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Objective To identify a core set of preliminary items considered as important for the very early diagnosis of systemic sclerosis (SSc). Methods A list of items provided by European League Against Rheumatism (EULAR) Scleroderma Trial and Research(EUSTAR) centres were subjected to a Delphi exercise among 110 experts in the field of SSc. In round 1, experts were asked to choose the items they considered as the most important for the very early diagnosis of SSc. In round 2, experts were asked to reconsider the items accepted after the first stage. In round 3, the clinical relevance of selected items and their importance as measures that would lead to an early referral process were rated using appropriateness scores. Results Physicians from 85 EUSTAR centres participated in the study and provided an initial list of 121 items. After three Delphi rounds, the steering committee, with input from external experts, collapsed the 121 items into three domains containing seven items, developed as follows: skin domain (puffy fingers/puffy swollen digits turning into sclerodactily); vascular domain (Raynaud's phenomenon, abnormal capillaroscopy with scleroderma pattern) and laboratory domain (antinuclear, anticentromere and antitopoisomerase-I antibodies). Finally, the whole assembly of EUSTAR centres ratified with a majority vote the results in a final face-to-face meeting. Conclusion The three Delphi rounds allowed us to identify the items considered by experts as necessary for the very early diagnosis of SSc. The validation of these items to establish diagnostic criteria is currently ongoing in a prospective observational cohort.

Background The prognostic and theragnostic role of histopathological subsets in systemic sclerosis interstitial lung disease (SSc-ILD) have been largely neglected due to the paucity of treatment options and the risks associated with surgical lung biopsy. The novel drugs for the treatment of ILDs and the availability of transbronchial cryobiopsy provide a new clinical scenario making lung biopsy more feasible and a pivotal guide for treatment. The aim of our study was to investigate the usefulness of lung biopsy in SSc ILD with a systematic literature review (SLR). Methods PubMed, Embase and Cochrane databases were searched up to June 30, 2023. Search terms included both database-specific controlled vocabulary terms and free-text terms relating to lung biopsy and SSc-ILD diagnostic and prognosis. The SLR was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA). Studies were selected according to the PEO (population, exposure, and outcomes) framework and Quality assessment of diagnostic accuracy studies (QUADAS) were reported. Results We selected 14 articles (comprising 364 SSc-ILD patients). The paucity and heterogeneity of the studies prevented a systematic analysis. Diffuse cutaneous SSc was present in 30–100% of cases. Female predominance was observed in all studies (ranging from 64 to 100%). Mean age ranged from 42 to 64 years. Mean FVC was 73.98 (+/-17.3), mean DLCO was 59.49 (+/-16.1). Anti-Scl70 antibodies positivity was detected in 33% of cases (range: 0-69.6). All patients underwent surgical lung biopsies, and multiple lobes were biopsied in a minority of studies (4/14). Poor HRCT-pathologic correlation was reported with HRCT-NSIP showing histopathologic UIP in up to 1/3 of cases. Limited data suggest that SSc-UIP patients may have a worse prognosis and response to immunosuppressive treatment compared to other histopathologic patterns. Conclusions The data from this SLR clearly show the paucity and heterogeneity of the studies reporting lung biopsy in SSc ILD. Moreover, they highlight the need for further research to address whether the lung biopsy can be helpful to refine prognostic prediction and guide therapeutic choices.

Objective. In the last decades, the number of foreigners in Tuscany has considerably increased with a multiethnic distribution. We reviewed the main rheumatic diseases in the foreign population resident in Tuscany and also reported the experience at the Rheumatology Division of the University Hospital of Careggi, Florence, in order to identify the areas of origin of these patients and the main rheumatic diseases observed in them. Methods. The collaboration with the Tuscan Region provided data about foreign patients residing in Tuscany on January 1, 2021 (country of origin, chronic diseases). Moreover, we conducted a retrospective review of the clinical charts of our Rheumatologic Division from January 1, 2019, to December 31, 2020. Results. In Tuscany, on January 1, 2021, there were 61,373 patients with chronic inflammatory rheumatic diseases, and 3994 of them (6.51%) were foreigners. Most patients were born in Europe (39.03%), followed by the Balkans (15%), South America (11.27%), and North Africa (10.31%). Inflammatory joint diseases, Sjögren syndrome, and systemic lupus erythematosus were the most frequent diseases. In the period 2019-2020, 511 foreign patients visited our Rheumatology Division and mainly originated from the Balkans (34.64%), South America (18%), and European countries (16.44%). In these patients, chronic inflammatory joint diseases and connective tissue diseases (systemic sclerosis, Sjögren syndrome, and systemic lupus erythematosus) were the most prevalent diseases. Conclusions. This study provides a picture of the rheumatic diseases affecting foreign patients residing in Tuscany that are in agreement with the epidemiological data previously provided.

