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Fever of Unknown Origin

Definition. Fever higher than 38.3 Celsius on several occasionsDuration of fever for at least three weeksUncertain diagnosis after one week in the hospital. Definition. UnremarkableHistory/physicalCBC w/ diffBlood culturesChemistries with LFTsHepatitis serology if appropriateUA/Urine cultureChest film.

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Fever of Unknown Origin

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    1. Fever of Unknown Origin Morning Report 1/20/2009 Jason Haag

    2. Definition Fever higher than 38.3 Celsius on several occasions Duration of fever for at least three weeks Uncertain diagnosis after one week in the hospital

    3. Definition Unremarkable History/physical CBC w/ diff Blood cultures Chemistries with LFTs Hepatitis serology if appropriate UA/Urine culture Chest film

    4. Etiology Connective tissue diseases 22 percent Infections 16 percent Malignancies 7 percent Miscellaneous (drugs, clot, factitious) 4 percent No diagnosis 51 percent

    5. Infections Tuberculosis Especially in immunodeficiency Normal CXR 15-30% of cases Abscess Usually in abdomen or pelvis Predisposed by diabetes, recent surgery, steroid tx Osteomyelitis In cases with nonlocalized symptoms consider vertebral or mandibular osteo

    6. Infections Bacterial Endocarditis/abscess Culture negative cases Coxilla 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

    7. Connective Tissue Diseases Adult Still’s Disease Daily fevers, arthritis, and evanescent rash Giant Cell Arteritis Headache, vision loss, arthritis Jaw claudication Polyarteritis nodosa Takayasu’s arteritis Wegner’s granulomatosis Cryoglobulinemia

    8. Malignancy Leukemia/lymphomas Typically determined by bone marrow biopsy or CT/MRI imaging Myelodysplastic syndrome With dysplastic changes in blood line Multiple myeloma

    9. Malignancy Renal cell carcinomas Present with fever 20% of cases Hepatitic metastases Required for most other adenocarcinomas to cause fever Atrial myxomas Present with fever 1/3 of cases Also with arthralgias, emboli, hypergammaglobulinemia

    10. Drugs “Drug fever” Eosinophilia and rash in only 25% of cases Antibiotics Sulfa, PCN, Vancomycin, Antimalarials Antihistamines H1 and H2 blockers Antiepileptics Barbiturates and phenytoin

    11. Drugs NSAIDs Antihypertensives Hydralazine, methyldopa Antiarrythmics Quinidine, procainamide Stop for 72 hours and monitor for improvement/defervescene

    12. Factitious Fever Underlying psychiatric condition Typically in women and healthcare professionals Besides manipulation of thermometers fever can be induced by Taking meds which pt is allergic to Injecting foreign matter parenterally Milk, urine, culture media, feces

    13. Other Disordered heat homeostasis Follows hypothalamic dysfunction typically after massive CVA or anoxic brain injury Hyperthyroidism Dental abscess Less common infections Pulmonary Q fever, leptospirosis, psittacosis, tularemia Nonpulmonary Syphillis, disseminated gonococcemia, Whipple’s disease, RMSF Alcoholic hepatitis Fever, hepatomegaly, jaundice

    14. Other Pulmonary embolism/DVT Hematoma Hip, pelvis, retroperitoneum Pheochromocytoma Adrenal insufficiency Familial Mediterranean fever

    15. Diagnosis History and physical with focus on Travel Animal contacts Immunosuppression Drug history Localizing symptoms

    16. Laboratory Work-up Chem-10 CBC w/ differential ESR or CRP TB skin test HIV antibody Rheumatoid factor CK ANA SPEP Blood cultures x 3 separated by space and time off antibiotics

    17. Imaging Recommend if appropriate CXR CT Abdomen/Pelvis or Chest Replaced exploratory laparotomy Helpful in localized abscess, LAD Not recommended unless otherwise indicated Bone scan

    18. Biopsy Bone marrow biopsy Malignancy, TB Liver biopsy Sarcoidosis, TB Lymph node biopsy Lymphoma, infection Temporal artery biopsy Giant cell arteritis

    19. Therapy Empiric antibiotics are not recommended given Possible suppression without cure Abdominal abscess Unknown length of treatment Endocarditis Steroids also may be consider However must be relatively certain no infection present Must be certain not to interfere with inflammatory workup Steroids or antibiotics empirically rarely aid in diagnosis and risk harm to patient

    20. Outcome Many 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

    21. References Bleeker-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. Uptodate.com

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