Search Results (31)

Sjögren’s disease (SjD) is a chronic autoimmune disease characterized by lymphocytic infiltration and dysfunction of the exocrine glands, with manifestations extending beyond glandular sicca symptoms to multiple extraglandular systems. Although the pathogenesis of SjD remains incompletely understood, growing evidence indicates that a complex cytokine network involving both innate and adaptive immune pathways plays a central role in disease development. This narrative review summarizes recent updates on cytokine signaling in SjD across three clinically relevant domains. In glandular inflammation, activation of salivary gland epithelial cells through Toll-like receptor pathways triggers type I interferon (IFN) signaling via plasmacytoid dendritic cells, while IFN-γ, Th17-related cytokines (IL-6, IL-17, IL-22), BAFF/APRIL, and chemokines (CXCL10, CXCL12, CXCL13) collectively sustain local inflammation and ectopic lymphoid organization. The BAFF/APRIL axis, a systemic type I IFN signature, and IL-21–follicular helper T cell–B cell interactions primarily drive systemic immune activation, which together underlie autoantibody production, hypergammaglobulinemia, and a lymphoma-prone phenotype. In contrast, constitutional symptoms such as fatigue, pain, and dryness frequently dissociate from classical inflammatory activity and are better explained by neuroimmune–metabolic mechanisms, including the IFN-γ–IDO–kynurenine pathway and symptom-associated proteomic signatures. Collectively, these findings underscore the heterogeneous nature of SjD, in which glandular inflammation, systemic immune activation, and constitutional symptoms are driven by distinct yet partially overlapping cytokine pathways. Recognizing this heterogeneity has direct implications for cytokine-targeted therapy, suggesting that future trials should stratify patients by disease phenotype (IFN-high, B cell-dominant, and symptom-dominant) rather than treating SjD as a uniform population. Full article

Background and Clinical Significance: Childhood-onset Sjögren’s disease (cSjD) is a rare autoimmune disorder that remains challenging to diagnose because of its heterogeneous clinical presentation and the frequent absence of classic sicca symptoms at disease onset. Recurrent parotitis and systemic manifestations often predominate in pediatric patients, contributing to diagnostic delay and potential irreversible glandular damage. Early recognition is essential to prevent complications and improve long-term outcomes. Case Presentation: We report the case of a 17-year-old female diagnosed with primary Sjögren’s disease following a prolonged history of recurrent parotid involvement and progressive glandular dysfunction. Comprehensive evaluation revealed positive anti-SSA antibodies, hypergammaglobulinemia, characteristic salivary gland ultrasonography abnormalities, and a positive minor salivary gland biopsy, resulting in fulfillment of all domains of the 2016 ACR/EULAR classification criteria. The patient also exhibited unusual vascular findings, including carotid atheromatous calcifications in the absence of traditional cardiovascular risk factors. Conclusion: This case highlights the diagnostic complexity of cSjD and underscores the value of a multimodal diagnostic approach integrating clinical assessment, serology, imaging, and histopathology. The presence of early vascular abnormalities broadens the spectrum of potential extraglandular manifestations and emphasizes the need for comprehensive evaluation and long-term monitoring in affected patients. Full article

