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Objective To characterize the systemic phenotype of primary Sjögren’s syndrome at diagnosis by analysing the EULAR-SS disease activity index (ESSDAI) scores. Methods The Sjögren Big Data Consortium is an international, multicentre registry based on worldwide data-sharing cooperative merging of pre-existing databases from leading centres in clinical research in Sjögren’s syndrome from the five continents. Results The cohort included 10 007 patients (9352 female, mean 53 years) with recorded ESSDAI scores available. At diagnosis, the mean total ESSDAI score was 6.1; 81.8% of patients had systemic activity (ESSDAI score ≥1). Males had a higher mean ESSDAI (8.1 vs 6.0, P 65 years, P Conclusion The systemic phenotype of primary Sjögren’s syndrome is strongly influenced by personal determinants such as age, gender, ethnicity and place of residence, which are key geoepidemiological players in driving the expression of systemic disease at diagnosis.

COVID-19 outbreak has quickly spread worldwide, causing a high pressure on the health-care system. In Italy, from March 8, 2020, all the deferrable clinical activities have been suspended to increase the health care offer for COVID-19 patients. The hospital organization has been modified also in order to assure non-COVID-19 patients assistance. The Scleroderma Unit of ASST Pini-CTO Hospital, in Milan, in the region mostly hit by SARS-CoV-2 in Italy, follows more than 600 patients affected by systemic sclerosis (SSc). Patients with SSc need a close follow-up with a regular screening of organ involvement and frequent intravenous treatments. All SSc patients have been educated about ministerial directives to limit COVID-19 spread. The organization of our Scleroderma Unit has been quickly rethought to assure SSc patients assistance in safety for them and for health-care workers during urgent visits or infusion therapies. Using electronic way of communication with frequent virtual contact and guarantying home deliveries of some therapies, we allowed a continuity of care also outside the Hospital.

Background In previous studies, we demonstrated that the NEMO score, i.e. the cumulative number of microhaemorrhages (MHEs) and microthromboses (MTs), observed in nailfold videocapillaroscopy was a good indicator of the steady state level of disease activity (DA) in patients with systemic sclerosis (SSc) when the European Scleroderma Study Group (EScSG) index was considered the gold standard. Aim of the study To verify whether the NEMO score could be (i) a valid tool to assess DA, even when the modified European Scleroderma Trials and Research (EUSTAR) index was considered to be the comparator, and (ii) a sensitive method to capture the DA overtime changes. Patients and methods The NEMO score and the EScSG and EUSTAR indices were contemporarily assessed at baseline (T0) and after a follow-up of 4–56 months (T1) in 98 patients with SSc. The differences (Δ) between the T1 and T0 values of the NEMO score and the EScSG and EUSTAR indices were calculated and compared to each other. Results NEMO score values were very closely correlated with the corresponding values of the EScSG and EUSTAR indices both at T0 and T1 observations (p p p Receiver operating characteristic (ROC) curve analysis showed the NEMO score had a good sensitivity and specificity in classifying patients with a predefined level of DA (scores ≥ 3.0 and ≥ 2.5 for the EScSG and EUSTAR indices, respectively, p Δ values of the NEMO score were significantly correlated with the corresponding values of both the EScSG and EUSTAR indices. Weighted Cohen’s k level of agreement between Δ values of the NEMO score and those of the EScSG and EUSTAR indices was moderate (0.55 and 0.59, respectively). Conclusions NEMO score proves to be a feasible, non-invasive, and valid tool to assess steady state levels and changes over time of DA in patients with SSc. Thus, it can represent an alternative or complementary method to measure this disease status entity in this disorder.

Backgrounds The organization of minor salivary glands (MSG) infiltrates, in patients with Sjögren’s syndrome (SS), associates with disease severity and progression. Aberrant regulation of lymphocyte autophagy is involved in autoimmunity, and in previous work, we provided the first evidence of upregulated autophagy in CD4+ T cells infiltrating SS MSG. The aim of this study was to further explore autophagy in SS infiltrating and circulating lymphocytes and to investigate its role in disease histopathological progression. Methods After collection of 20 SS MSG, the presence of lymphocyte aggregates (foci) and the formation of germinal center (GC)-like structures were observed by H&E and confirmed by immunohistochemistry. The expression of autophagy-related genes, Atg5 and MAP1LC3A, was detected by RT-PCR on microdissected salivary gland tissue and control tonsils. In MSG and tonsils, autophagic lymphocytes were identified by the detection of the autophagosome protein LC3B visualized as LC3 puncta staining by immunofluorescence. Peripheral blood autophagy was assessed by flow cytometry in SS and healthy controls (HC). Results Real-time PCR demonstrated higher expression in the autophagy genes Atg5 and MAP1LC3A in MSG GCs as compared to both small foci (p = 0.0075, p = 0.0002) and GCs from tonsils (p = 0.0001, p = 0.0037). In MSG, LC3 puncta staining was detectable on both CD3+ and CD20+ lymphocytes; in tonsils, LC3 puncta was almost undetectable on all lymphocytes. Compared to HC (n = 20), flow cytometry did not reveal any increase of autophagy in SS circulating lymphocytes (n = 30). Conclusions In SS MSG, lymphocytes’ autophagy is a feature of infiltrating T and B cells and is associated with histological severity. Interestingly, in MSG aberrant regulation of autophagy is detectable in GC-like structures possibly indicating its involvement in the development and persistence of the autoimmune process within the lesions.

