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A 29-year-old mother of 3 children presents to your office with “high fever.” She was in her usual state of health until 3 days ago when she noticed malaise. The following day, she felt “hot” and noted sharp chest pain when she took a deep breath. That night, her temperature was 102.5°F. She then developed shortness of breath and a dry cough and so presents to you today for evaluation.

  • What additional questions could you ask to try and distinguish between the different major categories of fever?
  • How might understanding the pattern of fever help you narrow your differential?
  • What alarm symptoms would indicate the need for an urgent evaluation?

Temperature regulation in the human body is controlled by hypothalamic nuclei that maintain a set point. Several mechanisms work together to achieve temperature homeostasis. For example, shivering and vasoconstriction generate heat, raising the temperature to the set point. Sweating and cutaneous vasodilation lower the temperature by increasing heat loss. Fever occurs when the set point itself is raised to a higher level and the body responds by raising the temperature. Macrophages and monocytes produce cytokines in response to various stimuli, which cause the hypothalamus to raise the set point.

Normal temperature is defined as 98.6°F, although the overall mean oral temperature for healthy persons aged 18 to 40 years is actually 98.2°F ± 0.4°F with a diurnal variation (daily oscillations from 0.9°F to 2.4°F). Temperature can be measured orally or rectally; rectal temperatures measure 1°F greater than oral values.1

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FeverA rise in body temperature in response to endogenous cytokines. The exact lower cutoff for fever varies from 99.4°F to 100.4°F. A recent study suggests that with modern thermometers, an early morning temperature of greater than 99.0°F or an evening temperature of 100.0°F should be considered abnormal.1
HyperthermiaAn elevation in body temperature due to loss of homeostatic mechanisms and inability to increase heat loss in response to environmental heat, as in heat stroke. Can reach levels > 105.8°F.
Fever of unknown origin (FUO)Fever that lasts 3 weeks or longer with temperatures exceeding 100.9°F with no clear diagnosis despite 1 week of clinical investigation.2

Fever is the third most common cause for visits to the emergency department and is listed in the top 20 reasons for visits to the ambulatory clinic.3,4 Given that many conditions raise the temperature set point, the differential diagnosis of fever is broad.

Most acute febrile illnesses are readily diagnosed based on history, examination, and laboratory testing, and many resolve on their own. Prevalence data are unfortunately limited, but a few studies have addressed the etiology of fever in specific populations, including hospitalized patients and those with FUO.2,5–7

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Patient SettingEtiologyPrevalence
Hospitalized patientsCommunity-acquired infection51%
Nosocomial ...

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