POS0433 CAN INTERLEUKIN 33 (IL-33) BE CONSIDERED A VALUABLE BIOMARKER IN THE EARLY STAGES OF SYSTEMIC SCLEROSIS? ANALYSIS OF A MONOCENTRIC COHORT

Background:The ScS approach has changed considerably in recent years especially concerning the very early diagnosis of the disease (VEDOSS) at the time when the patient is still in an undifferentiated form (UCTD) at risk of developing SSc (1, 2). Of great value are different clinical, instrumental and laboratory findings, such as specific autoantibodies and Nailfold VideoCapillaroscopy (NVC), able to identify those cases progressing into overt SSc. IL-33 cytokine is known to exert pro-fibrotic effects through its membrane receptor ST2 on immune cells and myofibroblasts and recent studies suggest that it can be released following endothelial cell activation at the onset of SSc (3, 4).Objectives:Our aim has been to evaluate IL-33 serum levels in a monocentric cohort of VEDOSS patients, looking for the possible association with clinical phenotype and disease progression, focusing on the microvascular capillaroscopic changes.Methods:Fourty-seven VEDOSS patients underwent a complete clinical, instrumental and laboratory evaluation, including NVC and specific SSc autoantibodies. At baseline serum IL-33 levels were measured using an ELISA assay. In 32 of them we also had a second serum sample at a follow-up time of at least 24 months (range 24 to 96 months).Results:During the follow-up time, 17 patients were subsequently reclassified as having ScS whereas 30 remained VEDOSS. The "progressor" subjects positively correlated with the presence of anti-Topoisomerase I antibodies (p>0,004). IL-33 concentrations had a median value of 427.2 pg/ml (IQR 967.9 pg/ml) at baseline and of 130.4 pg/ml (IQR 399 pg/ml) at the follow up, showing a statistically significant difference independently from the progression of the disease (p=0.03). Besides significantly higher levels were detected in those patients with more severe NVC changes, defined as "active" pattern (p<0.05). Among the 47 VEDOSS patients, 12 started some kind of vascular therapy. In these patients serum IL-33 concentrations significantly lowered during the follow-up respect to those without any treatment (p<0.03)Conclusion:The analysis of our data confirms previous report (5) on higher IL-33 serum levels in the very early stages of UCTD patients at risk for SSc, regardless of their progression in established SSc, although related to more severe microvascular NVC involvement. The lowering of IL-33 serum levels that we detected in the follow up of our patients, may be linked to the well-known endothelial changes during the progression of the SSc and seems also to be partially affected by treatments. Investigation on a greater number of patients are needed to better understand our findings.References:[1]J. Avouac et al. Ann Rheum Dis 2011[2]G Valentini et al. Clin Exp Med 2017[3]Manetti M, et al. Ann Rheum Dis 2010[4]Terras S et al. Ann Rheum Dis 2013[5]Vettori S, et al. J Clin Immunol 2014Disclosure of Interests:None declare

Occupational Therapy Treatment to Improve Upper Extremity Function in Individuals with Early Systemic Sclerosis: A Pilot Study

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/146446/1/acr23522.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/146446/2/acr23522_am.pd

POS1185 IMPACT OF LOCKDOWN DURING COVID-19 PANDEMIC ON THE ONSET OF POST-TRAUMATIC STRESS DISORDER (PTSD) IN SYSTEMIC SCLEROSIS PATIENTS: A CASE-CONTROL STUDY

