Fatigue is difficulty initiating and sustaining activity due to a lack of energy and accompanied by a desire to rest. Fatigue is normal after physical exertion, prolonged stress, and sleep deprivation.
Fatigue occurs most often as part of a symptom complex, but even when it is the sole or main presenting symptom, fatigue is one of the most common symptoms.
Patients may refer to certain other symptoms as fatigue; differentiating between them and fatigue is usually, but not always, possible with detailed questioning.
Weakness, a symptom of nervous system or muscle disorders, is insufficient force of muscular contraction at maximum effort. Disorders such as myasthenia gravis and Eaton-Lambert syndrome can cause weakness that worsens with activity, simulating fatigue.
Dyspnea on exertion, an early symptom of cardiac and pulmonary disorders, can decrease exercise tolerance, simulating fatigue. Respiratory symptoms usually can be elicited upon careful questioning or develop subsequently.
Somnolence, a symptom of disorders causing sleep deprivation (eg, allergic rhinitis, esophageal reflux, painful musculoskeletal disorders, sleep apnea, severe chronic disorders), is an unusually strong desire to sleep. Yawning and lapsing into sleep during daytime hours are common. Patients can usually tell the difference between somnolence and fatigue. However, deprivation of deep nonrapid eye movement sleep can cause muscle aches and fatigue, and many patients with fatigue have disturbed sleep, so differentiating between fatigue and somnolence may be difficult.
Fatigue can be classified in various temporal categories, such as the following:
Recent fatigue: < 1 month duration
Prolonged fatigue: 1 to 6 months duration
Chronic fatigue: > 6 months duration
Chronic fatigue syndrome is one cause of chronic fatigue. There are now 2 other terms for chronic fatigue syndrome—myalgic encephalomyelitis and systemic exertion intolerance—although there is no clear delineation between these at this time. Patients with COVID-19 may have symptoms that last for weeks or even months, which is known as "long COVID" or "long-haul COVID" and resembles postviral fatigue (and can be called post-viral fatigue syndrome) and chronic fatigue syndrome (1).
Reference
1. Wong TL, Weitzer DJ. Long COVID and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)-A Systemic Review and Comparison of Clinical Presentation and Symptomatology. Medicina (Kaunas). 2021;57(5):418. Published 2021 Apr 26. doi:10.3390/medicina57050418
Etiology of Fatigue
Most serious (and many minor) acute and chronic illnesses produce fatigue. However, many of these have other more prominent manifestations (eg, pain, cough, fever, jaundice) as the presenting complaint. This discussion focuses on disorders that can manifest primarily as fatigue.
The most common disorders manifesting predominantly as recent fatigue (lasting < 1 month) are
Stress and/or depression
The most common causes manifesting predominantly as prolonged fatigue (lasting 1 to 6 months) are
Sleep disturbances (eg, sleep apnea)
The most common causes manifesting predominantly as chronic fatigue (lasting > 6 months) are
Myalgic encephalomyelitis/systemic exertion intolerance disease/chronic fatigue syndrome
Postviral fatigue syndrome
Psychologic causes (eg, depression)
Drugs
Several factors commonly cause or contribute to a chief complaint of fatigue, usually prolonged or chronic fatigue (see table Some Factors Commonly Contributing To Prolonged Or Chronic Fatigue ).
Some Factors Commonly Contributing To Prolonged Or Chronic Fatigue
Category | Examples |
|---|---|
Chronic disorders | Chronic kidney disease, rheumatologic disorders (eg, giant cell arteritis, rheumatoid arthritis, systemic lupus erythematosus) |
Drugs | |
Endocrine disorders | Adrenal insufficiency*, diabetes, hyperthyroidism* (usually apathetic), hypothyroidism, pituitary insufficiency |
Infections | Cytomegalovirus infection, endocarditis, fungal pneumonias, hepatitis, HIV/AIDS, mononucleosis, parasitic infections*, tuberculosis, SARS, COVID-19 |
Psychologic disorders | Anxiety, depression, domestic violence, drug addiction, panic disorder, somatization disorder |
Disorders of unknown cause | Myalgic encephalomyelitis/chronic fatigue syndrome, fibromyalgia, idiopathic fatigue |
Other causes | Anemias, cancers, deconditioning, pregnancy*, undernutrition, hypercalcemia*, multiple sclerosis |
* Usually does not cause chronic fatigue. | |
Evaluation of Fatigue
Fatigue can be highly subjective. Patients vary in what they consider to be fatigue and how they describe it. There are also few ways to objectively confirm fatigue or tell how severe it is. History and physical examination focus on identifying subtle manifestations of underlying illness (particularly infections, endocrine and rheumatologic disorders, anemia, and depression) that can be used to guide testing.
