Search

Pain is the main symptom of entheseal diseases (enthesopathies) despite a paucity of nerve endings in the enthesis itself. Eicosanoids, cytokines, and neuropeptides released during inflammatory and repeated non-physiological mechanical challenge not only stimulate or sensitize primary afferent neurons present in structures adjacent to the enthesis or but also trigger a "neuro-vascular invasion" that allows spreading of nerves and blood vessels into the enthesis. Nociceptive pseudo-unipolar neurons support this process by releasing neurotransmitters from peripheral endings that induce neovascularization and peripheral pain sensitization. This process may explain the frequently observed dissociation between subjective symptoms, i.e. pain and the structural findings in imaging in entheseal disease.

Objectives It has recently become possible to assess lung vascular and parenchymal changes quantitatively in thoracic CT images using automated software tools. We investigated the vessel parameters of patients with SSc, quantified by CT imaging, and correlated them with interstitial lung disease (ILD) features. Methods SSc patients undergoing standard of care pulmonary function testing and CT evaluation were retrospectively evaluated. CT images were analysed for ILD patterns and total pulmonary vascular volume (PVV) extents with Imbio lung texture analysis. Vascular analysis (volumes, numbers and densities of vessels, separating arteries and veins) was performed with an in-house developed software. A threshold of 5% ILD extent was chosen to define the presence of ILD, and commonly used cut-offs of lung function were adopted. Results A total of 79 patients [52 women, 40 ILD, mean age 56.2 (s.d. 14.2) years, total ILD extent 9.5 (10.7)%, PVV/lung volume % 2.8%] were enrolled. Vascular parameters for total and separated PVV significantly correlated with functional parameters and ILD pattern extents. SSc-associated ILD (SSc-ILD) patients presented with an increased number and volume of arterial vessels, in particular those between 2 and 4 mm of diameter, and with a higher density of arteries and veins of Conclusion In SSc patients CT vessel parameters increase in parallel with ILD extent and functional impairment, and may represent a biomarker of SSc-ILD severity.

Background/Aims CCL24 is a novel target that was found to play a dual role in advancing pro-inflammatory and pro-fibrotic processes in systemic sclerosis (SSc). Previous studies reported that skin and serum CCL24 levels are elevated in SSc and that blocking of CCL24 was effective in preventing and attenuating experimental-induced fibrosis in murine models as well as interfering with endothelial cell activation. Here we tested the concentration of CCL24 in an observational cohort of patients with SSc and available clinical follow-up to determine its clinical value in predicting fibrotic and vascular complications of the disease. Methods Consecutive patients from a single-centre observational cohort were enrolled in this analysis. Clinical data were collected according to the EUSTAR minimal essential data set. Serum Concentration of CCL24 was measured by Luminex assay (Myriad RBM) and defined as “high” for patients over the upper quartile of the healthy control population (110 ng/ml). Interstitial lung disease (ILD) was defined by at least 10% parenchymal involvement at a high-resolution CT scan of the chest, while digital ulcer (DU) disease was defined by the presence of current or history of DU in the previous 6 months. Progressive fibrotic ILD was defined as previously described, according to Erice's criteria within 24 months. Clinical features were compared between CCL24 high vs low by Chi-Square and T-student tests. R software was employed for statistical analysis. Results 189 SSc patients (13% male) fulfilling 2013 ACR/EULAR classification criteria were enrolled in this study. Median (IQR) disease duration was 4 (IQR 2-10) years. 37 (27%) had diffuse cutaneous SSc, 60 (32%) had ILD, and 90 (48%) had DU disease. 52 patients (26%) were CCL24 High. These patients had a higher prevalence of DU (60%, p = 0.042), a higher median (IQR) mRSS [4(2-7) vs 2(0-5), p = 0.036) and showed a higher prevalence of ILD (42% vs 28%, p = 0.055); this was more significant among patients with limited cutaneous SSc (7% vs 12%, p = 0.037). Most importantly, among patients with PF-ILD (19/43 with available 24-month follow-up), 44% had significantly higher CCL24 serum concentration at baseline, compared to stable patients (1150 [817-1593] vs 725 [460-955]; p = 0.017). Consistent with these findings, in patients with ILD, having high CCL24 gave double the chance of progressing within 24 months (66% vs 32% of CCL24 low; p = 0.03). Conclusion We show here that within the context of an observational cohort of unselected patients, CCL24 serum concentration is associated with the presence of DU as well as worse skin and lung fibrotic involvement, suggesting that this molecule may be involved in both vascular and fibrotic manifestations of SSc. These results informed the rationale for a target-enriched basket randomized controlled trial to test the biological and clinical effect of CCL24 inhibition in SSc across cutaneous disease subsets. Disclosure E. De Lorenzis: None. A. Mor: None. R. Ross: None. S. Di Donato: None. R. Aricha: None. H. Levi: None. I. Vaknin: None. F. Del Galdo: Other; FDG received consultancies and research support from Abbvie, AstraZeneca, Boheringer-Ingelheim, Capella, Chemomab, Ergomed, Janssen, Kymab, Mitsubishi-Tanabe.

