Fatigue is a state of being without energy for a prolonged period of time. The word fatigue is used in two contexts: in the medical sense, and in the sense of normal tiredness.
In the medical sense, fatigue is seen as a symptom, and is sometimes associated with medical conditions including autoimmune disease, organ failure, mood disorders, heart disease, infectious diseases, and post-infectious-disease states. However, fatigue is complex and in up to a third of primary care cases no medical or psychiatric diagnosis is found.
In the sense of tiredness, fatigue often follows prolonged physical or mental activity. Physical fatigue results from muscle fatigue brought about by intense physical activity. Mental fatigue results from prolonged periods of cognitive activity which impairs cognitive ability, can manifest as sleepiness, lethargy, or directed attention fatigue, and can also impair physical performance.
Definition Fatigue in a medical context is used to cover experiences of low energy that are not caused by normal life.
A 2021 review proposed a definition for fatigue as a starting point for discussion: "A multi-dimensional phenomenon in which the biophysiological, cognitive, motivational and emotional state of the body is affected resulting in significant impairment of the individual's ability to function in their normal capacity".
Another definition is that fatigue is "a significant subjective sensation of weariness, increasing sense of effort, mismatch between effort expended and actual performance, or exhaustion independent from medications, chronic pain, physical deconditioning, anaemia, respiratory dysfunction, depression, and sleep disorders".
Terminology The use of the term fatigue in medical contexts may carry inaccurate connotations from the more general usage of the same word. More accurate terminology may also be needed for variants within the umbrella term of fatigue.
Comparison with other terms Tiredness Tiredness which is a normal result of work, mental stress, anxiety, overstimulation and understimulation, jet lag, active recreation, boredom, or lack of sleep is not considered medical fatigue. This is the tiredness described in MeSH Descriptor Data.
Exhaustion Exhaustion is a state of extreme tiredness.
Sleepiness
Sleepiness refers to a tendency to fall asleep, whereas fatigue refers to an overwhelming sense of tiredness, lack of energy, and a feeling of exhaustion. Sleepiness and fatigue often coexist as a consequence of sleep deprivation. However sleepiness and fatigue may not correlate. Fatigue is generally considered a longer-term condition than sleepiness (somnolence).
Classification "Fatigue" is categorised as ICD-11 code MG22.
Presentation
Common features Distinguishing features of medical fatigue include: unpredictability, variability in severity, fatigue being relatively profound/overwhelming, and having extensive impact on daily living, lack of improvement with rest, where an underlying disease is present, the amount of fatigue is often not commensurate with the severity of the underlying disease.
Differentiating features Differentiating characteristics of fatigue that may help identify the possible cause of fatigue include: Post-exertional malaise; a common feature of ME/CFS,. Increased by heat or cold; MS fatigue is in many cases affected in this way. Flare-ups and Remissions; Some fatigue diseases have flareups of a few weeks (lupus, fibromyalgia). Other fatigue diseases may have longer patterns of activity and remission, or no remissions at all (MS). Variability within a day; Some fatigues (rheumatoid arthritis (RA), cancer-related fatigue) seem to often be continual (24/7), whilst others (MS, Sjögren's, lupus, brain injury) often vary in intensity at different times within a day. A 2010 study found that Sjögren's patients reported fatigue after rising, an improvement in mid-morning, and worsening later in the day, whereas lupus (SLE) patients reported lower fatigue after rising followed by increasing fatigue through the day. ME/CFS symptoms can be continual, or can fluctuate during the day, from day to day, and over longer periods. Fibromyalgia fatigue can be continual or variable. The pace of onset may be a related differentiating factor; MS fatigue can have abrupt onset. Feeling of weight; some fatigues, including that caused by MS, create a sense of weight or gravity; "I feel like I have lead weights attached to my limbs ... or I am being pulled down by gravity."
Some people may have multiple causes of fatigue.
Causes
Fatigue is complex and can be driven and maintained by a potentially wide range of biopsychosocial factors. Tiredness is a common medically unexplained symptom. In up to a third of fatigue primary care cases, no medical or psychiatric diagnosis is found.
Adverse life events Adverse life events have been associated with fatigue.
Drug use A 2021 study in a Korean city found that alcohol consumption was the variable with the most correlation with overall fatigue. A 2020 Norway study found that 69% of substance use disorder patients had severe fatigue symptoms, and particularly those with extensive use of benzodiazepines. Causality, as opposed to correlation, were not proven in these studies.
Digital screen use The protracted use of digital screens—such as those associated with computers, laptops and smartphones—can cause eye fatigue, and induce a general state of mental and physical exhaustion. Specific symptoms may include sore eyes, blurred vision, headaches and associated orthopedic issues such as a sore neck and back. These symptoms collectively are known as computer vision syndrome (CVS) or in colloquial parlance as screen fatigue.
Sleep disturbance Fatigue can often be traced to poor sleep habits. Sleep deprivation and disruption is associated with subsequent fatigue. Sleep disturbances due to disease may impact fatigue. Caffeine and alcohol can disrupt sleep, causing fatigue.
