HCV-Related Cryoglobulinemic Vasculitis: An Overview

Abstract

Cryoglobulinemic vasculitis (CV) is a small and medium-size vasculitis characterized by the occurrence in the serum of reversibly precipitating proteins, named cryoglobulins and immunochemically formed by an IgM component (monoclonal or polyclonal) with rheumatoid factor activity and a polyclonal IgG component (mixed cryoglobulins). CV is almost invariably associated to chronic HCV infection. In addition to the typical purpura/asthenia/arthralgia syndrome, the pleomorphic clinical picture often includes membrano-proliferative glomerulonephritis and motor-sensory axonopathy. Hemorrhagic alveolitis, gastrointestinal vasculitis, heart failure and hyperviscosity syndrome are less frequently observed. The amount of cryoprecipitate, named cryocrit, is not strictly related to the clinical severity of CV and to the viral load. Rheumatoid factor activity and low levels of the complement C4 (sometimes also of C3 and CH50) are unfailing serological abnormalities. The pathogenetic mechanism of CV is still incompletely defined, but it can be essentially ascribed to the formation of HCV particles/IgG/IgM macromolecular complexes that are good acceptors of C1q and can therefore bind to the C1q receptors on the endothelial cells. This would eventually trigger the onset of a leukocytoclastic vasculitis. Although with wide geographic variations, CV can progress to non-Hodgkin lymphoma (NHL), possibly through an impaired regulatory control of B-cell growth. In Italy, approximately 5 % of B-cell NHLs seem to be HCV-related. Therapy of CV should be adapted to each patient’s condition. Low daily doses of corticosteroids can mitigate arthralgias and possibly prevent flares, but their long-term administration should be avoided for their inevitable side effects. Pulsed intravenous infusions of corticosteroids can prevent organ damage in the course of severe vasculitis flares. High rates of sustained virologic responses can be achieved with the use of the new interferon-free, all-oral direct acting antiviral agents. In patients with refractory/relapsing or with severely active CV, characterized by B-cell clonal expansion, a B-cell depleting therapy with rituximab often results in a satisfactory control of clinical features, although the viral load may sometimes transiently increase. Low-grade and indolent HCV-related NHLs have been found to undergo complete or partial remission following anti-HCV therapy. Finally, double filtration plasmapheresis can contribute to the improvement and possibly healing of chronic ulcers on the legs.