Fatigue & Chronic Fatigue Syndrome

Essentials of Diagnosis

• Inquire about

  • Weight loss

  • Fever

  • Sleep-disordered breathing

  • Medications; substance use

General Considerations

Fatigue

• As an isolated symptom, accounts for 1–3% of visits to generalists

• Lifetime prevalence is about 25%

• Fatigue or lassitude and the closely related complaints of weakness, tiredness, and lethargy are often attributed to

  • Overexertion

  • Poor physical conditioning

  • Sleep disturbance

  • Obesity

  • Undernutrition

  • Emotional problems

• Fatigue of unknown cause or related to psychiatric illness exceeds that due to physical illness, injury, alcohol, or medications

Chronic fatigue syndrome

• Diagnosis lacks a gold standard

• Compared with persons who do not have chronic fatigue, persons with chronic fatigue syndrome

  • Report a greater frequency of childhood trauma and psychopathology

  • Demonstrate higher levels of emotional instability and self-reported stress

• Neuropsychological and neuroendocrine studies reveal abnormalities in most patients but no consistent pattern; for example, one study found neuroinflammation in the brain of patients with chronic fatigue syndrome that correlated with severity of neuropsychological symptoms

• Older patients demonstrate a greater disease impact than younger patients

Symptoms and Signs

Fatigue

• Clinically relevant fatigue is composed of three major components

  • Generalized weakness (difficulty in initiating activities)

  • Easy fatigability (difficulty in completing activities)

  • Mental fatigue (difficulty with concentration and memory)

• Important diseases that can cause fatigue include

  • Hyperthyroidism and hypothyroidism

  • Heart failure

  • Infections (endocarditis, hepatitis)

  • Chronic obstructive pulmonary disease

  • Sleep apnea

  • Anemia

  • Autoimmune disorders

  • Multiple sclerosis

  • Irritable bowel syndrome

  • Parkinson disease

  • Cerebrovascular accident

  • Cancer

• Other causes

  • Alcohol use disorder

  • Vitamin C deficiency (scurvy)

  • Side effects from medications (eg, sedatives and beta-blockers)

  • Psychological conditions (eg, insomnia, depression, anxiety, panic attacks, dysthmia, and somatic symptom disorder)

• Mononucleosis and sinusitis are common outpatient infectious causes

• Although frequently associated with Lyme disease, severe fatigue as a long-term sequela is rare

Chronic fatigue syndrome

• Also called systemic exertion intolerance disease (SEID)

• Diagnosis of SEID requires the presence of all three of the following:

  • 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 that is

    • Often profound

    • New or definite onset (not lifelong)

    • Not the result of ongoing excessive exertion

    • Not substantially alleviated by rest

  • Postexertional malaise

  • Unrefreshing sleep

• In addition, the patient must have at least one of the following:

  • Cognitive impairment

  • Orthostatic intolerance (lightheadedness, dizziness, and headache that worsen with upright posture and improve with recumbency)

Differential Diagnosis

• Depression

• Insufficient sleep

• Infection, eg, tuberculosis, hepatitis, endocarditis, HIV, Lyme disease

• Diabetes mellitus

• Heart failure

• Chronic obstructive pulmonary disease

• Chronic kidney disease

• Hypercalcemia

• Fibromyalgia

Diagnosis

Laboratory Tests

• Obtain

  • Complete blood count

  • Erythrocyte sedimentation rate

  • Blood urea nitrogen [BUN]

  • Serum electrolytes

  • Serum glucose

  • Serum creatinine

  • Serum calcium

  • Liver biochemical tests

  • Thyroid function tests

  • Urinalysis

  • Tuberculin skin test

  • Screening questionnaires for psychiatric disorders

• Other tests to be performed as clinically indicated

  • Serum cortisol

  • Antinuclear antibody

  • Rheumatoid factor

  • Immunoglobulin levels

  • Lyme serology in endemic areas

  • HIV antibody

Imaging

• A longitudinal MRI study of patients with chronic fatigue syndrome showed no abnormal patterns in rate and extent of

  • Brain atrophy

  • Ventricle volume

  • White matter lesions

  • Cerebral blood flow

  • Aqueductal cerebrospinal fluid flow

Medications

• Treat affective or anxiety disorder only if present

• Treat postural hypotension with fludrocortisone, 0.1 mg orally daily, and increased dietary sodium

• Psychostimulants, such as methylphenidate, have shown inconsistent results in treatment of cancer-related fatigue

• Rintatolimod, an immune modulator

  • May improve some measures of exercise performance

  • FDA approved in 2018 for parenteral use in a compassionate care program

Therapeutic Procedures

• Resistance training and aerobic exercise lessens fatigue in a number of chronic conditions, including

  • Heart failure

  • Chronic obstructive pulmonary disease

  • Arthritis

  • Cancer

• Treatment of chronic fatigue syndrome involves a comprehensive multidisciplinary intervention

  • Optimal medical management of coexisting disorders, eg, depression

  • Cognitive-behavioral therapy

  • Graded exercise program

  • Therapeutic care (a complementary medicine modality that uses acupressure) reduces fatigue in some patients with breast cancer receiving chemotherapy

• 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

Prognosis

• Although few patients are cured, the treatment effect can be substantial

• Full recovery is eventually possible in many cases

• Not associated with increased all-cause mortality, but one study showed a substantial increased risk of completed suicide

When to Refer

• Infections not responsive to standard treatment

• Hyperthyroidism or hypothyroidism that is difficult to control

• Severe psychological illness

• Malignancy

When to Admit

• Failure to thrive

• Fatigue severe enough to impair activities of daily living