Background/Aims Anti-CCP positive individuals with musculoskeletal (MSK) symptoms and subclinical synovitis on ultrasound (US) are at high risk of developing inflammatory arthritis (IA). Treatment initiation in these individuals is not accepted practice as they do not have clinical synovitis. We aimed to determine whether imaging characteristics change when individuals with pre-RA progress to IA in order to inform the optimal window of opportunity for therapeutic interventions. Methods Anti-CCP+ at-risk individuals with MSK symptoms from the Leeds CCP cohort were selected for having US subclinical synovitis [Grey scale (GS)≥1 and Power Doppler (PD)≥1] prior to IA development and an US scan performed at clinical synovitis onset. The US protocol included the metacarpophalangeal joints (MCPJs), proximal interphalangeal joints (PIPJs), wrists, elbows, knees, second-fifth metatarsophalangeal joints (MTPJs), extensor carpi ulnaris (ECU) and finger flexor tendons (FFTs). US PD and GS synovitis were scored semi-quantitatively (0-3) according to EULAR/OMERACT. At patient level, total GS and PD scores were compared between scans. Change on US in the joints that became clinically swollen was also assessed. Wilcoxon signed-rank tests were conducted for comparisons. Results Forty-six CCP2+ at-risk individuals were identified (Table). The median US scan interval was 3.5 months (IQR 1.25-8.75). At patient level the overall burden of PD in the joints increased at IA progression, trending towards significance [3 (IQR 1.25-5) vs 4 (IQR 2-7.25) p = 0.063]. Overall burden of GS did not increase. There was an increase in PD in the MCPJs [0 (IQR 0-2) vs 1.5 (IQR0-3) p = 0.008] and MCP and wrist joints combined [1 (IQR 0.25-3) vs 2 (IQR 1.25-4.75) p = 0.002]. GS at the elbows also significantly increased. At joint level PD [1 (IQR(0-2) vs 2 (IQR 0-3) p = 0.036] increased in joints swollen at progression and GS increased with a trend towards significance. Non-swollen joints did not change. Conclusion A marked increase in US joint inflammation is seen when CCP+ at-risk individuals with subclinical synovitis on US progress from pre-RA to clinical arthritis. This is particularly evident in the MCPJs, wrist joints and joints that become clinically swollen. Intervening when at-risk individuals have subclinical synovitis may represent a window of opportunity to prevent the rapid increase in joint inflammation which accompanies the onset of joint swelling. Disclosure K. Harnden: None. A. Di Matteo: None. D. Esperança Almeida: None. E. De Lorenzis: None. L. Duquenne: None. L. Garcia-Montoya: None. J. Nam: None. P. Emery: None. K. Mankia: None.

Background/Aims Vascular involvement in systemic sclerosis (SSc) is known to start even before clinical diagnosis, driving digital ulcer (DU) disease. Later in the disease natural history, it can cause pulmonary artery hypertension (PAH) among other manifestations. Despite the proven immune origin of scleroderma, vascular involvement is not currently targeted by immune driven interventions. Similarly, few data are available on immune or inflammatory biomarkers and outcome measures of vascular disease in SSc. Digital artery volume index (DAVIX) has been recently proposed as an imaging surrogate outcome measure of vascular disease activity in SSc. Methods 86 patients attending our scleroderma program were consecutively enrolled for the evaluation of serum IFN score as previously described [2]. Clinical features, including presence or history of DUs, presence of PAH and DLCO, were recorded. DAVIX of the dominant hand’s fingers was calculated using time of flight magnetic resonance imaging analysed through IAG proprietary algorithm, as previously described [1]. Medians were compared by Mann-Whitney-Wilcoxon test; correlation with clinical parameters was performed using Spearman’s or Pearson test, as appropriate (R). Results 62 patients fulfilled the 2013 ACR/EULAR classification criteria for SSc (diffuse cutaneous 24.6%, limited cutaneous 75.4%), whereas 23 were classified as very early diagnosis of scleroderma (criteria score between 6 and 8). 23 patients had DU disease (history of DUs in the previous 24 weeks, presence of DUs at baseline assessment, or onset of new DUs during the following 24 weeks). 18 patients had reduced DLCO (1.8 (suspected PAH). DAVIX showed a negative correlation with disease duration (r=-0.33 and p = 0.003) and with FVC/DLCO ratio (r=-0.34 and p = 0.009). Patients with DU disease presented lower DAVIX than patients without (p = 0.018). DAVIX showed a significant correlation with serum IFN score (r=-0.24, p Conclusion DAVIX correlated both with presence of DU disease, DLCO and disease duration. The correlation of DAVIX and serum IFN score does support the notion of innate immune involvement in vascular disease manifestations of SSc. Prospective testing in the context of randomised controlled trials will determine the value of DAVIX as a surrogate outcome measure of vascular disease severity in SSc. S. Di Donato: None. M. Hughes: None. K. Geloshi: None. E. De Lorenzis: None. V. Kakkar: None. R. Ross: None. P. O'Connor: None. O. Kubassova: Consultancies; Image Analysis Group CEO. F. Del Galdo: Grants/research support; Abbvie, AstraZeneca, Boeringher-Ingelheim, Capella, Chemomab, Janssen, Kymab, Mitsubishi-Tanabe.

Background/Aims Hand impairment is a major driver of disability and reduced quality of life in Systemic Sclerosis (SSc) patients. It is multifactorial and the risk and predictability of functional deterioration are unknown. The aim of this study is to describe hand function changes and predictors of functional deterioration in an observational cohort of SSc patients. Methods Consecutive SSc patients were longitudinally evaluated every 6 months for 3 years for SSc-related hand involvement. Patient-reported hand symptoms were captured with Cochin Hand Disability Score (CHFS), Raynaud Condition Score (RCS) and overall pain intensity on a visual analogue scale (VAS pain). Their minimal clinical important difference (MCID) and patient-acceptable symptom state (PASS) were evaluated according to validated thresholds. Clinical association with CHFS change over time and 36-month clinically meaningful worsening (MCID-Wor) were assessed via ANOVA and binomial logistic regression, respectively. Results One-hundred-seventy-six SSc patients were enrolled in this analysis, 13.6% of them were male and the mean age was 55.1± 12.3 years, the median disease duration was 5.0 years and 31.8% presented a diffuse cutaneous variant. Overall, CHFS worsened over time (p Conclusion SSc-related hand disability affects more than one-third of patients and tends to worsen over time in both cutaneous subsets despite the current standard of care. Identifying patients at risk of deteriorating hand function should inform targeted intervention strategies to prevent hand disability in SSc. Disclosure E. De Lorenzis: None. V. Kakkar: None. S. Di Donato: None. M. Wilson: None. L. Green: None. B. Alcacer-Pitarch: None. F. Del Galdo: Other; FDG received consultancies and research support from Abbvie, AstraZeneca, Boheringer-Ingelheim, Capella, Chemomab, Ergomed, Janssen, Kymab, Mitsubishi-Tanabe.

