Case Presentation: We present a 61 year old female with a history of hypertension and rheumatoid arthritis well controlled on Humira who presented to the ED with tachycardia and tachypnea, found to have profound lymphocytic leukocytosis and altered mental status. The patient’s family reported a history of fatigue and confusion for 4 days as well as a submandibular mass growing over several weeks. Physical exam revealed a diffuse, nonpainful cervical lymphadenopathy. Cross sectional head imaging revealed bilateral bulky centrally necrotic cervical and supraclavicular lymph nodes. Further imaging revealed bulky mediastinal, retroperitoneal and pelvic lymph nodes consistent with lymphoma. Initial lab studies notably showed a leukocytosis of 65.0 with 72% lymphocytes which increased to 83.3 on hospital day (hd) two. Inflammatory markers including ferritin and d-dimer were elevated. She did not have evidence of a coagulopathy or tumor lysis syndrome.The patient’s initial presentation and studies were most concerning for a newly diagnosed hematologic malignancy such as a lymphoma converting to leukemia and possible concomitant sepsis. Also considered, however, were hemophagocytic lymphohistiocytosis (HLH), an atypical viral or fungal infection, and autoimmune syndromes. She was treated for sepsis and admitted for expedited work up. Malignant hematology and radiology were consulted for assistance with bone marrow and lymph node biopsies. On hd two her peripheral flow cytometry did not show a monoclonal pattern and the bone marrow biopsy demonstrated normocellular marrow. Her Epstein Barr Virus (EBV) IgG and nuclear capsid antibody returned positive. Subsequently her EBV viral quantitative PCR showed 227,697 copies/mL. All other infectious studies were unremarkable. Her lymph node biopsies showed atypical T-cell infiltrates with scattered EBV-positive cells and areas of necrosis. The patient returned to her baseline mental status and reported improvement in her symptoms. She was discharged on hd six with cessation of her Humira.
Discussion: Infectious mononucleosis is known to mimic hematologic malignancies. Additionally, EBV is a known cause of lymphoproliferative disorders particularly in immunocompromised individuals. This patient’s case was felt to be an atypical and severe presentation of infectious mononucleosis with EBV viremia leading to a profound, transient lymphocytosis. The clinical picture was further obscured by a lack of typical symptoms or demographics. Interestingly, her severe infection was likely a result of her chronic immunosuppression via adalimumab but her findings mimicking lymphoma seemed to be an exaggerated immune response. The initial concern for acute leukemia and sepsis necessitated admission to a medicine team and expedited collaborative care. This case teaches valuable lessons for hospital medicine physicians to keep an open mind when approaching unusual cases and to not let initial imaging impressions cause anchoring.
Conclusions: • EBV can rarely cause a profound, acute lymphocytosis that can mimic leukemia and lymphoma• Hospitalists should keep a broad differential that includes malignancies, infections and autoimmune conditions when confronted with undifferentiated, severe leukocytosis and early involvement of consultants can help expedite these workups• Immunosuppressed patients are at higher risk for complications of EBV and should be monitored closely in the inpatient setting in severe cases