Pyrexia of Unknown Origin

Question 1

What is the definition of a fever?

Answer 1

Elevation of body temperature above normal

Question 2

How does body temperature vary over the course of the day?

Answer 2

Low in the early morning and high in the early evening

Question 3

What are pyrogens?

Answer 3

Substances which cause fever

Question 4

Give examples of pyrogens and how they work?

Answer 4

• Endogenous e.g. cytokines
• Exogenous e.g. endotoxins from G -ve bacteria
• Act of hypothalamic thermoregulatory centre to cause reduced heat loss and hence fever

Question 5

What is the Petersdorf and Beeson definition of pyrexia of unknown origin?

Answer 5

• Temp > 38.3C
• Recorded on multiple occassions
• Present for at least three weeks
• Defied diagnosis after one week of hospital evaluation

Question 6

What is the modern definition of pyrexia of unknown origin?

Answer 6

No diagnosis after

• 3 outpatient visits
• 3 days in hospital
• 1 week of outpatient investigation

Question 7

What is the definition of nosocomial PUO?

Answer 7

PUO developed in hospital which is undiagnosed after 3 days

Question 8

What is the definition of neutropenic PUO?

Answer 8

Undiagnosed fever on a patient with neutrophils <500m3

Question 9

What is the definition of HIV associated PUO?

Answer 9

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

Question 10

What are the most common causes of classical PUO?

Answer 10

Infection, malignancy, inflammatory and no diagnosis

Question 11

What are the commonest causes of HIV - related PUO?

Answer 11

Mycobacterium tuberculosis, mycobacterium avium, more than one causative disease and unknown.

Question 12

How can PUO be assessed?

Answer 12

History: travel, occupation, hobbies, FH, PMH, drug history and pattern of fever
Exam: include skin, eyes, oral cavity, nails and lymph nodes

Question 13

What initial investigations can be done for PUO?

Answer 13

CXR, urinalysis + microscopy, FBC, WCC, CRP + ESR, blood cultures, U&Es, creatinine and LFTs

Question 14

List the indications for further investigations for PUO

Answer 14

• Tropical travel: blood for malaria, dengue and HIV and bone marrow for leishmaniasis
• New Murmur: ECHO
• Headaches: temporal artery biopsy
• Micro Haematuria: auto antibodies +/- renal biopsy and USS
• TB Contact: sputum smear, bone marrow and mantoux
• Drug Misuse: BBV screen

Question 15

Which imaging techniques can be used for PUO?

Answer 15

-White cell scan
-CT
CT PET
-USS

Question 16

Which invasive investigations can be used to try and diagnose PUO?

Answer 16

Biopsy: bone marrow and liver are common as part of a blind investigation

Question 17

What are the management options for PUO?

Answer 17

Therapeutic trial

• Rarely used
• Suspected TB infection: anti-TB therapy
• Suspected vasculitis or connective tissue disorder: steroids

Question 18

What is a fabricated fever?

Answer 18

• Fever is real but self induced
• Self injection is common
• Microbiology may be biggest clue
• Patient may continue despite being very sick
• Needs psychiatric expertise

Question 19

What are the potential outcomes of PUO?

Answer 19

• Spontaneous resolution (commoner in young patients)
• Some patients respond to NSAIDs or steroids
• Regular re-appraisal required