Official Journal of the Italian Society of Rheumatology. Founded in 1949. Reumatismo is a reference publication for professionals in the field, being the official journal of the Italian Society of Rheumatology (SIR). The journal offers a space for the dissemination of original studies, research and proceedings of Italian conferences, thus contributing to the advancement of scientific knowledge in the field of rheumatology. The articles published cover a wide range of topics, from autoimmune and inflammatory diseases to new therapies and diagnostic approaches, with the aim of providing useful insights for clinical practice and research. With this, ‘Reumatismo’ aims to be not only an important resource for professionals, but also a platform for dialogue and the exchange of ideas within the Italian and international rheumatology community.
PAGEPress Scientific Publications, Pavia, Italy
Welcome to the 62nd National Congress of the Italian Society of Rheumatology!
Dear Colleagues, It is with great pleasure that I welcome you to the 62nd National Congress of the Italian Society of Rheumatology, which is once again being held in the familiar setting of the Rimini Conference Centre, a place that has become symbolic for our scientific community. The Congress is an essential event for all of us, not only for professional development, but also for discussion, collective growth and strengthening the bonds within our society. This year, the Congress has once again been accredited by the ECM (Italian Continuing Medical Education) to allow for even wider participation and to meet the needs of all colleagues. The programme for this edition has been designed to offer a dynamic journey, rich in innovative content, open to interdisciplinary dialogue and future challenges. This year marks the 75th anniversary of the founding of the SIR, and to mark the occasion, we will be organising an opening ceremony that will include a session dedicated to the evolution of rheumatology: from its historical roots to new perspectives linked to artificial intelligence, with two highly knowledgeable speakers capable of conveying passion and enthusiasm. In addition to the plenary sessions and institutional symposia, we are also confirming the formulas that have been so successful over the years: the Hands On courses, the “Meet the Expert” sessions, the “Question Time” sessions and the traditional Review Course on Saturday morning, which will offer participants the opportunity to update themselves on topics of great practical impact. Ample space will also be reserved for oral presentations (including those in English) and poster displays, where we will have the opportunity to take stock of the research activities of national groups. As every year, we will reward the authors of the best presentations. We are also renewing the “Verso EULAR” initiative, which highlights the contribution of our young scientific community. Our colleagues from SIRyoung will once again be protagonists this year, with a space dedicated to them, demonstrating our ongoing commitment to the younger generation. There will also be activities for health professionals, coordinated by For-Rheuma, and meetings with patient associations, key partners in the treatment process and in dialogue with institutions. Once again this year, we will have our usual convivial and sporting event with the SIR RUN. After the great success of last year's edition, on Wednesday evening, running enthusiasts will be able to try their hand at two routes, 5 and 10 km, or a 5 km walking route. As always, the success of this Congress depends on the quality of each of your contributions. I am confident that this edition will once again offer valuable insights, strengthening our sense of belonging to a vibrant, authoritative and constantly evolving Society. In this spirit, and on behalf of the entire Executive Committee, I wish you stimulating days, rich in content and fruitful professional and personal relationships. Enjoy the Congress! Andrea Doria, President of the SIR
62nd National Congress of the Italian Society of Rheumatology
Copyright (c) 2025 the Author(s) https://creativecommons.org/licenses/by-nc/4.0
CO:01:1 | Efficacy and safety of rituximab across the four phenotypes of IgG4-related disease: a European multi-center cohort study of 115 patients
Background. IgG4-related disease (IgG4-RD) is a rare, immune-mediated fibroinflammatory disorder that affects various organs. Four distinct clinical phenotypes have been described based on organ involvement, yet it is unknown whether treatment response to B-cell depletion varies across them. This study aimed to evaluate the efficacy and safety of rituximab (RTX) across the four IgG4-RD phenotypes in a large real-world European cohort. Materials and Methods We retrospectively analyzed prospectively collected data from adult patients with IgG4-RD treated with RTX at three tertiary centers in Europe—Oslo University Hospital (Norway), San Raffaele Scientific Institute (Milan, Italy), and LMU University Hospital (Munich, Germany). Patients were categorized into four phenotypes: pancreato-hepato-biliary, retroperitoneum and aorta, head and neck-limited, and Mikulicz’ and systemic disease. The primary endpoint at 6 months was a composite of treatment response (gretaer than 2-points decrease in responder index [RI]), absence of flare, and low-dose or no glucocorticoid (lower than 7.5 mg). Secondary endpoints included flare, remission, GC discontinuation, and safety events at 6 and 12 months. Results. We included 115 patients: 33 (28.7%) had pancreato-hepato-biliary disease, 22 (19.1%) retroperitoneal and aortic disease, 19 (16.5%) head and neck-limited disease, and 41 (35.7%) Mikulicz’ and systemic disease. All phenotypes showed comparable response to RTX, with 80 patients (70%) achieving the primary endpoint. However, the retroperitoneum and aorta phenotype had the lowest remission rate at 6 months (4.5% vs 18.2–36.6%, p=0.025), and the head and neck-limited phenotype had the highest flare rate at 12 months (38.9% vs 4.8–25.0%, p=0.006) (Figure 1). Fulfillment of the 2019 ACR/EULAR classification criteria was lower in these two phenotypes. Higher baseline RI score and criteria fulfillment predicted treatment response. Safety profiles were similar across phenotypes. Infusion reactions were most frequent in the head and neck-limited group (31.6%, p=0.021), and infection rates were not significantly different. Conclusions. In this multicenter European study, RTX was effective across all IgG4-RD phenotypes, though patients with retroperitoneum and aorta or head and neck-limited disease appeared less treatment responsive, including lower remission and higher flare rates. These phenotypes also showed lower rates of classification criteria fulfillment, suggesting potential under-representation in clinical trials. Our findings emphasize the need for phenotype-oriented treatment strategies and encourage inclusive trial designs in IgG4-RD.
CO:01:2 | BAG3 in systemic sclerosis: possible therapeutic target and biomarker for pulmonary fibrosis
Background: BAG3 (Bcl2-associated athanogene 3) regulates apoptosis and autophagy while inducing fibroblast-to-myofibroblast transformation. In systemic sclerosis (SSc), myofibroblasts drive skin and organ fibrosis, with interstitial lung disease (ILD) affecting ~50% of patients as the leading mortality cause. BAG3 serum levels correlate with diffuse cutaneous SSc and nintedanib treatment response. This study investigated BAG3's role in SSc pathophysiology using complementary experimental approaches. Methods: Immunohistochemistry assessed BAG3 expression in lung tissue from SSc patients (N=3) and healthy controls (N=5). For in vivo studies, bleomycin-induced pulmonary fibrosis was established in mice (N=23), followed by vehicle (N=11) or anti-BAG3 mAb treatment (20 mg/kg twice weekly, N=12) from day 7-28. Label-free shotgun proteomics using SP3 protocol analyzed lung samples, with Proteome Discoverer 2.4 software processing protein expression data. Results: BAG3 dysregulation was demonstrated across multiple experimental platforms. Immunohistochemistry analysis (Figure 1A) showed significant BAG3 overexpression in SSc lung specimens versus controls, with quantitative analysis confirming elevated BAG3 mean intensity (p=0.0002) (Figure 1B). In the bleomycin-induced pulmonary fibrosis model (Figure 1C), anti-BAG3 mAb treatment markedly reduced fibrotic areas compared to PBS controls (Figure 1D, p=0.02). Comprehensive nanoLC-Orbitrap-MS/MS proteomic analysis revealed distinct molecular signatures between groups. Heat map clustering (Figure 1E) and principal component analysis (Figure 1F-G) demonstrated separation of experimental groups, with anti-BAG3 treated animals displaying proteomic profiles distinct from bleomycin-induced pathology. Functional pathway analysis (Figure 1H) revealed BAG3 inhibition significantly modulated key biological processes, downregulating harmful pathways including apoptosis (-8.095), fibrosis (-9.756), necrosis (-9.101), and respiratory inflammation (-2.806), while activating protective mechanisms including cell survival (14.579) and viability (14.244). Conclusions: This study establishes BAG3 as central to SSc-associated fibrosis. Significant BAG3 overexpression in SSc lung tissue provides compelling evidence for its pathogenic role. Anti-BAG3 monoclonal antibody therapeutic efficacy, coupled with comprehensive proteomic evidence showing restored protective pathways, strongly supports BAG3 as a promising therapeutic target. The dual modulation suggests multifaceted mechanisms addressing multiple SSc pathogenesis aspects. These findings identify BAG3 as both therapeutic target and biomarker for SSc-ILD treatment response monitoring, warranting investigation in larger cohorts and clinical translation studies.
CO:01:3 | Which PRO reflects remission best? Bridging the gap between patient and physician in systemic lupus erythematosus
Objective. Systemic lupus erythematosus (SLE) exerts a substantial burden on patients’ quality of life (QoL). Even if in SLE the goal is represented by the achievement of remission, in order to minimize damage accrual, many patients still report a reduced QoL. Currently the definition of remission does not include patient’s perspective. This study aims to identify which patient reported outcomes (PROs) may be the most suitable to be integrated into the definition of remission, in order to reflect the patient's viewpoint. Materials and Methods. A 10-year retrospective analysis of SLE patients was conducted. Demographics, clinical (disease duration, fibromyalgia, anxiety and depression, death), clinimetrics (SLEDAI-2k, SLICC/Damage Index (SDI), and therapeutic data were collected. The following PROs: Short Form Health Survey (SF)-36, Health Assessment Questionnaire (HAQ), The Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), Visual Analogue scale (VAS)-pain scale and VAS- global health (GH) were recorded. A heatmap based on a correlation matrix (R >=|0.6| moderate, >0.4-<0.6 acceptable) between PROs and clinimetric indices and between different PROs was built. Then we analyzed correlation between PROs and patients in remission (REM), in lupus low disease activity (LLDAS) and with active disease, also integrating PROs in the definition of clinical status of REM and LLDAS. Results. Out of 111 patients (mean age 47.3±13.7 years; disease duration 15.1±7.4 years), 6 (5.4%) were male (see Table1). FACIT-F , found <34 in 55 patients (49.5%), showed weak correlation with SLEDAI (R=-0.25; p=0.01) and SDI (R=-0.25 p=0.01);VAS-pain >=4 was found in 54 patients (48.6%) and weakly correlated with SLEDAI (R=0.21; p=0.02) (Fig. A). HAQ , altered (>=0.5) in 46 patients (41.4%), weakly correlated with SLEDAI (R=0.19; p=0.04) while VAS-GH and SF-36 did not correlate significantly with SLEDAI. FACIT-F demonstrated a moderate inverse correlation with HAQ (R=-0.60; p<0.0001), acceptable with VAS-pain (R=-0.54) and VAS-GH (R=-0.45) (p<0.0001), a substantial positive correlation with the SF-36 physical domains (R=0.70; p<0.0001) and with Mental component Summary (R=0.62; p<0.0001). None of the PROs evaluated correlated with prednisone daily dose. Adding FACIT>=34 to the definition of REM and LLDAS, both REM + FACIT>=34 group (Figures B and C) and LLDAS + FACIT-F>=34 group (Figures D and E) showed lower scores of VAS-pain, VAS-GH, HAQ (p<0.05) and higher SF-36 scores (p>0.05) than REM, LLDAS and active disease groups not including the definition of FACIT>=34. Conclusions: The weak correlation between PROs and SLEDAI or SDI highlights the limitation of relying solely on clinical indices. Nevertheless FACIT-F emerged as a suitable PRO among those tested to complement the definition of remission or LLDAS, as when added to clinical definition status it captures disease burden not reflected by traditional measures.
CO:01:4 | Identify predictors of relapse in idiopathic inflammatory myopathies: insights from an international cohort
Background. Idiopathic inflammatory myopathies (IIM) are a group of rare and heterogeneous diseases. One of the greatest challenges in IIM management is defining and predicting disease flares, which are inconsistently characterized across studies. The aim of the study was to identify predictors of relapse in a retro-prospective, multi-centric IIM cohort during the first two years of disease. Methods. Patients with IIM subsets—dermatomyositis (DM), polymyositis (PM), anti-synthetase syndrome (ASyS), connective tissue disease-associated IIM (CTD-IIM), or immune-mediated necrotizing myopathy (IMNM)—were included if >=18 yrs and with >= 2 years of follow-up. Relapse was defined as a change in disease activity requiring escalation of immunosuppressive therapy and/or steroids. Patients were classified as monocyclic (no relapse in the first 2 years), polycyclic (>=1 relapse in the first 2 years), or chronic continuous. Clinical characteristics across subgroups were compared using chi-square, Mann–Whitney U, or Student’s t-test. Predictors were identified through multivariable logistic regression. Results. Of 297 screened patients, 91 were excluded due to missing data. A total of 206 patients were included (155 female; median age at diagnosis 46.9 years). 82 (39.8%) were DM, 56 (27.2%) ASyS, 40 (19.4%) CTD-IIM, 14 (6.8%) PM, and 14 (6.8%) IMNM. During the first 2 years of disease, 84 patients (40.8%) had monocyclic course, 67 (32.5%) polycyclic course, and 55 (26.7%) chronic continuous course. No significant differences in disease course distribution were observed across IIM subsets, although PM and IMNM were more frequently associated with chronic or relapsing patterns (64.2% vs. 35.8%). Myositis autoantibodies were not significantly linked to any disease course. Relapses occurred despite stable treatment for over one year in approximately one-third of cases. Most relapses involved muscle (61.9%), particularly in PM/IMNM (89%), whereas the frequency was notably lower in ASyS (43.2%), where ILD was the leading cause of relapse (61.4%). Refractory disease was the predominant phenotype in PM/IMNM (55.6%) and ASyS (52.3%), while drug tapering was most frequent cause implicated in DM (30%) and CTD-IIM (31%). Muscle and cardiac involvement at baseline were less frequent in monocyclic patients. A more severe disease phenotype—reflected by higher levels of muscle enzymes, and both PtGA and PhGA—was more commonly associated with non-monocyclic disease. Notably, non-monocyclic patients had received baseline low-dose steroids (<0.25 mg/kg; 78.9% vs. 21.1%, p = 0.019) and intravenous immunoglobulins (10.0% vs. 26.0%, p = 0.004). Multivariable analysis confirmed baseline muscle involvement, CK levels, and PtGA as independent predictors of relapse. - Conclusions. In this large, diverse IIM cohort, non-monocyclic disease (polycyclic and chronic continuous) was associated with baseline myositis, higher serum muscle enzymes, higher global activity scores, and lower steroid induction dosage. These findings highlight the potential value of flare predictors and advocate for standardized definitions of disease activity/relapse in IIM.
CO:02:1 | Frequency and predictors of disease progression in contemporary seronegative undifferentiated arthritis in a treated-to-target early arthritis clinic
Background. With the introduction of the 2010 classification criteria for rheumatoid arthritis (RA), the characteristics of undifferentiated arthritis (UA) have shifted towards mostly seronegative, less inflammatory and persistent forms. However, as many as 10-30% of UA patients may still progress to RA or chronic RA-like arthritis. Predictors of disease progression in contemporary UA are at present unexplored. Aim of this study was to analyze the clinical characteristics and outcomes of patients presenting with UA after the introduction of the 2010 criteria. Methods: The study population was selected from a monocentric inception cohort of patients with new-onset inflammatory arthritis (symptom duration < 12 months; at least 3 swollen joints or, in case of <3 joints, a positive squeeze test or morning stiffness >30 min). After careful exclusion of differential diagnoses, patients classified as UA were followed at 3-month intervals. Treatment with conventional synthetic disease modifying anti-rheumatic drugs (csDMARDs; methotrexate -MTX- if not contraindicated) was started in case of persistent disease activity (DAS28 >3.2) and positive judgement of the treating rheumatologist. Outcomes of interest were RA development and/or escalation to a csDMARD within the first 24 months. Results: Of a total population of 1528 patients enrolled in the years 2011-2019, 431 (28.2%) were diagnosed with UA. Patients were seronegative in 95% of the cases. The vast majority (71.9%) had exclusive involvement of hand joints (wrists and/or small joints, 30% monoarticular), 20.9% had combined involvement of hand and large joints, and the remaining 7.2% had exclusive involvement of large joints (70% monoarticular). During the 24-month observation period, 45 (13.1%) of the 344 patients with complete data for at least 6 months developed RA criteria, and 84/291 additional patients among those remaining UA (28.9%) required escalation to csDMARDs (MTX in 87%). At multivariable analysis, independent predictors of RA or csDMARD start were large joint involvement, raised C-reactive protein (CRP) levels, symmetric arthritis and arthritis of >5 joints. In a classification tree analysis investigating the interrelationship of the individual variables (Figure 1), the most powerful split was involvement of large joints (57.5%), with further increased risk in case of concomitant hand joint arthritis (79.2%). Among patients with exclusive small joint involvement, CRP >0.5 mg/dl was the next split (47.5%) and, in case of normal acute phase reactants, presence of polyarthritis (38%). Conclusions: Patients with contemporary UA may exhibit chronic disease progression in more than one third of cases. A model including the pattern of joint involvement and acute phase reactants predicts disease outcomes with good accuracy.
CO:02:2 | Effectiveness of tumor necrosis factor inhibitors in rheumatoid arthritis: real world data from an Italian National Registry
Tumor necrosis factor inhibitors (TNFi) remain a cornerstone in the management of rheumatoid arthritis (RA), representing the first-line biologic therapy for most patients. This study aimed to assess the real-world effectiveness of TNFi in RA patients. To this purpose, we retrospectively analysed data from RA patients treated with TNFi and enrolled in an Italian national registry. Baseline demographic and clinical characteristics included age, sex, body mass index (BMI), tobacco use, comorbidities, rheumatoid factor and ACPA positivity, line of biologic therapy, VAS pain, patient and physician global assessment, DAS28, CDAI, SDAI, HAQ-DI, use of concomitant glucocorticoids (including dose), and csDMARD co-therapy. Changes in disease activity, quality of life, and steroid use were assessed at 12 months. Remission rates were evaluated at 3, 6, 12, 24, and 60 months. Drug survival was analyzed at 6, 12, 24, and 60 months. Discontinuations and reasons for treatment withdrawal were also recorded. Baseline demographic and clinical characteristics are summarized in Table 1. A significant reduction in disease activity (measured as DAS28, CDAI and SDAI), quality of life and proportion of patients in steroid therapy was observed at 12 months, with DAS28 remission rates of 36% at 3 months, 45%% at 6 months, 44%% at 12 months, 59% at 24 months, and 50% at 60 months. TNFi survival rates were 87.5% at 6 months, 76.8% at 12 months, 63.8% at 24 months, and 44.3% at 60 months. The overall drug survival is depicted in Figure 1A. A significant reduction in treatment survival was observed when TNFi were prescribed at third or further therapeutic line (Figure 1B), while co-therapy with csDMARDs had no influence on survival on treatment (Figure 1C). A total of 942 treatment discontinuations were recorded during follow-up. The main reason for treatment discontinuation was represented by loss of efficacy (30.5% of patients), while adverse events led to suspension in 11.6% of cases. In summary, in this real-world Italian cohort, TNFi therapy was associated with a sustained reduction in disease activity, increasing remission rates over time, and good long-term treatment persistence up to 5 years.
CO:02:4 | Whole blood hypercoagulable profiles in patients with rheumatoid arthritis
Background: Rheumatoid arthritis (RA)-associated disease activity is accompanied by abnormalities in the coagulation-fibrinolysis system, potentially increasing the risk of venous and arterial thromboembolism. The aim of this case-control study was to evaluate the hemostatic system functions in a group of RA patients by whole blood rotation thromboelastometry and impedance aggregometry. Methods: Whole blood rotation thromboelastometry and impedance aggregometry were performed in RA patients (cases) treated with biological and targeted synthetic disease-modifying anti-rheumatic drugs (b/tsDMARDs) and compared 1:1 with age (± 3 yrs) and sex-matched healthy individuals (controls). In each enrolled participant, global coagulation monitoring was assessed by whole blood rotational thromboelastometry (ROTEM®, Instrumentation Laboratory-Werfen) and whole blood impedance aggregometry (Multiplate® Analyser, Roche Diagnostics) tests. Variables assessing disease activity, demographics and cardiovascular risk were assessed. Univariate analyses (independent T-test, Pearson correlation) were performed. Results: The study population included 30 RA patients on b/tsDMARDs and 30 controls. The cases (mean age 56.2±11.6 years, 90% female) had a mean disease duration of 17.8±9.1 years; most received methotrexate (60%) and low-dose prednisone (1.2±2.1 mg/day); NSAIDs were used by 47%. No participants were taking antiplatelet or anticoagulant medications. Disease activity and inflammatory markers were generally low (SDAI: 10.1±8, CRP 3.5±4.3 mg/L, ESR 23±18.5 mm/h). A history of VTE was reported in 7% of patients, while no previous MACE events were documented. Regarding cardiovascular risk factors: 10% were current smokers, 53% had hypercholesterolaemia, 27% had hypertension and only one patient had diabetes mellitus. Thromboelastometry and aggregometry showed excellent internal validity, as several measurements significantly and strongly correlated with inflammatory markers, disease activity, and lipids (Figure 1). In INTEM, EXTEM and FIBTEM tests, maximum clot firmness (MCF) was significantly increased in RA patients compared with controls (p<0.001 in all three comparisons) (Table 1). A significant difference in platelet aggregation was found between RA patients and healthy controls in each of the tests considered (Table 1). Patients taking glucocorticoids at the time of blood sampling had MCF in INTEM and EXTEM significantly higher than those patients who were not (p=0.011 and p=0.020, respectively; Table 2). Thrombin receptor activating peptide (TRAP)-induced platelet aggregation was significantly higher in patients taking oral glucocorticoids than in those who were not (p=0.0006; Table 2). Use of NSAIDs did not affect outcomes. Analysis of data stratified by type of drug used is still in progress. Conclusions: Hypercoagulability can be detected by whole blood thromboelastometry and impedance aggregometry in RA patients and correlates with disease activity. The clinical implication of these findings deserves further investigations.
CO:03:1 | Distinct breath metabolomic signature in systemic sclerosis patients with pulmonary arterial hypertension
Background/Purpose: Pulmonary arterial hypertension (PAH) is a severe complication of systemic sclerosis (SSc), associated with high morbidity and mortality. Accurate and early diagnosis of SSc-PAH is essential to initiate targeted therapies that may improve outcomes by counteracting key pathophysiological mechanisms. Breathomics, the analysis of volatile organic compounds (VOCs) in exhaled breath, has emerged as a promising non-invasive tool, as VOCs reflect underlying metabolic and pathological processes. This study investigates the potential of breathomics in SSc-PAH, both for disease understanding and diagnosis. Methods: 14 SSc patients with a diagnosis of PAH confirmed by right heart catheterization, 28 age- and sex-matched SSc patients without PAH, and 36 matched healthy controls (HCs) were enrolled in a single-center, case-control observational study. Exhaled breath VOCs were collected using the ReCIVA® breath sampler connected to a clean air supply (CASPER®). Samples were trapped on sorbent tubes and analyzed by thermal desorption gas chromatography–mass spectrometry (TD-GC-MS) at Owlstone Medical. VOCs were chemically identified according to Metabolomics Standards Initiative (MSI) criteria, and blank air samples were analyzed to distinguish true breath compounds from environmental contaminants. Data were analyzed using linear regression, adjusting for relevant covariates and excluding outliers. Results: all SSc participants were female and predominantly affected by lcSSc (n = 23, 63.4%) and mostly tested positive for ACA (n = 40, 85%). The mean age was 68 ± 9 years, with no differences between the SSc-PAH and SSc-noPAH groups. A total of 1.382 VOCs were analyzed; of these, 186 were confirmed to be genuinely present “on breath” and annotated with high confidence (MSI tier 1 or 2). Among these, 55 VOCs significantly differentiated SSc-PAH from SSc-noPAH, and 40 differentiated SSc-PAH from healthy controls. Notably, 32 VOCs distinguished SSc-PAH from both comparator groups (p < 0.05 and |fold change| > 1.5) (Figure 1). Findings of interest included: a reduction in terpenes in SSc-PAH, potentially reflecting impaired vasodilatory capacity (Figure 2); a decrease in sulfur-containing compounds, suggestive of reduced control over vasoconstriction; a reduction end-products (i.e. 1-pentene) of allyl organosulfur derivates with anti-inflammatory properties; an increase in pyrazines, possibly indicative of enhanced gut permeability; and elevated levels of the uremic toxin m-cresol, which has been associated with endothelial dysfunction. Conclusions: breathomics revealed a distinct metabolic signature in SSc-PAH, distinguishing it from both SSc without PAH and healthy controls. The identified VOCs not only hold promise as non-invasive biomarkers for early diagnosis but also shed light on key pathogenic mechanisms of PAH, including impaired vasoregulation, increased gut permeability, and endothelial dysfunction. These findings support the role of breath analysis as a valuable tool for both clinical and mechanistic insights in SSc-PAH.
CO:04:1 | Bone properties and biomechanics in patients with psoriatic disease: a cross-sectional study with high-resolution peripheral quantitative computed tomography
Background. Psoriatic disease has a complex effect on bone metabolism, resulting in both pathological bone formation and bone resorption. However, microstructural changes in cortical and trabecular compartment remain poorly understood. The aim of this study was to investigate the prevalence and determinants of bone microarchitectural damage in patients with psoriatic disease. Methods. We performed a cross-sectional study on patients with Psoriasis (PsO), Psoriatic arthritis (PsA) and age-matched healthy controls (HC) recruited into the department of Dermatology and Rheumatology of AOUI of Verona center. We conducted High-Resolution peripheral Quantitative Computed Tomography (HRpQCT) of the radius and finger joints of the non-dominant hand data. Bone microstructure parameters and Finite Element Analysis (FEA) were calculated. Results. Fifty-one patients with PsO and thirty-nine patients with PsA were consecutively enrolled in the study. Twenty-four age-matched HC were enrolled as well. Distal radius Bone Mineral Density (BMD) levels were lower in patients with PsA e PsO compared with HC. On distal radius FEA analysis we found a significant reduction of stiffness in PsA compared to both HC and PsO patients. Proximal and distal region of distal interphalangeal (DIP) BMD were lower in PsO compared to PsA. In contrast, PsA patients had lower stiffness and cortical thickness compared to PsO. Nail involvement in psoriatic disease was negatively associated with bone stiffness at the proximal and distal region of DIP. Conclusions. Psoriatic disease negatively impacts bone integrity, particularly in PsA patients. Patients with psoriatic disease seemed to have lower bone density and more microarchitectural alteration. Nail involvement was associated with decreased bone stiffness in psoriatic disease.
CO:05:1 | Predicting one-year disease activity in systemic lupus erythematosus using machine learning and explainable AI
Background: Systemic lupus erythematosus (SLE) is a chronic, multisystem autoimmune disease characterized by marked heterogeneity in clinical presentation, disease course, and response to therapy. This variability makes it particularly challenging to predict disease flare-ups in clinical practice, despite their profound implications on prognosis and quality of life. Objectives: This study aimed to develop a machine learning model to predict the risk of disease activity events in SLE patients within a 12-month time frame, based on clinical status, recent history, and long-term disease trajectory. Methods: We built a structured dataset (SLE Data Mart) from electronic health records using data mining and NLP techniques. It includes demographic, therapeutic, clinical, and laboratory information from SLE patients seen at our University Hospital. Patients had at least one outpatient visit and one hospitalization coded as ICD9 710.0 or 695.4. The outcome—an activity event within 12 months—was defined as any of the following: neurological, renal, or vascular symptoms; new organ domain involvement; or hospitalization for SLE. Input features described current contact, past 12 months, and prior clinical history, expressed as binary or continuous variables. Univariable selection (Chi-Square, Mann-Whitney U tests) identified features significantly associated with the outcome (p < 0.05). Selected variables were used to train multiple models (Logistic Regression, SVC, Decision Tree, Random Forest, XGBoost), evaluated by 5-fold cross-validation. The model with the highest AUC was selected and interpreted using SHAP to identify key predictors. Results: The dataset included 262 SLE patients and 5,952 contacts between 2012–2020. Most patients were female (88%), with a median age of 43 years and median follow-up of 6 years. Patients had a median of 16 contacts each. The cohort was split into training (70%) and testing (30%) sets. Overall, 48% of contacts were associated with an activity event. Univariable selection retained 125 of 192 variables (Table 1). Significant predictors included younger age at contact (median 44 years, p < 0.0001) and abnormal labs (e.g., proteinuria, albuminuria). The best-performing model (AUC = 0.70) identified renal involvement—especially proteinuria >=0.5 g/24h and albuminuria—as the most impactful predictors. SHAP analysis also highlighted the protective role of therapy step-down and of the current hematological or cutaneous involvement (Figure 1). Conclusion: Renal abnormalities strongly predict future SLE activity, but other factors, including hematological and cutaneous involvement, prior therapy changes, and overall disease history, significantly contribute to to determine the risk for an activity event at 12 months. Acknowledgements. This study was conducted with the unrestricted support of AstraZeneca.
CO:05:2 | An OMERACT study for the development of an algorithm for automatic identification of calcium pyrophosphate deposition by ultrasound: the Crystal Artificial Intelligence Monitoring Study
Background. Calcium pyrophosphate deposition (CPPD) is one of the most frequent causes of chronic arthropathy in individuals over 60. Ultrasound (US) has recently become central in the diagnostic process, with the OMERACT group defining elementary US lesions and a standardized scoring system. Despite its increasing use, US remains operator-dependent and requires specialized expertise to reduce diagnostic variability. This study aims to develop an Artificial Intelligence (AI) tool capable of automatically identifying and grading CPPD in knee menisci using US images. Materials and Methods. This project is part of an international initiative to develop AI algorithms for detecting and scoring elementary US lesions in CPPD and gout. Nineteen rheumatologists from ten countries contributed a total of 446 high-quality US images of CPPD in the knee menisci, previously classified by expert consensus into four grades (0 to 3). Each image was manually annotated to isolate the meniscal region using 3DSlicer software. A deep learning approach based on transfer learning was employed, utilizing convolutional neural networks (CNNs) pretrained on the ImageNet dataset. The models were fine-tuned on the collected dataset and trained using standard techniques including early stopping, data augmentation (rotation, shift, zoom, flipping), and class weighting to handle data imbalance. The dataset was split into training (80%) and validation (20%) subsets while preserving grade distribution. Model performance was evaluated using standard classification metrics: accuracy, precision, recall, and F1-score. All processes were implemented using Python, OpenCV, and TensorFlow-Keras frameworks. Results. The image dataset showed an unbalanced distribution: 9% grade 0, 18% grade 1, 48% grade 2, and 25% grade 3. The highest accuracy obtained for binary classification (CPPD presence vs. absence) was 0.69. The model showed acceptable performance in identifying grades 0, 2, and 3, while classification of grade 1 was less reliable. Precision and recall values were generally consistent across the grades, with the exception of grade 1, which showed lower precision. These results reflect both the potential and the limitations of the current model in handling the CPPD grading task with a relatively small and imbalanced dataset. Conclusions. Although the model demonstrates initial potential, its current performance is below the threshold required for clinical application. The limited dataset size and imbalance across grades likely constrained the deep learning model’s accuracy. Future development will focus on expanding the dataset, achieving better grade distribution, applying cross-validation techniques, and exploring advanced approaches such as semantic segmentation. These steps are essential to improve model reliability and enable its use in real-world diagnostic workflows (see Table below)..
CO:05:3 | Radiomics and machine learning for differentiating rheumatoid arthritis-associated interstitial lung disease and idiopathic pulmonary fibrosis with usual interstitial pneumonia pattern
Background. While Idiopathic Pulmonary Fibrosis (IPF) and Rheumatoid Arthritis-associated Interstitial Lung Disease (RA-ILD) can manifest identical Usual Interstitial Pneumonia (UIP) patterns on HRCT, their underlying histopathology reveals fundamentally different disease processes—IPF driven by aberrant fibroblast proliferation and excessive collagen deposition versus RA-ILD's autoimmune-mediated inflammation. This pathological divergence translates to dramatically different prognoses and treatment responses, yet current imaging interpretation cannot reliably capture these microscopic differences. Radiomics offers a revolutionary approach: extracting hundreds of quantitative features that may encode histopathological signatures within standard HRCT images. Combined with machine learning, this technology might unveil tissue-level distinctions invisible to visual analysis, potentially transforming a diagnostic challenge into a data-driven classification. Our aim was to develop a radiomic-based framework for distinguishing IPF from RA-ILD in UIP-pattern patients. Methods. We conducted a retrospective analysis of patients with confirmed UIP pattern diagnosed in tertiary centres. Whole-lung volumes were semi-automatically segmented using 3DSlicer (v5.4.0, https://tinyurl.com/mr339kmm). 120 radiomic features were extracted via PyRadiomics (v3.0.1). Features underwent z-score standardization and multicollinearity assessment Two distinct XGBoost models were developed to address different clinical scenarios: Standard Model: Leveraged all radiomic features to maximize discriminative performance. - Extent-Aware Model: Excluded volume-related features and incorporated mesh volume as a covariate to control for disease severity, ensuring classification based on intrinsic tissue characteristics rather than disease burden. Model performance was evaluated using 5-fold cross-validation with area under the receiver operating characteristic curve (AUC) as the primary metric. Results. The study included 72 patients: 42 with IPF (male 73.8%, median age 78, IQR 8) and 30 with RA-ILD (female, 63.3%, median age 72. IQR 12.5). Standard Model achieved near-perfect discrimination (AUC 0.99±0.01), driven by first-order intensity features: Image-original_Mean (overall lung density); Image-original_Maximum/Minimum (attenuation extremes); Extent-Aware Model maintained robust performance (AUC 0.77±0.09) using texture-based features: original_glcm_Id (texture homogeneity); original_firstorder_10Percentile (lower intensity distribution); original_glszm_ZonePercentage (homogeneous zone proportion) IPF median survival 5.5 months versus 29.5 months for RA-ILD. Conclusions. Radiomics with machine learning demonstrates exceptional potential for differentiating IPF from RA-ILD in UIP-pattern patients. The near-perfect accuracy suggests quantitative biomarkers capture disease-specific signatures beyond visual assessment. Crucially, the extent-aware model's success indicates fundamental tissue architecture differences between conditions, independent of disease severity. Implementing radiomic analysis could enable earlier diagnosis and timely disease-specific therapy.
CO:06:1 | Predictors of damage accrual in a monocentric cohort of patients with Behçet’s syndrome (BS) evaluated with BS overall damage index in real-life clinical practice
Objectives. Behçet’s syndrome (BS) is a rare chronic multisystemic inflammatory disease associated with increased risk of morbidity, disability and mortality. Consistent assessment of damage and prevention of damage accrual is therefore crucial in daily clinical practice. This study aims to assess damage progression in our cohort of patients with BS using Behçet’s Syndrome Overall Damage Index (BODI), to evaluate BODI across time and the associations of BODI score with demographic and clinical features to identify potential independent predictors of damage accrual. Methods. We conducted a retrospective observational monocentric study including patients with BS. BODI scores (range: 0-46; higher scores indicate greater damage) were calculated at T0 (diagnosis/first visit) and T1(last follow-up). Demographic, clinical features and treatments were retrieved. Patients were stratified according to BODI scores and comparisons were made using Mann-Whitney test or Chi-square test. Logistic regression models were used to identify potential independent predictors of damage accrual (BODI>=1) at T0 and T1, including BODI score variations (deltaBODI) between T0 and T1. Results. We included 155 patients (56.8% females), median age at diagnosis 36 years [IQR 26-44], median disease duration at last follow-up 9 years [IQR 5-13], and median diagnostic delay 2 years [IQR 0-6]. Most were Italians (80%) and 63.8% (81/127) had HLA-B*51. Among clinical cumulative manifestations the most frequent were oral ulcers (96.8%), skin lesions (66.5%), musculoskeletal manifestations (55.5%) and genital ulcers (54.8%), while ocular, neurological, vascular, gastrointestinal and cardiopulmonary involvement occurred in 40%, 21.9%, 21.9%, 17.4%, and 11% respectively. Median BODI at T0, T1 and deltaBODI were 0 [IQR 0-1; min 0, max 7], 0 [IQR 0-2; min 0, max 17], 0 [IQR 0-1; min 0, max 17] respectively; 27.6% (42/152) of patients had deltaBODI>=1. Patients with BODI>=1 at T0 or T1 as compared to those with BODI=0 were older at diagnosis, had a higher frequency of neurological, vascular and cardiopulmonary manifestations, and received more often glucocorticoids and cs-DMARDs (Table 1). Patients with deltaBODI>=1 compared to those with deltaBODI=0 were older at diagnosis and had a higher frequency of ocular, neurological and vascular manifestations (Table 1). On multivariate analysis, older age was the only independent predictor of damage accrual at T0 and T1 and over time (deltaBODI>=1), while male sex was an independent risk factor for BODI>=1 at T1 (Table 2). The effects of the interactions of different variables on the risk of damage accrual are also reported in Table 2. Conclusions. In our cohort of BS patients older age at diagnosis and male sex were identified as predictors of damage accrual. These findings emphasize the need for early and ongoing damage assessment, guiding tailored therapeutic strategies to prevent long-term complications. Future perspectives include evaluation of BODI trends at defined intervals and their relationship with treatment regimens.
CO:06:2 | Deep immunophenotyping in patients with juvenile localized scleroderma reveals two distinct immunological endophenotypes
Background. The aim of this project is to perform immunophenotyping of patients with JLS and healthy controls to assess dysregulated immunological pathways in JLS, and to identify biomarkers able to predict clinical features. Methods. We included in this study pediatric patients diagnosed with linear and mixed JLS. Peripheral blood mononuclear cells (PBMCs) and plasma samples at diagnosis or treatment escalation were identified retrospectively and retrieved from our biobank. We included only patients whose first available blood sample was obtained at time of diagnosis and before the initiation of any treatment. Levels of 50 cytokines were measured in the plasma by protein array (RayBiotech). Lymphocyte and monocyte subsets were analysed with a 26-colour flow cytometry panel and acquired on a FACSymphony (BD). Results. We identified samples at baseline from 11 patients with JLS and 10 controls. Cytokine array identified 15 cytokines that were significantly elevated in JLS patients compared to controls. Using Principal Component Analysis (PCA), we observed a distinct distribution between patients and controls, with approximately 50% of patients clustering away from controls, and the remaining 50% aligning closely with them (Figure 1A). Patients clustering near controls exhibited the lowest cytokine levels and were designated as non-inflammatory JLS (no_inf JLS), whereas those clustering away had the highest cytokine levels and were classified as inflammatory JLS (inf_JLS) (Figure 1A). We then validated the results of the cytokine array in ELISA: CXCL9, CXCL10, and CXCL13 were consistently elevated in all patients with inf_JLS, at baseline and during longitudinal follow-up, while cytokine levels in patients with no_inf JLS remained within normal ranges (Figure 1B). We then performed a 26-parameter staining of PBMCs, allowing comprehensive evaluation of major lymphocytes and monocytes subsets by flow cytometry. Our analysis identified 81 subpopulations of interest; a PCA analysis highlighted significant differences in the distribution of lympho-monocytic subsets between JLS patients and controls (Figure 1C). Within lymphocyte subsets, significant differences were observed in the frequency of activated CD4+ T cells, predominantly within the central memory (CM) subset. Patients stratified into inf_JLS and no_inf JLS groups based on cytokine levels showed minimal differences in cellular subpopulations upon PCA. However, two subpopulations demonstrated significant variability: activated CD4+ T cells (CD38+ HLA-DR+) and terminally differentiated effector memory CD4+ T cells (TEMRA) expressing PD1, were significantly expanded in patients with inf_JLS (Figure 1D). Conclusions. This study identified two distinct groups of patients with JLS: a non-inflammatory group, characterized by normal levels of circulating proinflammatory cytokines, and an inflammatory group, marked by elevated levels of circulating cytokines. Our data showed a higher frequency of activated CD4+ T cells, suggesting a central role of activated T cells in JLS pathogenesis, particularly in patients within the inflammatory group.
CO:06:3 | Clinical and laboratory markers for distinguishing VEXAS from Schnitzler's syndrome in male patients with skin involvement: insights from the International AIDA Network Registries
Background: VEXAS syndrome and Schnitzler’s disease are rare adult-onset autoinflammatory conditions that often present with overlapping clinical and laboratory features, particularly in the early stages. Both disorders are characterized by systemic inflammation, recurrent fever, cutaneous involvement, and elevated inflammatory markers. A common hallmark is the presence of urticarial rash, frequently associated with monoclonal gammopathy of undetermined significance (MGUS). Given these similarities—especially in older male patients—differential diagnosis may be particularly challenging, underscoring the need for specific clinical and laboratory markers to guide classification and management. As prognosis differs between the two entities, the present study was undertaken to identify the clinical and laboratory parameters that should raise suspicion for VEXAS syndrome among patients under evaluation for Schnitzler’s disease. Methods: Data from patients with Schnitzler’s syndrome and VEXAS syndrome were obtained from the respective international AutoInflammatory Disease Alliance (AIDA) Network registries. Inclusion criteria for patients affected by VEXAS syndrome required the presence of a pathogenic or likely pathogenic mutation in the UBA1 gene. For patients with Schnitzler’s syndrome, the inclusion criteria required the fulfillment of Strasbourg diagnostic criteria. Male patients diagnosed with Schnitzler’s syndrome were compared to VEXAS patients who presented with urticarial skin manifestations. Clinical and laboratory features were analyzed using univariate and multivariable logistic regression models to identify variables associated with VEXAS syndrome. Results. A total of 19 VEXAS patients and 18 patients with Schnitzler’s syndrome were enrolled. At univariate binary logistic regression, the diagnosis of VEXAS syndrome was associated with the age at disease onset (OR=1.08, 95% CI. 1.01-1.16, p=0.02), haemoglobin levels (OR=0.44, 95% CI. 0.26-0.77, p=0.003), the presence of anaemia (OR=13.9, 95% CI. 3.4-5.7, p=0.02), leucocytosis (OR=0.04, 95% CI. 0.06-0.22, p<0.001), lymphadenopathy (OR=7.8, 95% CI. 1.41-45.4, p=0.02), and thrombocytopenia (OR=13.5, 95% CI. 1.47-123.7, p=0.02). In the multivariable logistic regression analysis with the stepwise forward selection approach, the diagnosis of VEXAS syndrome was significantly associated with the age at disease onset (OR: 1.13, 95% CI: 1.02–1.30, p=0.04)), the presence of lymphadenopathy (OR: 67.49, 95% CI: 5.36–3284.89, p=0.007), and thrombocytopenia (OR: 12.02, 95% CI: 1.07–315.86, p=0.06). Figure 1 shows the probability of a VEXAS diagnosis based on age at disease onset, in the presence or absence of the other two variables. Conclusions: The study provides a comparative framework that highlights specific clinical, and laboratory features distinguishing VEXAS syndrome from Schnitzler’s syndrome in male patients with cutaneous involvement. Specifically, patients with lymphadenopathy, thrombocytopenia, anemia, particularly in older age, and in the absence of leucocytosis, are more likely to be affected by VEXAS syndrome.
PO:01:003 | Sex-based differences in 2 years treatment outcomes with b/ts-DMARDs in psoriatic arthritis: from real-world evidence to predictive modeling from the Gruppo Italiano Studio Early Arthritis (GISEA) prospective registry
Background. Psoriatic arthritis (PsA) presents several evidence of sex-related disparities, highlighting critical gaps in our understanding and management of PsA. This study aimed to evaluate b/ts-DMARDs effectiveness, drug survival and clinical response predictors in PsA patients, related to biological sex. Patients and Methods. PsA patients starting a b-/ts-DMARDs between January 2016 and December 2023 were included in this multicentre real-world observational study based on the Italian GISEA prospective registry. Demographic, laboratory and clinical data were collected at baseline and at four-months interval thereafter.Logistic regression was used to investigate the association between selected variables and MDA achievement at T4, reporting as adjusted odds ratio (adjOR) with 95% confidence interval (CI), adjusting for age, BMI, csDMARDs and steroid user and baseline DAPSA score. Results. A total of 4197 PsA patients were enrolled, comprising 1714 males (mPsA) and 2483 females (fPsA). Comparing to fPsA patients, mPsA were characterized by a higher BMI (p=0.01), longer disease duration (p=0.0001) and more frequent psoriasis (p<0.0001).Moreover, mPsA compared to fPsA exhibited a higher prevalence of the oligoarticular pattern (p=0.003), higher CRP levels (p<0.0001), and more presence of erosion (p=0.045), but lower DAPSA score (p<0.0001). Significant differences in clinical improvement were observed at each time point between mPsA and fPsA in terms of DAPSA remission and MDA achievement. Furthermore, female gender had a negative impact on retention rates of b/ts-DMARD therapy only at first- or second-line compared to male gender (p<0.0001 and p=0.023, respectively). PsA patients who achieved MDA at T4 were more likely to be male (p<0.0001), have an oligoarticular pattern (p<0.0001), lack enthesitis involvement (p<0.0001), be free of fibromyalgia comorbidity (p<0.0001) and be b-/ts-DMARDs naïve (p=0.001). Based on these findings, the five features were considered in a predictive model of MDA achievement at T4 with adjOR 9.826 (95% CI 3.215-30.035). Finally, fPsA with fibromyalgia (fibro/fPsA; n: 363) compared to fPsA without fibromyalgia (not-fibro/fPsA; n: 1132) were characterized by lower psoriasis involvement (p=0.015), associated to lower PASI (p=0.005), higher enthesitis involvement (p<0.0001), associated to higher LEI (p<0.0001), higher axial involvement (p<0.0001) and higher DAPSA (p=0.001). Furthermore, not-fibro/fPsA patients demonstrated significantly better clinical response compared to fibro/fPsA in terms of DAPSA remission and MDA achievement. Conclusions. This large, multicentre real-world observational study reveals striking significant sex-related differences in clinical features, disease activity and treatment response among PsA treated patients. Notably, mPsA patients demonstrated better outcomes at every time points of follow-up compared to fPsA. The study also identified key predictive factors, including biological sex, for early MDA achievement, highlighting the importance of integrating sex-specific approaches into PsA management.
PO:01:004 | Real-world retention of IL-17 inhibitors in psoriatic arthritis: impact of prior IL-17 exposure across multiple treatment lines in the “BIRRA” multicentre cohort
Background. Several studies have explored cycling versus switching strategies in psoriatic arthritis (PsA) when TNF inhibitors are used as biological DMARD (bDMARD). Conversely, real-world evidence regarding cycling strategies within other bDMARD classes is lacking. In this study, we aimed to evaluate the retention rate of interleukin-17 inhibitors (anti-IL17) in patients with PsA, focusing on the differences between those receiving their first anti-IL17 agent and those previously exposed to anti-IL17 therapy. Methods. This was a multicentre, retrospective, observational study. All consecutive patients with PsA treated with an anti-IL17 bDMARD were included. The baseline assessment encompassed demographic and clinical characteristics, including disease domains and activity scores, IL-17 exposure status, number of prior bDMARD lines, and concomitant therapies. The primary outcomes were: a. the retention rate of anti-IL17 agents in IL-17 naïve versus IL-17 experienced patients; b. predictors of treatment discontinuation. Results. A total of 868 patients were included (59.3% female; median age 56 [48-63] years). The majority were receiving their first anti-IL17 agent (89.3% IL17 naïve vs 10.7% IL17 experienced). Secukinumab was the most frequently prescribed bDMARD (70.8%), followed by ixekizumab (28.6%), and bimekizumab (0.6%) (Figure 1.A.). At baseline, IL17 experienced patients more commonly exhibited axial involvement compared to IL17 naïve patients (59.1% vs 35.4%) and had received a higher median number of previous bDMARDs (4 [3-5] vs 2 [1-3] lines, respectively). Secukinumab was more frequently prescribed in IL17 naïve patients (76.9% vs 20.4%), whereas ixekizumab was preferentially used in IL17 experienced individuals (Figure 1.A.). Median follow-up for the overall cohort was 15.2 [7.0-33.8] months, for a total exposure of 20’014 patient-months. At 12 months, the estimated retention rate was 77.6% vs 77.0% in naïve vs experienced patients respectively, dropping at 61.7% vs 54.0% at 24 months. Although Kaplan–Meier curves suggested a numerically lower persistence among IL17 experienced cases, this difference did not reach statistical significance (log-rank p = 0.068) (Figure 1.B.). In multivariable Cox regression analysis, male gender, a lower number of prior bDMARDs, and treatment with Secukinumab were associated with higher odds of drug survival, whereas axial involvement increased the risk of discontinuation. Prior IL17 exposure was associated with a non-significant trend towards a lower risk of discontinuation (Figure 1.C.). Conclusions. Our findings suggest that, in the real-world PsA clinical practice, prior exposure to an IL17 inhibitor may not compromise the retention of a subsequent agent from the same class. Conversely, drug survival was influenced by gender, axial involvement, the specific bDMARD prescribed, and the cumulative number of prior bDMARDs. Recycling within the IL17 inhibitor class may represent an effective strategy. Nevertheless, further studies are warranted to better define the clinical contexts in which this approach could be most appropriate.
PO:01:005 | Exploring the relationship between alexithymia, pain perception, and disease burden in a cohort of patients with psoriatic arthritis
Background. Psoriatic arthritis (PsA) is a chronic inflammatory disease that affects joints and periarticular structures. It is well established that PsA exerts a significant negative impact on quality of life of affected individuals, inducing functional impairment and related disability. Joint pain and stiffness may be misinterpreted or exaggerated by PsA patients, ultimately leading to unsuccessful chances of remission. We aimed to evaluate the potential impact of alexithymia and pain catastrophizing on clinical features, disease activity and comorbidities in PsA. Methods. A total of 166 PsA patients, fulfilling the 2006 CASPAR criteria, were enrolled. Time frame spanned from January to December 2024. The 20-item Toronto Alexithymia Scale (TAS-20) questionnaire along with Pain catastrophizing scale (PCS) were administered to all recruited patients. Clinical and demographic characteristics, along with disease activity measures, inflammatory indices and concomitant presence of fibromyalgia were recorded. Quality of life was assessed via the SF-36 questionnaire. Statistical analysis employed chi-square and T student tests, as well as Rho Spearman for correlation analysis. A statistical p<0.05 was considered significant. Results. We divided patients into remission-LDA (DAPSA<14) and MoDA-HDA (DAPSA>14) and compared the two groups. Significant differences were noted among groups regarding diagnostic delay (31.7±41 vs 61.8±64.5 months, p<0.001) and comorbidities burden (e.g. dyslipidaemia 32 vs 33±50, p 0.020; osteoporosis 13 vs 18±27.3, p 0.021; anxiety/depression 6 vs 13±19.7, p 0.007). As expected MoDA-HDA group exhibited a greater prevalence of bDMARDs changes and more csDMARDs and NSAID/COXIB usage. We also found a significant difference between the two groups in the clinical domains, like enthesitis (n 55 vs 53±80.3, p <0.001) and dactylitis (18 vs 23±34.8, p 0.014) (Table 1). Other significant differences were found in laboratory indices (e.g. CRP (mg/dl) 0.6±0.8 vs 1.8±2.7, p <0.001), TAS total score (42.5±16.9 vs 62.7±16.7, p <0.001), Beck’s Depression Inventory (6.7±3.1 vs 12.9±9.2 vs, p <0.001), and for all items of the Short Form Health Survey 36 (SF-36) (Table 2). Within the Rho correlation analysis, strong correlations emerged in the TAS total score (Pain Catastrophizing Scale Total: Rho 0.7439; PCS rumination: Rho 0.663; PCS magnification: Rho 0.712; PCS helplessness: Rho 0.666; WPI+SSS: Rho 0.698; WPI: Rho 0.630) (Table 3). Conclusions. This study suggests that disease activity is related to a higher disease burden including indirect index of mood disorders. The assessment of alexithymia should be an integral part of the comprehensive management of PsA patients and it might have an impact on disease activity score evaluation. Being aware of these hurdles could guide the clinician in the correct diagnostic-therapeutic framework.
PO:01:015 | Assessment of the impact of the co-occurrence of psoriasis on the clinical and therapeutic pattern of a single-centre cohort of patients with spondyloarthritis associated with chronic inflammatory bowel disease
Background. To assess the influence of the co-presence of psoriasis (PsO) on the clinical and therapeutic pattern of a single-centre cohort of patients with spondyloarthritis (SpA) associated with chronic inflammatory bowel disease (IBD). Methods. This study represents a preliminary phase of an ancillary analysis of the DIAMANTE project (Early diagnosis of spondyloarthritis in a cohort of patients with chronic inflammatory bowel disease), developed with the overall objective of determining the prevalence, predictors and outcomes of SpA in a cohort of subjects with IBD, in the context of close and structured collaboration between gastroenterologists and rheumatologists. Within the DIAMANTE cohort, two subgroups of patients were identified for the study: patients with SpA and a concomitant personal diagnosis of PsO (Group 1: IBD+SpA+PsO) and patients with a diagnosis of SpA alone (Group 0: IBD+SpA). For both groups, the following demographic, clinical and therapeutic data were recorded and compared: gender, association between IBD patterns, peripheral joint involvement, axial involvement, history of dactylitis, need for biological therapy, multi-resistance to targeted drugs (discontinuation due to ineffectiveness of at least two small molecule biological drugs). A significance threshold of p<0.05 was used with Fisher's and X² tests. Results. Data from 665 consecutive patients with IBD recruited from November 2023 to April 2025 were analysed. Within this cohort, 95 (14%) had a concomitant diagnosis of SpA; among these, 21 (22%) also had a diagnosis of PsO (IBD+SpA+PsO group), while 74 (78%) had only SpA associated with IBD (IBD+SpA group). Comparative analysis of the two groups revealed significant, albeit only trending towards statistical significance, differences in terms of female prevalence (71% vs 54%, p=0.15), frequency of peripheral involvement (62% vs 49%, p=0.28) and use of biologic drugs (91% vs 77%; p=0.17). Most notably, a significantly higher frequency of multidrug resistance to biological drug treatment was observed in patients with concomitant PsA compared to patients with IBD and SpA alone (29% vs 11% p=0.04). No significant differences were observed in terms of destruction of the different IBD conditions (ulcerative colitis, Crohn's disease, undifferentiated forms) between the two study groups. Conclusions. In patients with SpA associated with IBD, the simultaneous association with PsO, another extra-articular domain typical of the spectrum of spondyloarthropathies, was also frequently demonstrated. The results of this exploratory analysis suggest that it would be useful to investigate, in larger prospective case series, the impact that this dual combination of extra-articular manifestations may have on disease characteristics and, in particular, on treatment management.
PO:01:006 | Increased risk of cancer recurrence or mortality associated with DMARDs?
Background. Our study endeavoured to investigate the real-life use of immunosuppressants after cancer diagnosis in patients with spondyloarthritis (SpA) and rheumatoid arthritis (RA) and the associated risk of cancer recurrence or mortality. Methods. We retrospectively enrolled all patients with invasive cancer and SpA, psoriatic arthritis (PsA) or RA referred to two Italian centres between 2015 and 2024. Invasive cancer was defined as any solid or haematologic cancer with histological characteristics of invasiveness. Cancer recurrence or progression were recorded consulting oncologic reports. After correction for the immortal bias, we performed a survival analysis using a model with cumulative incidence for competing events and subdistribution hazard ratios (SHR) estimates. Results. Overall, we included 120 patients with SpA/RA (39 SpA, 37 PsA, 44 RA) who developed invasive cancer. Most patients were undergoing csDMARDs and bDMARDs treatment before cancer diagnosis, or initiated immunosuppressants (including TNF, IL-6, IL-17, IL-23, JAK inhibitors and CTLA4a) after cancer diagnosis. 24 (20%) patients experienced a cancer relapse or progression, of whom 7 subsequently died. 2 other patients died of other causes during follow-up. Treatment with bDMARDs/JAKi before and after cancer did not appear to significantly increase the risk of recurrence and/or death (SHR p-value = 0.26; SHR p-value= 0.78), after correction for treatment before cancer diagnosis. RA was significantly associated with a higher risk of recurrence (SHR p-value <0.05). Early introduction of bDMARDs, particularly in RA, increased the risk of recurrence/death (HR p-value <0.05). Conclusion. The management of patients with SpA and RA who develop cancer may require initiation of immunosuppressants before the 5-year safety cutoff in the most severe cases. Among biologics, IL6i, IL17i and IL23i have proven to be the safest classes for use in patients with rheumatic diseases who develop cancer (1,2). 1. Atzeni F, Carletto A, Foti R, et al. Incidence of cancer in patients with spondyloarthritis treated with anti-TNF drugs. Joint Bone Spine. 2018;85(4):455-459. doi:10.1016/j.jbspin.2017.08.003 2. Scagnellato L, Collesei A, Doria A, et al. Comorbidities in the Spondyloarthritis GISEA Cohort: an average treatment effect analysis on patients treated with bDMARDs. Clin Exp Rheumatol. Published online February 8, 2023. doi:10.55563/clinexprheumatol/q38lu0
PO:01:007 | Modulation of cellular senescence in psoriatic arthritis: exploring the potential impact of b/tsDMARDs treatment on telomere length, mtDNA copy number, and oxidative damage
Background. Inflammation and cellular senescence are interrelated processes involved in aging and chronic diseases. In Psoriatic Arthritis (PsA), excessive reactive oxygen species may contribute to telomere shortening and mitochondrial dysfunction. By reducing inflammation, biologic and targeted-synthetic disease modifying anti-rheumatic drugs (b/tsDMARDs) could influence senescence pathways. This study aimed to evaluate biomarkers of cellular senescence in PsA patients receiving b/tsDMARDs, specifically telomere length (TL), mitochondrial DNA (mtDNA) copy number, and oxidative damage at therapy initiation (T0) and after 12 months (T12). Methods. PsA patients starting b/tsDMARDs (TNF-alpha-i,IL17i, or JAKi) were enrolled and monitored over 12 months using DAPsA scores to classify them as Responders or non-Responders. Blood samples were collected at baseline (T0) and at 12 months (T12); age- and sex-matched healthy controls (CTRLs) were also included. TL and mtDNA copy number were measured in PBMCs using quantitative PCR. Oxidative DNA damage in telomeric and mitochondrial regions was assessed via qPCR after enzymatic digestion with FPG, measuring DeltaCt values. Statistical comparisons were performed using non-parametric or paired tests as appropriate, with significance set at p =< 0.05. ROC curves were used to assess discriminative potential of TL and mtDNA copy number. Results. Our cohort included 50 PsA patients and 34 CTRLs, with a prevalence of female participants in both groups. PsA patients had a mean disease duration of 7.41 ± 6.43 years. (Table 1) PsA patients showed significantly shorter TL compared to CTRLs (median TL:0.025 vs. 0.050; p = 0.005). (Figure 1) TL positively correlated with disease duration (p = 0.042) and BMI (p = 0.011), and was higher in patients with metabolic comorbidities (p = 0.025). Telomeric oxidative damage showed no significant group difference but tended to increase in patients with longer disease duration and higher DAPsA. mtDNA copy number was significantly reduced in PsA patients versus CTRLs (median:16.43 vs. 26.71; p < 0.0001)(Figure 2) and correlated with BMI (p = 0.007). No significant difference in oxidative mtDNA damage was observed. ROC analysis showed that TL (AUC= 0.729) and mtDNA copy number (AUC= 0.760) discriminated PsA from CTRLs with moderate sensitivity and high specificity. A combined model yielded an AUC of 0.828 with 93.7% specificity. After 12 months of treatment, 36 patients were classified as Responders. In these, TL significantly increased compared to baseline (median TL at T12: 0.055; p = 0.0009), reaching values comparable to CTRLs. This effect was confirmed in subgroups treated with TNF-alpha-i (p = 0.04) and IL17i (p = 0.02).(Figure 3) mtDNA copy number did not significantly change post-treatment. Conclusions. This study provides novel insights suggesting the potential use of TL and mtDNA copy number as biomarkers for assessing cellular senescence in PsA. b/tsDMARDs may have a modulatory effect on telomeric attrition and senescence pathways.
PO:01:008 | Active sacroiliitis at magnetic resonance enterography increases the risk of axial spondyloarthritis in Crohn’s disease patients, while greater age and disease duration are protective factors: a monocentric retrospective cohort study
We aim to estimate the incidence of IBD-SpA in a population of Crohn’s disease (CD) patients and to identify risk factors associated with the development of IBD-SpA. This retrospective observational cohort study included all consecutive patients with a CD diagnosis followed by our IBD outpatient clinic who underwent at least one magnetic resonance enterography (MRE) between 2011 and 2023. Patients without a full scan of sacroiliac joints (SIJs) on MRE, having other rheumatic diseases, diagnosed with SpA before CD diagnosis, missing key clinical or imaging data, death or lost to follow-up at the time of data collection, were excluded. The identification of new onset IBD-SpA during the follow-up was based on the fulfillment of the ASAS classification criteria. Baseline demographic and clinical data, and immunosuppressive therapies performed were collected. Presence of articular and intestinal lesions at MRE was established according to the most recent definitions by ASAS and the Society of Abdominal Radiology, respectively. Incidence rates were calculated as the number of new cases of SpA divided by the total person-time at risk, expressed per 1,000 person-years. Log-rank test and univariate Cox proportional hazards regression analyses were performed to estimate hazard ratios (HR) for categorical and continuous predictors. A total of 147 CD patients [M:F 1:1, median age (IQR) 46.3 (23.3) years, median CD duration (IQR) was of 4.50 (16.4) years] were selected. Descriptive statistics of the sample are shown in Table 1. The incidence rates of overall, axial, and peripheral IBD-SpA were 3.8, 2.1, and 1.7 cases per 1,000 person-year, respectively. A stricturing CD behavior (HR: 0.22; 95% CI: 0.05–0.93; p=0.040), baseline mesalazine treatment (HR: 0.24; 95% CI: 0.06–0.99; p=0.049), greater age (HR: 0.94; 95% CI: 0.89–1.00; p=0.035), and CD duration (HR: 0.84; 95% CI: 0.72–0.97; p=0.019), were associated with a reduced risk of developing IBD-arthritis. The sub-analysis conducted for each subset of arthritis revealed an increased risk of axial IBD-SpA for active sacroiliitis (HR 6.08; 95% CI 1.11-33.4; p=0.038), and ankylosis of SIJs on MRE (HR 47.7; 95% CI 2.99-763.4; p=0.006), while revealed a reduced risk for baseline mesalazine treatment (HR 0.20; 95% CI 0.04-1.11; p=0.067), greater age (HR: 0.93; 95% CI: 0.86–1.00; p=0.040) and CD duration (HR: 0.84; 95% CI: 0.71–0.99; p=0.033). An increased risk of peripheral IBD-SpA emerged only for ankylosis of SIJs (HR 24.6; 95% CI 2.23-271.8; p=0.009). A reduced incidence rate of IBD-SpA was associated with a stricturing CD behavior, baseline mesalazine treatment, increasing age and CD duration. Active sacroiliitis at baseline MRE was associated with the development of axial IBD-SpA; mesalazine therapy, greater age and CD duration were protective factors. Table 1: descriptive statistics of the sample.
PO:01:010 | Survival of second-line treatment with TNF inhibitors vs. IL-23 inhibitors after failure of a first TNF inhibitor: a real-life observational study from the Italian multicenter BIRRA cohort in patients with psoriatic arthritis
Background. Since 2021, IL-23 inhibitors (IL-23i) such as guselkumab, and since 2022 risankizumab, have been available for the treatment of psoriatic arthritis (PsA). However, after failure of a first tumor necrosis factor inhibitor (TNFi), switching to a second TNFi remains common. This study aims to compare second-line drug survival between “cycling” (second TNFi) and “swapping” (IL-23i) in Italian real-life clinical practice. Materials and Methods. A multicenter retrospective observational study was conducted on PsA patients treated with second-line TNFi or IL-23i. Drug survival was analyzed using Cox regression, considering age, sex, disease duration and domains (peripheral, axial, or mixed), disease activity, year of prescription, concomitant use of DMARDs or corticosteroids, and type of second-line treatment. Results. A total of 269 patients were included (62.8% female; median age 56.0 [47.0–64.0] years), of whom 191 (71.0%) were treated with TNFi and 78 (29.0%) with IL-23i (70 with guselkumab and 8 with risankizumab). Compared with patients receiving a second TNFi, those treated with IL-23i had more severe disease at treatment initiation (longer disease duration and higher DAPSA scores) (Figure 1A). A more recent year of prescription was significantly associated with reduced drug survival, with an approximately ninefold increased relative risk per year (HR 9.17 [5.52–15.24], p<0.001). Mixed (axial and peripheral) PsA was associated with a higher risk of treatment failure compared with peripheral PsA (HR 2.94 [1.64–5.29], p<0.001). Use of IL-23i as second-line therapy was associated with a 91% lower risk of failure compared with TNFi (HR 0.09 [0.04–0.24], p<0.001) (Figure 1B). When including disease activity (DAPSA) and restricting the analysis to patients with peripheral or mixed PsA, the significant variables remained largely unchanged: year of prescription (HR 14.44 [7.32–28.49], p<0.001); axial and peripheral vs peripheral PsA (HR 2.71 [1.39–5.27], p=0.003); IL-23i vs TNFi (HR 0.10 [0.03–0.31], p<0.001); while disease activity had no effect on drug survival (HR 0.98 [0.96–1.01], p=0.166). Conclusions. The recent availability of multiple therapeutic options has led to reduced treatment survival, likely reflecting improved clinical management of patients with PsA. Switching to an IL-23 inhibitor after failure of a TNFi is associated with greater effectiveness compared with cycling to a second TNFi, even in patients with more severe disease and regardless of PsA clinical activity. Longer follow-up studies are needed to confirm these findings and to assess potential differences within the IL-23 inhibitor class.
PO:01:014 | Differential inflammatory responses of CD14+ and CD14– synoviocytes in psoriatic arthritis: implications for pathogenesis and targeted therapies
Background. Investigating the inflammatory response of synoviocytes in patients with psoriatic arthritis (PsA) is crucial due to their central role in disease pathogenesis. Recent studies have reported upregulation of interleukin-6 (IL-6) and activation of the transcription factor NF-κB as key mechanisms in PsA development. Although the role of dendritic-like CD14 synoviocytes remains unclear, these cells have been shown to contribute to the initiation and maintenance of inflammation. Furthermore, impaired dendritic cell function has been associated with dysregulated inflammatory responses that may promote chronic inflammation. Therefore, this study aimed to explore the molecular responses of non-dendritic CD14 synoviocytes under basal conditions and after stimulation with inflammatory mediators, and to characterize the basal molecular profile of CD14 synoviocytes. Materials and Methods. Fibroblast-like synoviocytes (FLS) were isolated from synovial membranes of healthy donors (h) and PsA patients. CD14 FLS were selected using immunomagnetic beads and cultured under basal conditions (wt), whereas CD14 FLS were stimulated for 24 hours with LPS and IFNγ. Cells were analyzed at passage 6 (P6) by real-time PCR. Healthy donor FLS were also analyzed by flow cytometry (FACS) at passages 2 (P2) and 6 (P6) for CD90 and CD14 expression. Results. Under basal conditions, healthy CD14 FLS (h-FLS CD14 ) exhibited higher CD64 expression than PsA CD14 FLS. Following inflammatory stimulation, h-FLS CD14 showed increased expression of all analyzed genes compared to PsA-FLS CD14 , except for HLA-DR (Fig. 1). In PsA-FLS CD14 , expression of macrophage-associated markers (CD14, Mer-TK, CD64) decreased, whereas all other genes were upregulated except CD90, CDH-11, and NF-κB (Fig. 2). FACS analysis prior to selection revealed that h-FLS wt at P2 consisted of CD14 /CD90 (67%), CD14 /CD90 (3%), and CD14 /CD90 (8%) populations. Upon activation, the CD14 /CD90 population remained nearly unchanged (64%), while CD14 /CD90 (5%) and CD14 /CD90 (15%) subsets increased. After magnetic selection and expansion (P6), h-FLS CD14 wt were predominantly CD14 /CD90 (93%), with minimal CD14 /CD90 (0.8%) and CD14 /CD90 (0.01%) populations (Fig. 3). Conclusions. The differential expression of surface markers and inflammatory genes between h-FLS and PsA-FLS highlights distinct responses to inflammatory stimuli. The higher expression of pro-inflammatory markers in h-FLS CD14 suggests a stronger inflammatory capacity compared with PsA-FLS CD14 , whereas PsA-FLS CD14 display a more inflammatory phenotype under basal conditions. These findings underscore the dynamic nature of synovial cell populations in response to inflammation and indicate that detailed phenotypic characterization of synoviocytes is essential for developing more effective therapeutic strategies in PsA management. Moreover, elucidating the phenotypic differences between CD14 and CD14 synoviocytes may aid in identifying novel biomarkers for early diagnosis and personalized treatment of PsA.
PO:01:015 | Evaluation of the impact of concomitant psoriasis on the clinical and therapeutic pattern of a monocentric cohort of patients affected by spondyloarthritis associated with inflammatory bowel diseases
Background. To evaluate the influence of concomitant psoriasis (PsO) on the clinical and therapeutic pattern of a monocentric cohort of patients affected by Spondyloarthritis (SpA) associated with inflammatory bowel diseases (IBD). Materials and Methods. This study represents a preliminary phase of an ancillary analysis of the DIAMANTE project (Early diagnosis of spondyloarthritis in a cohort of patients affected by inflammatory bowel disease), developed with the general objective of determining the prevalence, predictors, and outcomes of SpA in a cohort of IBD patients, within the context of a close and structured collaboration between gastroenterologists and rheumatologists. Within the DIAMANTE cohort, two subgroups of patients were identified for the study: patients with enteropathic SpA and a concomitant personal diagnosis of PsO (Group 1: IBD+SpA+PsO), and patients with a diagnosis of SpA only (Group 0: IBD+SpA). For both groups, the following demographic, clinical, and therapeutic data were recorded and compared: sex, association with IBD pattern, peripheral joint involvement, axial involvement, history of dactylitis, need for biologic therapy, and multi-resistance to “targeted” drugs (defined as discontinuation due to inefficacy of at least two biologic drugs or small molecules). A p-value <0.05 was considered statistically significant using Fisher’s exact test and the Chi-square test. Results. Data from 665 consecutive patients with IBD recruited between November 2023 and April 2025 were analyzed. Within this cohort, 95 (14%) had a concomitant diagnosis of SpA; among these, 21 (22%) also had a diagnosis of PsO (Group IBD+SpA+PsO), while 74 (78%) had only SpA associated with IBD (Group IBD+SpA). Comparative analysis between the two groups showed notable—though only trending toward statistical significance—differences in terms of female prevalence (71% vs 54%, p=0.15), frequency of peripheral involvement (62% vs 49%, p=0.28), and use of biologic drugs (91% vs 77%, p=0.17). Most notably, a significantly higher frequency of multi-resistance to biologic treatment was observed in patients with concomitant PsO compared to those with IBD and SpA only (29% vs 11%, p=0.04). No significant differences were observed regarding the distribution of different IBD types (ulcerative colitis, Crohn’s disease, indeterminate forms) between the two study groups. Conclusions. In patients with SpA associated with IBD, a frequent concomitant association with PsO—another extra-articular domain typical of the spondyloenthesitis spectrum—was demonstrated. The results of this exploratory analysis suggest the usefulness of further investigating, in larger prospective cohorts, the impact that such a dual combination of extra-articular manifestations may have on disease characteristics and, in particular, on therapeutic management.
PO:02:016 | Real-world evidence of upadacitinib over two years in Italian patients with axial spondyloarthritis
Background. This real-life investigation, conducted across multiple centres in Italy, aims to assess the 2-year effectiveness and safety of upadacitinib, a selective JAK1 inhibitor approved for the treatment of axial spondyloarthritis (axSpA). The study includes patients with both radiographic and non-radiographic axSpA and evaluates: (a) clinical outcomes at 6, 12, and 24 months; (b) drug retention rate (DRR); and (c) the influence of treatment line (LoBT), axSpA subtype, and sex on achieving low disease activity (LDA) and very low disease activity (VLDA). By analysing real-life clinical practice data, our analysis provides insight into the long-term therapeutic role of upadacitinib in managing axSpA, particularly in previously-treated patients or those with limited therapeutic options. Methods. Consecutive patients with axSpA, who received upadacitinib between December 2022 and January 2025, were prospectively evaluated across multiple Italian centres. Data collected included baseline disease characteristics, comorbidities, prior and ongoing treatments, and follow-up duration. The primary endpoints were treatment effectiveness and safety, as well as drug retention rate (DRR), assessed at 6, 12, and 24 months from treatment initiation (T0). Effectiveness was evaluated using clinimetric indices, while safety outcomes included infections and adverse events (AEs). Secondary endpoints included the impact of biologic treatment history (bDMARDs), axSpA subtype (radiographic vs. non-radiographic), and sex on the achievement of low disease activity (LDA), defined as BASDAI <4 and/or ASDAS <2.1, and very low disease activity (VLDA), defined as BASDAI <2 and/or ASDAS <1.3, at each time point. Results. A total of 203 patients were included in the analysis [48% male; median age at diagnosis: 44 years; 22.7% HLA-B27 positive -36.6% observed in Northern Italy); 71% with non-radiographic axSpA]. The median number of prior treatment lines was 3 (range: 1–12). At follow up, 170 patients were evaluable at 6 months (T6), 130 at T12 and 62 at T24. Overall, upadacitinib demonstrated a statistically significant improvement in effectiveness outcomes at 6 months, which was sustained over time at 12 and 24 months (Figure 1), regardless of LoBT, axSpA subtype, or sex. Of note, LDA at 24 months was more frequently achieved in the nr-axSpA subset (91.3% vs. 56.3%), while VLDA at 12 months was more commonly associated with female patients (41.5% vs. 21.4%). Remarkably, the DRR was consistently high throughout the observation period, with rates of 92%, 80%, and 55% recorded at 6, 12, and 24 months, respectively. Treatment was discontinued in 40 patients, with 22 cases attributed to primary or secondary loss of effectiveness and 2 cases due to adverse events. Conclusions. Upadacitinib demonstrated a favourable safety and effectiveness profile across the axSpA population, regardless of prior treatment lines, axSpA subtype, or sex. Among evaluable patients sustained remission and consistent drug retention were observed over the two-year follow-up period.
