Extraglandular Manifestations Research Articles

Glandular involvement in primary Sjögren's syndrome patients with interstitial lung disease-onset and sicca-onset, a single centre cross-sectional study.

Primary Sjögren's syndrome (pSS) is an autoimmune exocrinopathy classically presenting with sicca symptoms. Nonetheless, disease onset with extraglandular manifestations, including interstitial lung disease (ILD), is increasingly reported. However, studies investigating pSS patients presenting with ILD (pSS-ILD) are limited.Aim of this study was to better characterise the phenotype of pSS patients presenting with ILD in comparison to pSS patients with classicsicca-onset. We especially investigated whether the two groups differed in glandular involvement comparing functional, imaging andhistologic findings, as well as patient reported outcome (PRO). Consecutive newly diagnosed pSS patients, all fulfilling the ACR/EULAR 2016 criteria, were included in this cross-sectional study from September 2016 to October 2021. Presence of ILD at pSS diagnosis was defined based on clinical findings, imaging assessment and pulmonary function tests (PFT). In addition to functional tests, a minor salivary gland biopsy was performed in all cases, recording number of foci, focus score (FS) and GC-like structures. Salivary glands ultrasonography (SGUS) was graded using the OMERACT semiquantitative scoring system (0-3) based on parenchyma inhomogeneity. PRO including ESSPRI, OHIP and OSSDI were collected.Extraglandular clinical features and biological abnormalities included in the ESSDAI were recorded. Data were expressed as mean±SD for continuous variables and as absolute frequencies and percentages for categorical variables. Chi-Square test and Mann-Whitney U-test and ANOVA were performed for comparisons of categorical variables and continuous variables, respectively. We included 178 newly diagnosed pSS patients (F:M=158:20). ILD was the first pSS manifestation in 11 (6%) cases, 8 F and 3 M, with a median time from ILD onset to pSS diagnosis of 2 years (25-75 IQ 1-4.5). Of the 11 pSS-ILD patients, HRCT pattern was defined as NSIP in 4, UIP in 4, NSIP+OP in 2 and LIP in 1 patient. Dyspnoea on exertion or chronic cough were reported by 7/11 (63.6%) patients.In comparison to sicca-onset patients, pSS-ILD patients presented an older age at diagnosis (55±13 vs. 70±7, p= 0.001) and a higher ESSDAI (3.9±4.7 vs. 12.3±4.3, p=0.001), driven by the pulmonary domain. Regarding glandular involvement, pSS-ILD patients reported milder xeropthalmia (VAS 5.8±3.1 vs. 2.8±3.5, p=0.002) and significative lower scores in OSDI (35.6±24.9 vs. 15.3±22.9, p=0.04) and OHIP (4.8±4.4 vs. 1.4±3.8, p=0.04), despite no significant differences observed between the two groups in ocular tests and unstimulated salivary flow rate. With respect to histology, no significant differences were found in number of foci, FS and GC-like structures. We observed a significantly different distribution of the SGUS OMERACT score in the two groups: none of pSS-ILD patients presented a SGUS OMERACT score ≥2 in the submandibular glands (SG), in contrast to 41/132 (31.1%) of the patients in the classical sicca-onset group (p=0.03). Finally, no significant differences were observed between the two groups with respect to non-pulmonary extraglandular manifestations, serologic features and other biological parameters. ILD-onset pSS patients represent an atypical phenotypic subset, with less pronounced sialadenitis structural changes in salivary glands, and with sicca symptoms probably overshadowed by the respiratory disease.

Effect of lymphotoxin blockage on different stages of Sjogren's syndrome in an animal model

AbstractBackgroundLymphotoxin (LT) is an important mediator in Sjogren's syndrome (SS), both in patients and in animal models. Deletion of the LT alpha gene prevented the development of disease manifestations in the interelukin alpha transgenic mouse (IL14αTG) mouse model of SS.AimsThe current study was designed to evaluate the use of LT inhibitors at different stages of the disease in IL14αTG mice.Materials and MethodsIL14αTG mice were treated with anti‐LTa monoclonal antibody, LTb receptor‐immunoglobulin fusion protein (LTBR‐Ig) or isotype control during different stages of disease and analysis of salivary gland function, immunoglobulins, autoantibodies and histology of internal organs performed.Results and DiscussionThe inhibitors were very effective in maintaining salivary gland function and preventing infiltration of the glands with lymphocytes when used in the early stages of the disease. Blocking LT at later stages of the disease did not recover salivary gland function but was still effective in limiting extra glandular manifestations including eye disease and tumor development. Some differences were noted in the effectiveness of anti‐LTα versus LTBR‐Ig in limiting particular disease manifestations.ConclusionLT inhibitors deserve further investigation in the management of SS at whatever stage is identified.

