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Aim. To assess the efficacy of belimumab in joint and skin manifestations in a nationwide cohort of patients with SLE. Methods. All patients with skin and joint involvement enrolled in the BeRLiSS cohort were considered. Belimumab (intravenous, 10 mg/kg) effectiveness in joint and skin manifestations was assessed by DAS28 and CLASI, respectively. Attainment and predictors of DAS28 remission (

Paget disease (PD) is a chronic disorder resulting in enlarged and misshapen bones, caused by disorganized bone remodeling. This case involves a 64-year-old man with prostatic adenocarcinoma and PD of some skeletal areas with increased uptake shown on 18 F-fluoro-methyl-choline (FMC) positron emission tomography/ computed tomography (PET/CT) performed for cancer restaging. Besides this feature, Paget disease may mimic metastases on PET/CT using various radiotracers, including 18 F-FMC PET/CT. In particular, this case highlights the potential of multiparametric disease characterization on PET. Therefore, in suspected cases, in which differential diagnosis is difficult, histology can be a helpful tool for diagnostic purposes.

During the past decades autoimmune diseases have been usually treated with immunosuppressive drugs mostly active on T-Cell mediated responses. Only in recent years, with our extended knowledge of the pathogenic mechanisms of autoreactive disorders and the tremendous development of new therapeutic monoclonal antibodies, anti-B-Cell therapies have emerged as a new option for treating autoimmune diseases. The rationale for this changeover from T-Cell to B-Cell targeted therapies resides in the recently accumulated evidence of the role of B-Cells in the pathogenesis of autoimmune diseases and in the generation of tissue damage. Targeting memory and effector BCells may then disrupt the production of pathogenic antibodies, counteract the role of B-Cells in sustaining antigen presentation to T-Cells and block the synthesis of B-Cell activation cytokines. The anti-CD20 monoclonal antibody Rituximab was first introduced more than 20 years ago for the treatment of CD20+ chronic B-lymphoproliferative disorders, and was then successfully experimented in the treatment of an ever-increasing spectrum of autoimmune diseases. Newer anti-CD20 monoclonal antibodies have been introduced more recently, which vary in their biological effects. The need for laboratory indicators that may help the rational usage and follow-up of anti-CD20 treatments has now emerged, due to the high variability of individual response, to the markedly different outcomes in the various diseases and to the controversial role of pathogenic autoantibodies as indicators of disease activity. Flow cytometric (FCM) analyses to identify and enumerate the B-cell functional subsets in the peripheral blood have been developed in recent years. They can be used to assess the degree and the persistence of memory B-Cell depletion, the quality and the timing of B-Cell reconstitution, along with the highly sensitive FCM counting technique needed for the detection of extremely low cell levels. The long-term aim of this innovative approach is to provide clinicians with a tool for a safer and more rational usage of anti-CD20 agents.

Rheumatoid arthritis (RA) is a systemic inflammatory disease, which primarily causes symmetric polyarthritis. An extrarticolar involvement is common, and the commonly involved organ is lungs. Although cardiac disease is responsible for most RA-related deaths, pulmonary disease is also a major contributor, accounting for ~10–20% of all mortality. Pulmonary disease is a common (60–80% of patients with RA) extra-articular complication of RA. Optimal screening, diagnostic, and treatment strategies of pulmonary disease remain uncertain, which have been the focus of an ongoing investigation. Clinicians should regularly assess patients with RA for the signs and symptoms of pulmonary disease and, reciprocally, consider RA and other connective tissue diseases when evaluating a patient with pulmonary disease of an unknown etiology. RA directly affects all anatomic compartments of the thorax, including the lung parenchyma, large and small airways, pleura, and less commonly vessels. In addition, pulmonary infection and drug-induced lung disease associated with immunosuppressive agents used for the treatment of RA may occur.

18F-fluorodeoxyglucose positron emission tomography/computed tomography (18-FDG-PET/CT) is a functional imaging technique which is an established tool in oncology, and has also demonstrated a role in the field of inflammatory diseases, such as large vessel vasculitis (LVV). In the last few years, it is known that atherosclerotic lesions with inflammation, detected by FDG-PET, are high-risk structural features and more likely to lead to subsequent progression of atherosclerosis with more clinical complications.

Immune checkpoint inhibitors (ICIs) targeting cytotoxic T-lymphocyte associated protein-4 (CTLA-4), programmed cell death protein-1 (PD-1), and its ligand PD-L1 are established cancer immunotherapies for solid tumor and hematologic malignancies. These therapies are involved in immune-related adverse events (irAE), both general and rheumatic ones. In general, immune-related adverse events (irAE) management includes drug-holding, tapering doses of corticosteroids, and specific immunosuppression for clinically severe cases, such as infliximab or mycophenolate.

© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ., Objectives: To determine factors associated with COVID-19-related death in people with rheumatic diseases. Methods: Physician-reported registry of adults with rheumatic disease and confirmed or presumptive COVID-19 (from 24 March to 1 July 2020). The primary outcome was COVID-19-related death. Age, sex, smoking status, comorbidities, rheumatic disease diagnosis, disease activity and medications were included as covariates in multivariable logistic regression models. Analyses were further stratified according to rheumatic disease category. Results: Of 3729 patients (mean age 57 years, 68% female), 390 (10.5%) died. Independent factors associated with COVID-19-related death were age (66-75 years: OR 3.00, 95% CI 2.13 to 4.22; >75 years: 6.18, 4.47 to 8.53; both vs ≤65 years), male sex (1.46, 1.11 to 1.91), hypertension combined with cardiovascular disease (1.89, 1.31 to 2.73), chronic lung disease (1.68, 1.26 to 2.25) and prednisolone-equivalent dosage >10 mg/day (1.69, 1.18 to 2.41; vs no glucocorticoid intake). Moderate/high disease activity (vs remission/low disease activity) was associated with higher odds of death (1.87, 1.27 to 2.77). Rituximab (4.04, 2.32 to 7.03), sulfasalazine (3.60, 1.66 to 7.78), immunosuppressants (azathioprine, cyclophosphamide, ciclosporin, mycophenolate or tacrolimus: 2.22, 1.43 to 3.46) and not receiving any disease-modifying anti-rheumatic drug (DMARD) (2.11, 1.48 to 3.01) were associated with higher odds of death, compared with methotrexate monotherapy. Other synthetic/biological DMARDs were not associated with COVID-19-related death. Conclusion: Among people with rheumatic disease, COVID-19-related death was associated with known general factors (older age, male sex and specific comorbidities) and disease-specific factors (disease activity and specific medications). The association with moderate/high disease activity highlights the importance of adequate disease control with DMARDs, preferably without increasing glucocorticoid dosages. Caution may be required with rituximab, sulfasalazine and some immunosuppressants.

