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Background Nonthyroidal Illness Syndrome (NTIS) can be detected in many critical illnesses. Recently, we demonstrated that this condition is frequently observed in COVID-19 patients too and it is correlated with the severity the disease. However, the exact mechanism through which thyroid hormones influence the course of COVID-19, as well as that of many other critical illnesses, is not clear yet and treatment with T4, T3 or a combination of both is still controversial. Aim of this study was to analyze body composition in COVID-19 patients in search of possible correlation with the thyroid function. Methods and findings We report here our experience performed in 74 critically ill COVID-19 patients hospitalized in the intensive care unit (ICU) of our University Hospital in Rome. In these patients, we evaluated the thyroid hormone function and body composition by Bioelectrical Impedance Analysis (BIA) during the acute phase of the disease at admission in the ICU. To examine the effects of thyroid function on BIA parameters we analyzed also 96 outpatients, affected by thyroid diseases in different functional conditions. We demonstrated that COVID-19 patients with low FT3 serum values exhibited increased values of the Total Body Water/Free Fat Mass (TBW/FFM) ratio. Patients with the lowest FT3 serum values had also the highest level of TBW/FFM ratio. This ratio is an indicator of the fraction of FFM as water and represents one of the best-known body-composition constants in mammals. We found an inverse correlation between FT3 serum values and this constant. Reduced FT3 serum values in COVID-19 patients were correlated with the increase in the total body water (TBW), the extracellular water (ECW) and the sodium/potassium exchangeable ratio (Nae:Ke), and with the reduction of the intracellular water (ICW). No specific correlation was observed in thyroid patients at different functional conditions between any BIA parameters and FT3 serum values, except for the patient with myxedema, that showed a picture similar to that seen in COVID-19 patients with NTIS. Since the Na+/K+ pump is a well-known T3 target, we measured the mRNA expression levels of the two genes coding for the two major isoforms of this pump. We demonstrated that COVID-19 patients with NTIS had lower levels of mRNA of both genes in the peripheral blood mononuclear cells (PBMC)s obtained from our patients during the acute phase of the disease. In addition, we retrieved data from transcriptome analysis, performed on human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM)s treated with T3 and we demonstrated that in these cells T3 is able to stimulate the expression of these two genes in a dose-dependent manner. Conclusions In conclusion, we demonstrated that measurement of BIA parameters is a useful method to analyze water and salt retention in COVID-19 patients hospitalized in ICU and, in particular, in those that develop NTIS. Our results indicate that NTIS has peculiar similarities with myxedema seen in severe hypothyroid patients, albeit it occurs more rapidly. The Na+/K+ pump is a possible target of T3 action, involved in the pathogenesis of the anasarcatic condition observed in our COVID-19 patients with NTIS. Finally, measurement of BIA parameters may represent good endpoints to evaluate the benefit of future clinical interventional trials, based on the administration of T3 in patients with NTIS.

Objectives Urinary tract involvement is a seldom-reported manifestation of SSc that could compromise patients’ quality of life. This study compares lower urinary tract symptoms (LUTS) in SSc patients and in healthy subjects and their association with clinical and diagnostic parameters. Methods LUTS were assessed through self-reported questionnaires in 42 SSc patients and 50 matched healthy subjects. Statistical analyses were performed to explore LUTS in the two populations and their association with SSc variables, including nailfold videocapillaroscopy patterns, SSc-related antibodies and DXA parameters. Results SSc patients showed significantly higher prevalence and severity of urinary incontinence (UI) and overactive bladder (OAB) than healthy controls (P < 0.005, P < 0.01). SSc was a strong predictor of LUTS, independent of demographic data, comorbidities and treatments (odds ratio 5.57, 95% CI 1.64–18.88). In SSc patients OAB positively correlated with sarcopenia (P < 0.001), and both OAB and UI significantly correlated with reduced BMD (P < 0.05, P = 0.001). UI positively correlated with Scl70 antibodies (P < 0.05) and ciclosporin treatment (P = 0.001) and negatively with RNA polymerase III antibodies (P < 0.05); OAB positively correlated with calcinosis (P < 0.005) and negatively with methotrexate treatment (P < 0.05). Nailfold videocapillaroscopy ‘active’ and ‘late’ patterns were predominant among SSc patients presenting urinary symptoms, although no statistical correlation was found. Conclusion For the first time urinary tract involvement was found to be significantly higher in SSc patients than in healthy matched controls. In addition, sarcopenia, bone damage and calcinosis appeared significantly correlated with LUTS, suggesting a possible interplay.

Background: Systemic sclerosis (SSc) is characterized by immune system alterations, vascular damage and fibrosis (1). Macrophages seem to have an emerging role in SSc, and the characterization of their polarized phenotype, starting from the dichotomic definition of classically activated (M1) or alternatively activated (M2) macrophages, is a recent research topic of interest (2). Objectives: The study investigated a possible imbalance in the distribution of circulating cells expressing M1 and M2 markers in SSc patients (pts) compared to healthy subjects (HSs), and the presence of circulating cells co-expressing M1 and M2 surface markers. Possible correlations between their percentage and selected SSc clinical aspects were investigated. Methods: In the study 55 SSc pts (50 females/5 males, mean age 64±13 yrs), fulfilling the new EULAR/ACR criteria for SSc diagnosis, and 27 age-matched HSs (25 females/2 males, mean age 57±7 yrs) were enrolled after written informed consent. Nailfold videocapillaroscopy (NVC), evaluation of SSc-related antibodies and pulmonary functional tests were performed. In particular, circulating cells belonging to the leukocyte and monocyte populations (CD45+and CD14+cells) were investigated by flow cytometry (FC) using the surface markers characterizing M1 (CD80, CD86, TLR2, TLR4) and M2 phenotypes (CD204, CD206, CD163). Statistical analysis was performed using Mann-Whitney and Kruskal-Wallis tests, and correlations were explored by bivariate Pearson’s analysis. Results: Increased circulating cells showing an M2 phenotype and characterized as CD204+CD206+CD163+cells was observed in SSc pts compared to HSs (p Conclusion: The study identified a circulating cell population expressing both M1 and M2 surface markers, which is increased together with circulating M2 cells in SSc pts, in particular affected by ILD and high PAP, suggesting their possible involvement in the pathogenesis of those disease complications. Further evaluations are in progress. References: [1] Cutolo M, et al. Nat Rev Rheumatol. 2015;11:569-71. 2. Stifano G, et al. Curr Rheumatol Rep. 2016;18:2. Disclosure of Interests: None declared

Background: Tenderness, swelling and loss of motility of the joints are the main determinants of the disability function (DF) of Rheumatoid Arthritis (RA) patients (RApts)1. The evaluation of DF is performed by Patient Reported Outcomes (PROs), like Health Assessment Questionnaire (HAQ)2. The lack of objective evaluation of DF is one of the most important “unmet needs” in RA. The Hand Test System (HTS, ETT) is an engineered glove, nowadays applied for neuroscience studies to evaluate hands motility with interesting perspectives of use in other clinical research fields3-4. Objectives: To quantify the DF of RApts by the analysis of speed and right execution of fingers opposition movement in both hands, evaluated by HTS. To verify the correspondence with the HAQ. Methods: In this pilot study 14 consecutives RApts (3 males, 11 females, age 61 ± 11,5 years, mean duration of disease 11,21 ± 5,07 years), classified according to 2010 ACR/EULAR criteria5, and 13 healthy controls (HC – 7 males, 6 females, age 50 ± 15 years) were enrolled from the RA clinic. After consent, all participants undergone HTS test that recognizes the touches between the finger tips during the opposition movements of the hands in standard sequences of movements, after dressed the glove. A multiple finger evaluation (MFE) and a single finger evaluation (SFE) were performed using a dedicated software that provided the physician the following quantitative parameters: Touch Duration (TD), Inter Tapping Interval (ITI) and Movement Rate (MR). Average time for hand 2 minutes. RApts compiled the HAQ and a tender and swollen joint count of the hands was performed. Continue variables were summarized as mean and standard deviation (SD) or median and interquartile range (IQR), discrete variables were summarized with count and percentage. Variables with skewed distribution was converted to natural logarithm. T-test was used to compare log glove parameters between groups. Pearson’s r and p value were used to report the correlation between log-converted glove parameters and HAQ score. Results: In MFE, glove parameters TD and ITI were significantly higher in RApts (TD 257.34 ± 123.93 ms, ITI 377.8 ± 211.35 ms) than HC (TD 172.25 ± 59.36 ms, ITI 177.98 ± 78.53 ms) (p = 0.004 and p Conclusion: HTS is a new easy and totally safe tool that seems to quantify in an objective manner the hand DF in RApts. The significant correlation found with HAQ underlines the value and veracity of self-assessment tools in clinical practice. Further studies are ongoing with larger number of RApts to validate its application to monitor the improvement or the worsening of RA in order to optimize pharmacological treatments. The study is now extended in other Rheumatic and Musculoskeletal Diseases. Reference [1] Hakkinen A, et al. Ann Rheum Dis. 2005; 64:59–63. 2 Fries J, et al. Arthritis Rheum. 1980; 23:137–45. 3 Bonzano L, et al. Eur J Neurol. 2019;26(1):162-167. 4 Signori A, et al. PLoS One. 2017 Oct 18;12(10): e0186524. 5 Aletaha D, et al. Ann Rheum Dis. 2010;69(9):1580-8. Disclosure of Interests: None declared

Background Fibroblast-to-myofibroblast transition and extracellular matrix (ECM) overproduction represent fundamental events in chronic inflammation, that characterise several diseases, including psoriasis (1,2). Transforming growth factor-β1 (TGFβ1), plays an important role as a profibrotic mediator (3). Phosphodiesterases (PDE)4 act as proinflammatory enzymes via degradation of cAMP. PDE4 are expressed in normal skin fibroblasts (Fbs) and overexpressed in psoriatic skin Fbs and myofibroblasts (2). Objectives This study investigated how apremilast (an oral PDE4 inhibitor small molecule used for the treatment of psoriasis and psoriatic arthritis) might interfere with intracellular signalling for the fibroblast-to-myofibroblast transition and the synthesis of profibrotic ECM proteins induced by TGFβ1 in primary cultures of healthy human skin Fbs. Methods Human skin Fbs were isolated from 7 voluntary healthy subjects after signing informed consent and EC approval. The cultured Fbs were stimulated with TGFβ1 10ng/ml alone or in combination with apremilast 1μM and 10μM for 4, 16 and 24 hours. Other aliquots of Fbs were also previously stimulated with TGFβ1 for 4 hours and then treated with apremilast 1μM and 10μM for 4, 16 and 24 hours always in the presence of TGFβ1. Genes and related protein expression of α-smooth muscle actin (αSMA), type I collagen (COL-1) and fibronectin (FN) were investigated by qRT-PCR and Western blotting (WB). Smad proteins (the main signal transducers for receptors of TGFβ1) and extracellular signal–regulated kinases (ERKs), which are implicated in mediating TGFβ1 effects, were investigated by WB after 15, 30 and 60 minutes of apremilast treatment combined with TGFβ1 stimulation. Results Apremilast significantly downregulated the phosphorylation of Smad 2 and 3, at 15 minutes, and that of Erk1/2, after 30 minutes (p Conclusion Apremilast inhibited the fibroblast-to-myofibroblast transition in vitro, as well as the profibrotic activity induced by TGFβ1 in cultured skin Fbs by downregulating specific intracellular signalling pathways Smad 2/3 and Erk 1/2. These results might partially explain some of the downregulating effects on skin Fbs overactivity during treatment of skin lesions of psoriasis and that of psoriatic patients with apremilast. Reference [1] Clarke DL, et al. Fibrogenesis & Tissue Repair 2013, 6:20. 2. Schafer PH, et al. Cell Signal. 2016;28:753-63. 3. Carthy JM. J Cell Physiol.2018;233:98-106. Disclosure of Interests None declared

