PO:23:048 | Clinical and serological differences of an Italian Sjögren’s disease cohort according to three geographic macro-area localization

Maria Letizia Currò¹, Roberto Dal Pozzolo², Giacomo Cafaro², Valeria Manfrè³, Gaetano La Rocca⁴, Alessia Alunno⁵, Francesco Carubbi⁵, Nicoletta Del Papa⁶, Viktoriya Pavlych⁷, Angelica Gattamelata⁸, Letizia Pia Di Corcia⁹, Pamela Bernardini¹⁰, Luca Quartuccio³, Chiara Baldini⁴, Paola Cipriani⁷, Roberta Priori⁸, Onorina Berardicurti⁹, Serena Guiducci¹⁰, Fabiola Atzeni¹, Elena Bartoloni² | ¹Unità di Reumatologia. Università di Messina, Italy; ²SC Reumatologia. Università di Perugia, Italy; ³Unità di Reumatologia. Università di Udine, Italy; ⁴Unità di Reumatologia. Università di Pisa, Italy; ⁵Divisione di Medicina Interna e Nefrologia. Università di L'Aquila, Italy; ⁶Dipartimento di Reumatologia. Università di Milano, Italy; ⁷Unità di Reumatologia. Università di L'Aquila, Italy; ⁸UOC Reumatologia. Università Sapienza Roma, Italy; ⁹Unità di Reumatologia. Università Campus Biomedico Roma, Italy; ¹⁰Unità di Reumatologia. Università di Firenze, Italy

Objectives. Sjögren’s disease (SjD) is driven by a complex interplay of genetic predisposition, immunologic factors and environmental exposures. Increasing evidence suggests that geo-epidemiological and socio-environmental factors may modulate disease expression and influence both clinical manifestations and management. However, little is known about such variability in Italian cohorts. This study investigates geographic differences in clinical, serological, and comorbidity profiles in an Italian SjD cohort and explores potential disparities in diagnostic and therapeutic approaches across geographic macro-areas.

Methods. A retrospective analysis was performed on a SjD cohort fulfilling 2002 AECG and/or 2016 ACR/EULAR criteria grouped into three macro-areas of Italy: North, Center, and South. Demographic, clinical, serological, histological, and comorbidity data were compared using chi-square and Kruskal-Wallis tests, with Holm-Bonferroni correction.

Results. 1231 patients, 95% female, with mean age at diagnosis of 53 years (42-63), were included. The majority were of Caucasian ethnicity (96.8%). Median ESSDAI score at onset was 2 (range 1-4) and median ESSPRI score 5.66 (range 4-7.33). When patients were stratified according to the three geographical regions, no differences were observed in sex distribution or ethnicity. Patients from the South were diagnosed at an older age compared to those from the North and Center (55 vs 51 years, p=0.001, for both). Xerostomia and xerophthalmia were similarly prevalent in the North and South, but significantly less frequent in the Center (p<0.001). South patients had higher frequency of activity in constitutional and articular domains compared to North and Center (p<0.001). The biological domain showed the lowest frequency of activity in the South, consistent with a less active immunological phenotype in older patients. Lymphoma prevalence was highest in the North (8.8%) compared to the Center (3.2%, p=0.014) and South (0.5%, p<0.001). Salivary gland biopsy was less frequently performed in the North (29.8%) compared to the Center (67%) and South (73%) (p<0.001), with lower focus scores (FS) in Northern and Southern patients. Despite fewer biopsies and lower FS, Northern patients showed higher rates of hematologic malignancies, possibly reflecting referral bias to high-specialty centers. Regarding comorbidities, hypertension was less prevalent in the North (p<0.001), obesity more frequent in the South (p<0.001), hypercholesterolemia and former smoking more common in the Center (20.4%, p=0.005 and 21%, p<0.001). Despite these differences in traditional cardiovascular (CV) risk factors, major CV events did not differ significantly across regions, supporting that disease-related, beyond traditional risk factors, may drive CV risk in SjD.

Conclusions. This study provides the first evidence of a geo-epidemiological pattern in SjD severity in Italy, highlighting how geographic origin is associated with disease phenotype and comorbidities. Regional disparities likely reflect environmental, socio-cultural, and healthcare system factors, underscoring the need for context-specific, personalized disease management strategies.