Background: Belimumab was recently approved for treatment of lupus glomerulonephritis (LN). Aim: To evaluate renal response and its predictors in LN patients receiving belimumab in real-life. Patients and methods: We considered all patients fulfilling the SLEDAI-2K renal items and/or having estimated glomerular filtration rate (eGFR)≤60 ml/min/1.73 m2, with positive anti-dsDNA and/or low C3/C4 enrolled in the multicentre Italian lupus cohort BeRLiSS (BElimumab in Real LIfe Setting Study), treated with monthly IV Belimumab 10 mg/kg over standard treatment. Primary efficacy renal response (PERR), defined as proteinuria ≤0.7 g/24 h, eGFR≥60 ml/min/1.73 m2 without rescue therapy, was considered as primary outcome. Complete renal response (CRR; proteinuria

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OBJECTIVES: Italy was one of the first countries significantly affected by the coronavirus disease 2019 (COVID-19) epidemic. The Italian Society for Rheumatology promptly launched a retrospective and anonymised data collection to monitor COVID-19 in patients with rheumatic and musculoskeletal diseases (RMDs), the CONTROL-19 surveillance database, which is part of the COVID-19 Global Rheumatology Alliance. METHODS: CONTROL-19 includes patients with RMDs and proven severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) updated until May 3rd 2020. In this analysis, only molecular diagnoses were included. The data collection covered demographic data, medical history (general and RMD-related), treatments and COVID-19 related features, treatments, and outcome. In this paper, we report the first descriptive data from the CONTROL-19 registry. RESULTS: The population of the first 232 patients (36% males) consisted mainly of elderly patients (mean age 62.2 years), who used corticosteroids (51.7%), and suffered from multi-morbidity (median comorbidities 2). Rheumatoid arthritis was the most frequent disease (34.1%), followed by spondyloarthritis (26.3%), connective tissue disease (21.1%) and vasculitis (11.2%). Most cases had an active disease (69.4%). Clinical presentation of COVID-19 was typical, with systemic symptoms (fever and asthenia) and respiratory symptoms. The overall outcome was severe, with high frequencies of hospitalisation (69.8%), respiratory support oxygen (55.7%), non-invasive ventilation (20.9%) or mechanical ventilation (7.5%), and 19% of deaths. Male patients typically manifested a worse prognosis. Immunomodulatory treatments were not significantly associated with an increased risk of intensive care unit admission/mechanical ventilation/death. CONCLUSIONS: Although the report mainly includes the most severe cases, its temporal and spatial trend supports the validity of the national surveillance system. More complete data are being acquired in order to both test the hypothesis that RMD patients may have a different outcome from that of the general population and determine the safety of immunomodulatory treatments.

Introduction Alveolar haemorrhage (AH) is considered an important cause of morbidity and early mortality in anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitides (AAV). Objectives The aim of this study was to identify predictors of outcome in patients with AH-AAV and to evaluate outcome and causes of death in this subset. Materials and methods A multicenter retrospective study was conducted in 29 Italian Centers. Clinicians were asked to recruit all patients diagnosed with AAV-associated AH during the last 10 years, from 2007 to 2016. Univariate and multivariable analysis were performed. Results One-hundred and six patients were included (median age at onset of 55 years [IQR 42–67]). The majority were ANCA-positive (PR3 57.1%, MPO 33.7%) and 72.6% had also renal involvement. At presentation, anaemia was shown in 97 (92.4%) patients, hemoptysis in 54 (51.9%), respiratory failure in 68 (66.7%), of whom 48 (70.6%), requiring respiratory support. At the end of the 37 months [IQR 13–77] follow-up, 19/106 (17.9%) patients were dead. The main causes of death were active disease and infections. By stepwise regression analysis, age >65 years (HR 3.66 [95% CI 1.4–9.51], p = 0.008) and the need for respiratory support (HR 4.58 [95% CI 1.51–13.87], p = 0.007) at AH onset were confirmed to be predictive of mortality. Conclusions Predictors of outcome in AAV-AH were determined. Factors related to the patient's performance status and the severity of the lung involvement strongly influenced the outcome. Balancing harms and benefits for the individual patient in induction and maintenance treatment strategies is crucial.

