Pyrexia of Unknown Origin Flashcards
What is a fever?
Elevation of body temperature above normal (37oC)
What is the variation of normal body temperature?
Normal body temperature has variation up to 0.8oC daily, being low in early morning and high in early evening
Fever is a normal part of what?
Systemic inflammatory response syndrome (SIRS)
What does SIRS stand for?
Systemic inflammatory response syndrome
What is a pyrogen?
Substances that cause fever
What are examples of pyrogens?
- Endogenous
- Cytokines
- Exogenous
- Endotoxins from G-ve bacteria
What do pyrogens act on?
Hypothalamic thermoregulatory centre to cause reduced heat loss and hence fever
What does PUO stand for?
Pyrexia of unknown origin
What is pyrexia of unknown origin?
Pyrexia with no diagnosis after:
- 3 outpatient visits or
- 3 days in hospital or
- One week of outpatient investigation
What are the different classes of PUO?
- Classical PUO
- Nosocomial PUO
- Develops in hospital, undiagnosed after 3 days
- Neutropenic PUO
- Undiagnosed fever in patient with neutrophils <500/mm3
- HIV associated PUO
- Fever in patient with HIV present and undiagnosed for more than 3 days in an inpatient or 4 weeks as outpatient
What is nosocomial PUO?
- Develops in hospital, undiagnosed after 3 days
What is neutropenic PUO?
- Undiagnosed fever in patient with neutrophils <500/mm3
What is HIV associated PUO?
- Fever in patient with HIV present and undiagnosed for more than 3 days in an inpatient or 4 weeks as outpatient
What are some causes of classical PUO?
- Infection
- Malignancy
- Collagen (inflammatory)
- Other
What are the most common causes of HIV associated PUO?
- Mycobacterium tuberculosis
- Mycobacterium ovium
- Unknown
What parts of the history are important for assessment for PUO?
- Travel, occupation, hobbies, family history, past medical and surgical history, drug history, pattern of fever
What part of the examination are important for assessment for PUO?
- Skin, eyes, oral cavity, nails and lymph nodes
What are the initial investigations for PUO?
- Simple things first
- Chest X-Ray
- Urinalysis and urine microscopy
- Full blood count and differential white cell count
- C-Reactive Protein and Erythrocyte Sedimentation Rate (acute phase reactants)
- Blood cultures taken at times of fevers
- Urea, creatinine, electrolytes, liver function tests
What are some further investigations for PUO?
What is a limitation of imaging for PUO?
- Cannot always differentiate between infection and inflammation
- Anatomical changes may not be present in immunocompromised hosts
What imaging may be done for PUO?
- USS
- CT
- MRI
- Radio-labelled white cell scan
- Isotope bone scan
What invasive investigations may be done for PUO?
- Obtain tissue for culture and histology (biopsy)
- Bone marrow and liver often examined as part of blind investigation
- Malignancy, TB, lymphoma
What is the treatment of PUO?
Therapeutic trial:
- Rarely used, but used if
- Suspected mycobacterial infection (anti-tuberculosis therapy)
- Suspected vasculitis or connective tissue disorder (steroids)
What is a fabricated fever?
Fever is real but self-induced:
- Microbiology may be strongest clue
- Psychiatric expertise should be sought
Describe the outcome of PUO?
Spontaneous resolution of PUO more common in young people
Some patients respond to NSAIDs or steroids
Regular re-appraisal required
What are most HIV-related PUOs caused by?
3/4 patients:
- Mycobacterium tuberculosis
- Mycobacterium avium
- Unknown
- More than one causative disease
