Evaluation of fatigue

Fatigue may be a symptom of almost any medical condition. For the purpose of this topic, the differentials discussed concentrate on people presenting with fatigue or where fatigue is the only symptom. Conditions in which fatigue may not necessarily be an initial complaint, but is still regarded as a markedly significant and debilitating symptom, are also included.

Definition

There are numerous definitions and classifications of fatigue, reflecting the multitude of interpretations, depending on being a patient, a physician, a biologist, or a physiologist. A common and practical definition defined fatigue as a sensation of exhaustion during or after usual activities, or a feeling of inadequate energy to begin these activities.[1]Chen MK. The epidemiology of self-perceived fatigue among adults. Prev Med. 1986 Jan;15(1):74-81. http://www.ncbi.nlm.nih.gov/pubmed/3714661?tool=bestpractice.com

Epidemiology

Primary-care-based surveys have shown that between 11% and 33% of patients report significant fatigue, resulting in approximately 7 million office visits per year in the US. Fatigue is also a common complaint in the general population, with a prevalence between 4.3% and 21.9%.[2]Hickie IB, Hooker AW, Hadzi-Pavlovic D, et al. Fatigue in selected primary care settings: sociodemographic and psychiatric correlates. Med J Aust. 1996 May 20;164(10):585-8. http://www.ncbi.nlm.nih.gov/pubmed/8637460?tool=bestpractice.com [3]Wessely S, Chalder T, Hirsch S, et al. The prevalence and morbidity of chronic fatigue and chronic fatigue syndrome: a prospective primary care study. Am J Public Health. 1997 Sep;87(9):1449-55. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1380968 http://www.ncbi.nlm.nih.gov/pubmed/9314795?tool=bestpractice.com [4]Kroenke K, Wood DR, Mangelsdorff AD, et al. Chronic fatigue in primary care. Prevalence, patient characteristics, and outcome. JAMA. 1988 Aug 19;260(7):929-34. http://www.ncbi.nlm.nih.gov/pubmed/3398197?tool=bestpractice.com [5]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 Feb-May;15(1-2):57-64. http://www.ncbi.nlm.nih.gov/pubmed/12745311?tool=bestpractice.com [6]Steele L, Dobbins JG, Fukuda K, et al. The epidemiology of chronic fatigue in San Francisco. Am J Med. 1998 Sep 28;105(3A):83S-90S. http://www.ncbi.nlm.nih.gov/pubmed/9790487?tool=bestpractice.com [7]Galland-Decker C, Marques-Vidal P, Vollenweider P. Prevalence and factors associated with fatigue in the Lausanne middle-aged population: a population-based, cross-sectional survey. BMJ Open. 2019 Aug 24;9(8):e027070. https://www.doi.org/10.1136/bmjopen-2018-027070 http://www.ncbi.nlm.nih.gov/pubmed/31446404?tool=bestpractice.com

