Characteristic clinical and immunologic features of Sjögren's disease patients presenting with major salivary gland swelling at diagnosis.

INTRODUCTION/OBJECTIVES: Sjögren's disease (SjD) is a heterogeneous systemic autoimmune disorder with diverse clinical presentations. While sicca symptoms are considered hallmark features, a substantial proportion of patients present with non-sicca manifestations. Although major salivary gland swelling is a recognized feature, its potential implications for baseline evaluation and clinical characterization at diagnosis remain incompletely understood. We aimed to classify SjD patients according to presenting symptoms at diagnosis and to characterize the clinical features of patients presenting with major salivary gland swelling. METHOD: We conducted a retrospective observational study of patients with SjD who were enrolled at a tertiary referral center between June 2020 and March 2025. Patients were categorized by the predominant presenting symptom documented at diagnosis. Baseline clinical indices, imaging, laboratory findings, and treatment status were assessed at cohort enrollment. Clinical features were compared between patients presenting with major salivary gland swelling and those with other presenting symptoms. RESULTS: Among 731 patients with SjD, major salivary gland swelling was the presenting symptom at diagnosis in 48 (6.6%). These patients were significantly younger at diagnosis and had higher objective disease activity despite comparable patient-reported symptom burden. Salivary gland ultrasonography demonstrated more severe abnormalities. Lymphadenopathy, hypergammaglobulinemia, and low C3 levels were more frequent. In multivariable analysis, younger age and low C3 remained independently associated with major salivary gland swelling presentation. CONCLUSIONS: Major salivary gland swelling as a presenting symptom at diagnosis was associated with a distinct SjD phenotype. Recognition of this presentation may support a more comprehensive baseline clinical and immunologic evaluation. Key Points • Major salivary gland swelling as a presenting symptom represents a clinically meaningful phenotype of Sjögren's disease. • This phenotype is characterized by younger age, higher systemic disease activity, and more severe ultrasonographic glandular involvement. • Recognition of this presentation may support a more comprehensive baseline clinical and immunologic evaluation.