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Fever of Unknown Origin

Fever of Unknown Origin. 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. Definition. Unremarkable History/physical CBC w/ diff Blood cultures Chemistries with LFTs

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Fever of Unknown Origin

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  1. Fever of Unknown Origin

  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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