Background:Social distancing due to COVID-19 pandemic had a major impact on the mental health of general population, with a high prevalence of post-traumatic stress disorder (PTSD) related symptoms1, 2. Psychological repercussions were notably found in people with chronic diseases, including systemic sclerosis (SSc) patients, where an increasing of anxiety symptoms, related also to low financial resources, emerged3.Objectives:To evaluate the impact of COVID-19 lockdown on the onset of PTSD in patients with SSc, firstly during the total confinement period (March-April 2020) and then at the time of less restrictive government measures, following the RT index lowering (June-July 2020)4.Methods:We carried out a case-control study on 57 SSc patients, according to the ACR/EULAR 2013 criteria, and on 57 healthy subjects as control group (HC), matched by sex and age. At T0 (March-April) and T1 (June-July) both populations received the "Impact of Event Scale Revised" questionnaire (IES-R) by e-mail, with a cut-off of ≥ 33 defining probable diagnosis of PTSD5. A multivariate analysis of possible factors influencing IES-R score, such as age, number of cohabitating people and weekly outings count, was performed in SSc patients at both times of the survey.Results:At T0 we found a significantly greater number of SSc patients with IES-R score ≥ 33 compared to HC (26/45.6% vs 13/22.8%; median value [quartiles] 31 [19.5;42.5] vs 24 [15.5; 32]; p-value 0.046). At T1, we obtained data from 44 SSc patients and 35 HC but no significant difference was noticed (18 / 40.9% vs 8 / 23.5%; 26 [15.25; 38] vs 26.5 [20.75; 32.5]; p> 0.05). SSc patients also had significantly fewer weekly outings than HC, both at T0 (p <0.001) and T1 (p <0.001) (Table 1). The multivariate analysis performed at T0 on SSc patients showed a significant association of IES-R ≥33 score with age (p 0.025) and with a lower count of weekly outings (p 0.002). The latter data negatively correlated with an IES-R ≥33 score in SSc patients (r -0.267, p 0.004).Conclusion:We found a significantly higher prevalence of PTSD in SSc patients compared to HC at the strictest lockdown time, turning into comparable when government measures were less restrictive, due to the minimum RT index values recorded in Italy. Older age and lower count of weekly outings were associated with PTSD in SSc patients during the lockdown, whereas the count of weekly outings was lower than in HC during both the examined periods. The results of this study indicate that COVID-19 lockdown had a worse impact in SSc patients, where the fewer weekly outings may depend on their clinical condition and on a greater concern about their health6. These findings strengthen the World Scleroderma Foundation recommendations regarding care to the psychological frailty of SSc patients7.References:[1]Wang C, Brain Behav Immun. 2020.[2]Dubey S, Psychiatr Pol. 2020.[3]Thombs BD, J Psychosom Res. 2020 Dec.[4]https://covid19.infn.it/grafici/?chart=italia,rt,covidstat[5]Weiss, D. S., & Marmar, C. R. (1996). The Impact of Event Scale - Revised, Assessing. psychological trauma and PTSD (pp. 399-411).[6]Orlandi M, Clin Rheumatol. 2020[7]Matucci-Cerinic M, Ann Rheum Dis. 2020Table 1.Descriptive analysis of study population: T0 (Time 0), T1 (Time 1), SD (Standard Deviation), IES-R (Impact of Event Scale-Revised).SSc patient groupHS groupFemale:male ratio at T046:746:7Mean age ± SD at T059±12.851±8.7IES-R ≥33 score n°/% at T026/45.6%*13/22.8%IES-R ≥33 score n°/% at T118/40.9%8/23.5%IES-R score at T0, median value [quartiles]31 [19.5;42.5]24 [15.5;32]IES-R score at T1, median value [quartiles]26 [15.25; 38]26.5 [20.75; 32.5]N° of weekly outings at T0, median value [quartiles]2 [1;3.5]4 [2;10]**N° of weekly outings at T1, median value [quartiles]5 [3;6]14 [6.75;15]***p<0.046; **p<0.001Disclosure of Interests:None declared

COVID-19 and systemic sclerosis: analysis of lifestyle changes during the SARS-CoV-2 pandemic in an Italian single-center cohort

The outbreak of SARS-CoV-2 has changed the habits and lives of people worldwide. Patients affected by systemic sclerosis (SSc) experienced constant fear because of their immunocompromised status. The aim of this study was to investigate the prevalence of SARS-CoV-2 infection and to analyze the lifestyle changes in a single-center cohort of SSc patients and if these changes were more severe than in the general population. During the Italian lockdown, we supplied two surveys to our 184 SSc patients. In the first one, filled by 110 patients, we asked if SARS-CoV-2 had infected them or if they experienced signs and symptoms consistent with COVID-19. The second survey, performed by 79 SSc patients and 63 healthy subjects, included questions about the lifestyle adopted during this specific period. Among our patients, COVID-19 was diagnosed only in one case, while three other subjects reported signs and symptoms suggestive for the disease. Regarding the second survey, our patients greatly changed their lifestyle during the pandemic, adopting more restrictive isolation measures, because of their awareness of frailty. To date, we do not dispose of enough data to speculate about the risk of COVID-19 among immunocompromised patients, although in our SSc patients their frailty seems to have been their shelter. Pending more accurate epidemiological studies, it is essential to share as much data as possible to better understand the impact of COVID-19 on SSc patients’ health.• The lifestyle adopted by SSc patients during the first months of COVID-19 pandemic was characterized by more stringent isolation rules than general population.• The prudential behavior of patients with SSc during Italian lockdown should be considered as a possible bias when analyzing the risk of SARS-CoV-2 disease in these subjects, as well as a protective factor against infection

