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The concern about the offspring’s health is one of the reasons for a reduced family size of women with rheumatic diseases (RD). Increased risk of autoimmune diseases (AD) and neurodevelopmental disorders (ND) has been reported in children born to patients with RD. Within a nationwide survey about reproductive issues of women with RD, we aimed at exploring the long-term outcome of their children. By surveying 398 patients who received their diagnosis of RD during childbearing age (before the age of 45), information about the offspring were obtained from 230 women who declared to have had children. A total of 148 (64.3%) patients were affected by connective tissue diseases (CTD) and 82 (35.7%) by chronic arthritis. Data on 299 children (156 males, 52.1%; mean age at the time of interview 17.1 ± 9.7 years) were collected. Twelve children (4.0%), who were born to patients with CTD in 75% of the cases, were affected by AD (8 cases of celiac disease). Eleven children had a certified diagnosis of ND (3.6%; 6 cases of learning disabilities); 9 of them were born to mothers with CTD (5 after maternal diagnosis). No association was found between ND and prenatal exposure to either maternal autoantibodies or anti-rheumatic drugs. Absolute numbers of offspring affected by AD and ND were low in a multicentre cohort of Italian women with RD. This information can be helpful for the counselling about reproductive issues, as the health outcomes of the offspring might not be an issue which discourage women with RD from having children.

To investigate how the different components of sleep dysfunction described in SLE patients combine together in sleep clusters. We conducted a cross-sectional study on a perspective cohort of 79 SLE patients (mean age 8.2 ± 14.3 years). Sleep was evaluated using Pittsburgh Sleep Quality Index (PSQI). Clusters were defined using the single components of PSQI in a hierarchical clustering model. We used Beck Depression Inventory, Hamilton Anxiety Rating Scale, and Medical Outcomes Study Short Form 36 (SF36) to measure depressive symptoms, anxiety, and quality of life, respectively. Three sleep clusters were identified. The cluster 1 (N = 47) is characterized by the lowest values of PSQI total score. The cluster 2 (N = 21) presents higher values of sleep latency, but sleep duration similar to cluster 1. In cluster 3 (N = 11), we found sleep latency increased as in cluster 2, but the highest values of PSQI total score and reduced sleep duration. Scores of anxiety and sedentary time were higher in clusters 2 and 3 than in cluster 1. Cluster 3 presented the highest scores of depression and reduced mental and physical components of SF36. The combination of different sleep components in SLE patients allowed us to identify three patterns of dysfunction: a first cluster with better sleep latency and duration, a second with increased sleep latency but conserved duration, and a third with impairment of both latency and duration. The stratification of sleep disorders in clusters might be useful for the personalization of therapy in relation to sleep cluster membership.

Despite recent improvements in the treatment of systemic lupus erythematosus (SLE), disease activity, comorbidities and drug toxicity significantly contribute to the risk of progressive irreversible damage accrual and increased mortality in patients with this chronic disease. Moreover, even lupus patients in remission often report residual symptoms, such as fatigue, which have a considerable impact on their health-related quality of life. In recent decades, SLE treatment has moved from the use of hydroxychloroquine, systemic glucocorticosteroids and conventional immunosuppressive drugs to biologic agents, of which belimumab is the first and only biologic agent approved for the treatment for SLE to date. Novel therapies targeting interferons, cytokines and their receptors, intracellular signals, plasma cells, T lymphocytes and co-stimulatory molecules are being evaluated. In the context of a holistic approach, growing evidence is emerging of the importance of correct lifestyle habits in the management of lupus manifestations and comorbidities. The aim of this paper is to provide an overview of current pharmacological and non-pharmacological treatment options and emerging therapies in SLE.

Background Patients with juvenile idiopathic arthritis (JIA) may require several hospital admissions over the disease course, due to flares or persistently active arthritis, with a negative impact on the patients’ and family’s daily life. To provide timely intervention and support the patients’ and families’ quality of life, in 2018 an afternoon outpatient service for intraarticular glucocorticoid injections (IAGI) in JIA has been created at the study center. Objectives To evaluate the patients’ and caregivers’ assessment of the outpatient service for IAGI in JIA; to investigate demographic and clinical features of patients entering the service. Methods All consecutive JIA patients and their caregivers seen at the IAGI outpatient service from February 2018 to January 2019 completed a satisfactory questionnaire just after the IAGI procedure. The patient’s part included: satisfaction on the overall service and on dedicated personnel (yes/no, why), procedure pain assessment (VAS 0-10, 0=none; 10 worst); whereas the caregiver’s part: satisfaction on the overall service (yes/no, why), facilitation of family burden (yes/no, why). Demographic and clinical data of patients, including previous hospitalization for IAGI under general sedation or local anesthesia and geographical provenance, were registered during the questionnaire completion. Descriptive analysis was performed on data. Open answers were synthetized in items. Results All of the 46 JIA patients seen at the IAGI outpatient service and their caregivers completed the questionnaire. Patients were mostly females (78%) with early disease onset (median 4.8 years) and positive ANA status (61%). The majority (52%) had persistent oligo-JIA, followed by extended oligo-JIA (26%), RF-negative polyarthritis (17%), ERA and systemic JIA (2%, respectively). The median age at IAGI was 14.7 years (IQ 11.3-19.5). Forthy patients (87%) had previous hospitalization for IAGI, mostly under general sedation (64%). All patients, except a 12 year old girl (0.02%) with uncontrolled needle phobia and previous IAGI in general sedation, (99.98%) and all caregivers (100%) were satisfied with the IAGI outpatient service. In Table 1 reasons of satisfaction are detailed in items. Procedural pain was median rated 3 (IQ 2-6). Most of the families came from the city or province of the study center (76%); 17% from other provinces of the same geographical region; 7% from other regions. Conclusion The results outline the afternoon IAGI outpatient service foster the management of flares or persistently active arthritis in JIA patients, particularly at older ages, with high rate of satisfaction and lower impact on patients’ and family burden compared to hospital admission and, of note, despite moderate pain rating and multiple site injections. This supports the development of Diagnostic Therapeutic Care Pathways for JIA patients, in the view of improving patients’ quality of life and also towards resource optimization. References [1] Minden K. What are the costs of childhood-onset rheumatic disease?Best Pract Res Clin Rheumatol2006;20:223-40. [2] Cavazzana L, Fornili M, Filocamo G, Agostoni C, Auxilia F, Castaldi S. Hospital clinical pathways for children affected by juvenile idiopathic arthritis. Ital J Pediatr2018;44:139. Disclosure of Interests Hanan Jadoun: None declared, Aurora Pucacco: None declared, Angela Aquilani: None declared, Andrea Uva: None declared, Fabio Basta: None declared, Rebecca Nicolai: None declared, Fabrizio De Benedetti Grant/research support from: Abbvie, SOBI, Novimmune, Roche, Novartis, Sanofi, Pfizer, Silvia Magni-Manzoni Consultant for: Abbvie, Speakers bureau: Abbvie

