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ALTERATION OF BODY TEMPERATURE:
³Normal´ body Temperature
Fever
Hyperpyrexia
Hyperthermia
NORMAL BODY TEMPERATURE
The normal body temperature is said to be 37°C (98.6°F) but
the maximal normal temp. range from 37.2°C (98.6°F) at 6
am to 37.7°C (99.9°F) at 4 pm.
The rectal temp. are generally 0.4°C (0.7°F) higher than oral
reading.
Fever is a protective response to infectious & Injury.
Elevated temp. enhances the body¶s innate defense by
making condition less favorable for infectious
microorganism to thrive by:-

1. Elevated temp decreases the levels of Iron in blood

stream, thus inhibiting their growth.

2. People with fever tends to eat less and rely more on

protein & fat sources for energy, which decreases blood
sugar level upon which bacteria normally thrive.

3. There are some bacteria/ microorganism. That are heat

sensitive and do not grow well at elevated body temp.
FEVER: Also known as ³Pyrexia´ or a Febrile response
and archaically known as µargue¶, is a medical symptom.
Fever is caused by resetting of the hypothalomus µset
point¶ by PG¶s a process mediated by cytokins, this
elevated thermoregulatory ³set point means that the
previous ³normal body temp.´ would be considered
hypothalamic.

HYPERTHERMIA: is a uncontrolled increase in body temp

that exceeds the body¶s ability to lose heat without an
elevation of the hypothalamic ³set point´.
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 (Arnow and Flaherty, 1997)
Fever that does not resolve spontaniously in the
period expected for self-limited infection and whose
cause cannot be ascertained despite considerable
diagnostic effort´.
³A prolonged febrile illness without an established
etiology despite intensive evaluation and diagnostic
testing´ ± Up To Date
New definition / Classification developed by Durack
& Street:
2 weeks of fever and 3 days of inpatients
investigation or 3 outpatient visits without finding a
source of fever.
CLASSIFICATION OF PUO
Category of PUO Definition Common etiologies
1. Classic Temperature >38.3ÛC Infection, malignancy,
(100.9ÛF) Collagen vascular
disease
Duration of >3 weeks
Evaluation of at least 3
outpatient visits or 3 days in
hospital
2. Nosocomial Temperature >38.3ÛC Clostridium difficile
Patient hospitalized >= 24 entercolitis, drug-
hours but no fever or induced PE, Septic
incubating on admission thrombophlebitis,
sinusitis
Evaluation of at least 3
days
3. Immune Temperature Opportunnistic
deficient >38.3ÛC bacterial
(neutropenic) Neutrophil count infections,
<=500 per mm³ aspergilloisis,
candidiasis,
herpes virus
4. HIV-associated Temperature Cytomegalo virus,
>38.3ÛC, duration mycobacterium
of >4 weeks for aviumintracellular
outpatients, > 3 e complex,
days for pneumocystitis
inpatients, HIV carinii pneumonia,
infection drug induced,
confirmed. kaposi¶s sarcoma
lymphoma
 !


Infection (30%)
ë Sepsis
Abscess : Intra abdominal, cholecysititis /
cholangitis
Urinary tract infection:
Prostatitis
Dental and sinus infections
Bone and joint infections
ë Imported infections, e.g.. Malaria, dengue, brucelloiss
ë Enteric fevers
ë Endocarditis (HACEK)
j
 
(20%)
Lymphoma and myeloma
Leukaemia
Solid tumours (renal, liver, colon, stomach, pancreas)
C   d d  (15%)
$ Vasculitic disorders (incl. Polyarteritis nodosa and
rheumatoid disease with vasculitis)
$ Temporal arteritis/polymyalgia rheumatica
$ Stystemic lupus erythematosus (SLE)
$ Still¶s disease
$ Polymysositis
$ Rheumatic fever
Miscellaneous (20%)
; Inflammatory bowel disease
; Liver disease: cirrhosis and granulomatous hepatitis
; Sarcoidosis
; Drug reactions
; Atrial myxoma
; Thyrotoxicosis
; Hypothalamic lesions
; Familial Mediterranean fever