Recommendations for evaluation and diagnosis of extra-glandular manifestations of primary sjogren syndrome: results of an epidemiologic systematic review/meta-analysis and a consensus guideline from the Brazilian Society of Rheumatology (articular, pulmonary and renal)

Sjogren's Syndrome (SS) is an autoimmune disease characterized by lymphocytic infiltration of the exocrine glands and other organs, associated with sicca syndrome but also with systemic involvement with varying degrees of severity. Despite their importance, these systemic manifestations are not routinely evaluated and there is no homogenous approach to their diagnosis or evaluation. To close this gap, a panel of experts from the Brazilian Society of Rheumatology conducted a systematic review and meta-analysis on the identification of epidemiologic and clinical features of these manifestations and made recommendations based on the findings. Agreement between the experts was achieved using the Delphi method. The first part of this guideline summarizes the most important topics, and 11 recommendations are provided for the articular, pulmonary, and renal care of SS patients.

Distal renal tubular acidosis and nephrocalcinosis as initial manifestation of primary sjögren's syndrome.

There is a well-established association between primary Sjögren's syndrome and distal renal tubular acidosis (dRTA). dRTA is a relatively infrequent manifestation of primary Sjögren's syndrome which can present with life-threatening electrolyte abnormalities while, in some patients, it could be the first manifestation of the syndrome. We report the case of a 35-year-old woman who presented with unexplained episodes of generalized weakness, severe hypokalemia, nephrocalcinosis, and normal anion gap metabolic acidosis. Subsequent evaluation revealed primary Sjögren's syndrome as her underlying condition. The patient responded well to potassium supplementation, sodium bicarbonate, and oral prednisolone. After four years of follow-up, there were no other extraglandular manifestations, the renal function remained stable and the acidosis was partially improved without the need for oral bicarbonate. This case demonstrates that dRTA could be the initial manifestation of primary Sjögren's syndrome and highlights the necessity for increased vigilance for patients presenting with persistent hypokalemia or nephrocalcinosis so that an early diagnosis can be made allowing for better control and prevention of disease progression.

The TLR7 agonist imiquimod mediates immune activation in primary Sjögren’s syndrome

Abstract Primary Sjögren’s syndrome (pSS) is a systemic autoimmune disease characterized by chronic inflammation of exocrine tissue, resulting in loss of tears and saliva. Patients also experience many extra-glandular disease manifestations. Treatment for pSS is palliative, and there are currently no treatments available that target disease etiology. Previous studies in our lab demonstrate that Myd88 is crucial for pSS pathogenesis in the NOD.B10Sn-H2b (NOD.B10) pSS mouse model, although the way in which Myd88-dependent pathways become activated in disease remains unknown. Based on its importance in other autoimmune diseases, we hypothesized that TLR7 activation accelerates pSS pathogenesis. We administered the TLR7 agonist Imiquimod (Imq) to pre-disease NOD.B10 females 3 times a week for 6 weeks (n = 8). Parallel experiments were performed in which age and sex-matched controls received a base cream lacking Imq (n = 9). Saliva was collected following pilocarpine injection before and after treatment. Animals were euthanized, spleens and cervical lymph nodes (cLNs) harvested, and flow cytometry was performed. Imq-treated animals exhibited lymphadenopathy, splenomegaly, and decreased salivary flow. Both cLNs and splenocytes from Imq-treated animals demonstrated an increase in the percentage of activated/memory T cells (CD4+, CD44+, CD62L−) and TLR7 expressing B cells (B220+, CD69+, TLR7+). The percentage of B and CD4+ T cells expressing TLR7 was increased in spleen and cLNs following Imq administration. Aged-associated B cells (ABCs) (B220+, CD23−, CD21−, T-bet+ ) were also expanded in the spleens of Imq-treated mice. In summary, activation of TLR7 mediates adaptive immune activation and promotes expansion of the ABC subset in pSS. Supported by NIH/NIDCR R01DE29472