PO:02:017 | Difficult-to-treat psoriatic arthritis: clinical and ultrasonographic predictors in a real-life cohort
Background. To investigate clinical and ultrasound (US) features as potential predictors of difficult-to-treat (D2T) psoriatic arthritis (PsA). Methods. and materials In this retrospective study, we enrolled patients diagnosed with PsA followed at our outpatient clinic (January 2020-September 2024). D2T-PsA was defined as the persistence of disease activity upon failure of >= 2 lines of biological or targeted synthetic DMARDs (b/tsDMARDs). Demographic, clinical and US data were collected. 'Index' US was defined as the assessment performed in patients before fulfilment of D2T-PsA definition. Four expert rheumatologists conducted all US assessments with a high-frequency (15-24 MHz) Esaote MyLabX8 linear probe, following EULAR and OMERACT definitions (1). Synovitis, tenosynovitis, and bone erosions were evaluated in wrists, metacarpophalangeal (MCP), proximal interphalangeal (PIP) of the hands, metatarsophalangeal (MTP) joints, shoulders, knees and ankles. Baseline predictors of D2TPSA were analysed using Cox regression adjusted for potential baseline confounders. Results. 152 patients were included, 81 classified as D2T-PsA and 71 as non-D2T. Clinical and demographic features are shown in Table 1. A diagnostic delay of >= 1 year independently predicted development of D2T-PsA (HR 1.74, 95% CI 1.05–2.88, p=0.032) in the whole cohort (fig 1) as well as in subgroups with predominant peripheral (n=143, HR 1.73, 95% CI 1.37–2.90, p=0.036) or axial involvement (n=61, HR 3.18, 95% CI 1.22–8.27, p=0.018). In the latter group, baseline fibromyalgia (HR 2.45, 95% CI 1.12–5.36, p=0.025) and enthesitis (HR 2.49, 95% CI 1.08–5.73, p=0.033) were also predictive of D2T phenotype. Among patients <40 years (n=26), a diagnostic delay of >= 1 year remained a significant risk factor for D2T-PsA (HR 4.78, 95% CI 1.25–18.28, p=0.022), in association with fibromyalgia (HR 9.04, 95% CI 2.20–37.07, p=0.002) and female sex (HR 68.26, 95% CI 3.22–1445.71, p=0.007). At index US, patients who would later become D2T displayed a higher prevalence of PIP synovitis (85.7% vs 14.3%, p=0.050), higher GLOESS score at the 1st MTP joint bilaterally (0.10 ±0.33 vs 0, p=0.022) and a higher grade of tenosynovitis at the extensor carpi tendons (0.11 ± 0.33 vs 0.02 ± 0.14, p=0.054). A higher baseline mean GLOESS score at the 1st MTP joint emerged as independent predictor of D2T-PsA (HR 3.93, 95% CI 1.76–8.78, p<0.001), while wrist synovitis was inversely associated with the risk of D2T phenotype (HR 0.29, 95% CI 0.14–0.59, p<0.001). Conclusions. Delayed diagnosis of PSA independently predicts D2T-PsA, regardless of axial or peripheral involvement, emphasizing the need for early diagnosis to improve outcomes and prevent refractoriness. Impending D2T-PsA patients also show distinct US features, including higher wrist extensor tenosynovitis and more severe bilateral 1st MTP synovitis, supporting the role of clinical–US integration for early recognition and management. Reference 1. Bruyn et al. J Rheumatol 2019
PO:02:018 | After-SECs: clinical predictors of secukinumab retention in psoriatic arthritis patients with inadequate response to anti-tumor necrosis factor therapy
Background. A range of molecular targets is currently available for the treatment of psoriatic arthritis (PsA). Identifying clinical predictors of treatment persistence is critical for optimizing therapeutic strategies, as drug retention is often used as a proxy for long-term efficacy and safety. This study aimed to evaluate predictors of secukinumab (SEC) retention in PsA patients who previously discontinued the anti-TNF agent adalimumab (ADA). Methods. PsA patients who initiated SEC following ADA discontinuation between 2019 and 2024 were retrospectively analyzed. Clinical data were collected through systematic chart reviews, including demographic characteristics, involved disease domains, prior treatments, and metabolic comorbidities [e.g., increased body mass index (BMI), diabetes]. SEC treatment persistence was assessed over a follow-up period of up to 36 months. Survival analysis was performed using SEC discontinuation as the event, with demographic and clinical variables as predictors. Results. Among 327 PsA patients treated with SEC during the study period, 67 had previously discontinued ADA – 54 (81%) due to inadequate response and 13 (19%) due to adverse events. Patients’ characteristics are detailed in Table 1. Over a median follow-up of 1.6 years (Interquartile Range (IQR) 0.7–2.4), 26 SEC discontinuations were recorded, corresponding to an incidence rate of 24.8 per 100 patient-years. SEC retention rates at 12, 24, and 36 months were 69.8% (95% Confidence Interval (CI) 59.3–82.2), 61.6% (95% CI 49.7–76.5), and 49.1% (95% CI 36.0–67.0), respectively. The presence of enthesitis (Hazard Ratio (HR) 0.28, 95% CI 0.08–0.96) and concomitant active skin psoriasis (HR 0.21, 95% CI 0.08–0.59) were significantly associated with a lower risk of SEC discontinuation. Conclusions. Secukinumab showed higher retention rates in PsA patients with enthesitis and active skin psoriasis after ADA discontinuation. No significant associations were found with demographic variables or metabolic comorbidities. These findings may assist clinicians in identifying patients who are more likely to benefit from IL-17 inhibition following anti-TNF therapy failure.
PO:02:023 | Monocentric analysis of systemic glucocorticoids in PsA: the art of balancing prescriptive appropriateness and risk factor management
Objective: Psoriatic Arthritis (PsA) is a pleiomorphic disease. The latest guidelines1 recommend glucocorticoids (GCs) preferentially as local therapy, emphasising that the use of systemic GCs may raise further safety issues, especially due to the high prevalence of comorbidities and cardiovascular risk factors in PsA. Literature data regarding the prevalence of GCs in PsA are scarce. The aim of this study is to analyse, in a monocentric cohort, the prevalence, dosage, and variables associated with GCs prescription in PsA. Materials and Methods: PsA patients whose latest assessment was by 31 May 2025 were recruited in a cross-sectional manner. Data analysed included disease characteristics, comorbidities, ongoing therapies and relevant GCs dosages. Student's t-test and Mann-Whitney test were used for continuous variables, and Chi-square or Fisher’s exact test for categorical variables. Results: A total of 244 patients diagnosed with PsA were enrolled (mean age 55.7 years, males 123 (50.4%), peripheral PsA phenotype 186 (76.2%), axial 16 (6.6%), enthesitis 6 (2.5%), mixed 36 (14.7%)). Demographic and clinical characteristics of the population are shown in Table 1. Patients with PsA on GCs therapy (GCs+) were 24/244 (9.8%), with a median dosage of 2.5 mg prednisolone equivalent. Comparison between the GCs+ and GCs- groups showed similar characteristics in terms of disease duration (median 12 vs 14 years, p= 0.708), similar distribution among disease subsets (p= 0.343), and similar disease manifestations (dactylitis 20.8% vs 23.8%, p= 0.732; associated IBD 4.2% vs 0.5%, p= 0.189; enthesitis detected by LEI Index, p= 0.789). The two groups (GCs+ vs GCs-) differed significantly in terms of disease activity [median DAPSA 10.2 (4.2–14.7) vs 4.1 (1.2–7.2), p<0.001], even when stratified by moderate/high disease activity (33.3% vs 6.9%, p<0.001), and in b/tsDMARD prescription (54.2% vs 81.2%, p=0.002). The distribution of comorbidities was significantly different between GCs+ and GCs-, particularly for the prevalence of osteoporosis (33.3% vs 9.2%, p<0.001), fragility fractures (16.7% vs 3.7%, p=0.022), liver disease (25% vs 6.9%, p=0.003), and dyslipidaemia (20.8% vs 32.6%, p=0.006). Conclusions: Our data confirm that systemic GCs are prescribed in real-life practice. Their use appears reserved for more active disease, where therapeutic optimisation has not yet been achieved. However, the use of systemic GCs is not without side effects, particularly those related to osteoporotic comorbidities.
PO:02:024 | Development of anti-drug antibodies in patients with peripheral and/or axial spondyloarthritis treated with infliximab or adalimumab: a monocentric cross-sectional study
Background.The evaluation of the prevalence of anti-drug antibodies (ADABs) against infliximab (IFX) or adalimumab (ADA) in a monocentric cohort of patients affected by axial and/or peripheral spondyloarthritis (SpA), the variables associated with this phenomenon, the frequencies of suspected drug-related adverse events (DRAEs), and the frequencies of subsequent therapeutic choice. Materials and Methods. Cross-sectional study. All patients affected by axial and/or peripheral SpA (ASAS 2009/2011) who underwent a blood sampling (baseline) for IFX or ADA ADABs serum measurement for a suspected DRAEs or a disease relapse in the period time between 01/01/2020 and 01/01/2025, were included. Demographic and clinical data, and previous treatments at baseline, and subsequent therapeutic choices, were retrospectively gathered. Results. Forty patients (M:F 1:1, median age 51.6 (IQR 19.1)) affected by SpA (peripheral 50.0%, axial 35.0%, both 15.0%) were selected. Median disease duration was 8.3 (IQR 8.6) years. PsO and IBD were present in 32.5% and 12.5% of cases, respectively. ADABs serum measurement for IFX and ADA were 10/40 (25.0%) and 30/40 (75.0%), respectively. Median BASDAI and DAPSA at baseline were 4.4 (IQR 3.8) and 16.8 (IQR 6.8), respectively. An active axial (BASDAI>4) and/or peripheral (DAPSA>4) disease was present in 60% (12/20) and 92.3% (24/26) of cases, respectively. Median bDMARD treatment duration was of 2.5 years (IQR 4.5). Overall positivity for ADABs was 17.5% (IFX-ADABs 1/10, 10.0%, ADA-ADABs 6/30, 20.0%). Spearman matrix of correlation revealed a negative correlation between ADABs titer and the relative drug titer (ρs=-0.590, p<0.0001). Positivity for ADABs was associated to HLA-B27 negativity (p=0.036) and a lower median age (p=0.022). None of ADABs positive patients were under concomitant cDMARDs treatment (0.0% vs 27.3%, p=0.174). Reasons for ADABs serum measurement were secondary failure in 75.0% of cases and suspected DRAEs in 25.0% of cases. Ten AEs were recorded: 2 cases of arthritis, 1 case of psoriasis-like rash, 3 cases of hypertransaminasemia, 1 case of suspected uveitis, 1 case of suspected neuropathy, 1 case of suspected drug-induced lupus erythematosus, and 1 case of depression relapse. After blood sampling for ADABs measurement, in 35.0% of cases the treatment remained unchanged, in 32.5% was switched into another TNFαi (61.5% Etanercept, 23.1% Certolizumab, 15.4% Golimumab), and 32.5% swapped to another mechanism of action (53.8% IL17A inhibitor, 38.5% JAK inhibitor, 7.7% IL23 inhibitor). Conclusions. ADABs positivity is a frequent phenomenon in SpA patients treated with TNFαi. In our cohort, ADABs positivity was associated with younger age and HLA-B27 positivity.
CO:07:3 | Does articular and entheseal structural damage drive pain and patient-driven reported outcomes in difficult-to-treat psoriatic arthrtis patients? Results from a cross-sectional study
Background. To assess difficult-to-treat psoriatic arthritis (D2T-PsA) and determine whether articular and entheseal structural damage, assessed by ultrasound (US), may drive pain and patient-driven outcomes in D2T-PsA. Methods. A multicenter cross-sectional study was conducted on PsA patients treated with b/tsDMARDs. For each patient, complete demographic data were recorded. Eligible participants were required to meet the following inclusion criteria: age >=18 years; diagnosis of PsA fulfilling the CASPAR criteria; classification as D2T-PsA, defined by failure of >=2 classes of b/tsDMARDs (with different mechanisms of action) following the failure or contraindication of >=1 csDMARD, and persistently active disease (DAPSA >14); Presence of at least one clinically significant site, defined as a tender and/or swollen joint or a tender enthesis for peripheral disease. Sonographic evaluations were performed by expert sonographers, blinded to clinical data, using the US damage score from the UPSTREAM study calculated as follow: [number of (entheseal calcifications count + entheseal bone irregularity count)*2.98 + number (tendon lesion count)* 1.1 + number (entheseal erosion count)*0.9 + number (joint erosion count*0.7 + number (joint osteoproliferation count + enthesophytes count)*0.54]. Moreover, we use Spearman rho correlation coefficient to evaluate possible correlations between US damage score and clinical features including pain on NRS, HAQ, DAPSA, PsAID, physician global assessment of disease activity on NRS (PhGA), patient global assessment of disease activity (PtGA) on NRS and deltaPtGA-PhGA. Results: A total of 517 patients with PsA identified, 191/517 (36.9%) patients were on their second mechanism of action b/tsDMARDs. Of whom, 53 out of 191 patients (27.7%) met the criteria for D2T-PsA and were included in the analysis. Table 1 shows the clinical and US characteristics of the 53 D2T patients. Of these, 34 (64.1%) showed at least one site of active inflammation at US evaluation, while 19 showed no signs of active inflammation. The median (IQR) US damage score of the 53 D2T patients was 9.88 (4.76-23.56). Notably, the US damage score negatively correlates with tender joint count (rho -0.27, p=0.04) but positively correlates with swollen joint count (rho +0.27, p=0.05). Moreover, considering each item of the total US score, both the number of joint erosions and the number of joint osteopythes/osteoproliferation correlates positively with PhGA (rho +0.41, p=0.002) (rho +0.27, p=0.04) and correlates negatively with deltaPtGA-PhGA (rho -0.30, p=0.02) (rho -0.31, p=0.02) (table 2). No significant correlation was detected between pain and PtGA with US damage score. In patients without US signs of inflammation, no significant correlation was found between each comparison. Conclusions. Preliminary results of our study in D2T PsA patients showed that articular damage is associated with PhGA and swollen joints, but not with pain, suggesting that patient-driven outcomes are potentially driven by inflammation rather than damage itself.
CO:07:1 | Assessing bone fragility in systemic sclerosis: results of the Sclerobone multicentric study
Background: Considering the limited and conflicting data regarding prevalence and risk factors of osteoporosis (OP) in systemic sclerosis (SSc), we aimed at evaluating a large population of patients at several Italian institutions. Enrollment started in October 2024 and will end in October 2025. Materials and Methods: We are investigating the presence of OP in randomly selected subjects fulfilling the 2013 ACR/EULAR SSc classification criteria using a partially retrospective design. Exclusion criteria include ongoing pregnancy, cancer, metabolic bone diseases other than OP, and therapies interfering with bone health; exceptions are chronic kidney disease, anti-osteoporotic drugs, glucocorticoids (GC), and proton pump inhibitors. OP was defined as history of fragility fractures (FX) and/or of bone mineral density (BMD) values with T-scores < -2.5 or Z-scores < -2.0. BMD is evaluated using DXA scans within 12 months before enrollment or performed at enrollment. Demographic and anthropometric data, menopausal status, dietary calcium intake, Charlson Comorbidity Index (CCI), and concurrent medications are assessed. Sarcopenia, when detected with the SARC-F+EBM questionnaire, is evaluated with functional tests such as hand grip strength, chair stand test, and gait speed. A characterization of SSc is performed, including age at diagnosis, disease duration, and organ involvement. The cumulative SSc-related damage is expressed with the Scleroderma Clinical Trials Consortium Damage Index (SCTC-DI). We provide the results of the pre-planned interim analysis performed in April 2025; the final analysis is planned in October 2025. Results: The interim analysis focused on 315 patients, with a mean age at enrollment of 63.2±11.3 years. They were diagnosed with SSc at a mean age of 51.2±12.4 years and had been affected for a median time of 10 years (interquartile range - IQR 12). Females made up the majority (n = 292; 92.7%) of the cohort, with 266 (91.1%) having been postmenopausal for a mean time of 17.3±10.1 years. The mean BMI was 24.3±4.4 kg/m², and 16.8% of patients were sarcopenic. Dietary calcium intake was insufficient (<700 mg) in 70.4% of cases, and optimal (>1000 mg) only in 3.9%. Approximately 30% of patients were taking GCs. The mean CCI score was 3.7±1.6, suggesting a 10-year mortality risk of approximately 40%. The median SCTC-DI score was 3 (IQR 3). Our main finding was that OP affected 136 (43.2%) subjects: 84 (61.8%) had reduced BMD values only, and 52 (38.2%) had a history of FX. Conclusions: Our interim analysis showed that 43.2% of patients were affected by OP, suggesting a potentially high burden in SSc. To identify any predictive factors of OP in SSc, the final analysis will include correlations with SSc organ involvement, biochemical markers, densitometric values, sarcopenia, body composition parameters, and FX risk calculations with the DeFRA algorithm.
CO:07:6 | Hidden in plain sight: fibromyalgia prevalence and correlates in 3,000 non-clinical Italian subjects
Background. To determine the prevalence of fibromyalgia according to the ACR2016 criteria in a non-clinical Italian population and to identify significant demographic, clinical and lifestyle correlates. Materials and Methods. A voluntary survey was distributed across various Italian regions to randomly selected individuals from the general population. The survey included questions regarding demographic information, ACR 2016 fibromyalgia diagnostic criteria, sleep quality measures, physical activity levels, and comprehensive health history. Descriptive statistics, group comparisons, and multivariate logistic regression were employed to analyze data. Results. 3.000 participants were recruited (68.5% female, mean age 36.17±15.91, mean BMI 23.70±3.97). 5.1% (Table 1) met the ACR 2016 diagnostic criteria, with a WPI of 8.42±2.54 and SS score of 8.33±2.01, compared to 1.50±1.50 and 3.36±2.14 respectively in non-fibromyalgia subjects (p<0.0001). Fibromyalgia prevalence was higher in females (6.76%) than males (1.48%, p=0.0001), with increased prevalence in older age groups (Figure 1. 3.54% in 18-30y vs 8.23% in 51-60y, p=0.001). BMI extremes showed higher prevalence (8.11% in BMI<18.5 and 10.29% in BMI>29.9 vs 4.11% in normal BMI, p=0.0014). Those who reported physical inactivity showed higher fibromyalgia prevalence (6.46% in sedentary, 3.57% in those exercising 3-4 times/week, p=0.04). Also, fibromyalgia was more prevalent among those reporting very poor sleep (49.32%) compared to very good sleep (1.00%, p<0.001). Sleep duration was shorter in the fibromyalgia group (5.99±1.65 vs 6.85±1.00 hours, p<0.0001). In females, fibromyalgia prevalence was highest in those with surgical menopause (17.46%), followed by physiological menopause (11.04%), compared to 3.64% in those with regular cycles (p=0.001). Family history of fibromyalgia (Table 2) was higher in the fibromyalgia group (28.76% vs 6.99%, p<0.0001), as was family history for other rheumatologic disorders. In non-fibromyalgia subjects, fibromyalgia family history was associated with higher SS total scores (3.86±2.02 vs 3.32±2.15, p=0.0004) and sub-scores. In fibromyalgia subjects, WPI was higher in those with family history (9.14±2.91 vs 8.14±2.33, p=0.046). Multivariate analysis revealed gender-specific associations. In males, associations with fibromyalgia diagnosis included sleep duration (OR=0.29, 95%CI 0.16-0.52), positive family history (OR=8.90, 95%CI 2.35-33.74), and a non-linear BMI relationship. In females, fibromyalgia was associated with sleep duration (OR=0.62, 95%CI 0.53-0.72), family history (OR=4.11, 95%CI 2.65-6.37), and menstrual irregularities, especially surgical menopause (OR=3.02, 95%CI 1.19-7.67). Conclusions. This study identifies a 5.1% prevalence of fibromyalgia in a non-clinical Italian population, with higher frequency in females. Increased prevalence was found with older ages, BMI extremes, physical inactivity and poor sleep quality. Menstrual irregularities demonstrated relationships with fibromyalgia prevalence, with elevated rates among women with surgical menopause. Family history correlated with WPI and SS scores, as well as fibromyalgia diagnosis, suggesting potential genetic factors.
CO:08:1 | Aquaporin-4 downregulation in dysphagic idiopathic inflammatory myopathies: association with Type 2 fiber damage and inflammation
Background. To assess whether Aquaporin-4 (AQP4) expression in skeletal muscle is altered in idiopathic inflammatory myopathies (IIMs), particularly in dysphagic patients, and to explore its association with muscle fiber type, regeneration, inflammation, and tissue damage. Methods. Muscle biopsies from 54 IIM patients (25 dysphagic: 11 DM, 7 PM, 2 IBM, 2 IMNM, 3 OM; 29 normophagic: 9 DM, 4 ASyS, 4 PM, 4 IBM, 8 IMNM) and 6 non-inflammatory controls were analyzed using immunofluorescence and confocal microscopy. AQP4 immunolocalization was assessed alongside markers of fiber type (MHCfast), regeneration (neonatal myosin), inflammation (CD68), and matrix remodeling (MMP2). Morphometric parameters (fiber diameter, area, atrophy factor, variability coefficient) were quantified. Clinical correlations were examined using MMT-8 and the Myositis Damage Index (MDI). Results. A significant reduction in AQP4-positive myofibers was observed in dysphagic IIM patients compared to normophagic patients and controls, predominantly affecting type 2 fibers. Dysphagic muscles showed marked hypotrophy, with reduced fiber diameter and area, and increased variability and atrophy indices. These changes were mainly driven by AQP4-negative type 2 fibers (Figure 1A-B). Dysphagic patients showed a significantly higher percentage of AQP4-negative fibers co-expressing neonatal myosin (p<0.001 vs normophagic IIMs and healthy controls), indicating impaired regeneration. AQP4-negative fibers were more frequently surrounded by CD68-positive macrophages and MMP2-positive vessels (p<0.001 vs healthy controls). The proximity of inflammatory and vascular cells to AQP4-negative sarcolemmas suggests inflammation-induced AQP4 loss. Anti-HMGCR-positive IMNM cases (red circles and triangles in Figure 1A) exhibited the most severe AQP4 reduction and fiber damage. In the overall IIM cohort, the percentage of AQP4-positive type 1 myofibers correlated positively with MMT-8 scores (r:0.383, p<0.01), while AQP4-negative type 1 and type 2 fibers correlated inversely (r:-0.389, p<0.01; r:-0.288, p<0.05, respectively). No significant correlation emerged with CK levels. MDI was negatively correlated with AQP4-positive type 1 (r:-0.433, p<0.01) and type 2 (r:–0.265, p=0.05) fibers, and positively correlated with AQP4-negative type 1 (r:0.442, p<0.01) and type 2 (r:0.265, p=0.05) fibers. Conclusions. AQP4 loss in type 2 myofibers is a distinctive feature of dysphagic IIM patients and reflects myofiber damage, inflammation, and regenerative failure. AQP4 downregulation may represent a novel histopathological marker of disease severity and tissue vulnerability in IIMs.
PO:02:027 | Fast food, slow damage: ultra-processed foods, Western diet and inflammatory arthritis. A systematic scoping review
Background. Western dietary patterns, characterized by high intake of ultra-processed foods (UPFs), added sugars, and saturated fats, have been increasingly implicated in promoting systemic inflammation and disrupting gut microbiota composition. These mechanisms may influence the onset, progression, and comorbidities of chronic inflammatory arthritides. This systematic scoping review aimed to summarize current evidence on the association between Western diet (WD) or UPF consumption and the risk, activity, and related outcomes in rheumatoid arthritis (RA), axial spondyloarthritis (axSpA), and psoriatic arthritis (PsA). Methods. We conducted a systematic review including randomized controlled trials, observational studies (cohort, case-control, cross-sectional), and preclinical models assessing the relationship between WD or UPF intake and disease-related outcomes in RA, axSpA, or PsA. Exclusion criteria comprised narrative reviews, editorials, case reports, and studies not specifically addressing both the dietary exposure and relevant disease outcomes. A comprehensive literature search was conducted in PubMed, Embase, Scopus, Web of Science, and the Cochrane Library, with the final search on May 18, 2025 and no time limit applied. Reference lists were manually screened, and forward citation tracking was performed using Google Scholar. Risk of bias was not formally assessed, consistent with the exploratory nature of this scoping review. Data were synthesized narratively and tabulated by dietary exposure, outcomes, and key findings. Results. During screening, we assessed 165 papers. Only 10 studies involving over 244,000 individuals were included. Eight studies addressed RA, comprising 7 clinical and 1 preclinical investigation. Across these, greater UPF consumption or adherence to WD was consistently associated with adverse outcomes. Cohort studies reported an increased RA incidence with adjusted hazard ratios between 1.04 and 1.17; case-control analyses found odds ratios up to 1.84. Inflammatory markers were elevated, including CRP (+0.01 to +0.097 mg/L), ESR (+2 to +3.985 mm/h), and HbA1c (+0.02% to +0.04%). Effects on disease activity were variable (DAS28: +0.01 to +0.49; SJC: up to +0.6 joints). Cardiometabolic risk indicators, such as Framingham score, glucose, insulin, and visceral fat, also worsened with higher UPF intake. Alterations in gut microbiota were documented in both clinical and murine RA models. For axSpA, 1 prospective study (n=140) found no significant association between UPF intake and disease activity. No eligible clinical studies were found for PsA, though one preclinical model demonstrated that WD exposure exacerbated joint and skin inflammation and induced dysbiosis. Conclusions. Current evidence supports a detrimental association between WD or UPF intake and inflammatory and metabolic outcomes in RA. Data on axSpA are scarce and inconclusive, and clinical evidence in PsA is lacking. These findings underscore the need for targeted dietary research in spondyloarthritis and support the incorporation of nutritional assessment into comprehensive rheumatologic care.
CO:07:2 | Quantitative computed tomography analysis of pulmonary disease in systemic sclerosis: correlation between radiomics and pulmonary function tests
Background and objectives. High-resolution computed tomography (HRCT)-based radiomic analysis is gaining attention as a tool for quantifying interstitial lung disease (ILD) in systemic sclerosis (SSc). Pulmonary function tests (PFTs) are standard for functional assessment but have limited sensitivity in early disease stages. We aimed to explore the potential of HRCT-derived radiomic features in SSc patients with and without ILD. Methods. In this cross-sectional study, we enrolled SSc subjects who underwent both HRCT and PFTs. Radiomic parameters—skewness, kurtosis, high-attenuation areas (pHAA-700 and pHAA-600;-250), and lung volume—were extracted. Participants were classified into four groups based on HRCT pattern: no ILD, non-fibrosing NSIP (nfNSIP), fibrosing NSIP (fNSIP), and usual interstitial pneumonia (UIP). ANOVA with post-hoc comparisons, linear regressions, and ROC analyses were conducted to assess diagnostic performance and associations with PFTs. Results. Ninety-three subjects were enrolled. All radiomic parameters significantly differed across ILD patterns (p<0.001 for skewness, kurtosis, pHAA metrics; p=0.005 for lung volume). PFT values also varied among subgroups (ppFVC p=0.005; ppTLC p<0.001; ppDLCO p=0.004). Radiomic parameters were moderately correlated with ppFVC, ppTLC, and ppDLCO in ILD patients (R ranging in absolute terms from 0.33 to 0.58, p<0.001), with significant interaction terms (PFT parameter*presence of ILD). ROC analysis showed that skewness (AUC 0.897, p=0.0073) and kurtosis (AUC 0.890, p=0.010) outperformed ppTLC (AUC 0.744) in identifying ILD. Conclusions. Radiomic analysis discriminate between SSc patients with and without ILD, seemingly outperforming conventional the ppTLC assessment. The relationship between radiomics and PFTs appeared predominantly in subjects with ILD while was undetectable in those without ILD.
PO:03:036 | Psoriatic arthritis: does pre-existing treatment with cs/bDMARDs for psoriasis influence the characteristics and outcomes of joint disease?
Background. Several studies have shown that treatment of psoriasis with cs/bDMARDs reduces the risk of developing psoriatic arthritis. The aim of this study is to investigate and compare the characteristics of patients who developed psoriatic arthritis without having ever received any systemic therapy (cs/bDMARD-naïve) with those who developed it despite ongoing treatment with cs/bDMARDs (cs/bDMARD-experienced), in order to understand whether treatment differences influence the characteristics and outcomes of joint disease. Materials and Methods. This analysis represents a preliminary phase of a retrospective study conducted on a cohort of patients with psoriatic arthritis, divided into two groups based on whether or not they were receiving cs/bDMARD therapy at the onset of joint disease. For all patients, demographic (age at disease onset and at diagnosis, sex, smoking status), clinical (fibromyalgia, BMI, oligoarticular/polyarticular onset, axial involvement, dactylitis), clinimetric (DAPSA, physician VAS, patient VAS, SPARS, HAQ), and therapeutic data (use of cs/bDMARDs at disease onset, multidrug resistance) were collected and compared. Results. A total of 224 consecutive patients with psoriatic arthritis were enrolled, of whom 45 (20%) developed the disease despite ongoing cs/bDMARD therapy, while the remaining 179 (80%) developed psoriatic arthritis without having received any systemic treatment. No significant differences were observed between the two groups in terms of M/F ratio (p=0.567), age at arthritis onset (p=0.180), age at diagnosis (p=0.776), oligoarticular/polyarticular pattern (p=0.349), prevalence of axial involvement (p=0.197), radiographic damage (p=0.491), physician VAS (p=0.851) and patient VAS (p=0.340), DAPSA (p=0.585), HAQ (p=0.609), or multidrug resistance (p=0.308) (Table 1, Figure 1). A trend toward a higher prevalence of dactylitis was observed among DMARD-naïve patients compared with those receiving cs/bDMARD therapy at disease onset (38.2% vs. 25.0%, p=0.101), although this did not reach statistical significance (Table 1, Figure 1). Conclusions. Although previous studies have reported that the use of cs/bDMARDs for psoriasis may be associated with a reduced risk of developing psoriatic arthritis, among patients who develop the arthropathy despite ongoing systemic treatment, the disease pattern and outcomes do not appear to differ significantly from those of patients who have never received systemic therapy. An expansion of the present study to a larger cohort is needed to confirm these findings.
PO:04:048 | Assessment of chronic and residual pain in axial spondyloarthritis in a single-center cohort of patients treated with anti-tnf agents
Materials and Methods: Patients diagnosed with AxSpA (according to the ASAS 2009 criteria) who had been treated with anti-TNF agents for at least six months and had undergone a minimum of two outpatient visits spaced by at least six months were included. The following definitions were applied: chronic pain—VAS pain ≥40 at the last two outpatient visits at least three months apart; residual pain—VAS pain ≥20 and ASDAS <1.3 at the last visit. Collected variables included BASMI, ASDAS-CRP, patient VAS, last-week VAS (0–100), HAQ, BASFI, BASDAI, age, sex, BMI, disease duration, radiographic damage, and comorbidities. Statistical analyses were performed using Student’s t-test or Mann–Whitney test for quantitative variables and the Chi-square or Fisher’s exact test for qualitative variables. Results: A total of 264 patients were enrolled (see Table). Among them, 33 (12.5%) had residual pain and 67 (25.5%) had chronic pain. In patients with residual pain, no significant differences were observed compared with controls regarding age (52 ± 45.4 vs. 53 ± 52 years; p = 0.43), male sex (66.6% vs. 61%; p = 0.57), disease duration (14.2 vs. 14.9 years; p = 0.94), or HLA-B27 positivity (66.7% vs. 87%; p = 0.48). Residual pain was less frequent in patients with non-radiographic AxSpA (21.2% vs. 39.8%; p = 0.019) and was associated with significantly higher VAS scores (30 [20–46] vs. 10 [10–20]; p = 0.0008). No significant differences were found for BASMI, BMI, CRP, or comorbidities. In the chronic pain group, males were more represented (52% vs. 16%; p = 0.008), with later disease onset (33 vs. 29.3 years; p = 0.03) and higher HLA-B27 positivity (58% vs. 11.6%; p = 0.04). These patients showed increased values for ASDAS-CRP (2.59 vs. 0.92; p < 0.0001), BASDAI (5.8 vs. 1.5; p < 0.0001), and VAS at the last visit (50 [50–70] vs. 10 [10–10]; p < 0.001). The presence of fibromyalgia (34% vs. 7%; p < 0.001) and discopathies (61% vs. 39%; p < 0.001) was significantly associated with chronic pain. No significant differences were observed in other clinical or radiographic variables. Conclusions: Despite effective disease control with biologic therapy, patients with AxSpA may continue to experience pain, which can be classified as either chronic pain - often associated with comorbidities such as fibromyalgia or discopathies that affect pain mechanisms - or residual pain, reflecting a mismatch between perceived pain and disease activity indices (ASDAS-CRP, BASDAI) and indicating a suboptimal response to therapy. These findings highlight the need for comprehensive patient management in clinical practice, emphasizing strategies to minimize pain through accurate clinical assessment and appropriate multimodal pharmacological treatment in patients with AxSpA.
CO:07:4 | Clinical and psychosocial domains in fibromyalgia: a multidimensional questionnaire approach for personalized management. Results from an Italian monocentric study
Background. Fibromyalgia (FM) is a chronic disorder marked by widespread pain, fatigue, sleep disturbance and psychological distress. Their interplay impairs functioning, underscoring the need for multidimensional assessment to guide personalized care. Objectives are: a) examine relationships among clinical and psychosocial symptom domains using validated questionnaires; b) compare symptom severity, demographics and diagnostic delay across severity stratified groups; c) identify independent predictors of global and domain specific symptom burden. Methods. In this monocentric cross-sectional study, FM patients diagnosed according to 2016 ACR criteria between 2019-2025 completed Revised Fibromyalgia Impact Questionnaire (FIQR), Polysymptomatic Distress Scale (PDS), modified Fibromyalgia Assessment Scale (FASmod), Insomnia Severity Index (ISI), Zung Depression Scale (ZUNG), and State-Trait Anxiety Inventory (STAI-Y1). Demographic data were recorded. Spearman’s rho was used to assess correlations. Patients were stratified into severity groups based on validated cut-offs. Group differences were evaluated using Mann–Whitney U tests. Multivariable linear regression identified independent predictors of FIQR total, FIQR Physical, FIQR Symptoms and PDS scores. Results. 443 patients (97% female) were included, median age 52 years (IQR 43–58), median age at diagnosis 46 (37–52), median diagnostic delay 4 years (2–10). Median questionnaire scores indicated substantial symptom burden: FIQR total 63 (49–76), PDS 21 (18–25), FASmod 27 (23–32), ISI 17 (12–20), ZUNG 51 (45–57), STAI-Y1 56 (46–64). Severity thresholds are illustrated in Figure 1. FIQR total correlated strongly with somatic burden (PDS, =0.61), fatigue (FASmod, =0.68), insomnia (ISI, =0.54), depression (ZUNG, =0.54), and anxiety (STAI-Y1, =0.44), all p<0.0001. Depression and anxiety showed a particularly strong association (=0.72, p<0.0001). Insomnia correlated significantly with both physical and psychosocial domains (=0.39–0.58, p<0.0001). Figure 2. No significant correlations were found between questionnaire scores and demographic variables. Patients classified as high severity in one domain also exhibited significantly higher symptom scores across all other physical and psychosocial domains (p<0.0001). Longer diagnostic delays were linked to higher somatic severity and symptom onset after age 46 (p<0.05), but not with anxiety or depression severity. Multivariable models showed global impact (FIQR total) was predicted by PDS, FASmod, ISI and ZUNG (adjusted R² = 0.68); somatic severity (PDS) by FASmod and FIQR total (adjusted R² = 0.62); FIQR Physical by ISI, FASmod and PDS (adjusted R² = 0.61); FIQR Symptoms by FASmod, ZUNG, ISI and PDS (adjusted R² = 0.65). Conclusions. These findings confirm an interplay between somatic and psychosocial symptoms in FM, with insomnia as key mediator. Higher somatic burden, later onset and prolonged diagnostic delay underscore the need for earlier recognition and profiling. Although mood disturbances correlate with symptom severity, they do not affect diagnostic timing. Targeted interventions for fatigue, insomnia and somatic symptoms enhance outcomes.
PO:04:051 | Application of REMS in the assessment of fragility score and bone mineral density in axial spondyloarthritis and psoriatic arthritis with axial involvement
Background. Axial spondyloarthritis (axSpA) and axial psoriatic arthritis (axPsA) are known to differ in imaging features (radiography and magnetic resonance imaging) and treatment response. These conditions may also present differences in bone mass quality and bone mineral density (BMD). Radiofrequency Echographic Multi Spectrometry (REMS) is an emerging technique for bone assessment that analyzes raw, unfiltered ultrasound signals acquired during scanning of the lumbar spine and proximal femur. Unlike conventional DXA, REMS minimizes artifacts from ectopic calcifications such as syndesmophytes and osteophytes, commonly observed in these diseases. This study aimed to compare T-scores obtained with REMS and DXA to evaluate REMS reliability in assessing BMD in axSpA and axPsA, and to explore qualitative and quantitative differences in bone mass between these patient cohorts. Materials and methods. Adult patients admitted to the Rheumatology Unit of AOU Senese and Florence Careggi were included. Participants had a confirmed diagnosis of axSpA or axPsA and were receiving treatment with biological disease-modifying antirheumatic drugs (bDMARDs) or Janus kinase inhibitors (JAKi). Patients with a prior diagnosis of osteoporosis, ongoing osteoporosis treatment or previous vertebral fractures were excluded. All patients underwent lumbar spine and femoral DXA as well as REMS scans in the same anatomical sites. BMD and Fragility Score were compared between groups. A variable (Δ) was defined as the difference between REMS and DXA T-scores at the lumbar spine and femur. Results. Twenty-five patients were enrolled (13 axSpA; 12 axPsA) with comparable age and sex distribution. No significant differences in Δ T-scores at the lumbar spine and femur were observed compared to the general population. Concordance between REMS and DXA T-scores was assessed in relation to diagnosis (axSpA vs PsA), BMI and age. For the lumbar spine, T-score concordance was not statistically significant (p = 0.606); whereas femoral measurements showed significant concordance (p = 0.003), although the intraclass correlation coefficient (ICC) was below an acceptable range. No significant Δ differences were observed according to diagnosis or BMI at either site. A negative correlation between age and femoral Δ was noted (p = 0.02). Conclusions. Consistent with limited existing literature, REMS demonstrates potential reliability for qualitative and quantitative assessment of bone mass in patients with axSpA and axPsA at the lumbar spine. Regarding the femur, REMS-DXA concordance did not show significant differences, highlighting the need for further validation in larger cohorts.
CO:07:5 | Enhanced fibroblast signatures in females with early rheumatoid arthritis highlights a potential basis for poorer treatment outcomes
Background. To investigate whether 1) cellular and molecular characteristics of synovial tissue (ST) differ between sexes in early, treatment-naïve rheumatoid arthritis (RA) at baseline and 6 months; 2) treatment modulates synovial histopathology and molecular signatures differently in males and females. Methods. 202 early RA patients [142 females (70%), 60 males (30%)] enrolled in the Pathobiology of Early Arthritis Cohort (PEAC) who met the 2010 ACR/EULAR classification criteria were analyzed. Clinical and laboratory data, and ultrasound-guided synovial biopsies of active joints were collected at baseline and 6 months. Histological analysis included Krenn synovitis scoring and immunohistochemistry for macrophages, T, B and plasma cells. Based on published criteria, three synovial pathotypes were identified [1]. RNA-seq was performed on ST samples, followed by differential gene expression analysis with DESeq package and cell-type deconvolution via MCP-counter. Adjusted p<0.05 was considered significant. Results. At baseline, a higher proportion of males showed Diffuse-Myeloid (DM) and Lympho-Myeloid (LM) pathotypes (45% and 41%) compared to females (39% and 38%), while the Fibroid (F) pathotype was more prevalent in females (23% vs 14%). Median synovitis scores were higher in males [4.5 (2.8-6)] than female [3 (2-5), p=0.073]. LM pathotype and high Krenn scores were more common in small joints in males than females (LM 38% vs 16%, p=0.0291; Krenn 5-9 50% vs 10%, p=0.005), while in large joints were more prevalent in females (LM 74% vs 14%, Krenn 5-9 70% vs 14%, p<0.001), suggesting a preferential articular involvement. Thirty-two genes were differentially expressed at baseline (1 upregulated in females, 31 in males); several male-upregulated genes (UTY, KDM5D, RPS4Y1, USP9Y, DDX3Y, EIF1AY) correlated with immune cell infiltration and tended to be more expressed in ST with high Krenn score and LM pathotype. At 6 months, females showed a smaller reduction in SJC and fewer reached a EULAR-CRP good response, despite more aggressive treatments (Figure 1A). Improvement in Krenn score was more frequent in males (74% vs 58%). After treatment, 546 genes were differentially expressed (88 upregulated in females, 458 in males). Pathways related to extracellular matrix, angiogenesis and epithelial-to-mesenchymal transition were enriched in females (Figure 1B). Fibroblast-related genes (POSTN, HAPLN1, FGFR3) were significantly upregulated in females and overexpressed in the F pathotype. MCP-counter analysis confirmed increased fibroblast abundance in females (p=0.012) (Figure 1C). Conclusions: Molecular profiling revealed sex-specific disease mechanisms, with enhanced fibroblast and matrix remodelling signatures in females, suggesting that fibroblast activity—previously associated with poor therapeutic response [2] and treatment refractoriness [3]—may contribute to reduced treatment efficacy. Further studies are needed to directly assess the mechanism linking fibroblast signatures and therapeutic response in females. References p]:pt-0 [&>p]:mb-2 [&>p]:my-0"> Humby F, Lewis M, Ramamoorthi N, Hackney JA, Barnes MR, Bombardieri M, et al. Synovial cellular and molecular signatures stratify clinical response to csDMARD therapy and predict radiographic progression in early rheumatoid arthritis patients. Ann Rheum Dis. 2019;78(6):761-72. p]:pt-0 [&>p]:mb-2 [&>p]:my-0"> Nerviani A, Di Cicco M, Mahto A, Lliso-Ribera G, Rivellese F, Thorborn G, et al. A pauci-immune synovial pathotype predicts inadequate response to TNFα-blockade in rheumatoid arthritis patients. Front Immunol. 2020;11:845. p]:pt-0 [&>p]:mb-2 [&>p]:my-0"> Rivellese F, Humby F, Bugatti S, Fossati S, Girotto G, et al. B cell synovitis and clinical phenotypes in rheumatoid arthritis: relationship to disease stages and B cell targeted therapy. Nat Med. 2022;28(9):2041-2052.
PO:04:054 | Clinical efficacy and drug retention rate of upadacitinib in patients with axial spondyloarthritis: results from a single-center observational study
Background. This single-center study aimed to evaluate the clinical efficacy of upadacitinib (UPA) in patients with axial spondyloarthritis (axSpA) and to assess its long-term treatment persistence. A secondary objective was to identify potential predictors of treatment persistence with UPA. Materials and Methods. All adult patients diagnosed with axSpA and treated with UPA for at least six months were included. Clinical data were retrospectively collected at baseline and after 3, 6, and 12 months of therapy. Outcome measures included changes in disease activity assessed by ASDAS-CRP and BASDAI, pain intensity evaluated using a visual analogue scale (VAS), and functional limitation measured with the BASFI. The UPA drug retention rate (DRR) at 18 months was estimated using Kaplan–Meier survival analysis, and the influence of potential modifying factors was assessed using the log-rank test. Results. A total of 49 patients (35 F, 14 M) with a mean ± SD age at baseline of 50.3 ± 12.7 years were included. Median (IQR) baseline values were: ASDAS-CRP = 3.2 (1.2), BASDAI = 6.5 (3.2), BASFI = 4.1 (3.2), and VAS-pain = 7.0 (3.0). From month 3 onward, there was a statistically significant reduction in median ASDAS-CRP (p < 0.01), BASDAI (p < 0.01), BASFI (p = 0.047), ESR (p = 0.02), and VAS-pain (p < 0.01). At month 6, further decreases were observed in ESR (p < 0.01), ASDAS-CRP (p < 0.01), BASDAI (p < 0.01), and BASFI (p = 0.02). A significant improvement in BASFI (p < 0.01) was also recorded between months 6 and 12, while the other parameters reached a plateau (Fig. 1). At the last follow-up, 85.4% of patients remained on UPA therapy; seven patients had discontinued treatment (n = 1 primary inefficacy; n = 5 adverse events). The UPA DRR at 6, 12, and 18 months was 95.5%, 85%, and 81.3%, respectively (Fig. 2). Sex (p = 0.32), BMI (p = 0.07), radiographic SpA (p = 0.88), prior bDMARDs use (p = 0.54), and fibromyalgia (p = 0.08) did not significantly affect treatment persistence. Conclusions. This study confirms the efficacy of upadacitinib in achieving a rapid reduction in disease activity and pain among patients with axSpA, with significant improvements detectable from month 3 and progressive enhancement of functional capacity up to month 12. The observed DRR indicates sustained long-term effectiveness and a favorable tolerability profile, which appear to be independent of sex, BMI, treatment line, or coexisting fibromyalgia.
PO:04:056 | Willingness of patients with psoriatic arthritis to participate in pharmacological and nutritional clinical trials: a cross-sectional study
Background. Psoriatic arthritis (PsA) is a chronic inflammatory disease that significantly affects patients’ quality of life. Clinical trials are fundamental tools for improving therapeutic strategies and disease management; high patient adherence is desirable to reduce selection bias and ensure the generalizability of the results. However, data regarding patients’ willingness to participate in pharmacological and nutritional interventional studies are currently limited. The aim of this study is to evaluate the willingness of patients with PsA to participate in pharmacological and nutritional clinical trials, and to identify clinical and demographic factors potentially associated with such willingness. Materials and Methods. A cross-sectional, non-profit survey was conducted using a structured questionnaire administered consecutively to patients attending the rheumatology clinic between October 31, 2024 and January 7, 2025. For each participant, demographic data (sex, age, education level, body mass index [BMI]) and clinical data (disease duration, disease activity, current therapy, and comorbidities) were collected. Descriptive analysis was used to characterize the cohort. Results. A total of 225 patients with PsA were enrolled, with a mean age of 57.68 years (range: 28–85). The sample included 96 female participants (42.6%), with a mean BMI of 25.81. The median disease duration was 14 years; 94.2% of patients had disease activity ranging from remission to low activity. The main results are shown in Figure 1. Overall, 186 patients (82.7%) expressed willingness to participate in clinical studies; among these, 129 (57.3%) were willing to take part in both pharmacological and nutritional trials, while 45 patients (20%) reported willingness to participate exclusively in nutritional studies. Chi-square analysis did not reveal statistically significant associations between sex, BMI, education level, disease duration, and willingness to participate (p > 0.05 for all variables analyzed). Conclusions. Patients with PsA showed a greater inclination to participate in dietary intervention studies compared to pharmacological ones. This attitude was not significantly associated with sex, education level, BMI, disease duration, or disease activity. However, further studies with larger samples are needed to confirm these preliminary findings and to better explore the determinants of participation willingness in different patient subgroups. These results highlight the importance of personalized recruitment strategies, tailored to patients’ therapeutic and behavioral interests, in order to optimize enrollment and promote heterogeneous representation within clinical trials.
PO:04:061 | Higher prevalence of baseline comorbidities in patients developing difficult to treat psoriatic arthritis
Background. To evaluate baseline comorbidities as influencing factors for Difficult to Treat Psoriatic Arthritis (D2T-PsA) onset. Methods. This is a retrospective case-control study, on PsA patients who had started their first bDMARD from September 2023 to May 2024 (T1). Those who had completed 1 year of continuous b/tsDMARDs therapy (T2) were enrolled. Demographic and clinical data were collected (Table 1) referred to T1, joint ultrasound (US) was performed at both evaluations. At T2, patients were divided in 2 groups: 1) D2T-PsA: according to Lubrano et al. with strictly inflammatory signs of active PsA (i.e. ultrasound-proven enthesitis/synovitis/tenosynovitis); 2) low disease activity (LDA): DAPSA<14, no ultrasound signs of active PsA. Descriptive statistics, Chi-square test, and Student’s t-test were used to compare baseline characteristics between groups. Logistic regression was used to estimate odds ratios for the association between baseline variables and D2T-PsA. Results. Out of 224 patients enrolled, 168 (75.0%) and 54 (25%) were included in the LDA and D2T-PsA groups respectively. No significant differences were found in demographic characteristics between groups at T1. On the other hand, several baseline features and comorbidities appeared associated with 1 year incidence of D2T-PsA. Namely: smoking habit (p<0.001), presence of uveitis (p=0.01), dactylitis (p=0.03), axial disease (p<0.001), US proven bone erosions (p=0.03) and non-alcoholic fatty liver disease (NAFLD, p<0.001). Similarly, baseline number of swollen joints was associated to D2T-PsA development (p=0.04), while HAQ and VAS pain resulted higher in those achieving LDA at T2 (p=0.01 and 0.04, respectively). Furthermore, presence of different clinical features and comorbidities at T1 were associated with higher odds of developing D2T-PsA after 5 years (Table 2); including: smoking habit, HLA-B27, uveitis, enthesitis, axial disease, bone erosions at US and NAFLD. No significant relation was found for the other variables, including disease activity parameters. Conclusions. Here, we have evaluated how basal clinical characteristics and comorbidities may influence the development of inflammatory-driven D2T-PsA. Reported data show how peculiar PsA features – pre-existing to bDMARD administration – are more prevalent in those that will develop D2T-PsA. Likewise, their presence also increases the odds of developing D2T-PsA. D2T-PsA represents a highly burdening condition, where inflammatory-driven forms are difficult to distinguish and manage correctly. In this context, as highlighted by recent publications from GRAPPA, pre-existing clinical conditions may reduce treatment response. Hence, understanding how they may influence D2T development is pivotal. While additional data are needed to understand how baseline features may influence therapy failure, from presented data it is possible to speculate that the baseline burden of PsA might be influential in its future development. References - Singla S et al. RMD Open 2024;10:e003809 - Chimenti MS et al. Biologics. 2020 Aug 20;14:53-75. - Lubrano E et al Rheumatol Ther 2023;10:1119–25
CO:08:2 | Impact of comorbidities on clinical-serological phenotype of primary Sjögren's disease: a retrospective analysis of a multicenter cohort
Background. Primary Sjögren's disease (SjD) is characterized by significant phenotypic heterogeneity frequently associated with other autoimmune diseases or different comorbidities, which influence clinical course, phenotypic expression, quality of life and therapeutic approach. However, their clinical relevance is underestimated. We evaluated clinical and laboratory differences at diagnosis in SjD patients stratified according to presence or absence of concomitant autoimmune diseases and selected comorbidities, in order to outline their impact on clinical phenotype. Methods: A multi-center SjD chort was retrospectively analyzed. Clinical-demographic characteristics, disease activity by ESSDAI, dryness, pain and fatigue degree by ESSPRI and serological variables were collected at diagnosis. Traditional cardiovascular (CV) risk factors were recorded as cumulative data. For study aim, the following comorbidities were considered as cumulative parameter at the last follow-up: fibromyalgia, autoimmune thyroiditis, non-hematologic cancers, primary biliary cholangitis (PBC), celiac disease (CD) and history of severe infections. Results. 1231 SjD patients were included. Patients with fibromyalgia (132/1231, 10.7%) were characterized by younger age at diagnosis (mean 49.7 vs. 52.1 years, p=0.048), lower ESSDAI (2.04 vs. 3.52, p=0.029), higher ESSPRI (6.9 vs. 5.1, p=0.000), higher frequency of obesity (p=0.009) and lower anti-Ro (p=0.049), anti-La (p=0.016) and rheumatoid factor prevalence (p=0.000). Patients with autoimmune thyroiditis (263/1231, 21.4%) had higher age at diagnosis (mean 52.3 vs. 50 years, p=0.031), higher ESSDAI (4.12 vs. 3.15, p=0.034) and higher frequency of anti-Ro52 and Ro60 (p=0.01 and p=0.03, respectively), a serological finding also observed in patients with PBC (26/1231, 2.1%) (anti-Ro 52, p=0.02; anti-Ro60, p=0.000). Patients with CD (27/1231, 2.2%) were younger (mean 43 vs. 52 years, p=0.002) and had higher prevalence of anti-Ro52 (p=0.039) and Ro60 (p=0.025). Patients with history of non-hematologic cancers (98/1231, 8%) were older at diagnosis (mean 55 vs. 51 years, p=0.017) and characterized by higher prevalence of hypertension (p=0.000) and history of severe infections (p=0.022). Patients with history of severe infections (45/1231, 3.6%) had higher frequency of extraglandular involvement and higher prevalence of anti-Ro60 (p=0.005), hypertension (p=0.02) and hypercholesterolemia (p=0.002). Conclusions. Comorbidities may significantly influence clinical and immunological phenotype of SjD. The study allowed to identify three distinct phenotypes at diagnosis. Patients with fibromyalgia are characterized by higher prevalence of subjective symptoms but lower disease activity and reduced antibody positivity. In contrast, patients with concomitant autoimmune diseases show higher antibody positivity and greater disease activity. Non-hematologic cancers and history of severe infections identify subgroups characterized by greater systemic involvement, older age and a higher prevalence of CV comorbidities. Early identification of specific comorbidities can be useful for prognostic stratification and personalized follow-up pathways.
PO:05:066 | Atypical diagnosis and manifestation of spondyloarthritis: a case report
Background. The aim of this case report is to illustrate how the initially most likely diagnosis is not always the correct one. Case report. A 57-year-old woman, with an unremarkable past medical history, presented to our attention following ophthalmologic referral after a first episode of acute non-granulomatous unilateral anterior uveitis, associated with arthralgias involving the shoulder and knee girdles, and prolonged morning stiffness (90 minutes). She denied previous episodes of arthritis, RS3PE, headache, transient visual loss, diplopia, scalp dysesthesias, enthesitis, dactylitis, or inflammatory low back pain. There was no personal or family history of psoriasis or inflammatory bowel disease. Based on laboratory findings (elevated nonspecific inflammatory markers), clinical presentation (EUL 3/3 with painful arc and prolonged stiffness), and ultrasound evidence (bilateral subacromial–subdeltoid bursitis with long head biceps tenosynovitis, knee and shoulder synovitis), a diagnosis of polymyalgia rheumatica (PMR) was initially made. Treatment with tapering prednisone (starting at 12.5 mg/day) was initiated, with an excellent initial response. At subsequent visits, the patient reported recurrence of symptoms at prednisone doses below 7.5 mg/day, leading to the addition of methotrexate 15 mg/week as a corticosteroid-sparing agent. Due to poor clinical response and frequent need for NSAIDs to control symptoms, a repeat joint ultrasound was performed, confirming previous findings and revealing polyenthesitis (involving subscapularis, supraspinatus, and distal patellar tendons) with bilateral microerosions. Laboratory testing showed positivity for HLA-B27. In light of these new findings, the diagnosis was revised to HLA-B27–positive peripheral spondyloarthritis with a polymyalgia-like onset, and anti–TNFα therapy (adalimumab) was initiated. Over the following months, progressive loss of drug efficacy was observed, with new-onset inflammatory pain involving the cervical spine and anterior chest wall, exacerbated by inspiration. MRI revealed bilateral sternoclavicular synovitis and inflammatory involvement of the manubriosternal junction and interspinous ligament from C7 to D1. Based on these findings, the diagnosis was further revised to combined axial and peripheral HLA-B27–positive spondyloarthritis, complicated by acute non-granulomatous anterior uveitis. The patient was switched to a second anti–TNFα agent (certolizumab), achieving good clinical response and stable remission. Conclusions. This case highlights the importance of a broad and dynamic diagnostic approach, even in the presence of clinical pictures apparently consistent with common conditions such as PMR. The polymyalgia-like onset represented a diagnostic challenge, which was overcome only through close follow-up, targeted joint imaging, and immunogenetic assessment. Spondyloarthritis may present with atypical phenotypes, mimicking other rheumatologic diseases. Therefore, meticulous attention to clinical and instrumental details is essential to avoid diagnostic delays and ensure timely initiation of appropriate treatment.
PO:05:069 | Risankizumab efficacy in peripheral and axial involvement: monocentric experience
Risankizumab, an anti–IL-23 monoclonal antibody, is approved for the treatment of peripheral psoriatic arthritis (PsA), and increasing evidence suggests its potential efficacy in patients with concurrent axial involvement. This study presents a preliminary monocentric real-world experience on the use of risankizumab in PsA, with clinical follow-up over six months of treatment. 34 patients with PsA treated with risankizumab at our center were included in this study. Of these, 18 had peripheral involvement only, while 16 presented both peripheral and axial involvement. Clinical assessments included DAPSA for peripheral disease, ASDAS-CRP and modified BASDAI (mBASDAI) for axial involvement. Patients were further stratified by treatment line (naïve to fourth-line) and therapy regimen (monotherapy vs. combination with methotrexate). The aim was to evaluate the evolution of clinical parameters over the course of treatment. Moreover, MRI was used to assess sacroiliac joint inflammation in patients with axial involvement. At baseline (T0), all patients underwent clinical evaluation using DAPSA, ASDAS-CRP, and mBASDAI scores, with regular follow-up assessments over six months (T6). Among the 16 patients with both peripheral and axial involvement, there was a marked improvement in ASDAS-CRP and mBASDAI scores, indicating a beneficial effect of risankizumab in reducing both axial and peripheral symptoms, as shown in the graphs. Regarding treatment lines, 8.8% of patients were treatment-naïve, while 58.8% received risankizumab as second-line, 20.6% as third-line, and 8.8% as fourth-line therapy. Risankizumab was administered in combination with methotrexate (MTX) in 70% of cases, and as monotherapy in 30%, demonstrating efficacy across both treatment regimens, including in patients with prior biologic exposure. As a representative case, MRI images from a 50-year-old female with axial PsA are included, showing marked improvement after six months of risankizumab. Our findings are consistent with current literature supporting the efficacy of risankizumab in peripheral PsA, while also offering new insights into its potential benefits for patients with concurrent axial involvement. This therapeutic effect may be attributed to the distinct pathophysiology of axial PsA (axPsA) compared to ankylosing spondylitis (AS). According to McGonagle et al., axPsA is primarily driven by ligament-centered inflammation, in contrast to the deep bone inflammation of AS. This anatomical and immunological distinction provides a mechanistic rationale for the observed clinical efficacy of IL-23 inhibitors in axPsA—despite their failure in AS—by targeting soft tissue immune responses more responsive to IL-23 modulation. Our center’s experience confirms the efficacy of risankizumab not only in peripheral PsA but also in patients with axial PsA (axPsA), showed in clinical and clinimetric indices improvement. These findings contribute valuable real-world data to the growing body of evidence supporting the therapeutic potential of risankizumab in PsA, including cases with axial involvement.
CO:08:4 | Paraproteinemias in Sjögren’s disease: cryoglobulinemia and monoclonal component define distinct phenotypes with a synergistic lymphoproliferative risk
Background. A distinctive feature of Sjögren’s disease (SjD) is the persistent activation of B lymphocytes, which may progress to lymphoma development, particularly of the MALT type. The presence of cryoglobulinemia (CRYO) and circulating monoclonal component (MC) represent two manifestations of B-cell hyperactivity and are recognized risk factors for lymphoproliferative evolution. However, it remains unclear whether CRYO and MC identify distinct clinical phenotypes. Objective. To assess whether CRYO, MC, or their combination define different SjD phenotypes in terms of disease activity (ClinESSDAI) and lymphoproliferative risk. Materials and Methods. This retrospective, multicenter study included patients enrolled by Italian centers of the GRISS (Italian Sjögren's Disease Research Group), who met the 2016 ACR/EULAR classification criteria. Patients were divided into four groups: (a) isolated MC, (b) isolated CRYO, (c) CRYO+MC, and (d) none of the above (controls). The following markers associated with increased risk of lymphoproliferative evolution were analyzed: rheumatoid factor (RF), low C4 levels, anti-La/SSB positivity, salivary gland swelling, lymphopenia, and lymph node enlargement. Disease activity was assessed based on the presence of one or more ClinESSDAI domains. Finally, the prevalence of lymphoma was evaluated across the four groups. The prevalence of risk indicators, lymphoma, and ClinESSDAI domains was analyzed for each group. Differences among groups were calculated using Fisher’s exact test, Kruskal–Wallis, and Chi-square tests. Results. A total of 1202 patients were included: 58 (4.8%) in the MC group, 32 (2.6%) in the CRYO group, 35 (2.9%) in the CRYO+MC group, and 1077 (89.7%) controls. The CRYO+MC and CRYO groups showed a significantly higher prevalence of the following lymphoproliferation-related markers: RF, low C4, anti-La, and lymph node enlargement. Salivary gland swelling and lymphopenia were more frequent only in the CRYO+MC group. [Table 1] Regarding ClinESSDAI domains, the CRYO+MC and CRYO groups exhibited a significantly higher prevalence of constitutional, cutaneous (due to purpura), renal, and peripheral nervous system (PNS) domains. Haematologic and lymphoadenopathy domains, as well as the diagnosis of lymphoma, were more frequent in the CRYO+MC group. [Table 2] Conclusions. CRYO, either isolated or associated with MC, is a marker of enhanced B-cell activity (RF, low C4, anti-La, lymph node enlargement) and predominantly affects ClinESSDAI domains consistent with a vasculitic phenotype (constitutional, cutaneous, renal, and PNS). Markers of lymphoproliferation, such as salivary gland swelling, lymphopenia, lymphoadenopathy domain involvement, and lymphoma diagnosis, are more frequent in patients with CRYO+MC. These findings suggest that the CRYO+MC combination represents the true marker of lymphoproliferative activity, conferring a significantly higher risk of lymphoma development compared with CRYO alone, and even more so compared with isolated MC.
CO:08:5 | Clinical impact of anti-Ro52 antibodies in idiopathic inflammatory myopathies: insights from a multicenter Italian cohort
Background. Anti-Ro52 antibodies are frequently found in idiopathic inflammatory myopathies (IIM), with a prevalence up to 30%, and are strongly associated with antisynthetase syndrome (ASyS), interstitial lung disease (ILD), and dysphagia (1;2;3). Their co-occurrence especially with anti-Jo1 or anti-MDA5, have been linked to more severe disease, including rapidly progressive ILD (1). However, they do not always correlate with worse prognosis (4). This study aimed to assess the clinical relevance of anti-Ro52 in IIM, focusing on disease phenotype and systemic involvement. Methods. This multicenter study (five Italian centers) included all patients with IIM positive for anti-Ro52 and/or myositis-specific antibodies (MSA). Patients were stratified into three groups: isolated anti-Ro52, anti-Ro52+MSA, and MSA-only. Clinical and laboratory features were collected, with emphasis on pulmonary involvement assessed by pulmonary function tests (PFTs) and high-resolution CT. Results. A total of 242 patients were included (median age: 63 years, IQR 53.75-73; median disease duration: 5 years, IQR 3-12; median follow-up: 60 months, IQR 25-120). Ro52+MSA patients showed the highest prevalence of antisynthetase syndrome (p<0.001). Baseline median DLCO was lower in Ro52+MSA (65%, IQR 54–74) than in Ro52-only (73%; IQR 62–78), and MSA (75.5%; IQR 68–84) patients. DLCO and DLCO/VA remained consistently lower in Ro52+MSA. Significant differences were observed at multiple timepoints between Ro52+MSA and the other groups for DLCO and DLCO/VA. FVC did not differ significantly, though lower medians were seen in Ro52+MSA patients (Table 1-2). ILD and dyspnoea were more frequent in Ro52+MSA (61.7% and 47.6%, respectively; p < 0.001 and p = 0.010). Arthritis showed a borderline difference (p = 0.050), with lower prevalence in Ro52-only patients. Myositis and peak CPK levels were statistically less frequent in Ro52-only patients. Raynaud’s phenomenon was not observed in Ro52-only cases (p = 0.002). ESR was higher in Ro52+MSA patients (p = 0.024), while no differences in CRP were observed. Cutaneous features varied: Gottron’s papules and mechanic’s hands were strongly associated with Ro52+MSA patients (p < 0.001), while periungual telangiectasias were more common in Ro52-positive individuals, especially in those with isolated Ro52. Conversely, sclerodactyly and puffy hands were more commonly seen in MSA patients (p < 0.001). Conclusions. Anti-Ro52 positivity, especially with MSA, defines a distinct IIM phenotype characterized by ILD, elevated ESR, and specific cutaneous features. The increased ILD prevalence in Ro52+MSA may relate to the higher frequency of antisynthetase syndrome and possible co-occurance with anti-Jo1, though subgroup analysis was limited by small numbers. The low number of isolated anti-Ro52 patients also limits comparisons, supporting the need for further studies in larger cohorts. References 1. Allameen NA, Lai YW, Lian G, Lee TZ, Selvakumaran S, Tan RYT, Xu C. Physiotherapy and occupational therapy in rheumatoid arthritis: Bridging functional and comorbidity gaps. Best Pract Res Clin Rheumatol. 2025;39(1):102032. 2. Decker MR, Grace KT, Holliday CN, Bevilacqua KG, Gottlieb A, Black MC. Safe and stable housing for intimate partner violence survivors: A framework for policy and practice. Am J Public Health. 2022;112(7):1012-1020. 3. Valle AR, Zuntini AR, Smith SA, Vasconcelos TNC, Barnes RW, et al. Phylogenomics and the rise of the angiosperms. Nature. 2024;616(7981):785-791. 4. Pepper AE, Liu X, Ciannamea S, Xu DL, et al. Immune receptor mimicking hormone receptors: a new paradigm in plant biology. Stress Biol. 2023;3(1):14.
PO:05:074 | A clinical case of a patient affected by long-standing psoriatic arthritis and multiple comorbidities treated with an anti-IL-23 therapy
Background. We describe the case of a patient affected by long-standing psoriatic arthritis, multiple joint deformities, and erythrodermic psoriasis, who was treated with an anti-IL-23 agent as first-line therapy. Materials and Methods. A 58-year-old patient, living below the poverty line, unemployed since the onset of joint symptoms, underweight (BMI 14.9 kg/m²), smoker (20 pack-years), with previous HBV and HCV infections, affected by chronic kidney disease (stage II) and depressive syndrome, presented to our clinic in March 2024 because of multiple joint pain and swelling, functional limitations, erythema, and desquamation involving the entire body surface. He reported that he had never been treated until then. Results. Physical examination and clinometric evaluation showed a PASI score of 39.2 and a DAPSA score of 55.9. Laboratory tests revealed red blood cells 3,180,000/mm³, hemoglobin 9.7 g/dL, white blood cells 15,800/mm³, neutrophils 74%, lymphocytes 16%, platelets 737,000/mm³, creatinine 1.8 mg/dL, uric acid 8.3 mg/dL, ESR 120 mm/h, and CRP 7.9 mg/dL. Radiographs of the hands and feet showed multiple deformities (ankylosis, erosions, and bone proliferation). A diagnosis of long-standing polyarticular psoriatic arthritis, erythrodermic psoriasis, and probable reactive thrombocytosis was made. In April 2024, lamivudine prophylaxis was started to prevent HBV reactivation, and in June 2024, therapy with an anti-IL-23 drug was initiated. At the follow-up visit in September 2024, the patient reported improvement in osteoarticular and cutaneous symptoms; clinometric indexes showed PASI 28.6 and DAPSA 24.6. Laboratory tests revealed white blood cells 9.0 × 10³/μL, neutrophils 50.5%, lymphocytes 33.2%, red blood cells 3.13 × 10 /μL, hemoglobin 10.8 g/dL, platelets 530 × 10³/μL, creatinine 1.40 mg/dL, uric acid 6.1 mg/dL, CRP 3.6 mg/dL, and ESR 113 mm/h. During follow-up, the clinical picture remained stable, without viral reactivation, new infections, worsening of renal involvement, and with improvement in depressive symptoms. Conclusions. The clinical case we present shows the efficacy and safety of anti-IL-23 therapy in a patient with long-standing disease and multiple comorbidities.
CO:08:6 | Prevalence, incidence and survival in interstitial lung disease secondary to primary Sjögren’s syndrome. Results from the “EMERGE” longitudinal study
Background. Interstitial lung disease (ILD) is a severe pulmonary complication of primary Sjögren’s syndrome (pSS), but its prevalence, natural history and survival are not completely understood. Our study aimed to investigate prevalence, incidence, and impact on survival of ILD in a cohort of unselected consecutive pSS patients. We furtherly aimed to identify clinical and serological features associated with ILD, to characterize radiological findings, and to evaluate potential prognostic factors for death. Methods. All consecutive pSS patients referred to our centre were enrolled in the study. In patients without ILD, a careful assessment for respiratory symptoms and velcro crackles was performed at enrolment and every six months. High resolution computed tomography (HRCT) was requested in case of new-onset dyspnoea, persistent dry cough, or detection of velcro crackles. Results. We enrolled 257 pSS patients, 233 females and 24 males. Mean age at enrolment was 64.8 ± 12.6 years, with a pSS duration of 83.9±78 months. At enrolment, ILD was detected in 61/257 patients with a prevalence of 23.7%. During a mean follow-up of 42.6±14.6 months, 3 new cases of ILD were recorded, with an incidence of 0.41 new cases for 100 patients/year. In a model including sex, age at pSS diagnosis, erythro-sedimentation rate (ERS), antinuclear antibodies, sicca syndrome, and smoking habit, multivariate analysis showed a direct association between ILD and male sex, age at pSS diagnosis, and ESR>40 mmh, and an inverse correlation with sicca syndrome. A nonspecific interstitial pneumonia (NSIP) was detected in 40.6% of cases, usual interstitial pneumonia (UIP) in 31.3%, organizing pneumonia in 3.1%, lymphocytic interstitial pneumonia in 18.8%, and indeterminate patterns in 6.3%. During the follow-up, 21 patients (8.2%) died. A statistically significant difference was recorded between the overall survival of patients without (88.4%±5.5) and with ILD (66.5%±11.7) (p<0.001). The estimated mean survival time was 53.4±1.7 and 60.8±0.6 months, respectively for ILD and non-ILD groups (p<0.001). A fibrotic pattern was associated to a worse survival rate, while no difference was observed between UIP and NSIP patterns, with a survival rate of 48.0%±3.8 and 51.9%±2.3 for UIP, respectively (p=0.19), Anti-SSA antibody was a protective factor for death (HR 0.19; CI95% 0.04-0.87; p=0.03), while the age at diagnosis of pSS (HR 1.09; 1.02-1.17; p=0.01), and the extent of ILD at HRCT (HR 1.06; 1.02-1.10; p=0.001) were directly associated to an increased risk of death. Radiologic ILD pattern didn’t affect the prognosis of pSS-ILD patients. Conclusions. In pSS, ILD can be identified in a high number of patients, and its severity significantly influences the prognosis of the disease. Of interest, radiologic ILD patterns didn’t influence the risk of death; therefore, a careful monitoring, within a multidisciplinary team, should be ensured to all pSS-ILD patients
PO:06:078 | Is difficult-to-treat rheumatoid arthritis less severe in patients with autoantibody-negative disease? retrospective analysis from a monocentric cohort.
Background. Patients with rheumatoid arthritis (RA) are at higher risk of radiographic progression, joint damage, disability, and extraarticular manifestations when autoantibodies – such as rheumatoid factor (RF) and anti-citrullinated peptide antibodies (ACPA) are presents. Moreover, most of RA cohorts report an association between autoantibodies and polyrefractory – or difficult-to-treat (D2T) disease. However, at the moment, no data evaluated whether autoantibody-negative D2T is actually less severe than its seropositive counterpart. Methods. Data were retrieved from a cohort of RA patients under targeted-therapy [Turin Targeted-Therapies clinic (TTT), n=636], followed from the year 2000 onwards. D2T disease was defined according to the European Alliance of Associations for Rheumatology (EULAR) criteria; patients who interrupted drugs for safety/adverse events were excluded. Time-to-develop the D2T state (defined as the difference between disease onset and the time point when fulfilling the D2T criteria) was stratified for autoantibody status by Mann-Whitney U analysis. Also, disease activity state, joint deformities, extraarticular manifestations, the number of swollen joints on 28 evaluated (SJC28), the number of tender joints on 28 evaluated (TJC28), pain expressed by a visual analogue scale (VAS), the health assessment questionnaire (HAQ), and other patient reported outcomes were evaluated at the D2T time point both in seropositive and -negative patients by multivariate linear logistic regression or Mann-Whitney U test, as appropriate. Results. From the original cohort, 189/636 (30%) interrupted at least two targeted therapies, and 132/636 (21%) fulfilled EULAR D2T criteria, 100 of them (76%) with seropositive RA. Time-to-achieve the D2T state was significantly shorter in seronegative vs. seropositive patients (mean Rank 58.89 for seronegative vs. 77.04 for seropositive; p=0.024). At the D2T-time point, patients with autoantibody-positive RA had more extraarticular manifestations [OR (95% CI) of 8.64 (1.08-69.04); p=0.042], joint deformities [OR (95% CI) of 2.842 (1.11-7.29); p=0.030], and a higher number of SJC28 (p<0.001), compared to seronegative ones. On the opposite, in face of a similar DAS28 and grade of disability expressed by the HAQ (p=ns), autoantibody-negative RA patients showed higher values of VAS pain (p=0.006), patient global assessment (PGA) (p<0.001), ad morning stiffness (p=0.009). Conclusions. D2T disease is similarly impactful in autoantibody-positive and -negative patients with RA. Despite a lower number of swollen joints, deformities and extraarticular features, patients with autoantibody-negative D2T RA are burdened by worst patients reported outcomes, suffering from much pain and morning stiffness. Strategies aimed to reduce the symptomatic burden of RA in seronegative patients are urgently needed.
