Table 1.

Potential second-line investigations for pyrexia of unknown origin

InfectionInflammatoryNeoplasticMiscellaneous
Echocardiogram, preferably TOE
Line cultures if the patient has an
intravascular device
Lumbar puncture
Lymph node biopsy
Malaria screen (RDT and three malaria
films on consecutive days)
PET-CT
Serology for viral hepatitis
Specialised serological or molecular tests
Spinal MRI
Sputum test for culture (consider an induced sputum test if the patient is not expectorating)
Stool samples for culture, PCR and OCP
Syphilis serology
Two to three peripheral blood cultures
Urine culture, plus three early morning urines for TB culture in sterile pyuria
Wound swabs
ANA
ANCA
Anti-CCP
Antiphospholipid antibodies (lupus anticoagulant and anticardiolipin)
Complement levels
Cryoglobulins
CT chest, abdomen and pelvis
Ferritin
Joint aspiration to detect crystals
LDH
MR or CT angiography
PET-CT
Rheumatoid factor
Serum ACE level
Serum electrophoresis
Serum urate
Temporal artery biopsy
Urine for Bence Jones protein
Colonoscopy
CT chest, abdomen and pelvis
Echocardiogram, preferably
TOE
LDH
PET-CT
Serum calcium
Serum electrophoresis
Tissue, lymph node and/or bone marrow biopsy for histology
Urine for Bence Jones protein
Pituitary screen
Synacthen test
Thyroid function tests
  • Note: This is not a comprehensive list of investigations to be carried out in every patient with PUO but instead a list of tests that should only be performed when there is a reasonable pretest probability of the condition investigated being present.

  • ACE = angiotensin converting enzyme; ANA = anti-nuclear antibodies; ANCA = antineutrophil cytoplasmic antibody; Anti-CCP: anti-cyclic citrullinated peptide; CT = computed tomography; LDH = lactate dehydrogenase; MR(I) = magnetic resonance (imaging); OCP = ova, cysts and parasites; PET-CT = positron emission tomography–computed tomography; PCR = polymerase chain reaction; RDT = rapid diagnostic test; TB = tuberculosis; TOE = transoesophageal echocardiogram