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Cryoglobulins are complexes of circulating immunoglobulins that precipitate when subjected to low temperatures. Whereas some cryoglobulins (type I) are relatively benign, others (type II) activate complexes of IgM antibodies directed against polyclonal IgG molecules that are associated with conditions such as nephritis, vasculitis, and cutaneous lesions (palpable purpura). Moreover, type II–III mixed cryoglobulinemia (MC) can be associated with hepatitis C virus (HCV) infection or can progress to non-Hodgkin lymphoma. In some patients, MC is ameliorated by therapy that targets associated infections or neoplasms, but, in other patients, disease is progressive despite such treatment. The CD20 monoclonal antibody rituximab is effective in mana…