Background: Paediatric systemic lupus erythematosus (pSLE) is an autoimmune disorder of childhood characterized by the production of autoantibodies against nuclear antigens. In the last decade, several studies showed an up-regulation of genes induced by type I interferons (IFNα) in peripheral blood and tissues of pSLE patients2. It has been reported that the expression of this group of genes, known as the type I IFN signature, correlates with disease activity2. More recently, also the type II interferon (IFNγ) has been implicated in pSLE; however, its precise role has not been clarified yet3. Objectives: To investigate the role of IFNγ in the pathogenesis of pSLE evaluating: 1) the expression levels of IFNγ-related genes in the peripheral blood of pSLE patients; 2) the possible cross-talk between IFNγ and type I IFNs. Methods: Expression levels of IFNα-induced genes (IFI27, IFI44L, IFIT1, RSAD2, ISG15, SIGLEC1), IFNγ-induced genes (CXCL9, IDO1) and IFNγ itself were analysed by quantitative PCR (qPCR) in whole blood of pSLE patients and healthy donors (HDs). We developed a type II IFN score similarly to the type I IFN score described by Crow4. Peripheral blood mononuclear cells (PBMCs) from 6 HDs were stimulated in vitro with recombinant human IFNγ and IFNα2b; gene expression was evaluated by qPCR. CXCL9 and CXCL10 in sera and supernatants from stimulated cells were measured by ELISA. Whole blood of pSLE patients and HD was incubated with an anti-IFNγ neutralizing antibody and isotype control, and later type I and type II signatures were assessed. For each patient, SLEDAI was calculated. Results: Expression levels of both IFNα-induced genes, IFNγ-induced genes and IFNγ were upregulated in pSLE patients with active disease (n = 21) compared to HDs and pSLE patients with inactive disease (n = 17). The type II IFN score correlated with the SLEDAI (r = 0.64, P In order to study a possible crass-talk between type I and type II IFNs, we stimulated in vitro HD PBMCs with recombinant IFNα2b and IFNγ for 6 hours: we analysed the expression levels of type I and type II IFN signatures and assessed the production of CXCL9 and CXCL10 in the supernatants. IFNα2b strongly up-regulated the expression of IFNγ, CXCL9 and IDO1. On the other hand, IFNγ induced the expression of the 6 IFNα-related genes. IFNγ, but not IFNα2b, induced the release of CXCL9 in supernatants. Both IFNγ and IFNα2b induced the production of CXCL10. IFNγ also up-regulated the expression levels of both TLR7 and TLR9, two potent inducer of IFNα. Finally, whole blood of pSLE was incubated with an anti-IFNγ neutralizing antibody for 24 hours: the type II signature was significantly downregulated (P Conclusion: Our data suggest a potential role of IFNγ in the pathogenesis of pSLE. IFNγ-induced genes in whole blood and CXCL9 in serum are increased in pSLE patients. Type I and type II signatures are not strictly interferon-specific as IFNγ can induce the expression of type I genes. Moreover, blocking of IFNγ in the blood of pSLE patients reduces the type II signature confirming the presence of IFNγ in the blood of pSLE patients. IFNγ also induces the expression of TLR7 and TLR9, and IFNα induces the expression of IFNγ, thus establishing a positive crosstalk between IFNα and IFNγ that potentiate their reciprocal biological activity in pSLE. References [1] Petri M, et al. Lupus. 2009Oct;18:980-9. [2] Munroe M, et al. Ann Rheum Dis2016;75:2014-2021. [3] Rice GI, et al. Lancet Neurol2013;12:1159-69. Disclosure of Interests: Gian Marco Moneta: None declared, Claudia Bracaglia: None declared, Ivan Caiello: None declared, Raffaele Pecoraro: None declared, Chiara Farroni: None declared, Fabio Basta: None declared, Luisa Bracci-Laudiero: None declared, Rita Carsetti: None declared, Fabrizio De Benedetti Grant/research support from: Abbvie, SOBI, Novimmune, Roche, Novartis, Sanofi, Pfizer, Emiliano Marasco: None declared

