The approach to pyrexia of unknown origin

Maintenance of body temperature within a relatively narrow range is an important homeostatic mechanism to ensure optimal cell and organ function. Not surprisingly, the body has developed a system of control mechanisms to achieve this physiological goal. An increase in body temperature, either as fever or hyperthermia, can be an important indicator of systemic illness or disorders that result in loss of homeostatic mechanisms. For most patients, a careful history and physical examination leads to an obvious diagnosis but occasionally temperature increases persist in the absence of an obvious cause. Diagnostic investigations in these patients may be challenging and frustrating for clinicians.
A distinction should be made between hyperthermia, in which the body’s temperature set-point is unchanged, and true fever, in which the set-point temperature is increased. Hyperthermia may occur when heat production exceeds the capacity of the body to dissipate heat (e.g. with sustained high-intensity exercise) or when the body’s heat dissipation mechanisms are not performing optimally (e.g. anhidrosis). Hyperthermia is also associated with heat stroke, malignant hyperthermia, central nervous system disorders and certain drug or toxin reactions such as erythromycin administration to foals. These types of abnormalities do not respond well to treatment with antipyretic drugs. […]