Typical age of onset of chronic fatigue syndrome is 29-35 years, and the usual trigger is a stressor; these can include infection, such as flulike illness or infectious mononucleosis; surgery; pregnancy; or psychological stress. However, the condition is largely multifactorial in origin. Other uncommon symptoms include nausea, jaw pain, abdominal pain, alcohol intolerance, chest pain, shortness of breath, morning stiffness, irritability, anxiety, and weight loss.
The etiology of chronic fatigue syndrome is unknown, but many explanations have been speculated, including infectious, autonomic, immunologic, allergic, and psychiatric origins. Epstein-Barr virus was thought to be causal because symptoms overlap with those of infectious mononucleosis; however, further studies have proved otherwise. Other viruses that have been implicated include cytomegalovirus, measles, human herpesvirus 6, human T-cell lymphotropic virus, and coxsackievirus. No conclusive data supports a causal relationship.
Inconsistent studies show increased lymphocyte markers, decreased natural killer cell activity, immune deregulation, and increased interferon activity, and a viral infection has been hypothesized as a trigger to a cascade of immune abnormalities that ultimately cause chronic fatigue. Because the syndrome is characterized by cognitive defects, some studies indicate that it might be mediated by the central nervous system. Cerebral white-matter lesions in frontal lobes have been identified using MRI and regional cerebral blood flow abnormalities as compared with controls.
Because of a lack of objectivity in the diagnosis, many clinicians disregard chronic fatigue symptoms as a manifestation of clinical depression. Although depression does overlap, some symptoms not typical of depression are also present: for example, lymphadenopathy, sore throat, and postexertional malaise. In addition, anhedonia and guilt are not seen in patients with chronic fatigue syndrome and are commonly seen in depression.
Patients with chronic fatigue syndrome have a higher incidence of atopic disease, elevated levels of eosinophilic cationic proteins, and positive skin tests to allergens, which suggests a possible role of allergens in the pathogenesis.
Diagnostic testing includes a CBC; complete metabolic profile; blood glucose, ESR, and CRP measurement; and ANA titer to rule out common conditions, such as anemia, diabetes, kidney disease, and autoimmune disease. Because the main purpose of diagnostic testing is to rule out other causes of chronic fatigue syndrome, the work-up includes tests for endocrine disorders (hypothyroidism, adrenal insufficiency), rheumatologic disorders (systemic lupus erythematosus, rheumatoid arthritis, fibromyalgia), infectious causes (hepatitis, AIDS, tuberculosis) and cancer (lymphoma, leukemia).
Polysomnography for sleep disorders and tests for assessment of cognition should be considered. Decreased cortisol levels after exercise, erratic breathing pattern, measurement of maximal oxygen consumption in cardiopulmonary exercise testing, low natural killer cell counts, immunoglobulin deficiency, and elevated interferon alpha levels have been implicated in patients with chronic fatigue syndrome.
Possible complications of chronic fatigue syndrome include lifestyle restriction, limitation of physical activity, social isolation, poor job performance, anxiety, and depression.
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