CO:09:1 | The impact of sex and gender on fibromyalgia syndrome: data from the Italian Fibromyalgia Registry
Background. Studies have shown that the majority of fibromyalgia (FM) patients are women, with an average global female-to-male ratio of 3:1. Although differences in the perception, description, and expression of pain between sexes have been documented, the impact of sex and gender on FM disease severity and burden remains controversial. Moreover, despite the availability of various disease severity measures, the potential occurrence of gender-related differential item functioning (DIF) within these questionnaires has not been explored. Consequently, it is unclear whether these tools are equally sensitive in both men and women with FM. The primary aim of this study was to assess potential sex differences in disease severity using data from a web-based FM patient registry. The secondary aim was to investigate the presence of gender-related DIF in three disease-specific questionnaires: the Polysymptomatic Distress Scale (PDS), the modified Fibromyalgia Assessment Status (ModFAS), and the revised Fibromyalgia Impact Questionnaire (FIQR). Methods. The study population comprised male and female patients, pair-matched for age and body mass index (BMI), diagnosed with FM according to the 2010/2011 American College of Rheumatology (ACR) criteria, and recruited from five Italian rheumatology centers. Data collected for each patient included sociodemographic characteristics (age, sex, marital status, education level, and BMI) as well as scores from the three FM-specific questionnaires. Multiple linear regression models were used to examine associations between sex and disease activity measures. Further analyses stratified by sex assessed how sociodemographic factors differentially impacted FM outcomes. DIF was analyzed using a hybrid Ordinal Logistic Regression/Item Response Theory (OLR/IRT) approach. Results. Data from 331 male and 331 female patients were retrospectively analyzed. Demographic characteristics are shown in Table 1. Multivariate analysis revealed that female sex was significantly associated with greater physical disability (FIQR physical function beta=1.686, p<0.001), but not with overall disease severity (PDS beta=0.304, p=0.5) (Table 2). In sex-stratified analyses, being married was significantly associated with both disease severity (PDS beta=1.730, p=0.04) and disease impact (FIQR total beta=-7.658, p<0.001) among women, whereas BMI was significantly associated with disease impact (FIQR total beta=0.962, p<0.001), disease and symptoms severity (ModFAS beta=-0.19, p=0.02; SSS beta=-0.090, p=0.02) among men (Figure 1). Significant gender-related DIF was observed for only one item in the Symptoms Severity subscale of the PDS. Conclusions. These findings suggest that women with FM experience greater physical impairment than men, despite similar overall disease severity. Additionally, the study highlights a complex interplay between sociodemographic factors and FM severity and impact, with differing effects across sexes. Finally, the minimal gender-related DIF observed supports the validity of the three FM-specific questionnaires for use in both male and female patients.
PO:06:079 | Weighing the burden: how body mass index shapes clinical outcomes in rheumatoid arthritis. Insights from a large Italian cohort
Background. Body mass index (BMI) may influence the clinical presentation and progression of rheumatoid arthritis (RA). Understanding its impact is crucial to optimizing disease management and tailoring treatment strategies. This multicenter, cross-sectional study aimed to evaluate the impact of BMI on RA management in a real-world setting. Methods. Patients diagnosed with RA based on the 2010 ACR/EULAR Classification Criteria were enrolled from 18 academic rheumatology centers. Clinical charts were reviewed to collect demographic data, treatment information, and disease activity measures. Data were analyzed using appropriate statistical methods with GraphPad Prism v9. Results. A total of 1,432 RA patients were included (mean age 61±10 years; 81.4% female; median disease duration 120 months; 70% RF/ACPA positive). The median BMI was 25 (IQR 22.4–28.1), with males presenting significantly higher BMI values (p<0.001). Obesity (BMI >30 kg/m²) was observed in 14.7% of patients, with no significant sex difference. Overweight (BMI 25–30 kg/m²) was more common in males (1.5-fold, p<0.001), while underweight (BMI <20 kg/m²) was 10 times more prevalent in females (p<0.0001). BMI correlated positively with age, disease duration, blood pressure, triglycerides, CRP levels, and disability (assessed by HAQ-DI), but not with disease activity scores (DAS28-ESR or CDAI). A significant inverse correlation was observed with HDL cholesterol (r = -0.16, p < 0.0001). Smoking habits and diabetes prevalence (7.1%) were not significantly affected by BMI; notably, nearly half of diabetic patients were overweight or obese. The 10-year cardiovascular risk (SCORE-2) was similar between obese and non-obese RA patients. Regarding treatment, 43.5% of patients were on corticosteroids (mean prednisone-equivalent dose 4.9±3.4 mg/day), 68.7% on csDMARDs (80% on methotrexate), and 57.3% on b/tsDMARDs, with one-third receiving monotherapy. Obese patients were more likely to be treated with bDMARDs (64.3% vs. 56.1%, p=0.03; OR 1.41) and tsDMARDs (18.2% vs. 9.8%, p=0.007; OR 2.1), while no significant differences emerged for corticosteroid or csDMARD use. Conclusion. This study highlights the influence of BMI on RA management in a large Italian real-life cohort. While BMI did not significantly affect disease activity, it was associated with increased disability and influenced therapeutic decisions, particularly the use of b/tsDMARDs. Gender differences were evident in BMI distribution, suggesting the need for personalized approaches in RA care based on body composition and sex-specific factors.
CO:09:3 | Effectiveness and safety of nintedanib in autoimmune systemic diseases: real life data from an Italian multicentre study (Island group) of the Italian Society of Rheumatology
Background. Nintedanib (NTD) has been shown to be useful to slow functional decline of progressive fibrosing interstitial lung disease also in Autoimmune Systemic Diseases (ASDs) beside systemic sclerosis (SSc) and rheumatoid arthritis (RA) after the positive results of the INBUILD trial. Here we describe the effectiveness and safety of NTD in ASDs in a real-life setting. Materials and Methods. The clinical data of ASDs patients with ILD (excluded SSc and RA) treated with NTD from 17 Italian centres were retrospectively evaluated at 12 months prior to NTD introduction; at baseline, and at 12 months after NTD introduction. The following parameters were recorded: ASD clinical features, NTD tolerability, pulmonary function tests (PFTs). Progressors were defined as a drop in %pFVC >= 5 and/or %pDLCO >= 10 within 12 months. Results. 114 ASD-ILD patients (46.5% male, mean age 69 ± 10 years, median disease duration 5.5 (2-12) years) treated with NTD were identified. Disease features are summarized in Table 1. The most common ASD was anti-synthetase syndrome (31, 27.2%) and the most common antibody was anti-Ro52 (44, 38.6%), most (57.9%) had been previously treated with immunosuppressants. At baseline, 107 (93.9%) patients were on immunosuppressants (see Table 1), with 74 (64.9%) patients on steroid with a median dose of 5 (1.25 – 7.5). Baseline HRCT was available in 109 patients and it showed an UIP pattern in 43 (39.4%) and a NSIP pattern in 66 (60.6%) patients. A significant decline in %pFVC and in %pDLCO was observed in the 12 months prior to NTD introduction (82.4 ± 21 versus 71 ± 16, p <0.001 and 51 ± 17 versus 44 ± 13, p <0.001, respectively) with 54 (69%) being classified as progressors. At 12 months after NTD introduction, follow-up data were available for 54 patients and they showed an improvement in both %pFVC (72 ± 15 to 75 ± 17, p < 0.001) and %pDLCO (43 ± 15 to 45 ± 17; p < 0.001); moreover, the percentage of progressors was significantly lower (69% versus 26%, p < 0.001). The dosage of NTD was reduced to 100 mg BID in 44 (38.6%) patients after a median time of 5 (3 – 9) months, and suspended in 19 (16.7%) patients after a median time of 3 (1-8) months, see Figure 1. During the follow-up, 10 (8.8%) patients died. Conclusions. In a real-life clinical scenario, NTD, in combination with immunosuppressants, may improve lung function in patients with ASDs. NTD seems to be well-tolerated and the rate of drug suspension is low. Our data support early evaluation of ILD in wide range of ASDs in order to identify patients eligible for antifibrotic drug in association to immunosuppressants.
PO:06:082 | Correlation between ultrasonographic parameters and the Krenn synovitis score in patients with chronic infiammatory arthropathy undergoing ultrasound-guided synovial biopsy: a prospective cohort study
Background. The aim of this study is to analyze, in a cohort of patients with chronic inflammatory arthropathy, the correlation between ultrasonographic parameters and the Krenn Synovitis Score (KSS) – a validated semi-quantitative scale for the histological classification of synovitis, used to evaluate the degree of synovial inflammation. Materials and Methods. We included patients aged ≥18 years with a diagnosis of RA, according to the 2010 ACR/EULAR classification criteria, or PsA, according to the CASPAR criteria, were recruited. Eligible participants were required to be candidates for initiation or modification of DMARD therapy and to have complete ultrasonographic data at baseline, defined as a polyarticular assessment using the Global OMERACT–EULAR Synovitis Score (GLOESS) and ultrasound evaluation of the biopsy site. Each patient underwent an ultrasound-guided synovial biopsy of a clinically involved joint (knee or wrist). Synovial tissue specimens were evaluated by an experienced pathologist to determine the KSS. Statistical analyses were conducted using Spearman’s rank correlation coefficient, a non-parametric measure of association. Results. A total of 63 patients were evaluated (58 with RA and 5 with PsA). Among them, 92% (58/63) had failed at least one csDMARD, and 51% (32/63) had failed at least one b/tsDMARD. The mean (SD) polyarticular GLOESS value was 15 (12), while the median (IQR) KSS was 6 (4.00, 6.00) (Table 1). GLOESS (rho = 0.23, p = 0.013), gray-scale (GS) intensity (rho = 0.35, p < 0.001), and the degree of joint effusion (rho = 0.27, p = 0.004) at the biopsy site showed a positive correlation with the KSS (Figure 1). Regarding the KSS sub-items, a positive correlation was observed between all ultrasound variables and the degree of inflammatory infiltrate on histological examination (rho = 0.38, p < 0.001 for GS; rho = 0.30, p = 0.002 for effusion; rho = 0.23, p = 0.014 for PD). No statistically significant correlation was found between Power Doppler (PD) signal intensity of the examined joint and the overall KSS (rho = 0.16, p = 0.1), lining score (rho = 0.10, p = 0.3), or stroma score (rho = –0.05, p = 0.6). Conclusions. In the examined patient cohort, a positive correlation was observed between the polyarticular GLOESS score and the KSS, as well as between ultrasonographic parameters at the biopsy site and the degree of inflammatory infiltrate on histological assessment. Moreover, only specific ultrasound variables such as gray-scale intensity and the extent of joint effusion at the biopsy site showed a positive correlation with KSS, whereas no such correlation was confirmed for the Power Doppler (PD) signal. These findings, together with the rho values indicating a weak correlation, suggest that synovitis is influenced by factors not fully identifiable through ultrasound assessment alone, supporting the role of KSS and synovial biopsy as valuable tools for a more accurate characterization of chronic inflammatory arthropathies.
CO:09:4 | Erosive hand osteoarthritis: the impact of comorbidities in the context of joint disease
Background. This study aimed to determine whether cardiovascular and osteometabolic comorbidities are associated with the radiographic hallmarks of erosive hand osteoarthritis (EHOA), specifically osteophytes, joint space narrowing (JSN), malalignment, central erosions, sclerosis, and subchondral cysts. We also evaluated how these comorbidities relate to clinical and serological measures of disease activity, including pain (VAS), validated disease questionnaires, swollen and tender joint counts, and inflammatory markers. Materials and Methods. We enrolled patients exhibiting at least one central erosion in a proximal (PIP) or distal (DIP) interphalangeal joint, excluding any with metacarpophalangeal erosions. Each participant underwent a comprehensive clinical assessment by an expert rheumatologist and completed the VAS for pain, the AUSCAN index, and the DREISER algo-functional scale. We collected demographic, clinical, metabolic, and bone-metabolic data such as BMI, blood pressure, laboratory values, and bone-densitometry results. Radiographs were scored using the Altman system after specific training to ensure inter-reader reliability; we graded osteophytes, JSN, malalignment, central erosions, sclerosis, and cysts. Comorbidities were quantified with the Charlson Comorbidity Index (CCI), metabolic syndrome defined per Adult Treatment Panel (ATP) III criteria, and ten-year fracture risk estimated via the DeFRA score. Results. Eighty-seven patients (77% female; mean age 63.2 ± 8.9 years) were analysed. Radiographic scores of the different joints analysed are detailed in Table 1 . Cardiovascular risk factors were present in 76.8% of subjects: 48.2% had total cholesterol > 200 mg/dL, 9.1% were obese (BMI > 30 kg/m²), 6.9% had fasting glucose > 126 mg/dL, and 28.7% were hypertensive (>140/90 mmHg). Sixteen patients (18.4%) had osteoporosis, and 28.3% (17/60) of those with DEXA data available had lumbar T-scores <–2.5. Pain (VAS) correlated with swollen (r=0.44, p < 0.01) and tender (r=0.47, p < 0.01) joint counts. AUSCAN and DREISER scores correlated strongly with VAS (r=0.63 and r=0.52, p < 0.01). Disease duration correlated with total radiographic score (r=0.57, p < 0.01). In regression analyses, osteoporosis was associated with increased osteophyte formation (p=0.013), and JSN was associated with diabetes (p=0.043).Osteoporosis was also associated with higher DREISER (p0.018) and AUSCAN (p=0.024) scores; lower lumbar T-scores correlated with worse VAS (p= 0.045), AUSCAN (p=0.0009), and DREISER (p=0.015), and inversely correlated with inflammatory markers. Conclusions. Our findings indicate that individual cardiovascular and osteo-metabolic comorbidities contribute to structural joint damage and disease progression in EHOA. The association between osteoporosis and increased osteophyte formation suggests that reduced bone density may induce an osteoprolipherative response. Furthermore, lower T-scores correlate with worse hand-function scores, underscoring the detrimental impact of bone-density loss on daily activities. A multidisciplinary strategy with rigorous risk-factor control may improve long-term outcomes for EHOA patients.
PO:06:083 | Clinical characteristics and outcomes of late- and young-onset rheumatoid arthritis in relation to autoantibody status
Background. Ageing of the society is progressively increasing the incidence of rheumatoid arthritis (RA) in the ederly, but the clinical characteristics and outcomes of late-onset RA (LORA) remain debated. If, on the one-hand, some forms of LORA have traditionally been regarded as more benign, older age is also reported as a risk factor for disease refractoriness. Aim of this study was to investigate the clinical outcomes of newly diagnosed LORA in comparison with young-onset RA (YORA) in the setting of a standardized treatment protocol, taking into account possible differences according to autoantibody status. Methods. Data were retrieved from a monocentric inception cohort of patients with new onset (symptoms <12 months) RA, tightly followed at 3-months intervals and treated according to a treat-to-target strategy with progressively increasing doses of methotrexate (MTX). Patients were classified as LORA based on the newly proposed cut-off of >= 70 years. Outcomes of interest included proportions of patients in remission at 6 and 12 months, and doses of MTX at each time point. Analyses were stratified for positivity of anti-citrullinated protein autoantibodies (ACPA). Results. Among 812 patients with early RA, 239 (29.2%) had LORA. Collectively, compared with YORA, LORA presented with higher inflammatory features, including numbers of involved joints and acute phase reactants (Table 1). After 6 and 12 months of treatment, rates of remission according to the DAS28, SDAI and Boolean criteria were comparable between LORA and YORA. Doses of MTX at 12 months did not differ (mean [SD] 13.8 [4.9] vs 13.9 [5.9] mg/w). LORA was significantly less frequent among ACPA-positive patients (16.4% vs 34.8%, p<0.001). However, in this latter serologic subgroup, LORA was characterized by more unfavourable outcomes compared with YORA, with lower rates of remission at each time point in spite of comparable doses of MTX (Table 1). At multivariable analyses corrected for gender, baseline disease activity and use of prednisone, LORA predicted failure to achieve remission at 12 months with an ORs (95% CI) of 2.7 (0.09-0.77). In contrast, in ACPA-negative patients, LORA was characterized by more frequent achievement of remission according to any criterion and at each time-point compared with YORA (Table 1). Also, the required dose of MTX tended to be lower in LORA. In ACPA-negative RA, LORA predicted early remission with an adjusted OR (95% CI) of 1.98 (1.08-3.64). Conclusions Older age at onset has opposite outcomes in RA in relation to the autoantibody status. In ACPA-positive patients, those with LORA exhibit poorer response to first line-treatment with MTX. In contrast, the ACPA-negative subgroup of LORA has an overall milder course of the disease, with more frequent achievement of good clinical outcomes and lower therapeutic burden.
CO:09:6 | Risk of disease flare during pregnancy and postpartum in inflammatory arthritis: association with therapy discontinuation in the prospective P-RHEUM.it study
Background: There is still a significant unmet need for robust data on pregnancy outcomes in patients with autoimmune rheumatic diseases (ARD), both regarding disease flare and obstetric complications. To address this gap, the Italian Registry of Pregnancies in Rheumatic Diseases (P-RHEUM.it) was designed as a nationwide, web-based longitudinal observational cohort study to collect data about pregnancy in ARD between 2018 and 2023. This analysis focuses on patients with inflammatory arthritis (IA) enrolled in the registry, aiming to describe pregnancy outcomes with special attention to disease flare during pregnancy and postpartum. We also assessed the relationship between treatment discontinuation, treatment at baseline, and flare risk. Materials and methods: Patients with rheumatoid arthritis (RA), undifferentiated arthritis (UA), juvenile idiopathic arthritis (JIA), psoriatic arthritis (PsA), and spondyloarthritis (SpA) were included. Treatment discontinuation is defined as ongoing therapy in the last 12 months, interrupted upon positive pregnancy test. Flare was defined when at least one of the following disease-specific criteria was met: • RA/UA/JIA: a variation of DAS28-CRP between two visits > 1.2, or > 0.6 if DAS28 at previous visit was > 3.2 • PsA: a variation of DAPSA > 4 or > 1.1 between two visits • SpA: variation of ASDAS >= 0.9 The same definitions of flares were applied during the post-partum period up to 6 months after delivery. Results: A total of 393 patients were included. Cohort characteristics (demographics, disease activity, use or discontinuation of medications during pregnancy) are reported in Table 1 and data on DAS-28, DAPSA and ASDAS during the follow-up in Table 2. During pregnancy, 167/393 patients (42.5%) experienced a flare; in postpartum, 12/248 (4.8%). Flare risk was higher in patients with active disease in the 12 months before pregnancy (p<0.001). Discontinuation of anti-TNF and NSAIDs used in the year before pregnancy was also associated with flare (p<0.001 and p=0.02, respectively). A BMI >30 was linked to increased flare risk (p=0.04), while cDMARD use at baseline and a patient global assessment (PGA) reflecting better health status were protective (p=0.001 and p<0.001). In multivariate analysis, logistic regression was performed: PsA and SpA diagnosis, active disease and anti-TNF discontinuation remained independent predictors (OR 1.02, 95% CI 1.01–1.03, p=0.02; OR 2.19, 95% CI 1.19–4.03, p=0.01). Among patients assessed with DAS28, an increase in disease activity during pregnancy was observed following anti-TNF withdrawal (Figure 1). Conclusions: These findings highlight the importance of planning pregnancy during periods of well-controlled disease and emphasize the need to educate patients on the safety and importance of continuing pregnancy-compatible therapies. Additionally, close monitoring throughout pregnancy and the postpartum period is crucial.
on behalf of the P-Rheumit Investigators
PO:06:084 | Interstitial lung involvement in rheumatoid arthritis patients treated with abatacept: a prospective observational study
Background. Abatacept has been suggested to be a safe and effective drug for the treatment of rheumatoid arthritis (RA) complicated by interstitial lung disease (ILD), one of the most severe extra-articular manifestations of RA. Objectives. In this prospective multicentre observational study, we aimed to evaluate the effectiveness and safety of abatacept on RA-ILD. Concurrently, the study aimed to evaluate the incidence of new diagnosis of ILD in RA patients treated with abatacept. Methods. We enrolled all consecutive RA patients already under treatment with abatacept for at least three months referred to 12 rheumatological centres in Italy. ILD patients were followed according to the current clinical practice: forced vital capacity (FVC%) was repeated every six months, while chest high resolution computed tomography (HRCT) was performed annually or when respiratory symptoms worsened. In patients without ILD at baseline, a careful assessment for respiratory symptoms and velcro crackles was performed at enrolment and every six months. HRCT was requested in case of new-onset dyspnoea, persistent dry cough, or detection of velcro crackles. Results. We enrolled 325 RA patients treated with abatacept. Among them, ILD was already present in 20.6% of cases. A usual interstitial pneumonia (UIP) pattern was detected 25.4% of cases. The two-year retention rate of abatacept was 79.6% ±3.8 and 76.8%±10.6 in patients without and with ILD, respectively, without difference between the two groups. Two cases of infectious pneumonia were reported in ILD group, requiring a transient discontinuation of abatacept. No patients discontinued abatacept for a worsening of lung function, and no episodes of acute exacerbation of ILD were observed during the study. At the end of follow-up, the radiological picture remained stable in 71.6% of subjects, improved in 13.4%, and worsened in 14.9%. A worsening at HRCT was recorded in 29.4% of cases of UIP, and only in 10% of patients with other ILD patterns (p not significant). Regarding lung function tests, FVC improved in 13.4% of cases, remained unchanged in 74.6%, and worsened in 11.9%. During the 24-month period of follow-up, 2 patients developed ILD, with an incidence of 0.39 new ILD cases/100 patients/year. Conclusions. Our study confirmed the safety and the effectiveness of abatacept in this population of difficult to treat RA patients. Of interest, ILD didn’t affect the retention rate of the drug. Moreover, lung function and HRCT features improved or remained stable in about 85% of patients, suggesting a role for abatacept in the treatment of RA-ILD. Concurrently, we observed a low rate of new cases of ILD, with an incidence rate of 0.39 new ILD cases/100 patients/year. Controlled studies, specifically developed in RA-ILD population, will be necessary to define the efficacy and safety of abatacept compared to other biologic DMARDs.
CO:10:1 | High-grade synovitis and histological pathotype distribution in patients with advanced osteoarthritis undergoing joint replacement: a more inflammatory disease than we thought?
Background. Osteoarthritis (OA) has traditionally been regarded as a degenerative disease, with inflammation playing only a marginal role. However, recent evidence suggests that synovitis may significantly contribute to OA pathophysiology. This study aimed to describe the grade of synovitis and the distribution of synovial histological pathotypes in patients with advanced OA undergoing joint replacement, and to explore associations with clinical, laboratory, and radiographic variables. Materials and Methods. A retrospective observational study was conducted on patients with OA who underwent primary total hip or knee arthroplasty between 2000 and 2024. Synovial membrane samples collected during surgery were analyzed histologically using hematoxylin-eosin staining and immunohistochemistry. The Krenn synovitis score was applied to assess inflammation severity. Based on cellular composition, samples were classified into three main synovial pathotypes: lympho-myeloid, diffuse myeloid, and pauci-immune. Clinical and laboratory data (including ESR, CRP, BMI, Kellgren-Lawrence grade, and rheumatologic history) were retrieved from medical records. Associations between histological features and clinical parameters were evaluated through univariate and multivariate logistic regression. Resulus. Ninety-nine patients were included (mean age 74 ± 11 years; 51.5% female). High-grade synovitis (Krenn score above 4) was observed in 62.6% of cases. The most frequent synovial pathotype was lympho-myeloid (57.6%), followed by pauci-immune (30.3%) and diffuse myeloid (12.1%). No significant differences in synovitis grade or pathotype distribution were found between hips and knees (Figure 1). The Krenn score was significantly higher in lympho-myeloid samples (mean 5.8 ± 1.0 vs. 4.3 ± 1.1; p < 0.001). Histology revealed greater cellularity, organized lymphoid aggregates, and abundant CD20+, CD3+ infiltrates in this pathotype, along with increased synovial hyperplasia and neoangiogenesis. At multivariate analysis, Kellgren-Lawrence grade was independently associated with the lympho-myeloid pathotype (OR 1.763; 95% CI 1.041–2.984; p = 0.035; figure 2). Elevated ESR (>20 mm/h) showed a non-significant trend toward association (OR 1.622; p = 0.091), while age, sex, BMI, and CRP were not predictive. Lympho-myeloid pathotype was associated with higher VAS pain scores (mean 7.2 vs. 6.0; p = 0.048) and longer disease duration (mean 9.6 vs. 6.4 years; p = 0.031). Conclusions. This study reveals a high prevalence of both high-grade synovitis and the lympho-myeloid pathotype in patients with advanced OA undergoing joint replacement. These findings challenge the traditional view of OA as a purely degenerative disease and support the concept that distinct inflammatory phenotypes may exist within OA. The presence of structured immune infiltrates and their association with structural damage, pain severity, and disease chronicity suggest a pathogenic and prognostic role of synovial inflammation. Further studies are warranted to define the clinical implications of synovial pathotypes and their relevance for therapeutic strategies.
PO:06:092 | Early achievement of remission confers better outcomes than low disease activity in both seropositive and seronegative patients with new-onset rheumatoid arthritis
Background. Although remission is the ideal target in patients with rheumatoid arthritis (RA), stringent definitions are difficult to achieve. In the absence of clear data demonstrating the real benefit of remission over low disease activity (LDA), the two targets often remain interchangeable in clinical practice. Aim of our study was to compare the outcomes of patients with early RA achieving remission vs LDA, taking into account possible differences in relation to autoantibody status. Methods. Data were retrieved from a monocentric inception cohort of patients with new onset (symptoms <12 months) RA, tightly followed at 3-months intervals and treated to achieve a target of LDA (DAS28 <3.2). Patients achieving remission (DAS28 <2.6) within month 6 and month 12 from treatment start were compared with those in LDA for clinical and functional outcomes at 1 year. These included: inflammatory remission (swollen joint count – SJC28 and C-reactive protein – CRP- levels both < or =1); resolution of pain (VAS pain < or =20 mm and < or =10 mm); normalization of physical function (HAQ <0.5). Analyses were stratified for positivity of anti-citrullinated protein autoantibodies (ACPA). Results. From a total cohort of 816 patients with new-onset RA, 759 (93%) had at least 6 months of follow-up and were considered for analyses. Of these, 218 (28.7%) achieved early DAS28 remission within month 6, and 176 (23.2%) were in LDA. An additional proportion of 8.7% and 9.2% achieved remission and LDA, respectively, at later points within month 12. Early remission and LDA differed significantly in inflammatory variables, such as SJC28 (mean [range] 1.2 [0-7] vs 2.2 [0-12], p<0.001) and CRP (mean [range] 0.3 [0-3.7] vs 0.5 [0-6.2] mg/dl, p=0.006). Differences were confirmed in both ACPA-positive and -negative patients. In contrast, at later time points, LDA had similar inflammatory burden as compared with remission (mean SJC28 ~1.5 in both), in spite of worse patient-reported outcomes (mean [SD] PGA 25.7 [25] vs 16.6 [21.1], p=0.04). Early achievement of remission was associated with significantly better 1 year outcomes than LDA, including suppression of inflammation, resolution of pain, and normalization of physical function (Figure 1A-D). The benefits of early remission over LDA were confirmed in both ACPA-positive (Figure 1E-H) and -negative patients (Figure 1I-L). In contrast, when remission was achieved at later time points, the advantages over LDA were no longer detectable (data not shown). Conclusions. Early remission is an achievable target that confers better outcomes as compared with LDA in patients with both seropositive and seronegative RA. Our data reinforce the concept that, in clinical practice, all patients with new-onset RA should be intensively managed and brought to remission in the first 6 months.
CO:10:2 | Common variable immunodeficiency patients complicated by autoimmune and inflammatory rheumatic manifestations reveal high frequency of genetic variants potentially linked to inborn errors of immunity
Background. Common variable immunodeficiency (CVID) is the most frequent clinically symptomatic primary immunodeficiency; its clinical spectrum is highly variable, ranging from isolated recurrent infections to autoimmune (AID) and inflammatory rheumatic diseases (IRD), which may even be the unique manifestation at disease onset [1]. CVID is mainly a polygenic disease, even if recent studies employing whole-genome and exome sequencing analysis have highlighted that 15–30% may display a monogenic origin [2]. Aim of the study is to describe our CVID patients (pts) cohort, highlighting AID and IRD, and to describe genetic variants possibly linked to immunodeficiency and autoimmunity and therapeutic implications. Methods. This is a monocentric observational retrospective study considering CVID pts followed since 1985 to 2024. Diagnosis was made according to European Society for Immunodeficiency criteria [3]. A next generation sequencing (NGS) analysis of genes potentially linked to hypo-agammaglobulinemia and to antibody deficiency was executed when considered clinically appropriate. Results. Eighty-three pts with a CVID diagnosis were included. CVID total cohort description and comparisons between CVID pts with and without AID are reported in Table 1. Autoimmune cytopenia was the most common autoimmune manifestation occurring in 22.9% of the pts, with immune thrombocytopenia being the most prevalent. Immunosuppressive treatment was necessary in 89.5% of the pts affected by autoimmune cytopenia; in 5 cases, due to refractory cytopenia, rituximab was employed, achieving persistent remission in 4 pts. A diagnosis of IRD was made in 12 pts; 75.0% suffered from inflammatory arthritis. In one pt with Adenosine Deaminase 2 deficiency, genetic analysis aided in employing a target therapy leading remission of the IRD (Table 2). Genetic analysis for variants potentially leading to CVID had been performed in 37.3% of pts; analysis resulted positive in 41.9% of the tested. Genetic variants potentially linked to inborn errors of immunity (IEI) were found in more than half of pts with AID, much more frequently than in other CVID pts (56.5% vs 0.0%; p:0.010). The identified genetic variants are reported in Table 3. Conclusions CVID can be complicated by a wide spectrum of clinical pictures, including AID and IRD, being in our cohort inflammatory arthritis in most of the cases, categorized as a form of Spondyloarthritis in about two thirds. Notably, CVID pts affected by AID and IRD showed a higher frequency of genetic variants potentially leading to IEI; in one case genetic testing aided in orienting IS treatment, leading to remission of the IRD. Nowadays genetic analysis has still limited implications in influencing treatments in CVID, but in the future it might help in targeting precise mechanisms in patients with AID and IRD. References p]:pt-0 [&>p]:mb-2 [&>p]:my-0"> Thalhammer J, Kindle G, Nieters A, et al. Initial presenting manifestations in 16,486 patients with inborn errors of immunity include infections and noninfectious manifestations. J Allergy Clin Immunol. 2021 Nov;148(5):1332-1341.e5. p]:pt-0 [&>p]:mb-2 [&>p]:my-0"> Maffucci P, Quinti I, Pulvirenti F, et al. Genetic Diagnosis Using Whole Exome Sequencing in Common Variable Immunodeficiency. Front Immunol. 2016 Jun 2;7:220. p]:pt-0 [&>p]:mb-2 [&>p]:my-0"> Seidel MG, Kindle G, Gathmann B, et al. The European Society for Immunodeficiencies (ESID) registry clinical criteria for inborn errors of immunity diagnosis. Clin Exp Immunol. 2019;197(2):205-214.
PO:06:093 | Clinical and ultrasound phenotyping comparison between Difficult-To-Treat Rheumatoid Arthritis (D2TRA) and non-D2TRA patients: experience from a monocentric cohort
Background. To investigate clinical and ultrasound (US) findings as potential predictors of difficult-to-treat rheumatoid arthritis (D2TRA).1,2 Methods. Patients diagnosed with D2TRA assessed at our clinic between 2020 and 2024 were enrolled in the study and compared with a group of consecutive non-D2TRA patients. Demographic, US and clinical data were retrospectively collected. The first US available before developing D2TRA was analyzed. All US assessments were performed by four expert rheumatologists from our center using an Esaote MyLabX8 US machine equipped with a high-frequency (15–24 MHz) linear probe. US evaluation included the detection of synovitis, tenosynovitis and bone erosions. Assessed joints encompassed wrists, metacarpophalangeal (MCP), proximal interphalangeal (PIP), shoulders, knees and ankles. Regarding synovitis, GS and PD were considered in accordance with EULAR and OMERACT criteria.3,4,5 GLOESS grading system was also applied.6 Logistic and Cox regression models adjusted for baseline confounders was used for multivariable analysis. Results. One hundred thirty-six patients were recruited, median (±IQR) follow-up 18.75 (11.42-25.92) years, 80 of them fulfilling EULAR criteria for D2TRA. No significant differences were found between D2TRA and non-D2TRA groups regarding baseline demographics and comorbidities except for fibromyalgia, which was significantly more frequent in D2T cohort (Table 1). On survival univariate analysis, exposure to tsDMARDs was associated to longer time-to-D2T development (HR [CI] : 0.51, [0.26 - 0.99], p=0.046) (Figure 1). 136 US were included in the study. At the time of US examination, patients further-to-be D2T displayed higher DAS28 scores (median [IQR]: 4.30 [3.67-5.40] vs 2.70 [2.02-4.41], p<0.01). A significantly higher prevalence of wrist synovitis (n [%]: 62 [77.5%] vs. 31 [57.4%], p=0.023) and higher wrist GLOESS scores (mean [sd]: 2.67 [1.91] vs 1.77 [1.94]; p=0.007) were observed in furhter-to-be D2T patients (Figure 2). At the multivariable logistic analysis, wrist synovitis (OR 2.79, 95%CI 1.27-6.33, p=0.01) and fybromialgia (OR 4.14, 95%CI 1.22-19.3, p=0.03) independently predicted D2TRA. Conclusions. In our cohort, fybromialgia and US-documented wrist synovitis independetly predicted D2TRA. Our results highlight the critical role of targeted US beside clinical assessment for risk stratification across RA patients. REFERENCES 1. Bellis et al. The role of musculoskeletal ultrasound in difficult-to-treat RA: Insights from a systematic literature review. Autoimmun Rev. 2025 2. Nagy G et al. EULAR definition of difficult-to-treat rheumatoid arthritis. Ann Rheum Dis. 2021 3. Möller I et al. The 2017 EULAR standardised procedures for ultrasound imaging in rheumatology. Ann Rheum Dis 2017. 4. Costantino et al. EULAR recommendations for the reporting of ultrasound studies in rheumatic and musculoskeletal diseases. Ann Rheum Dis 2021. 5. Bruyn et al. OMERACT Definitions for Ultrasonographic Pathologies and Elementary Lesions of Rheumatic Disorders. J. Rheumatol 2019. 6. Naredo E et al.The OMERACT ultrasound task force - status and perspectives. J Rheumatol 2011.
CO:10:3 | Clinical response to JAK inhibitors or non-TNFi-targeted biologicals according to synovial tissue characteristics in patients with difficult-to-treat rheumatoid arthritis
Background. Patients meeting the EULAR difficult-to-treat rheumatoid arthritis (D2TRA) definition are classically non-responders to TNF inhibitors (TNFi). As such, they can be treated with biological drugs with other mechanisms of action (OMA; tocilizumab, sarilumab, abatacept, rituximab) or Janus Kinase inhibitors (JAKi). The aim of the study was to investigate whether characteristics of synovial tissue may predict treatment response to OMA or JAKi in D2TRA patients. Materials and Methods: The MATRIX-D2T was a prospective cohort, multi-centre study that included RA patients with moderate to high disease activity undergoing ultrasound-guided synovial tissue biopsy (UGSTB) at two institutions. In this post-hoc analysis, patients were eligible for inclusion if they fulfilled the EULAR D2TRA definition. The primary outcome was a change in CDAI after six months; the secondary outcome was low disease activity (LDA or CDAI<=10). Predictors were synovial grading according to Krenn Synovial Score (2-4, low grade; 5-9, high grade); synovial pathotypes (lympho-myeloid, diffuse-myeloid, pauci-immune fibroid); and the count of lymphoid aggregates. Outcome comparisons between treatment groups (JAKi vs. OMA) were assessed through repeated measures ANOVA corrected for ACPA titre. Results. Among 132 patients undergoing USGTB during the study period, 26 patients met the study criteria and were included (mean (SD) age 58 (11) years, duration 15 (10) years, females 62%). Twelve patients initiated JAKi and 14 OMA; the two groups were comparable for baseline characteristics (Table 1). The median (IQR) number of failed b/tsDMARDs was 3 (3), and for csDMARDs, it was 2 (3). Median (IQR) KSS was 5 (7). After 6 months, the mean (SD) CDAI significantly decreased more in JAKi than OMA (mean difference -10.7, 95% CI -19.4 to -2.0, p=0.018). Compared to OMA, a stronger CDAI decrease with JAKi was shown in patients having high-grade synovitis only (Figure 1a-b), with no clear association with synovial pathotypes or the presence of lymphoid aggregates. Patients in LDA were numerically more frequent in JAKi recipients (n=6/12, 50%) compared to OMA (n=3/14, 21.4%; p=0.218; Figure 1c). Conclusions. Our results suggest that UGSTB may help predict clinical response to JAKi or OMA in DT2RA patients. However, the sample size was small, and results must be confirmed in larger independent cohorts.
PO:06:094 | Exploring the relationship between inflammation and collagen deposition in synovial tissue and clinical outcomes in active arthritis: insights from a monocentric pilot study
Background. Synovial collagen remodelling may mirror chronic inflammation and repair processes, potentially serving as a structural correlate of disease activity in arthritis. Based on this, the aim of this study was to investigate the relationship between synovial inflammatory histopathology and collagen remodelling in patients with active rheumatoid arthritis (RA) or psoriatic arthritis (PsA). Methods. US-guided synovial biopsies were obtained from inflamed joints (knee/wrist) in 30 patients (18 RA, 12 PsA) with active arthritis, undergoing therapeutic re-evaluation.Synovial inflammation was evaluated considering Krenn Synovitis Score (KSS), immunohistochemical analysis (sublining CD68, CD3, CD20, CD138), pathotype classification, and evaluation of neutrophil infiltration.For 12 patients (RA, PsA),3-micrometer sections were stained with fresh Picrosirius red,then digitized via brightfield and polarized light microscopy for morphometry and collagen typing.Stained area and collagen maturation index were quantified using computer-aided image analysis.Clinical disease activity was recorded at baseline and at 3-month follow-up. Results. The mean age of patients was 52 years and 64.5% were female;the mean disease duration was 5.6 years. Mean KSS was 4.5±0.5 in RA and 4.2±0.5 in PsA. 17 (56.7%) patients were classified as lympho-myeloid, 10(33.3%) as diffuse-myeloid,and 3(10%) as pauci-immune pathotype.Moreover, neutrophil infiltration of ST was present in 12(40%) of the overall cohort and was associated with higher KSS (p = 0.003).Higher KSS also tended to correlate with the number of previous bDMARDs, and pathotype distribution differed by prior biologic exposure (p = 0.029);notably, patients with a pauci-immune synovitis had received the highest number of previous bDMARDs. Considering collagen deposition,the mean collagen area was 39.48±7.52% in RA and 40.79±12.09% in PsA, while the mean collagen maturity index was 0.73±0.04 and 0.72±0.03, respectively.No associations were found between collagen parameters and sex, age, disease duration, or biopsy site. In RA, collagen area showed a trend toward inverse correlation with CD68+ macrophage infiltration (p = 0.057). In PsA, both collagen area and maturation index were inversely correlated with inflammatory infiltrate, B cells, and plasma cells (all p = 0.04). Additionally, disease duration in PsA was positively associated with both collagen area(p = 0.025) and collagen maturity index (p = 0.017), suggesting that long-standing disease may promote extracellular matrix stabilization. Importantly, a significant inverse correlation between collagen area and collagen maturity index was observed in RA (p = 0.047). At 3-month follow-up, histological pathotype was associated with DAS28 response: responders more frequently showed a diffuse-myeloid profile, while no responders were mostly observed among pauci-immune cases. Conclusions. Synovial immune cell infiltration is associated with collagen remodelling in both RA and PsA, with distinct patterns linked to disease duration and tissue organization.The inverse correlation between collagen area and maturity in RA suggests matrix expansion during active synovitis.
CO:10:4 | Lung vasculature quantification on computed tomography predicts new onset of interstitial lung disease in systemic sclerosis
Interstitial lung disease (ILD) is common in systemic sclerosis (SSc) and a major cause of death. While clinical risk factors for ILD onset at 1-year and long-term follow-up have been identified (1,2), risk stratification remains suboptimal. Pulmonary vascular volume (PVV) on HRCT is linked to both presence and severity of SSc-ILD (3). Here, we investigate the potential of radiomics in identifying patients at risk of developing ILD. We included patients from a single referral centre, with no ILD on baseline HRCT and at least one clinical and HRCT follow-up. Images 1) were assessed for presence/absence of ILD at all timepoints, 2) underwent lung texture analysis (LTA,Imbio), quantifying PVV, normal lung, lung pathologies (hyperlucency, ground-glass, reticular, honeycombing), as percentage of the lung volume, for whole lungs and upper, middle, lower zones. Univariable and multivariable prediction models were developed to identify risk factors for ILD onset, using Cox regression and generalizes estimating equation (GEE) analysis for ILD onset ever and at 1-year, the latter allowing for multiple observations of the same patient. Both models were adjusted for the established clinical risk factors (1,2). Among 248 SSc patients with no ILD at baseline HRCT, new onset of ILD occurred in 54 (22%) cases over a median follow-up of 39(24-72)months. Patients developing ILD were more frequently males, with diffuse skin involvement, anti-topoisomerase I antibodies and shorter disease duration (Table I). Additionally, patients with new onset ILD over the study period presented higher values of PVV across all lung zones at baseline HRCT (Table II). In multivariable Cox regression analysis, new ILD onset was independently predicted by PVV% from the whole lung [HR 1.054 (1.030-1.078)], as well as from each individual zone. When integrating the PVV% of each single zone with the clinic risk factors in the multivariable analysis, we observed the significant, independent impact of the lower zone PVV% [HR 1.217 (1.113–1.332)], in addition to the known risk associated with clinical features [HR 3.281 (2.145–5.021)] (Figure I-A). Focusing on 1-year ILD onset, we analysed 279 follow-up visits from 193 patients and observed 22 (11.4%) new onset ILD (Table I). On univariable GEE, we confirmed the association of PVV from the whole lung on ILD onset, with particular focus on the middle and upper zones, alongside the clinical risk factors. In the multivariable model adjusted for clinical risk factors, PVV% of the upper zone remained significantly associated with ILD onset [OR 4.127 (1.016–16.761)] (Figure I-B). PVV% from HRCT scans of SSc patients without ILD can predict new onset of ILD at both 1-year and long-term follow-up, supporting the use of radiomics in risk phenotyping. References. p]:pt-0 [&>p]:mb-2 [&>p]:my-0"> Petelytska L, Bonomi F, Cannistrà C, Fiorentini E, Peretti S, Torracchi S, et al. Different definitions of disease severity, progression and activity in systemic sclerosis: data from the EUSTAR database. Arthritis Rheumatol. 2023;75(Suppl 9):Abstract 1234. p]:pt-0 [&>p]:mb-2 [&>p]:my-0"> Hoa S, et al. Arthritis Rheumatol. 2025. p]:pt-0 [&>p]:mb-2 [&>p]:my-0"> Occhipinti M, Bosello S, Sisti LG, Cicchetti G, de Waure C, et al. Quantitative and semi-quantitative computed tomography analysis of interstitial lung disease in systemic sclerosis. PLoS One. 2019;14(11):e0224982. doi:10.1371/journal.pone.0224982.
PO:07:095 | Clinical impact of therapeutic modification following changes in AIFA reimbursement criteria for JAK inhibitors in patients with RA in remission/low disease activity: analysis of the multicenter JAK-SWAP RER study in Emilia-Romagna
Background. Since March 2023, AIFA has introduced new reimbursement criteria for JAK-inhibitors (JAKis), restricting their use to patients with rheumatoid arthritis (RA) without specific risk factors and with previous failure of bDMARD therapy. These restrictions have influenced prescribing behavior, leading in some cases to treatment changes in patients already receiving JAKis. The primary objective of this study is to evaluate the frequency of maintenance of remission/low disease activity (REM/LDA) at 6 months, and to identify potential associated factors, in patients undergoing treatment modification compared with those who continued the ongoing therapy. Materials annd Methjods. In this prospective, multicenter, observational cohort study, we enrolled patients with RA in stable REM/LDA for at least 6 months on JAKi therapy (03/2023–07/2024), for whom a therapeutic modification was proposed (dose reduction, treatment discontinuation with switch to another bDMARD, or discontinuation without switching) due to non-fulfillment of AIFA reimbursement conditions. At 6-month follow-up (T6), the frequency of REM/LDA maintenance was assessed, while additional therapeutic modifications (cs/b/tsDMARDs) and adverse events (AEs) were evaluated during the 12-month total follow-up. Associations between clinical-demographic characteristics and T6 outcomes were analyzed using univariate logistic regression. Results. A total of 127 patients were enrolled (Table 1). Among them, 36 underwent JAKi modification at baseline (17 switches, 14 dose reductions, 5 discontinuations), while 91 maintained JAKi therapy, of whom 16 remained eligible for reimbursement according to AIFA criteria (Figure 1A). At T6, 109 patients were reassessed. Maintenance of REM/LDA at T6 was significantly less frequent in the group that modified therapy at baseline compared to those who continued treatment (23 (76.7%) vs 73 (92.3%), p=0.024; OR 0.27, 95% CI 0.08–0.88) (Figure 1B). Univariate analysis showed that dyslipidemia and history of malignancy were associated with reduced REM/LDA maintenance, whereas first-line bDMARD use correlated with greater clinical stability (Table 2). Patients who modified therapy at baseline showed a higher frequency of further treatment changes (19 (54.3%) vs 26 (29.6%), p=0.010) and a higher mean (SD) number of AEs (0.43 (0.85) vs 0.23 (0.62), p=0.12) during the 12-month follow-up (Table 3). Conclusions. The analysis of the JAK-SWAP RER study suggest that modifying an effective JAK inhibitor regimen in clinically stable RA patients is associated with poorer clinical outcomes at 6 months, an increased need for further treatment changes, and a trend toward a higher rate of AEs. A conservative management approach should be preferred in patients in REM/LDA, even following changes in reimbursement criteria, particularly in those treated in later therapeutic lines.
CO:10:5 | Beyond major glands: high-resolution ultrasound mapping of labial salivary and lacrimal gland involvement in Sjögren’s disease
Background: Ultra-high frequency ultrasound (UHFUS) has emerged as a valuable tool for assessing the lacrimal glands (LGs) and labial salivary glands (LSGs) in patients with Sjögren’s disease (SD). However, only a few studies have investigated the diagnostic utility of evaluating these two gland types in combination. This study aimed to determine whether assessing both the number of glands involved and the severity of their involvement, based on the presence of very hypoechoic areas (VHA), could enhance diagnostic accuracy and support phenotypic stratification in patients with suspected SD. Methods: Consecutive patients with suspected SD, undergoing LSG biopsy, were included. LSGs and LGs were examined using 48 MHz and 18 MHz probes, respectively. Glandular inhomogeneity was evaluated using a semiquantitative OMERACT score ranging from 0 to 3 for each gland, and a combined score for the LSGs and LGs was calculated (range 0–6). We specifically investigated the presence of very hypoechoic areas ( either lymphoma pattern and/or multiple very hypoechoic areas pattern (1,2)). Serum from each patient was tested for anti-Ro52, anti-Ro60, and anti-SSB/La abs, evaluating the quantitative titer of the autoantibodies with band densitometry. Results: A total of 71 subjects (10 males, 61 females) were enrolled in the study, of whom 28 fulfilled the ACR 2016 classification criteria for Sjögren’s disease (SD). Cohen’s kappa analysis demonstrated moderate concordance in grayscale assessment between LGs and LSGs (k = 0.600, p < 0.001). Receiver operating characteristic (ROC) curve analysis showed that both LG and LSG UHFUS scores, using an optimal cut-off of 2, could effectively differentiate patients with SD from sicca controls, with area under the curve (AUC) values of 0.836 (95% CI: 0.702–0.970) and 0.899 (95% CI: 0.807–0.991), respectively. The combined score yielded excellent diagnostic accuracy (AUC = 0.909, 95% CI: 0.820–0.997; Fig. 1, A-B). All individuals with UHFUS scores >2 in both LGs and LSGs were diagnosed with SD. Patients exhibiting positive UHFUS findings in both gland types ('double positive') displayed significantly higher levels of tissue inflammation, autoantibody titers, and ESSDAI scores compared to those with abnormalities limited to a single gland type. Conversely, patients with UHFUS scores <2 across all glands had the lowest levels of inflammatory biomarkers and autoantibody titers (Fig. 1, C). An increasing burden of VHAs was associated with elevated histological inflammatory markers, autoantibody titers, immunoglobulin levels, and ESSDAI scores, while C4 and lymphocyte counts decreased accordingly (Fig. 1, D). Conclusions: Evaluating multiple exocrine glands increases diagnostic power. Furthermore, as in joint ultrasound, a higher number and greater severity of exocrine gland abnormalities is associated with increased systemic disease activity and heightened biohumoral responses. References. 1) Lorenzon et al., CER, 2021 2) Fulvio et al., CER 2022.
PO:07:096 | Safety of filgotinib in the treatment of rheumatoid arthritis: results from the multicentre SOFIA study
Background. To evaluate safety of filgotinib in terms of frequency, severity, and type of adverse events (AEs) and to identify predictors of AEs in a multicentre cohort of patients with rheumatoid arthritis (RA). Materials and Methods. This is a prospective multicentre study that included patients with RA (ACR/EULAR 2010 criteria) treated with filgotinib in six different Italian centres. At follow-up visits, conducted every 3-6 months, AEs were recorded and classified as attributable to drug use with almost certain/high/low/no probability according to clinical judgement. AEs were described as severe in accordance with the EMA definition. Possible risk factors for AEs were examined using the t-test, chi-square test or Fisher's exact test as appropriate. The analysis was performed using SPSS version 29. Results. A total of 190 patients with RA were enrolled, with a mean age of 59±11 years and a mean disease duration of 17±10 years. The mean baseline Charlson Comorbidity Index (CCI) was 2±1 (Table 1). Out of 463 follow-up visits, 128 AEs and one death were recorded, the latter considered unlikely to be associated with filgotinib use (Table 2). The most frequent AEs were infections (53 events), only 5 of which were classified as severe (9.5%). We recorded 18 AEs attributable to cardiovascular risk, all of which were considered mild except for one serious cardiovascular event, which was judged unlikely to be drug-related (Table 2). Overall, in 8% of cases, AE was considered almost certainly associated with the use of the drug, while in 27% of cases, the association was denied (Table 2). AEs caused discontinuation of therapy in 14 cases (7.3% of patients). The only factor associated with AEs that emerged at multiple time points was male gender (6 months p=0.04, 12 months p=0.02, 24 months p=0.04). Besides, a lower baseline CCI was associated with a significant reduction in AEs at 24 months (p<0.001). Conclusions. In a large cohort of patients with RA, non-severe infections were the most frequent AE. No clinical or therapeutic risk factors (e.g., concomitant use of csDMARDs, steroid dose) associated with AEs emerged. As expected, the presence of comorbidities, assessed using the CCI, was associated with an increased risk of AEs in the long term.
CO:10:6 | Impact of pregnancy on organ damage in systemic lupus erythematosus: a prospective multicenter study
Background. Pregnancy in systemic lupus erythematosus (SLE) is associated with increased risk of fetal and maternal complications, as well as a higher risk of disease flares. Data on pregnancy’s impact on damage accrual in SLE are limited. We aimed to assess the role of pregnancy and related factors in damage increase in SLE patients. Methods. Consecutive patients fulfilling the 2019-ACR/EULAR SLE criteria were prospectively enrolled at pregnancy detection and monitored every 4 weeks at two referral centers. At baseline, demographic, clinical, and treatment data were collected. Disease activity was assessed by SLE Disease Activity Index-2k score(SLEDAI-2k); flares during pregnancy by the modified SELENA-SLEDAI flare index. Remission was defined by DORIS-criteria, and low disease activity state (LLDAS) by the Asian Pacific definition. Disease was defined as active if SLEDAI-2K>4. Pregnancy outcomes included preeclampsia, premature membrane rupture <37 gestational-weeks, small for gestational-age, intrauterine growth restriction, intrauterine fetal death and birthweight <2500 gr. Damage accumulation was assessed using the SLICC Damage Index score over two years pre-pregnancy, one year pre- and one year post-pregnancy. Factors influencing damage accrual during pregnancy were analyzed by logistic regression. To assess the effect of pregnancy per se on damage accrual, we examined this relationship using a cross-over design. The year before pregnancy was compared with the year post-pregnancy in terms of damage accrual; results are expressed as delta damage. Results. We analyzed 165 pregnancies in 122 patients. Figure1 shows demographic, clinical, and serological features; Figure2 reports obstetric outcomes and first pregnancy visit data. At conception, 26 pregnancies(15.8%) had pre-existing damage(mean 1.1, SD±0.32). In the year after pregnancy, 29 cases (17.6%) had a SLICC score of 1 or higher(mean 1.24, SD ±0.51), including 3 new damage cases in previously unaffected patients. 7 patients (4.4%) presented increased damage post-pregnancy, consisting of osteoporotic fracture, malignancy, cerebrovascular event, scarring alopecia, cognitive impairment, and diabetes mellitus. Only 1 new damage event(cataract) occurred in the year before pregnancy. At logistic regression of the cross-over analysis, pregnancy per se was not significantly associated with SLICC increase (OR 3.61, 95% CI). Exploring variables potentially associated with damage accrual, with a multivariate logistic regression analysis we found that pre-existing organ damage (OR 8.24, 95% CI) and disease activity at the beginning of pregnancy (OR 6.65, 95% CI) were independently associated with post-pregnancy damage accrual. No associations emerged with age, disease duration, overlap syndromes, or ongoing therapies during pregnancy. Conclusions. In SLE patients followed at tertiary centers, pregnancy per se was not linked to damage accrual. However, in patients with pre-existing damage and active disease at conception, damage accrual should be considered in the pre-conceptional counselling. These results highlight the need for organ damage prevention strategies and pregnancy planning during disease control
PO:07:099 | Survival on therapy of certolizumab pegol in rheumatoid arthritis, psoriatic arthritis, and spondyloarthritis: 8-year data from an Italian multicenter register
Background. To evaluate the persistence in therapy of certolizumab pegol in a multicenter Italian registry of patients affected by rheumatoid arthritis (RA), psoriatic arthritis (PsA) or axial and peripheral spondyloarthritis (SpA). Materials and Methods. Data were collected prospectively from a multicenter Italian registry of patients with RA, PsA, and SpA treated with certolizumab pegol through March 2025. Persistence in therapy was calculated using the Kaplan-Meier method for the three diagnoses. Comparative subanalyses of retention rate were performed using Cox regression across the different populations, by treatment line, sex, concomitant csDMARD, and rheumatoid factor positivity. Results. A total of 1167 patients were included in the analysis. Of these, 401 were affected by RA (87.8% female, mean age [± standard deviation (SD)] 50.5 [±14.6] years, mean disease duration 10.5 [±9.3] years, 50.4% in first-line biologic, 54.9% in combination with csDMARDs), 448 by PsA (73% female, mean age [±SD] 48.5 [±14] years, mean disease duration 7.6 [±6.7] years, 38.4% in first-line biologic, 65% in combination with csDMARDs) and 318 by SpA (76.4% female, mean age 47.7 [±13.7] years, mean disease duration 7 [±7.4] years, 44.3% in first-line biologic). The retention rate in the RA, PsA, and SpA groups was 78.2%, 74.2%, and 75.5% at 12 months, 63.3%, 56.6%, and 60.4% at 24 months, and 52.7%, 48.5%, and 53.5% at 36 months, respectively. At 8 years, the retention rate was 33.8%, 27.6%, and 35.6% in RA, PsA, and SpA, with no significant difference between the three diagnoses (Figure). Among patients who discontinued the drug in the RA, PsA, and SpA groups, 19.2%, 27%, and 20.1% discontinued due to inefficacy, and 3%, 6.7%, and 6.6% due to adverse events, respectively. In subanalyses stratified by treatment line, first-line survival in RA was not different from second-line survival, but significantly superior to subsequent lines; conversely, in PsA and SpA the retention rate in the first line was statistically higher than in the other treatment lines. In the three indications, survival on therapy was not significantly different between the two sexes. In subjects with RA, survival was longer with biological monotherapy compared to the combination with csDMARDs, while no significant difference was found in PsA and SpA. In RA, rheumatoid factor positivity or negativity was not associated with different retention rates. Conclusions. In our registry data on certolizumab pegol, we observed a high treatment persistence at 3 years in all indications, and in approximately one third of patients at 8 years, supporting the real-life efficacy and safety of this treatment in RA, PsA and SpA.
CO:11:2 | Systemic lupus erythematosus with major neuropsychiatric involvement treated with anifrolumab: literature review and a case report
Background. Anifrolumab is a biologic agent approved for the treatment of Systemic Lupus Erythematosus (SLE). Clinical trials evaluating its efficacy (TULIP-1 and TULIP-2) excluded patients with active neuropsychiatric manifestations (NPSLE). The aim of this study was to review the published cases of NPSLE treated with Anifrolumab (ANI) and to describe a clinical case from our cohort. Materials and Methods. A literature search was conducted on Medline/PubMed and Embase for reports of NPSLE patients treated with ANI. In addition, we describe a case from our local cohort. Results. The literature review identified seven published cases of NPSLE successfully treated with ANI, including two with confusional states, one with acute psychosis, one with headache, one with cerebral vasculitis, one with aseptic meningitis, and one with demyelinating polyneuropathy. The data are summarized in Table 1. We also report the case of a 63-year-old woman with a 26-year history of SLE and antiphospholipid syndrome (APS), who initially presented with polyarthritis, lymphopenia, an ischemic stroke, and positivity for ANA, anti-dsDNA, anti-Ro/SSA, lupus anticoagulant, anti-cardiolipin IgG, and hypocomplementemia. Over the years, she experienced a relapsing-remitting course characterized by cutaneous vasculitis of the hands and feet, thrombocytopenia, leukopenia, and epileptic seizures with spatiotemporal disorientation. Electroencephalography revealed left-hemispheric irritative electrical abnormalities, interpreted as secondary to ischemic damage. The patient’s treatment history included several immunosuppressants—cyclophosphamide, azathioprine, mycophenolate mofetil, belimumab, and hydroxychloroquine (discontinued due to gastrointestinal intolerance, INR abnormalities, and arrhythmia). Levetiracetam was escalated to 2500 mg/day due to worsening seizures, without achieving clinical remission (DORIS). In 2022, following prednisone tapering to 5 mg/day, disease flare occurred with hand vasculitis, malar rash, alopecia, leukopenia (1700/µl), and thrombocytopenia (95,000/µl). Anifrolumab was initiated, and prednisone was increased to 10 mg/day. At the 3-month follow-up, mucocutaneous and hematologic manifestations had resolved, and seizure frequency had decreased (from 2/week to 1 every 8 weeks). After 6 months of ANI treatment, the patient achieved complete clinical remission (CLASI = 0, cSLEDAI-2K = 0) with prednisone tapered to 2.85 mg/day. Conclusions. The results from both the literature review and our clinical case suggest that Anifrolumab may be effective in managing neuropsychiatric manifestations of SLE. In our experience, a remarkable improvement was also observed in the hematologic domain. Although these findings are encouraging, they warrant confirmation in dedicated clinical trials, emphasizing the need for personalized therapeutic strategies in SLE management.
PO:07:101 | Efficacy and safety of methotrexate in a cohort of patients affected by early-onset rheumatoid arthritis: a monocentric real-life study
Background. Methotrexate (MTX) is the first-line Disease Modifying Anti-Rheumatic Drug (DMARD) in the treatment of rheumatoid arthritis (RA). According to EULAR guidelines, patients with RA should start immunosuppressive therapy at the time of diagnosis, achieve clinical improvement within 3 months, and remission within 6 months. The objective of this monocentric, retrospective, real-life study was to evaluate the achievement of the therapeutic target in a cohort of patients affected by early-onset RA treated with MTX. Further objectives were to evaluate the MTX ability to act as a “steroid sparing” agent, assess its safety, and the monotherapy maintenance rate. Materials and Methods. Patients attending the Early Arthritis Clinic from 2006 to the present, affected by RA (ACR 2010 criteria) who had started MTX therapy within 24 weeks from symptom onset, were enrolled. Demographic, clinical, pharmacological, clinimetric indices, and any adverse events associated with therapy were recorded at baseline (T0) and during follow-up until MTX discontinuation or switch to biotechnological therapy. Results. Table 1 reports demographic and clinical data of the 78 enrolled patients. Graph 2 shows disease activity according to DAS28-PCR and SDAI (2a; 2b) and the percentage of Boolean remission (2c) at follow-up. The median time to achieve remission or low disease activity was 3 months, both according to DAS28-PCR and SDAI (graph 3a). Referring to remission only, the median was 6 months according to DAS28-PCR, while it was 24 months according to SDAI and Boolean Remission 2.0 definition (graph 3b). It emerged that in patients treated with MTX, the mean prednisone dose progressively decreases by 0.08 mg per month, while the probability of continuing steroid therapy decreases by 10% for each month of treatment. Therapy persistence was 7 years in half of the patients (graph 4a), while the median MTX monotherapy maintenance was 6 years (graph 4b). Conclusions. To our knowledge, this is the first monocentric study that evaluated in real life the efficacy and safety of MTX in early RA patients. MTX confirms its role as an anchor drug in the treatment of RA, with a probability of achieving the therapeutic target already at 3 months in two-thirds of patients with recent disease onset. Our data confirm the higher stringency of SDAI and Boolean Remission 2.0 compared to DAS28-PCR. MTX significantly reduces the steroid dose until discontinuation. Finally, in our cohort, it showed a good safety and clinical efficacy profile, with good therapy persistence.
CO:11:4 | Unveiling frailty in active systemic lupus erythematosus in the modern era of rheumatology: first real-life use of the SLICC-FI in a cohort diagnosed after 2000
Background. In patients with active systemic lupus erythematosus (SLE), therapeutic decisions should consider frailty, which reflects disease activity, organ damage, and comorbidities. The SLICC Frailty Index (SLICC-FI) has proven useful in predicting mortality, damage accrual, and hospitalizations. This study applied the SLICC-FI in an active SLE cohort to estimate frailty prevalence and identify key clinical determinants. Materials and Methods. This was a retrospective analysis of prospectively collected data from a monocentric SLE cohort fulfilling the 2019 EULAR/ACR classification criteria. Eligible patients were diagnosed after 2000 and had active disease requiring therapeutic modification. The SLICC-FI (FI) was calculated at study entry using a modified 37-item version (clinician-reported variables only). Based on FI score, patients were classified as robust (FI < 0.03), relatively less fit (0.03 < FI < 0.10), less fit (0.10 < FI< 0.21), or frail (FI > 0.21). Demographic, clinical, and serological data were collected. Results. A total of 119 patients were included (94.1% female; mean age 37.1 ± 10.7 years; median disease duration 12 years IQR). At study entry, median SLEDAI was 8 (IQR), median SLICC was 1 (range 1–4); median daily dose of glucocorticoids (GC) was 4 mg (IQR). The mean FI was 0.20 ± 0.08; 5.9% (7/119) were relatively less fit, 53.8% (64/119) less fit, and 40.3% (48/119) frail, no patients were categorized as robust. The most important determinants of frailty in frail patients are shown in Figure 1. No differences emerged between frail and non-frail patients in age at diagnosis, disease duration, SLICC, SLEDAI, or baseline steroid dose. Regarding cumulative organ involvement, kidney (p=0.028), articular (p=0.023), constitutional (p=0.006), and pulmonary (p=0.005) systems were significantly more affected in frail patients. Frail patients were more frequently SSA-positive (p=0.025), SSB-positive (p=0.007), and had more overlap syndromes (Sjogren or APS; p=0.04), but not more Sjogren’s diagnoses. Other autoantibody profiles did not differ. Comorbidities were more frequent among frail patients (p=0.013), although fibromyalgia prevalence was similar. No differences emerged in the number of immunosuppressants used during the disease history; however, all patients with more than four therapy changes were frail, particularly those treated with MMF (p=0.008) and MTX (p=0.41). Other analyses are shown in Figure 2. Conclusions. Application of the SLICC-FI in a real-life active SLE cohort revealed a high prevalence of frailty, also in patients with a relatively recent disease history and treated with more recent therapeutic approaches. This tool allows comprehensive assessment of clinical vulnerability and may assist therapeutic decisions in complex cases. Further analyses are ongoing to evaluate its prognostic value for treatment response and long-term outcomes.
PO:07:102 | Predicting success with baricitinib in rheumatoid arthritis: efficacy across ages and serological profiles
Background. Evaluate the real-world effectiveness of baricitinib in 423 rheumatoid arthritis (RA) patients, compare outcomes in <65 years (n=264) versus 65 years and older (n=159) patients, and identify predictors of DAS28-ESR remission/LDA at 6 and 12 months. Methods. Retrospective multicenter cohort; recorded baseline age, sex, disease duration, and comorbidities. DAS28-ESR was measured at baseline, 6 and 12 months; remission was defined as DAS28-ESR <2.6 and LDA as <3.3. Response predictors were assessed by multivariate logistic regression, reporting OR with 95% CI and p values. Results. Median age was 59 years (IQR 51–67); 79% female; median disease duration 76 months (IQR 31–157). Patients of 65 years and older experienced longer disease duration (94 vs 65 months; p<0.01) and higher rates of diabetes (16% vs 5%; p<0.01), dyslipidemia (47% vs 19%; p<0.01) and hypertension (62% vs 33%; p<0.01). Median DAS28-ESR fell from 5.42 (IQR 4.84–6.06) at baseline to 3.71 (IQR 2.83–4.59) at 6 months and 3.29 (IQR 2.42–4.19) at 12 months (both p<0.01). Remission/LDA was achieved by 246/422 (58.3%) at 6 months and 259/423 (61.2%) at 12 months. Age of 65 and older was not associated with response at 6 months (OR 0.71; 95% CI 0.44–1.14; p=0.16) or 12 months (OR 0.83; 95% CI 0.55–1.24; p=0.37). ACPA-positivity independently predicted remission/LDA at 6 months (OR 2.32; 95% CI 1.43–3.77; p<0.01) and 12 months (OR 1.71; 95% CI 1.12–2.59; p<0.01). Conclusion. Baricitinib significantly reduced RA disease activity over 12 months regardless of age or comorbidities, with ACPA-positivity as a strong independent predictor of clinical response.
CO:11:5 | Laboratory preliminary results from an open label, prospective, phase ii descriptive pilot trial of belimumab therapy for refractory and/or non criteria manifestations of antiphospholipid syndrome
Background. The aim of this study was to evaluate preliminary laboratory results of the BLAST trial. Belimumab was given for 40 weeks in 15 patients positive for antiphospholipid antibodies (aPL) showing refractory and/or non criteria APS manifestations. Materials and Methods This is an open-label, single-centre trial. Laboratory endpoints were determined at baseline, 8, 20 and 40 weeks. Outcomes included routine tests, aPL, thrombin generation assay, lymphocytes immunophenotyping and BAFF determination. Results. We observed a reduction of aPL levels following 40 weeks of treatment: 60% showed a reduction of aCL IgG levels, 53% showed a reduction of aB2GPI IgG levels , 47% showed a reduction of aB2GPI Domain I levels, 33% showed a reduction of aPS/PT IgG levels and 40% showed a reduction of aPS/PT IgM levels (Figure 1). When considering TGA profile, a normalization of the curves were observed following treatment: 40% of patients showed a normalization of TGA parameters at week 40, meaning a reduction of tLag and tPeak and an increase of Peak and AUC. Table 1 summarizes the delta of aPL levels and TGA parameters between week 40 and baseline. When analyzing aPL levels and TGA parameters, significant correlations were demonstrated showing a normalization of the thrombogram and reduction of aPL levels following treatment. This finding was confirmed for the following specificities: aPS/PT IgG [tLag (p=0.001/Pearson+0.4), tPeak (p=0.001/Pearson+0.4), Peak (p=0.001/Pearson-0.4) and AUC (p=0.002/Pearson-0.4)]; aCL IgG [tLag (p<0.001/Pearson+0.6), tPeak (p<0.001/Pearson+0.6), Peak (p<0.001/Pearson-0.5) and AUC (p=0.002/Pearson-0.4)]; aB2GPI IgG [tLag (p<0.001/Pearson+0.6), tPeak (p<0.001/Pearson+0.6), Peak (p=0.001/Pearson-0.4) and AUC (p=0.002/Pearson-0.4)]; aB2GPI Domain I [tLag (p<0.001/Pearson+0.5), tPeak (p<0.001/Pearson+0.5), Peak (p=0.001/Pearson-0.4) and AUC (p=0.002/Pearson-0.3)]. When considering the whole cohort, a statistically significant reduction of BAFF serum levels was observed after 8 weeks of treatment. CD20+ and CD19+ cells significantly decreased after 20 weeks. In the subgroup of patients showing a complete response after 40 weeks of treatment, a significant reduction of BAFF was observed at week 8, starting from higher levels of BAFF at baseline. In this case, CD20+ and CD19+ cells showed a statistically significant reduction after 40 weeks of treatment. Conclusions. The use of Belimumab was associated with a change in the immunological/prothrombotic profile when evaluated by changes in the aPL levels at week 40 and the normalization of the thrombogram as shown in the TGA testing. These are preliminary laboratory results of the BLAST trial, to be confirmed after all 20 enrolled patients finish 2 years treatment.
PO:07:103 | Tocilizumab use in patients with rheumatoid arthritis and malignancy: a monocentric experience
Background. In 2024, the EULAR published a set of points to consider for initiating targeted therapy in rheumatoid arthritis (RA) patients with a history of malignancy, indicating TNF inhibitors are preferred in solid tumors, while rituximab is recommended for hematological malignancies. Although the interleukin-6 receptor inhibitor tocilizumab (TCZ) showed a favourable oncological safety profile, the EULAR taskforce did not issue specific recommendations in favour of its use in this clinical context due to a lack of robust evidence. Our aim was to evaluate in a single-center study the oncological safety of TCZ in RA patients with prior malignancy. Methods. Within the cohort of patients followed at the Arthritis Clinic of our hospital, we retrospectively identified RA patients (according to 2010 ACR/EULAR criteria) treated with TCZ for at least 3 months following cancer diagnosis, either active or in remission at treatment start. Data were collected on the characteristics of both rheumatologic and oncologic diseases, treatments before and after TCZ, and outcomes including rheumatic disease activity (based on the Disease Activity Score, DAS28) and oncologic response (complete remission, partial response, stable disease, progression, relapse). Results. We identified and included 34 patients who met the study criteria. Their demographic, rheumatologic, and oncologic characteristics are summarized in Table 1. Patients had a median age of 60 years (IQR, 51-69) at RA diagnosis and 68 years (IQR, 62-75) at TCZ start. TCZ was started in 21 patients in remission and in 13 with active malignancy. Median interval between cancer diagnosis and TCZ start was 35 months (IQR, 11–70). Ten patients had another bDMARD between cancer diagnosis and TCZ start. Two patients were already on TCZ at cancer diagnosis and continued uninterrupted. Median TCZ duration was 19 months (IQR 8–43). Concomitant csDMARDs were used in 19 cases, and methotrexate was the most frequently used (11 cases). TCZ treatment was also associated with a significant reduction in disease activity, with a decrease in DAS28 from 5.50 (IQR 4,46 – 6,68) at the visit before TCZ start to 2.28 (IQR 1.52 – 2.85) at the last follow-up visit during TCZ therapy. Among patients with malignancy in remission, only one case of cancer recurrence (lung adenocarcinoma) was observed (Figure 1). No cancer progression occurred in patients with active malignancy. No discontinuations were due to oncologic concerns while TCZ was stopped for lack of efficacy in 4 patients (Table 1). Conclusions. In this single-center cohort, TCZ showed a favourable oncologic safety profile in RA patients with prior malignancy, including those with active cancer at treatment start. No cancer progression was observed; only one recurrence occurred. Further prospective studies are needed, but these findings suggest TCZ may be a safe and effective option in RA patients with prior malignancy.
CO:11:6 | Off-therapy remission in systemic lupus erythematosus: the BLys lupus flare index (BLyFI) as a decision tool for immunosuppressive therapy withdrawal in remitted patients
Background. The most recent literature regarding the discontinuation of immunosuppressive therapy (IS) in patients with systemic lupus erythematosus (SLE) in remission highlights that approximately one in four patients experience a relapse. We have learned how flare-ups impact the extent of accumulated damage, caused on the one hand by disease activity and on the other by prolonged exposure to IS therapy. This clearly supports the need for a tool that guides clinicians towards safe management of therapy in patients in remission. We therefore evaluated several serological biomarkers, such as anti-native DNA, C3, C4, anti-C1q, anti-PTX3, APRIL, BLyS, C3a and C3c. Based on the results observed, we created an algorithm capable of estimating the risk of relapse in patients in remission following the discontinuation of IS therapy. Materials and methods. We conducted a retrospective study of 57 patients with SLE who had discontinued IS therapy after achieving remission. Clinical SLEDAI-2K = 0, associated with stable background therapy and/or a prednisone dose ≤5 mg/day, identified remission status. Flares were defined according to the SLEDAI-Flare-Index. A multivariate logistic regression model was applied to evaluate the association between the risk of flare and clinical and serological data collected in the 6 months following discontinuation of IS therapy. The variables found to be significant were then combined to create a flare predictor algorithm. Results. Fifteen patients (26.3%) experienced a relapse, on average 4.35 (± 4.1) years after discontinuation of IS therapy. Serum BLyS levels were significantly higher in patients with relapse (median 0.869 ng/mL, IQR 0.669–1.262; p = 0.033) than in patients who remained in remission. Maintenance therapy with hydroxychloroquine (HCQ) at the time of IS therapy discontinuation showed a protective effect (OR = 0.21; p = 0.019). BLyS values, native anti-DNA antibody positivity, remission greater than 3 years at the time of IS therapy discontinuation, and HCQ use, weighted as shown in Figure 1, provided the optimal combination for constructing a flare prediction algorithm (AUC = 0.779; SE = 100%; SP = 62.9%). All patients who experienced a flare-up had a BLys Lupus Flare Index (BLyFI) value greater than the cut-off of -3.43. Conclusions. Through the combination of serum BLyS levels with other variables readily available in clinical practice, we have developed a non-invasive tool capable of predicting the risk of relapse in patients in remission candidates for discontinuation of immunosuppressive therapy.
