Search Results (229)

Background: Sensorineural hearing loss (SNHL) has increasingly been recognized as an extra-articular manifestation of systemic autoimmune rheumatic disease (SARDs), but its burden and clinical characteristics remain inconsistent. This systematic review and meta-analysis evaluated the prevalence, risk, audiometric characteristics, diagnostic methods and prognostic factors of SNHL in patients with major SARDs. Methods: A systematic search of the PubMed, Scopus and Cochrane Library databases was conducted between 25 June and 3 July 2026 in accordance with PRISMA 2020 guidelines. Observational studies evaluating SNHL in patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), primary Sjögren syndrome (pSS) and systemic sclerosis (SSc) were included. Meta-analyses using a random-effects model were performed to estimate pooled prevalence and odds ratios (OR). Subgroup analyses, meta-regression, sensitivity analysis, publication bias assessment and certainty of evidence evaluation were performed. Results: Twenty-two studies met the eligibility criteria and were included. The pooled prevalence of SNHL was 50% (95% CI: 13–87%, p < 0.001) in patients with RA, 61% (95% CI: 22–95%, p < 0.001) in SLE, 31% (95% CI: 5–67%, p < 0.001) in pSS and 28% (95% CI: 14–44%, p < 0.001) in SS. Patients with RA (OR 1.92; 95% CI: 1.29–2.87) and SLE (OR 21.68; 95% CI: 4.65–100.99) had significantly increased odds of SNHL compared to healthy controls. Hearing loss was predominantly mild, bilateral, and cochlear in origin, and affected high or extended high frequencies. Longer disease duration and greater disease activity were associated with worse hearing thresholds. In exploratory analyses of RA studies, sample size, study setting, and study design were significant study-level moderators of heterogeneity. Conclusions: SNHL is reported with appreciable prevalence across several major systemic autoimmune rheumatic diseases, although prevalence estimates are highly heterogeneous and should be interpreted cautiously. Comparative evidence supports increased odds of SNHL in RA, whereas the magnitude of the association in SLE remains uncertain because of the limited and imprecise evidence. Evidence establishing increased comparative risk in pSS and SSc remains insufficient. Audiological assessment may be particularly relevant in patients with longstanding or active disease. Full article

Pulmonary involvement in primary Sjögren’s syndrome (pSS) is common and exhibits significant clinical heterogeneity, particularly in cases where interstitial lung disease (pSS-ILD) develops. Reported variability in prevalence, radiologic phenotypes, and clinical outcomes indicates both underlying biological diversity and differences in classification criteria, case ascertainment, and diagnostic approaches. Pulmonary manifestations may be subclinical, and early interstitial abnormalities are frequently undetected due to the limited sensitivity of chest radiography. Presentations such as ILD-first or non-sicca onset, seronegative disease, and coexisting or mimicking conditions, including lymphoproliferative disorders and amyloidosis, increase the difficulty of diagnosis. High-resolution computed tomography (HRCT) demonstrates a wide range of patterns, including inflammatory, fibrotic, and mixed phenotypes, which often overlap and change over time. Reliance on pattern-based categorization may not adequately reflect the underlying pathobiology; for example, those with usual interstitial pneumonia (UIP)-like morphology have significant prognostic implications within the pSS spectrum. A structured, multidomain assessment that integrates symptoms, pulmonary function, and HRCT findings, ideally inside a multidisciplinary discussion (MDD), may boost diagnostic accuracy and risk stratification. Nevertheless, heterogeneity in definitions and reporting continues to impede comparability across patient cohorts. Additional research is necessary to standardize phenotyping frameworks and identify predictors of disease progression to inform individualized diagnostic and management strategies. Full article

