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EBMG

Fatigue

Essentials

  • Fatigue may manifest as either inability to initiate activity, unusually marked fatigue whilst performing activities or difficulty with memory and concentration.
  • Diseases and medication possibly causing fatigue should be identified through the patient's history, physical examination and any follow-up investigations indicated.
  • Unexplained fatigue continuing for more than 6 months is called idiopathic fatigue.

Causes of fatigue

Assessment

Medical history

  • This is the most important examination.
  • Clarify what the patient means by fatigue: is it physical fatigue, due to an excessive workload or lack of sleep, or is it mental fatigue?
  • Has the patient experienced previous episodes of fatigue? A completely new symptom suggests an organic cause.
  • Inability to complete tasks often suggests organic fatigue, whereas unspecific fatigue is often associated with lack of initiative.
  • If fatigue is the sole or main symptom, it is more rarely caused by an organic disease than if it is one among many symptoms.
  • Ask about the following issues concerning the fatigue:
    • onset: sudden or gradual
    • course: steady, improving or becoming worse
    • daily variation
    • aggravating or alleviating factors: whether exertion aggravates it, whether rest helps
    • effect on daily life
    • need for adjustment at work or in hobbies.
  • Address aspects of the patient's life style:
    • the amount and quality of sleep
    • dietary and exercise habits
    • use of alcohol or other intoxicants
    • use of drugs, particularly sedative or hypnotic drugs.
  • Address the patient's situation:
    • employment status, threat of unemployment, any burnout Burnout
    • relationship with partner, family setup, any violence
    • other stress factors in personal life, such as the health of family members, financial situation.
  • Physical disorders are usually also associated with other, more specific, symptoms, such as
    • weight change
    • sweating
    • pain
    • nausea.
  • Of psychiatric disorders, signs of the following should be sought:
    • depression
    • bipolar disorder
    • anxiety
    • somatisation.
  • Are there signs of impaired cognition or is there any information about this available?

Clinical findings

  • The aim of a thorough clinical examination is to detect signs and symptoms of a physical disease.
    • General appearance
    • Mental alertness
    • Abnormal skin changes: pallor, jaundice, bruises
    • Abnormal findings on palpation: internal organs, lymphadenopathy
    • Signs of hypothyroidism or hyperglycaemia
    • Auscultation of the heart and lungs, blood pressure (orthostatic hypertension), oedema
    • Neurological examination: reflexes, muscle tone

Workup

  • If laboratory tests are used to search for diseases that are unlikely to be present, the number of false positive results will be high, leading to unnecessary follow-up investigations.
  • Laboratory tests will elucidate the cause of fatigue in only about 5% of patients.
  • Essential investigations that are warranted in all patients:
    • Basic blood count with platelets, fasting blood glucose, plasma TSH
  • Other basic investigations, as considered appropriate:
    • ESR, CRP
    • Ferritin
    • ALT, GT
    • Transcobalamin-bound vitamin B12 (holotranscobalamin)
    • Plasma creatinine, chemical urinalysis
    • HBA1c
    • Sodium, potassium
  • Possible further tests performed only as indicated by the symptoms or by patient history
    • Chest x-ray, ECG
    • Plasma CK, Ca (albumin-corrected), serum cortisol
    • Antibody assays to diagnose infections (HIV antibody and antigen, HCV, EBV, Borrelia)
    • Autoimmune disease tests (antinuclear antibodies, rheumatoid factor, anti-CCP antibody assays)
    • Coeliac disease tests

Idiopathic fatigue and chronic fatigue syndrome (SEID)

  • Unexplained fatigue continuing for more than 6 months is called idiopathic fatigue.
    • In various data sets, no explanation is found for fatigue in 10 to 30% of patients.

Chronic fatigue syndrome

  • The term “chronic fatigue syndrome” (CFS) has been widely used. Other terms used for the condition over the years include myalgic encephalomyelitis (ME) or the combination ME/CFS. In 2015, the American Insitute of Medicine (IOM) proposed a new name: “systemic exertion intolerance disease” (SEID). The terminology is still unestablished.
  • There are several different sets of criteria for CFS/ME/SEID 3.
  • The IOM uses the following criteria 2:
    1. A substantial reduction or impairment in the ability to engage in pre-illness levels of occupational, educational, social, or personal activities, that persists for more than 6 months and is accompanied by fatigue, which is often profound, is of new or definite onset (not lifelong), is not the result of ongoing excessive exertion, and is not substantially alleviated by rest.
    2. Post-exertional malaise*
    3. Unrefreshing sleep*
  • At least one of the two following manifestations is also required:
    1. Cognitive impairment*
    2. Orthostatic intolerance (symptoms being aggravated in the upright position)
  • Symptoms marked with an asterisk (*): If the patient has these symptoms, they must be present at least half of the time and they must be at least moderately severe.
  • The criteria do not address the cause, pathophysiology, pathogenesis or treatment of the syndrome.

Treatment of chronic idiopathic fatigue

  • Identify and address aetiological physical and psychological causes.
  • There is no known curative treatment but symptoms subside in a significant proportion of patients with time. The patient should be informed about this.
  • Treatment should concentrate on alleviating the symptoms and improving the functional capacity in cooperation with the patient.
  • A supportive attitude and listening to the patient's symptoms are essential.
  • In many cases, it is better to make follow-up appointments early in the course of treatment rather than agreeing that the patient should see the doctor if he starts feeling worse.
  • A regular life and pacing activity to how the patient feels can be helpful.
  • Good results have been obtained with cognitive behavioural therapy.
    • Patients with a positive approach to the treatment show improved illness behaviour and better coping with symptoms.
    • The treatment aims at affecting patients' attitudes and behavioural models hindering recovery.
    • See Cognitive psychotherapy Cognitive Psychotherapy.
  • Graded exercise therapy (GET) Exercise Therapy for Chronic Fatigue Syndrome has given similar results to cognitive behavioural therapy (CBT).
    • To avoid soreness and overexertion, the targets should be kept moderate. For example, the target could be light exercising for about 30 minutes at a pulse rate below 100/minute. In patients with severe symptoms, the initial targets can be considerably less demanding.
    • The level of demand should be increased gradually.
    • Many types of exercise, such as walking, swimming, cycling or exercising at a gym are suitable.
  • Medication can be used as required by any associated symptoms.
  • The cognitive and exercise therapies are not necessarily suitable for patients who fulfill the diagnostic criteria for SEID, at least not in the way and with the intensity suggested. The views concerning optimal treatment for patients with SEID differ, and the efficacy of all treatments should be evaluated on an individual basis.

    References

    • Leaviss J, Davis S, Ren S, et al. Behavioural modification interventions for medically unexplained symptoms in primary care: systematic reviews and economic evaluation. Health Technol Assess 2020;24(46):1-490. [PubMed]
    • Institute of Medicine of the National Academies. Beyond myalgic encephalomyelitis/chronic fatigue syndrome: redefining an illness. February 2015.
    • Brurberg KG, Fønhus MS, Larun L, et al. Case definitions for chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME): a systematic review. BMJ Open 2014;4(2):e003973. [PubMed]