Retroperitoneal fibrosis: a case of a patient (63y/o) treated with low-dose methotrexate (MTX) and 6-methylprednisolone (6-MP)

Retroperitoneal fibrosis (RPF), is a rare fibroinflammatory disease. The pathogenesis of RPF is still unclear and numerous theories have been reported such as environmental factors, immunologic process, genetic component, local inflammation and advanced atherosclerosis. RPF is characterized by the presence of a particular retroperitoneal fibrotic tissue which is white, woody and involving retroperitoneal structures such as the great vessels, ureters and psoas muscle. The main complication of RPF is the obstruction of local structures such as the ureters due to the fibrosis and the treatment of this aspect represents the main challenge for this pathology. RPF medical treatment consists of corticosteroids or/and immunosuppressive therapy. We report a case of a patient (63y/o) affected by idiopathic RPF treated with low-dose methotrexate (MTX) and 6-methylprednisolone (6-MP) for two years, describing and confirming the effectiveness and safety of a long-term low-dose MTX and 6-MP treatment

Interleukin-13 (IL-13)in autoimmune rheumatic diseases: relationship with autoantibody profile

Objective: Several cytokines play a role in the production of autoantibodies such as RF and ANA by B-lymphocytes; the role of IL- 13 in this process has not been previously studied. We investigated the relationship between the serum concentration of this cytokine and circulating autoantibodies. Methods: IL-13 serum levels, as well as RF and ANA, were evaluated in 282 patients with autoimmune rheumatic diseases including RA (n=84), SLE (n = 114), SS (n = 52) and Scl (n =32). Results: Serum levels of IL-13 (pg/ml) were significantly higher in patients with RA (p < 0.00003), SLE (p < 0.03), SS (p < 0.0007), or Scl (p < 0.025) compared to controls. IL-13 serian levels correlated with those of RF in RA (p < 0.00001), SLE (p < 0.003) and Scl (p < 0.03). IL- 13 levels were higher in RA (p<0.0003), SLE (p<0.005) and Scl (p<0.05) patients with RF than in patients,without RE SS patients with anti-SSA/Ro antibodies had significantly higher IL-13 levels than SS patients without this autoantibody (p < 0.04). No statistically significant correlation was found between IL-13 levels and any other antinuclear autoantibody, total immunoglobulin levels or the main clinical features of each disease. Conclusion: The evidence of higher IL- 13 levels in our RA, SLE, SS and Scl patients confirms that this cytokine is involved in the pathogenesis of autoimmune rheumatic diseases. The relationship of this cytokine with RF in RA, SLE and Scl, as well as with antiSSA/ Ro antibody in SS, strengthens the hypothesis that it plays a role in autoantibody production. However the different autoantibody synthesis by Bcells recognises different pathways depending on the underlying autoimmune disease

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

Soluble P-selectin levels in synovial fluid and serum from patients with psoriatic arthritis

Objective: P-selectin is an adhesion molecule expressed by activated endothelial cells and platelets favouring the leukocyte adherence to microvascular endothelium. A soluble form of this molecule has been described, whose serum levels were found to be elevated and correlate with disease activity in rheumatoid arthritis (RA) patients. Aim of this study was to determine soluble P-selectin levels in synovial fluid (SF) and serum from patients with psoriatic arthritis (PsA), where it has never been investigated, to define its involvement in PsA synovial damage. Methods: we analysed, by ELISA, soluble P-selectin serum and SF levels in 100 patients presenting a knee joint effusion: 38 of them presented PsA, 40 RA and 22 osteoarthritis (OA). We examined the main clinical and laboratory parameters of these patients. Soluble P-selectin serum levels were also detected in 15 healthy subjects. Results: soluble P-selectin SF levels were significantly higher in PsA and RA patients respect to OA subjects. Soluble P-selectin SF levels were lower than those found in serum and the SF/serum ratio was higher in PsA and RA patients respect to OA. Soluble P-selectin serum levels were not significantly different among patients and controls. No correlation was found between SF and serum levels of soluble P-selectin and the main clinical parameters. Conclusions: our study of soluble P-selectin in PsA reveals a prominent local role of this molecule, with no differences respect to RA. Histological findings may be of help in understanding the role of this adhesion molecule in PsA

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

[Usefulness of anti-cyclic citrullinate peptide antibody determination in synovial fluid analysis of patients with rheumatoid arthritis].

