title: Cryoglobulinemic vasculitis.
abstract: OBJECTIVE
  Cryoglobulinemic vasculitis is an immune-complex-mediated systemic vasculitis involving small-medium-sized vessels. A causative role of hepatitis C virus in over 80% patients has been definitively established, with heterogeneous geographical distribution. This review focuses on recent etiopathogenetic, clinico-diagnostic, and therapeutical studies.
  
  
  RESULTS
  Hepatitis C virus cannot be integrated into the host genome; it may exert a chronic stimulus to the immune system. The interaction between hepatitis C virus envelope protein E2 with B-cell CD 81 receptor may increase the frequency of VDJ rearrangement in antigen-reactive B lymphocytes. One consequence is the activation of various protooncogenes, including anti-apoptotic Bcl-2. The extended B-cell survival is responsible for autoantibody and immune-complex production, including mixed cryoglobulins; some malignancies, mainly B-cell lymphomas, may complicate cryoglobulinemic vasculitis. Environmental or viral/host genetic cofactors should be relevant in the pathogenesis of hepatitis C virus-related diseases. Cryoglobulinemic vasculitis may overlap with other diseases (systemic vasculitides, Sjögren's syndrome, autoimmune hepatitis, lymphoma), which should be carefully considered for a correct diagnosis and treatment. Cumulative survival of cryoglobulinemic vasculitis is significantly lower compared with the general population. Therapeutic strategies for cryoglobulinemic vasculitis include etiologic (antiviral), pathogenetic (cyclophosfamide, rituximab), or symptomatic (steroids, plasmapheresis) treatments, which should be tailored to the individual patient according to the severity/activity of clinical symptoms.
  
  
  CONCLUSIONS
  Cryoglobulinemic vasculitis represents a crossroads among autoimmune and lymphoproliferative disorders; as hepatitis C virus infection is the major causative factor, cryoglobulinemic vasculitis is an important model for etiopathogenetic studies of virus-related diseases.
authors.affiliation: Chair and Rheumatology Unit, Department of Internal Medicine, University of Modena e Reggio Emilia, Medical School, Modena, Italy. clferri@unimore.it
authors.forename: Clodoveo
authors.initials: C
authors.lastname: Ferri
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Mascia
mesh_terms: D003449:Cryoglobulinemia / Q000175:diagnosis / Q000188:drug therapy / Q000276:immunology* / Q000821:virology; D016174:Hepacivirus; D006526:Hepatitis C / Q000150:complications / Q000276:immunology*; D006801:Humans; D014657:Vasculitis / Q000175:diagnosis / Q000188:drug therapy / Q000276:immunology* / Q000821:virology