Fever of Unknown Origin



Fever of unknown origin (FUO) implies

  • A febrile illness (38.3°C on multiple occasions)
  • Present for >14 days
  • No apparent source despite careful history taking, physical exam, and preliminary lab studies


  • Etiology has changed as the use of more sensitive tests (e.g., MRI, polymerase chain reaction [PCR] tests) permits earlier detection of many conditions that caused FUO in the past.
  • Fever resolves in 40–60% of children without identification of a specific cause.
  • FUO in the pediatric population is more often an unusual presentation of a common disease than a common presentation of an unusual disease.
  • Common infectious causes
    • Respiratory infections (otitis media, mastoiditis, sinusitis, pneumonia, pharyngitis, peritonsillar/retropharyngeal abscess)
    • Systemic viral syndrome
    • Infectious mononucleosis (Epstein-Barr virus [EBV], cytomegalovirus [CMV])
    • Urinary tract infection (UTI)
    • Bone or joint infection
    • Enteric infection (Salmonella, Yersinia enterocolitica, Yersinia pseudotuberculosis, Campylobacter jejuni)
    • Cat-scratch disease
  • Less common infectious causes
    • Tuberculosis (TB)
    • Lyme disease
    • Rickettsial disease (Rocky Mountain spotted fever, ehrlichiosis, anaplasmosis)
    • Malaria
    • CNS infection (bacterial or viral meningoencephalitis, intracranial abscess)
    • Dental or periodontal abscess
    • Subacute bacterial endocarditis (SBE)
    • HIV infection
    • Human herpes viruses
    • Acute rheumatic fever
  • Other infectious causes
    • Q fever
    • Brucellosis
    • Toxoplasmosis
    • Syphilis
    • Parvovirus B19
    • Endemic fungi (histoplasmosis, blastomycosis, coccidioidomycosis)
    • Psittacosis
    • Typhoid (Salmonella spp.)
    • Chronic meningococcemia
  • Possible noninfectious causes
    • Collagen vascular disease (systemic juvenile idiopathic arthritis [JIA], systemic lupus erythematosus, dermatomyositis, sarcoidosis, vasculitis syndrome)
    • Malignancy
    • Kawasaki syndrome
    • Inflammatory bowel disease (IBD)
    • Drug fever
    • Hyperthyroidism
    • Factitious fever or Munchausen syndrome by proxy
    • Centrally mediated fever
    • Periodic fever syndromes
    • Kikuchi-Fujimoto disease (histiocytic necrotizing lymphadenitis)

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