Background A consensus on digital ulcer (DU) definition in systemic sclerosis (SSc) has been recently reached (Suliman et al., J Scleroderma Relat Disord 2:115-20, 2017), while for their evaluation, classification and categorisation, it is still missing. The aims of this study were to identify a set of essential items for digital ulcer (DU) evaluation, to assess if the existing DU classification was useful and feasible in clinical practice and to investigate if the new categorisation was preferred to the simple distinction of DU in recurrent and not recurrent , in patients with systemic sclerosis (SSc). Methods DeSScipher is the largest European multicentre study on SSc. It consists of five observational trials (OTs), and one of them, OT1, is focused on DU management. The DeSScipher OT1 items on DU that reached ≥ 60% of completion rate were administered to EUSTAR (European Scleroderma Trials and Research group) centres via online survey. Questions about feasibility and usefulness of the existing DU classification (DU due to digital pitting scars, to loss of tissue, derived from calcinosis and gangrene) and newly proposed categorisation (episodic, recurrent and chronic) were also asked. Results A total of 84/148 (56.8%) EUSTAR centres completed the questionnaire. DeSScipher items scored by ≥ 70% of the participants as essential and feasible for DU evaluation were the number of DU defined as a loss of tissue (level of agreement 92%), recurrent DU (84%) and number of new DU (74%). For 65% of the centres, the proposed classification of DU was considered useful and feasible in clinical practice. Moreover, 80% of the centres preferred the categorisation of DU in episodic, recurrent and chronic to simple distinction in recurrent/not recurrent DU. Conclusions For clinical practice, EUSTAR centres identified only three essential items for DU evaluation and considered the proposed classification and categorisation as useful and feasible. The set of items needs to be validated while further implementation of DU classification and categorisation is warranted. Trial registration Observational trial on DU (OT1) is one of the five trials of the DeSScipher project (ClinicalTrials.gov; OT1 Identifier: NCT01836263 , posted on April 19, 2013).

The aim of this study was to evaluate in systemic sclerosis (SSc) retrospectively the effect of Bosentan and Sildenafil and their combination on Raynaud’s phenomenon (RP), function, and capillaroscopic patterns. One hundred and twenty-three SSc patients (mean age ± sd, 57.69 ± 14.07 years) were retrospectively evaluated and divided into two groups according to American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification score: group 1 score < 10, group 2 score > 10. Each group was divided into three subgroups according to treatment: Bosentan, Sildenafil, and Bosentan + Sildenafil. Nailfold videocapillaroscopy (NVC), Scleroderma Health Assessment Questionnaire (SHAQ) and Raynaud Condition Score (RCS) were performed at baseline and after 3 and 6 months. In Bosentan (29 patients: 12, group 1; 17, group 2), NVC changed significantly in both groups, after 3 and 6 months ( p  = 0.00439, group 1; p  = 0.00035, group 2). In group 1, the “active” and the “late” patterns reduced, and the “aspecific” increased. In group 2, there was a reduction of late patterns, a worsening of SHAQ ( p  < 0.005) and an improvement of RCS ( p  = 0.00014). In Sildenafil (63 patients: 35, group 1; 28, group 2), after 3 months, NVC patterns changed significantly in both groups( p  = 0.042 group 1, p  = 0.00089 group 2). In group 1, the late and early patterns increased, and the aspecific decreased. In group 2, a significant change of NVC pattern was observed also after 6 months ( p  = 0.00089): the late pattern increased while the active one reduced. After 6 months, SHAQ was significantly reduced in group 1 ( p  = 0.00027) and in group 2 ( p  = 0.0043). RCS improved in both groups ( p  = 0.0042, group 1; p  = 0.0016, group 2). Combination therapy (Bosentan + Sildenafil) (31 patients: 14, group 1; 17, group 2) induced significant changes on NVC only in group 1 after 3 ( p  = 0.00256) and 6 months ( p  = 0.000349) with a reduction of the late and active patterns and an increase of the early pattern. In both groups, after 6 months, SHAQ ( p  < 0.05, group 1; p  = 0.00049, group 2) and RCS significantly reduced (group 1, p  = 0.00024; group 2, p  = 0.0021). Patients treated with Bosentan + Sildenafil show a significant improvement of RCS and NVC. This combination therapy may exert a vascular activity achieving an amelioration of the structure of microvasculature in SSc.

