Pyrexia of Unknown Origin
Dr. P. Ramakrishnan, Dr. Shyamala Menon, Dr. Geetha Philip, Dr. Pavithran, Dr. Jose Francis

Definition
Pyrexia of unknown origin (PUO) is one of the knottiest
diagnostic problems and variously defined by different
authors, over the years, depending on the clinical set up
and available facility at that time. The widely accepted
definition is one from Petersdorf and Beeson, “fever of more
than 101oF (38.3oC)of three weeks duration, undiagnosed
after one week’s study”. In clinical practice in India, the
term PUO may be used to denote any fever of more than ten
days’ duration, undiagnosed after all the basic investigations
are performed.
Aetiology
The common causes of PUO are shown below :
Infections : Pulmonary and extra-pulmonary tuberculoses,
malaria, typhoid, leptospirosis, visceralleishmaniasis,
brucellosis, deep abscesses (liver subphrenic and pelvic),
SBE, urinary tract infection, HIV, viral and fungal infections
and infection due to implanted or indwelling devices.
Malignant diseases : Lymphomas, leukaemias, solid tumours
like hepatoma, renal cell carcinomia, carcinomia pancreas,
and carcinoma stomach.
Connective tissue diseases : SLE, rheumatoid arthritis,
polyarteritis nodosa, polymyalgia, polymyositis,
dematomyositis.
Miscellaneous : Sarcoidosis, thyroiditis, inflammatory bowel
disease, pulmonary thromboembolism, atrial myxomas,
factitious fever, injection abscesses.
Drug fever : Amionoglycosides, anti-epileptics, INH,
alphamethyldopa.
Changing pattern of Diseases
In recent years one often sees atypical or changed pattern of
clinical presentations of hitherto common ailments. Partially
treated patients also have a modified clinical picture.
Extra-pulmonary tuberculosis, falciparum malaria with renal
failure, neuro-typhoid, renal typhoid, leptospirosis with DIC
and ARDS, infection of implants and catheters are some of
the examples.
Approach to a case of PUO
The basic approach to a case of PUO is outlined below :
History : Occupation (leptospirosis); Contact with infection
(tuberculosis), animals (brucellosis); Presence of primary /
secondary immunocompromised stated; Recent operation
or dental treatment; Drug history; Psychiatric history from
relatives.
Signs : General examination for evidence of jaundice,
anaemia, skin and mucosal lesions and lymphadenopathy;
Abdominal examination for organomegaly, masses and
ascites; Heart murmurs.
Investigations : Routine blood counts, ESR, blood smear for
malarial parasites, urine examination; Blood culture and
urine culture; Serology for typhoid, leptospirosis, brucellosis
and tuberculosis; Chest X-ray; Ultrasound abdomen; Mantoux
test, tests for HIV; Further investigations; Tissue biopsy and
bone marrow aspiration, CT, MRI and guided biopsies, ANA
anti DNA, Weil-Felix test.
Therapeutic trial : Anti-microbial therapy; anti-tubercular
drugs / antibiotics; Corticosteroid therapy.