Clinical and experimental rheumatology最新文献

Objectives: The role of major salivary gland ultrasound (SGUS) in evaluating Sjögren's disease (SjD) continues to be debated. This study aims to assess the effectiveness of two SGUS scores (OMERACT and Hocevar et al.) in identifying lymphoma in SjD patients. A secondary aim is to explore the correlation between SGUS findings and histological characteristics of the parotid salivary glands.

Methods: Consecutive adult SjD patients with a clinical indication for parotid gland biopsy between September 2018 and October 2023 were included. Ultrasound images were anonymised and assessed according to the OMERACT and Hocevar et al. scores. The histological assessment performed by the pathologist included the evaluation of lymphoma presence, focus score (FS), lymphoepithelial lesions (LELs), germinal centres (GCs), multiple focal lymphocytic sialadenitis/lymphoepithelial sialadenitis (MESA/LESA), and features of non-specific sialadenitis.

Results: Among the 57 patients included in the study, 24 (42%) were diagnosed with lymphoma. Neither the OMERACT nor the Hocevar et al. score were effective in identifying lymphoma (OMERACT score: odds ratio 1.10, 95% CI: 0.91-1.34; p=0.305; Hocevar et al. score: odds ratio 1.03, 95% CI: 0.97-1.10; p=0.300). In the remaining 33 patients without lymphoma diagnosis but at higher risk of lymphoma development, regression analysis showed significant associations between ultrasound scores and histopathological features. LELs were linked to higher OMERACT (β=3.57, 95% CI:1.53-5.61; p=0.001) and Hocevar et al. scores (β=8.16, 95% CI: 1.45-14.87; p=0.019). Additionally, the FS was correlated with both OMERACT (β=0.26, 95% CI: 0.09-0.43; p=0.004) and Hocevar et al. scores (β=0.57, 95% CI: 0.03-1.12; p=0.040).

Conclusions: The current SGUS scores seem not to allow identifying lymphoma in SjD patients with high clinical suspicion. However, the correlation between advanced histological lesions and SGUS scores raises the opportunity of developing new SGUS scores with a prognostic rather than diagnostic or classificatory significance.

Objectives: To analyse intraobserver and interobserver reliability of colour Doppler (CD) ultrasonography of the major salivary glands (SGUS) in patients clinically suspected of Sjögren's disease (SjD).

Methods: One hundred consecutive outpatients visiting the University Medical Center Groningen for a diagnostic trajectory because of a suspicion of SjD were evaluated using CD ultrasonography of the submandibular and parotid salivary glands. All images were independently assessed by four observers (two experienced observers, one lesser experienced resident, one inexperienced trainee) in two sessions using the Outcome Measures in Rheumatology (OMERACT) CD scoring system (scale 0-3). A total score was calculated as the sum of the scores of the 4 glands (scale 0-12). Intra- and interobserver reliability, and reliability of live versus static scores were determined. Factors influencing variability in scores were analysed.

Results: Intraobserver weighted Cohen's kappa's of individual glands ranged from 0.23 (inexperienced observer) to 0.81 (experienced observer). Intraclass Correlation Coefficients (ICCs) for intraobserver reliability of the total CD score ranged from 0.53 (inexperienced observer) to 0.90 (experienced observer). The ICC for intraobserver reliability of live scoring compared to static images was 0.72. ICCs for interobserver reliability of the total CD score were 0.81 for session 1 and 0.71 for session 2. Patient variance was 74.1%, whereas residual variance contributed 15.5% to the total variance.

Conclusions: CD SGUS is a reliable imaging technique to visualise intraparenchymal vasculature in patients suspected of SjD, and therefore could be an asset in daily clinical practice. It requires, however, experience and prior training.

Objectives: Regular physical activity is recommended in patients with rheumatic diseases. In order to uniformly measure physical activity, our aim was to perform field testing of the modified Short QUestionnaire to ASsess Health enhancing physical activity (mSQUASH) in Sjögren's disease (SjD), together with other rheumatic diseases, and to investigate construct validity and test-retest reliability of the mSQUASH in patients with SjD.

Methods: The mSQUASH was tested by conducting semi-structured interviews in patients with SjD (n=10), systemic lupus erythematosus (n=10), giant cell arteritis/polymyalgia rheumatica (n=10) and axial spondyloarthritis (n=13) to check for understandability, interpretation and relevance. For construct validity (n=263 SjD), the association of mSQUASH to other patient-reported outcome measures was analysed using Spearman correlations. It was hypothesised that correlations are highest for physical-related outcomes, with fair to moderate correlations due to partly overlapping constructs. For test-retest reliability (n=75 SjD), intra-class correlation coefficients (ICCs) were calculated and Bland-Altman analysis was performed.

Results: All patient groups perceived the mSQUASH as relevant and easy to complete. Some minor adaptations and clarifications were implemented. As expected, mSQUASH total score showed fair associations with ESSPRI total score (ρ=-0.30) and EQ-5D total score (ρ=-0.34). Within the subdomains, correlations were higher for ESSPRI fatigue and pain compared to dryness and highest for EQ-5D activity and mobility. Test-retest reliability was good, with an ICC of 0.84. Bland-Altman analysis showed no systemic bias, but limits of agreement were wide.

Conclusions: The mSQUASH is a feasible, valid and reliable questionnaire to assess daily physical activity in SjD patients.