Bosentan, a dual endothelin receptor antagonist, may reduce blood pressure by blocking the vasoconstrictor effect of endothelin-1. In systemic sclerosis (SSc) nailfold videocapillaroscopy (NVC); allows diagnostic and follow-up of microvascular damage. Distinct NVC patterns have been identified for the evaluation of severity of SSc microvascular damage. The objective of this study is to evaluate the modification of the microvasculature under Bosentan therapy in SSc patients with pulmonary arterial hypertension (PAH). Nine patients with PAH related to SSc in New York Heart Association classes III–IV were treated with Bosentan 125 mg twice a day. NVC optical probe videocapillaroscopy equipped with 100× and 200× contact lenses and connected to image analyse software was performed before and after 12 months of Bosentan therapy to evaluate the modification of microvasculature. Nine PAH SSc patients treated with Iloprost were used as controls. Before Bosentan therapy, seven patients showed at NVC severe loss of capillaries with large avascular areas and vascular architectural disorganisation which are typically “late” SSc pattern. After 12 months of Bosentan, NVC pattern changed in seven patients from “late” into “active” SSc pattern. The disappearance of avascular areas and capillary haemorrhages was the most striking result. Two patients had an “active” SSc pattern, not modified by Bosentan treatment. These data show that Bosentan may improve NVC pattern in SSC and the presence of new capillaries suggests that it may favour angiogenesis. Bosentan may improve and stabilise the microvasculature in long-term treatment modulating the structural modifications detected by NVC.

BackgroundAt early stages, SSc lung involvement is characterised by Ground Glass Opacities (GGO) at High Resolution Computed Tomography (HRCT). However, HRCT scan is not able to provide functional information and to discriminate between an “active inflammatory” and an “established fibrotic” GGO. 18Fluoro-Deoxy-d-Glucose (18F-FDG) Positron Emission Tomography/Computed Tomography (PET/CT) is able to detect metabolic activity picking up inflammation and provides both morphologic and metabolic data.ObjectivesThe aim of this study was to evaluate, if 18F-FDG PET/CT scan may identify the inflammatory component of GGO in SSc interstitial lung disease.MethodsSeven patients with SSc (1 male and 6 females; mean age 59.56 y±9.15 SD; median disease duration 5 years,2–11 who underwent 18F-FDG PET/CT scan because of cancer screening, were retrospectively analysed. HRCT images analysis led to classification of pulmonary segments as “negative” (normal morphology) and ”positive” (GGO). Furthermore, the “Warrick score” was used as a staging tool for SSc-ILD. Mean Standardised Uptake Value (mSUV) of segmental parechima was normalised (nmSUV) by comparison with the values of selected control subjets.ResultsNo SSc patient was affected by cancer. Three patients had a Warrick Score >0, while 4 patients did not had any lung involvement (Warrick Score=0). The 3 patients with a Warrick Score >0 had also skin involvement with a median mRSS 6 (2–7) and pathological lung FDG uptake. In “positive” segments of SSc patients, nmSUV was significantly higher than in the lung segments of the control population (mean estimation 1.53; C.I. 1.42–1.65, p<0.0001). In “negative” segments of SSc patients, with a Warrick score >0, the nmSUV was significantly higher than in segments of the control population (mean estimation 1.29; C.I. 1.22–1.37, p<0.0001). Lung segments with GGO showed an nmSUV higher (21%) than “negative” segments (C.I. 0.13–0.28, p<0.0001) of patients with Warrick score >0. “Negative” lung segments of patients with Warrick Score >0 showed a 32% higher 18F-FDG uptake than “negative” lung segments of patients with Warrick Score=0. (C.I. 0.17–0.48, p<0.0001). (figure 1)Abstract THU0425 – Figure 1a) Differences in 18F-FDG uptake between “positive” segments of Warrick score >0 SSc patients, “negative” segments of Warrick score >0 SSc patients and “negative” segments of Warrick score=0 SSc patients vs attended normalised control value (=1); b) Differences in 18F-FDG uptake between “positive” lung segments of SSc patients