S.11.1 Influence of digital ulcer healing on disability and daily activity limitations in SSc

Objective. We previously showed that DU significantly increased global and hand disability with a significant impact on activities of daily living (ADLs) and work disability. This study aims to evaluate the impact of digital ulcer (DU) healing on disability and daily activity limitations in SSc. Methods. From January 2008 and June 2009, we prospectively evaluated 189 SSc patients for DU history, disability, employment and occupational status during meetings of the French SSc Patient Association (n = 86, 45.5%) or during hospitalization (n = 103, 54.5%)1. Among the 60 patients with at least one active DU at baseline (M0), 40 patients were followed longitudinally over 6 (3) months. These patients were evaluated for DU history, global and hand disability, health-related quality of life (HRQoL), daily activity limitation and employment status. Results. The median (IQR) age was 57.5 (43.5-68) years and the median (IQR) disease duration was 8.3 (3-16.5) years. Twenty-two (55%) patients had diffuse SSc and 34 (85%) were females. At baseline, a mean of 2.9 (2.8) DU per patient was reported. Thirty-three (82.5%) patients had ischaemic DU, 7 (17.5%) patients had >1 DU associated with calcinosis and 13 (32.5%) patients had mechanical DU. Thirteen (32.5%) patients had >4 DU at baseline. Among the 40 patients, 16 (40%) patients showed complete ulcer healing. In these patients with DU, the presence of calcinosis was associated with a lower probability of healing (P = 0.03). Comparison between healed and no-healed DU patients showed an improvement of hand disability provided by an improvement of the Cochin Hand Function score (P = 0.05)) and a trend towards HAQ domain dressing and grooming (P = 0.06) between M0 and M6 (3) visit in healed patients but not in no-healed patients. Concerning HRQoL, there were no difference for Mental and Physical component Scores of SF-36 but significant improvement of Bodily Pain score (P = 0.04) and Physical Role score (P = 0.05) between M0 and M6 (3) visit in patients with healed DU. The absence of healing was associated with significantly decreased work productivity (P = 0.05), whereas the performance in ADL was not significantly decreased (P = 0.15). Patients who were on sick-leave and who received some help for household tasks at the time of active DU were more likely to heal. Conclusion. For the first time, we provide prospective data with evidence that DU healing is associated with an improvement in hand function. Sick leave was associated with better healing of D

Helicobacter pylori and Upper Endoscopy in Systemic Sclerosis: A Cross-sectional Study in the Real World

BACKGROUND/AIMS: A role for Helicobacter pylori in triggering systemic sclerosis (SSc) has been proposed, but data are conflicting. In previous studies, infection has been generally searched for by using serology. We designed this study to assess H. pylori prevalence in SSc patients with histology of gastric mucosa, considered the criterion standard for infection diagnosis. METHODS: This cross-sectional study enrolled 30 SSc patients who complained of upper gastrointestinal symptoms. All underwent upper endoscopy with gastric biopsies. Endoscopic alterations were recorded, and gastric mucosa biopsies were used for both histological examination and searching for H. pylori. The role for proton-pump inhibitor (PPI) therapy was considered. Fisher exact test was used for statistical analysis. RESULTS: Data of 28 SSc patients were available, 14 with ongoing PPI therapy. Helicobacter pylori infection at histology was detected in 14.3% patients, and it equally occurred in patients with or without PPI therapy. Erosive esophagitis/Barrett esophagus was detected in 26.6% of cases. Among patients with PPI therapy, 30% received half dose only. The prevalence of intestinal metaplasia was low (14.3%). Endoscopic esophageal alterations were significantly more frequent in those patients showing anti-Scl70 antibody positivity. CONCLUSIONS: This study showed that prevalence of H. pylori is very low in SSc patients, so that it seems not having a role in triggering SSc. Management of gastroesophageal diseases in SSc patients needs to be improved, and looking to the autoimmune profile may be of help. Thus, collaboration between rheumatologist and gastroenterologist is highly recommended

