4. Pyrexia of Unknown Origin Flashcards
What is the normal temperature of humans?
37 degrees
What is the definition of a Fever?
Elevation of body temperature above normal (37 degrees)
How much can body temperature vary during a fever?
0.8 degrees daily
Note - this tends to be with Circadian Rhythm: Low early in the morning, high in the early evening
What is Fever a common and major part of?
Systemic Inflammatory Response Syndrome (SIRS)
What is the definition of a Pyrogen?
A substance which causes a Fever
What are the 2 types of Pyrogens?
- Endogenous (e.g. Cytokines)
- Exogenous (e.g. Endotoxins from Gram Negative bacteria)
What is the function of Pyrogens, in the body?
They act on the Hypothalamic Thermoregulatory Centre to cause reduced heat loss, and hence Fever
What is the Diagnostic Criteria for Pyrexia of Unknown Origin?
Temperature of > 38.3 degrees recorded on multiple occasions, which is:
1. Present for at least 3 weeks
2. No diagnosis after 3 outpatient visits
3. No diagnosis after 3 days in hospital
4. No diagnosis after 1 week of outpatient investigation
What are the 4 different types of Pyrexia of Unknown Origin?
- Classical Pyrexia of Unknown Origin
- Nosocomial Pyrexia of Unknown Origin
- Neutropenic Pyrexia of Unknown Origin
- HIV-Associated Pyrexia of Unknown Origin
What is Nosocomial Pyrexia of Unknown Origin?
Pyrexia of Unknown Origin which develops in hospital, and is undiagnosed after 3 days
What is Neutropenic Pyrexia of Unknown Origin?
An undiagnosed Fever in a patient which Neutrophils < 500/mm3
What is HIV-Associated Pyrexia of Unknown Origin?
Fever in a patient with HIV infection - present and undiagnosed for more than 3 days in an inpatient or 4 weeks in an outpatient
What are the main causes of HIV-Associated Pyrexia of Unknown Origin?
- Mycobacterium Tuberculosis (21%)
- More than 1 causative disease (20%)
- Mycobacterium Avium (18%)
- Unknown (16%)
What percentage of Classical Pyrexia of Unknown Origin remains undiagnosed?
26%
What is the order of the Algorithm to diagnose Pyrexia of Unknown Origin?
- Complete History and Physical Assessment
- Full blood and Urine tests
- CT of Abdomen / Pelvis with contrast
- Assign most likely category (from History):
- a) Infection
- b) Malignancies
- c) Autoimmune Conditions
- d) Miscellaneous
What will the following investigation be, if Tropical Travel is indicated?
- Bloods for malarial parasites
- HIV
- Bone Marrow for Leishmaniasis
What will the following investigation be, if a New Murmur is indicated?
Echocardiography (Tans-Oesophageal may be indicated)
What will the following investigation be, if Headaches are indicated?
- Temporal Artery Biopsy
- CT PET
What will the following investigation be, if Micro-heamaturia is indicated?
- Autoantibodies +/- Renal Biopsy
- (Polyarteritis) Uktrasound (Renal Ca)
What will the following investigation be, if TB contact is indicated?
- Sputum Smear
- Bone Marrow
- Mantoux
What will the following investigation be, if Drug Misuse is indicated?
Screen for blood-borne viruses
What imaging techniques are used in Pyrexia of Unknown Origin?
- CT- PET (most useful)
- MRI
- Ultrasound
What are the disadvantages of imaging in Pyrexia of Unknown Origin?
- It is hard to do if they have some direction
- Cannot always differentiate between infection and inflammation
- anatomical changes may not develop in immunocompromised hosts
What invasive investigations can be used for Pyrexia of Unknown Origin?
- Tissue Graft for Culture and Histology
- Bone Marrow and Liver are often examined as part of a blind investigation
- Diagnostic Laparotomy (Rarely necessary)
What is the treatment for Pyrexia of Unknown Origin?
Therapeutic Trial (Rarely used) used for:
1. Suspected Mycobacterial infection (unlikely is no response within 2 weeks (use anti-TB therapy))
2. Suspected Vasculitis / Connective-Tissue Disorder (response of Temporal-Arteritis is dramatic (use Steroids))
What is a Fabric Fever Pyrexia of Unknown Origin
The fever is real but self-induced (like by self-injection)
What is the most helpful tool in diagnosing “Fabricated Fever Pyrexia of Unknown Origin”?
Microbiology - multiple different organisms on a blood culture
Note - the patient will often continur despite being verry sick, psychiatric expertise should be sought
What are the common outcomes of Pyrexia of Unknown Origin?
- Spontaneous Resolution (commoner in young compared with old)
- Some patients respond to NSAID’s / Steroids
- Regular Re-appraisal required