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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
| 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<0.001 |
| Raynaud n (% ) | 14 (29.8 ) | 1 (5.9 ) | 3 (17.6 ) | p<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<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<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 + (>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<0.001 |
| C3 (<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<0.001 |
| C4 (<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<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