PO:08:113 | Shaping rheumatoid arthritis treatment: clinical and demographic drivers of tsDMARDs versus bDMARDs prescription post-EMA pronouncement on JAK inhibitors - insights from the AMBI-RA study
Background. The AMBI-RA study aimed to assess the influence of clinical and demographic factors on the choice between JAK inhibitors (JAKis), TNF inhibitors (TNFis), and non-TNFi bDMARDs in patients with rheumatoid arthritis (RA), before and after the publication of the EMA safety recommendations on JAKis (January 2023). Six-month outcomes were analyzed to determine whether these recommendations affected the achievement of therapeutic targets. Materials and Methods. In this single-center, ambidirectional cohort study, clinical, laboratory, and clinimetric data were collected at baseline and after 6 months of follow-up following the initiation of a new therapeutic line with JAK inhibitors (JAKis), TNF inhibitors (TNFis), or non-TNFi bDMARDs in patients with rheumatoid arthritis (RA). Patients were divided into two cohorts: retrospective (pre-EMA) and prospective (post-EMA). The association between clinical and demographic factors and treatment selection was assessed using univariate and multivariate logistic regression analyses. Additionally, we evaluated the relationship between these factors and non-response at 6 months, defined as failure to achieve remission or low disease activity (REM/LDA) according to DAS28-CRP, or early discontinuation of the bDMARD due to lack of efficacy. Results. A total of 539 treatment courses were analyzed: 300 in the retrospective cohort (pre-EMA: 2019-2022) and 239 in the prospective cohort (post-EMA: 2023-09/2024). Following the EMA safety recommendations, the use of TNFis increased from 32% to 41.4%, while JAKi prescriptions declined from 26% to 16.3%. TNF is also became the most frequently prescribed first-line agents, rising from 51.6% to 74%, whereas JAKis and non-TNFi bDMARDs decreased from 18% to 4.1% and from 30.5% to 21.9%, respectively (Table 1). Except for older age, the EMA-identified risk factors did not significantly influence JAKi prescriptions in the prospective cohort. TNFis were consistently associated with first-line use in both cohorts, while non-TNFi bDMARDs were positively associated with older age and negatively associated with first-line use in the prospective cohort (Tables 2-3). Regarding treatment outcomes at 6 months, remission (REM) rates decreased from 45.1% to 33.1%, low disease activity (LDA) from 58.6% to 49.3%, and non-responder rates increased from 41.8% to 50.6%. Moreover, first-line treatment was the only factor significantly and negatively associated with non-response at 6 months in the retrospective cohort, but not in the prospective one, suggesting a possible loss of the clinical benefit historically linked to first-line therapy (Table 4). Conclusions. The AMBI-RA study represents the first attempt, through an ambidirectional design, to compare the association between clinical and demographic variables and the prescription of b/tsDMARDs before and after the EMA safety recommendations on JAK inhibitors. The analysis of their impact on the examined cohort suggests a lower effectiveness of first-line treatment strategies, which have shifted predominantly toward TNFis in the post-EMA period. Future multicenter studies are warranted to further explore how regulatory decisions by international agencies may influence therapeutic target achievement in clinical practice.
CO:12:4 | Predicting 12-month clinical relapse in Takayasu arteritis using [18F]FDG PET and convolutional neural networks
Background. Takayasu arteritis (TAK) is a large-vessel vasculitis with fluctuating disease activity and a lack of validated biomarkers for relapse prediction. While [18F]FDG PET provides diagnostic sensitivity, its prognostic role remains debated. This study aimed to assess whether convolutional neural networks (CNNs) applied to baseline [18F]FDG PET scans can predict clinical relapses within 12 months in patients with TAK. Methods. We retrospectively analysed [18F]FDG PET scans acquired from patients with TAK between 2013 and 2023 at a tertiary centre. All scans were harmonised using a liver-based standardisation method to correct inter-scanner variability. Clinical relapse was defined as recurrence of TAK-related signs or symptoms, based on blinded chart review. CNNs were trained using four architectures: Baseline model (4 convolutional layers), Residual bottleneck model (3 blocks), and two models retrieved from the MONAI library – ResNet18 and DenseNet121. The dataset was split into training, validation, and test sets. To address class imbalance, we applied class weighting, early stopping, and 10-fold subsampling of the majority class. Data augmentation techniques included RandAffine and RandAxisFlip. Performance was evaluated using accuracy, class-specific precision and recall, specificity, and normalised Matthews correlation coefficient (nMCC). Results. A total of 306 scans from 74 patients with TAK (median age: 47 years [range: 14–75]; 62 females) were included. Sixty-four scans (21%) were followed by clinical relapse within 12 months. Of these, 25 were correctly identified by blinded nuclear medicine readers. The Baseline model-1 achieved the best overall performance with 82% accuracy, 85% precision for class 0, 62% precision for class 1, 38% recall, 94% specificity, and 70% nMCC. DenseNet121-2 yielded 81% accuracy, 100% precision for class 1 (relapse), 8% recall, 100% specificity, and 62% nMCC, maintaining 100% precision and specificity in the subsampled test set. Performance metrics for all models are summarised in Figure 1. Compared to standard visual PET interpretation, which correctly identified fewer than 40% of relapses, CNN-based models significantly improved predictive performance (Figure 2). Conclusions. This is the first study applying CNN-based [18F]FDG PET analysis to predict 12-month clinical relapse in patients with TAK, involving one of the largest PET datasets in this disease. Despite the retrospective design and class imbalance, CNNs demonstrated strong performance in identifying those likely to remain in remission. These findings support the use of imaging-based computational tools to inform treatment tapering and follow-up strategies in patients with TAK.
PO:07:111 | Worsening of patient-reported outcomes is an early predictor of disease flare in patients with rheumatoid arthritis in course of treatment with conventional synthetic disease modifying anti-rheumatic drugs
Background. Rheumatoid arthritis (RA) has a relapsing-remitting course that impedes the achievement of sustained remission and impairs quality of life in many patients. The ability to predict flares of the disease could assist personalized management and treatment approaches. Aim of this study was to test whether longitudinal variations in measures of disease activity and patient-reported outcomes (PRO) after the achievement of stable disease control could predict imminent flares in patients with RA. Methods. From a larger dataset of 817 patients with early RA (duration of symptoms at referral <12 months) undergoing a treat-to-target strategy with methotrexate (MTX) and followed tightly at 3-month intervals, we extracted those who had achieved at least low disease activity (DAS28 <3.2) at two consecutive visits during the first year of treatment. Flare was defined as any increase in DAS28 >1.2, or final DAS28 >3.2 at the visit immediately following the achievement of stable disease control. Longitudinal variations of swollen and tender joint counts, C-reactive protein (CRP) levels, patient global assessment of disease activity (PGA) and pain scores in course of stable DAS28 <3.2 were tested for their ability to predict disease flare. Results. We analyzed 927 visits from 309 patients with early RA achieving stable disease control (DAS28 <3.2 in two consecutive occasions) during the first year of treatment. Flare at the subsequent visit was experienced by 21.4% of the patients. Demographic variables, disease activity measures, autoantibody status, dose of MTX and glucocorticoids at the first visit in DAS28 <3.2 failed to predict future RA flare. As shown in Figure 1A, B, the number of swollen joints an CRP levels remained stable until the time of flare. In contrast, worsening of PGA and VAS pain scores pre-dated the occurrence of flare (Figure 1C, D). Using the Youden index to derive a cut-point that optimally balanced sensitivity with specificity, an increase in PGA >10 mm could identify impending flares with an AUC (95% CI) of 0.68 (0.58-0.79). After stratification for the autoantibody status, the most predictive cut-off of PGA increase was >7 mm in autoantibody-positive and >23 mm in autoantibody-negative patients. Conclusions. In patients with early RA, longitudinal variations of PROs are early warning signs of impending flares in both autoantibody-positive and -negative subjects. Our study adds to the growing body of evidence that supports the use of PROs for monitoring of RA patients.
CO:12:5 | Aortic inflammation and aneurysm risk in giant cell arteritis: a multicenter imaging study
Background. The study’s aims were to evaluate the prevalence of aortitis and aortic aneurysm in patients with newly diagnosed giant cell arteritis (GCA), to estimate the rate of aortic growth, and to identify clinical and imaging predictors of aortic aneurysm development. Materials and Methods. We conducted a retrospective cohort study involving patients with new-onset GCA from two European centers. Included patients underwent baseline thoracic aortic imaging (PET/CT or MRI) within 6 months of the diagnosis and had at least one follow-up imaging of the thoracic aorta at least 6 months later. Aortitis was defined by FDG uptake (equal or greater than grade 2 according to Meller’s scale) on PET/CT or vessel wall thickening/oedema on MRI. Outcomes included aortic diameter and prevalent aortic aneurysms at baseline, aortic growth during follow-up assessed by annualized area changes in mm2/year per segment, and incident aneurysms. Analyses were performed at both patient’s and aortic segment’s level. Multivariable regression models were adjusted for sex and age. Results. A total of 157 patients were included, (mean age 67.9±9.1 years; 69.4% female). Aortitis was present in 93/154 (60.4%) patients at baseline (detected in 32.6% of MRIs and in 71.2% of PET/CT scans) and was associated with younger age (66.5 vs 69.7 years, p=0.028) and fewer cranial ischemic symptoms at disease onset (18.5% vs. 41.7%, p=0.002). Baseline aortic aneurysms were identified in 19.6% of patients and in 5.8% of aortic segments, predominantly in the mid-ascending aorta. Aortitis at baseline was associated with larger aortic diameters (beta = 0.184; p<0.0001) and higher odds of prevalent aneurysm (ORadj=2.3; 95% CI: 1.0–5.1). Over a median follow-up of 30 months, incident aneurysms developed in 9.8% of patients and 4.1% of aortic segments without baseline dilation (Figure). Baseline aortic diameter was the strongest predictor of aortic growth (beta= 0.088; p=0.006) and incident aneurysm formation (HRadj=3.9; 95% CI: 2.0–7.3). Visual symptoms were associated with smaller aortic area increase (beta= -0.111; p=0.038). Mean annual growth of the aortic area ranged from 0.00 to 0.03 mm2/year, without differences between patients with or without baseline aortitis. Aortitis increased the risk of aneurysm progression only among patients already on glucocorticoids at time of baseline imaging, although not reaching statistical significance (HRadj=3.2, 95% CI 0.65-15.7). Conclusions. Aortic involvement is common in GCA patients at diagnosis, and baseline aortitis was associated with prevalent aneurysms and larger aortic diameters but not with subsequent risk of aneurysm formation. Instead, baseline aortic diameter was the most robust predictor of aortic enlargement and aneurysm formation in our cohort. These findings support the hypothesis that inflammation contributes to the initial damage while its progression could be self-perpetuating. Early morphological imaging assessment and longitudinal monitoring of aortic dimensions are necessary in GCA patients.
PO:08:114 | The adjuvanted recombinant zoster vaccine is effective in preventing herpes zoster among patients ≥50 years of age with selected autoimmune diseases in the united states: a real-world database analysis (2018–2021)
Background. The adjuvanted recombinant zoster vaccine (RZV) was approved by the US Food and Drug Administration (FDA) for HZ prevention in adults ≥50 YOA in 2017 and for adults ≥18 YOA who are at increased risk of HZ due to immunodeficiency or immunosuppression in 2021. Autoimmune disease (AID) patients are at increased risk of developing HZ compared to the general population. This real-world evidence (RWE) study assessed RZV vaccine effectiveness (VE) in patients ≥50 YOA with selected AIDs (rheumatoid arthritis, inflammatory bowel disease, systemic lupus erythematosus, multiple sclerosis, psoriasis and psoriatic arthritis). Materials and Methods. This retrospective matched cohort study was conducted in patients ≥50 YOA with selected AIDs using Optum’s de-identified Clinformatics Data Mart database from Jan 2018 to Dec 2021. Patients who received 2 doses of RZV (RZV 2-dose cohort) were matched (1:3) by age, medication category and propensity scores to unvaccinated counterparts (non-RZV cohort) [Figure 1]. Incidence rates (IRs) of HZ and VE were calculated overall, stratified by condition, age, gender, time interval between the 2 doses, and time since vaccination. Cox regression models were used to estimate hazard ratios (HRs). VE as % was calculated as (1−HR) × 100. A similar approach was used to evaluate VE for patients who received 1 RZV dose. Results. We identified 36,645 RZV vaccinated and 109,229 matched non-RZV vaccinated AID patients. Median follow-up was 1.29 (interquartile range [IQR]: 0.73–2.12) and 1.07 (IQR: 0.59–1.95) years for RZV and non-RZV cohorts. IR of HZ was 4.33/1,000 person-years (PY) in the RZV 2-dose cohort and 12.86/1,000 PY in the non-RZV cohort, resulting in an overall VE of 66.3% (95% confidence intervals [CIs]: 61.4–70.7) for AID patients. IRs and VE overall and stratified by each selected AID and variables are presented in Figure 2. Overall VE for AID patients who received 1 RZV dose was 58.3% (95% CIs: 45.8–68.0). Conclusions. This analysis provides RWE that RZV vaccination is effective in preventing HZ in patients ≥50 YOA with selected AIDs. Our findings are consistent with the available literature on RZV effectiveness, which shows that RZV vaccination is beneficial to specific patient groups.
PO:08:116 | Rheumatoid nodulosis: incidence, clinical/instrumental description, and phenotypic correlations in patients with rheumatoid arthritis treated with b-DMARDs. A real-life analysis from a monocentric cohort
Background. Rheumatoid nodulosis is the most common cutaneous manifestation of rheumatoid arthritis (RA), with an estimated prevalence of 20–30%. Less frequently, it involves the lungs (<1%), presenting as rheumatoid pulmonary nodulosis. This preliminary study describes a group of RA patients treated with b-DMARDs, analyzing the prevalence of pulmonary and extrapulmonary nodules and potential clinical associations. Materials and Methods. A retrospective, monocentric, observational study was conducted on 82 RA patients treated with b-DMARDs for at least 12 months. One patient was excluded due to insufficient data. Demographic and clinical features, presence and type of nodules (radiological/histological), and variations in DAS28 at baseline and after 12 months of b-DMARD therapy were analyzed. Results. Of the 82 patients, 65 were women (79.3%), with a median age of 62.5 years and a median disease duration of 11.8 years. Active smoking was reported in 18.3% and previous smoking in 29.3% of cases. RF and CCP tests were negative in about 23% of patients. At diagnosis, 2 patients were untreated; 24 were on monotherapy (predominantly methotrexate), and 56 on combination therapy. The median time between diagnosis and initiation of biologic therapy was 6.14 years (mean 10.33; skewness 1.13). At baseline, DAS28-4v indicated high disease activity in 30.5% of patients, moderate activity in 41.5%, and remission in 13.4%. After 12 months, 50% achieved remission, 62.2% showed clinical improvement, 20.7% remained stable, and 6.1% worsened. The mean DAS28 reduction was similar across different b-DMARD classes, consistent with literature data. Pulmonary nodules were detected in 23 patients, extrapulmonary in 12, and multiple-site nodules in 5. Among patients with pulmonary nodules, 6 had overlap syndromes (Sjögren’s, systemic sclerosis, or mixed connective tissue disease), and 65.2% were current or former smokers. Nodules were bilateral in 15 cases, cavitated in 3, and located randomly, in the pleural mantle, or parenchyma. In 12 cases, the pulmonary background was altered (ILD or emphysema). Histological data were available in only 4 cases, with one showing findings consistent with RA. The estimated prevalence of rheumatoid pulmonary nodulosis was 1.21%. The mean DAS28 reduction was comparable among anti-TNFα, anti-IL6, and anti-CD20 agents, with moderate variability, in line with published studies. Overall efficacy was good, although the limited sample size reduced comparative power. Conclusions. Preliminary results show a prevalence of rheumatoid pulmonary nodulosis consistent with existing literature and confirm the overall efficacy of b-DMARDs in reducing DAS28. Study limitations include lack of a control group, small sample size, and limited histological data. Further studies are needed to better clarify potential correlations between biologic therapy and nodulosis development.
PO:08:117 | Association between the use of oral contraceptives and the development of rheumatoid arthritis: a systematic review and meta-analysis
Background. Rheumatoid arthritis (RA) is a chronic inflammatory joint disease that significantly impacts patients' quality of life, particularly affecting women. Although previous research has suggested that oral contraceptive (OC) use might influence the risk of developing RA, earlier meta-analyses have yielded inconsistent results. Given these conflicting findings and the emergence of new data, we performed an updated systematic review and meta-analysis of observational studies to clarify the association between OC use and RA risk. Materials and Methods. A systematic literature review and meta-analysis were conducted by searching MedLine (via PubMed), Scopus, and Cochrane databases up to March 2025. Observational studies examining the relationship between OC use and RA risk were included. Odds ratios (OR) and corresponding 95% confidence intervals (CI) were calculated. Additionally, cumulative meta-analysis was performed to assess temporal trends in risk estimates over time. Results. Our analysis demonstrated that ever use (current or prior use) of OCs is associated with a statistically significant reduction in RA risk (OR 0.80, 95% CI 0.70-0.91). In contrast, the associations for current use (OR 0.59, 95% CI 0.34-1.02) and past use (OR 0.83, 95% CI 0.69-1.01) were less definitive, likely due to substantial heterogeneity among studies. Cumulative meta-analysis revealed a modest temporal trend toward a protective effect of OC use. Conclusions: This meta-analysis supports a protective association between current or prior OC use and the development of RA, highlighting the potential role of hormonal factors in RA pathogenesis. CONCLUSIONI This meta-analysis supports a protective association between current or prior OC use and the development of RA, highlighting the potential role of hormonal factors in RA pathogenesis.
PO:08:118 | “Posting Arthritis”: rheumatoid arthritis vs. juvenile idiopathic arthritis contents on social media
Background. Social media platforms are among the most popular sources used by patients and caregivers to obtain information on health-related topics, including rheumatological diseases (1). The aim of this study was to evaluate the social media content related to the most common types of autoimmune arthritis in both adults and children, rheumatoid arthritis (RA) and juvenile idiopathic arthritis (JIA). We also aimed to assess differences between adult and pediatric rheumatology content and between content published by health professionals (HPs) and non-health professionals (NHPs). Methods and Materials The 150 most popular posts related to RA (assessed through “rheumatoid arthritis”) and JIA (assessed through “juvenile idiopathic arthritis,” “juvenile rheumatoid arthritis,” and “juvenile arthritis”) were evaluated on the popular social media platforms Instagram, Facebook, and TikTok. For each content, either photo or video, we collected data on the type of content creator, engagement metrics (likes, comments, saves, shares, and interactions), and the primary purpose of the content. For videos, additional data on views and duration were recorded. Educational videos were evaluated using validated and standardized tools: quality was assessed using the Journal of the American Medical Association (JAMA) Benchmark Scale, while understandability and actionability were measured using the Patient Education Materials Assessment Tool for Audiovisual Materials (PEMAT-A/V). The presence of disinformation was categorized as “absent,” “minimal,” or “significant.” Results We included 1.713 posts (572 on RA and 1.141 on JIA) from TikTok (666; 39%), Instagram (590; 34%), and Facebook (457; 27%), achieving 179.9 million views and 5.4 million interactions. NHPs were the majority of creators (1.336; 78%), mostly consisting of patients (801; 47%), while rheumatologists (34; 2%) and pediatric rheumatologists (17: 1%) were a minority. Most content was shared for reporting a patient experience (844; 49%), while educational posts were a significant portion of the sample (502; 29%). Among educational content, videos related to RA were more viewed (26.738 [5.998-130.437] vs 1.034 [62-9.052], p<0.0001), with more interactions (922 [189-3.338] vs 40 [4-298], p<0.0001), of greater understandability (PEMAT-A/V 77.8 [63.6-90] vs 71.4 [60-85.7], p=0.044), and actionability (PEMAT-A/V 66.6 [33.3-100] vs 50 [33.3-66.7], p=0.003) than those related to JIA (Figure 1). Overall, videos created by HPs were of higher quality than those shared by NHPs (JAMA 3 [3-3] vs 3 [2-3], p=0.012), while photos by NHPs were more liked (218 [46-388] vs 89 [14-297], p=0.046) and commented (10 [3-34] vs 2 [1-8], p<0.0001), showing a higher engagement. Conclusions. There is a growing use of social media for educational purpose by patients and caregivers. However, the number of HPs as content creators is still limited. HPs could significantly impact the dissemination of accurate and understandable knowledge to patients and caregivers through these modern communication channels.
PO:08:121 | Correlation between SENS score and perceived disability in a monocentric cohort of patients affected by rheumatoid arthritis: preliminary analysis of 209 patients
Bacgound. To demonstrate the correlation between structural joint damage, measured through the SENS score, and perceived disability in a monocentric cohort of patients affected by Rheumatoid Arthritis (RA). Materials and Methods. Out of a cohort of 1262 patients, 209 consecutive patients affected by RA (diagnosis according to the 2010 ACR/EULAR classification criteria) were evaluated. For each patient, demographic, clinical, and treatment characteristics were collected: sex, date of birth, disease duration, therapy with b-DMARDS, cs-DMARDS and steroids, positivity for rheumatoid factor and/or anti-CCP, BMI, CRP, fibromyalgia, comorbidities, Visual Analogue Score (VAS), Disease Activity Score 28 (DAS28), Health Assessment Questionnaire (HAQ). The SENS score was calculated on the most recent X-rays of hands and feet available. The correlation between HAQ and SENS (total, hands and feet) was evaluated using the correlation coefficient r. Moreover, a multivariate analysis was performed with other variables known to be associated with the HAQ score. Results. The patients (74% female) had a mean age of 63.5 (55–72) years and a disease duration of 13.65 (5.8–23.7) years. The remaining characteristics of the patients are shown in the table. The median total SENS score was 10 (4–25). Patients showed greater erosive damage in the hands compared to the feet (SENS score hands 8 (1–16.33); SENS score feet 2 (0–5). A positive linear correlation was found between erosive damage, both total and for hands and feet separately, and the HAQ score; total SENS score vs HAQ r = 0.33, p = 0.001; hands SENS score vs HAQ r = 0.33, p = 0.001; feet SENS score vs HAQ r = 0.23, p = 0.008. The multivariate analysis showed an independent association with total SENS score (p = 0.0009), age (p = 0.0217), and fibromyalgia (p = 0.0146). No independent association was found with BMI, presence of comorbidities, disease duration, or DAS28. Conclusions. The study highlighted a linear correlation between erosive damage expressed by SENS and the degree of perceived disability. Erosive damage resulted independently associated with perceived disability together with age and fibromyalgia. This study confirms the importance of the systematic evaluation of erosive damage.
PO:08:126 | Use of upadacitinib in real-life: the experience of Calabrian rheumatology
Background. Upadacitinib (UPA), demonstrated efficacy and safety in the treatment of Rheumatoid Arthritis (RA) in several randomized clinical trials (RCTs) and in long-term extension (LTE) studies. However, it is well known that experiences in real world evidence (RWE) play a pivotal and complementary role to RCTs. On this basis, Calabrian rheumatologists has decided to collect data aiming at providing futher evidences on the efficacy and safety of UPA in RA patients. Materials and Methods. To evaluate efficacy and safety, 87 RA patients (>18 years old) were enrolled retrospectively from January 2021 to December 2023 from 11 different Rheumatology Units in Calabria. Data were collected at baseline and the at 3, 6, 12 and 24 months from the start of therapy, including demographic features, prior therapies, comorbidities, RA features, clinimetric data and adverse events (AEs). Of the 87 enrolled patients, 80.5% are women. The mean age is 61.4 ± 10.9 years. The median disease duration is 96 months. The mean BMI is 26.07± 5.23. Eight patients (9.3%) had a history of previous cardiovascular events, ten patients (11.6%) were smokers and two patients (2.3%) ex smokers. Ten patients (11.8%) had a concomitant diagnosis of diabetes, thirty patients (34.9%) had hypertension, two (6.9%) hyperuricemia, thirteen patients (36.1%) had dyslipidemia, three patients (3.5%) had recurrent infections and five patients (5.8%) had a family history of neoplasm. No patients had a history of thromboembolism and four patients (4.6%) had previous events of herpes zoster (HZ), only 6 patients receveid vaccine anti-HZ virus. Twenty-five patients (71.4%) had a positivity for rheumatoid factor (RF) and twenty-two (61.6%) were positive to anti-citrullinated protein antibodies (ACPA). Ninenty-three percent of patients were previously treated with at least one bDMARDs and only one patient with another tsDMARD. During the follow-up, four patients discontinued UPA for lack of efficacy (n=1) or for adverse events (n=3). Results. We observed a significant reduction of pain, number of tender/swollen joints and a significant reduction of inflammatory parameters was observed at T3, T6, T12 and T24. A significant percentage of patients reached remission (DAS28, CDAI and SDAI) at T3 and a significant steroid-sparing was observed at T3. This Calabrian cohort is a picture on the use of UPA in clinical practice including 87 patients. Among these, 53 patients (60.9%) had at least one risk factors identified by EMA and almost all patients showed an inadeguate response to bDMARDs. Only six patients were vaccinated for HZ. Although this cohort was at high risk to develop HZ and MACE, only 4 patients discontinued therapy for adverse events, no CV events were observed. At T24, only two patients developed a Zoster infection. Conclusions. Our data confirmed the good safety profile of UPA reported in RCT and in RWE studies. Regarding efficacy, these results confirmed data reported in RCT on the reduction of pain, inflammation and in the improvement of clinical parameters, especially in the so-called difficult-to-treat patients.
PO:09:134 | The impact of intra-articular hyaluronic acid injections on osteoarthritis synovitis: a study on synovial tissue of total knee arthroplasty patients
Background. Intra-articular hyaluronic acid injections (IA-HA) represent a therapeutic strategy widely used to manage knee osteoarthritis, aiming to reduce pain and to improve joints’ range of movement. However, the effect of this treatment on histological synovial inflammation is still quite unexplored. Krenn’s score is a validated semi-quantitative histopathological scoring system to evaluate synovitis and it is particularly useful in identifying inflammation in advanced osteoarthritis patients. Objective. Evaluating the correlation between IA-HA treatment and synovial inflammation, which was measured by Krenn’s score, in total knee arthroplasty (TKA) patients. Methods. We included 108 patients affected by knee osteoarthritis who had undertaken TKA. 48 patients, who had been treated with steroid intra-articular injections, were excluded from the analysis to avoid confounding factors. Out of the remaining 60 patients, 45/60 had been treated with IA-HA in the pre-operative period and 15/60 had not been treated with IA-HA. We then calculated the mean time from knee osteoarthritis diagnosis and TKA (yearsOATKA) and we analysed the bivariate correlation between total number of intra-articular hyaluronic acid injections (NHAinj) and the time from diagnosis to surgery. During the surgical procedure of 36 patients, it was taken a sample of synovial membrane for histopathological analysis and Krenn’s score evaluation. Statistical analysis included the evaluation of the correlation between Krenn’s score and the number of intra-articular injections, as well as the comparison between groups (IA-HA vs non-IA-HA) to identify differences in synovial inflammation. Results. Patients treated with IA-HA (n=45) had a mean time from diagnosis to TKA of 10,91 years (SD: 8,96), in comparison to those non treated with IA-HA (n=15), whose mean time was 5,33 years (SD: 3,94). Mean Krenn’s score in IA-HA patients (n=26) was 3,0 (SD: 1,88), while in non-IA-HA patients (n=10) was 2,4 (SD: 0,84). The bivariate correlation analysis between total number of intra-articular injections and time to TKA, using Spearman’s coefficient (since the variables had a non-normal distribution), showed a statistically significant result (p=0,006) (Figure 1). However, the correlation between total number of intra-articular injections and Krenn’s score classes was not statically significant (p > 0,05 for all analyses). It is important to recognise that the sample size and the unbalanced distribution between Krenn’s classes reduce the power of statistical analysis (Figure 2). Conclusions. Our study confirms that patients treated with hyaluronic acid have a longer mean time from diagnosis to TKA, which, despite already being known in literature, suggests that performing IA-HA helps delaying surgery. On the other hand, we did not find a significant association between intra-articular hyaluronic acid injections and a reduction in synovial inflammation, the latter one histologically measured by Krenn’s score. These results suggest a possibly modulating role for IA-HA on synovitis, even in an advanced stage of osteoarthritis, yet there is a need for further studies considering the phenotypic variance of osteoarthritis and the episodic nature of inflammation in this disease.
PO:09:139 | Comparative evaluation of GPT-4.0, Claude 4, and MedGEMMA in automatic Kellgren-Lawrence grading of knee osteoarthritis
Background. Automated grading of knee osteoarthritis (OA) severity using the Kellgren-Lawrence (KL) scale is a critical task in musculoskeletal radiology. Recently developed multimodal large language models (LLMs) offer the potential to interpret clinical images alongside text, but their performance on fine-grained ordinal classification tasks remains poorly characterized. Methods. We evaluated three multimodal LLMs—Open AI GPT-4o (vision-enabled), Anthropic Claude 4, and the open source Google MedGEMMA—on their ability to predict KL grades from knee radiographs in a publicly available, expert-annotated dataset¹. Model predictions were compared to ground truth labels using exact match accuracy, ±1 tolerance accuracy (i.e., prediction within one KL grade)(Figure 1), and macro-averaged precision and recall. Confusion matrices were also analyzed to examine misclassification trends. Results. The dataset included 100 radiographic images, equally distributed across KL grades: • Grade 0: 20 images • Grade 1: 20 images • Grade 2: 20 images • Grade 3: 20 images • Grade 4: 20 images GPT-4o demonstrated the best overall performance with 26% exact match accuracy, 63% ±1 tolerance accuracy, macro precision 0.38, and macro recall 0.26. Claude 4 and MedGEMMA each reached 21% exact match, 58% ±1 tolerance, with macro precision/recall of 0.23/0.21 and 0.20/0.21, respectively (Figure 2). All models exhibited frequent misclassification between adjacent KL grades, particularly underestimating moderate to severe OA (grades 3–4). Conclusion. Although GPT-4o outperformed the other models, its accuracy remains insufficient for clinical reliability. These findings reveal that current multimodal LLMs, while promising, still struggle with ordinal radiographic interpretation tasks. Targeted training on medical imaging datasets and improved domain adaptation are necessary to enhance their diagnostic utility. ¹
PO:10:146 | Dorsal myelopathy in a patient with radiographic axial spondyloarthritis
Background. Neurological involvements in axial spondyloarthritis (axSpA) are uncommon but can lead to serious complications. Among these, the occurrence of an epidural fluid–cellular collection is extremely rare and scarcely reported, representing a significant diagnostic challenge in differentiating infectious, neoplastic, and inflammatory etiologies. We describe the case of a patient with radiographic axSpA complicated by dorsal myelopathy secondary to an inflammatory epidural collection. Materials and Methods. A 29-year-old man with a history of inflammatory back pain and family history of spondyloarthritis presented with worsening thoracolumbar pain, sphincter dysfunction, and progressive lower limb paraparesis. Laboratory investigations revealed elevated CRP (22.6 mg/L), HLA-B27 positivity, and a positive TB Quantiferon test. Contrast-enhanced spinal MRI demonstrated a large posterior epidural fluid–cellular collection extending from D4 to D6, causing spinal cord compression and signal alterations consistent with myelopathy. Bone marrow edema was also observed in the cervical, thoracic, and lumbar vertebrae, as well as in the sternal manubrium. Radiographic imaging showed syndesmophytes, bilateral sacroiliac ankylosis, and thoracolumbar Romanus lesions. The patient underwent neurosurgical decompression with laminectomy and paravertebral tissue biopsy. Results: Histopathological analysis revealed compact and trabecular bone with preserved architecture, surrounded by fibro-adipose tissue showing inflammatory infiltrates occasionally organized into small B- and T-cell germinal-like centers, consistent with a reactive inflammatory process. Microbiological studies, including cultures and PCR for Mycobacterium tuberculosis, were negative. PET-CT did not reveal hypermetabolic foci suggestive of lymphoproliferative disease. Given the high disease activity (ASDAS-CRP 4.76; BASDAI 7.4), HLA-B27 positivity, and characteristic radiological features of axSpA, an inflammatory etiology for the epidural collection was strongly supported. Conclusions. We report an atypical complication of radiographic axial spondyloarthritis presenting as dorsal myelopathy due to an inflammatory epidural collection. To our knowledge, similar cases have not been previously described. Early recognition and multidisciplinary management are essential to ensure appropriate diagnosis and treatment.
PO:10:149 | Efficacy of anifrolumab in a case of systemic lupus erythematosus with pulmonary involvement
Background. Pulmonary involvement in systemic lupus erythematosus (SLE) is a heterogeneous and usually non-severe complication, affecting 50–70% of patients (and up to 4–5% at disease onset). Pleuro-parenchymal manifestations include pleuritis (30%), interstitial lung disease (ILD, 1–15%), and lupus pneumonitis (1–4%), the latter often requiring differential diagnosis from infectious forms. Vascular manifestations comprise pulmonary arterial hypertension (PAH, 0.5–17.5%), diffuse alveolar hemorrhage (DAH, 1–5.4%), and venous thromboembolism (VTE, 9%; 35–42% in the presence of antiphospholipid antibodies), as well as acute reversible hypoxemia (ARH). Rare forms include airway disease and shrinking lung syndrome. Anifrolumab, a monoclonal antibody that blocks the type I interferon receptor, has shown efficacy in moderate to severe SLE, particularly for mucocutaneous, articular, and serological manifestations. According to European guidelines, Anifrolumab is recommended as first-line therapy for extra-renal (non–major organ) manifestations, especially cutaneous, and as add-on therapy for severe disease. We report a case of SLE with lupus pneumonitis and antiphospholipid syndrome (APS) successfully treated with Anifrolumab. Materials and Methods. A 45-year-old Caucasian man, with no significant past medical history, experienced three episodes of bilateral pneumonia (bibasilar consolidations) since mid-2022, all requiring hospitalization. One episode was complicated by pulmonary embolism and another by a generalized rash, both treated with antibiotics and corticosteroids. Laboratory findings revealed positivity for ANA (1:2560, homogeneous nuclear pattern), anti-dsDNA, anti-Ro52, anti-nucleosome, anti-histone antibodies, rheumatoid factor, and lupus anticoagulant. Rheumatologic assessment revealed Jaccoud arthropathy and widespread erythematous maculopapular lesions on the trunk, back, and limbs. Given the absence of infectious findings (including negative BAL), the pulmonary abnormalities were attributed to autoimmune disease. A diagnosis of SLE with cutaneous involvement (histologically confirmed subacute cutaneous lupus erythematosus), pulmonary and articular manifestations, and associated APS was established. The patient started oral anticoagulation, high-dose corticosteroids, hydroxychloroquine (discontinued due to cutaneous reaction), and rituximab (1 g × 2), achieving initial improvement. Rituximab was discontinued after the second course due to an adverse reaction, followed by recurrence of bilateral pneumonia and cutaneous flare. Consequently, Anifrolumab 300 mg every 4 weeks was initiated. Results. After six months of Anifrolumab therapy, HRCT showed marked improvement, inflammatory markers normalized, and the patient reported substantial improvement in respiratory, cutaneous, and articular symptoms, allowing progressive corticosteroid tapering. Conclusions. Anifrolumab represents a promising therapeutic option for patients with severe SLE manifestations who are refractory to or intolerant of conventional treatments. Modulation of the type I interferon signaling pathway may play a key role in achieving systemic disease control. In patients with pulmonary involvement, a multidisciplinary approach and careful differentiation from infectious causes are essential.
PO:10:150 | A case of pulmonary hypertension in Whipple's disease
Background. Whipple’s disease is a rare and multisystemic disorder caused by T. whipplei and pulmonary hypertension (PH) is a rare complication. Case presentation. A 41-year-old Caucasian woman, with wrist arthritis and elevated inflammatory markers was diagnosed with seronegative arthritis in 2017. She was initially treated with hydroxychloroquine (ineffective), and anti- inflammatory drugs. We first evaluate her in 2022 with mild articular pain, occasional low-grade fever < 38°C, non-specific perivascular dermatitis and elevated inflammatory markers C-Reactive Protein (CRP 50 mg/L), Serum Amyloid A (SAA, 182 mg/L). Routine, immunological and infectious blood tests were negative or in normal range. PET and CT scans showed mediastinal, mesenteric, axillary and inguinal enlarged lymph nodes and a tru-cut biopsy showed non-specific micro-granulomatous inflammation. In the suspect of an autoinflammatory disease Colchicine was started with no clinical improvement and persistent elevated inflammatory markers (CRP 45 mg/L, SAA 76 mg/L). In July 2023, Anakinra was started with clinical improvement and CRP reduction but persistently elevated SAA (56 mg/L). NGS for recurrent periodic fever resulted negative. In March 2024, the patient was hospitalized for dyspnoea. HRTC showed dilation of pulmonary arteries and lymph nodes enlargement. Because echocardiography revealed elevated pulmonary pressure the patient underwent right heart catheterization (RHC) that showed mild pre-capillary PH. The patient was discharged with diuretic therapy. The patient was admitted again in April and immediately referred an Italian center for PH. RHC confirmed precapillary PH [mean PAP 34 mmHg; cardiac output 4.4 l/min; pulmonary vascular resistance 6.1 uW]. Vasoreactivity testing with nitric oxide was positive. Spirometry revealed severe reduction of DLCO (34%). Diuretic and 5 mg tid of sildenafil were started. The repeated lymph node biopsy showed granulomas suggestive for lymph node sarcoidosis. Anakinra was discontinued, prednisone and methotrexate were started. Immediately the patient developed diarrhoea, and the gastroscopy enabled Whipple's disease to be diagnosed (PAS positive macrophages at the jejunal biopsy) and antibiotic was started: ceftriaxone iv for fifteen days and then cotrimoxazole. On 25th June 2024 , sildenafil was discontinued because RHC showed normalization of the haemodynamic profile (mPAP 19 mmHg) confirmed also on 12th September 2024. Learning points for clinical practice Whipple’s disease must be considered as a possible cause of reversible PH. References. Boumaza A et al. Lancet Infect Dis 2022;22: e280-e291.
PO:10:153 | Isolated sarcoidosis of the parotid gland: a rare case of unilateral presentation
Sarcoidosis is a chronic multisystem inflammatory disease of unknown etiology, histologically characterized by non-necrotizing granulomas. Pulmonary and mediastinal lymph node involvement is most common, but the skin, eyes, liver, spleen, and salivary glands may also be affected. Salivary gland involvement is rare (<6%) and isolated unilateral presentation is even more exceptional. We describe the case of a 52-year-old Caucasian woman, with no previous medical conditions, who presented with progressive enlargement of the right parotid gland over approximately two months. She reported no systemic or local symptoms (xerostomia, dysphagia, dyspnea, skin lesions). Physical examination revealed an oval mass of approximately 5 cm, with irregular borders, non-tender and poorly mobile, along with enlarged submandibular and cervical lymph nodes (up to 2 cm), mobile and painless (Fig. 1a). Blood tests showed elevated serum ACE levels (124 U/L; normal range 13.3–63.9), mildly elevated ESR (17 mm/h), normal calcium levels, negative Quantiferon test, and normal liver and kidney function. Ultrasound revealed solid, hypoechoic, vascularized lesions (up to 29×15 mm) in the anterior portion of the gland, compatible with pathological lymph nodes (Fig. 1b). MRI confirmed right parotid nodules up to 17 mm with irregular margins, marked diffusion restriction, and minimal central enhancement. Similar lesions were observed in the ipsilateral submandibular and supraclavicular regions (Fig. 1c and 1d). Fine-needle aspiration revealed non-necrotizing granulomas composed of CD68-positive epithelioid histiocytes, multinucleated giant cells, and lymphocytic infiltrate, with no evidence of infection or malignancy. Chest CT excluded mediastinal or pulmonary involvement. The left parotid gland was unaffected. A diagnosis of isolated sarcoidosis of the right parotid gland was therefore made. Treatment was initiated with prednisone 25 mg/day for 14 days, followed by gradual tapering. After two months, the swelling had completely resolved, with no clinical recurrence. Parotid involvement in sarcoidosis is known, typically associated with Heerfordt’s syndrome. However, isolated unilateral forms are extremely rare. In the review by Ungprasert et al. (2016), only 1 out of 345 patients presented isolated parotid sarcoidosis, and no unilateral cases in Caucasian patients were reported. Differential diagnosis with neoplastic or infectious conditions is essential to avoid inappropriate surgical intervention. Ultrasound and MRI provide useful diagnostic clues, but biopsy is necessary for confirmation. The presence of non-caseating granulomas in the absence of infectious agents is the key diagnostic criterion. Response to corticosteroids is generally favorable. This case highlights the importance of considering sarcoidosis in the differential diagnosis of parotid swelling, even in the absence of systemic signs, to ensure timely treatment and avoid unnecessary invasive procedures. References Ungprasert P, Crowson CS, Matteson EL. Clinical characteristics of sarcoid arthropathy: A population-based study. Arthritis Care Res (Hoboken). 2016;68(5):695-9.
PO:10:154 | Pudendal nevralgia as an unusual presenting symptom of axial spondyloarthritis
Background. The aim of the present study was to describe a case of axial spondyloarthritis (axSpA) presenting unusually with symptoms of pudendal neuralgia. Case report: S.F., woman, 32 years old. In October 2024, four months after surgical removal of epidermoid cysts complicated by phlegmon in the genito-inguinal region, the patient developed burning and paresthetic pain localized in the inguinal and ischial areas, which later radiated to the genital region, lower buttocks, thighs, and transiently to the legs. Pelvic pain progressively worsened, extending to the perineal and anal regions and severely impaired the ability to maintain a seated position. An electromyography of the lower limbs prescribed by the general practitioner resulted negative. In December 2024, the patient underwent a rheumatologic consultation at our center and a neurology consultation was requested, in addition to routine blood tests. The neurologist, recommended a pelvic magnetic resonance (MRI), suspecting pudendal neuralgia due to possible post-surgical neurogenic injury. MRI findings included: bilateral active sacroiliitis (Figure 1); enthesitis at the insertion sites of tendinous and ligamentous structures at the level of the ischial tuberosity and antero-inferior portion of the pubic symphysis; edema in the adipose tissue underlying the ischiopubic rami and urogenital triangle. No signs of pudendal nerve lesions or space-occupying masses were detected. Laboratory tests revealed: ESR: 60 mm/h; CRP: 1.1 mg/dL; negative rheumatoid factor and anti-citrullinated peptide antibodies. The Schober test was measured at 4 cm. The BASDAI score was 7.6. HLA typing revealed the presence of B35-44 loci. An axSpA diagnosis was made, in accordance with the 2009 ASAS classification criteria, and treatment with adalimumab was initiated. Discussion: Although it is possible that pudendal neuralgia may be part of the symptomatology of axSpA in more advanced stages — due to calcification of the sacrotuberous and sacrospinous ligaments and subsequent entrapment of the nerve within Alcock’s canal — it is highly unusual for it to represent the initial manifestation of axSpA. In the case report, pudendal nerve irritation appears related to extrinsic compression exerted by edema of the tissues underlying the ischiopubic rami and the urogenital triangle, as well as inflammation of the entheses located near the nerve’s anatomical pathway (specifically at the ischial tuberosity and pubic symphysis insertions). Conclusions: To the best of our knowledge, this is the first reported case in literature of pudendal neuralgia as the presenting symptom of axial SpA. In the differential diagnosis of pudendal neuralgia —which includes repetitive microtrauma, pelvic fractures, pelvic surgery, childbirth, neurological diseases, and neoplastic masses — early axial SpA should also be considered. MRI remains the imaging modality of choice in the differential diagnostic workup.
PO:10:155 | Etanercept-induced lupus in a patient with rheumatoid arthritis: diagnostic challenges and multidisciplinary therapeutic approach
Background. To present a case of anti-TNFα drug-induced lupus (DIL) in a patient with rheumatoid arthritis (RA) and progressive respiratory complications. Materials and Methods: Review of clinical records and multidisciplinary follow-up. Results: A 60-year-old female smoker with a history of GERD, bronchial asthma, and OSAS was diagnosed with RA in 2022 due to polyarthritis (ANA 1:320, low-titer RF, negative ACPA). After failure of methotrexate, abatacept and tocilizumab, etanercept was initiated. In April 2024, purpuric lesions appeared on the upper back and chest, associated with resting dyspnea and a right-sided pleural effusion on chest X-ray, initially treated as parapneumonic. In May 2024, the patient was hospitalized for a widespread maculopapular rash and active arthritis (SDAI 39.3). Laboratory tests showed elevated ESR and CRP, ANA 1:1280, positive anti-dsDNA, anti-histone, and anti-nucleosome antibodies. ENA, ANCA and antiphospholipid antibodies were negative. Skin biopsy was consistent with a drug-induced toxic-allergic rash. Chest CT revealed post-inflammatory bibasal atelectasis. A diagnosis of etanercept-induced DIL was made based on clinical and serological criteria. The biologic was discontinued and steroid therapy, azithromycin, and antihistamines were started, with subsequent cutaneous improvement. However, dyspnea persisted with bilateral pleural effusion and severe mixed ventilatory syndrome requiring nocturnal CPAP. In September 2024, due to anti-dsDNA normalization and ongoing arthritis (with previous methotrexate failure), filgotinib 200 mg/day was started, achieving good cutaneous and joint response (SDAI 12.1 at 3 months). In December 2024, the patient was rehospitalized for acute type I respiratory failure due to worsening bilateral pleural effusion, treated with oxygen therapy, nebulization bronchodilator therapy and levofloxacin. In March 2025, due to residual debilitating dyspnea, medical cannabis was initiated. Discussion. Anti-TNFα DIL occurs in 0.1–0.5% of treated patients, more frequently in elderly women. Clinical features are variable: cutaneous involvement is present in up to 80% of cases. Diagnostic criteria include drug exposure, compatible clinical manifestations, positive ANA/anti-dsDNA, and improvement after discontinuation. The recurrent, antibiotic-resistant nature of pleural effusions suggests possible immune-mediated etiology. Early recognition is crucial to prevent systemic progression. Filgotinib has shown efficacy in controlling both articular and cutaneous disease activity, representing a valuable therapeutic alternative. The use of medical cannabis for refractory dyspnea highlights the importance of personalized, symptom-oriented approaches. Conclusions. This case illustrates the complex management of RA complicated by etanercept-induced DIL. Persistent respiratory manifestations, steroid-related complications, and intolerance to conventional DMARDs require a multidisciplinary, patient-tailored approach, emphasizing early DIL recognition and the selection of safe and effective alternative therapies.
PO:10:157 | Sjögren’s syndrome with cryoglobulinemia associated with POEMS syndrome
Background. We report the clinical case of a patient affected by Sjögren’s syndrome (SS) and cryoglobulinemic purpura presenting with a progressive sensorimotor polyneuropathy. Materials and Methods. A retrospective analysis was conducted in a patient with progressive sensorimotor polyneuropathy and diagnosis of Sjögren’s Syndrome. Laboratory investigations revealed the presence of cryoglobulins and an IgG-lambda monoclonal gammopathy of undetermined significance (MGUS). Results. The patient, diagnosed with Sjögren’s Syndrome characterized by sicca symptoms, multiple lymphadenopathies, recurrent swelling of the submandibular and parotid glands, and positivity for anti-SSA/Ro, rheumatoid factor (IgM), and IgG-lambda MGUS, developed acute painful paresthesias and lower limb weakness in March 2025. Physical examination revealed bilateral ascending purpura up to the knees, associated with sensorimotor deficits and pitting edema of the lower limbs. Electromyography demonstrated a sensorimotor axonal polyneuropathy with marked distal muscle denervation. Laboratory tests confirmed the presence of cryoglobulins (cryocrit 8%), low C4 complement levels, positive rheumatoid factor (IgM), and an IgG-lambda monoclonal component of undetermined significance. Given the suspicion of POEMS syndrome, serum VEGF (vascular endothelial growth factor) levels were measured and found to be elevated. Additional endocrinological tests showed reduced testosterone levels and hyperprolactinemia. Bone marrow biopsy excluded progression to multiple myeloma. The coexistence of polyneuropathy, MGUS, endocrinopathy, elevated VEGF, and lower-limb edema supported the diagnosis of POEMS syndrome. Rituximab therapy was initiated, resulting in marked clinical improvement, with resolution of both the Sjögren’s syndrome related cryoglobulinemia and the POEMS associated manifestations, including regression of polyneuropathy and normalization of endocrine abnormalities. Conclusions. This case suggests that Sjögren’s syndrome, concomitant with MGUS, may be associated with POEMS syndrome, resulting in neuropathic damage. From a pathogenetic perspective, this manifestation could be secondary either to cryoglobulinemia (widely described in SS) or to paraneoplastic disorder such as POEMS syndrome. This finding highlights a possible association between these two diseases, underlines the need for careful differential diagnosis in patients with autoimmune connective tissue diseases presenting with atypical neurological features to allow early identification of paraneoplastic syndromes or underlying plasma cell disorders, and demonstrates the efficacy of Rituximab in treating both Sjögren’s syndrome associated cryoglobulinemia and POEMS syndrome.
PO:11:158 | Osteomyelitis of the jaw: a rare mimick of giant cell arteritis
Background. Osteomyelitis of the jaw is a complication of odontogenic infections, primarily involving the dentate portion of the mandible. Osteomyelitis of the mandibular condyle is exceptionally rare, and spread may occur via hematogenous or contiguous routes (1). We here present a case of osteomyelitis of the mandibular condyle initially diagnosed as Horton's arteritis. Case report. An 87-year-old woman with a recent diagnosis of giant cell arteritis underwent rheumatological evaluation (Figure 1). The patient had been complaining for 1 year of non-NSAIDs-responsive headache in the temporal and preauricular regions and jaw claudication. A few months earlier the headache onset, she underwent a tooth extraction with the positioning of a mobile prosthesis. The patient reported that she was first evaluated by a neurologist who, considering the elevation of inflammatory lab tests (CRP 2.8 mg/dL), diagnosed Horton's arteritis and started prednisone 50 mg/day, with remission of the symptoms, but relapse at steroids tapering. At the first rheumatological evaluation, the patient reported pain in the right temporal region, greater at night, with a sense of ear fullness, hyporexia, and weight loss. In laboratory tests conducted under a low-dose steroids regimen (prednisone 7.5 mg/day), a modest increase in inflammation (CRP 1.5 mg/dL) was observed. For a better diagnostic review, the steroids were discontinued, and the patient underwent a temporal artery Doppler ultrasound, which detected no arteritis-compatible abnormalities. Given the worsening of pain, the rise in inflammation (CRP 4 mg/dL) and the swelling of the soft tissues upon discontinuation of the steroids, the patient underwent an 18FDG-PET/CT scan, which excluded vascular uptake but demonstrated intense uptake of the mandibular condyle, pterygoid muscle, and zygomatic bone. She also underwent a contrast-enhanced CT scan, which revealed erosions and periosteal reaction in the jaw, suggestive of osteomyelitis, along with inflammation of the adjacent soft tissues. Conclusions. Mandibular condyle osteomyelitis is a rare complication of dental infections and invasive dental procedures. The associated symptomatology (temporal headache, difficulty in chewing) may resemble giant cell arteritis. An accurate medical history, which also examines previous dental history and pain features, may guide the diagnosis. Anyway, radiologic exams and/or temporal artery biopsy are still necessary for differential diagnosis.
PO:11:162 | DRESS syndrome: a case treated with mepolizumab
Background. DRESS syndrome is a serious delayed drug hypersensitivity reaction and it’s a medical emergency that requires rapid recognition and treatment. Symptoms do not always occur immediately after drug administration, and this latency can make diagnosis difficult and delay identification of the causative drug. Corticosteroids are the first-line therapy. Endovenous immuniglobulines can be used in combination with corticosteroids, and cyclosporine is considered a second-line therapy for patients unresponsive to steroids. Biologics, such as anti-IL-5 agents, should be considered in refractory cases. Materials and Methods. Retrospective data collection from the medical records. Results. A 50-year-old Caucasian patient was admitted on June 26th 2024, for pleuropericarditis, fever, and skin rash. He underwent treatment with indomethacin and colchicine, with initial benefit. On July 7th, dyspnea on exertion, increased pleural effusion, and worsening skin rash occurred, so oxygen therapy and antihistaminic treatment were started. Subsequently, pitting edema was observed in all four limbs, and the first evidence of hypereosinophilia (>13,000/mm3) was detected at the blood test on July 8th. Indomethacin and colchicine were discontinued due to suspected adverse reactions. In the suspicion of EGPA (eosinophilic granulomatosis with polyagitiis) the following were requested: skin biopsy (eosinophilic infiltrate without signs of vasculitis ENT, pulmonary, hematological (excluding organ involvements), and nephrological evaluations (no signs of glomerular disease). In the meantime, therapy with methylprednisolone 60 mg/day was started with subsequent reduction of the eosinophil count and stabilization of the pulmonary involvement, but worsening of renal function (creatinine 4.7 mg/dl), reduction of the platelet count (26,000/mm3), haptoglobin consumption, increased transaminases, reduction of C3 and C4, negativity of ANCA (Antineutrophil Cytoplasmatic Antibodies) PR3 (proteinase 3) and MPO (myeloproxidase) and increase of the hemolysis indices with schistocytes. In the suspicion of Hemolytic Uremic Syndrome he was treated with a cycle of plasmapheresis and Eculizumab. During hospitalization the patients began to complain about paresthesias with EMG documentation of polyneuropathy in the 4 limbs. Due to worsening of the respiratory symptoms, he underwent orotracheal intubation (26/07) and then tracheostomy. Subsequently, progressive improvement of the respiratory function was observed, with consequent removal of the tracheocannula, but worsening of the polyneuropathy and onset of bilateral ocular ischemic angiopathy. A diagnosis of DRESS was made, endovenous immunoglobulin therapy was initiated, and steroids were continued. Given the renal status and the concomitant infection (Pseudomonas in the respiratory material) treatment with mepolizumab 300 mg per month (for a total of 4 doses) was initiated over cyclosporine, with subsequent resolution of the DRESS. Conclusions. Mepolizumab shew effectiveness in a case of refractory DRESS and may represent a valid alternative for the treatment of forms refractory to steroid and immunosuppressive therapy.
PO:11:167 | Subtle symptoms masking a challenging diagnosis: a clinical case of intestinal vasculitis in systemic lupus erythematosus
Background. Lupus enteritis is a rare but potentially life-threatening manifestation of systemic lupus erythematosus (SLE). This report highlights the importance of early diagnosis and prompt treatment, by describing a case of SLE complicated by intestinal involvement, initially presenting with nonspecific symptoms. Materials and Methods. A 59-year-old woman with Sjögren’s syndrome (diagnosed in 2021), intolerant to disease modifying antirheumatic drugs (DMARDs) and with urticarial–angioedema reactions to NSAIDs, paracetamol, antibiotics and glucocorticoids (GCs), was first admitted in November 2024 to the Internal Medicine Unit for abdominal pain, diarrhea, vomiting and fever. Contrast-enhanced abdominal computed tomography (ceCT) revealed a right common iliac artery dissection and a penetrating aortic ulcer. In the absence of surgical indication, she was discharged with a diagnosis of viral gastroenteritis and started empirical antibiotics and anti-platelets. Due to persistent fever, periorbital edema and hypocomplementemia, she was transferred to our Rheumatology Unit. On admission, she had fever, purpura on the lower limbs, diffuse alopecia and erythematous–pomphoid lesions on the chest and trunk. Laboratory tests showed hemoglobin 9.2 g/dL, CRP 14 mg/L (normal values <5), ESR 49 mm/h, ANA 1:640 (granular pattern), anti-SSA/SSB positive, anti-dsDNA negative, direct Coombs test positive, C3 45 mg/dL (nv<90), C4 4 mg/dL (nv<12), hypergammaglobulinemia (27.2%). During hospitalization, she developed recurrent urticaria–angioedema episodes unrelated to drug exposure: allergologic evaluation suggested Urticaria–Angioedema Syndrome (normal C1q inhibitor). She was diagnosed with “SLE and Urticaria–Angioedema Syndrome” (SLEDAI=15, Physician Global Assessment [PGA]=1.5), and treated with GCs pulses, azathioprine and omalizumab. In January 2025, she was readmitted for palatal petechiae, urticarial lesions on face and trunk, periorbital edema and palpable purpura on the lower limbs. Worsening fever (up to 39.4°C), diarrhea with hematochezia and vomiting prompted review of the previous ceCT, revealing trilaminar thickening of two-thirds of the small intestine compatible with the “target sign” and mesenteric stranding due to lymphatic–vascular congestion (Figure 1A). Results. Clinical and radiological findings were consistent with lupus enteritis (SLEDAI=15, PGA=2.5). She was treated with GCs pulses and cyclophosphamide (Cyc) 500 mg (Eurolupus protocol). After the second Cyc infusion, fever, diarrhea and urticarial lesions resolved. Follow-up CT enterography confirmed complete resolution of the intestinal involvement (Figure 1B). For the persistence of purpura on the lower limbs (SLEDAI=12, PGA=1.1), in April she started rituximab and hydroxychloroquine, followed by mycophenolate mofetil as maintenance, achieving in September 2025 complete remission (SLEDAI=0, PGA=0). Conclusions. This case highlights how nonspecific symptoms may conceal severe disease manifestations, delaying diagnosis and treatment. Therefore, early recognition and strong induction therapy are crucial to achieve disease control, prevent organ damage and avoid potentially fatal complications.
PO:11:171 | Subcutaneous tocilizumab use in a young-onset mixed connective tissue disease patient with multiple treatment failures
Background. Mixed Connective Tissue Disease (MCTD) is a systemic autoimmune disorder characterized by the presence of anti-U1 ribonucleoprotein (U1-RNP) antibodies associated with clinical features commonly observed in systemic lupus erythematosus, systemic sclerosis, rheumatoid arthritis (RA), and polymyositis/dermatomyositis. The pediatric-onset form of the disease is among the rarest entities in pediatric rheumatology. Case Report. We present the case of a 21-year-old Pakistani woman diagnosed with MCTD at the age of 11 (2015), with onset characterized by Raynaud’s phenomenon (scleroderma capillaroscopic pattern), polyarthritis, and recurrent parotitis. Laboratory findings showed ANA 1:640 speckled pattern, anti-U1-RNP 643 U/mL, rheumatoid factor (RF) 1750 IU/mL, and elevated ESR and CRP. She was treated in the pediatric setting with oral corticosteroids, hydroxychloroquine (HCQ) 300 mg/day, and methotrexate (MTX) up to 20 mg/week. In 2021, due to partial disease control, mycophenolate mofetil (MMF) 1.5 g/day was added, achieving a good response. At age 18 (2022), upon transfer to our care, she presented with active arthritis and elevated inflammatory markers. Instrumental assessment ruled out cardiac and pulmonary involvement. In December 2022, arthritis of the hands and wrists persisted, with ESR 120 mm/h and CRP 2.3 mg/dL (normal <1 mg/dL). Prednisone (PDN) was increased up to 12.5 mg/day and MMF to 2 g/day (in combination with MTX 20 mg/week and HCQ 300 mg/day). Throughout 2023, she experienced recurrent episodes of painful left parotid swelling without fever (ESR 120, CRP 4.5 mg/dL), which responded to tapered corticosteroid therapy (PDN 25 mg/day). In early 2024, she developed progressive fatigue, worsening arthritis of hands and feet, bilateral parotid swelling, and persistently elevated inflammatory markers. MTX was replaced with azathioprine for approximately four months, without clinical improvement (MMF 2 g + HCQ 200 mg + PDN 15 mg/day). In April 2024, azathioprine was discontinued and therapy with rituximab (1 g at T0 and T15) was initiated but suspended after the second infusion due to a mucocutaneous allergic reaction. In October 2024 (ESR 138, CRP 3.1 mg/dL), off-label use of subcutaneous tocilizumab 162 mg weekly was requested and approved (in combination with MTX 10 mg/week and HCQ 200 mg/day). After five months of treatment, the disease is well controlled. The patient no longer presents active arthritis or acute parotitis episodes, prednisone was tapered to 5 mg/day, and inflammatory markers improved (ESR 84 mm/h, CRP 0 mg/dL). Conclusions. Tocilizumab is a humanized monoclonal antibody targeting the IL-6 receptor, approved for use in RA, juvenile idiopathic arthritis, and giant cell arteritis. Only a few reports in the literature describe tocilizumab use in MCTD, all in pediatric cases with articular involvement. Given its proven efficacy in juvenile idiopathic arthritis, we decided to usetocilizumab in this patient, obtaining a favorable response on arthritis, systemic disease activity, and parotitis. This therapy requires careful clinical and laboratory monitoring.
PO:11:172 | Not all vasculitis look the same: a difficult diagnosis
Background. Vasculitides represent a heterogeneous group of systemic inflammatory diseases, often difficult to classify and requiring multidisciplinary management. Case Report. We present the case of a 68-year-old woman with a thoracic aortic aneurysm and a history of recurrent episodes of pneumonia with pleuritis. Since March 2024, she reported worsening pruritus (with a history of contact dermatitis) and alopecia. Starting in October, low-grade fever (T max 38°C), exertional dyspnea, and weight loss appeared. Chest CT scan showed bronchiolar wall thickening with fibrotic-disventilatory strands and an aortic aneurysm (53–55 mm). Admitted to cardiac surgery, on 14/03/2025, she underwent replacement of the ascending aorta with a Dacron valved conduit and aortic valve repair/plasty. Histological examination documented a marked lymphomonocytic infiltrate with tertiary germinal centers in the intima, involvement of the vasa vasorum, mucinoid degeneration, neoangiogenesis of the tunica media, and adventitial thickening with hyalinosis, consistent with giant cell aortitis , even in the absence of granulomas and macrophages and skip lesions. From May 5 to 23, she was admitted to our Rheumatology department for diagnostic work-up. Color Doppler ultrasound of the carotid and vertebral arteries, temporal arteries, renal arteries, and aortic axis was normal. FDG-PET scan showed vascular uptake solely in the ascending aorta, and multiple pulmonary accumulations (right lower lobe, parascissural regions, apices, hilar/paratracheal lymph nodes). HRCT revealed vague peribronchial consolidations suggestive of inflammation. Serology was negative for active infections (Quantiferon, EBV, CMV, HIV, Toxoplasma, Treponema pallidum); ANCA, ENA, RF, IgG4, anti-DNA, and liver autoantibodies were negative. ACPA was weakly positive; Lupus Anticoagulant (LAC) and IgG anticardiolipin antibodies were positive, leading to the initiation of anticoagulation therapy with warfarin (INR target 2.5). ESR 62 mm/h, CRP 9 mg/dL, eosinophils 780 mm³. Blood cultures were negative. Starting on May 13, therapy was initiated with prednisone 25 mg daily at a reduced dosage due to suspected infection, and a reduction in inflammation was observed (ESR 44 mm, CRP 0.09 mg/dL). BAL (bronchoalveolar lavage) for atypical mycobacteria investigation was proposed and is ongoing. A diagnosis of giant cell aortitis with pulmonary involvement (micronodules and tree-in-bud pattern) was made. Excluded diagnosis: Syphilis (negative serology and histology), tuberculous vasculitis (absence of granulomas, dissemination, reactive lymph nodes on PET, CT, and lymph node ultrasound, negative Quantiferon), EGPA (absence of asthma/rhinitis, fixed pulmonary infiltrates, negative ANCA), SLE (initially suspected due to alopecia, dermatitis, and ANA+, but excluded by a dermatologist who diagnosed eczematous atopic dermatitis and alopecia areata).
PO:11:175 | Dermatomyositis and immunosuppressant treatment: a case of Staphylococcus aureus pneumonia in a hospitalized patient
Background. Dermatomyositis (DM) is an autoimmune connective tissue disorder characterized by cutaneous manifestations and muscular involvement. Staphylococcus aureus nosocomial pneumonia is an infection with a high mortality rate, typically characterized by lower respiratory tract symptoms, pulmonary infiltrates on chest X-ray, and at least one positive blood culture in the absence of other sources of bacteremia. Clinical case. At the time of admission, the 49-year-old male patient exhibited a heliotrope rash on the face and 'V' of the neck, shawl sign, and Gottron's papules (Figure 1.d). He also experienced progressive proximal muscle weakness affecting the shoulder and pelvic girdles, along with new-onset dysphagia (Dysphagia Risk Assessment Scale [DRAS]: 10), confirmed by fibrolaryngoscopy exam. Autoimmunological workup revealed positive antinuclear antibodies (ANA) at a titer of 1/640 and positive anti-fibrillarin autoantibodies. Thigh MRI showed diffuse inflammatory oedema of the pelvic girdle muscles (Figure 1.c). Inflammatory markers were within normal limits, while creatine phosphokinase (CPK) was 579 U/L, aspartate aminotransferase (AST) was 73 U/L, and alanine aminotransferase (ALT) was 66 U/L. On these bases, a diagnosis of DM was established. Treatment was initiated with Methotrexate (MTX) 15 mg/week and Methylprednisolone (MPDN) 1 mg/kg. This regimen led to an improvement in the cutaneous manifestations and partial remission of asthenia, though dysphagia persisted. Consequently, off-label intravenous immunoglobulin (IVIG) at 2 g/kg was requested. Concurrently, approximately two weeks into MTX + MPDN treatment and prior to the first IVIG administration, the patient developed productive cough, general clinical deterioration, episodes of pyrexia (max 38.5°C), and a painful oedematous-pustular lesion on the right hand at a venous access site. Concomitantly, inflammatory markers rose (C-reactive protein [CRP] 77 mg/L, procalcitonin [PCT] 0.19 ng/mL), and blood cultures were positive for Staphylococcus aureus. A chest X-ray revealed an excavated nodule in the right subclavian region (Figure 1.b), which was confirmed by computed tomography (CT) of the chest (Figure 1.a), showing multiple excavated nodules consistent with Staphylococcus aureus infection. Empirical antibiotic therapy was initiated with Ceftriaxone 2g, subsequently adjusted to Piperacillin and Tazobactam 4/0.5g and Linezolid 600mg for 10 days. During treatment, the patient showed progressive clinical and laboratory improvement. Upon completion of antibiotic therapy and confirmation of negative blood cultures and negative echocardiogram exam for endocarditis, the first cycle of IVIG was commenced. Conclusion. This case highlights the critical importance of accurate infectious risk assessment and its management in immunocompromised patients, such as those with DM, who often undergo invasive supportive procedures and receive high-dose immunosuppressive therapies. It also underscores the necessity of promptly initiating broad-spectrum empirical antibiotic therapy upon the identification of positive blood cultures.
PO:12:178 | Don't count your chickens before they hatch! Analysis of cardiovascular definitions in studies on rheumatic diseases: a systematic literature review
Background. Interest in defining the cardiovascular (CV) burden of rheumatologic diseases has progressively increased. The focus has been on rheumatoid arthritis (RA), but an increased CV risk has also been recognized in connective tissue diseases (CTD). FDA provided a definition of major cardiac adverse event (MACE), and WHO states a definition of cardiovascular diseases (CVD). Nonetheless, there is a considerable variability regarding the denotation of CV outcomes and exposures among both observational studies and clinical trials (RCT). This leads to a lack of reproducibility that hinders future research and possible interventions. The primary aim of this review is to investigate the variability of CV definitions in the scientific literature on CTD and RA. Secondary aims are to compare the use of FDA MACE definition according to study design, pharmacological intervention, and diseases evaluated. Methods. A systematic search from PubMed, Embase and Cochrane Central Library was performed from January 2008 to 22 May 2025. Literature screening and data extraction were independently performed by two researchers. The research included papers on Systemic Lupus Erythematosus, primary Antiphospholipid Syndrome, Systemic Sclerosis, Sjogren Syndrome and RA. We divided CV definitions into categories: “MACE”, “CVD”, “other MACE definition” or “other CVD definition” if the authors referred to the composite endpoint as MACE or CVD without it matching the original standard definitions. When CV definitions did not fit into the above categories, they were referred to as “other CV events”. We reported studies where an instrumental tool was employed as CV outcome, or the CV definition was not provided. Results. From an initial pool of 7644 articles, 549 were included in the final evaluation (Fig. 1). FDA MACE and WHO CVD definitions were employed respectively in 49 and 27 articles (Table 1). 38 articles fell under the “other MACE definition” category, 31 studies under “other CVD definition” and 170 papers reported “other CV events”. In 204 articles an instrumental technique was used to assess CV outcome, while in 31 cases CV definition was not otherwise specified. FDA MACE definition was used in 55.5% of RCT and in 6.5% of observational studies (p<0.001). MACE was more frequently used as endpoint in observational studies if they concerned a pharmacological intervention (2.7% vs 0.56%, p<0.001). A MACE definition not in accordance with that of FDA appeared in 14.8% of RCTs and in 6.7% of observational studies. There was a significant underemployment of MACE in papers on CTD compared to papers on RA (1.7% vs 13.2%, p<0.001). Conclusions. Standard definitions of MACE and CVD are rarely applied and frequently misused, especially in real world studies. There is a need for standardization among the rheumatologic community to increase reproducibility and ensure useful results.
PO:12:180 | Echocardiographic screening of pulmonary hypertension in a multidisciplinary cohort of patients with interstitial lung disease
Background. Pulmonary hypertension (PH) may complicate parenchymal lung diseases, and current international guidelines recommend echocardiographic study of patients with suspected PH. Right heart catheterization (RHC) is recommended if hemodynamic results can modify the therapeutic approach. The objective of the study is to verify, by means of echocardiography, the prevalence of PH and/or right ventricular dysfunction in a cohort of patients with ILD (Interstitial Lung Disease) followed in a multidisciplinary pneumo-rheumatological outpatient clinic, and to evaluate any associated clinical, serological, or radiological findings. Materials and Methods. Consecutive patients with ILD attending the multidisciplinary outpatient clinic of a third-level national reference center for lung transplantation, excluding patients with already known PH. All patients underwent a Standard 2-D and Doppler echocardiogram with a Vivid E9 or Vivid E80 machine (GE Medical Systems, Norway); clinical, laboratory, and radiographic data were collected. When required by clinical suspicion or for inclusion in the lung transplant list, RHC was performed, and information was collected. Statistical analysis was conducted using SPSS (IBM for Mac (v13)). Results. 113 patients were included, 66 women and 47 men. The mean age was 67.94 15 15.62 years, and the follow-up was 9.6 (3-13) years. Diagnoses were distributed as follows: 60 (53%) ILD in Systemic Sclerosis (SSc), 19 (17%) with anti-synthetase syndrome (ASSD), 8 (7%) interstitial pneumonia with autoimmune features (IPAF), 4 (3.5%) with rheumatoid arthritis (RA), 22 (19.5%) with idiopathic pulmonary fibrosis (IPF). 53/113 (47%) patients were smokers/ex-smokers, 28 (25%) had chronic respiratory failure requiring oxygen therapy, 35 (31%) desaturated during the six-minute walk test, with a mean distance of $395.8 \pm 87.6$ m, 29 (26%) were taking an antifibrotic agent. Mean respiratory functional parameters were(%) 106,8±19,7, TLC (%) 72,8±21,8, IT 80,21±7,3, DLCO (%) 58,9±21,2 BNP or NTproBNP were alterati (>50 o >300 pg/mL) in 32 (28.3%) patients. On echocardiographic evaluation, mean FEVs was 59,45±4,75% mean E/A was 0,86±0,08, mean PAPs was 26,5±10,6 mmHg, mean TAPSE was 22.5±3.6 mm; ACT (acceleration time) was reduced in 60 (53%), and a notch was present in the pulmonary artery flow in 28 (26%). During follow-up, 9 (8%) patients underwent RHC: 3/9 (33%) had PAPm (mean Pulmonary Artery Pressure) >20 mmHg and in 9/9, the PAWP (Pulmonary Artery Wedge Pressure) was <15 mmHg. Mean PAPm was 21.42 ±12.1 mmHg, median PVR (Pulmonary Vascular Resistance) was 3.7 (2.18-2.99) WU. The patients who developed PH already showed significant baseline differences in FVC% (60.4 ±23.4 vs 87.5 ±22.4, p<0.01), DLCO ($9.7 ± 60.4 p<0.01), PAPs (42.6 ± 5.6 vs 25.2 ± 9.8, p<0.01), % of notch in PA flow (75%$vs 21.8%, p<0.05). Radiographic pattern and specific autoantibodies did not show significant associations with PH. Conclusions. Echocardiographic screening of patients with ILD demonstrates that the development of pulmonary hypertension is a frequent complication and is associated with specific clinical, functional, and respiratory characteristics already at baseline, which are capable of distinguishing subjects at higher risk who should be subjected to diagnostic confirmation with RHC.