Atteintes articulaires dans le syndrome de Sjögren primitif

Joint involvement is one of the most common extra-glandular manifestations in primary Sjögren's syndrome (pSS), affecting almost half of the patients with clinical arthritis in 16 %. Most commonly, these are symmetrical arthritis, affecting fewer than 5 joints. Ultrasound shows grade 1 or 2 synovitis, with a positive doppler signal in less than a fourth of cases, and tenosynovitis, mostly of the finger flexors. Radiographs should not show erosion. In presence of erosions on ultrasound or MRI, which may be found on MCP and wrists, RA with secondary SS should be excluded. Five to 10 % of patients with SSp have anti-CCP antibodies. The presence of anti-CCP antibodies does not necessarily exclude the diagnosis of SSp, but it should alert to the risk of further development of RA, therefore requiring radiographic follow-up even if the pSS has been evolving for many years. Joint involvement has a good prognosis and appears to be a predictor of a favourable clinical course. Treatment should be guided by the level of clinical activity and should be based on NSAIDs or corticosteroids ±hydroxychloroquine. Synthetic disease-modifying anti-rheumatic drugs should be offered for corticosteroid sparing.

Beyond Systemic Lupus Erythematosus and Anti-Phospholipid Syndrome: The Relevance of Complement From Pathogenesis to Pregnancy Outcome in Other Systemic Rheumatologic Diseases.

Evidence about the relevance of the complement system, a highly conserved constituent of the innate immunity response that orchestrates the elimination of pathogens and the inflammatory processes, has been recently accumulated in many different rheumatologic conditions. In rheumatoid arthritis, complement, mainly the classical pathway, contributes to tissue damage especially in seropositive subjects, with complement activation occurring in the joint. Data about complement pathways in psoriatic arthritis are dated and poorly consistent; among patients with Sjögren syndrome, hypocomplementemia exerts a prognostic role, identifying patients at risk of extra-glandular manifestations. Hints about complement involvement in systemic sclerosis have been recently raised, following the evidence of complement deposition in affected skin and in renal samples from patients with scleroderma renal crisis. In vasculitides, complement plays a dual role: on one hand, stimulation of neutrophils with anti-neutrophil cytoplasmic antibodies (ANCA) results in the activation of the alternative pathway, on the other, C5a induces translocation of ANCA antigens, favouring the detrimental role of antibodies. Complement deposition in the kidneys identifies patients with more aggressive renal disease; patients with active disease display low serum levels of C3 and C4. Even though in dermatomyositis sC5b-9 deposits are invariably present in affected muscles, data on C3 and C4 fluctuation during disease course are scarce. C3 and C1q serum levels have been explored as potential markers of disease activity in Takayasu arteritis, whereas data in Behçet disease are limited to in vitro observations. Pregnancies in women with rheumatologic conditions are still burdened by a higher rate of pregnancy complications, thus the early identification of women at risk would be invaluable. A fine-tuning of complement activation is required from a physiological progression of pregnancy, from pre-implantation stages, through placentation to labour. Complement deregulation has been implicated in several pregnancy complications, such as recurrent abortion, eclampsia and premature birth; low complement levels have been shown to reliably identify women at risk of complications. Given its physiologic role in orchestrating pregnancy progression and its involvement as pathogenic effector in several rheumatologic conditions, complement system is an attractive candidate biomarker to stratify the obstetric risk among women with rheumatologic conditions.

Discordant Predictions of Extraglandular Involvement in Primary Sjögren's Syndrome According to the Anti-SSA/Ro60 Antibodies Detection Assay in a Cohort Study.

Electrophoresis-derived techniques for anti-SSA/Ro60 KDa (anti-SSA) antibodies detection have been progressively replaced by methods using non-native antigens. We aimed to compare the patients’ phenotypes and the occurrence of extraglandular manifestations in primary Sjögren’s syndrome according to the method used to detect anti-SSA antibodies. Sera from patients with a diagnosis of pSS according to ACR/EULAR 2016 criteria between 2008 and 2017 were tested for anti-SSA antibodies using methods with non-native antigens (magnetic bead multiplex assay; line immunoassays) and one with native antigens (counterimmunoelectrophoresis (CIE)). The population was split into three groups according to anti-SSA antibodies status: absence (SSA−), presence in any method except for CIE (SSA+CIE−), and presence in CIE (SSA+CIE+). The patients in the SSA+CIE+ group (n = 70, 42.7%) were ten years younger and presented more immunological activity compared with both the SSA− (n = 80, 48.8%) and SSA+CIE− groups (n = 14, 8.5%). The SSA− and SSA+CIE− groups were poorly distinct. The presence of anti-SSA antibodies solely in CIE was significantly associated with the occurrence of extraglandular manifestations of pSS (HR = 4.45 (2.35–8.42)). Contrary to CIE, methods using non-native antigens to detect anti-SSA antibodies were unable to predict the occurrence of systemic expression of pSS.