IntroductionNintedanib (NTD) has been shown to be effective in systemic sclerosis (SSc)-interstitial lung disease (ILD). Here we describe the efficacy and safety of NTD in a real-life setting.MethodsPatients with SSc-ILD treated with NTD were retrospectively evaluated at 12 months prior to NTD introduction; at baseline and at 12 months after NTD introduction. The following parameters were recorded: SSc clinical features, NTD tolerability, pulmonary function tests and modified Rodnan skin score (mRSS).Results90 patients with SSc-ILD (65% female, mean age 57.6±13.4 years, mean disease duration 8.8±7.6 years) were identified. The majority were positive for anti-topoisomerase I (75%) and 77 (85%) patients were on immunosuppressants. A significant decline in %predicted forced vital capacity (%pFVC) in the 12 months prior to NTD introduction was observed in 60%. At 12 months after NTD introduction, follow-up data were available for 40 (44%) patients and they showed a stabilisation in %pFVC (64±14 to 62±19, p=0.416). The percentage of patients with significant lung progression at 12 months was significantly lower compared with the previous 12 months (60% vs 17.5%, p=0.007). No significant mRSS change was observed. Gastrointestinal (GI) side effects were recorded in 35 (39%) patients. After a mean time of 3.6±3.1 months, NTD was maintained after dose adjustment in 23 (25%) patients. In nine (10%) patients, NTD was stopped after a median time of 4.5 (1–6) months. During the follow-up, four patients died.ConclusionsIn a real-life clinical scenario, NTD, in combination with immunosuppressants, may stabilise lung function. GI side effects are frequent and NTD dose adjustment may be necessary to retain the drug in patients with SSc-ILD.

Objectives Survival and death prognostic factors of SSc patients varied during the past decades. We aimed to update the 5- and 10-year survival rates and identify prognostic factors in a multicentre cohort of Italian SSc patients diagnosed after 2009. Material and methods Patients who received a diagnosis of SSc after 1 January 2009 and were longitudinally followed up in four Italian rheumatologic centres were retrospectively assessed up to 31 December 2020. Overall survival of SSc patients was described using the Kaplan–Meier method. Predictors of mortality at 10-year follow-up were assessed by the Cox regression model. A comparison of our cohort with the Italian general population was performed by determining the standardized mortality ratio (SMR). Results A total of 912 patients (91.6% females, 20% dcSSc) were included. Overall survival rates at 5 and 10 years were 94.4% and 89.4%, respectively. The SMR was 0.96 (95% CI 0.81, 1.13), like that expected in the Italian general population. Pulmonary arterial hypertension (PAH) and interstitial lung disease (ILD) associated with pulmonary hypertension (PH) significantly reduced survival (P Conclusions In the past decade, SSc patients have reached similar mortality of that expected in the Italian general population. Male gender, diffuse cutaneous involvement, comorbidities and PAH with or without ILD represent the main poor prognostic factors.

This guideline will provide a practical roadmap for management of SSc that builds upon the previous treatment guideline to incorporate advances in evidence-based treatment and increased knowledge about assessment, classification and management. General approaches to management as well as treatment of specific complications will be covered, including lung, cardiac, renal and gastrointestinal tract disease, as well as RP, digital vasculopathy, skin manifestations, calcinosis and impact on quality of life. It will include guidance related to emerging approved therapies for interstitial lung disease and account for National Health Service England prescribing policies and national guidance relevant to SSc. The guideline will be developed using the methods and processes outlined in Creating Clinical Guidelines: Our Protocol. This development process to produce guidance, advice and recommendations for practice has National Institute for Health and Care Excellence accreditation.

Depression is commonly associated with psoriatic arthritis (PsA), but its risk factors in these patients are largely unrecognized. Pro-inflammatory cytokines involved in the pathogenesis of PsA have been associated with depression in patients without autoimmune diseases. The aim of this study was to establish whether PsA patients with and without depressive symptoms differed for general or clinical variables and serum cytokines milieu.One hundred and fifty consecutive patients with PsA were screened for depressive symptoms with Hospital Anxiety and Depression Scale (HADS-D). Patients with and without depressive symptoms were compared according to the prevalence of general risk factors for depression, comorbidities, PsA features and serum IL-6, TNF-α, and IL-17A.Fifty-eight patient (38.7%) had a depressive mood. Depressive symptoms were associated with female sex (p = 0.03) and current smoking (p = 0.05). Patients with and without depressive symptoms did not differ for general risk factors for depression and comorbidities. Depressed patients had more frequently psoriatic nail disease (p = 0.02) and significant physical disability (HAQ-DI ≥ 0.5) (p0.01) and were more frequently in moderate or high disease activity according to DAPSA score (p = 0.01). Depressed patients had higher serum IL-6 (p0.01) and comparable serum IL-17A and TNF-α. A cutoff of 2.27 pg/ml of serum IL-6 had the best ability to predict an HADS-D ≥ 8 (AUC 0.666 ± 0.044; p0.01). Multivariate logistic regression analysis confirmed that serum IL-6 ≥ 2.27 pg/ml was independently associated with depressive symptoms (OR 3.5; CI 1.6-7.8; p0.01).Higher serum Il-6 is associated with depressive symptoms. This association suggests a direct role of systemic inflammation in the modulation of mood in PsA patients. Key Points • High PsA disease activity and physical disability are associated with depression. • Higher serum levels of IL-6 are independently associated with depression in PsA. • IL-6 might play a direct role in the development of depression in PsA patients.

Objective To outline the clinical, histological and prognostic features of systemic sclerosis (SSc) endomyocardial biopsy-proven myocarditis with respect to those of diverse endomyocardial biopsy-proven virus-negative myocarditis (VNM). Methods We retrospectively analysed data from three cohorts of endomyocardial biopsy-proven myocarditis: SSc-related VNM (SSc-VNM); isolated VNM (i-VNM); and VNM related to other systemic autoimmune diseases (a-VNM). The degree of myocardial fibrosis was expressed as relative percentage and fibrotic score (0–3). Clinical data, cardiac enzymes, echocardiogram, 24 h ECG Holter and cardiac magnetic resonance were obtained at baseline and during follow-up. Non-parametric tests were used. Results We enrolled 12 SSc-VNM [11 females, mean age 49.3 (14.2) years; seven diffuse-SSc, five early-SSc], 12 i-VNM [12 females, mean age 47.7 (10.8) years] and 10 a-VNM [four females, mean age 48.4 (16.3) years] patients. SSc patients had higher degrees of myocardial fibrosis as assessed by both percentage [SSc-VNM: 44.8 (18.8)%; a-VNM: 28.6 (16.5)%; i-VNM: 24.9 (10.3)%; P = 0.019] and score [SSc-VNM: 2.3 (0.8); a-VNM: 1.4 (1.1); i-VNM: 1.2 (0.7); P = 0.002]. Myocardial fibrosis directly correlated with skin score (r = 0.625, P = 0.03) and number of ventricular ectopic beats on 24 h ECG Holter in SSc patients (r = 0.756, P = 0.01). Dyspnoea class was higher at presentation in SSc-VNM patients (P = 0.041) and we found heart failure only in SSc patients (25%) (P = 0.05). At cardiac magnetic resonance, myocardial oedema was nearly undetectable in SSc-VNM patients compared with others (P = 0.02). All patients received immunosuppressive treatment. The number of patients who died during follow-up due to cardiac complications was significantly higher in SSc-VNM patients (50%), as compared with a-VNM (0%) and i-VNM (8.3%) patients (P = 0.006). Patients who died during follow-up had higher degrees of myocardial fibrosis [52.2 (11.6)% vs 27.5 (12.9)%, P = 0.024; fibrotic score: 2.83 (0.41) vs 1.4 (0.9), P Conclusion SSc has unique clinical and histological features, as it tends to present more frequently with heart failure and a higher dyspnoea class and to show higher degrees of myocardial fibrosis. These specific features are paralleled by a worse cardiac prognosis.

