Abstract
Mixed cryoglobulinemia syndrome (MC) is a systemic vasculitis involving kidneys, joints, skin, and peripheral nerves. While many autoimmune, lymphoproliferative, and neoplastic disorders have been associated with this disorder, hepatitis C virus (HCV) is known to be the etiologic agent in the majority of patients. Therefore, clinical research has focused on anti-viral drugs and, more recently, on the new, highly potent Direct-acting Antiviral Agents (DAAs). These drugs assure sustained virologic response (SVR) rates >90%. Nevertheless, data on their efficacy in patients with HCV-associated cryoglobulinemic vasculitis are disappointing, possibly due to the inability of the drugs to suppress the immune-mediated process once it has been triggered.Despite the potential risk of exacerbation of the infection, immunosuppression has traditionally been regarded as the first-line intervention in cryoglobulinemic vasculitis, especially if renal involvement is severe. Biologic agents have raised hopes for more manageable therapeutic approaches, and Rituximab (RTX), an anti CD20 monoclonal antibody, is the most widely used biologic drug. It has proved to be safer than conventional immunosuppressants, thus substantially changing the natural history of HCV-associated cryoglobulinemic vasculitis by providing long-term remission, especially with intensive regimens.The present review focuses on the new therapeutic opportunities offered by the combination of biological drugs, mainly Rituximab, with DAAs.
Highlights
Mixed cryoglobulinemia syndrome (MC) is an idiopathic or secondary vasculitis characterised by the presence of mixed cryoglobulins in the circulation, and deposition in target organs
The present review focuses on the new therapeutic opportunities offered by the combination of biological drugs, mainly Rituximab, with Direct-acting Antiviral Agents (DAAs)
Pathogenetic scenario of cryoglobulinemic nephritis Chronic stimulation by hepatitis C virus (HCV) infection sustaining the synthesis of IgM rheumatoid factor Abnormal kinetics and tissue deposition of the HCV-containing ICs Ineffective cryoglobulin clearance by monocyte/macrophages, which are implicated in perpetuating glomerular damage
Summary
Mixed cryoglobulinemia syndrome (MC) is an idiopathic or secondary vasculitis characterised by the presence of mixed cryoglobulins in the circulation, and deposition in target organs. Most of the cases that were previously described as “idiopathic or essential” are associated with www.impactjournals.com/oncotarget the presence of hepatitis C virus (HCV) infection [27]. Circulating (usually asymptomatic) cryoglobulins are detectable in up to 40% of patients with chronic hepatitis C. Long-term HCV infection, older age and genetic background all represent predisposing factors for the development of MC [1,8,9]. Renal manifestations involve only 0.1-0.2% of HCV-infected, but the presence of glomerulonephritis is a major long-term prognostic factor for MC
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