Sections View Full Chapter Figures Tables Videos Annotate Full Chapter Figures Tables Videos Supplementary Content + Download Section PDF Listen ++ For further information, see CMDT Part 2-10: Fatigue & Chronic Fatigue Syndrome + Key Features Download Section PDF Listen +++ +++ 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 + Clinical Findings Download Section PDF Listen +++ +++ 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 + Treatment Download Section PDF Listen +++ +++ 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 + Outcome Download Section PDF Listen +++ +++ 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 + References Download Section PDF Listen +++ + +Bjørklund G et al. Chronic fatigue syndrome (CFS): Suggestions for a nutritional treatment in the therapeutic approach. Biomed Pharmacother. 2019 Jan;109:1000–7. [PubMed: 30551349] + +Clark LV et al. Guided graded exercise self-help plus specialist medical care versus specialist medical care alone for chronic fatigue syndrome (GETSET): a pragmatic randomised controlled trial. Lancet. 2017 Jul 22;390(10092):363–73. [PubMed: 28648402] + +Donnachie E et al. Incidence of irritable bowel syndrome and chronic fatigue following GI infection: a population-level study using routinely collected claims data. Gut. 2018 Jun;67(6):1078–86. [PubMed: 28601847] + +Jones K et al. Role of dietary modification in alleviating chronic fatigue syndrome symptoms: a systematic review. Aust N Z J Public Health. 2017 Aug;41(4):338–44. [PubMed: 28616881] + +Kinkead B et al. Massage therapy decreases cancer-related fatigue: results from a randomized early phase trial. Cancer. 2018 Feb 1;124(3):546–54. [PubMed: 29044466] + +Komaroff AL. Advances in understanding the pathophysiology of chronic fatigue syndrome. JAMA. 2019 Jul 5;322(6):499–500. [PubMed: 31276153] + +Twisk FNM. Myalgic encephalomyelitis, chronic fatigue syndrome, and chronic fatigue: three distinct entities requiring complete different approaches. Curr Rheumatol Rep. 2019 May 9;21(6):27. [PubMed: 31073713] + +Vink M et al. Cognitive behavioural therapy for myalgic encephalomyelitis/chronic fatigue syndrome is not effective. Re-analysis of a Cochrane review. Health Psychol Open. 2019 May 2;6(1):2055102919840614. [PubMed: 31080632] + +Wilshire CE et al. Rethinking the treatment of chronic fatigue syndrome-a reanalysis and evaluation of findings from a recent major trial of graded exercise and CBT. BMC Psychol. 2018 Mar 22;6(1):6. [PubMed: 29562932]