Differential Diagnosis for a 70-year-old Male with Autoimmune Hemolytic Anemia and Lymphadenopathy

Single Most Likely Diagnosis

• Chronic Lymphocytic Leukemia (CLL): Given the patient's age, presentation with autoimmune hemolytic anemia (AIHA), and lymphadenopathy, CLL is a strong consideration. CLL is known to cause AIHA due to the production of autoantibodies, and it often presents with lymphadenopathy and can have a variable course.

Other Likely Diagnoses

• Lymphoma (including Hodgkin and Non-Hodgkin Lymphoma): The presence of mediastinal and hilar lymphadenopathy along with AIHA could suggest lymphoma. Both Hodgkin and non-Hodgkin lymphomas can cause AIHA and typically present with lymphadenopathy.
• Systemic Lupus Erythematosus (SLE): Although the ANA is negative, which makes SLE less likely, it's still a consideration due to the AIHA and potential for lymphadenopathy. SLE can have a wide range of presentations, and AIHA is one of its manifestations.
• Castleman Disease: This rare disorder can present with lymphadenopathy and can be associated with autoimmune phenomena, including AIHA.

Do Not Miss Diagnoses

• Infectious Causes (e.g., Mycobacterial, Fungal): Although less likely given the information, infectious causes of lymphadenopathy and AIHA (such as mycobacterial or fungal infections) could be deadly if missed. The history of fever 5 days prior could suggest an infectious etiology.
• Drug-Induced AIHA: Certain drugs can induce AIHA, and it's crucial to review the patient's medication history to rule out this possibility.

Rare Diagnoses

• Cold Agglutinin Disease: This condition is characterized by the production of cold-reactive autoantibodies that can cause hemolysis. It can be primary or secondary to infections or lymphoproliferative disorders.
• Paroxysmal Nocturnal Hemoglobinuria (PNH): Although PNH typically presents with nocturnal hemoglobinuria, it can also cause AIHA. The normal bone marrow biopsy makes this less likely but does not rule it out entirely.

Approach

1. Detailed History and Physical Examination: Focus on symptoms suggestive of underlying malignancy, infections, or autoimmune diseases.
2. Laboratory Tests:
   • Flow Cytometry: To evaluate for CLL or lymphoma.
   • Serologic Tests: For infectious diseases if suspected.
   • Imaging: Further evaluation of lymphadenopathy with PET-CT if necessary.
   • Bone Marrow Biopsy: Although the initial bone marrow was normal, a repeat or more detailed examination might be warranted based on flow cytometry results.
3. Treatment: Directed at the underlying cause, with consideration for corticosteroids for AIHA and specific treatments for any identified malignancy or infection.