Clinically relevant fatigue is composed of three major components: generalized weakness (difficulty in initiating activities); easy fatigability (difficulty in completing activities); and mental fatigue (difficulty with concentration and memory). Important diseases that can cause fatigue include hyperthyroidism and hypothyroidism, HF, infections (endocarditis, hepatitis), COPD, sleep apnea, anemia, autoimmune disorders, multiple sclerosis, irritable bowel syndrome, Parkinson disease, cerebral vascular accident, and cancer. Solution-focused therapy has a significant initial beneficial effect on the severity of fatigue and quality of life in patients with quiescent inflammatory bowel disease.
Alcohol use disorder, vitamin C deficiency (scurvy), side effects from medications (eg, sedatives and beta-blockers), and psychological conditions (eg, insomnia; depression; anxiety; panic attacks; dysthmia; and somatic symptom disorder, formerly called somatization disorder) may be the cause. Common outpatient infectious causes include mononucleosis and sinusitis. These conditions are usually associated with other characteristic signs, but patients may emphasize fatigue and not reveal their other symptoms unless directly asked. The lifetime prevalence of significant fatigue (present for at least 2 weeks) is about 25%. Fatigue of unknown cause or related to psychiatric illness exceeds that due to physical illness, injury, alcohol, or medications.
Although frequently associated with Lyme disease, severe fatigue as a long-term sequela is rare.
B. Chronic Fatigue Syndrome/Systemic Exertion Intolerance Disease
A working case definition of chronic fatigue syndrome indicates that it is not a homogeneous abnormality, there is no single pathogenic mechanism (Figure 2–1), and no physical finding or laboratory test can be used to confirm the diagnosis. Other conditions identified as causing chronic fatigue include myalgic encephalitis and neurasthenia, each with specific diagnostic criteria creating inconsistent diagnoses and treatment plans. In 2015, the Institute of Medicine (now called the National Academy of Medicine) recommended using the term systemic exertion intolerance disease (SEID). Diagnosis of SEID requires the presence of all of the following three symptoms:
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.
Classification of chronic fatigue patients. ALT, alanine aminotransferase; BUN, blood urea nitrogen; Ca2+, calcium; CBC, complete blood count; ESR, erythrocyte sedimentation rate; PO43–, phosphate; TSH, thyroid-stimulating hormone; UA, urinalysis.
In addition, the patient must have at least one of the following two manifestations: (1) cognitive impairment or (2) orthostatic intolerance (lightheadedness, dizziness, and headache that worsen with upright posture and improve with recumbency).
The evaluation of chronic fatigue syndrome or SEID includes a history and physical examination as well as complete blood count, erythrocyte sedimentation rate, chemistries (blood urea nitrogen [BUN], serum electrolytes, glucose, creatinine, calcium, liver biochemical tests, and thyroid function tests), urinalysis, tuberculin skin test, and screening questionnaires for psychiatric disorders. Other tests to be performed as clinically indicated are serum cortisol, antinuclear antibody, rheumatoid factor, immunoglobulin levels, Lyme serology in endemic areas (although rarely a long-term complication of this infection), and HIV antibody. More extensive testing is usually unhelpful, including antibody to Epstein-Barr virus. There may be an abnormally high rate of postural hypotension. MRI scans may show brain abnormalities on T2-weighted images—chiefly small, punctate, subcortical white matter hyperintensities, predominantly in the frontal lobes, although a 2010 study found no such abnormalities. Brain MRI is not routinely recommended.