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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.

The 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, regional migratory osteoporosis, and reflex sympathetic dystrophy. Magnetic resonance imaging is used for early diagnosis and monitoring of its progression. Early differentiation from other aggressive conditions with longterm sequelae is essential in order to avoid unnecessary treatment. The aim of this monocentric trial was to test the efficacy and the safety of amino-bisphosphonate neridronate administered in two different regimens in patients with BMES. 192 patients with BMES secondary to osteoarthritis localized in the knee, hip, wrist or foot were randomly assigned to intravenous (iv) infusion of 100 mg neridronate given four times over 10 days (Group A, 72 subjects) or alternatively to iv infusions of 100 mg every 21 days over 3 months (Group B, 120 subjects). Magnetic resonance image (MRI) was performed at baseline and after 180 days. We assessed a 0-100 mm pain visual analogue scale (VAS) in each patient, too. Outcomes were MRI changes and VAS changes. A control group (35 patients) was enrolled too, treated conservatively with non-steroidal anti-inflammatory drugs and articular rest. 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 the control group (P

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.

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.

© 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

Not available

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

The Schnitzler syndrome (SCS) is a rare, late-onset acquired autoinflammatory syndrome often underdiagnosed. The diagnosis is based on the Lipsker and recently on validated Strasbourg diagnostic criteria (chronic urticarial rash, monoclonal gammopathy, intermittent fever, arthritis, arthralgia, bone involvement, hepatomegaly, splenomegaly, lymphadenopathy, dermal infiltration of neutrophils and laboratory markers of inflammation). Conventional therapies including anti-histamines, anti-inflammatory drugs, corticosteroids and immunosuppressive drugs that are usually ineffective. Recently the gold standard therapy of SCS are considered IL-1 blocking agents as anakinra, canakinumab, rilonacept that led to a significant control of clinical symptoms, even if a relapse could appear at suspension of the treatment. We report a case of a 63-year-old man with a recent diagnosis of SCS - after 6 years of symptoms of disease - refractory to several conventional immunosuppressive therapies and treated with anakinra, with sustained remission of clinic manifestations during treatment at 24 months of follow up.

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 (

Objectives: To validate the clinical significance of anti-IFI16 autoantibodies in SSc and assess their associations with serological markers of SSc. Methods: A semi-quantitative ELISA was used to detect anti-IFI16 autoantibodies in the sera of 344 SSc patients from seven Italian hospitals and 144 healthy controls. SSc-associated autoantibodies [anti-RNA polymerase III (anti-RNAP III) antibodies, anti-centromere, anti-topo I] and IF patterns were evaluated using commercial assays. Statistical analyses were performed to test clinical and serological associations. Results: The results of this study confirm a significant prevalence (29%) of anti-IFI16 antibodies in the SSc population (n = 344). Anti-IFI16 antibodies were also detected in 30% of the SSc patients who tested negative for both ACAs and anti-topo I (anti-Scl70) antibodies. In this subgroup of patients, anti-IFI16 antibodies were significantly associated with the limited cutaneous form of SSc with a sensitivity of 40% and a specificity of 81%. Moreover, analysis of the distribution of anti-RNAP III antibodies vs anti-IFI16 in the same SSc population showed that they were mutually exclusive. IIF revealed no association between anti-IFI16 and fluoroscopic patterns, due to a lack of IFI16 autoantigen in HEp-2 cells. Anti-IFI16 antibody levels were also significantly associated with heart involvement. Conclusions: Anti-IFI16 autoantibodies are frequently detected in SSc, displaying clinical and laboratory associations, and being particularly useful for diagnosis and disease classification in patients who are negative for other SSc serological markers. © The Author 2010. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved.

We describe a case of acute ischemia of the 2nd, 3rd and 4th fingers of the right hand secondary to peripheral vascular occlusive disease induced by repeated intra-arterial cocaine injections. The complete occlusion of the distal arteries resolved following treatment with iloprost, a synthetic stable analogue of prostacyclin PGI2, in addition to anticoagulants and antibiotics.