Background Glucocorticoid injections in periarticular sites (PAGI) such as tendons and bursae often complete the local treatment of active disease in juvenile idiopathic arthritis (JIA). However, the use of PAGI and their role in the achievement of disease remission has seldom been studied. Objectives To identify the clinical features of JIA patients treated with PAGI at the study center in a 6 years period, the sites most frequently injected, the frequency of and the time for achieving local remission. Methods Records of JIA patients treated with PAGI at the study center from 2012 were retrospectively reviewed. Demographic and clinical features, including ongoing systemic treatment, sites of injection, procedure setting, type and dosage of glucocorticoid injected, time to achieve local remission (complete or partial when one/some of the injected sites were in remission and one/some showed persistent synovitis), frequency of remission of the injected sites at the last follow-up and side-effects were recorded. Results In a total of 293 procedures 647 tendons and 26 bursae were injected in 191 patients. Most of the patients were females (74%), with ILAR oligoarticular JIA subtype (50% persistent, 23% extended), followed by RF-negative polyarthritis (23.2%), RF-positive polyarthritis (0.7%) and systemic JIA (1.3%), with a median age of 8.2 years (IQ 4.7-11.3) at the PAGI. All procedures were ultrasound-guided, 281 (96%) under general sedation. Acetate methylprednisolone was used in 96% of the procedures (average dosage 0.45 mg/kg/tendon, 0.89 mg/kg/bursa), whereas trimcinolone exacetonide in 4%. In 255 procedures (87%) patients experienced remission in the injected sites after a median of 2.6 months (IQ 1.9-3.5). Forthy-seven patients (24.6%) underwent to repeated injections in the same sites after at least 3 months from the 1st procedure. A total of 96 tendons and 9 bursae were re-injected during 69 procedures (23.5%). At the last follow up, after a median period of 29.4 months (IQ 15-45.48) from PAGI, patients experienced complete local remission in 259 (88.4%) injected procedures and partial local remission in 23 (7.8%). In 53 procedures with repeated injection(s) in the same site(s) (77%), patients were in local remission at the last follow up. In 77 procedures (26.3%) patients presented flare of disease in periarticular sites. Concerning concomitant therapy, at the time of each PAGI 115 patients (39.2%) were not on treatment, 137 (46.7%) were on methotrexate, 29 (9.9%) on methotrexate and biologics, 8 (2.7%) on biologics and 4 (1.5%) received others. Patients were started with a new treatment in around three months following 139 (47.4) procedures due to poor control of disease. In 156 (53.2%) procedures, patients experienced complete/local remission and maintained the same treatment before or after the injection at the last follow up in a median period of 20.8 months (IQ 12.67- 39.35). Of notice, 81.4% of patients who experienced complete remission following the injection were not on concomitant treatment; 85.9% of patients who experienced complete remission at the last follow up did not receive concomitant treatment. In 24 injection procedures (8.2%) patients showed only mild local side effects (atrophy and hypopigmentation). Conclusion PAGI are a safe option in the management of JIA. In our cohort, patients treated with PAGI had more frequently persistent oligoarticular JIA subtype; acetate methylprednisolone was by far the most frequently used glucocorticoid. In 88.4% procedures patients experienced remission at last follow up. However, further investigations are mandatory to assess the role of concomitant therapy in achieving and maintaining remission. Disclosure of Interests Andrea Uva: None declared, Lucilla Rava’: None declared, Hanan Jadoun: None declared, Angela Aquilani: None declared, Fabio Basta: None declared, Rebecca Nicolai: None declared, Fabrizio De Benedetti Grant/research support from: Abbvie, SOBI, Novimmune, Roche, Novartis, Sanofi, Pfizer, Silvia Magni-Manzoni Consultant for: Abbvie, Speakers bureau: Abbvie

Background The discomfort and anxiety related to the medical care of patients with juvenile idiopathic arthritis (JIA), ampered by frequent and ongoing visits, diagnostic tests, medications and hospital stays, can negatively impact on the compliance during examinations and procedures, particularly intraarticular glucocorticoid injections (IAGI) in local anesthesia. A dedicated personnel for supporting patients and their caregivers may provide them relief, thus contributing also to a more serene environment for operators. Objectives To identify an appropriate approach for the relief of JIA patients most critical issues related to IAGI in local anesthesia. To provide preliminary validation of the approach identified. Methods In the first part of the study the nurse of the IAGI outpatient service at the study center had conversation with all consecutive JIA patients and caregivers seen at the service, while preparing them to IAGI in local anesthesia and while on discharge. In agreement with the patient, the nurse synthetized in keywords and registered each patients most relevant feelings with regard to the IAGI procedure. Patients and caregivers were also asked to suggest feasible tools for a better acceptance of the procedure. The results were discussed within the JIA team, who selected in a questionnaire the most frequently reported keywords and identified the most feasible among the proposed supportive tools. Secondly, all consecutive JIA patients seen at the service were asked to complete the feeling-status questionnaire after the IAGI. As the tools were available, the questionnaire was completed after IAGI procedures tool-supported. Statistics included descriptive analysis and Students t-test for comparison between feelings rating by patients with and without supportive tools (significance: p-value Results From the list of keywords obtained by the first 10 patients with the nurse, the most reported -stress, anxiety, fear, and anger- were included in a feeling questionnaire composed of a VAS 0-10 (0=none, 10=worst) for each keyword. Among the suggested supportive tools the JIA team identified as feasible: colored drawings/pictures in the procedure room and the availability of favourite songs/videoclips/cartoons on tablet just prior and during IAGI. Forthy-one patients completed the questionnaire in a mean time of 22 seconds. Among them, 24 (59%) were supported by the selected tools, been meantime available, during IAGI procedure. *VAS 0-10, 0=none, 10=worst Conclusion Our preliminary results highlight that a setting for IAGI more comfortable for patients provide an improvement in the JIA patients feelings rating undergoing injection procedures in local anesthesia. The nurses attitude to patients and the teamwork were fundamental in collecting the patients perspective and in adapting their suggestions to the IAGI outpatient service environment. Acknowledgement We acknowledge the Associazione Malattie Reumatiche Infantili (AMREI) Onlus for its support to the initiative Disclosure of Interests Aurora Pucacco: None declared, Hanan Jadoun: None declared, Angela Aquilani: None declared, Fabio Basta: None declared, Andrea Uva: None declared, Rebecca Nicolai: None declared, Fabrizio De Benedetti Grant/research support from: Abbvie, SOBI, Novimmune, Roche, Novartis, Sanofi, Pfizer, Silvia Magni-Manzoni Consultant for: Abbvie, Speakers bureau: Abbvie

