PYREXIA OF
UNKNOWN ORIGIN
PRESENTED BY:
TANVI SINGLA

Regulates normal body temperature
Normal Rectal temp. being
97.7-99.5°F
Oral temp. being 0.7°F
lower than rectal
while axillary being 1.2°F
lower than rectal.
Daily normal variation
being 0.5-1°F
With evening temperatures
being higher than the
morning
If body temp. exceeds
normal variation in an
individual, that’s called
FEVER

Liebermiester’s Rule: With each degree centigrade
rise in body temp. , heart rate increase by 8 per min
Except in those diseases where relative bradycardia
sets in.

DEFINITION
PETERSDORF
AND BEESON
1961
TEMP> 101°F
ON SEVERAL
OCCASIONS
DURATION OF
FEVER > 3
WEEKS
FAILURE TO REACH
DIAGNOSIS
DESPITE 1 WEEK OF
INPATIENT INV.

DURACK & STREET’S CLASSIFICATION
CLASSIC
PUO
• 3 OUTPATIENT VISITS OR 3 DAYS IN HOSPITAL W/O ELUCIDATION OF CAUSE
• OR 1 WEEK OF “INTELLIGENT AND INVASIVE” AMBULATORY INV.
NOSOCOMIAL
PUO
•IN HOSPITALISED PATIENTS TEMP> 101°F DEVELOPS ON SEVERAL OCCASIONS WHO IS
RECEIVING ACUTE CARE AND WHOM WAS NOT MANIFEST OR INCUBATING AT TIME OF
ADMISSION
•3 DAYS OF INV. INCLUDING ATLEAST 2 DAYS INCUBATION OF CULTURES
NEUTROPENIC
PUO
•TEMP> 101°F ON SEVERAL OCCASIONS IN PATIENTS WHOSE NEUTROPHIL
COUNT IS <500uL(n 2-7x10^3) OR EXPECTED TO FALL WITHIN 1-2 DAYS
•NO SPECIFIC CAUSE IDENTIFIED 3 DAYS OF INV. INCLUDING ATLEAST 2 DAYS INCUBATION OF
CULTURES
HIV-
ASSOCIATED
PUO
• >101°F ON SEVERAL OCCASIONS OVER A PERIOD OF >4 WEEKS FOR
OUTPT. OR >3 DAYS FOR INPT. WITH HIV
•NO SOURCE REVELAED OVER 3 DAYS INV. INCLUDING 2 DAYS
INCUBATION OF CULTURES

COMMON CAUSES OF PUO
TB being the no. 1
DRUG FEVER

INFECTIONS
Bacterial Infection: Common etiologies
•Chronic sinusitis
•Mastoiditis
•Salmonellosis
•Abscesses(subdiaphragmatic,liver,renal,retroperitoneal,
paraspinal)
•Chronic prostatitis
•Pyelonephritis
•Bacterial endocarditis(esp if caused by HACEK group)
•Osteomyelitis(esp in cases of implantation of
prostheses)

Uncommon
•Leptospirosis
•Brucellosis
•Chlamydia
•Rickettsial infections(Q fever, Scrub Typhus,
Rocky Mountain Spotted fever)

•TB meningitis
•Spinal TB
•Bone and joint TB
•Grannulomatous hepatitis
•Abdominal TB
•Genitourinary TB
•Tubercular lymphadenopathy

VIRAL:
• CMV
•EBV
•HIV
FUNGAL:
•Blastomycosis
•Histoplasmosis
•Cryptococcus
PARASITIC
•Malaria
•Toxoplasmosis
•Leishmaniasis

NEOPLASMS
All kinds of

AUTO-IMMUNE DISORDERS
•SLE
•Vasculitis
•Adult still’s disease
•Temporal arteritis

MISCELLANEOUS
Hyperthyroidism
Phaechromocytoma
Metabolic disorders
DRUG FEVER:
•Antimicrobials(Beta lactum
antibiotics)
•Cardiovascular (Quinidine)
•Antineoplastic
•Antiepileptic (phenytoin)

A 45 year old man was admitted to the ICU
with acute MI, thrombolysed and
reperfused, but then went into persistent
hypotension following a cardiac arrest. He
developed fever on Day 5. Routine blood
investigation showed a polymorpho-
nuclear leucocytosis. Blood culture was
diagnostic.
What could it be???

