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Flashcards in Pyrexia of Unknown Origin Deck (25)
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1
Q

Define fever

A

›elevation of body temperature above normal (37C)

2
Q

How does body temperature follow circadian rhythm?

A

›variation of up to 0.8C daily (circadian rhythm):
low in early morning, high in early evening

3
Q

What are pyrogens?

A

›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

4
Q

What is SIRS?

A

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

5
Q

What is the modern definition of PUO?

A

No diagnosis after 3 outpatient visits or 3 days in hospital or one week of outpatient investigation

6
Q

What are the types of PUO?

A

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)

7
Q

What are the common causes of HIV PUO?

A

Mycobacterium tuberculosis

Mycobacterium avium

Unknown

More than one causative disease

8
Q

What are the common causes of fever?

A

Infections (TB, HIV, endocarditis)

Malignancy (lymphoma, metastatic disease, renal cancer)

Inflammatory (temporal arteritis, IBD, SLE, vasculitis)

Other (drug fevers, venous thrombosis, sarcoidosis)

9
Q

What are the necessary investigations for a suspected infection?

A

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

10
Q

What are the relevant tests if you suspect malignancies?

A

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

11
Q

What are the relevant investigations for autoimmune conditions?

A

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

12
Q

What are important things to uncover in the history for PUO?

A

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

13
Q

What is important to uncover in the examination?

A

žExamination – be thorough

including skin, eyes, oral cavity, nails and lymph nodes

repeated examination often
worthwhile

14
Q

What are the initial investigations for PUO?

A

žInitial 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

15
Q

What is the investigation for tropical travel?

A

›Blood for malarial parasites, Dengue, - Less likely if >21 days since return

HIV, bone marrow for leishmaniasis

16
Q

What is the investigation for a new murmur?

A

echocardiography (trans-oesophageal echo may be needed)

17
Q

What is the investigation for Headaches?

A

temporal artery biopsy (TA) or CT PET

(CT PET to investigate potential malignancies in the brain)

18
Q

What are the investigations for Micro-haematuria?

A

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

19
Q

What is the investigation for TB contact?

A

Sputum smear stained with ZN stain

Bone marow

Mantoux

20
Q

fWhat are the investigations for potential drug misuse?

A

screen for blood-borne viruses

21
Q

What are the common invasive investigations to obtain tissue for culture and histology

A

bone marrow and liver
often examined as part
of blind investigation

Malignancy, TB, lymphoma

Temporal artery biopsy

diagnostic laparotomy

–Rarely necessary

22
Q

Pyrexia of Unknown Origin -treatment?

A

žTherapeutic trial

›Rarely used

›suspected Mycobacterial infection (anti-tuberculous therapy) (rifampicin, isoniazid, pyrazinamide, ethambutol)

›suspected vasculitis or conn. tissue disorder
(steroids)

žDiagnosis of Mtb unlikely if no response to chemotherapy within two weeks

žResponse of temporal arteritis to steroids is dramatic - usually within 48 hrs

23
Q

What is a fabricated fever?

What are the features on blood culture?

A

žFabricated 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

24
Q

What are the outcomes of PUO?

A

žSpontaneous resolution of PUO commoner in young compared with old patient

žSome patients with no diagnosis respond to NSAIDs or steroids (steroid responsive PUO)

žRegular re-appraisal required

The answer may not become apparent for many months

25
Q
A