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Objective We aimed to systematically review the literature to retrieve evidence on the diagnostic and prognostic value of musculoskeletal ultrasound for a treat to target (T2T) approach in RA. Methods Eight research questions were developed addressing the role of ultrasound (including different ultrasound scores and elementary lesions) for diagnosis, monitoring and prognosis of RA. PubMed and EMBASE were searched (2005–2020). Articles on RA and reporting data on musculoskeletal ultrasound were included and extracted according to the underlying questions, and risk of bias assessed according to the study design. Results Out of 4632 records, 60 articles were included. Due to clinical heterogeneity, meta-analysis was not possible. Ultrasound better predicted disease relapses with respect to clinical examination in patients in remission, while both methods performed similarly in predicting response to therapy, achievement of remission and radiographic progression. Ultrasound was superior to clinical examination in diagnosing joint involvement using another imaging modality, such as magnetic resonance imaging, as reference. Limited ultrasound scores performed like more extensive evaluations for the detection of joint inflammation and for outcome prediction. Higher ultrasound scores of synovitis were linked to poor outcomes at all disease stages, but a specific cut-off distinguishing between low- and high-risk groups did not emerge. Conclusions These data confirm the pivotal role of ultrasound when evaluating synovial inflammation and when identifying RA patients at higher risk of relapse. Further research is needed to better define the role of ultrasound in a T2T management strategy in moderately-to-highly active RA.

The diagnosis and classification of primary Sjögren's syndrome (pSS) relies on labial biopsy, whereas the role of open parotid biopsy is mainly reserved to evaluate the lymphoproliferative complications. Recently ultrasound-guided core needle biopsy (US-guided CNB) appeared as a novel and safe technique useful in lymphoma assessment, however, its potential role in the diagnosis of pSS has never been assessed.The main aim of this study was to evaluate the diagnostic value of US-guided CNB of the parotid glands in patients affected by pSS.Patients affected by pSS who underwent US-guided CNB for a suspected glandular lymphoma were included. Adequacy of the samples and histopathological features related to pSS were analysed.US-guided CNB was performed on 29 parotid glands. The biopsied samples were adequate for diagnosis in 28/29 (96.5%) cases. Fifteen patients showed pathologic features of parotid lymphoma. Among the remaining patients, 9/13 presented focus score≥1; LELs were present in 8/13 patients, and GCs in 11/13. In 8 cases the histological features were coherent with MESA/LESA. Acinar atrophy, fibrosis and duct dilatation were also evaluated.This preliminary study suggests the possible usefulness of US-guided CNB for the diagnosis of pSS by enabling the collection of adequate salivary gland tissue to assess the FS, GCs, LELs, and other histopathologic features also useful in the management of pSS patients.

Objective Persistent (≥2 months) major salivary gland enlargement in primary SS (pSS) patients is a well-known sign of possible involvement by B cell lymphoma. The study aimed to evaluate the diagnostic accuracy and safety of US-guided core needle biopsy (CNB) of major salivary glands compared with open surgical biopsy. Methods Prospective pSS patients (cases) with clinically persistent salivary gland enlargement underwent US-guided CNB and were compared with retrospective pSS patients (controls) submitted to open surgical biopsy. The features analysed were pre-biopsy clinical and laboratory findings, adequacy of the material for histology and diagnostic-rendered and biopsy-related complications (reported by the patient with a questionnaire and clinically verified). Results Thirteen cases underwent US-guided CNB: in nine, biopsy was performed on the parotid gland and in four it was performed on the submandibular gland. Sufficient material was obtained for pathological diagnosis in all samples. The final diagnoses were 5 (38.5%) B cell lymphoma, 1 (7.7%) lymphoepithelial sialadenitis, 4 (30.7%) other sialadenitis (granulomatous consistent with sarcoidosis, IgG4-related disease, chronic sclerosing, diffuse chronic) and 3/13 (23.1%) miscellaneous lesions. Thirteen controls underwent open surgical biopsy of the parotid. In one, inadequate material was obtained, while in 12 (92.3%) the pathologic diagnoses were 4 (33.3%) B cell lymphoma, 2 (16.7%) lymphoepithelial sialadenitis, 4 (33.3%) uncertain lymphoproliferative lesions and 2 (16.7%) miscellaneous lesions. Six cases (46.1%) reported six transient complications and 12/13 (92.3%) controls had 2 persistent and 14 transient complications. Conclusion US-guided CNB represents a novel, clinically relevant and safe approach for the management of pSS patients with parotid or submandibular persistent enlargement.

