Normal body temperature is maintained by a complex regulatory system in the anterior hypothalamus. Development of fever begins with release of endogenous pyrogens into the circulation as the result of infection, inflammatory processes, or malignancy. Microbes and microbial toxins act as exogenous pyrogens by stimulating release of endogenous pyrogens, including cytokines such as interleukin-1, interleukin-6, tumor necrosis factor, and interferons. These cytokines reach the anterior hypothalamus, liberating arachidonic acid, which is metabolized to prostaglandin E2. Elevation of the hypothalamic thermostat occurs via a complex interaction of complement and prostaglandin-E2 production. Antipyretics (acetaminophen, ibuprofen, aspirin) inhibit hypothalamic cyclooxygenase, decreasing production of prostaglandin E2. Aspirin is associated with Reye syndrome in children and is not recommended as an antipyretic. The response to antipyretics does not distinguish bacterial from viral infections.
The pattern of fever in children may vary, depending on ageand the nature of the illness. Neonates may not have a febrileresponse and may be hypothermic, despite significant infection,whereas older infants and children younger than 5 years of agemay have an exaggerated febrile response with temperatures ofup to 105° F (40.6° C) in response to either a serious bacterialinfection or an otherwise benign viral infection. Fever to this degree is unusual in older children and adolescents and suggests a serious process. The fever pattern does not reliably distinguish fever caused by infectious microorganisms from that resulting from malignancy, autoimmune diseases, or drugs.
Children with fever without a focus present a diagnostic challenge that includes identifying bacteremia and sepsis. Bacteremia, the presence of bacteria in the bloodstream, may be primary or secondary to a focal infection. Sepsis is the systemic response to infection that is manifested by hyperthermia or hypothermia, tachycardia, tachypnea, and shock (see Chapter 40). Children with septicemia and signs of central nervous system dysfunction (irritability, lethargy), cardiovascular impairment (cyanosis, poor perfusion), and disseminated intravascular coagulation (petechiae, ecchymosis) are readily recognized as toxic appearing or septic. Most febrile illnesses in children may be categorized as follows:
Fever of short duration accompanied by localizing signs and symptoms, in which a diagnosis can often be established by clinical history and physical examination
Fever without localizing signs (fever without a focus), frequently occurring in children younger than 3 years of age, in which a history and physical examination fail to establish a cause
Fever of unknown origin (FUO), defined as fever for >14 days without an identified etiology despite history, physical examination, and routine laboratory tests or after 1 week of hospitalization and evaluation
Fever or temperature instability in infants younger than3 months of age is associated with a higher risk of serious bacterial infections than in older infants. These youngerinfants usually exhibit only fever and poor feeding, without localizing signs of infection. Most febrile illnesses inthis age group are caused by common viral pathogens, butserious bacterial infections include bacteremia (caused by group B streptococcus [GBS], Escherichia coli, and Listeria monocytogenes in neonates; and Streptococcus pneumoniae, Haemophilus influenzae, nontyphoidal Salmonella, and Neisseria meningitidis in 1to 3-month-old infants), urinary tract infection (UTI) (E. coli), pneumonia (S. pneumoniae, GBS, or Staphylococcus aureus), meningitis (S. pneumoniae,