Pyrexia of Unknown Origin (PUO)

Abstract

Petersdorf and Beeson defined pyrexia of unknown origin (PUO) in 1961. It is defined as an illness more than three weeks’ duration, with a fever > 38.3°C on several occasions and failure to reach a diagnosis after one week of in-patient investigation. Additional categories have now been added. These include: ● Nosocomial PUO in hospital patients: This is defined as fever of 38.3°C on several occasions caused by a process not present or incubating on admission, where initial cultures are negative and diagnosis remains unknown after three days of investigations. Fever is often related to hospital factors such as surgery, use of biomedical devices (e.g. intravascular devices/urinary catheters), C. difficile infection, and decubitus ulcers related to immobilization. ● HIV- associated PUO: This is defined as fever (as in Nosocomial PUO) for four weeks as an outpatient or three days as an in- patient. The commonest causes of fever are typical and atypical mycobacterial infections, cryptococcosis, and Cytomegalovirus (CMV). Lymphoma may cause fever in up to 25% of cases. ● Neutropenic PUO: This includes patients with a fever (as in Nosocomial PUO) with neutrophils < 1.0 x 109/L, with initial negative cultures and an uncertain diagnosis after three days. Bacterial infection is the commonest cause and should be treated empirically. The causes of a PUO can be categorized as infection (30–40%), neoplasia (20–30%), collagen-vascular and autoimmune diseases (10–20%), and miscellaneous (10–20%). The commonest causes of localized bacterial infections causing PUO are infective endocarditis, intra- abdominal or pelvic infections, oral cavity infections, osteomyelitis, and infected peripheral vessels. These conditions include: ● Infective endocarditis (IE): ■ Organisms associated with indolent onset (e.g. Streptococcus viridans, Enterococcus species, coagulase- negative staphylococci). ■ HACEK organisms (e.g. Haemophilus, Aggregatibacter, Cardiobacterium, Eikenella, Kingella). ■ Culture-negative endocarditis (e.g. Chlamydia, Coxiella, or Bartonella). ■ Non- infective endocarditis: ● Marantic endocarditis, associated with malignancy. ● Libman Sacks endocarditis, associated with systemic lupus erythematosus (SLE). ● Intra-abdominal infections. ■ Abscesses: ● Hepatic (GI tract or biliary in origin). ● Splenic (associated with IE). ● Sub-phrenic (associated with previous surgery). ● Pancreatic (post-pancreatitis).