To identify the distribution of patients with systemic lupus erythematosus (SLE) in clusters according to the levels of health-related quality of life (HRQoL), entity of pain, fatigue and depression.We performed a hierarchical cluster analysis. The following measures were used as clustering variables, after canonical transformation: the SF36 physical and mental component summary (PCS and MCS), the Beck Depression Inventory II (entity of depression), the Facit-Fatigue, all assessed during the last visit. Consecutive SLE patients were enrolled from two Italian cohorts. Lupus remission was retrospectively assessed over a period of 5 years before the last visit and was defined as a continuative period of no clinical disease activity according to SLEDAI2K and the maximum dose of prednisone allowed of 5 mg/day.We enrolled 130 female SLE patients. We identified three clusters. The first cluster (43 patients) was characterised by the highest levels of MCS and PCS and the lowest entity of pain, fatigue and depression. Cluster 2 (35 patients) was defined by a reduction of MCS and increase of pain, fatigue and depression; conversely, PCS levels were similar to cluster 1. In cluster 3 (52 patients) we found a reduction of MCS and increase of depression and fatigue (similar to cluster 2) but also a decrease in PCS levels and Bodily Pain (meaning increase in pain). In cluster 3 we found a decreased prevalence of remission ≥5 years.Identification of clusters of patients according to HRQoL levels could be useful to improve SLE management, aiming at personalised medicine.

Objective To evaluate the impact of duration of remission on the health-related quality of life (HRQoL) of patients with systemic lupus erythematosus (SLE). Methods We conducted a 5-year retrospective study on two Italian cohorts. Remission was defined as a continuative period of no clinical disease activity, according to the Systemic Lupus Erythematosus Disease Activity Index 2 K, and a permitted maximum prednisone dose of 5 mg/day. HRQoL was measured using the 36-Item Short-Form Health Survey (SF36) during the last visit. Results We enrolled 136 female SLE patients. During observation, 15 (11%) patients had been in remission for ≥1 and Conclusion Lupus remission could improve the HRQoL of SLE patients, particularly when associated with appropriate management of depression and fatigue.

Objective The reproductive choices of women affected by rheumatic diseases (RD) can be influenced by several factors, including the quality of physician-patient communication. We conducted a survey on reproductive issues aiming at exploring the unmet needs of women with RD during childbearing age. Methods We administered 65 multiple-choice and 12 open-answer questions about pregnancy counselling, contraception, use of drugs during pregnancy and other women reproductive issues to 477 consecutive women with RD aged 18–55 years followed-up in 24 rheumatology centres in Italy. Analysis was restricted to 398 patients who received their diagnosis of RD before the age of 45. According to the RD diagnosis, patients were subdivided into 2 groups: connective tissue diseases (n = 249) and chronic arthritis (n = 149). Results At the time of interview, women in both groups had a mean age of 40 years. Nearly one third of patients in each group declared not to have received any counselling about either pregnancy desire nor contraception. A smaller family size than desired was reported by nearly 37% of patients, because of concerns related to maternal disease in one fourth of the cases. A “Disease Knowledge Index” (DKI) was created to investigate the degree of patients’ information about the implications of their RD on reproductive issues. Having received counselling was associated with higher DKI values and with a positive impact on family planning. Conclusion Italian women of childbearing age affected by RD reported several unmet needs in their knowledge about reproductive issues. Strategies are needed to implement and facilitate physician-patient communication.

The B cell activating factor (BAFF), or B lymphocyte stimulator (BLyS), is a B cell survival factor which supports autoreactive B cells and prevents their deletion. BAFF expression is closely linked with autoimmunity and is enhanced by genetic alterations and viral infections. Furthermore, BAFF seems to be involved in adipogenesis, atherosclerosis, neuro-inflammatory processes and ischemia reperfusion (I/R) injury. BAFF is commonly overexpressed in Systemic Lupus Erythematosus (SLE) and strongly involved in the pathogenesis of the disease. The relationship between BAFF levels, disease activity and damage accrual in SLE is controversial, but growing evidence is emerging on its role in renal involvement. Belimumab, a biologic BAFF inhibitor, has been the first biologic agent licensed for SLE therapy so far. As Rituximab (RTX) has been shown to increase BAFF levels following B cell depletion, the combination therapy of RTX plus belimumab (being evaluated in two RCT) seems to be a valuable option for several clinical scenarios. In this review we will highlight the growing body of evidence of immune and non-immune related BAFF expression in experimental and clinical settings.

To assess clinical and psychosocial factors related to alexithymia in systemic sclerosis (SSc). We enrolled 40 consecutive SSc patients in a cross-sectional study evaluating alexithymia with Toronto Alexithymia scale (TAS-20). We measured Beck Depression inventory (BDI), Hamilton Anxiety rating scale (HAM-H), 36-Items Short-Form Healthy Survey (SF-36), Functional Assessment of Chronic Illness Therapy (FACIT)—Fatigue, Visual Analog Scale (VAS) pain, Pittsburgh Sleep Quality Index (PSQI), Satisfaction with Appearance Scale (SWAP), and Mouth Handicap in Systemic Sclerosis (MHISS). The prevalence of alexithymia was 42%. Alexithymic patients presented increased depressive (p = ≤ 0.001) and anxiety symptoms (p = ≤ 0.001), sleep disorders (p = 0.03), pain (p = 0.02), esthetic concerns (p = 0.03), disability in activities (p = 0.03) and reduced scores of SF-36 in mental components summary (MCS) (p = ≤ 0.001) and physical components summary (PCS) (p = 0.01). We found significant correlations with sleep disorders (r = 0.41, p = ≤ 0.001), BID (r = 0.35, p = 0.04), facial image dissatisfaction (r = 0.35, p = 0.04), mouth disability (r = 0.51, p = 0.005), depressive (r = 0.6, p = ≤ 0.001), and anxiety symptoms (r = 0.48, p = ≤ 0.001), fatigue (r = − 0.45 p = 0.005), SF-36 PCS (r = − 0.51, p = ≤ 0.001) and MCS (r = − 0.65, p = ≤ 0.001). In multiple linear regression analysis, SWAP facial was the only variable associated with TAS-20 [0.99 (0.48) p = 0.05]. Alexithymia correlates with several psychosocial factors but seems strongly related to facial image dissatisfaction.