Primary Sjögren’s syndrome (pSS) is a chronic and heterogeneous disorder characterized by a wide spectrum of glandular and extra-glandular features. The hallmark of pSS is considered to be the immune-mediated involvement of the exocrine glands and B-cell hyperactivation. This leads pSS patients to an increased risk of developing lymphoproliferative diseases, and persistent (>2 months) major salivary gland enlargement is a well-known clinical sign of possible involvement by B cell lymphoma. Better stratification of the patients may improve understanding of the mechanism underlying the risk of lymphoproliferative disorder. Here, we summarize the role of different imaging techniques and a bioptic approach in pSS patients, focusing mainly on the role of salivary gland ultrasonography (SGUS) and a US-guided core needle biopsy (Us-guided CNB) as diagnostic and prognostic tools in pSS patients with persistent parotid swelling.

Salivary gland ultrasonography (SGUS) has proven to be a promising tool for diagnosing various diseases manifesting with abnormalities in salivary glands (SGs), including primary Sjogren's syndrome (pSS). At present, the major obstacle for establishing SUGS as a standardized tool for pSS diagnosis is its low inter/intra observer reliability. The aim of this study was to address this problem by proposing a robust deep learning-based solution for the automated segmentation of SGUS images. For these purposes, four architectures were considered: a fully convolutional neural network, fully convolutional “DenseNets” (FCN-DenseNet) network, U-Net, and LinkNet. During the course of the study, the growing HarmonicSS cohort included 1184 annotated SGUS images. Accordingly, the algorithms were trained using a transfer learning approach. With regard to the intersection-over-union (IoU), the top-performing FCN-DenseNet (IoU = 0.85) network showed a considerable margin above the inter-observer agreement (IoU = 0.76) and slightly above the intra-observer agreement (IoU = 0.84) between clinical experts. Considering its accuracy and speed (24.5 frames per second), it was concluded that the FCN-DenseNet could have wider applications in clinical practice. Further work on the topic will consider the integration of methods for pSS scoring, with the end goal of establishing SGUS as an effective noninvasive pSS diagnostic tool. To aid this progress, we created inference (frozen models) files for the developed models, and made them publicly available.

Background: To compare the clinical, serological and histologic features between male and female patients with Sj&ouml, gren&rsquo, s syndrome (SS) and explore the potential effect of gender on lymphoma development. Methods: From a multicenter population (Universities of Udine, Pisa and Athens, Harokopion and Ioannina (UPAHI)) consisting of consecutive SS patients fulfilling the 2016 ACR/EULAR criteria, male patients were identified, matched and compared with female controls. Data-driven multivariable logistic regression analysis was applied to identify independent lymphoma-associated factors. Results: From 1987 consecutive SS patients, 96 males and 192 matched female controls were identified and compared. Males had a higher frequency of lymphoma compared to females (18% vs. 5.2%, OR = 3.89, 95% CI: 1.66 to 8.67, p = 0.0014) and an increased prevalence of serum anti-La/SSB antibodies (50% vs. 34%, OR = 1.953, 95% CI: 1.19 to 3.25, p = 0.0128). No differences were observed in the frequencies of lymphoma predictors between the two genders. Data-driven multivariable logistic regression analysis revealed negative association of the female gender with lymphoma and positive association with lymphadenopathy. Conclusion: Male SS patients carry an increased risk of lymphoma development. Although statistics showed no difference in classical lymphoma predictors compared to females, data-driven analysis revealed gender and lymphadenopathy as independent lymphoma-associated features.

This study aimed to: i) perform an ultrasonographic (US) evaluation of the lacrimal glands (LGs) in healthy subjects in order to define the sonographic elementary lesions which could be identified in the LGs and describe their frequencies in healthy subjects; ii) test the intra and inter-rater agreement between four rheumatologists; iii) preliminary assess whether the elementary lesions of the LGs let us differentiate healthy subjects from primary Sjögren's syndrome (pSS) patients.A consensus meeting was held to define the sonographic lesions to be evaluated. Healthy subjects and pSS patients underwent lacrimal glands ultrasound (LGUS) examinations in two Italian Rheumatology Clinics. A web-based reliability exercise was performed on healthy subjects' images by four rheumatologists. Afterward, images of pSS patients were evaluated for the presence of the sonographic lesions previously defined and compared to the US findings in healthy subjects.Fifty-seven healthy subjects and 17 pSS patients were evaluated. The intra and inter-rater reliability score was good-excellent for almost all the agreed US features assessed (glandular parenchyma visibility, size, homogeneity, hypoechoic areas, hyperechoic spots, fibrous gland appearance, fatty deposition). Among the LGUS elementary lesions in pSS patients compared with healthy subjects, we detected a significantly difference in glandular inhomogeneity [13/33 (39.4%) vs. 9/63 (14.3%), p=0.01], and in fibrous gland appearance [3/33 (9.1%) vs. 0/63 (0%), p=0.04].In this preliminary study, LGUS proved to have a good-excellent intra and inter-rater reliability. The glandular parenchyma inhomogeneity and the fibrous gland appearance could help differentiate pSS patients from healthy subjects.