Objective To investigate predictors of response, remission, low disease activity, damage, and drug discontinuation in patients with systemic lupus erythematosus (SLE) who were treated with belimumab. Methods In this retrospective study of a multicenter cohort of SLE patients who received intravenous belimumab, the proportion of patients who achieved remission, low disease activity, and treatment response according to the SLE Responder Index 4 (SRI-4) was determined, and the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI) was used to score disease damage yearly over the follow-up. Predictors of outcomes were analyzed by multivariate logistic regression with the results expressed as odds ratios (ORs) and 95% confidence intervals (95% CIs). Results The study included 466 patients with active SLE from 24 Italian centers, with a median follow-up period of 18 months (range 1-60 months). An SRI-4 response was achieved by 49.2%, 61.3%, 69.7%, 69.6%, and 66.7% of patients at 6, 12, 24, 36, and 48 months, respectively. Baseline predictors of response at 6 months included a score of ≥10 on the SLE Disease Activity Index 2000 (SLEDAI-2K) (OR 3.14 [95% CI 2.033-4.860]) and a disease duration of ≤2 years (OR 1.94 [95% CI 1.078-3.473). Baseline predictors of response at 12 months included a score of ≥10 on the SLEDAI-2K (OR 3.48 [95% CI 2.004-6.025]) and an SDI score of 0 (OR 1.74 [95% CI 1.036-2.923]). Baseline predictors of response at 24 months included a score of ≥10 on the SLEDAI-2K (OR 4.25 [95% CI 2.018-8.940]) and a disease duration of ≤2 years (OR 3.79 [95% CI 1.039-13.52]). Baseline predictors of response at 36 months included a score of ≥10 on the SLEDAI-2K (OR 14.59 [95% CI 3.54-59.79) and baseline status of current smoker (OR 0.19 [95% CI 0.039-0.69]). Patients who were in remission for ≥25% of the follow-up period (44.3%) or who had low disease activity for ≥50% of the follow-up period (66.1%) accrued significantly less damage (P = 0.046 and P = 0.007). A baseline SDI score of 0 was an independent predictor of achieving low disease activity in ≥50% of the follow-up period and remission in ≥25% of the follow-up period. Our findings suggest that the lower the baseline damage, the greater the probability of achieving remission over the course of ≥25% of the follow-up. Further, there was a negative association between the number of flares reported prior to belimumab initiation and the frequency of belimumab discontinuation due to inefficacy (P = 0.009). Conclusion In patients with active SLE and low damage at baseline, treatment with belimumab early in the disease may lead to favorable outcomes in a real-life setting.

Background:LN is still a severe manifestation of Systemic lupus erythematosus (SLE) and multitarget therapy is needed to control the disease especially in refractory cases.Objectives:To evaluate renal response in SLE patients with glomerulonephritis (GN) treated with Belimumab in real-life setting.Methods:Patients with proteinuria >0.5 g/24 h and/or active sediment at baseline enrolled in a multicentre Italian cohort of SLE patients (BeRLiSS study), treated with monthly iv Belimumab 10 mg/kg plus standard of care were considered in this study. Complete renal response (CRR) was defined as proteinuria 2 and no rescue therapy. Primary efficacy renal response (PERR) was defined as proteinuria ≤0.7 g/24 h, eGFR ≥60ml/min/1.73m2 and no rescue therapy. Prevalence and predictive factors of CRR and PERR at 12 and 24 months after Belimumab initiation were analyzed by multivariate logistic regression analysis.Results:A total of 91 patients were considered in this study, 79 female, mean age 40.51±9.03 years, mean disease duration 12.18±8.15 years, median follow-up time after Belimumab initiation 22 months. Twenty patients had baseline proteinuria ≥0.5 2 at baseline. Immunosuppresants were taken by 70 (76.9%) patients: 47 micofenolate, 15 azathioprine and 5 ciclosporine. Sixty patients (65.9%) were on antimalarials. During follow-up 34 (37.4%) patients achieved CRR. Among them 5 (14.7%) patients relapsed and 29 (85.3%) patients maintained remission. Mean time to achieved CRR was 9.71±5.91 months.High levels of baseline proteinuria were a negative independent predictor of CRR and PERR at 6 months (OR 0.044 CI95% 0.006-0.320 p=0.002 and OR 0.232 CI95% 0.091-0.596 p=0.002) and 12 months (OR 0.029 CI95% 0.002-0.556 p=0.019 and OR 0.056 CI95% 0.009-0.327 p=0.001). High levels of baseline creatinine were a negative independent predictor of renal response. Renal response at 6 months was a strong predictive factor of renal response at 12 and 24 months.Conclusion:Belimumab is an effective add-on therapy in the treatment of GN in real-life practice setting.Disclosure of Interests:None declared

