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ObjectivesAge is the strongest risk factor of Giant Cell Arteritis (GCA), implying a possible pathogenetic role of cellular senescence. To address this question, we applied an established senescence specific multi-marker algorithm in tissue artery biopsies (TABs) of GCA patients.MethodsSeventy five positive TABs from GCA patients and 22 negative from patients with Polymyalgia Rheumatica (PMR) were retrospectively retrieved and analyzed. Senescent cells and their histologic origin were identified with specific cellular markers; IL-6 and MMP-9 were investigated as components of the senescent associated secretory phenotype (SASP) by triple co-staining. GCA or PMR artery culture supernatants were applied to primary skin fibroblasts with or without IL-6 blocking agent to explore the induction of IL-6 associated cellular senescence.ResultsSenescent cells were mainly present in GCA arteries at higher proportion compared to PMR (9.50% vs 2.66% respectively, pConclusionsSenescent cells with inflammatory phenotype are present in GCA arteries and are associated with the tissue inflammatory bulk. These findings might suggest a potential implication in disease pathogenesis by perpetuating inflammation and affecting vascular remodeling via IL-6 dependent mechanisms.

A cross-sectional single-center study was conducted to assess cytokine levels in aqueous humor (AH) and plasma of three different uveitis entities: definite ocular sarcoidosis (OS), definite OS associated with QuantiFERON®-TB Gold test positivity (Q + OS) and presumed tubercular uveitis (TBU).Thirty-two patients (15 OS, 5 Q + OS, 12 TBU) were included.Quantification of selected cytokines was performed on blood and AH samples collected before starting any treatment. Statistical analysis was conducted using the Kruskal-Wallis test, the Mann-Whitney or Fisher test and the Principal Component Analysis (PCA).IL-6, IL-8 and IP-10 levels were higher in AH samples than in peripheral blood. In AH samples, BLC, IL-8 and IP-10 were significantly higher in definite OS than in presumptive TBU. There were no statistically significant differences in terms of cytokine levels between Q + OS and presumptive TBU. PCA showed a similar cytokine pattern in the latter two groups (IFNγ, IL-15, IL-2, IP-10, MIG), while the prevalent expression of BLC, IL-10 and MIP-3 α was seen in definite OS.The different AH and plasma cytokine profiles observed in OS compared to Q + OS and TBU may help to differentiate OS from TBU in overlapping clinical phenotypes of granulomatous uveitis (Q + OS).

BackgroundUltrasound (US) is recommended as the first line imaging test in patients with suspected Giant Cell Arteritis (GCA). Traditionally, the US halo sign has been used for diagnosis. We have recently described a composite Halo Score that allows to quantify vascular inflammation on US. Prospective studies on response and disease monitoring are lacking.ObjectivesTo prospectively assess the role of US in diagnosing and monitoring GCA patients. We report early baseline and 12-month data on our current recruitment in a study that has suffered disruption from the pandemic.MethodsHAS GCA (IRAS#264294) is an ongoing, prospective, multicentre study recruiting from referrals of suspected GCA to fast-track clinics. Based on the Southend GCA clinical pre-test probability score (SPTPS)1, patients were stratified in to low, intermediate and high risk categories2. Temporal and axillary US Halo Scores were calculated from the halo thickness and extent in bilateral temporal arteries, parietal and frontal branches (TAHS) and axillary arteries (AAHS). These scores were summed (TAHS x1 plus; AAHS x3) to generate a Total Halo Score (THS)3.Mann Whitney U test was used to compare baseline features between GCA and controls. Wilcoxon signed rank test was used to evaluate disease features at baseline and at 12 months in GCA patients. Sensitivity (Sn), Specificity (Sp) and ROC curve were calculated, where applicable. P value Results202 patients (71 GCA, 131 controls) have been recruited thus far: 23 completed 12-month follow up assessment; 6 were lost to follow up (4 died, 2 withdrew consent due to pandemic). Demographics, clinical features, and US results are shown (Table 1).Table 1.Baseline features of GCA patients and controlsGCA (n=71)Controls (n=131)P-valueAge, median (IQR)75 (70-81)68 (62-76)0.001Female, n (%)38 (54)89 (68)0.05SPTPS category, n (%) Low risk0 (0)59 (45) Intermediate risk16 (23)49 (37)0.04 High risk55 (77)23 (18)Halo score (HS), median (range) Temporal artery HS12 (0-22)2 (0-17) Axillary artery HS12 (0-21)6 (0-18) Total HS21 (2-40)8 (0-29)Clinical features, n (%) Temporal headache53 (75)93 (71)0.62 Scalp tenderness36 (51)40 (31)0.006 Jaw claudication38 (54)9 (7) PMR symptoms29 (41)35 (27)0.06 Constitutional symptoms42 (59)29 (22) Visual disturbance40 (56)58 (44)0.11 Vision loss21 (30)9 (7)AA, axillary artery; GCA, Giant cell arteritis; TA, Temporal arteryAmong GCA patients, 50 had cranial, 5 large-vessel and 16 mixed phenotypes. Diseases were diagnosed by US and additional tests such as PET CT.Jaw claudication (54%) and constitutional symptoms (59%) were the dominant features in GCA patients. Median age was 75 years in GCA (54% females) and 68 years in controls (68% females). GCA and controls were stratified by SPTPS to Low risk (0% vs 45%; Sn-undefined, Sp-98), Intermediate risk (23% vs 37%; Sn-81, Sp-98) and High risk (77% vs 18%; Sn-98, Sp-91). Optimal SPTPS cut-off point was ≥12 (Sn-89, Sp-76).Median THS was 21 in GCA and 8 in controls. Optimal cut-off Halo Score in diagnosis was TAHS ≥5 (Sn-89, Sp-86), AAHS ≥11 (Sn-55, Sp-75), THS ≥15 (Sn-79%, Sp-86%). Baseline Halo Score and CRP levels showed positive correlation (spearman rank correlation). Among the 23 patients who completed 12-months follow up, median TAHS, AAHS and THS reduced from 12 to 2, 12 to 6 and 21 to 10, respectively (Figure 1).ConclusionAlong with SPTPS, Halo Score successfully discriminates GCA from non GCA mimics and. HS is effective in showing 12-month response. This score may be a useful marker to monitor GCA disease activityReferences[1]Laskou F et al. Clin Exp Rheumatol. 2019[2]Sebastian A et al. RMD Open. 2020[3]Sebastian A et al. BMC Rheumatol. 2020Disclosure of InterestsAlwin Sebastian: None declared, Alessandro Tomelleri: None declared, Pierluigi Macchioni: None declared, Giulia Klinowski: None declared, Carlo Salvarani: None declared, Abdul Kayani: None declared, Mohammad Tariq: None declared, Diana Prieto-Peña: None declared, Edoardo Conticini: None declared, Muhammad Khurshid: None declared, Sue Inness: None declared, Jo Jackson: None declared, Kornelis van der Geest Speakers bureau: Roche, Grant/research support from: Mandema stipend, Bhaskar Dasgupta: None declared