Objective Persistent (≥2 months) major salivary gland (SG) enlargement in primary Sjögren's syndrome (pSS) patients is a well-known sign of possible involvement by B-cell lymphoma. The study aimed to evaluate the diagnostic accuracy and safety of ultrasound-guided core needle biopsy (US-guided CNB) of major SGs in comparison to open surgical biopsy. Methods Prospective pSS patients (cases) with clinically persistent SG enlargement underwent US-guided CNB, and were compared to retrospective pSS patients (controls) submitted to open surgical biopsy. The features analyzed were pre-biopsy clinical and laboratory findings, biopsy-related complications (reported by the patient with a questionnaire and clinically verified), adequacy of the material for histology and diagnosis rendered. Results Thirteen cases underwent US-guided CNB: in 9/13 biopsy was performed on the parotid and in 4/13 on the submandibular gland. Sufficient material was obtained for pathological diagnosis in all samples. The final diagnoses were: 5/13 (38.5%) B-cell lymphoma, 1/13 (7.7%) lympho-epithelial sialadenitis, 4/13 (30.7%) other sialadenitis (granulomatous consistent with sarcoidosis, IgG4-related disease, chronic sclerosing, diffuse chronic) and 3/13 (23.1%) miscellaneous lesions. Thirteen controls underwent open surgical biopsy of the parotid, in one inadequate material was obtained, in 12 (92.3%) the pathologic diagnoses were: 4/12 (33.3%) B-cell lymphoma, 2/12 (16.7%) lympho-epithelial sialadenitis, 4/12 (33.3%) uncertain lymphoproliferative lesions, 2/12 (16.7%) miscellaneous lesions. 6/13 (46.1%) cases reported 6 transient complications, and 12/13 (92.3%) controls 2 persistent and 14 transient complications. Conclusion US-guided CNB represents a novel, clinically relevant and safe approach to the management of pSS patients with parotid or submandibular persistent enlargement.

OBJECTIVES: Italy was one of the first countries significantly affected by the coronavirus disease 2019 (COVID-19) epidemic. The Italian Society for Rheumatology promptly launched a retrospective and anonymised data collection to monitor COVID-19 in patients with rheumatic and musculoskeletal diseases (RMDs), the CONTROL-19 surveillance database, which is part of the COVID-19 Global Rheumatology Alliance. METHODS: CONTROL-19 includes patients with RMDs and proven severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) updated until May 3rd 2020. In this analysis, only molecular diagnoses were included. The data collection covered demographic data, medical history (general and RMD-related), treatments and COVID-19 related features, treatments, and outcome. In this paper, we report the first descriptive data from the CONTROL-19 registry. RESULTS: The population of the first 232 patients (36% males) consisted mainly of elderly patients (mean age 62.2 years), who used corticosteroids (51.7%), and suffered from multi-morbidity (median comorbidities 2). Rheumatoid arthritis was the most frequent disease (34.1%), followed by spondyloarthritis (26.3%), connective tissue disease (21.1%) and vasculitis (11.2%). Most cases had an active disease (69.4%). Clinical presentation of COVID-19 was typical, with systemic symptoms (fever and asthenia) and respiratory symptoms. The overall outcome was severe, with high frequencies of hospitalisation (69.8%), respiratory support oxygen (55.7%), non-invasive ventilation (20.9%) or mechanical ventilation (7.5%), and 19% of deaths. Male patients typically manifested a worse prognosis. Immunomodulatory treatments were not significantly associated with an increased risk of intensive care unit admission/mechanical ventilation/death. CONCLUSIONS: Although the report mainly includes the most severe cases, its temporal and spatial trend supports the validity of the national surveillance system. More complete data are being acquired in order to both test the hypothesis that RMD patients may have a different outcome from that of the general population and determine the safety of immunomodulatory treatments.