PO:12:186 | Clinical, functional, and microvascular features in the early diagnosis and management of pulmonary hypertension in systemic sclerosis: the importance of multimodal screening strategies
Background. Pulmonary hypertension (PH) is one of the most severe and potentially life-threatening complications of systemic sclerosis (SSc), with a major impact on prognosis and patient quality of life. It is often related to microvascular dysfunction and, in some cases, to interstitial lung involvement. Early diagnosis is essential but remains challenging, as initial symptoms are frequently nonspecific and may overlap with other manifestations of the disease. In this context, the use of multimodal screening strategies combining clinical, functional, imaging, and microvascular assessments may significantly improve early identification of patients at risk. Objectives. To assess the prevalence of PH in a cohort of patients with SSc, and to analyze its correlations with pulmonary function parameters, echocardiographic findings, and microvascular abnormalities observed through nailfold videocapillaroscopy. Materials and Methods. We conducted a retrospective analysis of 120 patients with SSc followed at our center. Pulmonary hypertension was defined echocardiographically as a systolic pulmonary artery pressure greater than 30 mmHg. All patients underwent high-resolution computed tomography (HRCT) of the chest, pulmonary function tests, echocardiography, and nailfold videocapillaroscopy. Clinical, serological, and instrumental data were collected and analyzed. Statistical analysis included t tests, chi-square tests, and logistic regression. Results. Twenty-seven percent of patients met criteria for PH. Subjects with PH exhibited a significant reduction in DLCO (mean 47.2 ± 13.3 vs 58.8 ± 11.8; p<0.001), a lower FVC/DLCO ratio, and signs of right ventricular dysfunction (mean TAPSE: 19.5 ± 3.8 mm vs 23.1 ± 3.1 mm; p<0.001). Capillaroscopic findings showed a significantly higher prevalence of the “late” pattern in patients with PH (62% vs 23%; p<0.01), characterized by avascular areas, giant capillaries, and loss of microvascular architecture. sPAP was inversely correlated with DLCO (r = –0.56) and positively correlated with capillaroscopic damage score (r = 0.42). A significant association between anti-centromere antibody positivity and PH was also observed (p=0.03). Conclusions. Our findings confirm a high prevalence of PH among patients with SSc and highlight its association with impaired pulmonary function, right-heart dysfunction, and advanced microvascular damage on videocapillaroscopy. The integration of pulmonary function tests, echocardiography, and nailfold videocapillaroscopy may represent a non-invasive and effective approach for the early identification of patients at risk of developing PH. These results support the adoption of integrated, multidisciplinary screening models in clinical practice to ensure early diagnosis and monitoring of pulmonary hypertension in systemic sclerosis. Future prospective studies will be essential to confirm these data and to evaluate their long-term prognostic impact.
PO:13:188 | Menstrual alterations among women with rheumatoid arthritis: a comparative study across treatment modalities with focus on JAK inhibitors
Background. Rheumatoid arthritis (RA) often affects women during reproductive age. While the reproductive safety of conventional and biologic DMARDs is well described, evidence regarding Janus kinase inhibitors (JAKi) remains limited. Recent studies on human ovarian sections have demonstrated the expression of the JAK-STAT pathway in granulosa cells, suggesting a possible alteration of menstrual characteristics in women taking JAKi. This study aimed to assess menstrual alterations among women with RA receiving different treatment classes, with particular focus on JAKi. Methods. We conducted a cross-sectional study at rheumatology and gynecology centers using structured questionnaires to evaluate menstrual cycle characteristics before and during therapy. Clinical and treatment data were collected. Menstrual outcomes were compared across treatment groups using chi-square tests. Multivariable logistic regression assessed the association between JAKi use and amenorrhea, adjusting for disease activity (DAS28). Results. A total of 100 women with RA were included. The median age was 34.8 years (IQR 27.0–42.8), BMI 26.0 (IQR 24.0–27.0), and DAS28 score 2.99 (IQR 2.70–3.24) (Table 1). Thirty patients (30.0%) were treated with JAK inhibitors: Upadacitinib (n=17, 56.7%), Filgotinib (n=11, 36.7%), and Baricitinib (n=2, 6.7%) (Figure 1). Amenorrhea during therapy was reported by 10 patients (10.0%). Metrorrhagia was reported by 20 patients (20.0%), and menorrhagia by 14 patients (14.0%). Changes in menstrual frequency were noted in 41 patients (41.0%), including increased frequency in 12 (12.0%) and decreased frequency in 29 (29.0%). There were no statistically significant differences in these outcomes across treatment groups (p > 0.25 for all) (Figure 2). In multivariable analysis adjusting for DAS28, JAKi use was not associated with increased odds of amenorrhea (adjusted OR = 3.05, 95% CI: 0.31–30.37; p = 0.341). Conclusions. In this cross-sectional study of women with RA, treatment with JAK inhibitors was not associated with an increased risk of menstrual alterations, including amenorrhea, metrorrhagia, or menorrhagia. These preliminary findings suggest a reassuring gynecologic safety profile for JAK inhibitors, but confirmation in larger, prospective studies is needed.
PO:13:189 | Greater impact of psoriatic arthritis in females: is this mediated primarily by disease activity?
Background. Sex-related differences have been observed in psoriatic arthritis (PsA), with women often reporting a higher disease burden. Previous studies suggest that female patients experience more pain, fatigue, and reduced quality of life. However, it remains unclear whether this increased disease impact is primarily mediated by disease activity. Objective To evaluate whether the higher disease impact (measured by PSAID) observed in female patients with PsA is mediated by disease activity (measured by DAPSA). Methods. A cross-sectional study was conducted on consecutive patients who met CASPAR criteria for PsA. Demographic, clinical, and lifestyle information was collected, including socio-economic characteristics and comorbidities (with a focus on fibromyalgia). Disease activity was assessed using the Disease Activity index for Psoriatic Arthritis (DAPSA), and disease impact was measured using the Psoriatic Arthritis Impact of Disease (PSAID) questionnaire. Comparisons between males and females were performed using Mann-Whitney U or Chi-square tests. Mediation analysis was conducted following the Baron and Kenny approach, testing the significance of each association across three linear regression models: (1) total effect of sex on PSAID; (2) effect of sex on DAPSA; and (3) effect of DAPSA on PSAID adjusted for sex (Figure). All models were adjusted for age, BMI, comorbidity index (RDCI), and fibromyalgia. Results were expressed as beta (95% confidence interval). Results. A total of 136 PsA patients were included (54% female; mean age 58.9±12.0 years). The characteristics of female and male patients are displayed in Table. No major differences in disease manifestations were observed between sexes. Fybromialgia was more frequent in males. Females consistently reported higher scores in patient-reported outcomes, including DAPSA components related to pain and global disease activity, and across all PSAID items. In multivariable analysis, all associations required for mediation were significant: male sex was associated with lower PSAID scores ( = -1.73, 95% CI: -2.60 to -0.85) and lower DAPSA scores ( = -2.89, 95% CI: -5.57 to -0.22), while DAPSA was positively associated with PSAID ( = 0.20, 95% CI: 0.15 to 0.25), supporting a mediating role of DAPSA. However, the indirect effect through DAPSA accounted for 33% of the total effect of sex on PSAID, indicating partial mediation. Conclusions. Disease activity explains only part of the higher disease impact experienced by female PsA patients. Additional contributor, such as altered pain perception, fibromyalgia, and possibly psychosocial or cultural factor, may significantly influence disease burden. These findings underscore the need for individualized, sex-aware management strategies and further research into non-inflammatory drivers of disease impact in PsA.
PO:14:195 | Real-world effectiveness of anifrolumab in achieving treatment targets and reducing systemic lupus erythematosus disease burden: 6-month interim analysis of the REVEAL study
Background. Following the recent approval of anifrolumab (ANI) for the treatment of moderate-to-severe Systemic Lupus Erythematosus (SLE), real-world data remain limited beyond those from clinical trials. Real-world eVidencE of Anifrolumab in systemic Lupus erythematosus (REVEAL) is a 5-years, multicenter, prospective, observational study designed to collect real-life data on ANI use, which are currently scarce especially from the patient’s perspective. This analysis evaluates the effectiveness of ANI in routine clinical practice and its impact on disease burden and patients’ quality of life (QoL). Materials and Methods. Adult SLE patients (2019 EULAR/ACR criteria) were enrolled at ANI prescription across referral Italian centers. Data on demographics, clinical history, prior treatments and organ damage (SLICC-DI) were retrospectively collected from medical charts at enrolment. Patients were evaluated at baseline and after 1, 3 and 6 months of ANI treatment, assessing disease activity (SLEDAI-2K, SLE-DAS, Physician Global Assessment (PhGA), CLASI, joint count), concomitant therapies, and QoL through Patient Reported Outcomes (PROs, including Patient Global Assessment (PtGA), Lupus Impact Tracker (LIT) and FACIT-F). Achievement of remission (DORIS criteria) or low disease activity state (LLDAS5, modified from Franklin) at 3 and 6 months was assessed. Results. We included 236 patients (92.8% female, 92.4% Caucasian) from 25 centers. ANI was most frequently prescribed for mucocutaneous (66.5%) and articular involvement (49.2%), followed by haematological manifestations (22.5%, mainly leukopenia (36/236, 15.3%) and thrombocytopenia (25/236, 10.6%)). Thirteen patients (5.5%) had fever attributable to SLE per SLEDAI-2K. Table1 depicts detailed baseline characteristics of the cohort. Notably, in 100 patients (42.4%) ANI was the first biologic and 20 (8.5%) were naïve to immunosuppressants; 38 patients (16.1%) started ANI within 2 yrs of SLE diagnosis. In 18 cases (7.6%) ANI was added to antimalarial monotherapy and 2 patients (0.8%) received ANI alone. As shown in Table2, all disease activity measures progressively improved, alongside a significant reduction in GCs daily dose. PROs also improved significantly, with changes detectable as early as week 4 and sustained over time (Table2, Figure1). At baseline, a significant correlation was observed between PtGA and SLEDAI-2K, SLE-DAS, PhGA and CLASI-activity (rs>=0.259, p<=0.001), between LIT and PhGA, CLASI-activity and tender joints (rs>=0.204, p<=0.03), and between FACIT-F and tender joints (rs=-0.256, p=0.036). As for treatment outcomes, at 3 months, 30/176 patients (17.0%) achieved remission and 85/176 (48.3%) were in LLDAS5; at 6 months, 37/140 (26.4%) were in remission and 80/140 (57.1%) reached LLDAS5. Conclusions. In this real-world Italian cohort, ANI showed early and sustained effectiveness, with a substantial proportion of patients achieving remission or LLDAS5 by 6 months. The treatment was also associated with improved QoL and reduced GC exposure. These findings support ANI use in routine clinical settings and highlight the value of incorporating patient’s perspective in monitoring SLE outcomes.
PO:14:197 | Safety of biologic and conventional immunosuppressants in an Italian cohort of patients with systemic lupus erythematosus: a longitudinal analysis from the Lupus Italian Registry pharmacoepidemiologic study promoted by the Italian Society of Rheumatology
Background. The safety of biologic immunosuppressants in systemic lupus erythematosus (SLE) has been demonstrated in several interventional studies. However, estimates from unselected, real-world clinical populations remain scarce. This study aims to assess the safety of biologic immunosuppressants used as monotherapy (MONO-BIS) or in combination (COMB-BIS), compared to the exclusive use of non-biologic immunosuppressants (NBIS), in patients with SLE starting a new immunosuppressive treatment. Materials and Methods. LIRE is a prospective, multicentre, pharmacoepidemiologic observational study promoted by the Italian Society of Rheumatology (SIR) (full list of investigators: https://redcap.reumatologia.it/surveys/?s=LWL7WJM4KHDR97CC). SLE patients who started a new immunosuppressive therapy between 2015 and 2022 were followed every six months for up to 5 years. Adverse events (AEs) were classified according to CTCAE v4.0 criteria and categorized as serious adverse events (SAEs), infections (INF), adverse events of special interest (AESI: infections, neoplasms, cardiovascular events), hospitalizations (HOSP), and deaths (DEA). Incidence rates and relative risks of AEs were estimated using weighted Cox models adjusted for baseline treatment indication. In addition to demographic factors, estimates were adjusted for anti-DNA antibody positivity, organ involvement (SLEDAI and/or BILAG), disease damage (SLICC-DI), disease activity (SLEDAI-2K), concomitant hydroxychloroquine use, and cumulative steroid dose (>10 g). Results. Among the 338 included patients (87% women), 179 started NBIS, 55 MONO-BIS, and 104 COMB-BIS therapy. Belimumab (39%), rituximab (7%), mycophenolate (31%), and methotrexate (21%) were the most frequently used immunosuppressants. Infections were more frequent among BIS users (40%) compared to NBIS (18%), with higher rates in COMB-BIS (42%) than in MONO-BIS (35%). The COMB-BIS group had a higher prevalence of lupus nephritis (46%), higher cumulative corticosteroid exposure (>10 g prednisone equivalent: 58%), and a longer mean disease duration (12.6 years). The COMB-BIS group showed a significantly higher risk of AEs compared with NBIS (HR [95% CI]: 1.90 [1.29–2.79]), while the MONO-BIS group showed a non-significant increase (1.35 [0.76–2.40]). The risk of infections was significantly higher in COMB-BIS (2.82 [1.41–5.63]), and higher but not significantly so in MONO-BIS (2.49 [0.85–7.29]). Conclusions. In this Italian real-world study, biologic drugs were associated with a higher risk of AEs when used in combination with NBIS, particularly infections occurring in the first months after treatment initiation. However, no relevant differences were found in serious adverse events (SAEs) or mortality within 24 months. These findings highlight that in patients with multi-organ involvement, the use of combined immunosuppressive therapy should be carefully evaluated and personalized according to individual clinical profiles, to balance therapeutic efficacy and the risk of adverse events.
PO:14:202 | Use of anifrolumab in the treatment of the hematological manifestations of systemic lupus erythematosus: a single-centre case series
Background. The efficacy of anifrolumab has been documented in several studies (1,2), however data regarding its use in the haematological domain of SLE remain limited (3). The aim of this case series is to describe a single-centre experience with anifrolumab in patients with SLE predominantly affecting the haematological domain, particularly thrombocytopenia and haemolytic anaemia. Materials and Methods. We retrospectively evaluated data from six patients with haematological involvement treated with intravenous anifrolumab at a dosage of 300 mg every four weeks. Assessments were performed at baseline (T0) and after one (T1), three (T3), and six months (T6) of therapy. Changes in complete blood counts and corticosteroid dosages were analysed. Results. Among the six patients, five had thrombocytopenia and one had haemolytic anaemia. All patients were corticosteroid-dependent at baseline. The epidemiological and clinical characteristics of the cohort are detailed in Tables 1 and 2. Four patients with thrombocytopenia received anifrolumab therapy for at least six months. In these cases, an increase in platelet counts was observed, allowing a reduction in corticosteroid therapy — in two cases to a prednisone dose below 5 mg/day, and in one case complete discontinuation was achieved. At the time of reporting, one patient has been treated for three months, showing an improvement in platelet count after the first infusion and a reduction in corticosteroid dosage after the third one (Figure 1). A single patient was treated with anifrolumab for haemolytic anaemia and lymphopenia. At six months after treatment initiation, improvements were observed in lymphocyte counts, haemoglobin levels and haptoglobin values, previously undetectable, allowing a reduction in corticosteroid dosage (Figure 2). No significant adverse events occurred during treatment. In one case, therapy was discontinued after twelve months due to loss of efficacy and diagnosis of colon cancer. In this instance, a paraneoplastic aetiology as a contributing factor to the worsening and refractoriness of thrombocytopenia could not be entirely excluded. Conclusions. Based on our data, haematological involvement in SLE may represent a potential therapeutic target for anifrolumab. However, the small number of cases precludes any definitive conclusions. Expanding data collection to a larger, multicentre cohort would be valuable to explore potential predictors of response, which could account for the observed variability in both the magnitude and timing of clinical responses.
PO:14:203 | Impact of anifrolumab on depressive symptoms in systemic lupus erythematosus: results from a single-centre prospective observational study
Background. Systemic Lupus Erythematosus (SLE) is a complex autoimmune disease characterised by multisystem involvement, where neuropsychiatric manifestations, including depression, are prevalent. Dysregulated activation of the type I interferon (IFN) pathway contributes to SLE pathogenesis and has been implicated in depressive behaviour through mechanisms such as serotonin modulation and neurogenesis inhibition. Anifrolumab, a monoclonal antibody targeting the Type I IFN receptor, is effective in reducing SLE disease activity and glucocorticoid burden. However, its potential impact on depressive symptoms remains underexplored. The aim of this study is to assess the impact of intravenous anifrolumab 300 mg on depressive symptoms in adult patients with moderately to severely active SLE, alongside secondary outcomes evaluating patient-reported quality of life. Materials. This single-centre, prospective, observational study enrolled adult SLE patients meeting 2019 EULAR/ACR classification criteria with autoantibody positivity and active disease (SLEDAI-2K >=6). Participants received 300 mg of anifrolumab intravenously every 4 weeks in combination with standard-of-care (SOC). Depression severity was assessed using Beck’s Depression Inventory (BDI) and Patient Health Questionnaire-9 (PHQ-9) at baseline, 3, 6, and 12 months. Patient-reported outcomes included FACIT score and Lupus Quality of Life (Lupus QoL). Wilcoxon signed-rank test was used to compare with baseline median values of all variables at different timepoints. Cohen’s effect size was calculated to outline clinical impact of treatment. Results. Thirty-two (32) patients have been enrolled. Female sex is predominant (n=25; 78%), with a mean age of 46 (SD ± 14.0) and disease duration of 11 years (SD ± 9). The commonest disease manifestations were cutaneous and musculoskeletal, observed in 93% of the sample. Four patients (14%) had a history neuropsychiatric SLE. A clinically relevant reduction in median BDI and PHQ-9 scores was observed at 12 months compared with baseline (Cohen’s d -0.51 and -0.26 respectively) (Figure1). FACIT and LupusQoL scores exhibited strong improvement (Cohen’s d -0.62 and +0.97 respectively at 12 months). Lupus QoL improvement was obsterved in all domains, particularly pain (12.0 vs. 8.0, p=0.018, effect size +0.98), and burden to others (12.0 vs 7.0, p=0.017, effect size +0.97) (Table 1). Moreover, anifrolumab improved systemic and cutaneous disease activity at 12 months (median SLEDAI-2k 4.0 vs. 8.5 at baseline, p=0.002; median CLASI-A 0.0 vs. 3.0 at baseline, p=0.015). All 11 patients treated for at least 12 months were glucocorticoid-free at last follow-up and 8 (73%) met DORIS remission criteria. Conclusions. Anifrolumab may alleviate depressive symptoms in patients with SLE and may also improve both their quality of life and disease activity. These findings suggest that, by the inhibition of interferon signalling, anifrolumab may contribute to the improvement of depressive symptoms.
PO:14:204 | Risk stratification in systemic lupus erythematosus patients: improving the performances of a prediction model
Background. Systemic lupus erythematosus (SLE) has an unpredictable course, with alternating periods of remission and activity. Predicting disease activity in the medium term could allow timely therapeutic adjustments. To support this, a Random Forest machine learning model was developed to predict the likelihood of an activity event within 12 months, using features from the patient’s current contact, previous visit, and overall disease history. Objectives: · To evaluate the performance of the main model; · To analyze characteristics of patients with low prediction reliability; · To demonstrate improved prediction through a cascade model. Methods. The main model generates a predicted probability (PP) of an activity event within 12 months. A threshold of 0.45 was used to classify patients as high (PP > 0.45) or low risk (PP < 0.45). Cases close to the threshold were flagged as uncertain and analyzed further. Reliability boundaries were established based on distributions of true positives and negatives (Figure 1). Patients with uncertain predictions (“weak” cases) were compared to those with strong predictions using Mann-Whitney or Chi-squared tests (Table 1). To improve reliability for weak cases, a decision tree model (cascade model) was developed using a reduced feature set (e.g., demographic and treatment variables not used in the main model). This model provided rule-based predictions for cases where the main model’s predictions lacked confidence. Results. The study included 262 SLE patients with 5,952 recorded contacts from 2012 to 2020. Seventy percent of the data was used for model training and 30% (1,845 contacts) for evaluation. In the test set, 590 contacts were classified as weak predictions, while 1,255 were confidently predicted. Weak cases were associated with older age, male gender, higher serosal, vascular, and cutaneous involvement, greater corticosteroid use, and lower antimalarial use. Use of Rituximab was linked to improved reliability, suggesting better disease control. The main model achieved an AUC of 74.2% after excluding weak predictions. The integration of the cascade model enabled more accurate predictions for weak cases, slightly increasing the overall AUC to 74.3%. Conclusions. Combining the main model with a cascade decision tree extends the range of reliable predictions while maintaining accuracy. This integrated system enhances personalized care in SLE by supporting timely and individualized treatment decisions, potentially improving outcomes through better anticipation of disease activity. This work was supported by an unrestricted grant from AstraZeneca
PO:14:205 | Primary antiphospholipid antibody syndrome: association between new classification criteria manifestations and a higher-risk disease phenotype
Background. The 2023 ACR/EULAR classification criteria for primary antiphospholipid antibody syndrome (PAPS) included new disease manifestations contributing to the definition of the syndrome. However, their prognostic role and association with clinical and serological features have yet to be well elucidated. Aim of the study was to evaluate prevalence of new criteria manifestations both in a PAPS and in an antiphospholipid antibodies (aPL) carrier cohort. Additionally, we investigated their associations with PAPS clinical and serological characteristics. Methods. We enrolled a cohort of PAPS patients meeting the Sapporo classification criteria. Demographic, clinical and serological data were retrospectively collected, including type of first thrombotic/obstetric event, recurrence, presence of traditional cardiovascular (CV) risk factors (hypertension, dyslipidemia, diabetes, chronic kidney failure), serologic profile, ongoing treatments. The presence of the new manifestations included in the 2023 ACR/EULAR classification criteria was also evaluated. Same parameters were collected from a cohort of aPL carriers. Patients with autoimmune diseases were excluded. Categorical variables were compared using the 2 test, continuous variables were compared using t-test or Mann-Whitney U test. Variables with statistical significance were further tested in a binary logistic regression model. Results. 65 PAPS patients, 41 with thrombotic, 16 with obstetric syndrome, 8 with both, and 66 aPL carrier were enrolled (Table 1). PAPS patients showed significantly higher prevalence of new classification criteria manifestations compared to aPL carriers, as expected. Moreover, PAPS patients had higher prevalence of CV risk factors compared to carriers, but similar aPL serologic profiles. Among the PAPS cohort, 19 patients had at least one New classification Criteria manifestation in their clinical history (NC-PAPS). Particularly, 2 patients had cardiac valve thickening, 9 livedoid vasculopathy and 10 thrombocytopenia. Our results showed that NC-PAPS have higher prevalence of thrombotic PAPS, while the other group showed higher prevalence of obstetric syndromes. Looking at thrombotic PAPS, NC-PAPS patients showed significantly higher prevalence of arterial events and higher prevalence of recurrences. They also showed higher prevalence of Lupus Anticoagulant, anti-cardiolipin (ACLA) IgG and triple positivity (Table 2). Traditional CV risk factors were comparable between the two groups. Finally, NC-PAPS patients were more likely to be under hydroxychloroquine treatment compared to PAPS. In a multivariate analysis including arterial events as dependent variable, NC-PAPS and triple positivity as covariates, NC-PAPS patients resulted to have 5-times higher probability to have history of arterial events, independently of triple aPL positivity (OR 5.2, 95%CI 1.5-17.6). Conclusions. New classification criteria manifestations seem to be more prevalent in PAPS patients with history of arterial events, thrombotic recurrence and in patients with LA, ACLA-IgG and triple positivity, suggesting their correlation with a higher-risk disease phenotype.
PO:14:206 | Factors impacting subjective cognitive impairment in systemic lupus erythematosus patients: clearing away the lupus brain fog
Background. Systemic lupus erythematosus (SLE) patients (pts) often suffered from an impairment in cognitive functions, but a universal definition of “brain fog” does not exist. The objective of the study was to evaluate the prevalence of subjective impairment and objective mental alterations (depression, cognition, fatigue) adopting screening tools validated in SLE; also we aimed to investigate which factors were associated with brain fog. Methods. A Cross-sectional study was conducted enrolling adult SLE pts. Brain fog referred to the presence of mental alterations (i.e.; memory, concentration, attention...) as reported by SLE participants. To minimize contribution of type B symptoms, we made a subanalysis of brain fog involving pts with active disease, namely lupus fog. Demographic, clinical, therapeutic data were collected (Table). Serum anti-ribosomal P antibodies (anti-RibP) were quantified using ELISA kits. Cognitive deficits were assessed by a neuropsychologist exploring deficits in 8 cognitive domains with a battery of neuropsychological tests and screened using the Montreal Cognitive Assessment (MoCA) test performed by certified personnel (cut-off<26/30). Depressive symptoms were evaluated using the Center for Epidemiologic Studies Depression Scale (CES-D) (>15). Fatigue was measured using FACIT-F (<34). Chi-squared test and the Mann-Whitney test were used for univariate analysis (UV-A); multivariate analysis (MV-A) was performed building logistic regression models including variables showing p <0.10. Results. 114 SLE pts were enrolled (Table), 105 female (92.1%), mean age 43.7 years (+-12.2). Brain fog was found in 54% pts, with memory deficit reported in 49.1%, attention in 38.6%, concentration in 10.5% and afasia nominum in 5.3%. CES-D>15 was altered in 53.3%, MoCA<26 in 45% and FACIT<34 in 52.9%. At UV-A, an association emerged between the presence of brain fog and CES-D (Fig1A, score p<0.001), FACIT (Fig1A, score p=0.012), fibromyalgia (p<0.001), the neuropsychiatric involvement (p=0.015), anti-RNP (p=0.014), anti Rib-P (p=0.018) and disease duration (p=0.045). No association was found with MoCA test, the battery of neuropsychological test, disease activity scores or treatment. At MV-A, an independent association between brain fog and fibromyalgia (OR=34.6; 95%CI 2.3-523.1, p=0.011), CES-D score (OR=1.1 per unit, 95%CI 1.0-1.2, p=0.033) and disease duration (OR=1.1 per year, 95%CI 1.0-1.2, p=0.038) emerged. Out of 46 pts with clinically active disease, 21 were classified as lupus fog, resulting associated at UV-A with CES-D (Fig2A, score p=0.034), FACIT (Fig2A, score p=0.024) , fibromyalgia (p=0.017). MV-A showed independent association between lupus fog and FACIT score (OR=-0.146; 95%CI -0.275 to -0.017). Conclusion. Brain fog is frequent in SLE pts, but did not correlate with cognitive dysfunction, but with longer disease duration, depressive symptoms, fibromyalgia and in active pts with fatigue. Our findings suggest that SLE pts may have a negative perception about proper cognitive performances, without having a real impairment, supporting the need for assessing depressive and fatigue symptoms during clinical visits.
PO:14:207 | Nailfold capillaroscopy in systemic lupus erythematosus: microvascular alterations and their clinical relevance
Background. Nailfold videocapillaroscopy (NVC) is a valuable tool for assessing microvascular abnormalities in connective tissue diseases. While well established in systemic sclerosis, its role in systemic lupus erythematosus (SLE) remains less defined. This study aims to systematically analyze capillaroscopic patterns in SLE patients, describe their most frequent features, and compare them with findings observed in individuals with primary Raynaud’s phenomenon (pRP). Methods. We retrospectively analyzed NVC images from 64 SLE patients (mean age 49.5 years) and a matched control group of 70 pRP patients. Parameters assessed included capillary density, giant capillaries, microhemorrhages, neoangiogenesis, ectasias, tortuosity, and capillary loss. Findings were correlated with clinical and serological markers, including organ involvement and autoimmune markers (ANA, ENA, antiphospholipid antibodies). Results. NVC abnormalities were observed in 58 (90.6%) of SLE patients. The most frequent alterations in SLE were tortuosity (76.6%), ectasia (42.2%), microhemorrhages (29.7%), neoangiogenetic features (20.3%), and giant capillaries (10.9%). Compared to pRP patients, SLE patients exhibited a significantly higher prevalence of giant capillaries and angiogenetic features (p = 0.028 and p < 0.001, respectively). An SSc-like pattern was detected in 7.8% of cases, though no direct correlation was found with autoimmunity markers or clinical manifestations. Notably, both neoangiogenetic features and giant capillaries demonstrated a strong positive correlation with interstitial lung disease (ILD) (p = 0.012 and p = 0.021, respectively), highlighting the potential role of capillaroscopic markers in identifying lupus patients at risk for pulmonary involvement. Conclusion. Capillaroscopic alterations serve as key microvascular markers in SLE, providing insights into their prevalence and clinical significance. The strong correlation between neoangiogenesis, giant capillaries, and ILD underscores vascular involvement in pulmonary manifestations. NVC emerges as a valuable non-invasive tool for early ILD identification, potentially improving diagnosis and risk stratification. The detection of an SSc-like pattern in some cases reinforces the concept of shared vascular dysfunction among autoimmune diseases, highlighting the need for further research. Future studies should focus on refining the predictive role of capillaroscopic parameters, evaluating their impact on ILD progression, and integrating NVC into routine clinical assessments to improve early detection and personalized management strategies for patients with SLE and other connective tissue diseases.
PO:15:208 | Impact of disease control on organ damage accrual in patients with systemic lupus erythematosus with and extra-renal flares: a 12-month single-center longitudinal study
Background. Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by periods of flare and remission, often leading to progressive organ damage. This study aimed to describe damage accrual occurring early after a disease flare in SLE patients and to identify potential predictors. Methods. A 12-month longitudinal study was conducted involving SLE patients who met the 2019 EULAR/ACR criteria and experiencing an extra-renal flare between 2015 and 2024. At study entry, demographic and clinical variables were collected. Disease activity was measured using the Systemic Lupus Erythematosus Disease Activity (SELENA-2K). Active organ involvement was categorized according to the BILAG domains. Disease status was evaluated using the modified Lupus Low Disease Activity State (LLDAS5), defined by a daily prednisolone dose of less than 5 mg, and the Definition of Remission in SLE (DORIS). Organ damage was quantified using the SLICC-DI at baseline (T0) and after 12 months (T12). Results. A total of 98 extra-renal flares were recorded. At T0, the median SLEDAI score was 7 (IQR 4–10). Active manifestations manifestations were: musculoskeletal 79%, mucocutaneos 69 %, hematological 65%, serositic 27%, renal 24%, neuropsychiatric 7%. At T0, 29 patients (29.6%) had pre-existing organ damage, with a median SLICC score of 2 (IQR 1–3); of these, 21 (%) had pre-existing glucocorticoids (GCs)-related damage. At T12, althought the median SLICC score resulted similar to the baseline one (median =2, IQR 1–3), in 39 patients (39.8%) at least one item of organ damage was recorded, indicating de-novo damage development in 10 cases. Moreover, in a total of 15 patients (15.33%) an increase in the SLICC score was recorded (deltaSLICC). In 46,6 (%) of patients who developed new damage at T12, the damage was GCs-related. A comparison of patients with and without organ damage is repoted in table 2. Univariate analysis revealed that the SLEDAI-2K score at flare (OR 1,1, p=0.005) and, in particular, cardiorespiratory (OR 9,8, p=0.001) and neuropsychiatric involvement at flare (OR 11.5, p =0.05 ) were significantly associated with an increase in SLICC-DI. In the multivariable analysis, no baseline variables remained associated with the damage accrual; the cumulative GCs dose at T12 was independently associated with damage accrual (OR 1.0007, p < 0.05). Conclusions. This study highlights the fact that damage accrual can occur early after an extra-renal flare; thus, flare prevention is of crucial importance to protect the patients from organ damage accumulation. Moreover, in this cohort, higher GC exposure was paralleled by organ damage accrual emphasizing the need for an effective disease control of the disease activity by minimizing GC exposure in flairing patients.
PO:15:217 | Improved efficacy and safety outcomes in patients with systemic lupus erythematosus treated with belimumab vs. immunosuppressants, in addition to antimalarials and glucocorticoids: a post-hoc summary of five phase 3 trials
Background. To assess efficacy and safety of BEL relative to being on IS at baseline, in combination with standard treatment (ST) which includes AM and GC, using pooled data from past clinical trials in patients with SLE. Materials and Methods: This post hoc pooled Week 52 data for adults with active SLE from 5 Phase 3 trials (BLISS-52 [NCT00424476]; BLISS-76 [NCT00410384]; North East Asia [NCT01345253]; BLISS-SC [NCT01484496]; EMBRACE [NCT01632241]). In these studies, patients were randomised to receive BEL or placebo (PBO) in addition to ST. This summary grouped patients by study treatment: an IS cohort (receiving PBO and IS at baseline, defined as pre-treatment) and a BEL cohort (BEL 10 mg/kg IV or 200 mg SC, and no baseline IS); all patients received AM and GC at baseline. Efficacy endpoints included proportion of patients with SRI-4 response through 52 weeks, and cumulative GC dose (mg) between baseline and Week 52. Adverse events (AEs) and serious AEs (SAEs), also included data from an additional Phase 2 trial (LBSL02 [NCT00071487]). Results: Of the pooled population (N=3086), 552 patients were in the BEL cohort and 358 in the IS cohort. Baseline characteristics were similar between cohorts (Table 1). A higher proportion of BEL patients vs IS patients were SRI-4 responders at most time points, with a difference of 22% at Week 52 between BEL (61%) and IS (39%) cohorts (Figure 1A). The mean (SD) cumulative GC dose decreased by −192 (2510.8) mg atWeek 52 in the BEL cohort and increased by 339 (4725.5) mg in the IS cohort (Figure 1B). Fewer patients had AEs and SAEs in the BEL vs IS cohort (AEs: 79% vs 90%; SAEs: 11% vs 20%), with one death reported in the BEL cohort (pneumonia; treatment-unrelated). Fewer patients in the BEL vs IS cohort discontinued treatment due to AEs (6% vs 8%). Most common AEs were infections and infestations (53% vs 64%). The most frequent SAEs were infections and infestations (BEL: 4% vs IS: 8%). Conclusions: This post hoc summary adds clinical data supporting the benefits of initiating BEL in patients not receiving IS at baseline versus PBO and IS at baseline, in those not well controlled with AM and GC at baseline. Patients treated with BEL but not IS were also able to reduce GC dose even if taper was not mandated, and had fewer AEs.
PO:15:218 | Evaluation of leukocyte expression of ecto-nucleotidase in patients with systemic lupus erythematosus
Background. Ecto-nucleotidases are membrane proteins that modulate the immune response through the extracellular conversion of pro-inflammatory mediators ATP and NAD into adenosine, a molecule with immunosuppressive functions. These enzymatic reactions are mediated by ectonucleotidases CD39 and CD73 and, to a lesser extent, by CD38, CD157, CD203a and CD203c. In systemic lupus erythematosus (SLE), alterations in serum ATP levels and adenosine receptors suggest a dysregulation of these pathways. Therefore, the aim of the study was to characterise the expression of ectonucleotidases in B and T lymphocytes, natural killer (NK) cells and dendritic cells (DCs) of patients with SLE, evaluating the association with disease activity status. Methods. Consecutive patients diagnosed with SLE according to the 2019 EULAR/ACR criteria and healthy controls matched for age and sex were enrolled. Clinical-demographic data were collected and peripheral blood mononuclear cell samples were collected and analysed by spectral flow cytometry for the detection of CD39, CD73, CD38, CD157, CD203a and CD203c. Patients were stratified according to disease remission status according to the DORIS definition. Results. The study included 57 SLE patients with a female-to-male ratio of 10:1 and a median age of 45 years (Table 1). Compared to controls, patients had reduced expression of CD73 in naïve B lymphocytes and cytotoxic T lymphocytes (Figure 1 A/B). Overall, there was increased expression of CD157, CD38, CD203a, and CD203c in mature B lymphocytes, T helper lymphocytes, DCs, and NK cells. In addition, there was an increase in CD39+ and CD73+ in NK cells, while the proportion of CD39+ was increased in DCs. In patients in remission according to the DORIS definition, an increase in CD39+ Treg cells was observed compared to those who did not achieve remission (Figure 1 C). Conclusions. This study is the first to conduct a comprehensive analysis of the expression of ecto-nucleotidases in different leukocyte populations of patients with SLE. Significantly, a reduction in the expression of CD73, an enzyme essential for the synthesis of extracellular adenosine, was found in the naïve B lymphocytes and cytotoxic T lymphocytes of patients. Since adenosine exerts an immunosuppressive action, the reduction in its peri-cellular concentration could promote the activation of these lymphocyte populations. Conversely, several cell types showed increased expression of ectonucleotidases. Since the expression of these enzymes is induced by various pro-inflammatory cytokines, this phenomenon could constitute a compensatory mechanism aimed at reducing excessive concentrations of the pro-inflammatory mediators ATP and NAD. Patients in remission according to the DORIS definition showed an increase in CD39+ Tregs, cells that exert an immunosuppressive action by depleting extracellular ATP, suggesting a possible role for these cells in disease remission.
PO:15:219 | Nailfold capillaroscopic abnormalities in systemic lupus erythematosus: comparison with healthy controls and clinical-immunological correlations. Preliminary data
Background. This study aims to evaluate capillaroscopic abnormalities in systemic lupus erythematosus (SLE) patients versus healthy controls and investigate correlations between microvascular changes and clinical or immunological features. It also seeks to support the diagnostic and prognostic value of nailfold videocapillaroscopy (NVC) in SLE, following prior evidence of heterogeneous microvascular involvement (1). Methods. This observational, case-control study included 105 patients diagnosed with SLE and 59 healthy controls, evaluated between January and June 2025. All participants underwent NVC performed by trained operators using standardized protocols. Capillaroscopic parameters assessed included average capillary density, presence of tortuous, dilated, and giant capillaries, neoangiogenesis, hemorrhages, and scleroderma or scleroderma-like pattern. Clinical data were collected through structured interviews and medical chart reviews, including vascular manifestations such as acrocyanosis, Raynaud’s phenomenon (RP), and digital ulcers, as well as smoking status, beta-blocker use, and autoantibody profiles. Statistical analyses included chi-square and t-tests for group comparisons, Fisher’s exact test for categorical variables, and calculation of odds ratios with 95% confidence intervals to explore associations between capillaroscopic findings and clinical-immunological variables. Results. Compared to controls, SLE patients more frequently presented with Raynaud’s phenomenon (p=0.001) and acrocyanosis (p=0.003), while no significant differences were observed in smoking habits. Capillaroscopy revealed a significantly lower capillary density in SLE patients (p<0.001), and a higher frequency of tortuous (p=0.043), dilated (p=0.001), and giant capillaries (p=0.014). Neoangiogenesis (p<0.001) and scleroderma-like patterns (p=0.027) were exclusively observed in SLE patients (Table 1). Within the SLE cohort, associations between capillaroscopic abnormalities and clinical or immunological features were evaluated, only statistically significant associations are reported here. Acrocyanosis was associated with giant capillaries (p=0.030), while RP was significantly correlated with dilated (p=0.007), giant capillaries (p=0.045), and scleroderma-like patterns (p=0.013). Patients with vasculitis or digital ulcers showed an increased prevalence of capillary density <7/mm (p=0.025), giant capillaries (p=0.002), and scleroderma-like patterns (p=0.040). Anti-Sm antibody positivity was associated with neoangiogenesis (p=0.043) and dilated capillaries (p=0.012), while anti-U1RNP positivity correlated with neoangiogenesis (p=0.043) (Table 2). Conclusions. SLE patients display distinct and significant nailfold capillaroscopic abnormalities when compared to healthy controls. Specific alterations, such as neoangiogenesis, giant capillaries, and scleroderma-like patterns, show meaningful associations with vascular symptoms and autoantibody profiles. These preliminary findings highlight the potential of NVC as a non-invasive, supportive tool for microvascular assessment, disease monitoring, and clinical stratification in SLE. References. Cutolo M, Paolino S, Pizzorni C, Smith V. Vitamin D, steroid hormones, and autoimmunity. Ann N Y Acad Sci. 2018;1411(1):107-119. doi:10.1111/nyas.13524
PO:15:220 | Outcomes of extra renal flares in systemic lupus erythematosus: longitudinal analysis of a monocentric cohort
Background. Lupus low disease activity state (LLDAS) and remission are key therapeutic targets in systemic lupus erythematosus (SLE), associated with better long-term outcomes. This study aimed to evaluate the frequency of LLDAS achievement 12 months after an extra-renal flare and to identify clinical and serological predictors in a monocentric SLE cohort. Methods. This observational cohort study included SLE patients with an extra-renal disease flare between 2017 and 2024. Patients were assessed at the flare occurrence (T0) then at 3 (T3), 6 (T6), and 12 months (T12). Active organ involvement at flare was categorized based on BILAG domains, and disease activity at T0 and follow-up was evaluated by SLEDAI-2K score. At each time point, the attainment of clinical remission (based on the DORIS definition, excluding the physician global assessment [PGA]) and/or LLDAS-5 (according to modified criteria: excluding the PGA and requiring a prednisone dose < = 5 mg/day) was recorded. Univariate and multivariable logistic regression analysis of potential predictors were performed. Results. 98 patients were included. Demographic, clinical, and therapeutic characteristics are summarized in Table 1. During the follow-up, SLEDAI-2K score progressively declined from a median of 7 (4-10) to 2 (0-4); at 12 months, 67 (69.0%) patients were in LLDAS5 and 38 (38.7%) were in remission. As shown in figure 1, clinical outcomes assessed at 3, 6, and 12 months demonstrated a gradual increase in the proportion of patients achieving LLDAS5 and clinical remission. Comparison between those who reached LLDAS-5 at T12 and those who did not is detailed in Table 2. Patients not achieving LLDAS-T12 received significantly higher cumulative 6-methylprednisolone doses (2786.2 ± 349.6 mg vs 1740.3 ± 158.8 mg, p = 0.002) and higher daily doses at T12 (7.07 ± 1.38 mg/day vs 2.95 ± 0.24 mg/day, p < 0.001). In univariate analysis, variables associated with the achievement of LLDAS5 at 12 months resulted: SLEDAI-2k score at flare (7.4 ± 5.5, p < 0.005), male sex (93.3% vs. 64.6%, p = 0.027), the presence of anti-dsDNA antibodies at flare (p = 0.014). However, in multivariable logistic regression, only the baseline SLEDAI score remained significantly associated with LLDAS5 at 12 months (OR 0.89, 95% CI 0.82–0.97). An additional key finding is that no specific BILAG domain manifestation was independently associated with the achievement of LLDAS5 at T12; however, hematologic (OR 0.15, p= 0.015) and mucocutaneous involvement (OR 0.29, p= 0.018) were both negatively associated with remission at T12. Conclusions. This study demonstrated that in real-life setting, achievement of treatment targets with standard of care remains suboptimal, especially in patients with high disease activity, mucocutaneous and hematological manifestations. Interestingly, patients not achieving targets required significantly higher doses of 6-MP, highlighting the importance of early disease control and tailored treatment strategies.
PO:15:221 | Proteins upregulated in thrombotic antiphospholipid syndrome link to platelet function in contrast with non-antiphospholipid-related thrombosis: insights from two systematic reviews
Background. Antiphospholipid syndrome (APS) is a systemic autoimmune disorder characterized by thrombosis, pregnancy morbidity, and other clinical manifestations in the presence of antiphospholipid antibodies (aPL). Despite advances in research since its identification in 1983, no targeted therapies beyond anticoagulation have been developed, and the 10-year mortality rate remains at 9.3%. This study aims to inform future therapeutic strategies by exploring proteomic differences between thrombotic APS (tAPS) and non-aPL-related thrombosis. Methods. We conducted two systematic literature reviews (SLRs) following PRISMA guidelines to identify upregulated proteins in tAPS and in non-aPL-related thrombosis. Eligible studies were controlled observational studies focused on proteomic analysis. Upregulated proteins were used as input for gene cluster analysis, followed by gene enrichment analysis utilizing Gene Ontology (GO). Network analysis was conducted. Results. Out of 108 and 209 records screened, 7 studies on tAPS and 13 on non-aPL-related thrombosis met the inclusion criteria (Figure 1). A total of 118 proteins were found to be upregulated in tAPS, compared to 319 in non-aPL-related thrombosis. Cellular component enrichment revealed that the upregulated proteins in tAPS originate from blood microparticle, membrane attack complex and vesicle lumen. Similarly, the upregulated proteins in non-aPL-related thrombosis originate from blood microparticle, vesicle lumen and secretory granules. GO enrichment analysis highlighted distinct biological processes: in tAPS, the top terms were platelet aggregation, platelet activation, and blood coagulation. Conversely, in non-aPL thrombosis, the leading processes were hemostasis, blood coagulation, and wound healing, with platelet-related processes ranking only seventh. Notably, the upregulation of platelet-related proteins in tAPS patients was observed even outside the acute phase, suggesting a persistent alteration in platelet-related pathways. Furthermore, molecular function analysis showed that tAPS-related proteins are predominantly involved in receptor and protein complex binding, whereas non-aPL-related thrombosis proteins are mainly involved in enzymatic activity (Figure 2). Conclusion. Our findings highlight the central role of platelet-related processes in tAPS pathogenesis. By elucidating the unique proteomic and functional characteristics of tAPS, this study provides a foundation for future research into targeted therapies that address platelet involvement in APS pathogenesis.
PO:15:222 | Post-hoc analysis of the BeRLiSS-JS registry: efficacy of belimumab on thrombocytopenia
Background. We have seen clear evidence that belimumab is both effective and safe in treating systemic lupus erythematosus (SLE), showing good results across different disease domains. However, when it comes to hematologic manifestations, especially thrombocytopenia, the evidence remains limited. Aim. To assess the efficacy of belimumab in hematologic manifestations, in particular thrombocytopenia, in a nationwide cohort of patients with SLE. Methods. This study was based on a multicenter national cohort, involving 14 leading SLE referral centers across Italy. In particular, we enrolled 443 patients (n= 443) who met one of the following classification criteria for SLE: the ACR 1997 revised criteria, the SLICC 2012 criteria, or the EULAR/ACR 2019 criteria. In addition, all participants needed to be on either intravenous (10 mg/kg monthly) or subcutaneous treatment (200 mg weekly) with belimumab and have active disease at the time of enrollment. A positive serology was required, along with either joint or skin involvement. Among them we identified 44 patients with thrombocytopenia, defined as a platelet count <150,000/mm³ (Table 1). The efficacy of belimumab was assessed by evaluating the improvement in mean platelet count and the proportion of patients achieving platelet count normalization. The average daily dose of corticosteroids was also calculated at baseline and every 6 months. Univariate analyses were performed using paired t-tests and ANOVA for repeated measures, with SPSS version 29. Results. Among patients with thrombocytopenia at baseline, platelet values increased significantly from a mean ± SD baseline value of 110.2±38.1×109/l to 176.6 ± 88.7 ×109/L at 48 months (p=0.004) (Graph 1) and the rate of thrombocytopenic patients decreased to 45% at 48 months. Glucocorticoids users decreased numerically, but not significantly, from a baseline value of 93.2% to 80% at 48 months (Graph 2); specularly, the percentage of low-dose PDN users, defined as a daily dose of prednisone <5 mg, increased from baseline (36.4%) to month 48 (90%); statistical significance was found also at month 6 (68.3%, p=0.001) and month 12 (81.6%, p=0.033). Mean GC dose (expressed as PDN equivalents) declined significantly from a mean ± SD baseline value of 10.8 ± 9.6 mg/d to 4.4 ± 5.5 mg/d at 48 months. During follow up, platelet values did not differ significantly between patients on IS in addition to belimumab compared to those on belimumab alone (p=0.66). Moreover, IS use did not significantly influence platelet value changes during follow up (respectively, p=0.65 and p=0.53) (Graphs 3 and Graph 4). Conclusion. Add-on therapy with belimumab led to clinical improvement in a significant proportion of patients with thrombocytopenia in a real-life setting. Therapy with belimumab was associated with a glucocorticoid-sparing effect. This effect does not appear to depend on the co-administration of a conventional immunosuppressant.
PO:16:231 | Differential clinical features of systemic lupus erythematosus patients on biological therapies: insights from a monocentric cohort
Background. to compare the clinical profile of patients prescribed with either BEL or ANI and assess preliminary efficacy of ANI in a monocentric cohort of systemic lupus erythematosus (SLE) patients. Methods. we performed an observational study on consecutive patients with active SLE prescribed with a biological drug at our clinic between July 2023 to July 2024, with a follow-up of at least 6 months from baseline (start of biologic). Clinical, demographic and serological data were collected at baseline, at 3 and 6 months. Disease activity was measured through the SLE-disease activity index 2000 (SLEDAI-2K) and the SLE-disease activity score (SLEDAS) including assessment of active serology. For skin involvement, ANI patients had their CLASIa (Cutaneous LE Disease Area and Severity Index) calculated. Comparisons between continuous and categorical variables were carried out using parametric or non parametric tests as appropriate. We used Friedman’s test to repeat measures and compare paired samples. Categorical variables were expressed as n (%) and continuous variables as mean±standard deviation (SD). Results. we included 15 SLE patients (Table 1) with a mean follow-up of 8.90 (6.10) months since start of biologic, receiving either BEL (7, 46.6%) or ANI (8, 53.4%). The main organ involvement encompassed skin rash and arthritis in the ANI group (both 62.5%), and skin rash (41%) and arthritis (71%) in the BEL group. BEL and ANI group did not differ in terms of baseline disease activity; more patients were serologically active (positive anti-dsDNA and/or low complement) in the BEL group while not reaching statistical significance. Organ damage was significantly lower at baseline in the BEL group. Out of 8 patients on ANI, 3 (37.5%) had to stop the drug after a mean time of 3.50±2.78 months due to inefficacy (1 case) or adverse events (2 cases: recurrent vaginal bleeding and pneumonia requiring ICU admission). No withdrawals were seen in the BEL group within the follow-up. Both SLEDAI-2K and SLEDAS decreased significantly in both ANI and BEL groups (Table 2). ANI patients further displayed a significant decrease in CLASIa as well between baseline and T6 (10.71±10.57 vs. 3.14±5.39, p=0.023), indicating improvement of skin involvement. Prednisone daily dosage was quickly tapered in the BEL group Relative to ANI group, patients prescribed with BEL had received a significantly lower number of traditional immunosuppressants before the initiation of the biological drug (p<0.001, Table 1); no patients on BEL had received any other biologic before. Conclusions. in our consecutive cohort of SLE patients receiving biologics in the last 18 months, both drugs showed similar efficacy in decreasing disease activity. BEL was prescribed earlier than ANI in disease history and confirmed a steroid-sparing potential, underscoring the importance of early treatment in active SLE.
PO:16:232 | Belimumab step-down dose spacing in patients with systemic lupus erythematosus in persistent clinical remission: experience from a multicentric cohort
Background. To evaluate the feasibility and safety of belimumab (BEL) dose spacing and withdrawal in patients with systemic lupus erythematosus (SLE) who were in long-standing remission on BEL. Methods. Patients above 18 years of age with a diagnosis of SLE and persistent disease remission while on BEL were enrolled. Persistent remission was defined as >6 months on stable immunosuppressive therapy without experiencing a clinical flare of SLE (i.e. clinical SLE disease activity index [C-SLEDAI] less or equal to 2). All the patients started BEL spacing at enrolment. Patients were assessed by an experienced rheumatologist with physical examinations and laboratory tests every 12 weeks for 24 months for disease activity and damage accrual according to Systemic Lupus International Collaborative Clinics/American College of Rheumatology (SLICC/ACR) Damage Index. If the patient was in clinical remission (C-SLEDAI less or equal to 2 and absent [British Isles Lupus Assessment Group] BILAG A or B items), BEL was tapered as follows: - Step 1: BEL 200 mg subcutaneous (SC) every 10 days OR 10 mg/Kg intravenous (IV) every 6 weeks - Step 2: BEL 200 mg SC every 14 days OR 10 mg/Kg IV every 8 weeks - Step 3: BEL 200 mg SC every 21 days OR 10 mg/Kg IV every 12 weeks - Step 4: stop BEL Primary outcome: number of disease flares during follow-up. Secondary outcomes: progression of SLICC/ACR damage index, death. Results. Twenty-two patients were enrolled (Table 1), 21 were females (95.5%), with a mean age of 48±10 years. Mean disease duration was 21±11 years. Seven patients (31.8%) had a history of lupus nephritis. At the start of BEL spacing, 6 patients were on glucocorticoid (GC) therapy at a mean dose of 4.4±1.7 mg/day Prednisone equivalents), and 15 were taking Hydroxychloroquine (HCQ). Patients were treated with BEL for an average of 6±3 years before enrolment. Patients were observed for a median of 21 (Q1–Q3: 16–24) months. Five patients were stopped BEL during follow-up. One patient on BEL SC every 14 days experienced a disease relapse (C-SLEDAI 4) and was started HCQ at 15 months. One patient who stopped BEL had a C-SLEDAI of 1 and low complement at baseline and during the follow-up. She developed anti-dsDNA positivity and was initiated Azathioprine at month 21. None of the patients had to return to the previous BEL step nor required an increase in GC dose. No major disease relapses, deaths nor increases in SLICC/ACR organ damage index were reported during the follow-up. Conclusion. Progressive BEL dose spacing and withdrawal, paired with close monitoring for disease activity, can be a feasible and safe approach for SLE patients in long-standing remission on BEL.
PO:16:233 | Efficacy of voclosporin on nephritis in patients with variable gain of function of TLR7 affected by lupus: clinical case
Background. We present the case of a 45-year-old woman diagnosed with systemic lupus erythematosus (SLE) in 2022, following the identification of a hemizygous gain-of-function variant in the TLR7 gene, detected during family screening for type I interferonopathy. The family history revealed that her eldest daughter died in 2023 from severe type I interferonopathy with neurological, vasculitic, and intestinal involvement; her younger son is currently under follow-up for the same condition. The patient’s medical history includes facial photodermatitis during adolescence and idiopathic thrombocytopenia at age 24, treated with steroids. In 2022, concomitant with the genetic finding, laboratory results showed hypocomplementemia, hypergammaglobulinemia, ANA 1:160 (speckled pattern), borderline anti-dsDNA, and negative antiphospholipid antibodies. Treatment with mycophenolate mofetil and hydroxychloroquine was initiated. In 2023, she developed thrombosis of the right femoroiliac axis and femoral tripod, treated with embolectomy and anticoagulant therapy. Subsequently, she experienced recurrent pleural and pericardial effusions. In November 2023, the first evidence of proteinuria up to 6 g/24 h led to a renal biopsy showing focal endocapillary proliferative glomerulonephritis (consistent with class III lupus nephritis). Treatment with mycophenolate mofetil 2 g/day was continued. In April 2024, due to persistent proteinuria in the absence of other laboratory or clinical signs of disease activity, a repeat renal biopsy revealed membranous glomerulonephritis (stage I), consistent with class V lupus nephritis. Based on the histological findings and the limited efficacy of previous therapies, voclosporin was added to the treatment regimen. A few weeks after introducing voclosporin, a progressive reduction in proteinuria was observed, reaching values of approximately 900 mg/24 h (as shown in Figure 1), without significant side effects or deterioration in renal function. Conclusions. This case highlights a favorable response to voclosporin in a patient with genetically determined SLE caused by a TLR7 gain-of-function variant. This mutation induces mesangial proliferative glomerular injury with immune deposits, resembling that seen in conventional lupus nephritis. Voclosporin, through modulation of T-cell activity and podocyte stabilization, proved effective in this setting as well. Although SLE is generally a polygenic autoimmune disease, the identification of monogenic lupus cases has provided valuable insights into its pathogenesis. TLR7 plays a pivotal role in lupus, and gain-of-function variants have been linked to lupus-like proliferative glomerulonephritis. The present case supports the use of voclosporin in combination with mycophenolate mofetil in patients with nephritis associated with a hemizygous TLR7 gain-of-function variant. Future studies will be needed to explore the efficacy of voclosporin in selected genetic subgroups, paving the way for targeted therapies based on immunogenetic profiles.
PO:16:235 | Anifrolumab in systemic lupus erythematosus: real-life experience of a single-center cohort
Background. Anifrolumab (ANI) is a monoclonal antibody directed against type 1 interferon receptor. Its use in the treatment of patients with systemic lupus erythematosus (SLE) is becoming more frequent in clinical practice. The aim of this study is to evaluate the efficacy of ANI in SLE without active renal involvement. Methods. Data were prospectively collected from SLE patients (according to the ACR, SLICC, or EULAR/ACR classification criteria) undergoing treatment with ANI. Specifically, SLEDAI-2K, SLE Disease Activity Score (SLEDAS), painful/swollen joint count (SJT/TJC), and CLASI (Cutaneous LE Disease Area and Severity Index) were acquired before the start of therapy and subsequently every 3 months for the first year of therapy. Platelet count (PC) and lymphocyte count (LC), complement levels, anti-dsDNA antibody titers, and daily prednisone dose (PDN) were also collected at the same frequency. The SDI (SLICC/ACR damage index) was assessed at baseline and after 6 months. Finally, rates of remission (SLEDAI-2K=0 with PDN ≤5 mg/day), clinical remission (clinical SLEDAI-2K=0 with PDN ≤5 mg/day) and modified lupus low disease activity state (SLEDAI-2K ≤4 without major organ involvement and no new manifestations, with PDN≤7.5 mg/day) were obtained. The T-test and Wilcoxon test for paired data were used to compare the various timepoints. Results. Since September 2023, 22 patients with SLE have been treated with ANI: of these, 11 (50%) for skin involvement, 10 (45%) for joint involvement, while hematological and serosal involvement were present in 4 (18%) and 2 (9%) patients, respectively. In 8 patients (36%), ANI was administered before conventional immunosuppressants (IS). Reductions in the mean SLEDAI-2K (p = 0.016 at 6 months and p = 0.007 at 9 months), SLEDAS (p < 0.001 at 6 months), CLASI (p = 0.008 at 6 months and p = 0.043 at 9 months), TCJ (p = 0.009 at 6 months and p = 0.033 at 9 months), SJC (p = 0.023 at 6 months) and LC (p = 0.021 at 6 months and p = 0.007 at 9 months) were encountered. No changes were found in PC, hypocomplementemia rates, elevated anti-dsDNA antibody titers or SDI at 6 months (Figure 1). A trend toward reduced prednisone use was observed. Rates of remission, clinical remission, and modified lupus low disease activity state are shown in Figure 2. Treatment was discontinued in 3 patients (2 due to ineffectiveness and 1 due to sepsis). There were no cases of herpes zoster. Conclusions. ANI has been shown to reduce disease activity, with major impact in the cutaneous and articular domains. Further data are needed to evaluate its effect on hematological and serositis manifestations.
PO:16:236 | Achieving a low disease activity state with a corticosteroid dose of 5 mg or less: observational study with anifrolumab in patients with systemic lupus erythematosus in Italy
Background. Despite recent improvements in the management of systemic lupus erythematosus (SLE), patients still face a high risk of morbidity and mortality. Sustained remission is the goal of SLE management, although it is rarely achieved in clinical practice. When remission cannot be reached, the Lupus Low Disease Activity State (LLDAS) represents an alternative Treat-to-Target objective. In Italy, real-world data are lacking on the achievement and maintenance of LLDAS, remission, and corticosteroid tapering in patients treated with anifrolumab. Therefore, a study was designed with the primary objective of describing the proportion and characteristics of patients who achieve LLDAS5 and remission during treatment with anifrolumab in Italian clinical practice, and with the secondary objective of defining a glucocorticoid tapering scheme to inform clinical practice. Materials and Methods. DAHLIA is an Italian, multicenter, prospective, observational cohort study conducted in accordance with Good Clinical Practice (GCP). The study population will include 245 Italian adult patients of both sexes with SLE, according to EULAR/ACR criteria, who are prescribed initiation of anifrolumab therapy for the first time in the context of routine Italian clinical practice, in line with the approved and reimbursed label. The primary objective is to describe the proportion and characteristics of patients who achieve LLDAS with a corticosteroid (prednisone) dose equal to or less than 5 mg (LLDAS5) at week 52. Secondary objectives include assessment of the estimated cumulative probability of achieving LLDAS5 over the course of the study; the percentage of flares following glucocorticoid reduction to a dose equal to or less than 5 mg/day; the cumulative probability of achieving DORIS remission; the persistence of DORIS remission; and the description of a glucocorticoid tapering scheme used in routine clinical practice. The sample size was estimated based on results from analyses of LLDAS achievement in the TULIP trials, the number of participating centers, and the potential study dropout rate. The study period for each participant will last 104 ± 1 weeks from treatment initiation or until discontinuation of anifrolumab, loss to follow-up, or death. Participating patients, who do not attend the visit after the first infusion, will be included only in the safety analysis. Data will be collected starting from the first day of anifrolumab treatment, as part of routine clinical practice. Conclusions. The multicenter observational DAHLIA study will collect real-world evidence from Italian clinical practice, identifying the characteristics of patients treated with anifrolumab who achieve the LLDAS5 target and DORIS remission. In addition, it will help to identify a glucocorticoid tapering scheme in patients with SLE treated with anifrolumab.
PO:16:238 | Cardiovascular risk in systemic lupus erythematosus patients: comparison among Framingham Score, QRISK3, and SLECRE
Background. Systemic lupus erythematosus (SLE) is a multisystemic autoimmune disease associated with a high risk of developing cardiovascular (CV) events (1). The aim of this study is to analyse the performance of the main CV risk calculators, Framingham Score, QRISK3, and SLECRE (2), in predicting CV events at 10 years. Methods. We enrolled 82 SLE patients, with a minimum follow-up of 10 years and complete data on SLE features, disease activity (as SLEDAI-2K) and CV risk factors. Clinical and serological data were collected from clinical charts. CV risks were calculated at the CV event (at the last follow-up for controls) and 10 years before. A p-value lower than or equal to 0.05 was considered statistically significant. Results. Figure 1 shows demographic, CV risk data of the 82 patients (Table 1), and the distribution of 27 CV events (Graphic 1). CV events were associated with male sex (p: 0.01), longer SLE history (p: 0.014), and higher values of SLEDAI-2K at the event and 10 years before (p: 0.0023 and p: 0.0003, respectively). No differences in autoantibodies’ or clinical data were detected between groups. Considering risk factors, higher systolic pressure (p: 0.007) and chronic kidney disease (p<0.0001) were the only items associated with CV events, 10 years before. Stratifying patients in low (<10%), intermediate (11-20%), and high (>20%) CV risk, only SLECRE >20%, assessed 10 years before the CV event or before the last follow-up, was significantly associated with the CV event development at 10 years [OR: 5 (IC 95%: 1.8–13.6); p: 0.002]. FRS and QRISK3 stratification did not differ between CV event development and controls. Only anti-beta2glycoprotein-I, anti-dsDNA antibodies, lupus nephritis, and complement reduction were associated with SLECRE >10%, assessed 10 years before the last available, independently from CV event occurrence. Conclusion. SLECRE calculator demonstrated the best performance in identifying patients at risk to develop CV events at 10 years, compared with Framingham Score and QRISK3. This is due to the inclusion of differently weighted items, such as traditional CV risk factors, disease activity and lupus anticoagulant. References 1. Schoenfeld SR, et al. The epidemiology of atherosclerotic cardiovascular disease among patients with SLE: a systematic review. Semin Arthritis Rheum. 2013;43:77–95. 2. Sivakumaran J, et al. Assessment of cardiovascular risk tools as predictors of cardiovascular disease events in systemic lupus erythematosus. Lupus Science and Medicine 2021;8:e000448.
PO:16:241 | Prevalence and associated factors of premature ovarian insufficiency in women with systemic lupus erythematosus: the role of human herpesviruses HHV-7 and HHV-8
Background. Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease that primarily affects women of reproductive age. Fertility may be impaired by intrinsic factors, such as disease activity, flares, and organ damage, as well as by extrinsic factors, including treatment-related effects. Premature ovarian insufficiency (POI), a condition characterized by reduced reproductive potential, represents a significant issue in SLE. Anti-Müllerian hormone (AMH), produced by ovarian follicles, is a reliable indicator of ovarian reserve, while elevated follicle-stimulating hormone (FSH) levels associated with 4–6 months of amenorrhea or oligomenorrhea remain the gold standard for POI diagnosis. The aim of this study was to assess the prevalence of POI in a monocentric cohort of women with SLE and to examine its association with clinical, immunological, therapeutic features, and viral serologies. Materials and Methods. We included women aged 18–45 years with a diagnosis of SLE according to the 1997 ACR, 2012 SLICC, and/or 2019 EULAR criteria, treated with hydroxychloroquine and/or conventional or biologic immunosuppressants, excluding cyclophosphamide (CYC), and enrolled between 2014 and 2023. Data collected through a secure electronic system included medical history, disease characteristics and activity (SLEDAI-2K, PGA), treatments, and hormonal profile (LH, FSH, prolactin, progesterone, and AMH). Viral serologies included HHV-6, -7, and -8. Categorical variables were expressed as frequencies and percentages, and continuous variables as mean ± standard deviation (SD). POI was defined as AMH <1 ng/mL or FSH >40 IU/L. Results. Seventy-nine women with SLE were enrolled (Table 1). POI defined by AMH <1 ng/mL was observed in 53.1% of patients, while 30.4% met the criteria based on FSH >40 IU/L. No statistically significant differences were found in disease activity, autoimmune serological profile, clinical manifestations, or treatments between patients with and without POI, regardless of the definition used. Patients with POI had higher exposure to CYC and higher cumulative doses, although without statistical significance. Regarding viral serologies (Table 2), the seroprevalence of anti-HHV-7 IgG and IgM and anti-HHV-8 IgM was significantly associated with POI defined by FSH values. Conclusions. Our study suggests a possible role of human herpesviruses HHV-7 and HHV-8 in the impairment of female fertility in patients with SLE. The involvement of HHVs in reproductive dysfunction, conception difficulties, and spontaneous abortion—mainly linked to HHV-6, but also to HHV-7 and HHV-8—has been described in the literature. The observed results support the hypothesis of a potential impact of these viruses on ovarian function and follicular reserve, providing a novel perspective on the viral contribution to reproductive impairment.
PO:17:248 | Prevention of human papillomavirus infection in women with systemic lupus erythematosus: a single-center cross-sectional study
Background. Women with systemic lupus erythematosus (SLE), especially those treated with immunosuppressants, have a greater risk of developing cervical cancer related to the human papilloma virus (HPV). Vaccination against HPV and screening for early detection of HPV are safe and effective prevention measures. The objectives of this study are to evaluate vaccine coverage and adherence to the HPV infection screening programs in women with LES, as well as investigate the incidence of infection in these patients. Methods. A cross-sectional study was conducted by administering an anonymous survey on vaccination and infection screening adherence to consecutive SLE patients attending our center's Lupus Clinic. Data on HPV infection and HPV vaccination in women were analyzed. Results. From March to June 2025, 45 women with SLE completed the survey (Table 1). Among these patients, 67% (30/45) expressed uncertainty regarding the safety of vaccines for patients with SLE, while 60% (27/45) reported not knowing which vaccinations are recommended. Regarding HPV vaccination coverage, only 3/45 (6.7%) reported having been vaccinated against HPV, while the majority (33/45, 73.3%) reported not having been vaccinated: 58% (19/33) of unvaccinated patients were in treatment with glucocorticoids (GCs), 82% (27/33) with conventional disease-modifying antirheumatic drugs (cDMARDs), and 27% (9/33) with biological disease-modifying antirheumatic drugs (bDMARDs). Figure 1 describes the reasons that led patients not to undergo vaccination. The main barriers were the lack of recommendation by the doctor (19/33, 56.7%) and lack of information about the vaccine (9/33, 27.3%). 27/45 patients (60%) reported regularly undergoing PAP tests or HPV DNA tests, while 12 (26.7%) declared they did not. Finally, 5/45 patients (11.1%) reported having been diagnosed with HPV infection. Conclusions. In our study, HPV vaccination coverage was suboptimal in patients with SLE, and the lack of promotion and information about the vaccine was the main barrier. Adherence to screening for early HPV diagnosis was also suboptimal. This underscores the importance of the referring specialist's role in providing information and promoting adherence, in order to improve the level of prevention in these patients.
PO:17:250 | Effectiveness and safety of the recombinant zoster vaccine in patients ≥18 years of age with systemic lupus
Background. The recombinant zoster vaccine (RZV) is FDA-approved for herpes zoster (HZ) prevention in adults ≥50, and immunocompromised adults ≥18 at increased HZ risk, which may include those with SLE or MS. This retrospective cohort study interim analysis assessed 2-dose RZV vaccine effectiveness (VE) in patients with SLE or MS, and severe SLE flare risk. Materials and Methods. Adults aged 18+ years with MS or SLE were identified within 7 insurers databases between 2018 or 2021-2023. In the analyses for determining VE, adults completing the 2-dose RZV series were matched 1:4 against unvaccinated controls, and patients with HZ one year prior to vaccination were excluded. The parameter for determining VE was the first episode of HZ ≥31 days after the administration of the second dose of RZV. For safety analyses, adults with SLE receiving RZV dose 1 or 2 were separately matched 1:4 to unvaccinated patients, excluding those with severe SLE flare 90 days prior to index. Safety outcome was the presence or absence of flare ≤90 days after index. Adjusted hazard ratios (HR) and VE were estimated using weighted Cox models to balance confounders. Results. Vaccinated patients had more immunosuppressive use and fewer comorbidities, emergency department visits and hospitalisations before weighting. VE cohorts included 1,308 and 6,025 commercially insured RZV-vaccinated patients with SLE and MS, respectively, and 2,284 and 8,705 Medicare patients. RZV 2-dose VE (95% confidence interval [CI]) in commercially insured patients was 54% (18-74) and 81% (70-88) in SLE and MS, respectively, and 70% (50-82) and 64% (51-74) in Medicare patients. SLE safety cohorts comprised 2,775 commercially insured patients receiving 4,196 RZV doses and 4,227 Medicare patients receiving 6,602 RZV doses. HR (95% CI) of severe SLE flare was 0.94 (0.72-1.24) in commercially insured patients, and 0.91 (0.75-1.11) in Medicare patients. Conclusions. RZV 2-dose VE ranged from 54-81% and RZV was not associated with severe SLE flare. These data justify efforts to increase RZV vaccination among patients with SLE and MS.
PO:17:252 | The choice between belimumab and anifrolumab: analysis of a monocentric cohort
Background. Belimumab (BEL) and Anifrolumab (ANI) are currently the only biologic drugs authorized for the treatment of Systemic Lupus Erythematosus (SLE). The aim of the study is to analyze the factors associated with the therapeutic choice between BEL and ANI in a monocentric cohort of patients affected by SLE. Materials and Methods. We conducted a prospective observational study on consecutively enrolled patients affected by SLE and treated with BEL or ANI starting from June 2022, the date when the compassionate use of ANI began. Clinical, clinimetric, serological, and therapeutic data (prednisone, previous and concomitant therapy) were collected. Univariate analysis was performed using the chi-square or Fisher’s test for categorical variables and the Mann-Whitney or Student’s t test for continuous variables; for multivariate analysis, logistic regression models were created selecting variables with p<0.05. Results. The study included 22 patients treated with ANI (21 women, 95.5%) and 39 with BEL (35 women, 89.7%). The demographic, clinical, and therapeutic characteristics of the two groups at baseline are reported in the table, together with the results of the univariate analysis. In multivariate analysis, the use of ANI was preferentially associated with a chronic-active disease course (OR 17.8; 95% CI 3.5-91.7; p<0.001) and with active cutaneous manifestations (OR 9.9; 95% CI 1.5-66.5; p<0.017). In particular, the sub-analysis of cutaneous involvement showed an association between the preferential use of ANI compared with BEL in patients with subacute lupus (OR 12.7; 95% CI 2.0-79.4; p<0.006) and alopecia with lupus hair (OR 6.2; 95% CI 1.7-22.0; p<0.005). The use of BEL was significantly associated with a relapsing-remitting disease course (OR 10.7; 95% CI 2.3-50.1; p=0.002) and with the presence of active arthritis (OR 5.3; 95% CI 1.2-23.0; p<0.002). In particular, the sub-analysis of articular involvement showed a preferential association between the use of BEL and the subtype of non-deforming and non-erosive arthritis (OR 6.5; 95% CI 1.8-23.8; p<0.004). Although univariate analysis showed more active serology, with anti-DNA positivity (p=0.015) and complement consumption (p=0.061), in patients treated with BEL, these differences were not significant in multivariate analysis. No significant differences emerged between the two groups in terms of corticosteroid dose and concomitant use of hydroxychloroquine (HCQ). However, a greater number of patients treated with ANI were taking methotrexate, in relation to the predominant cutaneous involvement. Conclusions. The choice of biologic drug in patients with active SLE currently appears to be mainly guided by the clinical phenotype, in line with evidence from registration trials. Real-life studies and the development of predictive biomarkers of response to specific biologic drugs will allow for better personalization of therapy within the framework of precision medicine.
PO:17:253 | Unveiling the gap: a multicenter study on factors driving patient-physician discrepancies in assessing disease activity in systemic lupus erythematosus
Methods. Systemic lupus erythematosus (SLE) involves flares and remissions. This study explores discrepancies between physicians’ and patients’ reported disease activity and aims to identify key influencing factors. Methods. Data from SLE patients monitored consecutively between March and July 2024 at two Lupus Clinics were collected. Disease activity was assessed using a 0–3 visual analog scale for both Patient and Physician Global Assessment (PGA, PhGA). Results. The study included 280 adult SLE patients(92.5% women, 93% Caucasian). The median age at enrollment was 46 years(IQR 37–58), with a median age at diagnosis of 29 years(IQR 20–38.5). The median follow-up duration was 169 months(IQR 107–296). Twenty-nine percent had primary schooling, 36% completed high school, and 30% held a university degree. Most patients were employed, 10% students, 11% unemployed, 17% retired. Over the course of disease, ACLE was observed in 50% of patients, SCLE in 9% and 22% had CCLE. Mucosal, tumid, or hypertrophic SLE occurred in 1% of cases. Ulcers were present in 29% of patients, nonscarring alopecia in 24%, arthritis in 55%, pleuritis in 9% and pericarditis in 16%. Renal involvement occurred in 37% of patients(biopsy-confirmed glomerulonephritis class III/IV in 23% and class II/V in 10%). Neurological manifestations affected 9% of patients, hemolytic anemia 10%, leukopenia/lymphopenia 60% and thrombocytopenia 22%. Concomitant conditions included antiphospholipid syndrome(10%), overlap connectivitis(6%), fibromyalgia(11%) and depressive syndrome(14%). The last median SLEDAI was 2 (IQR 0–2) and the median SLEDAS was 0.37 (IQR 0.37–1.5). Steroid therapy was used by 45% of patients, DMARDs by 94%, biologic drugs by 22% and antidepressants/anxiolytics by 32%. The median SLICC Damage Index was 0 (range 0–8). The median PGA and PhGA scores were 0.58 and 0: 82% of patients achieved SLEDAS Low Disease Activity, while remission criteria were met by 73% (DORIS) and 77.5% (SLEDAS). PGA and PhGA showed strong concordance(p<0.001, Figure 1), yet scores differed by >0.5 points in 52% of cases, with PGA generally higher(PhGA exceeded PGA in only 8 patients). Certain factors significantly influenced PGA, PhGA or both (Table 1). An increase in PGA is also associated with corticosteroids (p = 0.040), higher daily steroids dose (p=0.004), methotrexate (p = 0.020), biologics (p = 0.001), antidepressants (p = 0.003), older age (p=0.002), elevated SLEDAS (p=0.028) and higher PSD scores (p<0.001), while an increase in PhGA is linked to the use of methotrexate (p = 0.025), azathioprine (p = 0.011) and biologics (p < 0.001). Better quality-of-life scores were linked to lower PGA (p<0.001). Conclusions. Contrary to existing literature, this study found concordance between patients’ and physicians’ assessments of SLE activity, likely due to the high remission rates and specialized care in Lupus Clinics. Nevertheless factors such as skin involvement, hemolytic anemia, steroid use, depression, fibromyalgia, and lower education were associated with higher scores, while renal involvement, employment, and higher education correlated with lower scores.
