Pyrexia of Unknown Origin

Question 1

What is the definition of pyrexia with unknown origin?

Answer 1

Fever - elevation of body temp above 38C, part of inflammatory response syndrome
Pyrogens - substances which cause fever, endogenous and exogenous which act on hypothalamus to cause reduction of heat loos

Question 2

What is Petersdorf and Beeson?

Answer 2

Temp. above 38C
Recorded on multiple occasions and present for at least 3 weeks
Defied diagnosis after one week of hospital evaluation

Question 3

What is the modern definition of pyrexia of unknown origin?

Answer 3

3 outpatient visits or 3 days in hospital or one week of outpatient investigation

Question 4

What are the types of pyrexia of unknown origin (PUO)?

Answer 4

Classical PUO
Nosocomial PUO - develops in hospital and undiagnosed after 3 days
Neutropenic PUO - undiagnosed fever with neutrophils above 500
HIV-associated PUO - fever in patient with HIV - present for more than 3 days inpatient

Question 5

What are the main causes of classical PUO?

Answer 5

Infections
Tumours
Inflammatory
Miscellaneous - ex. PE
Also undiagnosed

Question 6

What are some causes of HIV related PUO?

Answer 6

Mycobacterium tuberculosis
Mycobacterium avium
Pneumocystis
Unknown
More than one causative agent

Question 7

What is involved in the history and examination of PUO assessment?

Answer 7

History - travel, hobbies, FH, past medical and surgical history, drug history and pattern of fever
Exam - eyes, skin, oral, nails and lymph nodes
Repeated examinations

Question 8

What is a feature of Still’s disease?

Answer 8

blanching rash which can be fliting

Question 9

What are the initial investigations for pyrexia with unknown origin?

Answer 9

Chest X-ray, urinalysis, FBC, WCC, C-reactive protein and erythrocyte, blood cultures taken at times of fever, urea, creatinine, electrolytes and LFTs

Question 10

What could be a further investigation for tropical travel?

Answer 10

Blood for malarial parasites, dengue, HIV, bone marrow for leishmaniasis
Less likely if more than 21 days after return

Question 11

What could be used for further investigation of new heart murmur?

Answer 11

Echocardiogram

Question 12

What investigation could be used for further investigation of micro. haematuria?

Answer 12

Auto-antibodies and possible renal biopsy
US

Question 13

What further investigation can be done for TB contact?

Answer 13

Sputum smear, bone marrow and mantoux

Question 14

What further investigation could be done for drug misuse?

Answer 14

Screen for blood borne viruses

Question 15

Are imaging techniques good investigation for PUO?

Answer 15

More valuable if have some indication
Can’t differentiate between infection and inflammation
Anatomical changes may not develop in immunocompromised host

Question 16

What imaging techniques can be used for PUO?

Answer 16

CT scan - ex. liver abscess
CT PET scan - ex. arteritis
US - ex. small vegetation on mitral valve

Question 17

When are invasive investigation used for PUO?

Answer 17

Obtain tissue for culture and histology
Bone marrow and liver often examined as part of blind investigation - malignancy, TB and lymphoma
Diagnostic laparotomy - rare

Question 18

What is the treatment for pyrexia of unknown origin?

Answer 18

Therapeutic trial - rare, suspected mycobacterial infection and vasculitis
Diagnosis of mycobacterium TB is unlikely if no response to chemo after 2 weeks

Question 19

What is fabricated fever?

Answer 19

Fever is real but self induced, self injection common, microbiology usually strongest clue
Psychiatric expertise should be sought

Question 20

What is the outcome of PUO?

Answer 20

Spontaneous resolution of PUO commoner in young patients
Some patient with no diagnosis respond to NSAIDs and steroids
Regular re-appraisal required

Question 21

How many PUO patients remain undiagnosed?

Answer 21

1 in 4