BackgroundEnlargement of the major salivary glands (SGs) is a major risk factor for B-cell lymphoma among patients with primary Sjögren’s syndrome (pSS). Ultrasound-guided core needle biopsy (US-guided CNB) could be a novel technique to manage SG enlargement among patients with pSS.ObjectiveAccordingly, this study’s main aim was to evaluate the safety, patient tolerance and diagnostic accuracy of US-guided CNB procedure for patients with pSS with major SG enlargement.MethodsPatients with clinical diagnosis of pSS and a clinical indication for SG biopsy consecutively underwent US-guided CNB between September 2019 and June 2021. These patients were evaluated clinically 1, 2 and 12 weeks after US-guided CNB. Patients were asked to complete a questionnaire about postprocedural complications as well as periprocedural pain, using the Visual Analogue Scale. Complications were categorised as transient (persistent (≥12 weeks).ResultsUS-guided CNB was performed on 30 major salivary glands (22 parotid glands and 8 submandibular glands). The procedure was well tolerated. Transient complications—such as haematoma, swelling—were observed among 43% of patients, and mean periprocedural pain was low. However, no persistent complications were reported during the study’s follow-up period.ConclusionUS-guided CNB represents a novel approach for the management of patients with pSS with SG enlargement. The procedure showed remarkable patient safety and tolerance, allowing adequate glandular sampling and a definite diagnosis for almost all participating patients without long-term complications.

Background:The UPSTREAM (NCT03330769) is a 24-month multi-center prospective cohort study that primarily aims to evaluate the additional value of musculoskeletal ultrasound (msk-US) over clinical examination in predicting 6-month minimal disease activity in Psoriatic Arthritis (PsA). (1)Objectives:To develop and preliminarily validate an activity msk-US score and a damage msk-US score for PsA using the UPSTREAM database.Methods:Patients classified with PsA according to CASPAR criteria and starting a new course of therapy for clinically active peripheral joint disease were eligible. The information regarding objectives, study design, clinical and US assessment has already been published (1). The msk-US examination was performed in 42 joints, 36 tendons, 12 entheses and 2 bursae defined through a web-based exercise (2). The sonographic elementary lesions were allocated to disease activity [i.e. synovitis (sy), tenosynovitis (ts), peritendinitis (pt), bursitis (bs) all evaluated both in Grey Scale (GS) and Power Doppler (PD) and active enthesitis (en)] and to damage (i.e. joint erosion, bone proliferation, tendon tear, enthesophyte, calcification and irregular enthesis bone profile). Hands and feet X-ray were assessed using the modified Sharp-Van der Heijde (mSVH) score. A principal component (PC) analysis (PCA) was performed for each score and the number of PCs was defined by means of parallel analysis using baseline data. Each PC was normalized (n) taking into account the proportion between the observed value (e.g. sy-GS count) and the maximum expected value (e.g. 42 for sy-GS). Spearman’ correlation was used to investigate the construct and discrimination validity of the new scores.Results:Between February 2017 and May 2020, 312 PsA patients (155 men), with a mean (SD) age of 52.8 13.4, were enrolled from 19 centers; 22 expert sonographers were involved with substantial agreement for US lesions evaluated (k ≥0.7). The median [IQR] disease duration was 1.3 [0.1-6.1] years and the median [IQR] tender joint and swollen joint counts were 6 [3-13] and 2 [1-5], respectively. The weight derived from PCA for each sonographic lesions and the final equation for calculating the scores are reported in Figure 1 (1A activity and 1B damage). The final msk-US activity score [n(ts-GS + ts-PD)*2.87] + [n(bs-GS + bs-PD)*1.76] + [n(pt-GS + pt-PD)*1.43] + [n(active en)*1.00] + [n(sy-GS)*0.83] + [n(sy-PD)*0.45] has the best construct and discrimination validities according to a significant correlation with all clinical variables usually related to clinical activity (Table 1). The msk-US damage score correlated with mSVH score, HAQ and other clinical variables (Table 1).Table 1.VariablesMsk-US activity scoreMsk-US damage scoreSpearman correlationP-valueSpearman correlationP-valueESR0.1960.0020.0750.235CRP0.2090.0680.254TJC0.3380.286SJC0.3380.0720.221Dactylitis count0.284-0.0610.306LEI0.1940.0010.214Physician GA0.150.0120.0160.793Patient GA activity0.1380.018-0.0730.221Patient GA pain0.1990.001-0.0270.648HAQ0.2380.1460.014BASDAI0.2370.1750.003PSAID-90.70.0040.1480.013DAPSA0.3920.228Sharp van Der Heijde score0.1150.20.2660.003Figure 1.Conclusion:These newly developed and preliminary validated msk-US activity and damage scores could be used in patients with PsA in the context of observational and controlled trials.References:[1]Canzoni M et al. BMJ Open. 2018;8:e021942.[2]Zabotti A et al. Ann Rheum Dis 2018;77:1537–1538.Acknowledgements:Alberto Batticciotto; Oscar Massimiliano Epis; Luisa Arcarese; Luca Navarini; Marta Caprioli; Mirco Magnani; Roberta Ramonda; Marco Amedeo CimminoDisclosure of Interests:Alen Zabotti: None declared, Matteo Piga: None declared, Anna Zanetti: None declared, Marco Canzoni: None declared, nicola boffini: None declared, valentina picerno: None declared, Giovanni Zanframundo: None declared, Ettore Silvagni: None declared, Ivan Giovannini: None declared, BERND RAFFEINER: None declared, Palma Scolieri: None declared, Paola Mancini: None declared, Simone Parisi: None declared, Alessandra Bortoluzzi Grant/research support from: GSK, Garifallia Sakellariou Consultant of: Consultant for Abbvie and Novartis, Orazio De Lucia: None declared, Ilaria Tinazzi: None declared, Fabiana Figus: None declared, Luca Idolazzi Speakers bureau: Received grants as speaker for Eli Lilly, UCB, Celgene, MSD, Abbvie, Novartis, Paid instructor for: Paid instructor for UCB during Product specialist Meeting, Mariagrazia Lorenzin: None declared, Sara Zandonella Callegher: None declared, Alberto Cauli: None declared, Greta Carrara: None declared, Carlo Alberto Scirè: None declared, Annamaria Iagnocco: None declared

