American-European Consensus Group Criteria Research Articles

Clinical Profile of Patients with Primary Sjögren's Syndrome with Non-Identified Antinuclear Autoantibodies.

Objectives-The aim of the present study was to characterize the clinical phenotype of patients with primary Sjögren's syndrome (pSS) with non-identified antinuclear antibodies (ANA) in comparison with that of patients with pSS with negative ANA, positive typical ANA (anti-Ro/SSA and/or La/SSB) and positive atypical ANA. Methods-We conducted an observational, retrospective monocentric study at the Erasme University Hospital (Brussels, Belgium). Two hundred and thirty-three patients fulfilling the 2002 American-European Consensus Group criteria for pSS were included in this study. The patients were subdivided according to their ANA profile and demographics. The clinical and biological data of each subgroup were compared. Moreover, the relationships between these data and the ANA profiles were determined by multiple correspondence analysis. Results-In our cohort, 42 patients (18%) presented a non-identified ANA-positive profile. No statistically significant difference could be observed between non-identified ANA patients and ANA-negative patients in terms of age and/or ESSDAI score at diagnosis. There were significantly more frequent articular manifestations, positive rheumatoid factor (RF), and the use of corticosteroids in anti-Ro/SSA-positive patients compared to ANA-negative (p ≤ 0.0001) and non-identified ANA-positive patients (p ≤ 0.01). However, a significantly higher proportion of RF positivity and corticosteroid treatment was observed in non-identified ANA-positive patients compared to ANA-negative patients (p < 0.05). Conclusions-For the first time to our knowledge, our study has characterized the clinical phenotype of patients with pSS with non-identified ANA at diagnosis. The non-identified ANA-positive patients featured mostly a clinical phenotype similar to that of the ANA-negative patients. On the other hand, the non-identified ANA-positive patients were mainly distinguished from the ANA-negative patients by a greater proportion of RF positivity and the need for corticosteroid use due to articular involvement.

Ultrasonography in the diagnosis of suspected primary Sjögren's syndrome and concordance with salivary gland biopsy: a Spanish single-center study.

The study aims to evaluate the utility of major salivary gland ultrasonography for diagnosis of primary Sjögren's syndrome (pSS) and to assess its concordance with minor salivary gland biopsy (MSGB). A cross-sectional study of 72 patients with suspected pSS was performed. Demographic, clinical, and serological data were collected. MSGB was performed, as was ultrasonography. The ultrasound technician was blind to clinical, serological, and histological data. The validity of ultrasonography compared with MSGB, the American-European Consensus Group (AECG), and American College of Rheumatology (ACR)/European Alliance of Associations for Rheumatology (EULAR) criteria was assessed by calculating the percentage of agreement, sensitivity, specificity, positive and negative predictive values, and area under the curve (AUC). Based on MSGB as the gold standard, the percentage of agreement between both tests was 78% (AUC 0.75). Based on the ACR/EULAR criteria, the percentage of agreement was 83% (AUC 0.78) for ultrasonography and 81% (AUC 0.83) for biopsy. Sensitivity and specificity were 90% and 67%, respectively, for ultrasonography and 76% and 90% for biopsy. The results were similar with the AECG criteria. The intra- and inter-observer variability was good (κ > 0.7). Significant differences were observed for positive anti-Ro52 values and hypergammaglobulinemia in pathological ultrasound scans. Diagnostic ultrasonography is as useful as MSGB in pSS. Therefore, it could be included in the classification criteria. In this cohort, it proved more sensitive than MSGB and could be used as an initial test for patients suspected of having pSS. MSGB could be used in cases where clinical and serological results are inconclusive. Key Points • Major salivary gland ultrasonography adds diagnostic value similar to that of MSGB, thus potentially enabling this invasive procedure to be avoided. • Ultrasonography could be included in the classification criteria for primary Sjögren's syndrome. • Given that ultrasonography is more sensitive and less specific than MSGB, it could be used as an initial diagnostic test in patients with suspected Sjögren's syndrome. • Biopsy should be performed in those cases where ultrasonography, clinical, and serological data are inconclusive.

Clinical and Serological Profile of Sjögren’s Syndrome Patients in a Tertiary Care Center in Kashmir, North India

Abstract Background: Sjögren’s syndrome (SS) is a chronic autoimmune illness characterized by lymphocyte infiltration and exocrine gland inflammation. SS has been considered a rare disorder in India, and data on its clinical manifestations and serology are lacking from North India. Aim: We aimed to study clinical manifestations, organ involvement, and autoantibodies in SS patients from Jammu and Kashmir. Methods: This was a single-center observational prospective study. A total of 50 patients satisfying the American-European Consensus Group criteria were included in the study. Data regarding subjective and objective evidence of disease were compiled. Extraglandular manifestations in the form of musculoskeletal, renal, pulmonary, and neurological were also recorded. Results: Of the 50 patients, 29 were primary SS and 21 were secondary SS. Female preponderance was observed with a female-to-male ratio of 24: 1. Xerostomia was the most common symptom present in all of the patients. The most common extraglandular involvement was musculoskeletal followed by renal and pulmonary. Conclusions: Early onset of the disease by a decade is a surprising observation in this study and rest of the Indian literature compared to western literature.