Background Systemic sclerosis (SSc) is a chronic autoimmune disease, characterized by microvascular damage and progressive fibrosis. Among clinical complications, abnormal body composition and sarcopenia have been reported in SSc patients(1,2). Nailfold videocapillaroscopy (NVC) is a safe diagnostic tool to assess microvascular progressive damage and may predict severe organ involvement in SSc(3). Objectives The aim of this study was to evaluate body composition in SSc patients and assess possible differences between patients with specific NVC patterns of microangiopathy. Methods 38 patients (6 men and 32 women) fulfilling ACR 2013 criteria for SSc underwent NVC to assess their NVC patterns (“Early”, “Active” and “Late” pattern)(4) and DXA to evaluate body composition(5). In particular we analyzed: total mass, total lean mass, total fat mass, bone mineral content(BMC), and bone mineral density(BMD) in seven body areas(head, upper limbs, lower limbs, trunk, spine, ribs, pelvis). Sarcopenia was diagnosed in patients with reduced skeletal muscle index (RSMI) below 5.45 Kg/m2 for females and 7.25 Kg/m2 for males(6). Statistical analysis was performed by non parametric tests. Results The mean age of patients was 64±11 years, mean disease duration 19.2 ±7.6 years, mean Rodnan skin score(mRSS) 11.5±9.3, and mean RSMI 6.3±1.05 g/cm2. All the patients showed a NVC “scleroderma pattern”: in particular 15 patients showed the “Late” pattern, 15 patients the “Active” pattern and 8 patients the “Early” NVC pattern. The “Late” NVC pattern group comparing to “Early/Active” group showed significantly lower total mass(58287±8217 vs 67238±11437 gr, p=0.01), lean mass(35249±3646 vs 41230±7954 gr, p= 0.05), RSMI(5.8±0.92 vs 6.6±1.02 g/cm2, p=0.02), BMC(1839±339 vs 2183±502 gr, p= 0.04), trunk BMD(0.70±0.12 vs 0.87±0.13 g/cm2, p=0.05) and spine BMD(0.91±0.17 vs 1.08±0.18 g/cm2, p=0.008). No statically significant difference between the two group was observed regarding total fat mass, total body BMD and BMD at upper limbs, lower limbs, head, ribs and pelvis. Interestingly, 24% of SSc patients were found affected by sarcopenia, and the most of sarcopenic patients showed the “Late” NVC pattern(67%). Comparing age, disease duration, mRSS between sarcopenic and non sarcopenic patients there was no difference between the groups, but sarcopenic patients presented a statistically significant lower BMI(p=0.02). Conclusion This study demonstrates in SSc patients a relationship between a more severe microvascular damage (”Late” SSc pattern) and the body composition, characterized by lower weight, total lean mass, bone mineral content and sarcopenia, without any significant variation in total fat mass. These clinical conditions seem not to be associated with severity of skin involvement and/or disease duration. Reference: [1] Caimmi C, et al. Clinical Rheumatology 2018;37:987-997.2.Thais FM, et al. Clin Rheumatol 2013;32:1037-44.3.Smith V, et al. J Rheumatol. 2013;40:2023-8.4.Cutolo M, et al. J Rheumatol 2000;27:155-60.5.Haarbo J, et al. Clin Physiol 1991;11:331-41.6.Baumgartner RN, et al. Am J Epidemiol 1998;147:755-63. Disclosure of Interests None declared

Background Hand arthralgia is often reported by breast cancer patients treated with adjuvant hormonal therapy. Aromatase inhibitors (AIs) improve survival in postmenopausal women with hormone-sensitive breast cancer, but can cause joint pain and stiffness (2). Low concentration of vitamin D in adults can cause musculoskeletal pain and joint discomfort (1). No data are available to date, on serum concentrations of (25-hydroxyvitamin D) [25 (OH) D3] vitamin D in AI-treated patients and possible relationship with arthralgia. Objectives To evaluate possible correlation between different 25 (OH) D3 serum concentrations and hand arthralgia in patients with breast cancer treated with AIs. Methods All patients that during the AIs therapy develop arthralgia referred to the rheumatologist; they reported the pain following the VAS (visual analogic scale) and contemporary performed a sample blood for dosage of vitamin D as well as biomarkers for inflammation and autoimmunity to exclude concomitant immune/inflammatory rheumatic musculoskeletal causes. Results In a group of 63 women taking AIs (mean age 62.3±9.8years; disease duration from first assumption of AIS 10.6±3.2 months) 81% reported hand arthralgia and stiffness within the first year of follow-up; the most prevalent site of pain localization was bilateral hands (85%). Symptom was associated with minimal increase of serum parameters of inflammation (the mean value of C-reactive protein was 7.1±3.0 mg(L (normal value 0-5) but negative autoimmune profile (negative rheumatoid factors and anticitrullinated protein antibodies). The mean 25(OH)D3 serum concentration was 18.4± 8.5 ng/ml. Only 9% of women had an adequate (≥ 30 ng/ml) [25 (OH) D3] vitamin D serum levels, 70% were insufficient (> 10 Conclusion Vitamin D serum concentrations in women treated with AIs are at lowest ranges in the majority of the patients analysed, but no apparent interference with musculoskeletal symptoms was found related to the different concentrations; the cause of arthralgia might be better related to estrogen deficiency induced by AIs their self. References [1] Kathryn R, et al. 2017 Ther Adv Musculoskelet Dis.9(6):131-135 [2] Hsieh KP, et al. 2014. PLoS One, 9, e87027. Disclosure of Interests None declared

Background Systemic lupus erythematosus (SLE) patients shown an increased risk of low bone mass as a result of multifactorial events: physical inactivity, persistent inflammation, low vitamin D levels (photosensitivity) and glucocorticoid treatment. Trabecular Bone Score (TBS), is an index extracted from the dual-energy X-ray absorptiometry (DXA) that provides an indirect measurement of bone axial microarchitecture and allows to get information about bone quality in several rheumatic diseases (1-4). Objectives The aims of this study were to examine the prevalence and risk factors for low bone mineral density (BMD) (osteoporosis or osteopenia) in female patients affected by SLE and to compare with matched healthy subjects (CNT). Methods 40 female patients (mean age 47±14 years) affected by SLE and 40 age- matched CNT (mean age 49±8 years) were enrolled. Bone Mineral Density (BMD, g/cm2) of the lumbar spine (L1-L4) was analyzed using a DXA scan (GE, Lunar Prodigy) Lumbar spine TBS was derived for each spine DXA examination using the TBS index (TBS iNsight Medimaps). Results The mean BMD±SD was 0.85±0.22 g/cm2 at the lumbar spine and 0.64 ± 0.32 g/cm2 at the hip in SLE patients. The prevalence of osteopenia was 39.0% and 16.4% of osteoporosis in SLE patients. Most of SLE patients (70%) presented a bone loss that was significantly lower when compared with control group (p 10 mg/day) was associated with the preservation of BMD at the lumbar spine but not in spinal trabecular bone as observed by TBS analysis. Conclusion SLE is associated with significant trabecular bone loss, which could not be caused by glucocorticoid therapy. This study confirms the role of TBS as new and safe diagnostic tool for the quantification of the bone quality in chronic and systemic inflammatory rheumatic diseases, such as SLE. References [1] Cutolo M, et al. Ann Rheum Dis.2009;68 446-7; 2 Dey M, et al. Lupus. 018;271547-1551; 3 Ruaro B, Casabella A,et al. Rheumatology (Oxford). 2018;57:1548-1554. 4 Ruaro B, Casabella A,et al. Clin Rheumatol. 2018Nov;37(11):3057-3062. Disclosure of Interests None declared

Background: The fibrosis in systemic sclerosis (SSc) progresses from microvascular alterations, immune system activation, and increased extracellular matrix protein synthesis into the skin and internal organs, primarily mediated by myofibroblasts.1 Myofibroblasts are characterized by a higher expression of α-smooth muscle actin (αSMA) and by the overproduction of type I collagen (COL1) and fibronectin (FN).2 Although myofibroblasts primarily derive from fibroblasts differentiation and transition, circulating fibrocytes represent a further important source.3 Nintedanib is a tyrosine kinase inhibitor that interacts with several inflammatory and profibrotic pathways implicated in the pathogenesis of fibrosis, including those of platelet derived growth factor receptors, vascular endothelial growth factor receptors and fibroblast growth factor receptors.4 Objectives: To investigate, in primary cultures, the effects of nintedanib on the differentiation of circulating fibrocytes and on the profibrotic activity of skin fibroblasts isolated from the same SSc patients. Methods: Circulating fibrocytes and fibroblasts were obtained from peripheral blood and skin biopsies, respectively, from three untreated SSc patients with diffuse skin involvement (mean age 55±6 yrs). To investigate the complete differentiation, fibrocytes were maintained in DMEM at 20% of foetal bovine serum, either with or without treatment with nintedanib at the concentrations of 0.1μM and 1μM for 8 days.5 Fibrocytes were characterized as CD45+CXCR4+COL1+cells, and their percentage was detected by Flow Cytometry analysis.6 Fibroblasts were grown until the 3dr culture passage and then maintained in normal growth medium with or without nintedanib treatment for 4, 24 and 48 hours. The gene expressions of αSMA, COL1 and FN were evaluated by qRT-PCR. Results: Nintedanib reduced the percentage of differentiated SSc fibrocytes (CD45+CXCR4+COL1+cells), already at the concentration of 0.1μM compared with untreated fibrocytes. In cultured SSc skin fibroblasts, nintedanib 1μM downregulated αSMA, COL1 and FN expressions already after 4 hours of treatment, and this effect was also maintained after 24- and 48-hours’ treatment. Nintedanib 0.1μM downregulated the αSMA expression at all timepoints, whereas the downregulation of COL1 and FN expressions was observed at 4 and 24 hours, with no more effect at 48 hours of treatment compared with untreated cells. Conclusion: Initial experiments seem to indicate an evident in vitro concentration-dependent antifibrotic activity of nintedanib on SSc fibrocytes and skin fibroblasts from the same SSc patients; in particular by reducing the fibrocyte differentiation as potential source of myofibroblasts and contrasting the profibrotic activity of already activated fibroblasts/myofibroblasts. These results have translational implications in clinical trials using nintedanib in SSc patients. References: [1] Furue M, et al. Immunol Res 2017;65:790−7. [2] Kendall RT, et al. Front Pharmacol 2014;5:123. [3] Strieter RB, et al. J Leukocyte Biol 2009;88:111−8. [4] Huang J, et al. Ann Rheum Dis 2017;76:1941–8. [5] Cutolo M, et al. Arthritis Res Ther 2018;20:157. Disclosure of Interests: None declared

Background: Non-specific abnormalities (i.e. capillary enlargements) are usually found at the nailfold videocapillaroscopy (NVC) analysis in patients affected by primary Raynaud’s phenomenon (PRP). We have previously demonstrated that capillary diameter is an independent predictor for development of systemic sclerosis (SSc) associated secondary Raynaud’s Phenomenon (SRP), so that progression to SRP is unlikely for subjects affected by RP when average nailfold capillary diameter is under 30 μm [1]. However, until now these findings have not been clearly classified in a defined pattern able to really predict the evolution to a scleroderma-pattern. Objectives: This pilot study aimed to identify in a cohort of SSc patients a “very early” NVC pattern at high risk of evolution in the already defined NVC scleroderma-patterns. Methods: We selected the NVCs of 273 patients affected by SSc (according to 2013 ACR criteria) who presented one of the validated NVC scleroderma patterns (81 with “Early” pattern, 84 with “Active” pattern, 92 with “Late” pattern, 16 with “scleroderma-like” pattern) (2). Among the 273 SSc patient with an established NVC scleroderma-pattern, a number of 54 subjects who had previously NVC analyses performed before the development of the scleroderma-pattern were enrolled. Time of evolution was calculated, and a detailed pilot study of capillaroscopic characteristics was random executed on 10 of those patients. The analysis included the number and the limbs diameters (arterial, venous, and apical) of capillaries with a diameter over 30 μm, together with the total number of capillaries and microhemorrhages, in 16 images per subject. Results: All the 54 patients (100%) showed enlarged capillaries with an average diameter over 30 μm in their previous NVC. At the follow up, thirty-one patients (57%) developed an “Early” scleroderma pattern in the following 3 years, 6 patients (11%) developed an “Active” pattern in 4 years, 3 patients (6%) evolved in “Late” NVC pattern in 5 years, whereas 14 patients (26%) developed a “scleroderma-like pattern” in 4 years. The average time of evolution in a scleroderma-pattern was 4 years. The detailed pilot morphological analysis conducted on 10 patients revealed an average total number of capillaries of 8.6/mm at last non-specific NVC analysis; among these 2.66 (31%) capillaries showed a diameter over 30 μm. The mean value diameter of the most dilated capillary was 35.74 μm (arterial limb 33.34 μm, apical limb 43.94 μm, venous limb 30 μm); the mean value for microhemorrhages was 0.6/mm. The mean number of capillaries reduced from 8.6±0.8 to 6.9±2.2/mm (p=0.01) during follow-up (4 years). Conclusion: Present detailed pilot study demonstrates that SSc patients showed a significant increase of nailfold capillary diameter over 30 μm before development of a validated NVC scleroderma-pattern at follow up. Even if this is an independent predictor for development of SSc as previously demonstrated, the data could help in intercepting patients with RP at higher risk of evolution in a validated SSc NVC pattern. Reference [1] Trombetta AC, et al. J Rheumatol. 2016;43:599-606. 2. Cutolo M, et al. J Rheumatol2000;27:155-60. Disclosure of Interests: None declared

