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Last updated: October 9, 2025View editorial policy

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Differential Diagnosis for Fever of Unknown Origin

The differential diagnosis for fever of unknown origin (FUO) is broad and can be categorized based on the likelihood and potential impact of missing a diagnosis. Here's a structured approach:

  • Single Most Likely Diagnosis
    • Infections: Such as tuberculosis, endocarditis, or abscesses. These are common causes of FUO and should be considered first due to their prevalence and the availability of effective treatments.
  • Other Likely Diagnoses
    • Connective Tissue Diseases: Like systemic lupus erythematosus (SLE) or rheumatoid arthritis (RA). These conditions can present with fever and are relatively common.
    • Neoplasms: Including lymphomas and leukemias. These can cause prolonged fever and are important to diagnose early for effective management.
    • Chronic Inflammatory Diseases: Such as Crohn's disease or ulcerative colitis. These conditions can cause recurrent fevers and are part of the differential for FUO.
  • Do Not Miss Diagnoses
    • Endocarditis: Although mentioned under infections, it's crucial due to its high mortality if untreated. The presentation can be subtle, especially in the elderly or those with prosthetic valves.
    • Neutropenic Fever: In patients with neutropenia, any fever is considered a medical emergency due to the high risk of severe infection.
    • Central Nervous System (CNS) Infections: Like meningitis or encephalitis, which require prompt diagnosis and treatment to prevent serious complications or death.
  • Rare Diagnoses
    • Whipple's Disease: A rare, systemic bacterial infection that can cause fever, weight loss, and malabsorption.
    • Familial Mediterranean Fever: An inherited condition characterized by recurrent episodes of painful inflammation in the abdomen, chest, or joints, often accompanied by fever.
    • Adult-Onset Still's Disease: A rare inflammatory disorder that can cause fever, rash, and joint pain, among other symptoms.

Each of these diagnoses has a unique set of clinical features, laboratory findings, and imaging characteristics that can help guide the diagnostic process. A thorough history, physical examination, and judicious use of diagnostic tests are essential for narrowing down the differential diagnosis for fever of unknown origin.

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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