Pyrexia of unknown origin

Keywords: PUO


Appropriate Tests

PUO is defined as undiagnosed fever of more than 3 weeks duration.

Careful and repeated clinical history and examination; Full blood count, Blood film, White cell count differential; C-Reactive protein; Bilirubin, Alkaline phosphatase, Aspartate aminotransferase, Alanine aminotransferase, Gamma glutamyltransferase, Lactate dehydrogenase.

Note whether and where patient has been travelling (see Guideline on Pathology testing in the Emergency department: Appendix 2.).

Bacterial infection, especially

Blood culture (repeated); MCS urine; Faeces MCS and antigen.


See Endocarditis (infective)

Abscess, especially

  • Intra-abdominal


Ascending cholangitis

See Cholestasis

Urinary tract infection




Typhoid fever



Urine for mycobacteria testing; collect early morning specimens (three).



Fungal infection


Cryptococcal infection

Cryptococcal Ag, Cerebrospinal fluid examination, if appropriate.

Protozoal infection



Malaria, Parasites blood - repeated thin and thick blood films, if indicated.



Viral infection


Cytomegalovirus infection


HIV infection


Drug fever


Malignancy, especially

Fine needle aspiration biopsy, Lesion biopsy; as appropriate. Tumour markers are unreliable as a screening test for occult malignancy.

Renal cell carcinoma


Hepatocellular carcinoma


Disseminated carcinoma


Hodgkin lymphoma


Lymphoma (non-Hodgkin)


Atrial myxoma




Connective tissue diseases




Granulomatous hepatitis

See Hepatitis - Granulomatous



Crohn's disease


Familial Mediterranean fever

Clinical diagnosis.

C-Reactive protein (intermittent elevation); biopsy of appropriate tissue only if clinical features suggest amyloidosis.

Occult haematoma, especially

  • Retroperitoneal haematoma


Factitious fever