BackgroundCryofibrinogenemia (CF) is a rare disorder characterized by the presence of an abnormal protein in the plasma that precipitates when cooled and redissolves at room temperature (1). CF is rarely symptomatic, therefore it is often underestimated. Nevertheless, the cryoprecipitation of native fibrinogen could induce thrombotic occlusion of small and medium sized vessels; as a consequence, this condition could become potentially lethal without the proper treatments. CF is classified into an essential and secondary form. The association of CF with Systemic Sclerosis (SSc) is described in literature (2-4); however, the role of this phenomenon it is not completely clarified, especially because some clinical aspects could be similar in both conditions.ObjectivesThe aim of our study was to analyze the clinical, laboratory, instrumental and therapeutic features of SSc patients with cryofibrinogenemia, with particular attention to the possible prevention strategy and appropriate therapy of SSc digital ulcers.Methods101 SSc patients (M:F 1:13) referring to the SSc Unit-Rheumatology Unit of our University Hospital have been tested both for cryofibrinogen and cryoglobulins from February 2020 to January 2022. Clinical, laboratory, instrumental features and ongoing therapies were collected.ResultsPatients with diffuse cutaneous form, limited cutaneous form, and sine-scleroderma subsets were 20 (19,8%), 79 (78,2%), and 2 (2,0%), respectively. The overall positivity for CF was 69,3%, of which 90,7% as isolated CF and 9,3% in addition to cryoglobulins. No correlation between CF positivity and positivity for rheumatoid factor, Scl-70, CENP B, anti-fibrillarin, anti-U1RNP, anti-Th/To, anti-Ku, anti-MDA5, anti-mitochondrial, anti-SSA, anti-SSB, anti-citrullinated peptide, anti-phospholipids, anti-CORE, and anti-HCV antibodies was observed. An inverse correlation trend between CF positivity and anti-RNAP3 antibodies positivity (OR=0.0577, 95% CI 0.0029-1.1537, p=0.0620) was noted. No significant correlation between CF positivity and interstitial lung disease, pulmonary arterial hypertension (PAH), history of digital ulcers, and amputation was recorded; however, considering cryocrit sample ≥1%, a correlation between the presence of an estimated pulmonary arterial systolic pressure (ePASP) higher than 30 mmHg and the positivity of CF was obtained (OR = 2.71, 95% CI 1.01-7.28, p=0.0482). The same association was achieved if we considered patients without endothelin receptor antagonist therapy (n=47) and CF positivity (OR=6.19, 95% CI 1.19-32.2, p=0.0304). Furthermore, no correlation between CF positivity and the presence of digital ulcers at the moment of the blood sampling was verified; however, if we stratified patients according to their ongoing treatments (absence of an endothelin receptor antagonists therapy plus PDE5 inhibitors), a significant correlation between digital ulcers and CF positivity emerged (OR=8.14, 95% CI 1.03-64,5, p=0.0470, n=91).ConclusionOur preliminary results on this issue are extremely interesting as they can open new perspectives on the identification of cryofibrinogen as possible prognostic marker that could be involved in the pathogenesis of scleroderma digital ulcers and PAH. Moreover, therapies which are currently used for the treatment of PAH and the management of digital ulcers, could determine circulating cryofibrinogen disappearance, with possible challenging future impact on SSc therapeutic approaches.References[1]Michaud M, Pourrat J. Cryofibrinogenemia. J Clin Rheumatol Pract Rep Rheum Musculoskelet Dis. aprile 2013;19(3):142–8.[2]Kao L, Weyand C. Vasculitis in Systemic Sclerosis. Int J Rheumatol. 30 settembre 2010;2010:e385938.[3]Kocoloski A et al, Successful management of secondary cryofibrinogenaemia using bosentan therapy. Rheumatol Oxf Engl. 1 ottobre 2018;57(10):1868–70.[4]Barrett MC et al, Cryofibrinogenaemia and acute gangrene in systemic sclerosis. Postgrad Med J. ottobre 1986;62(732):935–6.Disclosure of InterestsNone declared

BackgroundApremilast, an inhibitor of the phosphodiesterase 4, is indicated for Psoriatic Arthritis (PsA) treatment. The 3 years retention rate, an outcome indirectly related to efficacy, observed in clinical trials [1] is 55,5%. A single subsequent real world setting study [2] suggested a lower efficacy as it reported that the six months retention rate was about 57%.ObjectivesThe main aim of this retrospective observational study is the assessment of apremilast 3 years retention rate in a real world PsA patients’ cohort. Moreover, the secondary objective is reporting the reasons of apremilast suspension and the most relevant factor related to treatment persistence.MethodsIn thirteen Italian rheumatological referral centers, all PsA consecutive patients who received apremilast were enrolled. Anamnestic data, treatment history and PsA disease activity (DAPSA) at baseline and after 6 and 12 months were recorded. The Kaplan-Meier curve and the Cox analysis computed the apremilast retention rate and treatment persistence-related risk factors. A p-value < 0.05 was considered statistically significant.ResultsThe three-hundred-twenty-four enrolled patients (median age 60 [InterQuartile Range IQR 52-67] yrs; female prevalence 57,0%) median observation period was 17 [IQR 7-36] months (6848 patients-months). The apremilast retention rate at 6, 12 and 36 months was, respectively, 95%, 86% and 66% (Figure 1). The main discontinuation reasons were: primary inefficacy (40% of interruptions), secondary inefficacy (18%) and gastro-intestinal intolerance (17%%). The oligo-articular onset was the only factor associated to apremilast persistence (Hazard ratio 0.57 IQR 0.34-0.96). Sex, age, and sever comorbidities (cancer, chronic infections etc) were not related to treatment discontinuation. The basal DAPSA (24.1, IQR 18.5-32.0) decreased after 6 and 12 months (respectively 14.5, IQR 10.1-22.6 and 10.5, IQR 8,0-15.2). Remission or minimal disease activity (DAPSA < 15) was achieved after 12 months in 38.0% of patients.ConclusionAlmost two third of PsA patients receiving apremilast were still in treatment after 3 years. The study’s data, confirmed its efficacy and safety profile. Apremilast appear a good treatment choice in patients with oligo articular PsA or burdened by severe comorbidities.References[1]Mease et al. ACR Open Rheumatology (2020)[2]Favalli et al Clin Exp Rheum (2020)Disclosure of InterestsAlarico Ariani Speakers bureau: Zentiva, Consultant of: Boeringher, Amgen, Bristol-Meyers-Squibb, Novartis, Sanofi, Novo Nordisk, Lilly, Janssen, Bruno Farmaceutici, Simone Parisi: None declared, Patrizia Del Medico: None declared, antonella farina: None declared, elisa visalli: None declared, Aldo Molica Colella: None declared, Federica Lumetti Consultant of: Amgen, rosalba caccavale: None declared, Palma Scolieri: None declared, Romina Andracco: None declared, Francesco Girelli: None declared, Elena Bravi: None declared, Matteo Colina: None declared, Veronica Franchina: None declared, Ilaria Platé: None declared, eleonora Di Donato Consultant of: Novartis, Giorgio Amato: None declared, Carlo Salvarani: None declared, Francesco De Lucia: None declared, Daniele Santilli Consultant of: Novartis, eugenio arrigoni: None declared, Flavio Mozzani Consultant of: Novartis, Abbvie, Rosario Foti: None declared, Gilda Sandri: None declared, Vincenzo Bruzzese: None declared, Marino Paroli: None declared, Enrico Fusaro: None declared, Andrea Becciolini: None declared

Despite intensive investigations, about 30% of stroke cases remains of undetermined origin. After exclusion of common causes of stroke, there is a number of rare heritable and non-heritable conditions, which often remain misdiagnosed, that should be additionally considered in the diagnosis of cryptogenic stroke. The identification of these diseases requires a complex work up including detailed clinical evaluation for the detection of systemic symptoms and signs, an adequate neuroimaging assessment and a careful family history collection. The task becomes more complicated by phenotype heterogeneity since stroke could be the primary or unique manifestation of a syndrome or represent just a manifestation (sometimes minor) of a multisystem disorder. The aim of this review paper is to provide clinicians with an update on clinical and neuroradiological features and a set of practical suggestions for the diagnostic work up and management of these uncommon causes of stroke. The identification of these stroke causes is important to avoid inappropriate and expensive diagnostic tests, to establish appropriate management measures, including presymptomatic testing, genetic counseling, and, if available, therapy. Therefore, physicians should become familiar with these diseases to provide future risk assessment and family counseling.

BackgroundPatients with autoimmune systemic diseases (ASDs) can be counted among frail populations as regards the predisposition to COVID-19 due to the frequent visceral organ involvement and comorbidities, as well as the ongoing immunomodulating treatments.ObjectivesOur long-term multicenter telephone survey prospectively investigated the prevalence, prognostic factors, and outcomes of COVID-19 in Italian ASD patients during the first 3 pandemic waves.MethodsA large series of 3,918 ASD patients (815 M, 3103 F; mean age 59±12SD years) was consecutively recruited at the 36 referral centers of COVID-19 & ASD Italian Study Group. In particular, ASD series encompassed the following conditions: rheumatoid arthritis (n: 981), psoriatic arthritis (n: 471), ankylosing spondylitis (n: 159), systemic sclerosis (n: 1,738), systemic lupus (172), systemic vasculitis (n: 219), and a miscellany of other ASDs (n: 178). The development of COVID-19 was recorded by means of telephone survey using standardized symptom-assessment questionnaire (1).ResultsA significantly increased prevalence of COVID-19 (8.37% vs 6.49%; pInterestingly, a significantly higher COVID-19-related death rate was observed in systemic sclerosis patients compared to the Italian general population (6.29% vs 2.95%; p=0.018). Other adverse prognostic factors to develop COVID-19 were the patients’ older age, male gender, pre-existing ASD-related interstitial lung involvement, and chronic steroid treatment. Conversely, patients treated with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) showed a significantly lower prevalence of COVID-19 compared to those without (3.58% vs 46.99%; p=0.000), as well as the chronic administration of low dose aspirin in a subgroup of SSc patients (with 5.57% vs without 27.84%; p=0.000).ConclusionThe cumulative impact of COVID-19 on ASD patients after the first 3 pandemic waves revealed less severe than that observed during the first phase of pandemic (1), especially with regards to the death rate that was comparable to the Italian general population in spite of the increased prevalence of complicating COVID-19 in the same ASD series.Ongoing long-term treatments, mainly csDMARDs, might usefully contribute to generally positive outcomes of in this frail patients’ population.Of note, a significantly increased COVID-19-related mortality was recorded in only SSc patients’ subgroup, possibly favored by pre-existing lung fibrosis. Among different ASD, SSc deserves special attention, since it shares the main pathological alterations with COVID-19, namely the interstitial lung involvement and the endothelial injury responsible for diffuse microangiopathy.Besides SSc, the patients’ subgroups characterized by older age, chronic steroid treatment, pre-existing interstitial lung disease, and/or impaired COVID-19 vaccine response (1-3), may deserve well-designed prevention and management strategies.References[1]Ferri C, et al. Ann Rheum Dis. 2020 Oct 14 doi: 10.1136/annrheumdis-2020-219113.[2]Ferri C et al. J Autoimmun. 2021 Dec;125:102744. doi: 10.1016/j.jaut.2021.102744.[3]Visentini M et al. Ann Rheum Dis. 2021 Nov 24. doi: 10.1136/annrheumdis-2021-221248Disclosure of InterestsNone declared