Childhood-onset primary Sjögren’s syndrome in a tertiary center in China: clinical features and outcome

ObjectivesTo characterize the clinical features and outcomes of childhood-onset primary Sjögren’s syndrome (pSS).MethodsPatients less than 18 years old who were diagnosed with pSS by paediatric rheumatologists were included, and all patients were applied the 2002 American-European Consensus Group (ACEG) criteria, the 2016 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) criteria for pSS, or the 1999 proposed juvenile pSS criteria. The electronic medical records of patients with pSS from 2013 to 2020 were collected and analysed.ResultsThirty-nine patients were included. Of them, 27 (69.2%), 38 (97.4%) and 35 (89.7%) patients fulfilled the AECG criteria, ACR/EULAR criteria and proposed juvenile pSS criteria, respectively. The female:male ratio was 3.9:1. The median ages at first signs or symptoms and at diagnosis were 9.2 (4.7, 14.5) years and 10.9 (6.3, 15.0) years, respectively. The main clinical manifestations were rash or purpura (20, 51.3%), followed by fever (12, 30.8%), glandular enlargement/recurrent parotitis (10, 25.6%), and dry mouth and/or dry eyes (9, 23.1%). Twenty-eight (56.4%) patients had systemic damage, the most common of which was haematological involvement (14, 35.9%), followed by hepatic (13, 33.3%) and renal involvement (8, 20.5%). Thirty-eight (97.4%) patients underwent labial minor salivary gland biopsy, and all exhibited focal lymphocytic sialadenitis. All patients had a global ESSDAI score ≥ 1 at diagnosis, and the median total score at diagnosis was 8 (2, 31). Thirty-six (92.3%) patients were followed up for a median time of 23.6 (7.9, 79.5) months, and three patients developed systemic lupus erythematosus (SLE) at follow-up times of 13.3, 38.8 and 63.8 months.ConclusionsThe presentation of childhood-onset pSS is atypical, and extraglandular manifestations and systemic involvement are more common than in adult-onset pSS. Labial salivary gland biopsy is vital for patients with probable pSS. Some patients may develop SLE over time.

OA34 Juvenile Sjogren’s Syndrome: the need for validated paediatric diagnostic criteria. A retrospective review from a tertiary rheumatology centre

Introduction/BackgroundSjögren’s syndrome (SS) is a chronic multi-system autoimmune disease, characterised by inflammation of the exocrine glands, predominantly salivary and lacrimal glands resulting in xerostomia and xerophthalmia.Juvenile-onset-SS (jSS) is rare; however, it is probably under-recognised and under-diagnosed. There are no studies reporting accurate incidence or prevalence of jSS. Description/MethodDiagnosing jSS can be challenging. The cardinal signs and symptoms are non-specific. There is no gold standard biomarker-of-disease. Between 1965–2002 eleven-diagnostic criteria-sets were developed, none of which have gained universal acceptance or been validated in a paediatric-population. Until recently, the most widely used criteria were those developed by the American-European-Consensus-Group (AECG).It remains well recognised that international consensus on classification is important for standardisation, particularly in relation to research and monitoring treatment outcomes. Subsequently, the 2016 ACR/EULAR classification criteria for SS were developed. However, there remains a paucity of validated criteria for diagnosis of jSS. Paediatric focussed criteria are required as features of SS in children differ from those in adults. Children experience less dryness and more frequently experience systemic symptoms and parotid enlargement. Applying adult criteria to a paediatric population may lead to mis- and/or under-diagnosis. Bartunkova et al. (1999) proposed paediatric criteria for diagnosis of jSS. These have not been validated.ObjectivesTo describe the clinical, laboratory and imaging characteristics of children diagnosed with jSS at Great Ormond Street Hospital (GOSH) over a ten-year periodTo apply AECG and the proposed paediatric criteria to our cohort and report percentage fulfilling each criteriaMethodsRetrospective chart review of children diagnosed with jSS from January 2012 - January 2022 at GOSH. Demographic, clinical, laboratory and imaging findings were documented. Features at presentation were compared to the AECG and proposed paediatric SS diagnostic criteria. Percentage of the cohort fulfilling diagnostic criteria for each was calculated.Discussion/ResultsTwenty-eight cases of jSS were diagnosed from January 2012 - January 2022, 22 female (79%). Referring clinicians to Paediatric Rheumatology included Paediatricians (n = 21,75%), Ophthalmologists (n = 1,3.6%), Rheumatologists (n = 1,3.6%), Dermatologists (n = 1, 3.6%), Nephrologists (n = 2,7.1%) and Oral surgeons (n = 2,7.1%). Main reasons for referral included facial swelling, lymphadenopathy, history of rash, constitutional symptoms, and positive investigation findings suggestive of jSS i.e. autoantibody profile and US salivary glands. Median age at diagnosis was 11 years (3.4-14.8). The most common presenting feature was facial swelling (n-18,64%), followed by lethargy (n = 12,43%) and rash (n = 11,39%). Reports of dry eyes (n = 7, 25%) and mouth (n = 9, 32%) were reported less frequently. Laboratory features identified included anaemia, elevated amylase and ESR, positive ANA and Ro, and hyper IgG. All children who had an USS of their salivary glands had features consistent with a diagnosis of jSS (n = 24,86%). Eleven children had salivary gland biopsy, ten (91%) of which provided tissue confirmation of the jSS diagnosis. A total of 8/28 (28.6%) cases satisfied the AECG criteria; 22/28 (78.6%) satisfied the proposed paediatric SS diagnostic criteria.Key learning points/ConclusionConclusionA low percentage of our cohort fulfilled the AECG diagnostic criteria, therefore we would suggest application of adult criteria for diagnosis of jSS maybe unhelpful. Inclusion of recurrent parotitis and additional laboratory features of the in the proposed paediatric criteria may increase sensitivity. Our cohort highlights the need for validated jSS diagnostic criteria as paediatric and adult presentations of SS can differ.