Patients with autoimmune diseases are particularly prone to infections due to both the underlying immune dysfunction and the use of immunosuppressive therapies. Sjögren's disease (SjD) serves as a valuable model for studying the complex interplay between autoimmunity and infections. This review focuses on the infection risks associated with SjD, emphasising key areas such as oral, respiratory, and urogenital infections, along with complications arising from systemic infections. The role of infections in SjD-associated lymphoma treatment complications is also addressed. Additionally, the recent COVID-19 pandemic has highlighted the vulnerability of autoimmune patients to severe viral infections, complicating disease management. While biologic therapies, including predominantly rituximab and belimumab have become increasingly utilised, they carry inherent risks of infections due to their immunosuppressive effects. Emerging therapies, such as ianalumab, iscalimab, dazodalibep, and remibrutinib, show efficacy in reducing disease activity but also present infection risks, with reports of upper respiratory infections and serious cases, including pneumonia and COVID-19. By exploring these infection-related challenges, this review underscores the importance of understanding the infection-autoimmunity relationship to improve outcomes for patients with SjD and similar autoimmune conditions.

Objectives: To compare two different rituximab (RTX)-based therapeutic approaches on vasculitic and lymphoproliferative-related disease activity and on non-Hodgkin lymphoma (NHL) development in a cohort of patients affected by cryoglobulinaemic vasculitis secondary to Sjögren's disease (Sjögren-CryoVasc).

Methods: Three Sjögren-CryoVasc treatment groups were identified: 1) early RTX induction followed by maintenance; 2) late RTX induction with possible on-demand retreatment; 3) no RTX treatment. The following outcomes were evaluated: a) changes in cumulative ESSDAI, considering vasculitic-related and lymphoproliferative-related domains and changes in ESSDAI specific to each single vasculitic-related and lymphoproliferative-related domain; b) development of NHL; c) occurrence of persistent hypogammaglobulinemia associated with serious infections.

Results: 13 Sjögren-CryoVasc patients were identified: 1) 5/13 treated earlier with RTX with subsequent maintenance; 2) 5/13 treated late with RTX with possible on-demand retreatment; 3) 3/13 not treated with RTX. The two RTX groups showed a decrease in the ESSDAI score with group 1 showing the most substantial reduction (p=0.028). Patients receiving RTX exhibited significant improvement in cutaneous, PNS, and articular vasculitic-related ESSDAI domains (p=0.007; p=0.006; p=0.03, respectively). By contrast RTX did not greatly affect the lymphoproliferative-related ESSDAI domains, even if an improvement was noted in the glandular and nodal domains for group 1 (p=0.03; p=0.03, respectively). No differences in NHL occurrence or safety concerns were observed between the groups.

Conclusions: RTX is an effective and safe treatment to control Sjögren-CryoVasc disease activity with a greater impact when administered earlier with a maintenance regimen. RTX alone cannot, however, affect the possible evolution of Sjögren-CryoVasc into an overt NHL.

Sjögren's disease is a systemic autoimmune disorder characterised by hyperactivation of B-cells and cytokine production. The condition may evolve from an asymptomatic, indolent course, with glandular involvement, to several extra-glandular systemic manifestations up to lymphoma development. Recent efforts have been undertaken to identify patient phenotypes at risk of developing specific extraglandular manifestations in order to improve patient management. A more detailed understanding and characterisation of pathogenetic mechanisms, operating during the course of the disease, may facilitate earlier diagnosis, enable subphenotyping of patients and suggest novel therapeutic modalities to address the unmet needs of the disease in the upcoming years. In this review, following the others of this series, we will summarise the most recent literature on Sjögren's disease pathogenesis and clinical features focusing in particular on new insights into Sjögren's disease molecular stratification and therapeutic advances in the era of precision medicine.

Objectives: We investigated the prevalence of anti-thyroid autoantibodies and thyroid dysfunction, and their association with clinical and laboratory features in Korean patients with primary Sjögren's syndrome (pSS) without overt thyroid illnesses.

Methods: We consequently included 196 pSS patients (190 women) and cross-sectionally collected clinical and laboratory data including the EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) and Patient Reported Index (ESSPRI). The fatigue-dominant group was defined as those in the highest quartile of the fraction of fatigue, calculated as the ESSPRI fatigue score divided by the total ESSPRI score. Thyroid stimulating hormone (TSH), free T4 (fT4), anti-thyroglobulin (TG), anti-thyroid peroxidase (TPO), and anti-TSH receptor antibody (TRAb) were measured.

Results: Of 196 patients, 31 (15.8%) were positive for anti-TG, 28 (14.3%) for anti-TPO, and 28 (14.3%) for TRAb. Subclinical hypothyroidism (S-Hypo) was identified in 23 (11.7%) patients. Anti-TG had no correlations with thyroidal function or pSS-related features. Meanwhile, anti-TPO was significantly associated with TSH levels or anti-centromere antibody. TRAb-positive patients exhibited significantly higher ESSDAI and clinical ESSDAI scores. Moreover, the most influential independent predictor for TRAb was lymphopenia (odds ratio [OR] = 5.541), which has been known as a prognostic factor. Additionally, significant bidirectional associations were found between the fatigue-dominant group (OR = 3.482) and anti-TPO-positive S-Hypo (OR = 7.586) in multivariate regression analyses.

Conclusions: Latent thyroid autoimmunity, particularly TRAb and anti-TPO, may be associated with clinical and laboratory manifestations of pSS, such as disease activity or fatigue, even without overt thyroid dysfunction.