Background: Frailty is a condition characterized by the reduction of the individual’s homeostatic reserves, leading to an increased vulnerability to stressors and an increased risk of unfavourable events. The aging of the population and the consequent need to implement new paradigms of care and assistance, have given this tool a growing interest in many medical disciplines1. In rheumatology, however, the interest is still limited2. The Frailty Index (FI), developed on an arithmetical model of deficit accumulation, is an accurate tool for assessing frailty, providing an estimate of the biological aging. Objectives: Creation of a FI to be used in clinical practice in patients with Sjogren’s syndrome (SS) and evaluation of the correlations with patient‘s age, duration of illness, activity and disease damage at baseline and in the following 5 years. Methods: The FI is composed by a checklist of non-predefined variables (deficits) constituted by symptoms, signs, diseases, disabilities, and laboratory findings. The deficits must meet these criteria: age-related; associated with negative outcomes; multidimensional (referring to different domains of the health status); present in at least 1%, but not more than 80% of the sample. To each variable is assigned the value of 0 (= no deficit) or 1 (= deficit). The FI is the ratio between deficits presented by the individual and the total number of deficits considered, thus providing a measure of frailty ranging between 0 (no frailty) and 1 (maximum of frailty)3. A FI was developed for patients with SS consisting of 43 items (17 comorbidities, 14 signs and symptoms, 5 disabilities and 7 laboratory findings). Statistical analysis was performed with Spearman’s test for correlation assessment, the Mann Whitney test for comparing non-parametric variables was used. Results: FI was administered to a first small group of 30 female consecutive patients recruited as outpatients at the clinic dedicated to SS. The average age was 57.2 yrs, mean age at diagnosis 52.7 yrs and average disease duration 4.7 yrs. At the time of completing the FI, the average disease activity (ESSDAI) was 3.4, the mean value of the damage (SjSDDI) 1.6 and the average score of FI equal to 0.21. A statistically significant correlation between FI and age has been reported (p = 0.017). No significant correlations between frailty and duration, activity and disease damage have been highlighted at the moment. Conclusion: For the first time a FI was developed for patients with SS consisting of 43 items. The data shows a relationship between age andFI. The correlation is statistically significant, similarly to what is reported in the literature for other conditions. This confirms that FI is indeed an objective marker of aging and even though the sample population is young (average age = 57.2 years), FI maintains its main properties. This tool can be used to assess the health status of patients, making it possible to identify those at greater risk of trajectories or unfavourable outcomes. It is currently being administered the FI to patients with SS whose clinical course will be evaluated in the next 5 years (complications, mortality, hospitalization, institutionalization and disability). References [1] Canevelli M, et al, Promoting the Assessment of Frailty in the Clinical Approach to Cognitive Disorders, Front. Aging Neurosc 2017 [2] Rockwood MR, et al, FI to Measure Health Status in People with SSc, J Rheum 2014 [3] Searle SD, et al, A standard procedure for creating a FI, BMC Geriatrics2008 Disclosure of Interests: None declared