BackgroundMusculoskeletal pain is an important feature in patients (pts) with anterior acute uveitis (AAU), as a symptom of spondyloarthritis (SpA). Fibromyalgia (FM), which is more prevalent in pts with chronic inflammatory diseases, has a widely recognized effect on both differential diagnosis and evaluation of outcome measures in SpA.ObjectivesTo estimate the prevalence of primary FM and concomitant FM and SpA in a cohort of pts with AAU, and to compare clinical and ultrasonographic findings in SpA pts with (SpAFM+) and without (SpAFM-) concurrent FM and SpA.Methods152 consecutive pts affected by AAU from the Immunology Eye Unit (AUSL-IRCCS Reggio Emilia, Italy) were enrolled.A complete rheumatological assessment, including 68/66 peripheral joint count, Leeds Enthesitis Index (LEI) and Maastricht Ankylosing Spondylitis Enthesitis Score (MASES), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), and Fibromyalgia Impact Questionnaire (FIQ) was performed.Using an Esaote MyLabClass, 18-6MHz linear multifrequency transducer, 6 entheses (lateral epicondyle, distal quadriceps insertion, proximal and distal patellar tendon insertions, calcaneal insertion of Achilles tendon and plantar fascia) were evaluated bilaterally for the presence of any elementary lesion, structural damage and active enthesitis, according to OMERACT definitions2.Pts were classified as having SpA and/or FM according to ASAS criteria and 2010 ACR diagnostic criteria for FM, respectively.Results103 pts were diagnosed with anterior acute non granulomatous uveitis (AANGU) and 49 with anterior acute granulomatous uveitis (AAGU) (F/M 93/59, age 46.2±12.3 years, BMI 25±5.1, disease duration 43.8±85.2 months).14 pts (9.2%) met the ACR criteria for FM, of whom 8 pts had concomitant FM and SpA. All FM pts had AANGU. FM pts showed significantly higher enthesitis count and report worse disease activity and function scores (Table 1). Fulfillment of ASAS criteria was associated with FM (p=0.004).Table 1.Demographic and clinical data of FM patients (results for continuous variables expressed as mean ± standard deviations, for discrete variables as n° and percentage)FM + (14)FM - (138)pOR (95%CI)Age48 ± 11.746.1 ± 12.40.569Female10 (71.4%)83 (60%)0.409BMI24.7 ± 5.525 ± 5.20.831AANGU14 (100%)89 (64.5%)0.005SpA8 (57%)30 (22%)0.0044.8 (1.6 – 14.9)ax-SpA6 (43%)18 (13%)0.0045 (1.6 – 16.1)Psoriasis2 (14.3%)9 (6.5%)0.268IBP7 (50%)19 (14%)0.0016.3 (2 – 19.9)Buttock pain9 (64%)24 (17%)8.6 (2.63 – 27.8)History of enthesitis7 (50%)20 (14.5%)0.0015.8 (1.9 – 18.6)TJC2.6 ± 3.80.6 ± 1.80.072LEI1.9 ± 1.20.5 ± 1MASES3.8 ± 3.40.8 ± 20.07BASDAI5.1 ± 1.71.8 ± 1.7BASFI2 ± 1.40.6 ± 1.2FIQa0.6 ± 0.60.3 ± 0.80.176FIQb4.2 ± 2.31.1 ± 1.8FIQc1.9 ± 2.40.4 ± 1.30.044FIQd38.9 ± 13.516.2 ± 13.9SpAFM+ pts more frequently reported an history of enthesitis [75% vs 23.3% p=0.011 OR 9.9 (95% CI 1.6 – 60.2) and buttock pain [75% vs 33.3% p=0.034 OR 6 (95% CI 1.02 – 35.3)] when compared with SpAFM-, whereas no significant differences in LEI, MASES, joint count, and inflammatory back pain (IBP), as well as in sex, age and BMI were observed.BASDAI, FIQb and FIQd were increased in SpAFM+ (6±1.1 vs 3.4±1.8 pAbnormal US findings were detected in 35/38 SpA pts (92.1%), without significant differences in elementary lesions and structural damage between SpAFM+ and SpAFM-. At patient-level, a significantly higher percentage of SpAFM+ pts had at least one active enthesitis, as compared with SpAFM- (25% vs 3.4%, p = 0.048).ConclusionComorbid FM was frequent in SpA associated with AANGU, affecting both clinical presentation and outcome measures, whereas no FM patients were found in the AAGU group. In our cohort the role of ultrasonography in discriminate SpAFM- from SpAFM+ is not clear.References[1]Balint PV et al. Ann Rheum Dis 2018;77(12):1730-35.Disclosure of InterestsNone declared

BackgroundSystemic Sclerosis (SSc) is a connective tissue disease, characterized by endothelial dysfunction, autoimmunity abnormalities and fibrosis of the skin and internal organs. The exact pathogenetic mechanisms that propagate SSc vasculopathy are still not completely understood. A complex network of interactions between endothelial cells, pericytes, myofibroblasts, and the extracellular matrix (ECM) has been implicated but it is currently unclear what drives the activation of fibroblasts and the increased ECM deposition responsible for the fibrotic changes well known in SSc.ObjectivesUsing RNA sequencing (RNA-seq), our goal was to identify potential functional pathways possibly involved in SSc pathogenesis and markers that could potentially be used to better understand endothelial dysfunction and fibrosis mechanisms in SSc patients.MethodsRNA-seq analysis was performed on RNA obtained from biopsies from 3 SSc patients and 3 age- and sex-matched healthy controls (HC) enrolled in our University Hospital between January 2019 and December 2020. The samples were transferred to a labelled cryovial and immediately stored in liquid nitrogen. RNA extraction followed standard methodologies. RNA from each sample was used to generate sequencing libraries that were sequenced according to proper transcriptomic analyses. To identify potential functional pathways that could be involved in SSc pathogenesis, we performed gene set enrichment analysis (GSEA) of differentially expressed genes (DEGs). GSEA was applied on the entire list of genes that compose the RNA-seq expression matrix. Genes were ranked based on their fold change calculated between groups of each pairwise comparison and analyzed by GSEA in pre-ranked mode. We adopted the “classic” enrichment statistic, the recommended approach for RNA-sequencing data.ResultsAccording to GSEA analysis of DEGs applied to SSc and HC, we identified 305 DEGs that were upregulated or downregulated at least 2-fold. In particular, 175 genes were upregulated and 130 genes were downregulated. A marked upregulation of genes involved in Wnt signaling, including Wnt family members, was present in HC if compared with SSc. The upregulation of collagen type VI, extracellular matrix protein 2, vascular endothelial growth factor D, among others, was also observed. Conversely, a marked downregulation of late cornified envelope and of genes encoding for keratins, was present in HC versus SSc samples. GSEA revealed that HC were characterized, among others, by gene signatures related to stromal stem cells proliferation, cytokine-cytokine receptor interaction, macrophage-enriched metabolic network, whereas SSc tissues were enriched in signatures related to keratinization, cornification, retinoblastoma (RB) 1 and tumour suppressor (TP) 53 signaling. Figure 1 displays GSEA in HC vs SSc tissues.Figure 1.GSEA in HC vs SSc tissues.Enrichment of gene signature was analyzed in transcriptomic data from HC and SSc samples.ES=enrichment score. NES=normalized enrichment score. FDR=false discovery rate.ConclusionAccording to our preliminary data, RNA-seq, differential gene expression and pathway analysis revealed that SSc patients show a discrete pattern of gene expression associated with keratinization, extracellular matrix generation, and negative regulation of angiogenesis and stromal stem cells proliferation. Further analysis on larger numbers of patients are needed; however, our results provide an interesting framework for the development of biomarkers representing vascular injury and fibrotic changes in SSc in order to explore potential future therapeutic targets.Disclosure of InterestsNone declared