Background Many studies and review have been published concerning the use of hight does of immunoglobulin (IVG) in treatment of polymiositis (PM) or dermatomyositis (DM). Usually this treatment is not employed as first-line therapy, but in relapsing or in no response to conventional immunomodulator therapies. Normally the standard doses of IVG is 2 g/kg in 5 days, very rarely in 2 days and the treatment is usually continued for 3-6 months. Adverse effects are generally few and generally tolerable. Objectives We report our case series in which IVG were used a first therapeutic choice in order to induce a faster remission in acute PM-DM presentation. Methods We observed 15 patients (pts) (4M/11F) mean age 42,6 y (28-72 y) affected by acute PM – DM. Nobody developed a paraneoplastic syndrome. At the onset the mean values of serum creatin kinase (CPK) were 2980 U/l (nv All patients after an initial treatment with corticosteroids (3 pts received also high dose 6-metilprednisolon 1gr/day for 3 days) were treated her with immunoglobulin at a dose of 2g/kg distributed in 5 days for 6 months. Results After 3 infusions the CPK and MG levels were reduced to 70% compared to baseline and normalized after 5 infusions. The mean dosage of corticosteroid was gradually reduced and some immunosuppressant agents (Cyclosporin A in 2 pts, Mycophenolate Mofetile in 2 pts, Azathioprine in 3 pts), were gradually introduced while the other patients continued with a minimum dose of prednisone (5 mg/day), maintaining a complete remission. Dysphagia, short breath, mydriasis were completely resolved, a mild legs weakness persisted until the 6ht month, at HRCT also reticular pattern were improved. Conclusions The treatment with IVG in severe or rapidly progressive PM-DM has been documented in many open-label trials to be effective, especially in pts with lung involvement and esophageal involvement. Adverse effects were generally tolerable and therefore, it may propose the use of IGV use is suggested to induce a faster remission and to allow a faster tapering of the corticosteroid and introduction of immunosuppressive drugs. References Wan DX et al. Rheumatology 2012;31:801-6. Danieli MG et al. Autoimmun Rev 2014;13:1048-54. Disclosure of Interest None declared

Background Systemic Sclerosis (SSc) is an autoimmune disease characterized by fibrosis and vasculopathy. In patients with active SSc increasing values of the Th17 subset and of pro-fibrotic interleukins such as IL6, IL1 and IL17 were demonstrated, as compared to healthy controls. Iloprost, a stable prostacyclin analogue, has been shown to down regulate pro-inflammatory cytokines, but its role on T cells modulation is not completely understood Objectives To evaluate functional T cells subsets in patients with early SSc (eSSc) in basal conditions and after Iloprost treatment Patients and Methods A total of 7 previously untreated female patients with eSSC (mean age 41.7 years) were enrolled in this study. Two patients were positive for anti-scl70 autoantibodies and five for anti-centromer antibodies, with a mean skin score of 12 (nobody presented digital ulcers) and Medseger score of 5.1 (range 4.8 – 6.7). All patients were treated with i.v. Iloprost (0.3ng/kg for 6 hours in continuous infusion for 5 days). The analysis of T cells subsets, including Th1, TH2, Th17, quiescent CD8 (CD8+/CD38-/HLADR-) and activated CD8 (CD8+/CD38+/HLADR+) was carried out on peripheral blood samples by 8-color flow cytometry. Patients were studied first in basal condition and after 5 days of therapy. Fifteen healthy subjects were studied as controls. Results Our results shown: a) Low basal absolute values of CD4+T cells in patients with eSSc (mean 776.5/mL, range 424.8/mL-1520.4/mL) vs control group (mean 1048.1/mL, range 642/mL -1683/mL); b) Lower values of percent and absolute CD4+TH17+ cells in the eSSc group, mean 7.66% vs 12.59% (range 4.2% - 12.1% vs 2.7% - 20.3%, p Conclusions The literature data on T cell regulatory subsets in eSSc are scanty. Our approach included the phenotypic evaluation of CD4+Th17+ cells using CCR6 and CXCR3, so that our measured levels may be higher than those using direct intracellular IL17 evaluation. The low baseline level of CD4+Th17+ cells may be related to the very early phase of the disease, whereas the increase in activated CD8+ cells can be related to the anti-inflammatory and anti-fibrotic effects of Iloprost References Truchetet ME et al. Ann Rheum Dis 2012; 71: 2044-2050. Liu W et al. Prostaglandins Leukot Essent Fatty Acids 2013; 89: 335-344. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.5774