Intravenous iloprost is currently recommended in the treatment of Raynaud's phenomenon (RP) refractory to oral therapy and of digital ulcers (DUs) related to systemic sclerosis (SSc). In real-life practice there is a huge heterogeneity about the Iloprost regimens used.A survey was carried out on SSc patients that interrupted Iloprost infusion to compare acral vascular symptoms just before Iloprost withdrawal and just after the missed infusion. Severity, and frequency of RP, new DUs onset or aggravation of those pre-existing were reported. Last available capillaroscopic images were also evaluated.The analysis includes 50 patients. After iloprost withdrawal, 11 patients reported a RP worsening because of enhanced intensity (p = 0.007). Only 8 patients of them also complained of an increased frequency (p = 0.07). None of the patients experienced digital ulcers for the first-time during quarantine. Among the 27 patients with a history of digital ulcers, 9 reported worsening and 7 recurrence of DUs. Overall, 17 patients (34.0 %) complained of a worsening of SSc vascular acral manifestations, namely RP or DUs. Reduced capillary density was associated with RP worsening, in particular, each unit increase of capillary density corresponds to an average 44 % decrease in the odds of RP worsening (OR 0.56, CI 95 % 0.36-0.97, p = 0.037). As for RP worsening, the aggravation of DU was associated with a lower capillary density.Low capillary density can predict a worsening of both RP and DUs in controlled quarantine conditions within a month after iloprost discontinuation in SSc patients.

A 42-year-old woman with a 15-year history of psoriatic disease with skin, nail and joint involvement presented for routine follow-up visit. The patient did not complain of relevant articular symptoms, physical examination was unremarkable excepted for feet nail onychodystrophy and routine laboratory tests were unaltered.

Background: Cardiovascular events (CVEs) are the first cause of death in patients with psoriatic arthritis (PsA). Depression is a recognized risk factor in cardiovascular events and is frequently associated with PsA. Flow-mediated dilatation (FMD) is a widely used method for assessing endothelial dysfunction, a parameter with strong prognostic implications for CVEs. The study aims to explore the relationship between FMD, depressive symptoms and serum cytokines in a cohort of patients with PsA.Patients and Methods: FMD was assessed in 50 consecutive PsA patients aged between 30 and 75 years without known cerebrovascular and coronary heart disease or diabetes. Depressive symptoms were reported using the related subscale of the Hospital Anxiety and Depression Scale (HDS). Disease features, activity indexes, and adjusted Framingham risk score (aFRS) were calculated. Serum level of IL-6, TNF-α, and IL-17A were also assessed.Results: In PsA patients (age 50.7 ± 10.2 years, male 42%, disease duration 5.9 ± 3.3 years, Disease Activity in PSoriatic Arthritis (DAPSA) score 14.0 ± 9.4) FMD inversely correlated with the severity of depressive symptoms according to HDS (ρ = −0.339, p = 0.016), age (ρ = −0.507, p = 0.001), aFRS (rs = −0.453, p < 0.001), duration of PsA (ρ = −0.507, p = 0.001), intensity of pain (ρ = −0.507, p = 0.001), and DAPSA (ρ = −0.507, p = 0.001). No statistically significant correlation was found between FMD or HDS and serum cytokines concentrations. HDS predicted FMD in a model adjusted for age, aFRS, PsA duration, and pain intensity (β = −0.271, p = 0.008), with depressive symptoms contributing directly to 6.4% of the variance.Conclusions: Depressive symptoms correlate with endothelial dysfunction with an exposure-response pattern in our cohort of PsA patients.

Multidisciplinary team (MDT) discussion is the gold standard in the management of interstitial lung disease (ILD). The rheumatologist is not routinely involved in MDT, even if up to 20% of ILD are related to systemic autoimmune rheumatic diseases (SARD). The study aims to assess the agreement and its variation over time between rheumatologists and pulmonologists in the screening of SARD and between rheumatologists and an MDT extended to rheumatologists (eMDT) in evaluating the progression of SARD. We computed the agreement between the pulmonologist and rheumatologist in the identification of red flags for SARDs of 81 ILD cases and between the rheumatologist alone and eMDT in the confirmation of 70 suspected SARD-ILD progressions. The agreement between rheumatologists and pulmonologists was moderate for the detection of autoimmunity test positivity (&kappa, = 0.475, p &lt, 0.001) and family history of SARD (&kappa, = 0.491, p &lt, 0.001) and fair for the identification of extrapulmonary symptoms (&kappa, = 0.225, p = 0.064) or routine laboratory abnormalities consistent with SARD. The average agreement between the rheumatologist and eMDT in the identification of ILD progression was moderate (&kappa, = 0.436, p &lt, 0.001). The class of agreement improved from the first to the third semester. The average agreement with the rheumatologist ranged from fair to moderate, suggesting that a shared evaluation of SARD-ILD in eMDT could improve the diagnostic work-up and the evaluation of ILD progression.

