Synopsis
Investigate prolonged unexplained fever through a disciplined exposure-led and syndrome-led process that identifies time-critical infection without indiscriminate testing or premature empirical treatment.
- Confirm that fever is objectively present, sustained or recurrent, and not explained by measurement error, normal diurnal variation or transient self-limited infection.
- Repeat the history because diagnostic clues emerge over time: travel, animals, occupation, dental work, implants, medicines, immune suppression, sexual exposure and family origin all matter.
- Examine repeatedly for lymph nodes, rash, murmurs, temporal tenderness, synovitis, hepatosplenomegaly, spinal tenderness, focal neurological signs and device or surgical-site changes.
Key red flags
Persistent bacteraemia, a new murmur, embolic features, prosthetic valve, cardiac device or injection exposure raises infective endocarditis and requires multiple cultures and echocardiographic planning.
Investigation priorities
Confirm the phenotype and capture new localising clues over time.
Management branches
Documented recurrent fever with no high-risk physiology and no established diagnosis after initial assessment.
- Reconstruct the timeline and exposures, repeat a complete examination, verify fever and stop non-essential medicines safely when drug fever is plausible.
- Obtain a focused first-tier screen and cultures before antimicrobials, then select serology, imaging and specialty referral from genuine potential diagnostic clues.
Fever continues despite negative first-line cultures, imaging and targeted serology in a clinically stable patient.