Background: Autophagy is a lysosome mediated catabolic process that promotes cell survival during stress conditions. Aberrant regulation of autophagy is involved in the pathogenesis of a widening spectrum of autoimmune disorders: in particular, activation of autophagy pathway is implicated in aberrant survival of activated T cells. We recently demonstrated that autophagy is up-regulated in CD4+ T lymphocytes from patients with Sjogren’s Syndrome (SS) both in peripheral blood and tissue. Moreover, aberrant autophagy correlates with systemic disease activity. Little is known on the role of autophagy in B cells homeostasis in SS. Objectives: To investigate the activation of the autophagy pathway in lymphocytes infiltrating salivary gland in SS and peripheral blood from patients with SS. Methods: Frozen SS minor salivary glands (MSG) from 20 patients were sectioned and evaluated with immunohistochemistry (IHC) by staining for CD3+, CD20+, and CD21+. MSG sections, sequential to IHC, were stained by Cresyl Violet and microdissected (Laser Capture Microdissection) in order to isolate and collect small infiltrates, large CD21- infiltrates, and large CD21+ infiltrates (GC-like structures). Microdissected GC from frozen human tonsils were used as control. The expression of autophagy genes Atg5 and MAP1LC3II (expressed as 2^deltaCT normalized to GADPH) was determined by qPCR on microdissected tissue. For studies on peripheral blood, 19 SS patients and 11 healthy controls were enrolled, and autophagy, expressed as the ratio between Mean Fluorescence Intensity and the isotopic control (rMFI), was evaluated by Cyto-ID® Autophagy detection kit in T lymphocytes (CD4+ and CD8+) and B lymphocytes (CD19+) using a FACSCalibur cytometer. Results: Expression of the autophagy genes Atg5 and MAP1LC3 was significantly higher in the GCs from SS salivary glands compared to control tonsils (p Immunophenotyping studies revealed activation of the autophagy pathway in both circulating CD19+ and CD4+ lymphocytes from SS (p=0.04 and p=0.03 compared to HC); conversely, no pathway activation was detected in CD8+ cells. Of note, in patients with SS activation of autophagy was most marked in circulating CD19+ B cells compared the other subsets [(CD19+ vs CD4+ (p Conclusion: Our findings revealed that the autophagy pathway is aberrantly activated in lymphocytes infiltrating salivary glands of SS patients. Of note, progressively higher expression levels of autophagy genes mirrored the severity and extension of inflammatory infiltrates. Immunophenotyping studies revealed that activation of autophagy is preeminent in B cells. Thus, activation of autophagy emerges as a feature of both infiltrating and circulating SS lymphocytes, and as mechanism possibly implicated in the activation and survival o?f autoreactive cells. Disclosure of Interests: Serena Colafrancesco: None declared, Antonina Minniti: None declared, Roberta Priori: None declared, Marta Vomero: None declared, cristiana barbati: None declared, Francesca Arienzo: None declared, Valentina Iannizzotto: None declared, Elena Pipi: None declared, Joana Campos: None declared, Saba Nayar: None declared, Francesco Ciccia Grant/research support from: CELGENE, PFIZER, Consultant for: UCB, NOVARTIS, CELGENE, PFIZER, LILLY, Paid instructor for: UCB, NOVARTIS, CELGENE, PFIZER, LILLY, JANSSEN, Speakers bureau: UCB, NOVARTIS, CELGENE, PFIZER, LILLY, JANSSEN, MSD, ROCHE, AMGEN, Francesca Barone Grant/research support from: GlaxoSmithKline, Roche, UCB Pharma, Actelion, ONO Pharmaceutical, Consultant for: GlaxoSmithKline, Roche, Actelion, ONO Pharmaceutical, Guido Valesini: None declared, cristiano alessandri: None declared

Career situation of first and presenting author Post-doctoral fellow. Introduction Sjogren’s syndrome (SS) is an autoimmune condition characterised by systemic B cell activation, autoantibody production and ectopic germinal centers (GC) formation within salivary gland (SG). The extent of SG infiltrate has been proposed as biomarker of disease severity. Plasma levels of CXCL13 correlate with GC activity in animal models and disease severity in SS, suggesting its potential use as a surrogate serum marker to monitor local B cell activation. Objectives To evaluate the potential role of CXCL13 as biomarker of SG pathology in two independent SS cohorts. Methods 109 patients with SS were recruited at Sapienza University of Rome (Italy) (n=60), or at Queen Elizabeth Hospital in Birmingham and Barts Health NHS Trust in London (n=49). Both sera and matched paraffin-embedded minor SG biopsy were available. Sicca (n=57) and healthy subjects (HS) (n=19) sera were used as control. CXCL13 gene expression was also assessed in 25 frozen SGs. Results CXCL13 serum levels were higher in SS patients [90.3 (84.2) pg/ml], compared to both sicca [61.9 (38.6) pg/ml), p=0.0005] and HS [36.5 (40.18) pg/ml, p Conclusions Our data foster the use of CXCL13 to monitor the extent of local pathology in SS and its validation in longitudinal clinical studies. Both serum and tissue expression of CXCL13 correlate with SS histological severity, suggesting a major role of this chemokine in SG lymphocytes recruitment and organization. Disclosure of Interest None declared.

Objective: Neonatal Lupus (NL) is a rare syndrome caused by placental transfer of maternal anti-SSA/Ro and anti-La/SSB autoantibodies to the fetus. The rarity of this condition requires the establishment of multidisciplinary registries in order to improve our knowledge.Method: Inclusion criteria in this retrospective study were the maternal confirmed positivity for anti-SSA/Ro and/or anti-SSB/La antibodies, and the presence of II or III degree congenital heart block (CHB) in utero or neonatal period (up to 27 days after birth).Result: Eighty-nine cases of CHB were observed in 85 women with 88 pregnancies that occurred between 1969 and 2017. CHB was mostly detected in utero (84 cases, 94.2%), while five cases were observed in the neonatal period. A permanent pacemaker was implanted in 51 of 73 children born alive (69.8), whereas global mortality rate was 25.8% (23 cases): 16 in utero, five perinatal, and two during childhood. By univariate analysis, factors associated with fetal death were pleural effusion (p = 0.005, OR > 100; CI 95% 2.88->100 and hydrops (p = 0.003, OR = 14.09; CI 95% 2.01–122). Fluorinated steroids (FS) were administered in 71.4% pregnancies, and its use was not associated with better survival. Some centers treated all cases with fluorinated steroids and some centers did not treat any case. CHB was initially incomplete in 24 fetuses, and of them five cases of II degree block reverted to a lower degree block after treatments. Recurrence rate in subsequent pregnancies was 17.6% (3 out of 17). A prophylactic treatment was introduced in 10 of these 16 subsequent (58.8%) pregnancies, mostly with FS or high dose intravenous immunoglobulins.Conclusion: This is the first report from the Italian Registry of neonatal lupus/CHB. The live birth rate was nearly 80%, with nearly two thirds of the children requiring the implantation of a pacemaker. The management of fetuses diagnosed with CHB was heterogeneous across Italian Centers. The registry at present is mainly rheumatological, but involvement of pediatric cardiologists and gynecologists is planned.