BackgroundSystemic Sclerosis (SSc) is a complex autoimmune disease characterized by vascular damage, immune activation and fibrosis of skin and internal organs (1,2). One of the most common and severe SSc manifestations is interstitial lung disease (ILD) (3).ObjectivesEvaluate tolerability and safety profile of Nintedanib in patients with SSc-related ILD.MethodsWe enrolled 11 consecutive patients (6 female, 5 male, Mean age 62.7 ± 8 SD, disease duration (from the first Non-Raynaud symptom) 8 years (± 7SD) who referred to our Scleroderma Units during the last twelve months. Patients fulfilled EULAR/ACR classification criteria (4) for SSc. Patient was assessed by means of clinical evaluation (baseline and every three months), High Resolution computed tomography (every six month, or sooner), respiratory function test (every three to six months), laboratory work up, nailfold videocapillaroscopy, echocardiogram, and clinical questionnaires (BORG and mMRC).ResultsNSIP was the most frequent HRCT pattern (5 pts, 45%), followed by UIP and UIP/NSIP pattern (respectively 3 pts & 3 pts, 27%). 9 patients showed more than 20% of HRCT pulmonary fibrosis involvement. Only 1 patient had a history of smoking. mRSS was 9.23 (±10SD) points with any significant improvement during the twelve months follow-up (10 ±10SD). 8 pts were on Micophenolate Mophetil (MMF) (7 of them on MMF + steroids), 8 patients were on steroids (mean dose 5 mg/day of Prednisone or equivalent), 3 on rituximab. Main FVC was 2347 ml [+/- 1051 ml] (61.3% predicted) remaining stable. The mmRC decrased from 2.36 at baseline to 2.27 at the end of the follow up and Borg ameliorated from 7.27 at baseline to 6. Two patients were on oxygen therapy (O2 3l/min) with any significant airflow adjustment. Three patients reported irrepressible diarrhea, one patient had a partial intestinal obstruction, one had pulmonary arterial hypertension worsening with an immediate drug withdraw, one patient presented nausea, one irritability. Three patients had a clinical irrelevant weight loss (less than 2 Kg).Conclusionwe report a preliminary real-life experience on the use of Nintedanib in SSc-related patients, focusing in particular to its tolerability and safety profile. Nintedanib is well tolerated with a low rate of definitive discontinuation due to SAE. Diarrhea is a very frequent adverse event (approximately 5 episodes a day) and had led to dose reduction and/or treatment re-challenge in the majority of patients. Diarrhea seems to ameliorate reducing daily dose of MMF (1 gram/day) or precribing loperamide along with diosmectite and probiotics. FVC, mRSS, HRCT and capilalroscopy pattern remained stable. Further studies are desirable to confirm the usefulness of Nintedanib in progressive ILD, but based on our experience we support the combined use of the anti-fibrotic therapy plus immunomodulatory drugs in early stages of SSc-related ILDReferences[1]LeRoy EC, Black C, Fleischmajer R, Jablonska S, Krieg T, Medsger TA, et al. Scleroderma (systemic sclerosis): classification, subsets and pathogenesis. J Rheumatol [Internet] 1988 [cited 2015 Nov 19];15:202-5. Available from: http://www.ncbi.nlm.nih.gov/pubmed/3361530[2]TUFFANELLI DL, WINKELMANN RK. Systemic scleroderma, A clinical study of 727 cases. Arch Dermatol [Internet] 1961 [cited 2016 May 23];84:359-71. Available from: http://www.ncbi.nlm.nih.gov/pubmed/13778561[3]Hoffmann-Vold AM, Maher TM, Philpot EE, Ashrafzadeh A, Barake R, Barsotti S, et al. The identification and management of interstitial lung disease in systemic sclerosis: evidence-based European consensus statements. Lancet Rheumatol Lancet Publishing Group; 2020;2:e71-83.[4]Van Den Hoogen F, Khanna D, Fransen J, Johnson SR, Baron M, Tyndall A, et al. 2013 classification criteria for systemic sclerosis: An American college of rheumatology/European league against rheumatism collaborative initiative. Ann Rheum Dis BMJ Publishing Group; 2013;72:1747-55.Disclosure of InterestsNone declared

BackgroundOver 80% of patients affected with SLE experience skin involvement. The anti-BLyS drug belimumab was shown effective in ameliorating mucocutaneous SLE manifestations in clinical trials and real-life studies. Cutaneous response is quantified through the CLASI (cutaneous lupus erythematosus area and severity index). Clinically relevant improvements are defined as decreases of ≥50% (CLASI50) or 70% (CLASI70) from baseline values.ObjectivesTo assess rates and predictors of CLASI50 and CLASI70 in the Berliss multicentric SLE cohort1 of patients treated with belimumab.MethodsBaseline and ongoing features of patients with baseline active skin involvement (CLASI>0) were assessed in relationship to the chosen outcomes CLASI50 and CLASI70 at 24 and 52 weeks. A subanalysis on patients with CLASI≥5 was as well conducted. Logistic regression was employed to identify predictors of response.Results172 patients displayed skin involvement at baseline (CLASI>0). Of those, 124 displayed at least a 12-month-follow-up and were included in the analysis. Seventy-seven (62.1%) patients reached CLASI50 at 24 weeks and 91 (77.8%) at 52 weeks; 87 (70.2%) reached CLASI70 at 24 and 99 (79.8%) at 52 weeks. Baseline predictors of CLASI50 at 24 weeks were CLASI-damage (CLASI-d) (OR [95%CI], p; 0.79 [0.65-0.98] 0.03) and disease duration (0.93[0.86-0.99], 0.011). No baseline predictors of CLASI70 at 24 weeks emerged, however having achieved a CLASI50 response at 24 weeks portended CLASI50 and 70 response through week 52 (pTable 1.Predictors of CLASI-A Response at Week 24 and 52 by Baseline CLASI-A at 50% and 70% Response ThresholdsTimepointOutcomeVariableOR[95%CI] pCLASI>024 weeksCLASI50CLASI-d0.79 [0.65-0.98] 0.030Disease duration0.93[0.86-0.99], 0.011CLASI70CLASI-d0.93 [0.74-1.16], 0.51Disease duration0.97 [0.97-1.02], 0.1852 weeksCLASI50CLASI50 at 24 weeks14.3[4.88-44.42], CLASI70CLASI50 at 24 weeks6.22 [2.00-19.34], 0.002CLASI≥524 weeksCLASI50CLASI-d0.72 [0.53-0.98], 0.037Disease duration0.93 [0.66-1.00], 0.071CLASI70Antimalarials6.61 [1.20-36.29] 0.032Smoking0.15 [0.03-0.83], 0.03452 weeksCLASI50CLASI50 at 24 weeks22.0 [2.47-196.05], 0.006CLASI70CLASI50 at 24 weeks1.24 [0.06-25.08], 0.88CLASI, cutaneous lupus erythematosus area and severity index; CLASI-d, CLASI damage; CLASI50 and CLASI70: decrease ≥50% or ≥70% in CLASI from baseline. OR and 95%CIs are estimated using a logistic regression model with stratification factors as covariates (SLEDAI-2K at baseline, baseline prednisone dosage).ConclusionEarlier use of belimumab favors achievement of skin response among SLE patients and attainment of a prompt response predicts further response. Use of antimalarials reinforces while smoking hampers a more profound CLASI improvement over time.References:[1]Gatto M, et al. Arthritis Rheumatol. 2020 Aug;72(8):1314-1324Disclosure of InterestsMariele Gatto Speakers bureau: GSK, Grant/research support from: GSK, Roberto Depascale: None declared, Angela Tincani: None declared, Giacomo Emmi: None declared, Salvatore Scarpato: None declared, Fabrizio Conti: None declared, Marcello Govoni: None declared, Marta Mosca: None declared, Maria Gerosa: None declared, Enrica Bozzolo: None declared, Valentina Canti: None declared, Armando Gabrielli: None declared, Elisa Gremese: None declared, Salvatore De Vita: None declared, francesco ciccia: None declared, Carlo Salvarani: None declared, Maurizio Rossini: None declared, Paola Faggioli: None declared, Antonella Laria: None declared, Amato De Paulis: None declared, Roberto Gerli: None declared, Enrico Brunetta: None declared, Alessandro Mathieu: None declared, Carlo Selmi: None declared, Rossella De Angelis: None declared, Simone Negrini: None declared, Margherita Zen: None declared, Andrea Doria Speakers bureau: GSK, Eli Lilly, Roche, Grant/research support from: GSK, Luca Iaccarino Speakers bureau: GSK, Grant/research support from: GSK

