liver function tests, urinalyses, and blood and urine cultures.If the patient has neurologic symptoms, CSF studiesmay be considered. These tests should be performedbefore initiating treatment to prevent contamination ofresults.The evaluation of FUO should be targeted if any findingson history, physical examination, or laboratory andimaging evaluation direct suspicion toward an organsystem or diagnosis. A patient with known tick exposure,rash, and hyponatremia should receive serologic evaluationfor Rocky Mountain spotted fever, Lyme disease,ehrlichiosis, anaplasmosis, or babesiosis, depending onthe endemic region or travel history. (49) When decidingwhich laboratory tests to order, it is important to note thatuncommon presentations of common diseases are morelikely to cause FUO than uncommon or rare diseases.A well-appearing child with fever, rash, lymphadenopathy,and transaminitis is more likely to have Epstein-Barr virus orcytomegalovirus infection rather than HLH or systemic lupuserythematosus. In a nonacute patient, ruling out commoncauses of FUO before testing for uncommon causes orperforming invasive testing can minimize the likelihood ofdealing with false-positive, false-negative, or equivocal resultsfor rare diseases.We have established an initial diagnostic algorithm basedon the broad etiologic categories of FUO that may be performedif a practitioner is suspicious for a particular diseaseprocess (Fig 2). The recommended evaluation provides diagnostic“first steps” in the evaluation of these categories thatmay be performed before referral for specialized or invasivetesting. This tiered approach to FUO can decrease overallcosts and the use of invasive testing.MANAGEMENT AND EMPIRIC TREATMENTThe initial management of FUO remains an area of debate.Pediatric FUO is often overtreated because most cases arecaused by benign or nonacute disease. Physician concernfor serious illness or parental pressure can lead to empirictreatment before sufficient evaluation. Physicians may beinclined to start antipyretics, corticosteroids, or antibioticsfor an unknown disease process, which can affect futurelaboratory data, imaging, or treatment. Many cases of FUOresolve without a diagnosis and empiric treatment may maskthe diagnosis of life-threatening oncologic, infectious, andautoimmune diseases. Empiric treatment should be initiatedwith caution and in conjunction with judicious testing.The first step in the management of FUO is to discontinueall nonessential pharmacologic agents, including antipyreticmedications. Drug fever can manifest at any timeafter starting a medication, with an overall incidence of up to5%. (50) Drug fever is a common source of FUO and can becaused by any agent, including antibiotics, ibuprofen, andacetaminophen (Table 3). Once the drug is discontinued,fever usually abates within 24 hours or two half-lives of thedrug, typically resolving within 72 to 96 hours. (51) If drugfever is suspected and the patient is taking multiple medications,eliminating one drug at a time may be helpful inidentifying the offending agent. However, other causes offever should be explored, based on history and physical
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