Objectives SS is an autoimmune condition characterized by systemic B-cell activation, autoantibody production and ectopic germinal centres’ formation within the salivary gland (SG). The extent of SG infiltrate has been proposed as a biomarker of disease severity. Plasma levels of CXCL13 correlate with germinal centres’ activity in animal models and disease severity in SS, suggesting its potential use as a surrogate serum marker to monitor local B-cell activation. The aim of this study was to evaluate the potential role of CXCL13 as a biomarker of SG pathology in two independent SS cohorts. Methods 109 patients with SS were recruited at Sapienza University of Rome (Italy) (n = 60), or at Queen Elizabeth Hospital in Birmingham and Barts Health NHS Trust in London (n = 49). Both sera and matched minor SG biopsy were available. Sicca (n = 57) and healthy subjects’ (n = 19) sera were used as control. Results CXCL13 serum level was higher in SS patients compared with controls. Correlations between its serum levels and a series of histomorphological parameters, including size of the aggregates and the presence germinal centres', were observed. Conclusion Our data foster the use of CXCL13 to monitor the extent of local pathology in SS and its validation in longitudinal clinical studies.

Systemic Sclerosis (SSc) is a complex autoimmune disease, characterized by high mortality and morbidity. The heterogeneity in terms of extent, severity, and rate of progression of skin and internal organ involvement gives rise to many difficulties in finding the optimal therapeutic interventions for SSc and, to date, no disease-modifying agents are available. In this scenario, it is not surprising that SSc was one of the first autoimmune diseases challenged with high-dose immunosuppressive treatment followed by autologous hematopoietic stem cell transplantation (AHSCT). In the last decades, AHSCT has emerged as a treatment option for refractory SSc through a reduction of the aberrant immune cells, followed by re-constitution of a new, self-tolerant immune system. After several case series and pilot studies, more recently three randomized controlled trials have shown a benefit in skin involvement, organ functions and quality of life measures in AHSCT compared to monthly cyclophosphamide. In addition, although AHSCT presents a certain risk of mortality, it has been shown that the overall survival is better, compared to the cyclophosphamide group. Current evidence suggests that SSc patients who are most likely to benefit from AHSCT are early, active, with rapidly progressing diffuse skin disease, and mild involvement of internal organs. As the studies have progressed, it has become evident the need for a more rigorous patient selection, the optimization of transplant and post-transplant procedures, and the intervention of multidisciplinary teams of specialists to increase the safety and efficacy of AHSCT in SSc.

Background A randomized controlled trial (RCT) was performed to confirm preliminary uncontrolled data indicating that regional adipose tissue (AT) grafting (G) is effective in inducing ischemic digital ulcer (IDU) healing in patients with systemic sclerosis (SSc). Patients and methods SSc patients with IDUs were randomized to be blindly treated with AT-G or a sham procedure (SP). AT-G consisted of injection, at the base of the finger with the IDU, of 0.5–1 ml AT after centrifugation of fat aspirate. The SP consisted of false liposuction and local injection of saline solution. The primary endpoint was to compare the cumulative prevalence of healed IDUs in the two groups within the following 8 weeks. Results AT-G and the SP were carried out in 25 and 13 patients, respectively. The two groups were comparable for age, gender, disease duration, and SSc subtypes. IDU healing was observed in 23/25 and 1/13 patients treated with AT-G and the SP, respectively (p

Objectives To take a “high-definition” picture of the main features of primary Sjogren syndrome (SjS) following a worldwide data-sharing cooperative merging of international clinical SjS databases. Methods The Big Data Sjogren Project Consortium is an international, multicentre registry created in 2014 including leading clinical centres in SjS of the 5 continents that shared a harmonised data architecture and conducted cooperative online efforts to refine collected data of primary SjS patients fulfilling the 2002 classification criteria. Results By January 2018, the participant centres had included 10 475 patients from 22 countries, including 7637 (73%) patients from Europe, 1420 (14%) from America, 1186 (11%) from Asia, 167 (1.4%) from Australia and 65 (0.6%) from Africa. The cohort included 9781 (93%) women and 694 (7%) men, with a mean age at diagnosis of primary SjS of 53 years. The frequencies of fulfilment of the 2002 criteria were 92% for dry eye, 94% for dry mouth, 83% for abnormal ocular tests, 82% for positive minor salivary gland biopsy, 78% for abnormal oral diagnostic tests and 76% for positive anti-Ro/La antibodies. The frequency of positive immunological markers at diagnosis was 79% for ANA, 73% for anti-Ro, 49% for RF, 45% for anti-La, 13% for low C3 levels, 14% for low C4 levels and 7% for cryoglobulins. Conclusions International data sharing-based projects merging disperse clinical registries may be essential tools to increase current knowledge and to improve patient care in specific systemic autoimmune diseases. Disclosure of Interest None declared

