Lecture 4: Pyrexia of Unknown Origin (PUO)

Question 1

describe fever

Answer 1

• elevation of body temperature above normal 37C.
• part of the systemic inflammatory response syndrome (SIRS)

Question 2

describe pyrogens

Answer 2

• substances which cause fever
• endogenous e.g. cytokines
• exogenous e.g. endotoxins from gram negative bacteria.
• act as hypothalamic thermoregulatory centre to cause reduced heat loss and hence fever.

Question 3

PUO definition

Answer 3

Modern definition, fever with no diagnosis after:
- 3 outpatient visits or
- 3 days in hospital or
- one week of outpatient investigation

Question 4

describe nosocomial PUO

Answer 4

• fever which develops in hospital and is undiagnosed after 3 days of investigation including two days of cultures.

Question 5

describe neutropenic PUO

Answer 5

• fever in a patient with a neutrophil count of < 500 cells/mm3 which is undiagnosed after three days of investigation

Question 6

describe HIV-associated PUO

Answer 6

• fever in a patient with HIV infection which has been present and undiagnosed for more than three days in an inpatient or four weeks in an outpatient.

Question 7

list the causes of HIV-related PUO in 75% of patients

Answer 7

• mycobacterium tuberculosis
• mycobacterium avium
• uknown
• more than one cause

Question 8

PUO initial investigations following a full history and examination

Answer 8

• CXR
• urinalysis and microscopy
• FBC and differential WCC
• CRP and ERSR
• blood cultures taken at times of fevers
• urea, creatinine, electrolytes, LFTs

Question 9

PUO further investigations based on specific indications

tropical travel, new murmur, headaches, microhaematuria, TB, drug abuse

Answer 9

Tropical travel:
- blood for malarial parasites, dengue, HIV, bone marrow for leishmaniasis.
- less likely if > 21 says since return

New murmur:
- ECHO

Headaches:
- temporal artery biopsy

Microhaematuria:
- autoantibodies +/- renal biopsy, (polyarteritis) ultrasound (renal Ca)

TB contact:
- sputum smear
- bone marow
- Mantoux

Drug misuse:
- screen for blood-borne viruses

Question 10

PUO invasive investigations

Answer 10

• obtain tissue for culture and histology
• bone marrow and liver often examined as part of blind investigation: malignancy, TB, lymphoma
• diagnostic laparotomy: rarely necessary.

Question 11

what are the most frequent connective tissue disorders recognised to be causing a PUO?

Answer 11

• temporal arteritis
• systemic vasculitides

Question 12

list the tumours are most commonly associated with PUO?

Answer 12

• lymphoma
• Hodgkin’s disease
• renal cell carcinoma
• hepatocellular carcinoma
• leukaemia

Question 13

management of patient with PUO

Answer 13

• If the patient is clearly unwell and without a diagnosis then a trail of antituberculous
  therapy or steroids should be considered.
• For patients with suspected tuberculosis the
  diagnosis becomes likely if there is a response within one week of starting anti-tuberculous
  therapy.
• Steroids will often improve a fever as well as patient well being but the response
  to steroids in patients with giant cell arteritis or Still’s disease is dramatic and should be
  seen after 24-72 hours.