In 1912, Windaus reported that atherosclerotic plaques from aortas of human subjects contained over 30-fold higher concentrations of cholesterol than did normal aortas1, and in 1913 the Russian pathologist Nikolai Anitschkow2, feeding pure cholesterol to rabbits, produced marked hypercholesterolemia and severe atherosclerosis of the aorta. In 1974, Brown and Goldstein discovered the low-density lipoprotein (LDL) receptor and the regulation of cholesterol metabolism in the cells3, and in 1976 Akira Endo4 discovered a fungal metabolite that could block cholesterol synthesis by inhibiting the enzyme hydroxymethylglutaryl CoA. These key steps paved the way to the understanding of LDL cholesterol (LDL-C) levels as one of the primary targets in prevention of ischemic heart attacks and to the discovery of statins as the therapeutic drug capable of reducing the cardiovascular (CV) risk. Since they were first approved in 1987, statins have represented substantial potential for safe, effective, and inexpensive primary prevention of ASCVD (atherosclerotic CV diseases). Among the several risk factors defined in the last 20 years, inflammation and inflammatory biomarkers such as high-sensitivity C-reactive protein (hsCRP) and interleukin 6 have arisen as predictors of future CV events, along with conventional LDL-C or high-density lipoprotein cholesterol (HDL-C). Randomized trial data have also shown that statins reduce not only hsCRP but also CV event rates independently of their effect on LDL-C level. This led to a focus on a further effect of statins: their antiinflammatory effect5,6,7, which appears particularly important in all rheumatic diseases [the chronic arthritides as well … Address correspondence to Dr. G.F. Ferraccioli, Institute of Rheumatology, Universita Cattolica del Sacro Cuore, Via Moscati 31, 00168 Rome, Italy. E-mail: gianfranco.ferraccioli{at}unicatt.it

Background Depression is one of the most common comorbidities in patients with Psoriatic Arthritis (PsA) but risk factors for mood disorders in these patients are still largely unrecognized. Pro-inflammatory cytokines involved in the pathogenesis of PsA have been also associated with depressive symptoms in patients without systemic autoimmune diseases. Objectives The aim of this study is to determine risk factors for depressive symptoms and compare serum cytokines concentrations in subjects with and without depressive symptoms in a court of PsA patients. Methods Eighty consecutive patients with PsA were screened for depressive symptoms with depression subscale of the Hospital Anxiety and Depression Scale (HADS-D). A validated cut-off of 8 was used to define patients with significative depressive mood. Patients with and without depressive symptoms were compared for the prevalence of general risk factors for depression, comorbidity, psoriatic disease age of onset, duration, activity and domains affected, treatment and serum levels of IL-6, TNF-α and IL-17A. Results Mean disease duration of skin disease and articular disease was 18.8 ± 15.3 years and 9.0 ± 11.1 years, respectively. All patients had a history of peripheral arthritis, 41.3% had dactylitis, 38.8% had enthesitis, 21.3% had spondylitis 82.5% had a psoriatic skin disease and 51.2% had psoriatic nail disease. According to DAPSA index, 20.0% were in remission, 50.0% in Low Disease Activity, 20.0% in Moderate Disease Activity and 10.0% in High Disease Activity. Thirty-five (43.8%) were in Minimal Disease Activity. Thirty-three patients (41.3%) had depressive symptoms according to HADS. Patients with and without depressive symptoms did not differ in terms of age, gender, comorbidity, general risk factors of depression, psoriatic disease age of onset, duration, domains affected, DAPSA activity, MDA achievement, PASI, HAQ, VAS pain, the intensity of treatment, serum TNF-α IL-17A and IL-23. Serum levels of IL-6 were higher in patients with depressive symptoms. (2.99±2.58 vs 1.54±1.60 pg/dl; p=0.006). A cut-off of 2.27 pg/ml of serum IL-6 had the best ability to predict a HADS≥8 according to higher Youden Index of the ROC curve (AUC 0.682±0.061; p=0.006). Multivariate logistic regression analysis revealed that serum IL-6≥2.27 pg/ml was a predictor of depressive symptoms even when adjusted for DAPSA, HAQ and PASI (OR 3,06; CI 1.14-8.20; p = 0.026). Conclusion Higher serum Il-6 is associated with depressive symptoms independently from articular and cutaneous disease activity and degree of disability. This association suggest a direct role of systemic inflammation in the modulation of mood in PsA patients. References [1] Husni ME, et al. The psychosocial burden of psoriatic arthritis. Semin Arthritis Rheum2017. [2] Ogata A, et al. Pathological Role of Interleukin-6 in Psoriatic Arthritis. Arthritis2012. [3] Hodes GE et al. Integrating Interleukin-6 into depression diagnosis and treatment. Neurobiol Stress 2016. [4] Zigmond AS et al. The Hospital Anxiety and Depression Scale. Acta Psychiatr Scand 1983. Disclosure of Interests Enrico De Lorenzis: None declared, Gerlando Natalello: None declared, Dario Bruno: None declared, Giacomo Tanti: None declared, Giovanni Battista Canestrari: None declared, Maria Rosaria Magurano: None declared, Clara Di Mario: None declared, Barbara Tolusso: None declared, Giusy Peluso: None declared, Elisa Gremese Consultant for: AbbVie, BMS, Celgene, Janssen, Lilly, MSD, Novartis, Sanofi, UCB, Roche, and Pfizer, Speakers bureau: BMS, Speakers bureau: Roche, Speakers bureau: AbbVie, BMS, Celgene, Janssen, Lilly, MSD, Novartis, Sanofi, UCB, Roche, and Pfizer

