Fever
&
Fever of Unknown Origin
Prof Emine ALP MESE, MD,PhD
Infectious Diseases & Clinical
Microbiology
After this lecture you suppose to:
• Remember the pathogenesis of fever
• Learn the definitions: normal body temp,
fever, circadian ryhtm, fuo, hyperprexia and
hyperthermia
• Describe the fever patterns
Body Temperature
Body temperature is
regulated at the level of
the hypothalamus.
In a neutral temperature
environment, the
metabolic rate of humans
produces more heat than
is necessary to maintain
the core body
temperature at 37°C.
http://www.siemenslab.de/researc
h_detection.html
Hypotalamic
Set point
37°C
Hyphot. starts
Cooling
mechanisms
Blood temp
37°C
Hyphothalamus
Blood temp
37°C
Hyphot. starts
warming
mechanisms
Behavioral changes:
Seek warm rooms, add
extra clothing, and
reduce activity.
Warming
Mechanisms
Heat conservation:
vasoconstriction
Heat production:
shivering, nonshivering
thermogenesis,
increased metabolic
activity,
Heat loss are accelerated
through vasodilation and
sweating.
Cooling
Mechanisms
Behavioral changes are also
triggered at this time and
removal of insulating clothing
or bedding takes place.
Loss of heat by sweating and
vasodilation continue until the
temperature of the blood
supplying the hypothalamus
matches the lower setting.
Not everybody has exactly the
same body temperature
There is a range for each
individual!
18–40 years:
mean oral temperature is
36.8° ± 0.4°C
Circadian rythm
A.M vs P.M.
0.5°C
Normal body temperature is low in the early morning (6 a.m.)
and high in evening (4-6 p.m.) varying 0.5°C (0.9°F) over the
course of the day (Circadian rythim is also controlled in the
thermoregulatory center).
FEVER
Elevation in core body temperature above the daily
range for an individual.
Characteristic feature of most infections but is also
found in a number of noninfectious diseases such as
autoimmune and autoinflammatory diseases.
Temp AM >37.2°C
Temp PM >37.7°C
FEVER
FEVER
> =37.8° C orally
(> =38.2° C rectally
0.4 more than oral measurement)
The thermostat setting in the
hypothalamic thermoregulatory
center shifts upwards during a
fever.
PGE2
UptoDate
Pyrogens
Exojen
pyrogens
Endojen
pyrogens
LPS of
IL 1
Gr – bacteria
(endotoxins)
TNF alpha
S. aureus toxintoxc shock synd
INF gamma
IL 6
Causes of fever
Infectious (most common)
Neoplastic
Inflammatory (including rheumatic,
nonrheumatic, and drug-related)
Approach to Fever
History…
Any clue helps!
Laboratory tests…
CBC
BS
UA
PA CXR
Liver enzymes
Blood/urinary culters
……
What r u looking for?
Fever & Rash
Photo courtesy of
Stephen E. Gellis, MD
Courtesy of LindseyBaden
Courtesy of Yale Resident’s Slide Collection
Fever after travel
Flu
STD
etc
Flu,
STD
etc
Flu
STD
etc
SFV
Malaria
Yellow fever
Ebola
Hepatitis
etc
Tb
Brucellosis
Sandfly
F
Tb
Parasi
tes
malar
ia
Fever, weight loss, night sweats
BRUCELLOSIS!
MALIGNITIES!
Fever & arthritis
Fever and neck stiffness
Fever and LAP
Fever Patterns
Febris continua
39,2
39,1
39
38,9
38,8
38,7
38,6
38,5
38,4
38,3
38,2
1
2
3
4
5
6
7
8
9
10
11
12
13
Temperature remains above normal throughout the day and does
not fluctuate more than 1 °C in 24 hours,
Lobar pneumonia, typhoid, urinary tract infection, brucellosis, or
typhus.
Febris intermittant—hectic intermittan
41
40
39
38
37
36
35
1
2
3
4
5
6
7
8
9
10
11
12
13
The temperature elevation is present only for a certain period,
later cycling back to normal
Malaria, kala-azar, pyaemia, or septicemia.
Febris remittans
41
40
39
38
37
36
35
34
1
2
3
4
5
6
7
8
9
10 11 12 13
Temperature remains above normal throughout the day (not
returns to normal) and fluctuates more than 1 °C in 24 hours, e.g.,
infective endocarditis, tuberculosis, mycoplasma inf. etc.
Febris recurrence
39,5
39
38,5
38
37,5
37
36,5
36
35,5
35
34,5
1
2
3
4
5
6
7
8
9
10 11 12 13 14 15 16
Febrile episodes are separated by normal temperature for more than
one day, e.g. Borrelia infection (relapsing fever), rat bite fever, dengue
fever (saddleback fever), malaria (tertian and quartan fever), Pel-Ebstein
fever.
