chronic fatigue syndrome; myalgic encephalomyelitis; neurasthenia; systemic exertion intolerance disease (CFS)
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Introduction
A controversial illness that shares symptoms with major depression, fibromyalgia & somatoform disorders. Also known as: nervous exhaustion, Icelandic disease, atypical poliomyelitis, chronic mononucleosis.
Etiology
- unknown
- suspected or hypothesized etiologies
- infection
- Epstein-Barr virus (EBV) infection
- enterovirus
- retrovirus
- human retrovirus XMRV is found in 67-87% of patients with chronic fatigue syndrome versus 3-4% of healthy controls[4][5]
- retrovirus XMRV findings disputed[6]
- other agents
- trauma
- immune dysfunction
- cellular
- decreased number of natural killer (NK) cells
- NK cell dysfunction
- reduced lymphocyte proliferation
- increased production of gamma interferon
- increase or decrease in CD8 cells
- humoral
- autoantibodies
- partial hypogammaglobulinemia
- decreased IgG subclasses
- polyclonal activation of B cells
- circulating immune complexes
- other immunologic factors
- cellular
- neurochemical disturbances
- comorbidities common (also see differential diagnosis)[18]
- infection
Epidemiology
- > 80% female
- average age is late 30's
- > 95% are white
Pathology
- mild hypocortisolism caused by central underproduction of corticotropin-releasing factor (CRF)[3]
Genetics
- overexpression of WASF3 disrupts mitochondrial respiration & may mediate exercise intolerance in chronic fatigue syndrome[23]
Clinical manifestations
- major criteria
- persistent or relapsing fatigue
- exclusion of other chronic conditions
- malignancy
- autoimmune disease
- chronic psychiatric disorders
- may have non-psychiatric depression, somatization, anxiety disorder &/or panic disorder
- chronic inflammatory disease & rheumatic disease
- may have fibromyalgia, check for trigger points
- chronic infectious state
- exclude inadequately treated Lyme disease
- adverse pharmaceutical effects & substance abuse
- endocrinopathy
- severe obesity
- minor criteria
- signs
- low-grade fever
- non-exudative pharyngitis
- palpable or tender cervical or axillary lymph nodes
- symptoms
- generalized muscle weakness
- chills
- sore throat
- myalgias
- post-exertional malaise & prolonged fatigue after physical activity which had been well tolerated in the past
- migratory arthritis without erythema or swelling
- neuropsychological complaints
- sleep disturbances, unrefreshing sleep
- generalized headache
- acute (hours) or subacute (days) development of symptoms
- signs
- other (also see diagnostic criteria)
- atopy (allergies) is common
- orthostatic intolerance, cognitive impairment, & pain are common[18]
- substantial impairment in both physical & mental function occur at some point[18]
- fever, lymphadenopathy & muscle atrophy are not features
Diagnostic criteria
- diagnosis requires both 2 major criteria plus 8 minor criteria.