Background Belimumab is the unique biologic therapy available for patients with SLE. Objectives To investigate effectiveness and safety of belimumab in SLE patients in clinical practice. Methods 458 active SLE patients (ACR criteria) from 24 Italian Centers, mean±SD age 43.5±11.3 years; mean±SD disease duration 12.3±8.7 years, were treated with belimumab (10 mg/kg day 0, 14, 28 and then every 28 days), as add-on therapy. SLEDAI-2K, anti-dsDNA, C3, C4, prednisone daily dose, DAS-28, 24H proteinuria, CLASI, PGA, Fatigue (VAS 0-10) were recorded at baseline and every 6 months. Flares were defined according to SFI. Response was evaluated according to SRI-4. Statistics were performed by pairs T-test, chi-square test and multiple logistic regression (SPSS, version 22.0). Results Mean±SD follow-up was 21.2±15.3 months (range 3-60). Most common features treated with belimumab were articular in 67%, mucocutaneous in 55%, and renal in 17% of cases. Improvement of clinical and serological variables, including daily prednisone dosage, was observed (Table). SRI-4 is summarized in the Figure. At the end of follow-up 293 patients (66%) were still on belimumab. Most common cause of discontinuation were inadequate response (36%), AEs (31%), and pregnancy (8%). Mean number of flare during belimumab treatment compared with the corresponding period before belimumab initiation decreased (p 9,998 infusions were analyzed. 784 AEs were observed in 330 patients, SAEs were 43 in 36 patients. No severe infusion reactions were observed; 16 patients had infective SAEs, and 22 non infective SAEs. Conclusion We confirmed the effectiveness, the steroid sparing effect and good safety profile of belimumab in our cohort. Disclosure of Interests Luca Iaccarino: None declared, Francesca Saccon: None declared, Alessandro Mathieu: None declared, Matteo Piga: None declared, Angela Ceribelli: None declared, Carlo Selmi Grant/research support from: Abbvie, Janssen, MSD, Novartis, Pfizer, Consultant for: Abbvie, Alfa-Sigma, Biogen, BMS, Celgene, Eli-Lilly, GSK, Janssen, Merck Sharp and Dohme, Novartis, Pfizer, Roche, Sanofi-Genzyme, YCB, Speakers bureau: Abbvie, Alfa-Sigma, Biogen, BMS, Celgene, Eli-Lilly, GSK, Janssen, Merck Sharp and Dohme, Novartis, Pfizer, Roche, Sanofi-Genzyme, YCB, Paolo Cardinaletti: None declared, Armando Gabrielli: None declared, Andrea Di Matteo: None declared, Rossella De Angelis: None declared, Paola Faggioli: None declared, Antonella Laria: None declared, Micaela Fredi: None declared, Francesca Regola: None declared, Laura Andreoli: None declared, Giulia Pazzola: None declared, Carlo Salvarani: None declared, Francesco Puppo: None declared, Simone Negrini: None declared, Marcella Prete: None declared, Vito Racanelli: None declared, Elisa Gremese Consultant for: AbbVie, BMS, Celgene, Janssen, Lilly, MSD, Novartis, Sanofi, UCB, Roche, and Pfizer, Speakers bureau: BMS, Speakers bureau: Roche, Speakers bureau: AbbVie, BMS, Celgene, Janssen, Lilly, MSD, Novartis, Sanofi, UCB, Roche, and Pfizer, Maria Gerosa: None declared, Tania Ubiali: None declared, Enrica Bozzolo: None declared, Valentina Canti: None declared, Fabrizio Conti: None declared, Fulvia Ceccarelli: None declared, Elena Bartoloni Bocci: None declared, Roberto Gerli: None declared, Antonio Lobasso: None declared, Amato De Paulis: None declared, Ginevra De Marchi: None declared, Salvatore De Vita Grant/research support from: Roche, Pfizer, Abbvie, Novartis, BMS, MSD, Celgene, Janssen, Consultant for: Roche, Alessandra Bortoluzzi: None declared, Marcello Govoni Paid instructor for: Pfizer, Roche, Speakers bureau: Pfizer, Abbvie, MSD, Roche, Eli-Lilly, Celgene, Sanofi, Janssen, Francesco Benvenuti: None declared, Margherita Zen: None declared, Marta Mosca Paid instructor for: GlaxoSmithKline, Lilly, UCB, Chiara Tani: None declared, Maurizio Rossini: None declared, Giovanni Orsolini Speakers bureau: Grunenthal, Mariele Gatto: None declared, Salvatore Scarpato: None declared, Enrico Brunetta: None declared, Aurora Zumbo: None declared, Gabriele Valentini: None declared, SERENA FASANO: None declared, Giacomo Emmi: None declared, Maria Letizia Urban: None declared, Giacomo Tanti: None declared, Angela Tincani Consultant for: UCB, Pfizer, Abbvie, BMS, Sanofi, Roche, GSK, AlphaSigma, Lillly, Jannsen, Cellgene, Novartis, Andrea Doria: None declared

Good’s syndrome (GS) or thymomaassociated immunodeficiency is a rare clinical entity that should be ruled out in patients with thymoma who develop severe, recurrent bacterial infections and opportunistic viral and fungal infections. There are no treatment protocols established, hence, early recognition is imperative to avoid complications. We report the case of a 42-year-old female, known for a previous thymectomy for giant thymoma who has suffered for a long time from recurrent pulmonary and urinary tract infections and cold sores. In March 2016 she referred to our unit complaining of fever, cough, chest pain, and cold sores due to Herpes simplex virus (HSV), confirmed serologically as HSV-1. Chest X-ray showed left pneumonia due to Streptococcus pneumoniae. She started antibiotics (amoxicillin/clavulanic acid associated with azithromycin) with gradual improvement. Given her history she was studied for an underlying immunodeficiency: IgG, IgA, and IgM were significantly low or absent, as well as all IgG subclasses; blood and bone marrow aspirate leucocyte immunophenotyping showed complete absence of B lymphocytes and reduced CD4+ T cells. In light of: i) thymoma; ii) B lymphocyte deficit; iii) hypogammaglobulinemia; iv) recurrent infections, GS was diagnosed and pre-emptive immunoglobulin treatment, associated with HSV and Pneumocystis jiroveci prophylaxis (Acyclovir for HSV and Sulfamethoxazole- Trimethoprim for P. jiroveci) were started. Since then the patient has no longer presented any infectious episodes.

Background: Rituximab (RTX) is being increasingly used in treatment of several autoimmune diseases, including Rheumatoid Arthritis (RA).RTX induces a deep depletion of all peripheral B-Cell subsets (memory and naive B-cells). During the B-Cell repopulation phase, occurring approximately after 3 months of RTX administration, B-precursors and naive cells reappear.Several studies have shown that relapsing RA patients are characterized by a relative expansion of memory B cells during the B-Cell repopulation phase Objectives: The aim of this study was to quantify the memory B-Cell compartment in RA patients with different disease activity scores, evaluated by DAS28, during RTX treatment Methods: 26 RA patients under RTX treatment were studied. At the end of th treatment 8/26 showed high-to-moderate activity risk (median DAS28=4.8) and 18 low activity risk or remission (median DAS28=2.69). After a median of 3 months from last RTX infusion, B-Cell subsets (precursors, naive, memory B cells and plasma cells) were quantified in peripheral blood by flow cytometry, using a panel of 8 markers (CD3, CD4, CD8, CD19, CD20, CD27, CD38 and CD45). B naive cells were identified as CD19+ CD20+ CD27-, B memory cells were identified as CD19+ CD20+ CD27+, plasma cells as CD19+ CD38++ CD27++ CD20- and B precursors as CD19+ CD38++ CD20- CD27-, respectively. Percent and absolute values were calculated for each subset. In adition 10 healthy subjects were included as negative control group (NC). Results: The median percent and absolute values of B naive cells, B memory cells and plasma cells identified in NC, non-responder RA patients with high/moderate disease activity and responder RA patients with low disease activity or in remission are reported in Table 1. The virtual absence of peripheral B-Cell was defined as Conclusion: We used a sensitive and easily applicable flow cytometric multicolor panel that allowed the accurate and standardized identification and enumeration of peripheral blood B-Cell subsets. As reported by other studies, higher levels of memory B-Cells were found in non responder RA patients treated by RTX, approaching those of healthy individuals. References [1] Lopez J. Clin Exp Rheumatol2018; Dec 19. Sellam J. Arthritis Rheum 2011; 63: 3692-3701.Dass S. Arthritis Rheum2008; 58: 2993-2999 Disclosure of Interests: None declared

