Pyrexia of unknown origin

Question 1

What is a normal temp

Answer 1

around 37, but often variations with individuals

Question 2

What is a fever

Answer 2

elevation of body temperature above normal (37C)

inflammatory response

Question 3

What are pyrogens , give examples of endogenous and exogenous

Answer 3

substances which cause fever
endogenous e.g. cytokines
exogenous e.g. endotoxins from G-ve bacteria
act at hypothalamic thermoregulatory centre to cause reduced heat loss and hence fever

Question 4

What are the different types of PUO? - describe them

Answer 4

Classical PUO
Nosocomial PUO - develops in hospital, undiagnosed after 3 days

Neutropenic PUO - undiagnosed fever in patient with neutrophils <500/mm3

HIV-associated PUO - HIV infection, more than three days in an inpatient or four weeks in an outpatient.

Question 5

Causes of classical PUO? (4)

Answer 5

infections
tumour disease - malignancy
inflammatory conditions
pulmonary emboli

Question 6

Causes of HIV - puo? (4)

Answer 6

mycobacterium tuberculosis
mycobacterium avium
unknown
more than one causative disease

Question 7

Pyrexia of Unknown Origin -assessment - main things to ask

Answer 7

History – take your time
travel, occupation, hobbies, family history, past medical and surgical history, drug history, pattern of fever(drenching sweats)

Examination – be thorough
including skin, eyes (fundoscopy tb), oral cavity (ulcers in IBD) , nails ( endocarditis) and lymph nodes
repeated examination often worthwhile (rashes)

Question 8

Initial investigations (7-9)

Answer 8

Chest X-Ray
Urinalysis and urine microscopy
Full blood count and differential white cell count - 3 sets
C-Reactive Protein and Erythrocyte Sedimentation Rate (acute phase reactants)
Blood cultures taken at times of fevers
Urea, creatinine, electrolytes, liver function tests

Question 9

further investigation

1. foreign travel
2. new murmur
3. Headaches
4. Micro. Haematuria
5. TB contact
6. drug misuse

Answer 9

1. Blood for malarial parasites,Dengue, HIV, bone marrow for leishmaniasis
   Less likely if >21 days since return
2. echocardiography (trans-oesophageal echo may be needed) (endocarditis)
3. temporal artery biopsy (TA)(giant cell arteritis) - raised CRP, high ESR , long history fever
4. Auto-antibodies +/- renal biopsy, (polyarteritis) ultrasound (renal Ca)
5. sputum smear, bone marrow, Mantoux,
6. screen for blood-borne viruses

Question 10

Invasive investigations

Sometimes use diagnostic?

Answer 10

• samples of tissue for culture and histology
• bone marrow and liver often examined as part of blind investigation
  Malignancy, TB, lymphoma

laparotomy - lymph node abnormal on CT pet but not accessible on biopsy

Question 11

Pyrexia of Unknown Origin -treatment

Answer 11

• Therapeutic trial, risk it can mask new signs and features - toxicity - suspected Mycobacterial infection (anti-tuberculous therapy)
  suspected vasculitis or conn. tissue disorder(steroids)

Diagnosis of Mtb unlikely if no response to chemotherapy within two weeks
Response of temporal arteritis to steroids is DRAMATIC - usually within 48 hrs

Question 12

Pyrexia of Unknown Origin - Fabricated fever (5)

Answer 12

• fever is real but self-induced
• self injection common
• microbiology may be strongest clue
• patient often continues despite being very sick
• psychiatric expertise should be sought rather than direct confrontation

Question 13

Pyrexia of Unknown Origin - outcome (3)

Answer 13

• Spontaneous resolution of PUO commoner in young compared with old patient
• Some patients with no diagnosis respond to NSAIDs or steroids (steroid responsive PUO)
• Regular re-appraisal required

diagnosis may declare itself at a later stage