2. Introduction
Body teperature is normally maintained within
1-1.5°c in arange of 37-38° c ,normal body
temperature is generally cosidered to be 37°c
.
Low levels occur at 6 A.M and higher levels
at 4 - 6 P.M
3. • Normal body
temperature is
maintained by a complex
regulatory system in the
anteroir
hypothalamus,preoptic
area,temperature
sensitive area,thermal
set point .
4. Pathogenesis of fever
Pyrogens
Substances mediate the elevation of core body temperature.
Exogenous and endogenous pyrogens.
Exogenous pyrogens:
Derived from outside the host ,like Microorganisms, toxins and
microbial products,large molecule ,can not pass blood brain barrier
It induce release of endogenouse pyrogens from macrophages.
5. Endogenous pyrogens
derived from the
macrophages ,small
molecule ,can pass blood
brain barrier.
•Pyrogen cytokines trigger
hypothalamus to release
PGE2 resulting in resetting
of thermostatic
temperature,activation of
vasomotor center
,vasodilatation and heat
production.
6. Pyrexia of Unknown Origin
• Original Definition (by Petersdorf and Beeson, 1961)
• Temperatures ≥ 38.3ºC (101ºF) on several
occasions
• Fever ≥ 3 weeks
• Failure to reach a diagnosis despite 1 week of
inpatient investigations or 3 outpatient visits .
7. Pyrexxia of Unknown Origin
New definition;
temperature > 38 ° c,
lasting for more than 14 days
without an obvious cause despite a comlete
history, physical examination and routine
screening laboratory evaluation.”
8. Factors that may make it difficult to find a
cause include:
A common illness that does not have the usual
symptoms,sinusitis may be a symptomatic.
Illness, whose other symptoms appear later
Illnesses who may have a delayed positive
test
Person is unable to communicate about other
symptoms .
Genetic condition that causes periodic fevers.
9. common causes of PUO
Infection
(40%)
Malignancy
(25%)
Autoimmun
e Disease
(15%)
Others/
Miscellaneo
us (10%)
Undiagnose
d (10%)
10. Classification Durack and Street’s classification
Classical
Nosocomial
Neutropenic
PUO associated with HIV infection
11. Classic PUO
Temperature >38.3°C (100.9°F)
Duration of >3 weeks
Evaluation of at least 3 outpatient visits or 3 days in
hospital
Etiologies
I. Infections
II. Malignancies
III. Collagen Vascular Disease
Others/Miscellaneous which includes drug-induced fever.
12. 1. Infections
Bacterial: abscesses, TB,
complicated UTI,
endocarditis, osteomyelitis,
sinusitis, prostatitis,
cholecystitis, empyema,
biliary tract infection,
brucellosis, typhoid,,,, etc.
Viral: CMV, infectious
mononucleosis, HIV, etc.
Parasite: Malaria,
toxoplamosis,
leishmaniasis, etc.
Fungal: histoplasmosis, etc.
As duration of fever
increases, infectious etiology
decreases
Malignancy and factitious
fevers are more common in
patients with prolonged FUO.
13. 2 . Malignancies
Haematological
Lymphoma
Chronic leukemia
Non-haematological
Renal cell cancer
Pancreatic cancer
Colon cancer
Hepatoma
17. Fever pattern
Continuous fever: e.g. lobar
pneumonia, typhoid, urinary
tract infection,brucellosis.
Intermittent fever:
e.g. malaria, pyaemia,
or septicemia..
Remittent
fever: e.g, infective
endocarditis.
Pel-Ebstein fever
; Hodgkin's lymphoma
18. Nosocomial PUO
Temperature >38.3°C
Patient hospitalized ≥ 24 hours but no fever or incubating on admission
Evaluation of at least 3 days
More than 50% of patients with nosocomial PUO
are due to infection.
Focus on sites where occult infections may be
sequestered, such as:
- Sinusitis of patients with NG or oro-tracheal tubes.
- Prostatic abscess in a man with a urinary catheter.
25% of non-infectious cause includes:
- Acalculous cholecystitis,
- Deep vein thrombophlebitis
- Pulmonary embolism.
19. Immune deficient/ Neutropenic PUO
Temperature >38.3°C
Neutrophil count ≤ 500 per mm3
Evaluation of at least 3 days
Patients on chemotherapy or immune deficiencies are
susceptible to:
- Opportunistic bacterial infection
- Fungal infections such as candidiasis
- Infections involving catheters
- Perianal infections.
Examples of aetiological agent:
- aspergillus
- Candida
- CMV
- Herpes simplex
20. HIV-associated PUO
Temperature >38.3°C
Duration of >4 weeks for outpatients, >3 days for inpatients
HIV infection confirmed
HIV infection alone may be a cause of fever.
Common secondary causes include:
- Tuberculosis
- CMV infection
• Non-Hodgkin's lymphoma
- Drug-induced fever
26. Travel
Residental area
Occupation
Contact with domestic / wild animal / birds :
Diet history
Sexual orientation
Close contact with TB patients
36. STAGE 3 [CONT] ; Imaging
Studies
Chest radiograph
CT of abdomen or pelvis with
contrast agent
Gallium 67 scan
MRI of brain
PET scan
Transthoracic or transesophageal
echocardiography
Venous Doppler study
38. Pyrexia of Unknown Origin
The majority of disease remaining after an
initial NEGATIVE work-up are:
1. Neoplasm
2. Seronegative Collagen Vascular Disease
3. TB
4. Drug
5. Elderly with Endocarditis
6. HIV with or without infection or malignancy
7. Implanted prosthetic devices
8. Travel … New Exposure
38
39. Stage 4
Therapeutic trials:
Empirical treatment with corticosteroids or NSAIDS or
antimicrobials
Antimycobacterial agents in AIDS & neutropenic
Blind therapy;
40. Therapeutic Trials
Limitation and risk of empirical therapeutic
trials:
Rarely specific
Underlying disease may remit spontaneously false
impression of success.
Disease may respond partially and this may lead
to delay in specific dx
SE drugs can be misleading.
40
41. Therapy withheld until cause is found
Empirical corticosteroids or anti inflammatories in
temporal arteritis.
Vital sign instability & neutropenia –
Fluoroquinolones + piperacillin,
vancomycin + ceftazidime/cefepime/
carbapenem with or without aminoglycoside,
42. Therapeutic Trials
What is the best
therapy for PUO
patient?
To hold therapeutic
trials in the early
stage … demolish…
except in:
Patient who is very
sick to wait.
All tests have failed
to uncover the
etiology.
42
43. Prognosis
Prognosis is determined primarily by
the underlying disease.
Outcome is worst for neoplasms.
FUO patients who remain
undiagnosed after extensive
evaluation generally have a
favorable outcome and the fever
usually resolves after 4-5 weeks.
43
44. Summary
FUO is often a diagnostic
dilemma,quandary.
Infections comprise ~30% of cases
Bone marrow biopsies are of low
diagnostic yield
Diagnostic approach should occur in a
step-wise fashion based on the H&P
Patient’s that remain undiagnosed
generally have a good prognosis
44
45. References
NELSON ESSENSSIALS OF PEDIATRICS 6th
ED.
Harrison’s principles of internal medicine
18th edition.
Mandell, Bennet & Dolin’s, principle of infectious
disease 6th edition.