Background: Rheumatoid arthritis (RA) is associated with muscle loss, osteoporosis and an increased risk of fractures. Sarcopenia is a syndrome in which muscle mass loss is linked to functional loss.Trabecular Bone Score (TBS), is an index extracted from the dual-energy X-ray absorptiometry (DXA) that provides an indirect measurement of bone axial microarchitecture and allows to get information about bone quality [1-3]. Objectives: The aims of this study were to examine associations between bone mineral density, bone quality, fat mass and lean mass in the whole body in female patients with RA and healthy controls (CNT). Methods: 55 female patients (mean age 58±12 years) affected by RA and 55 CNT (mean age 52±16 years) were enrolled. Bone Mineral Density (BMD, g/cm 2) of the lumbar spine (L1-L4) and whole body expressed by Relative skeletal mass index (RSMI) was analyzed using a DXA scan (GE, Lunar Prodigy). Lumbar spine TBS was derived for each spine DXA examination using the TBS index (TBS iNsight Medimaps).For all subject was calculate the Body Mass Index (BMI, kg/m2). According to the anthropometric equation [4], sarcopenia was defined as RSMI Results: The mean BMD±SD compared by RA and CNT was 0.894±0.127 g/cm2 vs 1.298±0.672 g/cm2 at the lumbar spine and 0.694±0.842 g/cm2 vs 1.132±0.998 g/cm2 on total hip, respectively, all p Conclusion: This study show that sarcopenia is frequent in RA patients, mostly on those classified as normal or overweight according to BMI. Therefore TBS and BMD values, as demonstrated could have a key role in a bone-muscle feedback in chronic systemic inflammatory rheumatic diseases, such as RA. References [1] Cutolo M et al. Autoimmun Rev 2011:12;84-7 2. Ruaro B, Casabella A, et al. Rheumatology (Oxford). 2018;57:1548-1554. 3.Ruaro B, Casabella A, et al. Rheumatology (Oxford). 2018;57:1548-1554 4. Baumgartner RN et al., J Epidemiol. 147:755–763 Disclosure of Interests: None declared

Objective: The aim of this study was to identify any correlations between microvascular damage, assessed by nailfold videocapillaroscopy and skin impairment, evaluated by three different methods, the modified Rodnan skin score (mRSS), skin high-frequency ultrasound (US) and the plicometer skin test (PST) in systemic sclerosis (SSc) patients. Methods: Sixty-three SSc patients and 63 healthy subjects were enrolled. Nailfold videocapillaroscopy (NVC) was used to assess the nailfold capillaroscopy pattern ("Early", "Active" or "Late"), according to the Cutolo classification. All subjects were assessed by mRSS, US and PST to evaluate their dermal thickness (DT) in the seventeen skin areas of the body usually evaluated by mRSS (zygoma, fingers, hands, dorsum of hands, forearms, arms, chest, abdomen, thighs, legs, feet). Statistical evaluation was performed by nonparametric tests. Results: All the three methods demonstrated progressively higher values of skin impairment in patients with "Early", "Active" or "Late" pattern of nailfold microangiopathy (for mRSS p < 0.01, US p < 0.02 and PST p < 0.02). A positive correlation was also observed in SSc patients between the three methods used to evaluate skin involvement (mRSS vs US, mRSS vs PST, PST vs US, p < 0.0001 respectively). Conclusions: This study demonstrates that there is a correlation between two of the most important aspects to classify and monitor the SSc patients, i.e. microvascular damage progression (evaluated by NVC) and skin damage (assessed by mRss, US and PST).

Rheumatic and musculoskeletal diseases (RMDs) are chronic systemic immune/inflammatory conditions characterized by the interaction between gene predisposition, autoimmunity and environmental factors. A growing scientific interest has focused on the role of diet in RMDs, suggesting its significant contribution to the pathogenesis and prognosis of these diseases. It is now clear that diet can directly modulate the immune response by providing a wide range of nutrients, which interfere with multiple pathways at both the gastro-intestinal and systemic level. Moreover, diet critically shapes the human gut microbiota, which is recognized to have a central role in the modulation of the immune response and in RMD pathogenesis. We hereby provide an in-depth analysis on the role of the microbiota in RMDs and on nutritional intervention as an integral part of a multidisciplinary approach. Particular attention will be given to the Mediterranean diet, as the only diet proven to support substantial benefits in RMD management.

Background and aim Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease; the clinical manifestations are correlated with continuum multiarticular synovitis, cartilage and bone damage, and defeat of joint function, that causes disability. Involvement of internal organs is also frequent. Between the inflammatory cells involved in RA, macrophages play a key role. These cells can polarize in different phenotype and mediate the immune/inflammatory reaction as well as the reparatory phase when possible. The properties of these cells are mediate by the body's environmental factors. In this systematic review, all English-speaking articles concerning the role of M1 (pro-inflammatory) or M2 (anti-inflammatory) macrophages in RA were systematically reviewed and categorized according to their polarized-function in RA, especially in the synovial tissue. Analyses of the endogenous molecules and the drugs that could modulate M1 and M2 activity in RA were achieved. Methods A sensitive search was developed in Pubmed, Web of Science, Ovid Med-Line, Embase Database and Science Direct Database (la both from Elsevier) to identify articles to increase the highlighting on the role of macrophages M1 and M2 in RA using the following terms: ((M1 AND M2) AND Rheumatoid Arthritis). All selected papers were read and discussed by two independent reviewers. The selection process was based on title, abstract and full text level. Relevant data were extracted and analyzed using a standardized template designed for this review. Results In total 39 resulting articles were selected and categorized according to description of M1/M2's role in RA. Data from humans, mice and rats were subcategorized, thus in every section were highlighted the contribute, in peripheral blood and synovial tissue, of both polarized macrophages; section for endogenous molecules and drugs that favor the switch from M1 to M2 macrophages were carried out. The most evinced relevant results, were that in RA blood and in the synovial tissue, there isn't a clear distinction phase with M1 or M2 macrophages (by membrane marker analysis); rather there is M1 and M2 subset disequilibrium and by deeply analyses of mRNA gene and cytokine produced, it emerged that a non-coherent expression inner marker match with membrane molecules, and also the tissue section can define the marker expressed. Conclusion This systematic review emphasizes that the rigid classical subdivision of M1 and M2 macrophages, as well as the different samples' results comparison, might be questionable. In addition, it is suggested, when taking samples from RA patients, to carefully consider their therapies in order to analyze the M1 and M2 macrophages behavior without drug influence. In line with the advances in M1 and M2 knowledge, and the progression in the single-cell methodologies by identification of individual cell molecular markers, therapeutic approaches seem possible to favor the anti-inflammatory macrophage response in RA (e.g. M2 polarization).

Objectives The aim of this six-month open feasibility study was to evaluate skin blood perfusion and clinical symptom changes during aminaphtone treatment in patients with either primary or secondary Raynaud's phenomenon to systemic sclerosis. Methods Ninety-two patients referring for Raynaud's phenomenon have been enrolled in November during routine clinical assessment, after informed consent. Aminaphtone was administered 75 mg twice daily in addition to current treatments to forty-six patients. Skin blood perfusion was measured by Laser Speckle Contrast Analysis (LASCA) at the level of fingertips, periungual areas, dorsum and palm of hands, and face at baseline (W0), after one (W1), four (W4), twelve (W12) and twenty-four (W24) weeks of treatment. Raynaud's condition score (RCS) and both frequency and duration of Raynaud's attacks were assessed at the same time. Results Compared with the control group, despite colder period of the year, aminaphtone treated patients showed a progressive statistically significant increase of blood perfusion, as well as a decrease of RCS, frequency of Raynaud's attacks/day and their duration, from W0 to W12 in all skin areas. From W12 to W24 no further increase of blood perfusion was observed. The results were similar in both primary and secondary Raynaud's phenomenon patients. Five weeks after aminaphtone discontinuation blood perfusion values were significantly higher than those at baseline in the majority of skin areas. Conclusion This study demonstrates that aminaphtone treatment increases skin blood perfusion and improves Raynaud's phenomenon clinical symptoms, with sustained efficacy up to 6 months, even in patients with systemic sclerosis. A randomized, blind, controlled, clinical trial including a larger number of subjects is advisable to confirm these early results.

Background:Vitamin D regulates the innate and adaptive immune system responses and low vitamin D levels have been associated with the increased risk of respiratory tract infections (1). Vitamin D deficiency has been recently reported to interfere with the prognosis of COVID-19 (2,3).Objectives:The aim of this study was to correlate the 25OH-vitamin D serum levels with lung involvement and disease severity, in a cohort of elderly patients hospitalized for SARS-CoV-2 infection.Methods:Sixty-five COVID-19 patients (mean age 76±13 years) and sixty-five sex- and age-matched control subjects (CNT) were included in the study. Respiratory parameters (PaO2, SO2, PaCO2, PaO2/FiO2), clinical and laboratory parameters (including 25OH-vitamin D, D-dimer, C-reactive protein) and type of radiological pulmonary involvement were collected at hospital admission. Statistical analysis was performed by non-parametric tests.Results:Vitamin D sufficiency (>30 ng/ml), insufficiency (between 20 and 30 ng/ml), deficiency (between 10 and 20 ng/ml) and severe deficiency (2 (p=0.05), PaO2 (p=0.03), PaO2/FiO2 (p=0.02). A statistically significant negative correlation was found between vitamin D serum levels and severity of radiologic pulmonary involvement: vitamin D was significantly lower in COVID-19 patients with either diffuse/severe interstitial lung involvement (p=0.05) or multiple lung consolidations (p=0.0001) than in those with mild radiological lung involvement. Significantly lower vitamin D serum levels were found in COVID-19 patients who died during hospitalization, compared to those who survived (median 3 vs 8 ng/ml, p=0.05). Finally, a statistically significant negative correlation was found between vitamin D serum levels and D-dimer (p=0.04), C-reactive protein (p=0.04) and disease duration (p=0.05).Conclusion:This study confirms that severe vitamin D deficiency is associated with more severe lung involvement, longer disease duration and risk of death in elderly COVID-19 patients.References:[1]Cutolo M, et al. RMD Open. 2020; 6(3):e001454.[2]Bilezikian JP, et al. Eur J Endocrinol. 2020; 183(5):R133-R147.[3]Weir EK, et al. Clin Med (Lond). 2020; 20:e107-e108.Disclosure of Interests:None declared

