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Objective To report baseline data of SLE patients enrolled in the Lupus Italian Registry (LIRE). Methods Patients affected by SLE aged ≥ 16 years were consecutively recruited in a multicenter prospective study comparing two cohorts: patients starting biologic immunosuppressants (BC) and patients starting non-biologic immunosuppresants (NBC). Results 308 patients were enrolled, 179 in NBC and 129 in BC. Mean age at disease onset and at diagnosis was significantly higher in NBC (p = 0.023, p = 0.045, respectively). Disease duration was longer in BC (p = 0.022). Patients in BC presented arthritis more frequently (p = 0.024), those in NBC nephropathy (p = 0.03). Quality of life was worse in BC (p = 0.031). Anti-dsDNA, low C3, were significantly more frequent in BC (p Conclusion The predominant organ involvement was different in the two cohorts: kidney involvement predominated in NBC, joint involvement in BC. Despite the younger age at disease onset, patients of the BC had a longer disease duration and more frequently had taken a cumulative prednisone dosage greater than 10 g. Even the pattern of clinical manifestations inducing to prescribe biological rather than conventional immunosuppressants was quite different. Keywords: Autoantibody(ies), autoimmune disease, belimumab, cohort studies, glucocorticoids, immunosuppressants, rituximab, systemic lupus erythematosus

In this paper, we report a challenging case of a middle-age woman who developed antimelanoma differentiation-associated protein-5 dermatomyositis (anti-MDA5 DM) with interstitial lung disease (ILD) and was successfully treated with rituximab (RTX), after failure of a first-line therapy.

Immune checkpoints are small molecules expressed by immune cells that play critical roles in maintaining immune homeostasis. Immune checkpoint inhibitors (ICPIs) are new cancer drugs that target self-tolerance pathways exploited by tumors to escape immune destruction, such as cytotoxic T-lymphocyte antigen 4 (CTLA-4) and programmed cell death 1 (PD-1) or its ligand (PD-L1). Several ICPIs have been approved by Food and Drug Administration, increasing overall survival with different cancers. However, their use can determine development of many different inflammatory side effects, that are defined immune-related adverse effects (irAEs); among others, rheumatological irAEs can develop in these patients. Currently, we have limited data about these adverse effects; particularly, few evidence come from clinical trials about patients with pre-existing autoimmune diseases because they were excluded from them. Therefore we analysed the existing scientific literature dealing with this issue, in order to answer to different clinical questions. According to all reviewed data, rheumatological irAEs are not infrequent, in both previously diseased and undiseased patients, but they are often mild and reversible. Close monitoring and interdisciplinary management and monitoring is necessary in order to ensure best care. Many questions remain unanswered or not completely answered; further data are necessary to implement our knowledge in this field and to standardize and optimize clinical practice.

Osteoarthritis (OA) is the most common rheumatic disease and the leading cause of disability and work impairment in elderly individuals. It is characterized by progressive degenerative changes in the diarthrodial joints at the level of hyaline cartilage, cortical bone, synovium and periarticular tissues (i.e., ligaments and bursae). Being a valuable tool in the assessment of joint abnormalities and due to its numerous advantages in comparison to other imaging techniques, in the last decades musculoskeletal ultrasound has been increasingly utilized in OA. Its characteristic of being a real-time technique, combined with its limited costs, feasibility and sensitivity to detect a wide range of pathological changes has led to increasing applications of this tool in the diagnosis and monitoring of OA.