- impaired day-to-day function accompanied by fatigur
- malaise following physical, cognitive, or emotional exertion
- unrefreshing sleep
- plus either orthostatic intolerance or cognitive impairment
- symptoms must be present for 6 months
- at least half the time, symptom intensity must be moderate to severe[10][22]
Laboratory
- no specific laboratory tests to confirm chronic fatigue syndrome
- avoid unnecessary testing[1]
- exclusion testing
- recommended[1] (no evidence base provided)
- complete blood count with differential
- thyroid function tests
- serum glucose
- other as indicated by history & physical
- recommended[1] (no evidence base provided)
- Epstein-Barr virus titers of little utility
- non-specific findings
- atypical lymphocytes
- relative lymphocytosis
- mild elevation of liver function tests
Diagnostic procedures
as indicated by history & physical
- skin-testing may be positive for many seasonal & environmental antigens
- PPD
- sleep study
- electrical impedance assay
Complications
* lower than that for affective disorders, personality disorders, or alcoholism[12]
Differential diagnosis
- depression
- anxiety
- fibromyalgia
- somatoform disorder
- chronic viral disease - chronic viral hepatitis
- malignancy
- rhinitis
- endocrine disorders
- chronic inflammatory state
- rheumatologic diseases
- chronic psychiatric disease
- sleep disorder
Management
- individually tailored program required[1]
- no therapy is beneficial for all patients
- no FDA-approved medications
- regular follow-up to monitor symptoms
- cognitive behavioral therapy of benefit[1][9]
- internet-based cognitive-behavioral therapy effective in treating teenagers[7]
- benefit modest & weak[17]
- graded exercise program of benefit[1][9]
- benefit modest & weak[17]
- sleep hygiene[1]
- treatment of underlying atopy (allergies) if present
- mental health evaluation (rule out other diagnoses)
- antidepressants may be of some benefit
- of no benefit
- experimental therapy
- acyclovir (Zovirax)
- immunoglobulin
- magnesium sulfate
- Ampligen (low benefit to risk ratio)
- essential fatty acid
- 5 hydroxytryptophan
- patient education
- support groups
- progressive exercise program
- nutritional guidance
- emphasis on control of symptoms rather than cure
More general terms
Additional terms
- depression
- fibromyalgia syndrome (fibromyositis, fibrositis)
- somatoform (psychosomatic) disorder; somatic symptom & related disorders (SSRD)
References
- ↑ 1.0 1.1 1.2 1.3 1.4 1.5 1.6 1.7 Medical Knowledge Self Assessment Program (MKSAP) 11, 15, 16, 17, 18, 19. American College of Physicians, Philadelphia 1998, 2009, 2012, 2015. 2018, 2021.
- ↑ Saunders Manual of Medical Practice, Rakel (ed), WB Saunders, Philadelphia, 1996
- ↑ 3.0 3.1 3.2 Journal Watch 21(10):83, 2001 Cleare AJ et al Urinary free cortisol in chronic fatigue syndrome. Am J Psychiatry 158:641, 2001 PMID: https://www.ncbi.nlm.nih.gov/pubmed/11282703
- ↑ 4.0 4.1 Lombardi VC et al. Detection of an infectious retrovirus, XMRV, in blood cells of patients with chronic fatigue syndrome. Science 2009 Oct 8; http://dx.doi.org/10.1126/science.1179052 PMID: https://www.ncbi.nlm.nih.gov/pubmed/19815723
- ↑ 5.0 5.1 Lo S-C et al. Detection of MLV-related virus gene sequences in blood of patients with chronic fatigue syndrome and healthy blood donors. Proc Natl Acad Sci U S A 2010 Aug 23 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/20798047 <Internet> http://dx.doi.org/10.1073/pnas.1006901107
- ↑ 6.0 6.1 Journal Watch: June 1, 2011 Science Has Doubts About Its 2009 Study Linking Retrovirus with Chronic Fatigue
Knox K et al No Evidence of Murine-Like Gammaretroviruses in CFS Patients Previously Identified as XMRV-Infected http://www.sciencemag.org/content/early/2011/05/31/science.1204963.full.pdf
