Chronic Fatigue Syndrome (CFS)
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Chronic fatigue syndrome (CFS) is a disorder characterized by unexplained profound fatigue that is worsened by exertion. The fatigue is accompanied by cognitive dysfunction and impairment of daily functioning that persists for more than 6 months.
CFS was originally termed myalgic encephalomyelitis (ME) because British clinicians noted a skeletal muscle component manifesting as chronic fatigue and an encephalitic component manifesting as cognitive difficulties. However, this term is inappropriate because of a lack of encephalomyelitis in laboratory and imaging studies, and myalgia is not a core symptom of the disease. [1]
In 2015, the Institute of Medicine (IOM) proposed that the condition be renamed systemic exertion intolerance disease (SEID) to better reflect the condition’s hallmark defining symptom, postexertional malaise. [2]
The cause of CFS is unknown, and there are no direct tests to diagnose CFS. If the source of the fatigue can be explained, the patient probably does not have CFS. The diagnosis is one of exclusion that meets the clinical criteria below.
A diagnosis of CFS requires the following three symptoms: [1]
At least one of the following must also be present:
CFS is a biological illness, not a psychologic disorder. The exact pathogenesis is unknown. Numerous mechanisms and molecules have been implicated that lead to abnormalities in immune dysfunction, hormonal regulation, metabolism and response to oxidative stress to include impaired natural killer cell function and/or T-cell function, elevated cytokines, and autoantibodies (rheumatic factor, antithyroid antibodies, antigliadin, anti–smooth muscle antibodies, and cold agglutinins). [3, 4] Infections have been suspected; however, no causal role has been established.
Many viruses have been studied as potential causes of CFS; however, no definitive causal relation has been determined. Historically, human herpesvirus type 6, enterovirus, rubella virus, Candida albicans, bornavirus, Mycoplasma, Chlamydia pneumoniae, retroviruses, coxsackie B virus, cytomegalovirus, and xenotropic murine leukemia virus-related virus have been studied and have not been found to cause CFS. [5, 6, 7, 8, 9, 10, 11, 12] Some people infected with Epstein-Barr virus, Ross River virus, Coxiella burnetii, or Giardia have developed criteria for CFS, but not all individuals with CFS have had these infections. [3]
Environmental factors have also been suspected as a trigger for CFS; however, no specific factors have been identified.
CFS affects 836,000 to 2.5 million Americans. [1] An estimated 84%-91% of individuals with the condition have not been diagnosed; therefore, the true prevalence is unknown. Overall, CFS is more common in females than in males and occurs most commonly in young to middle-aged adults. [13] The average age of onset is 33 years, although cases have been reported in patients younger than 10 years and older than 70 years. Patients with CFS experience loss of productivity and high medical costs that contribute to a total economic burden of $17-24 billion annually. [1]
CFS has no cure, its symptoms can persist for years, and its clinical course is punctuated by remissions and relapses. One prospective study suggests that approximately 50% of patients with CFS can return to part-time or full-time work. [14] Longer duration of illness, severe fatigue, comorbid depression, and anxiety are factors associated with a poorer prognosis. [15] Good outcomes are associated with less fatigue severity at baseline, a sense of control over symptoms, and no attribution of the illness to a physical cause. [16] Despite the considerable burden of morbidity associated with CFS, there is no evidence of an increased risk of mortality.
For patient education resources, see the Back, Ribs, Neck, and Head Center, as well as Chronic Fatigue Syndrome, Fibromyalgia, and Fatigue.
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Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Centers for Disease Control and Prevention. Available at https://www.cdc.gov/me-cfs/index.html. June 29, 2018; Accessed: August 21, 2018.
Montoya JG, Holmes TH, Anderson JN, Maecker HT, Rosenberg-Hasson Y, Valencia IJ, et al. Cytokine signature associated with disease severity in chronic fatigue syndrome patients. Proc Natl Acad Sci U S A. 2017 Aug 22. 114 (34):E7150-E7158. [Medline].
Lombardi VC, Ruscetti FW, Das Gupta J, et al. Detection of an infectious retrovirus, XMRV, in blood cells of patients with chronic fatigue syndrome. Science. 2009 Oct 23. 326(5952):585-9. [Medline].
Lo SC, Pripuzova N, Li B, Komaroff AL, Hung GC, Wang R, 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 Sep 7. 107(36):15874-9. [Medline]. [Full Text].
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Maggi F, Focosi D, Lanini L, et al. Xenotropic murine leukaemia virus-related virus is not found in peripheral blood cells from treatment-naive human immunodeficiency virus-positive patients. Clin Microbiol Infect. 2012 Feb. 18(2):184-8. [Medline].
Knox K, Carrigan D, Simmons G, et al. No evidence of murine-like gammaretroviruses in CFS patients previously identified as XMRV-infected. Science. 2011 Jul 1. 333(6038):94-7. [Medline].
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Surveillance report 2017 – Chronic fatigue syndrome/myalgic encephalomyelitis (or encephalopathy): diagnosis and management (2007) NICE guideline CG53. National Institute for Health and Care Excellence. Available at http://go.nature.com/2d4ckro. 20 September 2017; Accessed: 21 August 2018.
Vink M, Vink-Niese A. Multidisciplinary rehabilitation treatment is not effective for myalgic encephalomyelitis/chronic fatigue syndrome: A review of the FatiGo trial. Health Psychol Open. 2018 Jul-Dec. 5 (2):2055102918792648. [Medline]. [Full Text].
