SHORT DESCRIPTION ABOUT PYREXIA OF UNKNOWN ORIGIN BY DR. ANAND SINGH BHADORIYA (MBBS)

1. Pyrexia of Unknown Origin

2. Historical Perspective
1878 Invention of thermometer
Carl Wunderlich
1907 First series on prolonged fever
Richard C Cabot - 784 cases
Typhoid fever - 75%
Sepsis - 9%
TB - 7%

3. Historical Perspective
1961 Diagnostic criteria for PUO
(Petersdorf & Beeson)
Illness of at least 3 weeks duration
Fever of >38.3 oC on several occasions
Undiagnosed after 1 week study in hospital

5. PUO Redefined
Durack & Street (1991)
‘Classic’ PUO
Nosocomial PUO
Neutropaenic PUO
HIV associated PUO
Episodic PUO

6. Definition of PUO
Classic PUO
Fever > 38.30C
>3 weeks
3 outpatient visits or
3 days in hospital

7. Nosocomial PUO
Fever > 38.30C, >3 days,
not present or incubating on admission,
negative cultures after 2 days
Neutropenic PUO
Fever > 38.3 0C, >3 days,
< 500 polymorph neutrophils/mm3,
negative cultures after 2 days
HIV-associated PUO
Fever > 38.30C,
>4 weeks for outpatients or
> 3 days for inpatients,
HIV infection confirmed

8. Aetiology of PUO
Infection Neoplasm
CT disorders Miscellaneous
Undiagnosed

10. Infections
Infective Endocarditis
Abscesses
TB
Typhoid, Lyme’s disease
Kala azar, Toxoplasmosis
HIV, EBV, CMV
Candida superinfection

11. Neoplasm
Lymphomas – NHL, HD
Renal cell Carcinoma
Metastatic adenocarcinoma in liver
Leiomyosarcomas of GIT
Atrial myxomas
Aleukaemic leukaemia

12. Connective tissue disorders
Adult Still’s disease
Temporal arteritis + polymyalgia rheumatica
Wegener’s granulomatosis
Cryoglobulinaemia
Polyarteritis nodosa

13. Miscellaneous
Granulomatous diseases
Crohn’s disease
Sarcoidosis
Granulomatous hepatitis
Alcoholic hepatitis
Pulmonary emboli
Subacute thyroiditis
Drug fevers

14. Undiagnosed fevers
Mortality rate 5 yrs after discharge - 3%
Fever abates without treatment in 75%

15. HIV associated PUO
PUO occurs with low CD4 cell count <100/µL
Fever persists for a mean of 42 d before diagnosis
Time taken for diagnosis same as in Classic PUO
Infections commonest cause –
TB, DMAC, PCP, CMV
Leishmaniasis
Disseminated histoplasmosis
Lymphoma, the cause in 7% cases

16. HIV associated PUO
Respiratory tract Pneumocystis, Myc TB,
MAI, CMV
CNS Toxoplasma
GIT Salmonella, Shigella,
Campylobacter
Genital tract, disseminated T pallidum, N gonorrhoeae

18. Nosocomial PUO
Vascular line related staphylococci
Other device related staphylococci, Candida
Transfusion related hepatitis, CMV
Pneumonia (Ventilator) Gm - rods, incl
Pseudomonas
Post-op abscesses Gm – rods, anaerobes
Postgastric surgery systemic candidiasis

19. Neutropaenic PUO
Vascular- line related staphylococci
Oral infection Candida, HSV
Pneumonia Gm – rods, Candida,
Aspergillus, CMV
Soft tissue Mixed aerobes, and
anaerobes

20. Approach to FUO
Stage 1 History
Physical examination
Screening tests
Stage 2 Review history
Repeat physical examination
Specific diagnostic tests
Non-invasive investigations
Sage 3 Invasive tests
Stage 4 Therapeutic trials

21. Investigations in PUO
•Potential diagnostic clues (PDCs) should guide
investigations. Screening tests – low yield
•Non-invasive lab tests diagnosis in ¼ cases
•BMC not justified for routine initial evaluation
BM examination - diagnostic yield 0 – 14%
•Liver biopsy - diagnostic yield – 14%
•Abdominal CT, USG - for all cases of PUO
CT/USG guided biopsy – diagnostic yield

22. Newer modalities
Cultivation dependent microbial detection
Sequence- based molecular methods
Newer diagnostic technologies
High density micro-arrays
Improved nucleic acid subtractive methods
Novel bioassays for toxin activity

23. Newer modalities
Helical CT
MRI
Gallium 67 citrate scan
Tc-99m Ciprofloxacin scan
FDG PET

24. Outcome of PUO
“…90% of patients with FUO should have a
diagnosable condition, the remaining patients will
recover. Patients should rarely die with a diagnosis
of FUO.”
Petersdorf 1992

25. Take-home Message
Uncommon manifestations of common disorders
more likely to be the cause than rare diseases
Keys to successful diagnosis
Diligent history taking & examination &
Perseverance