Background: Salivary gland dysfunction is a central manifestation of Sjögren’s syndrome, but the relationship between quantitative salivary impairment and salivary microcrystallization remains insufficiently defined. This study aimed to assess unstimulated and stimulated whole salivary flow and salivary pH in patients with primary and secondary Sjögren’s syndrome and to explore salivary microcrystallization indices as complementary descriptive markers of salivary physicochemical patterns. Materials and Methods: This cross-sectional observational study included 126 patients diagnosed with primary or secondary Sjögren’s syndrome. Unstimulated whole salivary flow, stimulated whole salivary flow, and salivary pH were assessed under standardized conditions. Salivary dysfunction severity was classified according to predefined functional salivary parameters. Salivary microcrystallization was evaluated microscopically on dried saliva samples and expressed using the IMK-RFR and IMK-RFS indices. Differences between disease subtypes and associations between salivary parameters, microcrystallization indices, and dysfunction severity were analyzed. Results: The mean unstimulated salivary flow rate was 0.272 ± 0.246 mL/min, while the mean stimulated salivary flow rate was 1.04 ± 0.50 mL/min. In unadjusted analyses, patients with primary Sjögren’s syndrome showed lower unstimulated and stimulated salivary flow rates than patients with secondary Sjögren’s syndrome. Both salivary flow parameters were inversely associated with salivary dysfunction severity. In an exploratory internal consistency ROC analysis, unstimulated salivary flow showed good internal agreement with grade ≥ 3 salivary dysfunction, while stimulated salivary flow showed very high internal agreement. Salivary pH showed limited internal consistency with dysfunction severity. Firth penalized logistic regression indicated that stimulated whole salivary flow remained associated with grade ≥ 3 salivary dysfunction after adjustment for unstimulated salivary flow. IMK values described salivary microcrystallization patterns within the Sjögren’s syndrome cohort; however, they were not robustly correlated with salivary flow, pH, or dysfunction severity. Conclusions: Salivary flow assessment remains a simple, non-invasive, and clinically relevant method for evaluating glandular dysfunction in Sjögren’s syndrome. In this cohort, primary Sjögren’s syndrome was associated with lower salivary flow rates, but these unadjusted findings should be interpreted as descriptive. Salivary microcrystallization provided exploratory information on qualitative salivary patterns, but its clinical value remains limited and requires methodological standardization and validation in larger prospective studies. Full article

Background/Objectives: Sjögren’s disease (SjD) is a chronic autoimmune disorder characterized by a wide range of clinical manifestations, often leading to delayed diagnosis. This study aimed to evaluate and compare the clinical and laboratory characteristics of patients with primary and secondary SjD and those with sicca symptoms without SjD. Methods: This comparative cross-sectional study included 84 participants enrolled between 2019 and 2024: 27 patients with primary Sjögren’s disease (pSjD), 4 with secondary Sjögren’s disease (sSjD), and 53 with sicca symptoms without SjD (non-SjD/NSjD). Primary SjD was diagnosed according to the 2016 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) classification criteria. Results: Compared with NSjD patients, those with pSjD and sSjD had significantly lower unstimulated whole saliva (UWS) and stimulated whole saliva (SWS) flow rates (p < 0.001), a higher prevalence of antinuclear antibodies (ANA) (twice as frequent) (p = 0.005), and higher frequencies of anti-SSA/Ro60, anti-SSA/Ro52, anti-SSB/La, and rheumatoid factor (RF) positivity (p = 0.002, p = 0.003, p = 0.005, and p = 0.019, respectively). In addition, SjD patients had higher EULAR Sjögren’s Syndrome Disease Activity Index (ESSDAI) scores (p = 0.026) and more frequently demonstrated a focus score (FS) ≥ 1 on minor labial salivary gland (MLSG) biopsy (p < 0.001). Serum vitamin D levels were lower in pSjD patients than in NSjD patients; however, the difference was not statistically significant (57.8 ± 20.4 vs. 70.6 ± 18.3; p = 0.259). Conclusions: Patients with pSjD exhibited distinct clinical and laboratory characteristics compared with those with sicca symptoms without SjD. Sialometry, anti-SSA antibodies, and MLSG biopsy were identified as the most important diagnostic tools for differentiating SjD from NSjD. Full article

Objective: Chronic lung diseases (CLDs), for example, interstitial lung disease, manifest as an extra-articular complication of rheumatoid arthritis (RA). The contribution of anti-bactericidal permeability-increasing protein antibodies (BPI Abs) in lung involvement in RA or primary Sjögren’s syndrome has been reported. Studies related to anti-BPI Abs in RA with CLD are infrequent. Here, the involvement of anti-BPI Abs with RA and CLD complications was evaluated. Methods: Enzyme-linked immunosorbent assays were used to measure anti-BPI Abs in RA sera. Results: Higher anti-BPI Ab amounts were present in the RA with usual interstitial pneumonia (UIP) than without CLD (mean ± standard deviation, 10.4 ± 23.5 [ng/mL] vs. 1.3 ± 3.8, p = 0.0020). Area under the curve values of receiver operating characteristic curves for anti-BPI Ab and Krebs von den lungen-6 were alike between RA with UIP and without CLD (0.8616, 95% CI 0.8184–0.9048; 0.8716, 95% CI 0.8151–0.9282, p = 0.5933, respectively). A relationship between anti-BPI Ab and anti-carbamylated protein Ab levels was observed in RA patients (rho 0.3508, p = 1.47 × 10⁻¹⁴). Conclusions: Anti-BPI Abs were related to UIP in RA patients and might be biomarkers for UIP. These findings predict anti-BPI Abs involvement in UIP pathogenesis in RA. Full article

