Pyrexia of Unknown Origin (PUO) is defined as a fever over 38.3°C on multiple occasions for more than 3 weeks without a diagnosis after a week of inpatient investigations. Common causes include infections like tuberculosis, abscesses, or endocarditis, inflammatory conditions such as adult Still's disease or systemic lupus erythematosus, and malignancies. A thorough history, physical exam, and baseline investigations are crucial, along with repeating tests and considering more invasive procedures if needed. The diagnostic approach involves 4 stages: collecting a detailed history, comprehensive exam, initial non-invasive investigations, and potentially empirical therapy or therapeutic trials if the cause remains unknown.

1. Pyrexia of Unknown Origin(PUO)
ASCITES AND HEPATORENAL SYNDROME
BY
Dr/ Mahmoud S. Desoky

2. Importance
 One of the most challenging problems a physician
faces in practice
 A truly significant test of his clinical skills
 A thorough and detailed history with a good clinical
examination and relevant investigations are necessary
in every patient of prolonged pyrexia.

3. “Humanity has three great enemies :
Fever, famine and wars. Of these by far
the greatest, the most terrible is fever” -
Sir William Osler (1849-1919).
In the 19th century, febrile illness
caused more than 2/3rd of total
deaths.

7. PUO
Definition
Petersdorf and Beeson defined pyrexia of unknown
origin (PUO) in 1961
It is defined as:
• A temperature greater than 38.3°C on several
occasions.
• More than 3 weeks of illness.
• Failure to reach a diagnosis, after 1 week of
inpatient investigation.
NBT : 37.2 c(98.9)

8. S
Classification

10. PUO(Causes)
Infection
• Tuberculosis (especially extra-
pulmonary)
• Abscesses (intra-abdominal, pelvic,
dental, renal, perinephric)
• Endocarditis
• Osteomyelitis
• Epstein-Barr virus mononucleosis
• Cytomegalovirus
• Cat scratch disease
• Lyme disease
• Prostatitis

11. PUO(Causes)
inflammation
• Adult Still’s disease (adult
juvenile rheumatoid arthritis)
• Polymyalgia rheumatica
• Temporal arteritis
• Rheumatoid arthritis
(especially late onset)
• Systemic lupus erythematosus
• Inflammatory bowel disease

12. PUO(Causes)
Malignancy
• Leukemia and lymphoma
• Metastatic cancers
• Renal cell carcinoma
• Colon carcinoma
• Hepatoma
• Myelodysplastic syndromes
• Pancreatic carcinoma
• Sarcomas

13. PUO(Causes)
Miscellaneous
• Drug-induced fever
• Complications from cirrhosis
• Factitious fever
• Hepatitis (alcoholic,
granulomatous, or lupoid)
• Deep venous thrombosis
• Sarcoidosis
• Mediterranean familial fever
• Hyperthyroidism

14. Approach of Patient with PUO
The first and foremost step is to establish that
fever really exists. Strict oral temperature
record must be kept. Detailed history and
physical examination has probably not more
significance in any other category of patients
than PUO. Clinical evaluation should be
repeated frequently and a thorough review
of patients with already done investigations
should be taken.
Approach to PUO

15. 4 stages of assessment
Stage 1: history
Stage 2: examination
Stage 3: Investigations
Stage 4: Therapeutic trial
Approach to PUO

16. History
A detailed, careful, day by day history of symptoms,
signs previous treatment given, response to
treatment, all investigations and patient’s general
condition
Some guiding points for history of fever could be :
1. Since when
2. Onset - acute or gradual
3. Rigors, is it daily or on alternative days
4. Diurnal variation
5. Response to previous treatment
6. Associated symptoms(wt. loss, headache. Myalgia.

17. History of associated symptoms should be
taken in same details for each symptom.
Weakness, myalgia, headache, vague
abdominal discomfort, burning of
micturition (during fever) can be due to
fever itself.
Interpretation of symptoms is very
important and sometimes very difficult.
Existing data shows that only about half
patients with abdominal complaints and one
fourth with CNS (central nervous system)
symptoms had disease at the corresponding
site.

18. Highest yield questions include asking about
past medical history (e.g. recurrent TB,
metastatic cancer, Crohn’s disease),
medications, family history (e.g.
Mediterranean familial disease), animal
contact (e.g. psittacosis from parakeet
contact), sexual history (e.g. rectal
abscesses from anal penetration), and
travel history (e.g. amoebiasis)

19. social practices including drug use,
unusual diet (e.g. unpasteurised
products), and environmental
exposures may also be helpful

20. Physical Examination
 Documentation of fever and exclusion
of factitious fever (may be up to 10% of
cases)
 An adequate physical exam is one that
looks at every system for subtle clues,
including full neurological, head and
neck, musculoskeletal, dermatological,
and fundoscopic exams.

21. Investigations
 baseline investigations i.e. CBC, ESR,
LFT, RFT, CXR (chest X-ray), ECG, urine
stool, sputum for AFB (acid fast
bacillus) and blood cultures.
Repetition of some of these basic
investigations like CXR and blood
culture give positive result in
significant number of patients.

22. Investigations
 Non invasive : USG abdomen, USG neck for lymph node, CT scan of
chest and abdomen or other specific areas, 2D echo (two dimensional
echocardiography), trans-esophageal echo, infectious disease serology
like brucella, rickettsia, ANA (antinuclear antibodies) ds-DNA (double
stranded deoxyribo nucleic acid), C-ANCA, P-ANCA (P - Antineutrophilic
cytoplasmic antibodies), C3 (complement 3), C4 (complement 4) levels,
ACE (angiotensin converting enzyme) levels, ferritin, thyroid function
tests and tumor markers [like PSA (prostate specific antigen), CEA
(carcino embryonic antigen)].
Specific investigations

23. Investigations
Invasive : Lymph node excision biopsy,
lumbar puncture, aspiration of pleural / ascitic
/ synovial fluid, skin biopsy, liver biopsy, bone
marrow biopsy and biopsy of a lesion shown
on radiological investigation.
Specific investigations

24. Empirical therapy
Treat. Of infective endocarditis and sepsis
anti tuberculosis therapy
anti malarial
anti rheumatic
metronidazol
Usually not advisable.
only if fever cause is not oblivious after several days and patient is
deteriorates

25. Summary

26. Thank you