PUO – Pyrexia of Unknown Origin
Print Friendly, PDF & Email

almostadoctor app banner for android and iOS almostadoctor iPhone, iPad and android apps almostadoctor iOS app almostadoctor android app


This is also sometimes called fever of unknown origin (FUO)
It is strictly defined as:
  • Temperature greater than 38.3’
  • Duration of longer than 3 weeks
  • During which time there has been at least:
    • Three separate outpatient appointments, OR
    • 3 days in hospital, OR
    • 1 weeks worth of ‘intelligent and invasive investigation’
    • And the cause has still not been found
There are five causes of PUO’s:
  1. Infection (23%)
    1. Abscesses – lungs, liver, pelvic, subphrenic, perinephric
    2. Empyema – bacterial causes
    3. TB
    4. Parasites
    5. Fungus
    6. HIV
    7. Typhus
  2. Connective tissue disease (22%)
    1. Rheumatoid arthritis
    2. Polymyalgia
    3. Still’s disease
  3. Tumours (20%)
    1. Especially lymphoma’s!
  4. Drug reactions (3%)
  5. Miscellaneaous (14%) e.g. alcoholic hepatitis, granulatomous conditions, PE, stroke, sarcoid conditions, Crohn’s, UC)
In 25% of cases, a PUO remains undiagnosed.
Often, a PUO will occur when a person has been travelling. You should find out if this is the case, and where the patient has been. You will then need to consult an expert in that area, as there may be many rare foreign diseases that you do not know about that the patient could have contracted.


Take a detailed history! Obviously this is more important than ever in the presence of vague symptoms. Things to consider in the history are; sexual behaviours, travel, eating raw meat, work, hobbies, drugs abuse, immunosupression, bites, cuts, lumps, itching.
  • Stage One – FBC, ESR, U&E, CRP, FBC, blood cultures (take several from different veins at different times – also allow for longer culture time that may be needed to detect some rare causes, such as Brucella), HIV, sputum MC&S (specifically for TB), MSU, stools, CXR
  • Stage Two – keep taking the history for new symptoms, or newly remembered details (such as details of travel). CT, rheumatoid factor, ECG, marrow, consider withdrawing drugs (if patient is taking any). One at a time for 48 hours each.
  • Stage Three – follow any leads that previous tests have uncovered. Repeat serology and check for changes.
  • Stage four – start treatment for TB, endocarditis, vasculitis or try a trial of aspirin / steroids.
Causes of an intermittent fever
Types of intermittent fever
  • Daily spikes – TB, abscess,
  • Saddleback fever – a fever for 7 days, then normal for 3, Legionnaire’s disease, Colorado tick fever, Borrelia
  • Longer periods – Pel-Epstein


Read more about our sources

Related Articles

Dr Tom Leach

Dr Tom Leach MBChB DCH EMCert(ACEM) FRACGP currently works as a GP and an Emergency Department CMO in Australia. He is also a Clinical Associate Lecturer at the Australian National University, and is studying for a Masters of Sports Medicine at the University of Queensland. After graduating from his medical degree at the University of Manchester in 2011, Tom completed his Foundation Training at Bolton Royal Hospital, before moving to Australia in 2013. He started almostadoctor whilst a third year medical student in 2009. Read full bio

Leave a Reply