Background Primary Sjögren’s syndrome (pSS) is a common chronic autoimmune disease characterized by lymphocytic infiltration of exocrine glands and peripheral lymphocyte perturbation. In the current study, we aimed to investigate the possible pathogenic implication of autophagy in T lymphocytes in patients with pSS. Methods Thirty consecutive pSS patients were recruited together with 20 patients affected by sicca syndrome and/or chronic sialoadenitis and 30 healthy controls. Disease activity and damage were evaluated according to SS disease activity index, EULAR SS disease activity index, and SS disease damage index. T lymphocytes were analyzed for the expression of autophagy-specific markers by biochemical, molecular, and histological assays in peripheral blood and labial gland biopsies. Serum interleukin (IL)-23 and IL-21 levels were quantified by enzyme-linked immunosorbent assay. Results Our study provides evidence for the first time that autophagy is upregulated in CD4+ T lymphocyte salivary glands from pSS patients. Furthermore, a statistically significant correlation was detected between lymphocyte autophagy levels, disease activity, and damage indexes. We also found a positive correlation between autophagy enhancement and the increased salivary gland expression of IL-21 and IL-23, providing a further link between innate and adaptive immune responses in pSS. Conclusions These findings suggest that CD4+ T lymphocyte autophagy could play a key role in pSS pathogenesis. Additionally, our data highlight the potential exploitation of T cell autophagy as a biomarker of disease activity and provide new ground to verify the therapeutic implications of autophagy as an innovative drug target in pSS. Electronic supplementary material The online version of this article (doi:10.1186/s13075-017-1385-y) contains supplementary material, which is available to authorized users.

Baseline Essdai/ Das Scores In 8061 Patients With Primary Sjogren Syndrome : Characterization Of Systemic Disease

Background: Mortality rate in patients infected by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) can be related to the presence of comorbidities like diabetes, cardiovascular and pulmonary diseases. On the contrary, few data exist on the impact of CoronaVirus Disease 2019 (COVID-19) on patients with rheumatic disorders, namely in those having pulmonary involvement and treated with immunosuppressive agents. The present survey is aimed at knowing the impact of COVID-19 in a cohort of patients with systemic sclerosis (SSc). Methods: Telephone interviews were carried out during the COVID-19 outbreak in patients with SSc followed in a Rheumatic Disease Unit in Italy. Patients were asked for confirmed SARS-CoV-2 infection, symptoms suggestive of COVID-19, and modification of their therapy. Results: A total number of 526 patients with SSc were contacted and interviewed. Of them, 270 and 256 had limited cutaneous and diffuse cutaneous SSc, respectively. Interstitial lung disease (ILD) was present in 45% of patients and most of them (68.2%) were treated with immunosuppressive therapy. Only two patients were hospitalized for COVID-19-related pneumonia, and one of them died despite invasive ventilator support. An additional 11 patients reported flu-like symptoms compatible with a mild form of COVID-19. Nobody modified the therapy during the COVID-19 outbreak. Conclusion: Despite the large prevalence of ILD and immunosuppressive therapies, which can be considered risk factors for the occurrence and severity of incidental viral infections, the impact of COVID-19, in terms of mortality rate and morbidity, does not appear particularly severe in this large cohort of patients with SSc. Possible mechanisms influencing this figure are discussed.

Objective.The differential diagnosis between rheumatic diseases and infectious conditions is a great challenge in clinical practice. Adult-onset Still’s disease (AOSD) is a rare systemic inflammatory syndrome that shares several clinical and laboratory variables with sepsis. Interleukin (IL)-18 is overexpressed in AOSD, suggesting a possible role as a disease biomarker. The aim of our study was to detect IL-18 serum levels in a cohort of patients with AOSD and sepsis and to address its possible role as a biomarker for differential diagnosis.Methods.A group of unselected patients with AOSD diagnosed according to the Yamaguchi criteria and consecutive patients with sepsis diagnosed according to the American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference criteria were enrolled. The clinical and laboratory data were collected. In the AOSD group, disease activity was assessed by Pouchot’s and Rau’s criteria. IL-18 serum levels were detected by ELISA.Results.Thirty-nine patients with AOSD and 18 patients with sepsis were enrolled. Two out of 18 patients with sepsis (11.1%) also fulfilled the Yamaguchi criteria. A significant difference was found in IL-18 serum levels between patients with active and inactive disease (p < 0.001), and it positively correlated with disease activity (p = 0.0003), ferritin serum level (p = 0.016), and erythrocyte sedimentation rate (p = 0.041). IL-18 was significantly increased in patients with AOSD when compared with sepsis (p = 0.014). For a cutoff of 148.9 pg/ml, this test had a specificity of 78.3% and a sensitivity of 88.6%.Conclusion.We have demonstrated that IL-18 can be a biomarker for differential diagnosis between AOSD and sepsis.

