Pyrexia of unknown origin (PUO).

Pyrexia of unknown origin (PUO).

The classic definition of pyrexia of unknown origin (PUO) is a fever of at least 3 weeks' duration with daily temperature elevation above 101°F, and remaining undiagnosed after 1 week of intensive study in the hospital.

However, with the availability of several investigations on outpatient basis, and appearance of several immunodeficiency diseases, a new classification of pyrexia of unknown origin has been evolved. Here, PUO is divided into four types:

Classic PUO: Fever of at least 3 weeks' duration with temperature recorded as more than 101°F (38.3°C) on several occasions, and the cause is not found despite three outpatient visits or 3 days of hospitalisation or 7 days of 'intelligent' ambulatory investigations.

Nosocomial PUO: A temperature of >38.3°C (101°F) developing on several occasions in a hospitalised patient who is receiving acute. care and in whom infection was not manifest or incubating on admission. It is also mandatory that the cause of fever is not found on 3 days of investigations, including at least 2 days' incubation of cultures.

Neutropenic PUO: A temperature of more than 38.3°C (101°F) developing on several occasions in a patient whose neutrophil count is below 500/L or is expected to fall to that level in 1 or 2 days. Again, it is also mandatory that the cause of fever is not found on 3 days of investigations, including at least 2 days' incubation of cultures.

HIV-associated PUO: A temperature of more than 38.3°C (101°F) developing on several occasions over a period of more than 4 weeks for outpatients or more than 3 days for hospitalised patients with HIV infection. It is also mandatory that the cause of fever is not found on 3 days of investigations, including at least 2 days' incubation of cultures.

Aetiology

Patients with classic PUO usually do not have rare diseases, but suffer from common diseases with atypical presenta¬tions.

40% cases — Infections.

20% cases — Neoplasms (primary or metastatic).

20% cases — Connective tissue diseases.

10% cases — Miscellaneous disorders.

Common causes of prolonged fever

Infections

Tuberculosis, malaria, typhoid, infective endocarditis, urinary tract infections, intrarenal and perinephric

abscesses, pyogenic and amoebic liver abscesses, subphrenic abscess, retroperitoneal abscess, pelvic inflammatory diseases.

Neoplasms

Lymphomas, leukaemias, gastrointestinal malignancies, metastatic tumours of liver, hypemephroma,

atrial myxomas.

Autoimmune disoreders disorders

Systemic lupus erythematosus, rheumatoid arthritis, temporal arteritis, polyarteritis nodosa (PAN).

Unclassified

Drug fevers (sulphonamides, aminoglycosides, penicillins), multiple pulmonary thromboembolism,

haemolytic anaemias, granulomatous hepatitis, cyclic neutropenia,

Psychogenic fevers Habitual hyperthermia, factitious fever, fabricated fever.

Periodic fevers-Familial Mediterranean fever (polyserositis).

In neutropenic patients, infections include perianal infections, aspergillosis and candidaemia.

In nosocomial PUO, causes include catheter infections, urinary tract infections, septic thrombophlebitis and drug fever.

In HIV patients, tuberculosis and other infections are common.

Diagnostic approach to PUO

Most pyrexias of 'unknown origin' are atypical or obscure presentations of common diseases rather than due to obscure diseases.

'There is no substitute for observing the patient, talking to him and thinking about him'.

History should be reviewed with particular emphasis on family history, occupational history, and history of recent travel.

Careful and repeated physical examination is of crucial importance. This should include a detailed examination of the skin, optic fundus and lymph nodes. The heart should be examined for murmurs, and abdomen for splenic enlargement.

The pattern of fever should be documented, with simultaneous pulse record.

Laboratory tests

Complete blood counts, ESR and peripheral smear examination for parasites and abnormal cells.

Microscopic examination and culture of urine.

Culture, and examination of the stool for ova, parasites and occult blood.

Aerobic and anaerobic cultures of the blood.

Blood chemistries including renal and liver function tests.

Mantoux test and fungal skin tests.

Gastric aspirate examination by smear and culture for tubercle bacilli.

Serological tests including ASO titre, rheumatoid factor, antinuclear antibodies, viral antibody titres, Paul Bunnell test, and brucella agglutination test.

Radiographic examination including chest radiography, barium GI series, echocardiography, ultrasonography of abdomen and pelvis, CT scan of abdomen and thorax, and isotope scans.

Bone marrow biopsy, liver biopsy, and lymph node biopsy.

Diagnostic surgical procedures like peritoneoscopy, laparoscopy, bronchoscopy and exploratory laparotomy may rarely be required.