Pyrexia of Unknown Origin

Question 1

Define fever

Answer 1

Elevation of body temperature above normal (37C)

Part of SIRS

Question 2

What is normal body temperature?

Answer 2

37C

But fluctuation of 0.8C during the normal circadian rhythm (lowest in the morning, highest at night)

Question 3

What are pyrogens?

Answer 3

Substances which cause fever

Question 4

How do pyrogens work?

Answer 4

Act on the hypothalamic thermoregulatory centre to cause reduced heat loss in the body –> fever

Question 5

Give examples of pyrogens

Answer 5

Exogenous pyrogens include endotoxins from gram -ve bacteria (LPS)

Endogenous pyrogens include cytokines

Question 6

Define pyrexia of unknown origin

Answer 6

3 outpatient visits
3 days in hospital
OR
1 week of outpatient investigation for a fever without diagnosis

Question 7

What are the 4 types of PUO?

Answer 7

Classic
Nosocomial
Neutropenic
HIV-associated

Question 8

What is classic PUO?

Answer 8

Follows original definition of PUO

Question 9

What are the five categories of classic PUO?

Answer 9

Infection (e.g. TB, endocarditis, abscesses)
Malignancy (e.g. leukaemia)
Connective tissue dx (e.g. temporal arteritis/RA)
Miscellaneous (e.g. alcoholic hepatitis)
Undiagnosed (most common)

Question 10

What is nosocomial PUO?

Answer 10

Fever that develops in hospital and is undiagnosed after 3 days

Question 11

What is neutropenic PUO?

Answer 11

Undiagnosed fever in a patient with neutrophils <500/mm3

Question 12

What is HIV-associated PUO?

Answer 12

Undiagnosed fever occurring in an HIV patient which is present and undiagnosed for more than 3 days as an impatient, or four week as an outpatient

Question 13

What is the most common cause for HIV-associated PUO?

Answer 13

Mycobacterium tuberculosis (then mycobacterium avium)

Common for multiple causative agents/unknown

Question 14

How do you assess a patient with PUO?

Answer 14

History, examination, investigations and imaging if necessary

Question 15

What are the key things to ask in your history of a patient with PUO?

Answer 15

Hx of travel, occupation, hobbies, drug history, PMH, FG, pattern of fever

Question 16

What are key things to include in your examination of a patient with PUO?

Answer 16

Check skin, eyes, oral cavity, nails, lymph nodes

May be worthwhile repeating!

Question 17

What investigations may you carry out in someone with PUO?

Answer 17

CXR, urinalysis, urine microscopy, FBC, differential WCC, ESR, CRP, blood culture (from time of fever), urea, creatinine, electrolytes, LFTs

Question 18

When might imaging be valuable?

What imaging might you do?

Answer 18

If you have some direction

E.g.s - CT, USS, MRI, PET with FDG marker

Question 19

If a patient presents with PUO & hx of tropical travel, what investigations may be useful?

Answer 19

Blood for malarial parasite, dengue, HIV testing, bone marrow testing for leishmaniasis
Less likely if >21 days since return

Question 20

If a patient presents with PUO & a new murmur, what investigations may be useful?

Answer 20

Echocardiogram

Question 21

If a patient presents with PUO & new headache, what investigations may be useful?

Answer 21

Temporal artery biopsy

Question 22

If a patient presents with PUO & microhaematuria, what investigations may be useful?

Answer 22

Auto-antibodies +/- renal biopsy (polyarteritis), USS (renal Ca)

Question 23

If a patient presents with PUO & hx contact with TB, what investigations may be useful?

Answer 23

Sputum smear, bone marrow testing, Mantoux test

Question 24

If a patient presents with PUO & hx of drug misuse, what investigations may be useful?

Answer 24

Screen for blood borne viruses

Question 25

When might you do a therapeutic trial in someone with PUO?

Answer 25

Anti-TB therapy if suspected TB (diagnosis of TB unlikely if no response to treatment within 2 weeks)
Steroids for suspected vasculitis/connective tissue disease - expect dramatic response (usually within 24h), esp with temporal arteritis

Question 26

What might be a clue that a patient’s fever is fabricated?

Answer 26

Patient often continues despite being quite sick

Question 27

What should you do in the case of a fabricated fever?

Answer 27

Seek psychiatric help as opposed to confronting the patient

Question 28

Some patients with no diagnosis response to which two drugs?

Answer 28

Steroids or NSAIDs