BackgroundAxial Spondyloarthritis (axSpA) can be distinguished in radiographic axSpA (r-axSpA) and non-radiographic (nr-axSpA). Secukinumab (SEC) is a novel treatment for axSpA, but data from real-life are still missing.ObjectivesTo evaluate, in a multicentric-Italian-cohort of axSpA patients on SEC followed for 24-months: a)the long-term effectiveness and safety of SEC; b)the drug-retention-rate and low-disease-activity (LDA) measured as BASDAIMethodsConsecutive patients with active axSpA (diagnosis according Assessment of SpondyloArthritis International Society ASAS criteria), who started SEC treatment, were evaluated prospectively. Data on disease characteristics, previous/ongoing treatments and imaging were collected. Disease-activity/functional/clinical scores and biochemical values were recorded at baseline (T0), at 6 (T6), 12 (T12), and 24 (T24) months. Effectiveness was evaluated over-time with descriptive statistics; multivariate Cox and logistic regression models were used to evaluate predictors of drug-discontinuation and LDA at T6. Infections, adverse events were recorded.Results249 patients (47.8% male; median age 51 years) were enrolled; 40.9% had HLA-B27; 53.8% had r-axSpA and 46.2% nr-axSpA. SEC was prescribed in 28.9% naïve and in 71.1% non-naïve patients. SEC effectiveness was shown as an improvement in several outcomes, such as ASDAS [T0=3.5(2.9-4.4) vs. T24=1.9(1.2-2.4);p=0.02] and BASDAI [T0=6.5(5.0-7.5) vs. T24=2.8(1.8-4.0);p=0.03]. After 24-months of treatment, 90.7% of naïve and 75.3% of non-naïve patients achieved LDA (BASDAITable 1.Clinical, functional, disease activity and serological parameters of naïve (n=72) and non-naïve (n=177) axSpA patients during the 24-month follow-upT0T6T12T24BASMI [0-10], median (IQR)naïve2.0 (1.0-4.0)2.0 (0.0-3.3)1.0 (0.0-2.8)1.0 (0.0-2.0)non-naïve4.0 (1.0-7.0)4.0 (1.0-7.0)2.0 (1.0-4.0)2.0 (1.0-3.0)pp=0.03p=0.04nsnsHAQ-S [0-8], median (IQR)naïve0.8 (0.5-1.3)0.5 (0.0-1.0)0.3 (0.0-1.0)0.1 (0.0-0.5)non-naïve1.1 (0.8-1.5)1.0 (0.4-1.3)0.6 (0.4-0.9)0.7 (0.1-0.9)pp=0.04p=0.04p=0.04p=0.04ASDAS [0-6], median (IQR)naïve3.3 (2.7-3.9)2.1 (1.6-2.7)2.0 (1.2-2.8)1.3 (1.0-2.2)non-naïve3.7 (2.9-4.7)2.9 (2.0-3.7)2.1 (1.9-3.1)2.3 (1.6-2.3)pnsnsnsp=0.04ESR [0-25](mm/h), median (IQR)naïve14.0 (6.0-27.0)10.0 (4.0-19.5)8.0 (3.1-12.8)5.0 (2.0-15.0)non-naïve18.5 (10.0-31.3)15.0 (8.0-25.0)12.0 (6.0-20.0)12.0 (6.0-19.0)pp=0.04p=0.04p=0.04p=0.04Legend: BASMI: Bath Ankylosing Spondylitis Metrology Index; HAQ: Health Assessment Questionnaire modified for spondyloarthritis; ASDAS: Ankylosing Spondylitis Disease Activity Score; ESR: erythrocyte sedimentation rateConclusionIn a real-life clinical-setting, SEC proved to be safe and effective in axSpA, mainly in naïve-patients, with a notable drug-retention-rate. No differences were observed between r-axSpA and nr-axSpA.AcknowledgementsContributing authors of the Spondyloartritis and Psoriatic Arthritis SIR Study Group “Antonio Spadaro”: Alberto Cauli, MD, PhD, Rheumatology Unit, Department of Medical Sciences, AOU and University of Cagliari, Cagliari, Sardegna, Italy; Angelo Semeraro, MD, Rheumatology Unit, Martina Franca-ASL Taranto, Puglia, Italy; Leonardo Santo, MD, Rheumatology Unit, ASL BT Andria – DSS4 Barletta, Italy, Barletta-Andria-Trani, Puglia, Italy; Emanuela Praino, MD, Rheumatology Unit, ASL BT Andria – DSS4 Barletta, Italy, Barletta-Andria-Trani, Puglia, Italy; Giorgio Amato, MD, Rheumatology Unit, A.O.U. Policlinico S. Marco, Catania, Sicilia, Italy; Nicolò Girolimetto, MD, Rheumatology Unit, Department of Internal Medicine, Azienda USL-IRCCS, Istituto di Ricovero e Cura a Carattere Scientifico, Reggio Emilia, Emilia Romagna, Italy.Disclosure of InterestsGiacomo Cozzi: None declared, Mariagrazia Lorenzin: None declared, Maria Sole Chimenti: None declared, Salvatore D’Angelo: None declared, Antonio Marchesoni: None declared, Carlo Salvarani: None declared, Ennio Lubrano: None declared, Luisa Costa: None declared, Ylenia Dal Bosco: None declared, Elena Fracassi: None declared, Augusta Ortolan: None declared, Mario Ferraioli: None declared, Antonio Carriero: None declared, elisa visalli: None declared, RICCARDO BIXIO: None declared, Francesca Desiati: None declared, ALBERTO BERGAMINI: None declared, elisa pedrollo: None declared, Andrea Doria Grant/research support from: Novartis, Abbvie, Pfizer, MSD, Janssen, Rosario Foti: None declared, Antonio Carletto: None declared, Roberta Ramonda Grant/research support from: Novartis, Abbvie, Pfizer, MSD, Janssen

BackgroundMixed cryoglobulinaemic vasculitis (MCV) is an immune-complex-mediated systemic vasculitis characterized by heterogeneous clinical manifestations mainly involving skin, kidney and peripheral nervous system.Despite reassuring safety data from EULAR Coronavirus Vaccine (COVAX) physician-reported registry, a significant proportion of patients with autoimmune diseases reported unwillingness to get vaccinated against SARS-CoV-2 infection in the preliminary results of the COVAD study, due to concerns about the lack of long-term safety data, and fear of associated side effects and disease flare.ObjectivesAims of this multicentre Italian study were to investigate the prevalence of vaccination against SARS-CoV-2 in Italian population of MCV patients, to explore the reason for the missed vaccination, and to investigate short and long-term side effects of the vaccine, including vasculitis flare.MethodsAll MCV patients referring to 12 Italian centres were investigated about vaccination and possible both short- (within 48 hours) and long-term (within 30 days) adverse events (AE), classified according to FDA Toxicity Grading Scale for preventive vaccine clinical trials, and possible disease flares. Patients with MCV related to lymphoproliferative disorders or connective tissue diseases were excluded from the study.The baseline variables were expressed as percentages or mean±standard deviation. The differences between continuous variables were analysed using the Mann–Whitney nonparametric test. The chi-squared test, or Fischer’s exact when appropriate, were used for categorical variables (absolute numbers and percentages) regarding baseline characteristics.ResultsA total of 416 patients, 69.2% females and 30.8% males, with a mean age of 70.4±11.7 years, were included in the study.Only 7.7% of patients were not vaccinated, mainly for fear of adverse events (50%) or for medical decision (18.8%). Corminaty was the vaccine most frequently used (80.5%). Interestingly, 6 patients (1.44%) were with a heterologous vaccination (usually AstraZeneca-Corminaty).Considering ongoing treatment, not vaccinated subjects were more frequently treated with chronic glucocorticoid therapy and/or Rituximab (p=0.049 and p=0.043 respectively).AE were recorded in 31.7% of cases, mainly mild and self-limiting (grade 1). More severe adverse events, such as flare of vasculitis, were observed in 5.3% of cases.AE were not associated with the kind of vaccine used and with the clinical manifestations of vasculitis. Patients with active MCV showed a lower frequency of short-term (within 48 hours) adverse events, but patients affected by peripheral neuropathies or skin vasculitis frequently showed a flare of their symptoms, recorded in 40% and 25% of cases, respectively. Finally, patients under glucocorticoid treatment were more prone to develop a vasculitis flare within a month after vaccination.ConclusionVaccination in MCV patients has been performed in a high percentage of patients showing a good safety. Other than patients’ fear, treatments with rituximab and glucocorticoids are the main reasons for delaying vaccination, and it should be considered by the physician before starting therapy. Vasculitis flares were observed in about 5% of cases, in line with that observed in other autoimmune diseases. Specific attention should be reserved to people with purpura or peripheral neuropathy, for the increased risk of exacerbation of their symptoms.References[1]Visentini M et al Flares of mixed cryoglobulinaemia vasculitis after vaccination against SARS-CoV-2 2021[2]Machado PM et al Safety of vaccination against SARS-CoV-2 in people with rheumatic and musculoskeletal diseases: results from the EULAR Coronavirus Vaccine COVAX physician-reported registry 2021[3]Sen P et al COVAD Study Group. COVID-19 vaccination in autoimmune disease COVAD survey protocol 2022[4]Scarpato S et al Italian Group for the Study of Cryoglobulinaemia GISC. Provisional recommendations for SARS-CoV-2 vaccination in patients with cryoglobulinaemic vasculitis 2021Disclosure of InterestsNone declared

