Pyrexia of Unknown Origin (PUO) Flashcards
what is normal temperature?
37 centigrade is normal
Varies a lot between people and time of day
Lower in morning
Pyrexia of Unknown Origin - Definitions
what is a fever?
elevation of body temperature above normal (37C)
variation of up to 0.8C daily (circadian rhythm):
low in early morning, high in early evening
Part of the systemic inflammatory response syndrome (SIRS)
Pyrexia of Unknown Origin - Definitions
What are pyrogens? and what types are there?
substances which cause fever
endogenous e.g. cytokines
exogenous e.g. endotoxins from G-ve bacteria
act at hypothalamic thermoregulatory centre to cause reduced heat loss and hence fever
Raised __ and __ that goes along with the fever
RR
HR
what is the old (Petersdorf and Beeson (1961)) and modern definitions of pyrexia?
Petersdorf and Beeson (1961):
› temp > 38.3C
› recorded on multiple occasions
› present for at least three weeks
› defied diagnosis after one week of hospital evaluation
Modern definition is broader i.e. No diagnosis after:
› 3 outpatient visits or
› 3 days in hospital or
› One week of outpatient investigation
What are the different types of Pyrexia of Unknown Origin?
Classical PUO
Nosocomial PUO
Neutropenic PUO
HIV-associated PUO
what is Nosocomial PUO?
develops in hospital, undiagnosed after 3 days
Nosocomial in a hospitalised patient
what is Neutropenic PUO?
undiagnosed fever in 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
what are the different causes of classical PUO?
Categorised in 4/5 main areas
Infections
Tumour disease
Inflammatory diseases
Other
No diagnosis
Pyrexia of Unknown Origin - assessment
what information should you gather in a history?
travel, occupation, hobbies, family history, past medical and surgical history, drug history, pattern of fever
Pyrexia of Unknown Origin - assessment
what should you examine?
including skin, eyes, oral cavity, nails and lymph nodes
repeated examination often worthwhile
what initial investigations would you do? (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) (ESR should be elevated)
Blood cultures taken at times of fevers
Urea, creatinine, electrolytes, liver function tests
Pyrexia of Unknown Origin - further investigation
what investigation would you do for an indication of Tropical travel?
Blood for malarial parasites, Dengue, HIV, bone marrow for leishmaniasis
Less likely if >21 days since return
Pyrexia of Unknown Origin - further investigation
what investigation would you do for an indication of a new murmur?
echocardiography (trans-oesophageal echo may be needed)
Pyrexia of Unknown Origin - further investigation
what investigation would you do for an indication of a headache?
temporal artery biopsy (TA)
Pyrexia of Unknown Origin - further investigation
what investigation would you do for an indication of Micro. Haematuria?
Auto-antibodies +/- renal biopsy, (polyarteritis) ultrasound (renal Ca)
Pyrexia of Unknown Origin - further investigation
what investigation would you do for an indication of Tb contact?
sputum smear, bone marrow, Mantoux,
Pyrexia of Unknown Origin - further investigation
what investigation would you do for an indication of durg misuse?
screen for blood-borne viruses
:Imaging techniques
› more valuable if they have some “_______”
› cannot always differentiate between _______ and ____________
› anatomical changes may not develop in ________________ hosts (e.g. neutropenic patients and abscesses)
(white cell scan shown below)
direction
infection and inflammation
immunocompromised
what is shown here?
Liver abscess
What technique is shown here?
CT PET scan for PUO
Positron Emission tomography
Fluorodeoxyglucose marker (FDG)
taken up greater in cells that are inflammed
what invasive procedures can be carried out?
obtain tissue for culture and histology
bone marrow and liver often examined as part of blind investigation - Malignancy, TB, lymphoma
diagnostic laparotomy - Rarely necessary
what is the treatment?
Therapeutic trial
- Rarely used
- suspected Mycobacterial infection (anti-tuberculous therapy)
- suspected vasculitis or conn. tissue disorder
(steroids)
Diagnosis of Mtb unlikely if no response to chemotherapy within two weeks
Response of temporal arteritis to steroids is dramatic - usually within 48 hrs
how is fabricated fever caused, its diagnosis and its effects?
fever is real but self-induced
self injection common
microbiology may be strongest clue
patient often continues despite being very sick
psychiatric expertise should be sought rather than direct confrontation
what is the outcome of pyrexia of unkowning origin?
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
Summary:
Most PUOs are not due to ______
Careful and _______ history and examination is crucial
Imaging is most valuable if it has some “_______” i.e. don’t just do ______ scans
Therapeutic trials are a ____ ______!
About 1 in 4 patients remain ________
infection
repeated
direction
random
last resort
undiagnosed