Multimodal Assessment and Characterization of Sicca Syndrome.

Background: Sicca syndrome represents a heterogeneous group of conditions, such as Sjögren syndrome, causing xerophthalmiaand xerostomia. This study characterizes in depth patients with Sicca syndrome and evaluates salivary gland ultrasound (SGUS).Methods: Principal component analysis and hierarchical clustering of clinical parameters, such as ESSPRI, ESSDAI and laboratory data, were performed on all referrals for assessment of Sicca symptoms between October 2018 and March 2021. SGUS and labial gland biopsies were compared across groups.Results: A total of 583 patients were assessed. Objective dryness was confirmed in 73% of the patients. Cluster analysis identified 3 groups with post-hoc analysis confirming distinct phenotypes: Somatic Group (283/583; 49%) with more frequent symptoms but limited objective dryness; Dry Without Autoimmune Features (DAFneg, 206/584; 35%), and Dry With Autoimmune Features (DAFpos, 94/584;16%). DAFpos patients had highest autoantibody titers (anti-SSA(Ro) 240 vs. 3.6 vs. 3.8; p < 0.001), most extra-glandular manifestations (p < 0.001), and highest median SGUS Score (DAFpos: 8 [IQR 4–10] vs. SG: 2 [1–4] vs. DAFneg 4 [2–5]; p < 0.001). No tangible correlation with primary Sjögren syndrome criteria was observed.Discussion: SGUS score correlated with a subset of patients with Sjögren syndrome, identified in the DAFpos cluster. This study highlights heterogeneity within sicca and, indeed, Sjögren syndrome, highlighting the need for further studies.

P046 A review and retrospective case series of paediatric Sjögren’s syndrome from Southern Africa

Abstract Background Paediatric Sjögren’s syndrome (pSS) is an uncommon autoimmune paediatric disease, rarely reported in children in Africa. It remains an important consideration in a child with parotid swelling. Here, we present a retrospective case-series of four patients from a paediatric rheumatology clinic in South Africa and discuss some of the difficulties of diagnosis in our context. Methods We performed a retrospective analysis of patients who attend the Red Cross War Memorial Hospital Paediatric Rheumatology clinic between 2010 and 2019. Result The four patients diagnosed with Sjögren’s all had varied presentations and disease courses. There were 3 females and 1 male and the ages at diagnosis ranged from 6 to 19 years old. The time to diagnosis was prolonged and ranged from 1 month to 10 years. Two patients with primary pSS presented with extra-articular manifestations of arthritis, abdominal pain and fatigue, followed by dry mouth, dry eyes, parotid swelling and and suggestive histopathology. The remaining 2 patients had a secondary pSS due to juvenile onset SLE and tuberculosis respectively. Conclusion In less resourced settings the diagnosis of pSS is often delayed. Both patients with primary pSS had preceding extra-glandular manifestations. In less resourced settings, infectious diseases may present as pSS and associated rheumatic diseases causing secondary pSS must be considered.

ПОРАЖЕНИЕ ПОЧЕК ПРИ ПЕРВИЧНОМ СИНДРОМЕ ШЕГРЕНА (КЛИНИЧЕСКИЙ СЛУЧАЙ)

This article presents a clinical case of primary Sjogren's syndrome with a detailed description of the clinical and laboratory dynamics of the disease and its extraglandular manifestations based on the analysis of the data obtained during the patient's hospitalizations in the rheumatology department of the Grodno University Clinic in the period from March 2018 to June 2021.

