Pyrexia of Unknown Origin Flashcards
Classical PUO
- Fever >38.3 on several occasions
- Persisting without diagnosis for >3 weeks
- with >1 week investigation in hospital\
- excludes fever with apparent causes or other self-limiting diseases
But questionable areas:
- diurnal rhythm of body temp
- is 3 wks required to rule out self-limiting disease?
- most investigations can be done out-patient
New expanded definitions to categorise and help consider microbiological hypothesis + relevant antibiotics coverage
Nosocomial PUO
- Fever >38.3
- infection not present nor incubating on admission
- negative cultures after 2 days
Neutropenic PUO
- Fever >38.3
- neutrophil <0.5 or 500/mm3
- negative culture after 2 days
HIV-associated PUO
- Fever >38.3
- > 3 weeks in outpatient/ >3 days in hospital
- HIV serology +ve
- negative culture after 2 days
Causes of classical PUO
Infections (30-40%)
Neoplasms (20%)
Connective tissue diseases (20%)
Miscellaneous conditions e.g. “fake fever”
“No diagnosis”
Specific pathogens causing infections, clinical entities
Extrapulmonary TB e.g. spine, kidney (deep seated infection requiring extensive imaging and maybe invasive techniques)
Typhoid fever
Malaria
Bartonella, Q fever, Fastidious organisms
Clinical entities:
- subacute bacterial endocarditis
- intra-abdominal abscesses
- biliary tract infections
- complicated UTI e.g. renal stones, pyelonephritis
Approach: Hx
Fever patterns
- duration: very long e.g. >3 months = unlikely due to infection
- malaria: tertian/ quartan patterns
- a/w night sweats (TB)
- but not always sensitive and specific
TOCC: travel, occupation, contact (animals), cluster
Fam Hx, Social Hx
PMH: transfusion history (HIV/ HBV not screened before 1980s)
Medication Hx: alcohol, substance abuse, health supplement
Approach: PE
Key finding can be very subtle Verify presence of fever Particularly observe - skin rash/lesions - eye/ fundi - oral cavity - lymph nodes - abdomen
Approach: Ix
Baseline blood tests (CBC, RLFT, cultures of blood/urine +/- other suspicions)
Baseline imaging e.g. CXR
Further tests as guided by clinical clues
Note: if prevalence is extremely low, post-test probability can be low (<50%) e.g. need to consider false +ves
What if initial Hx, PE and Ix doesn’t yield a probable diagnosis?
REVIEW AND REPEAT Hx and PE
More specific Ix or invasive tests could be considered
Repeated sampling of blood/ urine may be required - alert lab if fastidious organisms are DDx
Further tests e.g. specific Ab, serological tests, malaria blood smears (if travel hx +ve), CT, nuclear medicine testing
Invasive tests - directed evaluation
Biopsy: LN, BM (TB, blood malignancy), liver, skin, temporal artery (temporal arteritis esp in elderly)
Exploratory laparoscopy/ laparotomy rarely needed now (have MRI, CT)
Therapeutic Trials
Steroids/ Prostaglandin inhibitors
- ONLY WHEN NON-INFECTIOUS CAUSE IS LIKELY (otherwise will mask fever and false affirmation of improvement)
- repeated PE, all baselines consistent, thorough Hx, non-invasive Ix -ve –> still no microbiological Dx –> suspect CTD
Empirical antibiotics
- NOT in classical PUO: no indication after prolonged fever, not urgent
- INDICATED in neutropenic PUO/ HIV associated PUO as diseases can progress rapidly
- Anti-tuberculous trial: full course (after all Ix exhausted)
Indication for antibiotics in neutropenic and HIV associated PUO
Neutropenic PUO is MEDICAL EMERGENCY!! - very immunocompromised
- medication/ chemo targets fast turnover cells causing mucositis (intestines, mouth etc.) –> intestinal bacteria enter blood and cause infection
==> need BROAD SPECTRUM antibiotics covering aerobic gram -ve and anaerobes
HIV associated
- antibiotics depends on diagnostic clues
- more prone to CMV, cryptosporidosis, salmonella dissemination etc
- treatments are different for each
