Purpose of Review
Unexplained fatigue is commonly reported in the general population, with varying severity. Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) sits at the extreme of the fatigue continuum, yet more individuals experience unexplained prolonged fatigue (1–6-month duration) or chronic fatigue (> 6 months) that, although debilitating, does not fulfil ME/CFS criteria. This review examines the empirical literature comparing symptoms for those with prolonged fatigue, chronic fatigue and ME/CFS.
Substantial overlap of self-reported psychological, physical and functional impairments exists between chronic fatigue and ME/CFS. The conversion rate from prolonged or chronic fatigue to ME/CFS is not understood. Current research has failed to uncover factors accounting for differences in fatigue trajectories, nor incorporate comprehensive, longitudinal assessments extending beyond self-reported symptoms.
Distinguishing factors between prolonged fatigue, chronic fatigue and ME/CFS remain poorly understood, highlighting a need for longitudinal studies integrating biopsychosocial approaches to inform early management and targeted rehabilitation strategies.
This is a preview of subscription content, log in to check access.
Buy single article
Instant access to the full article PDF.
Price includes VAT for USA
Subscribe to journal
Immediate online access to all issues from 2019. Subscription will auto renew annually.
This is the net price. Taxes to be calculated in checkout.
Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance
van’t Leven M, et al. Fatigue and chronic fatigue syndrome-like complaints in the general population. Eur J Pub Health. 2009;20(3):251–7.
Ricci JA, Chee E, Lorandeau AL, Berger J. Fatigue in the US workforce: prevalence and implications for lost productive work time. J Occup Environ Med. 2007;49(1):1–10.
Rupp I, Boshuizen HC, Jacobi CE, Dinant HJ, van den Bos GAM. Impact of fatigue on health-related quality of life in rheumatoid arthritis. Arthritis Rheum. 2004;51(4):578–85.
Finsterer J, Mahjoub SZ. Fatigue in healthy and diseased individuals. Am J Hosp Palliat Care. 2014;31(5):562–75.
Wilson J, Morgan S, Magin PJ, van Driel M. Fatigue—a rational approach to investigation. Aust Fam Physician. 2014;43(7):457–61.
American Psychiatric Association, Diagnostic and statistical manual of mental disorders (DSM-5®). 2013: American Psychiatric Pub.
Fukuda K, Dobbins JG, Wilson LJ, Dunn RA, Wilcox K, Smallwood D. An epidemiologic study of fatigue with relevance for the chronic fatigue syndrome. J Psychiatr Res. 1997;31(1):19–29.
Steele L, Dobbins JG, Fukuda K, Reyes M, Randall B, Koppelman M, et al. The epidemiology of chronic fatigue in San Francisco. Am J Med. 1998;105(3):83S–90S.
Fukuda K, Straus SE, Hickie I, Sharpe MC, Dobbins JG, Komaroff A. The chronic fatigue syndrome: a comprehensive approach to its definition and study. Ann Intern Med. 1994;121(12):953–9.
Brurberg KG, Fønhus MS, Larun L, Flottorp S, Malterud K. Case definitions for chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME): a systematic review. BMJ Open. 2014;4(2):e003973.
McCrone P, et al. The economic cost of chronic fatigue and chronic fatigue syndrome in UK primary care. Psychol Med. 2003;33(2):253–61.
Sabes-Figuera R, McCrone P, Hurley M, King M, Donaldson AN, Ridsdale L. The hidden cost of chronic fatigue to patients and their families. BMC Health Serv Res. 2010;10(1):56.
Lloyd A, Pender H. The economic impact of chronic fatigue syndrome. Med J Aust. 1992;157(9):599–601.
Reynolds KJ, Vernon SD, Bouchery E, Reeves WC. The economic impact of chronic fatigue syndrome. Cost effectiveness and resource allocation. 2004;2(1):4.
Whiting P, Bagnall AM, Sowden AJ, Cornell JE, Mulrow CD, Ramírez G. Interventions for the treatment and management of chronic fatigue syndrome: a systematic review. Jama. 2001;286(11):1360–8.
Joyce J, Hotopf M, Wessely S. The prognosis of chronic fatigue and chronic fatigue syndrome: a systematic review. QJM. 1997;90(3):223–33.
Malouff JM, Thorsteinsson EB, Rooke SE, Bhullar N, Schutte NS. Efficacy of cognitive behavioral therapy for chronic fatigue syndrome: a meta-analysis. Clin Psychol Rev. 2008;28(5):736–45.
Castell BD, Kazantzis N, Moss-Morris RE. Cognitive behavioral therapy and graded exercise for chronic fatigue syndrome: a meta-analysis. Clin Psychol Sci Pract. 2011;18(4):311–24.
Romano GF, et al. Fibromyalgia and chronic fatigue: the underlying biology and related theoretical issues. Adv Psychosom Med. 2015;34:61–77.