Correlation of peripheral CD4+GranzB+CTLs with disease severity in patients with primary Sj\xf6gren\u2019s syndrome

IntroductionPrimary Sjögren’s syndrome (pSS) is a chronic systemic autoimmune disease which has focal lymphocytic infiltration including a majority of CD4+ T cells. This study was to investigate the correlation of peripheral granzyme B (GranzB)-expressing CD4+ T cells with disease severity and histological lesion in patients with pSS.MethodsWe recruited 116 pSS and 46 health control (HC) using flow cytometry to examine the percentage of CD4+GranzB+CTLs in the peripheral blood, and immunofluorescence to test their expression in the labial gland.ResultsThe percentage of CD4+GranzB+CTLs was significantly upregulated in pSS than in HC (7.1 ± 4.9% vs 3.1 ± 1.9%, p < 0.0001) and positive correlation with ESSDAI. The frequency of them was markedly higher in pSS with extraglandular manifestations. After excluding the other risk factors associated with pSS, they were still related to ESSDIA and extraglandular manifestations independently (p < 0.05), and they are the risk factor of extraglandular involvement (odds ratio = 1.928). Moreover, they could be observed in the LSGs. ROC curve analysis indicated that the area under the curve (AUC) of CD4+GranzB+CTLs was 0.796 to predict the activity of pSS and 0.851 to presume extraglandular manifestations. The best diagnostic cutoff point was 4.865 for pSS patients.ConclusionIn this study, we provide new evidence indicating the involvement of CD4+GranzB+CTLs over activation in the pathophysiology of pSS, which may serve as a new biomarker to evaluate the activity and severity of pSS.

Serum interferon-α2 measured by single-molecule array associates with systemic disease manifestations in Sjögren's syndrome.

ObjectivesType I IFN (IFN-I) activation is a prominent feature of primary SS (pSS), SLE and SSc. Ultrasensitive single-molecule array (Simoa) technology has facilitated the measurement of subfemtomolar concentrations of IFNs. Here we aimed to measure IFN-α2 in serum from pSS, SLE and SSc using a Simoa immunoassay and correlate these levels to blood IFN-stimulated gene (ISG) expression and disease activity.MethodsSerum IFN-α2 was measured in patients with pSS (n = 85 and n = 110), SLE (n = 24) and SSc (n = 23) and healthy controls (HCs; n = 68) using an IFN-α Simoa assay on an HD-X analyser. IFN-I pathway activation was additionally determined from serum by an IFN-I reporter assay and paired samples of whole blood ISG expression of IFI44, IFI44L, IFIT1, IFIT3 and MxA by RT-PCR or myxovirus resistance protein 1 (MxA) protein ELISA.ResultsSerum IFN-α2 levels were elevated in pSS (median 61.3 fg/ml) compared with HCs (median ≤5 fg/ml, P < 0.001) and SSc (median 11.6 fg/ml, P = 0.043), lower compared with SLE (median 313.5 fg/ml, P = 0.068) and positively correlated with blood ISG expression (r = 0.66–0.94, P < 0.001). Comparable to MxA ELISA [area under the curve (AUC) 0.93], IFN-α2 measurement using Simoa identified pSS with high ISG expression (AUC 0.90) with 80–93% specificity and 71–84% sensitivity. Blinded validation in an independent pSS cohort yielded a comparable accuracy. Multiple regression indicated independent associations of autoantibodies, IgG, HCQ treatment, cutaneous disease and a history of extraglandular manifestations with serum IFN-α2 concentrations in pSS.ConclusionSimoa serum IFN-α2 reflects blood ISG expression in pSS, SLE and SSc. In light of IFN-targeting treatments, Simoa could potentially be applied for patient stratification or retrospective analysis of historical cohorts.

Hypokalemic Paralysis Leading to Respiratory Failure: An Unusual Presentation of Sjogren’s Syndrome

Sjogren’s Syndrome (SS) is a chronic multisystemic autoimmune inflammatory disorder with predominant exocrine gland involvement resulting in dryness of the eyes and mouth. Among extra glandular manifestations, renal involvement is commonly seen, which can be in the form of Renal Tubular Acidosis (RTA). SS may at times present as mild hypokalaemia with distal RTA but severe hypokalemia resulting in respiratory failure is rare. Here we report a case of twenty-five-year-old female presenting in emergency room with flaccid quadriparesis and hypercapnic respiratory failure. Further evaluation revealed hypokalemia (Potassium (K+) 1.6mmol/L) with distal renal tubular acidosis along with a background of primary Sjogren’s Syndrome. We illustrate that the possibility of Sjogren’s Syndrome should be considered in a young female who present with rapidly progressive weakness, hypokalemia and distal renal tubular acidosis with respiratory failure.