Background:Persistent enlargement of major salivary glands (SGs) is one of the main risk factors for B-cell lymphoma in primary Sjögren’s syndrome (pSS). The Ultrasound-guided Core Needle Biopsy (US-guided CNB) could be a novel technique for the management of SGs enlargement in pSS (1).Objectives:To evaluate the procedure safety and the patient tolerance of US-guided CNB in pSS patients with major SGs enlargement.Methods:Consecutive patients, with either definite or clinically suspected pSS, and with clinical indication for SGs biopsy due to persistent glandular enlargement were screened for US-guided CNB from September 2019 to December 2020. All patients were evaluated clinically between 1 and 2 weeks and 12 weeks following US-guided CNB. All patients were asked to complete a questionnaire to report post-procedural complications (Figure 1, English version) and intra- and post-procedural pain Visual Analogue Scale (VAS). The complications were classified as transient (Results:US-guided CNB was performed in 21 glands (12 parotid and 9 submandibular glands) in 20 pSS patients. 16/20 (80%) patients fulfilled the ACR-EULAR classification criteria for pSS (2). The mean age at the time of biopsy was 62.1 (±11.7) years. US-guided CNB was well tolerated, no long-term complications were reported in the follow-up period (mean 9.5 ±5.7 months). Only transient complications were noticed in 11 patients (55%). In particular, two cases of local swelling at the biopsy site lasting no more than 6 days, one case of local bleeding and subsequently hematoma of the submandibular area, one case of transient facial paresis (lasting less than one hour), seven cases of post-procedural mild local pain, that resolved within 10 days without the need of analgesics (Table 1). The procedure was well tolerated, with a very low reported intra-operative pain (mean VAS 1.74 ±2.49) and a mean post-operative pain VAS of 1.39 (±2.33). The biopsy sampling was diagnostic in 19/20 patients (95%).Conclusion:US-guided CNB represents a novel approach for the management of pSS patients with SGs enlargement. This procedure shows a remarkable patient safety and tolerance, allowing an adequate glandular sampling and definite diagnosis in almost all the studied patients.References:[1]Zabotti A, Zandonella Callegher S, Lorenzon M, Pegolo E, Scott CA, Tel A, et al. Ultrasound-guided core needle biopsy compared with open biopsy: a new diagnostic approach to salivary gland enlargement in Sjögren’s syndrome? Rheumatology (Oxford) 2020.[2]Shiboski CH, Shiboski SC, Seror R, Criswell LA, Labetoulle M, Lietman TM, Rasmussen A, Scofield H, Vitali C, Bowman SJ, Mariette X; International Sjögren’s Syndrome Criteria Working Group. 2016 American College of Rheumatology/European League Against Rheumatism Classification Criteria for Primary Sjögren’s Syndrome: A Consensus and Data-Driven Methodology Involving Three International Patient Cohorts. Arthritis Rheumatol. 2017 Jan;69(1):35-45. doi: 10.1002/art.39859. Epub 2016 Oct 26. PMID: 27785888; PMCID: PMC5650478.Table 1.Description of complicationsComplications of US-guided CNBPatients presenting complications, n/N (%)11/20 (55%)Description of transient complicationsSwelling at biopsy site, n2Bleeding, n1Hematoma, n1Local Pain, n7Local infection, n0Sialocele or fistula, n0Anaesthesia/paraesthesia, n0Transient facial palsy (< 1 hour), n1No persistent complications reportedAll the above specified complications were transient (< 12 weeks). No persistent complications were reported in the follow up.Figure 1.Post-biopsy complication QuestionnaireDisclosure of Interests:Alen Zabotti Speakers bureau: UCB, Novartis, Janssen, Paid instructor for: Amgen, Consultant of: Janssen, Ivan Giovannini: None declared, Sara Zandonella Callegher: None declared, Valeria Manfrè: None declared, Michele Lorenzon Consultant of: not relevant for this study, Enrico Pegolo: None declared, Cathryn Ann Scott: None declared, Alessandro Tel: None declared, Massimo Robiony Consultant of: not relevant for this study, Grant/research support from: not relevant for this study, Chiara Zuiani Consultant of: not relevant for this study, Grant/research support from: not relevant for this study, Salvatore De Vita Consultant of: GSK, Roche, Grant/research support from: not relevant for this study