Objective Some of the manifestations of mixed cryoglobulinemia syndrome (MCS) can be severe or life-threatening, and should be rapidly contained but, as the therapeutic approaches to such conditions are largely based on anecdotal data, a consensus conference was organised by the Italian Group for the Study of Cryoglobulinemia (GISC) with the aim of providing a set of recommendations based on an in-depth survey of the available data and expert opinion. Methods The consensus panel, which included specialists working in different medical fields involved in the management of MCS patients, was first asked to divide the manifestations of MCS into severe or life-threatening conditions on the basis of their own experience, after which a complete literature review was carried out in accordance with the Cochrane guidelines for systematic reviews. Results Therapeutic plasma exchange (TPE) was considered the elective first-line treatment in the case of life-threatening manifestations of MCS (LT-MCS) and patients with severe clinical symptoms (S-MCS) who fail to respond to (or who are ineligible for) other treatments. The data supporting the combined use of cyclophosphamide and TPE were considered limited and inconclusive. High-dose pulsed glucocorticoid (GCS) therapy can be considered the first-line treatment of severe MCS, generally in association with TPE. Rituximab (RTX)-based treatments should be considered in patients with skin ulcers, peripheral neuropathy or glomerulonephritis, and in patients with persistent LT-MCS after TPE. In patients with hepatitis C virus-related MCS with S-MCS, viral eradication should be attempted as soon as a patient's condition allows the use of direct-acting antivirals.

Background:Osteoporosis is a recognized health problem and the burden of the disease is mostly associated with the occurrence of hip and vertebral fracture.Objectives:This study was aimed at evaluating the prevalence of osteoporosis in Italian postmenopausal women, defined by DeFRA calculation as a 10 years fracture risk equal or higher than 20%.Methods:This is a monocenter cohort study evaluating 1850 post-menopausal women aged 50 years and older. All the participants were evaluated as far as anthropometrics. Defra questionnaire was administered and calculated with bone mineral density (DXA) measured at lumbar spine and femoral neck.Results:The prevalence of osteoporosis as assessed by DeFRA was 29.8% in the whole population, according to literature. The frequency of a risk fracture equal or higher than 20% varied from 7.9% in the group aged 50-59 years to 35% in subjects aged >80. Among clinical risk factors for fracture, the presence of a previous fracture (spine primarily) was the most commonly observed.Conclusion:Our data showed that about one third of post-menopausal women aged 50 and older in Italy has osteoporosis on the basis of DeFRA algorithm, with a high 10 years fracture risk. A previous fracture is the most common risk factor. The data should be considered in relation to the need to increase prevention strategies and therapeutic intervention.Disclosure of Interests:None declared

Background:Bone Marrow Edema Syndrome (BMES) is a severely disabling pain syndrome without a definite treatment and refers to transient clinical conditions with unknown pathogenic mechanism, such as transient osteoporosis of the hip (TOH), regional migratory osteoporosis (RMO), and reflex sympathetic dystrophy (RSD). Magnetic resonance imaging is used for the early diagnosis and monitoring the progression of the disease. Early differentiation from other aggressive conditions with long-term sequelae is essential in order to avoid unnecessary treatment.Objectives:Aim of this monocentric trial was to test the efficacy and the safety of the amino-bisphosphonate neridronate in patients with BMES administered in two different regimens.Methods:192 patients with BMES secondary to osteoarthritis localized to knee, hip, wrist or foot were randomly assigned to I.V. infusion of 100 mg neridronate given four times over 10 days (Group A, 72 subjects) or alternatively to I.V. infusions of 100 mg every 21 days over 3 months (Group B, 120 subjects). At baseline and after 180 days we performed an MRI. We assessed a 0-100 mm pain VAS in each patient, too. Outcomes were to evaluate the MRI changes and the VAS changes. A control group (35 patients) was enrolled too, treated conservatively with NSAIDs and articular rest.Results:we observed a significant improvement in MRI with the resolution of bone marrow lesions present at the baseline (p0.1). Both groups showed a significant clinical and radiologic improvement compared with control group (pConclusion:In patients with BMES, the infusions of neridronate 100 mg every 21 days over 3 months or alternately every 3 days over 10 days are associated with clinically relevant and persistent benefits without significant differences between the two treatment-schedules. These results provide conclusive evidence that the use of bisphosphonates, at appropriate doses, is the treatment of choice BMES.Disclosure of Interests: :None declared

