Fever is generally defined as a temperature of ≥100.4°F (38.0°C) and is one of the most common reasons why children and their caregivers seek medical attention. Endogenous or exogenous pyrogens trigger release of prostaglandins, most notably prostaglandin E2, which in turn signals the hypothalamus to elevate the body's thermoregulatory set-point by regulating endocrinologic, autonomic, and behavioral responses. However, normal body temperature varies substantially by factors such as the time of day, degree of physical exertion, and ambient temperature.
While the underlying cause of fever is often discernible by history or physical exam, many children have unexplained fever despite initial evaluation. The distinction between patients who have "fever without source" and "fever of unknown origin" is important. The vast majority of children who present acutely with fever without source (or fever of unclear source) have underlying infections, typically requiring urgent evaluation and empiric treatment (especially in young children). In contrast, fever of unknown origin is not well defined in children. It has been historically used to describe a subacute presentation of a single illness of at least 3 weeks' duration during which a fever >38.3°C (100.9°F) is present for most days and the diagnosis is unclear after 1 week of intense investigation.[1] The most common causes are infections, inflammatory/vasculitic disorders, and malignancies.[2] These children require a more deliberate, comprehensive, and prolonged evaluation, and frequently do not need urgent empiric therapy. There is an increased emphasis on unusual presentations of common illness and on esoteric causes.
This topic addresses acute and subacute causes of fever in which no cause is readily discernible based on the history and physical exam.