Sjogren’s syndrome (SS) mainly affects the exocrine glands, resulting in a wide range of disturbing sicca symptoms, such as dry mouth, dry eyes, xerotrachea, and dry vagina. However, extraglandular disease manifestations can also occur in a non-negligible percentage of patients. Indeed, up to 75 % of patients with SS present extraglandular systemic features, which may be severe in about 10–20 %. Extraglandular disease includes neurological, joint, renal, and hematological manifestations.

Objective.To assess the quality of sexual life of women with primary Sjögren syndrome (pSS) and to identify its correlations with disease activity and damage, quality of life, and mood disorders.Methods.The quality of sexual life of 24 women with pSS was assessed with the Female Sexual Function Index (FSFI). Twenty-four healthy women, matched by age and hormonal status, were enrolled as controls. Mood disorders and quality of life were investigated using the Hospital Anxiety and Depression Scale (HADS) and the Medical Outcomes Study Short Form-36. Patients underwent a gynecological visit with vaginal pH measurement, cervicovaginal swabs, and Pap smears. Disease activity and damage were assessed by the European League Against Rheumatism Sjögren syndrome disease activity and damage indexes.Results.Patients with pSS showed a pathological mean FSFI score (19.1 ± 7.33) significantly different from controls (p = 0.004), both in menstruating women (p = 0.006) and in menopausal women (p = 0.03). Major differences between the 2 groups were detected in dyspareunia (p < 0.005), lubrication (p = 0.006), desire (p = 0.004), and arousal (p = 0.018). The FSFI score was inversely correlated with age (p = 0.008) and anxiety HADS (p = 0.031). No early anatomical changes, swabs, and Pap smear alterations were revealed in patients with pSS; however, vaginal pH was higher than normal in premenopausal patients (6.0 ± 0.77).Conclusion.Both premenopausal and postmenopausal women with pSS have a worse sexual quality of life. We reported a greater prevalence of dyspareunia that is statistically significant when compared with controls. The FSFI could be a useful tool to assess this topic, but has been neglected in the care of patients with pSS heretofore.

To analyze our five-year experience with a telephone helpline service for patients suffering from chronic rheumatic diseases and provide the patients' perspective derived from a dedicated survey.A telephone service (contact center) was set up in the rheumatology unit at Sapienza University of Rome, Italy, in September 2007. It is managed by operators from a medical service society who collect the patients'calls. Daily reports with medical issues are transmitted to the physicians who are supposed to call back shortly. A year after the institution of the contact center, a questionnaire was administered to a group of patients to address the level of satisfaction.A total of 39,076 calls were registered between September 2007 and August 2012. Each month, an average of 20% of the calls were made by patients referring to our rheumatology unit for the first time and an average of 68.5% patients phoned to request medical consultation. Demographic analysis demonstrated a prevalence of middle-aged female patients. The majority of patients filling in the questionnaire declared an intention to use it again in the future. Furthermore, 85.7% of callers reported full satisfaction with respect to the responses received to their requests.A telephone helpline may provide extra-clinical advice and support for patients with rheumatic diseases. Although these services cannot replace clinical appointments, they should be encouraged both to assure patients easy access to medical counseling and to optimize the daily clinical workload of physicians.

Objective.To investigate pregnancy and fetal outcomes in patients with primary Sjögren syndrome (pSS).Methods.An obstetric history of 36 women with established diagnosis of pSS at pregnancy was obtained from a multicenter cohort of 1075 patients. In a subgroup case-control analysis, 12 deliveries in patients with pSS were compared with 96 control deliveries.Results.Thirty-six women (31 with anti-SSA/Ro and/or anti-SSB/La antibodies) with an established diagnosis of pSS had 45 pregnancies with the delivery of 40 newborns. Two miscarriages, 2 fetal deaths, and 1 induced abortion were recorded. Mean age at the first pregnancy was 33.9 years; mean number of pregnancies was 1.25; 18/40 (45%) cesarean births were delivered; mean pregnancy length was 38.5 weeks (range 32–43), with 6 preterm deliveries. The mean Apgar score at 5 min was 8.9, mean birthweight was 2920 g (range 826–4060 g). Congenital heart block (CHB) occurred in 2/40 (5%) newborns. The reported rate of breastfeeding for at least 1 month was 60.5%. In 4/40 pregnancies (10%) a flare of disease activity was observed within a year from delivery. In the case-control subgroup analysis, 12 deliveries were compared with 96 controls and no significant differences were found.Conclusion.Patients with pSS can have successful pregnancies, which might be followed by a mild relapse. CHB was the only cause of death for offspring of mothers with pSS.

