Pyrexia of Unknown Origin Flashcards
What is the normal body temperature
37oC
- BUT has a variation of up to 0.8C daily (circadian rhythm - low to high throughout day))
what is considered to be a fever
elevation of the body temp above 37oC
- part of the systemic inflammatory response syndrome (SIRS)
what are pyrogens
substances that cause fever
what are the 2 types of pyrogens
endogenous - eg cytokines
exogenous - eg endotoxins from gram-ve bacteria
how do pyrogens cause a fever
pyrogens act at the hypothalamic thermoregulatory centre to cause reduced heat loss and hence fever
what symptoms are seen in SIRS
pulse >90
temp <35 or >38
RR >20
WCC >12 or <5
what are the signs/symptoms of sepsis
SIRS + evidence of bacterial infection
what are the signs/symptoms of severe sepsis
organ underperfusion - oliguria, confusion, acidosis
ALSO
SIRS + evidence of bacterial infection
what are the signs/symptoms of septic shock
irreversible hypotension despite fluid resus
ALSO
SIRS + evidence of bacterial infection
AND
organ underperfusion - oliguria, confusion, acidosis
what is the definition of pyrexia of unknown origin (PUO)
- temp >38.3oC
- recorded on multiple occasions
- present for at least 3 weeks
no diagnosis after:
- 3 outpatient visits OR
- 3 days in hospital OR
- one week of outpatient investigation
ie MULTIPLE FEBRILE EPISODES THAT DEFY DIAGNOSIS
what are the 4 types of PUO
classical PUO
nosocomial PUO
neutropenic PUO
HIV-associated PUO
what is nosocomial PUO
PUO that develops in hospital, undiagnosed after 3 days
what is neutropenic PUO
an undiagnosed fever in a patient with neutrophils <500/mm3
what is HIV-associated PUO
fever in a patient with HIV infection - present and undiagnosed for more than three days in an inpatient or four weeks in an outpatient
name 2 possible causes of PUO
?wound infection
?multiple pulmonary emboli
what bacterium commonly cause HIV-rassociated PUO
mycobacterium tuberculosis
mycobacterium avium
COMMONLY ALSO
unknown
more than one causative disease
what are the 4 groups of diseases that cause PUO
infections (most common - 1in4)
malignancies
autoimmune/inflammatory
other/miscellaneous
what aspects of the history are important for PUO
- travel
- occupation and hobbies (exposure to allergens)
- family history and age onset - familial fevers e.g. TNF receptor associated periodic syndrome (TRAPS)
- past medical/surgical history
- drug history
what aspects of the examination are important for PUO
BE THOROUGH
- include skin, yes, oral cavity, nails, lymphs
- repeated examinations often needed
what are the initial investigations that can be done for PUO
SIMPLE THINGS FIRST
- Chest X-Ray
- Urinalysis and urine microscopy
- FBC and differential white cell count
- CRP and ESR
- Blood cultures taken at times of fevers
- Urea, creatinine, electrolytes, liver function tests
prolonged cultures often needed
how many blood cultures should be taken before ruling out infection
3 negative blood cultures
what further investigations would a tropical travel history require
- blood: malarial parasites, dengue
(but less likely if >21 days since return) - HIV, bone marrow for leishmaniasis
what investigations would a new murmur require
ECG (trans-oesophgeal echo may be needed)
what investigations would headaches require
- temporal artery biopsy (TA)
- CT PET
what investigations would micro-haematuria require
- auto-antibodies +/- renal biopsy (polyarteritis)
- ultrasound (renal Ca)
what investigations would TB contact require
- sputum smear
- bone marrow
- Mantoux test/skin patch test
what investigations would a history of drug misuse require
screen for blood borne viruses
what are the imaging techniques used in PUO
- contrast CT - FIRST
- CT PET
- transoesophageal ECG
what can CT PET images show
- looks at uptake of marker - uptake bigger at areas of inflammation
- shows large vessel vasculitis
- can be a diagnostic technique
what are some limitations of imaging techniques in PUO
can’t always differentiate between what is inflamed and what is infected
anatomical changes may not develop in immunocompromised hosts - e.g. neutropenic patients and abscesses
what are the invasive investigations used for PUO
- tissue for culture/histology
- bone marrow/liver/TA biopsy
- diagnostic laparotomy
what do biopsies in PUO most commonly find
malignancy, TB, lymphoma
what are the treatments for PUO
therapeutic trial:
?mycobacterial infection = anti-tuberculous therapy
?vasculitis or conn. tissue disorder = steroids
what is a fabricated fever
a fever that is real but self-induced
- commonly from self injection
what is the strongest clue to diagnose a fabricated fever
microbiology - multiple different organisms on blood culture at different times
what is important to include if a fabricated fever is suspected in a patient with PUO
psychiatric expertise rather than direct confrontation
what are the common outcomes of PUO
young - spontaneous resolution
elderly - more likely to persist
no diagosis - can still respond well to NSAIDS or steroids (steroid responsive PUO)
regular check ups required