Clinical and laboratory evaluation of sicca complaints: distinctive aspects of primary, secondary and non-Sjogren syndrome

BackgroundSjögren Syndrome (SS) is a systemic autoimmune disease with a wide spectrum of manifestations that can lead to misdiagnosis. This study describes and compares demographic, clinical, serological, and histopathological data from subjects with SS and non-Sjögren Syndrome (NSS). It also details specific features within the primary SS (pSS) and secondary SS (sSS) groups identifying sub-groups.MethodsThe sample included individuals referred to an academic medical center in Brazil for investigation of SS from 2012 to 2020. Patients were retrospectively classified as primary SS (pSS), secondary SS (sSS), or NSS, based on the American-European Consensus Group criteria (AECG-2002), after multi-professional clinical and laboratory evaluation.ResultsA total of 676 individuals were screened and 510 (75.4%) completed the assessments; 198 patients were classified as pSS, 149 as sSS, and 163 as NSS. Symptoms and glandular dysfunction tests were similar in the groups. Concerning pSS, extraglandular manifestations were present in 59% of patients; the elderly had more dry symptoms and peripheral neurological disorders; and 2.5% developed non-Hodgkin lymphoma. In sSS, each overlap promoted distinct clinical and laboratory variants. Several alternative diagnoses were identified as a cause of sicca complex in NSS group.ConclusionsThe diagnosis of SS remains a challenge behind dryness. Up to 31% of the suspected cases had other conditions associated to the symptoms. Histopathological analysis of LSG and SSa determined the diagnostic. Aging in pSS and overlap disease in sSS were responsible for distinct phenotypes and characteristic sub-groups in SS.

SJÖGREN SENDROMUNDA ULTRASON ELASTOGRAFİ BULGULARI

Background/Aims: In Sjögren’s syndrome the basic histopathology in all affected organs is progressive lymphocyte infiltration This causes a change in tissue elasticity in the major salivary glands. The purpose of this study is to investigate salivary gland stiffness in primary Sjögren’s syndrome via shear wave elastography.&#x0D; Material and Methods: According to the 2016 American European Consensus Group criteria, 47 female cases were included in the study as the "patient group" by two rheumatologists. A total of 41 healthy female volunteers, who were in a similar age group and had no symptoms of dry mouth or sicca, and no diagnosis of salivary gland disease, constituted the "control group" of the study .The paired parotid and submandibular glands of all subjects were examined with shear wave elastography. The study was conducted between October 2018-October 2019&#x0D; Results: In our study, there was a significant difference in both parotid glands' tissue elasticity values in both speed and kPA values in cases with pSS compared to the control group. However, when the submandibular glands were evaluated, no significant difference was found between the two groups. In our study, no relationship was found between the duration of symptoms and elasticity values.&#x0D; Conclusions :The fact that shear wave velocity (m / sec) and elasticity value (kPA) values are higher in the evaluation of the parotid gland by SWE technique in patients with pSS than the control group makes SWE an easy, non-invasive, and effective imaging method in Sjögren's Syndrome.