Lloyd AR, Meer JW. The long wait for a breakthrough in chronic fatigue syndrome. BMJ. 2015;350:h2087 An editorial discussing the current limitations of research and current understanding of therapies for ME/CFS.
Hickie IB, et al. Fatigue in selected primary care settings: sociodemographic and psychiatric correlates. Med J Aust. 1996;164(10):585–8.
Skapinakis P, Lewis G, Mavreas V. Temporal relations between unexplained fatigue and depression: longitudinal data from an international study in primary care. Psychosom Med. 2004;66(3):330–5.
Hickie I, et al. The temporal stability and co-morbidity of prolonged fatigue: a longitudinal study in primary care. Psychol Med. 1999;29(4):855–61.
Jason LA, Jordan KM, Richman JA, Rademaker AW, Huang CF, Mccready W, et al. A community-based study of prolonged fatigue and chronic fatigue. J Health Psychol. 1999;4(1):9–26.
Martin A, Chalder T, Rief W, Braehler E. The relationship between chronic fatigue and somatization syndrome: a general population survey. J Psychosom Res. 2007;63(2):147–56.
Solomon L, Nisenbaum R, Reyes M, Papanicolaou DA, Reeves WC. Functional status of persons with chronic fatigue syndrome in the Wichita, Kansas, population. Health Qual Life Outcomes. 2003;1(1):48.
Buchwald D, Pearlman T, Umali J, Schmaling K, Katon W. Functional status in patients with chronic fatigue syndrome, other fatiguing illnesses, and healthy individuals. Am J Med. 1996;101(4):364–70.
Buchwald D, Umali P, Umali J, Kith P, Pearlman T, Komaroff AL. Chronic fatigue and the chronic fatigue syndrome: prevalence in a Pacific Northwest health care system. Ann Intern Med. 1995;123(2):81–8.
Skapinakis P, Lewis G, Meltzer H. Clarifying the relationship between unexplained chronic fatigue and psychiatric morbidity: results from a community survey in Great Britain. Int Rev Psychiatry. 2003;15(1–2):57–64.
Sulheim, D., et al., Cognitive dysfunction in adolescents with chronic fatigue: a cross-sectional study. Archives of disease in childhood, 2015: p. archdischild-2014-306764.
Evengård B, et al. Differences between patients with chronic fatigue syndrome and with chronic fatigue at an infectious disease clinic in Stockholm, Sweden. Psychiatry Clin Neurosci. 2003;57(4):361–8.
De Gucht V, et al. Differences in physical and psychosocial characteristics between CFS and fatigued non-CFS patients, a case-control study. Int J Behav Med. 2016;23(5):589–94 A recent comparison of patients with ME/CFS, and fatigued patients who do not meet diagnostic criteria for ME/CFS.
Darbishire L, Ridsdale L, Seed P. Distinguishing patients with chronic fatigue from those with chronic fatigue syndrome: a diagnostic study in UK primary care. Br J Gen Pract. 2003;53(491):441–5.
Binder LM, Storzbach D, Anger WK, Campbell KA, Rohlman DS, of the Portland Environmental O, et al. Subjective cognitive complaints, affective distress, and objective cognitive performance in Persian Gulf War veterans. Arch Clin Neuropsychol. 1999;14(6):531–6.
Kinsinger SW, Lattie E, Mohr DC. Relationship between depression, fatigue, subjective cognitive impairment, and objective neuropsychological functioning in patients with multiple sclerosis. Neuropsychology. 2010;24(5):573–80.
Weis J, Poppelreuter M, Bartsch H. Cognitive deficits as long-term side-effects of adjuvant therapy in breast cancer patients:‘subjective’complaints and ‘objective’neuropsychological test results. Psycho-Oncology. 2009;18(7):775–82.
Cockshell SJ, Mathias JL. Cognitive functioning in people with chronic fatigue syndrome: a comparison between subjective and objective measures. Neuropsychology. 2014;28(3):394–405.
Wearden A, Appleby L. Cognitive performance and complaints of cognitive impairment in chronic fatigue syndrome (CFS). Psychol Med. 1997;27(1):81–90.
Cvejic E, Birch RC, Vollmer-Conna U. Cognitive dysfunction in chronic fatigue syndrome: a review of recent evidence. Curr Rheumatol Rep. 2016;18(5):24.
Meeus, M., et al. Heart rate variability in patients with fibromyalgia and patients with chronic fatigue syndrome: a systematic review. In Seminars in arthritis and rheumatism. 2013. Elsevier.
Martínez-Martínez L-A, Mora T, Vargas A, Fuentes-Iniestra M, Martínez-Lavín M. Sympathetic nervous system dysfunction in fibromyalgia, chronic fatigue syndrome, irritable bowel syndrome, and interstitial cystitis: a review of case-control studies. JCR: J Clin Rheumatol. 2014;20(3):146–50.
Togo F, Natelson BH. Heart rate variability during sleep and subsequent sleepiness in patients with chronic fatigue syndrome. Auton Neurosci. 2013;176(1–2):85–90.
