Fever: What, Why, How?
Definition of fever
• Common medical sign and patient felt symptom
• Elevated temperature of > 37.20C (mid-morning oral) or
> 37.80C (other times of the day).
• The core temperature is elevated due to re-setting the
thermoregulatory set-point in the hypothalamus.
• This elevation is controlled hyperthermia/ pyrexia as
opposed to uncontrolled hyperthermia which results
from failed thermoregulatory mechanisms ie: body
produces or absorbs more heat than it can dissipate eg.
Heatstroke, NMS and serotonin syndrome with some
drugs, overheating while wearing PPE, thyrotoxicosis
and pheochromocytoma.
Fever: What’s normal?
Site
Normal (0C)
Fever (0C)
Axilla
36.4
>36.9
Oral
36.8
>37.3
Rectal
37.3
>37.7
From this we can see there are some places that we shouldn’t go near
Skin temp
Core
temp
Hypothalamus
thermostat
Peripheral
receptors
Via lateral
spinothalamic
tract
Effector mechanisms that
increase/ decrease temp
Central
thermoreceptors
Causes of fever
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Influenza
HIV
Malaria
Pyelonephritis
Dengue fever
Infective mononucleosis
SLE
Sarcoidosis
IBD
Kawasaki disease
Leukaemia/ Lymphoma
Hepatobiliary sepsis
Infective endocarditis
PID
CMV
Drug hypersensitivities
Causes of fever
• Persistent fever that escapes diagnosis is
called Pyrexia of Unknown Origin (PUO/ FUO)
• Fevers of less than 3 days duration are often
due to self-limiting viral infection of
respiratory tract, although pneumonia and
UTI’s (esp. in females) are also common
causes.
Fever in recently returned traveller:
Murtagh
Probability diagnosis for Australia:
• Malaria 27%
• Respiratory tract infection (eg. Influenza) 24%
• Gastroenteritis 14%
• Dengue fever 8%
• Bacterial pneumonia 4%
Fever in recently returned traveller:
Murtagh
Serious disorders not to be missed
• Malaria
• TB
• Typhoid
• Encephalitis
• Bacterial meningitis
• Melioidosis
• Amoebiasis
• HIV seroconversion
Fever in recently returned traveller:
Murtagh
Pitfalls (often missed)
• CMV
• EBV
• Infective endocarditis
• Dengue
Mechanisms of fever
• Endogenous pyrogens are also known as cytokines and are
part of the innate immune system, as produced by
macrophages after their TLR’s are activated.
• The major endogenous pyrogens are IL-1, IL-6 and TNFa.
• Exogenous pyrogens include LPS and other endotoxins from
bacteria. LPS is bound by LPS binding protein (an acute
phase protein) and this complex binds to the CD14
receptors of macrophages, resulting in cytokine release (IL1, IL-6 and TNFa).
• All these cytokines eventually end up interacting with
endothelial receptors on vessel walls or microglial cells to
activate the arachidonic acid pathway.
Mechanisms of fever
Arachidonic acid  Prostaglandin H2  Prostaglandin E2 with the help of
COX-2 and PGE2 synthase enzymes
Mechanisms of fever
• PGE2 acts on the Prostaglandin EP3 receptors
in the preoptic area of the hypothalamus,
•  stimulation of the sympathetic output
evoking non-shivering thermogenesis to
produce body heat coupled with peripheral
vasoconstriction to decrease heat loss.
Biological role of fever
Fever plays an important role in body’s defences against
infection since fever:
• Activates T-cell production
• Increases effectiveness of some IFN
• Limits the replication of some viruses/ bacteria
• Increases phagocytosis
• Increased Ig production
Some study actually found reduced mortality in those
infections with significant fever…
But you die when temp rises over 430C
CASE study in fever:
You are a SMO in ED at Mareeba hospital
P.C.
BM, an irritable, but tired 11 year old girl presents
with her worried parents and a 24 hour history of
fever. Her main concern is headache and body aches
and pains with an itchy rash especially on her lower
extremities.
CASE study in fever:
P.C.Hx.
BM has just come back from 2 weeks of camping in her
school holidays when she started complaining of a
headache and fevers.
Her parents noticed she seemed very tired and treated
the headache and fevers with paracetamol, ibuprofen and
increased water intake, which appeared to work for a
while.
Over the past few days they have worsened and
headache is now 8/10 pain and is now accompanied by
generalized myalgia. Eye movement is painful.
Her parents brought her in quickly because they think its
Dengue fever – since she had it while overseas 18 months
ago, they confirm she experienced some diarrhoea.
CASE study in fever:
DDx?
CASE study in fever:
DDx?
• Gastroenteritis?
• Malaria?
• Measles?
• Melioidosis?
• Dengue?
• DHF?
• Meningitis?
CASE study in fever:
DDx
• Gastroenteritis? – why the rash?
• Malaria? – no resp symptoms
• Measles? – no cough
• Melioidosis? – no resp symptoms
• Dengue?
• DHF?
• Meningitis? – no neck stiffness
CASE study in fever:
Medical Hx?
Prev. Dengue fever illness 18 months ago after
family trip to Southeast Asia
CASE study in fever:
O/E
• Temp: 400C
• Bilateral cervical and inguinal lymphadenopathy
• Tender abdomen
• BP 90/50, HR 88, RR 23
• No organomegaly
While examining the patient, she vomits and has a
nose bleed straight shortly thereafter
CASE study in fever:
Dx = Early stage of Dengue Haemorrhagic Fever
Incubation periods of travel related infections
Short (<10 days)
• Influenza
• Dengue
• Yellow fever
• Plague
Incubation periods of travel related infections
Intermediate (10-21 days)
• Malaria
• Typhoid fever
• Scrub typhus
• Q fever
• African trypanosomiasis
Incubation periods of travel related infections
Long (>21 days)
• Malaria
• Hepatitis
• Rabies
• Schistosomiasis
• TB