In the primary care setting, a medical or psychiatric diagnosis is found in the majority of patients presenting with fatigue (at least two-thirds).[8]Prins JB, van der Meer JW, Bleijenberg G. Chronic fatigue syndrome. Lancet. 2006 Jan 28;367(9507):346-55. http://www.ncbi.nlm.nih.gov/pubmed/16443043?tool=bestpractice.com [9]Wessely S, Chalder T, Hirsch S, et al. Psychological symptoms, somatic symptoms, and psychiatric disorder in chronic fatigue and chronic fatigue syndrome: a prospective study in the primary care setting. Am J Psychiatry. 1996 Aug;153(8):1050-9. http://www.ncbi.nlm.nih.gov/pubmed/8678174?tool=bestpractice.com [10]Cathebras PJ, Robbins JM, Kirmayer LJ, et al. Fatigue in primary care: prevalence, psychiatric comorbidity, illness behavior, and outcome. J Gen Intern Med. 1992 May-Jun;7(3):276-86. http://www.ncbi.nlm.nih.gov/pubmed/1613608?tool=bestpractice.com [11]Okkes IM, Oskam SK, Lamberts H. The probability of specific diagnoses for patients presenting with common symptoms to Dutch family physicians. J Fam Pract. 2002 Jan;51(1):31-6. http://www.ncbi.nlm.nih.gov/pubmed/11927060?tool=bestpractice.com [12]Walker EA, Katon WJ, Jemelka RP. Psychiatric disorders and medical care utilization among people in the general population who report fatigue. J Gen Intern Med. 1993 Aug;8(8):436-40. http://www.ncbi.nlm.nih.gov/pubmed/8410409?tool=bestpractice.com ​ A Dutch study identified a specific diagnosis in 63% of patients presenting to a general practitioner with general weakness or tiredness for any length of time.[11]Okkes IM, Oskam SK, Lamberts H. The probability of specific diagnoses for patients presenting with common symptoms to Dutch family physicians. J Fam Pract. 2002 Jan;51(1):31-6. http://www.ncbi.nlm.nih.gov/pubmed/11927060?tool=bestpractice.com One study identified the most common diagnoses, in descending order, as viral illness, upper respiratory infection, iron-deficiency anemia, acute bronchitis, adverse effects of a medical agent in the proper dose, and depression or other mental disorder.[13]Bates DW, Schmitt W, Buchwald D, et al. Prevalence of fatigue and chronic fatigue syndrome in a primary care practice. Arch Intern Med. 1993 Dec 27;153(24):2759-65. http://www.ncbi.nlm.nih.gov/pubmed/8257251?tool=bestpractice.com The most frequent psychiatric illnesses included major depression, panic disorder, and somatization disorder. A systematic review and meta-analysis of studies reporting on the differential diagnosis of tiredness in primary care found serious somatic disease was a rare cause. The prevalences of the following causes were found to be: anemia (2.8%); malignancy (0.6%); serious somatic disease (4.3%); depression (18.5%).[14]Stadje R, Dornieden K, Baum E, et al. The differential diagnosis of tiredness: a systematic review. BMC Fam Pract. 2016 Oct 20;17(1):147. https://www.doi.org/10.1186/s12875-016-0545-5 http://www.ncbi.nlm.nih.gov/pubmed/27765009?tool=bestpractice.com

The prevalence of fatigue seems to be higher in women than men, due to iron deficit as a consequence of menstruation, and to psychosocial factors.[1]Chen MK. The epidemiology of self-perceived fatigue among adults. Prev Med. 1986 Jan;15(1):74-81. http://www.ncbi.nlm.nih.gov/pubmed/3714661?tool=bestpractice.com [6]Steele L, Dobbins JG, Fukuda K, et al. The epidemiology of chronic fatigue in San Francisco. Am J Med. 1998 Sep 28;105(3A):83S-90S. http://www.ncbi.nlm.nih.gov/pubmed/9790487?tool=bestpractice.com [7]Galland-Decker C, Marques-Vidal P, Vollenweider P. Prevalence and factors associated with fatigue in the Lausanne middle-aged population: a population-based, cross-sectional survey. BMJ Open. 2019 Aug 24;9(8):e027070. https://www.doi.org/10.1136/bmjopen-2018-027070 http://www.ncbi.nlm.nih.gov/pubmed/31446404?tool=bestpractice.com [15]Bensing JM, Hulsman RL, Schreurs KM. Gender differences in fatigue: biopsychosocial factors relating to fatigue in men and women. Med Care. 1999 Oct;37(10):1078-83. http://www.ncbi.nlm.nih.gov/pubmed/10524374?tool=bestpractice.com [16]Verdon F, Burnand B, Stubi CL, et al. Iron supplementation for unexplained fatigue in non-anaemic women: double blind randomised placebo controlled trial. BMJ. 2003 May 24;326(7399):1124. http://www.bmj.com/cgi/content/full/326/7399/1124 http://www.ncbi.nlm.nih.gov/pubmed/12763985?tool=bestpractice.com [17]Vaucher P, Druais PL, Waldvogel S, et al. Effect of iron supplementation on fatigue in nonanemic menstruating women with low ferritin: a randomized controlled trial. CMAJ. 2012 Aug 7;184(11):1247-54. http://www.ncbi.nlm.nih.gov/pubmed/22777991?tool=bestpractice.com ​​

Classification

Fatigue can be divided into categories based on origin, attribution, and duration of symptoms. The origin of fatigue may be:

• Central (brain-derived)

• Peripheral (usually a neuromuscular origin).