Background and Clinical Significance: IgG4-related disease (IgG4-RD) is a chronic fibroinflammatory, immune-mediated multisystem disorder that can mimic neoplastic, infectious, or autoimmune conditions. Among its head-and-neck manifestations, IgG4-related dacryoadenitis and sialadenitis, historically referred to as Mikulicz disease, should be distinguished from the classical Mikulicz syndrome, which describes secondary lacrimal and salivary gland enlargement due to other systemic disorders. Renal involvement, most commonly in the form of IgG4-related tubulointerstitial nephritis (IgG4-TIN), is less frequent but carries major prognostic implications because delayed diagnosis may lead to irreversible kidney damage. Case Presentation: A 49-year-old man with no relevant past medical history presented with a 2-year history of intermittent polyuria and foamy urine. Laboratory testing revealed advanced kidney dysfunction, with serum creatinine of 4.2 mg/dL, estimated glomerular filtration rate of 16 mL/min/1.73 m², and proteinuria of 2874 mg/day. Physical examination showed bilateral parotid enlargement, upper eyelid edema, lacrimal gland enlargement, and sicca symptoms, raising suspicion for IgG4-related dacryoadenitis and sialadenitis (Mikulicz disease). Further work-up demonstrated marked eosinophilia, polyclonal hypergammaglobulinemia, and significantly elevated serum IgG4 levels (3180 mg/dL), while infectious serologies and autoimmune studies were negative. Kidney biopsy revealed plasma cell-rich tubulointerstitial nephritis with lymphoplasmacytic and eosinophilic infiltrates, interstitial fibrosis, tubular atrophy, and more than 40 IgG4-positive plasma cells per high-power field, supporting the diagnosis of IgG4-related tubulointerstitial nephritis in the setting of systemic IgG4-RD. Treatment with prednisone followed by mycophenolate mofetil led to improvement in glandular manifestations and a partial reduction in proteinuria, but renal recovery remained incomplete. The patient subsequently developed a severe pulmonary infection complicated by sepsis and oligoanuric acute kidney injury superimposed on chronic kidney disease, and ultimately progressed to end-stage kidney disease requiring chronic maintenance hemodialysis. Conclusions: This case highlights that a Mikulicz disease phenotype may represent the initial manifestation of systemic IgG4-RD and should prompt evaluation for extraglandular involvement, particularly renal disease. In patients with glandular enlargement, eosinophilia, hypergammaglobulinemia, and unexplained renal dysfunction, IgG4-RD should be actively considered. Kidney biopsy remains essential for diagnostic confirmation and prognostic assessment, as delayed recognition may result in irreversible renal damage and progression to end-stage kidney disease. Full article

Background/Objectives: Childhood-onset Sjögren disease (cSjD) is a rare autoimmune disorder with heterogeneous manifestations and ongoing diagnostic challenges, as there are no validated paediatric criteria. Our study aims to characterise the clinical, laboratory, and imaging features of children diagnosed with cSjD at a single Romanian paediatric rheumatology centre between 2015 and 2025 and contextualise these findings within the most recent literature. Methods: A retrospective review of 15 consecutive cSjD patients was conducted, including clinical features, autoantibodies, imaging, biopsy findings, treatment, and outcomes. Results: Our cohort showed a significant female predominance (80%) and a broad age range at disease onset (3–15 years). Extraglandular manifestations were more common at presentation than glandular phenotypes (53.3% vs. 40%). Lupus-like extraglandular presentations frequently led to initial misdiagnosis as childhood-onset systemic lupus erythematosus (SLE) in our cohort. Sicca symptoms were present at diagnosis in only 3 of 15 patients (20%) and developed later during follow-up in an additional 4 patients (26.7%). Notably, the cohort included novel findings, such as an unprecedented presentation with acute exudative pericarditis complicated by cardiac tamponade. Anti-SSA antibodies and salivary gland ultrasound abnormalities were highly prevalent (86.7% and 100%, respectively). Anti-SSB antibodies were detected in seven patients (46.7%), with titres showing more variability than those of anti-SSA, ranging from just above the positivity threshold to mildly elevated levels. The association with macro-creatine kinase type I was another distinctive feature of this series. Chronic musculoskeletal pain and dryness were our patients’ most frequently reported symptoms at the last assessment, affecting up to 5/15 (33.3%) in each domain. One patient showed irreversible ocular damage during our study. Conclusions: Extraglandular presentations of cSjD are highly heterogeneous and diagnostically challenging, often occurring without glandular symptoms. Lupus-like systemic features—including facial vasculitic purpura, with or without arthralgia, and occasional pericarditis, as observed in our cohort—may contribute to frequent initial diagnostic misattribution to SLE. Early salivary gland ultrasonography, targeted autoantibody testing, and selective biopsy are essential for timely diagnosis, underscoring the urgent need for paediatric-specific validated classification criteria. Full article

Sjögren’s syndrome is a chronic autoimmune disease marked by lymphocytic infiltration of the exocrine glands and the development of sicca symptoms, yet some patients also develop extraglandular involvement. Imaging has become relevant for describing these systemic features and supporting clinical assessment. This review discusses the roles of ultrasonography, elastography, computed tomography, and magnetic resonance imaging in evaluating multisystem disease associated with Sjögren’s syndrome. Ultrasonography and elastography help assess muscular involvement by showing changes in echogenicity and stiffness that reflect inflammation and later tissue remodeling. In joints, ultrasound can detect synovitis, tenosynovitis, and early erosive changes, including abnormalities not yet evident on examination. Pulmonary disease, most often with interstitial lung involvement, is best evaluated with high-resolution computed tomography, which remains the most reliable imaging modality for distinguishing interstitial patterns. Magnetic resonance imaging is valuable in assessing neurological complications. It can reveal ischemic and demyelinating lesions, neuromyelitis optica spectrum features, or pseudotumoral appearances. Imaging is also essential for detecting lymphoproliferative complications, for which ultrasound and magnetic resonance imaging can reveal characteristic structural and diffusion-weighted imaging findings. When combined with clinical and laboratory information, these imaging methods improve early recognition of systemic involvement and support accurate monitoring of disease progression in Sjögren’s syndrome. Full article

