONUKLEOZO-PODOBNYI SINDROM KHRONICHESKII, МОНОНУКЛЕОЗО-ПОДОБНЫЙ СИНДРОМ ХРОНИЧЕСКИЙ, ПОСТВИРУСНЫЙ УТОМЛЕНИЯ СИНДРОМ, УСТАЛОСТИ СИНДРОМ ХРОНИЧЕСКИЙ, УТОМЛЕНИЯ СИНДРОМ ПОСТВИРУСНЫЙ, УТОМЛЕНИЯ СИНДРОМ ХРОНИЧЕСКИЙ, ХРОНИЧЕСКОГО УТОМЛЕНИЯ СИНДРОМ, ЭНЦЕФАЛОМИЕЛИТ МИАЛГИЧЕСКИЙ, ЭПШТЕЙНА-БАРРА ВИРУСНЫЙ СИНДРОМ ХРОНИЧЕСКИЙ
Korean 바이러스성 후의 피로 증후군
Croatian SINDROM KRONIČNOG UMORA
Polish Zespół zmęczenia powirusowy, Zespół mononukleozopodobny przewlekły, Zespół zmęczenia przewlekłego, Zespół wirusa Epsteina-Barr przewlekły, Zespół przewlekłego zmęczenia
Hungarian virusfertőzés utáni fáradtság syndroma k.m.n., virusfertőzés utáni fáradtság syndroma, Myalgiás encephalomyelitis, Royal Free betegség, Krónikus fáradtság syndroma, ME
Norwegian Utmattelsessyndrom, kronisk, Kronisk utmattelsessyndrom, Kronisk tretthetssyndrom, Kronisk trøtthetssyndrom, Trøtthetssyndrom, kronisk, Myalgisk encefalopati, Postviralt utmattelsessyndrom, Tretthetssyndrom, kronisk, ME
Derived from the NIH UMLS (Unified Medical Language System)

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