Background:Systemic sclerosis (SSc) is a complex autoimmune connective tissue disease characterized by self-amplifying microvascular damage sustained by autoimmune response and progressive skin and visceral fibrosis. Besides, SSc patients show higher incidence of bone micro/macroarchitectural damages and bone fractures. Emerging data demonstrate that high serum levels of homocysteine (Hcy) could modulate osteoclastogenesis and are recognized as risk factors for osteoporosis (2). Furthermore, serum levels of Hcy were found to be higher in SSc patients than in healthy controls (3).Objectives:to evaluate the bone status according to HCy serum levels in a cohort of SSc patients.Methods:20 female patients fulfilling ACR 2013 criteria for SSc underwent a dual-energy X-ray absorptiometry scan (DXA) (Lunar Prodigy) to evaluate bone status. We analysed bone quantity and quality respectively by bone mineral density (BMD) and trabecular bone score (TBS). According to the WHO criteria, osteoporosis was defined as a bone density of 2.5 standard deviations below that of a young adult (T-Score). Fasting blood samples were obtained from all patients in order to test serum Hcy level and bone turnover markers after obtaining the informed consent. All subjects underwent morphometric spine X-Ray to evaluate vertebral fractures. Statistical analysis was performed using non-parametric tests.Results:The mean age of patients was 64.15 ± 10.8 years with a mean disease duration of 9.1 ± 2.3 years. The mean modified Rodnan Skin Score (mRSS) was 10.7 ± 8.5. All patients showed a “scleroderma pattern” at nailfold Videocapillaroscopy (NVC): in particular, 7 patients showed the “Late” pattern, 9 patients the “Active” pattern and 4 patients the “Early” NVC pattern. Hyperomocisteinemia (HHcy) was found in 25% of patients. Interestingly, SSc patients with the “Late” NVC pattern showed a significantly higher serum level of Hcy compared to the “Early/Active” group (11.15 ± 4.4 vs 17.17 ± 6.4, p=0.03). No significant differences were observed in relation to the autoantibody profiles. Of note, 60% of patients with HHcy were found osteoporotic and 40% had bone fractures.Considering the bone status, patients with Hcy showed a significantly lower TBS (p=0.03); the average values of BMD on the lumbar spine (p=0.79) and femoral neck (p=0.13) were found lower compared to, but without any statistical significance. Furthermore, no significant differences were observed in bone turnover markers according to Hcy levels.Conclusion:The study demonstrates a relationship between higher levels of Hcy and lower TBS values within SSc patients, particularly in those with most severe microvascular damage al NVC (“Late” SSc pattern). Therefore it is concluded that higher serum levels of Hcy associate to both bone microarchitectural and microvascular damage in SSc.References:[1]Cutolo M et al Expert Rev Clin Immunol 2019; 15: 753-64[2]Behera J et al. J Cell Physiol 2017;232(10):2704-2709[3]Yan-lie Zhang et al. Rheumatol 2018; 28(4):681-689Disclosure of Interests:None declared

Background:Microvascular damage is a frequent feature in connective tissue diseases (CTDs) and can be easily detected trough nailfold videocapillaroscopy (NVC) (1,2). Mixed and Undifferentiated connective tissue diseases (MCTD and UCTD) do not show a specific and unique NVC pattern (3). However, a variety of microvascular abnormalities can occur in these two CTDs, both non-specific or specific for the scleroderma like-pattern (3-5).Objectives:To retrospectively assess and compare nailfold microangiopathy observed by NVC in MCTD and stable UCTD versus primary Raynaud’s phenomenon (PRP) (6). In addition, the aim was to correlate NVC findings with serum levels of autoantibodies (Abs) against extractable nuclear antigen (ENA) detected in UCTD.Methods:Files of fourty-six MCTD patients (Kasukawa’s criteria) (mean age 42.8±16 SD years), fourty-seven UCTD patients (mean age 47.7±16.1 SD years), fifty-one PRP (mean age 45.9±17.3 SD years) were retrospectively evaluated in the study. Among UCTD and MCTD patients 95% of both showed Raynaud’s phenomenon. Main NVC parameters (i.e. dilated capillaries, giant capillaries, microhemorrhages, abnormal shapes and number of capillaries) and related semiquantitative scale (score 0–3 for every parameter), were analyzed and compared between the two distinct CTD groups and PRP. Furthermore, ENA Abs (in particular, Ro/SSA, La/SSB, Scl70 and Jo1) were evaluated. The CTD patients were receiving different immunosuppressive treatments. Statistical analysis was performed by non-parametric tests.Results:Among UCTD group, 36% of patients showed a normal NVC pattern, 53% had non-specific NVC abnormalities and 11% had a scleroderma like-pattern. The latter was significantly more frequent in MCTD than in UCTD (pConclusion:NVC features in UCTD patients seem very close to the pattern observed in PRP (mostly non-specific capillary abnormalities), conversely in MCTD the scleroderma-like pattern was found significantly prevalent together with a significant capillary number reduction. The transition from the scleroderma-like to the scleroderma pattern (mean systemic sclerosis) is matter of actual investigation.References:[1]Cutolo M. et al. Best Pract Res Clin Rheumatol 2008; 22:1093-108.[2]Sulli A, Ann Rheum Dis. 2008;67:885-7.[3]Smith V. et al. Autoimmunity Reviews 2020; 19:102458.[4]De Holanda Mafaldo DA, et al. Lupus. 2007; 16:254–8.[5]Smith V, et al. Ann Rheum Dis 2010; 69: 1092-96.[6]Antunes M, et al. RMD Open. 2019, 26;4.Disclosure of Interests:None declared

Background and aim: Vitamin D deficiency is frequently reported in patients with SARS-CoV-2 infection. The aim of this study was to correlate the 25OH-Vitamin D serum concentrations with clinical parameters of lung involvement, in elderly patients hospitalized for SARS-CoV-2 infection. Methods: Sixty-five consecutive COVID-19 patients (mean age 76 ± 13 years) and sixty-five sex- and age-matched control subjects (CNT) were analyzed. The following clinical parameters, including comorbidities, were collected at admission: type of pulmonary involvement, respiratory parameters (PaO2, SO2, PaCO2, PaO2/FiO2), laboratory parameters (including 25OH-vitamin D, D-dimer, C-reactive protein). Results: Significantly lower vitamin D serum levels were found in COVID-19 patients than in CNT (median 7.9 vs 16.3 ng/mL, p = 0.001). Interestingly, a statistically significant positive correlation was observed between vitamin D serum levels and PaO2 (p = 0.03), SO2 (p = 0.05), PaO2/FiO2 (p = 0.02), while a statistically significant negative correlation was found between vitamin D serum levels and D-dimer (p = 0.04), C-reactive protein (p = 0.04) and percentage of O2 in a venturi mask (p = 0.04). A negative correlation was also observed between vitamin D serum levels and severity of radiologic pulmonary involvement, evaluated by computed tomography: in particular, vitamin D was found significantly lower in COVID-19 patients with either multiple lung consolidations (p = 0.0001) or diffuse/severe interstitial lung involvement than in those with mild involvement (p = 0.05). Finally, significantly lower vitamin D serum levels were found in the elderly COVID-19 patients who died during hospitalization, compared to those who survived (median 3.0 vs 8.4 ng/mL, p = 0.046). Conclusions: This study confirms that 25OH-vitamin D serum deficiency is associated with more severe lung involvement, longer disease duration and risk of death, in elderly COVID-19 patients. The detection of low vitamin D levels also in younger COVID-19 patients with less comorbidities further suggests vitamin D deficiency as crucial risk factor at any age.

Background:muscle actin (aSMA)+cells involved in the overproduction of extracellular matrix proteins, primarily fibronectin (FN) and type I collagen (COL1) at the level of damaged tissues (1). These cells may originate from different cell types including fibroblasts, endothelial and epithelial cells, and fibrocytes (1). Circulating fibrocytes are bone marrow progenitor cells expressing specific markers of hematopoietic (CD34, CD45, and MHC class II) and stromal cells (COL1 and COL3), chemokine receptors (CCR2, CCR7), and CXCR4 (2). CXCR4 regulates fibrocyte migration into injured tissues allowing their differentiation into fibroblasts/myofibroblasts (2).In vitro, fibrocytes differentiate from circulating CD14+monocytes showing an antigen-presenting capability through the expression of HLA-DR and costimulatory molecule CD86 (2). CTLA4-Ig fusion protein (abatacept) interacts with CD86 on cell surface of antigen presenting cells (APCs), such as macrophages and endothelial cells (3,4).Objectives:To investigate the possible effect of CTLA4-Ig treatment on cultured human fibrocytes and skin fibroblasts isolated from the same systemic sclerosis patients (SSc pts).Methods:Fibrocytes isolated from the peripheral blood mononuclear cells of SSc pts and healthy subjects (HSs) were cultured on fibronectin-coated plates in DMEM at 20% of FBS; for further 8 days (T8) to allow their complete differentiation. Differentiated fibrocytes were maintained in growth medium or treated with CTLA4-Ig at different concentrations (10, 50, 100, and 500μg/ml) for 3 hours. Fibroblasts were isolated from the skin biopsies of the same patients and HSs, cultured until the 3rdpassage in RPMI at 10% FBS and then treated with CTLA4-Ig for 24 and 48 hours. Fibrocytes were characterized as CD45+CXCR4+COL1+cells and the expression of CD86 and HLA-DR was also evaluated. The gene expression of aSMA, COL1, CXCR4, TGFb1 and CD86 was investigated by quantitative real-time polymerase chain reaction in cultured fibrocytes and skin fibroblasts. In cultured skin fibroblasts, COL1 and fibronectin synthesis was evaluated by Western blotting.Results:Treatment with CTLA4-Ig for 3 hours significantly downregulated aSMA and COL1 gene expression in cultured SSc fibrocytes at T8 (pConclusion:Due to their high expression of CD86, circulating fibrocytes seem to be more responsive to CTLA4-Ig treatment than the skin fibroblasts isolated from the same SSc patient.References:[1]Cutolo M et al. Expert Rev Clin Immunol. 2019;15:753-64.[2]Bucala R. Mol Med.2015;2:S3-5.[3]Cutolo M et al. Clin Exp Rheumatol. 2015;33:250-4.[4]Brizzolara R et al. J Rheumatol. 2013;40:738-40.Disclosure of Interests:Stefano Soldano: None declared, Paola Montagna: None declared, Sabrina Paolino: None declared, Elisa Alessandri: None declared, Carmen Pizzorni: None declared, Greta Pacini: None declared, Federica Goegan: None declared, Alberto Sulli Grant/research support from: Laboratori Baldacci, Carlotta Schenone: None declared, Vanessa Smith Grant/research support from: The affiliated company received grants from Research Foundation - Flanders (FWO), Belgian Fund for Scientific Research in Rheumatic diseases (FWRO), Boehringer Ingelheim Pharma GmbH & Co and Janssen-Cilag NV, Consultant of: Boehringer-Ingelheim Pharma GmbH & Co, Speakers bureau: Actelion Pharmaceuticals Ltd, Boehringer-Ingelheim Pharma GmbH & Co and UCB Biopharma Sprl, Maurizio Cutolo Grant/research support from: Bristol-Myers Squibb, Actelion, Celgene, Consultant of: Bristol-Myers Squibb, Speakers bureau: Sigma-Alpha

