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Rheumatology Advance Access published online on June 12, 2007
Rheumatology, doi:10.1093/rheumatology/kem132
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© The Author 2007. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Review

Hepatitis C-associated mixed cryoglobulinaemia: a crossroad between autoimmunity and lymphoproliferation

D. Saadoun1,2, D. A. Landau1,2, L. H. Calabrese3 and P. P. Cacoub1,2

1Université Pierre et Marie Curie-Paris 6, CNRS, UMR 7087 2AP-HP, Hôpital Pitié-Salpêtrière, Service de Médecine Interne, Paris, F-75013 France 3Department of Rheumatic and Immunologic Diseases, Cleveland Clinic Lerner, Cleveland, OH, USA

Correspondence to: Prof. Patrice Cacoub, MD, PhD, AP-HP, Hôpital Pitié-Salpêtrière, Service de Médecine Interne, Paris, F-75013 France. E-mail: patrice.cacoub{at}psl.aphp.fr


  Abstract

Hepatitis C virus (HCV) infection is the second most common chronic viral infection in the world with a global prevalence of about 2%. Chronic HCV infection is commonly associated with a number of extrahepatic complications. Circulating mixed cryoglobulins (MCs) are detected in 40–60% of HCV-infected patients whereas overt cryoglobulinaemia vasculitis develops in only 5–10% of the cases. MC reflects the expansion of B cells producing a pathogenic IgM with rheumatoid factor (RF) activity. Because cryoglobulin-producing B cells in HCV are mostly monoclonal, HCV-associated MC can be viewed as a benign B cell lymphoproliferative condition. The disease expression of MC vasculitis is variable, ranging from mild clinical symptoms (purpura, arthralgia) to fulminant life-threatening complications (glomerulonephritis, widespread vasculitis). The overall risk of non-Hodgkin's lymphoma in patients with HCV-MC is estimated to be 35 times higher than that in the general population. This review will focus on recent advances in our understanding of the clinical course, complications, pathophysiology and treatment of those immune-mediated disorders.

KEY WORDS: HCV infection, Mixed cryoglobulinaemia, Vasculitis, Non-Hodgkin's lymphoma

Submitted 7 January 2007; revised version accepted 11 April 2007.
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