N d   
    

(15%)
Ten leading causes of classic PUO among adults at
community hospitals in the United States
Cause % of total
Lymphoma 16
Collagen vascular disease 16
Abscess 13
Undiagnosed cause 09
Solid tumor 08
Thrombosis or haematoma 07
Granulomatous disease, nonmycobacterial 05
Endocarditis 05
Mycobacterial disease 05
Viral disease 05
Remaining causes 11
100
Source: Adapted from Kazanjian 1992
A Prospective study of 100 cases. Kajariwal
D et al. JPGM 2001; 47: 104-7
Infection esp. TB 53%
Neoplasms 17%
Collagen Vascular Disease 11%
Miscellaneous 5%
Undiagnosed 14%
4 ALUATION & APPROACH TO `IAGNOSIS
1. H
  d Ph

4
 
i. Onset : Sudden in pneumonia, pyelitis,
influenza etc.
Gradual ± Typhoid, typhus, pulmonary TB
ii. Rigors : Malaria, filaria, UTI, cholangitis, Hepatic
abscess, septicemia, etc.
iii. Headache : Meningitis, typhoid at onset, encephalitis,
ICSOL & dengue.
iv. Body ache : Dengue, viral fever, secondary syphilis, rat
bite fever etc.
v. Sweating : Malaria, miliary TB, rheumatic fever, hepatic
abscess
 vi. Delirium : Typhoid, septicemia meningitis,
pneumonia etc.
vii. Wt. loss : TB, Chronic suppurative disease like
empyema, lung abscess,
thyrotoxicosis, polyarthritis

other symptoms like association diarrhoea, vomiting, sore

throat, urinary frequency helps in diagnosis.
PAST HISTORY
History of RF, VHD, TB of any form, syphilis, filariasis etc.
P4RSONAL HISTORY
R d   d  in kalazar, Mediterrarean
fever, Trypanosomeasis
I

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   & S

h .
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h  R   

 d  
R  

Occupation- Weil¶s disease
T 
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R 
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  ..-
j
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C h
 
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d  A 

S d.
I d   A
I  h

C  h d   
d 
   d

Brucellosis (cattle)
Psittacosis (Birds)
Leptospirosis (rats & dogs)
Rat bite fever
C  h   with TB or other family member
having infections.

F 

h
 A h  R h C

    

d  .
P

 
U     
 
I C   A < 6
 
d
A. Infections (65%)
B. Neoplastic disease (8%)
C. Autoimmune disease (8%)
D. Miscellaneous (13%)
E. No Diagnosis (6%)

II C   A 6  14
 
d
A. Infections (38%)
B. Neoplastic disease (4%)
C. Autoimmune disease (23%)
D. Miscellaneous (17%)
E. No Diagnosis (19%)
III C   A > 14
 
d
A. Infections (36%)
B. Neoplastic disease (19%)
C. Autoimmune disease (13%)
D. Miscellaneous (25%)
E. No Diagnosis (7%)

II C   A > 65
 
d
A. Connective tissue disease (30%)
1. Temporal arteritis
2. Polymyalgia rheumatica
B. Infection (25%)
C. Cancer (12%)
D. No diagnosis (8%)
E. Reference.
I   P d
I. I   < 10 d

A. Travelers Diarrhea
B. Dengue fever (common)
C. Yellow fever
D. Spotted fever
E. Meningococcemia

II. I   < 21 d


A. Leptospirosis B. Viral hemorrhagic fever
C. Malaria (common) D. Enteric fevers
1. Typhoid Fever (common)
2. Paratyphoid
E. Typhus F. East African Trypanosomiasis
III. I   > 21 d

A. HIV
B. Hepatitis-A (common) & others hepatitis
C. Malaria (common, symptoms may be delayed)
D. TB
E. Amoebic liver abscess
F. Brucellosis
G. Leishmaniasis
Ph


 
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Physical Examination:
1.Temperature: Type of fever
i. Intermittent- with high peaks,
Malaria, acute pyelonephritis, septicemia,
filariasis
ii. Continuous- within range of 2F typhoid, miliary
TB, pneumonias
iii. Periodic or undulating- Hodgkin¶s, relapsed
typhoid, brucellosis
iv. Double rise- Kalazar, malaria, liver abscess,
& Ecoli infections.
2. Pulse rate:
Relative bradycardia- Typhoid, meningitis, dengue,
weil¶s disease

