Treatment

The approach depends upon the severity of the disease. Plasmapheresis may reduce the levels of cryoglobulin. Any underlying condition should be treated where possible including hepatitis C (1).

• In patients who are asymptomatic, careful monitoring for manifestations of cryoglobulinaemia such as ulcers, acrocyanosis, digital gangrene, and purpura is usually sufficient. Patients should initially be followed every 2-3 months. (1,2)
• For patients with mild to moderate manifestations (purpura, weakness, arthralgia, arthritis, mild neuropathy), lower doses of corticosteroids with shortest duration of treatment to control symptoms should be considered. Long-term use of corticosteroids is not recommended. (3)
• Patients with moderate to severe manifestations (leukocytoclastic vasculitis, mononeuritis multiplex, glomerulonephritis) require urgent immunosuppressive treatment before initiating therapy for chronic HCV infection. (4)

Rituximab (a monoclonal antibody targeted to CD20 on B cells) may be considered in selected patients (who do not have evidence of active HIV or hepatitis B infection) with: (5)

• moderate to severe or severe-rapidly progressive MC
• cryoglobulinaemic vasculitis
• comorbidities that preclude other therapies

References

1. Sise ME, Bloom AK, Wisocky J, et al. Treatment of hepatitis C virus-associated mixed cryoglobulinemia with direct-acting antiviral agents. Hepatology. 2016 Feb;63(2):408-17.
2. American Association for the Study of Liver Diseases; Infectious Diseases Society of America. HCV guidance: recommendations for testing, managing, and treating hepatitis C​. Oct 2022 [internet publication].
3. Dammacco F, Lauletta G, Vacca A. The wide spectrum of cryoglobulinemic vasculitis and an overview of therapeutic advancements. Clin Exp Med. 2023 Jun;23(2):255-72.
4. Muchtar E, Magen H, Gertz MA. How I treat cryoglobulinemia. Blood. 2017 Jan 19;129(3):289-98.
5. Quartuccio L, Bortoluzzi A, Scirè CA, et al. Management of mixed cryoglobulinemia with rituximab: evidence and consensus-based recommendations from the Italian Study Group of Cryoglobulinemia (GISC). Clin Rheumatol. 2023 Feb;42(2):359-70.