Background:In Systemic Sclerosis (SSc) fibrosis is due to microcirculation damage with capillary necrosis, arteriolar intimal proliferation and local ischemia. loprost (ILO) is used IV for the treatment of severe Raynaud phenomenon (RP) and digital ulcers (DU) in (SSc). We have already described (1) an improvement of peripheral vascularization with ILO, observed after 3 years treatment by capillaroscopy with an increase in the capillary number and mild regression of avascular areas and pericapillar oedemaObjectives:Our aim was to observe capillaroscopic changes in a cohort of 26 patients treated with ILO, once a month (25 – 50 ng each infusion) for an average time of 15 yearsMethods:We evaluated the initial and 2019 capillaroscopic picture of 26 SSc patients (24 W,2 M; median age 63.8Y) in continuous treatment with monthly infusion of ILO from 2004 to today. 6/26 were SCL70 positive;the remainder was positive for anticentromere AbResults:We documented stability of capillaroscopic picture in 62% of patients,an improvement in 19% and a worsening (mainly from early to active pattern) in 19%. Low adherence to therapy was observed among the worsened patients. Out of 8 patients with onset ulcers, only 3 patients still have skin ulcers, all with late stable capillaroscopic picture from onset.We have not documented serious adverse eventsConclusion:Our observations confirm the efficacy and safety of ILO in the treatment of SSc even after many years of treatment, resulting in a stabilization of microvascular damage, independent of disease severity.References:[1]Possible role of iloprost (stable analog of PG12) in promoting neoangiogenesis in systemic sclerosis. Faggioli P, Giani L, Mazzone A. Clin Exp Rheumatol. 2006 Mar-Apr;24(2):220-1. No abstract availableDisclosure of Interests:None declared

Background:Systemic sclerosis (SSc) is a systemic autoimmune disease characterized by progressive cutaneous and internal organ fibrosis. Orofacial manifestations are disabling and treatment options are limited. Fat Tissue Grafting (FTG) can be used for treating facial manifestations of the fibrosis.Objectives:In this study, we aimed to assess the safety and efficacy of FGT of our cohort of patients with SSc.Methods:We enrolled 20 SSc (18 W, 2 M) patients, from 2016 to 2019, suffering from facial sclerosis and restricted mouth opening capacity. FTG was carried out in accord with modified Colemans’ procedure (1): fat tissue was taken from periumbilical or trochanteric areas and was injected in 8 different points around the mouth. No side effects or adverse reactions have been documented. Evaluations included mouth opening capacity by measuring interincisal distance, oral functionality (MHISS scale) and patient global satisfaction (by Global Health scale).Results:A 11 mm (8 - 18mm range) median increase of interincisal distance was reported at month 6 and in 80% of patients at month 12, too (pConclusion:Our results showed that FTG improved mouth opening capacity and that aesthetic and functional results were satisfying to about 90% of the patients; long-term effects of this type of treatment are currently unknown. However, our and litterature data at 12 months follow-up seems to confirm the benefits in long term, despite the filling effect is over.This study – that’s one of the largest case series described right now (2) - supports the possible therapeutic role of autologous FTG in improving facial scleroderma both in aesthetic and in functional aspects.References:[1]Coleman SR. Structural fat grafting: more than a permanent filler. Plast Reconstr Surg. 2006; 118: 108S-20S[2]Fat Grafting for the Treatment of Scleroderma.Strong AL, Rubin JP, Kozlow JH, Cederna PS. Plast Reconstr Surg. 2019 Dec;144(6):1498-1507. doi: 10.1097/PRS.0000000000006291.Disclosure of Interests:None declared

Background Myasthenia gravis(MG) is an autoimmune disease frequently associated with antibodies against the acetyl-choline receptor. These antibodies contribute to the characteristic defects in neuromuscular transmission. Inflammatory myopathies, as polymyositis(PM), are immune-mediated neuromuscular diseases. PM and MG present both with muscle weakness and other similar features; electrophysiological and laboratory features of each of them are distinct. In Literature there are only few reports about PM and MG association Objectives To evaluate the prevalence of MG in patients with PM in our case series Methods We enrolled patients with PM/DM visited in our Centre in past 10 years;diagnoses of PM/DM were based on Bohan and Peter criteria. The follow-up was conducted until December 2017 Results We made 17 PM/DM diagnosis:14 F and only 3 M aged 41–85 years (mean 65 y). We found 6 patients (42,8%) with association of PM ad MG. They are all F, aged 51–78 years (mean 61 y) who developed inflammatory myositis confirmed by increasing of CK, EMG, autoantibodies pattern positivity and deltoid biopsy. Paraneoplastic, post-infectious or post-vaccinal syndromes was excluded. At the onset all presented progressive proximal muscle weakness and pain and asthenia. After initial treatment with oral corticosteroids (0.5–1 mg/kg/day methylprednisolone) a minimal response was observed only as improvement of asthenia and decreasing of CK levels. After one month of therapy 2 patients developed a bilateral palpebral ptosis, one disphagya and mild dyspnea, one a severe intestinal pseudo-obstruction,2 a mild dysarthria, ipovision and a worsening of muscular tone. Pyridostigmine test was positive in all patients;antiAChR antibodies levels were high. We started high doses corticosteroids (methylprednisolone 500–1000 mg/day for 5 days)and pyridostigmine (180–240 mg/day)with smart improvement. After this we introduced an immunosuppressant:azathioprine in 3 patients, mycophenolate mophetile in 4 patients. At the same time, because of the severity of the disease, monthly cycles of high doses IgV (20 g/kg in 5 days) were performed in 5 patients.A stable remission was achieved and maintained in all patients Conclusions This is one of the largest case series of patients with PM/DM-MG overlap. Our findings suggest that this association is not so rare and that patients affected by PM presenting palpebral ptosis, diplopia, gastrointestinal or oral symptoms, bulbar symptoms, weakness, asthenia, should be evaluated to exclude a concomitant MG, despite the absence of thymic pathology.A patient with PM-MG overlap should allow us for proper management of both conditions. This may include a more adequate therapy providing simultaneous association between immunosuppressant, pyridostigmine and, if necessary, a short time of high doses IgV therapy References [1] Santos E,et al. Inflammatory myopathy associated with myasthenia gravis with and without thymic pathology:Report of four cases and literature review. Autoimmun Rev2017Jun;16(6):644–649. [2] 2 Sanguesa Gomez C, et al. Dermatomyositis and myastenia gravis:An uncommon association with therapeutic implications. Reumatol Clin 2015 Jul-Aug;11(4):244–6. [3] Paik JJ, et al. The Co-Existence of Myasthenia Gravis in Patients with Myositis:A Case Series. Semin Arthritis Rheum. 2014 June;43(6):792–796. Disclosure of Interest None declared