Although salivary glands are highly vascularized, the microvascular endothelial barrier has only recently emerged as a pivotal determinant of glandular homeostasis and disease. This review synthesizes current understanding of the salivary gland endothelial barrier, with particular emphasis on the regulation of tight junctions (TJs). Structurally, the barrier comprises endothelial cells interconnected by TJs and adherens junctions, supported by a basement membrane and pericytes. Among TJ components, claudin-5 serves as a key endothelial-specific regulator of paracellular permeability, and is dynamically modulated by biochemical and mechanical stimuli during saliva secretion. Cholinergic, adrenergic, and neuropeptide signaling pathways coordinate to fine-tune endothelial permeability to meet the fluctuating secretory demands. Conversely, under pathological conditions, such as Sjögren’s syndrome, radiation-induced injury, diabetes mellitus, fibrotic diseases, and salivary gland tumors, the integrity of the endothelial TJ complex is impaired. These pathologies are characterized by aberrant TJ expression, mislocalization, and signaling-mediated junctional disassembly, which trigger vascular leakage and immune cell infiltration—two key processes that act as primary drivers of glandular dysfunction. Collectively, these findings enrich our understanding of the microvascular mechanisms that link endothelial barrier function to salivation, and highlight that the restoration of junctional integrity is a promising therapeutic strategy for salivary gland diseases. Full article

Background/Objectives: Primary Sjögren’s syndrome (pSS) is a chronic autoimmune rheumatic disease that clinically presents with symptoms of xerostomia and xerophthalmia, as well as a wide range of other symptoms that may affect patients’ daily functioning and life satisfaction. The main purpose of this study was to assess their health-related quality of life (HRQoL) using both general and disease-specific questionnaires. Methods: This cross-sectional observational research with prospective data collection was conducted at the Rheumatology Clinic of the University Clinical Centre of Kragujevac. Participants were divided into two groups: patients with oral manifestations (oral manifestations group) and those presenting with xerostomia only, without other oral lesions or symptoms (xerostomia-only group). A complete clinical examination of the patient’s oral cavity was performed by one doctor of dental medicine. HRQoL was evaluated using various generic and disease-specific instruments. Results: A total of 80 participants were included in the study, of whom 40 were in the oral manifestations group and 40 in the xerostomia-only group. Patients with oral manifestations had significantly higher scores across all PSS-QoL domains compared with the xerostomia-only group (p < 0.001). A statistically significant difference in the total EQ-5D result was detected between groups (0.7 (0.3) vs. 0.8 (0.1), p < 0.001). In multivariable regression analysis (R² = 0.921), the ESSPRI score (β = 0.418, p < 0.001) and the presence of oral manifestations (β = −1.155, p < 0.001) were significant independent predictors of impaired HRQoL, while disease activity showed no significant association (p = 0.895). Conclusions: Patients with primary Sjögren’s syndrome presenting with oral manifestations have poorer HRQoL compared with participants with xerostomia only. Symptom burden, including dryness, pain, fatigue, and oral manifestations, may be associated with decreased HRQoL, in contrast to disease activity. Full article

Background and Clinical Significance: Hyperviscosity syndrome (HVS) is a rare complication of primary Sjögren’s syndrome (pSS). While therapeutic plasma exchange (TPE) is the standard treatment to clear pathogenic immunoglobulins, its execution can trigger severe, atypical systemic risks. Case Presentation: A 60-year-old woman with pSS and extreme polyclonal hypergammaglobulinemia (total protein 100 g/L, IgM 41 g/L) presented with an acute hyperviscosity crisis, causing retinopathy, neurological deficits, and skin ischemia. Emergency TPE with 5% albumin replacement successfully reduced IgM by ~90% (to 6.39 g/L), resolving HVS symptoms. However, 20 min post-procedure, the patient suffered sudden hemodynamic collapse (BP 50/30 mmHg) and developed multiple massive, expanding soft-tissue hematomas. Laboratory tests revealed a coagulopathy consistent with plasma protein depletion following therapeutic plasma exchange, characterized by severe hypofibrinogenemia (1.35 g/L) and a 50% reduction in total serum protein. TPE was permanently discontinued. The patient was successfully stabilized using aggressive fluid resuscitation, vasopressors, and fresh frozen plasma (FFP) transfusions, followed by maintenance therapy with rituximab. Conclusions: In conclusion, clinicians should remain vigilant that severe hyperviscosity syndrome can be driven by a polyclonal increase in immunoglobulins rather than just monoclonal entities; furthermore, managing this condition requires careful balancing of TPE efficacy against its potential to trigger profound depletion coagulopathy. Full article

