Ab0862 the Impact of the Age in Major Relapses of Cryoglobulinemic Vasculitis Related to Primary Sjögren’s Syndrome

Background: Cryoglobulinemic vasculitis related to primary Sjögren's syndrome (CV-pSS) is a rare condition, yet it is known to be associated with high disease activity and risk of lymphoma (NHL) in pSS1. Data on the impact of age at diagnosis of CV are scarce. Objectives: The aim of this study was to evaluate the impact of age in the frequency of major relapses and clinical response in CV-pSS patients. Methods: Patients with pSS referred to the Rheumatology Unit of Udine and diagnosed with CV from January 2003 to January 2021 were retrospectively collected. The inclusion criteria were the documented positivity of cryoglobulins in pSS patients and the fulfillment of classification criteria of CV2. The exclusion criteria were the concomitant HCV and/or HBV infections and asymptomatic cryoglobulinemia. Major relapses were defined as the recurrences of clinical symptoms and signs requiring additional treatment beyond glucocorticoids (GCs). Results: 20 pSS patients (90% females) with CV were included. In according to the age of CV diagnosis, patients were divided in three groups: Figure 1A. During the follow up (median time: 9 years IQR 5-14), at least one major relapse occurred in 86% (6/7), 29% (2/7), and 0% of patients in each group (p-value 0.005), respectively (Figure 2). The main manifestation at relapse was the cutaneous and/or nervous involvement. A complete clinical response was achieved in 4/8 relapsing patients with rituximab (RTX) alone. Three out of 8 patients required a combination therapy belimumab (BELI) plus RTX, and one patient received a BTK inhibitor. At last follow-up, the median BVASv3 was 3/33 (IQR 0-3) and patients mainly complained articular and nervous involvement (Figure 1B). A complete immunological response was documented in 29%, 29%, and 50% of patients in each group (p-value=0.716), respectively. Two out of 20 patients developed chronic hypogammaglobulinemia (IgG≤600mg/dL), not complicated by recurrent infections. Concerning the lymphoproliferative risk, nine out of 20 patients experienced NHL in their medical history (4/7, 2/7, 3/6 in each group, respectively). The onset of NHL was closely associated (within ±3years) with the CV onset in 5/9 patients, while it preceded (2/9) or followed (2/9) CV onset with a median time span of approximately ±11 years. Conclusion: In CV-pSS patients, an earlier onset of CV may be correlate with a higher probability of experiencing at least one major relapse despite the treatment. The lymphoproliferative risk in CV-pSS is increased and not influenced by the age at CV diagnosis. REFERENCES: 1 Quartuccio L, Baldini C, Priori R, et al (2017) Cryoglobulinemia in Sjögren Syndrome: A Disease Subset that Links Higher Systemic Disease Activity, Autoimmunity, and Local B Cell Proliferation in Mucosa-associated Lymphoid Tissue. J Rheumatol 44:1179–1183. https://doi.org/10.3899/jrheum.161465 2 Quartuccio L, Isola M, Corazza L, et al (2014) Validation of the classification criteria for cryoglobulinaemic vasculitis. Rheumatol Oxf Engl 53:2209–2213. https://doi.org/10.1093/rheumatology/keu271 Acknowledgements: NIL. Disclosure of Interests: None declared.