Pyrexia of Unknown Origin Flashcards

(41 cards)

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
Further investigation in a patient with new/changing heart murmur
Echocardiography
26
Further investigation in a patient with headache/jaw claudication
Temporal artery biopsy | CT/PET
27
Further investigation in a patient with microscopic haematuria
ANCA | Renal US
28
Further investigation in a patient with risk of TB
Contact history, travel and past TB Sputum culture Early morning urine culture Bone marrow and liver biopsies
29
Further investigation in a patient with IVDA or high risk sexual contact
HIV antibody | Hepatitis B and C serology
30
When are invasive investigations indicated in PUO?
If diagnosis is not made through non-invasive techniques
31
Common invasive investigations of PUO
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
Imaging modalities used in patients with PUO
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
What are CT and MRI dependent on?
Anatomical changes which take time to develop or which may not develop normally in an immunocompromised host
34
Role of therapeutic trials
Rarely used Suspected mycobacterial infection - anti-TB therapy Suspected vasculitis or connective tissue disorder - steroids
35
Management of patients with PUO
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
When is the chance of unexplained PUO resolving higher?
More likely in younger patients < 35 years than in the elderly
37
Affect of steroids in PUO
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
Outcomes of PUO
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
What is factitious fever?
Situations in which the patient has manipulated the temperature recordings to fabricate the existence of a fever
40
What is fabricated fever?
Fever which is genuinely present but which has developed as a consequence of self-induced infection e.g. self injection with faeces
41
Treatment of fabricated fever
Psychiatric management rather than directly confronting the patient