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

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

doi:10.1016/j.semarthrit.2020.07.013

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

Semin Arthritis Rheum. 2020 Oct;50(5):846-853. doi: 10.1016/j.semarthrit.2020.07.013. Epub 2020 Jul 27.

Authors

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

Affiliations

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: [email protected].

PMID: 32896698
DOI: 10.1016/j.semarthrit.2020.07.013

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.

Keywords: Cryoglobulinemia; HCV infection; Sjögren's syndrome; Vasculitis.

Publication types

Multicenter Study

MeSH terms

Cryoglobulinemia* / complications
Hepacivirus
Hepatitis C* / complications
Humans
Lymphoma*
Retrospective Studies
Sjogren's Syndrome* / complications
Vasculitis* / complications