Background Osteoarthritis (OA) is characterized by progressive loss of cartilage, deterioration of subchondral bone and mild synovial inflammation. Classified for a long time as a non-inflammatory arthropathy, a growing number of evidences has suggested that OA course could be driven by systemic and localized inflammation. In particular, serum levels of Interleukin (IL)-6 have been associated with higher prevalence of osteophytes in older adults with knee OA. Furthermore, high levels of other inflammatory cytokines have been identified in serum and synovial fluid of OA patients. Objectives In the present cross-sectional study, we aimed at analyzing the correlation between articular inflammatory state, reflected by ultrasonographically-detected synovitis, and the serum levels of 27 cytokines, chemokines and growth factors in a cohort of primary knee OA. Methods We consecutively enrolled 47 patients (M/F 16/31, mean age ±SD 63.8±7.8 years, mean onset interval ±SD 70.0±78.6 months) affected by knees OA according to clinical and radiographic ACR criteria. Patients were excluded if they had received non-steroidal anti-inflammatory drugs or other analgesics within the 2 days before enrollment. Pain was assessed with a 100-mm visual analogue scale (VAS), and the Lequesne algo-functional index was used to measure the OA severity. BMI was registered. Each patient underwent ultrasonographic (US) assessment of both knees performed by a single operator. According with OMERACT definitions, we assessed the presence of synovial effusion, synovial hypertrophy and power Doppler. These elementary lesions were scored according to a semi-quantitative scale (0 = absent, 1 = mild, 2 = moderate and 3 = severe), the sum of them allows obtaining a total score of the patient9s inflammatory state (0–18). Finally, blood samples for laboratory assays were obtained and commercially available multiplex bead based immunoassay kits (Human 27-plex, Bio-Rad laboratories, Hercules, CA) were used to measure concentrations of IL-1β, IL-1RA, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12, IL-13, IL-15, IL-17, FGF-Basic, G-CSF, GM-CSF, interferon-γ, IP-10, MCP-1, MIP-1α, MIP-1β, PDGF, RANTES, TNF, VEGF. Results At the study enrollment, OA patients showed a mean±SD US synovitis score of 4.4±2.7, a mean±SD VAS pain rating of 53.3±16.6 mm (range 18–90 mm), a mean±SD Lequesne index of 10.2±4.2 (range 1.5–19), a mean±SD BMI of 26.8±4.2 (range 20–34.7). Positive correlations among US synovitis score and serum levels of IL-6 (r=0.3, p=0.01), IL-2 (r=0.3, p=0.01), IL-5 (r=0.3, p=0.01), IL-7 (r=0.3, p=0.03), MIP-1b (r=0.3, p=0.01), VEGF (r=0.3, p=0.02) were found. Moreover, US synovitis score positively correlated with Lequesne index (r=0.4, p=0.004) and BMI (r=0.4, p=0.04). Conclusions The results of the present study confirmed that OA may be associated with systemic inflammatory changes, as demonstrated by the positive correlation between US synovitis and several inflammatory cytokines serum levels. Disclosure of Interest None declared

Objectives To compare power Doppler (PD) vs colour Doppler (CD) semiquantitative and quantitative scoring of synovial vascularization (RA) and to evaluate the relationship between semiquantitative and quantitative scores in patients with rheumatoid arthritis (RA). Methods One hundred RA patients underwent B-mode, PD, and CD assessments of 12 joints at two European centres. Each joint with synovial hypertrophy detected on B-mode was semiquantitatively scored (0–3) for PD (SPD score) and CD (SCD score) synovial signal. PD and CD synovial signal were also quantitatively scored (0–100%) (QPD and QCD scores, respectively) using a software for counting the colour fraction. Results We found SH in 184 joints. SPD and SCD agreed in 92.3% (95% CI: 88.4; 96.2%) of paired scores, with Kendall rank correlation coefficient tau-b=0.95. Significant differences between marginal distributions of SPD and SCD were not found (p=0.565). QPD and QCD scores were highly correlated (Pearson9s coefficient=0.70) but Blamd-Altman plot showed insufficient agreement, being the QCD scores systematically slightly higher than the QPD scores. The distribution of QPD and QCD values between SPD and SCD scores, respectively, showed significant differences between grade 0 and grade 1 (p Conclusions SPD and SCD scores were concordant and QPD and QCD scores highly correlated although were not concordant. There was consistency between SPD and SCD moderate and severe scores and QPD and QCD scores. There was an overlapping between SPD and SCD mild and moderate scores regarding QPD and QCD scores. Disclosure of Interest None declared

Polymyalgia rheumatica (PMR) is a relatively frequent disease affecting individuals older than 50 years and is character- ized by inflammatory involvement of the shoulder and hip girdles and the neck. Clinical manifestations are represented by pain and morning stiffness in this regions. An extensive and comprehensive assessment of the inflammatory status is crucial in PMR patients, including imaging evaluation. This narrative review reports the current available data in the literature about the role of musculoskeletal ultrasound in PMR.

Gout is a frequent inflammatory disease induced by the deposition of monosodium urate crystals in joints and extra-articular tissues. The natural history of the disease includes four different phases: asymptomatic hyperuricemia, acute attacks, intercritical phase, and chronic tophaceous gout. Imaging techniques have several applications in the diagnosis, clinical monitoring and management of the disease but particularly, musculoskeletal ultrasound is able to detect a wide set of abnormalities in gout. This review reports the most relevant findings detectable by ultrasound and the current available data in the literature regarding the role of musculoskeletal ultrasound in gout..