Even though primary Sjögren disease (pSjD) is mainly associated with sicca symptoms, there are extraglandular manifestations of the disease which affect the quality of life of patients the most and may even be life-threatening. Among the most severe, polyneuropathy and myopathy are worth mentioning. Additionally, clinical observations suggest a higher prevalence of fibromyalgia (FM) in this group of patients, clouding physicians’ assessment and potentially leading to unsuccessful therapeutic decisions. The aim of our study was to evaluate the frequency of pSjD and FM co-occurrence as well as to find the most effective screening tools and markers of such overlap. A total of 97 consecutive patients with diagnosed pSjD were incorporated in the study after obtaining their informed consent. Participants completed a set of broadly available questionnaires, including Fibromyalgia Survey Questionnaire, SF-36 and EULAR Sjögren’s Syndrome Patient-Reported Index (ESSPRI). Data on their laboratory results was collected in the dedicated database. Moreover, patients underwent electroneurographic (ENG) and electromyographic (EMG) testing. Central nervous system (CNS) abnormalities were detected using MRI. Objective disease activity was evaluated based on EULAR Sjögren’s Syndrome Disease Activity Index (ESSDAI). The mean age was 55.3 (range 19.0–78.0 years, SD = 13.9). The disease duration ranged from 2 to 42 years (M = 9.03 years, SD = 7.1 years). Nearly half of the participants (n = 44, 45%) met diagnostic criteria of FM. Interestingly, the diagnosis of FM correlated with CNS involvement. There was no significant correlation between FM and either polyneuropathy/myopathy nor laboratory findings (however, C3c and folic acid concentrations were near the level of significance—mean 1.2 vs. 1.29; p = 0.075 and mean 11.35 vs. 9.21; p = 0.071, respectively). Within the subcategories of SF-36 and ESSPRI scales, significant positive correlation was noted with ESSPRI total score and ESSPRI pain score (neuropathic subcategory), while a negative correlation was found with SF-36 vitality score, physical functioning score, and the SF-36 total score. FM is common among pSjD patients and should be considered rather a comorbidity requiring different therapeutic approaches. At the fast-paced clinical environment, a concise ESSPRI assessment may be helpful in the initial screening of patients at risk of FM. Even though the origin of this phenomenon is unknown, the concepts of central sensitization and microglia polarization may be potential explanations and more molecular research in this direction could benefit the pSjD patients. Full article

Peripheral blood serves both as a source of effector immune cells that migrate to exocrine glands and as a reflection of the immunological changes occurring in patients with Sjögren’s disease (SjD). These changes may be linked to the clinical state of these patients. We analyzed total cell counts in the peripheral blood, as well as frequencies of individual leukocyte subpopulations, membrane expression levels of CD38 and CD157, and serum concentrations of soluble sCD38 and sCD157 in SjD patients (n = 40) and age-matched healthy controls (n = 20). Hierarchical clustering based on the cell count of leukocyte subpopulations was employed to identify distinct patient subgroups. Associations between these clusters and clinical parameters were subsequently evaluated. Key findings included a reduction in lymphocyte counts and their subpopulations, alongside increased CD38 expression on CD38⁺ B cells (p = 0.047) and, unexpectedly, on monocytes (p = 0.014) when comparing patients and controls. The involvement of innate immunity was further supported by the differential expression of CD157 across patient samples. Patients with low cell counts exhibited reduced CD157 expression on monocytes and granulocytes (p < 0.02), tested positive for anti-Ro antibodies, and reported severe fatigue. Our findings suggest that innate immune cells, such as monocytes and granulocytes in peripheral blood, are also likely to contribute to the manifestation and progression of SjD. The differential expression of CD157 may reflect distinct immunopathological states and warrants further investigation, as its precise role in exocrine gland involvement and extra-glandular manifestations lies beyond the scope of this study. Full article