with Warrick score>0 vs “negative” segments of the same patients; c) Differences in 18F-FDG uptake “negative” lung segments of patients with Warrick Score>0 vs “negative” lung segments of patients with Warrick Score=0ConclusionsMorphologically “positive” GGO segments show an increased 18F-FDG uptake suggesting the existence of a metabolically active (inflammatory) GGO. However, in patients with GGO, negative lung segments showed a higher nmSUV than negative lung segments in patients without GGO. This may suggest that PET/CT may disclose an underlying inflammatory process, which cannot yet be evidenced by HRCT. Further studies on a larger population are warranted to confirm these data and possibly provide a prognostic significance of PET/CT positivity in SSc patients.Disclosure of InterestNone declared

BackgroundIn rheumatoid arthritis (RA), interstitial lung disease (ILD) is a frequent pulmonary manifestation which is responsible for a high morbidity and mortality. Chest high resolution computed tomography (HRCT) is the imaging gold standard for the diagnosis and characterisation of ILD. Recently, the use of lung ultrasonography (US) has been suggested as a valid, less invasive and radiation-free tool in the pulmonary screening process.ObjectivesTo review the reliability of lung US as a screening tool for the diagnosis of ILD in RA patients.MethodsA systematic literature search in several databases was conducted following the PICO framework on July 2022. Two researchers independently screened abstracts and titles, and full texts were subsequently reviewed to determine eligibility (original research articles enrolling adult RA patients undergoing lung US and HRCT). Data from eligible articles were extracted and risk of bias (RoB) was assessed with validated tools. Owing to extensive interstudy heterogeneity, narrative summaries had to be used to present the data.ResultsOut of 690 retrieved papers, only 7 were eligible and only 5 of them enrolled a control group (Table 1). All studies had a cross-sectional design and no follow-up data were available. Although all studies relied on the US identification of B-lines, the number of intercostal spaces assessed as well as the threshold/score to classify the findings as ILD or no-ILD varied across studies. Furthermore, some studies also focused on the irregularities of the pleural line. The sensitivity of lung US ranged between 62.2 and 97.1% while specificity ranged between 89 and 100%. However, the studies’ heterogeneity did not allow any comparison. In RA patients with neither respiratory symptoms nor previous ILD diagnosis, the concordance in identifying pathological findings between US and HRCT ranged between 90 and 100%.ConclusionOur Systematic Literature Review shows that lung US may have a role as screening tool for ILD in RA and also in asymptomatic patients. The implementation of the routine use of lung US in RA might allow an early identification and a prompt treatment of RA-ILD patients as well. However, the harmonization of US findings is required to allow either for the comparison of research studies and for a broad implementation of lung US in clinical practice.Table 1.Characteristics and main findings of studies with a control groupPatients N, typeControls N, typeComparatorUS Se%US Sp%Thresholds for Se and Sp calculationGutierrez202274 RA w/o ILD74 NSHRCT9289≥ 6 B-lines in 14 ICS*Fotoh202175 RA-ILD75 RA w/o ILDHRCT88100LUS score ≥ 5.5 in 14 ICS °Mena-Vazquez 202035 RA-ILD36 RA w/o ILDHRCT, PFT62.291.35.5 B-lines in 8 ICSMoazedi-Furst 201525 RA w/o ILD40 NSHRCTNRNRNAMoazedi-Furst 201464 RA w/o ILD40 NSHRCT97.197.3Multiple B lines, irregularities ofthe pleural line > 2.8 mm*Semi-quantitative scale of B-line number: 0 = normal (≤ 5 B-lines); 1 = slight (≥ 6 and ≤ 15); 2 = moderate, (≤ 16 and ≥ 30); 3 = severe (≥ 30).°LUS score= number of B lines contained in each ICSRA, rheumatoid arthritis; ILD, interstitial lung disease; NS, normal subjects; ICS, intercostal space; Se, sensitivity; Sp, specificity; US, ultrasonography, HRCT, high resoluation computed tomography; PFT, pulmonary function test; w/o, without; NR, not reportedREFERENCES:NIL.Acknowledgements:NIL.Disclosure of InterestsNone Declared.