Background Autophagy is now considered as a major regulator in trafficking events that activates innate and adaptive immunity and consistent evidence supports its role in autoimmunity (1). Primary Sjogren9s syndrome (pSS) is a systemic autoimmune disease characterized by infiltration of exocrine glands by T and B cells that, producing chemokines and cytokines, coordinate the chronic inflammatory process. No data on the role of autophagy in pSS are available in humans, although studies in mice demonstrated its involvement in the salivary and lacrimal gland homeostasis (2,3). Objectives We investigated the autophagy process in salivary gland tissue and in peripheral T lymphocytes from pSS patients to evaluate its possible implication in the pathogenesis of the disease. Methods 30 patients with pSS, 20 patients with sicca syndrome or non-specific-chronic-sialoadenitis and 30 healthy donors were studied. Peripheral T lymphocytes were isolated by standard procedures. Salivary gland biopsies were evaluated by i) H&E to assess histological pattern, the severity of inflammatory infiltrate and the presence of germinal centers, ii) RT-PCR for the expression of autophagy-related genes and IL-23p19 and IL-21 mRNA. Autophagy-related proteins (LC3, Atg5, p62/SQSTM1) were detected in peripheral T lymphocytes by western blot and in salivary gland by immunohistochemistry and immunofluorescence. IL-21 and IL-23p19 serum levels were measured by ELISA. Results Autophagy is up-regulated in T cells from the salivary glands, but not from the peripheral blood, of pSS patients and it is correlated with disease activity and damage indexes. Autophagy is also correlated with the local expression of the pro-inflammatory cytokines IL-21 and IL-23p19, but not with serum levels of these cytokines. Conclusions Our data show that, in pSS, T cells present high levels of autophagy, which may up-regulate the expression of pro-inflammatory cytokines, providing evidence for a role of this process in the pathogenesis of pSS and identifying a possible therapeutic target. References Pierdominici M, Vomero M, Barbati C et al. FASEB J. 2012; 26: 1400-1412. Morgan-Bathke M, Lin HH, Chibly AM et al. J Dent Res. 2013; 92: 911-917. Seo Y, Ji YW, Lee SM, et al. Cell Death Dis. 2014; 5: e1309. Disclosure of Interest None declared

Background Primary Sjogren Syndrome (pSS) and Systemic Lupus Erythematosus (SLE) express a significant overlap in their clinical and immunological aspects. Moreover, SS often presents clinical and immunological manifestations included in the SLE classification criteria. A secondary SS (diagnosis according to AECG criteria) has been described in about 9-19% of SLE cases. Few data is available regarding the prevalence of a true overlap of the two disorders. Objectives To investigate the prevalence of patients with pSS who can be classified as having an overlap syndrome with SLE considering both the 1997-revised ACR criteria and the new criteria proposed in 2012 by the Systemic Lupus International Collaborating Clinics (SLICC). Methods Charts from patients with pSS (diagnosis according to AECG criteria) were retrospectively evaluated in order to collect clinical and laboratory data. Results Two-hundred seventy patients with pSS [8M, 262 F, mean age 57.8±12,5 years, mean age at diagnosis 52.6 years ±12.5, mean follow-up 5.6 years (range 0–42 years)] were considered. Taking into account the 1997-ACR criteria, 11 patients (4.1%) could be classified as having an overlap with SLE (SS-SLE). Considering the new SLICC criteria, the number of patients raise to 18 (6.7%). Both considering the old and the new criteria, the most frequent items satisfied by the SS-SLE group were: ANA, leukopenia, oral ulcer and arthritis (Table). The items responsible for the increasing number of patients fulfilling the new criteria were low complement and the presence of leukopenia, thrombocytopenia or hemolytic anemia since these are considered separately in the new criteria. Compared to the remaining patients with pSS (246 F, 8M, mean age at diagnosis 53.3±12.4 years), the SS-SLE group (18 F, mean age at pSS diagnosis 47.9±13.1 years) showed a significantly higher frequency of leukopenia (77.7% in SS-SLE vs 14.2% in pSS; p Conclusions The occurrence of a true overlap between SS and SLE is relatively infrequent and the new SLICC criteria may allow a higher sensitivity to detect such condition. The items responsible for the increased sensitivity are both the introduction of hyopocomplementemia and the separate consideration of different hematological disorders in the new classification criteria. In patients with SS-SLE, hypocomplementemia, leukopenia and arthritis appear to be the most frequent manifestations. Disclosure of Interest None declared