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Jefferson R Roberts, MD Chief of Rheumatology Service, Tripler Army Medical Center; Assistant Clinical Professor of Medicine, Uniformed Services University of the Health Sciences
Jefferson R Roberts, MD is a member of the following medical societies: American College of Physicians, American College of Rheumatology, Society for Simulation in Healthcare
Disclosure: Nothing to disclose.
Mary L Lan, MD, MPH Resident Physician, Department of Medicine, Tripler Army Medical Center
Disclosure: Nothing to disclose.
Michael W Price, MD Chief, Medical Specialty Clinic #1, Tripler Army Medical Center; Instructor in Medicine, Uniformed Services University of the Health Sciences, F Edward Herbert School of Medicine
Michael W Price, MD is a member of the following medical societies: American Society of Tropical Medicine and Hygiene, Armed Forces Infectious Diseases Society, Infectious Diseases Society of America
Disclosure: Nothing to disclose.
Michael A Kaliner, MD Clinical Professor of Medicine, George Washington University School of Medicine; Medical Director, Institute for Asthma and Allergy
Michael A Kaliner, MD is a member of the following medical societies: American Academy of Allergy Asthma and Immunology, American Association of Immunologists, American College of Allergy, Asthma and Immunology, American Society for Clinical Investigation, American Thoracic Society, Association of American Physicians
Disclosure: Nothing to disclose.
Michael Stuart Bronze, MD David Ross Boyd Professor and Chairman, Department of Medicine, Stewart G Wolf Endowed Chair in Internal Medicine, Department of Medicine, University of Oklahoma Health Science Center; Master of the American College of Physicians; Fellow, Infectious Diseases Society of America; Fellow of the Royal College of Physicians, London
Michael Stuart Bronze, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, American Medical Association, Association of Professors of Medicine, Infectious Diseases Society of America, Oklahoma State Medical Association, Southern Society for Clinical Investigation
Disclosure: Nothing to disclose.
Burke A Cunha, MD Professor of Medicine, State University of New York School of Medicine at Stony Brook; Chief, Infectious Disease Division, Winthrop-University Hospital
Burke A Cunha, MD is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, Infectious Diseases Society of America
Disclosure: Nothing to disclose.
Bryan D Carter, PhD Professor of Child Psychology in Psychiatry and Behavioral Sciences, Chief Psychologist in Division of Child and Adolescent Psychiatry, Director of Predoctoral Internship in Clinical Child/Pediatric Psychology, Director of Postdoctoral Fellowship Program in Pediatric Psychology, Director of Pediatric Consultation-Liaison Service to Kosair Children’s Hospital, University of Louisville School of Medicine
Bryan D Carter, PhD is a member of the following medical societies: American Psychological Association
Disclosure: Nothing to disclose.
Thomas M Kerkering, MD Chief of Infectious Diseases, Virginia Tech Carilion School of Medicine
Thomas M Kerkering, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, American Public Health Association, American Society for Microbiology, American Society of Tropical Medicine and Hygiene, Infectious Diseases Society of America, Medical Society of Virginia, and Wilderness Medical Society
Disclosure: Nothing to disclose.
Leonard R Krilov, MD Chief of Pediatric Infectious Diseases and International Adoption, Vice Chair, Department of Pediatrics, Professor of Pediatrics, Winthrop University Hospital
Leonard R Krilov, MD is a member of the following medical societies: American Academy of Pediatrics, American Pediatric Society, Infectious Diseases Society of America, Pediatric Infectious Diseases Society, and Society for Pediatric Research
Disclosure: Medimmune Grant/research funds Cliinical trials; Medimmune Honoraria Speaking and teaching; Medimmune Consulting fee Consulting
Mark R Schleiss, MD American Legion Chair of Pediatrics, Professor of Pediatrics, Division Director, Division of Infectious Diseases and Immunology, Department of Pediatrics, University of Minnesota Medical School
Mark R Schleiss, MD is a member of the following medical societies: American Pediatric Society, Infectious Diseases Society of America, Pediatric Infectious Diseases Society, and Society for Pediatric Research
Disclosure: Nothing to disclose.
Russell W Steele, MD Head, Division of Pediatric Infectious Diseases, Ochsner Children’s Health Center; Clinical Professor, Department of Pediatrics, Tulane University School of Medicine
Russell W Steele, MD is a member of the following medical societies: American Academy of Pediatrics, American Association of Immunologists, American Pediatric Society, American Society for Microbiology, Infectious Diseases Society of America, Louisiana State Medical Society, Pediatric Infectious Diseases Society, Society for Pediatric Research, and Southern Medical Association
Disclosure: Nothing to disclose.
Julian M Stewart, MD, PhD Associate Chairman of Pediatrics, Director, Center for Hypotension, Westchester Medical Center; Professor of Pediatrics and Physiology, New York Medical College
Julian M Stewart, MD, PhD is a member of the following medical societies: American Academy of Pediatrics
Disclosure: Nothing to disclose.
Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference
Disclosure: Medscape Salary Employment
Robert W Tolan Jr, MD Chief, Division of Allergy, Immunology and Infectious Diseases, The Children’s Hospital at Saint Peter’s University Hospital; Clinical Associate Professor of Pediatrics, Drexel University College of Medicine
Robert W Tolan Jr, MD is a member of the following medical societies: American Academy of Pediatrics, American Medical Association, American Society for Microbiology, American Society of Tropical Medicine and Hygiene, Infectious Diseases Society of America, Pediatric Infectious Diseases Society, Phi Beta Kappa, and Physicians for Social Responsibility
Disclosure: Novartis Honoraria Speaking and teaching
Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference
Disclosure: Nothing to disclose.
Chronic Fatigue Syndrome (CFS)
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