Sicca syndrome associated with immune checkpoint inhibitor therapy.

Cancer immunotherapy, which seeks to stimulate a patient's own immune system to combat cancer, is quickly becoming a central pillar of cancer therapeutics and has resulted in the development of many novel anticancer therapies. One subtype of cancer immunotherapy, immune checkpoint inhibitors (ICIs), has revolutionized cancer treatment and changed the standard of care for multiple indications. However, the advent of ICIs has produced a wide variety of inflammatory side effects termed immune-related adverse events (IRAEs), including ICI-induced Sicca syndrome. This article outlines the clinical features of ICI-induced Sicca syndrome and assesses its reported incidence in clinical trials, case series, and case reports across numerous cancers and treatment modalities. Presentations of ICI-induced Sicca syndrome in patients with pre-existing Sjӧgren's disease and with extra-glandular manifestations will also be explored. The pathophysiological mechanisms underlying IRAEs, including ICI-induced Sicca syndrome, will be evaluated through an examination of existing literature. Finally, the various treatment and management strategies as well as aims for future work will be discussed and reviewed.

Cardiac involvement in primary Sjӧgren's syndrome.

Primary Sjӧgren's syndrome (pSS) is an autoimmune-mediated, inflammatory, and systemic connective tissue disease (CTD), especially in middle-aged women, which often involves multiple systems and organs of the body. In fact, the heart is an important target organ in patients with pSS. In recent years, it has been confirmed that the morbidity of cardiac involvement has increased in patients with pSS, and cardiovascular disease (CVD) is one of the main causes of death. The increased risk of CVD in pSS patients is associated with a great variety of risk factors, such as age, gender, hypertension, diabetes mellitus, dyslipidemia, disease duration, extra-glandular manifestations, therapeutic drugs of pSS, and so on. Early recognition and effective treatment of CVD may play a crucial role in improving adverse cardiovascular prognosis. Whereas cardiac involvement is closely related to patient prognosis and survival, the cardiac involvement of patients with pSS remains poorly studied. Therefore, this article reviews the cardiovascular risk factors, clinical manifestations of cardiac involvement, cardiovascular biomarkers, and therapeutic strategies of pSS patients.

Treatment strategies for Sjögren's syndrome with childhood onset: a systematic review of the literature.

ObjectivesSS with childhood onset is a rare autoimmune disease characterized by heterogeneous presentation. The lack of validated classification criteria makes it challenging to diagnose. Evidence-based guidelines for treatment of juvenile SS are not available due to the rarity of disease and the paucity of research in this patient population. This systematic review aims to summarize and appraise the current literature focused on pharmacological strategies for management of SS with childhood onset.MethodsPubMed and MEDLINE/Scopus databases up to December 2020 were screened for suitable reports highlighting pharmacological treatment of SS with childhood onset using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2009 reporting checklist. Animal studies were excluded.ResultsA total of 43 studies (34 case reports, 8 mini case series and 1 pilot study) were eligible for analysis. The studies retrieved included girls in 88% (120/137) of cases and had very low confidence levels. HCQ was prescribed for parotid swelling, as well as in association with MTX and NSAIDs in patients with arthritis and arthralgia. Corticosteroids such as long courses of oral prednisone and i.v. methylprednisolone were commonly prescribed for children with severe disease presentations. Rituximab was mainly indicated for mucosa-associated lymphoid tissue lymphoma and renal and nervous system complications. Other conventional DMARDs were prescribed in selected cases with extraglandular manifestations.ConclusionVarious therapies are used for the management of juvenile SS and are prescribed based on expert clinician’s opinion. There are currently no good-quality studies that allow clinical recommendations for treatment of SS with childhood onset.

Primary Sjögren's Syndrome: A Retrospective Cohort Study of Burden of Illness in Sweden.