PO:17:254 | Systemic lupus erythematosus with pulmonary involvement: clinical insights from an Albanian cohort
Background. Systemic Lupus Erythematosus (SLE) is a chronic autoimmune disease that can significantly affect the lungs leading to irreversible damage, resulting in reduced life quality and varied mortality rates. It can impact all parts of the lung although respiratory symptoms display later. Despite the high frequency, lung involvement in SLE remains understudied. Objectives. To evaluate the extent of pulmonary involvement in SLE patients and identify factors associated with its occurrence and severity. Materials and Methods. A retrospective cohort study from January 2024 to January 2025 was conducted at our hospital, including SLE patients >18 years old, fulfilling the ACR and/or SLICC diagnostic criteria. Data regarding demographics, disease, pulmonary involvement, and laboratory markers were extracted from the hospital records. R software version 4.2 was used to carry out statistical analysis. Results. 45 SLE patients were included; 44.4% (n = 20) were aged 41 years and older, 93.4% (n = 42) females. Around 17.7% had Kidney Disease (KD), 11.1% had hypertension, 4.4% had diabetes and 2.2% had hypothyroidism and deep vein thrombosis. Pulmonary involvement was present in 22 (48.8%) SLE patients, in the form of pleural effusion (45.5%), interstitial lung disease (13.6%), lupus pneumonitis (13.6%), pleuritic (13.6%), pulmonary embolism (9.3%) and pulmonary hemorrhage (4.5%). The most frequent respiratory symptoms reported by SLE patients were: dyspnea (25%), chest pain (20%), and cough (20%) while fever (16.7%), palpitation (13.8%), and hemoptysis (4.5%) were less frequent. KD and hypertension were significantly associated with pulmonary involvement; (χ2=3.307, p=0.026) and (χ2=7.762, p=0.02), respectively. Even the seropositivity for ANA, anti-DNA (ds), and low C4 were significantly associated with pulmonary involvement, (χ2=3.237, p=0.021), (χ2=4.672, p=0.023) and (χ2=8.2467, p=0.01), respectively. Conclusions. More than one-fifth of SLE patients develop pulmonary complications with pleural effusion being the most common manifestation. Dyspnea, chest pain, and cough are the most frequent respiratory symptoms reported in these patients. KD, hypertension, seropositivity for ANA and anti-DNA (ds) with low C4 were significantly associated with lung involvement. This study provides valuable insights into factors linked to pulmonary involvement in SLE further contributing to a better understanding of this complex autoimmune disease toward proactive management to improve patient outcomes.
PO:17:255 | Efficacy and safety of voclosporin in the management of lupus nephritis: a case series
Background. Voclosporin (VOC) is a new drug approved for treating and managing lupus nephritis (LN) in patients with Systemic Lupus Erythematosus (SLE), according to EULAR recommendations. The aim of this study is to describe a case series of patients with long-standing SLE treated with VOC for active LN, refractory to multiple therapies, and persistent proteinuria. Materials and Methods. Demographic, clinical, histological, therapeutic and comorbidity data were recorded for patients with SLE (2019 EULAR/ACR criteria) treated with VOC, who were followed at our Lupus Clinic in collaboration with Nephrologists. A descriptive analysis of the cases was conducted. Results. Characteristics of 3 patients (2F, 1M), with a mean disease duration of 22.33±12.01 years at enrolment, are reported in the Table and Figures. Case 1 (F, 74 years old): patient with 34-year history of SLE with renal, articular, cutaneous and pulmonary involvement. In 2024, she developed nephrotic syndrome (proteinuria: 5 g/day). A renal biopsy was performed, revealing a class V LN. She was treated with mycophenolate mofetil (MM) 2 g/day and ramipril 5 mg/day with little benefit (proteinuria: 2.58 g/day after 6 months). Following discussion of the case with Nephrologists, she began therapy with VOC, leading to a rapid reduction in proteinuria (0.6 g/day after 1 month and 0.22 g/day after 6 months) and achievement of remission according to DORIS criteria (REM). Despite good subjective tolerance, the patient experienced an increase in serum creatinine (from 0.6 to 1.0 mg/dl) with a GFR of 58 ml/min, which required refinement of antihypertensive therapy. Case 2 (F, 57 years old): SLE onset with nephrotic syndrome in 2014; in 2021 she presented with a relapse, and renal biopsy showed mesangioproliferative LN (Class II). She started treatment with belimumab, suspended after 3 months due to intolerance (fever, arthralgia, and general malaise). She was then started on VOC, with a subsequent reduction in proteinuria in 4 months (from 0.95 to 0.38 g/day) and achievement of REM. The patient reported hypertrichosis on the upper limbs. Case 3 (M, 54 years old): patient with LN with a relapsing-remitting course (renal biopsy in 2001: class IV LN; in 2008: class IIIA; in 2020: class II). He was treated with cyclophosphamide, azathioprine and glucocorticoids. Due to persistent proteinuria, he started MM but showed worsening values (2,59 g/day), for which he started VOC (a biopsy was not performed due to a nephrological contraindication): in 4 months proteinuria decreased from 2.44 to 0.38 g/day, and REM was achieved. Nevertheless, serum creatinine increased and hypertension worsened, therefore amlodipine was added. Conclusions. Despite the brief clinical follow-up, VOC has proven effective in reducing proteinuria and glucocorticoid doses in patients with multi-refractory LN. However, adverse effects have emerged, thus close clinical-laboratory monitoring is considered necessary.
PO:18:271 | Managing concomitant sle and psoriasis: the role of anifrolumab in a clinical case
Background. Systemic Lupus Erythematosus (SLE) is a chronic systemic autoimmune disease characterized by the interaction of genetic, environmental, and immunological factors. The type I interferon (IFN-I) pathway, particularly IFN-alpha, represents a central element in its pathogenesis. IFN-I is produced by pDCs and other cells in response to exposure to immune complexes containing DNA or RNA, and it promotes the activation and differentiation of B and T cells, the maturation of DCs, and the expression of pro-inflammatory cytokines. Anifrolumab is a human monoclonal antibody that binds to the type I interferon receptor (IFNAR1), inhibiting the activity of all type I interferons. Interferons, particularly IFN-gamma and type I IFN, also play a crucial role in the pathogenesis of psoriasis: pDCs can be activated by nucleic acids released from damaged keratinocytes or by immune complexes, producing IFN and contributing to the inflammation. Methods and Results. A 57-year-old woman presented with a diagnosis of inverse psoriasis and undifferentiated connective tissue disease, previously treated with Hydroxychloroquine (discontinued due to an allergic reaction) and then with Methotrexate and Cyclosporine. Laboratory tests showed ANA positivity (1/640 speckled pattern), anti-dsDNA and anti-SSA/Ro60 positivity, ESR 44 mm/h, CRP 18.1 mg/L. On physical examination, she presented with erythematous, desquamative, and infiltrated lesions in the intergluteal fold, buttocks, submammary and retroauricular regions, alopecia and a malar rash. A diagnosis of Systemic Lupus Erythematosus was made, and initially treatment with Cyclosporine 300 mg/day was maintained. One year later, blood tests showed an increase in ESR and CRP, mild anemia, and 24-hour proteinuria of 884 mg/24h. The patient also presented with a painful swelling of the right sternoclavicular joint, and ultrasound documented inflammatory involvement (consistent with Tietze's syndrome). Cyclosporine therapy was suspended, and treatment with Methotrexate and Prednisone was initiated. One month later, at the follow-up visit, tests showed a reduction in proteinuria (168 mg/24h) and inflammatory markers, as well as the resolution of the sternoclavicular swelling, so prednisone taper was started. At subsequent follow-ups, the patient showed clinical stability in laboratory tests; however, a strong psoriatic component persisted with erythema in the submammary, inguinal, retroauricular, elbow, intergluteal fold, and left calf regions. An erythematous lesion also appeared on the V of the chest. Therefore, after screening to initiate biotechnological drug therapy, treatment with Anifrolumab 300 mg/month was scheduled. Conclusions. Type I interferon is a common pathogenetic driver in both SLE and psoriasis. Anifrolumab, by blocking the type I IFN receptor, has demonstrated clear efficacy in SLE, reducing disease activity and improving clinical outcomes. Its targeted action on the IFN-I pathway suggests a potential benefit for psoriasis as well, by acting on a shared inflammatory mechanism. The introduction of Anifrolumab in this patient could offer a potential benefit for both conditions.
PO:18:276 | Use of anifrolumab in the treatment of difficult-to-treat manifestations in systemic lupus erythematosus
Background and Objective. To describe our experience with the use of anifrolumab (AFM) in a small single-center cohort of patients (pts) with systemic lupus erythematosus (SLE), with particular focus on the management of refractory manifestations. SLE is a systemic autoimmune disease that can affect virtually any organ or system. Refractory manifestations represent an unmet need in disease management, as they are associated with higher glucocorticoid (GC) exposure, increased risk of cumulative organ damage, and reduced quality of life (QoL). Type I interferons (IFN-I) play a key role in antiviral defense; however, in SLE patients, IFN-I signaling pathways are upregulated both in genetic predisposition and in epigenetic changes characteristic of the disease, contributing to disease onset and activity. Several clinical and laboratory features of SLE—including lymphopenia—are associated with the overexpression of IFN-I–regulated genes, providing a strong rationale for targeting this pathway. Anifrolumab, a monoclonal antibody that inhibits the type I interferon receptor, offers new therapeutic perspectives in this setting. Materials and Methods. We report on 5 female SLE patients aged 35–64 years, followed from September 2024 to the present. Four pts presented with cutaneous involvement: acute cutaneous lupus (n=2), subacute cutaneous lupus (SCLE)(n=1), and discoid lupus with scarring alopecia (DLE) (n=1). One pt exhibited predominant constitutional (persistent remittent fever up to 39.5°C for ~1 year, fatigue) and hematologic involvement (leukopenia–lymphopenia). These manifestations prompted initiation of AFM therapy. Previous manifestations (currently in remission) included articular (3 pts), serosal (pleural effusion, 1 pt), and renal involvement (class III glomerulonephritis, 1 pt). At the time of our observation, pts (previously followed in other Centers) were receiving hydroxychloroquine (except the pt with constitutional/hematologic involvement, due to intolerance) and GCs (except the pt with DLE, who had discontinued GCs due to lack of efficacy on cutaneous disease). Three of the five pts had a remote history of traditional immunosuppressant use. Anti-dsDNA antibodies were present in 3 pts, and C4 was reduced in 4 pts. Results. Treatment with AFM led to improvement in all cutaneous manifestations, with complete remission in two cases, after only a few months of therapy. A marked clinical benefit was also observed in the DLE case, a notoriously refractory manifestation (CLASI score improved from 17 [T0] to 8 [T5]). The pt with persistent fever and leukopenia–lymphopenia—also typically refractory—experienced rapid resolution of symptoms and improvement in fatigue (SLEDAI decreased from 6 [T0] to 2 [T2]). All pts were able to taper GCs, with complete withdrawal achieved in two pts with cutaneous disease. Conclusions. Our findings confirm the efficacy of AFM, as previously demonstrated in clinical trials, across selected SLE disease domains. They highlight the potential to extend precision medicine principles to SLE management and to consider AFM as a valuable therapeutic option for difficult-to-treat manifestations.
PO:18:277 | Clinical case report of the management of a patient suffering from systemic lupus erythematosus and associated polyneuropathy
Background. The aim of this presentation is to show how a girl with systemic lupus erythematosus (SLE) was diagnosed with a rare complication, how her treatment was chosen based on her characteristics as a SLE patient with associated peripheral nervous system complications, and how her condition was successfully treated without causing any long-term effects. Methods. Clinical findings during the visit electromyography and nerve conduction tests for diagnosis blood test examinations to monitor the patient's condition The patient was visited several times with examinations and tests scheduled after diagnosis and their follow-up to monitor the effectiveness of therapy and to observe any clinical improvements indicating resolution of the complication and remission of the clinic related to SLE. Results. After the therapy and as a result of improvements attributable to the correct choice and management of the therapy, there was a remission of her pathology, a resolution of complications, and it was possible to reduce the dosage of the corticosteroid Conclusions. The management of SLE could be very difficult and related to a correct clinical approach in the first steps of the visits to know exactly the various complications associated to disease and to make the best choices of therapy for the patient
PO:19:281 | Mitochondrial dysfunction in Still’s disease: a preliminary analysis of mtDNA copy number and TFAM expression
Background. Still’s disease (SD) is hypothesized to arise from the interaction between environmental and genetic factors that trigger an inappropriate activation of the innate immune system, leading to excessive production of proinflammatory cytokines. Oxidative stress—one of the main sources of DNA damage—plays a crucial role in several inflammatory disorders. Mitochondrial DNA (mtDNA) is particularly vulnerable to oxidative injury caused by reactive oxygen species (ROS), which are physiologically generated during mitochondrial respiration. The mitochondrial DNA copy number (mtDNA-CN) serves as a biomarker of mitochondrial function, and its maintenance depends on several nuclear-encoded genes, including the mitochondrial transcription factor A (TFAM). However, the role of oxidative stress and mitochondrial dysfunction in AOSD remains poorly understood. Objective: To compare mtDNA-CN and TFAM gene expression in patients with SD and healthy controls (CTRLs). Materials and Methods: Peripheral blood samples were collected for DNA and RNA extraction. mtDNA-CN and TFAM mRNA expression levels were quantified using quantitative PCR (qPCR). Statistical comparisons between groups were performed using ANOVA tests. Results: A total of 27 patients fulfilling Yamaguchi criteria for AOSD and 35 healthy CTRLs were enrolled. SD patients showed a significantly lower mtDNA-CN compared with CTRLs (p = 0.006). Conversely, TFAM mRNA expression was significantly higher in SD patients than in CTRLs (p = 0.02). A negative correlation between.....
PO:19:283 | Hospitalization profile and complications in patients with adult-onset Still’s disease: results from a retrospective study of 74 cases
Background. Adult-onset Still’s disease (AOSD) is a rare systemic inflammatory disorder that may follow a severe course with potentially life-threatening complications. The aim of this study was to describe hospitalization patterns and major complications in a retrospective cohort of patients with AOSD. Materials and Methods. A retrospective study was conducted on patients with AOSD followed between January 2009 and May 2025 at a single tertiary center. Demographic, clinical, and laboratory data at disease onset were collected, along with information on hospitalizations (number, duration, causes, and timing) and therapies administered during admission. The incidence of macrophage activation syndrome (MAS), its temporal relationship with disease onset, and the treatments employed were also evaluated. Data were analyzed descriptively using medians, interquartile ranges (IQR), and absolute frequencies. Results. Seventy-four patients were included (median age at onset 35 years, IQR 25–47; 50% female), with a median follow-up of 54 months (IQR 31–147). Forty patients (54%) experienced a single hospitalization, and 20 (27%) had two or more. Forty-six patients (62%) were hospitalized at disease onset, among whom 9 presented with MAS. Of those with MAS, 3 (33%) had a second hospitalization within 3 years. Among patients hospitalized at onset, the median length of stay was 21.2 days (IQR 14.8–27.5), and treatment included glucocorticoids (98%), anakinra (22%), and cyclosporine A (15%). During follow-up, 26 additional hospitalizations were recorded at a median of 29 months after diagnosis (IQR 1.5–88). The main causes of hospitalization were AOSD relapse (n=16, 62%; associated with MAS in 6 cases), infections (n=5, 19%), cardiovascular events (n=3, 12%), and neurological events (n=3, 11.5%). Relapses occurred while patients were receiving systemic corticosteroids at a median prednisone dose of 20 mg (IQR 7.2–37.5); 8 patients were on anakinra and 12 on methotrexate. Management included corticosteroid escalation in all cases, initiation of anakinra in 6 patients, and cyclosporine A in 4. Infectious complications included 2 upper respiratory tract infections, 4 pneumonias, 3 urinary tract infections, 1 E. coli urosepsis, 1 HBV hepatitis, 1 Granulicatella adiacens bacteremia, and 1 varicella-zoster virus reactivation. At the time of infection, patients were receiving a median of 1 mg prednisone (IQR 0–10.5); 2 were on anakinra, 4 on cyclosporine A, 2 on methotrexate, and 1 on canakinumab. Conclusions. AOSD is frequently associated with hospitalization, particularly at disease onset, with a substantial proportion of patients experiencing multiple admissions. MAS and infections are the most common—and potentially late—complications. Structured monitoring and careful adjustment of immunosuppressive therapy are essential to minimize relapses and reduce complications.
PO:19:286 | Genetic testing reveals an unexpected case of mevalonate kinase deficiency in a 37-year-old patient with AA renal amyloidosis and good response to colchicine
Mevalonate kinase deficiency (MKD) is a rare genetic autoinflammatory disease usually diagnosed in pediatric age. Case presentation. A 37-year-old male, born in Pakistan from consanguineous parents was first evaluated in March 2024 at the Nephrology Unit, where he was admitted for abdominal pain, peripheral and periorbital edema. Scrotal edema, peritoneal and pleural effusions were observed. Laboratory tests revealed: nephrotic syndrome (24h proteinuria max 12.4 g/day, albumin 1.8 g/dL); mild renal impairment (creatinine 1.5 mg/dL); hypogammaglobulinemia (IgG 1.37 g/L); raised levels of CRP (19 mg/L, normal value <5) and serum amyloid A (SAA; 286 mg/L, normal value <8). ANA, antiENA, antidsDNA, antiPLA2R, anti-phospholipid antibodies, cryoglobulins, C3, C4, serum and urine immunofixation, serum IgA were negative or in normal range. Renal biopsy showed amyloidosis (with glomerular, arteriolar and interstitial involvement) positively stained for AA. He reported hospital admission at the age of 2 with no clear diagnosis. Since infancy to 2007, he experienced periodic fever with abdominal pain, occurring approximately once a month and lasting 2-3 days. In the suspect of familial Mediterranean fever (FMF), colchicine was started (1 mg/day) and next generation sequencing (NGS) analysis of genes potentially linked to periodic fever was performed. Moreover, treatment with furosemide, canrenone, ramipril, statin, ezetimibe, dapaglifozin and warfarin (for catheter-associated deep vein thrombosis) was started. Two months after discharge, clinical condition improved (no more edema nor abdominal pain); SAA normalized; proteinuria decreased to 7 g/day. A clinical diagnosis of FMF was confirmed (Tel-Hashomer and Eurofever/Printo criteria). During the follow-up, due to creatinine and liver enzymes increase, a treatment adjustment was necessary, including colchicine reduction (0.5 mg/day). This resulted in an improvement of renal and hepatic function but a slight elevation of SAA. Proteinuria progressively decreased (3 g/24h). Soon after, the NGS result became available, demonstrating a homozygous variant (N205D; likely pathogenic according to ACMG standard) of the MVK gene. Canakinumab (150 mg/4 weeks) was started in November with initial good response. Conclusions. In the here presented case, clinical features and response to colchicine treatment initially led to clinical diagnosis of FMF but, unexpectedly, NGS revealed MVK gene mutation. Few cases of MKD presenting with AA amyloidosis in adult patients were so far described (1), but none of them responded to colchicine therapy. This case highlights the usefulness of genetic testing even in apparently well-defined cases, contributing to a better understanding of a rare disease such as MKD. References: 1 Rodrigues F, et al., Semin Arthritis Rheum. 2020 Dec;50(6):1370-1373.
PO:19:287 | Cardiac involvement in Still’s disease: a challenge in differential diagnosis
Background. To present and discuss a case of Still’s disease (SD) with significant cardiopulmonary involvement, underlining the importance of a comprehensive and multidisciplinary approach in achieving an accurate differential diagnosis. Materials and Methods. A 34-year-old man, previously healthy, presented with persistent high fever and pharyngodynia, followed by an evanescent erythematous rash, hepatosplenomegaly, polyarthralgia, and diffuse myalgia. Laboratory findings revealed elevated inflammatory markers (ESR 117 mm/h, CRP 143 mg/L) and hyperferritinemia (550 ng/mL). After exclusion of infectious, neoplastic, and autoimmune disorders, the diagnosis of SD was established (Yamaguchi’s criteria). Treatment with methylprednisolone (16 mg/day) led to only partial clinical improvement, while fever and arthromyalgic symptoms persisted. Upon admission to our unit, the patient started anakinra (100 mg subcutaneously daily). Within a few days, he developed urticarial lesions and cough. Suspecting an adverse reaction, Anakinra was discontinued and glucocorticoid increased. Despite withdrawal of the drug, clinical symptoms persisted and were soon associated with nocturia and exertional dyspnea. The patient was admitted to the emergency department, where a chest X-ray revealed increased bronchovascular markings, a congestive pattern, and blunting of the costophrenic angles. Chest high-resolution CT (HRCT) demonstrated bilateral pleural effusions and patchy ground-glass opacities. Transthoracic echocardiography showed reduced left ventricular ejection fraction (30–35%) and a moderate pericardial effusion without hemodynamic compromise. Cardiac cine-MRI confirmed pericardial effusion with myocardial wall thickening, in the absence of late gadolinium enhancement (LGE) within a non-ischemic dilated cardiomyopathy with hyopokinesia. The patient was transferred to the Cardiology Department, where, after thoracentesis, was treated for heath failure with dapaglifozin, dsacubritil/valsartan, furosemide. During hospitalization, he finally disclosed habitual cocaine use, previously omitted. Results. The initial clinical and imaging findings suggested a flare of SD with cardiac and pulmonary involvement. However, second-level imaging and the subsequently revealed toxicological history indicated the possibility of chronic myocardial damage related to cocaine abuse. The unrecognized substance use acted as a major confounding factor in differentiating between SD relapse and cocaine-induced cardiomyopathy. Conclusions. This case underscores the crucial importance of accurate and detailed anamnesis, including a systematic toxicological assessment, to avoid diagnostic errors. A multidisciplinary approach integrating rheumatology, cardiology, and radiology expertise is essential for distinguishing between disease activity and drug-induced organ damage in patients with systemic inflammatory disorders such as SD.
PO:20:002 | Respiratory function tests predict bone mineral density in autoimmune rheumatic disease patients
Background. Several studies suggest that pulmonary function, especially in terms of vital capacity (VC), forced vital capacity (FVC) and forced expiratory volume in the first second (FEV1), directly correlate with physical activity and in particular with the 6-minute walk test (6MWT). In this perspective pulmonary function may be associated with bone health. Moreover, this relationship between lung function and bone might be exacerbated in AIDs patients who develop interstitial lung disease or require glucocorticoid therapy. High-resolution peripheral quantitative computed tomography (HRpQCT) is a sensitive technique to measure bone mass and microarchitecture in humans. We therefore sought to investigate the relationship between lung function test and bone mineral density in patients with autoimmune rheumatic diseases. Methods. Patients affected by autoimmune rheumatic diseases were recruited from January to April 2025. Demographic data regarding age, gender, BMI, smoking habits, steroidal treatment, menopausal state, history of fracture and rheumatic disease were collected. HR-pQCT bone data from the distal radius and the tibia and pulmonary function test results were recorded. Pearson correlation test were performed between pulmonary function tests and HR-pQCT parameters of radius and tibia Results. 28 patients affected by AIDs were enrolled: 3 (10,71%) with rheumatoid arthritis, 9 (32,14%) with systemic lupus erythematosus, 15 (53,57%) with scleroderma and 1 (3,57%) with idiopathic inflammatory myopathy. 11(39,29 %) patients were male with an average age of 47,64±13,77 years and an average BMI 25,22 ± 11,29 kg/m2 . Among the patients, 14 (50%) had a history of smoking, 7 (29,17%) received glucocorticoid treatment and 8 (34.78%) had a history of fracture. Nine patients (32,14%) had confirmed interstitial lung disease. All the parameters calculated by HRpQCT in radius and tibia showed to positively correlate with the parameters of pulmonary function test [Table 1 and Table 2]. In particular the stronger association were between vital capacity, forced vital capacity and total lung capacity and the geometrical parameters of HRpQCT (total area, cortical perimeter, cortical area, trabecular area). Only the residual volume correlated inversely with the cortical BMD in both radius and tibia. Apparently, correlations were more frequent in radius than tibia. Conclusion. This study suggests that impairment of pulmonary function is associated with bone loss in patients with autoimmune rheumatic diseases. Since pulmonary function is a major determinant for physical activity, its impact on bone loss is conceivable. To confirm these results a larger population with autoimmune rheumatic diseases is required to assess the interaction between lung function and bone health.
PO:20:003 | Romosozumab effect on neutrophil-to-lymphocyte ratio in post-menopausal women at high risk of fracture
Background. Romosozumab (ROMO) is a monoclonal antibody targeting sclerostin (SOST), a key regulator of bone metabolism. It has been demonstrated that changes in SOST levels can affect distinct niches within the bone marrow that support hematopoiesis. To date, no clinical studies have explored the changes in complete blood count (CBC) parameters in patients receiving ROMO. The objective of of the present study was to investigate the effects of Romosozumab on CBC parameters in post-menopausal women at high risk of fracture. Methods. We conducted a 12-month prospective observational study in post-menopausal women with severe osteoporosis treated with ROMO 210 mg/monthly during one year between October 2023 an April 2025. CBC values were assessed at baseline, 6 and 12 months. Inclusion criteria were: - Treatment with romosozumab as deemed necessary by the treating physician Exclusion criteria were: - Exposure to bisphosphonates within 12 months from romosozumab initiation - Prior treatment with other anti-osteoporosis medications - No diagnosis of anemia or lymphoma or leukemia - No active bleeding or recipients of plasma, red blood cells derivates and platelets in the last 12 months Absolute changes in CBC were assessed with a mixed model for repeated measures. Results. A total of 113 post-menopausal women (mean age of 73.4±9.7 years) were included. Neutrophils levels slightly decreased over time, with a significant decrease at 6 months (p=0.022), that was not sustained at 12 months (p=0.500). Haemoglobin and lymphocytes levels showed no significant differences over the period of the study. In the overall trend across time points, there was a statistically significant decrease in the neutrophil-to-lymphocyte ratio (NLR) over the 12 months (2.0 ± 1.1 at baseline, 1.8 ± 1.1 at month 6, and 1.8 ± 1.2 at month 12; p=0.034), with a small effect size (Cohen’s = 0.22). Figure 1 shows the NLR over the 12 month study period. Conclusion. In post-menopausal women with severe osteoporosis, 12 months of ROMO treatment was associated with a statistically significant reduction in NLR, reflecting a potential modulation of systemic inflammation, though the clinical relevance of this modest shift remains uncertain and warrants further investigation.
PO:20:004 | Increase in serum Dkk1 levels attenuates the anabolic response to romosozumab in postmenopausal osteoporosis
Background. Romosozumab is a monoclonal antibody against sclerostin that initially exhibits potent anabolic effects in treating osteoporosis. However, its efficacy diminishes after 6 months, with bone formation markers declining despite continued therapy. We hypothesized that increased levels of Dickkopf-1 (Dkk1), a Wnt pathway inhibitor, may contribute to this attenuation by suppressing osteoblast activity. Methods. We conducted a 12-month prospective observational study on post-menopausal osteoporosis naïve to anti-osteoporosis treatment, treated with romosozumab. Serum levels of Dkk1, Procollagen Type I N-Terminal Propeptide (P1NP), C-terminal telopeptide of type I collagen (CTX), and sclerostin were measured at baseline (M0) and at 3 (M3), 6 (M6), and 12 months (M12). Bone mineral density (BMD) at the lumbar spine, femoral neck, and total hip was assessed at M0, M6, and M12. Associations between Dkk1 and P1NP were analyzed using linear mixed-effects models. Results. Fifty-nine post-menopausal women were included in the study. Dkk1 levels increased significantly from 38.9 pmol/L at M0 to 44.2 pmol/L at M12 (p 0.003). P1NP increased from 89.4 ng/mL at M0 to 115.4 ng/mL at M3 (p 0.004) but decreased to 61.5 ng/mL by M12 (p 0.001). CTX decreased significantly throughout the study (p 0.001). BMD increased significantly at all sites by M12 (lumbar spine +13.8%, femoral neck +6.3%, total hip +4.7%; all p 0.01). An inverse association was found between Dkk1 increase and P1NP decrease between M3 and M12 (estimate -0.909; p 0.032). We also found a steep increase in sclerostin serum levels as soon as M3 (from 36.3 pmol/L, SD 15.6, to around 1500 pmol/L at all time points, p 0.001). This increase can probably be attributed to the sequestration of sclerostin from the bone to the bloodstream by romosozumab. Serum marker changes (least square changes from marginal means of the MMRM) are shown in Figure 1. Conclusion. Romosozumab treatment is associated with a significant rise in Dkk1 levels, which correlates with a decrease in bone formation markers over time. Dkk1 may attenuate the anabolic effects of romosozumab by inhibiting Wnt signaling.
PO:20:005 | Sarcopenia and fracture risk in rheumatoid arthritis: correlation between SACR-F and fragility score measured by radiofrequency echographic multi-spectrometry
Background. To evaluate the effectiveness of the Fragility Score (FS), measured by Radiofrequency Echographic Multi-Spectrometry (REMS), in predicting fracture risk and its correlation with the risk of sarcopenia in patients with rheumatoid arthritis (RA). Materials and methods. We examined a population of patients aged >50 years diagnosed with RA according to the 2010 ACR/EULAR criteria. All subjects underwent bone assessment using both REMS and DXA. The SARC-F questionnaire was administered and fracture risk was calculated using the DEFRA and FRAX algorithms. Correlations between FS, DEFRA, FRAX, and SARC-F were determined using Pearson’s correlation coefficient and its confidence interval (P<0.05). Results. A total of 67 patients were enrolled, with a mean age of 66.94 ± 9.66 years; 60 were female (89.55%) and 7 male (10.45%). Mean DXA T-scores were: lumbar spine –1.73 ± 1.17 and femoral neck –1.99 ± 0.77; mean REMS T-scores were: lumbar spine –2.05 ± 0.90 and femoral neck –2.11 ± 0.79. Mean FRAX values were: hip fracture 11.33 ± 12.16 and major osteoporotic fractures 24.64 ± 16.07; DEFRA (in females) 42.98 ± 29.27; FS lumbar spine 43.89 ± 20.21; FS femur 41.57 ± 21.40; SARC-F 1.69 ± 1.59. A strong correlation was observed between the Fragility Score of both the lumbar spine and femur with the DEFRA and FRAX (for both major and hip fractures) fracture risk algorithms, with P-values <0.0001 for all correlations. A moderate correlation was found between SARC-F and bone structure quality assessed by the Fragility Score at the lumbar spine (r = 0.44, P<0.0001) and femur (r = 0.42650, P = 0.0002). Moreover, SARC-F showed a moderate correlation with fracture risk estimates obtained from DEFRA (r = 0.47390, P<0.0001), FRAX hip fracture (r = 0.39578, P = 0.0007), and FRAX major fractures (r = 0.37185, P = 0.0016). Conclusions. REMS provides the qualitative parameter FS, which enables prediction of 5-year fracture risk. In our study, FS correlated significantly with both FRAX and DEFRA. Having a tool that allows for shorter-term prediction of fragility fractures, compared to algorithms based on DXA, appears to be of fundamental importance for optimal management of patients with RA. Our findings also reveal a correlation between sarcopenia risk, as assessed by the SARC-F screening questionnaire, and fracture risk estimated by FRAX®, DEFRA, and FS. Therefore, sarcopenia should be considered by clinicians in the management of RA patients, as it represents an additional factor contributing to increased fragility fracture risk.
PO:20:010 | Coordinated outpatient pathway for osteoporosis: a new organizational model for osteoporosis management
Background. Osteoporosis requires a prompt diagnostic and therapeutic pathway to prevent fragility fractures. This study aimed to compare time required to complete the work-up and patient satisfaction levels between traditional outpatient model and a coordinated pathway. Materials and Methods: A retrospective study was conducted on 120 patients attending a dedicated setting. 55 patients were enrolled in coordinated pathway including specialist consultation, laboratory tests, vertebral morphometry, DEXA scan, and nutritional assessment. The remaining 65 followed a traditional diagnostic process with separate access to each service. Data were collected on waiting times for instrumental and laboratory tests, total time to complete the work-up, and perceived satisfaction (VAS scale 0–10). Statistical analyses were performed using independent t-tests and ANOVA. Results: The mean time to complete the diagnostic process was shorter in the coordinated pathway compared to the traditional group (7.8±1.3 days vs. 48.7±18.8 days;p < 0.01). Satisfaction scores were higher in the coordinated group (mean VAS 9.1/10vs7.2/10; p < 0.001). No significant differences were found in age, BMI, or comorbidities, confirming sample homogeneity. Discussion. Implementing a coordinated pathway for osteoporosis management reduces times and enhances patient satisfaction. This structured approach could serve as a replicable model for other chronic diseases.
PO:20:011 | Suspected tumor-induced osteomalacia in a patient with polymyalgia rheumatica and persistent hyperphosphaturic hypophosphatemia
Background. To describe the case of a patient with polymyalgia rheumatica (PMR) and suboptimal response to steroid therapy with the incidental finding of hyperphosphaturic hypophosphatemia, suspected for tumor-induced osteomalacia (TIO), to highlight the importance of a multidisciplinary approach and targeted diagnostic laboratory and instrumental workup. Materials and Methods. Male patient, 76 years old, with a functionally single kidney following nephrectomy of an ectopic kidney at age 33, medical history of arterial hypertension, dyslipidemia, OSAS, subcritical stenosis of the supraaortic trunks, and polyglobulia (JAK2 mutation negative, endogenous EPO within normal limits); on chronic therapy with NSAIDs as needed, antihypertensives, ASA 100 mg/day, statins, and benzodiazepines for anxiety-depressive syndrome. Symptom onset approximately 3 months prior with arthralgias of the shoulder and pelvic girdles, prolonged morning stiffness >2 h, functional limitation, and elevation of inflammatory markers. Underwent initial treatment with prednisone 37.5 mg/day with tapering as indicated by the general practitioner. Subsequent relapse upon discontinuation and therefore referred for urgent rheumatology evaluation with reintroduction of PDN 18.75 mg/day and slow tapering and initiation of antiresorptive therapy with risedronate, calcium, and vitamin D supplementation. Results. At 3-month rheumatology follow-up visit, reported recurrence of arthralgias and morning stiffness upon reduction of prednisone below 7.5 mg/day. Laboratory tests revealed CRP 2.1 mg/dL; serum calcium 9.9 mg/dL; serum phosphorus 2.0 mg/dL (normal range 2.7-5.1); serum magnesium 2.1 mg/dL; spot urine phosphorus 49.9 mg/dL; plasma creatinine 1.01 mg/dL; TmPO4/GFR 1.42 mg/dL (normal range >2.7). Given suspicion of TIO, intact and C-terminal FGF23 assays were requested, with values resulting inappropriately normal in relation to serum phosphorus levels. Systematic monitoring of serum phosphorus was concurrently initiated, with IV supplementation of fructose-1,6-diphosphate and oral potassium phosphate as needed, and introduction of calcitriol up to 0.5 µg/day. Gallium-DOTAPEPTIDE PET/CT extended to the appendicular skeleton was also requested, with results not yet available at the time of publication. Conclusions. Tumor-induced osteomalacia represents a rare cause of renal hyperphosphaturia and severe hypophosphatemia, frequently masked by nonspecific musculoskeletal symptoms in elderly patients; this case highlights the need to integrate clinical suspicion of PMR with complete biochemical investigations, including serum phosphate and TmPO4/GFR calculation, and to employ advanced imaging techniques for localization of FGF23-secreting neoplasms, in order to promptly direct the patient toward specific surgical or medical therapy and improve functional and metabolic outcome. Currently, burosumab, a recombinant human monoclonal antibody (IgG1) directed against FGF23, is approved in both children and adults for the treatment of FGF23-related hypophosphatemia secondary to phosphaturic mesenchymal tumors that cannot be curatively resected or localized.
PO:20:012 | Inflammatory markers and nutritional status in patients with osteoporotic fractures: preliminary analysis of a pilot study
Background. Chronic inflammation and malnutrition are emerging risk factors for bone fragility. This pilot study was designed to examine associations between inflammatory markers (ESR, CRP), nutritional status (albumin, total proteins), and metabolic parameters in patients with fragility fractures compared to non-fractured subjects. Materials and Methods. We enrolled 120 consecutive patients (12 men, 108 women), including 40 with fragility fractures. Data were collected on ESR, CRP, albumin, total proteins, liver, and hormonal profiles. Fractures were categorized as vertebral, femoral, and other sites. Non-parametric tests were used; significance was set at p<0.05. Results. Fracture patients had lower body weight (62±6 vs. 66±11 kg; p=0.017) and higher ESR and CRP (ESR 24±22 vs. 14±8; p=0.007; CRP 3.9±3 vs. 2.6±2.4; p=0.046). Vertebral fractures showed higher inflammation (ESR 25±21; CRP 4.5±3) and increased platelets (p=0.026). Other fractures had elevated CRP (4.9±2.7; p=0.016), liver enzymes (GammaGT 27.6±25; p=0.004), and calcitonin (1.8±1.5; p<0.001), with reduced albumin (4.1±0.3; p=0.04) and total proteins (6.2±0.67; p=0.013). Discussion. Systemic inflammation is associated with fragility fractures, especially vertebral. Fractures at other sites show nutritional and metabolic alterations, suggesting different mechanisms. These findings support multidimensional risk assessment and further studies in larger cohorts.
PO:20:014 | Post-partum osteoporosis: severe clinical presentation in absence of known risk factors
Background. Post-partum osteoporosis is a rare and under-recognized secondary osteoporosis that can manifest with multiple vertebral fractures in young women during the peripartum period. Early diagnosis and timely therapy improves outcomes. Materials and Methods. A 34-year-old woman in satisfactory health, without known osteoporosis risk factors, developed worsening low back pain two months after delivery during exclusive breastfeeding. Symptoms worsened, leading to bedridden status and functional impairment. A spine X-ray revealed L1 vertebral fracture; one month later, L4 fracture was detected. MRI confirmed recent L1, L2 and L4 fractures. DEXA scan showed severe osteoporosis with a lumbar T-score of -3.5 and a femoral of -2. Treatment with teriparatide 20 µg/day and cholecalciferol supplementation was started. Clinical and laboratory follow-up at 6 and 12 months were performed. Results. After 6 months, the patient reported clinical improvement with complete pain control, no new fractures, and resumption of physical activity. Laboratory tests were normal. Vitamin D was 27.6 ng/mL, PTH 64.4 pg/mL. At 12 months, bone density improved, and no further fractures occurred. Conclusions. This case underlines the importance of suspecting postpartum osteoporosis in persistent peripartum low back pain and demonstrates that early anabolic therapy with teriparatide can lead to rapid clinical and functional recovery, preventing further fractures.
PO:21:019 | Clinical phenotypes in IgG4-related disease: ACR/EULAR classification and practical limitations
Background. IgG4-related disease (IgG4-RD) is a rare, immune-mediated fibroinflammatory condition that can affect virtually any organ. Traditional diagnostic criteria (Umehara et al.) include clinical/radiological evidence of organ involvement, elevated serum IgG4, and specific histopathology. However, serum IgG4 elevation is inconsistent, and biopsy is not always feasible. The 2019 ACR/EULAR classification criteria introduced a point-based system (threshold ≥20) to improve disease classification. Materials and Methods. We retrospectively reviewed the clinical data of patients suspected to have IgG4-RD, which is defined by typical organ involvement, elevated serum IgG4 levels, and the exclusion of alternative diagnoses. Each patient was scored using ACR/EULAR criteria and assessed per diagnostic standards. Patients were grouped into four clinical phenotypes (head and neck, retroperitoneal/aortitis, systemic, pancreatobiliary) as described by Lanzillotta et al. Statistical analysis was performed using RStudio. Results. A total of 46 patients were included: 17 head and neck, 16 retroperitoneal/aortitis, 7 systemic, and 6 pancreatobiliary. Mean age was 57.9 years; 58.7% were male. The systemic phenotype showed the highest number of involved sites (mean 2.1). Serum IgG4 levels did not significantly differ among groups. Biopsy rates varied: 100% in systemic, 93.8% in head and neck, 83.3% in pancreatobiliary, and 31.2% in retroperitoneal/aortitis (p < 0.001). Definitive diagnosis was most frequent in systemic (85.7%), while retroperitoneal/aortitis was more often categorized as possible diagnosis (62.5%). Two patients (4.3%) failed to meet either diagnostic or classification criteria. All systemic cases scored ≥20 points. In the head and neck group, three scored below threshold, one of whom was not biopsied. Among retroperitoneal/aortitis patients, 66% scored <20, and none had undergone biopsy. One non-biopsied pancreatobiliary case also failed to meet the score threshold. Conclusions. The ACR/EULAR criteria improve classification of suspected IgG4-RD by incorporating clinical parameters. However, histopathology remains essential for accurate diagnosis and inclusion in clinical trials, especially in retroperitoneal/aortitis and head and neck phenotypes. Most non-biopsied retroperitoneal/aortitis cases did not meet classification thresholds. Histological evaluation supports more precise diagnosis in head and neck cases. Conclusions for other phenotypes are limited by small sample sizes, though biopsy was commonly performed.
PO:21:021 | The eyes tell the story: a clinical case of Rosah syndrome
Background. ROSAH syndrome is a rare autoinflammatory disease with autosomal dominant inheritance caused by gain-of-function missense mutations in the ALPK1 gene on chromosome 4. This leads to hyperactivation of the NF-κB signaling pathway and chronic cytokine-mediated inflammation (IL-1, IL-6, and TNF-alpha). ROSAH is an acronym for the following clinical findings: retinal dystrophy, optic nerve edema, splenomegaly, anhidrosis, and headache. Reports have documented approximately 70 cases since the first description in 2012. Materials and Methods. We describe the case of a 22-year-old woman who presented in 2021 with bilateral progressive visual loss, dyschromatopsia, frontal headache, and severe fatigue. Ophthalmologic examination revealed bilateral papilledema, vitreous inflammation, macular edema, retinal dystrophy, retinal vascular inflammation, and neurodegeneration of outer retinal layers. Neuroimaging was unremarkable, but lumbar puncture showed elevated opening pressure (27 mmHg). Splenomegaly (13 cm) was detected on abdominal ultrasound. Laboratory tests are reported in the Table. An initial diagnosis of atypical systemic lupus erythematosus (SLE) was made, and high-dose corticosteroids were started (pulsed methylprednisolone followed by tapering oral prednisone). Additional treatments included low-dose aspirin (100 mg/day) and acetazolamide (1250 mg/day). The patient was treated subsequently with steroid-sparing drugs: azathioprine (2 mg/kg/day) and hydroxychloroquine (200 mg/day) later switched to mycophenolate mofetil (3 g/day), and then rituximab (1 g every two weeks, 2 doses). These treatments improved visual acuity and vitreous inflammation but had a limited effect on papilledema and retinal dystrophy. For these conditions, corticosteroids were the only effective treatment. In 2023, the patient was referred to our center: attempts to taper corticosteroids and acetazolamide resulted in the recurrence of headaches and ocular symptoms, along with worsening macular edema. Additionally, she exhibited hypohidrosis. Clinical reassessment revealed that her father had progressive blindness and severe papilledema secondary to hypertensive hydrocephalus. Results. Given these findings, the patient underwent molecular genetic testing (next-generation sequencing (NGS) panel for autoinflammatory diseases). A heterozygous missense pathogenic variant in ALPK1 (c.710C>T; p.Thr237Met) was identified, confirming the diagnosis of ROSAH syndrome. In December 2024, treatment with tocilizumab (8 mg/kg every 4 weeks) was started. After 4 months, the patient showed significant improvement in papilledema and complete recovery of visual acuity along with resolution of systemic symptoms, despite continued tapering of prednisone (7.5 mg/day) and acetazolamide (750 mg/day). Conclusions. ROSAH syndrome is an emerging autoinflammatory disorder with limited documented cases. This report highlights its diagnostic complexity and therapeutic challenges. Tocilizumab, an anti-IL-6 receptor antibody, appears to be a well-tolerated and effective treatment, especially for ocular manifestations. Further studies are needed to better understand the pathogenesis and to establish standardized treatment protocols.
PO:21:028 | A difficult case of VEXAS syndrome: management of myelodysplastic syndrome associated with systemic inflammation and infectious complications
Background. This work describes a clinical case of VEXAS syndrome associated with myelodysplastic neoplasm, aiming to highlight the clinical and diagnostic features and the importance of a multidisciplinary approach to optimize treatment and improve the patient's prognosis. Materials and Methods. A 57-year-old male, with a medical history of type 2 diabetes and hypertension, presented between March and June 2024 with marked fatigue, migratory arthralgia in the lower limbs, subcutaneous nodules, an episode of left ear chondritis, and a 20 kg weight loss over 6 months, without fever or apparent infections. Laboratory findings included macrocytic anemia (Hb 6.8 g/dL, MCV 108 fl), without hemolysis, leukocytopenia (WBC 2270/mm³, PMN 1170/mm³), hyperferritinemia (842 µg/L), CRP 111 mg/L, and polyclonal hypergammaglobulinemia. Autoimmune markers (ANA, ENA, ANCA) and HCV/HBV serology were negative. CT scans of the head, chest, and abdomen (August 2024) revealed hepatosplenomegaly. In September, the patient developed a fever with chills, further weight loss, and petechiae at the base of all limbs. PET-CT showed increased lymph node, splenic, and skeletal uptake, while bone marrow biopsy identified myelodysplastic syndrome of the RAEB II subtype, with high IPSS and R-IPSS scores. Microscopic examination noted cytoplasmic vacuoles in granulocytes and blasts. VEXAS syndrome was confirmed by genetic testing identifying a mutation in the UBA1 gene (c.121A>G p.(Met41Val)). The treatment regimen included corticosteroids (methylprednisolone 1 mg/kg/day), with azacitidine as a bridge to transplant. Results. During follow-up, the patient showed a satisfactory clinical and laboratory response to steroid and antineoplastic drugs, with normalization of inflammatory markers, blood count, and regression of clinical manifestations. In January 2025, he was hospitalized for influenza A pneumonia during neutropenia and treated with antivirals, antibiotics, and corticosteroids. The steroid dose was tapered to 10 mg/day of prednisone, maintaining satisfactory clinical and laboratory control. A follow-up chest CT (3 months later) revealed persistent fibrotic changes and ground-glass opacities, consistent with an inflammatory pattern related to the syndrome. Azacitidine therapy resulted in partial remission, and the option of allogeneic stem cell transplantation was contemplated owing to the patient's youth and the poor prognosis linked to myelodysplasia. Conclusions. This case underscores the importance of early recognition of VEXAS syndrome, a rare autoinflammatory disorder that combines systemic inflammatory and hematological manifestations. Genetic diagnosis is essential for confirming the diagnosis and guiding treatment. A multidisciplinary approach, involving immunosuppressive therapy and consideration of allogeneic stem cell transplantation, is the most promising strategy to improve patient’s prognosis. Close clinical and radiological monitoring is crucial to manage infectious and inflammatory complications, optimizing the therapeutic choice and the patient's quality of life.
PO:22:029 | Impact of mepolizumab on idiopathic hypereosinophilic syndromes: analysis of a monocentric retrospective cohort
Background. Idiopathic hypereosinophilic syndromes (iHES) are characterized by persistent eosinophilia and eosinophil-mediated organ damage. Mepolizumab, an anti-interleukin-5 monoclonal antibody, has proven effective in reducing eosinophilic burden, controlling clinical manifestations, and decreasing the reliance on glucocorticoids (GCs). This study aims to evaluate the clinical and steroid-sparing efficacy of mepolizumab in a monocentric retrospective cohort of patients with iHES. Methods We enrolled patients with iHES, diagnosed at our Center according to the 2023 diagnostic criteria for HES (1), and treated with mepolizumab. Variables were analyzed immediately before mepolizumab initiation (t0) and at 1 (t1), 3 (t3), 6 (t6), 12 (t12), 18 (t18), and 24 (t24) months after treatment, using Wilcoxon test for paired data (significance: p < 0.05). Results. Eight patients were enrolled [M 50%, F 50%; median diagnostic delay: 6 (2-18) months]. Clinical features at onset are reported in Figure 1, Table 1. At iHES onset, median eosinophil count (EC) was 6,375 (4,570-12,282) cells/µl, 1 patient showed eosinophilia and 7 patients hypereosinophilia. The median time from diagnosis to mepolizumab initiation was 3 (0-14) months, with a median follow-up of 21 (5-24) months. Seven patients had received GCs before mepolizumab and were still on steroid therapy at the time of initiation. Furthermore, patient 2 had been treated with cyclosporine A for lichenified trunk eczema. At t0, 2 patients showed eosinophilia and 3 hypereosinophilia. A marked decrease in EC was observed as early as t1 [median t0: 980 (895-439) cells/µl; median t1: 116 (82-147) cells/µl; p: 0.0078], which was maintained at the last available follow-up [median at last follow-up: 70 (40-352) cells/µl; p: 0.0234]. At t6, 2 patients showed a significant rebound in ECs. In patient 1, hypereosinophilia persisted from t6 onward, and both GCs and dupilumab were introduced at t18. Patient 6 was hospitalized at t6 and later died from septic shock (notably, with a history of substance abuse) (Figure 1, Graphic 1). Overall, the median percentage reduction in EC was 90 (80-93) % (p: 0.0006). During follow-up, GCs were discontinued in 5 patients and later reintroduced in 3 cases due to iHES relapses. The comparison of GC daily dose at t0 and at the last available follow-up showed a significant reduction [median at t0: 50 (3-50) mg/day; median at last follow-up: 0 (0-5) mg/day; p: 0.0234]. The median number of iHES relapses before [1 (1-2)] and after [0 (0-1)] mepolizumab initiation showed a trend toward statistical significance, although not reaching it (p: 0.0655). Conclusions. Preliminary findings from our cohort suggest that mepolizumab may be effective in achieving clinical control and reducing GC dependence in patients with iHES. References: (1) Valent P, et al. Proposed refined diagnostic criteria and classification of eosinophil disorders and related syndromes. Allergy. 2023 Jan;78(1):47-59
PO:22:033 | Unraveling VEXAS syndrome: when skin manifestations and monoclonal gammopathy precede hematological myeloid alterations
Background. VEXAS (Vacuoles, Enzyme E1, X-linked, Autoinflammatory, Somatic) syndrome is a rare adult disease caused by somatic mutations in the UBA1 gene within hematopoietic stem cells (1). These mutations compromise the ubiquitin-activating E1 enzyme and lead to a heterogeneous clinical presentation that includes autoinflammatory signs—such as fever and skin involvement in 80% of cases, primarily manifesting as neutrophilic dermatosis, chondritis, and serositis—as well as hematological alterations in myeloid lineage cells, including macrocytic anemia, myelodysplastic syndrome, and stem cell vacuolization in the bone marrow (1, 2). Case report: P.L., is a 80 years old man who developed fever, weight loss, fatigue, and urticarioid rash in the lower limbs and dorsum: exams showed an increase of inflammation markers (CRP 250 mg/L, ferritin 2,500 ng/mL) and a newly discovered seric IgG-lambda monoclonal component (MC), while complete blood count, LDH, autoimmunity, and liver and kidney function were within the normal range; the first skin biopsy suggested eczema. Steroid therapy was started, with a temporary benefit that was lost during tapering. Three months later the patient developed pericarditis and started colchicine. Total-body CT and PET scans ruled out possible occult malignancies. Given the need of prolonged steroid therapy to control the symptoms and the new MC, a bone marrow biopsy (BMB) was performed (no signs of disease) alongside a new skin biopsy, positive for neutrophilic dermatosis. The patient started dapsone, but there was no improvement. After a rheumatologic consult, according to Strasburg criteria (chronic urticaria, MC, high inflammation markers) (4), the patient was diagnosed with Schnitzler syndrome (SchS) and started anakinra. Eventually, given the lack of improvement and the development of injection-site reactions, therapy switched to canakinumab with partial improvement. The patient then developed macrocytic anemia. Considering the failure of IL1 block, the atypical MC (IgG instead of IgM), pericarditis, and the recent onset of anemia, suspecting VEXAS syndrome, the UBA1 gene was analyzed, showing a p.Met41Thr mutation. VEXAS was confirmed. Conclusions. This case highlights how VEXAS syndrome must be taken into consideration in elder male patients with unexplained inflammatory and cutaneous manifestations, even when no typical vacuolization in the bone marrow(1-3), nor myeloid anomalies at the complete blood count (a characteristic feature described in almost every case report) can be seen and are, instead, preceded by clonal lymphoid anomalies (MC). VEXAS, therefore, can be considered a monoclonal gammopathy of clinical significace, even though it has not been officially included among them yet. Early recognition of UBA1 mutation is pivotal in order to timely diagnose and properly manage the disease. Lastly, the inefficacy of anakinra and the developement of injection-site reactions may give a diagnostic clue towards VEXAS. (2,3).
PO:22:039 | A rare form of interstitial lung disease: granulomatous and lymphocytic interstitial lung disease
Background. In August 2024, a 48-year-old man presented to the emergency department with worsening dyspnea and oxygen desaturation. His medical history was remarkable only for IgA deficiency, but he reported recurrent episodes of pneumonia over the previous two months, treated with multiple antibiotics without improvement. He was admitted to the Department of Pulmonology at our hospital because his chest X-ray showed pulmonary infiltrates, his inflammatory markers were high, and he needed oxygen therapy. Chest CT performed during hospitalization showed diffuse nodular consolidations and ground-glass opacities predominantly in the middle and lower pulmonary lobes bilaterally. Autoimmune screening (ANA, ENA, ANCA, RF, anti-CCP, and myositis blot), serum precipitins, and microbiological tests (blood cultures, galactomannan, β-D-glucan, CMV DNA, and Borrelia serology) were all negative. Rheumatologic evaluation revealed no signs or symptoms suggestive of connective tissue disease. During hospitalization, treatment with iv methylprednisolone 80 mg led to oxygen therapy withdrawal and improvement of pulmonary consolidations on chest CT. The patient was discharged with a diagnosis of organizing pneumonia and prescribed prednisone 50 mg daily with gradual tapering. In January 2025, a new pulmonary consolidation was observed on CT scan. To further clarify the clinical picture, the patient underwent bronchoalveolar lavage (showing 50% lymphocytes, 30% macrophages) and transbronchial biopsy. Histopathological examination revealed foci of organizing pneumonia, lymphocytic inflammation, and nonnecrotizing granulomas, findings suggestive of Granulomatous and Lymphocytic Interstitial Lung Disease (GLILD). The case was discussed at the multidisciplinary interstitial lung disease meeting (including radiologists, pulmonologists, pathologists, rheumatologists), where a diagnosis of GLILD secondary to IgA deficiency was confirmed. The patient began treatment with Rituximab 1000 mg, which was given twice, two weeks apart. At follow-up, the patient reported sustained clinical well-being and had resumed his work activities. Discussion. GLILD is a rare interstitial lung disease secondary to common variable immunodeficiency or selective IgA or IgG deficiency. The onset is often acute, presenting with cough and dyspnea, although asymptomatic cases have been described. According to literature data, high-resolution chest CT is the first-line imaging modality, typically showing peribronchovascular pulmonary nodules, ground-glass opacities, and reticulations in the lower lobes. Lung biopsy is the gold standard for diagnosis, usually revealing peribronchial lymphocytic infiltrates, non-necrotizing granulomas, follicular bronchiolitis, and foci of organizing pneumonia. Treatment generally consists of corticosteroids, while rituximab is indicated in refractory cases. There is no clear evidence supporting the efficacy of intravenous immunoglobulin replacement therapy in GLILD. Conclusions. GLILD is a rare autoimmune-associated interstitial lung disease with no established treatment guidelines. Therefore, a multidisciplinary approach is crucial for accurate diagnosis and optimal therapy.
PO:23:044 | Understanding fatigue through patients' eyes: development of a novel questionnaire capturing the complexity of real-life fatigue in Sjögren's disease
Background. Fatigue is one of the most frequent and impactful symptoms for patients with Sjögren's Disease (SjD), and one of the most challenging to measure. There are no PROs fully capturing fatigue as experienced by patients in their daily lives. The purpose of this study was to define a new PRO for assessing fatigue and its impact on the quality of life of patients with SjD, based on lived experiences and their own definitions of fatigue. Materials and Methods. A 15-item questionnaire was developed to capture different types of fatigue in SjD, based on a patient-authored essay published online. Items were formulated using patient-derived language and refined through expert review. Content validity was confirmed via CVI. A pilot phase with cognitive debriefing and patient feedback assessed clarity and relevance. Preliminary psychometric testing evaluated internal consistency. Items cover 15 distinct types of fatigue: basic fatigue, rebound fatigue, sudden fatigue, weather-related fatigue, molten lead phenomenon, tired-wired, flare-related fatigue, fatigue related to other physical causes, fatigue-related concentration impairment, stress/distress/anxiety/depression-related fatigue (SDAD), not sleeping well fatigue, normal aging fatigue, chronic illness fatigue, fatigue from trying to keep up with family and friends without a chronic illness, doctor fatigue. Results. 90 consecutive patients (female 93.4%) fulfilling SjD ACR/EULAR 2016 criteria, mean age 57.1 years (range 21–82), completed the questionnaire. The most frequently reported types of fatigue were SDAD (88.9%), basic (86.7%), and rebound (86.7%), while the least reported was weather-related (60%). The SDAD had the highest impact on quality of life (mean impact score 82.8%). Males more frequently reported SDAD (100%), doctor fatigue (100%), and not sleeping well (83.4%), while females reported rebound (89.3%), basic (88.1%), and SDAD (88.1%). Younger and older patients reported basic fatigue more frequently (85.7% and 100%, respectively), compared to middle-aged groups, reporting SDAD (36–59 years: 92.1%; 60–70 years: 87.5%). Rebound was the only type correlating with disease duration (r=0.22, p0.03). SDAD did not significantly correlate with ESSPRI, whereas strong correlations were observed between ESSPRI and other types of fatigue, particularly basic (r=0.54, p< 0.0001) and rebound (r=0.50, p< 0.0001). Certain types of fatigue strongly correlated with each other, such as basic and rebound (r=0.90, p< 0.0001), or specifically with other symptoms, such as flare-related and VAS global pain (r=0.41, p< 0.0001). No correlations were observed with ESSDAI or laboratory parameters, except for the molten lead phenomenon with CRP (r=0.55, p = 0.007). Conclusions. This novel SjD fatigue questionnaire captures aspects of real-life fatigue previously underrepresented in existing PROs and reveals heterogeneity in patient experiences. These differences underscore the importance of a fatigue-based patient profiling. Ongoing efforts focus on validating the questionnaire, stratifying patients based on fatigue, and establishing its role as an outcome measure.
PO:23:046 | Histopathological comparison between minor salivary gland biopsies from pediatric and adult patients with Sjögren’s disease: evidence of a more severe inflammatory profile in early-onset cases
Background. Pediatric-onset Sjögren’s disease (pSjD) presents distinct clinical and serological features compared with the adult form (SjD). While adults more frequently exhibit sicca symptoms such as xerophthalmia and xerostomia, parotid swelling and cutaneous involvement are the most common clinical manifestations in pSjD. From a serological perspective, pediatric patients less frequently test positive for ANA and anti-SSA/SSB antibodies but tend to show higher levels of rheumatoid factor (RF). The aim of this study was to compare the histopathological characteristics of minor salivary gland (MSG) biopsies between pediatric and adult patients with SjD. Materials and Methods. The study included 18 consecutive patients with pSjD followed at an Italian pediatric rheumatology center and 54 consecutively evaluated adult SjD patients from an adult rheumatology unit. All biopsy samples were examined by an expert pathologist at each site according to the EULAR recommendations for standardized histopathological assessment of minor salivary gland biopsies. Results. The surface area of biopsy specimens did not differ significantly between the two groups (p = 0.551). Pediatric patients displayed significantly higher focus scores (p = 0.0227) and a greater prevalence of ectopic germinal centers, as evidenced by increased CD21 (52.94% vs. 16.22%, p = 0.005) and Bcl6 expression (47.06% vs. 8.11%, p = 0.0011). Lymphoepithelial lesions were also more frequent in the pediatric cohort (55.56% vs. 18.92%, p = 0.0065), as was fibrosis (66.67% vs. 29.73%, p = 0.031). No significant differences were observed for glandular atrophy (p = 0.687) or ductal dilation (p = 0.128). When stratified by disease onset relative to menarche, prepubertal-onset patients exhibited a higher frequency of germinal centers and lymphoepithelial lesions than those with postpubertal-onset disease (p < 0.05). Conclusions. This study represents the first direct histopathological comparison of minor salivary gland biopsies between pediatric and adult patients with Sjögren’s disease. The findings confirm a more pronounced inflammatory pattern in pediatric patients, consistent with the higher clinical activity observed in this population. In particular, the increased frequency of ectopic germinal centers and lymphoepithelial lesions in prepubertal-onset cases suggests the possible involvement of age-dependent immunopathogenic mechanisms underlying early-onset pSjD. These results reinforce the pivotal role of minor salivary gland biopsy not only in diagnosis but also in disease prognostication, emphasizing the importance of early recognition and close clinical monitoring in pediatric patients.
PO:23:051 | Quantitative high-resolution computed tomography analysis in Sjögren’s disease-associated interstitial lung disease: CALIPER-derived imaging biomarkers for prognostic assessment
Background. Interstitial Lung Disease (ILD) is a frequent manifestation of Sjögren’s Disease (SjD), associated with significant morbidity and mortality. However, data on the prevalence of progressive-ILD in SjD remain scarce, and biomarkers for predicting progression are lacking. Computer-Aided Lung Informatics for Pathology Evaluation and Rating (CALIPER) is a validated CT-based software that quantifies ILD patterns such as ground-glass opacities, reticulation, honeycombing, and low attenuation areas. CALIPER-derived parameters correlate with pulmonary function tests (PFT) and outcomes in IPF and other autoimmune ILDs, but their role in SjD-ILD is unexplored. Our aim was to assess the prognostic value of CALIPER-derived parameters in SjD-ILD patients Materials and Methods. SjD patients (2016 ACR/EULAR criteria) with HRCT-confirmed ILD followed from Jan-2018 to Sep-2023 were retrospectively included if >/=1 HRCT was suitable for CALIPER analysis. Clinical, laboratory and PFT data were collected at baseline and follow-up. Progressive-fibrosing ILD (PF-ILD) was defined (ATS criteria) by >/=2 of: worsening symptoms, FVC decline >/=5% or DLCO >/=10%, or radiological progression within 1 year. CALIPER-derived ILD% (sum of ground-glass, reticular, honeycombing) and VRS% (vascular-related structures) were calculated. Visual ILD extent (Warrick score) and pattern were assessed by a thoracic radiologist Results. Twenty-three patients (F:M=18:5, mean age 66.2±9.5 yrs, mean follow-up 6.1±5 yrs) were enrolled. ILD patterns included NSIP (n=14), UIP (n=6), and NSIP+OP (n=3). Dyspnea and cough occurred in 21 and 19 patients respectively. Median baseline FVC and DLCO were 83% and 64%. Seventeen patients received immunosuppressants; none received antifibrotics. Seven required long-term oxygen (LTO2) and 7 developed PF-ILD. Baseline ILD% and VRS% demonstrated a moderate-strong correlation with FCV% and DLCO%, visual ILD quantification (Warrick score) and between them (table 1). VRS%, Reticulation%, and Honeycombing% were significantly higher in UIP (p=.021, .038, .047 respectively). On univariate regression analysis, VRS% (OR 3.2, 95%CI 1.1-9.1, p=.03) and ILD% (OR 1.13, 95%CI 1.01-1.3, p=.05) were associated with LTO2. According to ROC analysis, VRS% had an AUC of 0.813 (p=.019) with an optimal cut-off of 3.8% yielding a sensitivity of 71.4% and a specificity of 87.5% in predicting LTO2. ILD% had an AUC of 0.777 (p=.038) with a cut-off of 11.6% resulting in a 71.4% sensitivity and a 75% specificity in predicting LTO2. On univariate analysis VRS% (OR 2.8, 95%CI 1-8, p=.05) was associated with a PF-ILD behavior in the next year, with an AUC of 0.85 (p=.023) and an optimal cut-off of 3.8% resulting in a 83.3% sensitivity and 80% specificity. Conclusions. CALIPER-derived parameters correlate strongly with lung function and predict adverse outcomes in SjD-ILD. Automated HRCT analysis offers promising digital biomarkers for ILD assessment and risk stratification. Integrating these metrics with clinical and functional data could support early identification of progressive-ILD and guide therapy. Further validation in larger cohorts is warranted.
PO:23:052 | Muscular and myocardial involvement in antisynthetase syndrome: a retrospective real-life study
Background. Antisynthetase syndrome (ASS) is a systemic autoimmune disease characterized by anti-aminoacyl-tRNA synthetase antibodies positivity and clinically manifested by interstitial lung disease (ILD), myositis, and arthritis. This retrospective real-life study, evaluates longitudinal changes in clinical and laboratory markers, as well as corticosteroid therapy, in muscular and myocardial involvement of ASS during the first two years after referral to our center. Materials and Methods. We retrospectively studied 39 patients with ASS at baseline (first evaluation at our centre) and at 12 and 24 months of follow-up. Myositis and myocardial involvement were assessed, and the following parameters were recorded: CRP(mg/L), ESR(mm/h), CPK(U/L), aldolase(U/L), Troponin T(mg/L), NT-proBNP(pg/mL), and ejection fraction(%EF). Corticosteroids and immunosuppressants were also evaluated. Predictors of steroid suspension at 12 and 24 months were evaluated. Results. In our cohort, 79% were females, median age 63 (52-70) years, median disease duration 7 (3-7.5) years. 64% were positive for anti-Jo1 antibodies. 32 (82%) patients had IIM-ILD, 26 patients (67%) had myositis, 12 (31%) had myocardial involvement. Baseline features are summarized in Table 1. Modifications in immunosuppressive therapies over time in Figure 1. Among patients with myositis, CRP levels declined at 12 months (p=0.042), and stabilized at month 24 (p=0.092). ESR levels significantly decreased at both timepoints (p=0.021, p=0.021); CPK levels dropped at both 12 and 24 months; aldolase levels remained stable (see Table 2). The % of patients on oral corticosteroids decreased from 96% at baseline, to 73% at 12 months (p=0.077) and 62% at 24 months (p=0.016), with a significant dose reduction in both timepoints (p<0.001, p=0.027). In addition, the % of patients receiving corticosteroid boluses significantly dropped from 27% at baseline, to 4% at 12 months and 0% at 24 months (p=0.002). Among patients with myocardial involvement, 9 (75%) presented with myocarditis at baseline, 4 (44%) requiring hospitalization. Troponine T and NT-proBNP declined at both timepoints (see Table 2). %Ejection Fraction assessed by echocardiography improved at both timepoints (p=0.025, p=0.001). The % of patients receiving corticosteroid pulses decreased at 12 (p=0.063) and 24 months (p=0.031). At logistic regression analysis, the positivity for anti-Ro52 antibodies was the only factor negatively associated with steroid response at 12 months (OR 0.196, 95% CI 0.043–0.899), whereas no predictor of steroid suspension at 24 months was identified. Conclusions. In our cohort, a progressive improvement in muscular biomarkers in patients with myositis, and in cardiac function and laboratory parameters in those with myocardial involvement were observed. Over time, the use of immunosuppressants had a corticosteroid-sparing effect enabling a steroid-free remission in 38% of patients. These findings underscore the importance of a systematic assessment as well as an organ-specific follow-up in antisynthetase syndrome, suggesting that a tight follow up is needed in ASS patients to monitor disease response to treatment.
PO:23:055 | Overlap of systemic sclerosis and Sjögren’s disease: insights from an Italian case-control study
Background. Patients with systemic sclerosis (SSc) may refer sicca symptoms, mainly due to glandular fibrosis but also in the setting of coexisting Sjögren’s disease (SjD)[1,2]. This overlap was first described in 1965[3], but available data on the characteristics of patients with concurrent SSc and SjD remain limited and outdated. Materials and Methods. This case-control study aimed to characterize a large cohort of Italian patients with overlapping SSc and SjD (SSc/SjD), and to identify significant clinical and immunological differences compared to patients with isolated SSc or SjD. METHODS Patients included in the SSc/SjD cohort fulfilled both the 2013 ACR/EULAR classification criteria for SSc[4] and the 2016 ACR/EULAR criteria for SjD[5]. The control groups (1:2 ratio) consisted of patients with a diagnosis of SSc or SjD only, without further rheumatological overlap, consecutively seen between January and December 2024. The clinical data of the studied groups were extracted from the medical records and analysed with appropriate statistical tests using GraphPad Prism v9. Results. A total of 50 patients with SSc/SjD (98% women, mean age ± SD: 67±11 years) were included, compared to 100 patients with SSc alone and 100 patients with SjD alone. Patients with SSc/SjD were significantly older than those with isolated SSc (p<0.01) or SjD (p<0.001) and had a longer disease duration than patients with SSc (p<0.001). In terms of autoimmunity, SSc/SjD patients presented more frequently positive ANA (p<0.01), anti-CENP (p<0.0001), and anti-TopoI (p<0.0001) antibodies than those with SjD alone. Anti-SSA antibodies were more common in SSc/SjD than in SSc (p<0.0001), whereas anti-SSB antibodies were less common in SSc/SjD than in SjD (p<0.0001). Clinical features of the SSc/SjD group are detailed in Table. Sicca symptoms were more prevalent in SSc/SjD compared to SSc (p<0.0001). Interstitial lung disease (ILD) was more frequent in SSc/SjD than in SjD (p<0.0001), and comparable to SSc alone. However, SSc/SjD patients showed lower predicted diffusing capacity for carbon monoxide (DLCO) than both SSc (p=0.02) and SjD (p<0.01) groups. Cutaneous subsets and modified Rodnan skin scores (mRSS) were similar between SSc/SjD and SSc. The occurrence of telangiectasias, Raynaud’s phenomenon, digital ulcers, and osteolysis was comparable between SSc/SjD and SSc, although pitting scars were more frequent in SSc/SjD (p=0.01). The prevalence of pulmonary hypertension, gastrointestinal involvement, and calcinosis was also similar between SSc/SjD and SSc. Corticosteroid use was more common in SSc/SjD compared to SSc (p=0.04), whereas biologic agents use was less frequent in SSc/SjD than in SjD (p<0.05). Finally, fibromyalgia was less common (p<0.0001), and neoplasia occurred more frequently (p=0.02) in SSc/SjD than in SjD. Conclusions. Presence of neoplastic diseases and ILD with low DLCO characterize the SSc/SjD overlap. Therefore, active screening is recommended, as this may affect outcomes and indicate the need for a personalized approach.
PO:24:056 | Major salivary gland ultrasonographic features of lymphoma and high lymphoproliferative risk lesions in Sjögren’s disease: a systematic review
Background. Sjögren's disease (SjD) is burdened by significant lymphoproliferative risk. Up to date there is no established consensus on the salivary gland ultrasonographic (SGUS) features of lymphoma or of high lymphoproliferative risk (HLR) lesions (e.g., LELs, GCs, MESA/LESA). The aim is to systematically review existing literature on SGUS features of SjD patients complicated by SG Lymphoma or HLR lesions. Materials and Methods: a systematic review of existing literature (SLR) (January 1988 – January 2025) was conducted according to PRISMA 2020 guidelines (Prospero registration: CRD420251008467). Results: 15 studies (13 full text articles, 2 international conference abstracts) were included, with a predominantly moderate-low risk of bias (Figure 1). 13/15 described SGUS features of lymphoma, considering 121 total cases. 11/13 described the presence of focal lesions in lymphomas (8/11 quantitatively), identifying 45 focal lesions on 117 cases. These lesions were described with variable features, but commonly presented as a dominant glandular hypo- to anechoic mass on SGUS (Table 1). In 3/11 studies, the parenchyma surrounding the focal lesion was also assessed, with quantitative or inferable SGUS scores indicating moderate to severe involvement in all cases (Table 1). 10/13 studies described a diffuse glandular involvement (presence of SGUS abnormalities) in lymphoma cases (7/10 quantitatively), identifying 32 cases on 105 lymphomas. 4/10 studies quantitatively reported SGUS scores, with moderate-severe involvement in most cases (Table 2). 9/15 studies described HLR lesions, with a total of 161 quantifiable cases. In 4/9 a focal lesion in HLR cases was described, resulting in 11 focal lesions on 16 HLR cases considered, with descriptions and features as heterogeneous as lymphomas. Only 1/4 studies addressed SGUS features of the surrounding parenchyma, reporting a severe grade (Tab.2). 5/9 studies reported a diffuse involvement in the absence of mention of focal lesions in HLR lesions (only 3 quantitatively), identifying 77 cases on 149 HLR lesions. 2/5 of these studies address SGUS scores reporting quantitative measures, more frequently a moderate-severe involvement (Table 2). No prospective studies define SGUS’s role in detecting or predicting lymphoproliferative evolution. Conclusions: the SLR confirms that both major salivary gland lymphoma and HLR lesions in SjD can appear as a dominant focal lesion (mostly hypo-anechoic lesion/mass), or as a diffuse involvement (mostly moderate-severe SGUS scores). SGUS features are described with highly heterogenous methodology and terminology, thus highlighting the necessity of a standardization in the reporting measures.