The prevalence of Sjögren’s syndrome and sicca symptoms in patients with systemic sclerosis and alpha-smooth muscle actin expression in biopsy specimens from minor salivary glands

This study aimed to investigate the prevalence of sicca symptoms and secondary Sjögren’s syndrome (SjS) in patients with systemic sclerosis (SSc). Also this study aimed to evaluate the expression of α-smooth muscle actin (α–SMA) in minor salivary gland (MSG) specimens, a possible marker of fibrosis responsible for myofibroblastic transformation. Patients with SSc who were followed in Rheumatology outpatient clinic at a university hospital evaluated. The questionnaire of sicca symptoms and classification of SjS were evaluated according to the American–European Consensus Group (AECG) criteria. Histopathologic evaluations were done in MSG specimens investigating the presence of focal lymphocytic sialadenitis and glandular fibrosis, also assessing the expression of α–SMA. This cross-sectional study included 102 patients with SSc [91 females (89%), mean age 52.5 ± 12 years]. In this cohort 76 (75%) patients had sicca symptoms and 36 (35.3%) patients fulfilled the AECG criteria for SjS; all with limited form. Having SjS found to be associated with older age and the presence of positive anti-SS-A antibodies. On histopathologic examinations, glandular fibrosis was observed in 67 (80%) and lymphocytic sialadenitis was detected in 38 (45%) patients; but only 7 samples were positive for α–SMA. This study suggested sicca symptoms were found to be very common among patients with SSc. Also secondary SjS was detected in nearly one-third of patients with SSc; especially in limited subtype. Anti SS-A positivity and older age were detected as predictors for SjS. Histopathologic evaluations showed significant glandular fibrosis but rare α-SMA staining in patients with SSc.

Clinical manifestations in anti-Ro52/SS-A antibody-seropositive patients with Sjögren's syndrome

Background: The relationship between anti-Ro52/SS-A antibody (anti-Ro52) and the clinical manifestations of Sjögren's syndrome (SS) has not been fully clarified. We determined the clinical factors relevant to SS patients with anti-Ro52. Methods: We conducted a retrospective study of 149 subjects suspicious for SS and 50 healthy control subjects. We analyzed items of the American-European Consensus Group (AECG) criteria and the EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI). Results: SS was documented in 115 subjects. Anti-Ro52 was observed in 70 SS patients. Anti-Ro52 positivity showed a significantly higher association with anti-Ro60 positivity than with anti-centromere antibody (ACA) positivity (p < 0.05). Regarding the difference in the anti-Ro52 concentration, we observed six significantly relevant components: two AECG components and four non-AECG components. The anti-Ro52 concentration well-discriminated three clinical factors (ROC AUC >0.75), i.e., ACA seropositivity, ESSDAI score ≥1, and RF, and it moderately discriminated high serum IgG, focus score ≥1, and anti-La/SS-B antibody seropositivity (ROC AUC >0.7). A linear relationship between the ESSDAI score and the anti-Ro52 concentration was observed. Conclusion: A significant association between clinical factors (including the ESSDAI) and the anti-Ro52 concentration were revealed. Anti-Ro52 was more highly associated with anti-Ro60 positivity than with ACA positivity.

Integrated proteome and phosphoproteome analyses of peripheral blood mononuclear cells in primary Sjögren syndrome patients.

Primary Sjögren syndrome (pSS) is a common autoimmune disease. Here, we performed the first proteome and phosphoproteome analyses of peripheral blood mononuclear cells in pSS patients to obtain a comprehensive profile and identify the potential crucial proteins and pathways for the screening and evaluation of pSS patients. Peripheral blood mononuclear cells from 8 pSS-confirmed patients (American-European Consensus Group Criteria, 2002) and 10 normal controls were selected. Label-free quantitative proteomics was utilized to obtain quantitative information. In total, 787 proteins were identified as differentially expressed proteins, and 175 phosphosites on 123 proteins were identified as differentially phosphorylated proteins. We performed functional enrichment analyses with these proteins and phosphoproteins based on public database. Furthermore, protein-protein interaction network analyses were performed by using multiple algorithms. Using module and hub protein analyses, we identified 16 modules for the proteins, 2 clusters for the phosphoproteins and selected the top 10 hub proteins. Finally, we identified 22 motifs using motif analysis of the phosphosites and found 17 newly identified motifs, while 6 motifs were experimentally verified for known protein kinases. The findings distinguished pSS patients from normal controls at the peripheral blood mononuclear cells level and revealed potential candidates for use in pSS diagnosis.