History
History of present illness includes open-ended questions about what "fatigue" is, listening for descriptions that could suggest dyspnea on exertion, somnolence, or muscle weakness. The relationships between fatigue, activity, rest, and sleep should be elicited, as should the onset, time course and pattern, and factors that increase or decrease fatigue.
Review of systems should be thorough because potential causes of fatigue are so numerous and diverse. Among important nonspecific symptoms are fever, weight loss, and night sweats (possibly suggesting cancer, a rheumatologic disorder, or an infection). Menstrual history is obtained in women of child-bearing age. Unless a cause is evident, patients should be asked questions from screening questionnaires for psychologic disorders (eg, depression, anxiety, drug use disorder, somatoform disorders, domestic violence).
Past medical history should address known disorders. Complete drug use history should include prescription, over-the-counter, and recreational drugs.
Social history should elicit descriptions of diet, drug use, and the effect of fatigue on quality of life, employment, and social and family relationships.
Physical examination
Vital signs are checked for fever, tachycardia, tachypnea, and hypotension.
General examination should be particularly comprehensive, including general appearance and examination of the heart, lungs, abdomen, head and neck, breasts, rectum (including prostate exam and testing for occult blood), genitals, liver, spleen, lymph nodes, joints, and skin.
Neurologic examination should include testing of, at a minimum, mental status, cranial nerves, mood, affect, strength, muscle bulk and tone, reflexes, and gait.
Usually if fatigue is of recent onset, a more focused examination will reveal the cause. If fatigue is chronic, examination is unlikely to reveal a cause; however, thorough physical examination is an important way to build rapport with the patient and occasionally is diagnostically helpful.
Red flags
Chronic weight loss
Chronic fever or night sweats
Generalized lymphadenopathy
Muscle weakness or pain
Serious nonfatigue symptoms (eg, hemoptysis, hematemesis, severe dyspnea, ascites, confusion, suicidal ideation)
Involvement of > 1 organ system (eg, rash plus arthritis)
New or different headache or loss of vision, particularly with muscle pains, in an older adult
Interpretation of findings
In general, a cause is more likely to be found when fatigue is one of many symptoms than when fatigue is the sole symptom. Fatigue that worsens with activity and lessens with rest suggests a physical disorder. Fatigue that is present constantly and does not lessen with rest, particularly with occasional bursts of energy, may indicate a psychologic disorder.
In the absence of red flag findings, a thorough history, physical examination, and routine laboratory testing (plus tests directed at specific findings—see Interpretation of Selected Findings in Evaluating Fatigue) should suffice for an initial evaluation. If test results are negative, watchful waiting is usually appropriate; if fatigue worsens or other symptoms and signs develop, the patient is reevaluated.
Several causes can be considered for patients with prolonged or chronic fatigue and selected other common or specific clinical findings.
Interpretation of Selected Findings in Evaluating Fatigue
Symptoms | Possible Causes | Tests to Consider* |
|---|---|---|
Anorexia, abdominal pain, weight loss, or steatorrhea | Undernutrition secondary to gastrointestinal tract disorder, cancer | Endoscopy, MRI of abdomen, MRCP |
Anorexia, abdominal pain, weight loss, orthostatic hypotension, skin hyperpigmentation | Adrenal insufficiency | Blood electrolyte, cortisol, and ACTH levels; Sometimes synthetic ACTH 1-24 (Cortrosyn®) stimulation test |
Fever, night sweats, or weight loss | Infection, rheumatologic disorder (including vasculitis) | Chest x-ray, CBC, ESR, blood or other cultures, rheumatoid factor and ANA |
Dyspnea with cough or hemoptysis | HIV/AIDS (with Pneumocystis jirovecii pneumonia), fungal pneumonia, tuberculosis, COVID-19 | Chest x-ray, chest CT or PET-CT, HIV test, sputum cytology and/or culture, pulmonary function tests, PPD, molecular test for SARS-CoV-2 |
Dyspnea, orthopnea, and/or edema | Chest x-ray, renal function tests, echocardiography (if orthopnea) | |
Dyspnea, Roth spots, Janeway lesions, new or changing heart murmurs, IV drug use | Multiple blood cultures, echocardiography | |
Decreased exercise tolerance with dyspnea on exertion, pallor | Anemia | CBC |
Generalized lymphadenopathy | HIV test, CBC, EBV serologic tests | |
Combined arthritis, rash, and/or other organ involvement | Rheumatologic disorder (including vasculitis) | CBC, ESR, rheumatoid factor, ANA |
Jaundice, ascites, confusion | Liver tests, viral hepatitis serologies | |
Polydipsia, polyuria, increased appetite, weight gain or loss | Fasting plasma glucose level, HbA1C, glucose tolerance testing | |