PO:24:057 | Qualitative and quantitative analysis of nailfold videocapillaroscopy in patients with idiopathic inflammatory myopathies: focus on muscle histology
Background. Idiopathic inflammatory myopathies (IIM) are a group of autoimmune diseases characterized by inflammation of the muscle with clinical manifestations such as skin rash, interstitial lung disease, heart involvement or arthritis. Within IIM, we distinguish dermatomyositis (DM), immune-mediated necrotizing myopathy (IMNM), anti-synthetase syndrome (ASyS), inclusion body myositis (IBM), and Polymyositis (PM). Nailfold video-capillaroscopy (NVC) is a useful technique to study microvascular abnormalities in autoimmune diseases and a scleroderma-like (SL) pattern has been reported in about 70% of DM patients and in 35% of those with ASyS. Histologically, muscular findings are shared across IIM subgroups, such as sarcolemmal expression of MHC I and inflammatory infiltrates. Others are more specific: perifascicular atrophy (PFA) in DM or perifascicular necrosis (PFN) in ASyS. The aim of our study was to evaluate qualitatively and quantitatively the capillaroscopic alterations in IIM patients, for their possible associations with histological data. Materials and Methods. Patients with IIM who underwent muscle biopsy and NVC were prospectively enrolled. Morphological parameters were assessed qualitatively (number, length, distribution, and size of capillary loops, as well as microhemorrhages and neoangiogenesis). We also assigned a semiquantitative score (0–3) and other quantitative scores (total megacapillary count, mean of megacapillaries apex width, mean capillary density, number of hemorrhages, and mean of avascular areas). Results. We enrolled 20 patients including 9 with DM, 4 with ASyS, and 7 with PM. Table 1 presents the main clinical, histological, and capillaroscopic features of our cohort. Regarding capillaroscopic findings, we observed a significant association between the presence of a SL pattern and DM diagnosis (p=0.0098). Comparing the biopsies regardless of the type of idiopathic inflammatory myopathy (IIM), we observed a higher mean semiquantitative score in patients exhibiting perifascicular fiber hypotrophy compared to those without (mean 2, IQR 0–2 vs mean 0, IQR 0–1;p=0.0359), as well as a significant association with the presence of an SL pattern (p=0.0246). This group of patients also showed a marked reduction in capillary density (p=0.0190) and an increased mean number of avascular areas (p=0.0058). ASyS patients displayed a significant association with perifascicular necrosis (p=0.0010), consistent with previous reports, but also with perifascicular fiber hypotrophy (p=0.0260), whereas we did not confirm the described association with DM. Conclusions. To our knowledge, this study is the first to explore the relationship between NVC findings and muscle biopsy features in IIM patients using both qualitative and quantitative methods. Our data suggest a link between perifascicular muscle fiber hypotrophy—where muscle vasculature damage is believed to originate—and specific capillaroscopic abnormalities in DM and ASyS cases. Expanding our understanding of the underlying peripheral vasculopathy in the different forms of IIM requires a larger patient cohort and a deeper histological evaluation of muscular and vascular injury.
PO:24:058 | Serum ferritin as a biomarker in idiopathic inflammatory myopathies with interstitial lung disease: baseline levels and longitudinal trends
Background. Serum ferritin has been proposed as a biomarker of interstitial lung disease (ILD) in anti-MDA5 dermatomyositis (DM), but data on its role in other idiopathic inflammatory myopathies (IIM) with or without ILD are limited. This multicenter retrospective study aimed to evaluate serum ferritin as a specific and sensitive biomarker for IIM-ILD and to assess its correlation with clinical and immunological features, including a subanalysis on longitudinal ferritin changes in anti-MDA5 DM and antisynthetase syndrome (ASS) patients. Materials and Methods. We retrospectively included 139 adult patients with a definite diagnosis of IIM according to 2017 ACR/EULAR criteria, followed at referral centers in Siena, Palermo, Bari (Italy) and Lucknow (India). All had available baseline data on serum ferritin, muscle enzymes, inflammatory markers, lung function and myositis-specific antibodies: patients were grouped by ILD status and clinical phenotype. In a subgroup of 23 ILD patients (11 anti-MDA5 DM, 12 anti-Jo1 ASS), longitudinal data were analysed. Results. We enrolled 139 IIM patients (mean age 44.3±17.75 years), including 70 DM and 50 ASS , with 69 affected by ILD. Baseline ferritin was significantly higher in DM-MDA5 compared to DM-non-MDA5 (p=0.0073) and ASS (p=0.0006), and also differed between patients with and without ILD (p=0.0013) (figure 1). A ferritin cut-off of 303.5 ng/mL effectively excluded MDA5-DM at initial assessment, independently of CPK and CRP, suggesting ferritin’s specificity beyond systemic inflammation. A longitudinal subanalysis of 23 ILD patients (11 anti-MDA5 DM, 12 anti-Jo1 ASS) evaluated ferritin, disease activity, CRP, ESR, at baseline and up to 18 months. Despite ASS patients showing more extensive organ involvement (> 4 domains in 66%), baseline ferritin was higher in DM (median 312 vs 82 ng/mL, p=0.007), whereas CPK was elevated in ASS (median 336 vs 101 U/L, p=0.05). Over follow-up, DM patients demonstrated a progressive ferritin decline at 12 and 18 months (p=0.025 and p=0.017, figure 2), closely mirroring improvements in PhGA (p<0.05). ASS patients showed no significant ferritin changes (figure 2) despite clinical improvement. CRP and ESR fluctuated without consistent trends, limiting their value in monitoring disease activity. Conclusions. These data confirm serum ferritin’s utility as a diagnostic and dynamic biomarker specifically for anti-MDA5 DM-ILD. Its progressive decline may support its use in real-life clinical decisions, while the absence of a similar pattern in ASS highlights pathophysiological heterogeneity and the need for tailored approaches in IIM subtypes. Limitations include the retrospective design, small sample size in the longitudinal analysis, treatment variability, lack of standardized follow-up. Nonetheless, this study provides evidence supporting ferritin’s dual role in identifying and monitoring anti-MDA5 DM-ILD. Prospective studies in larger, diverse cohorts are warranted to validate these findings and potentially integrate ferritin into future disease activity scores.
PO:24:061 | Allodynia is highly prevalent in patients with Sjögren’s disease and correlates with immunobiological disease markers: preliminary results from the sjnapse project
Background. Neurological involvement in Sjögren’s disease (SjD) is frequently underdiagnosed due to the extreme variability and heterogeneity of clinical manifestations, the lack of standardized diagnostic criteria, and the absence of anti-SSA/anti-SSB autoantibodies in a substantial proportion of patients. The SjNAPSE Project (Sjögren’s Neuroinflammation Assessment, Pain, and Symptoms Evaluation) is a prospective, multicenter study designed to investigate neurological involvement in patients with SjD without a previous diagnosis of neuro-Sjögren and in the absence of comorbidities that could account for neurological manifestations. Materials and Methods. A total of 100 patients (95 females, 95%) fulfilling the 2016 ACR/EULAR classification criteria for SjD were consecutively enrolled. All participants completed the following questionnaires: Neuropathic Pain Symptom Inventory (NPSI), Patient Health Questionnaire-9 (PHQ-9), PainDetect Questionnaire (PD-Q), VAS pain, VAS fatigue, and VAS sicca. Sensory assessments for allodynia were performed according to the Leeds Assessment of Neuropathic Symptoms and Signs (LANSS), administered by the same examiner in each participating center. Patients who did not report pain or presented neurological involvement attributable to other known conditions were excluded. Results. Sixty-five patients (63 females, 96.92%) met the inclusion criteria. Among these, 40 patients (61.53%) tested positive for allodynia. The presence of allodynia showed a positive correlation with the scores of all administered questionnaires. Moreover, significant correlations were found between allodynia and rheumatoid factor (r = 0.85; p = 0.032), focus score (r = 0.47; p = 0.02), VAS pain (r = 0.64; p < 0.001), VAS fatigue (r = 0.55; p < 0.001), and ESSPRI (r = 0.50; p < 0.001). No significant correlation was observed with ESSDAI, although a positive trend was noted. An inverse trend was also observed between the presence of allodynia and anti-SSA antibody positivity. Only 5 patients (7.69%) with allodynia fulfilled the diagnostic criteria for concomitant fibromyalgia. Conclusions. According to the preliminary clinical results of the SjNAPSE Project, the presence of allodynia, objectively confirmed by sensory testing, is highly prevalent among patients with SjD and shows a positive correlation with multiple patient-reported symptom measures, including neuropathic pain, fatigue, depression, and anxiety. The correlation between allodynia and disease activity markers such as focus score and rheumatoid factor suggests a complex pathogenic substrate underlying patient-reported symptoms, warranting further investigation. Future aims include expanding the patient cohort and identifying potential biomarkers of neurological involvement to improve diagnostic accuracy.
PO:24:062 | Transcriptomic profile of salivary glands in patients with primary Sjögren’s syndrome and interstitial lung disease: implications for pathogenesis and risk stratification
Background. Primary Sjögren’s syndrome (pSS) is a chronic autoimmune inflammatory disease that typically develops in the absence of another systemic autoimmune disorder. Interstitial lung disease (ILD) represents the most frequent pulmonary manifestation of pSS and is associated with impaired lung function and potentially severe complications. Stratifying patients according to their risk of developing pSS-associated ILD (pSS-ILD) and identifying those at increased risk at an early stage may enable timely therapeutic intervention. Therefore, transcriptomic studies aimed at identifying differentially expressed genes across the three study groups may prove useful for the characterization of predictive disease factors. Materials and Methods. Transcriptomic analyses of inflammatory and immune-related gene panels were performed on patients with ILD, pSS, and pSS-ILD using the NanoString nCounter platform. RNA was extracted from FFPE-embedded minor salivary gland samples obtained from eight patients in each group. Only RNA samples with the highest DV200 values, as assessed by Bioanalyzer, were used for further analysis. Data were processed using the nSolver software, and genes showing significant up- or down-regulation with p < 0.05 were considered differentially expressed. Results. Gene expression analysis in patients with ILD revealed significant differences in immune and inflammatory responses compared to patients with isolated pSS. The up-regulation of TSLP, IL1RN, MAP2K6, JUN, IL1RL1, TNFRSF14, CXCL10, and IL7, along with the down-regulation of PIGR and ITGA6, signifies modified immunologic activity that may aid in clarifying the pathophysiology associated with ILD. Moreover, substantial gene expression variations were observed between pSS-ILD and isolated ILD. Elevated expression of HIF1A, NFATC3, FLT1, APP, and CD14, alongside diminished expression of transcription factors like MYC and FOS, indicates significant modifications in intracellular signaling pathways that may be involved in the pathogenesis of ILD. In addition, upregulation of HDAC4, C4A, and C7 in pSS-ILD patients compared to those with isolated pSS highlights further dysregulation of immune and inflammatory processes, suggesting the emergence of a profibrotic microenvironment capable of exacerbating lung injury. Conversely, down-regulation of CCL21 implies possible disturbances in lymphocyte trafficking and immune surveillance, further complicating disease pathogenesis. Conclusions. It is noteworthy that not all patients with pSS develop ILD, suggesting the possible contribution of genetic or environmental factors to disease manifestation and progression. In summary, the transcriptomic landscape distinguishing ILD, pSS, and their comorbidity provides crucial insights into disease pathogenesis. The differential expression of genes—particularly HDAC4, C4A, C7, and CCL21—offers valuable clues for future research focused on targeted therapies and precision medicine approaches for these complex clinical phenotypes.
PO:24:066 | Antibody profile in myositis and early risk of interstitial lung disease: clinical and laboratory correlations in patients with suspected rheumatologic disease
Background. Interstitial lung disease (ILD) is a frequent comorbidity not only in idiopathic inflammatory myopathies (IIM) but also in other rheumatologic disorders such as Sjögren’s syndrome, systemic sclerosis, and rheumatoid arthritis. Since ILD can represent a potentially life-threatening complication of these conditions, several recent studies have investigated possible risk factors useful for early diagnosis. The aim of this study was to assess the correlation between positivity for an antibody associated with IIM, together with clinical and laboratory data, and the risk of ILD at the time of diagnosis of a rheumatologic disease. Materials and Methods. In this single-center, cross-sectional study, patients were enrolled according to the following inclusion criteria: a) suspected rheumatologic disease with myositic involvement; b) evaluation between January 2022 and May 2025 at a tertiary care center; c) diagnostic work-up including a line immunoassay for myositis autoantibodies (Euroimmun blot) with at least one positive result; d) chest CT scan performed. Data were collected on age, sex, clinical manifestations, creatine kinase (CPK) levels, and antibody positivity (from 1+ to 3+). A multivariate logistic regression model was applied to analyze the relationship between these variables and the presence of ILD at the time of diagnosis. Results. A total of sixty-three patients were included (45 females, 18 males). Sixteen had ILD (documented by chest CT) at the time of rheumatologic disease diagnosis (polymyositis, dermatomyositis, Sjögren’s syndrome, undifferentiated connective tissue disease, antisynthetase syndrome, or systemic sclerosis). After adjusting for clinical and laboratory variables, the strongest risk factor for ILD at diagnosis was a strong positivity for anti-Ro52 antibodies (≥2–3+). Older age at diagnosis and CPK levels <300 U/L were also identified as independent risk factors associated with ILD at disease onset (FIG 1). Raynaud’s phenomenon and sex were not found to be significant risk factors. Conclusions. A clear positivity for anti-Ro52 antibodies, normal CPK levels, and older age appear to be risk factors for the presence of ILD at the time of diagnosis—not only in inflammatory myopathies but also in other rheumatologic diseases. The presence of these features should prompt clinicians to pay particular attention to the possible occurrence of interstitial lung disease.
PO:24:070 | Preliminary descriptive data from a single-centre cohort of patients with idiopathic inflammatory myopathy: focus on paraneoplastic and non-paraneoplastic patients
Background. Idiopathic inflammatory myopathies (IIMs) are a group of autoimmune disorders with heterogeneous clinical manifestations. The discovery of myositis specific autoantibodies (MSAs) brought great advances, because they are strongly associated with distinct clinical phenotypes and different prognosis. Among MSAs, anti-TIF1(a-TIF1) antibodies are considered a strong serologic marker for cancer-associated myositis (CAM, defined as myositis arising ± 3 years from cancer diagnosis). Approximately 70% of DM patients a-TIF1+ are diagnosed as having concominant cancer. The aim of this study is to describe our cohort of IIMs patients, focusing on CAM patients and IIM cases with a history of cancer. Materials and Methods. Medical records of 213 IIM patients followed up at our Myositis Clinic were reviewed. The demographic data, diagnosis, autoantibodies, laboratory profile, instrumental and clinical features at onset were collected.Patients with a history of cancer were then considered and divided into 2 groups: the first one, named “Concomitant” (CC), composed by CAM cases, and group 2, named “Not concomitant” (NCC), consisting of IIM patients with neoplasia onset outside the 3-year period.Normality of the distributions was assessed using the Kolmogorov-Smirnov test. Continuous variables were presented as means ±SD and compared with Student’s T-test. Categorical variables were presented as frequencies or percentages and compared with Chi-Square test and the Fisher’s exact test, as appropriate; associations of the crosstabs were verified using standardized adjusted residuals. A two-sided alpha level of 0.05 was used for all tests. Results. Data from the entire cohort were showed in Table 1. Within the cohort 28,6% (N=61) of patients developed a malignancy: 30 patients defined as CC group (49.2%) and 31 patients as NCC one (50.8%). DM was the IIM most frequent in CC group (p=0,025) and ASS in NCC one (p=0,043). As shown in Table 3, no clinical features are significantly associated with CC, while ILD (p=0,018), dyspnoea (p=0,034), arthritis (p=0,018), sclerodactyly (p=0,036) and mechanic's hands (p=0,048) are significantly associated with the absence of a paraneoplastic IMM.A-TIF1 antibody was found associated (p=0,005) with the CC group, while a-Jo1 antibody was mostly detected in the NCC group (p=0,002). MAA rates did not differ within the two groups. The most represented cancer in CC group was breast cancer (50%), followed by ENT and prostatic (16,7% and 16,6% respecitively). Metastatic cancer was found in 53,6%. A significantly higher number of stage IV cancer was found in the CC group compared to the NCC group (p=0,023) where instead a significant prevalence of stage 1 and 3 was recorded (p=0,006 and p=0,011 respecitively). No differences in the number of deaths were observed between the two groups. Conclusions. Anti-TIF1 is the only serological marker of CAM. These patients showed a more aggressive cancer since the IIM diagnosis with frequent metastasis rate, compared with IIM with a non concominant cancer.
PO:25:071 | Gender differences in Sjögren’s disease: clinical activity, illness perception, and emotional impact
Background. Sjögren’s Disease (SjD) is a systemic autoimmune disorder with a marked female predominance, characterized by a broad spectrum of clinical manifestations and a substantial impact on quality of life. Yet, gender-related differences in disease perception and emotional experience remain poorly investigated. This multicenter study, promoted by GRISS, aimed to explore these aspects. Materials and Methods. Eighty-six patients (30 men and 56 women) with primary SjD (ACR–EULAR criteria) were enrolled. Disease activity was assessed using the ESSDAI, while subjective symptom intensity was measured with the ESSPRI. Illness perception was evaluated through the Brief Illness Perception Questionnaire (BIPQ), which includes eight items addressing cognitive (consequences, timeline, personal control, treatment control, perceived symptoms), emotional (concern, emotional impact), and understanding dimensions. Emotional status was assessed using the Hospital Anxiety and Depression Scale (HADS), comprising the anxiety (HADS-A) and depression (HADS-D) subscales. Statistical analyses were performed with Student’s t-test or Mann–Whitney test for group comparisons, and Pearson or Spearman correlations to explore associations between variables. General characteristics are shown in Table 1; significant findings are summarized in Table 2. Results. Compared with women, men displayed significantly higher systemic disease activity (ESSDAI, p = 0.0102) but lower symptom intensity (ESSPRI, p = 0.0107). Women reported higher levels of anxiety (p = 0.0054) and depression (p = 0.0033) and perceived a greater emotional impact of the disease (BIPQ item 8, p = 0.0153). Correlations between illness perception and psychological distress revealed gender-specific patterns. In women, both HADS-A and HADS-D correlated with the disease’s impact on daily life (item 1), symptom intensity (item 5), and emotional burden (item 8); only HADS-A was associated with disease-related concern (item 6). In men, anxiety correlated with BIPQ items 1, 5, 6, and 8, whereas depression correlated with items 6 and 8. Conclusions. These findings underline the need to consider gender differences in the management of SjD, not only in terms of clinical presentation but also regarding subjective perception and psychological wellbeing. A personalized approach that incorporates patients’ emotional and cognitive profiles may enhance both the quality of care and the effectiveness of therapeutic interventions.
PO:25:073 | Pulmonary involvement and progressive interstitial lung disease in anti-synthetase syndrome: a single-center retrospective study
Background. Anti-synthetase syndrome (ASS) is a systemic autoimmune disease frequently associated with lung involvement. This single-center retrospective study aimed to longitudinally assess the clinical and instrumental evolution of patients with ASS and Interstitial Lung Disease (ILD) and to evaluate the rate of disease progression. Materials and Methods. Clinical and instrumental data, including spirometric parameters (%pFVC and %pDLCO), radiological patterns, and fibrotic extent according to HRCT visual scoring, were collected at three time points: baseline (first visit at our center), 12 ± 3 months, and 24 ± 3 months. Progressive ILD at 12 and 24 months was defined according to the ATS/ERS/JRS/ALAT 2022 guidelines (presence of at least two among worsening respiratory symptoms, decline in %pFVC ≥ 5% or in %pDLCO ≥ 10%, or radiological progression) and the INBUILD trial criteria (at least one among %pFVC decline ≥ 10%, 5–10% decline in %pFVC with worsening symptoms or radiological progression, or worsening of symptoms and radiological progression). Predictors of progression were analyzed. Results. Thirty-three patients with ASS-ILD were included. Patients and disease characteristics are summarized in Table 1. Twenty-five patients (76%) presented pulmonary involvement at disease onset. The most frequent radiological pattern was NSIP, observed in 23 patients (70%), followed by UIP in 6 patients (18%), OP in 2 patients (6%), and mixed NSIP-OP in 2 patients (6%). Fibrotic extent on HRCT was ≤10% in 15 patients (46%), 10–20% in 10 patients (30%), and >20% in 8 patients (24%). The distribution of NYHA functional class for dyspnea across the three time points is shown in Graphic 1. We observed an improvement from baseline in NYHA functional class for dyspnea (2, 4, and 2 patients moved from class IV, III, and II to class I, respectively, at both 12 and 24 months), as well as an improvement in exertional dyspnea at 24 months [24 (73%) vs 15 (45%); p = 0.0242], together with a progressive increase in %pFVC values at the two time points (Graphic 2, Table 2). Five (15%) and four (12%) patients were classified as progressors at 12 and 24 months, respectively. The characteristics of patients with INBUILD-defined progression at 24 months compared with those without progression are summarized in Table 3. No predictor of ILD progression was identified. Conclusions. In our cohort of patients with ASS-ILD, the %pFVC and NYHA functional classes improved over 12 and 24 months of follow-up. The proportion of progressors identified according to the two criteria was reduced (15% and 12%). No predictor of progression was identified.
PO:25:074 | Capillaroscopic assessment in interstitial lung disease: a comparative study between connective tissue disease-associated interstitial lung disease, interstitial pneumonia with autoimmune features, and idiopathic pulmonary fibrosis
Background. Nailfold videocapillaroscopy (NVC) is a validated, non-invasive tool for evaluating microvascular ab-normalities, increasingly explored in interstitial lung diseases (ILDs) with suspected autoimmune fea-tures. However, data on capillaroscopic patterns across ILD subtypes, especially in Caucasian popu-lations, are limited. Objectives: To compare NVC findings in patients with idiopathic pulmonary fibrosis (IPF), interstitial pneumonia with autoimmune features (IPAF), and connective tissue disease-associated ILD (CTD-ILD), and to assess correlations with autoantibody status—particularly myositis-specific antibodies (MSA – Jo-1, KS, PL7/PL12, NXP-2, MDA-5). Materials and Methods. Fifty-nine Caucasian ILD patients underwent NVC during routine evaluation. Based on multidiscipli-nary diagnosis, they were classified as IPF (n=9), IPAF (n=10), or CTD-ILD (n=40), further subdivided into systemic sclerosis (SSc, n=20) and non-SSc CTD-ILD (n=20). A validated 6-item semiquantitative scoring system (range 0–3 per item, max 18) was used; individual items are listed in Table 1. Clinical data included demographics and autoimmune serology (ANA, ENA, MSA). Statistical comparisons employed ANOVA and Student’s t-test. Results. Total capillaroscopic scores differed significantly across diagnostic groups: CTD-ILD (6.1±3.09), IPAF (4.6±3.31), and IPF (3.4±1.74) (p=0.0042). Within CTD-ILD, SSc patients showed higher scores than non-SSc (7.4±2.87 vs 4.8±3.22; p=0.0105). A four-group comparison confirmed this trend (p=0.0042). Among individual items, only “loss of capillaries” differed significantly across groups (p<0.0001), with highest scores in SSc. Subsequently, the total capillaroscopic score was analyzed in relation to autoimmune serology: it was not significantly different between MSA+ and MSA- pati-ents (5.21±3.51 vs 5.51±3.17; p=0.7805). After excluding the 9 patients with IPF, the comparison between MSA+ and MSA- subjects still revealed no significant difference in total score (5.21±3.51 vs 5.95±3.25; p=0.5052). Conclusions. Nailfold videocapillaroscopy reveals distinct microvascular alterations among ILD subtypes, with sig-nificantly higher scores in CTD-ILD—particularly in SSc—compared to IPAF and IPF. While no signifi-cant differences emerged in relation to MSA, the observed gradient in capillaroscopic severity across autoimmune categories underscores the potential value of NVC as a complementary tool in the early diagnostic workup of ILD, especially in identifying autoimmune-driven forms and possibly refining IPAF classification. These findings support the integration of capillaroscopy into multidiscip-linary ILD assessment, where it may assist in detecting early autoimmune features and guiding im-munological testing. Moreover, expanding the cohort in future studies may help uncover more ro-bust associations between NVC findings and specific autoantibody subsets, particularly MSA.
PO:25:075 | Cancer occurence in patients with idiopathic inflammatory myopathies: new insights from the analysis of a monocentric cohort
Background. Idiopathic inflammatory myopathies (IIMs) are rare systemic autoimmune disorders, associated with an increased risk of cancer. Data from International Guideline for IIMs-Associated Cancer Screening identified the following conditions as a risk factor for cancer development: Dermatomyositis (DM), Anti-TIF1-gamma and Anti-NXP2 positivity, age >40 years at onset, persistent high disease activity despite therapy, dysphagia and cutaneous necrosis. The objective of the study was to assess the prevalence of cancer in a single-centre cohort of patients with IIMs, exploring possible correlations among cancer development, demographic and clinical parameters. Materials and Methods. We retrospectively analysed the medical records of consecutive patients diagnosed with IIMs according to the 2017 EULAR classification criteria and followed at our Unit. Data about demography, autoantibody profile, organ involvement and comorbidities were collected. Intergroups comparisons were assessed by using Chi- square, t-test and ANOVA. P values <0.05 were considered significant. Results. A total of 220 IIMs patients [mean age 66.5±14.3, 77 men (35%)] were enrolled. Among them, 30 (15.8%) had a diagnosis of cancer: 5 prostate, 5 breast, 3 endometrium, 3 lung, 3 larynx, 2 melanoma, 2 colon, 1 nasopharyngeal, 1 thyroid, 1 liver, 1 basal cell carcinoma, 1 squamous cell carcinoma, 1 MALT and 1 osteosarcoma. In this subgroup of patients, the mean age was 74.5± 9.4 years and 16 patients were men (53.3%). An older age and male sex were risk factors for neoplasms (respectively p <0.001 and p=0.03). No IIM phenotype appeared to significantly influence tumor risk, however, some differences emerged. Indeed,no patients with Clinically Amyopathic DM (CADM) and Immune-Mediated Necrotizing Myositis (IMNM) developed cancer. On the contrary, in the subgroup of Anti-synthetase syndrome (ASS) we found that 7 on 30 patients (23%) developed a cancer. Autoantibodies positivity for anti-Ro52 and anti-TIF1-gamma was associated with a higher number of neoplasms (p=0.01 and p=0.02, respectively). Among organ involvement, oesophageal dysmotility was associated with cancer (p=0.04). None of the patients with calcinosis had malignancies. Among the different comorbidities, dysthymia, dyslipidemia, hypertension (p<=0.04), stroke (p=0.02) and hypothyroidism (p=0.03) were more frequent in IIMs patients with cancer. Conclusions. More than 15% of IIMs patients of our cohort had a diagnosis of cancer. Although this association is known from previous works, our analysis has allowed us to identify additional factors that may be associated with the development of neoplasia, such as antiRo52 positivity. Furthermore, cancer is not rare in ASS, showing a prevalence that is comparable to that already observed in DM. Finally, our results suggest that IIMs patients with cancer could have more frequently cardiovascular, psychiatric and endocrinological comorbidities. These preliminary data could help rheumatologists in the clinical profiling of this subgroup of patients and could be useful to optimize cancer screening in the assessment of IIMs patients, aiming at improving their management.
PO:25:079 | Anifrolumab in refractory dermatomyositis: a case report
Background. Dermatomyositis is a rare autoimmune disease characterized by multisystem involvement. Treatment can be challenging, particularly in refractory cases unresponsive to conventional therapies, for which standardized management protocols are lacking. An increased activation of the type I interferon (IFN-I) pathway has been demonstrated in patients with dermatomyositis, providing a rationale for the use of anifrolumab, a monoclonal antibody targeting the IFN-I receptor, already approved for systemic lupus erythematosus and particularly effective on cutaneous manifestations. Materials and Methods We report the case of a 57-year-old woman with anti–TIF-1γ–positive dermatomyositis, diagnosed in May 2024, with a history of high-grade serous ovarian carcinoma treated with surgery and chemotherapy (August 2024–February 2025). At rheumatologic evaluation in March 2025, the disease was clinically active with extensive cutaneous involvement, including heliotrope rash, malar rash without sparing of the nasolabial folds, diffuse erythema of the limbs, back, and décolleté, palmar and facial telangiectasias, and distal ulcers on the hands and right ear (Cutaneous Dermatomyositis Disease Area and Severity Index – CDASI: Activity 29, Damage 5). The patient also reported disabling myalgia and progressive gait impairment (Medical Research Council scale – MRC 45/60). Previous treatments (steroids, hydroxychloroquine, mycophenolate mofetil, intravenous immunoglobulins, and anakinra) were ineffective or discontinued due to adverse events, while rituximab was considered inappropriate because of her oncologic history. Therefore, monthly intravenous anifrolumab therapy was initiated. Results. After two months of anifrolumab treatment, marked clinical improvement was observed in both cutaneous (CDASI Activity 12; Damage 4) (Figure 1A–C, Figure 2A–B) and muscular domains (MRC 50/60), with no adverse events reported, including serious infections. The improvement allowed progressive corticosteroid tapering (from 25 mg to 5 mg of prednisone) without elevation of muscle damage markers or disease flare. Conclusions. This case suggests that anifrolumab may represent a promising therapeutic option for refractory dermatomyositis. Controlled studies are warranted to confirm its efficacy and safety in this indication.
PO:25:081 | Atypical onset of anti-SAE-1 positive dermatomyositis: paraneoplastic flame hemorrhages in urothelial carcinoma
Background. Flame hemorrhages are a manifestation of infectious endocarditis, as well as autoimmune or neoplastic diseases. Anti-SAE-1 antibodies (small ubiquitin-like modifier-activating enzyme, against enzymes involved in gene transcription mechanisms and apoptosis control) are specific for a form of dermatomyositis with mild skin and muscle involvement that can be associated with neoplasms. Materials and Methods. We describe the case of a 50-year-old patient who developed flame hemorrhages and acrocyanosis with positivity for anti-SAE-1 antibodies. Results. Following a urinary tract infection, treated with levofloxacin, she developed Raynaud's phenomenon, flame hemorrhages, and acrocyanosis (Figure 1). Increased PCR and ESR (1.42 mg/dL and 45 mm/h), blood count and biochemistry within normal limits. An upper limb Doppler ultrasound and a chest CT scan ruled out vascular pathologies of the upper extremities, and a transesophageal echocardiogram ruled out infectious endocarditis. Video capillaroscopy showed the absence of a frank scleroderma pattern but the presence of multiple flame hemorrhages and thrombosed capillaries (Figure 2). Regarding autoimmunity: ANA positive, fine dense speckled cytoplasmic (AC-19), anti-ENA, ANCA, APL, and LAC absent. Anti-SAE-1 tested positive on the rare myositis antibody panel. Acrocyanosis was treated with an iloprost infusion, with partial benefit. During the first-level paraneoplastic screening, a third-degree hydronephrosis of the left kidney and dilation of the ureter at its opening into the bladder were detected by abdominal ultrasound. Further investigation with an abdominal CT scan with contrast revealed a lymph node mass responsible for the ureteral dilation, and endoluminal vegetations were present in the bladder (Figure 3). A radical cystectomy was performed, with histological confirmation of high-grade urothelial carcinoma, with positive lymph nodes. Conclusions. The reported case is peculiar, as there are no similar cases described in the literature. It highlights the unusual initial manifestations of myositis and the importance of paraneoplastic screening in similar presentations when a correlation with neoplasms is suspected.
PO:25:082 | Progressive interstitial lung disease secondary to Sjögren's disease in a patient with inclusion body myositis complicated by dysphagia: a multidisciplinary approach and therapeutic challenges
Background. Inclusion Body Myositis (IBM) is a rare idiopathic inflammatory myopathy, characterized by an insidious onset with progressive muscle weakness and dysphagia. While its association with Sjögren’s syndrome (pSS) has been reported, this overlap is uncommon and often challenging to manage. We present the case of a patient affected by this dual condition, treated at our center. Case report. A 70-year-old man, a former smoker, with a medical history of hypertension, hypothyroidism, transient ischemic attack, and prior intestinal obstruction surgery, presented to rheumatologic evaluation in 2017 with progressive dysphagia and muscle weakness. A diagnosis of IBM was established and confirmed by muscle biopsy. The patient was subsequently treated with intravenous immunoglobulins and pyridostigmine, achieving clinical improvement. In 2023, the patient developed new-onset xerophthalmia, xerostomia, and progressive exertional dyspnea. The comprehensive diagnostic work-up included a chest CT scan showing subpleural reticular thickening, mainly in the posterior-basal segments of the lower lobes, in the lateral segments of the middle lobe, and in the superior segments of the lingula. Pulmonary function testing showed a restrictive ventilatory defect and a moderate drop in DLCO. Serological analysis showed anti-Ro52 antibody positivity, and minor salivary gland biopsy demonstrated a focus score of 1. The overall findings were consistent with pSS. In 2024, due to worsening dyspnea, a new chest CT was performed, showing disease progression with the appearance of pulmonary fibrosis (radiologic UIP pattern). The case was discussed during a multidisciplinary meeting involving radiologists, pulmonologists, and rheumatologists. Due to the clinical and radiological deterioration of pSS-associated interstitial lung disease, treatment with nintedanib 150 mg twice daily, prednisone 50 mg with gradual tapering, and cyclophosphamide according to the NIH protocol was initiated. Maintenance therapy with mycophenolate mofetil 2 g/day was subsequently introduced. At follow-up spirometry, pulmonary function remained stable, although CT imaging showed mild disease progression with increased bronchiectasis. The patient’s clinical and therapeutic management is ongoing under multidisciplinary follow-up. Conclusions. This case highlights two key aspects: the intrinsic complexity in managing inclusion body myositis associated with pSS, and the essential role of a multidisciplinary approach in defining not only the initial treatment but also subsequent therapeutic adjustments based on clinical and instrumental evolution. Furthermore, the combination of an immunosuppressive drug with an antifibrotic agent may represent an effective therapeutic strategy to achieve clinical, radiological, and functional stabilization of interstitial lung disease in patients with pSS.
PO:25:083 | Overlap between Sjögren’s syndrome and lichen sclerosus: beyond coincidence?
Background. Lichen sclerosus (LS) is a chronic, immune-mediated inflammatory condition that predominantly affects mucocutaneous areas, particularly the anogenital region. Although the etiopathogenesis of LS remains poorly understood, autoimmune, genetic, infectious, and traumatic mechanisms have been hypothesized.¹ Large-scale epidemiological studies are limited, but the estimated prevalence in the general population ranges from 0.05% to 0.3%. ²,³ In Italy, LS is classified among rare diseases (prevalence 5/10,000; exemption code RL0060). LS has been associated with several dermatological and immune-mediated conditions, including Hashimoto’s thyroiditis, psoriasis, vitiligo, alopecia areata, ulcerative colitis, systemic lupus erythematosus (SLE), and systemic sclerosis. However, the relationship between LS and systemic autoimmune diseases warrants further investigation. Although some case reports have described overlap between LS and Sjögren’s disease (SjD), this potential association remains poorly explored. Outcome: To further investigate the possible overlap between LS and SjD. Materials and Methods: Medical records of patients with SjD and non-Sjögren sicca syndrome consecutively evaluated at the Sjögren Clinic of our Rheumatology Unit over the past 12 months were reviewed. During each visit, patients were specifically asked whether they had ever received a diagnosis of LS. Those reporting a prior diagnosis of LS were subsequently re-evaluated to confirm the diagnosis. Results. A total of 378 patients with SjD (13 males, 365 females; mean age 55 years, range 24–79; mean disease duration since diagnosis 3.7 years) and 99 subjects with non-Sjögren sicca (6 males, 93 females; mean age 56.3 years, range 34–72; mean symptom duration 3.12 years) were included. Among patients with SD, 7/378 (1.8%) female patients had a confirmed diagnosis of LS (mean age 46.8 years, range 37–55). None of the subjects with non-Sjögren sicca had LS. Conclusions. Although no statistically significant differences were observed between SjD and non-Sjögren sicca, the prevalence of LS among patients with SjD was higher than that reported in the general population. This observation supports the hypothesis of shared etiopathogenic mechanisms, likely immune-mediated, as further suggested by the reported occurrence of SjD in approximately 1.5% of patients with LS. This comorbidity should always be investigated in patients with SjD. References Singh N, Ghatage P. Etiology, clinical features, and diagnosis of vulvar lichen sclerosus: a scoping review. Obstet Gynecol Int. 2020; 2020:7480754. Murphy R. Lichen sclerosus. Dermatol Clin. 2010;28(4):707-15. De Luca DA, Papara C, Vorobyev A, Staiger H, Bieber K, Thaçi D, Ludwig RJ. Lichen sclerosus: The 2023 update. Front Med (Lausanne). 2023;10:1106318. Guttentag A et al. Australas J Dermatol. 2025;66:135-141. Shiboski CH, Shiboski SC, Seror R, Criswell LA, Labetoulle M, Lietman TM, et al. The 2016 American College of Rheumatology and European League Against Rheumatism classification criteria for primary Sjögren's syndrome were developed through a consensus and data-driven methodology that involved three international patient cohorts. Arthritis Rheumatol. 2017;69(1):35-45.
PO:26:088 | Rheumatologic immune-related adverse events from immune checkpoint inhibitors: a monocentric retrospective study
Background. Since their introduction into oncological practice, immune checkpoint inhibitors (ICIs) have revolutionized the treatment of several malignancies. However, their use is associated with the development of immune-related adverse events (irAEs), which can occur at any time during therapy and represent one of the main challenges in clinical management. Among irAEs, rheumatologic manifestations constitute a relevant subgroup, whose complexity requires a multidisciplinary approach capable of balancing disease control without compromising oncological prognosis. The aim of this study is to evaluate the clinical features of a monocentric cohort of patients who developed rheumatologic irAEs. Materials and Methods. Among the patients followed at the outpatient clinic in our Center dedicated to irAEs, those with rheumatic symptoms were retrospectively identified. For each patient, demographic data, type of malignancy, administered ICI(s), characteristics of the rheumatologic irAEs, possible concomitant irAEs, administered immunosuppressive therapies, and oncologic and rheumatologic outcomes (defined through disease score based on the specific type of irAE) were collected. Results. Ninety-one patients met the inclusion criteria, and the demographic and oncological characteristics are reported in Table 1. The most frequently observed oncological histotype was pulmonary adenocarcinoma (n=34, 37%), while the most commonly administered ICI was pembrolizumab (n=52, 51%). In 12 (13%) cases, a combination of multiple ICIs was administered. Patients were also treated with another oncological therapy in 76 (84%) cases. The median interval between the start of ICI therapy and the onset of the rheumatologic irAE was 3 (IQR 1–8) months. As shown in Figure 1a, the most frequent form was arthritis (n=53, 45%). In 5 (5%) patients, an ICI-induced relapse of pre-existing rheumatologic disease was observed (rheumatoid arthritis 3 [60%], psoriatic arthritis 1 [20%], systemic lupus erythematosus 1 [20%]). ICI therapy was permanently discontinued in 24 (47%) cases. Eighty-four (92%) patients were treated with oral corticosteroids (median initial dose 25 [IQR 12–39] mg/day prednisone-equivalent) and 5 (5%) received intravenous corticosteroid pulses, 44 (48%) received at least one conventional immunosuppressant, and in 26 (28%) cases a biologic therapy was administered (Figure 1b). In 16 (18%) patients, multiple immunosuppressive therapeutic lines were required. Regarding the rheumatologic outcome, in 79 (87%) patients remission or low disease activity was achieved, while in 21 (23%) oncologic progression was observed at the end of follow-up. Conclusions. Our monocentric data confirms the clinical relevance of rheumatologic irAEs in patients treated with ICIs, highlighting their phenotypic heterogeneity and the frequent need for immunosuppressive treatments. These results contribute to expanding knowledge of the clinical and management profile of these manifestations, underlining the importance of an integrated rheumatologic follow-up.
PO:26:095 | Educational online webinars of European Reference Network on rare and complex connective tissue and musculoskeletal diseases for patients, caregivers and healthcare professionals: six years' experience
Background. The European Reference Network on Connective Tissue and Musculoskeletal Diseases (ERN ReCONNET), founded in 2017 by the European Union (EU) Commission, aimed to improve the management of rare connective tissue diseases (CTDs) across the EU. ReCONNET includes rare (Ehlers-Danlos Syndromes, IgG4-Related Diseases, Mixed Connective Tissue Disease, Relapsing Polychondritis) and complex with low prevalence (Antiphospholipid Syndrome, Idiopathic Inflammatory Myopathies, Sjögren’s Syndrome, Systemic Lupus Erythematosus, Systemic Sclerosis, and Undifferentiated Connective Tissue Disease) CTDs. Since 2019, ReCONNET Educational Committee organized free online webinars accessible live on Zoom platform and recorded on ReCONNET YouTube (YT) page. Aim of the study was to assess the interest and size of webinar viewers (wv) and views from patients/caregivers, HCPs, or both, for the different CTDs. Materials and Methods. Zoom live view data (available from October 2023) and YT views (available from 2019) were collected as of 2nd May 2025. Results. From 2019 up to 2025, ERN ReCONNET organized 73 webinars, totaling 147,030 YT views. Webinars on rare CTDs (n=20) collected 70,307 YT views (average 3,515±4,271 per webinar) and webinars on complex CTDs (n=53) totalized 76,723 YT views (average of 1,447±1,838 per webinar), the former with a significantly higher number of YT views per webinar (p<0.01). By considering Zoom data available from October 2023, live webinars targeted at patients/caregivers got 158 wv (6 webinars, average 26±18 per webinar); those for HCPs got 265 wv (11 webinars, average 24±9 per webinar) and those for both classes got 132 wv (6 webinars, average 22±15 per webinar) without statistically significant differences interclasses. The YT recording of the above webinars for patients/caregivers averaged 541±507 views (total of 3,244), those for HCPs 902±816 views (total of 9,925), and those for both classes 581±598 views (total of 3,486), without statistically significant differences interclasses. When the number of live wv and YT views was counted for rare vs complex CTDs, rare CTDs got 172 wv (5 webinars, average 34±17 per webinar) together with 6,993 YT views (average 1,399±345 per webinar). Webinars on complex CTDs collected 383 live wv (18 webinars, average 21±10 per webinar) and 9,662 YT views (average 537±642 per webinar) (Figure 1a). The difference between rare and complex CTDs was statistically significant for YT views (p<0.01), but not for wv. Linear regression analysis of YT views showed that the rare CTDs group exhibited a significantly steeper increase of views over time compared to the complex CTDs group (beta=1.85, p<0.001) (Figure 1b). Conclusions. ERN ReCONNET’s webinars achieved a considerable number of views on YT, with significantly higher interest for rare CTDs compared to complex low-prevalence CTDs. Main users of this educational experience were found to be HCPs, and further efforts are ongoing to attract more patients and caregivers.
PO:26:097 | Ultrasound evaluation of temporomandibular disorders: comparative analysis between inflammatory and degenerative patterns in patients with and without rheumatological pathologies
Background. Temporomandibular disorders (TMD) encompass a heterogeneous group of conditions with varying etiologies, either inflammatory or degenerative, that affect the temporomandibular joint (TMJ). Differentiating these mechanisms is crucial for targeted treatment, especially in patients with underlying rheumatologic diseases, where TMJ involvement may reflect systemic activity. The aim of this prospective, cross-sectional study is to evaluate the usefulness of ultrasound (US) in identifying inflammatory or degenerative alterations of the TMJ, comparing the results between patients with known inflammatory rheumatic diseases (arthritis, connective tissue diseases, and vasculitis), primary fibromyalgia, and symptomatic individuals without known rheumatologic conditions. Materials and Methods. A total of 312 subjects (272 patients + 40 healthy controls) were subjected to standardized TMJ clinical and ultrasound evaluation between 2018 and February 2025. The sample was divided into two groups: Group A, consisting of patients without inflammatory rheumatic disease + healthy controls (asymptomatic for TMD) + primary fibromyalgia (n = 110); and Group B, consisting of patients with inflammatory arthropathy or connective tissue disease (n = 202). Clinical signs and symptoms related to TMD were recorded for each subject included in the study. The ultrasound parameters analyzed included more specifically inflammatory characteristics (joint effusion, synovial hypertrophy, and Doppler signal -PD-), and degenerative-mechanical features (condylar surface irregularities, enthesophytes, erosions, joint space narrowing, calcifications, and disc dislocations). Results. Inflammatory ultrasound findings—such as synovitis, joint effusion, and PD signal—were significantly more frequent in Group B (p < 0.05). Physical examination alone did not reliably differentiate inflammatory involvement from mechanical involvement in the TMJ (66.4% vs. 33.6%, p = 0.634) (Figure 4). Degenerative findings, such as cortical irregularities, enthesophytes, and cartilage thinning, were also more frequent in Group B, although similar results were observed in Group A patients, likely due to possible chronic mechanical stress factors (e.g., bruxism). Unexpectedly, a PD signal was detected in some cases of fibromyalgia. Multivariate analysis identified joint erosions and cartilage thinning as the only ultrasound lesions significantly correlated with clinical TMJ symptoms. These results support US as a useful tool for distinguishing between inflammatory and mechanical alterations and for detecting subclinical TMJ joint involvement. Conclusions: US is confirmed as a valuable non-invasive tool for assessing different patterns of TMD, including at the TMJ level, complementing clinical evaluation and improving diagnostic accuracy.
PO:27:105 | Sleep disturbances in patients with polymyalgia rheumatica: correlations with disease activity, fatigue, and glucocorticoid dosage
Background. The aim of this study was to investigate the prevalence of sleep disturbances in patients with polymyalgia rheumatica (PMR) and to assess their possible correlation with disease activity, fatigue, and glucocorticoid (GC) dosage. Materials and Methods. Consecutive patients with PMR classified according to the 2012 ACR/EULAR provisional criteria and age- and sex-matched non-rheumatologic controls were enrolled. Demographic, clinical, and serological data, disease activity (PMR-activity score, PMR-AS, calculated using CRP); and current GC dose were recorded for all PMR patients. Both PMR patients and controls filled out questionnaires about their sleep quality and fatigue. These included the Pittsburgh Sleep Quality Index (PSQI), the Insomnia Severity Index (ISI), the Epworth Sleepiness Scale (ESS), and the Fatigue Severity Scale (FSS). Patients taking GC for conditions apart from PMR were excluded. Results are expressed as median/interquartile range (IQR). The χ² test, or Fisher’s exact test, was used for the comparison of categorical variables, as appropriate. Correlations were assessed using Spearman’s rank correlation coefficient. A p-value <0.05 was considered statistically significant. Results. A total of 42 PMR patients (M/F 13/29, age 74.5 years [IQR 12.75], disease duration 6 months [IQR 8], ESR 18 mm/h [IQR 23.75], CRP 0.49 mg/dL [IQR 0.94], PMR-AS 1.085 [IQR 3.09], GC dose 5 mg/day prednisone equivalent [IQR 2.5]) and 42 controls (M/F 20/22, age 67 years [IQR 9.75]) were included (Table 1). Questionnaire adherence was 84% among PMR patients (42/50 respondents) and 100% among controls. Six PMR patients (14.2%) were taking hypnotic medications. The prevalence of sleep disturbances assessed by PSQI was 45% in PMR patients vs. 21% in controls (p<0.05). The prevalence of insomnia, evaluated by ISI, was 38% in PMR patients vs. 28% in controls (p=ns). Daytime sleepiness assessed by ESS was 0% in PMR patients vs. 7% in controls (p=ns). Fatigue prevalence was 17% in patients vs. 2% in controls (p<0.05). Significant correlations were observed between PSQI and ISI scores and GC dosage (r=0.316, p=0.041 and r=0.323, p=0.037, respectively) (Table 2). Conclusions. In patients with PMR, the prevalence of sleep disturbances and fatigue was significantly higher than in controls, despite the use of hypnotics in some cases. Moreover, the correlation between sleep disturbances, fatigue, and GC use suggests a possible additional adverse effect of glucocorticoids—often overlooked but potentially detrimental to patients’ quality of life.
PO:27:108 | Delphi consensus on the shared management of patients with rheumatologic and oncologic diseases
Background. The intersection between rheumatologic and oncologic diseases, especially concerning the use of immunostimulatory cancer therapies, poses relevant clinical challenges. Immunotherapy may induce rheumatologic or autoimmune manifestations, while csDMARDs or bDMARDs can affect the efficacy and course of oncologic treatment. The aim of this project was to develop expert-based recommendations, through consensus between the Italian Society of Rheumatology and the Italian Association of Medical Oncology, to support the shared management of patients with concomitant rheumatologic disease and malignancy, as well as immune-mediated adverse events from cancer therapies. Materials and Methods. A modified Delphi process was conducted according to principles of anonymity, iterative feedback, and multidisciplinary involvement (18 clinicians including rheumatologists, oncologists, and methodologists). After a narrative literature review (54 articles, 1988–2024), three key assumptions and 11 consensus statements were defined. Each statement was rated (0–10) via Google Forms. Critical or low-consensus feedback was revised and re-voted. Consensus was achieved when at least 75% of respondents scored >7.5. Results. Three key assumptions and 11 statements were submitted to voting in two separate sessions. The three main assumptions were: (1) tumor development may result directly or indirectly from rheumatologic disease or its therapies; (2) clinical evaluation must consider both oncologic stage and rheumatologic activity; (3) clinical management should be shared between oncologist and rheumatologist. The first assumption did not reach consensus. Statements in Sections A and B achieved consensus (Figure 1). Section A addressed the onset of malignancy in rheumatologic patients. Experts agreed on shared management, individualized evaluation of therapeutic continuation, relevance of cancer history, possible DMARD withdrawal in remission, and joint management in severe or active cases. Paraneoplastic syndromes require oncologic treatment, possibly combined with immunosuppressants if indicated. Section B focused on the onset of rheumatologic conditions during cancer therapies. The crucial role of collaboration was highlighted to manage immune-related adverse events (irAEs), therapeutic escalation from symptomatic drugs to targeted agents (e.g., IL-6R, CD20, IL-17A, IL-23, PDE4 inhibitors), and the use of CTCAE criteria despite their limitations in classifying rheumatologic toxicity. Non-consensual statements were revised and re-voted: Section A, 4th (immunosuppressant discontinuation in remission); Section B, 1st and 4th (management of rheumatologic manifestations during ICI therapy). Conclusions. The consensus provides recommendations for multidisciplinary management of onco-rheumatologic patients based on clinical expertise. It represents a useful foundation to address clinical scenarios lacking strong evidence, pending prospective studies. Figure 1. Delphi Consensus: list of key assumptions and statements shared with experts. Columns from 0 to 10 report the percentage of votes expressed for each item.
PO:27:112 | The impact of rurality in chronic inflammatory rheumatic diseases in the province of Udine (2014-2023): analysis of clinical outcomes and potential complications
Background. Chronic inflammatory rheumatic diseases (IRDs) are immune-mediated disorders that may be affected by geographical barriers, such as rurality and distance from specialized centers, potentially limiting access to care. Evidence regarding the impact of these factors on clinical outcomes remains scarce and mostly derived from non-European settings. This study investigates, within an Italian hub-and-spoke healthcare model, the influence of rurality, distance from the referral center, and other factors, such as comorbidities, sex, age, and type of IRD, on clinical outcomes among patients residing in the province of Udine. Materials and Methods. The study conducted a retrospective cohort analysis using administrative healthcare data, encompassing all incident diagnoses of IRDs (chronic arthritis, connective tissue diseases, and systemic vasculitis) from 2014 to 2023. Rurality was defined as residence in areas with a population density <150 inhabitants/km²; distance from the specialized center was measured in kilometers, with a threshold of 27 km (75th percentile). Comorbidities were classified according to the Charlson Comorbidity Index (CCI): mild (CCI=1), moderate (CCI=2), severe (CCI≥3). Outcomes analyzed included first hospitalizations and emergency department (ED) visits for avoidable IRD-related complications (infections, cardiovascular events, osteoporotic complications) and all-cause mortality. Statistical analysis: multivariable Cox regression. Results. A total of 3,044 patients were included, 66.33% female, with a median follow-up of 4.9 (2.4–7.3) years. Median age at diagnosis was 57 (47–67) years. The distribution of IRDs was as follows: chronic arthritis (73.95%), connective tissue diseases (17.53%), and vasculitis (8.51%). Overall, 32.95% of patients lived in rural areas, and 24.31% resided more than 27 km from the center. Rurality and distance did not correlate with an elevated risk of hospitalization, emergency department visits, or mortality (p>0.05). Female sex was protective against ED visits and infection-related hospitalizations but associated with a higher risk of osteoporotic fractures. Being older and having more than one health problem at the same time were both strong predictors of hospitalization for all avoidable complications, especially in patients with moderate (CCI=2) and severe (CCI≥3) comorbidities. A similar trend was noted for preventable emergency department visits, with an increased risk in patients with CCI=2, CCI≥3, and older age; no emergency department visits were documented for osteoporotic complications. The risk of death went up with age and was higher in people with CCI=2 or CCI≥3. Women had a lower risk than men. Connective tissue diseases were also associated with increased mortality risk. All statistically significant hazard ratios are reported in the Figure. Conclusions: In the Province of Udine, rurality and distance do not influence clinical outcomes in patients with IRDs, suggesting that a centralized healthcare system may help mitigate inequalities in access to care. However, age, male sex, and comorbidity burden remain key negative determinants, underscoring the importance of early identification of high-risk patients and the adoption of integrated management strategies.
PO:28:116 | Glandular involvement in autoimmune diseases: a spectrum of differential diagnosis
Background. Sarcoidosis is a multisystem disease of unknown etiology, characterized by the presence of non-necrotizing granulomas in multiple organs. It is a clinical condition capable of mimicking several disorders. For an accurate differential diagnosis, histopathological examination of the affected organ is crucial, in addition to clinical, radiological, and laboratory findings. Case Report. We report the case of a patient with a suspected IgG4-related disease in a differential diagnosis of sarcoidosis. A 25-year-old Pakistani male, smoker, and stable worker was referred to rheumatologic evaluation in January 2025 for progressive, painless, bilateral periorbital and parotid swelling that had developed since November 2024. Ophthalmologic examination and subsequent orbital MRI confirmed the presence of bilateral glandular hypertrophy. The patient denied any infectious episodes preceding symptom onset. His past medical history included only a left-sided Bell’s palsy with lagophthalmos in 2021, occurring after the first dose of the SARS-CoV-2 vaccine, which resolved after a short course of corticosteroids. At the presentation, he denied dry cough, dyspnea, fever or low-grade fever, arthritis/arthralgia, visual impairment, erythema nodosum, cutaneous lesions, or gastrointestinal symptoms. Physical examination revealed painless swelling of the parotid, submandibular, and lacrimal glands, associated with conjunctival hyperemia and lagophthalmos. Palpable, non-tender, mobile lymph nodes were noted in the right retroauricular and left laterocervical regions; no joint inflammation was detected. Given the suspicion of an IgG4-related disease, hospital admission was planned. During hospitalization, the patient underwent • Laboratory tests: ESR 45 mm/h, CRP 0.5 mg/dL, ACE 66 U/L, severe vitamin D deficiency (<4 ng/mL), PTH 36.3 pg/mL; normal serum calcium, phosphate, and 24-hour urinary calcium (145.2 mg). The patient's IgG subclasses were within normal limits, and both autoimmune and infectious serologies were negative. • Whole-body FDG-PET: Increased radiotracer uptake in bilateral parotid glands, bilateral hilar and peribronchovascular regions, and ocular bulbs. • Abdominal ultrasound: Unremarkable. • Ocular immunology evaluation: There were no signs of granulomatous uveitis. Empirical treatment with oral prednisone (50 mg daily) was initiated. Subsequently, a biopsy of the left parotid gland was performed, showing a fibroinflammatory process with granulomas containing small necrotic foci, consistent with sarcoidosis. Chest CT revealed multiple peribronchovascular pulmonary nodules and hilar-mediastinal lymphadenopathy. A diagnosis of sarcoidosis involving the lacrimal and parotid glands, lymph nodes, and pulmonary parenchyma (Stage II) was therefore established. Corticosteroid therapy (prednisone 0.5 mg/kg/day) was maintained, and methotrexate 20 mg weekly was added as a steroid-sparing agent. At follow-up in March 2025, a marked clinical improvement was observed, with significant reduction of parotid and lacrimal gland swelling. This case highlights the importance of an appropriate differential diagnosis among granulomatous diseases and the pivotal role of histopathological confirmation in establishing a definitive diagnosis.
PO:28:126 | Effectiveness of the new AMEL system in the treatment of simple painful shoulder syndrome
Background. The term "shoulder periarthritis" refers to a group of conditions with a mixed degenerative-inflammatory pathogenesis and predominantly microtraumatic etiology, affecting the periarticular tendon structures (rotator cuff and long head of the biceps) and the subacromial bursa. Depending on the anatomical-pathological characteristics and anatomical location of lesions, different clinical pictures can occur. These syndromes are typically unilateral, with symptoms dominated by pain and restricted mobility. Among the various types of shoulder periarthritis, simple painful shoulder (SDs) is the expression of a small tendon lesion affecting the rotator cuff and characterized by the prevalence of the painful component over the limitation of joint motion. The analgesic-therapeutic efficacy and tolerability of Extremely Low Frequency (ELF) electromagnetic fields—modulated at a frequency of 100 Hz with a sinusoidal waveform and average induction of a few gauss—have been demonstrated in numerous studies conducted on various hyperalgesic pathologies, particularly of the musculoskeletal system. Materials and Methods. In this research, the authors evaluated a new type of pulsed magnetic field (PEMF) developed by AMEL, with frequency variation, whose frequency changes over time so that all permitted codes can be used during a single application. They compared it with a ELF field, a low-frequency magnetic field. For the purposes of comparison, 60 patients (28 females and 32 males), aged 37-66 years and diagnosed with simple shoulder pain, were enrolled. They were randomly divided into three groups of 20 subjects each and underwent treatment for 30 minutes per day for 20 days. One group was exposed to the AMEL PEMF, another to the ELF field, and a third to sham treatment. The sham field was included to rule out a placebo effect. Pain intensity and shoulder joint function were assessed before treatment, immediately after treatment, and at 30-day follow-up. Results. Patients treated with the AMEL PEMF and the ELF field completed therapy without adverse effects or the need for analgesic or anti-inflammatory medications. Both groups showed significant improvement in subjective pain and functional outcomes, which persisted at one-month follow-up. The sham group showed no significant changes. Notably, patients in the AMEL PEMF group exhibited a faster clinical response. Conclusions. It is well known that exposure to PEMFs has analgesic effects and has been introduced in the treatment of pain, and our preliminary study appears to support these findings. Based on the data collected, pulsed electromagnetic fields appear to be effective in the treatment of simple painful shoulders. The effects of the new AMEL PEMF system, due to its tolerability and absence of adverse effects, may be suitable for use in various pain-related conditions, pending confirmation by larger-scale studies.
PO:28:127 | Efficacy of b/ts-DMARDS therapy on depressive and anxiety symptoms in patients with chronic inflammatory joint diseases: preliminary results of a prospective study
Background. Depression and anxiety frequently co-occur in chronic inflammatory diseases, with a prevalence of up to 20% in psoriatic arthritis. These patients may experience an increased risk of depression due to the influence of chronic pain and limitations in daily activities. In addition to the psychological effects of chronic illness, new research shows that systemic inflammation may directly cause anxiety and depression through neuroinflammatory pathways involving pro-inflammatory cytokines like TNF-alpha, IL-1beta, IL-6, IL-8, IL-17, and IL-23. The aim of the study is to evaluate the effect of b/ts-DMARDs therapies on anxiety-depressive symptoms and their relationship with disease activity. Materials and Methods. We present a prospective single-center longitudinal study on a cohort of patients with psoriatic arthritis, rheumatoid arthritis, or axial spondyloarthritis starting b/ts-DMARDs therapy, either as first-line or subsequent treatment. Patients were assessed at baseline (T0) and at 3 months (T3) using HAQ, SF-36, SAS, and BDI, self-report questionnaires for functional disability, quality of life, and anxious and depressive symptoms. We will integrate the currently available data, which represent preliminary 3-month results, with ongoing follow-up. Statistical analyses included comparisons between T0 and T3, correlations between changes in psychometric scores and clinical and functional parameters, as well as analysis of the influence of sex, antidepressant use, and drug class administered. Results. A total of 37 patients were included (mean age 54.9 ± 15.1 years; 75.7% women). At 3 months, patients experienced a mean worsening in BDI score (+3.22, SD 8.01) and SAS score (+1.94, SD 5.83), while their HAQ score improved (-0.24, SD 0.43). No significant differences were found in BDI, SAS, or HAQ score changes based on sex or antidepressant therapy. However, patients treated with antidepressants showed a mean reduction in SAS (-2.33) compared to an increase in untreated patients (+2.38), a clinically relevant but not statistically significant finding (p = 0.19). HAQ improved more in patients with lower disease activity (SDAI) (r = -0.55, p = 0.0127). Changes in BDI and HAQ were significantly associated with perceived emotional limitations in daily activities (SF-36 "Role Emotional Limits," r = 0.49, p = 0.0049). Conclusions. In the first 3 months of b/ts-DMARDs therapy, an improvement in functional disability is observed, but no benefit on anxiety-depressive symptoms, which in fact tend to worsen. This may reflect patients' disappointment with a clinical response perceived as incomplete, especially when chronic pain persists from sequelae, osteoarthritis, or fibromyalgia, often indistinguishable from inflammatory pain. It is therefore evident the importance of properly communicating realistic therapeutic goals to patients and integrating psychosocial support in the management of chronic inflammatory joint diseases.
PO:29:138 | Cetylated fatty acids and fibromyalgia: efficacy and tolerability in a prospective study
Background. Fibromyalgia (FM) is a syndrome characterized by chronic widespread pain, fatigue, sleep disturbances, and cognitive impairment, in the absence of organic lesions. It is often associated with comorbidities such as headache, anxiety, irritable bowel syndrome, hypothyroidism, and endometriosis. (1) Currently classified among central sensitization syndromes, FM is thought to be sustained by dysfunction in nociceptive processing within the central nervous system. (2) Given the lack of a universally effective therapy and the limited tolerability of conventional pharmacological agents in many patients, there is growing interest in the use of nutraceutical supplements as adjunctive treatment. Among these, cetylated fatty acids (CFAs)—natural lipophilic esters of fatty acids and cetyl alcohol—have been reported to exhibit excellent tolerability and potential analgesic properties. (3)(4) It has been further hypothesized that such effects may, at least in part, be mediated through modulation of the endocannabinoid system, specifically via inhibition of monoacylglycerol lipase (MAGL), resulting in increased levels of 2-arachidonoylglycerol (2-AG) and subsequent activation of CB1 and CB2 receptors. (5) Materials and Methods. The study enrolled a total of 45 patients with fibromyalgia (FM), diagnosed according to the 2016 ACR/EULAR criteria (14 males, 31 females; mean age: 54 years). All participants received one stick per day of cetylated fatty acids (Lipocet®) for a duration of 60 days. The following outcome measures were evaluated: – Visual Analog Scale (VAS) for pain; – Fatigue Severity Scale (FSS); – Health Assessment Questionnaire (HAQ). Assessments were conducted at baseline (T0), after 40 days of treatment (T1), after 60 days of treatment (T2), and 30 days following treatment discontinuation (T3). Results. The analysis revealed a significant reduction in VAS and FSS scores between T0 and T1, as well as between T1 and T2. HAQ scores showed a significant improvement from T1 to T2. Following treatment discontinuation (T3), no statistically significant worsening was observed, and all parameters remained improved compared with baseline. Importantly, no patient discontinued treatment due to intolerance or adverse effects. Conclusions. Cetylated fatty acids demonstrated clinically relevant effects in reducing pain and muscle fatigue, with a concomitant improvement in quality of life among patients with fibromyalgia. The therapeutic benefit emerged within the initial weeks of treatment and persisted, at least partially, following treatment withdrawal. Considering their favorable safety and tolerability profile, and the absence of treatment-limiting adverse events, Lipocet® may be regarded as a promising complementary strategy within the multimodal management of fibromyalgia, particularly in individuals with suboptimal response or poor tolerability to conventional pharmacological therapies.
PO:29:139 | Modulation of autonomic dysfunction in fibromyalgia through auricular vagal nerve stimulation: preliminary results
Background. Fibromyalgia is frequently associated with dysautonomia, including orthostatic intolerance and impaired vascular tone, contributing to symptom chronicity and poor therapeutic response. Transcutaneous auricular vagus nerve stimulation (tVNS) has emerged as a novel strategy to modulate autonomic pathways and restore vagal balance. This pilot study explored the short-term effects of tVNS on autonomic function in fibromyalgia using the Nurosym® device. Materials and Methods. Twenty-five women (mean age 48.6 ± 7.3 years) with fibromyalgia (ACR 2016 criteria) underwent 56 self-administered tVNS sessions over 28 days. The intervention consisted of 30-minute stimulations twice daily via electrodes on the auricular tragus. Autonomic function was assessed using the COMPASS31 questionnaire; symptom severity was measured by the FIQR. Paired comparisons (T0 vs T1) were conducted using t-tests or Wilcoxon tests, with effect sizes reported as Cohen’s d. Results. tVNS significantly improved the overall COMPASS31 score (49.5 ± 9.2 vs 43.1 ± 8.8; p = 0.019, d = 0.68). The orthostatic domain showed the strongest improvement (p = 0.016), and a favorable trend emerged in the vasomotor domain (p = 0.05). These changes suggest enhanced autonomic regulation, particularly of cardiovascular homeostasis. Changes in COMPASS31 did not significantly correlate with FIQR scores (r = 0.21), possibly due to the short treatment duration or the dissociation between autonomic and subjective symptom modulation. Conclusions. These preliminary findings support the role of tVNS as a promising non-pharmacologic intervention to target dysautonomia in fibromyalgia. The rapid improvement in objective autonomic parameters—particularly orthostatic function—highlights the potential of vagal modulation in addressing one of the disorder’s core pathophysiological components. Further studies with larger samples and longer follow-up are warranted.
PO:29:141 | Assessing psychosomatic diagnoses and psychological distress in patients with fibromyalgia. The clinical utility of a multidisciplinary approach
Background. Fibromyalgia is a central sensitization syndrome characterized by chronic widespread musculoskeletal pain associated with fatigue, sleep disturbances, cognitive impairment, psychological difficulties, and somatic and neurovegetative symptoms. It affects approximately 2–8% of the general population, with a higher prevalence among females. It is a functional disorder, given the lack of biological markers for diagnosis. The aim of the present study was to evaluate whether a multidisciplinary assessment which includes tools to evaluate mental disorders and psychological distress in fibromyalgia might be associated with psychosomatic syndromes and whether the occurrence of psychosomatic syndromes may influence patients’ psychological distress and functioning. Methods. We assessed 151 patients with fibromyalgia who were attending the Rheumatology Unit of the Academic Hospital Careggi in Florence, Italy. A clinical psychologist evaluated psychosomatic syndromes by administering the Revised Semi-Structured Interview for Diagnostic Criteria for Psychosomatic Research (DCPR-R-SSI). Psychological distress, psychological well-being, mental pain and perceived loneliness were evaluated via self-report questionnaires: Symptom Questionnaire (SQ), PsychoSocial Index (PSI), World Health Organization-Five Well-Being Index (WHO-5), Mental Pain Questionnaire (MPQ), and UCLA Loneliness Scale (UCLA). Results. The sample included 143 females and 7 males, with a mean age of 54.23 ± 12.63 years. Most participants had a partner (62.7%) and were employed (58.6%). Nearly all patients (94%) presented at least one psychosomatic syndrome. Patients with three or more psychosomatic syndromes showed significantly higher levels of anxiety, somatization, depression, anger–hostility, psychological distress, abnormal illness, mental pain, and perceived loneliness (p < 0.05), along with lower levels of psychological well-being (p < 0.05). Conclusions. Psychosomatic syndromes in patients with fibromyalgia worsen the psychological distress, impair perceived well-being and complicate the clinical picture. These findings highlight the importance of a multidisciplinary assessment that considers psychosomatic aspects to enable a comprehensive evaluation of the patients.
PO:29:144 | Refractory localized pain in fibromyalgia and the importance of differential diagnosis: two cases of Bertolotti’s syndrome and avascular necrosis successfully treated with targeted therapy
Background. Fibromyalgia (FM) is a chronic widespread pain condition associated with multiple and heterogeneous systemic manifestations. It is currently regarded as a paradigmatic example of nociplastic pain, specifically a pain not attributable to direct nociceptive stimuli or neuropathic mechanisms, but rather to altered pain modulation processes due to peripheral and central sensitization (hyperalgesia and allodynia). FM may therefore present as a primary condition or coexist with other disorders that can influence its onset, course, and activity. We report two clinical cases of patients with refractory FM in whom an comprehensive diagnostic assessment revealed underlying osteoarticular disorders that responded to targeted treatment, leading to overall symptomatic improvement. Materials and Methods. The first patient, a 27-year-old woman diagnosed with FM two years earlier (according to the 2016 ACR/EULAR criteria: WPI 9, SSS 11) and with concomitant endometriosis and spasmophilia, complained of mixed low back pain poorly responsive to conservative therapy (amitriptyline, NSAIDs, neurotrophic supplements) and rehabilitation. Lumbosacral MRI revealed a left-sided L5 hemisacralization with hypertrophic transverse process articulating with the sacral ala (Castellvi type IIa), associated with subchondral bone marrow edema—findings consistent with Bertolotti’s syndrome (a lumbosacral transitional anomaly causing chronic low back pain). Intravenous neridronate treatment was initiated (100 mg per infusion, 4 infusions over 12 days). The second patient, a 73-year-old woman with a five-year history of FM (2016 ACR/EULAR criteria: WPI 8, SSS 10) under duloxetine therapy, presented with right hip pain initially attributed to myofascial iliopsoas syndrome in an osteoarthritic context. After failure of local infiltrative therapy, MRI demonstrated early avascular necrosis of the femoral head with subchondral bone edema. Combined treatment was started with intravenous neridronate and hyperbaric oxygen therapy (28 consecutive daily sessions). Results. In the first patient, pain intensity decreased from 8 to 4 on the VAS scale, with reduced need for NSAIDs and overall improvement in diffuse pain symptoms. In the second patient, VAS pain decreased from 8 to 5, with reduction in nocturnal pain, hyperalgesia, and allodynia, and partial resolution of bone marrow edema. A second combined treatment cycle was planned. Conclusions. These cases highlight the importance of a complete differential assessment in fibromyalgia patients presenting with refractory localized pain. The identification of coexisting structural conditions, as in the cases reported, can provide specific therapeutic targets, contributing to symptomatic improvement and better control of central sensitization. An integrated clinical approach—combining fibromyalgia diagnosis with the detection of concomitant somatic pathologies—represents a key strategy to optimize outcomes in patients with complex chronic pain.
PO:29:145 | Fibromyalgia in idiopathic inflammatory myopathies: is it time for rheumatologists to investigate it?
Background. Fibromyalgia (FM) is a complex syndrome characterised by chronic pain, fatigue and functional symptoms; it is often accompained by mood disorders. FM affects, on average, 2.3% of the European population with a profound impact on both physical and social aspects of quality of life (QoL). FM is known to be a frequent comorbidity in Connective Tissue Diseases (CTDs). Few data are available at present about the prevalence of FM in Idiopathic Inflammatory Myopathies (IIMs) and about the profile of IIM patients with FM. The objective of the study was to determine the prevalence of FM in a monocentric cohort of IIMs patients, evaluating possible correlations with clinical features, disease activity and parameters of QoL. Materials and Methods. We retrospectively analyzed medical records of consecutive patients diagnosed with IIM according to the EULAR/ACR 2017 criteria and regularly followed at our specialistic outpatient Myositis Clinic. We collected data about demography, subset and disease duration, organ involvement, autoantibody profile and comorbidities. Patients’ QoL was investigated through the following Patient Reported Outcomes (PROs): Short Form 36 (SF36), Hospital Anxiety and Depression Scale (HADS), Health Assessment Questionnaire (HAQ). The diagnosis of FM was confirmed following the 2016 American College of Rheumatology Fibromyalgia Diagnostic Criteria. Intergroups comparisons were assessed by using Chi-square, t-test and ANOVA. P values <0.05 were considered significant. Results. A total of 184 patients were enrolled, 119 (64,7%) female, with a mean age of 66,5±11.2 years and a mean disease duration of 9.9±5.2 years. Twenty-three patients (12,5%) had FM, all of them were female. Taking into account epidemiological and clinical characteristics of patients, a diagnosis of FM was significantly associated with female sex (p<0.001), muscular involvement (p=0.015), lung involvement (p=0.036), sicca syndrome (p=0.004). Regarding comorbidities, a significant correlation was highlighted between FM and obesity (p=0.024), osteopenia (p=0.026) and thyroid dysfunction (p=0.05). PROs analysis showed patients with FM had significantly higher values of HAQ (p=0.005) and significantly lower values on different items of SF36 (Physical Function p=0.019, Bodily Pain p=0.006, Vitality p=0.026). Conclusions. Our data showed, as expected, that the prevalence of FM in IIMs patients was higher than in the general population and similar to that of other CTDs (4,5). Moreover, these results confirm the deep relationship between FM and both female gender, sicca syndrome and thyroid dysfunctions. However, they also showed a higher risk of FM in IIMs patients with muscle or pulmonary involvement, or with a reduced bone mineral density, or in obese patients. PROs’ analysis confirmed a significant impact of FM on both physical and mental outcomes of IIM patients. Although preliminary, these results could help rheumatologists in profiling the characteristics of FM patients in IIMs in their routinary assessment, thus aiming at improving the management of this potentially disabling condition.