Xerostomia is a common and debilitating condition caused by salivary gland dysfunction, frequently associated with primary Sjögren’s syndrome and head and neck radiotherapy. Current management is largely symptomatic and does not address underlying glandular injury. Extracellular vesicles (EVs), including exosomes, have emerged as candidate mediators of intercellular communication that have been proposed for diagnostic and therapeutic applications; however, their translational relevance to xerostomia remains uncertain and is currently supported only by exploratory evidence. This scoping review aimed to map and interpret current evidence on EV-based approaches in xerostomia and salivary gland dysfunction. A scoping review was conducted in accordance with “Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR)” checklist. Twenty-five articles were included, comprising 14 primary studies and 11 review articles. Studies were analysed based on application focus, methodological characteristics, reported outcomes, and translational readiness. Most primary studies focused on EVs as diagnostic biomarkers or their roles in immune–epithelial signalling. Therapeutic research was limited and largely confined to human-relevant translational models, namely human peripheral blood mononuclear cell (PBMC) assays and freshly resected human salivary gland tissue-maintained ex vivo. Outcomes were predominantly molecular and cellular, with minimal assessment of salivary flow or patient-reported symptoms. The current evidence base, although biologically plausible, remains exploratory: most included studies are mechanistic, and no clinical efficacy studies in xerostomia were identified. A substantial gap therefore persists between molecular findings and clinically meaningful outcomes, and further translational research is required before any conclusions can be drawn regarding the clinical utility of EV-based approaches. Full article

Background: Autoimmune diseases such as primary Sjögren’s syndrome and type 1 diabetes are frequently complicated by hepatic injury, yet therapies that simultaneously target inflammation and parenchymal damage remain limited. Mitochondrial dysfunction with excessive reactive oxygen species (ROS) production drives a self-amplifying pathogenic loop by activating the cGAS-STING innate immune pathway. We previously observed that a Chinese herbal formula preserved mitochondrial ultrastructure in autoimmune NOD mice, and computational screening identified trifolirhizin—a natural pterocarpan flavonoid—as the candidate active constituent mediating this protection. Here, we investigated the hepatoprotective effects and underlying mechanisms of trifolirhizin in autoimmune-associated liver injury. Methods: Female NOD mice received trifolirhizin (5, 10, or 20 mg/kg/day) for four weeks, with C57BL/6J mice as healthy controls. Hepatic histopathology, inflammatory cytokines, mitochondrial ultrastructure (TEM), mitochondrial membrane potential (ΔΨm), and ROS levels were evaluated. Integrated transcriptomic and metabolomic profiling was performed to unbiasedly characterize protective mechanisms. In vitro, H₂O₂-induced oxidative stress was established in HepG2 cells. Cells were treated with trifolirhizin (15–25 µM) and assessed for antioxidant enzyme activities, ΔΨm, ROS production, glycolytic and mitochondrial respiration (Seahorse analysis), and cGAS-STING pathway protein expression. Pharmacological rescue experiments using the cGAS agonist cGAMP were conducted to test pathway dependency. Results: Trifolirhizin dose-dependently alleviated hepatic pathological damage and reduced pro-inflammatory cytokine levels in NOD mice. Multi-omics profiling revealed that oxidative stress responses, the mitochondrial electron transport chain, and glutathione metabolism were the most significantly restored pathways. Trifolirhizin preserved mitochondrial ultrastructure, restored ΔΨm, and attenuated ROS accumulation both in vivo and in vitro. Functionally, Seahorse analysis demonstrated that trifolirhizin rescued overall cellular bioenergetics, restoring both glycolytic capacity and mitochondrial respiratory parameters (basal respiration, ATP production, maximal respiration, and spare respiratory capacity). Mechanistically, trifolirhizin suppressed the cGAS-STING-TBK1-IRF3 axis, as evidenced by reduced expression of cGAS, p-STING, ZBP1, p-TBK1, and p-IRF3. Importantly, the cGAS agonist cGAMP abrogated the protective effects of trifolirhizin, confirming that the cGAS-STING pathway is functionally required for its action downstream of mitochondrial protection. Conclusion: Trifolirhizin attenuates liver injury in the nod mouse by preserving mitochondrial integrity, maintaining cellular energy metabolism, and thereby suppressing the ROS/cGAS-STING inflammatory cascade. These findings position trifolirhizin as a promising mitochondria-targeted therapeutic candidate for pSS-related hepatic complications and provide a mechanistic framework for discovering active compounds from mitochondrially active herbal formulations. Full article

