In intractable cases, tuberculosis, brucellosis, Lyme disease, hepatitis, bacterial endocarditis, mycoplasmal pneumonia, HIV, EBV, cytomegalovirus (CMV), coxsackie B, and other viral infections, and malaria, hookworm, giardiasis, and other parasitic infections need to be considered in the differential diagnosis, and an inquiry made for their characteristic symptoms, signs, and when appropriate, laboratory findings; however, such infections are infrequently found. There should also be a search for anemia, renal failure, chronic inflammatory disease such as temporal arteritis and polymyalgia rheumatica (sedimentation rate); an endocrine survey (thyroid, calcium, and cortisol and testosterone levels) and, in appropriate cases, an evaluation for an occult tumor are also in order in obscure cases. It must be remembered that chronic intoxication with alcohol, barbiturates, or other sedative drugs, some of which are given to suppress nervousness or insomnia, may contribute to fatigability. The rapid and recent onset of fatigue should always suggest the presence of an infection, a disturbance in fluid balance, gastrointestinal bleeding, or rapidly developing circulatory failure of either peripheral or cardiac origin. The features that suggest sleep apnea have been mentioned above and are discussed further in Chap. 18.
Finally, it bears repeating fatigue must be distinguished from genuine muscular weakness. The demonstration of reduced power, reflex changes, fasciculations, and atrophy sets the case analysis along different lines, bringing up for particular consideration diseases of the peripheral nervous system or of the musculature. Rare, difficult-to-diagnose diseases that cause inexplicable muscle weakness and exercise intolerance are otherwise inevident hyperthyroidism, hyperparathyroidism, ossifying hemangiomas with hypophosphatemia, some of the periodic paralyses, hyperinsulinism, disorders of carbohydrate and lipid metabolism, and the mitochondrial myopathies, all of which are discussed in later chapters of the book on disease of muscle.
Treatment of Fatigue
It has been our impression that most patients with ongoing complaints of very low energy without a clearly preceding febrile infection from the outset and without one of the medical illnesses associated with fatigue, have elements of depression. They are probably best treated with gradually increasing exercise levels and perhaps with antidepressant medication, although this regimen has not always been successful. There are reports of success in treating these patients with mineralocorticoids (predicated on the above-mentioned orthostatic intolerance), estradiol patches, hypnosis, and a variety of other medical and nonmedical treatments. Cognitive and behavioral therapies have been summarized in the Effective Health Care report by Bagnall and colleagues from the National Health Service Centre for Reviews and Dissemination and in the extensive review by Chambers and colleagues, neither of which came to a firm conclusion about the effects of treatment, but acknowledged that cognitive behavioral therapy and graded exercise therapy may be of value. A few patients with chronic fatigue exhibit the psychologic disorder related to litigation (“compensation neurosis”). Noteworthy is the frequency with which a similar syndrome has become the basis of court action against employers or claims against the government, as in the “building-related illness” (formerly “sick-building syndrome”). As alluded to earlier, attribution of fatigue to Lyme disease and obscure infections or allergies should be made cautiously if there is no firm evidence.
NERVOUSNESS, ANXIETY, STRESS,