Pyrexia of Unknown Origin

Pyrexia (or fever) of unknown origin (PUO) is defined as 'a documented fever persisting for >2 weeks, with no clear diagnosis despite intelligent and intensive investigation'. Occult infection remains the most common cause in adults.


Investigations

• A detailed history and examination is essential, and the examination should be repeated on a regular basis in case new signs appear. First-line investigations are usually repeated as results may have changed since the tests were first performed:
• Full blood count, including a differential WCC and blood film
• ESR and CRP
• Serum urea and electrolytes, liver biochemistry and blood glucose
• Blood cultures - several sets from different sites at different times
• Microscopy and culture of urine, sputum and faeces
• Baseline serum for virology
• Chest X-ray
• Serum rheumatoid factor and antinuclear antibody
• Second-line investigations are performed in conditions that remain undiagnosed and when repeat physical examination is unhelpful:
• Abdominal imaging with ultrasound, CT or MRI to detect occult abscesses and malignancy
• Echocardiography for infective endocarditis
• Biopsy of liver and bone marrow occasionally; temporal artery biopsy should be considered in the elderly
• Determination of HIV status (after counselling)

Management

• THe treatment is of the underlying disease
• Blind antibiotic therapy should not be given unless the patient is very unwell. In a few patients no diagnosis is reached after thorough investigations and in most of these the fever will resolve on follow-up

Causes

• Infection (20-40%)
• Pyogenic abscess, e.g. liver, pelvic, subphrenic
• Tuberculosis
• Infective endocarditis
• Toxoplasmosis
• Viruses: Epstein-Barr, cytomegalovirus
• Primary human immunodeficiency virus (HIV) infection
• Brucellosis
• Lyme disease
• Malignant disease (10-30%)
• Lymphoma
• Leukaemia
• Renal cell carcinoma
• Hepatocellular carcinoma
• Vasculitides (15-20%)
• Adult Still's disease
• Rheumatoid arthritis
• Systemic lupus erythematosus
• Wegener's granulomatosis
• Giant cell arteritis
• Polymyalgia rheumatica
• Miscellaneous (10-25%)
• Drug fevers
• Thyrotoxicosis
• Inflammatory bowel disease
• Sarcoidosis
• Granulomatous hepatitis, e.g. tuberculosis, sarcoidosis
• Factitious fever (switching thermometers, injection of pyogenic material)
• Familial Mediterranean fever
• Undiagnosed (5-25%)