Objective Neurological manifestations of Sjögren’s syndrome can be severe but also treatment-responsive. We aimed to systematically evaluate neurological manifestations of primary Sjögren’s syndrome and find clinical features allowing sufficient identification of affected patients (pSSN) among those with Sjögren’s syndrome without neurological involvement (pSS). Methods Para-/clinical features of patients with primary Sjögren’s syndrome (2016 ACR/EULAR classification criteria) were compared between pSSN and pSS. At our university-based center, patients with suggestive neurological symptoms undergo screening for Sjögren’s syndrome, and newly diagnosed pSS patients are thoroughly evaluated for neurologic involvement. pSSN disease activity was rated by the Neurological Involvement of Sjögren’s Syndrome Disease Activity Score (NISSDAI). Results 512 patients treated for pSS/pSSN at our site between 04/2018 and 07/2022 were included (238 pSSN patients [46%] vs. 274 pSS patients [54%], cross-sectional design). Independent predictors of neurological involvement in Sjögren’s syndrome were male sex [p < 0.001], older age at disease onset [p < 0.0001], hospitalization at first presentation [p < 0.001], lower IgG levels [p = 0.04] and higher eosinophil values (treatment-naïve) [p = 0.02]. Univariate regression additionally showed older age at diagnosis [p < 0.001], lower prevalence of rheumatoid factor [p = 0.001], SSA(Ro)/SSB(La) antibodies [p = 0.03; p < 0.001], higher white blood cell count [p = 0.02] and CK levels [p = 0.02] (treatment-naïve) in pSSN. Interpretation Patients with pSSN had different clinical characteristics than patients with pSS and represented a large proportion of the cohort. Our data suggest that neurological involvement in Sjögren’s syndrome has been underestimated. Intensified screening for neurologic involvement should be included in the diagnostic algorithm for Sjögren’s syndrome, especially in males of older age and with severe disease course requiring hospitalization.

Background: Sicca syndrome represents a heterogeneous group of conditions, such as Sjögren syndrome, causing xerophthalmiaand xerostomia. This study characterizes in depth patients with Sicca syndrome and evaluates salivary gland ultrasound (SGUS).Methods: Principal component analysis and hierarchical clustering of clinical parameters, such as ESSPRI, ESSDAI and laboratory data, were performed on all referrals for assessment of Sicca symptoms between October 2018 and March 2021. SGUS and labial gland biopsies were compared across groups.Results: A total of 583 patients were assessed. Objective dryness was confirmed in 73% of the patients. Cluster analysis identified 3 groups with post-hoc analysis confirming distinct phenotypes: Somatic Group (283/583; 49%) with more frequent symptoms but limited objective dryness; Dry Without Autoimmune Features (DAFneg, 206/584; 35%), and Dry With Autoimmune Features (DAFpos, 94/584;16%). DAFpos patients had highest autoantibody titers (anti-SSA(Ro) 240 vs. 3.6 vs. 3.8; p &lt; 0.001), most extra-glandular manifestations (p &lt; 0.001), and highest median SGUS Score (DAFpos: 8 [IQR 4–10] vs. SG: 2 [1–4] vs. DAFneg 4 [2–5]; p &lt; 0.001). No tangible correlation with primary Sjögren syndrome criteria was observed.Discussion: SGUS score correlated with a subset of patients with Sjögren syndrome, identified in the DAFpos cluster. This study highlights heterogeneity within sicca and, indeed, Sjögren syndrome, highlighting the need for further studies.

IntroductionPrimary Sjögren's syndrome (pSS) is associated with an increased prevalence of traditional risk factors and cardiovascular diseases (CVDs). The study aimed to identify specific risk factors for CVD in pSS patients.MethodsPSS patients with and without CVD were compared. All patients fulfilled the EULAR/ACR classification criteria. Patients with CVD presented at least one of the following manifestations: myocardial infarction, transient ischemic attacks, ischemic or hemorrhagic stroke, peripheral artery disease, coronary artery disease, and carotid plaques. Data were collected by a standardized protocol and review of medical records.Results61/312 (19.6%) pSS patients presented with CVD. Traditional risk factors such as hypertension, hypercholesterinemia and diabetes (p &lt; 0.05), pSS manifestations, in particular vasculitis (p = 0.033) and Raynaud's phenomenon (p = 0.018) were associated with CVD. Among patients with ischemic events (28/312, 9%), particularly cerebrovascular disease (n = 12/28, 42.9%), correlations with increased EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) (p = 0.039) and EULAR Sjögren's Syndrome Patient Reported Index (ESSPRI) (p = 0.048) were observed. Age at first cerebrovascular event was 55.2 [48.9–69.6] years. Multivariate analysis confirmed hypertension [odds ratio (OR) 3.7, 95% confidence interval (CI) 1.87–7.18, p &lt; 0.001], hypercholesterinemia (OR 3.1, 95% CI 1.63–5.72, p &lt; 0.001), male gender (OR 0.4, 95% CI 0.17–0.78, p = 0.009), Raynaud's phenomenon (OR 2.5, 95% CI 1.28–4.82, p = 0.007), and CNS involvement (OR 2.7, 95% CI 1.00–7.15, p = 0.048) as independent CVD predictors.ConclusionRaynaud's phenomen as well as vasculitis and high ESSDAI have shown a significant association to CVD. PSS patients with cerebrovascular events were younger than expected. Knowledge about risk factors may help clinicians to identify pSS patients at risk for CVD. After diagnosis of pSS, patients should be screened for risk factors such as hypertension and receive appropriate therapy to prevent or at least reduce sequelae such as infarction. However, further investigations are necessary in order to achieve a reliable risk stratification for these patients.

