Cryoglobulinaemic vasculitis at diagnosis predicts mortality in primary Sjogren syndrome: analysis of 515 patients

Objective. To evaluate the fulfilment of classification criteria for cryoglobulinaemic vasculitis (CV) at diagnosis in a large cohort of patients with primary SS and their correlation with poor outcomes. Methods. We included 515 consecutive patients tested for serum cryoglobulins who fulfilled the 2002 classification criteria for primary SS. CV classification criteria and serum cryoglobulins at diagnosis were assessed as predictors of death and lymphoma using Cox proportional-hazards regression analysis adjusted for age and gender. Results. Positive serum cryoglobulins were detected in 65 (12%) patients, of whom 21 (32%) fulfilled CV classification criteria. Compared with patients positive for cryoglobulins who did not fulfil CV criteria, patients with CV had a higher frequency of type II cryoglobulinaemia (86% vs 43%, P = 0.04), a higher mean cryocrit level (6.58% vs 1.25%, P < 0.001) and a higher cumulated mean EULAR-SS disease activity index score (35.3 vs 16.2, P < 0.001). After a mean follow-up of 110 months, 45 (9%) patients developed B-cell lymphoma and 33 (6%) died. Compared with patients without cryoglobulins, patients with cryoglobulins who fulfilled [hazard ratio (HR) = 7.47, 95% CI: 3.38, 16.53] and did not fulfil (HR = 2.56, 95% CI: 1.03, 6.35) CV criteria both showed a higher risk of B-cell lymphoma in the univariate analysis, but not in the multivariate models. Compared with patients without cryoglobulins, patients with CV had a higher risk of death in both the univariate (HR = 11.68, 95% CI: 4.44, 30.74) and multivariate (HR = 4.36, 95% CI: 1.32, 14.47) models. Conclusion. Patients with primary SS who fulfilled criteria for cryoglobulinaemic vasculitis at diagnosis are at higher risk of death.