Pyrexia of Unknow Origin

Question 1

Definition of Fever

Answer 1

• elevation of body temperature above normal (37C)
• variation of up to 0.8C daily (circadian rhythm): low in early morning, high in early evening
• Part of the systemic inflammatory response syndrome (SIRS)

Question 2

Definition of Pyrogens

Answer 2

substances which cause fever

• endogenous e.g. cytokines
• exogenous e.g. endotoxins from G-ve bacteria
• act at hypothalamic thermoregulatory centre to cause reduced heat loss and hence fever

Question 3

Classical PUO definition

Answer 3

Pyrexia with no diagnosis after

• 3 outpatient visits or
• 3 days in hospital or
• One week of outpatient investigation

Question 4

Nosocomial PUO

Answer 4

-develops in hospital, undiagnosed after 3 days

Question 5

Neutropenic PUO

Answer 5

-undiagnosed fever in patient with neutrophils <500/mm3

Question 6

HIV-associated PUO

Answer 6

-fever in a patient with HIV infection - present and undiagnosed for more than three days in an inpatient or four weeks in an outpatient

Question 7

PUO initial investigations

Answer 7

• Chest X-Ray
• Urinalysis and urine microscopy
• Full blood count and differential white cell count
• C-Reactive Protein and Erythrocyte Sedimentation Rate (acute phase reactants)
• Blood cultures taken at times of fevers
• Urea, creatinine, electrolytes
• Liver function tests

Question 8

Further investigations when history of tropical travel

Answer 8

• Blood for malarial parasites,Dengue, HIV, bone marrow for leishmaniasis
• Less likely if >21 days since return

Question 9

Further investigations when new murmur present

Answer 9

-echocardiography (trans-oesophageal echo may be needed)

Question 10

Further investigations when headaches present

Answer 10

-Temporal artery biopsy

Question 11

Further investigations when microscopic haematuria

Answer 11

• Auto-antibodies +/- renal biopsy (polyarteritis)

- Ultrasound (renal Ca)

Question 12

Further investigations when history of TB contact

Answer 12

• sputum smear
• bone marrow
• Mantoux

Question 13

Further investigations when history of drug misuse

Answer 13

-screen for blood-borne viruses

Question 14

Imaging techniques for PUO

Answer 14

• white cell scan
  - cannot always differentiate between infection and inflammation
  - anatomical changes may not develop in immunocompromised hosts (e.g. neutropenic patients and abscesses)
• CT
• CT PET
  - Fluorodeoxyglucose marker (FDG)-shows inflammation

Question 15

PUO treatment

Answer 15

Therapeutic trial

• Rarely used
  - suspected Mycobacterial infection (anti-tuberculous therapy)
  - diagnosis of mycobacterial tuberculosis unlikely if no response to chemotherapy within two weeks
  - suspected vasculitis or connective tissue disorder (steroids)
  - response of temporal arteritis to steroids is dramatic - usually within 48 hrs

Question 16

Fabricated fever

Answer 16

fever is real but self-induced

• self injection common
• microbiology may be strongest clue
• patient often continues despite being very sick
• psychiatric expertise should be sought

Question 17

PUO outcome

Answer 17

• Spontaneous resolution of PUO commoner in young compared with old patient
• Some patients with no diagnosis respond to NSAIDs or steroids (steroid responsive PUO)
• Regular re-appraisal required