Medications Fatigue may be a side effect of certain medications (e.g., lithium salts, ciprofloxacin); beta blockers, which can induce exercise intolerance, medicines used to treat allergies or coughs, and many cancer treatments, particularly chemotherapy and radiotherapy. Use of benzodiazepines has been found to correlate with higher fatigue.
Association with diseases and illnesses Fatigue is often associated with diseases and conditions. Some major categories of conditions that often list fatigue as a symptom include physical diseases, substance use illness, mental illnesses, and other diseases and conditions.
Physical diseases
autoimmune diseases, such as celiac disease, lupus, multiple sclerosis, myasthenia gravis, NMOSD, Sjögren's syndrome, rheumatoid arthritis, spondyloarthropathy and UCTD; this population's primary concern is fatigue; blood disorders, such as anemia and hemochromatosis; brain injury; cancer, in which case it is called cancer fatigue; COVID-19 and long COVID; endocrine diseases or metabolic disorders: diabetes mellitus, hypothyroidism and Addison's disease; fibromyalgia; heart failure and heart attack; HIV; inborn errors of metabolism such as fructose malabsorption; infectious diseases such as infectious mononucleosis or tuberculosis; irritable bowel syndrome; kidney diseases, e.g., acute renal failure, chronic renal failure; leukemia or lymphoma; liver failure or liver diseases, e.g., hepatitis; Low blood pressure; Lyme disease; mast cell activation syndrome; neurological disorders such as narcolepsy, Parkinson's disease, postural orthostatic tachycardia syndrome (POTS) and post-concussion syndrome; nutritional deficiencies, such as sodium, iron, vitamin B12, and folate deficiencies; physical trauma and other pain-causing conditions, such as arthritis; sarcoidosis; sleep deprivation or sleep disorders, e.g. sleep apnea; stroke; thyroid disease such as hypothyroidism;
Mental illnesses anxiety disorders, such as generalized anxiety disorder; developmental disorders such as autism spectrum disorder; depression; eating disorders, which can produce fatigue due to inadequate nutrition;
Other myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS); idiopathic chronic fatigue, a term used to describe chronic fatigue which does not have symptoms of ME/CFS. However ICF does not have a dedicated diagnostic code in the World Health Organization's ICD-11 classification;This includes a category MG22 Fatigue (typically fatigue following exertion but sometimes may occur in the absence of such exertion as a symptom of health conditions), and many other categories where fatigue is mentioned as a secondary result of other factors. 8E49 Postviral fatigue syndrome QE84 Acute stress reaction, Combat fatigue 6A70-6A7Z Depressive disorders 07 Sleep-wake disorders FB32.5 Muscle strain or sprain, causing muscular fatigue NF01.3 Heat fatigue, transient MA82.Y Voice disturbances, causing voice fatigue BD1Z Heart failure, unspecified, causing myocardial fatigue JA65.Y Conditions predominantly related to pregnancy, causing fatigue which complicates pregnancy SD91 Fatigue consumption disorder, causing coughing, fever, diarrhea, chest pain etc. MG2A Ageing associated decline in intrinsic capacity, causing senile fatigue NF07.2 Exhaustion due to exposure NF01 Heat exhaustion 6C20 Bodily distress disorder. Gulf War syndrome.
Primary vs. secondary In some areas, it has been proposed that fatigue be separated into primary fatigue, caused directly by a disease process, and ordinary or secondary fatigue, caused by a range of causes including exertion and also secondary impacts on a person of having a disease (such as disrupted sleep). The ICD-11 MG22 definition of fatigue captures both types of fatigue; it includes fatigue that "occur[s] in the absence of... exertion... as a symptom of health conditions."
Obesity Obesity correlates with higher fatigue levels and incidence.
Somatic symptom disorder In somatic symptom disorder the patient is overfocused on a physical symptom, such as fatigue, that may or may not be explained by a medical condition.
Scientifically unsupported causes The concept of adrenal fatigue is often raised in media but no scientific basis has been found for it.
Mechanisms
The mechanisms that cause fatigue are not well understood. Several mechanisms may be in operation within a patient, with the relative contribution of each mechanism differing over time.
Proposed fatigue explanations due to permanent changes in the brain may have difficulty in explaining the "unpredictability" and "variability" (i.e. appearing intermittently during the day, and not on all days) of the fatigue associated with inflammatory rheumatic diseases and autoimmune diseases (such as multiple sclerosis).
Inflammation Inflammation distorts neural chemistry, brain function and functional connectivity across a broad range of brain networks, and has been linked to many types of fatigue. Findings implicate neuroinflammation in the etiology of fatigue in autoimmune and related disorders. Low-grade inflammation may cause an imbalance between energy availability and expenditure.
Cytokines are small protein molecules that modulate immune responses and inflammation (as well as other functions) and may have causal roles in fatigue. However a 2019 review was inconclusive as to whether cytokines play any definitive role in ME/CFS.
Reduced brain connectivity Fatigue has been correlated with reductions in structural and functional connectivity in the brain, including in post-stroke, MS, NMOSD and MOG, and ME/CFS. This was also found for fatigue after brain injury, including a significant linear correlation between self-reported fatigue and brain functional connectivity.