Pyrexia of Unknown Origin
Most pyrexias result from a clearly defined illness, e.g. acute pyelonephritis or acute appendicitis, or from self-limiting viral infections, e.g. common cold. Pyrexia of unknown origin is defined as a temperature>38.3°C on several occasions, accompanied by more than three weeks of illness and failure to reach a diagnosis after one week of inpatient investigation. Most cases of pyrexia of unknown origin are unusual presentations of common diseases, e.g. tuberculosis, endocarditis, rather than rare or exotic illnesses.
History
A full and extensive history should be taken, noting especially travel abroad, contact with infection, contact with animals, bites, abrasions, rashes, diarrhoea. Check the drug history, including non-prescription drugs and drug abuse. Check for any recent history of surgery, particularly abdominal surgery. Is there any history of recent immunisations? Has the patient experienced night sweats, weight loss and general malaise?
Examination
A full physical examination should be carried out. This should be directed at every system of the body, checking particularly for lymphadenopathy and hepatosplenomegaly. Rectal and vaginal examination should be carried out.
Investigations
It may be necessary to carry out numerous and repeated investigations. It may also be necessary to withhold any drugs one at a time, to see if the temperature settles.
General Investigations
■ FBC, ESR
Hb ↓ malignancy, anaemia of chronic disease, e.g. rheumatoid arthritis. WCC ↑ infection, leukaemia. Lymphocytes ↑ viral infection. Platelets ↓ leukaemia. ESR ↑ malignancy, connective tissue disease, TB.
■ U&Es
Connective tissue disease affecting the kidneys.
■ LFTs
Biliary tract or liver disease, e.g. cholangitis, hepatitis.
■ Blood glucose
Diabetes – infections are more common in diabetics.
■ Blood culture
Streptococcus viridans suggests infective endocarditis. Isolation of coliforms suggests the possibility of intra-abdominal sepsis.
■ Viral antibodies
Hepatitis B, hepatitis C, infectious mononucleosis, HIV, CMV.
■ Sputum culture
Microscopy for tubercle bacilli and C&S.
■ Urine microscopy and culture
Microscopic haematuria in endocarditis. Haematuria in hypernephroma and blood dyscrasias. White cells – infection. Granular or red cell casts – renal inflammation, e.g. connective tissue disease. Proteinuria suggests renal disease.
■ Stool culture and microscopy
C&S. Ova, parasites and cysts on microscopy.
■ CXR
TB. Atypical pneumonia. Pneumonitis associated with HIV and Pneumocystis jiroveci. Secondary deposits. Hilar glands associated with sarcoidosis, TB and lymphoma.
Specific Investigations
■ Rheumatoid factor
Rheumatoid arthritis.
■ Serological tests
Q fever, brucellosis, leptospirosis.
■ Autoantibodies
Connective tissue disease.
■ Antistreptolysin O titre
Rheumatic fever.
■ Bone marrow aspirate
Leukaemia. Myeloma.
■ Lumbar puncture
White cells and organisms – meningitis. Blood – subarachnoid haemorrhage. Protein – Guillain–Barré syndrome.
■ US abdomen
Intraperitoneal abscesses.
■ Gallium scan
Localised infection.
■ Labelled white cell scan
Localised infection/abscess.
■ Renal biopsy
Glomerular disease. Malignancy.
■ Exploratory laparotomy
This may be necessary to exclude intra-abdominal sepsis.