Objective: The disease course in primary Sjögren's Syndrome (pSS) differs in different subsets of patients. The aim of this study was to clarify whether the pattern of organ involvement may improve the prediction of the very long-term disease outcome.Methods: We collected the data of 255 patients. The total European League Against Rheumatism (EULAR), EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) score was compared with the pattern of organ involvement, as differentiated by the single ESSDAI domains: (i) at disease diagnosis, and (ii) in the follow-up, by verifying the appearance of new ESSDAI domains and/or the worsening of already active ESSDAI domains.Results: The mean follow-up duration was 9.1 ± 6.9 years. At disease diagnosis, only the articular activity at baseline could predict the long-term outcome of pSS detected at last follow-up visit, being protective in terms of stable or improved disease activity, as measured by ESSDAI [OR 2.9 (1.6–5.4), p = 0.01]. In the follow-up, the onset, and/or worsening of either the peripheral nervous system (PNS) domain (by multivariate and univariate analysis), or the biological domain (only by univariate analysis) correlated with a higher disease activity at the last visit [PNS domain: OR 5.9 (2.4–14.5), p < 0.0001; biological domain: OR 1.9 (1.0–3.8), p = 0.043]. A significantly higher number of patients with articular involvement were taking hydroxychloroquine at the last follow-up visits, if compared with patients without (41/130, 31.5 vs. 13/125, 10.4%, p < 0.0001).Conclusion: Single organ disease manifestations of SS, herein identified as the articular, PNS and biologic involvement, are relevant to predict the very long-term outcome in pSS.

In primary Sjögren's syndrome (pSS) dryness of eye and mouth is the cardinal referred symptom. Assessing the rate of activity and damage in the salivary glands of pSS patients is essential to improve disease management. Up to now, a differentiation of activity and damage ultrasonographic (US) lesions is an open issue. The aim of this preliminary study was to identify US lesions which better correlate with loss of function of salivary glands in pSS.Salivary glands ultrasonography of consecutive patients with established pSS, fulfilling AECG and ACR/EULAR criteria was performed. The association between sialometry and Visual Analogue Scale (VAS) oral dryness and SGUS lesions was assessed trough univariate and multivariate analysis.In 75 established pSS patients, mean disease duration 12.4±7.2 years, the hyperechoic bands of parotid gland (PG) and submandibular gland (SMG) were significantly associated with sialometry (p0.001) and VAS oral dryness (PG p=0.002, SMG p0.001). The global glandular involvement (scored according to De Vita et al., 1992) was associated with sialometry (PG p=0.025, SMG p0.001) and with VAS oral sicca (PG p=0.015, SMG p0.001). The multivariate analysis selected the hyperechoic bands of PG and SMG as the variables independently associated with sialometry and the hyperechoic bands and the homogeneity in the SMG as associated with VAS oral dryness.These results indicate that salivary impairment in pSS, as objectively evaluated by sialometry, could be mainly associated with damage (i.e., hyperechoic bands) in established pSS. Additional follow-up studies and improved scoring tools are needed.

