Etiology of UFO (Fever of Unknown Origin)

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Fever of unknown origin (FUO) was defined in 1961 by Petersdorf and Beeson as the following: (1) a temperature greater than 38.3°C (101°F) on several occasions, (2) more than 3 weeks’ duration of illness, and (3) failure to reach a diagnosis despite 1 week of inpatient investigation. Diagnostic advances continuously modify the spectrum of FUO-causing diseases; for example, serologic tests have reduced the importance of the human immunodeficiency virus (HIV) and numerous rheumatic diseases (eg, systemic lupus erythematosus [SLE], juvenile rheumatoid arthritis [JRA], rheumatoid arthritis [RA]) as causes of FUO. (See Etiology and Serology.)

FUOs are caused by infections (30-40%), neoplasms (20-30%), collagen vascular diseases (10-20%), and numerous miscellaneous diseases (15-20%). The literature also reveals that, as previously mentioned, between 5 and 15% of FUO cases defy diagnosis, despite exhaustive studies.

FUOs that persist for more than 1 year are less likely to be caused by an infection or neoplasm and are much more likely to be the result of a granulomatous disease (the most common cause in these cases).

The following conditions are sources of FUO:

  • Abscesses
  • Tuberculosis
  • Urinary tract infections
  • Endocarditis
  • Hepatobiliary infections
  • Osteomyelitis
  • Rickettsia
  • Chlamydia
  • Systemic bacterial illnesses
  • Spirochetal diseases
  • HIV
  • Acquired immunodeficiency syndrome (AIDS)
  • Herpes viruses
  • Fungal infections
  • Parasitic infections
  • Lymphomas
  • Leukemias
  • Solid tumors
  • Malignant histiocytosis
  • Collagen vascular and autoimmune diseases
  • Sarcoidosis
  • Regional enteritis
  • Granulomatous hepatitis
  • Drug fever
  • Inherited diseases
  • Endocrine disorders
  • Peripheral pulmonary emboli and occult thrombophlebitis
  • Kikuchi disease
  • Factitious fever
  • Giant cell arteritis (GCA)
  • Polymyalgia rheumatica (PMR)
  • Polyarteritis nodosa (PAN)

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