Pyrexia of Unknown Origin Flashcards
What is a normal temperature?
37C
Fever
Elevation of body temperature above normal 37C
What response is fever part of?
The systemic inflammatory response (SIRS)
How does temperature vary throughout the day?
Variation of up to 0.8C daily (circadian rhythm)
- Low in the early morning
- High in the early evening
Pyogenes
Substances which cause fever
- Endogenous e.g. cytokine
- Exogenous e.g. endotoxins from gram negative bacteria
How do pygogenes cause fever?
They act at the hypothalamic thermoregulatory centre to cause reduced heat loss and hence fever
How is pyrexia of unknown origin defined?
Fever with no diagnosis after:
- 3 outpatient visits or
- 3 days in hospital or
- 1 week of outpatient investigation
Nosocomial PUO
Pyrexia which develops in hospital and is undiagnosed after 3 days
Neutropenic PUO
Undiagnosed fever in a patient with neutrophils <500mm^3
HIV associated PUO
Fever in a patient with HIV infection which is present and undiagnosed for more than 3 days in an inpatient stay or 4 weeks as an outpatient
Causes of classical PUO
- Infection
- Malignancy
- Inflammatory
- No diagnosis
What bacteria are commonly involved in HIV related PUO?
- Mycobacterium tuberculosis
- Mycobacterium ovium
- Unknown
- More than 1 causative agent
What history should be taken in PUO?
- Travel
- Occupation
- Hobbies
- Family history
- Past medical and surgical history
- Drug history
- Pattern of fever
What examination should be carried out when assessing PUO?
Repeated examination is often worthwhile
- Skin
- Eyes
- Oral cavity
- Lymph nodes
What initial investigations should be carried out for PUO?
- Chest X-Ray
- Urinalysis and urine microscopy
- Full blood count and differential white cell count
- C-Reactive Protein and Erythrocyte Sedimentation Rate
- Blood cultures taken at times of fevers
- Urea, creatinine, electrolytes, liver function tests
What investigations should be carried out if there is tropical travel in the history?
-Blood for malarial parasites, Dengue and HIV
-Bone marrow for leishmaniasis
(It is likely if >21 days since return)
What investigations should be carried out if there is a new heart murmur?
-Echocardiography (TOE may be required)
What investigations should be carried out if there is a history of headaches?
Temporal artery biopsy
What investigations should be carried out if there is micro haematuria?
- Auto-antibodies +/- renal biopsy (polyarteritis)
- Ultrasound (renal cancer)
What investigations should be carried out if there is a history of TB contact?
- Sputum smear
- Bone marrow
- Mantoux
What investigations should be carried out if there is a history of drug misuse?
Screen for blood-borne viruses
What are the limitations of imaging in PUO?
- Only valuable if directed
- Cannot always differentiate between infection and inflammation
- Anatomical changes may not develop in immunocompromised hosts (e.g. neutropenic patients and abscess)
What invasive investigations may be carried out for PUO?
- Obtaining tissue for culture and histology
- Bone marrow and liver are often examined as part of blind investigation (malignancy, TB, lymphoma)
- Diagnostic laparotomy (rarely necessary)
How is PUO treated?
Therapeutic trial
- Rare
- Can be used for suspected mycobacterial infection (unlikely if no response within 2 weeks)
- Can be used for suspected vasculitis or connective tissue disorder (steroids)
- Response of temporal arteritis to steroids is usually within 48 hours
What is a fabricated fever?
Self-induced fever
How should fabricated fever be treated?
Psychiatric expertise is best
What are the possible outcomes of PUO?
- 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 (The answer may not become apparent for many months)