Background Multidisciplinary Team (MDT) meetings are the current “gold standard” in interstitial lung disease (ILD) diagnosis. Requisite participants are respiratory physicians, radiologists and pathologists. A rheumatologist physician is not routinary involved in MDT even if up to 20% of ILD are related to connective tissue disease, rheumatoid arthritis or systemic vasculitis. Objectives The aim of this study is to evaluate the prevalence and predictors of systemic rheumatological diseases in a cohort of patients with ILD, evaluated by a rheumatology specialist on the advice of MDT in a university hospital. Methods Thirty-two patients with ILD, evaluated at dedicated MDT were referred to a rheumatologist in 2018, usually for autoantibodies positivity or clinical history suspected for a rheumatological disorder. Rheumatologic evaluation included physical examination, routinary blood and urine tests, serum levels of C3 and C4, ANA, Rheumatoid Factor (RF), ANCAs, anti-Sm, anti-RNP, anti-Ro/SSA, anti-La/SSB, anti-Sm, anti-Jo1, anti-dsDNA and anti-CCP antibodies. Family history of autoimmune diseases, presence of rheumatologic red flags (Raynaud’s phenomenon, photosensitivity, inflammatory skin manifestations, sicca syndrome, recurrent fever, inflammatory arthralgias, paresthesias, oral or genital aphthosis, thrombosis and recurrent miscarriages), respiratory symptoms and pulmonary function test were also evaluated. When indicated, capillaroscopy, joint imaging and salivary gland biopsy were performed. Results Twenty-one patients (65.6%) were female. At the time of rheumatological evaluation, the patients had a mean age of 64.4±12.6 years with a mean period of 21.1±39.6 months since the first identification of ILD on a CT scan. Twenty-five (78.1%) and 18 (56.3%) patients respectively complained exertional dyspnea and cough, 6 patients (18.8%) were on oxygen therapy and 13 (40.6%) had a FVC Conclusion Single clinical or laboratory abnormalities are not strongly associated to a rheumatological diagnosis in patients with ILD, suggesting that only a comprehensive rheumatological evaluation allows correct classification of the disease associated with ILD and is mandatory to make or exclude a diagnosis. In this study, we evaluated only preselected patients by ILD-MDT, but the results indirectly suggest that direct participation of rheumatologist to MDT is advisable to increase accuracy and reduce delay in diagnosis and treatment. Disclosure of Interests: Enrico De Lorenzis: None declared, Gerlando Natalello: None declared, Lucrezia Verardi: None declared, Silvia Laura Bosello: None declared, Elisa Gremese Consultant for: AbbVie, BMS, Celgene, Janssen, Lilly, MSD, Novartis, Sanofi, UCB, Roche, and Pfizer, Speakers bureau: BMS, Speakers bureau: Roche, Speakers bureau: AbbVie, BMS, Celgene, Janssen, Lilly, MSD, Novartis, Sanofi, UCB, Roche, and Pfizer

Background: Cardiovascular (CV) events are the leading cause of death in patients with psoriatic arthritis (PsA) but current cardiovascular risk prevention strategies in these subjects appear to be inadequate. The prevalence of depressive symptoms, even in the absence of a diagnosed depressive disorder, is greater in patients with PsA than in the general population. Objectives: The objective of the study is to evaluate the association between CV risk factors and depressive symptoms in a cohort of patients with PsA. Methods: We enrolled consecutive patients with PsA (CASPAR criteria) without a diagnosis of major depression or history of major CV events. The presence of significant depressive symptoms was defined by the Hospital Anxiety and Depression Scale (HADS) for scores ≥ 8. The subjects were characterized by disease phenotype, duration and activity (according to the DAPSA index) and immunosuppressive, antihypertensive, glucose-, urate- and lipid-lowering therapy. In order to assess the prevalence of traditional CV risk factors, patients were characterized by BMI, waist and hip circumference, blood pressure (BP), smoking habits, physical activity and familiarity for myocardial infarction, lipid, glucose and serum urate. The predicted risk of CV events was calculated by the Framingham Risk Score (FRS), Atherosclerotic Cardiovascular Disease (ASCVD) score and Systematic COronary Risk Evaluation (HeartSCORE) risk charts. Results: One-hundred patients with PsA were enrolled (males 47.0%, mean age 54.9±12.5 years, duration of illness 9.1±10.6 years) of which 20.6% were in remission, 43.3% in low disease activity, 28.8% in moderate disease activity and 10.3% in high disease activity according to DAPSA; 38% had significant depressive symptoms according to the HADS questionnaire. Patients without depressive symptoms had a higher mean age (57.8±12.3vs52.1±12.4 years, p=0.002) compared to patients with significant depressive symptoms but were comparable according to M:F ratio, duration and domains of psoriatic disease, PASI, DAPSA and immunosuppressive therapy. The presence of depressive symptoms was associated with a higher prevalence of obesity (34.2%vs9.7%, p=0.002) and “at risk” abdominal circumference (84.2%vs61.3%, p=0.015) and hip/waist ratio (81.6%vs50.0%, p=0.002). Moreover, these patients had more frequently a history of active or previous smoking (63.2%vs.40.3%, p=0.027) but did not differ according to lifestyle, BP, antihypertensive therapy or familiarity with myocardial infarction compared to patients without depressive symptoms. With regard to the metabolic profile, patients with and without depressive symptoms did not differ in terms of exposure to lipid- and glucose-lowering drugs and fasting glucose values. However, patients with depressive symptoms had increased atherogenic risk index more frequently (76.3%vs54.8%, p=0.046) and greater LDL/HDL ratio (2.6±1.2vs2.1±0.7, p=0.017) and serum triglycerides values (135.1±53.7 mg/dl vs 108.8±58.6 mg/dl, p=0.046). The estimated risk of cardiovascular events at 10 years for traditional risk factors was greater for patients with depressive symptoms (FRS 16.8±12.3vs10.4 ± 6.0, p=0.003; HeartSCORE 1.9±1.5vs1.1±1.0, p=0.011; ASCVD 11.7±8.8vs7.8±8.4, p=0.05). Conclusion: The presence of depressive symptoms is associated with a higher incidence of modifiable CV risk factors and a higher predicted risk of CV events in patients with PsA. Systematic research of depressive symptoms in patients with PsA could contribute to the correct assessment of CV risk, helping to implement more effective prevention strategies. Disclosure of Interests: Gerlando Natalello: None declared, Enrico De Lorenzis: None declared, Dario Bruno: None declared, Giacomo Tanti: None declared, Maria Rosaria Magurano: None declared, Barbara Tolusso: None declared, Giusy Peluso: None declared, Elisa Gremese Consultant for: AbbVie, BMS, Celgene, Janssen, Lilly, MSD, Novartis, Sanofi, UCB, Roche, and Pfizer, Speakers bureau: BMS, Speakers bureau: Roche, Speakers bureau: AbbVie, BMS, Celgene, Janssen, Lilly, MSD, Novartis, Sanofi, UCB, Roche, and Pfizer