Lung involvement is the most common extraglandular manifestation of primary Sjögren’s Disease (pSjD). There is an increasing interest in finding the clinical/serological risk predictors of this feature. A cross-sectional study evaluating anti-SSA/Ro antibodies, anti-SSB/La antibodies, rheumatoid factor, antinuclear antibodies, and the diffusing capacity of the lungs for carbon monoxide (DLCO) in 26 pSjD patients who presented interstitial changes on the chest CT scan was performed. The titres and positivity rates for anti-SSA/Ro (p = 0.02, p = 0.02) and anti-SSB/La antibodies (p = 0.01, p = 0.001) proved to be significantly increased in patients with abnormal DLCO. Anti-SSB/La antibodies’ titres seemed to be the best predictor for decreased DLCO–AUC 0.791 (0.587–0.994), p = 0.016. A close-to-significance decrease was found in the titres (p = 0.07) and positivity rates—p = 0.09 and OR of 0.15 (0.01–1.63)—of anti-SSB/La antibodies in patients with usual interstitial pneumonia (UIP), indicating their possible protective role against UIP. The lymphocytic interstitial pneumonitis (LIP) pattern on lung CT scan was significantly associated with the simultaneous positivity of the four examined serological markers (p = 0.03). The increase in anti-SSB/La antibody positivity rate in patients with LIP patterns was situated close to the significance level (p = 0.09). Quadruple positivity, as well as isolated anti-SSB/La positivity, could be risk factors for developing LIP in pSjD patients. Thus, anti-SSB/La antibodies might represent a marker of lung involvement in pSjD patients. Full article

Sjogren’s disease (SjD) is a systemic autoimmune disease primarily affecting the exocrine glands. Systemic manifestations, including hepatic involvement, are increasingly recognized. This study aimed to delineate the clinical features and associated factors of autoimmune hepatic involvement in SjD. A retrospective analysis was conducted on patients diagnosed with SjD at Seoul St. Mary’s Hospital over the past 10 years. Autoimmune hepatic involvement was defined by fulfilling diagnostic criteria for autoimmune hepatitis (AIH) or primary biliary cholangitis (PBC). Clinical, serological, and demographic data were obtained from medical records. Among 1119 patients with SjD, 51 (4.6%) had autoimmune hepatic involvement. AIH (64.7%) was the most common type, followed by PBC (27.5%) and overlapping disease (7.8%). Compared to those without hepatic involvement, affected patients were older at diagnosis (p = 0.003) and showed higher frequencies of thrombocytopenia, splenomegaly, anti-centromere antibody (ACA), and elevated antinuclear antibody titers as measured by indirect immunofluorescence (IFI-HEp-2) (all p < 0.001). Multivariable analysis identified splenomegaly, elevated IFI-HEp-2 titer, and ACA positivity as independent factors associated with hepatic involvement. Most patients responded well to immunosuppressive therapy, with only a small proportion (15.7%) progressing to liver fibrosis. Autoimmune hepatic involvement is relatively uncommon but clinically meaningful in patients with SjD. Full article

The aim of the paper was to characterize rheumatoid factor IgA, IgG, and IgM isotypes in patients with Sjögren’s syndrome (SS) subsets, based on the absence or presence of joint complaints of different etiologies. In total, 164 SS patients were grouped based on whether they had polyarthritis as an extraglandular manifestation (n = 73, SS+pa), rheumatoid arthritis as an associated autoimmune disorder (n = 46, SS+RA), or Sjögren’s syndrome without inflammatory joint pain (n = 45, SS). The highest IgA rheumatoid factor isotype levels were detected in SS patients, whereas the lowest levels were found in the SS+RA group, without a significant difference. Neither IgG nor IgM RF differed significantly between the patient subclasses. In addition to other disease-specific markers, seropositive patients who were seropositive for any RF isotype were significantly more frequently anti-Ro/SS-A and anti-La/SS-B positive and had higher ESSDAI levels. In SS and SS+pa patients, a strong negative correlation was observed between IgA RF and age, whereas a strong positive correlation was found between IgA RF and ESSDAI, RF, IgA, IgG, anti-Ro/SS-A, and anti-La/SS-B levels. High total IgG levels together with high IgA RF levels occurred most frequently in SS patients (p = 0.05), whereas the combination of normal IgG and high IgM RF was significantly more frequent in the SS+RA group. The co-occurrence of high total IgG and normal IgM RF did not differ significantly between the patient subsets; however, this was the combination with the highest sensitivity (94.5%) for SS+pa patients. Based on our findings, rheumatoid factor isotypes have an additive value in the differentiation of non-erosive polyarthritis and erosive rheumatoid arthritis during the disease course of patients with Sjögren’s syndrome. All rheumatoid factor isotypes predict a more severe disease course, but IgA RF may serve as a candidate for being an early, poor prognostic factor for SS patients. Full article