Interleukin 6 receptor inhibition in primary Sjögren syndrome: a multicentre double-blind randomised placebo-controlled trial

ObjectivesNo immunomodulatory drug has been approved for primary Sjögren’s syndrome, a systemic autoimmune disease affecting 0.1% of the population. To demonstrate the efficacy of targeting interleukin 6 receptor in patients...

The validity of salivary gland scintigraphy in Sjögren's syndrome diagnosis: comparison of visual and excretion fraction analyses.

The diagnostic validity of salivary gland scintigraphy in Sjögren's syndrome (SS) has not been conclusively defined. Whether a quantitative (excretion fraction) interpretation of scintigraphy is superior to a qualitative one (visual analysis) remains a matter of debate. We sought to determine whether the diagnostic discrimination of excretion fraction is higher compared to that obtained by visual analysis. Diagnostic test validity study that encompassed 137 suspected SS subjects who underwent scintigraphy for diagnostic purposes. Patients were diagnosed as SS and non-SS according to the rheumatologist's clinical judgment, and by using the American-European Consensus Group (AECG) and American College of Rheumatology (ACR) classification criteria. Visual analysis (normal vs. abnormal and Schall's classification grade) and excretion fraction scores were calculated. The diagnostic discrimination of these methods was compared through the area under the curve (AUC) analysis. Scintigraphy associations with SS clinical and laboratory features were assessed through multivariable regression analysis. Schall's classification AUC reached statistical significance in its diagnostic discrimination for SS clinical judgment (0.704 [95%CI 0.597-0.811]) and AECG criteria (0.764 [95%CI 0.641-0.886]). Similarly, submandibular excretion fraction was associated with SS diagnosis based on ACR (0.737 [95%CI 0.546-0.931]) and AECG criteria (0.715 [95%CI 0.597-0.833]). However, AUC comparisons between qualitative and quantitative methods did not yield statistically significant values. Both interpretation modalities were associated with SS serological features. Moreover, excretion fraction was also associated with salivary gland biopsy. SS diagnostic discrimination of excretion fraction is not superior to that obtained by qualitative visual analysis. Both qualitative and quantitative scintigraphy methods are associated with SS clinical and laboratory characteristics.

Clinical usefulness of anti-muscarinic type 3 receptor autoantibodies in patients with primary Sjögren's syndrome

To elucidate the clinical values of anti-M3R in Sjögren's syndrome (SS) in the largest cohort for an anti-M3R study. The plasma of 361 subjects (156 primary SS [pSS], 62 non-SS-sicca [SICCA], 40 systemic lupus erythematosus [SLE], 50 rheumatoid arthritis [RA], and 53 healthy controls [HC]) was screened using our modified On-Cell-Western assay. Saliva from pSS (n=37) compared to SICCA (n=26) was also analysed. The sensitivity and specificity of anti-M3R and its association with comprehensive clinical and laboratory features were determined. Plasma-anti-M3R was higher in pSS compared to other groups, differentiating pSS with good-to-excellent diagnostic power with a specificity of 85% and a sensitivity between 75% and 98%. pSS plasma-anti-M3R was positively correlated with ocular staining scores, anti-Ro/SSA, IgG, β2-microglobulin, ESR, and ESSDAI. It was negatively correlated with WBC, C4, and salivary scintigraphic indices. Saliva-anti-M3R was 3.59 times higher in pSS than in SICCA. Interestingly, the agreement between the 2002 American European Consensus Group criteria and the criteria substituted with plasma-anti-M3R for the lip biopsy reached 92%, with a significant kappa of 0.824. Anti-M3R enhances sensitivity and specificity for SS diagnosis, correlating with ocular dryness and glandular hypofunction, and the haematological/biological domains of the ESSDAI. Our findings also highlight the clinical significance of anti-M3R in SS diagnosis, especially where clinical assessments, such as lip biopsy, sialometry, or ocular evaluation, by multi-disciplinary specialists are limited.

Iguratimod treatment reduces disease activity in early primary Sjögren's syndrome: An open-label pilot study

Objectives To evaluate the efficacy and safety of iguratimod in patients with early primary Sjögren's syndrome (pSS). Methods Twenty-seven disease-modifying antirheumatic drug-naive female patients met the revised American-European Consensus Group criteria for pSS were enrolled in this open-label pilot study. Patients were treated with iguratimod 25 mg twice a day for 24 weeks. The disease activity was assessed with European League Against Rheumatism (EULAR) Sjögren's Syndrome Disease Activity Index (ESSDAI) and EULAR Sjögren's Syndrome Patient Reported Index (ESSPRI) at 12 and 24 weeks. Salivary and lacrimal gland function, laboratory, and subjective variables were also assessed. Generalized estimating equations were used to analyze parameters over time. Results ESSDAI (median, 5 versus 2 versus 2, p < .01), IgG (median, 26.6 versus 22.4 versus 21.4 g/L, p < .01) and rheumatoid factor (median, 119.9 versus 94.1 versus 83.8 lU/mL, p < .01) levels decreased significantly during iguratimod treatment. ESSPRI, salivary and lacrimal gland function, fatigue and health-related quality of life did not change during treatment. One patient experienced thrombocytopenia, and no other serious adverse effects were observed. Conclusion In this study, iguratimod treatment is safe and effective for improving disease activity and laboratory parameters in early pSS patients.

