Most children undergo at least one medical evaluation for a febrile illness before their third birthday, and nearly one third of pediatric outpatient visits are for fever. Fever is an increase in body temperature, usually by 1°C to 4°C, that is regulated by the central nervous system and mediated by endocrine, autonomic, and behavioral mechanisms. Although fever is a common manifestation of infection, it is a symptom of many diseases, both infectious and noninfectious.^1-3

PATHOPHYSIOLOGY

There is a normal diurnal variation that results in body temperatures that are approximately 0.5°C to 1°C higher in the late afternoon or early evening than in the early morning.^2,3 Body temperature is controlled by the thermoregulatory center in the anterior hypothalamus, where thermosensitive neurons respond to changes in blood temperature and signals from cold and warm receptors in skin and muscle.² Thermoregulatory mechanisms include the following:

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  Heat production by metabolic activity in the liver and muscles

  
  
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  Heat dissipation by the skin and lungs via redirection of blood flow to or from cutaneous vascular beds, sweating, tachypnea, and rigors (shivering)

  
  
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  Behavioral responses, such as seeking a cooler or warmer environment

Endogenous pyrogens, or cytokines, are small proteins that regulate immune, inflammatory, and hematopoietic processes and are important mediators of fever.² The most studied of these are the primary endogenous pyrogens interleukin (IL)-l, IL-6, tumor necrosis factor-α, and interferon-α and -γ. These cytokines are released by leukocytes in response to infectious agents or toxic reactions. Peripheral cytokines, also called acute-phase reactants, are released in response to inflammation and use several mechanisms to signal the brain to produce fever. Once the cytokines are released into the bloodstream, they are carried to the hypothalamus, where they stimulate the vascular endothelial cell production of prostaglandin E₂ (PGE₂). Specific E-prostanoid receptors within the hypothalamus then trigger the febrile response after the PGE₂ signal by resetting the hypothalamic temperature set point.^1,2

Heat production exceeding heat loss is another mechanism that leads to an elevated temperature, which occurs, for example, in the setting of malignant hyperthermia and salicylate poisoning. Defective heat loss is the third mechanism that leads to an elevated temperature and can occur with exposure to severe heat or inability to dissipate heat, as seen in ectodermal dysplasia.² Elevated temperatures due to these mechanisms are often referred to as fever, though the more accurate description is hyperthermia (see Definitions, below).

The diagnosis of fever is based on the measurement of core body temperature. Normal diurnal variations in temperature for an individual and normal differences in baseline temperature between individuals may be as much as 1.1 °C (2°F), but the generally accepted gold standard normal temperature is 37°C (98.6°F). Most clinicians consider any temperature above 38°C (100.4°F) to be a fever, especially in the immediate neonatal period. Beyond the first 2 to 3 months of life, a temperature greater than 38.3°C (101°F) is often used as the cutoff for fever, although many consider a temperature of 39°C (102.2°F) or higher the threshold that triggers an evaluation for a serious bacterial illness. The most accurate method of obtaining core body temperature is by a rectal thermometer. Oral, axillary, tympanic, and infrared temperature readings taken at home are less accurate but should be considered when taking a history.⁴

A thorough history and physical examination usually provide the most important clues in determining the cause of fever. Fever may be a sign of a benign, self-limited condition or may be indicative of a life-threatening illness. Important historical clues include the duration of fever, pattern of fever, and associated symptoms. A single spike of fever is typically not associated with an infectious disease, though it may be due to manipulation of catheters, drugs, and blood infusions. Viral infections typically are associated with a slow decline in fever over a week, whereas uncomplicated bacterial infections are associated with prompt resolution of fever within 24 to 48 hours of effective antibiotic administration.² Table 24-1 describes common fever patterns and the associated diseases. Since the fever pattern is so important, a home diary of daily fevers is an extremely valuable tool when evaluating a patient with prolonged fever. The past medical history of a patient with fever should include any history of immunodeficiencies, previous major illnesses, and immunization status. Additional information that is important to elucidate are sick contacts (especially those with similar symptoms), attendance in daycare or school, medications currently used (including prescriptions, over-the-counter medications, and alternative remedies), travel and exposure history (pets, insects, undercooked foods).²