Prolonged Fever

Differential Diagnosis

Common Diagnoses

Rare Diagnoses

  • Malaria and other Tropical Diseases
  • Lyme Disease
  • Tuberculosis, Syphilis
  • Actinomycosis
  • HIV Infection: AIDS
  • Infective Endocarditis
  • Factitious

Ready Reckoner

Key distinguishing features of the most common diagnoses

Generalised LymphadenopathyPossibleNoNoPossiblePossible
Local LymphadenopathyPossibleYesNoPossibleNo
Frequency of MicturitionNoNoYesNoNo
Rapid Weight LossPossiblePossibleNoYesPossible
Joint SwellingNoNoNoPossibleYes

Possible Investigations

Likely:FBC, ESR/CRP, LFT, U&E, Paul–Bunnell test, urinalysis, MSU.

Possible:CXR, autoimmune screen.

Small Print:Faecal calprotectin, blood cultures, malaria films, syphilis serology, HIV test and a variety of other secondary care-based tests.

  • FBC, ESR/CRP, U&E, LFT: Anaemia will be revealed in a variety of disorders (e.g. malignancy, connective tissue disorders); WCC raised in many inflammatory or infective processes and also some blood dyscrasias. Elevated ESR/CRP is a non-specific finding in many of the illnesses listed. Abnormal U&E or LFT may point to an underlying renal or hepatic problem.
  • Paul–Bunnell test: May be positive in glandular fever.
  • Urinalysis, MSU: May be proteinuria, haematuria and evidence of infection in chronic pyelonephritis.
  • CXR: Will show signs of malignancy (e.g. lung, lymphoma), occult infection and TB.
  • Autoimmune screen: May suggest a connective tissue disorder.
  • Faecal calprotectin: If symptoms suggest possible IBD.
  • Secondary care-based tests: A number of tests may be performed after referral to the specialist in cases which remain obscure after initial assessment and investigation. These include further microbiological tests (e.g. stool, blood cultures), blood tests (e.g. for malaria, syphilis and HIV), isotope scans, ultrasound and CT scans (for occult infection or malignancy), tuberculin testing (for possible TB) and esoteric tests for tropical diseases.

Top Tips

  • Prolonged fever is usually an uncommon presentation of a common disorder (unless there has been recent travel), so review the situation regularly and encourage the patient to report new symptoms, which may help reveal the diagnosis.
  • Refer early if the patient is unwell or has lost weight; if not, arrange initial investigations yourself.
  • Don’t always accept self-reporting of this symptom at face value. Flushing or sweating may be misreported as ‘fever’. If in doubt, get the patient to record the temperature over a period of time.
  • Always take a travel history, and specifically enquire about insect bites and compliance with antimalarial therapy. Remember, too, occupation and recent contact with infectious illness.

Red Flags

  • Tuberculosis is rare but on the increase in the UK. Consider this diagnosis, particularly in Asian immigrants and vagrants.
  • Itching with prolonged pyrexia suggests leukaemia or lymphoma.
  • Refer to a tropical medicine centre a patient with PUO who has recently been abroad somewhere exotic – in such a case, the differential is much wider and the possibility of an obscure pathology therefore much greater.
  • Factitious prolonged fever is rare, but possibly more common among health staff; beware the health worker with apparent fever but who never feels hot and who never appears unwell, especially if basic investigations are all normal.
  • Don’t forget the possibility of infective endocarditis in a patient with a cardiac murmur.

Published: 2nd August 2022 Updated: 10th April 2024

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