Objective To assess the interobserver reliability between sonographers with different levels of experience in detecting inflammatory and structural damage abnormalities in patients with knee OA. Methods After achieving consensus on definitions and scanning protocols, three ultrasonographers with different levels of experience in musculoskeletal US examined the knees of nine patients with OA. US examinations were conducted with independent blinded evaluations of inflammatory (joint effusion, synovial hypertrophy, power Doppler signal, Baker's cysts) and structural (osteophytes, cortical bone irregularities, femoral hyaline cartilage abnormalities, protrusion of the medial meniscus) lesions. All abnormalities were scored by applying a dichotomous scale (0-1). In addition, at each knee joint site global scores for joint inflammation, cortical bone abnormalities and cartilage damage were calculated by summing the single-lesion scores. Reliability was assessed using kappa (κ) coefficients. Results Seventeen knees were examined. Inflammatory abnormalities were observed with moderate to very good agreement (κ = 0.55-0.88) between the observers. From fair to very good agreement (κ = 0.31-0.82) was registered between sonographers for structural damage lesions. The overall κ was 0.716 for junior and 0.571 for beginner sonographers comparing their findings with those of senior sonographers. Conclusion This represents the first ultrasonographic study focusing on the analysis of interobserver reliability between sonographers with different levels of experience in demonstrating inflammatory and structural abnormalities in knee OA. Globally, even considering some variable results that were mainly obtained by the evaluation of single components of bone involvement, US offered a reliable assessment of a wide set of abnormalities in knee OA.

Background The anti-CD20 monoclonal antibody rituximab (RTX) is an effective treatment option for patients with systemic lupus erythematosus (SLE) refractory to conventional therapies. The safety of this drug has been widely analyzed in randomized controlled clinical trials in patients with rheumatoid arthritis (RA); on the contrary, there are few data on patients with SLE. Objectives We aimed to evaluate the safety and survival of treatment with RTX in patients with SLE and RA in a 10 years observational study. Methods We evaluated the clinical history and laboratory data of patients with SLE (1997 ACR revised criteria) and RA (2010 revised EULAR/ACR criteria) treated with RTX in the period between 2003 and 2013. In all the patients RTX was administered intravenously (IV) according to two different protocols: 1000 mg IV on days 1 and 14, or 375 mg/m 2 on days 1, 8, 15, and 22. Each protocol provided for additional cycles of treatment after an interval of at least 6 months. All patients in both groups received oral acetaminophen (1000 mg), methylprednisolone (125 mg IV), and chlorphenamine (10 mg IV) 30 minutes before each infusion to prevent infusion-related adverse events. Written informed consent was obtained from all patients enrolled in the study. In particular, we analyzed the following parameters: duration of therapy, number of cycles, interval between them, infusion-related (IR) and other adverse events leading to discontinuation of RTX treatment. Statistical analysis was performed using the Mann-Whitney test and Fisher9s exact test; the risk was calculated by dividing the number of events by the number of cases. Results Thirty-three patients with SLE (2M/31F, mean age 41.9±12.1 years, mean disease duration 183.6±74.4 months) and 80 RA patients (15M/65F; mean age 57.5±12.2 years; disease duration 151.2±81.6 months) were treated with RTX. SLE patients were significantly younger compared with RA patients (P Conclusions The results of our study highlight the long-term safety of treatment with RTX in patients with SLE and RA, with a low risk of infusion-related as well as infectious adverse events. The lower incidence of infusion-related AEs in the SLE patients might be related to the higher-dosage steroid therapy they received during the week before RTX infusion. Finally, physicians should be aware that IR adverse events are more likely to occur during the first cycle of therapy. Disclosure of Interest None declared

Background Power Doppler (PD) ultrasonography (US) is playing an increasing role in the evaluation of patients with inflammatory arthropathies, due to its ability in detecting inflammatory and structural abnormalities and the higher sensitivity compared with clinical evaluation. Several studies evaluated the role of US in diagnosis and follow-up of Rheumatoid Arthritis (RA) patients. A growing number of papers investigated the potential of US in the assessment of psoriatic arthritis (PsA). Indirect data suggested similar US findings in RA and PsA patients. However, to our knowledge, no study specifically designed to compare PDUS findings in RA and PsA patients has been performed. Objectives We assessed the ultrasonographic changes in terms of prevalence and severity of synovitis in clinically active RA and PsA patients. Methods In this cross-sectional study, we enrolled patients affected by RA and PsA with active peripheral joint involvement. The patients underwent clinical, laboratory and US evaluation. Disease activity was evaluated by the 28-joint DAS. We excluded all the patients in remission (i.e. DAS28 Results We enrolled 43 PsA (M/F 20/23; mean age 54.8±15.2 years; mean disease duration 112.6±70.8 months) and 70 RA patients (M/F 11/59; mean age 56.4±14.8 years; mean disease duration 158.7±40.4 months). DAS28 values resulted significantly higher in RA compared with PsA (5.3±1.1 versus 4.3±1.1, P=0.0001). US evaluation demonstrated a significantly higher prevalence of all US-detected lesion in RA patients compared with PsA (JE 60.9% versus 41.1%, P versus 31.3%, P versus 11.6%, P versus 1.5±2.1, P=0.03) and moderate disease activity (12.6±9.2 versus 7.4±6.7, P=0.01). Conclusions The present study demonstrate that PDUS synovitis is more severe in RA than in PsA patients, regardless of the disease activity. Concerning the prevalence of each US-detected abnormality, JE, SH and PD signal resulted significantly more frequent in RA patients than PsA. References Perricone C et al. The 6-joint ultrasonographic assessment: a valid, sensitive-to-change and feasible method for evaluating joint inflammation in RA. Rheumatology (Oxford) 2012;51:866-73. Disclosure of Interest None declared