Background Epilepsy may occur before, during or after SLE diagnosis, with a prevalence of 6.7%–14%. Recent works showed that a significant proportion of patients with not responding to antiepileptic drugs (AED)-resistant epilepsy harbour neural-specific autoantibodies. The detection of these antibodies may predict a favourable response to immunotherapy (75% of patients).1 A small number of recent studies have described the existence of antibodies directed against a-NA in neuropsychiatrics SLE (NPSLE), and data are contrasting.2 Objectives Evaluate the clinical features of epilepsy in patients with SLE. Evaluate any clinical-instrumental differences in epilepsy in patients diagnosed with epilepsy prior to many years of SLE. Evaluate antibodies associated with neurological phenotypes. Methods We retrospectively evaluated a SLE cohort for epileptic seizures. We single out 11 epileptic SLE patients (about 10%). A control group of 10 SLE patients with no NPSLE was matched for sex and age. Sera patients were tested for: ANA, a-ds-DNA, a-ENA, LAC, anticardiolipin IgG and IgM, anti-β2-glycoprotein IgG and IgM, a-nucleosomes, a-ribosomal. All sera were evaluated for the presence of autoantibodies directed to neural antigens by indirect immunofluorescence on frozen sections of mouse brain, cell-based assays (a-NA, a-NMDA). Results In our cohort of SLE patients with epilepsy we confirm the association between SLE and epilepsy of the mesial temporal lobe (MTLE). Six patients had epilepsy at least 5 years prior to SLE diagnosis (average 11.6 years)., the presence of minor symptoms suggestive of SLE (eg arthralgia, rash.) was reported many years before immunological diagnosis. Moreover seizure frequency was achieved when they started immunosuppressive drugs. Anti-NA antibodies were present in 6/11 (54%) of patients with SLE/epilepsy compared with 2/10 (20%) of the control group (p=0.05). We obtained specificity 0.80 (95% CI 0.44–0.97), and sensitivity 0.54 (95% CI 0.23–0.82). Among the other antibodies studied, we have not found any statistically significant difference between the two groups. Conclusions Anti-NA antibodies could be a useful biomarker of NPSLE, allowing a more precocious diagnosis and therefore a more early therapeutic intervention with improvement of long-term prognosis and quality of life. References [1] Iorio R, et al. 2015Eur J Neurol [2] Kampylafka EI, et al. 2016Lupus Disclosure of Interest None declared

Background Alexithymia describes the difficults of people in identifying, differentiating and articulating emotions of others and themselves and in discriminating those from bodily sensations, with a limited fantasy and a concrete, externally oriented cognitive style.1 A high prevalence of alexithymia has been found in patients with a variety of health conditions, including SLE.2 Previous authors identified mood states2 and quality of life3 as the main factors related to alexithymia in Systemic Lupus Erythematosus (SLE). Objectives Aim of our study was to assess the impact of clinical, immunological, psycho-social factors on the presence of alexithymia in Systemic Lupus Erythematosus (SLE). Methods We consecutively enrolled 104 patients in a cross-sectional study. Alexithymia was assessed using the Toronto Alexithymia scale (TAS-20). We also evaluated symptoms of mood disorders using BDI and HAM-H, quality of life using MOS-SF36, sleep disorders with PSQI and physical activity using IPAQ. Results The mean (standard deviation) TAS-20 score was 49.5 (15.6). The prevalence of alexithymia (TAS-20 ≥61) was 28%. Alexithymic patients (TAS-20 ≥61) were significantly older (p 0.0005), presented more severe depressive and anxiety symptoms (p Conclusions About a third of SLE patients presented a dysfunctional processing of emotion. It is necessary to carefully consider the symptoms of mood disorders to optimise SLE patient management. References [1] Taylor GJ, Bagby RM. Measurement of alexithymia. Recommendations for clinical practice and future research. Psychiatr Clin North Am. 1988Sep;11(3):351–66 [2] Vadacca M, Bruni R, Terminio N, Sambataro G, Margiotta D, Serino FM, Afeltra A. Alexithymia, mood states and pain experience in systemic lupus erythematosus and rheumatoid arthritis. Clin Rheumatol. 2014;33(10):1443–50.3. [3] Barbosa F, Mota C, Alves M, Alcântara C, Rossinol B, Patricio P, Barbosa A, Ferreira C. Alexithymia in systemic lupus erythematosus patients. Ann N Y Acad Sci. 2009Sep;1173:227–34 Disclosure of Interest None declared

To systematically review fatigue in systemic sclerosis (SSc) in terms of prevalence, features, correlates, predictors and management.We performed a literature search in PubMed (Medline), EBSCO and COCHRANE databases up to June 2017 selecting articles regarding fatigue in SSc. The articles finally selected fulfilled the following eligibility criteria: written in English, referred to fatigue in SSc, reporting original data, including validated questionnaires measuring fatigue.A total of 43 records were included. Fatigue in SSc has a prevalence similar to that of other rheumatic diseases and is one of the most prevalent and debilitating symptom experienced by SSc patients. Fatigue leads to a significant impairment of quality of life, parenting, household and work ability. Fatigue is associated with psychosocial factors (depression, pain and sleep disorders), sociodemographic factors and clinical manifestations of the disease (pulmonary and gastrointestinal involvement). Indeed, the relationship with scores of disease activity is uncertain. Pharmacological therapeutic approaches were broadly ineffective in reducing fatigue. More encouraging results concern physical activity, complementary and alternative medicine.Adequate management of fatigue could lead to a marked improvement of the patient's quality of life, also contributing to reduction in SSc indirect costs.