BackgroundPrimary Sjögren’s syndrome (pSS) is associated with an increased prevalence of traditional risk factors and cardiovascular diseases (CVDs).ObjectivesThe study aimed to identify specific risk factors for CVD in pSS patients.MethodsPSS patients with and without CVD were compared. All patients fulfilled the EULAR/ACR classification criteria. Patients with CVD presented at least one of the following manifestations: myocardial infarction, transient ischemic attacks, ischemic or hemorrhagic stroke, peripheral artery disease, coronary artery disease and carotid plaques. Data were collected by a standardized protocol and review of medical records.Results61/312 (19.6%) pSS patients presented with CVD. Traditional risk factors such as hypertension, hypercholesterinemia and diabetes (p<0.05), pSS manifestations, in particular vasculitis (p=0.033) and Raynaud’s phenomenon (p=0.018) were associated with CVD. Among patients with ischemic events (28/312, 9%), particularly cerebrovascular disease (n=12/28, 42.9%), correlations with increased EULAR Sjögren’s Syndrome Disease Activity Index (ESSDAI) (p=0.039) and EULAR Sjögren’s Syndrome Patient Reported Index (ESSPRI) (p=0.048) were observed. Age at first cerebrovascular event was 55.2 [48.9 – 69.6] years. Multivariate analysis confirmed hypertension (odds ratio (OR) 3.7, 95% confidence interval (CI) 1.87–7.18, p<0.001), hypercholesterinemia (OR 31 3.1, 95% CI 1.63–5.72, p<0.001), male gender (OR 0.4, 95% CI 0.17–0.78, p=0.009), Raynaud’s phenomenon (OR 2.5, 95% CI 1.28–4.82, p=0.007) and CNS involvement (OR 2.7, 95% CI 1.00–33 7.15, p=0.048) as independent CVD predictors.ConclusionRaynaud´s phenomenon as well as vasculitis and high ESSDAI have shown a significant association to CVD. PSS patients with cerebrovascular events were younger than expected. Knowledge about risk factors may help clinicians to identify pSS patients at risk for CVD. After diagnosis of pSS, patients should be screened for risk factors such as hypertension and receive appropriate therapy to prevent or at least reduce sequelae such as infarction. However, further investigations are necessary in order to achieve a reliable risk stratification for these patients.AcknowledgementsWe would like to express our gratitude to the staff of the Rheumatology Outpatients Department at Hannover Medical School for their continual help in organization of patients Reference styles.Disclosure of InterestsNone Declared.