Orofacial Motor Functions and Temporomandibular Disorders in Patients With Sjögren's Syndrome

Sjögren's syndrome (SS) induces difficulty in chewing and swallowing due to low salivary flow. However, these symptoms may be associated with other factors, such as orofacial myofunctional disorders and temporomandibular disorder (TMD), which have not been comprehensively assessed in this population. The aims of this study were to investigate orofacial muscles and functions as well as the presence of TMD in patients with SS compared with a group without SS and to analyze whether the patients' experience of limitations in orofacial functioning is associated with the orofacial functional status and muscle pain related to TMD. Women with SS based on the 2002 American-European Consensus Group criteria and volunteers paired by age and sex were compared. The examinations included the orofacial myofunctional evaluation with scores (OMES) protocol, tongue and lip strength measures, and electromyography of the masticatory muscles. TMD investigations included clinical examination, self-report of symptoms, and assessment according to the Jaw Functional Limitation Scale. Patients with SS present with impaired muscle and orofacial functions based on lower scores of all categories of OMES (P < 0.0001), tongue strength (P = 0.0003-0.0004), and masticatory muscle activity (P = 0.0002-0.007), as well as worse TMD signs and symptoms (P < 0.05) and jaw functional limitation (P < 0.0001-0.0003). Patients' experiences with limitation in mastication and swallowing were associated with orofacial myofunctional status and muscle pain related to TMD. Those disorders should be monitored along with disease control and must be addressed in the clinical evaluation to prevent nutritional and metabolic comorbidities in patients with SS.

Prevalence of Sj\xf6gren\u2019s syndrome in the general adult population in Spain: estimating the proportion of undiagnosed cases

To estimate the prevalence of Sjögren’s syndrome (SS) in the adult Spanish population we performed a population-based multicenter cross-sectional study. Cases were defined by the American-European Consensus Group criteria proposed in 2002. A total of 4,916 subjects aged 20 years or over were included. The estimated prevalence of SS (including primary and secondary forms) in the adult population in Spain was 0.33% (95% CI 0.21–0.53). Extrapolating to the total population of the country aged ≥ 20 years (around 37.7 million persons), there would be around 125,000 cases of SS in Spain. Considering only primary SS, the estimated prevalence was 0.25% (95% CI 0.15–0.43) or 1 person in 400. The prevalence of primary SS in Spain is comparable to that reported in other European studies with a similar design and diagnostic criteria. Based on these results, primary SS could not be considered a rare (orphan) disease. Only 50% of cases had already been diagnosed with SS prior EPISER 2016 study, confirming the existence of a non-negligible proportion of undiagnosed cases in the general population.

OP0302 IANALUMAB (VAY736), A DUAL MODE OF ACTION BIOLOGIC COMBINING BAFF RECEPTOR INHIBITION WITH B CELL DEPLETION, REACHES PRIMARY ENDPOINT FOR TREATMENT OF PRIMARY SJOGREN’S SYNDROME