Background Diffuse alveolar haemorrhage (DAH) is a rare and severe manifestation of ANCA-associated vasculitides (AAV). Objectives To identify predictors of survival in patients with AAV-DAH. Methods A retrospective study of 102 consecutive patients (50% females; mean age 59±17 years) from 27 Italian Centres diagnosed with AAV-DAH was planned. Cox regression unadjusted analyses were performed. Results Among AAV patients, 47% had Granulomatosis with Polyangiitis (GPA), 47% Microscopic Polyangiitis (MPA) and 6% Eosinophilic Granulomatosis with Polyangiitis (EGPA). At DAH onset, mean BVAS was 20±8 and most patients had renal involvement (RI). Admission to Intensive Care Unit was needed in 27% of patients, while ventilatory support (VS) was required in 46%. At least one cardiovascular risk factor (CVRF) was recorded in 48%. Over a median follow-up of 39 months (25%–75% IQR 66 months), 19/102 patients (18.6%) died (figure 1). All patients received high-dose glucocorticoids in association with Cyclophosphamide (CYC 78%, mean cumulative dose 8±7 g) or Rituximab (37%). Plasma exchange was performed in 46%. Infections occurred in 38%. Age>65 years (HR 3.05 [95% CI 1.18–7.9], p=0.04), CVRF ≥2 (HR 8.85 [95% CI [AG7] 2.34–33.50], p=0.01), BVAS (v.3) (HR 1.07 [95% CI 1.01–1.13], p=0.01) were associated with mortality, whereas FFS was not. The need for VS (HR 4.54 [95% CI 1.48–13.85], p=0.008) and infections (HR 3.98 [95% CI 1.48–10.69] were also associated with mortality. Conclusions Older age, VS, CVRF and infections affect the survival in AAV. There is a need for specific outcome measeures. Disclosure of Interest None declared

Background Bone Marrow Oedema Syndrome (BMES) is a severely disabling pain syndrome without a definite treatment well established. Objectives The aim of this monocentric prospective trial was to test the efficacy and the safety of the amino-bisphosphonate neridronate in patients with BMES administered in two different schedules. Methods one hundred seventy-three patients with BMES at various joints were consecutively assigned to I.V. infusion of 100 mg neridronate given four times over 10 days (Group A) or alternatively to I.V. infusion of 100 mg every 21 days over 63 days (Group B). At baseline (T0) and after 90 days from the first infusion we performed a MRI (T2). We assessed a 0–100 mm pain VAS in each patient at T0, at the day of the last infusion (T1: day 10 for group A and day 63 for group B) and at T2. Primary outcome was to evaluate the MRI changes, secondary endpoint was the VAS change. Results we observed a significant improvement in MRI with the resolution of bone marrow oedema present at T0 (p 0.1). Conclusions In patients with BMES, the infusions of neridronate 100 mg every 21 days over 3 months or alternately every 3 days over 10 days are associated with clinically relevant and persistent benefits without significant differences between the two treatment-schedules. These results provide conclusive evidence that the use of bisphosphonates, at appropriate doses, is the treatment of choice BMES Disclosure of Interest None declared

Introduction Catastrophic antiphospholipid syndrome (CAPS) is a rare and fatal condition secondary to antiphospholipid syndrome (APS) characterised by venous and/or arterial thromboembolism within a short period of time in the presence of positive AP antibodies. Thrombocytopenia is seen in >60% of cases. Here we report 2 cases of women with fatal CAPS.Case reports1.A 55-old female affected by APS (excluded overlap SLE), treated initialy with warfarin, due to previous DVT, than apixaban after a new EP episode, was admitted to our Unit for dyspnea: we found a mitral valve injury. After few days she developed a neurologic impairment with evidence of post-ischaemic alterations, likely embolics, and a sensory – motor neuropathy. We concluded for probable CAPS and started antibiotics plus high dose corticosteroids, unfractionated heparin and plasma exchange. However, we observed further worsening. The patient quickly succumbed to her illness. Case report 2. A 59-old female affected by SLE with CSN impairment and APS with thrombocytopenia and recurring DVT – EP episodes treated with low dose methylprednisolone, iloprost and heparin (warfarin suspension for severe thrombocytopenia impairment) was admitted to our Unit for appearance of diarrhoea with abdominal pain. Blood tests showed further worsening of platelet count. We started antibiotics with clinical improvement. Taking into account the patient history CT was performed, with evidence of massive arteriovenous and aortic arterial disease severe thrombotic obstruction. Two days later she developed acute pain on the left foot with massive venous thrombosis of the left femoro-popliteo axis. We started unfractionated heparin, despite low platelet value, as rescue therapy. Tthe patient progressively worsened with further progression of the arterial occlusions, until death, 3 days later. Conclusion CAPS can lead to acute multiorgan failure and can be associated with infections or SLE. Early recognition is essential for effective life-saving treatment. Management of these patients is complex, especially in those with thrombocytopenia. Anticoagulation plus steroids plus plasma exchange should are the first line therapy but our two cases show that they are not always applicable and effective. New therapies, such as rituximab and eculizumab, may be options, but time is a fundamental variable.

