PFAPA (periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis), familial Mediterranean fever, or cyclic neutropenia is in the differential for the diagnosis of the child with recurrent, intermittent fevers Additional noninfectious causes of prolonged fever include neoplasms, rheumatologic diseases, inflammatory bowel disease, drug fever, and factitious fever SYMPTOMATIC TREATMENT, DISPOSITION, AND PARENTAL GUIDANCE In general, antipyretic therapy should parallel the pathophysiologic basis of the fever When the fever is caused by altered hypothalamic set point, as in infection, antigen–antibody reactions, and malignancy, attempts to reset the “thermostat” with antipyretic medications are most likely to enhance patient comfort Antipyretics work via the inhibition of hypothalamic prostaglandin synthesis If fever is caused by imbalance of heat production and heat loss mechanisms, such as in heat stroke, urgent cooling by physical removal of heat is necessary and antipyretics will not help (see Chapter 90 Environmental Emergencies, Radiological Emergencies, Bites and Stings ) However, children at risk for recurrent febrile seizures not, unfortunately, tend to be protected by rapid use of “prophylactic” antipyretics at first sign of fever Acetaminophen and ibuprofen are currently the most commonly used pediatric antipyretic medications in the United States (aspirin is no longer recommended for routine antipyretic use in children because of its potential to cause severe gastrointestinal bleeding and its implication as an etiologic risk factor for Reye syndrome) The current dosage recommendation for acetaminophen is 10 to 15 mg/kg given every to hours, with a maximum of doses/day, resulting in 40 to 60 mg/kg/day Several reports and reviews have stressed that, although very rare, repetitive dosing of acetaminophen at the upper limit of, or just slightly above, recommended dosages may result in severe or fatal fulminant hepatic failure This is particularly the case for children who were fasting (because of vomiting or diarrhea with febrile illness), younger than age years, treated for several days, or treated with adult-intended preparations Ibuprofen is typically dosed at to 10 mg/kg/dose, given every to hours, with a maximum of doses/day (i.e., 30 to 40 mg/kg/day) Several studies have found that ibuprofen is more effective than acetaminophen in reducing fever at commonly used doses of each agent, especially in single-dose comparisons at and hours after administration However, the difference narrows and is of little clinical significance for most patients when antipyretic therapy is used repetitively over 12 to 24 hours or more, as typically prescribed for most