Case Presentation: A 68-year-old man with history of alcohol use and rheumatoid arthritis (RA) treated with methotrexate (MTX), hydroxychloroquine, and infliximab since 2006 presented with recurrent fevers, unintentional weight loss and weakness. When symptoms started 2 months prior, he was found to have mild transaminitis, hypoalbuminemia, prolonged international normalized ratio, and new pancytopenia, prompting discontinuation of MTX, hydroxychloroquine, and alcohol. Work-up for liver disease was unremarkable except for ferritin elevated to 3134 nanograms/milliliter. Imaging found nodular liver, ascites, and splenomegaly. Liver biopsy showed periportal and pericellular fibrosis without cirrhosis and sinusoidal dilation concerning for vascular outflow obstruction. The liver injury was attributed to alcohol and MTX.
On admission, he was febrile to 39 degrees Celsius and appeared fatigued. Exam was notable for jaundice, ascites, and splenomegaly. Lab work revealed persistent pancytopenia and cholestatic liver injury. Imaging showed splenomegaly and absence of lymphadenopathy. Infectious and rheumatologic workup, including diagnostic paracentesis, was unremarkable with the exception of Epstein-Barr Virus (EBV) IgG positive, IgM negative, and elevated viral load. He continued to be intermittently febrile with persistent pancytopenia and elevated liver function tests. A bone marrow biopsy revealed Hodgkin lymphoma with aspirate positive for EBV.
Discussion: Hospitalists frequently encounter patients with liver dysfunction and concomitant constitutional symptoms. Liver dysfunction is often seen in alcohol use, however, the presumptive diagnosis of MTX and alcohol-induced liver injury did not explain the recurrent fevers, weight loss, splenomegaly and acute pancytopenia. This prompted the need to explore other etiologies for his presentation.
A bone marrow biopsy yielded the unifying diagnosis of EBV-associated Hodgkin lymphoma. Hodgkin lymphoma can present extranodally in almost any tissue. When the liver is affected, there may be sinusoidal congestion and fibrosis that mimics alcohol-related cirrhosis, as with this patient.
Immunosuppression, such as MTX, predisposes patients to EBV reactivation and subsequent malignancies. The three major types of B-cell lymphomas linked to EBV are Burkitt, Hodgkin, and diffuse large B-cell. The incidence of Hodgkin disease is higher than non-Hodgkin in RA patients treated with MTX. When diagnosed early, Hodgkin lymphoma is highly treatable, however, delayed diagnosis is associated with significant mortality.
Conclusions: This case demonstrates that EBV-associated Hodgkin lymphoma can mimic cirrhosis and illustrates the risk of this developing in immunosuppressed individuals. Hospitalists need to keep an open mind and pursue rare etiologies when the working diagnosis fails to explain the full clinical picture, particularly when a delay in treatment impacts patient mortality.