Cauwenbergh D, et al. Malfunctioning of the autonomic nervous system in patients with chronic fatigue syndrome: a systematic literature review. Eur J Clin Investig. 2014;44(5):516–26.
Beaumont A, Burton AR, Lemon J, Bennett BK, Lloyd A, Vollmer-Conna U. Reduced cardiac vagal modulation impacts on cognitive performance in chronic fatigue syndrome. PLoS One. 2012;7(11):e49518.
Rahman K, Burton A, Galbraith S, Lloyd A, Vollmer-Conna U. Sleep-wake behavior in chronic fatigue syndrome. Sleep. 2011;34(5):671–8.
Burton A, et al. Reduced heart rate variability predicts poor sleep quality in a case–control study of chronic fatigue syndrome. Exp Brain Res. 2010;204(1):71–8.
Hurwitz BE, Coryell VT, Parker M, Martin P, LaPerriere A, Klimas NG, et al. Chronic fatigue syndrome: illness severity, sedentary lifestyle, blood volume and evidence of diminished cardiac function. Clin Sci. 2009;118(2):125–35.
Stewart JM. Chronic fatigue syndrome: comments on deconditioning, blood volume and resulting cardiac function. Clin Sci. 2009;118(2):121–3.
Fortney SM, Schneider VS, Greenleaf JE. The physiology of bed rest. Handbook of Physiology. Environ Physiol. 1996:889–939.
Baker R, Shaw E. Diagnosis and management of chronic fatigue syndrome or myalgic encephalomyelitis (or encephalopathy): summary of NICE guidance. BMJ: Br Med J. 2007;335(7617):446–8.
White PD, Goldsmith KA, Johnson AL, Potts L, Walwyn R, DeCesare J, 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;377(9768):823–36.
Price, J.R., et al., Cognitive behaviour therapy for chronic fatigue syndrome in adults. The Cochrane Library, 2008.
Larun L, et al. Exercise therapy for chronic fatigue syndrome. Cochrane Database Syst Rev. 2017;4.
Cairns R, Hotopf M. A systematic review describing the prognosis of chronic fatigue syndrome. Occup Med. 2005;55(1):20–31.
White PD, Grover SA, Kangro HO, Thomas JM, Amess J, Clare AW. The validity and reliability of the fatigue syndrome that follows glandular fever. Psychol Med. 1995;25(5):917–24.
Hickie I, Davenport T, Wakefield D, Vollmer-Conna U, Cameron B, Vernon SD, et al. Post-infective and chronic fatigue syndromes precipitated by viral and non-viral pathogens: prospective cohort study. Bmj. 2006;333(7568):575.
Katz BZ, Shiraishi Y, Mears CJ, Binns HJ, Taylor R. Chronic fatigue syndrome after infectious mononucleosis in adolescents. Pediatrics. 2009;124(1):189–93.
Candy B, et al. Predictors of fatigue following the onset of infectious mononucleosis. Psychol Med. 2003;33(5):847–55.
Buchwald DS, Rea TD, Katon WJ, Russo JE, Ashley RL. Acute infectious mononucleosis: characteristics of patients who report failure to recover. Am J Med. 2000;109(7):531–7.
Vollmer-Conna U, Piraino BF, Cameron B, Davenport T, Hickie I, Wakefield D, et al. Cytokine polymorphisms have a synergistic effect on severity of the acute sickness response to infection. Clin Infect Dis. 2008;47(11):1418–25.
Van Cauwenbergh D, et al. Malfunctioning of the autonomic nervous system in patients with chronic fatigue syndrome: a systematic literature review. Eur J Clin Investig. 2014;44(5):516–26.
Borovikova LV, Ivanova S, Zhang M, Yang H, Botchkina GI, Watkins LR, et al. Vagus nerve stimulation attenuates the systemic inflammatory response to endotoxin. Nature. 2000;405(6785):458–62.
Tracey KJ. Reflex control of immunity. Nat Rev Immunol. 2009;9(6):418–28.
Thayer JF, Hansen AL, Saus-Rose E, Johnsen BH. Heart rate variability, prefrontal neural function, and cognitive performance: the neurovisceral integration perspective on self-regulation, adaptation, and health. Ann Behav Med. 2009;37(2):141–53.
Craig AD. How do you feel? Interoception: the sense of the physiological condition of the body. Nat Rev Neurosci. 2002;3(8):655–66.
This work was supported by a grant from the Mason Foundation (National Medical Program: MAS2017F033).
Conflict of Interest
The authors declare that they have no conflict of interest.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
This article is part of the Topical Collection on Chronic Pain
About this article
Cite this article
Fatt, S.J., Cvejic, E., Lloyd, A.R. et al. The Invisible Burden of Chronic Fatigue in the Community: a Narrative Review. Curr Rheumatol Rep 21, 5 (2019). https://doi.org/10.1007/s11926-019-0804-2
- Myalgic encephalomyelitis
- Chronic fatigue syndrome