Reduced cardiac output and diminished pulmonary reserve are important causes of breathlessness and fatigue, which are brought out by mild exertion. Anemia, when severe, is another cause, probably predicated on a similar inadequacy of oxygen supply to tissues. Mild grades of anemia are usually asymptomatic, and tiredness is still far too often ascribed to it. An occult malignant tumor, for example, pancreatic, hepatic, or gastric carcinoma, may announce itself by inordinate fatigue. In patients with metastatic carcinoma, and especially lymphoma, leukemia, or multiple myeloma, fatigue is a usual and prominent symptom. Uremia is accompanied by fatigue; the associated anemia may play a role. Any type of nutritional deficiency may, when severe, cause lassitude; in its early stages, this may be the chief complaint. Weight loss and a history of alcoholism and dietary inadequacy provide the clues to the nature of the illness.
Pregnancy causes fatigue, which may be profound in the later months. To some extent the underlying causes, including the work of carrying excess weight and an anemia, are obvious; but if excessive weight gain and hypertension are associated, preeclampsia should be suspected.
A particularly difficult problem arises in the patient who complains of severe fatigue for many months or even years after a bout of infectious mononucleosis or some other viral illness. This has been appropriately called the postviral fatigue syndrome. The majority of patients are women between 20 and 40 years of age, but there are undoubtedly young men with the same illness. A few such patients had been found to have unusually high titers of antibody to Epstein-Barr virus (EBV), which suggested a causal relationship and gave rise to terms such as the chronic infectious mononucleosis or chronic EBV syndrome (Straus et al). However, subsequent studies made it clear that a majority of patients with complaints of chronic fatigue have neither a clear-cut history of infectious mononucleosis nor serologic evidence of this or another infection (Straus; Holmes et al). In some of these patients, the fatigue state has allegedly been associated with obscure immunologic abnormalities similar to those attributed (spuriously) to silicone breast implants or minor trauma. The currently fashionable designation for these abstruse states of persistent fatigue is the chronic fatigue syndrome (see Dawson and Sabin).
Some perspective is provided by the recognition that a malady of this nature, under many different names, has long pervaded western society, as described by Shorter in an informative history of the chronic fatigue syndrome. The attribution of fatigue to viral or Lyme infection and to ill-defined immune dysfunction are only the latest in a long line of putative explanations. At various times, even in our recent memory, colitis and other forms of bowel dysfunction, spinal irritation, hypoglycemia, brucellosis, and chronic candidiasis, multiple chemical sensitivity, retroviral infection, environmental allergies and recently, gluten sensitivity and minimally low testosterone among others, have been proposed without basis as causes of fatigue. At times, these spurious associations have only served to marginalize the disease and patients who suffer from it.