Pyrexia of Unknown Origin

Question 1

Which cytokines causes fever in infection?

Answer 1

PGE2, IL1, IL6 and TNFa - these cytokines mobilize energy via fat and protein breakdown to allow for increased body temp

These pyrogens work via the hypothalamus

Question 2

What is the risk of high fevers?

Answer 2

Seizures

Question 3

What is the definition of PUO?

Answer 3

‘Illness of more than 3 weeks duration, fever higher than 38C on several occasions after 1 week of investigations/

Question 4

What diseases show a daily spike pattern of fever?

Answer 4

Abscess, TB, schistomiasis

Question 5

What diseases show a twice daily spike in fever?

Answer 5

Leishmaniasis

Question 6

What is a saddleback fever pattern and in what diseases does it occur?

Answer 6

3-5 days of high temp followed by 3-5 days of resolution, occurring in waves

Dengue, legionairres, typhoid

Question 7

What is a pel-ebstein fever pattern and in what disease does it occur?

Answer 7

7 days fever, 7 days resolution, occurring in waves

Hodgkins lymphoma

Question 8

What diseases show a relapsing-remitting fever pattern?

Answer 8

Malaria, TB

Question 9

What happens to platelets in infection?

Answer 9

THROMBOCYTOPENIA - decreased numbers

Question 10

What are the 3 main causes of PUO?

Answer 10

1. Infection (abscesses, TB)
2. Malignancy (lymphoma, leukemia)
3. Connective tissue disorders/autoimmune (rheumatoid, SLE, still’s disease)

Question 11

Which drugs can cause PUO?

Answer 11

Antibiotics: sulphonamides, penicillins
Any vasodilators
Phenytoin, methyl dopa

Question 12

When taking a history of PUO, what MUST you ask?

Answer 12

• Time scale and fever pattern
• Sweats, shivers, chills, rigors
• Malaise
• Weight loss
• Rash
• Travel, occupation, animals, sexual etc etc
• Vaccination history

Question 13

What lab investigations could be done on someone with PUO?

Answer 13

Cultures (repeated from various sites including bacterial, fungal, mycobacterial, viral - as appropriate)

FBC, LFTs, U&E, glucose, TSH, (ferritin)

CRP and ESR sequentially
antibody titres (e.g. atypical LRTI, brucella…)
tailor to clinical features/risk factors…

Blood films (including malaria if ever exposed)

Autoantibodies (ANA, RhF….)

Question 14

What more advanced investigations could be done on someone with PUO?

Answer 14

Imaging:
U/S, CXR, CT, MRI scans

Aspiration or needle biopsy (lymph node, rectal, transbronchial… - as appropriate) – ‘Go where the money is.’
Laparoscopy (pelvic inflammatory disease, multiple peritoneal metastases or tuberculous peritonitis)
Needle biopsy of the liver
Remember to send to Microbiology (as well as for histology)
Bone marrow biopsy (good yield TB, typhoid, Brucella, tumour infiltration)
Barium studies
diagnostic surgical procedures other than above
Tuberculin test/IFNg (quantiferon/ elispot)