Background The treatment of Lupus Nephritis (LN) is an unmet need in the management of patients with Systemic Lupus Erythematosus (SLE). Case presentation We report two cases of women affected by Lupus Nephritis (LN) ISN/RNP Class IV with serological active disease, high disease activity and marked fatigue. In both cases, Mycophenolate mofetil (MMF), as induction therapy, was poorly tolerated because of gastrointestinal toxicity. Belimumab, together with low-doses of MMF, was effective as induction treatment leading to early achievement of complete renal response in these two selected cases of LN. Conclusions We also report a literature review concerning the efficacy and safety of Belimumab in Lupus Nephritis. Further studies are needed to evaluate the use of Belimumab to manage the renal involvement in patients with Systemic Lupus Erythematosus, waiting for the results of ongoing randomized clinical trials.

Background Systemic Lupus Erythematosus (SLE) is associated to a huge prevalence and incidence of cardiovascular diseases (CVDs) due to accelerated atherosclerosis. Several evidences demonstrated that metabolic syndrome (MeS) could contribute to CVDs burden in SLE. In general population, MeS components and, according to some reports, MeS itself are associated to worsened Health related Quality of Life (HR-QoL). In SLE patients, a severe decline of HR-QoL has been widely demonstrated. Objectives In the study, we evaluated the association between MeS, HR-QoL and QoL-related factors, such as depression, fatigue and physical activity. Methods We conducted a cross-sectional study with retrospective evaluation of disease activity, damage and therapies cumulative dosage. MeS was defined according to International Federation of Diabetes (IFD) criteria. All patients were evaluated to explore MeS IFD criteria and other CVD risk factors (familiar history, lifestyle, smoking). SLE disease activity and damage were evaluated using SELENA-SLEDAI and SDI indices, respectively. Disease flares were retrospectively assessed by SFI index. HR-QoL was quantified by SF-36 instrument. We used Beck Depression Inventory (BDI) to assess depression and Facit-Fatigue to evaluate fatigue. Physical activity was quantified using International Physical Activity Questionnaire (IPAQ) and expressed according to categorical IPAQ total score. Patients also completed Pittsburgh Sleep Quality Index (PSQI) exploring sleep pathology. Results We enrolled 55 SLE patients (2 male and 53 female). Mean age was 45±12.5. MeS prevalence was 23.6% and obesity (according to IFD definition) was recorded in 36.4% of patients. SLE patients with MeS presented reduced scores in SF-36 summary components MCS and PCS compared to patients without MeS (p 0.002 and p 0.04, respectively). The SF-36 individual components significantly decreased in MeS were the Mental Health, the Physical Rose and the Social Role (p 0.003, p 0.03, p 0.05, respectively). In multiple linear regression the values of MCS was significantly associated only to obesity (p 0.01), while neither MeS it self nor any MeS components were associated to PCS values. BDI score was significantly higher and Facit-Fatigue score was reduced in SLE patients meeting MeS criteria compared to subjects without MeS (p 13 (to have almost mild depression) [OR 0.05 (0.004–0.87)] and to be physically inactive (IPAQ=1) [OR 33.5 (2.3–496.4)]. Conclusions HR-QoL seems to be compromised in SLE patients with MeS, especially in mental components. Moreover, SLE patients with MeS often presented depression, are burdened by more severe fatigue and frequently are physically inactive. The presence of MeS in SLE was associated to the number of flare and, above all, to the physical inactivity, while not having depression seems exert a protective effect on MeS. Disclosure of Interest None declared

A growing body of evidence presents a link between chronic inflammatory rheumatic diseases and atherosclerosis. To evaluate subclinical carotid atherosclerosis in an elderly group of patients with primary Sjögren syndrome compared with a control group matched for age, sex, ethnicity and cardiovascular risk factors, we enrolled 18 patients with Primary Sjögren Syndrome (mean age 65±5.93 SD) and 18 mild Ostheoarthritic patients (mean age 66±5.94 SD) from the outpatient department of Rheumatology, University “Campus Bio-Medico, Rome, Italy, matched for age, sex, ethnicity and cardiovascular risk factors. A duplex Doppler sonographic study of carotids was performed in order to evaluate intima-media thickness (IMT), stiffness and haemodynamic parameters [resistivity and pulsatility indices (RI and PI, respectively)]. No significant difference was found between primary Sjögren syndrome and control patients in IMT, stiffness and haemodynamic parameters. The lack of significant difference in subclinical atherosclerosis between elderly primary Sjögren syndrome and control matched patients, indicates that traditional cardiovascular risk factors, immunologic alterations and chronic inflammation do not influence the progression of vascular damage in the carotid circulation of patients with median disease duration of 6.5 years.

Low levels of vitamin D play a role progression of cardiovascular diseases. Knowledge lacks whether a relationship exists between vitamin D levels and subclinical carotid atherosclerosis in patients with primary Sjögren's syndrome (pSS).We evaluated vitamin D levels and subclinical carotid atherosclerosis in 25 patients with pSS compared to 22 mild ostheoarthritic control patients (OCp).Intima-media thickness (IMT) and levels of vitamin D were significantly increased and decreased in pSS, respectively. No correlation was observed between low levels of vitamin D and IMT in pSS. Significant positive correlation between disease duration and IMT and negative between vitamin D levels and increased Sjögren syndrome disease activity index (SSDAI) and syndrome disease damage index (SSDDI) were also found in pSS.IMT of pSS with long disease duration is significantly increased with respect to that of OCp. Vitamin D deficiency does not play a role on IMT of pSS, whereas it plays a role in disease damage and activity. A long disease duration is associated with subclinical atherosclerosis in pSS.

