Long-term outcomes and prognosis of mixed cryoglobulinaemia: a European multicentre study of 1294 patients

Objectives: To assess the long-term outcomes and prognostic factors of patients presenting with all-cause mixed cryoglobulinaemia vasculitis (CryoVas). Methods: A European multicentre cohort study (EuroCryo) of 1294 patients presenting with all-cause CryoVas. Results: The main aetiology for CryoVas was Hepatitis C Virus ( HCV) with 469 (36%) cases, followed by essential forms (n = 344, 26%) and autoimmune conditions (n = 302, 23%), with Sjögren’s disease being the most common (n = 268, 21%). Over a median follow-up of 2.8 years, a total of 558 CryoVas patients experienced 661 severe events, notably 221 relapses, 52 severe infections and 45 lymphomas. The multivariable model for event-free survival retained a post-2014 diagnosis, male sex, older age, low C4 levels, positive Rheumatoid Factor and higher baseline creatinine levels as poor prognostic factors; HCV aetiology was protective. Factors associated with the occurrence of lymphoma were a post-2014 diagnosis, autoimmune aetiology, fever, fatigue and low C4 levels. Conclusion: HCV was for long considered a poor prognosis factor in CryoVas, and now those secondary to autoimmune conditions seem to evolve with a more severe course, notably carrying a higher lymphoma risk.