POS0827 HEPATOTROPIC VIRUSES WITH HIGHER RHEUMATOID FACTOR, BUT NOT RHEUMATIC DISEASES LINK TO PREVALENT CRYOGLOBULINEMIA. CORRELATION OF CLINICAL AND SEROLOGICAL MARKERS WITH ETIOLOGICAL CAUSES
Authors: S. Jeria Navarro, T. Franco, L. Alserawan, D. Lobo Prat, A. García-Guillén, L. Sainz Comas, H. Park, A. M. Millán Arciniegas, P. Moya, B. Magallares, C. Díaz-Torné, E. Moga, C. Juarez, H. Corominas
Journal: Annals of the Rheumatic Diseases (2021)

Background: Cryoglobulinemia (CG) is a rare phenomenon, which is defined as the persistent presence in serum of abnormal immunoglobulins (Igs) that precipitate in vitro at less than 37°C and dissolve when the temperature rises again. Is related to hematological disorders, infections and autoimmunes diseases. Objectives: To describe the differential clinical features, serological and demographics in a cohort of patients diagnosed with CG. Methods: We describe a retrospective cohort of 252 cryoglobulin (Cg) positive samples, obtained from a database from the immunology laboratory of a tertiary hospital (November 2018-November 2019). We obtained 182 patients with CG, classified according to their etiology into 4 groups: 1)Rheumatic diseases (RD) that includes rheumatoid arthritis, Systemic lupus erythematosus, Sjögren´s syndrome and Systemic scleroderma, 2)Hepatotropic viruses (HV) with patients diagnosed with Hepatitis C virus, B virus and both, 3)Hematological diseases (HD) and 4)Essential cryoglobulinemia (CGE). Demographic variables, clinical and serological data were collected. A comparative analysis was performed with the Mann-Whitney U test and the multivariate Kruskal-Wallis test, nonparametric variables were compared using a Wilcoxon test. Ten patients, with more than one disease from 4 groups, were excluded from the study. Results: Out of 182 reviewed patients, 172 were included in the study. Mean age at diagnosis was 59.7(±14.0). Demographic, clinical and laboratory characteristics are described in table 1. Mixed CG was the predominant subtype, in 116 (67.4%) patients. The most prevalent CG-associated diseases were HV infection with 91(53%) patients. CGE mostly presented with cutaneous manifestations (p=0.0001), particularly purpura. In RD group the presence of Raynaud and non-erosive arthritis (p=0.0001) was relevant. Laboratory findings showed that CG titration varies according to the etiology, being HD the one with the highest values with 292.2 (±546.2). There is significant difference in terms of the average of rheumatoid factor (RF) being higher in the group by CGE. On other hand, the group HV presented more consumption of complement, and showed the lowest average p=0.0001, without more severe clinical manifestations. RD (n=47 ) HV (n=91 ) HD (n=17 ) CGE (n=17 ) Gender,n(%) F 42 (89.4 ) 57 (62.6 ) 7 (41.2 ) 11 (64.7 ) Age at dg, years, (± SD ) 60.6 (±14 ) 59.6 (±13.1 ) 61.1(±16.6 ) 56.3(±20.8 ) p=0.8 CLINICAL CHARACTERISTICS Skin n (% ) 18 (38.3 ) 10 (11.0 ) 2 (11.8 ) 9 (52.9 ) p&lt;0.001 Raynaud n (% ) 14 (29.8 ) 1 (5.9 ) 3 (17.6 ) p&lt;0.001 Purpura n (% ) 6 (12.8 ) 9 (9.9 ) 2 (11.8 ) 6 (35.3 ) p=0.04 Acrocyanosis n (% ) 6 (12.8 ) 1 (5.9 ) p=0.0033 Ulcers n (% ) 3 (6.4 ) 2 (2.2 ) - 2 (11.8 ) p=0.19 Peripheric Neuro n (% ) 10 (21.3 ) 9 (9.9 ) 1 (5.9 ) 4 (23.5 ) p=0.13 N-E arthritis n (% ) 22 (46.8 ) 8 (8.8 ) 1 (5.9 ) 4 (23.5 ) p&lt;0.001 GMN n (% ) 5 (10.6 ) 3 (3.3 ) 1 (5.9 ) 3 (17.6 ) p=0.11 LABORATORY Cg (mg/dL) x (± SD ) 26.7 (±63.2 ) 65.8 (±256.5 ) 292.4 (±546.2 ) 47.59 (±79.1 ) p&lt;0.001 Isotype IgG, n (% ) G+M 26 (55.3 ) G+M 72 (79.1 ) M 8 (47.1 ) G+M 12 (70.6 ) β2M (≥1.8 mg/L), n (% ) 7/40 (17.5% ) 1/5 (20.0% ) 3/12 (25.0% ) - p= 0.44 RCP (mg/L) p 50 10.3 (±26.2 ) 3.9 (±3.0 ) 13.4 (±18.3 ) 8.5 (±12.0 ) p= 0.47 ESR (mm/h) p50 40.0 (±28.5 ) 20.3 (±20.2 ) 35.4 (±35.1 ) 24.5 (±25.0 ) p= 0.0003 RF + (&gt;20UI/mL), n (% ) 19/46 (41.3 ) 44/86 (51.2 ) 5/11 (45.5 ) 7/17 (41.2 ) p= 0.09 p50 90.6 (±175.9 ) 161.0 (±219.5 ) 94.8 (±135.6 ) 284.5 (±619.3 ) p&lt;0.001 C3 (&lt;85mg/dL), n % ) 20 (42.6 ) 47 (51.6 ) 3 (17.6 ) 3 (17.6 ) p= 0.13 x (± SD ) 90.1 (±28.6 ) 68.5 (±10.8 ) 99.1 (±29.0 ) 114.8 (±12.7 ) p&lt;0.001 C4 (&lt;12mg/dL), n (% ) 17 (36.2 ) 36 (39.6 ) - 3 (17.6 ) p= 0.02 x (± SD ) 15.6 (±9.0 ) 7.6 (±3.5 ) 20.4 (±7.4 ) 21.1 (±9.5 ) p&lt;0.001 Conclusion: In our cohort, not all patients with CG presented clinical manifestations being those associated with CGE and RD those with the highest skin and joint expression. The most prevalent association of CG continues to be the HV and we confirmed the characteristic decrease in C3 and C4 complement levels, together with the positivity for RF. Disclosure of Interests: None declared