BackgroundSicca syndrome represents a heterogeneous group of conditions, including Sjögren syndrome, causing xerophthalmia and xerostomia.ObjectivesThis study characterizes in depth patients with Sicca syndrome and evaluates salivary gland ultrasound (SGUS) in this cohort.MethodsPrincipal component analysis and hierarchical clustering of clinical parameters, including ESSPRI, ESSDAI and laboratory data were performed on all referrals for assessment of Sicca symptoms between October 2018 and March 2021. SGUS and labial gland biopsies were compared across groups.Results583 patients were assessed. Objective dryness was confirmed in 73% of patients. Cluster analysis identified 3 groups with post-hoc analysis confirming distinct phenotypes: Somatic Group (283/583; 49%) with higher reported symptoms but limited objective dryness; Dry Without Autoimmune Features (DAFneg, 206/532; 35%) and Dry With Autoimmune Features (DAFpos, 94/532; 16%). DAFpos patients had highest autoantibody titres (SSA 240 vs 3.6 vs 3.8; p<0.001), most extra-glandular manifestations (p<0.001) and highest median SGUS Score (DAFpos: 8 [IQR 4-10] vs SG: 2 [1-4] vs DAFneg 4 [2-5]; p< 0.001). No tangible correlation primary Sjögren syndrome criteria was observed.ConclusionSGUS score correlated with a subset of Sjögren syndrome patients, identified in the DAFpos cluster. This study highlights heterogeneity within Sicca and indeed Sjögren syndrome, highlighting the need for further studies.References[1]Chisholm DM, Mason DK. Labial salivary gland biopsy in Sjogren’s disease. J Clin Pathol. 1968;21(5):656-60[2]De Vita S, Lorenzon G, Rossi G, Sabella M, Fossaluzza V. Salivary gland echography in primary and secondary Sjogren’s syndrome. Clin Exp Rheumatol. 1992;10(4):351-6Table 1.Comparing and contrasting the clinical demographics and attributes of the entire cohort subdivided into the three groups identified through principal component analysis and subsequent hierarchical clustering. Results are shown as mean and interquartile range unless otherwise stated.SomaticDAFnegDAFposp N (%)283(49)206(35)94(16) Female, n (%)239(84)142(69)81(86%)<0.001 Age at Onset, yrs47.3[36.6-55.9]60.2[51.1-67.3]50.1[35.5-59.4]<0.001 BMI, kgm-226.1[23.0-31.0]24.7[21.7-27.7]24.6[22.4-28.0]0.003 Smoker, n (%)50(18)15(7)4(4)0.06ESSPRI Scores  - Dryness6[3-7]2[1-3]4[2-7]<0.001  - Limb Pain7[5-8]5[2-6]6[4-8]  - Fatigue8[6-9]3[2-5]5[3-8]Reported Symptoms Raynaud, n (%)86(30)51(25)44(47)0.006 Arthralgia, n (%)222(78)118(57)61(65)0.002 Myalgia, n (%)197(70)87(42)40(43)0.003 Stiffness, n (%)98(35)37(18)23(25)0.001 Parotitis, n (%)62(22)24(12)33(35)0.001 Sand corn, n (%)168(59)62(30)44(47)0.001 Ocular Inf, n (%)120(42)45(22)26(27)0.005ESSDAI  - Score5[2-12]5[0-11]11[4-17]<0.001Antibody Titres  - ANA ≥ 1:160178(63)152(74)44(47)<0.001  - RhF U/ml10.0[10.0-10.9]10.0[10.0-11.3]23.3[11.7-71.0]<0.001 - Alpha-Fodrin U/ml9[5-22]9[6-19]12[6-25]0.05  - anti-SSA(Ro) U/ml3.6[0.3-101.3]3.8[0.3-102.3]240.0[192.8-240.0]<0.001  - anti-SSB(La) U/ml0.4[0.3-3.4]0.3[0.3-1.9]73.1[3.8-312.5]<0.001Measurable Dryness Saxon, g3.5[2.4-4.9]4.2[3.3-5.3]2.3[0.6-3.7]<0.001 Schirmer, mm7.0[2.0-17.9]3.0[0.5-12.0]2.5[0.0-7.1]<0.001Labial Gland Biopsy, n (%) - Biopsy performed150(53)120(58)18(19) - Chisholm Score ≥366(44)64(53)9(50) - Median Score2[1-3]3[2-3]3[3-4]Salivary Gland Ultrasound, n (%) - SGUS = 039(14)39(19)1(1) - SGUS ≥673(26)55(27)38(41) SGUS Score2[1-4]4[2-5]8[4-10]<0.001Figure 1.A 3D scatterplot composed of the first 3 dimensions of the principal component analysis, identified as providing greatest inertia gain on hierarchical clustering. The Somatic Group (SG) are represented by the black points. Patients in the Dryness without autoimmune features (DAFneg) are represented by pink points and Dryness with autoimmune features (DAFpos) patients with green dots.AcknowledgementsWe would like to express our gratitude to the staff of the Rheumatology Outpatients Department at Hannover Medical School for their continual help in organization of patients: G Mielke, A Lahn, Dr. S Hirsch.Disclosure of InterestsEmelie Kramer: None declared, Tabea Seeliger: None declared, Thomas Skripuletz: None declared, Vega Gödecke: None declared, Sonja Beider: None declared, Alexandra Jablonka: None declared, Torsten Witte: None declared, Diana Ernst Grant/research support from: This study was financially supported by Novartis. The funder was not involved in the study design, collection, analysis, interpretation of data, the writing of this article or the decision to submit it for publication.