Adipokines discovery opened a new research field that investigates the interface and the relationship between immune response, nutrition, and metabolism. Leptin is the first adipokine discovered and exerts a wide spectrum of biologic function such as control of food intake and energy expenditure, modulation of insulin sensitivity, regulation of neuro-endocrine system and activation of immunity. Leptin involvement is described in many autoimmune diseases. In SLE, leptin seems playing a complex role, linking metabolic syndrome, atherosclerosis, and autoimmune disease activity.

The difficulty in identifying, differentiating and expressing emotions is a neuropsychological condition called alexithymia. During the last years it has grown the interest of scientific community for alexithymia, in particular in2 chronic conditions. Crescent literature data demonstrated that a considerable number of SLE patients present difficulty not only in identifying, differentiating, and articulating emotions but also in differentiating them from bodily sensations, configuring the alexithymia complaint. Alexithymia seems to be not related to SLE disease activity but tightly related to mood states. Identify proper pharmacological and psychological approach to alexithymia in SLE patients is a major challenge for future research.

Introduction Systemic Lupus Erythematosus (SLE) is associated to an increased prevalence of Metabolic Syndrome (MeS) and to a reduction of Quality of Life (QoL). The aim of this study is to evaluate the association between MeS and QoL in SLE. Methods SLE patients were consecutively enrolled in a cross sectional study. MeS was defined according to IFD definition. Therapy with glucocorticoids (GC) and antimalarial was analyzed as cumulative years of exposure. We used a cut off of 7.5 mg of prednisone to define high daily dose of GC. QoL was quantified using SF-36. We used BDI and HAM-H to assess symptoms of mood disorders. Fatigue was evaluated using Facit-Fatigue, physical activity using IPAQ, sleep quality using PSQI and alexithymia using TAS-20. Results We enrolled 100 SLE patients. MeS prevalence was 34%. Patients with MeS presented reduced scores in SF-36 MCS and PCS compared to patients without MeS (p 0.03 and p 0.004). BDI and HAM-H score were significantly higher in patients meeting MeS criteria compared to subjects without MeS (p 0.004, p 0.02). These results were confirmed after adjustment for confounders. Compared to patients without MeS, those with MeS presented higher age, lower education level, higher recent SELENA-SLEDAI, higher number of flares, increased SDI, longer cumulative exposure to high dose GC and shorter duration of antimalarial therapy. In the multiple logistic regression model, the variable associated to the Odds Ratio of having MeS were: the average of recent SELENA-SLEDAI (OR 1.15 p 0.04), the years of exposure to high dose of GC (OR 1.18 p 0.004), the years of exposure to antimalarials (OR 0.82 p 0.03) and the BDI score (OR 1.1 p 0.005). Conclusion A modern management of SLE should not miss to take all the possible measures to ensure an adequate QoL to SLE patients, with particular attention to those affected by MeS.

Background Endocannabinoid (eCB) system comprises endogenous lipid mediators (eCBs) like N -arachidonoylethanolamine (anandamide, AEA) and 2-arachidonoylglycerol (2-AG), along with their specific G protein-coupled type-1 (CB 1 ) and type-2 (CB 2 ) cannabinoid receptors, and the proteins responsible for eCB biosynthesis, inactivation, transport, and accumulation. In recent years, many studies have evaluated the role of eCBs in the homeostasis of the immune system. Notably, AEA and the eCB-like molecule N -palmitoylethanolamine (PEA) seem to be anti-inflammatory mediators, while 2-AG is implicated in both pro-inflammatory and anti-inflammatory functions. Moreover, the effects of eCBs on immune system seem to be mostly mediated by CB 2 , more expressed in immune cells than by CB 1 . The latter receptor, instead, is more implicated in neurotransmission. Several studies have already investigated the role of eCB system in different immune-mediated diseases, such as multiple sclerosis and type-1 diabetes. Objectives To investigate the role of eCB system in patients with systemic lupus erythematosus (SLE) and age and sex matched healthy subjects. Methods 10 female patients with SLE and 10 healthy subjects were enrolled from outpatient clinic of Campus Bio-Medico University of Rome. Every SLE patient was positive for anti-dsDNA antibodies and/or exhibited hypocomplementemia with or without hypergammaglobulinemia, ENA or aPL positivity. None of them was treated with biological therapy at the time of enrolment, nor with steroid bolus in the previous six months, while treatment with conventional immunosuppressants was allowed. SELENA-SLEDAI and BILAG were used to assess disease activity and SDI as damage index. AEA, 2-AG and PEA levels were quantified in plasma of SLE patients and healthy controls by using liquid chromatography-tandem mass spectrometry (LC-MS). Results No significant difference among ages was found in the two groups (SLE patients 37.9±5.9 years, healthy subjects 37.8±6.2, p=ns). In SLE patients, 80% of the subjects exhibited low C3, 50% low C4, 90% anti-dsDNA positivity; 30% of them were not taking glucocorticoids, 20% ≤5 mg of daily prednisone and 50% >5 mg of daily prednisone; 70% were taking conventional immunosuppressive treatment and 80% were taking hydroxychloroquine. Value of the disease activity score evaluated by SELENA-SLEDAI was assessed as 6±4.7; 10% of the patients exhibited at least 1 BILAG A and 60% at least 1 BILAG B; value of the damage index evaluated by SDI was assessed as 0.6±0.8. eCBs was significantly altered in SLE patients. In particular, plasma levels of 2-AG were significantly increased in SLE patients compared to healthy controls (p=0.005), while no differences were found in AEA and PEA concentrations between the two groups. Conclusions Our results demonstrate, for the first time, an alteration of eCB system in SLE patients; these data may help to better understand the role of lipid mediators in SLE pathogenesis. References Fezza F. et al. Molecules. 2014; 19:17078–106. Gruden G. et al. Br J Pharmacol. 2015. doi: 10.1111/bph.13226 Disclosure of Interest None declared