BackgroundThe pathogenesis of SpA has not been completely elucidated, but several pieces of evidence suggest that interleukin (IL)17-A plays a pivotal role in this group of diseases. Both anti-IL-17A drugs Secukinumab (SEC) and Ixekizumab (IXE) have shown efficacy in treating multiple facets of SpA. (2)ObjectivesOur study aimed to compare the effect of SEC and IXE in our cohort of patients with PsA or axSpA.MethodsWe retrospective analyzed our clinical database, enrolling patients with PsA or axSpA treated with SEC or IXE. We collected disease activity scales and scores at baseline (0) and after 3, 6 and 12 months of treatment: BASDAI (Bath Ankylosing Spondylitis Disease Activity Index), DAPSA (Disease Activity Index for Psoriatic Arthritis), VAS (Visual Analog Scale) for pain, PGA (Patient Global Assessment), and PHGA (Physician Global Assessment).ResultsWe selected 73 patients, 55 with PsA (75.30%) and 18 with axSpA (24.70%). In the SEC cohort, we found 52 patients, mainly females (73.00%), mean age of 57.00 ± 11.47 years; in the IXE cohort, there were 21 patients, 71.43% females, mean age of 53.81 ±11.17 years. Peripheral involvement was present in the majority of patients (88.46% vs. 100%), while axial involvement was predominant in SEC treated patients (61.54% vs. 28.57%). The presence of dactylitis was similar in the two groups (15.38% vs. 14.29%), enthesitis prevailed in SEC cohort (75.00% vs. 57.14%) while cutaneous psoriasis in the IXE cohort (44.23% vs. 80.95%). During follow-up, BASDAI and DAPSA decreased significantly in both SEC and IXE groups, especially in the first trimester, with a similar trend during the second trimester (significant only for SEC). When compared with each other, SEC and IXE appeared to have a similar effect on both scales, except for a significantly greater reduction of BASDAI in the first trimester for SEC, which however was no longer present when the values were adjusted for the starting BASDAI value (Table 1). Analyzing PGA, PHGA, and VAS pain, we observed a significant trend in reduction in the first trimester for both drugs, then maintained only for SEC, significantly greater for SEC than IXE in both trimesters. The analysis of the adjusted values confirmed the significant decrease in BASDAI DAPSA PGA PHGA and VAS for both SEC and IXE, especially until 6 months after baseline.ConclusionOur data confirmed that SEC and IXE are both valid options for the treatment of PsA and axSpA, without significant differences when comparing the two drugs.References[1]Dougados M. et al, “Spondyloarthritis”, Lancet. 2011 Jun 18; DOI: 10.1016/S0140-6736(11)60071-8[2]McGonagle DG. et al, “The role of IL-17A in axial spondyloarthritis and psoriatic arthritis: recent advances and controversies”. Ann Rheum Dis. 2019 DOI: 10.1136/annrheumdis-2019-215356Table 1.BASDAI and DAPSA variations between SEC and IXE during follow upMonthDrugChangeChangedifferenceChange adjChangedifference adjEstimate(CI95%)PEstimate(CI95%)pEstimate(CI95%)pEstimate(CI95%)pBASDAI0 vs 3SEC-1.20(-1.64 - -0.76)<.00010.73(0.13 – 1.33)0.0174-0.81(-1.21 - -0.41)<.00010.20(-0.37 - 0.77)0.4894IXE-0.47(-0.88 - -0.06)0.0256-0.61(-0.99 - -0.22)0.00193 vs 6SEC-0.71(-1.21 - -0.21)0.00480.41(-0.16 – 0.99)0.1620-0.75(-1.19 - -0.30)0.00090.12(-0.47 – 0.72)0.6819IXE-0.30(-0.60 - 0.002)0.0519-0.62(-1.01 - -0.25)0.00126 vs 12SEC-0.43(-0.82 - -0.04)0.02870.53(-0.18 – 1.24)0.1452-0.76(-1.28 - -0.23)0.00440.43(-0.32 – 1.18)0.2609IXE0.01(-0.50 – 0.70)0.7458-0.33(-1.01 – 0.34)0.3392DAPSA0 vs 3SEC-7.11(-8.51 - -5.71)<.00010.87(-3.59 – 5.34)0.7002-4.27(-5.85 - -2.69)<.00010.95(-1.87 – 3.78)0.5087IXE-6.23(-10.47 - -1.99)0.0040-3.32(-5.42 - -1.21)0.00203 vs 6SEC-1.51(-2.93 - -0.08)0.0374-0.95(-3.82 – 1.91)0.5160-2.79(-4.61 – 0.96)0.0027-0.35(-2.77 – 2.07)0.7776IXE-2.46(-4.95 – 0.03)0.0529-3.14(-5.07 - -1.21)0.00146 vs 12SEC-0.11(-1.77 – 1.54)0.89182.45(-3.79 – 8.69)0.4422-2.84(-5.05 – 0.63)0.01162.67(-3.70 – 9.05)0.4107IXE2.33(-3.68 – 8.35)0.4475-0.16(-6.72 – 6.38)0.9596Acknowledgements:NIL.Disclosure of InterestsNone Declared.