Background/Objectives: In Sjögren’s syndrome, exocrine glands are destructed in an autoimmune-mediated process. Obesity is known to influence a wide range of diseases. This study aimed to examine whether obesity has an impact on the disease course of our patients with Sjögren’s syndrome. Methods: Out of the regularly followed-up patients, 125 were grouped based on their body mass index (BMI). Below a BMI of 25, they were listed as “non-obese” (n = 45), whereas above a BMI of 25, they were categorized as “obese” (n = 80). Demographic, laboratory, and immunological parameters; Sjögren’s syndrome disease activity index; certain extraglandular manifestations; and treatment modalities were compared using biostatistical methods. Results: Among the examined cardiovascular and cerebrovascular co-morbidities, type 2 diabetes and hypertension were significantly more frequent in the obese group. Considering the associated further autoimmune disorders and extraglandular manifestations, in our patients, there were no significant differences between the two groups. Among laboratory parameters, gamma glutamil transferase, alanine transaminase, hemoglobin, hematocrit, lymphocyte rate, triglyceride, and c3 and c4 complement levels were significantly higher in the obese group, while the proportion of rheumatoid factor positivity and the neutrophil granulocyte rate were significantly lower. Immunoglobulin G, A, and M levels did not differ significantly between the two subsets. Obese patients needed steroid therapy significantly less frequently; however, statin therapy was remarkably more frequent in that group. Furthermore, the European League Against Rheumatism (EULAR) Sjögren’s syndrome disease activity index (ESSDAI) was significantly lower in the group of overweight patients. Conclusions: Our results suggest that several immunological parameters of obese patients are more favorable compared to those with normal body weight. Behind that, we might suspect either the beneficial effect of statin therapy and/or the obesity paradox. Full article

Background and Objectives: For persons with rheumatoid arthritis (RA), the accompanying systemic inflammatory conditions often insidiously damage extra-glandular organs, causing poor outcomes. Despite evidence manifesting the application of rehabilitation services (RSs), the association between RSs use and changes in the inflammatory response among persons with RA has not yet been established. With that in mind, this study aimed to evaluate changes in C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) before and after long-term RSs use. Materials and Methods: For this two-group pre and posttest study, medical data of 4505 persons with RA aged 20–70 years between 2012 and 2017 were retrieved from an electronic medical record database held by a hospital in Taiwan. Of them, 1387 subjects were categorized as RSs users, who received RSs at least six times within the first year of RA onset. Generalized estimating equations analysis was then employed to compare the changes in ESR and CRP at baseline, and at 12, 18, 24, 30, and 36 months after RA onset. Results: After adjusting for inherent differences and mature impact, those receiving standard care plus RSs were found to have a lower CRP level than those without receiving RSs. This benefit was maintained within a 3-year follow-up period. Additionally, a slight but nonsignificant reduction in ESR existed over the same timeframe. Conclusions: Integrating RSs into conventional care may be helpful to modulate the inflammation for RA patients, but further research via randomized controlled trials is needed to validate the application of RSs. Full article

