Differential Diagnosis for Pyrexia of Unknown Origin

Single Most Likely Diagnosis

• Infection: This is often the most common cause of pyrexia of unknown origin, with a wide range of possibilities including bacterial, viral, fungal, or parasitic infections. The justification for this being the single most likely diagnosis is due to the high prevalence of infections in the general population and the broad spectrum of infectious agents that can cause prolonged fever without an obvious source.

Other Likely Diagnoses

• Connective Tissue Diseases: Conditions such as rheumatoid arthritis, systemic lupus erythematosus, and polymyalgia rheumatica can present with fever of unknown origin. These diseases are characterized by autoimmune responses and can affect multiple systems in the body, making them a likely consideration in the differential diagnosis.
• Neoplasms: Both solid tumors and hematologic malignancies can cause prolonged fever without a clear infectious source. The mechanism may involve the production of pyrogenic cytokines by the tumor cells themselves.
• Drug Fever: Certain medications can induce fever as an adverse reaction. This is an important consideration, especially in patients who have recently started new medications.

Do Not Miss Diagnoses

• Endocarditis: Although not the most common cause, infective endocarditis is a critical diagnosis to consider due to its high morbidity and mortality if left untreated. It often presents with fever, heart murmur, and embolic phenomena.
• Abscesses: Deep-seated abscesses, such as those in the liver, spleen, or brain, can cause prolonged fever without obvious signs of infection. Imaging studies are crucial for diagnosis.
• Tuberculosis: TB can present in many forms, including as a fever of unknown origin, especially in immunocompromised patients or those from endemic areas.

Rare Diagnoses

• Familial Mediterranean Fever: A genetic disorder characterized by recurrent episodes of fever and inflammation, often accompanied by abdominal, chest, or joint pain.
• Whipple's Disease: A rare, systemic bacterial infection caused by Tropheryma whipplei, which can lead to malabsorption, weight loss, and fever.
• Castleman Disease: A rare disorder that involves an overgrowth of cells in the body's lymph nodes, which can cause fever, weight loss, and fatigue.

Each of these diagnoses requires careful consideration based on the patient's clinical presentation, history, and diagnostic findings to determine the underlying cause of the pyrexia of unknown origin.