Long-term outcomes and prognosis of mixed cryoglobulinemia: a European multicenter study of 1,294 patients.

Saadoun, David; Cacoub, Patrice; Retamozo, Soledad; Sebastiani, Marco; Vacchi, Caterina; Casato, Milvia; Visentini, Marcella; Brito-Zerón, Pilar et al. · Rheumatology (Oxford) · 2026

prospective_cohort · Level II

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Abstract

To assess the long-term outcomes and prognostic factors of patients presenting with all-cause mixed cryoglobulinemia vasculitis (CryoVas). A European multicentre cohort study (EuroCryo) of 1,294 patients presenting with all-cause CryoVas. The main aetiology for CryoVas was HCV with 469 (36%) cases, followed by essential forms (n = 344, 26%) and autoimmune conditions (n = 302, 23%) with Sjogren'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. 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. 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.