O D Argyropoulou1, V Pezoulas2, L Chatzis1, E Critselis3, S Gandolfo4, F Ferro5, L Quartuccio4, V Donati5, E Treppo4, C R Bassoli6, A Venetsanopoulou1, E Zampeli7, M Mavrommati8, P V Voulgari9, T E Exarchos10, C P Mavragani11, C Baldini6, F N Skopouli12, M Galli6, D Ι Fotiadis13, S De Vita4, H M Moutsopoulos14, A G Tzioufas15, A V Goules1. 1. Department of Pathophysiology, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece; Joint Rheumatology Academic Program, University of Athens, Athens, Greece. 2. Unit of Medical Technology and Intelligent Information Systems, University of Ioannina, Ioannina, Greece. 3. Proteomics Facility, Center for Systems Biology, Biomedical Research Foundation of the Academy of Athens, Athens, Greece; Department of Nutrition and Clinical Dietetics, Harokopio University of Athens, Athens, Greece. 4. Rheumatology Clinic, Department of Medical area, University of Udine, Udine, Italy. 5. Rheumatology Unit, Department of Clinical and Experimental Medicine, University of Pisa, Italy. 6. Infectious Disease Unit, Department of Clinical and Biomedical Sciences Hospita L. Sacco, Milan, Italy. 7. Institute for Autoimmune Systemic and Neurological Diseases, Athens, Greece. 8. Department of Internal Medicine and Autoimmune Diseases, Euroclinic of Athens, Greece. 9. Rheumatology Clinic, Department of Internal Medicine, Medical School, University of Ioannina, Ioannina, Greece. 10. Department of Informatics, Ionian University, Corfu, Greece. 11. Department of Physiology, Medical School, National and Kapodistrian University of Athens, Athens, Greece. 12. Department of Nutrition and Clinical Dietetics, Harokopio University of Athens, Athens, Greece. 13. Unit of Medical Technology and Intelligent Information Systems, University of Ioannina, Ioannina, Greece; Department of Biomedical Research, Institute of Molecular Biology and Biotechnology, FORTH, Ioannina, Greece. 14. Institute for Autoimmune Systemic and Neurological Diseases, Athens, Greece; Athens Academy of Athens, Chair Medical Sciences/Immunology, Greece. 15. Department of Pathophysiology, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece; Joint Rheumatology Academic Program, University of Athens, Athens, Greece. Electronic address: agtzi@med.uoa.gr.
Abstract
OBJECTIVE: To describe the clinical spectrum of cryoglobulinemic vasculitis (CV) in primary Sjögren's syndrome (pSS), investigate its relation to lymphoma and identify the differences with hepatitis C virus (HCV) related CV. METHODS: From a multicentre study population of consecutive pSS patients, those who had been evaluated for cryoglobulins and fulfilled the 2011 classification criteria for CV were identified retrospectively. pSS-CV patients were matched with pSS patients without cryoglobulins (1:2) and HCV-CV patients (1:1). Clinical, laboratory and outcome features were analyzed. A data driven logistic regression model was applied for pSS-CV patients and their pSS cryoglobulin negative controls to identify independent features associated with lymphoma. RESULTS: 1083 pSS patients were tested for cryoglobulins. 115 (10.6%) had cryoglobulinemia and 71 (6.5%) fulfilled the classification criteria for CV. pSS-CV patients had higher frequency of extraglandular manifestations and lymphoma (OR=9.87, 95% CI: 4.7-20.9) compared to pSS patients without cryoglobulins. Purpura was the commonest vasculitic manifestation (90%), presenting at disease onset in 39% of patients. One third of pSS-CV patients developed B-cell lymphoma within the first 5 years of CV course, with cryoglobulinemia being the strongest independent lymphoma associated feature. Compared to HCV-CV patients, pSS-CV individuals displayed more frequently lymphadenopathy, type II IgMk cryoglobulins and lymphoma (OR = 6.12, 95% CI: 2.7-14.4) and less frequently C4 hypocomplementemia and peripheral neuropathy. CONCLUSION: pSS-CV has a severe clinical course, overshadowing the typical clinical manifestations of pSS and higher risk for early lymphoma development compared to HCV related CV. Though infrequent, pSS-CV constitutes a distinct severe clinical phenotype of pSS.
OBJECTIVE: To describe the clinical spectrum of cryoglobulinemic vasculitis (CV) in primary Sjögren's syndrome (pSS), investigate its relation to lymphoma and identify the differences with hepatitis C virus (HCV) related CV. METHODS: From a multicentre study population of consecutive pSS patients, those who had been evaluated for cryoglobulins and fulfilled the 2011 classification criteria for CV were identified retrospectively. pSS-CV patients were matched with pSS patients without cryoglobulins (1:2) and HCV-CV patients (1:1). Clinical, laboratory and outcome features were analyzed. A data driven logistic regression model was applied for pSS-CV patients and their pSS cryoglobulin negative controls to identify independent features associated with lymphoma. RESULTS: 1083 pSS patients were tested for cryoglobulins. 115 (10.6%) had cryoglobulinemia and 71 (6.5%) fulfilled the classification criteria for CV. pSS-CV patients had higher frequency of extraglandular manifestations and lymphoma (OR=9.87, 95% CI: 4.7-20.9) compared to pSS patients without cryoglobulins. Purpura was the commonest vasculitic manifestation (90%), presenting at disease onset in 39% of patients. One third of pSS-CV patients developed B-cell lymphoma within the first 5 years of CV course, with cryoglobulinemia being the strongest independent lymphoma associated feature. Compared to HCV-CV patients, pSS-CV individuals displayed more frequently lymphadenopathy, type II IgMk cryoglobulins and lymphoma (OR = 6.12, 95% CI: 2.7-14.4) and less frequently C4 hypocomplementemia and peripheral neuropathy. CONCLUSION: pSS-CV has a severe clinical course, overshadowing the typical clinical manifestations of pSS and higher risk for early lymphoma development compared to HCV related CV. Though infrequent, pSS-CV constitutes a distinct severe clinical phenotype of pSS.