Pyrexia of unknown origin (PUO)

Question 1

What is the normal body temperature of humans?

How does this vary throughout the day?

Answer 1

37.0 celsius

Variation of 0.8 degrees throughout the day. Lowest in the morning, highest in the evening.

Question 2

generally, what causes body temperature to increase in a fever?

Answer 2

Part of the systemic inflammatory response syndrome (SIRS)

Question 3

What are pyrogens?

Answer 3

Substances which cause fever

Can be endogenous or exogenous

Question 4

Give an example of an endogenous pyrogen

Answer 4

Cytokines

Question 5

Give an example of an exogenous pyrogen?

Answer 5

endotoxins from Gram -ve bacteria

Question 6

How do pyrogens cause body temperature to increase?

Answer 6

act at hypothalamic thermoregulatory centre to cause reduced heat loss and hence fever

Question 7

What was the original definition (criteria for diagnosis) of pyrexia of unknown origin?

Answer 7

Temp >38.3

Recorded on multiple occasions

Present for at least 3 weeks

Defied diagnosis after one week of hospital evaluation

Question 8

What is the modern definition (criteria for diagnosis) for pyrexia of unknown origin

Answer 8

Pyrexia (>38.3) with no diagnosis after:

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

Question 9

What are the different types of Pyrexia of unknown origin (PUO)?

Answer 9

Classical PUO

Nosocomial PUO

Neutropenic PUO

HIV-associated PUO

Question 10

What is nosocomial PUO?

Answer 10

PUO that develops in hospital, undiagnosed after 3 days

Question 11

What is neutropenic puo?

Answer 11

undiagnosed fever in patient with neutrophils <500/mm³

Question 12

What is HIV-associated PUO?

Answer 12

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 13

What are the general causes of classical PUO?

Answer 13

Infection

Malignancies

Inflammatory conditions

Others

No cause found for about 25% of patients with this fever

Question 14

What are the main causes of HIV related PUO?

Answer 14

Mycobacterium infection

• Mycobacterium tuberculosis
• Mycobacterium avium

Tumours - such as lymphomas

PCP

Mixture of causes

Unkown - accounts for 16% cases

Question 15

After taking a history and doing an examination of a patient with PUO - you move onto investigation

What investigations are useful for PUO?

Answer 15

Chest x-ray - _{<em>(malignancies, TB)</em>}

Urinalysis & urine microscopy - _{<em>(vasculitis, renal malignancies)</em>}

FBC & differential white cell count - _{(HIV -> lymphopaenia)}

CRP & ESR - _{<em>(usu. elevated with fever)</em>}

Blood cultures - _{<em>(can identify infections such as Infective EndoC)</em>}

U&E’s, creatinine, LFTs

Question 16

What extra investigations would you consider for the following indications:

a) Tropical travel
b) New murmur
c) Headaches

Answer 16

a) Tropical travel
* Blood tests –> Malaria, Dengue, HIV, bone marrow for leishmaniasis
b) New murmur on examination

• ECHO to investigate for Endocarditis
• May need Trans-oesophageal ECHO

c) Headaches
* Temporal artery biopsy (TA) to investigate for Temporal arteritis (Giant cell arteritis)

Question 17

What extra investigations would you consider for the following indications?

a) Microscopic haematuria
b) TB contact
c) Drug misuse

Answer 17

a) Microscopic haematuria
* Auto-antibodies +/- renal biopsy, (polyarteritis) ultrasound (renal Ca)
b) TB contact
* Sputum smear, bone marrow, mantoux
c) Drug misuse
* Screen for blood borne viruses (HIV etc)

Question 18

If the following conditions are suspected, how would you manage the patient?

a) TB
b) Vasculitis
c) Connective tissue disorder

Answer 18

a) TB (suspected mycobacteria infection)

• anti-tuberculous therapy
• if no response within 2 weeks then MTB diagnosis unlikely

b) Vasculitis causes

• Steroid treatment
• Usually has dramatic response if diagnosis correct - if no response within a few days then diagnosis likely incorrect

Question 19

What is fabricated fever and how should it be handled?

Answer 19

Self induced fever in patients who usually have self-injected

Should bring in psychiatric help