Background:Primary Sjogren’s syndrome (pSS) is a multi-organ autoimmune disease mainly affecting excretory glands and characterised by B-cell hyperactivity. No approved systemic treatment is available. Ianalumab (VAY736) is an anti-B-cell activating factor (BAFF) receptor fully human monoclonal antibody, engineered for direct ADCC-mediated B-cell depletion.Objectives:This phase 2b study aimed at establishing a dose-response relationship over a range of VAY736 doses, using change from baseline (BL) in EULAR Sjogren’s Syndrome Disease Activity index (ESSDAI) over 24 Weeks (Wks) as primary endpoint. The study is ongoing with a second blinded treatment period up to Wk52. Here we report efficacy and safety Wk24.Methods:190 patients (pts) were randomised 1:1:1:1 to receive monthly s.c. doses of VAY736 (5, 50, 300mg) or placebo (PBO). Prior to 1st-dose of study treatment, pts received methylprednisolone i.v. 250mg. Eligible pts fulfilled American European Consensus Group (AECG) criteria, were anti-Ro/SSA+, had ESSDAI ≥6 and EULAR Sjogren’s Syndrome Patient Reported Index (ESSPRI) ≥5. Statistical methods included MCP-Mod to assess dose-response on change of ESSDAI from BL and responder rate analysis to calculate the proportion of pts with ≥3 points improvement on ESSDAI. Secondary endpoints included ESSPRI, Functional Assessment of Chronic Illness Therapy Fatigue (FACIT-F), Physician’s (PhGA) and Patient’s Global Assessments (PaGA), SF-36, stimulated salivary flow (sSF), Schirmer’s test.Results:Primary endpoint was met with statistically significant dose-response for ESSDAI (Figure). The largest ESSDAI reduction was 1.92 points over PBO for VAY736 300mg at Wk24. Responder rate analysis on ESSDAI revealed for 300mg vs PBO responder rates of 42/47 (89.4%) vs 30/49 (61.2%), a difference of 28.1% (p=0.0019). No differences were seen for 5mg and 50mg vs PBO. PhGA change from BL was significantly different between 300mg and PBO (p=0.022). A numerical trend for sSF improvement for VAY736 300mg compared to PBO was notable at Wk24 (p=0.092). For secondary endpoints ESSPRI and FACIT-F, VAY736 treatment showed no benefits over PBO. PBO responses were generally high. Incidence of treatment emergent AEs was comparable across all studied groups, whereby site injection reactions were most frequent, mostly mild and showed a dose-response.Conclusion:Primary endpoint assessing ESSDAI was met, showing statistically significant dose-response for ianalumab with clinically important improvement for 300mg vs PBO. Preliminary safety profile of ianalumab was good.Figure.ESSDAI Change from Baseline over Time up to Week 24 Reveals a Statistically Significant Dose Response RelationshipDisclosure of Interests:Thomas Dörner Grant/research support from: Janssen, Novartis, Roche, UCB, Consultant of: Abbvie, Celgene, Eli Lilly, Roche, Janssen, EMD, Speakers bureau: Eli Lilly, Roche, Samsung, Janssen, Simon J. Bowman Consultant of: Astrazeneca, Biogen, BMS, Celgene, Medimmune, MTPharma, Novartis, Ono, UCB, xtlbio, Glapagos, Speakers bureau: Novartis, Robert Fox Consultant of: Novartis, Pfizer and Lilly, Xavier Mariette Consultant of: BMS, Gilead, Medimmune, Novartis, Pfizer, Servier, UCB, Athena Papas Grant/research support from: Novartis, Consultant of: Novartis, Thomas Grader-Beck Grant/research support from: Abbvie, Celgene, Consultant of: Novartis, Lilly, Ben A Fisher Consultant of: Novartis, Roche, BMS and Servier, Filipe Barcelos Consultant of: Pfizer and Lilly, Salvatore De Vita Consultant of: Roche, Human Genome Science, Glaxo Smith Kline and Novartis, Hendrik Schulze-Koops Grant/research support from: Pfizer Inc, Robert J Moots: None declared, Guido Junge Shareholder of: Novartis, Employee of: Novartis, Janice Woznicki Shareholder of: Novartis, Employee of: Novartis, Monika Sopala Shareholder of: Novartis, Employee of: Novartis, Wen-Lin Luo Shareholder of: Novartis, Employee of: Novartis, Wolfgang Hueber Shareholder of: Novartis, Employee of: Novartis

A regulatory role for CD72 expression on B cells and increased soluble CD72 in primary Sjogren\u2019s syndrome

BackgroundCD72, a co-receptor of B cell receptor (BCR), has been reported to have both positive and negative effects on B cell functions in several immunological diseases. The B cell plays an important role in the pathogenesis of primary Sjogren’s syndrome (pSS). However, whether CD72 is involved in the process remains unknown. This study aimed to observe the possible role of CD72 in the pathogenesis of pSS.ResultsA total of 60 cases who fulfilled the American-European Consensus Group (AECG) criteria for the diagnosis of pSS and 61 gender and age-matched healthy controls were recruited in this study. The percentage of CD72+ B cells was 85.31 ± 8.37% in pSS patients and 76.91 ± 8.50% in healthy controls(p < 0.001). The percentage of CD72+ B cells was correlated to serum IgG levels in patients [β = 0.018(0.001–0.036), p = 0.034]. The level of serum soluble CD72 was significantly higher in pSS patients than the one in healthy controls (0.41 (0.29) vs 0.07 (0.08) ng/mL, p < 0.001).ConclusionsThe percentage of CD72+ B cells was upregulated in pSS patients and was correlated to the serum IgG level, which revealed the hyperactivity of B cells in this disease. The serum soluble CD72 level was also increased in pSS patients. These results indicated a potential role of CD72 in the pathogenesis of pSS.

