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.
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.
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%.
In the primary care setting, a medical or psychiatric diagnosis is found in the majority of patients presenting with recent fatigue (at least two-thirds). 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. 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. 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%).
Fatigue can be divided into categories based on origin, attribution, and duration of symptoms. The origin of fatigue may be:
Peripheral (usually a neuromuscular origin).
It may be attributed to:
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 chronic fatigue syndrome (also known as myalgic encephalomyelitis [ME]) and idiopathic chronic fatigue. Chronic fatigue syndrome 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 chronic fatigue syndrome in up to one third of cases. The US Institute of Medicine has clustered several key symptoms associated with chronic fatigue syndrome, and has proposed the term "systemic exertion intolerance disease" (SEID) as an alternative to chronic fatigue syndrome.
- Insomnia disorder
- Iron-deficiency anemia
- Iron deficiency without anemia
- Chronic heart failure
- Diabetes mellitus
- EBV infection
- Influenza infection
- Coronavirus disease 2019 (COVID-19)
- Long COVID
- Medication-induced fatigue
- Alcohol dependence
- Drug dependence
- HIV infection
- Acute myocardial ischemia
- Atrial fibrillation
- Obstructive sleep apnea/hypopnea syndrome (OSAHS)
- Obesity hypoventilation syndrome (OHS)
- Restless legs syndrome
- Celiac disease
- Addison disease
- Myelodysplastic syndrome
- Chronic myeloid leukemia
- Non-Hodgkin lymphoma
- Hodgkin lymphoma
- Cytomegalovirus infection
- Lyme disease
- Chronic renal disease
- Multiple sclerosis
- Parkinson disease
- Vitamin D deficiency (osteomalacia)
- Systemic lupus erythematosus
- Primary biliary cirrhosis
- Underlying malignancy (non-lymphoma)
- Chronic fatigue syndrome (myalgic encephalomyelitis)/systemic exertion intolerance disease
- Chronic idiopathic fatigue
- Heavy metal toxicity
Bernard Favrat, MD
University of Lausanne
Department of Ambulatory Care and Community Medicine
BF has received study grants and lecture/consultant fees from Vifor Pharma and Pierre Fabre Médicament. BF is an author of a number of references cited in this topic.
Jacques Cornuz, MD, MPH
University Hospital of Lausanne
Department of Ambulatory Care and Community Medicine
JC is an author of a reference cited in this topic.
Dr Bernard Favrat and Dr Jacques Cornuz would like to gratefully acknowledge Dr Idris Guessous and Dr Baptiste Pedrazzini, previous contributors to this topic.
IG is an author of a reference cited in this topic. BP declares that he has no competing interests.
Chris Martin, MD
Dr Moulds and Partners
Laindon Health Centre
CM has received an NHS salary greater than 6 figures USD. CM declares that he has no competing interests.
Benjamin Natelson, MD
Professor of Neurosciences
New Jersey Medical School
BN declares that he has no competing interests.
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