(1) Background: This study aimed to evaluate hypothalamic–hypophyseal (HH) axis involvement in Primary Sjögren’s syndrome (pSS) using MRI and assess its relationship with hypothalamic–pituitary–adrenal (HPA) axis dysfunction. (2) Methods: A total of 22 postmenopausal women with pSS and 17 healthy controls were enrolled. Midline sagittal T1-weighted MRI was used to measure pituitary gland height (PGH). Dynamic contrast-enhanced imaging assessed hypothalamic–hypophyseal (HH) microcirculation, while diffusion tensor imaging (DTI) evaluated hypothalamic microstructure. Biochemical variables, including cortisol and complement factors, were measured. Linear regression analysis was performed to identify predictors of PGH. (3) Results: Patients had a mean disease duration of 11.5 ± 6.7 years. PGH was significantly different in patients than in controls (3.6 ± 1.1 mm vs. 4.4 ± 0.6 mm, p = 0.004). Cortisol levels were also reduced (8.9 ± 4.6 µg/dL vs. 12.6 ± 4.7 µg/dL, p = 0.040), while ACTH levels were not significantly different. Dynamic imaging demonstrated delayed enhancement of the anterior pituitary lobe. DTI revealed no hypothalamic microstructural abnormalities. PGH was positively associated with C3 (p = 0.029). (4) Conclusions: pSS is associated with pituitary structural and functional alterations consistent with HPA axis hypofunction, likely reflecting immune-mediated pituitary involvement with preserved hypothalamic integrity. Full article

Background: Immune checkpoint inhibitors (ICIs) can induce a sicca-like syndrome that differs from primary Sjögren’s disease in both immunopathogenesis and clinical phenotype. Despite growing recognition of this entity, data describing real-world management and outcomes, particularly in the context of ICI discontinuation and rechallenge, remain limited. Methods: Patients with new onset of sicca syndrome or exacerbation of previous symptoms following ICI therapy were retrospectively identified and assessed. Results: Fifty-nine patients with diverse malignancies (including melanoma, gastrointestinal, genitourinary, etc.) and sicca syndrome following treatment with ICIs (most often pembrolizumab or nivolumab +/− ipilimumab) were evaluated. Acute-onset dry mouth, primarily CTCAE v6.0 grades 1 (n = 24, 40.7%) and 2 (n = 34, 57.6%), occurred at a median of 104 days after ICI initiation, sometimes with associated dry eye (n = 8, 13.6%). Most were managed conservatively with behavioral modification and over-the-counter therapies alone (n = 37, 62.7%) while others received sialagogues (n = 9, 15.3%), dexamethasone oral rinse (n = 11, 18.6%), and/or systemic corticosteroids (n = 16, 27.1%). Additional management strategies included de-escalation to ICI monotherapy (n = 5, 8.5%) or discontinued ICI (n = 6, 10.2%). Half of patients treated with corticosteroids demonstrated subjective improvement in symptoms while 75% improved following ICI discontinuation. Four patients underwent rechallenge after a median interruption of 564 days; all (n = 4) demonstrated sicca recurrence. Conclusions: In this largest cohort to date of ICI-associated sicca syndrome, we confirm frequent improvement with steroids and/or supportive care and suggest a greater than previously appreciated risk of recurrence with rechallenge. Full article

