CO:08:2 | Impact of comorbidities on clinical-serological phenotype of primary Sjögren's disease: a retrospective analysis of a multicenter cohort

Background. Primary Sjögren's disease (SjD) is characterized by significant phenotypic heterogeneity frequently associated with other autoimmune diseases or different comorbidities, which influence clinical course, phenotypic expression, quality of life and therapeutic approach. However, their clinical relevance is underestimated. We evaluated clinical and laboratory differences at diagnosis in SjD patients stratified according to presence or absence of concomitant autoimmune diseases and selected comorbidities, in order to outline their impact on clinical phenotype.   Methods: A multi-center SjD chort was retrospectively analyzed. Clinical-demographic characteristics, disease activity by ESSDAI, dryness, pain and fatigue degree by ESSPRI and serological variables were collected at diagnosis. Traditional cardiovascular (CV) risk factors were recorded as cumulative data. For study aim, the following comorbidities were considered as cumulative parameter at the last follow-up: fibromyalgia, autoimmune thyroiditis, non-hematologic cancers, primary biliary cholangitis (PBC), celiac disease (CD) and history of severe infections.   Results. 1231 SjD patients were included. Patients with fibromyalgia (132/1231, 10.7%) were characterized by younger age at diagnosis (mean 49.7 vs. 52.1 years, p=0.048), lower ESSDAI (2.04 vs. 3.52, p=0.029), higher ESSPRI (6.9 vs. 5.1, p=0.000), higher frequency of obesity (p=0.009) and lower anti-Ro (p=0.049), anti-La (p=0.016) and rheumatoid factor prevalence (p=0.000). Patients with autoimmune thyroiditis (263/1231, 21.4%) had higher age at diagnosis (mean 52.3 vs. 50 years, p=0.031), higher ESSDAI (4.12 vs. 3.15, p=0.034) and higher frequency of anti-Ro52 and Ro60 (p=0.01 and p=0.03, respectively), a serological finding also observed in patients with PBC (26/1231, 2.1%) (anti-Ro 52, p=0.02; anti-Ro60, p=0.000). Patients with CD (27/1231, 2.2%) were younger (mean 43 vs. 52 years, p=0.002) and had higher prevalence of anti-Ro52 (p=0.039) and Ro60 (p=0.025). Patients with history of non-hematologic cancers (98/1231, 8%) were older at diagnosis (mean 55 vs. 51 years, p=0.017) and characterized by higher prevalence of hypertension (p=0.000) and history of severe infections (p=0.022). Patients with history of severe infections (45/1231, 3.6%) had higher frequency of extraglandular involvement and higher prevalence of anti-Ro60 (p=0.005), hypertension (p=0.02) and hypercholesterolemia (p=0.002).   Conclusions. Comorbidities may significantly influence clinical and immunological phenotype of SjD. The study allowed to identify three distinct phenotypes at diagnosis. Patients with fibromyalgia are characterized by higher prevalence of subjective symptoms but lower disease activity and reduced antibody positivity. In contrast, patients with concomitant autoimmune diseases show higher antibody positivity and greater disease activity. Non-hematologic cancers and history of severe infections identify subgroups characterized by greater systemic involvement, older age and a higher prevalence of CV comorbidities. Early identification of specific comorbidities can be useful for prognostic stratification and personalized follow-up pathways.