Cold Blooded: Cryoglobulinemia Immune to Hepatitis C Treatment

Abstract

Cryoglobulinemia is a condition characterized by the production of antibodies which precipitate in cold temperatures within blood vessels leading to a systemic vasculitis. It is typically associated with lymphoproliferative/inflammatory disorders including lymphoma, connective tissue diseases and viral infections such as Hepatitis C virus (HCV) and Human Immunodeficiency Virus (HIV). Treatment of the underlying inflammatory disease is the mainstay for curing cryoglobulinemia. A 57-year-old male with a remote history of intravenous drug use, successful treatment of chronic Hepatitis C and a liver transplant following hepatocellular carcinoma presented to the hospital with a fever and confusion for several days. Physical exam was unremarkable except for altered mental status and disorientation. Initial labs including a CBC, TSH and Vitamins B12/folate were normal. Liver function test and BMP showed mild transaminitis and azotemia, respectively. The patient was oliguric and urinalysis was positive for hematuria and nephritic range proteinuria. Viral panel including HIV and hepatitis were negative. Imaging of the brain with CT scan was negative but a CT of the chest revealed mediastinal lymphadenopathy. Lymph node biopsy was positive for recurrent hepatocellular carcinoma. His symptoms progressed to include a truncal maculopapular rash, migratory arthralgia, and shivering. Despite initiating empiric broad spectrum antibiotics, there was no clinical improvement and blood/urine cultures were persistently negative. His deterioration progressed to include peripheral numbness, paresthesia, and the inability to ambulate. Investigation for a rheumatologic etiology was negative for autoantibodies however, C3 and C4 complement levels were low and follow up testing for cryoglobulins was positive. Within days, the disease process advanced rapidly with renal/liver failure, and ultimately became fatal. Although treatment of Hepatitis C has been the mainstay treatment of cryoglobulinemia, this unique case demonstrates that it may persist despite cure of the viral illness. Malignancies associated with production of cryoglobulins include those that alter B cell antibody production, primarily B-cell Lymphoma. Hepatocellular carcinoma is not a recognized malignancy associated with production of cryoglobulins, however, it is a recognized late complication of persistent cryoglobulinemia which may explain the recurrence of HCC in this patient despite negative Hep C.