Analysis of ocular surface damage and visual impact in patients with primary and secondary Sjögren syndrome

The objective of this study is to review the ocular surface changes and complications of patients with Sjögren syndrome and assess their visual impact. A retrospective, cross-sectional, observational, and descriptive study of patients with Sjögren syndrome diagnosed according to the American-European Consensus Group criteria was designed. Data including age, gender, the reason for consultation, associated systemic disease, visual acuity, and ocular complications were recorded. Dry eye tests including tear meniscus thickness; tear film break-up time; ocular surface staining (fluorescein and lissamine green); and Schirmer I test were performed. A total of 249 patients, 233 women (93.6%) and 16 men (6.4%) were studied. Meibomian gland dysfunction was found in 46% (n = 229 eyes) patients; shortened tear film break-up time in 44% (n = 220 eyes); decreased tear meniscus in 49% (n = 243 eyes); significant superficial punctate keratopathy in 49% (n = 242 eyes); a mean ocular surface staining score of 5.92 points; and a low score for Schirmer I test (mean = 5.4mm). Eyes with a 4 + corneal fluorescein score showed the worst BCVA (mean = 0.63 ± 0.66 LogMAR, ≤ 20/80 Snellen eq., 95% CI 0.29-0.97), compared to 1 + to 3 + scores (mean = 0.211 ± 0.37 LogMAR, 20/32 Snellen eq., 95% CI 0.53-1.15). Ten eyes (4.0%) presented central corneal ulceration with a mean visual acuity of 20/500 (96% visual loss). Ocular surface alterations related to severe dry eye and complications from Sjögren syndrome may have a significant impact on visual acuity. Secondary Sjögren syndrome to rheumatoid arthritis had the worse dry eye prognosis, visual outcome, and ocular complications.

P135 Sjögren's syndrome: a retrospective service evaluation of diagnosis and management in paediatric patients

Abstract Background Sjögren's syndrome is an inflammatory disorder involving the exocrine glands, characterised by dry eyes and mucosal surfaces, fatigue and arthralgia. Sjögren's may occur in isolation (primary) or secondary to another autoimmune condition and is considered rare in the paediatric population (incidence and prevalence unknown). Anecdotal reports of differences in clinical presentation and absence of validated paediatric classification criteria render reliable diagnosis challenging and optimal treatment pathways difficult to ascertain. The American-European Consensus Group (AECG) criteria are considered gold standard for diagnosis of primary Sjogren’s syndrome in adults. A 2017 BSR Sjögren's guideline recommends treating children according to the adult pathway. We report a multicentre service evaluation exploring the presentation and management of children with Sjögren's presenting to UK paediatric rheumatology services, with reference to existing adult criteria. Methods Retrospective study conducted using a standardised data collection proforma under local service evaluation permissions. Inclusion criteria: pre-existing diagnosis of either primary or secondary Sjögren's syndrome under 16 years of age. Each case was assessed against the current adult criteria and guidance (AECG and BSR). Results 20 patients (16 female) in eight UK centres with a mean age at diagnosis of 11 (range 2-16 years). 15 patients had primary Sjögren's, 3 secondary Sjögren's and 2 were not categorised. No primary Sjögren's patients fulfilled AECG diagnostic criteria. Dry eye symptoms were present in 13%, dry mouth symptoms in 53% and 14/15 patients were tested for anti Ro/La (100% anti-Ro positive, 43% anti-La positive). Objective ocular dryness (Schirmers or van Bijsterveld positive), objective oral dryness and labial gland focus score were not formally assessed in any patients. No primary Sjögren's patients fulfilled ACR EULAR diagnostic criteria and one patient fitted exclusion criteria. The most common primary Sjögren's symptoms included parotid pain or swelling (73%), dry mouth (53%), arthralgia (47%) and fatigue (40%). Rash and headaches were also described whereas fever and lymphadenopathy were not reported. Sicca symptoms were reported in 100% secondary Sjogren’s patients (66% had parotid pain or swelling.) Management of all patients was assessed against 2017 BSR guidelines. There was documented evidence in 75% of receiving education, diet and lifestyle advice. 50% were prescribed moisturising eye drops. Hydroxychloroquine treatment was considered in 75%; of these, 4% were not referred for annual eye screening. Conclusion Sjögren's syndrome is rare in children and specific paediatric guidance does not exist. Despite extensive investigations no primary Sjögren's patients fulfilled the AECG or ACR EULAR diagnostic criteria due to difficulty in obtaining objective evidence of oral or ocular dryness. These data suggest that primary paediatric presentations may differ from adult cohorts with frequent parotid pain or swelling and less self-reporting of sicca symptoms. Further work is needed to support development of paediatric specific guidelines for Sjögren's syndrome. Disclosures R. Close None. A. Lant None. E. Smith None. C.M. Anderson None. S. Deepak None. R. Foster None. K. Haslam None. L. Bray None. P. Dawson None. C. Bhat None. F. McErlane None.