Sjögren’s disease (SjD), or primary Sjögren’s syndrome (pSS), is a heterogeneous chronic autoimmune disorder with multiple clinical manifestations that can develop into non-Hodgkin’s lymphoma in mucosa-associated lymphoid tissue. SjD is one of the autoimmune diseases with the maximum delayed diagnosis due to its insidious onset, heterogeneous clinical features and varied course. It is increasingly recognized that extraglandular manifestations represent a clinical challenge for patients with SjD. The European League Against Rheumatism (EULAR) Sjögren’s Syndrome (SS) Disease Activity Index (ESSDAI) is a systemic disease activity index designed to measure disease activity in patients with primary Sjogren’s syndrome. It consists of 12 domains: cutaneous, pulmonary, renal, articular, muscular, peripheral nervous system, central nervous system, hematological, glandular, constitutional, lymphadenopathy and lymphoma, biological. More than a quarter of patients with pSS may have systemic features that are not included in the ESSDAI classification, i.e., various cardiovascular, ophthalmic, ENT, and other systemic or organ involvement that increase the magnitude of the systemic phenotype in the disease. The ESSDAI also excludes the gastrointestinal (GI) tract, and unfortunately, GI manifestations are not routinely assessed. Gastroesophageal reflux disease (GERD) is one of the most prevalent gastrointestinal disorders, impairing quality of life and consuming a large volume of medical resources. Recently carried out the Mendelian randomized trial confirmed the causal link between SjD and gastroesophageal reflux disease (GERD) and showed that GERD is a risk factor for SjD. This review aims to provide an overview of the research describing evidenced based links between Sjögren’s disease and gastroesophageal reflux disease, with the intention of ensuring that any systemic pathology in Sjögren’s disease is properly assessed and that management of the disease is directed towards the patient. A comprehensive literature search was carried out on PubMed, Web of Science, Scopus and the Cochrane Library databases. Two researchers searched for published studies indexed from inception to 1 September 2024 using the keywords ‘Sjögren’s syndrome’ OR ‘Sjögren’s disease’ AND ‘gastroesophageal reflux disease’ AND ‘microbiota’ OR microbiota dysbiosis’. We limited our search for scientific articles to human studies, and only included articles in English. Overall, there is a lack of evidence-based studies assessing the association between GERD and Sjögren’s disease and the changes in the microbiota associated with GERD in a multidisciplinary setting. Such studies are needed for the future, as this will improve the early diagnosis of Sjögren’s disease and the personalized management of the disease. Full article

Background: This study investigates the clinical characteristics and differences between primary Sjögren’s Syndrome (pSS) and secondary Sjögren’s Syndrome (sSS) in a cohort of 50 patients. Methods: Conducted across two academic facilities in North-East Romania, the study emphasizes the importance of glandular and extraglandular manifestations, focusing on salivary flow rates, pH levels, and buffer capacity. Patients were diagnosed using the 2016 ACR-EULAR classification criteria, with a detailed examination including salivary tests, biopsies, and antibody presence. Results: The findings highlight significant differences between pSS and sSS, particularly in salivary function, with pSS patients exhibiting more severe glandular dysfunction. The study also notes a higher prevalence of inflammatory joint involvement in sSS patients, often associated with rheumatoid arthritis. Statistical analysis revealed correlations between salivary parameters and disease progression, underscoring the necessity of tailored treatment strategies. The research suggests that lower salivary flow rates and altered pH levels in pSS patients contribute to compromised oral health, including increased dental cavities and periodontal disease. Conclusions: The study’s results contribute to a deeper understanding of Sjögren’s Syndrome and reinforce the need for multidisciplinary management to address both systemic and oral health complications in these patients. Full article

Aim of the study was to investigate the demographic data and disease course characteristics of patients with Sjögren’s syndrome (SS) and inflammatory joint pain of various origins and to search for factors that might help with the distinction of polyarthritis as an extraglandular manifestation and rheumatoid arthritis as an associated systemic autoimmune disorder. A total of 355 patients were retrospectively analyzed, 128 of whom served as controls (SS-C), while 159 had polyarthritis as an extraglandular symptom of Sjögren’s syndrome (SS-pa) and 68 were diagnosed as having associated rheumatoid arthritis (SS-RA). The patients without any inflammatory joint manifestations were significantly older than the SS-pa patients, while, for the SS-RA group, the difference was not significant. The onset of joint pain appeared significantly earlier in the SS-RA patients. Regarding either extraglandular manifestations or associated autoimmune disorders, there were significant differences between the controls and both SS-pa and SS-RA groups, while no significant difference was found between the SS-pa and SS-RA groups. Thus, laboratory and imaging methods should be used to differentiate between the two conditions, but laboratory biomarkers are even more important for early diagnosis. A ROC curve analysis showed an acceptable diagnostic accuracy in differentiating between SS-pa and SS-RA patients using a binary logistic regression model, where highly positive rheumatoid factor (RF) and anti-cyclic citrullinated peptide (CCP) values, kidney involvement, and anti-Ro/SS-A positivity were shown to significantly raise the odds of having RA, whereas anti-La/SS-B positivity seemed to have a protective role, since it significantly decreased the odds of having it. Further biomarkers are needed to better classify SS patient cohorts with inflammatory joint pain of different origins and, consequently, different management requirements. Full article