Cryoglobulinemic vasculitis in primary Sjögren's Syndrome: Clinical presentation, association with lymphoma and comparison with Hepatitis C-related disease.

M Mavrommati, A V Goules, A G Tzioufas, H M Moutsopoulos, S De Vita, D Ι Fotiadis, M Galli, F N Skopouli, C Baldini, C P Mavragani, T E Exarchos, P V Voulgari, O D Argyropoulou, E Zampeli, A Venetsanopoulou, C R Bassoli, E Treppo, V Donati, L Quartuccio, F Ferro, S Gandolfo, E Critselis, L Chatzis, V Pezoulas

Journal: Seminars in arthritis and rheumatism 2021;50(5):846-853

PMID: 32896698

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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.

Address: Department of Pathophysiology, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece; Joint Rheumatology Academic Program, University of Athens, Athens, Greece.; Unit of Medical Technology and Intelligent Information Systems, University of Ioannina, Ioannina, Greece.; 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.; Rheumatology Clinic, Department of Medical area, University of Udine, Udine, Italy.; Rheumatology Unit, Department of Clinical and Experimental Medicine, University of Pisa, Italy.; Infectious Disease Unit, Department of Clinical and Biomedical Sciences Hospita L. Sacco, Milan, Italy.; Institute for Autoimmune Systemic and Neurological Diseases, Athens, Greece.; Department of Internal Medicine and Autoimmune Diseases, Euroclinic of Athens, Greece.; Rheumatology Clinic, Department of Internal Medicine, Medical School, University of Ioannina, Ioannina, Greece.; Department of Informatics, Ionian University, Corfu, Greece.; Department of Physiology, Medical School, National and Kapodistrian University of Athens, Athens, Greece.; Department of Nutrition and Clinical Dietetics, Harokopio University of Athens, Athens, Greece.; 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.; Institute for Autoimmune Systemic and Neurological Diseases, Athens, Greece; Athens Academy of Athens, Chair Medical Sciences/Immunology, Greece.; 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: [email protected].

DOI: 10.1016/j.semarthrit.2020.07.013