Background:Medication adherence in the GLORIA trial, among elderly patients with rheumatoid arthritis, is measured with caps that register openings of the medication bottle. At each study visit, one or two medication bottles with cap (kits) are dispensed, each containing 90 capsules. Multiple steps are needed to come to a workable dataset to describe adherence.Objectives:To describe the steps that are needed to come from raw data to a workable dataset to analyze adherence data that are recorded by electronic caps.Methods:The medication bottle contains a cap with the ability to register cap openings. The raw dataset from the caps consist of an excel file with one opening event per row, recorded as date and time. One cap yields approximately 90 rows. First, the kit numbers were matched to the corresponding patient numbers, that are recorded in another excel file. Instances where two kits were dispensed were recorded with two kit numbers in one cell and need to be copied to two cells with one kit number. Second, the VLOOKUP function was used to combine dates and kit numbers. One row now contains all openings from one kit. Then, the number of days between first opening and each next opening date was calculated. A range of 90 days was made to calculate how many times the bottle was opened on each day of the 90-days period. The results were color-coded to visualize instances of zero, one or ≥two openings on a day.Results:The colored calendar matrix (Figure 1) can now be used to categorize adherence patterns.Conclusion:A monitoring cap seems a simple instrument to measure adherence. However, multiple steps and a lot of time are needed to come to a workable dataset for the study of adherence patterns.Acknowledgments:The GLORIA project is funded by the European Union’s Horizon 2020 research and innovation programme under the topic ‟Personalizing Health and Care’’, grant agreement No 634886.Disclosure of Interests:Linda Hartman: None declared, Elisa Alessandri: None declared, Reinhard Bos: None declared, Daniela Opris-Belinski Speakers bureau: as declared, Marc R Kok Grant/research support from: BMS and Novartis, Consultant of: Novartis and Galapagos, Hanneke Griep-Wentink: None declared, Ruth Klaasen: None declared, Cornelia Allaart: None declared, George Bruyn: None declared, Hennie Raterman Grant/research support from: UCB, Consultant of: Abbvie, Amgen, Bristol-Myers Sqibb, Cellgene and Sanofi Genzyme, Marieke Voshaar Grant/research support from: part of phd research, Speakers bureau: conducting a workshop (Pfizer), Nuno Gomes: None declared, Rui Pinto: None declared, Thomas Klausch: None declared, WIllem Lems Grant/research support from: Pfizer, Consultant of: Lilly, Pfizer, Maarten Boers: None declared

Background:Nailfold videocapillaroscopy (NVC) abnormalities in subjects with isolated Raynaud’s phenomenon (RP) may be present before transition to secondary RP(SRP) and development of a NVC “scleroderma pattern” and are known to predict for evolution to a connective tissue disease (CTD) within few years [1]. In a previous study, we have demonstrated that the very early increase of capillary diameter over 30 μm is an independent predictor for development of Systemic Sclerosis (SSc) associated SRP [2].Objectives:Present pilot retrospective study aimed to investigate in a cohort of patients affected by CTD–related RP the presence of very early capillaroscopic morphological and quantitative abnormalities in the acquired pictures of NVC performed before the development of the NVC scleroderma-pattern. In particular, the study was addressed to identify a “very early”scleroderma pattern, in order to intercept patients with RP at high risk of evolution in a CTD, specifically SSc.Methods:We selected the NVCs of 273 SSc patients presenting one of the validated NVC “scleroderma patterns”. We enrolled 26 SSc patients having a NVC analysis performed before the development ofthe “very early”NVC pattern. As controls, we evaluated 26 patients affected by other CTDs with stable non-scleroderma pattern over time. The 16 images per patient obtained by NVC examination were analyzed for total number of capillaries, number and the limbs diameters of capillaries with a diameter >30 μm, and microhemorrhages. Statistical analysis was performed using non-parametric tests.Results:All 26 SSc patients showed dilated capillaries with a diameter >30 μm in their previous NVC. Patients later developing scleroderma pattern had statically higher number and percentage of capillaries with a diameter >30 μm (p=0.0004 and p=0.0005), as well as a larger apical dilatation >40 μm (p=0.002). A progressive and significant increase in all capillary diameters were only detected in patients later diagnosed for SSc (apical p=0.006, venous p=0.02, arterial p=0.03). A significant homogeneous and progressive dilation was observed from the apical region and then involving both venous and arterial branches, only in SSc patients (p=0.002).Conclusion:Present pilot study demonstrates, for the first time that, before to develop a validated NVC scleroderma-pattern, all potential SSc patients present significant very early morphological and quantitative NVC changes. In particular, the progressive and homogeneous capillary loop dilation over 40 μm in over 40% of total number capillaries significantly could contribute to identify RP patients who will develop a SSc pattern after 4-5 years.References:[1]Cutolo M, Sulli A, Pizzorni C, Accardo S. Nailfold videocapillaroscopy assessment of microvascular damage in systemic sclerosis. J Rheumatol. 2000;27:155-60.[2]Trombetta AC, et al. J Rheumatol 2016;43:599-606.Disclosure of Interests:Monica Pendolino: None declared, Carmen Pizzorni: None declared, Sabrina Paolino: None declared, Federica Goegan: None declared, Emanuele Gotelli: None declared, Carlotta Schenone: None declared, Francesco Cattelan: None declared, Massimo Patanè: None declared, Elisa Alessandri: None declared, Alberto Sulli Grant/research support from: Laboratori Baldacci, Vanessa Smith Grant/research support from: The affiliated company received grants from Research Foundation - Flanders (FWO), Belgian Fund for Scientific Research in Rheumatic diseases (FWRO), Boehringer Ingelheim Pharma GmbH & Co and Janssen-Cilag NV, Consultant of: Boehringer-Ingelheim Pharma GmbH & Co, Speakers bureau: Actelion Pharmaceuticals Ltd, Boehringer-Ingelheim Pharma GmbH & Co and UCB Biopharma Sprl, Maurizio Cutolo Grant/research support from: Bristol-Myers Squibb, Actelion, Celgene, Consultant of: Bristol-Myers Squibb, Speakers bureau: Sigma-Alpha

Background:Lower urinary tract symptoms (LUTS) are an underdiagnosed but frequent manifestation in systemic sclerosis (SSc) [1]. LUTS pathogenesis in SSc is undetermined, mainly involving dysautonomia, fibrosis and a possible antibody-mediated damage [2]. Divergently from general population, female sex and advanced age are not reported to significantly impact LUTS in SSc [2].Objectives:To evaluate the potential influence of gender and hormone-related factors in LUTS prevalence and severity among SSc patients (Pts).Methods:A population of 42 SSc Pts and 50 age- and sex-matched healthy subjects (HSs) was evaluated. SSc diagnosis was based on 2013 ACR/EULAR criteria. Demographic data, medications interfering with pelvic floor dynamics and general comorbidities commonly associated with LUTS – diabetes mellitus, chronic heart failure, chronic obstructive pulmonary disease, peripheral neuropathy, pelvic organ prolapse, fecal incontinence – were recorded. Validated self-reported questionnaires derived from the International Conference on Incontinence were used to assess prevalence and severity of LUTS, namely of urinary incontinence (UI) and overactive bladder (OAB) [3]. Data were analysed using non-parametric tests. Apvalue Results:There were no significant differences in main demographic data between SSc Pts and HSs. Specifically, median age was 61 years (IQR 21-85)vs57 years (IQR 28-93) and female prevalence 83%vs84% in SSc PtsvsHSs, respectively. Amongst the female population, 83% of SSc Ptsvs84% of HSs was in post-menopausal state, with a median of 1 (IQR 0-3)vs1 (IQR 0-4) pregnancy by natural route, respectively. No woman of the study had received hormone replacement therapy or local hormonal therapies prior to the study. Similarly, there were not any significant differences in analysed comorbidities, while ongoing treatment was significantly different between the two populations, SSc patients more frequently receiving calcium channel blockers and glucocorticoids than healthy subjects (p< 0.001). In SSc Pts, statistically significant correlation was observed between stress UI and sex, with an increased female-to-male ratio (p< 0.005), but any significant difference was observed in US distribution depending on parity and menopausal state, nor on other analysed variables. Interestingly, female dominance has not resulted as a significant predictive factor for LUTS prevalence or severity in SSc Pts. In fact, in the regression analysis, SSc disease was the only significant predictor for LUTS (OR 3.45, 95% CI 1.41-7.95; p< 0.01), independently of other analysed variables, particularly of gender and hormone-related factors.Conclusion:This study confirms the absence of pathogenic female-gender participation in LUTS prevalence among SSc Pts. However, consistently with findings on general population, a significant increased prevalence of urinary symptoms, particularly of stress UI, in SSc female Pts has emerged [4]. It is therefore conceivable that hormonal factors may act as a catalytic circumstance rather than pathogenic players in LUTS progression during SSc disease.References:[1]John G et al. Arthritis Care Res (Hoboken) 2018;70(8):1218–27.[2]John G. Clin Rheumatol. 2020;39(1):5–8[3]Abrams P et al, J Urol. 2006;175:1063–6[4]Abelson B et al. Biol Sex Differ. 2018;9(1):45Disclosure of Interests:Greta Pacini: None declared, Sabrina Paolino: None declared, Federica Goegan: None declared, Pietro Francesco Bica: None declared, Elisa Alessandri: None declared, Carmen Pizzorni: None declared, Alberto Sulli Grant/research support from: Laboratori Baldacci, Emanuele Gotelli: None declared, Francesco Cattelan: None declared, Vanessa Smith Grant/research support from: The affiliated company received grants from Research Foundation - Flanders (FWO), Belgian Fund for Scientific Research in Rheumatic diseases (FWRO), Boehringer Ingelheim Pharma GmbH & Co and Janssen-Cilag NV, Consultant of: Boehringer-Ingelheim Pharma GmbH & Co, Speakers bureau: Actelion Pharmaceuticals Ltd, Boehringer-Ingelheim Pharma GmbH & Co and UCB Biopharma Sprl, Maurizio Cutolo Grant/research support from: Bristol-Myers Squibb, Actelion, Celgene, Consultant of: Bristol-Myers Squibb, Speakers bureau: Sigma-Alpha

Background:Systemic lupus erythematosus (SLE) patients shown an increased risk of low bone mass as a result of multifactorial events: physical inactivity, persistent inflammation, low vitamin D levels (photosensitivity) and glucocorticoid treatment. Trabecular Bone Score (TBS), is an index extracted from the dual-energy X-ray absorptiometry (DXA) that provides an indirect measurement of bone axial microarchitecture and allows to get information about bone quality in several rheumatic diseases (1-4).Objectives:The aims of this study were to examine the prevalence and risk factors for low bone mineral density (BMD) (osteoporosis or osteopenia) in female patients affected by SLE and to compare with matched healthy subjects (CNT).Methods:70 female patients (mean age 41±20 years) affected by SLE and 65 age- matched CNT (mean age 46±7 years) were enrolled. Bone Mineral Density (BMD, g/cm2) of the lumbar spine (L1-L4) was analyzed using a DXA scan (GE, Lunar Prodigy). Lumbar spine TBS was derived for each spine DXA examination using the TBS index (TBS iNsight Medimaps).Results:The mean BMD±SD was 0.47±0.57 g/cm2 at the lumbar spine and 0.78 ± 0.22 g/cm2 at the hip in SLE patients. The prevalence of osteopenia was 40.0% and was 19.4% of osteoporosis in SLE patients. Most of SLE patients (75%) presented a bone loss that was significantly higher when compared with control group (pConclusion:The study shows that the further TBS analysis, independently from the concomitant BMD value, is significatively lower then expected in SLE patients. The detection of the TBS, together with the BMD, may offer a more reliable indication of the real whole bone condition in chronic and systemic inflammatory rheumatic diseases, such as SLE.References:[1]Cutolo M et al. Ann Rheum Dis. 2009;68 446-7; 2 Dey M et al. Lupus. 018;271547-1551; 3 Ruaro B, Casabella A, et al. Rheumatology (Oxford). 2018;57:1548-1554. 4 Ruaro B, Casabella A, et al. Clin Rheumatol. 2018 Nov;37(11):3057-3062.Disclosure of Interests:Andrea Casabella: None declared, Sabrina Paolino: None declared, Elisa Alessandri: None declared, Vanessa Smith Grant/research support from: The affiliated company received grants from Research Foundation - Flanders (FWO), Belgian Fund for Scientific Research in Rheumatic diseases (FWRO), Boehringer Ingelheim Pharma GmbH & Co and Janssen-Cilag NV, Consultant of: Boehringer-Ingelheim Pharma GmbH & Co, Speakers bureau: Actelion Pharmaceuticals Ltd, Boehringer-Ingelheim Pharma GmbH & Co and UCB Biopharma Sprl, Barbara Ruaro: None declared, Carmen Pizzorni: None declared, Alberto Sulli Grant/research support from: Laboratori Baldacci, Maurizio Cutolo Grant/research support from: Bristol-Myers Squibb, Actelion, Celgene, Consultant of: Bristol-Myers Squibb, Speakers bureau: Sigma-Alpha