Paprotka T et al Recombinant Origin of the Retrovirus XMRV http://www.sciencemag.org/content/early/2011/05/31/science.1205292.full.pdf
Alberts B Editorial Expression of Concern http://www.sciencemag.org/content/early/2011/05/31/science.1208542.full.pdf - ↑ 7.0 7.1 Nijhof SL et al Effectiveness of internet-based cognitive behavioural treatment for adolescents with chronic fatigue syndrome (FITNET): a randomised controlled trial The Lancet, Early Online Publication, 1 March 2012 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/22385683 <Internet> http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2812%2960025-7/fulltext
Bleijenberg G and Knoop H Chronic fatigue syndrome: where to PACE from here? The Lancet, Early Online Publication, 1 March 2012 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/21334060 <Internet> http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2811%2960172-4/fulltext - ↑ Holgate ST, Komaroff AL, Mangan D, Wessely S. Chronic fatigue syndrome: understanding a complex illness. Nat Rev Neurosci. 2011 Jul 27;12(9):539-44. doi:http://dx.doi.org/ 10.1038/nrn3087. PMID: https://www.ncbi.nlm.nih.gov/pubmed/21792218
- ↑ 9.0 9.1 9.2 Reid S, Chalder T, Cleare A, Hotopf M, Wessely S. Chronic fatigue syndrome. Clin Evid (Online). 2011 May 26;2011 PMID: https://www.ncbi.nlm.nih.gov/pubmed/21615974
- ↑ 10.0 10.1 Institute of Medicine. Feb. 2015 Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Redefining an Illness. http://www.iom.edu/~/media/Files/Report%20Files/2015/MECFS/MECFS_ReportBrief.pdf
Ganiats TG Redefining the Chronic Fatigue Syndrome. Ann Intern Med. Published online 10 February 2015 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/25668185 <Internet> http://annals.org/article.aspx?articleid=2118972 - ↑ Komaroff AL Chronic Fatigue Syndrome: Biology, Diagnosis, and Management. Physician's First Watch, June 16, 2015 David G. Fairchild, MD, MPH, Editor-in-Chief Massachusetts Medical Society http://www.jwatch.org
Haney E et al Diagnostic Methods for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Systematic Review for a National Institutes of Health Pathways to Prevention Workshop. Ann Intern Med. 2015;162(12):834-840. <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/26075754 <Internet> http://annals.org/article.aspx?articleid=2322800
Smith ME, Haney E, McDonagh M et al Treatment of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Systematic Review for a National Institutes of Health Pathways to Prevention Workshop. Ann Intern Med. 2015 Jun 16;162(12):841-50. doi:http://dx.doi.org/ 10.7326/M15-0114. PMID: https://www.ncbi.nlm.nih.gov/pubmed/26075755
Komaroff AL Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Real Illness. Ann Intern Med. 2015;162(12):871-872. <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/26075760 <Internet> http://annals.org/article.aspx?articleid=2322808
Komaroff AL, Cho TA. Role of infection and neurologic dysfunction in chronic fatigue syndrome. Semin Neurol. 2011 Jul;31(3):325-37 PMID: https://www.ncbi.nlm.nih.gov/pubmed/21964849 - ↑ 12.0 12.1 12.2 12.3 Roberts E et al. Mortality of people with chronic fatigue syndrome: A retrospective cohort study in England and Wales from the South London and Maudsley NHS Foundation Trust Biomedical Research Centre (SLaM BRC) Clinical Record Interactive Search (CRIS) Register. Lancet 2016 Feb 9 PMID: https://www.ncbi.nlm.nih.gov/pubmed/26873808 Free Article
- ↑ Committee on the Diagnostic Criteria for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome; Board on the Health of Select Populations; Institute of Medicine. Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Redefining an Illness. Washington (DC): National Academies Press (US); 2015 Feb. The National Academies Collection: Reports funded by National Institutes of Health. PMID: https://www.ncbi.nlm.nih.gov/pubmed/25695122 Free Books & Documents, Free full text
