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



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.



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.



Patients with primary SS who fulfilled criteria for cryoglobulinaemic vasculitis at diagnosis are at higher risk of death.
Sjögren Syndrome Research Group, Laboratory of Autoimmune Diseases Josep Font, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Department of Autoimmune Diseases, ICMiD, Hospital Clínic, Barcelona, Spain.
Soledad
S
Retamozo
Sjögren Syndrome Research Group, Laboratory of Autoimmune Diseases Josep Font, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Department of Autoimmune Diseases, ICMiD, Hospital Clínic, Barcelona, Spain.
Hoda
H
Gheitasi
Rheumatology Clinic, Department of Medical and Biological Sciences, Azienda Ospedaliero Universitaria S. Maria della Misericordia, University of Udine, Udine, Italy.
Luca
L
Quartuccio
Sjögren Syndrome Research Group, Laboratory of Autoimmune Diseases Josep Font, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Department of Autoimmune Diseases, ICMiD, Hospital Clínic, Barcelona, Spain Rheumatology Clinic, Department of Medical and Biological Sciences, Azienda Ospedaliero Universitaria S. Maria della Misericordia, University of Udine, Udine, Italy.
Belchin
B
Kostov
Rheumatology Clinic, Department of Medical and Biological Sciences, Azienda Ospedaliero Universitaria S. Maria della Misericordia, University of Udine, Udine, Italy.
Laura
L
Corazza
Sjögren Syndrome Research Group, Laboratory of Autoimmune Diseases Josep Font, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Department of Autoimmune Diseases, ICMiD, Hospital Clínic, Barcelona, Spain.
Albert
A
Bové
Institut d'Investigacions Biomèdiques August Pi i Sunyer, Primary Care Centre Les Corts, CAPSBE, Primary Care Research Group, Barcelona, Spain.
Antoni
A
Sisó-Almirall
Sjögren Syndrome Research Group, Laboratory of Autoimmune Diseases Josep Font, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Department of Autoimmune Diseases, ICMiD, Hospital Clínic, Barcelona, Spain.
Myriam
M
Gandía
Sjögren Syndrome Research Group, Laboratory of Autoimmune Diseases Josep Font, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Department of Autoimmune Diseases, ICMiD, Hospital Clínic, Barcelona, Spain mramos@clinic.ub.es.
Manuel
M
Ramos-Casals
Rheumatology Clinic, Department of Medical and Biological Sciences, Azienda Ospedaliero Universitaria S. Maria della Misericordia, University of Udine, Udine, Italy.
Salvatore
S
De Vita
Sjögren Syndrome Research Group, Laboratory of Autoimmune Diseases Josep Font, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Department of Autoimmune Diseases, ICMiD, Hospital Clínic, Barcelona, Spain.
Pilar
P
Brito-Zerón
D003449:Cryoglobulinemia / Q000150:complications / Q000401:mortality*; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D016393:Lymphoma, B-Cell / Q000209:etiology / Q000401:mortality; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012189:Retrospective Studies; D012307:Risk Factors; D012859:Sjogren's Syndrome / Q000150:complications / Q000401:mortality*; D056647:Systemic Vasculitis / Q000150:complications / Q000401:mortality*
ESSDAI; Sjögren syndrome; cryoglobulinaemia; mortality; vasculitis