ObjectiveNon-specific musculoskeletal pain is common in subjects destined to develop psoriatic arthritis (PsA). We evaluated psoriatic patients with arthralgia (PsOAr) compared with psoriasis alone (PsO) and healthy controls (HCs) using ultrasonography (US) to investigate the anatomical basis for joint symptoms in PsOAr and the link between these imaging findings and subsequent PsA transition.MethodsA cross-sectional prevalence analysis of clinical and US abnormalities (including inflammatory and structural lesions) in PsOAr (n=61), PsO (n=57) and HCs (n=57) was performed, with subsequent prospective follow-up for PsA development.ResultsTenosynovitis was the only significant sonographic feature that differed between PsOAr and PsO (29.5% vs 5.3%, pConclusionTenosynovitis was associated with arthralgia in subjects with psoriasis. Baseline US evidence of enthesitis was associated with clinical PsA development in the longitudinal analysis. These findings are relevant for enriching for subjects at risk of imminent PsA development.

Background:Sjögren’s syndrome (SS) affects mainly individuals of the 4thor 5thdecade of life, although patients with early (≤35 years old) or late (≥65 years old) disease onset have been described in the literature. The clinical spectrum of the disease extends from mild dryness to severe systemic vasculitis and lymphoproliferative disorders. The phenotypic diversity of SS is defined by many factors, including age, since many parameters related to age may affect the clinical expression of the disease. Few studies have been conducted to study the effect of age on the clinical phenotype of SS, though with limited number of patients. Large and well-defined groups of SS are required to address such questions.Objectives:To study the clinical phenotype of SS patients with early and late disease onset and to explore the association of age with lymphoma development in a unified multicenter cohort.Methods:From a total cohort of 1997 consecutive SS patients who fulfill the 2016 EULAR/ACR criteria and are followed up in 5 clinical centers ([Universities ofUdine,Pisa andAthens,Harokopio andIoannina, (UPAHI)], those with either early (≤35 years) or late (≥65 years) disease onset were identified and matched according to gender and disease duration with middle aged controls whose disease onset was at the 4thor 5thdecade of life. Glandular manifestations, extra-glandular manifestations, serologic characteristics and histologic features were compared between the 2 age groups and the middle-aged control groups. Statistical analysis for categorical variables was performed by Fisher exact or chi-square tests and for continuous variables with t test or Mann-Whitney accordingly.Results:Three hundred seventy-nine (19%) SS patients with early and 293 (15%) with late disease onset were identified and compared with 353 and 285 middle aged SS controls respectively. The median disease duration of patients with early onset was 12 years (range:0-68) and for those with late disease onset was 5 years (range: 0-27). SS patients with early disease onset had statistically significant higher frequency of Raynaud’s phenomenon, lymphadenopathy, hypergammaglobulinemia, anti-Ro/SSA, anti-La/SSB, rheumatoid factor, salivary gland enlargement, low C4 complement levels, leukopenia and lymphoma (10,3% vs 5,7%, p= 0.03, OR= 1,91, 95% CI: 1,11-3,27) while SS patients with late disease onset had more frequently dry mouth, interstitial lung disease and lymphoma (6,8% vs 2,1%, p=0,01, OR= 3,4. 95%CI: 1,35-1,81).Conclusion:In a multicenter cohort of 1997 consecutive SS patients, those with early and late disease onset comprise more than one third of the total SS population. Patients with early disease onset, exhibit robust B cell responses with traditional risk factors for lymphoma as opposed to patients with late disease onset. Both age groups have increased lymphoma prevalence but presumably for different reasons, since late onset patients lack classical predictors of lymphoma. Therefore, these predictors deserve further study in different disease subsets.Disclosure of Interests:Andreas Goules: None declared, Ourania Argyropoulou: None declared, Vasileios Pezoulas: None declared, Francesco Ferro: None declared, Saviana Gandolfo: None declared, Valentina Donati: None declared, Marco Binutti: None declared, Sara Zandonella Callegher: None declared, Loukas Chatzis: None declared, Aliki Venetsanopoulou: None declared, Evangelia Zampeli: None declared, Maria Mavromati: None declared, Paraskevi Voulgari: None declared, Clio Mavragani: None declared, Chiara Baldini: None declared, Fotini Skopouli: None declared, Dimitris Fotiadis: None declared, Salvatore De Vita Consultant of: Roche, Human Genome Science, Glaxo Smith Kline and Novartis, Haralampos M. Moutsopoulos: None declared, Athanasios Tzioufas: None declared