IntroductionPrimary Sjögren’s syndrome (pSS) is an autoimmune disease that affects salivary and lachrymal glands and is associated with complex extraglandular manifestations. This study investigates the clinical and economic burden and disease course of pSS in Sweden.MethodsThis retrospective cohort study utilizes data from Swedish national registries and consists of patients at least 18 years of age diagnosed in secondary care with pSS, and matched members of the Swedish general population. Healthcare resource utilization (HRU) and costs were compared. The clinical burden of pSS during follow-up was explored via year-on-year prevalence of and time-to-first extraglandular manifestation. Employment status and retirement rates were used to investigate the impact of pSS on productivity.ResultsA total of 8884 patients with pSS and 88,233 general population comparators were included. Patients with pSS had significantly higher rates of HRU and higher healthcare costs than matched comparators, including twice as many outpatient visits. Costs were highest in year 1 post index before reducing in years 2 and 3 and stabilizing thereafter. Almost two-thirds of patients received their index diagnosis during an outpatient visit, and < 30% of diagnoses were from rheumatology departments. Overall, 41% of patients experienced a healthcare encounter that included a relevant extraglandular manifestation code during follow-up. Patients with pSS had significantly higher odds of early retirement than the general population at 5 years post index.ConclusionsPatients with pSS experience a high clinical and economic disease burden in Sweden.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40744-021-00314-y.

POS0718 CLINICAL CHARACTERISTICS ASSOCIATED WITH GLANDULAR INVOLVEMENT EVALUATED BY SALIVARY GLAND ULTRASONOGRAPHY IN SJÖGREN’S SYNDROME

Background:Sjögren’s syndrome (SS) is a systemic autoimmune disease characterized by periductal lymphocytic infiltration of the salivary and lacrimal glands, which results in reduced secretory functions and oral and ocular dryness (1). In addition, patients often have extraglandular manifestations, such as interstitial pneumonia and interstitial nephritis, and the appearance of autoantibodies such as anti-Ro/SS-A and La/SS-B antibodies. Salivary gland ultrasonography (SGUS) is typically used to evaluate the findings of salivary glands; thus, we can evaluate the severity of salivary gland disorders due to SS using SGUS in real time (2).Objectives:To identify clinical indices, including disease activity, associated with glandular involvement evaluated using SGUS in patients with SS.Methods:We enrolled patients with SS (n=115) and non-SS sicca subjects (n=90) who visited Nagasaki University Hospital between 1995 and 2019. The patients’ SS classifications were based on the 2002 American–European Consensus Group (AECG) SS classification criteria (3). The non-SS sicca subjects exhibited sicca symptoms but did not fulfill the AECG SS classification criteria. SGUS and clinical indices such as age, sex, the focus score (FS), sicca symptoms, the Saxon test results, Schirmer’s test results, anti-SS-A/Ro antibody positivity, anti-SS-B/La antibody positivity, anti-centromere antibody (ACA) positivity, serum immunoglobulin G levels, and the clinical European League Against Rheumatism SS disease activity index were examined. The ultrasonography (US) score was calculated based on SGUS imaging (hypoechoic area, hyperechoic band, and irregular border) (4).Results:The US score was significantly higher in patients with SS than that in non-SS sicca subjects. In addition, we found significant correlations between the US score and FS in patients with SS. Multivariate analysis revealed the FS, Saxon test positivity, and ACA positivity as the variables independently associated with the US score in patients with SS. These results were the same in the primary SS patient group (n=96). Patients with ACA positivity had significantly higher US scores compared to those in patients with ACA negativity, whereas the FS was not significantly high. In addition, patients with ACA positivity had significantly greater positivity of hyperechoic bands than that in patients with ACA negativity.Conclusion:This study indicated that ACA positivity, which is not reflected in sialadenitis of SS, is associated with the US score in patients with SS. These results suggest that US findings of patients with ACA positivity might show specific changes in salivary glands, such as fibrosis, and not only sialadenitis (5).

Treatment of Sjögren's syndrome: current therapy and future directions.

SS is usually described as having severe fatigue, dryness, diffuse pain, glandular swelling, and various extraglandular (systemic) manifestations. Clinical trials have generally failed because the vast majority of enrolled patients had no extraglandular manifestations at the time of enrolment but suffered from fatigue, dryness and pain that did not significantly respond to the study medication. A number of hypotheses on the pathogenesis of pSS have been put forward, including disturbances of innate and adaptive immunity as well as abnormalities of the interface between immune disorders and the neuro-endocrine system related to lacrimal and secretory gland dysfunction. Thus, future therapies must be designed for improvement of the symptoms of dry eyes and dry mouth, extraglandular disease, and fatigue and cognitive deficits. Given the inadequacies and limitations of current treatment options, we suggest that innovative directions involving interactions with neuroscientists and neuropsychiatrists together or combined with new immune targeting may be hold promise for better treating pSS.