In this article we will discuss about the Pyrexia of Unknown Origin (PUO):- 1. Causes of PUO 2. Infection of PUO 3. Laboratory Diagnosis.

Causes of PUO:

The most common causes of prolonged PUO are:

(a) Chronic infections;

(b) Tumours,

(c) Connective tissue disorders;

(d) Granulomatous diseases

(e) Drug hypersensitivity reactions (Table 94.1):

Causes of PUO

Infection of PUO:

Aetiology:

As a cause of PUO, infections account for about 35% cases. Without accurate determination of the nature and location of infection, many cases of PUO due to infecting agents, agents are eradicated by blind anti-microbial therapy.

(a) Bacterial Infections:

Due to repeated blood culture and widespread use of antibiotics, bacterial endocarditis due to streptococci is a sure cause of PUO; but antibiotic use or infection by highly fastidious organisms, fungi (Candida, Aspergillus), Rickettsiae and Bacteroides are important factors in culture-negative endocarditis.

Certain organisms (S. typhi, S. choleraesuis), Neisseria meningitidis and Brucella give rise to chronic intermittent bacteriaemia without prominent localised findings.

Sinusitis, mastoiditis, sub-acute osteomyelitis (particularly vertebral osteomyelitis), retroperitoneal abscesses and secondarily infected organised clot of an aortic aneurysm also present as PUO. Gram-negative bacilli (E. coli, Bacteroides and Salmonella have been recovered from these patients. In such patients, blood culture usually becomes intermittently positive.

Viral Infections:

(1) Infections mononucleosis due to Epstein-Barr virus.

(2) Cytomegalovirus infection

(3) Hepatitis A

Infected patient with these viral infection may suffer from prolonged febrile illness without prominent localised findings.

(C) Parasitic Infection:

(1) Protozoal diseases Malaria, amoebic hepatitis or liver abscess, visceral leishmaniasis (Kala-azar), toxoplasmosis, and trypanosomiasis.

(2) Metazoal Disease:

Filariasis, particularly during first year of infection.

Laboratory Diagnosis of PUO:

A. Hematology Rarely specific.

B. Biochemistry

Liver function tests reveal liver damage in relevant cases.

C. Bacteriology:

1. Blood culture-should be done

2. Anaerobic culture of pus

3. Mycobacterial culture

4. Urine culture.

D. Serology:

Useful in infections mononucleosis (Paul Bunnel test) enteric fever, hepatitis A, B infection, lyme disease, CMV infections and sometimes in amoebiasis.

Bacterial Disease Presenting as PUO

5. Skin Test:

Mantoux test for histoplasmosis, coccidioidomycosis, sarcoidosis (Kvelm-Siltz- bach skin test).

6. Other Tests:

(i) Immunologic tests (LE cells phenomenon, antinuclear antibody test in SLE etc.).

(ii) Biopsy of lymph node or other tissues.