- ↑ White PD, Goldsmith KA, Johnson AL et al Comparison of adaptive pacing therapy, cognitive behaviour therapy, graded exercise therapy, and specialist medical care for chronic fatigue syndrome (PACE): a randomised trial. Lancet. 2011 Mar 5;377(9768):823-36. PMID: https://www.ncbi.nlm.nih.gov/pubmed/21334061 Free PMC Article
- ↑ Yancey JR, Thomas SM. Chronic fatigue syndrome: diagnosis and treatment. Am Fam Physician. 2012 Oct 15;86(8):741-6. Review. PMID: https://www.ncbi.nlm.nih.gov/pubmed/23062157 Free Article
- ↑ 16.0 16.1 Roerink ME, Bredie SJ, Heijnen M et al Cytokine Inhibition in Patients With Chronic Fatigue Syndrome: A Randomized Trial. Ann Intern Med. March 7, 2017. <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/28265678 <Internet> http://annals.org/aim/article/2607809/cytokine-inhibition-patients-chronic-fatigue-syndrome-randomized-trial
- ↑ 17.0 17.1 17.2 Wilshire CE, Kindlon T, Courtney R et al. Rethinking the treatment of chronic fatigue syndrome - A reanalysis and evaluation of findings from a recent major trial of graded exercise and CBT. BMC Psychol. 2018 Mar 22;6(1):6 PMID: https://www.ncbi.nlm.nih.gov/pubmed/29562932 Free PMC Article https://bmcpsychology.biomedcentral.com/articles/10.1186/s40359-018-0218-3
- ↑ 18.0 18.1 18.2 18.3 18.4 18.5 Tucker ME. CDC Launches New ME/CFS Guidance for Clinicians. Medscape Medical News. WebMD Inc. July 13, 2018 https://www.medscape.com/viewarticle/899316
Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Centers for Disease Control and Prevention. Information for Healthcare Providers. Atlanta. July 12, 2018. https://www.cdc.gov/me-cfs/healthcare-providers/index.html - ↑ Fluge O, Rekeland IG, Lien K et al. B-lymphocyte depletion in patients with myalgic encephalomyelitis/ chronic fatigue syndrome: A randomized, double-blind, placebo- controlled trial. Ann Intern Med 2019 Apr 2; PMID: https://www.ncbi.nlm.nih.gov/pubmed/30934066 https://annals.org/aim/article-abstract/2729816/myalgic-encephalomyelitis-chronic-fatigue-syndrome-trial-fails-confirm-earlier-observations
Rowe PC. Myalgic encephalomyelitis/chronic fatigue syndrome: Trial fails to confirm earlier observations of rituximab's effectiveness. Ann Intern Med 2019 Apr 2 PMID: https://www.ncbi.nlm.nih.gov/pubmed/30934063 https://annals.org/aim/article-abstract/2729816/myalgic-encephalomyelitis-chronic-fatigue-syndrome-trial-fails-confirm-earlier-observations - ↑ 20.0 20.1 Esfandyarpour R, Kashi A, Nemat-Gorgani M, Wilhelmy J, Davis RW. A nanoelectronics-blood-based diagnostic biomarker for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Proc Natl Acad Sci U S A 2019 May 21; 116:10250. PMID: https://www.ncbi.nlm.nih.gov/pubmed/31036648 https://www.pnas.org/content/116/21/10250
- ↑ Komaroff AL. Advances in Understanding the Pathophysiology of Chronic Fatigue Syndrome. JAMA. Published online July 5, 2019. PMID: https://www.ncbi.nlm.nih.gov/pubmed/31276153 https://jamanetwork.com/journals/jama/fullarticle/2737854
- ↑ 22.0 22.1 Syrek R Trending Clinical Topic: Chronic Fatigue Syndrome Medscape September 3, 2021 https://reference.medscape.com/viewarticle/957514
- ↑ 23.0 23.1 Wang Pt, Ma J, Kim YC et al WASF3 disrupts mitochondrial respiration and may mediate exercise intolerance in myalgic encephalomyelitis/chronic fatigue syndrome. Proc Natl Acad Sci U.S.A. 2023. 120(34):e2302738120 August 14. https://www.pnas.org/doi/10.1073/pnas.2302738120
- ↑ Chronic Fatigue Syndrome National Institute for Health and Clinical Excellence http://guidance.nice.org.uk/CG53/guidance/pdf/English
Centers for Disease Control and Prevention Chronic Fatigue Syndrome (CFS) http://www.cdc.gov/cfs/general/index.html