Pyrexia of unknown origin Flashcards
What is a fevere?
○ elevation of body temperature above normal (37°C)
○ variation of up to 0.8°C daily (circadian rhythm): low in early morning, high in early evening
○ Part of the systemic inflammatory response syndrome (SIRS)
What are Pyrogens?
○ substances which cause fever
○ endogenous (produce them yourself) e.g. cytokines
○ exogenous e.g. endotoxins from G-ve bacteria
○ act at hypothalamic thermoregulatory centre to cause reduced heat loss and hence fever
Define PUO?
○ Petersdorf and Beeson (1961)
- temp > 38.3°C
- 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
○ Prolonged inflammatory response and only a minority of those are caused by infection
What can cause classical PUO
○ Infections - TB - HIV - Endocarditis ○ Malignancy - Lymhoma - Metastatic disease - Renal Ca ○ Inflammatory - Temporal arteritis - Inflammatory bowel disease - SLE - Vasculitis ○ Other - Drug fevers - Venous thrombosis - sarcoidosis
List the major disease categories which can present with a PUO
- Classical PUO
- Nosocomial PUO
- Neutroenic PUO
- HIV associated PUO
What causes Nosocomial PUO?
develoes in a hiosital, undiagnosed after 3 days
What causes Neutroenic PUO?
Undiagnosed fever in atient with neutrohils <500/mm^3
What are the main causes of HIV associated PUO?
- Mycobacterium teberculosis
- Mycobacterium avium
- Unknown
- Nore than one causative disease
What happens in 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
○ Have quite an impaired immune system
What would be included in history from someone with PUO?
○ Travel (particularly if people have spent time living abroad- prolonged periods of being abroad increases the causes of getting PUO)
○ occupation & hobbies – exposure to allergens
○ family history and age of onset - familial fevers e.g. tumour necrosis factor receptor-associated periodic syndrome – TRAPS (common in some parts of the world (cypris, Turkey))
○ past medical and surgical history
○ drug history
○ Pattern of fever (can sometimes be useful in some conditions
What would you look for in an examination from someone with PUO?
○ including skin, eyes, oral cavity, nails and lymph nodes
○ repeated examination often worthwhile
○ Might find a rash
What intial investigations would you do on someone with PUO?
○ Chest X-Ray
○ Urinalysis and urine microscopy
○ Full blood count and differential white cell count
○ C-Reactive Protein (CRP) and Erythrocyte Sedimentation Rate (ESR)- expect them all to have an elevation
○ Blood cultures taken at times of fevers
○ Urea, creatinine, electrolytes, liver function tests
What further investigations would you do on someone with PUO?
○ Tropical travel - Blood for malarial parasites, Dengue □ Less likely if >21 days since return - HIV, bone marrow for leishmaniasis ○ New murmur - Echocardiography (trans-oesophageal echo may be needed) ○ Headache Temporal artery biopsy (TA) or CT PET ○ Micro haematuria - Auto-antibodies +/- renal biopsy, (polyarteritis) ultrasound (renal Ca) ○ TB contact - Sputum smear - Bone marrow - Mantoux ○ Drug misuse - Screen for blood borne viruses
What are the contemporary imaging techniques available for use in
investigating PUO?
• Invasive investigations
○ obtain tissue for culture and histology
○ bone marrow and liver often examined as part of blind investigation
- Malignancy, TB, lymphoma
○ diagnostic laparotomy
- Rarely necessary
- Use it to get the difficult to reach lymph nodes
What is the“therapeutic trial”?
• 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