Objective: To assess the role of anti-cyclic citrullinated peptide (CCP) antibody detection in synovial fluid (SF) of RA patients compared to OA patients. Methods: We evaluated in 25 RA subjects and 14 OA patients, presenting a knee-joint effusion, the main clinical and laboratory parameters including the number of painful and/or swollen joints, Ritchie index, morning stiffness, ESR, CRP and analysis of SF obtained by therapeutic arthrocentesis. IgG anti-CCP (ELISA), rheumatoid factor (RF) and total IgG (nephelometry method) were measured in SF and paired serum samples. Results: We found anti-CCP antibodies and RF in 64% (16/25) and 60% (15/25) of RA sera, respectively; 72% (18/25) of RA patients were positive for anti-CCP antibodies or RF. We found a higher SF/serum ratio for anti-CCP (p<0.004) compared to that for total IgG. The calculation of anti-CCP concentration as IgG anti-CCP (units)/total IgG (g L-1) revealed higher values in SF than in serum (p<0.046) in RA patients. Among these, correlation analysis showed that anti-CCP/total IgG values in SF correlated with the relative concentration of serum anti-CCP/total IgG (rs=0.842; p<0.00001) and serum anti-CCP antibody levels (rs=0.799; p<0.0001). We did not find any correlation between SF anti-CCP levels and the main characteristics of SF as well as the clinical or laboratory parameters. Conclusion: Our study give evidence for a preferential production of anti-CCP antibodies at RA joint level, confirming the pathogenetic role of these autoantibodies. Moreover, SF determination of anti-CCP, corrected for the total amount of the corresponding immunoglobulin, may be helpful as diagnostic tool in selected cases

Role for familiarity and genetic features in the therapeutic response of psoriatic arthritis

Aim of the study: To analyze PsA patients with and without a familiar distribution for Ps and PsA, in order to better evaluate the genetic data, to verify the existence of different expression of the disease and finally to define the susceptibility to treatment in these patients. Materials and methods: 230 PsA patients were selected for familiar or sporadic distribution of the disease and were evaluated for the main clinical, demographic, radiological and laboratory features, as well as for the ongoing treatments. In each patient HLA class I (A,B,C) and II (DRB1, DQB1) antigens were typed with PCR-SSP method while MICA-A exon 5 microsatellite typing was performed by heteroduplex analysis in 122 subjects. Results: A familiar distribution for Ps and PsA was found in 68 patients (29.6%) although only two patients had familiarity for PsA. In the familiar PsA group the male prevalence was significantly higher respect to the sporadic one (p<0.001) and the more frequently involved relative was the father (28%). Mean age (p<0.006) and age at onset of Ps (p<0.004) and PsA (p<0.014) were significantly lower in familiar respect to sporadic PsA. Between the two groups no difference was found concerning the articular involvement, the radiological findings, the disease activity (including n° of painful/swollen joints), the inflammatory laboratory parameters (including ESR and CRP) and genetic aspects, incuding the frequencies of MICA-A alleles that were analysed in 30 patients with the familiar form and in 92 with the sporadic one. In the follow-up the therapeutic response to any evaluated treatment adopted for PsA did not show any significant difference in the two groups. All these results were confirmed even when the patients in the two groups were matchable for sex, age and disease duration. Conclusion: Our results confirm that familiar PsA is characterized by an early onset of the disease and by a male and fatherly predominance respect to the sporadic form, although the clinical-radiologic findings, the genetic typing and the therapeutic response do not permit us to identify any particular subset

Nailfold capillaroscopy in the rheumatological current clinical practice in Italy: results of a national survey

: This cross-sectional online study was designed by the study group on Capillaroscopy and Microcirculation in Rheumatic Diseases (CAP) of the Italian Society of Rheumatology (SIR) to provide an overview of the management of nailfold capillaroscopy in Italian rheumatology centers. Therefore, SIR distributed the survey to its members in July 2021, and each center's physician with the most expertise in capillaroscopy completed the questionnaire. The survey was completed by 102 centers, with at least one representative from each Italian region. Ninety-three centers perform capillaroscopy, and 52 (56) conduct more than 200 investigations annually. Seventy-eight (84%) of respondents have more than five years of experience with the technique, and 75 centers (80.6%) have received certification from specific national or international training courses. In 85 centers, a videocapillaroscope with 200x magnification is employed (91.4%). The average waiting period for the examination is 2.4 months, and less than 3 months in 64 of the locations (68.8%). The study demonstrates that capillaroscopy is an integral part of both the diagnostic phase of Raynaud's phenomenon and the monitoring of autoimmune connective tissue diseases (CTDs). However, the reporting methods and timing of patient followup are heterogeneous