Cold intolerance, weight gain, constipation, coarse skin | Hypothyroidism, pituitary insufficiency | Thyroid function tests |
Weight loss or atrial fibrillation in older patient | Hyperthyroidism (including apathetic) | Thyroid function tests |
Fatigue worse with exposure to heat, past neurologic symptoms (eg, numbness, ataxia, weakness), particularly > 1 episode | Brain and/or spinal cord MRI with contrast | |
Headache, jaw claudication, temporal artery tenderness or thickening, and/or muscle pains in an older adult | ESR, brain MRI or CT, temporal artery biopsy | |
Anxiety, sadness, anorexia, unexplained sleep disturbance | Anxiety, depression, domestic violence, somatization disorder | Clinical evaluation |
Recent sore throat, lymphadenopathy, splenomegaly | Mononucleosis, myalgic encephalomyelitis/systemic exertion intolerance disease/chronic fatigue syndrome | EBV serologic tests; CBC, ESR, TSH, chemistries (as for suspected chronic fatigue syndrome) |
Lymphadenopathy, splenomegaly | EBV serologic tests, sometimes CMV antibody testing | |
Frequent or opportunistic infections, candidiasis, lymphadenopathy, splenomegaly | HIV testing | |
Chronic, widespread musculoskeletal extra-articular pain, trigger points, irritable bowel symptoms, migraines, anxiety | ESR or C-reactive protein, CK, TSH, hepatitis C serology | |
Weight loss, steatorrhea, inadequate oral intake | ||
Constipation, lethargy, bone pain (eg, at night) | Serum chemistries, including calcium | |
Postexertional malaise, unrefreshing sleep, difficulty with concentration or short-term memory, orthostatic intolerance, sore throat, myalgias, headaches | Myalgic encephalomyelitis/systemic exertion intolerance disease/chronic fatigue syndrome | CBC, ESR, TSH, serum electrolytes, glucose, calcium, renal and liver tests |
* Choice of specific tests is dictated by which causes are clinically suspected. | ||
ACTH = adrenocorticotropic hormone; ANA = antinuclear antibodies; CBC = complete blood count; CK = creatine kinase; CMV = cytomegalovirus; EBV = Epstein-Barr virus; ESR = erythrocyte sedimentation rate; MRCP = magnetic resonance cholangiopancreatography; PET = positron emission tomography; PPD = purified protein derivative; TSH = thyroid-stimulating hormone. | ||
Testing
Testing is directed at causes suspected based on clinical findings. If no cause is evident or suspected based on clinical findings, laboratory testing is unlikely to reveal a cause. Still, many clinicians recommend testing with the following:
Complete blood count (CBC)
Ferritin
Erythrocyte sedimentation rate (ESR)
Thyroid-stimulating hormone (TSH)
Chemistries, including electrolytes, glucose, calcium, and renal and liver tests
Creatine kinase (CK) is recommended if muscle pain or weakness is present. HIV testing and testing for tuberculosis with purified protein derivative (PPD) placement or interferon-gamma release assays are recommended if the patient has risk factors. Chest x-ray is recommended if cough or dyspnea is present. Other testing, such as for infections or immunologic deficiencies, is not recommended unless there are suggestive clinical findings.
Diagnosis of myalgic encephalomyelitis/systemic exertion intolerance disease/chronic fatigue syndrome requires specific diagnostic criteria.
Treatment of Fatigue
Treatment to lessen fatigue is directed at the cause.
Patients with myalgic encephalomyelitis/systemic exertion intolerance disease/chronic fatigue syndrome and idiopathic chronic fatigue are treated similarly. They should be told clearly that the etiology is presently unknown. Treatment is more often successful if the practitioner is patient and nonjudgmental and acknowledges the real effects of fatigue.
Potential treatments include physical therapy (eg, graded exercise therapy) and psychologic support (eg, cognitive-behavioral therapy). Focusing on improving sleep and relieving pain may also help. Goals include returning to work and maintaining normal activity levels.
Geriatrics Essentials: Fatigue
Fatigue is more often the first symptom of a disorder in older patients. For example, the first symptom of pneumonia in an older woman may be fatigue rather than pulmonary symptoms. The first symptom of other disorders, such as giant cell arteritis, may also be fatigue in an older patient. Because serious illness may become apparent soon after sudden fatigue in older patients, the cause should be determined as quickly as possible. Fatigue is also somewhat more likely to be caused by giant cell arteritis or another serious physical disorder in older adults.
Key Points
Fatigue is a common symptom.
Fatigue caused primarily by a physical disorder usually increases with activity and lessens with rest.
Laboratory testing is low yield in the absence of suggestive clinical findings.
Successful treatment is more likely if the practitioner is patient and understanding.
