Pyrexia of unknown origin


Patients commonly develop transient febrile illnesses, often caused by viruses, which subside spontaneously and a definitive diagnosis is never made. Other fevers persist but a diagnosis is reached rapidly and treatment started. In a few patients fever persists and defies diagnosis.

The best definition of pyrexia or fever of unknown origin (PUO or FUO) was given by Petersdorf and Beeson in the United States in 1951 in a paper describing the results of a study which they carried out in 100 patients. They defined PUO as a temperature of 38.3°C or above persisting or recurring during a period of 3 weeks which included 7 days' investigation in hospital. Principal causes of PUO are illustrated in the first information box.

Petersdorf and Beeson found that only one-third of their patients eventually proved to have an infection (the most common being tuberculosis). Another third had malignant disease (the most common being a reticulosis), and onefifth diseases of connective tissue. The remainder had various less common disorders including factitious fever. This is a condition (factitious pyrexia) where an individual, who often has medical or nursing training, mimics pyrexia-for example, by placing the thermometer on a radiator; there is usually an underlying psychiatric disorder in these cases. The second information box illustrates the investigation of PUO. Repeated examination for the development of new signs is most important.

Malignant disease
  • Reticuloses (eg Hodgkin's disease)
  • Hypernephroma
Diseases of connective tissue
  • Polyarteritis nodosa
  • Still's disease
  • Lupus erythematosus
  • Tuberculosis (esp. lymph gland)
  • Endocarditis (e.g. Q fever)
  • Abscesses (liver, paraspinal, pelvic)
  • Malaria (esp. if suppressed by prophylaxis)
  • Visceral leishmaniasis
Other causes
  • Drug fever (esp. B-lactam antibiotics)
  • Factitious fever (self-induced)
  • Thrombophlebitis
  • Familial Mediterranean fever
  • Granulomatous diseases
Retake the history
  • Contact with infection (tuberculosis) or animals (brucellosis)
  • Sexual contacts (HIV)
  • Travel abroad (malaria)
  • Drug therapy (penicillins)
  • Occupation (leptospirosis)
  • Recent operations or dental treatment (abscess or endocarditis)
Repeat the examination
  • Heart murmurs (endocarditis)
  • Splenomegaly (visceral leishmaniasis)
  • Lymph glands (reticulosis, HIV)
  • Retinal changes (tuberculosis, CMV infection and disseminated candidiasis)
Review results of investigations (and repeat if indicated)
  • Re-examine radiograph (minimal lesion)
  • Biochemical results abnormal (liver involvement)
  • Haematology results abnormal (haematological malignancy)
  • Microbiology results abnormal (pyuria)
Consider further investigations
  • Serological investigations (brucellosis)
  • CT/MRI scanning (abdominal lymph glands, tumours)
  • Tissue biopsies (histology, culture and gene rearrangement studies-tuberculosis, malignancy)
Consider therapeutic trial (generally as a last resort)
  • Antimicrobial therapy (cryptic miliary tuberculosis)
  • Corticosteroid therapy (connective tissue disease)
  • Cytotoxic therapy (lymphoma)
Concepts of infection
Major manifestations of infection
Principles of management of infection
Diseases due to viruses
DNA viruses
Diseases due to chlamydiae
Diseases due to rickettsiae
Diseases due to bacteria
  • Streptococcal infections
  • Staphylococcal infections
  • Corynebacterial infections
  • Bacillus infections
  • Bordetella infections
  • Salmonella infections
  • Food poisoning
  • Dysentery
  • Other true bacterial infections
  • Mycobacterial infections
Diseases due to spirochaetes
  • Leptospira infections
  • Borrelia infections
  • Treponema infections
Diseases due to fungi (mycoses)
  • Cutaneous fungal infections
  • Subcutaneous fungal infections
  • Systemic fungal infections
Diseases due to protozoa
Diseases due to helminths
  • Trematode (fluke) infections
  • Cestode (tapeworm) infections
  • Nematode (roundworm) infections
  • Zoonotic helminth infections
Diseases due to arthropods
Sexually transmitted diseases
  • Sexually transmitted bacterial diseases
  • Sexually transmitted viral diseases
  • Miscellaneous conditions