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      Normal-Appearing Salivary Gland Ultrasonography Identifies a Milder Phenotype of Primary Sjögren's Syndrome

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          Abstract

          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.

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          Most cited references53

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          EULAR Sjogren's syndrome disease activity index: development of a consensus systemic disease activity index for primary Sjogren's syndrome.

          To develop a disease activity index for patients with primary Sjögren's syndrome (SS): the European League Against Rheumatism (EULAR) Sjögren's syndrome disease activity index (ESSDAI). Thirty-nine SS experts participated in an international collaboration, promoted by EULAR, to develop the ESSDAI. Experts identified 12 organ-specific 'domains' contributing to disease activity. For each domain, features of disease activity were classified in three or four levels according to their severity. Data abstracted from 96 patients with systemic complications of primary SS were used to generate 702 realistic vignettes for which all possible systemic complications were represented. Using the 0-10 physician global assessment (PhGA) scale, each expert scored the disease activity of five patient profiles and 20 realistic vignettes. Multiple regression modelling, with PhGA used as the dependent variable, was used to estimate the weight of each domain. All 12 domains were significantly associated with disease activity in the multivariate model, domain weights ranged from 1 to 6. The ESSDAI scores varied from 2 to 47 and were significantly correlated with PhGA for both real patient profiles and realistic vignettes (r=0.61 and r=0.58, respectively, p<0.001). Compared with 57 (59.4%) of the real patient profiles, 468 (66.7%) of the realistic vignettes were considered likely or very likely to be true. The ESSDAI is a clinical index designed to measure disease activity in patients with primary SS. Once validated, such a standardised evaluation of primary SS should facilitate clinical research and be helpful as an outcome measure in clinical trials.
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            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.

            To develop and validate an international set of classification criteria for primary Sjögren's syndrome (SS) using guidelines from the American College of Rheumatology (ACR) and the European League Against Rheumatism (EULAR). These criteria were developed for use in individuals with signs and/or symptoms suggestive of SS.
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              EULAR Sjogren's Syndrome Patient Reported Index (ESSPRI): development of a consensus patient index for primary Sjogren's syndrome.

              To develop a score for assessment of patients' symptoms in primary Sjögren's syndrome (SS): the EULAR SS Patient Reported Index (ESSPRI). Dryness, pain, somatic and mental fatigue were identified as the main symptoms of patients with primary SS, in studies developing the Profile of Fatigue and Discomfort (PROFAD) and Sicca Symptoms Inventory (SSI). It was suspected that a single 0-10 numerical scale for each domain was sufficient to assess these symptoms. These four scales were gathered to form the ESSPRI. 230 patients, from 12 countries completed the ESSPRI, SSI and PROFAD questionnaires and a 0-10 patient global assessment (PGA). Correlations between each symptom and PGA were obtained. Multiple regression modelling, using PGA as 'gold standard' was used to select domains and estimate their weights. PGA had good correlation with dryness, limb pain, fatigue and mental fatigue (r=0.49-0.59, all p<0.0001), but correlated less well with individual dryness features. In multivariate analysis, dryness, limb pain and fatigue, but not mental fatigue, were significantly associated with PGA; weights derived from the regression were identical for these three domains. Thus, ESSPRI was redefined as the mean of the three scales: dryness, limb pain and fatigue. Lastly, ESSPRI significantly correlated with PGA (r=0.70), PROFAD (r=0.73) and SSI (r=0.66). ESSPRI is a very simple index designed to measure patients' symptoms in primary SS. It has good construct validity and is well correlated with SSI and PROFAD. ESSPRI should now be validated for use as an outcome measure in clinical trials.
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                Author and article information

                Contributors
                Journal
                Front Med (Lausanne)
                Front Med (Lausanne)
                Front. Med.
                Frontiers in Medicine
                Frontiers Media S.A.
                2296-858X
                09 December 2020
                2020
                : 7
                : 602354
                Affiliations
                Rheumatology Clinic, Department of Medical Area, Azienda Sanitaria Universitaria Friuli Centrale , Udine, Italy
                Author notes

                Edited by: Alessia Alunno, University of Perugia, Italy

                Reviewed by: Gonçalo Boleto, Hôpitaux Universitaires Pitié Salpêtrière, France; Vasco C. Romão, University of Lisbon, Portugal

                *Correspondence: Salvatore De Vita salvatore.devita@ 123456asufc.sanita.fvg.it

                This article was submitted to Rheumatology, a section of the journal Frontiers in Medicine

                †These authors have contributed equally to this work

                Article
                10.3389/fmed.2020.602354
                7756091
                039d0f86-c1f4-4152-933b-28d48c791e78
                Copyright © 2020 Zandonella Callegher, Zabotti, Giovannini, Treppo, Quartuccio and De Vita.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 03 September 2020
                : 09 November 2020
                Page count
                Figures: 2, Tables: 3, Equations: 0, References: 55, Pages: 10, Words: 6398
                Categories
                Medicine
                Original Research

                ultrasoud,salivary gland,scoring system,primary sjogren's syndrome,follow-up,managment

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