Pyrexia of Unknown Origin Flashcards
Define fever
›elevation of body temperature above normal (37C)
How does body temperature follow circadian rhythm?
›variation of up to 0.8C daily (circadian rhythm):
low in early morning, high in early evening
What are pyrogens?
›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
What is SIRS?
Systemic inflammatory response syndrome
An inflammatory state affecting the whole body
Features raised body temperature, heart rate, respiratory rate and leucocytosis/leucocytopenia
A patient may be diagnosed with SIRS when two of these criteria are met
Common causes include trauma, burns, pancreatitis, ischaemia, haemorrhage
SIRS is closely related to sepsis, whereby patients satisfy criteria for SIRS but also have a proven infection
What is the modern definition of PUO?
No diagnosis after 3 outpatient visits or 3 days in hospital or one week of outpatient investigation
What are the types of PUO?
Classical
Nosocomial (develops in hospital, undiagnosed after 3 days)
Neutropenic (undiagnosed fever in patient with neutrophils less than 500 mm3)
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 common causes of HIV PUO?
Mycobacterium tuberculosis
Mycobacterium avium
Unknown
More than one causative disease
What are the common causes of fever?
Infections (TB, HIV, endocarditis)
Malignancy (lymphoma, metastatic disease, renal cancer)
Inflammatory (temporal arteritis, IBD, SLE, vasculitis)
Other (drug fevers, venous thrombosis, sarcoidosis)
What are the necessary investigations for a suspected infection?
Urine and sputum cultures
HIV test
Serology for CMV, EBV
ASO titre (antistreptolysin O, a substance produced by group A streptococcus bacteria)
Transthoracic/transoesophageal ultrasound. If diagnosis is not clear, then lumbar puncture, galium 67 scan, sinus films
What are the relevant tests if you suspect malignancies?
If haematologic - peripheral smear, and serum protein electrophoresis.
If diagnosis is not clear then bone marrow biopsy
If not haematologic - mammography, chest CT with contrast, Upper/lower endoscopy, bone scan, galium 67 scan
If diagnosis is not clear then MRI of the brain, biopsy of suspicious skin lesions or lymph nodes, liver biopsy, diagnostic laparoscopy
What are the relevant investigations for autoimmune conditions?
Rheumatic factor, ANA (anti-nuclear antibodies) - common in SLE and MCTD (multiple connective tissue disease)
If diagnosis is not clear then temporal artery biopsy and lymph node biopsy
What are important things to uncover in the history for PUO?
Travel
occupation & hobbies – exposure to allergens
family history and age of onset - familial fevers e.g. tumor necrosis factor receptor-associated periodic syndrome – TRAPS
past medical and surgical history
drug history
What is important to uncover in the examination?
Examination – be thorough
including skin, eyes, oral cavity, nails and lymph nodes
repeated examination often
worthwhile
What are the initial investigations for PUO?
Initial investigations
- simple things first
·Chest X-Ray
·Urinalysis and urine microscopy
·Full blood count and differential white cell count
·C-Reactive Protein (CRP) and Erythrocyte Sedimentation Rate (ESR)
·Blood cultures taken at times of fevers
·Urea, creatinine, electrolytes, liver function tests
What is the investigation for tropical travel?
›Blood for malarial parasites, Dengue, - Less likely if >21 days since return
HIV, bone marrow for leishmaniasis
What is the investigation for a new murmur?
echocardiography (trans-oesophageal echo may be needed)
What is the investigation for Headaches?
temporal artery biopsy (TA) or CT PET
(CT PET to investigate potential malignancies in the brain)
What are the investigations for Micro-haematuria?
Auto-antibodies with or without renal biopsy
(Polyarteritis) ultrasound (renal cancer)
Polyarteritis is a systemic necrotizing inflammation of the blood vessels, typically affects smal and medium sized arteries, typically affects the kidneys
What is the investigation for TB contact?
Sputum smear stained with ZN stain
Bone marow
Mantoux
fWhat are the investigations for potential drug misuse?
screen for blood-borne viruses
What are the common invasive investigations to obtain tissue for culture and histology
bone marrow and liver
often examined as part
of blind investigation
Malignancy, TB, lymphoma
Temporal artery biopsy
diagnostic laparotomy
Rarely necessary
Pyrexia of Unknown Origin -treatment?
Therapeutic trial
›Rarely used
›suspected Mycobacterial infection (anti-tuberculous therapy) (rifampicin, isoniazid, pyrazinamide, ethambutol)
›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
What is a fabricated fever?
What are the features on blood culture?
Fabricated fever
›fever is real but self-induced
›self injection common
›microbiology may be strongest clue
e.g. multiple different organisims on blood culture at different times
›patient often continues despite being very sick
›psychiatric expertise should be sought rather than direct confrontation
What are the 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