3. Anaemia: Malaria, Kalaza, Chronic sepsis

4. Lymph node:
Generalized- Hodgkin¶s disease, Tb, secondary
syphilis, lymphocytic leukemia
Localized- Plague, glandular fever.
Lymphogranuloma inguinale
5. Jaundice: With fever- infective hepatitis, weil¶s disease,
malaria, liver abscess, infectious mononucleosis.
6. Skin: Rashes- Typhoid, meningococcal meningitis, relapsing
fever, rat bite fever,
Petechial hemarrhages- septicemia, cerbrospinal
meningitis, malignant diphtheria.
7. Clubbing: Lung abscess, bronchiectasis, liver abscess
8. Nails: Transverse white band- undulant fever
9. Arthritis: RF, gout, meningococcemia, leukamia, PAN
10. Herpes labiales: in association with pneumococcal
pneumonia, Streptococcal infection, malaria and
meningococcemia.
11. Nodules: RF, RA, leprosy, erythema nodosum, PAN
Systemic Examination:
Chest findings: Lung abscess, TB
Pneumonia, Ca.
Heart: Bact. Endocarditis
Pericarditis
Myocarditis
Abdomen:
Splenomegaly: j

T
hd
K
- 
SBP
`. TB
L
h
Hepatomegaly: Malaria
Enteric fever
Kala-azar
Leukemia
Lymphoma
Amoebic liver abcess
Hepatocellular Ca.
R 

  
. Chronic pylonephritis
. Ca kidney
. Obstructive uropathy
R 

 
Perianal disease
Local sepsis or abscess
Rectal ± Carcinoma
Prostatic malignancy
Prostatitis
Genitalia:
Ulceration
Discharge
Testicular swelling.
N  
 
Coma Encephalitis Cerebral malaria
Signs of meningeal irritation Meningitis
Focal Sign Brain abscess
Cranial nerve palsy TBM

Fundus:
Hemorrhage and exudates Vasculitis
Roths spot Endocarditis
Choroids tubercle Milliary/Diss.TB
Disseminated fungal infection.
 I VE I I 
CBC
Uri l i
Bl f r
i ti t tf rf l i r l ri
t l i r
X-r t /
Bl Cultur - i , , ti i , rucell i

erum f r ti ies: cteri l, ir l ,fungal, r t al

er l gical test f r syphilis
CSF hen suspecting meningitis, encephalitis
Serum Immunoglobulins- BV CMV IgG, IgM
 COLLAGE VASCULAR DISEASE
GRANULOLOMATOUS DISEASE
Äests for nti antibodies
Complements
Anti eutrophil Cytoplasma antibodies
Cryoglobulins, heumatoid factor
Ähyroid profile for hyperthyroidism
HIV antibody tests
Hepatitis A, B, C iral antibody assay
I  Sd 
Abdominal radiographs for calcifications of adrenals
Routine Abdominal Ultrasound
IV urography
CT scans
MRI
I    d
  

d
Lumber puncture
Skin biopsy for rash
Lymph aspiration or biopsy
BMA or biopsy
Liver biopsy
Laparotomy or laparoscopy

Oh 
Endoscopic examination
Radionucleotide studies (VPRS, PA etc.)
Positron emission tomography (PET)
Echocardiography
 TR4ATj4NT
1. Emphasis on continuous observation and physicals
examination
2. Direct treatment toward the underlying cause.
3. Routine antipyretic is unacceptable in adult hospitalized
patient.
4. Routine use of antibiotic is not recommended for virus
infection.
5. Therapeutic trial of antibiotic are very difficult to interpret.
6. Empirical Th    

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A T
hd

A TB A A  .
 PROGNOSIS IN PUO

The overall mortality of PUO is 30-40% (age under 55

years: 5%; age over 55 years:30%).

Older patients are more likely to have a malignancy. If

no cause is found on exhaustive investigation, the long-
term mortality is low.

On long-term follow-up of these patents no single

disease features strongly and in most cases the fever
settles spontaneously.

About 15% of the patients with PUO have no diagnosis

or resolves spontaneously.
 CONCLUSION
PUO an Evasive clinical problem & difficult to detect
primary care physician first to encounter this condition
needs well planned, strategic approach to work-up the
patients with this problem.
Understanding etiology incorporating thorough history
taking & physical examination with more planned testing
can lead to finally discovery and treatment.
In most case, the causes of PUO is a familiar disease
with an uncommon presentation rather than a rare disease.
Avoid empirical therapy unless there are some modifiers
of disease and special circumstances.
Avoid subtherapeutic dosing and multiple empirical
therapies simultaneously.