Fever of Unknown Origin

1. See Also
   1. Fever
2. Types
   1. Classic Fever of Unknown Origin
      1. Daily or Intermittent Fever >= 38.3 C (101 F)
      2. Duration for 3 consecutive weeks
      3. No source by clinical evaluation
         1. Hospital evaluation for 3 days (previously 7) or
         2. Intensive outpatient evaluation for 7 days or
         3. Three outpatient visits
   2. Nosocomial Fever of Unknown Origin
      1. Daily or Intermittent Fever >= 38.3 C (101 F)
      2. Hospitalized >1 day without fever on admission
      3. Fever evaluation of 3 days of more
   3. Immune-Deficient Fever of Unknown Origin
      1. Daily or Intermittent Fever >= 38.3 C (101 F)
      2. Neutrophil Count <500 per mm3
      3. Fever evaluation of 3 days of more
   4. HIV-Associated Fever of Unknown Origin
      1. Daily or Intermittent Fever >= 38.3 C (101 F)
      2. Outpatient fever >4 weeks or
      3. Inpatient fever >3 days
3. Causes
   1. See Fever of Unknown Origin Causes
   2. See Fever of Unknown Origin Causes by Age
   3. See Fever in the Returning Traveler
   4. See Drug-Induced Fever
4. History
   1. See Fever of Unknown Origin History
5. Physical Exam
   1. See Fever of Unknown Origin Examination
6. Labs: First Line
   1. Complete Blood Count (CBC) with manual differential
   2. Erythrocyte Sedimentation Rate (ESR)
   3. Chemistry panel (e.g. Chem8)
   4. Liver Function Tests
   5. Blood Culture
   6. Urinalysis with Urine Culture
   7. Purified Protein Derivative (PPD)
   8. Chest XRay
   9. Consider CT Abdomen and Pelvis with contrast
      1. Source found in 19% of patients
7. Subsequent Evaluation to consider
   1. Infectious cause suspected
      1. Second line tests
         1. AFB Sputum Cultures
         2. Rapid Plasmin Reagin (RPR)
         3. HIV Test
         4. ASO Titer
         5. Monospot
      2. Third line tests
         1. Transesophageal Echocardiogram
            1. Evaluate for endocarditis
         2. Lumbar Puncture
         3. Sinus CT
         4. Gallium 67 Scan
   2. Non-Hematologic Malignancy suspected
      1. Second line tests
         1. Mammogram
         2. Chest CT
         3. Upper endoscopy
         4. Lower endocscopy
         5. Gallium 67 Scan
      2. Third line tests
         1. Brain MRI
         2. Enlarged lymph node biopsy
         3. Skin lesion biopsy
         4. Liver biopsy
         5. Exploratory laparoscopy
   3. Hematologic Malignancy suspected
      1. Peripheral Smear
      2. Serum Protein Electrophoresis
      3. Consider Bone Marrow Biopsy
   4. Autoimmune condition suspected
      1. Rheumatoid Factor
      2. Antinuclear Antibody
      3. Consider temporal artery biopsy
      4. Consider lymph node biopsy
8. Differential Diagnosis: Occult Bacteremia
   1. Consider hospitalization if fever >2 weeks
   2. Risk factors
      1. Age over 50 years
      2. Diabetes Mellitus
      3. Complete Blood Count: Leukocytosis and Left Shift
      4. Erythrocyte Sedimentation Rate >30
      5. Toxic appearance
      6. Immunocompromised patients
      7. Valvular heart disease
      8. Intravenous Drug Abuse
   3. References
      1. Mellors (1987) Arch Intern Med 147:666
9. References
   1. Libman in Noble (2001) Primary Care Medicine, p. 194
   2. Mackowiak in Mandell (2000) Infectious Disease, p. 622
   3. Cunya (1996) Infect Dis Clin North Am 10:111-27
   4. Mourad (2003) Arch Intern Med 163:545-51
   5. Roth (2003) Am Fam Physician 68:2223-8