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  • Temperature: The hypothalamic thermoregulatory center balances excess heat production from metabolic activity in muscle and liver with heat dissipation from the skin and lungs to maintain a normal body temperature of 36.8° ± 0.4°C (98.2° ± 0.7°F), with diurnal variation (lower in a.m., higher in p.m.).

  • Fever: an elevation of body temperature (>37.2°C/98.9°F in the morning and >37.7°C/99.9°F in the evening) in conjunction with an increase in the hypothalamic set point

  • Fever of unknown origin (FUO): generally refers to temperatures >38.3°C (>101°F) on several occasions over a defined period, with unrevealing investigations into its cause. FUO can be classified further into several categories:

    • Classic FUO: fever lasting >3 weeks where 3 outpt visits, 3 days in the hospital, or 1 week of “intelligent and invasive” ambulatory investigation does not elucidate a cause

    • Nosocomial FUO: at least 3 days of investigation and 2 days of culture incubation failing to elucidate a cause of fever in a hospitalized pt with no infection on admission

    • Neutropenic FUO: at least 3 days of investigation and 2 days of culture incubation failing to elucidate a cause of fever in a pt whose neutrophil count is <500/μL or is expected to fall to that level within 1–2 days

    • HIV-associated FUO: fever in an HIV-infected pt, lasting >4 weeks for outpatients or >3 days for hospitalized pts, where appropriate investigation (including 2 days' incubation of cultures) does not reveal a cause

  • Hyperpyrexia: temperatures >41.5°C (>106.7°F) that can occur with severe infections but more commonly occur with CNS hemorrhages

  • Hyperthermia: an uncontrolled increase in body temperature that exceeds the body's ability to lose heat without a change in the hypothalamic set point. Hyperthermia does not involve pyrogenic molecules.

  • Pyrogen: any fever-causing substance, including exogenous pyrogens (e.g., microbial toxins, lipopolysaccharide, superantigens) and pyrogenic cytokines (e.g., IL-1, IL-6, TNF)


  • Pathogenesis: The hypothalamic set point increases, causing peripheral vasoconstriction (i.e., heat conservation). The pt feels cold as a result of blood shunting to the internal organs. Mechanisms of heat production (e.g., shivering, increased hepatic thermogenesis) help to raise the body temperature to the new set point. Increases in peripheral prostaglandin E2 account for the nonspecific myalgias and arthralgias that often accompany fever. When the set point is lowered again by resolution or treatment of fever, processes of heat loss (e.g., peripheral vasodilation and sweating) commence.

  • Etiology Most fevers are associated with self-limited infections (usually viral) and have causes that are easily identified.


  • History: A meticulous history is essential, with particular attention to the chronology of events (e.g., in the case of rash: the site of onset and the direction and rate of spread; see below) and the relation of symptoms to medications, pet exposure, sick contacts, sexual contacts, travel, trauma, and the presence of prosthetic materials.

  • Physical examination: A thorough physical examination should be performed. A consistent ...

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