Background Interstitial lung d isease (ILD) is the leading cause of death in Systemic Sclerosis (SSc) but its pathogenesis is not fully understood. Esophageal disease is common in SSc and micro aspiration of both acid and non-acid gastroesophageal reflux could be involved in the pathogenesis of ILD. Esophagogastroduodenoscopy (EGD) is an essential tool to evaluate disease severity of upper gastrointestinal tract involvement in SSc. Objectives The objective of the present study is to assess the role of EGD in predicting pulmonary functional deterioration in SSc patients. Methods One hundred and fifty patients with SSc and suspected esophageal involvement underwent EGD. Pulmonary function tests were performed at baseline and after a 36-months follow-up. Patients were characterized for disease phenotype, BMI, smoking exposure and medication history. A significant ILD progression was defined as a relative decline >= 10% of FVC or a concomitant decline >= 5% of FVC and >= 15% of DLCO. Results One hundred and thirty-six patients (90.5%) were female with a mean age of 55.6 ± 13.8 years and 12.1% were active smokers. Fifty patients (33.3%) had a diffuse cutaneous disease; 37.4% and 40.8% were positive for anti-centromere and anti-Scl70 antibodies respectively. The mean disease duration from the first non-Raynaud symptom was 5.9±6.7 years. Sixty-one patients (40.8%) showed EGD signs of reflux esophagitis. Among them, 31.3% had an erosive form (9.5% grade A, 15.6% grade B, 4.8% grade C and 1.4% grade D according to Los Angeles classification). At the baseline, 23.1% of the patients had a FVC Conclusion SSc patients with erosive esophagitis present a higher risk of progression of interstitial lung disease. This evidence supports a role of micro-aspiration of gastric contents in the development of inflammation and fibrosis of the airways. Disclosure of Interests Enrico De Lorenzis: None declared, Gerlando Natalello: None declared, Laura Gigante: None declared, Lucrezia Verardi: None declared, Umberto La Porta: None declared, Giovanni Battista Canestrari: None declared, Ludovica Berardini: None declared, Silvia Laura Bosello: None declared, Elisa Gremese Consultant for: AbbVie, BMS, Celgene, Janssen, Lilly, MSD, Novartis, Sanofi, UCB, Roche, and Pfizer, Speakers bureau: BMS, Speakers bureau: Roche, Speakers bureau: AbbVie, BMS, Celgene, Janssen, Lilly, MSD, Novartis, Sanofi, UCB, Roche, and Pfizer

Heart involvement – often asymptomatic – is largely underestimated in patients with systemic autoimmune diseases (SADs). Cardiovascular events are more frequent in patients with SADs compared to the general population, owing to the consequences of inflammation and autoimmunity and to the high prevalence of traditional risk factors. Coronary microvascular disease (CMD) is a form of cardiac involvement that is increasingly recognised yet still largely neglected. CMD, the incapacity of the coronary microvascular tree to dilate when myocardial oxygen demand increases or when there is a microvascular spasm (or subclinical myocarditis), is increasingly reported because of the widespread use of new cardiac imaging tools, even in a subclinical phase. The assessment of myocardial coronary flow reserve (CFR) emerged as the most effective clinical tool to detect microvascular damage. The potential causes of microvascular damage, molecular and cellular inflammation along with a pathological CD39-CD73 axis, need always to be considered because data show that they play a role in the occurrence of acute coronary syndromes, heart failure and arrhythmias, even in the early asymptomatic stage. Data suggest that controlling disease activity by means of methotrexate, biologic drugs, antimalarial medications, statins and aspirin, according to indication, might reduce the cardiovascular risk related to macrovascular and microvascular damage in most patients with SADs, provided that they are used early and timely to control diseases. The need of new biomarkers and a careful assessment of myocardial CFR emerged as the most effective clinical tool to detect microvascular damage.

There is a need to identify the presence of bacterial pathogens in foods earlier than it is currently carried out. At present, pre-enrichment culture followed by selective agar plating is standard microbiological methods applied to detect Listeria monocytogenes and other bacterial pathogens with zero tolerance in food products. PCR and biosensor methods may shorten the time required to individuate contamination by L. monocytogenes in a pre-enrichment culture. In this paper, a protein chip immunosensor with a sensitivity of 100 CFU/mL was developed for Listeria spp. detection. The method provides a ten-fold increase in sensitivity compared with published work on bacteria immunosensing coupled to fluorescence detection. When 40 mL of Listeria spp. pre-enrichment culture were processed by immunoseparation, the limit of detection was lowered to 2.5 CFU/mL. The results obtained from the real food samples were confirmed by qPCR. We also showed the potential for multiplexing of the protein chip method demonstrating the selective detection of Listeria monocytogenes , Staphylococcus aureus , Salmonella spp., Escherichia coli , and Campylobacter spp. A future development is the integration into a system for rapid screening of pathogens contaminating food productions.

Objective Increasing evidence points to endothelial dysfunction as a key pathophysiological factor in coronavirus disease-2019 (COVID-19). No specific methods have been identified to predict, detect and quantify the microvascular alterations during COVID-19. Our aim was to assess microvasculature through nailfold videocapillaroscopy (NVC) in COVID-19 patients. Methods We performed NVC in patients with a confirmed diagnosis of COVID-19 pneumonia. Elementary alterations were reported for each finger according to a semi-quantitative score. Capillary density, number of enlarged and giant capillaries, number of micro-hemorrhages and micro-thrombosis (NEMO score) were registered. Results We enrolled 82 patients (mean age 58.8 ± 13.2 years, male 68.3%) of whom 28 during the hospitalization and 54 after recovery and hospital discharge. At NVC examination we found abnormalities classifiable as non-specific pattern in 53 patients (64.6%). Common abnormalities were pericapillary edema (80.5%), enlarged capillaries (61.0%), sludge flow (53.7%), meandering capillaries and reduced capillary density (50.0%). No pictures suggestive of scleroderma pattern have been observed. Acute COVID-19 patients, compared to recovered patients, showed a higher prevalence of hemosiderin deposits as a result of micro-hemorrhages (P = .027) and micro-thrombosis (P, Highlights • We assessed and accurately described peripheral microvasculature in COVID-19 patients through nailfold videocapillaroscopy. • Capillary alterations at the nailfold bed suggest a broad COVID-related microvascular involvement. • Different alterations in acutely-ill and recovered patients resemble a transition from acute to post-acute injury.

