The chimeric monoclonal antibody (IgG1/κ) rituximab (RTX) is directed against the CD20 antigen, expressed on the surface of normal (from pre-B to mature B lymphocytes) and malignant B lymphocytes. Since mixed cryoglobulinemia is sustained by a low-grade B lymphoproliferation exhibiting autoimmune features, there is a strong rationale for using RTX in the treatment of this disorder. Almost all clinical manifestations of mixed cryoglobulinemia may benefit from RTX treatment, and the antibody is generally well tolerated and safe. Caution should be exerted in patients with high cryoglobulin levels or hyperviscosity at baseline, because of possible flare syndrome. Although RTX can lead to an increase of HCV viremia, hepatitis re-activation is rarely observed. Prospective comparative trials are warranted in order to better evaluate the therapeutic impact of RTX and to define the best treatment approach