Capillaroscopy is an actual inexpensive imaging technique, used to examine, non-invasively and safely, the morphology of nailfold dermal papillary capillaries. Many studies agree in the statement that the capillaroscopy is one of the gold standard methods for non-invasive examination of the microcirculation and it plays an important role in screening in Raynaud’s phenomenon and in monitoring of systemic sclerosis and other rheumatologic diseases. There are also many reports on the possible use of nailfold capillaroscopy in the diagnosis and monitoring of many other diseases in internal medicine.

Purpose: The study aims at assessing the organizational and economic impact related to the use of a new portable syringe pump (Pompa Infonde®, Italfarmaco S.p.A., Cinisello Balsamo, Italy) at a hospital level. Methodology: Based on the HTA approach, the analysis assessed the organizational and economic impact of the new device at hospital level, using the traditional methods of Iloprost infusion as comparator. After a pilot evaluation, the organizational impact was assessed within 24 Italian hospitals. Structured interviews were conducted with clinicians and nurses. According to the Hospital-Based HTA approach, a questionnaire assessed the impact on human resources, training activities, internal meetings, spaces needed, facilities, clinical practice implications. Using Activity Based Costing approach, the economic evaluation was performed within the pilot center “Ospedale Civile” of Legnano, Italy. Findings: The new device leads to a positive managerial impact, with a substantial reduction of time to monitor patients by nurses. This resulted in a better management of human resources and in a reduction in nursing cost. Although a mild negative impact on training time for personnel, the structured interviews allowed the identification of three main areas of positive impact: (i) efficiency of internal processes, (ii) clinical pathways, (iii) synergies between wards. Originality: The organizational impact of Pompa Infonde®, showed that it is an efficient alternative to traditional methods, with benefits in the management of patients administered with Iloprost.

Summary Background Iloprost, prostacyclin (PGI2) analogue, effective in treatment of peripheral arterial disease, secondary Raynaud's phenomenon (RP) to connective tissue disease (CTD), vasculitis, pulmonary hypertension, is usually infused through peristaltic pump, or recently through a flow regulator. Materials and methods We tested a new portable syringe pump (Pompa Infonde®, Italfarmaco S.p.A., Cinisello Balsamo, Milano) on 120 patients affected by RP to CTD and cryoglobulinaemia, in iloprost therapy with a flow regulator. Results Iloprost infused through portable syringe pump is better tolerated, better appreciated by the patients and nurses and no difference was observed on therapeutic effects, with a lower incidence of side effects statistically significant. Only 3 patients were unable to tolerate the device (2 for changes in pressure and 1 for fear) and shifted to traditional method of iloprost infusion. Conclusions Iloprost infusion through the portable syringe Pompa Infonde® appears to be safe, better tolerated, more acceptable and equally effective compared to infusion through a flow regulator.

Summary Introduction Iloprost is a potent prostacyclin (PGI2) analogue that is effective in the treatment of peripheral arterial disease, vasculitis, pulmonary hypertension, and secondary Raynaud's phenomenon. Intravenous infusions are generally administered with the aid of a peristaltic pump to reduce the risk of adverse reactions caused by unintentional increases in the infusion rate. This increases the cost of care in terms of equipment and personnel and may limit the use of this drug. Materials and methods We retrospectively analyzed 18,432 iloprost infusions administered between 1999 and 2009 to 272 patients with systemic sclerosis (n = 253) and 19 with peripheral arterial disease (n = 19). All infusions were administered in the day hospital over 6 h with a normal IV set-up with a roller flow regulator. Flow rates were set to deliver iloprost at 1-2 ng/kg/min. Rates were verified by direct drop counts during the first 15-20 minutes of the infusion and at each subsequent check. Results There were no adverse events that were fatal, life-threatening, or associated with prolongation of hospitalization and very few events requiring intensive care or continuous monitoring. The latter included 4 cases of tachycardia/arrhythmia (extrasystoles in most cases), 3 cases of hypotension (systolic pressure 170/100 mmHg). All other adverse reactions were mild, reversible, and similar to those seen with iloprost infusion with peristaltic pump. Only one patient had to be switched to another prostanoid (due to intolerance). Discussion Iloprost infusion administered with a normal IV flow regulator appears to be as safe, well tolerated, and effective as traditional infusion with a peristaltic pump.

Background Iloprost has beneficial effects on microcirculation by preventing platelet and leukocyte reciprocal activation, which is known to lead to endothelial damage and acute thrombosis. This drug also reduces inflammatory system activation by decreasing αΜβ2 integrin expression on the phagocyte membrane, might have a role in the protection and restoration of endothelial integrity and might interact with coagulation cascade activation. Design Forty patients were enrolled: 29 with systemic sclerosis (SSc) and 11 with peripheral artery disease (PAD). Iloprost was administered for 5 days in the first group and for 21 days in second group of patients. To ascertain whether iloprost modifies the parameters of endothelial and coagulation cascade activations, the plasma concentrations of S-ICAM-1 and F1 + 2 were detected in patients at baseline, after 5 days and, in PAD patients only, after 21 days of iloprost therapy. S-ICAM-1 is the endothelial counter receptor for αΜβ2 integrin and is a marker of endothelial cell activation; and F1 + 2 is a marker of coagulation cascade activation. Results After infusion of iloprost a significant decrease of S-ICAM-1 was observed in both the SSc (P

Objective To assess fetal and maternal outcomes in women with systemic sclerosis (SSc). Methods Prospectively collected data on 99 women with SSc from 25 Italian centers were analyzed retrospectively. Women with SSc were observed during 109 pregnancies (from 2000 to 2011), and outcomes were compared to those in the general obstetric population (total of 3,939 deliveries). The maternal age at conception was a mean ± SD 31.8 ± 5.3 years, and the median disease duration at conception was 60 months (range 2–193 months). Results SSc patients, compared to the general obstetric population, had a significantly increased frequency of preterm deliveries (25% versus 12%) and severe preterm deliveries (