Background:Dietary interventions on top of standard of care may have an adjuvant effect on the improvement of the clinical response in patients with psoriatic arthritis (PsA) who are heavily burdened by metabolic comorbidities. The metabolic profile affect the clinical response to pharmacological treatment and cardiovascular risk in patients with PsA.Objectives:To investigate the efficacy of dietary interventions on top of standard of care in patients with psoriatic arthritis (PsA).Methods:A systematic literature search in five databases was conducted following the PICO framework. Two researchers independently screened abstracts and titles and full texts were subsequently reviewed to determine eligibility (original research articles enrolling: adult PsA patients (P), who underwent dietary interventions on top of standard of care (I) compared to no dietary intervention (C) and assessing efficacy on disease activity with validated outcomes, cardiovascular outcomes (O). Data from eligible articles were extracted and risk of bias (RoB) was assessed with validated tools. Owing to extensive interstudy heterogeneity, narrative summaries had to be used to present the data.Results:Of 410 references, six studies analysing the effect of different dietary interventions on clinical and serological outcomes were eligible for inclusion in the SLR. A total of 524 patients were recruited (316 of which assigned to the dietary intervention). Three studies evaluated caloric restriction, one study evaluated an intermittent fasting strategy, two RCTs assessed a supplementation of polyunsaturated fatty acids (PUFA) with or without hypocaloric diet compared to placebo. Five out of six studies explored the effects on disease activity scores (Table 1). Three studies, two of which without a control group showed significant improvements compared to baseline at up to 24 months. Minimal disease activity was more likely to be achieved by patients adhering to a hypocaloric diet compared to those in a free diet at 6 months. Intermittent fasting also seemed to improve disease activity but data were measured after the fasting period with no data on long-term follow up when regular food intake was restored. PUFA supplementation in patients adhering to a hypocaloric diet seemingly did not provide any additional benefit. However, it may be able to improve cardiovascular outcomes such as arterial stiffness.Conclusion:The results of our SLR, albeit with the limitation of most studies lacking a control group and often providing partial information on concomitant cardiovascular metabolic disorders and concurrent therapy, suggest that patients with PsA may benefit from a dietary intervention on top of pharmacological treatment to achieve a better clinical response. Further controlled studies are needed to explore other dietary patterns (e.g. Mediterranean diet) and better understand the potential of dietary intervention to ultimately facilitate its implementation in clinical practiceREFERENCES:NIL.Table 1. Summary of included studies assessing disease specific clinical outcomes. One included study is not shown in the table since it was focused only on cardiovascular outcomes.Acknowledgements:NIL.Disclosure of Interests:None declared.