1164 The Journal of Rheumatology 2005; 32:6 Case Report Persistent Cryoglobulinemic Vasculitis Following Successful Treatment of Hepatitis C Virus JAMES W. LEVINE, CARMEN GOTA, BARRI J. FESSLER, LEONARD H. CALABRESE, and SHELDON M. COOPER ABSTRACT. There is a well established link between type II mixed cryoglobulinemia (MC) and hepatitis C virus (HCV) infection, and HCV is believed to be the cause of cryoprotein formation and tissue deposi- tion. Successful treatment of HCV infection has resulted in resolution of cryoglobulinemia and vas- culitis. We describe 4 patients who had persistent MC and vasculitis despite successful eradication of HCV with antiviral therapy. (J Rheumatol 2005;32:1164–7) Key Indexing Terms: CRYOGLOBULINEMIA HEPATITIS C VIRUS VASCULITIS From the Rheumatology and Clinical Immunology Division, University of Vermont College of Medicine, Burlington, Vermont; Rheumatic and Immunologic Diseases Division, Cleveland Clinic Foundation, Cleveland, Ohio; and the Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, Birmingham, Alabama, USA. J.W. Levine, DO; S.M. Cooper, MD, Rheumatology and Clinical Immunology Division, The University of Vermont College of Medicine; C. Gota, MD; L.H. Calabrese, DO, Rheumatic and Immunologic Diseases, Cleveland Clinic Foundation; B.J. Fessler, MD, Division of Clinical Immunology and Rheumatology, The University of Alabama at Birmingham. Address reprint requests to Dr. S.M. Cooper, The University of Vermont College of Medicine, Given Building D305, 89 Beaumont Avenue, Burlington, VT 05405. E-mail: sheldon.cooper@uvm.edu Accepted for publication January 24, 2005. Hepatitis C virus (HCV), a worldwide pathogen, is the lead- ing cause for endstage liver disease and indication for liver transplant in the United States. HCV is also associated with a variety of immunologic extrahepatic manifestations, the best studied of which is the presence of elevated cryoglobu- lins in the serum. While up to 40%–50% of HCV infected patients have elevated levels of circulating cryoglobulins 1,2 , only a small proportion develop vasculitic sequelae in target organs such as the skin, peripheral nerve, and kidney 3 . There is strong evidence, particularly from studies of the composi- tion of the cryoglobulins themselves 2 as well as from immunohistologic studies of tissues such as skin 4 , that HCV is a cause of the formation of the cryoprotein and ultimate- ly its deposition in the target tissues. The most common type of cryoglobulinemia in patients with HCV is type II mixed cryoglobulinemia (MC), charac- terized by the presence of polyclonal Ig in association with a monoclonal Ig (typically IgM or IgG). Treatment of cryo- globulinemia is indicated when progressive organ-threaten- ing disease is present. Prior to the association of MC with HCV, treatment generally consisted of high dose glucocorti- coids, cytotoxic agents, and plasmapheresis. While described as effective, this therapy was often only transient- ly beneficial 5,6 . However, therapy directed against HCV with interferon-α (IFN-α) and more recently combined IFN-α and ribavirin has offered a new strategy for HCV associated cryoglobulinemia. This therapeutic strategy has been reported to be successful at achieving remission for HCV related MC 7-11 . In virtually all reports of successful treatment of HCV associated cryoglobulinemic vasculitis there has been a strong correlation between antiviral response and vasculitic response 11-13 . Particularly with cutaneous vasculitis, a sus- tained virologic response has been associated with effective and enduring remissions. In contrast, patients who either do not achieve an antiviral effect or who experience a relapse will have incomplete or transient improvement in the vas- culitis 7,8,14-17 . Thus recurrence of symptoms attributable to cryoglobulinemia is paralleled by recurrence of detectable HCV RNA in those who have received IFN therapy 7 . We recently identified 4 patients from 3 centers who had persistent symptomatic cryoglobulinemia despite successful and sustained HCV eradication with antiviral therapy. Data from these 4 patients were collected retrospectively and form the basis of this observational report. CASE REPORTS Pertinent details for each case are listed in Table 1. Patient 1. A 49-year-old man was diagnosed with HCV infection (genotype 2b) in 1999. In May 2001 he developed lower extremity petechiae and was found to have type II MC with an IgM kappa monoclonal component. Thrombocytopenia subsequently developed and he was treated with pred- nisone, which promptly improved the platelet count although petechiae per- sisted. Before antiviral therapy the viral load by HCV RNA assay (Roche Amplicor HCV Monitor) was > 850,000 IU/ml. He received a 24-week course of pegylated IFN-α and ribavirin starting in October 2002. Lower extremity petechiae resolved and subsequent testing for HCV RNA (Amplicor) revealed no detectable virus (sensitivity of < 600 IU/ml), but persistence of cryoglobulins. The cryocrit prior to antiviral therapy was 23% and remained between 10% and 20% throughout the period of obser- vation. The levels of C4 were < 10 mg/dl (normal 16–38) before and after antiviral therapy. In July 2003, 4 months after cessation of antiviral thera- Personal non-commercial use only. The Journal of Rheumatology Copyright © 2005. All rights reserved. www.jrheum.org Downloaded on November 25, 2022 from