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.