Strategies to prevent persistent or relapsed mixed cryoglobulinemia

ABSTRACT Introduction Mixed cryoglobulinemia (MC) are immune complexes that can deposit in small and medium size arteries and cause systemic vasculitis called cryoglobulinemic vasculitis (CryoVas). CryoVas most common clinical manifestations include purpura, arthralgia and/or arthritis, skin ulcers, peripheral neuropathy, nephritis, and may progress to more life-threatening illness. Hepatitis C virus (HCV) infection is the more frequent condition to be assessed in patients with MC, followed by connective tissue diseases and B-cell non-Hodgkin’s lymphoma. In HCV-related cases, the mainstay of CryoVas treatment is interferon free antiviral therapy. However, a significant proportion of patients who show HCV eradication will develop persistent CryoVas needing treatment intensification. Areas covered This review highlights key advances, recent clinical trial updates and ongoing studies on the management of persistent and refractory CryoVas. Therapeutic strategies and treatment agents to manage the disease are described. A literature review was performed by searching for available research studies published before January 2020 on the Medline (PubMed) database. Expert opinion Antiviral therapy with direct antiviral agents is the mainstay of treatment for patients with HCV-associated CryoVas. B-cell depleting strategies, mainly with rituximab, is the main therapeutic option in severe and refractory cases of infectious and noninfectious CryoVas. Ongoing trials are currently exploring other targeted biological treatments in this setting.