Background Adipokines are citkokines mainly secreted by adipose tissue and involved in a wide spectrum of processes including metabolism, insulin sensitivity, atherogenesis and immunity. Leptin is the first adipokine discovered and plays important immunological functions. Crescent scientific data confirm the leptin involvement in many human autoimmune diseases. We described leptin hyperexpression in sera of female SLE patients, especially in fertile age, in relation with metabolic parameters and disease activity Objectives To evaluate the basal leptin levels in SLE patients who develop disease flares and damage accrual in 3 years follow-up. Methods We performed a retrospective evaluation of basal serum leptin levels, metabolic parameters and SLE disease features in 20 female SLE patients. For all subjects, complete data concerning disease activity and damage were available over a period of almost 3 years after the baseline assessment. Metabolic parameters included basal insulin, glycaemia, HOMA-IR, plasma lipid profile, BMI, waist-hip ratio. SLE disease features were expressed as anti-dsDNA positivity, complement fraction C3 and/or C4 depletion, disease activity measured by SELENA SLEDAI and disease damage evaluated by SDI. SLE disease flares were assessed by revised SFI index. Number of disease flares was evaluated during the fist year of follow-up and at the end of a 3 years follow-up. SDI was measured at baseline and at the end of year 3. Results We found hyperexpression of basal leptin levels in SLE patients who developed almost 1 flare at year 1 compared to patients without flares (p 0.002). Basal leptin in subject with almost 1 flare at the end of the 3 years of follow-up was higher in comparison with patients who didn9t develop disease flares (p 0.0003). Basal leptin was increased in patients who presented almost 1 new point of SDI at the end of the 3 years follow-up versus patients without SDI increase (p 0.0003). The survival curve of the time without a lupus flare in subjects with leptin above 50 percentile significantly differed compared to subjects with leptin levels below 50 percentile (p 0.003). Patients with almost 1 flare at year 1 and year 3 and subject with almost 1 new SDI point at year 3 presented increased basal HOMA-IR, BMI and basal SELENA-SLEDAI. At baseline, leptin levels positively correlated with HOMA-IR (r 0.8, p Conclusions We found basal leptin hyperexpression in SLE patients who developed disease flares and damage accrual in a 3 years follow-up period. These patients presented increased insulin-resistance and disease activity at baseline and leptin was tightly related to both these aspects. Further studies are required to evaluate the possible role of leptin as predictor of SLE prognosis References Margiotta DPE, Vadacca M, Navarini L, Basta F, Afeltra A. The complex role of leptin in SLE: is leptin a key link between metabolic syndrome, accelerated atherosclerosis and autoimmunity. Lupus: Open Access 2016; accepted. Vadacca M, Margiotta DP, Navarini L, Afeltra A. Leptin in immuno-rheumatological diseases. Cell Mol Immunol 2011; 8:203–212. Vadacca M, Margiotta D, Rigon A, Cacciapaglia F, Coppolino G, et al. Adipokines and systemic lupus erythematosus: relationship with metabolic syndrome and cardiovascular disease risk factors. J Rheumatol 2009; 36:295–297. Disclosure of Interest None declared

Background Interstitial lung disease (ILD) is the most common manifestation of rheumatoid lung disease (RA-ILD). The prevalence of RA-ILD is somewhere between 10 and 50 percent, depending on the study. In analogy with Systemic Sclerosis associated ILD (SSc-ILD), high resolution computed tomography (HRCT) has become the gold standard for diagnosis of RA-ILD. Literature data describe a strong correlation between HRCT pattern of ILD and histopathological subtypes. Moreover, different systems for evaluating SSc-ILD on HRCT and several scoring methods have been proposed for RA-ILD. Because of the uncertainty of the effect of traditional DMARDs and biologic agents on the development and course of ILD in patients with RA, careful pre-treatment assessment and subsequent monitoring are required. We present the results of the follow-up to 1 year of a cohort of patients treated with DMARDs and maintained in the therapeutic target (DAS28 low disease activity or remission). Objectives To evaluate the change in respiratory function and ILD HRTC score in a cohort of patients treated to target. Methods 24 RA patients in DMARD monotherapy and low dose steroid (dose of prednisone Results 19 of 24 patients were in MTX monotherapy (mean MTX weekly dose: 12.5 mg) and 5 were in Leflunomide monotherapy. Mean RA disease duration was 4.8 yr (±0.6 SD). 20 of 24 patients presented HRCT signs of ILD with Warrick score ≥1. At time 0 mean HRTC score was 8 (±5 SD), mean extension score was 4 (±2 SD) and mean severity score was 4 (±3 SD). At time 1 yr mean HRTC score was 8,04 (±3,73 SD), mean extension score was 3,37 (±1,86 SD) and mean severity score was 4,66 (±2,11 SD) (p=NS). Mean DLCO was 74 (±21 SD) at time 0 and 66 (±18 SD) at the end of follow-up (p=NS). We found no statistically significant modification in total lung capacity (TLC) and Tiffenau index (FEV1/FVC) during follow-up. Conclusions As previously reported, we found high prevalence of RA-ILD. In our treated-to-target RA cohort in DMARD monotherapy, we have not detected neither functional nor radiological progression during 1 year follow-up. In our cohort the DMARD therapy has not worsened the ILD. We can speculate that control the activity of joint disease with a strategy to treat target may contribute to prevent lung disease progression. Disclosure of Interest None declared