We read with interest the letter by Bozzalla Cassione et al 1 about the role of telemedicine in their clinic during COVID-19 time. Telemedicine represents a useful tool not only in regions with limited access to healthcare2 but also in different settings like quarantine, when healthcare personnel became essential. Since the Italian National lockdown decision3 and the WHO announcement of the COVID-19 pandemic,4 enormous demand to handle the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection disease challenged the Italian healthcare system. Indeed, in the Fondazione Policlinico Universitario A. Gemelli (FPG) Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) in Rome, the delegated taskforce (Gemelli against COVID-19) gradually opened 14 COVID-19 dedicated wards, in accordance to the progressive increase of serious cases. Concomitantly, several clinics were remodulated to optimise the staff use and to avoid patient exposure to the hospital environment. The Division of Rheumatology of the FPG-IRCCS is a high-flux rheumatological centre, with almost 16 000 visits performed in the last year for chronic inflammatory arthritis (38%), connective tissue diseases (CTDs) (34%) and other rheumatic diseases (27%) (ie, osteoarthritis and fibromyalgia) from all Italian regions. Before the spread of COVID-19, our rheumatology service was organised to …

AimHumoral immunity and B cells are thought to play an important role in the pathophysiology of the systemic sclerosis (SSc). The production of free light chains (FLC) of immunoglobulins is abnormally high in several pathological autoimmune conditions and reflects B cell activation. Furthermore, FLCs demonstrated different biological activities including their capability to modulate the immune system, proteolytic activity and complement cascade activation. The aims of this study are to determine the FLC levels in patients with SSc compared with healthy controls (HC) and to study their possible association with organ involvement and disease characteristics.MethodsSixty-five patients with SSc and 20 HC were studied. Clinical and immunological inflammatory characteristics were assessed for all the patients with SSc. κ-FLC and λ-FLC, interleukin 6 (IL-6) and B cell activating factor levels were measured.ResultsThe mean serum κ-FLC levels and FLC ratio were significantly higher in patients with SSc compared with HC, while the serum λ-FLC levels were comparable.The levels of FLC were comparable in patients with diffuse skin disease and limited skin involvement, while κ-FLC levels were increased in patients with restrictive lung (forced vital capacity (FVC) ConclusionsFLC levels are elevated in SSc and high levels are associated with lung involvement and with a higher degree of inflammation, supporting a possible role of B cell activation in the pathophysiology of the disease.

Food pathogens are the cause of foodborne epidemics, therefore there is a need to detect the pathogens in food productions rapidly. A pre-enrichment culture followed by selective agar plating are standard detection methods. Molecular methods such as qPCR have provided a first rapid protocol for detection of pathogens within 24 hours of enrichment culture. Biosensors also may provide a rapid tool to individuate a source of Salmonella contamination at early times of pre-enrichment culture. Forty mL of Salmonella spp. enrichment culture were processed by immunoseparation using the Pathatrix, as in AFNOR validated qPCR protocols. The Salmonella biosensor combined with immunoseparation showed a limit of detection of 100 bacteria/40 ml, with a 400 fold increase to previous results. qPCR analysis requires processing of bead-bound bacteria with lysis buffer and DNA clean up, with a limit of detection of 2 cfu/50 ?l. Finally, a protein chip was developed and tested in screening and identification of 5 common pathogen species, Salmonella spp., E. coli, S. aureus, Campylobacter spp. and Listeria spp. The protein chip, with high specificity in species identification, is proposed to be integrated into a Lab-on-Chip system, for rapid and reproducible screening of Salmonella spp. and other pathogen species contaminating food productions.

There is a need to identify the presence of bacterial pathogens in foods earlier than it is currently carried out. At present, pre-enrichment culture followed by selective agar plating are standard microbiological methods applied to detect Listeria monocytogenes and other bacterial pathogens with zero tolerance in food products. PCR and biosensor methods may shorten the time required to individuate contamination by L. monocytogenes in a pre-enrichment culture. In this study, a protein chip immunosensor with a sensitivity of 100 bacteria/ml was developed for Listeria spp. detection. The method provides a 10 fold increase in sensitivity compared to published work on bacteria immunosensing coupled to fluorescence detection. When 40 ml of Listeria spp. pre-enrichment culture were processed by immunoseparation, the limit of detection (LOD) was lowered to 2.5 cfu/ml. The results were confirmed by a qPCR method whose sensitivity was of 0.1 cfu/ml. The method based on immunosensors combined with immunomagnetic separation (IMS) on pre-enrichment cultures may shorten the time required for species identification. We also showed the potential for multiplexing of the protein chip method demonstrating the selective detection of Listeria monocytogenes, Staphylococcus aureus, Salmonella spp., Escherichia coli, and Campylobacter spp. A future development is the integration into a system for rapid screening of pathogens contaminating food productions.

Nel SAL III sono riportate le attività in corso, terminate nel 2013 o che continuano nel 2014, in particolare la Task 7.3.3 - Messa a punto di sistemi di rilevamento dei patogeni tramite protein chip biosensori, DNA microarrays, e immunosensori, Lateral flow Assays. I tre metodi per la rivelazione su protein chip (anticorpo fluorescente, colorante lipidico fluorescente, marcatore di membrana fluorescente) saranno utilizzati contemporaneamente per la rivelazione di batteri a diluizioni spinte (100 CFU/ml). Saranno inoltre effettuati esperimenti di rivelazione mettendo a confronto la Real time PCR e i protein chips su colture in prearricchimento di Listeria e Salmonella da campioni prelevanti in azienda, ottimizzando le metodiche per segnalare la contaminazione entro le 18 ore.

A lateral flow (LF) device combined with quantum dots (QDs) technology was developed for rapid detection of a specific mycobacterial flavoprotein reductase (fprA). In order to develop the LF assay based on a double-antibody sandwich format, two monoclonal antibodies recognizing different epitopes located in separated fprA domains were identified. The first monoclonal antibody was immobilized onto the detection zone of a porous nitrocellulose membrane, whereas another monoclonal antibody was conjugated to QDs nanoparticles as a detection system. Using these monoclonal antibodies we recorded a good fluorescence signal, the intensity of which was directly proportional to the concentration of fprA protein. The use of antibodies conjugated with fluorescent semiconductor QDs via biotin-streptavidin bridge, allowed the detection of fprA protein at concentrations as low as 12.5 pg/μL in less than 10 min. The reported technology could be useful in the diagnostic investigation of Mycobacterium tuberculosis and other human pathogens in clinical specimens.