Differential Diagnosis for Fever of Unknown Origin

When approaching a case of fever of unknown origin (FUO), it's crucial to consider a broad range of potential causes, given the nonspecific nature of the presenting symptom. The differential diagnosis can be organized into several categories to help guide the diagnostic process and ensure that critical conditions are not overlooked.

• Single Most Likely Diagnosis

  • Infections: Such as tuberculosis, endocarditis, or abscesses. These conditions are often at the top of the list due to their potential severity and the fact that they can sometimes present with nonspecific symptoms, including fever without an obvious source.
  • Malignancies: Like lymphomas or leukemias. These can cause prolonged fever due to the disease process itself or due to associated infections.

• Other Likely Diagnoses

  • Autoimmune Disorders: Conditions such as rheumatoid arthritis, lupus, or giant cell arteritis can cause FUO. These diseases often have systemic manifestations and can be challenging to diagnose early in their course.
  • Inflammatory Bowel Disease: Crohn's disease and ulcerative colitis can present with fever among other symptoms, and their diagnosis might not be immediately apparent.
  • Drug Fever: Certain medications can induce fever without any other obvious cause. This is a diagnosis of exclusion but should be considered, especially in patients on multiple medications.

• Do Not Miss Diagnoses

  • Endocarditis: Although mentioned under likely diagnoses, it's worth reiterating due to its severity and the importance of early diagnosis. The presentation can be subtle, especially in the elderly or in intravenous drug users.
  • Neutropenic Fever: In patients with neutropenia, fever can be the only sign of a severe infection. Prompt recognition and treatment are critical to prevent high morbidity and mortality.
  • Central Nervous System (CNS) Infections: Such as meningitis or encephalitis. These conditions require urgent diagnosis and treatment to prevent long-term sequelae or death.

• Rare Diagnoses

  • Whipple's Disease: A rare, systemic bacterial infection that can cause fever, weight loss, and malabsorption, among other symptoms.
  • Familial Mediterranean Fever: An inherited condition characterized by recurrent episodes of fever and inflammation, often affecting the abdomen, chest, or joints.
  • Adult-Onset Still's Disease: A rare autoimmune disorder that can present with high fevers, 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 in narrowing down the differential diagnosis for a patient with fever of unknown origin.