High prevalence of capillary abnormalities in patients with diabetes and association with retinopathy

Aims To investigate the presence of capillary abnormalities in patients with Type1 and Type2 diabetes using nailfold videocapillaroscopy and to evaluate the possible correlation with the typical diabetes mellitus microangiopathic lesions detectable in retinal blood vessels. Methods Forty-nine patients with diabetes mellitus (21 with Type1 and 28 with Type2 diabetes) and 39 subjects without diabetes were enrolled. Ophthalmoscopy was performed on all patients and was followed by retinal fluorangiography when indicated. Subjects underwent nailfold videocapillaroscopy to evaluate density, length, morphology and distribution of capillary loops, presence of ectasia, microbleedings and blood flow modifications. A score (0-3) was applied to quantify features of nailfold videocapillaroscopy. Results Subjects with diabetes showed a significantly increased (P=0.0001) nailfold videocapillaroscopy score and significantly greater alterations of capillary length (P=0.004), distribution (P=0.02), morphology (P=0.0001), density (P=0.02) and flux (P=0.004), as well as presence of ectasic loops (P=0.009) and of oedema/exudates (P=0.03) compared with control subjects. In addition, patients with Type1 diabetes had a significantly higher score (P=0.01) and greater morphologic alterations (P=0.03) compared with subjects with Type2 diabetes. Nailfold videocapillaroscopy score also showed a positive correlation with retinopathy, detected by both ophthalmoscopy (P=0.0001) and fluorangiography (P=0.02), independently from sex, age, type of diabetes and all potential confounders. Moreover, nailfold videocapillaroscopy was capable of identifying alterations in almost 50% of patients with diabetes without retinopathy. Conclusions A high prevalence of nailfold capillary changes is detected in patients with diabetes using nailfold videocapillaroscopy. These abnormalities tightly correlate with retinal damage and may be expression of a generalized microvessel involvement in both Type1 and Type2 diabetes

New Autoantibody Specificities in Systemic Sclerosis and Very Early Systemic Sclerosis.

Chemokine (C-X-C motif) ligand 4 (CXCL4) is a biomarker of unfavorable prognosis in Systemic Sclerosis (SSc), a potentially severe autoimmune condition, characterized by vasculitis, fibrosis and interferon (IFN)-I-signature. We recently reported that autoantibodies to CXCL4 circulate in SSc patients and correlate with IFN-α. Here, we used shorter versions of CXCL4 and CXCL4-L1, the CXCL4 non-allelic variant, to search for autoantibodies exclusively reacting to one or the other CXCL4 form. Moreover, to address whether anti-CXCL4/CXCL4-L1 antibodies were present before SSc onset and predicted SSc-progression, we longitudinally studied two VEDOSS (Very Early Diagnosis of Systemic Sclerosis) patient cohorts, separating SSc-progressors from SSc-non-progressors. We found that anti-CXCL4-specific autoantibodies were present in both SSc and VEDOSS patients (both SSc-progressors and SSc-non-progressors). Anti-CXCL4-L1-specific autoantibodies were especially detected in long-standing SSc (lsSSc). Anti-CXCL4/CXCL4-L1 antibodies correlated with IFN-α and with specific SSc-skin features but only in lsSSc and not in early SSc (eaSSc) or VEDOSS. Thus, a broader antibody response, with reactivity spreading to CXCL4-L1, is characteristic of lsSSc. The early anti-CXCL4 autoantibody response seems qualitatively different from, and likely less pathogenic than, that observed in advanced SSc. Lastly, we confirm that anti-CXCL4 autoantibodies are SSc-biomarkers and uncover that also CXCL4-L1 becomes an autoantigen in lsSSc