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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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