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Infection > Pyrexia of Unknown Origin > Flashcards

Pyrexia of Unknown Origin Flashcards

1
Q

Definition of fever

A

Fever can be defined as any elevation in body temperature above the normal

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2
Q

How does body temperature vary in normal individuals

A

Varies slightly, up to 0.8 degrees, over any 24 hour period, from a low in the early morning to a high at 4-6pm

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3
Q

What are pyrogens?

A

Substances which cause fever

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4
Q

Features of pyrogens

A

May be exogenous e.g. endotoxins of gram negative bacteria or endogenous e.g. cytokines released from host cells in response to infection

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5
Q

How do pyrogens work?

A

Act by causing elevation of the set point of the hypothalamic thermoregulatory centre which in turn results in vasoconstriction, decreased peripheral heat loss and fever

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6
Q

How was pyrexia of unknown origin (PUO) defined by Petersdorf and Beeson?

A

A temperature greater than 38.3 degrees on multiple occasions during a period longer than three weeks that defied one week’s evaluation of the patient in hospital

i.e.;
Temp > 38.3
Recorded on multiple occasions 
Present for at least 3 weeks 
Defied diagnosis after one week hospital evaluation
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7
Q

When is PUO termed classical PUO?

A

When it develops in the non-compromised host

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8
Q

What is the modern definition of PUO?

A

Broader definition - no diagnosis after either;
3 outpatient visits
3 days in hospital
One week of outpatient investigation

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9
Q

Forms of PUO

A

Classical
Nosocomial
Neutropenic
HIV-Associated

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10
Q

Nosocomial PUO

A

Fever which develops in hospital and is undiagnosed after 3 days of investigation including 2 days of cultures

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11
Q

Neutropenic PUO

A

Fever in a patient with a neutrophil count of < 500 cells/mm3 which is undiagnosed after 3 days of investigations

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12
Q

HIV associated PUO

A

Fever in a patient with HIV infection which has been present and undiagnosed for more than 3 days in an inpatient or four weeks in an outpatient

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13
Q

Major causes of PUO

A 
Infection e.g. TB, HIV
Neoplasm e.g. lymphoma
Collagen disorder 
Miscellaneous e.g. drug fevers, venous thrombosis 
Inflammatory e.g. temporal arteritis 
Undiagnosed
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14
Q

Tumours most commonly associated with PUO

A 
Lymphoma 
Hodgkin's disease 
Renal cell carcinoma 
Hepatocellular carcinoma 
Leukaemia
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15
Q

Connective tissue disorders most commonly associated with PUO

A

Temporal arteritis

Systemic vasculitides

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16
Q

Causes of HIV related PUO

A 
Mycobacterium tuberculosis 
Mycobacterium avium 
Other mycobacteria 
Pneumocystis carinii pneumonia 
Cytomegalovirus 
Lymphoma 
Cryptococcosis 
Leishmaniasis 
Toxoplasmosis
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17
Q

Assessment of PUO

A

History
Examination - repeated
Second opinion

18
Q

Important aspects of history of a patient with PUO

A

Organised, systematic, open mind, no time pressure

Travel 
Occupation 
Drug and sexual histories
Ask specifically about chemical exposure and familial disorders 
Family history 
Age of onset 
Pattern of fever  
Rashes
19
Q

What might a history of transient skin rash be indicative of?

A

Diagnosis of connective tissue disease or chronic meningococcaemia

20
Q

Symptoms described by many patients which are suggestive of febrile illness but not sufficiently specific

A

Myalgia
Weight loss
Arthralgia
Shivers

21
Q

Important aspects of physical examination to remember

A 
Nails 
Oral cavity 
Skin 
Lymph nodes 
Eyes
22
Q

Initial investigations of PUO

A 
CXR 
Urinalysis and urine microscopy 
FBC and differential WCC 
C-reactive protein 
ESR 
Blood cultures if fever is present 
Urea
Creatinine 
Electrolytes 
LFTs
23
Q

Indications for further examination/investigation

A 
Travel to tropical areas 
New/changing heart murmur 
Headache/jaw claudication 
Microscopic haematuria
Risk of TB 
IVDA 
High risk sexual contact
24
Q

Further investigation in a patient with travel to tropical areas

A

Repeated blood films for malarial parasites
Blood films for borrelia and trypano-somiasis
Rickettsial, coxiella, Dengue, schistosoma, filarial and amoebic serology
HIV test
Bone marrow for leishmaniasis

25
Q

Further investigation in a patient with new/changing heart murmur

A

Echocardiography

26
Q

Further investigation in a patient with headache/jaw claudication

A

Temporal artery biopsy

CT/PET

27
Q

Further investigation in a patient with microscopic haematuria

A

ANCA

Renal US

28
Q

Further investigation in a patient with risk of TB

A

Contact history, travel and past TB
Sputum culture
Early morning urine culture
Bone marrow and liver biopsies

29
Q

Further investigation in a patient with IVDA or high risk sexual contact

A

HIV antibody

Hepatitis B and C serology

30
Q

When are invasive investigations indicated in PUO?

A

If diagnosis is not made through non-invasive techniques

31
Q

Common invasive investigations of PUO

A

Involves obtaining tissue for culture and histology
Bone marrow examination
Liver biopsy
Laparoscopy
Lung/lymph node/renal biopsy
In-situ hybridisation of biopsy to identify mycobacteria or viral nucleic acid
Diagnostic laparotomy role is decreasing and is rarely necessary

32
Q

Imaging modalities used in patients with PUO

A

CT and MRI to identify small abnormalities
Scintigraphy to detect changes due to inflammation/infection
Isotope bone scan to assess suspected bone or joint infection
Ventilation/perfusion scan to assess suspected multiple pulmonary emboli
Radiolabelled ciprofloxacin derivative to differentiate between infection and sterile inflammation

33
Q

What are CT and MRI dependent on?

A

Anatomical changes which take time to develop or which may not develop normally in an immunocompromised host

34
Q

Role of therapeutic trials

A

Rarely used
Suspected mycobacterial infection - anti-TB therapy
Suspected vasculitis or connective tissue disorder - steroids

35
Q

Management of patients with PUO

A

Most cases will be identifies within a week of intensive assessment
Decision must be made for remaining patients as to whether therapeutic trial is necessary
If clinically well - wait and keep situation under review
If clearly unwell - trial of anti-TB therapy or steroids should be considered

36
Q

When is the chance of unexplained PUO resolving higher?

A

More likely in younger patients < 35 years than in the elderly

37
Q

Affect of steroids in PUO

A

Often improve a fever as well as the patient being well
Response to steroids in a patient with giant cell arteritis or Still’s disease is dramatic and should be seen after 24-72 hours

38
Q

Outcomes of PUO

A

Spontaneous resolution - commoner in younger people
May respond to steroids to NSAIDs
Regular re-appraisal required - cause may not be apparent for several months

39
Q

What is factitious fever?

A

Situations in which the patient has manipulated the temperature recordings to fabricate the existence of a fever

40
Q

What is fabricated fever?

A

Fever which is genuinely present but which has developed as a consequence of self-induced infection e.g. self injection with faeces

41
Q

Treatment of fabricated fever

A

Psychiatric management rather than directly confronting the patient

Infection (14 decks)

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