BackgroundSystemic Sclerosis (SSc) is a connective tissue disease characterized by microvascular dysfunction, abnormal fibroblast activation and antibodies production, with cutaneous and visceral involvement. Hand-related manifestations include sclerosis, loss of elasticity, sclerodactyly, painful digital ulcers, atrophy, and gangrene. Autologous fat grafting is based on the implantation of adipose-derived stem cell (ADSCs) which have demonstrated to have pro-angiogenic, anti-inflammatory, regenerative, and immunosuppressive properties. This technique, combined with bone shaving, is believed to be effective in avoiding finger amputation in SSc-patients affected by digital gangrene.ObjectivesEvaluate our experience with the use of autologous fat grafting and bone shaving for the treatment of digital necrosis in patients affected by SSc.MethodsAccording to our schedule, we treated 7 female SSc patients with digital gangrene and exposed bone at the fingertips, enrolled in our University Hospital from March 2018 to January 2020. Digital gangrene was treated by a combination of bone shaving and autologous fat grafting in order to avoid amputation. During the bone shaving, necrotic tissue was removed until bone bleeding was obtained. This procedure could be repeated by trained rheumatologists every 2 weeks in our Clinic. The aim of this repeated debridement was to promote the progression of the granulation tissue inside the dead tissue of the finger. Autologous fat grafting consists of a surgical procedure of ADSCs implantation at the base of the finger. It is performed in order to empower the neurovascular bundle and improve tissue healing. This treatment could be performed every 3 months by trained plastic surgeons. The combination of these two techniques allows the maximum finger length preservation.ResultsComplete healing of all fingers was achieved in 6-12 months by performing bone shaving every 2 weeks and 2 treatments of autologous fat grafting. Results have proved to be long-lasting. At 1-year follow-up, patients did not present any recurrence. Every procedure was performed under local anaesthesia and appropriate analgesic therapy. A high degree of compliance and satisfaction of all patients was noted.ConclusionFinger amputation in Systemic Sclerosis should be avoided. This traumatic surgical procedure is responsible for microvascular damages worsening SSc-related vasculopathy. Stump ulcers often occurs and wound healing usually takes place by secondary intention. In our experience, the combination of bone shaving and autologous fat grafting has proven to be effective and safe in preserving the maximum amount of viable tissue and obtaining a long-lasting result in treated SSc patients.Disclosure of InterestsNone declared

BackgroundSystemic Sclerosis (SSc) is a life-threatening connective tissue disease characterized by endothelial dysfunction, autoimmune abnormalities and aberrant fibrosis. Several reports showed an increased risk of cancer in SSc compared to general population, including breast cancer (BC). The relationship between BC and SSc has long been discussed with contradictory results. In our recent Sclero-Breast study we analyzed clinical-pathological features of BC in SSc; we finally observed the development of BC with early stages and good prognosis among these patients.ObjectivesThe aim of this project was to explore the immunohistochemical (IHC) expression of potential biomarkers involved in the molecular pathways at the basis of SSc and BC etiophatogenesis as update analysis from the Sclero-Breast study.MethodsOur observational multicenter retrospective study, performed at Modena University Hospital and Reggio Emilia Hospital in northern Italy, enrolled 33 SSc women with a personal history of BC between January 2017 and December 2019. Clinical and pathological characteristics of BC and SSc were collected. For 22 patients, BC tissues were available and IHC analysis was performed using specific antibodies to evaluate biomarkers and pathways potentially involved. The antibodies used included: PI3K/mTOR/TGFβ/PDGFRα/PDGFRβ/VEGF/EGFR/IL-6/CTLA-4/PDL1. We also reported TILs percentage (stromal tumor-infiltrating lymphocytes) of each sample. The following scores were assigned for general IHC analysis: (-) negative, (1+) positive tumor cells 50%. For PDL1 we considered a positivity in case of PD-L1 expression ≥1% in infiltrating inflammatory cells. For TILs quantification we applied the score: 0 (negative), ≤ 50% (low-median expression), >50% (high expression).ResultsThe first IHC analysis was performed on the samples of invasive BC patients (20 pts) and showed a prevalence of high PI3K expression (score of 3+ in 55% of cases) with mTOR overexpression in 45%. A PDL1 positivity was detected in 30%, with high TILs expression in 30%. Biopsies from the 2 pts with ductal carcinoma in situ were characterized by a negativity of almost all parameters, except for a medium-high TILs expression reported (40%/90% respectively). See Figure 1. IHC analysis was also performed according to BC subtypes. The group of HR+/HER2 negative showed high PI3K expression (score 3+) in most of cases (59%) with mTOR overexpression in 50%. CTLA-4 and PDL1 were positive in 25%, with high TILs expression in 25%. HER2 positive patients showed a high PI3K positivity in 50% of cases with mTOR positivity (score 3+) in 25% and high TGFβ expression (score 3+) in 25%. PDL1 was positive in 50% with high TILs expression in 25%. In Triple Negative group, PI3K overexpression was found in 75% of pts with half of cases represented by mTOR score 3+. PDL1 was positive in 50% with high TILs representation (80% of total cell count) in 50% of pts.Figure 1.IHC analysis and TILs% expression in histological samples of SSc patients with invasive BC.ConclusionAccording to our results, SSc patients with BC showed high positivity for PDL1 and high TILs representations in all subtypes. Furthermore, the high expression of PI3K, did not always correlate with mTOR overexpression. Further investigations on larger numbers are needed; however, these aspects seem to confirm that SSc subjects might develop BC at good prognosis, suggesting again a de-escalation strategy of cancer therapies. Finally, the possibility to personalize oncological targeted treatments in this subset of fragile patients could be promising.Disclosure of InterestsNone declared

BackgroundPrevious studies have reported the utility of temporal artery examination for the diagnosis of GCA but no data are available on the correlation between clinical examination and the subsequent temporal artery biopsy (TAB) results of the biopsied vessel.ObjectivesEvaluate the predictive value of temporal artery (TA) examination in patients with suspected GCA on the results of TAB of the same vessel.Methods97 pts consecutively seen at our center because of suspected cranial arteritis between 01.01.2015 to 31.12.2021 were enrolled in the study. All patients had complete clinical examination, laboratory investigations (included ESR and CRP determination), clinical examination of the temporal arteries and their frontal and parietal branches for tenderness (P), reduced or absent pulse (R) and thickening (T). All patients underwent arterial ultrasound (US) followed by a TAB of the most US involved frontal branches. The presence of inflammatory infiltrate of the vessel wall or the inflammation of the periadventitial blood vessel were considered positive for the presence of arteritis. The clinical features of the biopsied vessel were compared with the histological results by chi square test and the correspondent OR with 95%CI. Sensitivity, specificity, negative and positive PV, negative and positive LR were calculated for every singular objective abnormalities.Results97 pts entered the study (F 56 (58%), mean age 73 ± 8, biopsy positive 56 (57%). At clinical examination of the biopsied vessel P was reported in 26 cases (27%) of TAB + and 10 (24.4%) in TAB- group (p=0.646, OR 1.24), R in 15 (15.5%) vs 2 (4.9%) (p=0.021, OR 5.69) and T in 16 (28.6%) vs 2 (4.9%) (p=0.003, OR 7.80), anyone (T or P or R) 30 (54.5% vs 11 (26.8%) (p=0.007, OR 3.27), presence of T or R 23 (41.8%) vs 4 (9.8%) (p=0.001, OR 6.65). Sensitivity, specificity, PPV, NPV, PLR, and NLR of any singular objective data and of US examination are reported in Table 1Table 1.SENS, SPEC, PPV, NPV. PLR, NLR, PRETEST probability, POST TEST probability of clinical objective examination and US results FOR TAB POSITIVITYSENSSPECPPVNPVPLRNLRPREPOSTTA EXAMINATIONTENDERNESS (P)0.2860.7560.6150.4371.170.940.570.61REDUCED/ ABSENT PULSE (R)0.2320.9510.8670.4764.760,800.580.87THICKENING (T)0.2860.9510.8890.4945.860.750.570.89ANYONE (P or R or T)0.5450.7320.7320.5452.030.550.570.73R or T0.4180.9020.8510.5364.280.650.570.85USHALO0.8750.6430.6360.8782.450.190.420.64CT+0.8780.6540.6540.8782.540.190.430.65ConclusionClinical examination (in particular reduced pulse and arterial thickening) of the temporal arteries is predictive of histological positivity of the TAB.AcknowledgementsGabriella Di TommasoDisclosure of InterestsNone declared