It may be attributed to:[8]Prins JB, van der Meer JW, Bleijenberg G. Chronic fatigue syndrome. Lancet. 2006 Jan 28;367(9507):346-55. http://www.ncbi.nlm.nih.gov/pubmed/16443043?tool=bestpractice.com

• Physical illness

• Psychological (e.g., psychiatric disorder), social (e.g., family problems), and physiological factors (e.g., old age)

• Occupational illness (e.g., workplace stress).

The duration of symptoms may refer to:

• Recent fatigue (symptoms lasting <1 month)

• Prolonged fatigue (symptoms lasting >1 month)

• Chronic fatigue (symptoms lasting >6 months).

When unexplained, clinically evaluated chronic fatigue can be separated into myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and idiopathic chronic fatigue.[18]Fukuda K, Straus SE, Hickie I, et al. The chronic fatigue syndrome: a comprehensive approach to its definition and study. International Chronic Fatigue Syndrome Study Group. Ann Intern Med. 1994 Dec 15;121(12):953-9. http://www.ncbi.nlm.nih.gov/pubmed/7978722?tool=bestpractice.com [19]Reid S, Chalder T, Cleare A, et al. Chronic fatigue syndrome. BMJ. 2000 Jan 29;320(7230):292-6. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1117488 http://www.ncbi.nlm.nih.gov/pubmed/10650029?tool=bestpractice.com ​ ME/CFS represents a small subset of those who report actual chronic fatigue. Even in patients with fatigue of 6 months or longer in duration, the prevalence is <40%. European studies have shown that patients with fatigue lasting longer than 6 months were given a diagnosis of ME/CFS in up to one third of cases.[9]Wessely S, Chalder T, Hirsch S, et al. Psychological symptoms, somatic symptoms, and psychiatric disorder in chronic fatigue and chronic fatigue syndrome: a prospective study in the primary care setting. Am J Psychiatry. 1996 Aug;153(8):1050-9. http://www.ncbi.nlm.nih.gov/pubmed/8678174?tool=bestpractice.com [13]Bates DW, Schmitt W, Buchwald D, et al. Prevalence of fatigue and chronic fatigue syndrome in a primary care practice. Arch Intern Med. 1993 Dec 27;153(24):2759-65. http://www.ncbi.nlm.nih.gov/pubmed/8257251?tool=bestpractice.com [20]Buchwald D, Umali P, Umali J, et al. Chronic fatigue and the chronic fatigue syndrome: prevalence in a Pacific Northwest health care system. Ann Intern Med. 1995 Jul 15;123(2):81-8. http://www.ncbi.nlm.nih.gov/pubmed/7778839?tool=bestpractice.com [21]Darbishire L, Ridsdale L, Seed PT. Distinguishing patients with chronic fatigue from those with chronic fatigue syndrome: a diagnostic study in UK primary care. Br J Gen Pract. 2003 Jun;53(491):441-5. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1314617 http://www.ncbi.nlm.nih.gov/pubmed/12939888?tool=bestpractice.com [22]Ridsdale L, Evans A, Jerrett W, et al. Patients with fatigue in general practice: a prospective study. BMJ. 1993 Jul 10;307(6896):103-6. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1693499 http://www.ncbi.nlm.nih.gov/pubmed/8343705?tool=bestpractice.com ​ The US Institute of Medicine has clustered several key symptoms associated with ME/CFS, and has proposed the term "systemic exertion intolerance disease" (SEID) as an alternative to ME/CFS.[23]Institute of Medicine. Beyond myalgic encephalomyelitis/chronic fatigue syndrome: redefining an illness. Washington, DC: The National Academies Press; 2015.