Gender-specific patterns of glandular and extraglandular involvement in Sjögren's disease: a retrospective cohort study.

BACKGROUND: Sjögren's disease (SjD) is a chronic systemic autoimmune disorder characterized by glandular dysfunction and variable extraglandular organ involvement. Although the disease predominantly affects women, the clinical expression of SjD may differ between genders.

OBJECTIVES: To evaluate gender-associated differences in glandular and extraglandular manifestations, systemic disease activity, and the predictive performance of serological markers for high disease activity in patients with SjD.

METHODS: This retrospective cohort study included patients fulfilling the 2016 ACR/EULAR classification criteria for SjD who were followed at a tertiary rheumatology center. Demographic characteristics, glandular manifestations, extraglandular organ involvement, laboratory findings, and systemic disease activity assessed using the EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) were recorded. High disease activity was defined as ESSDAI ≥ 5. Gender-stratified comparisons were performed, and receiver operating characteristic (ROC) analyses were conducted to evaluate the ability of serological markers to discriminate high disease activity.

RESULTS: A total of 191 patients were included (117 women and 74 men). Female patients more frequently presented with glandular symptoms, including xerostomia and xerophthalmia, as well as musculoskeletal manifestations such as arthralgia. In contrast, male patients exhibited a higher frequency of pulmonary involvement. Although mean ESSDAI scores were higher in men, multivariable logistic regression analyses adjusting for age, disease duration, and smoking status indicated that gender was not independently associated with high systemic disease activity. Instead, pulmonary involvement emerged as the strongest predictor of elevated ESSDAI scores. ROC analyses demonstrated limited discriminatory ability of conventional serological markers for identifying patients with high disease activity.

CONCLUSIONS: In this cohort of patients with Sjögren's disease, differences in systemic disease activity between genders appeared to be primarily related to patterns of organ involvement rather than gender itself. Pulmonary manifestations represented a major contributor to systemic disease burden, while conventional serological markers showed limited value for identifying high disease activity. Comprehensive organ-based evaluation may therefore be more informative than serological profiles for assessing systemic disease activity in SjD. Key Points • Male patients with Sjögren's disease exhibit significantly higher systemic disease activity compared with female patients, predominantly driven by pulmonary involvement. • Female patients demonstrate a glandular- and musculoskeletal-dominant phenotype, with more prominent sicca symptoms and arthralgia. • Conventional serological markers show limited ability to predict high disease activity in male patients. • Gender-stratified clinical assessment may improve risk stratification and individualized management in Sjögren's disease.