NOSOCOMIAL PUO
ETIOLOGY
Infections
Non infectious cause
Undiagnosed
Others
•Accounts for 50%
• suspects will be I/V lines, prothesis, septic
phlebitis
•Focused approach on sites where occult
infection may be present eg sinuses of intubated
patients.
Accounts for 25%
•Acalculous cholecystitis
•DVT
•Pulmonary Embolism
Includes drug fever,
withdrawal or
transfusion rxns or post
myocardial infarction
syndrome.
20% remains undiagnosed

A 14 year old boy was admitted with high grade
fever and pallor. On examination no
hepatosplenomegaly, lymphadenopathy or bone
tenderness were present. The blood counts were
as follows: Hb 8gm%, TLC 3800, P8 L86 E4 M2,
ESR 20 mm in 1st hr. Platelet count 2.5 lakhs.
What could it be???

NEUTROPENIC INFECTIONS
Patients on chemotherapy or immune deficiencies are more
susceptible to:
•Oppurtunistic bacterial infections
•Fungal infections like candidiasis
•Bacteremic infections
•Infections involving catheters
•Perianal infections
Most common etiological agents are:
•Aspergillus
•Candida
•CMV
•Herpes simplex

HIV – associated PUO
HIV Infection as such may be the cause
Other secondary causes are:
Pulmonary Tuberculosis
Pneumocystis Infection
Toxoplasmosis
Salmonellosis
Cryptococciosis
Cytomegalovirus infection
M. Avium or M. Intracellulare
Non-Hodgkin’s Lymphoma
Drug induced fever

PYREXIA
OF
UNKNOWN
ORIGIN
- A CLINICAL
APPROACH

HISTORY TAKING
History of present illness
1)Onset :
• Acute: Malaria, pyogenic infection
• Gradual: TB, typhoid fever
2) Character:
high grade- UTI, TB, malaria, drug
3) Pattern: Whether returns to normal or not
• Sustained/ persistent: typhoid, drugs

•Intermittent fever:
Daily spikes: Abscesses, TB, Schistosomiasis
Twice – daily spikes: Leishmaniasis
•Relapsing/recurrent fever: Non falciparum malaria,
Brucellosis, Hodgkin’s
4) Antecedents
-Prior to onset of fever:
•Dental extraction: infective endocarditis
•Urinary catheterization: UTI, bacteremia

5) Associated symptoms:
• Rigors and chills
 Bacterial, rickettsial and protozoal disease
Influenza, lyphoma, leukaemia, drug-induced
•Night sweats: TB, Hodgkin’s lymphoma
•Loss of weight: malignancy, TB
•Cough and dyspnoea: miliary TB, multiple pulm.
Emboli, CMV
•Headache: Giant cell arteritis
•Joint pain: RA,SLE, vasculitis

• Abd. Pain
– Cholangitis, biliary obstruction, perinephric abscess,
Crohn’s disease, dissecting aneuryms,
gynaecological infection
• Bone pain
– Osteomyelitis, lymphoma
• Sorethroat
– IM, retropharyngeal abscess, post-Streptococcal
infection
• Dysuria, rectal pain
– Prostatic abscess, UTI
• Altered bowel habit
– IBD, typhoid fever, schistosomiasis, amoebiasis
• Skin rash
– Gonococcal infection, PAN，NHL, dengue fever

• Past Medical History
– Malignancy = leukemia, lymphoma, hepatocellular ca
– HIV infection
– DM
– IBD
– collagen vascular disease-SLE, RA, giant cell arteritis
– TB
– Heart disease: valvular heart disease
• Past Surgical History
– Post splenectomy/ post- transplantation
– Prosthetic heart valve
– Catheter, AV fistula
– Recent surgery/ operation

• Drug History
– Drug fever occur within 3 months after
start of drugs
• may cause low grade fever, usually
associated with rash
• Due to the allergic reaction, direct effect of
drug which impair temperature regulation
(e.g. phenothiazine)
• E.g. Antiarrhythmic drug: procainamide,
quinidine; Antimicrobial agent: penicillin,
cephalosporin, hydralazine
– After fever: may modify clinical pictures,
mask certain infection e.g. SBE, antibiotic
allergy

Family History
–Anyone in family has similar problem:
TB, familial Mediterranian fever

• Social History
– Travel
• amoebiasis, typhoid fever, malaria,
Schistosomiasis
– Residental area
• malaria, leptospirosis, brucellosis
– Occupation
• farmers, veterinarian, slaughter-house workers =
Brucellosis
• workers in the plastic industries = polymer-fume
fever