Background Ultrasonography (US) is an imaging tool able to evaluate patients affected by inflammatory arthropathies, thanks to its ability in detecting inflammatory and structural abnormalities and to its higher sensitivity compared with clinical evaluation. Several studies evaluated the role of US in diagnosis and follow-up of patients with Rheumatoid Arthritis (RA), mainly focusing on joint synovitis. Few studies evaluated specifically the inflammatory tendon involvement. Objectives We aimed to evaluate the prevalence and clinical significance of tenosynovitis detected by US in patients with RA with moderate/high disease activity naive to biological treatment. Methods In this cross-sectional study, we enrolled patients affected by RA (1987 ACR criteria) candidate to start biological treatment. The patients underwent clinical, laboratory and ultrasonographic evaluation. Disease activity was evaluated using 28-joint DAS. Health assessment questionnaire (HAQ) was also administered. Bilateral high-resolution US at the level of flexor tendons of II and III finger and extensor tendon compartments at wrist level was performed. Moreover, II metacarpophalangeal (MCP), III MCP and radiocarpal (RC) joints were evaluated. Tenosynovitis, joint effusion (JE), synovial hypertrophy (SH) and PD were evaluated according to OMERACT definitions. All the lesions were graded according to a semi-quantitative scale ranging from 0 to 3 (0=absent, 1=mild, 2=moderate and 3=severe). Then, US inflammatory scores, calculated by adding the values given to each elementary lesion, were elaborated for every single joint or tendon. Finally, a global score was obtained by adding together the scores from each joint and tendon separately. Moreover, PD both at joint and tendon levels was evaluated also by using a dichotomous score (presence/absence). Results Forty-eight patients affected by RA were evaluated. In table the main clinical, laboratory and ultrasonographic features are summarized. Tenosynovitis was observed in 30/48 (62.5%) patients. Synovitis and erosions were identified in all patients. The presence of tenosynovitis was associated with high disease activity (defined as DAS28>5.1, P=0.015), with the positivity for rheumatoid factor (P=0.025) and with the presence of anti-CCP (P=0.023). Moreover, a positive correlation between the synovitis score and, respectively, the erosion score (P Conclusions We demonstrated that US-detected tenosynovitis is a relevant manifestation in RA patients. Indeed, it is associated with serologically positive patients and with higher disease activity. PD was confirmed to correlate with a more severe bone damage in terms of erosions observed by US. Disclosure of Interest None declared

Introduction: Musculoskeletal ultrasound (US) represents a valid, reliable and sensitive-to-change tool for the evaluation of patients suffering from rheumatic conditions. This method demonstrates a wide applicability and availability, finding place in the clinical practice in rheumatology outpatient clinic. Aim: To perform an epidemiological evaluation related to the use of US in a university rheumatology outpatient clinic. Material and methods: During a 3-month period, data concerning consecutive patients attending to the US Unit of Department of Rheumatology, Sapienza University of Rome were registered. We collected the demographic data, the diagnosis, the reason for the US examination, the examined joints, as well as the requesting physicians’ specialty. Results: In the October-December 2013 period, 572 patients (M/F 137/435; mean age±SD 55.2±15.8 years) were registered. The US examination was more frequently requested for the following diseases: rheumatoid arthritis (29.5%), osteoarthritis (10.6%), spondyloarthritis (9.1%), and connective tissue diseases (8.9%). In 239 of cases (41.8%), the US evaluation was requested for other indications. The US evaluation was requested slightly more frequently for monitoring (55.7%) compared to diagnosis (44.3%). The requesting physician was a rheumatologist in the majority of the cases (80.6%). The most frequent requested were the hand joints (28.9%) and wrists (23.3%). Conclusions: US examinations are most frequently used in the evaluation of patients with rheumatoid arthritis and mainly to monitor the disease. The exam is requested mostly by rheumatologists. The hand joints and wrists were the most frequently evaluated.