BackgroundThe ANCA-associated vasculitis patient-reported outcome (AAV-PRO) questionnaire is a 29-item disease-specific PRO measure for AAV[1]. The Italian version of the AAV-PRO questionnaire (AAV-PRO_ita) was translated in collaboration with Oxford and Bristol University (UK) and was preliminarily tested on a single-center Italian cohort[2].ObjectivesThe main objective of this multicentric study was to assess the internal consistency, feasibility, and reliability of the AAV-PRO_ita in a large cohort of Italian AAV patients. The secondary objective was to investigate the clinical characteristics of AAV patients associated with AAV-PRO_ita domains.MethodsThe AAV-PRO_ita is describes the following disease domains: (1) organ-specific and systemic symptoms and signs (SSS); (2) physical function (PF); (3) social and emotional impact (SEI). In this study, Italian-speaking AAV patients were recruited from Italian Centres (N=13) with a large experience in the diagnosis and treatment of systemic vasculitis, belonging to the Vasculitis Study Group of the Italian Society of Rheumatology. Inclusion criteria were: a confirmed diagnosis of GPA, MPA, or EGPA; ANCA positivity in at least once occasion or biopsy-proven AAV; and age ≥18 years old. Participants completed the AAV-PRO_ita at three different time-points: baseline, after 5-7 days, and at month 3.Results229 AAV-patients (56.3% women) with a median age of 61 (IQR 51-72) were recruited and completed the questionnaires. The subtype of AAV was mainly GPA (131, 57.2%), followed by EGPA (58, 25.3%), and MPA (40, 17.5%). Median BVASv3 at baseline was 0 (IQR 0-3), whereas the median BVASv3 at the onset of disease was 14 (IQR 9-20). Participants had a median duration of disease of 67 (IQR 24-126) months. Patients who experienced at least one relapse, one hospitalization, and one severe infection were 40.2%, 53.3%, and 24%, respectively. 83% of the patients were on immunosuppressant therapy and 71.6% were still receiving glucocorticoids (GC).AAV-PRO_ita questionnaire had good internal consistency (Cronbach’s Alpha range 0.81-0.93) and good test-retest reliability (ICCs range 0.93-0.96). Item response rates were high overall (maximum 0.87% missing data), supporting the feasibility of the questionnaire.Concerning the domains of the questionnaire, female AAV patients scored higher (i.e. worse) in all three domains, especially in the SEI domain (p-value0.3, p-valueConclusionThe AAV-PRO_ita questionnaire is a new 29-item, disease-specific PRO measure for use in AAV in the Italian language. It is a self-administered Italian questionnaire with good internal consistency, feasibility, and reliability. AAV-PRO_ita proved to be a useful tool to explore the AAV patient’s perception of quality of life, and it could become an important way of measuring the unmet needs of AAV patients.References[1]Robson, J.C. et al. Validation of the ANCA-Associated Vasculitis Patient-Reported Outcomes (AAV-PRO) Questionnaire. Ann. Rheum. Dis.2018, 77, 1157–1164, doi:10.1136/annrheumdis-2017-212713.[2]Treppo, E.; Palese, A.; Vita, S.D.; Quartuccio, L. AB0392 PRELIMINARY VALIDATION OF THE ITALIAN VERSION OF ANCA-ASSOCIATED VASCULITIS PATIENT-REPORTED OUTCOME (AAV-PRO_ita) QUESTIONNAIRE: FATIGUE AND CHRONIC PAIN AS UNMET NEEDS BY CURRENT TREATMENTS. Ann. Rheum. Dis.2021, 80, 1224–1224, doi:10.1136/annrheumdis-2021-eular.2123.AcknowledgementsWe thank the Italian Study Group on Systemic Vasculitis.Disclosure of InterestsNone declared

BackgroundSystemic Sclerosis (SSc) is a complex autoimmune disease characterized by vascular damage, immune activation and fibrosis of skin and internal organs 1. Raynaud phenomenon (RP) is frequently the first symptom of the disease and growing evidences are supporting the hypothesis the SSc may be a vascular disease, with a pivotal role of endothelial cells, particularly in the very early phase2,3. Robust data support the use of vascular active drug to treat RP and to prevent vascular complication4–7.ObjectivesThe use of prostacyclin analog (PA) is evertything but standardized, with different regimen used all around the Country. We report data on the use of PA in a multicentric regional reality to understand which regimen are prevalent (and why) and if there is the opportunity to standardized them.MethodsWe collected data from an online survey exploring different items related to the use of PA.ResultsSurvey was fullfilled by 12 sites: 5 university hospital and 7 local hospitals, 7 driven by Rheumatologist and 5 from internal medicine specialists with/without concomitant rheumatologists. PA are ubiquitarly used for SSc-related digital ulcers (SSc-DU) and secondary RP but only a half of sites use it for primary RP. Seventy-five percent of sites (9/12) dispense PA at least once a month, but some other (1 each one respectively) on weekly basis, every other month or every 7 weeks. Drug administration may last from 2 to 5 consecutive days (mean 1.91+/- 1.5SD) with drug dose ranging from 0.5 to 2 ng/Kg/min with a minimum variability from site to site. Our regional hospitals may count on overall 68 spots, some available as beds (outpatient or inpatient), some as reclining chair or chair (outpatients only). University centers have usually more assigned personnel than local hospital (on average: 2 versus 1.5 physicians, 2 versus 1.2 nurse). Sites are able to offer meals (except one) and are able to accomodate from 1 to 12 patients at the same time (mean 3.45, +/- 3.2SD).ConclusionPA has known benefit in vascular involvement in SSc patients. Despite a multicenter palcebo-control study8 defining time and dose of this drugs and subsequent data based on the same regimen9, there is no homogeneity in treatment administration. The unequal treatment, based on our data, seems due to limited resources and personnel. High variability has been found in regimen duration and administration frequency.References[1]Ferri, C. et al. Systemic sclerosis evolution of disease pathomorphosis and survival. Our experience on Italian patients’ population and review of the literature. Autoimmunity Reviews vol. 13 1026–1034 (2014).[2]Mulligan-Kehoe, M. J. et al. Antiangiogenic plasma activity in patients with systemic sclerosis. Arthritis Rheum.56, 3448–58 (2007).[3]Wigley, F. M. Vascular disease in scleroderma. Clin. Rev. Allergy Immunol.36, 150–75 (2009).[4]Brueckner, C. S. et al. Effect of sildenafil on digital ulcers in systemic sclerosis: Analysis from a single centre pilot study. Ann. Rheum. Dis.69, 1475–1478 (2010).[5]Kowal-Bielecka, O. et al. EULAR recommendations for the treatment of systemic sclerosis: A report from the EULAR Scleroderma Trials and Research group (EUSTAR). Ann. Rheum. Dis.68, 620–628 (2009).[6]Matucci-Cerinic, M. et al. Bosentan treatment of digital ulcers related to systemic sclerosis: Results from the RAPIDS-2 randomised, double-blind, placebo-controlled trial. Ann. Rheum. Dis.70, 32–38 (2011).[7]Herrick, A. L. & Wigley, F. M. Raynaud’s phenomenon. Best Practice and Research: Clinical Rheumatology (2020) doi:10.1016/j.berh.2019.101474.[8]Wigley, F. M. et al. Intravenous iloprost infusion in patients with Raynaud phenomenon secondary to systemic sclerosis: A multicenter, placebo-controlled, double- blind study. Ann. Intern. Med.120, 199–206 (1994).[9]Cappelli, L. & Wigley, F. M. Management of Raynaud Phenomenon and Digital Ulcers in Scleroderma. Rheumatic Disease Clinics of North America vol. 41 419–438 (2015).Disclosure of InterestsNone declared

Objective: Since of the last publication of last recommendations on primary large-vessel vasculitis (LVV) endorsed by the Italian Society of Rheumatology (SIR) in 2012, new evidence emerged regarding the diagnosis and the treatment with conventional and biologic immunosuppressive drugs. The associated potential change of clinical care supported the need to update the original recommendations. Methods: Using the grading of recommendations assessment, development and evaluation (GRADE)-ADOLOPMENT framework, a systematic literature review was performed to update the evidence supporting the European Alliance of Associations for Rheumatology (EULAR) guidelines on LVV as reference. A multidisciplinary panel of 12 expert clinicians, a trained nurse, and a patients’ representative discussed the recommendation in cooperation with an Evidence Review Team. Sixty-one stakeholders were consulted to externally review and rate the recommendations. Results: Twelve recommendations were formulated. A suspected diagnosis of LVV should be confirmed by imaging or histology. In active GCA or TAK, the prompt commencement of high dose of oral glucocorticoids (40-60 mg prednisone-equivalent per day) is strongly recommended to induce clinical remission. In selected patients with GCA (e.g., refractory or relapsing disease or patients at risk of glucocorticoid related adverse effects) the use of an adjunctive therapy (tocilizumab or methotrexate) is recommended. In all patients diagnosed with TAK, adjunctive therapies, such as conventional synthetic or biological immunosuppressants, should be given in combination with glucocorticoids. Conclusions: The new set of SIR recommendations was formulated in order to provide a guidance on both diagnosis and treatment of patients suspected of or with a definite diagnosis of LVV.

Vogt–Koyanagi–Harada (VKH) is an autoimmune disease characterized by inflammation in tissues that contain melanocytes. We aimed to increase the knowledge regarding immunological pathways deregulated in VKH disease. We compared the percentages of circulating natural killer (NK), NK T and T cells expressing the activatory markers: CD16, CD69, NK group 2D (NKG2D), natural cytotoxicity triggering receptor 3 (Nkp30), natural cytotoxicity triggering receptor 1 (Nkp46) and the inhibitory marker: NK group 2 member A (NKG2A) in 10 active VKH patients, 20 control subjects (CTR) and seven patients with Behçet disease (BD) by flow cytometry. Cytotoxic potential of NK cells was determined through the degranulation marker CD107a expression after contact with K562 cells by flow cytometry. Moreover, plasmatic levels of 27 cytokines were determined with a multiplex bead‐based assay. VKH patients showed higher percentages of NKG2D(pos) NK and NK T cells versus CTR. The cytotoxic potential of NK cells induced by K562 cells was comparable between VKH patients and CTR. Finally, higher concentrations of interleukin (IL)‐4, IL‐5, IL‐7, IL‐17 and platelet‐derived growth factor‐subunits B (PDGF‐bb) were detected in plasma of VKH patients versus CTR. The immune profile of VKH patients was similar to that of BD patients.