Background Psoriasis is a chronic inflammatory skin disease, and as all inflammatory processes, it could induce osteoclast activation1 ending up with osteoporosis. It is well known that a recognised contributing factor to bone strength, independent from bone mass, is micro-architectural damage; therefore, evaluation of microarchitecture seems to be necessary to get adequate information about bone quality health. Trabecular bone score (TBS) is a new tool to assess bone quality.2 To date, studies on TBS assessment in psoriasis are lacking, even if it was suggested to be correlated with inflammation and metabolic parameters.3 Objectives The aim of the study was to investigate bone quality and bone quantity in psoriatic patients without arthropathic involvement and its relationship with dermal disease activity (PASI). Methods Thirty-five psoriatic patients and thirty-four healthy controls were enrolled. We first assessed Body Mass Index (BMI), Bone Mineral Density (BMD) and Trabecular Bone Score (TBS) in both patients and healthy control. The Bone Mineral Density (BMD) (g/cm2) was analysed by dual-energy X-ray absorptiometry scan (Lunar Prodigy) and, using same machine, anteroposterior spine analysis was performed to evaluate TBS for L1-L4 using TBS insight Medimaps software. TBS >1.350 units was considered normal. Psoriatic patients were also divided in two subgroups according to skin lesion presentation (plaque psoriasis and guttate psoriasis) and dermal disease activity was measured by Psoriasis Area and Severity Index (PASI). Results In the psoriatic cohort (mean age 62.8±12.6 years, BMI 27.8±3.4 g/m2, disease duration 18.6±11.9 years, PASI 8.3±7.6) 36% of patients showed low bone mass, particularly, 33.3% showed osteopenia and 2.7% osteoporosis. There was not significantly statistical difference between mean BMD and TBS in psoriatic patients when compared to the healthy control group. However, in psoriatic patients a negative correlation between neck-BMD and PASI (p=0.003) was detected independently of sex and age. Conversely, TBS was not statistically correlated with PASI or with BMI. It was interesting to verify that the plaque psoriasis group showed a positive correlation between PASI and age (p=0.01). Conversely, PASI was negatively correlated with lumbar spine T-score (p=0.01) and both lumbar spine and femoral neck BMD (p=0.04 and p=0.02 respectively). Conclusions This pilot study suggests that in psoriasis, particularly in the plaque subgroup, the severity of skin involvement might correlate with bone mass but not with bone quality (TBS). Despite previous evidences, we can’t assess any correlation between TBS and metabolic parameters. Furthers studies with larger cohorts are needed on this topic. References [1] Attia EA, et al., J Dermatol2011; 50:30–35. [2] Silva Bc, et al., J Bone Miner Res2014;29:518–30. [3] Hernandez JL, et al., J Osteoporosis, 2016; 5747852 Disclosure of Interest None declared

Background Systemic sclerosis (SSc) as well as rheumatoid artrhritis (RA) patients present an increased risk of osteoporosis (OP) as a result of the chronic inflammatory state, low vitamin D, immobilisation and other causes. The Wnt/β-catenin pathway is signalling identified like a key promoters of the osteoblastogenesis hence of the new bone formation in inflammatory conditions. Dickkopf-1 (DKK1) is a natural inhibitor of Wnt signalling pathway that could be involved in promoting osteoclastogenesis through suppression of osteoprotegerin.1Trabecular Bone Score (TBS) is an index of bone quality extracted from dual-energy X-ray absorptiometry (DXA) analysis.2 Objectives In this study, bone mineral density (BMD) and Dkk-1 levels were evaluated in SSc patients, in order to investigate possible associations between systemic OP and/or osteopenia and Dkk-1 concentrations, according to their different nailfold videocapillaroscopic (NVC) patterns of microangiopathy (NVC patterns ‘Early’, ‘Active’, and ‘Late’)3 in SSc patients and to compare the results regarding bone quality with RA patients and healthy subjects (CNT). Methods Eighty-four SSc patients,98 rheumatoid arthritis (RA) and 60 CNT were studied. Dkk-1 serum levels were measured by ELISA methods (Quantikine Human DKK-1 Immunoassay R and D System, Minneapolis, USA). Bone Mineral Density (BMD, g/cm2) of the lumbar spine (L1-L4) was analysed by dual-energy X-ray absorptiometry (DXA) scan. Lumbar spine bone quality was derived from each spine DXA examination using the TBS analysis. Nailfold videocapillaroscopic (NVC) patterns were analysed as previous reported.3 25 hydroxyvitamin D (25(OH)D ng/ml) serum concentration was evaluated in all subjects. Results Serum DKK-1 levels were significantly higher in patients with SSc than in CNT (2892±1121 pg/ml vs 2044±692 pg/ml, p Conclusions The data obtained showed a significantly Increased of Dkk-1 serum concentrations together and a decreased bone mass (lower TBS and BMD) in SSc patients compared to CNT. The bone quality seems lower in SSc patients with more altered microvasculature (‘Late’ NVC pattern). References [1] Krishnan V, et al. J Clin Invest2006;116:1202–9. [2] Roux JP, et al. Osteoporosis Int2013;24:2455–60. [3] Cutolo M, et al. J Rheumatol2000;27:155–60. Disclosure of Interest None declared

Background Systemic sclerosis (SSc) patients may present muscle involvement in the form of myositis or non-inflammatory myopathy with different degree of weakness and muscle atrophy.1 Sarcopenia is described as a multifactorial syndrome with muscle mass loss associated to functional impairment; according to the anthropometric equation by Baumgartner et al. sarcopenia was defined as relative skeletal muscle mass index (RSMI) Objectives The aim of the study was to evaluate the associations between sarcopenia and other clinical factors in SSc patients. Methods 20 female patients fulfilling the ACR 2013 criteria for SSc (mean age 61.7±13.6 years, disease duration 86.2±67.1 months) were enrolled. The RSMI (Kg/m2) was evaluated by dual-energy X-ray absorptiometry scan (Lunar Prodigy). Nail fold videocapillaroscopic (NVC) patterns (early, active, late) were analysed. Serum 25(OH)2D concentration was tested by immunofluorescence. Non parametric statistical tests were used. Results Patients showed a modified Rodnan skin score (mRSS) 12.2±7.7, RSMI 6.01±0.97 Kg/m2, serum vitamin D (25(OH)2D) 22.01±13.1 ng/dL and CPK 70.16±31.8 U/L. In this cohort 23% of SSc patients were found affected by sarcopenia, and almost 42% showed the most advanced level of microvascular damage, as characterised by the NVC late pattern. However, no statistically relevant correlations was observed between RSMI, BMI, age, disease duration, CPK, mRSS, 25(OH)2D and active or late NVC patterns. Comparing age, disease duration, CPK and mRSS in both sarcopenic and non sarcopenic SSc patients there was no difference between the groups, however sarcopenic patients showed statistically significant lower BMI (p=0.02), lower RSMI (p=0.0008 and higher 25(OH)2D serum concentrations (p=0.01). Particularly, RSMI showed a strong negative correlation with age (p=0.01). No statistical differences were found when grouping the patients according to the positivity for serum anti-topoisomerase I Ab or according to cutaneous diffuse (dcSSc) or limited (lcSSc) systemic sclerosis. Conclusions This pilot study suggests that sarcopenia seems present in almost 25% of the SSc patients, particularly in a condition of advanced microcirculation failure (late NVC pattern), however does not seem to correlate with skin fibrosis or disease duration. The study had some limitations due to absence of control group and to the small patient sample analysed. Further larger studies would be necessary to better investigate the role of sarcopenia in SSc. Reference [1] Ranque, B., Authier, F.J., Berezne, A., Guillevin, L., Mouthon, L., 2007. Ann. N. Y. Acad. Sci. 1108, 268–282 Disclosure of Interest None declared

Background Systemic sclerosis (SSc) is associated with an increased risk of altered bone and fractures as a result of multiple factors, including treatment-related side effects, low vitamin D serum concentrations and reduced physical activity.1 Trabecular Bone Score (TBS) is an index extracted from dual-energy X-ray absorptiometry (DXA) analysis, that provides an indirect measurement of axial bone microarchitecture and bone quality(.2 Objectives The aim of this study was to evaluate possible correlation between bone quality, by TBS, and different levels of microvascular damage, as evaluated by nailfold videocapillaroscopy (NVC) patterns3 in SSc patients and to compare the results regarding bone quality with RA patients and healthy subjects (CNT). Methods Eighty-eight SSc patients, 98 rheumatoid arthritis (RA) patients and 60 CNT were studied. Bone Mineral Density (BMD, g/cm2) of the lumbar spine (L1-L4) was analysed by dual-energy X-ray absorptiometry (DXA) scan. Lumbar spine bone quality was derived from each spine DXA examination using the TBS analysis. NVC patterns were analysed as previous reported.3 All patients were subjected to 25 hydroxyvitamin D (25(OH)D ng/ml) serum dosage. Results TBS values were found statistically higher in SSc with a “Early” NVC pattern, compared to the “Active” or “Late” pattern (1.182±0.1, 1.101±0.8, 1.074±0.1 respectively, p Conclusions The bone quality seems lower in SSc patients with more altered microvasculature (“Late” NVC pattern). The data obtained showed also a significantly lower bone quality (lower TBS and BMD) in SSc and RA patients compared to CNT. The association between bone damage and the ”Late” advanced NVC pattern of microvascular damage, may suggest that tissue hypoxia/ischemia related to the diffuse microangiopathy might be a further promoting factor for osteoclastogenesis and bone loss. Our results support the development of a combined approach using both TBS and BMD for the assessment of bone microarchitecture/quality in SSc patients during their disease progression. References [1] Cutolo M, et al. Autoimmun Rev2011;12:84–7. [2] Roux JP, et al. Osteoporosis Int2013; 24:2455–60. [3] Cutolo M,et al. J Rheumatol. 2000;27:155–60. Disclosure of Interest None declared

Background Aminaphtone is a vasoactive drug that was recently demonstrated to improve both peripheral blood perfusion (BP) and clinical symptoms of Raynaud’s phenomenon (RP) in patients with either primary or secondary RP to systemic sclerosis (SSc).1–2 Objectives The aim of this study was to evaluate possible interferences of different treatment backgrounds on both skin BP and RP-related clinical symptoms in patients treated with aminaphtone, during a six-month follow-up. Methods Forty-six patients with active RP were enrolled during routine clinical assessment after informed consent (11 primary RP, mean age 49±19 SD years, mean RP duration 6±3 years; and 35 secondary RP to systemic sclerosis, mean age 61±17 years, mean RP duration 11±9 years). Aminaphtone was orally administered 75 mg twice daily in addition to current treatments, and all patients were on a stable drug regimen for at least two months, which remained unmodified during the follow-up. All patients were taking cardiaoaspirin. Six groups of treatment backgrounds were identified: 1) no further treatments (12 patients); 2) hydroxychloroquine (2 patients); 3) colchicine (5 patients); 4) methotrexate (3 patients); 5) cyclosporine A (6 patients); 6) mycophenolate (6 patients); 7) proton-pomp inhibitors (12 patients). Blood perfusion was measured by Laser Speckle Contrast Analysis (LASCA)3 at the level of fingertip, periungual areas, dorsum and palm of hands, and face at baseline (T0), after one (T1), four (T4), twelve (T12) and twenty-four (T24) weeks of treatment. Raynaud’s condition score (RCS) and both frequency and duration of Raynaud’s attacks were assessed at the same time. Statistical analysis was performed by non-parametric tests. Results During aminaphtone treatment, a progressive statistically significant increase of blood perfusion, as well as an improvement of RP clinical symptoms (decrease of RCS, frequency and duration of RP attacks/day), were observed in all above reported seven groups of RP patients with different treatments backgrounds from T0 to T12 in all skin areas (p Conclusions This study demonstrates that the increase of skin blood perfusion and the improvement of RP clinical symptoms is not influenced by different treatment backgrounds in RP patients treated with aminaphtone. These preliminary results should be further confirmed by a randomised blind clinical trial. References [1] Parisi S, et al. Am J Int Med2015;3;204–9. [2] Sulli A, et al. Arthritis Rheumatol2017;69:4122. [3] Ruaro B, et al. Ann Rheum Dis. 2014;73:1181–5. Disclosure of Interest None declared