Background Although muscle pain is relatively frequent in primary Sjogren Syndrome (pSS), a frank myositis is rare and reported only in 2.5-11% of patients. The most frequent symptoms are muscular weakness and myalgias and diagnosis is based on clinical, laboratory and histologic evaluation. Objectives To describe the prevalence and course of myositis in a multicenter cohort of patients with pSS. Methods Clinical and laboratory data from patients with a diagnosis of pSS were retrospectively collected. The clinical charts of patients with symptoms and/or signs of inflammatory myositis were carefully reviewed. Results One thousand one hundred seventy patients with pSS (52M, 1118 F, mean age 57.3 years; range 17–89 years) were considered. Mean age at diagnosis was 51±14 years and the mean follow up from diagnosis was 5.6 years (range 0–42 years). Ten female patients (0.85%) presented invalidating muscular weakness in the upper and lower limbs and/or severe myalgias. In 8/10 patients an increase of Creatine Phosphokinase (CK) serum level was present. A possible iatrogenic effect was excluded; in one case myositis started under statin therapy but didn’t disappear after drug discontinuation. In the 10 patients, mean age at pSS diagnosis was 47.4 years (range 14–68), while mean age of myositis diagnosis was 50.6 years (range 23–69). In six out of ten, muscular and sicca symptoms had occurred together at onset. Diagnosis of myositis was supported by clinical evidences and by the presence of increased CK serum levels. In 7/10 patients muscle biopsy was performed. In all biopsies signs of inflammation were present. In 1/7 patients (14.2%) the biopsy was typical of an inclusion body myositis, while in the remaining cases histological aspects of Dermatomyositis and Polymyositis (PM) were detected. Eight out of ten patients presented at least three criteria for inflammatory myopathy (according to Bohan and Peter criteria, 1975) suggesting a possible diagnosis of a true overlap syndrome. In one of these patients serum anti Jo-1 and anti RNP antibodies were detected. Six patients (60%) were successfully treated with DMARDs, while four (40%) did not respond. Thus, two were treated with IvIg, one showing complete remission of myositis, and the remaining two non-responder patients were treated with Rituximab, one showing complete remission. Conclusions Our retrospective study shows a lower prevalence of myositis in pSS than previously reported. Muscle involvement can occasionally represent the first symptom at disease onset. An overlap syndrome with inflammatory myopathies, above all PM, should be considered. Different therapeutic approaches can be used: DMARDs are effective in the majority of the patients, while IvIg and Rituximab may represent an available alternative therapeutic options in non-responder patients. Disclosure of Interest None Declared

Background Vasculitis in primary Sjogren’s syndrome (pSS) may be related to cthe presence of cryoglobulins (cryos) or hypergammaglobulinemia. Cryos reflect a high grade of B-cell lymphoproliferation, possibly leading to malignant lymphoma. Objectives Patients with pSS with cryos with or without vasculitis, and pSS with hypergammaglobulinemic vasculitis (hypergammaV) were retrospectively compared in a large cohort of consecutive patients. Methods Clinical, laboratory and histopathologic data in 1170 patients with pSS (1118 females, and 52 males, age at diagnosis 51±14 years) were collected. Univariate analyses were performed. Results cryos were tested in 850/1170 patients (72.6%), and detected in 59/850 (6.9%). Cryos were significantly associated with male sex (p=0.02), purpura (p

Background primary Sjogren’s syndrome (pSS) is the autoimmune disease with the highest risk of lymphoma. Lymphoma and mixed cryoglobulinemic vasculitis (CV) occur in a minority of cases, but they are the most relevant clinical features characterizing the B cell lymphoproliferation in pSS. Objectives to provide serological biomarkers associated with lymphoproliferative complications (B-cell lymphoma, cryoglobulinemic vasculitis (CV) and non malignant major salivary gland swelling) in primary Sjogren’s syndrome (pSS). Methods data in 1170 patients with pSS diagnosis were retrospectively collected. The analyses were then performed in patients fulfilling the following criteria: 1. European or AECG criteria, 2. Hepatitis C virus infection antibody negative, 3. serum cryoglobulins tested. Multinomial analyses (P 16 g/l), leucopoenia (

To assess the sleep quality in primary Sjögren's syndrome (pSS) patients and evaluate its relationship with the disease, quality of life and mood disorders.The sleep quality of 29 pSS women and 29 matched controls was assessed by the Pittsburgh Sleep Quality Index (PSQI). Seven domains are grouped according to three factors: F1 perceived sleep quality (subjective sleep quality, sleep latency, use of sleeping medication), F2 sleep efficiency (sleep duration, habitual sleep efficiency) and F3 daily disturbances (sleep disturbances, daytime dysfunction). These domains are scored as a single factor of global sleep quality. The Short Form Health Survey (SF-36), Functional Assessment of Chronic Illness Therapy (FACIT) fatigue scale and Hospital Anxiety and Depression Scale (HADS) were also administered. Disease activity and damage were evaluated with the EULAR Sjögren's syndrome disease activity index (ESSDAI), the Sjögren's Syndrome Disease Activity and Damage Indexes (SSDAI, SSDDI).The mean PSQI global score had higher pathological values (8.6±4.6) compared with controls (5.6±2.2) (p=0.002). F1 and F3 were significantly worse in cases (p=0.01, p=0.009). A negative correlation was found between SF-36 subscales and the global PSQI, F2 and F3. The anxiety HADS correlated with F2 and F3, while depression only with F3. No correlation with FACIT and disease indexes emerged.Using PSQI, an impaired sleep quality was demonstrated in pSS patients, especially with perceived quality and the daily disturbances. It is associated with a reduced quality of life but not with disease-related variables.