INTRODUZIONE L’introduzione dei farmaci biologici ha rivoluzionato l’approccio terapeutico nell’Artrite Idiopatica Giovanile a esordio Sistemico (SoJIA), modificando la storia naturale di questa malattia e migliorandone l’outcome globale. METODI Obiettivo principale dello studio era analizzare il tasso di persistenza in terapia (DRR) degli inibitori dell’Interleuchina (IL)-1 nei pazienti affetti da SoJIA. Obiettivi secondari dello studio erano: (1) esplorare l’influenza della linea biologica di trattamento, degli eventi avversi, dello specifico agente anti-IL-1 e del cotrattamento con disease modifying anti-rheumatic drugs (cDMARDs) sul DRR; (2) identificare eventuali fattori predittivi associati all’abbandono della terapia. Dati demografici, clinici e terapeutici relativi ai pazienti affetti da SoJIA trattati con anakinra e canakinumab in 15 centri italiani sono stati raccolti retrospettivamente ed analizzati. RISULTATI Sono stati arruolati 77 pazienti, corrispondenti a 86 regimi di trattamento. Il DRR cumulativo degli inibitori dell’IL-1 è risultato essere a 12-, 24-, 48- e 60- mesi di follow-up rispettivamente 79.9, 59.5, 53.5 e 53.5%. Non è stata riscontrata alcuna differenza statisticamente significativa stratificando per anakinra e canakinumab (p=0.056) e tra i pazienti trattati in monoterapia e quelli in cotrattamento con cDMARDs (p=0.058). Al contrario, differenze significative sono state individuate tra il gruppo dei pazienti biologic-naive e quello dei pazienti precedentemente trattati con altre terapie biologiche (p=0.038) e in relazione all’occorrenza di eventi avversi (AE) in corso di terapia (p=0.04). Nell’analisi di regressione, i pazienti precedentemente trattati con altre terapie biologiche (HR = 3.357 [CI: 1.341–8.406], p = 0.01) e quelli che presentavano AE (HR = 2.970 [CI: 1.186–7.435], p = 0.020) erano associati ad un hazard ratio maggiore relativamente al rischio di abbandono della terapia. Il treatment delay è risultato essere significativamente più elevato tra i pazienti che hanno abbandonato la terapia (p = 0.0002). CONCLUSIONI I risultati dello studio suggeriscono un eccellente DRR per anakinra e canakinumab, che può essere ulteriormente aumentato attraverso una più attenta gestione degli AE ed impiegando questi farmaci in prima linea in una fase precoce della malattia.

The original version of this article unfortunately contained a mistake. Figure 3 caption is incorrect and co-author name should be E.Tournier-Lasserve.

Background: Evidence on the efficacy of Mepolizumab (MEPO) in Eosinophilic Granulomatosis with Polyangiitis (EGPA) is scarce [1]. Objectives: To assess the efficacy and safety of MEPO in real-life clinical practice. Methods: We retrospectively included patients diagnosed with EGPA and treated with MEPO (100 or 300 mg/month). MEPO efficacy was evaluated in the first 12 months in terms of systemic disease and asthma control. The occurrence of any adverse event (AE) was recorded. Results: 142 patients were included (38% males; median age 46.4 (IQR 36.7-54.4); 110 and 32 on MEPO 100 and 300 mg/month, respectively). General, ear-nose-throat, pulmonary, and neurological symptoms significantly decreased during treatment (table 1). MEPO accounted for a significant reduction in the BVAS (figure 1) and for a steroid sparing effect (figure 2). The proportion of patients with asthma attacks decreased by 90% at 12 months compared to t0, and asthma-related emergency accesses dropped from 17.4% to 2.3%. Overall, 21.1% of patients had a non-serious AE.

Antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) is a group of systemic vasculitides that predominantly affect small vessels, including granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA). Pulmonary involvement is frequently observed in AAV patients, with various possible phenotypes in the different diseases. In the last years, among the possible types of lung involvement, a growing interest has been addressed to the interstitial lung disease (ILD). Prevalence of ILD is higher in MPA than in GPA; in fact, ILD has been reported in up to 45% of MPA patients and in 23% of GPA. Anti-MPO antibodies are the main ANCA subtype associated to ILD, in about 46-71% of cases, while anti-PR3 antibodies are reported in 0-29% of patients. High resolution computed tomography (HRCT) frequently detects interstitial lung abnormalities in AAV, up to 66% of patients with MPA, even if with an unclear clinical relevance, specifically in asymptomatic patients. Ground glass opacities, mainly consistent with diffuse alveolar hemorrhage (DAH), are the most frequent finding in MPA patients, but reticulations, interlobular septal thickening and honeycombing are also reported. ILD significantly affects quality of life and survival, with mortality increased 2 to 4 times, particularly higher in MPA patients with pulmonary fibrosis. Currently, immunosuppressive therapy is considered also as a possible treatment of ILD. However, a careful evaluation of progression and severity of lung involvement, should guide the treatment decision in the single patient. In this review, we discuss the available evidence on clinical features, diagnostic work-up, prognosis and management of AAV-ILD.

Background:In this large worldwide TAK registry, we report 209 patients treated with TNF-α antagonists and tocilizumab aiming to compare their safety and efficacy, and determine the predictive factors of treatment response and relapse.Objectives:To assess safety and efficacy of TNF-α antagonists and tocilizumab in patients with Takayasu arteritis (TAK).Methods:We conducted a retrospective multicenter study in referral centers from France, Italy, Spain, Israel, Japan, Tunisia and Russia about biological-targeted therapies in TAK during the period from January 2017 to September 2019 for the data collection.Results:Two-hundred nine patients with TAK [median age of 29 years [7-62], and 186 (89%) females] were included. They received either TNF-α antagonists [n=132 (63%) with 172 lines; infliximab (n=109), adalimumab (n=45), golimumab (n=8), certolizumab (n=6) and etanercept (n=5)], or tocilizumab [n=77 (37%) with 121 lines; intravenous and subcutaneous in 95 and 26 cases, respectively]. A complete response at 6 months was evidenced in 101/152 (66%) on TNF-α antagonists and 75/107 (70%) on tocilizumab, respectively. Age ≥ 30 years [OR= 2.09 [1.09; 3.99]] was associated with complete response, whereas vascular signs [0.26 [0.1;0.65]], baseline prednisone ≥ 20 mg/day [0.51 [0.28;0.93]] were negatively associated with the complete response to TNF-α antagonists or tocilizumab. During a median follow-up of 36 months, 103 relapses were noted. Supra-aortic branches and thoracic aorta involvements [HR 2.44 (1.06;5.65) and 3.66 (1.18;11.4), respectively], and systemic signs at baseline [HR 2.01 (1.30;3.11)] were significantly associated with relapse. The cumulative incidence of treatment discontinuation and relapse were similar in TNFα antagonists and tocilizumab. Fifty-eight (20%) adverse effects occurred on biological-targeted therapies of whom 37 (21%) and 21 (17%), (p=0.4) on TNF-α antagonists and tocilizumab, respectivelyConclusion:This large multicenter study shows high efficacy of biological-targeted treatments in refractory TAK. Efficacy, relapse and drug retention rate were equivalent with TNF-α antagonists and tocilizumab.Disclosure of Interests:None declared

Behcet’s disease (BD) is a systemic inflammatory disorder whose clinical hallmark is recurrent oral and genital ulcers variably associated with skin and organ involvement. BD is currently considered systemic vasculitis. Vascular involvement is typically characterized by thrombotic events and occurs in about 30% of patients, while cardiac involvement has lower frequency, ranging from 1–6% to 16.5%. Valvulopathies, coronary arteritis with or without myocardial infarction, aneurysms of the coronary arteries, myocarditis, pericarditis, endomyocardial fibrosis, arrhythmia, intracardiac thrombus formation of the heart chambers or of the aortic sinus, and pulmonary artery aneurysm are all possible manifestations of BD. Timely detection of cardiac involvement is pivotal for appropriate management. Echocardiography is the most widely used diagnostic tool and may be complemented by cardiac MRI and/or CT angiography in selected cases. Treatment of cardiac BD is challenging and still largely empirical. High-dose glucocorticoids and immunosuppressive agents are recommended. In this chapter, we review the spectrum of cardiac manifestations in the course of BD. We also analyze the role of the different imaging techniques for an accurate diagnosis, treatment options, and cardiac implications of therapy.