DefinitionFever higher than 38.3 Celsius on several

occasions

Duration of fever for at least three weeks

Uncertain diagnosis after one week in the hospital

DefinitionUnremarkable

History/physicalCBC w/ diffBlood culturesChemistries with LFTs

Hepatitis serology if appropriateUA/Urine cultureChest film

EtiologyConnective tissue diseases

22 percentInfections

16 percentMalignancies

7 percentMiscellaneous (drugs, clot, factitious)

4 percentNo diagnosis

51 percent

InfectionsTuberculosis

Especially in immunodeficiency Normal CXR 15-30% of cases

AbscessUsually in abdomen or pelvisPredisposed by diabetes, recent surgery,

steroid txOsteomyelitis

In cases with nonlocalized symptoms consider vertebral or mandibular osteo

InfectionsBacterial Endocarditis/abscess

Culture negative casesCoxilla burnetti (Q fever),

Tropheryma whipplei, Brucella, Mycoplasma, chlamydia, histoplasma, legionella, bartonella

HACEK organisms Haemophilus, actinobacillus,

cardiobacterium, eikenella, and kingella take 1 to 3 weeks to grow

Connective Tissue DiseasesAdult Still’s Disease

Daily fevers, arthritis, and evanescent rashGiant Cell Arteritis

Headache, vision loss, arthritis Jaw claudication

Polyarteritis nodosaTakayasu’s arteritisWegner’s granulomatosisCryoglobulinemia

MalignancyLeukemia/lymphomas

Typically determined by bone marrow biopsy or CT/MRI imaging

Myelodysplastic syndromeWith dysplastic changes in blood line

Multiple myeloma

MalignancyRenal cell carcinomas

Present with fever 20% of casesHepatitic metastases

Required for most other adenocarcinomas to cause fever

Atrial myxomasPresent with fever 1/3 of casesAlso with arthralgias, emboli,

hypergammaglobulinemia

Drugs“Drug fever”

Eosinophilia and rash in only 25% of casesAntibiotics

Sulfa, PCN, Vancomycin, AntimalarialsAntihistamines

H1 and H2 blockersAntiepileptics

Barbiturates and phenytoin

DrugsNSAIDsAntihypertensives

Hydralazine, methyldopaAntiarrythmics

Quinidine, procainamide

Stop for 72 hours and monitor for improvement/defervescene

Factitious FeverUnderlying psychiatric conditionTypically in women and healthcare

professionalsBesides manipulation of thermometers fever

can be induced byTaking meds which pt is allergic toInjecting foreign matter parenterally

Milk, urine, culture media, feces

OtherDisordered heat homeostasis

Follows hypothalamic dysfunction typically after massive CVA or anoxic brain injury

HyperthyroidismDental abscessLess common infections

Pulmonary Q fever, leptospirosis, psittacosis, tularemia

Nonpulmonary Syphillis, disseminated gonococcemia, Whipple’s disease,

RMSFAlcoholic hepatitis

Fever, hepatomegaly, jaundice

OtherPulmonary embolism/DVTHematoma

Hip, pelvis, retroperitoneumPheochromocytomaAdrenal insufficiencyFamilial Mediterranean fever

DiagnosisHistory and physical with focus on

TravelAnimal contacts ImmunosuppressionDrug historyLocalizing symptoms

Laboratory Work-upChem-10CBC w/ differentialESR or CRPTB skin testHIV antibodyRheumatoid factorCKANASPEPBlood cultures x 3 separated by space and time

off antibiotics

ImagingRecommend if appropriate

CXRCT Abdomen/Pelvis or Chest

Replaced exploratory laparotomy Helpful in localized abscess, LAD

Not recommended unless otherwise indicatedBone scan

BiopsyBone marrow biopsy

Malignancy, TBLiver biopsy

Sarcoidosis, TBLymph node biopsy

Lymphoma, infection Temporal artery biopsy

Giant cell arteritis

TherapyEmpiric antibiotics are not recommended given

Possible suppression without cure Abdominal abscess

Unknown length of treatment Endocarditis

Steroids also may be considerHowever must be relatively certain no infection

presentMust be certain not to interfere with inflammatory

workupSteroids or antibiotics empirically rarely aid in

diagnosis and risk harm to patient

OutcomeMany FUOs end up with no definitive diagnosis

About 50% of people without diagnosis improve within hospitalization or soon thereafter

15% have persistent fever that lasts at least 1 year

Rarely does death develop from FUOs

ReferencesBleeker-Rovers, CP, et al. A prospective

multicenter study on fever of unknown origin: the yield of a structured diagnostic protocol. Medicine (Baltimore) 2007; 86:26.

Petersdorf, RG. Fever of unknown origin: An old friend revisited. Arch Intern Med 1992; 152:21.

Hirshmann, JV. Fever of unknown origin in adults. Clin Infect Dis 1997; 24: 291.

Vandershueren, S, et al. From prolonged febrile illness to Fever of unknown origin: the challenge continues. Arch Intern Med 2003; 163: 1033.

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