–Contact with domestic / wild animal /
birds :
• Brucellosis, psittacosis (pigeons),
Leptospirosis, Q fever, Toxoplasmosis
–Diet history
• unpasteurized milk/cheese =
Brucellosis
• poorly cooked pork = Trichinosis
–Sexual orientation = HIV, STD, PID
–Close contact with TB patients

EXAMINATION
• General
Calm, conscious, oriented to time, place
and person
Ill/not ill
Built/Weight loss (chronic illness)
Vitals
CLIPJES(Skin rash)

HEAD AND NECK
• Feel temporal arteries (tender & thicken)
• Eyes – iritis/conjuctivitis (ct disease –
reiter syndrome)
• Jaundice (ascending cholangitis)
• Fundi – choroidal tubercle (miliary tb),
roth’s spot (ie) and retinal haemorrhage
(leukaemia)
• Lymphadenopathy

FACE AND MOUTH
• Butterfly rash
• Mucous membranes
• Seborrhoic dermatitis (HIV)
• Mouth ulcers (SLE)
• Buccal candidiasis
• Teeth & tonsils infection (abscess)
• Parotid enlargement
• Ears – otitis media

HANDS
• Stigmata of Infective Endocarditis
• Vasculitis changes
• Clubbing
• Presence of arthropathy
• Raynaud’s phenomenon

ARMS
• Drug injection sites
• Axillary nodes (lymphoma, sarcoidosis,
focal infection)
• Skin

CHEST
• Bony tenderness
• CVS – murmurs (ie atrial myxoma), rubs
(pericarditis)
• Resp – signs of pneumonia, TB, empyema
and lung ca

ABDOMEN
• Rose coloured spot
(typhoid fever)
• Hepatomegaly
(hepatic ca,
alcoholic hepatitis)
• Splenomegaly
(haemopoietic
malignancy,
malaria)
• Renal enlargement
(renal cell ca)
• Testicular
enlargement
(seminoma)
• Penis & scrotum –
discharge/rash
• Inguinal ligament

• Per rectal exam – mass/tenderness in
rectum/pelvis (abscess, ca, prostatitis)
• Vaginal Examination – collection of pelvic
pus/ Pelvic Inflammatory Disease

CENTRAL NERVOUS SYSTEM
• Signs of meningism (chronic tb meningitis)
• Focal neurological signs (brain abscess,
mononeuritis multiplex in polyarteritis
nodosa)

STAGE 1: LAB INVESTIAGTIONS
Stage 1: (screening tests)
1. Full blood count
(evalute anaemia, +nce of
blasts, thrombocytopenia)
2. ESR & CRP
3. LFTs
4. Blood culture
5. Serum virology
(EBV,CMV)
6. M/b panel
(LFT,LDH,creatinine)
7. Urinalysis and
culture
8. Sputum culture and
sensitivity
9. Stool and occult
blood
10. CXR
11. Mantoux test

STAGE 2: LAB INVESTIGATIONS
1. Repeat history and
examination
2. Protein
electrophoresis
3. CT (chest, abdomen,
pelvis)
4. Autoantibody
screen (ANA, RF,
ANCA, anti-dsDNA)
5. Echocardiography
6. Bone scan(osteomye.)
7. Lumbar puncture
8. Consider PSA, CEA
9. Temporal artery
biopsy
10.HIV test counselling

STAGE 3: LAB INVESTIAGTIONS
1. Bone marrow aspiration
2. Biopsy
3. Bronchoscopy
4. Exploratory laprotomy

STAGE 4: TREATMENT

• Continued observation and
examination
• Therapy based on probability of
various causes of fever in that setting
• Avoid shotgun empirical approach
• Antibiotic??- mask infection

Indication for immediate
empirical therapy
• Vital instability
• Neutropenia
• Nosocomial- if bacteremia, fungemia or
persistently high viral loads are a threat
• Cirrhosis, asplenia, immunosuppressive
drug use, exotic travel, environmental
exposures

• change IV lines(culture), drugs
stopped for 72 hours and empirical
therapy started
• Vancomycin (MRSA) with
piperacilin/tazobactum(broad
spectrum gram negative)

• Granulomatous hepatitis or positive
TST- therapeutic trial for TB upto
6wks
• Glucocorticoids and NSIADS- trial
only after ruling out any infections.
Dramatic response in autoimmune
diseases.
Last resort- if fever continues uptil 6 mnths

Initiation of empirical therapy
• Doesnot mark end of treatment
• Rather it commits physician to more
• Thoughtful
• Reeaxamination and
• Evaluation

HAPPY EARTH DAY
Thank you 