Saddleback fever
Initially pyrexia lasts for 2–3 days followed by a remission
lasting for 2 days and the fever reappears and continues for 2–
3 days, e.g. Dengue fever.
The Pel-Ebstein pattern
Fever lasting 3–10 days--followed by afebrile periods
of 3–10 days
Classic for Hodgkin’s disease and other lymphomas
Cyclic neutropenia
Fevers occur every 21 days and accompany the
neutropenia.
Fever & Pulse
For each 1 °C elevation of body
temperature
–O2 consumption increase 13%
–Heart rate increase 10-15/min
–Metabolic rate increase 10-15%
–Insensible water loss increase 300500ml/m2/day
Pulse-temperature deficits
Relative bradycardia = Faget’s sign
Typhoid fever
Brucellosis
Leptospirosis
Some drug-induced fevers,
Factitious fever
Relative tachycardia
Severe sepsis
Hypertiroidism
Shock
Anemia
Dyphteria
• Immunsupressive patients
• Alcoholics
• Chronic renal failure patients
• Elderly persons
they can remain without fever
Fever of Unknown Origin
The definition of FUO
• Fever higher than 38.3ºC on several occasions
• Duration of fever for at least three weeks
• Uncertain diagnosis after one week of study in
the hospital
by Petersdorf and Beeson in 1961
•
•
•
•
•
•
•
•
Prior to concluding that a patient has an FUO, the following
evaluation should have been performed and should have
been unrevealing:
History
Physical examination
Complete blood count, including differential and platelet count
Blood cultures (three sets drawn from different sites with an
interval of at least several hours between each set; in cases in
which antibiotics are indicated, all blood cultures should be
obtained before administering antibiotics)
Routine blood chemistries, including liver enzymes and bilirubin
If liver tests are abnormal, hepatitis A, B, and C serologies
Urinalysis, including microscopic examination, and urine culture
Chest radiograph
David H Bor. UpToDate
FUO Types
Classical FUO
Nosocomial FUO
Neutropenic FUO
HIV-Associated FUO
38.3 C
Causes of classical FUO
Infections
Localized pyogenic infections
Intravascular infections
Systemic bacterial infections (TB, Bruc.)
Fungal infections
Viral infections
Parasitic infections
1
Malignancies commonly associated with
FUO
Hodgkin’s disease
Non-hodgkin’s lymphoma
Leukemia
Renal cell carcinoma
Hepatoma
Colon carcinoma
Atrial myxoma
2
3 Inflamatory/otoimmun diseases
Other definitions
Hyperpyrexia
Hyperpyrexia is the term for an
extraordinarily high fever
>41.5C
(Most common in CNS hemorrhagies, may be
seen in severe infections..)
Hyperthermia
High body temperature but not
Fever!!
• Exogenous heat
exposure
• Endogenous heat
production
• Hypotahalamic set
point UNCHANGED!
• NO pyrogens!
• NO response to
antipyretics!
• Heat Stroke
• Drug induced
Hyperthermia
• Neuroleptic
malignant
syndrome
• Serotonin syndrome
• Malignant
hyperthermia
• Endocrinopathy
• CNS damage
Hyperthermia
Trigger fever
Amphetamines
Cocaine
Methylenedioxymethamphetamine
(MDMA, or Ecstasy)
Antipsychotics
Anesthetics
Heat production
β-Lactam antibiotics
Sulfa drugs
Phenytoin
Carbamazepine
Procainamide
Quinidine
Amphotericin B
Interferons
DRUG FEVER
• Fever out of proportion
to clinical picture!
• Associated findings:
– Rigor (43%), Myalgia
(25%), Rash (18%),
Headache (18%),
– Leukocytosis (22%),
Eosinophilia (22%),
Serum sickness,
Proteinuria
– Abnormal liver
function test
Onset: 1-3 weeks
after the start of
therapy
Duration: remits 23 days after
therapy is stoped
The autoinflammatory diseases
Adult and juvenile
Still’s disease
Recurrent fever
FMF
Hyper-IgD syndrome
Most autoimmune
diseases & all
autoinflammatory
diseases
Familial cold-induced autoinflammatory
syndrome
Neonatal-onset multisystem autoinflammatory
Disease
Blau’s syndrome, Schnitzler’s syndrome,
Muckle-Wells syndrome
TNF receptor–associated
periodic syndrome.
FACTITIOUS FEVER
Treatment of Fever
At these situations fever should absolutely be
dropped ;
• Children with a tendency to febrile
convulsions
• Pregnant women
• Elderly patients (delirium)
• Patients with impaired cardiac, pulmonary,
renal or cerebral function