Background Pulmonary involvement represents a major cause of death of scleroderma patients. Cyclophosphamide showed a small beneficial effect in RCTs. There is a rational for the use of tyrosine kinase inhibitors as potential therapy for systemic sclerosis (SSc) and other fibrosing disorders. Preliminary published clinical trials are inconclusive about imatinib efficacy and showed relevant side effects. Objectives To verify efficacy and tolerability of low dose of imatinib on lung and skin fibrosis in a cohort of scleroderma patients refractory to conventional therapy. Methods A phase II multicentric open trial, which included 30 consecutive patients affected by SSc, with active pulmonary involvement, refractory to cyclophosphamide. The study followed a ‘Simon’s two-stage design’. Patients were treated with oral Imatinib 200 mg/day for 6 months. A “good response” was defined as the improvement both of pulmonary function tests and HRCT-scan pattern. Secondary outcomes were cutaneous involvement (mRSS) and quality of life. Results Seventy-two patients were screened, 42 were excluded. The mean age was 50.83 ± SD 13.8 years and mean disease duration was 5.5 ± SD 4.1 years, 9 (30%) were males and 21 (70%) were females, all Caucasian. According to cutaneous involvement 14 (46%) had limited and 16 (53.3%) had diffuse cutaneous SSc; 93.3% were anti-SCL-70 positives. At the end of the study (month 12) we had 27 completers, 3 patients were lost prematurely because of death. Data refer to 26 patients. Seven of 26 (27%) met the criteria for response. As for mean changes in pulmonary function tests and PaO2 in the whole group, after therapy we observed a worsening of FVC (mean delta -2,74 ± SD 8,13%) and PaO2 (a mean delta of -2.27 ± SD 1.3), with a further worsening after stopping therapy. TLC and DLCO remained substantially stable. The analysis of thoracic HRCT showed a significant reduction in the number of pulmonary segments interested by a ground glass pattern, which persisted after completion of therapy. No changes were detected in the areas interested by a honeycombing pattern. We didn’t observe any significant improvement either in the skin fibrosis or in quality of life. Among serious adverse events we registered 4 cases not related with the experimental drug. Three patients died prematurely and one developed a severe pneumonia in the follow up phase. Concerning minor adverse events they were present in less than 20% of patients, mainly transient and well tolerated. Conclusions According to Simon’s protocol 27% of patients responded, instead of 30% of expected rate, nevertheless, this trial demonstrated that low dose of imatinib stabilized lung involvement in scleroderma patients after failure of conventional therapy with cyclophosphamide, with radiographic improvement of the alveolitis. There was no significant improvement of skin involvement. Except for the 4 SAE the low dose was well tolerated. Together with other published trials these data will provide useful suggestions to design future RCTs. Acknowledgements This study was partially funded by AIFA (Agenzia Italiana del Farmaco). Disclosure of Interest None Declared

Objective. The aim of this study is to evaluate the expression of Peripheral Benzodiazepine Receptors (PBRs) on leukocytes in patients affected by primary fibromyalgia and to argue their possible role in pain perception and in modulation of immunologic process. Methods. The expression of PBRs has been evaluated by flow cytometry on monocytes, on lymphocytes and on granulocytes in twenty patients with primary fibromyalgia, with indirect immunofluorescence methods. Results. Upregulation of leukocyte PBRs expression has been demonstrated in fibromyalgia. A statistically significant difference has been documented only in monocytes. The monocyte PBRs expression was 26.74 14.84 MIF in fibromyalgia versus 17.45 8.54 MIF in controls (P < 0.023). Upregulation of PBRs expression, although not statistically significant, was also observed in lymphocytes and granulocytes. Conclusions. The monocyte PBRs overincrease in fibromyalgia may be due to abnormalities in the regulation of pain or to inflammation. It might perhaps explicate the possible mechanisms of therapeutic response to benzodiazepine in fibromyalgia.