To investigate if indicators of a heavier involvement of mucosa-associated lymphoid tissue (MALT) in primary Sjögren's syndrome (pSS), i.e. persistent salivary gland (SG) swelling and cryoglobulinaemia, might better evaluate the lymphoma risk compared to the ESSDAI. Therefore, the current concept of disease activity of pSS should be re-evaluated, based solely on ESSDAI.A cohort of 255 pSS patients, including 30 pSS with B-cell lymphoma, was investigated. Three subgroups were distinguished, i.e. pSS developing lymphoma in the follow-up (n=12), pSS with lymphoma at cohort inclusion (n=18), and control pSS not developing lymphoma in the follow-up (n=225). SG swelling, cryoglobulinaemia and ESSDAI were evaluated at baseline, in the follow-up to one year before lymphoma diagnosis, and at lymphoma diagnosis.SG swelling and/or cryoglobulinaemia at baseline were significantly higher (p=0.0003) in pSS patients evolving into lymphoma if compared to pSS controls, while ESSDAI showed no significant difference. Both SG swelling and cryoglobulinaemia persisted and sometimes developed ex novo in the follow-up. SG swelling and cryoglobulinaemia were present in 24/30 (80%) cases the time of lymphoma diagnosis, and lymphoma itself was usually of MALT/marginal zone histotype (90%), leading to peculiar manifestation of lymphoma in pSS.The autoimmune and lymphoproliferative involvement of MALT is the biological substrate of pSS. If this involvement is heavier, as reflected by SG swelling and cryoglobulinaemia, disease activity may be considered higher, and the risk of lymphoma is increased. The current concept and evaluation of activity of pSS, based solely on the ESSDAI, needs revision.

Sjogren’s syndrome (SS) is a systemic autoimmune disease characterized by exocrine gland dysfunction and destruction, mainly localized at the level of salivary and lacrimal glands, leading to dryness of the mouth and eyes, as the most frequent symptoms of the disease. From a pathological point of view, SS is an exocrinopathy (i.e. an autoimmune epitheliitis of the exocrine glands) characterized by dense lymphocytic infiltrates of glandular tissue and B-cell hyperreactivity.

Objective: Salivary gland ultrasound (SGUS) is emerging as a valid tool in the management of primary Sjögren's syndrome (pSS). This study aimed to investigate whether pSS patients with normal-appearing or pathological SGUS findings showed different clinical, laboratory, and pathologic pSS-related features, and to compare the results by using two different SGUS scores.Methods: Consecutive pSS patients, according to the ACR-EULAR classification criteria, were evaluated. Salivary glands were scored using the early 1992 score by De Vita et al. and the latest 2019 OMERACT score, both being semiquantitative 0–3 scoring systems focused on ultrasonographic parenchymal inhomogeneity (grades 0 and 1, normal-appearing; grades 2 and 3, pathological). The patients were then divided into two groups: “SGUS normal-appearing” if all the salivary glands had normal-appearing parenchyma (grade 0 or 1), or “SGUS pathological” if the grade was 2 or 3 in at least one salivary gland. The associations between SGUS and pSS-related clinical, laboratory, and pathological features were then investigated in the two groups.Results: One hundred pSS patients were evaluated, the mean age (±SD) was 60.9 ± 12.0 years, and mean disease duration was 11.7 ± 7.2 years. Twenty-nine out of 100 (29%) patients were in the “SGUS normal-appearing” group and 71/100 (71%) were in the “SGUS pathological” group. A normal-appearing SGUS was significantly associated with the absence of anti-La/SSB antibodies (p < 0.001) and normal unstimulated salivary flow rate (p = 0.02) by both univariate and multivariate analyses. By univariate analysis, a normal-appearing SGUS was significantly associated also with the absence of rheumatoid factor (p = 0.002) and of serum monoclonal component (p = 0.003), ESSDAI < 5 (p = 0.03), and with a negative lip biopsy (p = 0.029). No associations were found with other items, including anti-Ro/SSA (p = 0.145), Schirmer's test (p = 0.793), ESSPRI (p = 0.47), and demographic data. No differences in these results were observed by using the two SGUS scoring systems.Conclusion: The SGUS allowed the identification of different phenotypes of pSS, and different SGUS scores focused on salivary gland inhomogeneity may be effective to this end.