Background The pathogenesis of systemic sclerosis (SSc) still remains unclear, however It is increasingly thought to result from interactions between environmental factors and epigenetic features leading to the onset and progression of SSc in genetically susceptible patients.1 Case reports of women with silicone breast implants who developed SSc have been published, but several case–control series and prospective studies in connective tissue diseases (including SSc) failed to find an increased risk of SSc associated with silicone cosmetic surgery.2 However, several byas may be recognised in these studies, i.e. heterogeneous cohorts of enrolled patients not selective for SSc, non homogeneous either disease duration or disease stage at study entry. For these reason the possible effect of silicone implants as immune adjuvants is not clear.3 Objectives Retrospective study to find out patients who developed SSc after cosmetic surgery. Methods The clinical files of 110 female patients with systemic sclerosis were retrospectively evaluated. Among these, four patients showing a history of silicone cosmetic surgery (3.6%) were identified, and clinical data collected. Results The clinical data of the four patients are below reported. 1. LS 28 year old female who underwent cosmetic breast prosthesis: two years later she complained of Raynaud’ phenomenon (RP), and one more year later aggressive diffuse cutaneous SSc, along with anticentromere antibodies (ACA) positivity. 2. PJ 38 year old female who underwent cosmetic breast prosthesis: one year later she experienced RP and one more year later aggressive diffuse cutaneous SSc; antinuclear antibodies were positive with a speckled patter, but specific SSc-related autoantibodies negative. 3. BS 33 year old female who underwent cosmetic breast prosthesis: two years later she complained of RP and one more year later limited cutaneous SSc with ACA positivity; SSc clinical condition partially improved and its progression stopped after breast prosthesis removal. 4. CM 58 year old female who underwent cosmetic lip silicone application: one year later she complained simultaneous onset of RP and aggressive diffuse cutaneous SSc with anti-Topoisomerase positivity; she died during follow-up. Conclusions This study reports a prevalence of 3.6% of silicone cosmetic surgery before SSc onset. The close temporal association between silicone implant and disease development suggests a possible role of silicone in SSc pathogenesis. Specifically addressed clinical studies or big-data studies need to rule out this matter. References [1] Denton C, et al. Lancet2017; 390: 1685–99. [2] Marie I, et al. Semin Immunopathol2015; 37:463–473. [3] Watad A, et al. Lupus. 2017; 26:675–681. Disclosure of Interest None declared

Background Patients affected by Rheumatoid Arthritis (RA) show an increased risk of low bone mass, as a result of multi-systemic disorders including toxic drug, low vitamin D levels, use of glucocorticoids and physical inactivity. Trabecular Bone Score (TBS), is an index extracted from the dual-energy X-ray absorptiometry (DXA) images, that provides an indirect measurement (Score) of bone axial microarchitecture and allows to get information about bone quality.1,2 Objectives The aim of this investigation was to evaluate by TBS the bone quality in AR patients (high risk population) receiving vitamin D supplementation from at least 3 months (1000 IU/die). Methods 108 female patients (mean age 61±8 years) affected by RA and 60 age- matched controls (CNT) (mean age 64±11 years) were analysed in winter time. Bone Mineral Density (BMD, g/cm2) of the lumbar spine (L1-L4) was analysed using a DXA scan (GE, Lunar Prodigy). Lumbar spine TBS (TBS iNsight Medimaps) was derived for each spine DXA examination. All patients were evaluated for serum 25 hydroxyvitamin D (25(OH)D) serum concentrations. Results RA patients showed lower 25(OH)D concentrations (18.4±1.3 ng/ml) than CNT (26.2±0.9 ng/ml; p Conclusions This study shows in RA patients a reduction of TBS values that seem placed side by side with reduced BMD values and in presence of serum 25(OH)D insufficiency. A more carefull analysis of the clinical status/treatments should let to better identify RA patients at higher risk of bone loss. Reference [1] . Cutolo M et al. Autoimmun Rev 2011:12;84–7,2. Avouac J, et al. Arthritis Care Res 2012;64:1871–8 Disclosure of Interest None declared

Background Epstein-Barr Virus (EBV) and cytomegalovirus (CMV) are among the most diffused virus in humans, with prevalence of 90% and 80% respectively in adult immunocompetent population 1,2 . Hypothesis for a role of EBV and CMV in systemic sclerosis pathogenesis was reported 3 . Objectives To evaluate the prevalence of EBV and CMV in a population of patients affected by SSc. As an exploratory aim, correlations with available clinical variables were evaluated. Methods A total of 49 patients (44 females and 5 males, age 65,6±9 years, 34 with limited cutaneous involvement and 14 with diffused cutaneous involvement) diagnosed according to the 2013 ACR/EULAR criteria 4 were randomly enrolled at their follow-up visit for a further more detailed analysis. After consent, all participants undergone serological testing for VCA-IgM, VCA-IgG and EBNA-IgG and CMV IgM and IgG, to determine prior or actual EBV and/or CMV infection. All SSc patients undergone also to clinical examination and instrumental evaluations according to SSc clinical standard follow up. Results Results for EBV seroprevalence were: VCA-IgM negative=43 (87%), positive=4 (8,2%), borderline=2 (4,1%) in all SSc patients. VCA-IgG resulted positive in 48 patients (98%) and EBNA-IgG resulted positive in 40 (81,6%) patients, borderline in 4 (8,2%) and negative in 5 (10,2%) patients. Forty-six (93,9%) patients resulted positive for CMV-IgG and 22 (44,9%) showed detectable CMV IgM. Consequently, EBV and CMV seroprevalence was significantly higher (p=0.01 and p=0.032 respectively) than that calculated in general population (90% and 80% respectively). Interestingly, the presence of higher CMV-IgM correlated linearly with higher pulmonary arterial pressure values (p=0.036) and was different in patients with or without sicca syndrome (p=0.012) and arthralgias (p=0.04). Finally, higher CMV-IgG correlated with diffused cutaneous SSc form (p=0.023) and nephropathy (p=0.036). Conclusions The seroprevalence of EBV and CMV positivity was found significantly higher in the sample of SSc patients. EBV seropositivity (VCA-IgG) was present nearly in the totality of patients (98%). Of relevance, the high presence of CMV-IgG (93%) and CMV-IgM (44.9%) in SSc patients: the last correlated linearly with higher pulmonary arterial pressure values. EBV and CMV infections, among the supposed triggers in several autoimmune diseases, might also play a role in SSc patients, at least with progressive disease. References [1] Rickinson AB, et al. Fields virology. Philadelphia: Lippincott Williams and Wilkins; 2001. pp. 2575–2627 [2] Kano Y1, et al. Dermatol Sci. 2000;22:196–204 [3] Arnson Y, et al. Ann N Y Acad Sci. 2009Sep;1173:627–32. [4] van den Hoogen F, et al. Ann Rheum Dis. 2013;72:1747–1755. Disclosure of Interest None declared

Objectives. SSc patients are recognized as presenting an increased risk of altered bone mass. The aim of this study was to assess the bone quality, by trabecular bone score (TBS), in SSc patients in correlation with different levels of microvascular damage, as evaluated by nailfold videocapillaroscopy (NVC), and to compare the results regarding bone quality with RA patients and healthy subjects (CNT). Methods. Eighty-four SSc patients, 98 RA patients and 60 CNT, were studied. BMD (g/cm(2)) of the lumbar spine (L1-L4) was analysed by DXA scan. Lumbar spine bone quality was derived from each spine DXA examination using the TBS analysis. NVC patterns were analysed. Results. A total of 56/84 SSc patients (66%) as well as 78/98 RA patients (80%) showed bone loss at DXA and BMD was found to be significantly lower than in the CNT (P< 0.001). Similarly, lumbar spine TBS was found to be significantly lower in SSc and RA patients than in CNT (P< 0.001). TBS values were found to be lower in SSc with a late NVC pattern, compared with the active or early pattern (late vs active and early pattern, P< 0.001). There was no statistically significant difference in the mean lumbar spine TBS between SSc and RA patients (P = 0.238). Conclusion. The data obtained showed significantly lower bone quality (lower TBS and BMD) in SSc and RA patients compared with CNT. The bone quality seemed lower in SSc patients with more altered microvasculature (late NVC pattern).

Systemic sclerosis is an autoimmune connective tissue disease characterized by early and persistent microvascular impairment which leads to functional and organic manifestations, with progressive fibrosis of the skin and internal organs. Morphological and functional assessment of the peripheral microvasculature is a must, not only for diagnosis but also for the prognosis and therapeutical follow-up of systemic sclerosis patients, as reported in recent studies. Nailfold videocapillaroscopy is the validated technique for the study of scleroderma microangiopathy as it is able to detect peripheral microvascular morphology and both classify and score the capillary abnormalities into different microangiopathy patterns (‘Early’, ‘Active’ and ‘Late’). Indeed, the possibility to early diagnose and follow the microvascular changes and the safety of the technique have made nailfold videocapillaroscopy a mandatory tool for patient evaluation and included its assessment in the new systemic sclerosis classification criteria. Important links between nailfold videocapillaroscopy patterns and systemic sclerosis clinical manifestations have been described.

Background Raynaud9s phenomenon and digital ulcers are common clinical skin manifestations of the microvascular dysfunction in systemic sclerosis (SSc). Although microvascular and macrovascular abnormalities frequently coexist in disease such as diabetes mellitus and other vascular diseases, the possible association between microvascular failure and macrovasculopathy in SSc patients has not been deeply investigated (1). Objectives The aim of the study was to estimate in SSc patients the macrovascular function by measuring of the Intima-Media Thickness (IMT) of high-caliber and periferic small-caliber arteries, and to evaluate the possible correlation with microvascular blood perfusion (BP) assessed by Laser Speckle Contrast Analysis (LASCA). Methods Twenty-nine female SSc patients (mean age 65.7±12.07 SD years, mean disease duration 97.3±68.01 SD months) were enrolled after informed consent. Carotid IMT was evaluated through B-mode US imaging (Esaote, Genoa) using transducer 18 MHz on both right and left common carotid arteries (CCA) as well as ulnar (UA) and radial arteries (RadA). Therefore, an average IMT score was obtained for any evaluated site. Peripheral BP was assessed by LASCA (Perimed-Sweden) at the level of fingertips, periungueal areas, dorsum and palm of both hands, and face. The BP values were reported as perfusion units (PU) (2). In addition nailfold videocapillaroscopy (NVC) in order to assess the microvascular morphological status was done by nailfold video capillaroscopy (NVC) considering the different progressive SSc patterns and the microangiopathy evolution score (MES) (3–4). Results A positive correlation was observed between CCA IMT and age (p=0.004) and disease duration (p=0.02). On the other hand, no significant correlations were observed between IMT of periferic small-caliber arteries (UA and RadA) and age or disease duration. Positive correlations were found between microvascular damage, as assessed by MES and IMT at the level of periferic small-caliber arteries.No significant correlation was observed between macrovascular involvement of high-caliber arteries and peripheral BP as assessed by LASCA. However, at the peripheral site a correlation was observed between RadA IMT and palm (p=0.05), periungueal (p=0.04) and dorsum of hand BP (p=0.0006), as assessed by LASCA. UA IMT showed a correlation limited to the dorsum of the hand (p=0.003). Conclusions Significant correlations seem to exist between increased IMT of periferic small-caliber arteries (macrocirculation) and altered peripheral BP (LASCA) at the level of hand microvessels (microcirculation) in SSc patients. These results were found strength by a further correlation with the microvascular damage (MES). References Hettema Me et al. Rheumatology (Oxford) 2008;47:578–83. Ruaro B et al. Ann Rheum Dis 2014;73:1181–5. Sulli A, et al. Ann Rheum Dis 2008;67:885–7. Cutolo et al. J Rheumatol 2000; 27;155.60. Disclosure of Interest None declared