Background/Objectives: Corneal epithelial thickness (CET) alterations reflect distinct mechanisms in aqueous-deficient and evaporative dry eye disease (DED) subtypes. In this study, we compare the CET profiles between patients with Sjögren’s syndrome (SS) and those with meibomian gland dysfunction (MGD) to elucidate the underlying mechanisms. Methods: We retrospectively analyzed 30 patients with SS and 30 age- and sex-matched with MGD. Assessments included corneal staining, Ocular Surface Disease Index (OSDI), tear meniscus height (TMH), non-invasive breakup time, lipid layer thickness (LLT), and anterior segment optical coherence tomography (AS-OCT) CET mapping. Regional CET and superior–inferior asymmetry were compared. Results: The SS group exhibited higher corneal staining scores (2.18 ± 1.23 vs. 1.03 ± 1.18, p = 0.001) and lower TMHs (0.14 ± 0.06 vs. 0.18 ± 0.07 mm, p = 0.013), while the MGD group reported greater OSDI scores (40.39 ± 22.49 vs. 31.25 ± 22.81, p = 0.029). A significantly thinner central epithelium (p = 0.043) and localized inferior paracentral thinning (2–5 mm zone, p = 0.008) were noted in SS. Corneal staining was identified as the primary independent predictor of central and inferior CET reduction in both groups. In the MGD group, LLT was associated with the preserved inferior CET (p = 0.045) and superior–inferior thickness difference (p = 0.015). Conclusions: Distinct structural signatures are observed between DED subtypes. SS features central/inferior thinning from aqueous deficiency-mediated friction, whereas MGD shows a relatively preserved epithelial thickness influenced by LLT. Regional CET analysis may provide mechanistic insights into DED subtyping. Full article

Background: Vestibular symptoms and objective vestibular dysfunction have been reported in patients with autoimmune and rheumatologic diseases, but available evidence remains fragmented and methodologically heterogeneous. Previous studies have often addressed audiovestibular involvement as a combined entity, limiting disease-specific interpretation of vestibular outcomes. Methods: A PRISMA 2020-based systematic review was conducted using predefined eligibility criteria targeting vestibular outcomes in autoimmune and systemic rheumatologic diseases. Observational studies reporting vestibular symptoms and/or objective vestibular test results were included. Vestibular data were extracted even when studies reported combined audiovestibular outcomes. Certainty of evidence was assessed using the GRADE approach. Results: Twenty-seven studies were included in the qualitative synthesis, comprising 14 primary observational studies and 13 reviews. Vestibular involvement was reported across multiple diseases, including systemic sclerosis, giant cell arteritis, ankylosing spondylitis, psoriatic arthritis, Behçet disease, primary Sjögren syndrome, rheumatoid arthritis, systemic lupus erythematosus, antiphospholipid syndrome, and vasculitic disorders. Objective vestibular abnormalities were most frequently identified using caloric testing, balance integration measures, videonystagmography, and video head impulse testing. Systemic sclerosis and giant cell arteritis showed more consistently reported vestibular findings, although heterogeneity in assessment methods precluded quantitative synthesis. Conclusions: Vestibular involvement occurs across autoimmune and systemic inflammatory diseases, but overall certainty of evidence remains limited. Standardized vestibular assessment and longitudinal studies are needed to better define disease-specific vestibular phenotypes. Full article

Background: Primary Sjögren’s syndrome (pSS) is a chronic autoimmune epithelitis characterized by lymphocytic infiltration of the exocrine glands. Although labial salivary gland biopsy remains the reference standard for diagnosis, it is invasive and may not always be feasible in routine practice. This study aimed to evaluate the diagnostic performance of parotid gland shear-wave elastography (SWE) and to investigate its relationship with histopathological findings in patients with suspected pSS. Methods: This prospective study included 93 participants (53 patients with pSS and 40 controls). Shear-wave elastography measurements of the parotid glands were obtained, and their association with histopathological findings was analyzed. Diagnostic performance was assessed using receiver operating characteristic (ROC) analysis. Multivariable logistic regression was performed to evaluate independent predictors of histopathological positivity. Results: Mean shear-wave elastography velocity values (m/s) were significantly higher in the pSS group than in controls (p < 0.001), and this difference remained significant after adjustment for age (adjusted β = 2.141, p < 0.001). ROC analysis demonstrated moderate discriminative performance for predicting histopathological positivity (AUC = 0.76, 95% CI: 0.61–0.89). The optimal cut-off value of 2.17 m/s yielded a sensitivity of 69.0% and a specificity of 94.1%. A moderate positive correlation was observed between right parotid elastography values and histopathological grade (r = 0.483, p < 0.001). In multivariable analysis, elastography mean and anti-SSA positivity showed positive but non-significant associations with histopathological positivity. The model demonstrated good calibration (Hosmer–Lemeshow p = 0.866) and high apparent discrimination (AUC = 0.947), with reduced performance after internal validation. Conclusions: Parotid shear-wave elastography is a non-invasive imaging method with moderate diagnostic performance in pSS. Elastography measurements correlate with histopathological involvement and remain significantly elevated after age adjustment. SWE may serve as a complementary tool for pre-biopsy risk stratification, particularly when biopsy is contraindicated or declined. Further validation in larger, independent cohorts is required. Full article