Differential Diagnosis for Persistent Fever

Given the patient's presentation of persistent fever for more than 45 days, weight loss, leukopenia, anemia (indicated by low hemoglobin), and elevated inflammatory markers (ESR, CRP) without a clear source of infection or comorbidities, the differential diagnosis can be categorized as follows:

• Single Most Likely Diagnosis

  • Tuberculosis (TB): The combination of persistent fever, weight loss, and leukopenia, especially in the context of a prolonged duration, raises a strong suspicion for TB. The normal blood cultures and lack of response to initial treatments for common infections also point towards TB, which can present with a wide range of symptoms and may not always have a clear source of infection.

• Other Likely Diagnoses

  • Lymphoma: Given the patient's weight loss, fever, and leukopenia, lymphoma is a consideration. Although the ferritin level is elevated, which can be seen in lymphoma, the absence of other specific findings like lymphadenopathy or splenomegaly does not make it the top choice but still keeps it in the differential.
  • Chronic Infections (e.g., Brucellosis, Endocarditis): Although blood cultures are normal, certain chronic infections can have negative cultures and present with prolonged fever and weight loss. Brucellosis, for example, can cause a prolonged febrile illness with weight loss and may have negative blood cultures if not specifically tested for.
  • Autoimmune Disorders (e.g., Systemic Lupus Erythematosus - SLE): SLE can present with fever, weight loss, leukopenia, and elevated inflammatory markers. However, specific autoantibodies and other characteristic findings are usually present.

• Do Not Miss Diagnoses

  • HIV/AIDS: Although not directly suggested by the information provided, HIV can cause a prolonged febrile illness with weight loss and leukopenia. It's crucial to rule out HIV due to its significant implications on management and prognosis.
  • Malignancy (other than lymphoma): Other malignancies, especially those involving the bone marrow, can present with similar symptoms. It's essential to consider and rule out malignancy due to its severe consequences if missed.
  • Fungal Infections: In immunocompromised patients or those with specific exposures, fungal infections can cause prolonged fever and weight loss. Although the patient has no mentioned comorbidities, the possibility of an underlying immunocompromised state (e.g., undiagnosed HIV) makes this a "do not miss" diagnosis.

• Rare Diagnoses

  • Whipple's Disease: A rare, systemic bacterial infection that can cause fever, weight loss, and malabsorption. It's rare but should be considered in cases of prolonged, unexplained symptoms.
  • Kikuchi-Fujimoto Disease: A rare condition that can present with fever, weight loss, and leukopenia, often affecting young women. It's self-limiting but can be confused with more serious conditions.
  • Adult-Onset Still's Disease: Characterized by high fevers, salmon-colored rash, and arthritis, among other symptoms. It's a diagnosis of exclusion and can be considered in patients with prolonged fever and systemic symptoms without a clear cause.