Background The modified Rodnan skin score (mRSS) is the validated method to evaluate the extension of skin involvement in systemic sclerosis (SSc) and to distinguish between patients with limited cutaneous skin involvement (lcSSc, skin involvement is confined to the extremities) or diffuse (dcSSc) (1,2). Recently several studies have demonstrated that skin high frequency ultrasound (US) is a valid and reproducible technique to measure dermal thickness (DT) in patients with SSc (3–6). Objectives To compare the values of DT obtained by two ultrasound transducers with different frequency (18 MHz and 22 MHz) in evaluating the DT in lcSSc patients and healthy controls. Methods Thirty-seven lcSSc patients (mean age 62±13SD years, mean disease duration 5±5SD years) and 37 healthy controls (CNT) sex and age matched were enrolled after informed consent. Both US transducers of 18 and 22 MHz (Esaote, Genova) were used to evaluate DT in the seventeen areas of the skin (zygoma, fingers, dorsum of hands, forearms, arms, chest, abdomen, thighs, legs, feet) of SSc patients where Rodnan skin score (mRSS) is usually assessed. Skin US was also performed in the same seventeen areas of CNT, looking for DT differences in comparison with lcSSc patients. Statistical analysis was carried out by non parametric tests. Results DT evaluated with the 22 MHz probe was found significantly higher in all body areas in comparison with the 18 MHz transducer, both in lcSSc patients (p Conclusions This study suggests that subclinical dermal involvement may be detectable by skin high frequency US already in patients with limited cutaneous SSc. This study confirms that DT can be better assessed in SSc patients by using a 22 MHz US probe, and suggests that DT might be underestimated by using US probes of lower frequency (18 MHz). However, the DT values obtained using both probes resulted significantly correlated together and with the mRSS. References Clements PJ, et al. Arthritis Rheum 2000;43:2445–54. Moore TL, et al. Rheumatology 2003;42:1559–63. Sulli A, et al. Ann Rheum Dis. 2014;73:247–51. Czirjak L, et al. Ann Rheum Dis. 2007;66:966–9. Hesselstrand R, et al. Rheumatology 2008;47:84–7. Kaloudi O, et al. AnnRheum Dis.2010;69:1140–3. Disclosure of Interest None declared

Background Systemic sclerosis (SSc) is a rare connective tissue disorder characterized by an increased synthesis and deposition of extracellular matrix in the skin and internal organs (1). Several studies described SSc as potential risk factor for osteoporosis, however, to date the bone quality in SSc is unclear (2). Trabecular bone score (TBS) has been recently proposed as an indirect measure of bone microarchitecture (3). Objectives The aim of this study was to assess bone microarchitecture in SSc patients and possible association with disease severity and microangiopathy. Methods Twenty-three female SSc patients (mean age 63.2±12.8 SD years, mean disease duration 92.8±66 SD months, mean Raynaud9s Phenomenon duration 142.6±126.1 SD months) were enrolled after written informed consent. The assessment of disease severity was performed using the Medsger9s severity scale (4). Bone Mineral Density (BMD) measurements at L1-L4, femoral neck and total hip, were performed using DXA Prodigy Densitometer (GE Lunar). TBS was derived for each spine DXA examination using the TBS index (TBS iNsight Medimaps). Nailfold videocapillaroscopy (NVC) was used to assess the microangiopathy based on nailfold video capillaroscopic pattern (NVC) analysis and the microangiopathy evolution score (MES) (5–6). Using the FRAX (Fracture Risk Assessment Tool) we also evaluate the 10-year risk of hip and major joints osteoporotic fracture. Results A positive correlation was observed between TBS and Medsger9s general organ score (r=0.5; p=0.01); no other correlations were found between TBS and Medsger9s score. Interestingly, TBS was positively and significantly correlated with modified Rodnam skin score (mRss) (p=0.01). When the patients were divided in two groups considering skin involvement by mRss, TBS was found significantly higher into the group with mRss >15 compared to the group with mRss Conclusions This study demonstrates in SSc patients a relationship between clinical disease severity (organ fibrosis/failure) and altered bone microarchitecture (TBS). In addition, skin involvement was found significantly correlated with altered quality of the trabecular bone architecture (TBS) and a significant increase of osteoporotic fracture risk (FRAX) was found correlated with kindey and lung involvement. References Varga J, Abraham D. J Clin Invest. 2007 Mar;117(3):557–67. Loucks J, Pope JE. Semin Arthritis Rheum. 2005 Feb;34(4):678–82. Silva BC et al. J Bone Miner Res. 2014 Mar;29(3):518–30. Medsger TA et al. Clin Exp Rheumatol. 2003;21(3 Suppl 29):S42–6. Sulli A, et al. Ann Rheum Dis 2008;67:885–7. Cutolo et al. J Rheumatol 2000; 27;155.60. Disclosure of Interest None declared

Background Aminaphtone (1,4-Dihydroxy-3-methyl-2-naphthyl-4-aminobenzoate) is a vasoactive drug that was recently demonstrated to improve the symptoms of Raynaud9s phenomenon (RP) and to down-regulate endothelin-1 production by endothelial cells (1–3). Objectives To evaluate skin blood perfusion and clinical symptom changes during aminaphtone treatment in patients with both primary and secondary RP, during a six-month follow-up. Methods Forty-six patients with active RP were enrolled during routine clinical assessment in November 2015 (11 primary RP, mean age 49±19SD years, mean RP duration 6±3 years; 35 secondary RP to systemic sclerosis, mean age 61±17 years, mean RP duration 11±9 years), after informed consent. Aminaphtone was administered 75 mg twice daily (off label) in addition to current treatments (the patients were on a stable drug regimen for at least two months before, which remained unmodified during the follow-up). Blood perfusion was measured by Laser Speckle Contrast Analysis (LASCA) and values recorded as perfusion units (PU) (4), at the level of fingertips, periungual areas, dorsum and palm of hands, and face, at baseline (T0), after one (T1), four (T4), twelve (T12) and twenty-four (T24) weeks of treatment. Raynaud9s condition score (RCS) and both frequency and duration of Raynaud9s attacks were assessed at the same time. Forty-six patients with RP (9 primary RP and 37 secondary RP to systemic sclerosis) not treated with aminaphtone were also enrolled as a control group and evaluated at T0 and T24. Results A progressive statistically significant increase of blood perfusion was observed from T0 to T12 in all skin areas analyzed (median PU at T0, T1, T4, T12, T24 respectively: fingertips 55, 88, 101, 107, 98 periungual areas 44, 88, 91, 92, 92; dorsum of hands 38, 61, 71, 75, 75; palm of hands 56, 85, 89, 94, 82; whole face 127, 138, 144, 159, 129; p Conclusions This study demonstrates that aminaphtone treatment seems able to increase skin blood perfusion and to improve RP symptoms, even in patients affected by systemic sclerosis. These preliminary results should be further confirmed by a randomized clinical trial, also to assess the role that aminaphtone plays in the treatment/prevention of disease clinical complications. References Parisi S, et al. Am J Int Med 2015;3;204–9. Scorza R, et al. Drugs R D 2008;9:251–7. Salazar G, et al. Eur J Pharmacol. 2016;782:59–69. Ruaro B, et al. Ann Rheum Dis. 2014;73:1181–5. Disclosure of Interest None declared

Background Systemic sclerosis (SSc) is characterized by the increase of dermal thickness (DT) (1). The modified Rodnan skin score (mRss) is the validated method to evaluate the severity of skin impairment (2,3). Several studies have reported the capability of high frequency skin ultrasound (US) to reflect the overall severity of the skin damage in SSc patients (4–5). The plicometer skin test (PST) is another method to evaluated cutaneous involvement in SSc patients (6). Objectives The aim of this study was to identify possible correlations between US, mRss and PST to evaluate DT in SSc patients with different patterns of nailfold microangiopathy. Methods Sixty-three SSc patients (mean age 64±11SD years, mean disease duration 7±6 years, 43 lcSSc and 20 dcSSc) and 63 sex and age matched healthy subjects were enrolled after written informed consent. All subjects were assessed by mRss, US and PST to evaluate the DT in the seventeen skin areas of the body usually evaluated by mRss (zygoma, fingers, hands, dorsum of hands, forearms, arms, chest, abdomen, thighs, legs, feet) (1–6). Nailfold videocapillaroscopy (NVC) was used to assess the proper pattern of microangiopathy and to calculate the microangiopathy evolution score (MES) (7–8). Statistical evaluation was performed by non-parametric tests. Results As expected, the group of SSc patients had a statistically significant higher DT, as evaluated by the three methods, at level of all areas when compared to the control group (p=0.0001). All methods demonstrated a progressively higher DT in patients with “Early”, vs. “Active” and vs “Late” pattern of nailfold microangiopathy (p Conclusions This study demonstrates a relationship between different methods to assess DT (US, mRss and PST) in SSc patients and a relationship between skin damage and microangiopathy impairment. References Moore TL, et al. Rheumatology 2003;42:1559–63. Sulli A, et al. Ann Rheum Dis. 2014;69:1140–3. Kaldas M, et al. Rheumatology 2009;48:1143–6. Hesselstrand R, et al. Rheumatology 2008;47:84–7. Kaloudi O, et al. Ann Rheum Dis. 2010;69:1140–3. Parodi MN, et al. Br JRheumatol. 1997;36:244–50. Sulli A, et al. Ann Rheum Dis 2008;67:885–7. Cutolo et al. J Rheumatol 2000; 27;155.60. Disclosure of Interest None declared

Microvascular damage and a decrease in peripheral blood perfusion are typical features of systemic sclerosis (SSc) with serious clinical implications, not only for a very early diagnosis, but also for disease progression. Nailfold videocapillaroscopy is a validated and safe imaging technique able to detect peripheral capillary morphology, as well as to classify and to score any nailfold abnormalities into different microangiopathy patterns. Capillaroscopic analysis is now included in the ACR/EULAR classification criteria for SSc. The decrease in peripheral blood perfusion is usually associated with microvascular damage in SSc, which may be studied by different methods. Several of these make use of safe laser technologies. This paper focuses on these new clinical aspects to assess SSc microvascular impairment.

Summary Chronic obstructive pulmonary disease (COPD) is a cluster of heterogenic disorders, characterized by expiratory flow limitation that is not completely reversible and in most cases progressive. COPD exacerbation represents one of the leading causes of ICU admission; while in the past patients with COPD exacerbation were treated with conventional pharmacological treatment plus O 2 , followed by invasive ventilation in case of treatment failure, an integrated approach combining noninvasive ventilation (NIV) as first-line treatment with conventional ventilation only in those patients who fail NIV or present contraindications seem able to offer optimal clinical results. The aim of this review is to discuss an updated approach for the optimal treatment of patients with COPD exacerbation, starting from a pathophysiological basis.

The aim of this study was to identify possible correlations between nailfold microangiopathy severity, finger dermal thickness (DT) and fingertip blood perfusion (FBP) in systemic sclerosis (SSc) patients.Fifty-seven SSc patients and 37 healthy subjects were enrolled. All patients were evaluated by nailfold videocapillaroscopy (NVC) to classify and score the severity of microangiopathy. Both modified Rodnan skin score (mRss) and skin high-frequency ultrasound were used to detect finger DT. Laser Doppler flowmetry (LDF) was employed to detect FBP.A positive correlation was found between nailfold microvascular damage severity and both ultrasound-DT (p=0.028) and mRss values (p0.0001). In particular, both ultrasound-DT and mRss were found progressively higher in patients with 'Early', 'Active' or 'Late' NVC pattern of microangiopathy. A negative correlation was observed between nailfold microvascular damage severity and FBP (p0.0001), showing the lowest FBP of the patients with more advanced NVC patterns. A negative correlation was observed between FBP, and both ultrasound-DT (p=0.007) and mRss values (p=0.0002). SSc patients showed a higher ultrasound-DT at the level of the fingers, as well as a lower FBP than healthy subjects (p0.0001).This study demonstrates a relationship between nailfold microangiopathy severity, DT and FBP in SSc patients.