PO:30:151 | Clinical characteristics and evolution of juvenile undifferentiated connective tissue diseases: results of a single-center study
Background. Juvenile undifferentiated connective tissue diseases (UCTD) represent a heterogeneous clinical entity characterized by symptoms suggestive of connective tissue disease without meeting the classification criteria. Currently, epidemiological and prognostic knowledge about the pediatric population is limited, with implications for clinical and therapeutic management. The aim of our work is to describe the clinical and serological characteristics of a single-center cohort of patients with juvenile UCTD, evaluating the clinical course and potential evolution toward defined connective tissue diseases. Materials and Methods. We conducted a retrospective study on 33 patients diagnosed with juvenile UCTD who were followed at our center from 2006 to 2025. Inclusion criteria: age 16 years or less at onset, disease duration of at least 12 months, at least one clinical sign suggestive of connective tissue disease, and positivity in at least two ANA or ENA tests. Demographic, clinical, serological, capillaroscopic, and therapeutic data were collected. Results. The demographic and clinical characteristics are shown in Table 1. All patients tested positive for ANA. In 7 patients, ANA negativity was observed at a mean follow-up of 12 months, associated with lower ESR values (p<0.01) and a reduced presence of other antibodies (ENA, aPL, anti-dsDNA) (p=0.003). 3 of these patients had a scleroderma pattern at baseline; In one case, the pattern remained stable, in another it regressed to a borderline pattern, and in the third to non-specific abnormalities. During a median follow-up of 36 months (18-49 months), 5 patients (15.2%) progressed to defined connective tissue disease: 2 cases of SS, 1 case of SLE, 1 case of Sjögren's syndrome, and 1 case of anti-Jo1+ myositis. These patients had an earlier onset age (12 years vs 14.5 years), were positive for ENA, anti-dsDNA, or aPL in 4 out of 5 cases, and showed capillaroscopy alterations in 3 cases (2 scleroderma patterns and 1 non-specific abnormalities). Hydroxychloroquine was used in 22 patients, with all showing at least a 50% improvement in symptoms, and only one experiencing a mild side effect (headache). Other therapies used were: corticosteroids (8 patients), methotrexate (6), calcium channel blockers (5), and topical vasodilators (8). Conclusions. We observed a high prevalence of skin manifestations, Raynaud's phenomenon, and inflammatory arthralgia. 15.2% of cases developed a defined connective tissue disease, confirming the risk of progression. Capillaroscopic anomalies, a young age of onset, and the presence of other antibodies beside ANA could be associated with a higher risk of progression. Patients with isolated ANA positivity showed a generally favorable course, higher rates of negativity, and improvements in capillaroscopy in most cases. Hydroxychloroquine has been shown to be well-tolerated and potentially useful. Prospective studies are needed to validate these results and identify patients at risk of progression early on.
PO:30:160 | A rare case of juvenile systemic sclerosis
Juvenile Systemic Sclerosis (jSSc) is a rare, autoimmune connective tissue disease with onset in the pediatric age; the pathogenesis appears to be mediated by adaptive immunity, with autoantibody production, endothelial dysfunction, proliferative vasculopathy leading to ischemia and tissue fibrosis with variable involvement of the skin and internal organs.1,2 The average age at diagnosis in the pediatric age is between 8 and 12 years, with a clear female prevalence. Compared to the adult-onset form, pulmonary involvement is more common and severe in juveniles, while renal involvement is less frequent.3,4 We present the rare case of a 16-year-old female patient with rapidly progressive diffuse cutaneous jSSc. The disease began in 2019 at the age of 11 with Raynaud’s phenomenon leading to digital ulcers. Physical examination revealed puffy hands and cutaneous fibrosis (J4S equal to 12.5/40). Thoracic auscultation showed normal vesicular breath sounds, no crackles. Serological tests showed ANA positivity at a titer of 1:1280 and anti-Scl70 antibodies. Capillaroscopy in 2023 showed a scleroderma pattern; the punch skin biopsy in 2022 showed dermal and hypodermal sclero-hyalinosis (score 2), mild perivascular and periannexal inflammatory infiltrate (score 1), and annexal atrophy (score 1), compatible with scleroderma. Pulmonary Function Tests (PFTs) in 2024 revealed moderate-to-severe restrictive syndrome (FVC 65%, FEV1 68%, DLCO/Va 94%.) and initial signs of fibrosis on 2024 thoracic HRCT (interlobular septal thickening <5%, ground-glass areas, emphysema, bronchiectasis not present on HRCT in 2021). Due to the relapsing nature of the digital ulcers, therapy was started with intravenous prostanoids and bosentan, with good control of the lesions. The patient was treated with rituximab every six months (2019–2023) then suspended due to recurrent infections, then with methotrexate (2019–2020 suspended due to ineffectiveness, resumed in 2023 and suspended in 2024 due to hypertransaminasemia). She is currently on therapy with mycophenolate mofetil (started in 2024, 600 mg/m2 twice a day), bosentan 125 mg/day since 2023, prednisone (5 mg/day), nifedipine as needed, gastroprotection, and monthly iloprost during the winter months. Despite the progressive nature of the disease, a reduction in recurrent trophic ulcers, improvement in cutaneous trophism, and a reduced progression of pulmonary fibrosis were noted, with improvement in semiannual Pulmonary Function Tests (2023 DLCO/Va 64%, FVC 56% - 2024 DLCO/Va 104%, FVC 65%). jSSc is a rare and complex disease. The scarcity of specific data in the pediatric population makes greater clinical characterization urgent to define targeted therapeutic strategies.
PO:31:163 | Safety and tolerability of home-based prostacyclin analogue therapy in vascular manifestations of the scleroderma spectrum: results of a monocentric study
Background. To evaluate the safety and perceived efficacy of home-based prostacyclin analogue infusions compared with hospital administration in patients with vascular manifestations of the Scleroderma Spectrum. Methods: In 2019, a pilot program for home-based Iloprost infusions was launched at the Local Health Authority (ASL) of Pescara. We performed a retrospective 6-year analysis including patients receiving home therapy for at least 6 months. Patients completed a structured questionnaire assessing: • frequency of vascular manifestations, • comparison between home (EL) and hospital (DH) administration in terms of side effects, • acceptability and overall impact of home treatment. Blood pressure values were collected before, during, and after each home infusion. Results. Thirty-four patients were included. Most reported subjective improvement of Raynaud’s phenomenon. A moderate positive correlation (ρ ≈ 0.47) was observed between the duration of home treatment and perceived benefit. Among the 5 patients with active digital ulcers, 4 reported improvement. Only two patients had pulmonary arterial hypertension; therefore, no conclusions were drawn for this subgroup. Eight side effects were evaluated on a 0–3 scale. Nausea, flushing, and headache were significantly reduced during home treatment (p < 0.05), while hypotension and diarrhea showed no significant differences. Elastomer pump acceptability was high: 100% of patients judged it easy to handle, 97% felt safe using it, and 88% reported improved quality of life. Regarding hemodynamic effects, systolic blood pressure showed a significant reduction during infusion (−4.6 mmHg; p = 0.0015) followed by recovery afterwards (+3.1 mmHg; p = 0.011). Diastolic pressure changes were milder, with a slight decline during infusion (−1.5 mmHg; p = 0.083) and a significant increase at the end (+2.8 mmHg; p = 0.026). Mean arterial pressure varied transiently and was well tolerated. Only one patient showed marked variability, suggesting the need for individualized monitoring in unstable cases. Conclusions. Home-based prostacyclin analogue infusions appear safe, well tolerated, and associated with high patient acceptance in the Scleroderma Spectrum. These findings support the implementation of home Iloprost therapy as an integral component of vascular management in this population.
PO:31:165 | Prevalence and incidence of skin telangectasia and their association with clinical features: analysis of the European Scleroderma Trials and Research cohort
Background. Skin telangiectasias (TAs) are common in systemic sclerosis (SSc) and suggested to be associated with a more severe vascular phenotype. The aim of our work was to analyse prevalence and incidence of TAs in a SSc multicentric cohort and their clinical correlations. Materials and Methods. SSc patients from the European Scleroderma Trials and Research (EUSTAR) database with baseline data on TAs were enrolled to analyse the prevalence and TAs and their clinical correlations (project CP156). During the follow-up we evaluated the incidence of TAs and compared disease features between patients with TAs from baseline, those developing TAs during the follow-up and those without. Results. A total of 8.088 patients with baseline data on TAs, of whom 4.050 presented TAs with a prevalence of 50.1% (IC 0.49-0.51). At baseline patients with TAs showed significant differences in disease phenotype compared to those without (Fig 1): a greater skin involvement (8.3±8.6 vs 7.0±7.8, p:<0.0001) and higher mean NT-proBNP values (456.4±1833.7 vs 304.4±2114.0, p:<0.0001) were observed in patients with TAs that also presented higher frequency of anticentromere antibodies (ACA) and lower prevalence of anti-topoisomerase I (Topo I) (p<0.0001 and 0.0278 respectively). Puffy fingers were more frequent in patients with TAs (1747 vs 1573, p:0.0147) and a significantly higher prevalence of digital ulcers (DUs) and digital pitting scars (DPS) (current or previous) was observed in TAs patients. The mean values of DLCO and DLCO/VA were lower in SSc patients with TAs (67.8±20.3 vs 73.8±20.5 and 76.3±18.3 vs 82.2±17.8 respectively, p<0.001) that also presented a higher frequency of ILD at HRCT (1293 vs 1017, p:<0.001). Echocardiographic abnormalities were more prevalent in TAs patients. The incidence of TAs was of 32.6% (IC 0.31-0.34) in a median observation time of 1.61 years (1.50-1.74) (Figure 2). The median follow-up time was of 1.02 years (0.701-1.56) for patients with TAs from baseline (group1: 4050 patients), 1.61 (1.01-3.01) for those developing TAs (group2: 1313 patients) and 2.78 (1.29-5.15) for those without TAs (group3: 2716 patients). Comparing disease features between the three populations at the end of follow-up we confirmed some of the data reported at baseline (Fig 3): patients with TAs from baseline or developing TAs during the follow-up had a more sever skin involvement, a greater prevalence of DUs, DPS, subcutaneous calcinosis, tendon friction rubs, joint involvement, ILD and also at the end of follow-up they presented lower LFTs parameters. Conclusions. Our data clearly show that TAs are associated with a more aggressive SSc phenotype from both a cardiovascular and pulmonary point of view. Our data have to be confirmed by future studies also evaluating whether the presence of TAs represents a risk factor for the development of organ complications.
PO:31:166 | S'/PAPs ratio in systemic sclerosis: a promising non-invasive index for early detection and prognosis of pulmonary hypertension. A step toward more accurate screening?
Background. Pulmonary hypertension (PH) is a severe and multifactorial complication in systemic sclerosis (SSc), with right ventricular (RV) involvement playing a pivotal prognostic role. Echocardiography remains the cornerstone for PH screening and monitoring. However, traditional indices such as TAPSE are limited by geometric assumptions, angle dependency, and operator variability. The systolic velocity of the tricuspid annulus measured by tissue Doppler imaging (TDI S') has emerged as a more accurate and reproducible parameter. Based on this, the S'/PAPs ratio—reflecting RV-arterial coupling—has been proposed as a valuable non-invasive tool for early detection and risk stratification in SSc-related PH. Nevertheless, clinical data in this specific setting are still scarce. Materials and Methods. A retrospective/prospective analysis was conducted on 200 SSc patients followed at the Scleroderma Unit of the University Hospital of Modena between 2020 and 2025. Among them, 19 had a confirmed diagnosis of PH based on hemodynamic criteria. Collected data included clinical, echocardiographic, respiratory, serological variables and outcomes. The main objective was to evaluate the diagnostic performance of the S'/PAPs ratio, identifying a reliable cut-off and comparing it with the established TAPSE/PAPs <0.55 threshold. Associations between S'/PAPs and patient characteristics were also explored. Results. ROC curve analysis identified five S'/PAPs cut-offs (0.328, 0.34, 0.36, 0.38, 0.40). For each, sensitivity, specificity, positive/negative predictive values, accuracy, likelihood ratios (LR positive/LR negative), and Youden index were calculated. The 0.40 cut-off demonstrated the best diagnostic performance, outperforming TAPSE/PAPs <0.55 in sensitivity (89% vs 74%), NPV (98% vs 97%) and LR negative (0.14 vs 0.26). Patients with S'/PAPs <0.40 showed worse clinical and echocardiographic profiles: older age (p=0.001), older age at diagnosis (p=0.038), higher prevalence of limited cutaneous subset (p=0.035), systemic hypertension (p=0.0001), reduced DLCO_Sb (p=0.041), lower 6-minute walk distance (p=0.001), and higher BNP levels (p=0.052). ECG abnormalities were also more frequent (right bundle branch block, p=0.005; atrial fibrillation/SVT, p=0.004), as well as pathognomonic echocardiographic signs of PH. Mortality and cardiovascular events during follow-up were significantly higher in the S'/PAPs <0.40 group (p=0.003). Conclusions. The S'/PAPs ratio is a simple, reproducible, and sensitive index for non-invasive assessment of RV function and afterload in SSc. A cut-off of 0.40 demonstrated superior diagnostic performance over TAPSE/PAPs, particularly in sensitivity and NPV, making it useful to rule out PH. The prospective analysis is ongoing to confirm the promising role of S’/PAPs ratio in SSc associated PH, in order to improve screening algorithm specificity, sensitivity and NPV and to reduce the number of referrals for right heart catheterization.
PO:31:167 | Increased M2 pro-fibrotic marker expression in circulating monocytes and cultured monocyte-derived macrophages in systemic sclerosis patients with progressive interstitial lung disease
Background. Systemic sclerosis (SSc) is a complex disease in which macrophages play a key role in driving progressive fibrosis of the skin and internal organs, especially the lungs1,2. Alternatively activated macrophages (M2) seem to promote fibrosis by releasing pro-fibrotic mediators3. Previous studies have identified M2 macrophages expressing pro-fibrotic markers, including hybrid M1/M2 cells expressing toll-like receptor 4 (TLR4), in lung tissues from SSc patients with interstitial lung disease (ILD)3. The aim of the study is to evaluate the phenotype and functional M2 markers in circulating monocytes and cultured monocyte-derived macrophages (MDMs) obtained from SSc patients (pts) with progressive ILD (prog-ILD), versus non-progressive ILD (no-prog-ILD), and without ILD (no-ILD). Materials and Methods. A total of 56 SSc pts, diagnosed per 2013 ACR/EULAR criteria, and 20 age-matched healthy controls (HC) were recruited with informed consent. Circulating monocytes from a subset of 37 SSc patients (10 prog-ILD, 14 no-prog-ILD, 13 no-ILD; mean age 65±13) and 20 HC were analyzed by flow cytometry for expression of M2 markers (CD204, CD163, CD206) and the M1 marker (TLR4). MDMs were generated from 29 SSc patients (13 prog-ILD, 10 no-prog-ILD, 6 no-ILD; mean age 64±14) and 5 HC, and evaluated for gene and protein expression of the same markers using RT-PCR, Western blotting, and ELISA for TGF-beta1 and Mer tyrosine kinase (MerTK). Statistical analyses employed non-parametric tests. Results. Prog-ILD SSc pts showed a higher percentage of hybrid (M1/M2) circulating TLR4+CD204+CD206+CD163+monocytes compared to no-prog-ILD and significantly higher compared to no-ILD SSc pts (p<0.05). Cultured MDMs from prog-ILD pts had significantly increased gene and protein expression of TGF-beta1 (p<0.05), and a trend toward elevated MerTK and CD206 levels compared to no-prog-ILD pts. When compared to no-ILD patients, prog-ILD MDMs showed significantly elevated expression of TGF-beta1, TLR4, and all evaluated M2 markers (p<0.05), with MerTK particularly elevated (p<0.01). Conclusions. Results highlight that SSc pts with ILD, particularly prog-ILD, exhibit an increased proportion of circulating monocytes with a hybrid M1/M2 phenotype and elevated expression of pro-fibrotic markers. Their derived macrophages also show heightened TGF-beta1 and MerTK levels. These findings suggest that TLR4+M2 monocytes and TGF-beta1-expressing macrophages may serve as potential biomarkers of progressive ILD in SSc.
PO:31:172 | Age and timing of onset of Raynaud's phenomenon and first non-Raynaud sign/symptom as prognostic factors in systemic sclerosis: a retrospective analysis from the systemic sclerosis progression investigation registry of the Italian Society for Rheumatology
Background. To investigate whether age and timing of Raynaud’s phenomenon (RP) and non-Raynaud’s phenomenon (NRP) onset influence systemic sclerosis (SSc) endotype and prognosis. Materials and Methods. We performed a cross-sectional study including patients from the SPRING Registry, fulfilling the SSc 2013 ACR/EULAR criteria(1). Patients were categorized into 4 groups based on age at RP (age-RP) and age at NRP (age-NRP) onset, according to quartiles’ distribution. Additionally, patients were divided into 3 groups based on RP onset timing:1) RP >1 year after NRP onset (NRP group); 2) RP and NRP within the same year (Simultaneous group, SG), 3) RP >1 year before NRP onset (RP group). Comparisons were performed using Chi-square, ANOVA, logistic, linear, and multinomial regression models. Kaplan-Meier and Cox regression were used to evaluate survival. Results. 1748 SSc patients were eligible for the study: 682 (39%) in the RP group, 1026 (58.8%) in the SG, and 39 (2.2%) in the NRP group. The RP group had a higher prevalence of anti-centromere antibodies (ACA, 41.5%), whereas the SG presented more anti-topoisomerase I antibodies (ATA, 41.1%), diffuse cutaneous SSc (dcSSc, 25.2%), and higher modified Rodnan Skin Score (mRSS) (5, IQR 2–10). The NRP group showed more pulmonary arterial hypertension (PAH, 15.8%) and less dcSSc (5.1%), without a distinct autoantibody profile. Dividing patients by age-RP quartiles, those in the youngest group (18–34 years) had more ATA (42.2%), dcSSc (23.4%), digital ulcers (DU, 29.2%) and digital pitting scars (DPS, 58.2%) while the oldest group (>56 years) had more cardiopulmonary involvement (35.3%) with higher systolic pulmonary arterial pressure (sPAP, 25±18 mmHg). Similar trends emerged with age-NRP stratification. Logistic regression showed that SG was associated with higher dcSSc prevalence vs RP (OR 1.491, 95% CI 1.032–2.154), independently of ATA and sex. Earlier age-RP predicted lower sPAP (beta -0.149, 95%CI: -0,297, -0,001) and mRSS (beta -0.053, 95%CI -0,094, -0,011). Among 943 patients with follow-up (median 24 months), estimated survival was comparable (RP 97%, NRP 95%, SG 94%). However, on multivariable regression, the SG had a significant higher mortality compared to the RP group, independently from patient’s age, sex, disease activity and Charlson Comorbidity Index (HR 1.975; 95%CI 1.002-3.893). Moreover, multinomial regression showed that female sex (OR 2.445, 95%CI 1.052-5.681) and ACA positivity (OR 2.004; 95%CI 1.550–2.597) were associated with the RP group. Older age-RP increased the likelihood of belonging to the NRP (OR 1.067; CI 1.042–1.092) or SG (OR 1.048; 95%CI 1.041–1.056) groups. ATA (OR 1.671; 95%CI 1.295–2.157;) and Anti-RNA Polymerase III Antibody (OR 4.002; 95%CI 1.151–13.914) positivity were linked to higher odds of inclusion in the SG. Conclusions. Timing of RP and NRP onset influences SSc endotype and prognosis. Simultaneous onset is linked to more severe disease and worse survival, highlighting the potential role in patient stratification.
PO:31:173 | Methotrexate monotherapy in early systemic sclerosis: a real-life monocentric Italian experience
Background. Systemic sclerosis (SSc) is a complex autoimmune disease with significant morbidity and mortality. Methotrexate (MTX) is one of the most prescribed immunosuppressants for SSc, particularly in patients with early diffuse cutaneous disease, with prescription rates of 30-50%. However, supporting scientific evidence remains limited. The objective of this study is to evaluate the efficacy of MTX monotherapy on the cutaneous component of SSc using the modified Rodnan Skin Score (mRSS) as the primary parameter. Materials and Methods. A retrospective monocentric study was conducted on patients with SSc treated with MTX monotherapy within the first two years of disease onset. The mRSS, MTX dosage, and prednisone equivalent were collected at baseline and at 3, 6, 12, and 24 months. Cutaneous improvement was defined as a reduction of > or = 5 points or > or = 25% from baseline mRSS. Disease activity was assessed using the EUSTAR Activity Index. Temporal variation was evaluated through analysis of variance (ANOVA) corrected for independent variables. Kaplan-Meier analysis was applied to estimate MTX therapy persistence, and survival curves were censored at MTX monotherapy discontinuation (intolerance, disease progression, combination with an additional drug, pregnancy). Results. The cohort included 92 patients, predominantly female (85%), with a median age of 50.75 years and a median disease duration of 1.08 years at MTX initiation. 77% had diffuse cutaneous SSc (dcSSc), and 72% were Scl70 positive (Table). Linear mixed-model analysis revealed a statistically significant variation in mRSS over time (p < 0.001). Estimated marginal means showed a progressive decline from baseline (9.745) to 24 months (6.603), with the most substantial improvement occurring after 3 months (-1.886), reaching the improvement criterion of > or = 25% (Figure 1). The EUSTAR Activity Index remained stable during follow-up (p = 0.213), consistently staying below the active disease threshold (> or = 2.5) (Figure 2). After two years of follow-up, 47 patients (51%) discontinued MTX monotherapy: 36 (39%) due to disease progression (25 cutaneous, 5 pulmonary, 6 combined) and only 9 (9.78%) due to intolerance. Rituximab was the most frequently added drug (30.43%). MTX persistence was 48.9% at 2 years, with a median survival time of 1.366 years. Patients with limited cutaneous SSc (lcSSc) showed better drug retention (median 1.749 years) compared to dcSSc patients (1.3 years). Figure 3: dcSSc (red line) and lcSSc (blue line). Conclusions. This observational study provides evidence that MTX can be effective as monotherapy in the early treatment of cutaneous SSc, especially in diffuse involvement. The lower persistence in patients with dcSSc likely reflects the more aggressive progression of cutaneous fibrosis and extra-cutaneous involvement that requires escalation to combination therapy.
PO:31:174 | Increased frequency of anti-RNA polymerase 3 antibodies in patients with systemic sclerosis and silicone breast implants: a multicentre study from the international European Scleroderma Trials and Research cohort
Background. Systemic Sclerosis (SSc) is a heterogeneous systemic autoimmune disease, in which distinct disease subsets can be identified with autoantibodies. In a large EUSTAR study including >4,000 SSc patients, anti-RNA polymerase III (anti-RNAP3) was positive in 4.5% and their clinical phenotype included malignancies synchronous to disease onset and specifically breast cancer. Noteworthy, one study from Italy and one from Japan reported a specific association of silicone breast implants (SBI) with anti-RNAP3 positivity in SSc females, raising the possibility of a new clinical association of this autoantibody. The study aims to analyse the characteristics of female SSc patients with SBI implanted before the disease onset, and to compare them with female SSc patients without SBI. Materials and Methods. International case-control study within the EUSTAR network (CP-117), including SSc females with SBI implanted before SSc onset (cases) and 2-3 SSc female patients without SBI (controls) matched for cutaneous subset, age at onset (±5 years) and disease duration (±2 years). Data regarding indication for SBI implantation and rupture (cases) and on breast cancer (cases and controls) were recorded. Results. 41 SSc patients with SBI (cases) and 119 matched controls were collected from 12 centres. Among 41 cases, the majority had SBI implanted for cosmetic reasons (82.9%) and had diffuse cutaneous involvement (dcSSc,58.5%), with anti-RNAP3 positivity in 31.7%. Anti-RNAP3+ patients, as compared to anti-RNAP3- had a tendency toward higher frequency of documented SBI rupture (p:0.089). As compared to 119 matched controls, patients with SBI had higher frequency of anti-RNAP3 positivity (31.7% vs 14.3%, p:0.020, [OR 2.78, 95% CI 1.20-6.42]). No difference in the rate of breast cancer was observed, with no cases of breast cancer synchronous in both groups. Clinical characteristics were similar in cases and controls, except for lower prevalence of clinically relevant arrythmias and higher prevalence of ever smoker in SBI patients (Table1). Interstitial lung disease (ILD) was slightly less frequent in SBI+ (46.3% vs 60.0%,p:0.144) with NSIP being the most frequent pattern in both groups. A tendency toward a better functional outcome in terms of pFVC% at last visit was observed for SBI+ ILD patients (p:0.087). Conclusions. In this multicentre international cohort, patients with SSc and SBI implanted before disease onset showed dcSSc in more than half of cases and had a higher rate of anti-RNAP3 positivity as compared to the expected frequency and to matched controls. SBI were mainly implanted for cosmetic reasons and no cases of synchronous breast cancer were detected in both groups, highlighting that the association with anti-RNAP3 with SBI is independent from the one with breast cancer previously documented. Clinical features were similar to those of matched controls, except for lower prevalence of arrhythmias in cases. Further enrichment of the cohort will allow subgroup analysis of SBI patients.
PO:31:175 | Characterizing gastrointestinal involvement in systemic sclerosis: insights from the national systemic sclerosis progression investigation registry of the Italian Society of Rheumatology
Background. Gastrointestinal (GI) involvement affects over 80% of patients with systemic sclerosis (SSc), contributing significantly to morbidity and representing the third leading cause of disease-related mortality. Symptoms can affect any GI tract segment and often appear early in the disease course. To date, no disease-specific treatment exists, and management remains symptomatic. The underlying mechanisms are not fully understood, and the clinical course is highly variable. This study aimed to identify SSc endotypes associated with GI involvement, determine clinical predictors of GI symptoms, and explore the relationship between disease duration and GI manifestations using data from the SSc Progression INvestiGation (SPRING) registry of the Italian Society of Rheumatology. Materials and Methods. Patients fulfilling the 2013 ACR/EULAR classification criteria and with available GI symptom data were included. GI involvement was defined by the presence of symptoms in at least one of the esophageal, gastric, or intestinal tracts. GI manifestations were classified as “upper GI involvement” (esophageal/gastric symptoms only) or “lower GI involvement” (intestinal symptoms regardless of upper GI symptoms). Chi-square and Student’s t-test were used for descriptive comparisons. Logistic regression was used to identify predictors of GI involvement; ordinal regression assessed predictors of increasing GI disease extent. Results. Among 2178 patients, 1917 met inclusion criteria. Of these, 1073 (56%) reported GI symptoms. Patients with GI involvement had longer disease duration (p<0.001) and more severe disease features, including diffuse cutaneous SSc (dcSSc), interstitial lung disease (ILD), and digital ulcers (DU) (all p<0.001). Autoantibody status, sex, and age were similar across groups. GI involvement increased with longer disease duration, peaking in those with >12 years of disease (62.3%, Figure 1). Logistic regression identified telangiectasias, tobacco exposure, dcSSc, ILD, DU, and longer disease duration as independent predictors of GI symptoms. Patients with more extensive GI involvement (both upper and lower) had higher prevalence of severe disease markers, including dyspnea, lower DLCO, and telangiectasias (all p<0.001, Table 1). Ordinal regression confirmed disease duration, female sex, ILD, DU, dcSSc, telangiectasias, and tobacco exposure as predictors of increasing GI extent. However, in a separate analysis focused on progression from upper to lower GI involvement, only DU, telangiectasias, and anti-centromere antibodies emerged as significant predictors, while disease duration was not. Conclusions. A more severe SSc phenotype is associated with both the presence and the extent of GI involvement. Key independent risk factors include disease duration, dcSSc, ILD, DU, and tobacco exposure. While disease duration plays a central role in the onset of GI symptoms, it does not appear to drive progression from upper to lower tract involvement, suggesting different mechanisms for initiation versus extension of GI disease.
PO:32:176 | Outcomes of upfront combination vs monotherapy with rituximab or mycophenolate mofetil for systemic sclerosis interstitial lung disease: results from a European Scleroderma Trials and Research cohort study
Background. Interstitial lung disease (ILD) is a major complication in systemic sclerosis (SSc) patients as it is associated with increased mortality and significant morbidity. Since combination therapies are foreseen as the future of SSc-ILD management, in this study we aimed to compare the outcomes at 12 months in patients with SSc-ILD treated with RTX alone, MMF alone, or upfront combination therapy (MMF + RTX). Materials and Methods. SSc patients meeting the 2013 ACR/EULAR criteria, with ILD confirmed by chest HRCT and available % predicted FVC (%pFVC) at baseline and 12 ± 3 months, were eligible for inclusion. Patients were grouped based on treatment initiated at baseline: (a) MMF alone, (b) RTX alone, or (c) upfront combination therapy (MMF + RTX). Patients on nintedanib or tocilizumab at baseline were excluded. Inverse probability of treatment weighting (IPTW) was used to adjust for confounding and treatment imbalances, following multiple imputation for missing data. Propensity score models incorporated the following variables: age, gender, disease subset (diffuse vs. limited), autoantibody status (ATA positivity), baseline FVC, and disease duration. Linear mixed-effects models were used to compare the change in %pFVC and DLCO% at 12 ± 3 months across groups. The proportion of patients with ILD progression (FVC decline >5%) was also estimated. Results. A total of 425 patients were included in the final analysis (250 MMF, 154 RTX and 21 combination therapy). At 12 months, FVC remained stable in all treatment groups. In model 1 (MMF vs. combination), the mean change in FVC was 2.28% (95%CI 0.10 — 4.40) for MMF vs 1.83% (95%CI -2.8 — 6.5) for the combination group (mean difference -0.44, 95%CI -5.70 — 4.80, p = 0.867). The mean change in DLCO was -1.35% (95%CI -3.92 — 1.21) for MMF vs -2.05% (95%CI -11.2 — 7.14) for the combination group (mean difference -0.7, 95%CI -10.0 — 8.61, p = 0.882). In model 2 (RTX vs. combination), the mean change in FVC was -0.93% (95%CI -3.29 — 1.43) for RTX vs 1.71% (95%CI -2.97 — 6.41) for the combination group (mean difference 2.65, 95%CI -2.52 — 7.82, p = 0.315). The mean change in DLCO was -0.35% (95%CI -3.48 — 2.78) for RTX vs -1.43% (95%CI -8.6 — 5.73) for the combination group (mean difference -1.08, 95%CI -8.71 — 6.54, p = 0.781). The proportion of patients with ILD progression at 12 months was similar across treatment groups: MMF 29.2% (95%CI 23.3-35.1), RTX 28.1% (95%CI 20.2-36.0), and combination therapy 27.4% (95%CI 5.9-48.8). Conclusions. This EUSTAR cohort analysis does not demonstrate a clear benefit of upfront combination therapy with MMF and RTX over treatment with either agent alone regarding FVC decline at 12 months in SSc-ILD patients.
PO:32:180 | Clinical and hemodynamic profile of patients with SSC-PAH with and without pulmonary veno-occlusive disease: a single-center study
Introduction. Signs of pulmonary veno-occlusive disease (PVOD) may be found in patients with pulmonary arterial hypertension (PAH), particularly in systemic sclerosis (SSc)¹. This association (PVOD/PAH) remains poorly characterized in SSc. We aimed to compare the clinical, echocardiographic and hemodynamic profile of patients with SSc-PAH with and without a concomitant diagnosis of PVOD, and their potential response to vasodilators. Materials and Methods. We retrospectively analyzed 23 patients with SSc-PAH diagnosed by right heart catheterization, followed at our center between 2017 and 2023. Data collected at diagnosis and after 12 months included clinical, laboratory, functional and imaging parameters. Multidisciplinary assessment allowed the identification of cases with clinical and radiological features suggestive of PVOD/PAH¹. Patients were divided into two groups (PVOD/PAH and non-PVOD/PAH) and data were compared at baseline and 12-month follow-up. Results. Twenty-three patients with SSc-PAH were enrolled in the study, of whom 6 (26%) had signs of PVOD/PAH. At PAH diagnosis, PVOD/PAH patients had higher values of mean pulmonary arterial pressure compared to non-PVOD/PAH (47.5±5.3 vs. 36.7±8.8 mmHg, p=0.011), but similar pulmonary vascular resistance. Age, sex, cardiovascular risk factors, SSc features, echo findings as well as cardiac biomarker values were similar between the two groups (Table 1). At follow-up, most PVOD/PAH patients (67%) were on monotherapy with endothelin receptor antagonists (ERA), and 33% on dual therapy (ERA + phosphodiesterase inhibitors). Only one case of pulmonary edema was recorded. In the non-PVOD/PAH group, most patients (53%) were on dual vasodilator therapy. On echocardiography, PVOD/PAH patients showed higher tricuspid regurgitation velocity (4.10±0.68 vs. 3.07±0.91 m/s; p=0.035) and worse right ventricular function (FAC 25.6±8.4% vs. 33.9±6.8%; p=0.046). Changes in NT-proBNP levels from baseline differed between groups (p=0.012), showing a trend toward increase in PVOD/PAH (p=0.076) and reduction in non-PVOD/PAH (p=0.069). At 12 months, 5 hospitalizations for heart failure in each group, and a total of 5 deaths (2 PVOD/PAH and 3 non-PVOD/PAH) were recorded, with similar event-free survival (p=0.101). Conclusions. PVOD is frequently associated with PAH in SSc and does not seem to be associated with specific SSc features. Vasodilators, at least on monotherapy, should be considered in PVOD/PAH, as they seem to be well tolerated. Nevertheless, at follow-up these patients exhibit unfavorable laboratory and echo profiles compared to those with SSc-PAH alone, highlighting the importance of early referral for lung transplantation.
PO:32:183 | Innovative use of integra dermal regeneration template on systemic sclerosis digital ulcers: a case report
Introduction. Digital ulcers (DU) are among the most frequent debilitating manifestations of systemic sclerosis (SSc), causing pain, disability, and impaired quality of life. In refractory cases, surgical procedures, including amputations, may be required. Integra® dermal regeneration template is a bilayer acellular dermal substitute composed of a porous collagen–glycosaminoglycan matrix and a temporary silicone layer. Although originally developed for burns and complex wounds, it has been increasingly used in reconstructive surgery. We report the first case of combined use of Integra and autologous fat grafting (AFG) for the treatment of refractory DUs in a patient with SSc. Case Report. A 45-year-old woman with diffuse cutaneous SSc (anti-Scl70 positive, mRSS 22), severe skin involvement, Raynaud’s phenomenon with digital resorption, esophageal and pulmonary disease, presented with refractory DUs despite maximal vasodilatory therapy (Iloprost, Selexipag, Bosentan) and immunosuppressants (MTX, RTX, MMF). She had previously undergone partial digital amputations and one AFG. In March 2025, due to progression of disease with multiple hard-to-heal DUs (Figure 1), a combined surgical approach was planned, consisting of debridement, Integra application to three digits of the right hand (I, II, IV), and bilateral AFG. The procedure, performed under local anesthesia, consisted of two phases: 1. Integra application: after surgical debridement, the matrix was hydrated, positioned, and sutured to wound margins with absorbable stitches (Figure 2). 2. AFG: adipose tissue was harvested by liposuction, purified by centrifugation, and injected into the hands at subcutaneous and perilesional levels. The fat, rich in mesenchymal stem cells (MSC), was distributed to dorsal and palmar aspects of all fingers and interdigital spaces. The postoperative course was uneventful. The silicone layer was removed after 10 days, revealing correct matrix integration and well-formed granulation tissue. At the 2 months follow-up, near-complete re-epithelialization in the II and IV digits was achieved while progressive healing of the I digit was noted (Figure 3). Moreover, a reduction of pain (mean numeric rating scale 7.3±1.9 at baseline versus 2.9±1.4 at follow-up) along with significant improvement in hand function was reported by the patient. Conclusions. Integra showed efficacy in providing structural support for skin regeneration even in SSc, where vascular impairment often compromises healing. It appeared beneficial in reducing contamination, promoting fibroblast migration, neovascularization, and neodermis formation. This case suggests that Integra may represent a promising therapeutic option for refractory DUs in SSc, particularly when combined with AFG, which provides regenerative, angiogenic, and immunomodulatory effects through MSC contained in adipose tissue.
PO:32:184 | Assessing the burden of Sars-Cov2 in systemic sclerosis-related interstitial lung disease patients: functional, clinical and therapeutic outcomes from an Italian cohort, a retrospective study
Background. Systemic sclerosis (SSc) is a rare immune condition mainly affecting connective tissues with interstitial lung disease (ILD) being a common feature of its clinical milieau. Among others, suffering from autoimmune systemic diseases (ASD) emerged as one of COVID-19 predisposing factors. Objective: the purpose of the present work was to assess the clinical, therapeutic and functional outcomes of a cohort of patients affected by SSc-related ILD (SSc-rILD). Materials and Methods. We retrospectively analysed data from medical charts of 64 SSc-rILD patients from our Rheumatology Unit of Bari clustered into two groups depending on whether they experienced COVID-19 (35 patients) or not (29 patients). Baseline characteristic intended as the ones acquired at the very last visit before COVID infection or, in the other group, before SARS-CoV2 outbreak, included skin pattern, autoimmune features, ongoing medications, clinical manifestations, respiratory function as assessed through spirometry and radiographic appearance evaluated as TC-scans of the lungs. This information was then newly investigated at the latest available follow-up date as long as COVID-19 outcomes. Standard descriptive statistics were employed to evaluate demographic, clinical and functional characteristics. SPSS IBM was the software of choice in our work. Results. The mean follow-up period was 46.3 (SD ±10.9) months for the non-COVID and 38.7 (±12.7) months for the COVID cohort. Diffuse cutaneous subset was found to be statistically more frequent in the COVID group (p=0.007) at baseline. The cohort resulted homogeneous when investigated for other demographical characteristics. The main highlight of our work comes from the evaluation of pulmonary functional index variations (Table 1): FVC and FEV1 showed a greater reduction in patients who experienced COVID, respectively -15.7% ±31.4% (vs -0.9%±14.8%, p=0.02) and -15.5% ±30.5% vs -1.7% ±13.9%, p=0.03. A similar trend was observed for DLCOc, -6.1% ±13.5% (vs -0.8% ±17.3%) despite not achieving statistical significance (Tab 1a). Same significance was found in COVID positive limited cutaneous subset subgroup for FVC and FEV1 reduction (p=0.01). In addition, in 2 of the 35 COVID cases (5.7%), the infection resulted in the death of the patients, with SARS-CoV2 being the only reason of death in both groups in the aforementioned follow-up period (Tab. 1b). No clear differences were noticed in ongoing or new onset treatment, while a trend of increasing percentage of digital ulcers, esophagophathy and pulmonary arterial hypertension was found, even if none of the aforementioned reached statistical significance. Conclusions. Our work highlights the risks related to SARS-CoV2 infection in delicate patients as SSc-rILD ones. Global pulmonary function loss advocates for the necessity of shrewd preventive strategies (as with vaccinations) and careful monitoring of the disease course in those experiencing COVID infection.
PO:32:185 | Deep-learning analysis of high-resolution computed tomography images predicts progression and mortality in systemic sclerosis related interstitial lung disease
Background. Interstitial lung disease (ILD) is a major complication in systemic sclerosis (SSc) patients, associated with substantial morbidity and mortality. Functional, imaging, and clinical measures of lung involvement could be biased in SSc due to its multiorgan nature and extra-articular involvement (e.g., cardiac, musculoskeletal). Artificial intelligence (AI) reading of high-resolution computed tomography (HRCT) has emerged as a novel tool for the objective and reliable assessment of pulmonary diseases. The aim of this study is to correlate AVIEW measures, an Deep learning based software for HRCT image assessment, with ILD-progression and disease-related mortality in SSc patients. Materials and Methods. The AVIEW software (Coreline Soft, South Korea) was employed to analyze HRCT images from a cohort of consecutive SSc-ILD patients at baseline and after 24±3 months. Quantitative analyses included lung volume, texture, airways, and vascular anatomy. Baseline metrics were assessed for their association with ILD progression, defined by clinical, functional, and imaging criteria based on the INBUILD study parameters over 24 months. Furthermore, changes in AVIEW-derived measurements between consecutive HRCT evaluations over the 24-month period were analyzed for their association with SSc-related mortality during the subsequent 36 months. All absolute measurements were normalized to body surface area. Results. A total of 146 HRCT scans from 73 SSc-ILD patients were assessed (mean age 58.4±14.3 years; male 16.4%; diffuse skin variant 49.3%). Thirty-one patients (42.4%) experienced ILD progression, which was predicted at baseline by higher percentages of ground glass opacities (GGO) (p=0.05) and reticulation (p=0.05), higher subpleural vessel volumes (p=0.017), and a tendency toward larger distal airways (p=0.066). Serial evaluations demonstrated that INBUILD progression was associated with a reduction in the percentage of normal lung (p=0.044) and absolute volumes (p=0.009), without significant changes in reticulation, GGO, vessels, or airways when considered individually. Twelve patients died due to SSc within 36 months following the second HRCT evaluation. Patients in the upper quartile for changes in reticular score and airway volume exhibited a higher mortality risk, independent of INBUILD progression (reticular score: OR 3.30, 95% CI 1.03–10.61, p=0.045; airway volume: OR 3.37, 95% CI 1.08–10.51, p=0.036) Conclusions. Deep learning-based assessment in SSc-ILD identified distinct modifications and prognostic significance in lung anatomical components, offering potential improvements in patient evaluation and stratification beyond conventional clinical tools.
PO:32:189 | Salivary gland alterations in systemic sclerosis: a comprehensive ultrasound study and autoantibody correlation
Background. Salivary gland involvement in systemic sclerosis (SSc) is often underrecognized, despite the potential clinical burden of sicca syndrome in affected patients. This study investigates the association between autoantibody profiles and salivary gland (SG) ultrasonographic findings in individuals with SSc. Materials and Methods. In this monocentric cross-sectional study, patients with SSc, classified according to the 2013 ACR/EULAR criteria, underwent clinical evaluation, immunoblot testing, and SG ultrasonography. Imaging assessments included grey-scale (GS) scoring based on the OMERACT scoring system; power Doppler ultrasound (PDUS), graded as 0 (normal) or 1 (pathological) for each SG; and shear wave elastography (SWE), with stiffness values measured in meters per second (m/s). Patients were stratified by autoantibody profile into the following groups: anti-centromere antibody (ACA) only, anti-topoisomerase I antibody (ATA) only, anti-Sjögren syndrome type A antibody (SSA) with or without additional antibodies, and other autoantibody positivity. Sicca syndrome was defined clinically as objective and/or subjective evidence of ocular (xerophthalmia) and/or oral (xerostomia) dryness, in the absence of Sjögren’s syndrome (SS) based on the 2016 ACR/EULAR criteria or other identifiable causes. Results. A total of 123 patients with SSc were included (median age 61 years [IQR 55–71], 89.4% female), distributed as follows: ACA+ 32.5%, ATA+ 26.0%, SSA+ 16.3%, and other autoantibody profiles 25.2%. Patients in the SSA+ group showed significantly higher GS scores compared to other groups (p < 0.001), indicating more severe salivary gland involvement. No significant differences were observed in PDUS scores (p = 0.872) or in SWE measurements (parotid glands: p = 0.422; minor salivary glands: p = 0.873), as reported in Table 1. Regarding GS alterations, the SSA+ group had the highest proportions of Grade 2 (36.8%) and Grade 3 (15.8%) lesions, while the ATA+ group had the highest proportion of Grade 0 lesions (75.0%), with a significant difference in the distribution across groups (p = 0.001). Overall, the prevalence of sicca syndrome was high (74.8%), with no significant difference between groups (p = 0.256). Notably, 5 patients (25%) in the SSA+ group met the classification criteria for SS. Conclusions. This study demonstrates a strong association between anti-SSA antibodies and severe salivary gland involvement in SSc, suggesting a potential direct tissue-damaging effect. Anti-SSA positivity was linked to Sjögren-like ultrasound changes regardless of other autoantibodies, while the prevalence of sicca symptoms remained high and consistent across groups—pointing to additional SSc-specific determinants of sicca syndrome that may not be fully captured by ultrasound assessment.
PO:33:190 | Travel distance to tertiary healthcare reflects disease severity and medication access in systemic sclerosis patients: insights from the Italian systemic sclerosis progression investigation registry of the Italian Society of Rheumatology
Background. Commuting poses a considerable burden and costs for patients with rare rheumatic diseases such as systemic sclerosis (SSc), who require care from tertiary medical centres. In a universal healthcare system, the selection of healthcare services is possibly influenced by geographical distribution, referral networks from primary care, and patient preferences. This study aims to evaluate whether longer commuting distances are associated with clinical variables and differences in medication access among Italian SSc patients receiving follow-up care at tertiary centres. Materials and Methods. The driving distance from the city of residence to the care centre was calculated using the Google Maps Distance Matrix API for anonymized patients with SSc from the Systemic Sclerosis Progression INvestiGation (SPRING) Italian registry. This distance was then correlated with clinical and drug history in an ordinal logistic regression analysis. Results. The characteristics of 1,782 patients were obtained from 38 centres across the country (Figure 1 and Table 1): 74.2% were categorized as short-distance commuters (traveling less than 100 km), 20.1% as intermediate-distance commuters (traveling 100-500 km), and 5.6% as long-distance commuters (traveling more than 500 km). Notably, 24.6% of the patients received care outside their residential administrative region. Patients with interstitial lung disease (ILD), pulmonary arterial hypertension, lower Forced Vital Capacity (FVC), reduced Diffusion Capacity for Carbon Monoxide (DLCO), anti-Scl70 positivity, and anti-centromere negativity had higher probability of traveling longer distances. Similarly, access to multiple immunosuppressants (cyclophosphamide, azathioprine, methotrexate, tocilizumab) and vasoactive/vasodilator drugs (Endothelin Receptor Antagonists (ERA), Phosphodiesterase Type 5 Inhibitors (PDE5i), iloprost) was associated with increased probability of long travel distances (Table 1). No significant differences were correlated to demographics or comorbidity burden. Conclusions. SSc patients with pulmonary complications are more likely to undertake longer commuting distances and have a higher likelihood of receiving advanced treatments. Public health strategies should aim to enhance accessibility to specialized care and advanced therapies for these patients, recognizing the impact of travel burden on healthcare access.
PO:33:191 | Evaluation of the living with pulmonary fibrosis questionnaire in patients with systemic sclerosis associated interstitial lung disease: monocentric results
Background. Purpose Interstitial lung disease (ILD) is a common manifestation of Systemic Sclerosis (SSc) and a leading cause of death. The assessment of respiratory symptoms, with lung physical examination and pulmonary function tests, represents a useful approach to monitoring pulmonary disease progression. However, there is currently no consensus on the optimal monitoring strategies for these patients. A specific patient-reported outcome measure (PROM), the Living with Idiopathic Pulmonary Fibrosis Questionnaire (L-IPF), has been validated for patients with idiopathic pulmonary fibrosis and has shown correlation with FVC% predicted and DLCO% values [1]. Its adapted version, the Living with Pulmonary Fibrosis Questionnaire (L-PF), is designed for patients with any fibrosing interstitial lung disease and was also used in the INBUILD study [2]. The aim of this study is to evaluate the L-PF in our patients with SSc-ILD. Materials and Methods. L-PF consists of 44 items, divided into two modules: Symptoms (subdivided into dyspnea, cough, and energy) and Impact. Scores for both modules range from 0 (no symptoms and/or impact) to 100 (maximum symptoms and/or impact). The correlation between L-PF and the Systemic Sclerosis Impact of Disease (ScleroID), a comprehensive PROM developed for SSc, was analysed. Data are presented as medians (interquartile range). SSc subgroups were compared using the Mann–Whitney U test and correlation analysis using the Spearman coefficient (rs). Results. L-PF was administered to 55 consecutive patients with SSc-ILD. Their demographic and clinical features are detailed in Table 1. A negative correlation was found between DLCO% and all L-PF domains: Cough (rs= -0.454, p=0.001), Total Symptoms (rs= -0.386, p=0.007), Impact (rs= -0.335, p=0.037), Dyspnea (rs= -0.285, p=0.047) and Energy (rs = -0.299, p=0.039). In addition, ScleroID correlated positively with all L-PF domains except Cough: Total Symptoms (rs=0.612, p<0.0001) (Figure 1), Impact (rs=0.634, p<0.0001), Dyspnea (rs=0.667, p<0.0001) and Energy (rs=0.544, p <0.0001). No significant correlations were observed with FVC%, ILD and SSc duration, or age. No significant differences in L-PF domain scores were observed when stratifying the cohort by sex, smoking status, age (< or > 60 years), cutaneous subset, antibody profile, ILD radiological pattern, FVC (< or > 75%), SSc duration, or ILD duration (< or > 10 years). Conclusions. In this cohort of patients with SSc-ILD, the L-PF questionnaire was correlated with DLCO values, which might reflect ILD effects and lung microvascular damage in SSc. Moreover, the correlation between L-PF and ScleroID, a validated measure of disease burden for SSc patients, suggests that L-PF might capture symptoms and impact of ILD also in them. The Authors thank GILS (Gruppo Italiano Lotta Sclerodermia) for kindly supporting the project
PO:33:194 | The role of anti-g protein-coupled receptors antibodies in the assessment of systemic sclerosis-primary heart involvement
Background. Primary heart involvement (pHI) is a major organ complication of systemic sclerosis (SSc), accounting for a significant share of SSc-related deaths. Since pHI is often asymptomatic and its presentation is highly variable, a multiparametric assessment is mandatory. Echocardiography is essential in pHI screening; coronary flow velocity reserve (CFR) assessed by echocardiography has been demonstrated to identify SSc patients with coronary microvascular dysfunction (CMD), which appears to be involved in the pathogenesis of SSc-pHI. Autoantibodies targeting G protein-coupled receptors (GPCRs) – specifically, anti-endothelin type A and anti-angiotensin 1 receptors antibodies (anti-ETAR and anti-AT1R) – have been associated with the microvascular manifestations of SSc, namely digital ulcers and pulmonary arterial hypertension. Our study aims to evaluate a possible association between anti-GPCRs antibodies and CMD in SSc patients. Materials and Methods. Adult patients fulfilling the 2013 ACR/EULAR classification criteria for SSc were enrolled; patients with pulmonary arterial hypertension, coronary artery disease or other cardiomyopathies were excluded. Demographic and clinical data were recorded, as well as the presence of pHI(1). Echocardiography with CFR assessment was performed on all patients by an experienced cardiologist: according to the literature, CFR < 2.5 was considered marker of CMD, while CFR values < 2 defined severe CMD. Serum levels of anti-ETAR and anti-AT1R antibodies were assessed by ELISA for each patient up to 3 months prior or following the echocardiographic assessment. The seropositive threshold was provided by the manufacturer (>10 U/ml). Results. Thirty-one patients were enrolled. The median disease duration was 1 year (IQR 1-4), the median age at enrolment was 58 (48-63) years, the majority of patients were females (71%), had diffuse cutaneous SSc (61%) and positive anti-topoisomerase I antibodies (55%). Clinically overt pHI was diagnosed in 26% patients, while CMD in 70%. CMD was not associated with organ involvement, including pHI, while CFR values < 2 were associated with pHI. Serum anti-ETAR and anti-AT1R levels strongly correlated with each other (p<0.001). Positive anti-ETAR and anti-AT1R were associated with significantly lower CFR values (p=0.002 and p=0.05), and both anti-ETAR and anti-AT1R titers inversely correlated with CFR values (rho =-0.41, p=0.03 and rho=-0.37, p=0.05, respectively). ROC curve analysis showed an acceptable performance of both anti-GPCRs in identifying CMD, with an area under the curve (AUC) of 0.74 for anti-ETAR and 0.72 for anti-AT1R antibodies. A positive correlation was observed between time from Raynaud’s phenomenon and anti-GPCRs titers (rho =0.36, p=0.04 and rho=0.38, p=0.02), while there was only a tendency for a correlation between anti-GPCRs titers and disease duration. Conclusions. Anti-ETAR and anti-AT1R antibodies appear to be associated with the development of CMD is SSc and their determination may be useful in the early assessment of SSc-pHI.
PO:33:195 | Evaluation of prevalence and role of anti-endothelin type a-receptor and anti-angiotensin ii type 1-receptor antibodies in a cohort of systemic sclerosis patients
Background. Systemic sclerosis (SSc) is a systemic, autoimmune, heterogeneous disease, characterized by fibrosis and vasculopathy of skin and internal organs. Disease prognosis is mainly driven by autoantibody profile and specific organs involvement. The renin-angiotensin and endothelin systems have been implicated in the pathogenesis of vascular dysfunction. Antibodies (abs) against the angiotensin II type 1-receptor (AT1R) and the endothelin type A-receptor (ETAR) have been hypothesized to play a pathogenetic role in SSc, although their role in SSc remains unclear. Severe vascular disease manifestations have been associated with higher titers of anti-AT1R and anti-ETAR abs, which also appear to predict SSc-related mortality. Aim of the study was to estimate the prevalence of these autoabs in an SSc cohort and to evaluate their possible correlation with clinical and laboratory characteristics. Materials and Methods. A cross-sectional monocentric study enrolling SSc patients was conducted. Demographic, clinical and laboratory data were collected and nailfold capillaroscopy was performed. Sera were tested by enzyme-linked immunosorbent assay for anti-AT1R and anti-ETAR abs, indirect immunofluorescence on Hep2 cells for anti-nuclear (ANA) abs, immunoblotting, fluorescent enzyme and chemiluminescence immunoassays for exctractable nuclear antigens (ENA) abs. Patients under anti-endothelin receptor antagonists were excluded. Categorical variables were compared using the chi-squared test, continuous variables were compared using t-test or Mann Whitney U test. Variables with statistical significance were tested in a multivariate regression model, corrected for selected confounders. Results. A population of 80 SSc patients was enrolled. 6 patients resulted to be positive for both anti-ETAR and anti-AT1R abs, 8 patients only for anti-ETAR abs. Table 1 shows demographic and clinical data of the study population. Characteristics of patients anti-ETAR/AT1R abs positive were compared to patients negative for both the autoabs: anti-ETAR/AT1R abs positive patients resulted to have a significant higher prevalence of ischemic digital ulcers (IDU) (p=0.017). Patients positive for anti-ETAR/AT1R abs had a significant higher risk of having IDU independently from ongoing treatment with prostanoids (OR 5.7, 95%CI 1-33.26). Figure 1 shows the proportion of patients with IDU in the two groups. Patients positive for anti-ETAR/AT1R abs showed higher risk for presenting an early scleroderma pattern at the capillaroscopy rather than the other patterns, although the result did not reach the statistical significance (OR 4.5, 95%CI 0.4-49.6). Normal capillaroscopy was the reference group. Finally, patients under steroid treatment showed half-risk of presenting anti-ETAR/AT1R abs positivity, although the result was not statistically significant (OR 0.5, 95% CI 0.11-2.28). Conclusions. Anti-ETAR/AT1R abs could be involved in peripheral vasculopathy in SSc patients, both in early and in late phases of the disease. Further studies are needed to evaluate their potential predictive value aimed at selection of patients at risk for early treatment or prevention therapy.
PO:33:197 | Systemic sclerosis and endothelial dysfunction: the passive leg movement technique in the assessment of no-mediated vascular impairment
Objectives: To evaluate nitric oxide (NO)-mediated vascular dysfunction in patients with Systemic Sclerosis (SSc) compared to age- and sex-matched healthy controls through passive leg movement (PLM). Materials and Methods: Twenty-one patients and twenty-one controls were enrolled. PLM was performed in a seated position, and blood flow (BF) was measured at the right common femoral artery (CFA), distal to the inguinal ligament and approximately 2 cm from the femoral bifurcation, by assessing flow velocity and vessel diameter. Baseline BF, peak flow (hyperaemia) during PLM, and the area under the curve (AUC) of BF over time were calculated. Patients were stratified according to phenotype (limited: lcSSc; diffuse: dcSSc), disease complications, and ongoing therapies. Results: The mean disease duration was 16.2 years (SD ±9.78). Fifteen patients (71%) had lcSSc. The most frequent autoantibodies were anti-centromere (47%) and anti-Scl70 (43%). Nine patients (43%) had a history of digital ulcers (DU), eight (38%) had pulmonary arterial hypertension (PAH), and eleven (52%) had interstitial lung disease (ILD). Seventeen patients (81%) were on vasoactive therapy and eight were taking immunosuppressive treatment (Table 1). At rest, CFA diameter and baseline BF were not significantly different between groups (p=0.14 and p=0.56, respectively). Both groups exhibited a PLM-induced response. Peak BF was significantly reduced in SSc patients (467.7 vs 552.5; p=0.038), as well as change from baseline (p=0.005). The AUC was also significantly lower in patients (p=0.01) (Figure 1). No differences were observed between lcSSc and dcSSc in terms of peak flow (p=0.34) or AUC (p=0.3). A higher modified Rodnan skin score (mRSS) correlated with a smaller CFA diameter (p=0.001). The presence of DU history did not affect the hyperaemic response (p=0.65). Patients with PAH showed a slightly higher peak flow (p=0.05), likely related to vasoactive therapies. No correlation was found between PLM-induced hyperaemia and vasoactive treatments. Patients on statins had significantly lower baseline BF compared to those not receiving statins (p=0.03), possibly related to the role of statins on endothelial function. Conclusions: PLM-induced hyperaemia is significantly reduced in SSc, highlighting the role of NO-mediated endothelial dysfunction in this disease, regardless of phenotype. PLM proves to be a valid technique for evaluating microvascular impairment in SSc. However, the absence of correlations between PLM response and drugs used, suggests the need for new endothelial-targeted drugs aimed at reversing vascular damage. Further studies are warranted to better define the role of PLM in SSc and its potential applications in clinical practice and therapeutic evaluation.
PO:33:200 | Analysis of risk factors associated with vertebral fractures in systemic sclerosis: evidence from the "Sclero-RER" study group
Background. Systemic sclerosis (SSc) is a rare disease characterised by fibrosis of the skin and internal organs, as well as vascular involvement. Recent evidence indicates that osteoporosis (OP) is a frequent comorbidity in patients with SSc, with an estimated prevalence of 27%. However, specific risk factors for vertebral fractures in these patients remain unclear. This study aims to identify both general risk factors (age, BMI, age at menopause, family history of fragility fractures, smoking, steroid therapy, and femoral and vertebral T-score) and SSc-related factors (disease duration, autoimmune profile, visceral involvement) associated with the presence of vertebral fractures in patients with SSc and suspected osteoporosis. Materials and Methods. A cross-sectional multicenter study conducted by the "Sclero-RER" group in Emilia-Romagna. Consecutive patients diagnosed with SSc (2013 ACR/EULAR criteria) were included, assessed with bone densitometry (DXA) and vertebral imaging. Collected data included: demographic parameters, disease duration, autoantibody profile, osteometabolic tests, organ involvement, and therapies. Statistical analysis used a stepwise logistic regression model to evaluate the association between risk factors and vertebral fractures (significance: p ≤ 0.05). Results. 103 patients were enrolled (97.1% women, all postmenopausal). Osteoporosis was present in 52.4%, 38.8% had at least one vertebral fracture, and 28.1% had osteopenia. In the model with general factors, a family history of major fragility fractures and the vertebral T-score were significant predictors. When integrating SSc-specific factors, only family history and gastrointestinal (GI) involvement remained associated with the occurrence of vertebral fractures (OR 13.8 p=0.03 and OR 1.6 p=0.05, respectively). Pulmonary involvement and diffuse cutaneous SSc (DcSSc) showed a non-significant trend. Conclusions. This study highlights that both general risk factors (family history of fragility fractures) and specific factors (GI involvement) in patients with SSc are associated with the presence of vertebral fractures. GI involvement, in particular, could negatively affect nutrient absorption, increasing the risk of fractures. These results support the use of targeted preventive strategies in patients with SSc and GI involvement, in order to reduce the risk of vertebral fractures. However, further studies will be necessary to confirm these associations.
PO:33:201 | Metabolic and functional state of circulating platelets in patients with systemic sclerosis
Background. Systemic Sclerosis (SSc) is a systemic autoimmune disease characterized by vasculopathy, inflammation and fibrosis. Microangiopathy manifests with Raynaud’s phenomenon and digital ulcers, but also visceral involvement. Endothelial dysfunction represents an early event, associated with imbalance in vasoconstriction–vasodilation, chronic hypoxia and altered angiogenesis. Platelets, besides their known role in hemostasis, recruit immune cells and release pro-fibrotic mediators. Recent studies show increased levels of platelet-derived products in SSc, suggesting higher platelet activity, although the use of antiplatelet therapy in this field remains controversial. Evidence on a complete phenotypic analysis of platelets in SSc is still limited. This preliminary study aims to investigate platelet functionality in SSc. Materials and Methods. This single-center study involved patients diagnosed with SSc according to the 2013 ACR/EULAR criteria, adults, not on antiplatelet therapy, in outpatient follow-up. As healthy controls, age- and sex-matched subjects without autoimmune diseases and not on antiplatelet therapy were enrolled. Blood samples were analyzed within 30 minutes after collection. Platelet activation and reactivity were evaluated by labeling diluted blood with Tyrode buffer, CD62P-PE and PAC1-FITC, in the absence or presence of agonists (ADP, convulxin, TRAP-6). To identify procoagulant platelets, staining with CD41-APC and Annexin V-PE was used, in buffer with Ca² and fibrin inhibitor. Mitochondrial functionality was studied with MitoTracker Green FM and MitoTracker CMXRos on washed platelets, with or without stimulation with agonists. Analysis was performed using BD Accuri C6 Plus flow cytometer and FlowJo™ and GraphPad Prism software version 10.4.2. Results. Eleven patients with SSc (mean age 58.4 ±11.7, F 11) and six healthy controls (age 54.7 ±13.6, F 6) were enrolled. Circulating platelets showed greater mass and mitochondrial membrane potential. Basal platelet activation was significantly higher in SSc patients, with greater expression of PAC1+ CD62P+ (4.4±9.3% vs 0.4±0.9%, p<0.05) and mean fluorescence intensity for PAC1 (243.8±330.0 vs 61.3±57.5, p<0.05) compared with controls. Moreover, platelets from SSc patients showed higher responsiveness following stimulation with ADP (a weak agonist), but not in response to stronger agonists mimicking thrombin or collagen. No significant differences emerged in the percentage of procoagulant or apoptotic platelets. Conclusions. This study shows increased basal platelet activation in SSc patients, with an altered response pattern to stimuli. Mitochondrial integrity suggests elevated platelet activity, implying their role in vascular damage and the possible reconsideration of antiplatelet therapy in SSc. Further studies on larger cohorts and better-characterized patients by disease form, duration, and activity will be needed to clarify platelet function in SSc pathophysiology.
PO:33:203 | Efficacy and safety of rituximab in eosinophilic fasciitis: report of three cases and systematic literature review
Background. Eosinophilic fasciitis (EF) is a rare inflammatory condition classified among scleroderma-like syndromes. Corticosteroids represent the first-line treatment, followed by conventional immunosuppressants. In refractory cases, other agents have been used, including rituximab (RTX), although it is not currently included in EF guidelines (1). Our study aimed to evaluate the efficacy and safety of RTX by describing three cases from our centre and conducting a systematic review of the literature. Methods. We included patients with a clinical and histological diagnosis of EF1 who were treated with RTX at our centre between 2010 and 2025. Demographic, clinical, laboratory, and instrumental data, as well as previous and concomitant therapies, were collected. Disease severity was assessed according to the Jinnin et al. score. A systematic review of the literature (01/2010–05/2025) was conducted in accordance with PRISMA guidelines using the Medline (PubMed) database, including studies published in English on adult patients with EF (population) treated with RTX (exposure), with the aim of evaluating efficacy and safety (outcomes). Results. Three patients with EF who were treated with RTX were identified. Demographic and clinical features are summarized in Table 1. All patients had typical skin involvement confirmed by histology. Physical triggers, infections, drugs, autoimmune diseases, oncological and hematological diseases were excluded. At the time of diagnosis, all patients presented with peripheral eosinophilia and were initially treated with corticosteroids and methotrexate. RTX was added due to progressive skin involvement and a worsening disease severity score. A rapid clinical improvement was observed in all cases, with a reduction in skin thickening, extent of involvement, and disease severity score. The mean daily corticosteroid dose at the last follow-up was 71% lower compared to the pre-RTX dose. In terms of safety, two non-serious adverse events were reported: hypogammaglobulinemia and an upper respiratory tract infection in one patient. A review of the literature identified ten additional cases of EF treated with RTX. Demographic, clinical, and treatment characteristics are reported in Table 2. RTX therapy was clinically effective in eight out of ten cases. Conclusions. Rituximab may represent an effective and safe therapeutic option for patients with EF who are refractory to corticosteroids and conventional DMARDs. Both our case series and the literature data support the use of RTX in EF unrelated to hematologic conditions, highlighting its potential as a steroid-sparing agent with a favourable safety profile.
PO:34:204 | Impact of anti-centromere antibodies on immunosuppressive therapy persistence in systemic sclerosis: a single-center case-control study
Background. Although in Systemic Sclerosis (SSc) the autoantibody profile is associated with different clinical and therapeutic phenotypes, it remains unclear whether it also affects patients’ persistence in immunosuppressive (IS) therapy. Through a case-control study, we aimed to evaluate whether the presence of specific autoantibodies is associated with a greater tendency to discontinue IS therapy in SSc patients. Materials and Methods. We conducted a retrospective analysis on a single-center cohort of 90 patients (M/F 4/86) affected by SSc, classified according to the 2013 ACR/EULAR criteria and treated with immunosuppressive drugs (IS). Thirty ACA-positive (ACA+) patients were identified and compared with 60 ACA-negative (ACA–) patients, including anti-Scl-70+, anti-RNAP III+, and non-specific ANA+ subjects, matched 1:2 for sex and age. A descriptive analysis of clinical, demographic, and instrumental characteristics was performed at the time of IS initiation (T0). Data regarding the first IS introduced and its clinical indications were also collected. During follow-up, conducted for up to 10 years or until the last documented visit, tolerability and causes of therapy discontinuation were evaluated. Persistence was analyzed using Kaplan–Meier curves, log-rank test, and Cox regression. Results. Table 1 reports the clinical, demographic, and instrumental characteristics of the 90 patients at T0. Table 2 describes, at baseline, IS use and clinical indications in the two groups. During follow-up, 8 ACA+ patients (27%) discontinued therapy compared to 7 ACA– patients (12%). Among ACA+ patients, the main reasons were clinical stability (25%) and gastrointestinal intolerance (25%) (Figure 1). In the ACA– group, discontinuation mainly occurred due to malignancy (28.5%), with no cases related to clinical stability. Persistence was significantly lower in ACA+ patients compared to ACA– (log-rank test, p = 0.0163), with a marked divergence between the 2nd and 6th year (Figure 2). In Cox regression analysis, ACA positivity was significantly associated with IS discontinuation (HR 12.26; 95% CI 1.65–133.4; p = 0.014), whereas no other variable (age, disease duration, mRSS, FVC%) was significantly associated with the outcome. Conclusions. In ACA+ SSc patients, persistence in immunosuppressive therapy was significantly lower than in ACA– patients, mainly due to clinical stability. ACA positivity confirmed to be an independent factor associated with early IS discontinuation. This finding suggests that in some patient subgroups, disease management may be feasible even without IS therapy, as treatment proved to have limited influence on the symptoms for which it was prescribed. These results support the potential role of serology not only in phenotypic definition but also in guiding more personalized therapeutic strategies. These preliminary data need to be validated in studies with larger sample sizes.
PO:34:205 | Optical coherence tomography angiography: a window on systemic sclerosis microangiopathy
Background. Vasculopathy represents the primum movens in Systemic sclerosis (SSc) pathogenesis and the determining cause of many of the clinical manifestations of the disease. Optical coherence tomography angiography (OCTA) is a non-invasive imaging technique that allows visualization of retinal blood vessels, providing information on their structure and blood flow. Some studies have documented the presence of retinal vascular alterations in patients with SSc, even in early stages of the disease. The aim of the study is to evaluate the microangiopathic alterations in the retina of SSc patients and to evaluate their correlation with the clinical manifestations of the disease and the alterations at the capillaroscopy. Materials and Methods. This is a case-control study comparing SSc patients with matched healthy controls (HC). The inclusion criteria for patients were: diagnosis of SSc or Very early SSc (VEDOSS), absence of maculopathy, no therapy with Hydroxychloroquine. The OCTA acquisition consisted of 3 x 3 mm scans of the superficial capillary plexus (SCP) and deep capillary plexus (DCP) of both the macula and the optic nerve, performed using Canon OCT HS100 with dilated pupils. The vascular density (VD) and the vascular length density (VLD) as long as foveal avascular zone (FAZ) were then calculated using dedicated software (OCT-HS100 Angio Expert AX®). Retinal thickness in the fovea and in the perifoveal region was also measured. Results. 82 eyes of 41 SSc patients (of which 11 were VEDOSS) were compared with 40 eyes of 20 HC. Patients showed significantly reduced VD values in all areas evaluated both at the SCP level (p<0.001) and at the DCP level (p<0.001). VLD values were also significantly reduced in patients compared to HC, both at the SCP (p<0.001) and DCP (p<0.001). Also at the optic nerve level, both VD and VLD values were significantly reduced at the SCP (p<0.001 for both) and at the DCP level (p=0.009 and p<0.001, respectively). Differently, FAZ values were not significantly different in patients versus HC. Retinal thickness of the parafovea was significantly increased in SSc patients (p=0.013). No significant difference was found by comparing the OCTA parameters of SSc patients with VEDOSS patients. Correlating retinal values with capillaroscopic parameters, the values of VD and VLD at the foveal level in DCP correlate with the presence of avascular areas (p=0.018 and p= 0.019, respectively) and neoangiogenesis (p=0.023 and p=0.025, respectively). In addition, the correlation between FAZ DCP and the presence of avascular areas is at the limit of significance (p=0.058). Conclusions. This study highlights that ocular microangiopathy is present in scleroderma patients since the early stages of the disease and correlated with capillaroscopic alterations. These data confirm the systemic nature of scleroderma microangiopathy suggesting that OCTA may represent an important tool for its evaluation.
PO:34:209 | Increased liver stiffness and fibrosis in systemic sclerosis: a single-center transient elastography cohort study.
Background. This study aims to evaluate and compare the liver stiffness (LS) and the prevalence of liver fibrosis in patients with systemic sclerosis (SSc) versus healthy controls (HCs). Additionally, within the SSc cohort, it sought to identify demographic, clinical, or serological factors having a potential role as predictors of increased LS and overt liver fibrosis. Materials and Methods. Data from a monocentric cohort of 94 SSc patients, diagnosed according to the ACR/EULAR 2013 classification criteria, and 50 gender - and age - matched HCs were analyzed. All SSc patients and HCs were screened for concomitant infective, metabolic or autoimmune hepatic disorders and excluded if positive. The LS was measured in all patients and HCs by the Transient Elastography (FibroScan®) performed by a trained gastroenterology clinician. A cut-offs of > = 5.4 kPa and > = 7.5 kPa were applied to define, respectively, increased LS and overt fibrosis. Demographic, clinical, treatment and laboratory data, including autoantibodies profile, were recorded in all SSc patients and analyzed as potential predictors of LS and overt liver fibrosis in uni-and multivariate analysis. Results. Out of the 94 SSc patients, 79 (84%) were female. The mean (SD) age at enrollment and disease duration were 58.4 (12.9) and 9.4 (7.6) years, respectively. SSc patients exhibited a significantly higher mean (SD) LS compared to HCs (5.12 ± 1.95 kPa vs 4.18 ± 0.98 kPa; p = 0.002). Similarly, SSc patients showed a significantly higher prevalence of increased LS (40.4% vs 10.0%, p < 0.001) and overt liver fibrosis (11.7% vs 0, p = 0.009). In univariate analysis anti-centromere antibody (ACA) positivity (40.9% vs 24%, p = 0.028.), and increased serum GOT levels (23.9 ± 9,4 vs 19.9 ± 5.9, p = 0.008) were significantly associated with increased LS. However, in multivariate analysis only telangiectasias (p= 0.010 ) and elevated GOT (p= 0.009) levels were confirmed to be independently associated with increased LS. No demographic, clinical or serological factors were associated with liver fibrosis. Conclusions. In SSc patients, increased liver stiffness (ranging up to overt fibrosis) occurs significantly more frequently than in healthy individuals, likely reflecting the disease's inherent pro-fibrotic nature. Although liver biopsy remains the diagnostic gold standard, Transient Elastography offers a valuable, non-invasive method for early detection of hepatic fibrosis. Larger, prospective longitudinal studies are warranted to better characterize the extent and clinical implications of liver involvement in SSc.
PO:34:212 | Orofacial manifestations in systemic sclerosis: preliminary observational study and update of a single-center experience
Background: Systemic sclerosis (SSc) is a rare autoimmune disease characterized by endothelial dysfunction, tissue fibrosis, and immune dysregulation, leading to increased morbidity and mortality. Orofacial involvement—often underestimated—includes reduced mouth opening, periodontal alterations, hyposalivation, and masticatory difficulties, with a potential negative impact on quality of life. The aim of this study, conducted in collaboration between rheumatologists and dentists, was to investigate the correlations between systemic disease features and oral health parameters in a preliminary SSc cohort. Materials and Methods: An observational study was conducted on 13 SSc patients (F/M 12/1) attending the Scleroderma Unit of the University Hospital of Modena. All patients fulfilled the 2013 ACR/EULAR classification criteria and were referred to the Dental Service for comprehensive evaluation. Demographic, clinical, serological, rheumatological, and dental parameters were assessed, including DMFT index, periodontal indices, mouth opening, salivary flow rate, and quality of life (SSc-HAQ). Statistical analyses included Spearman/Pearson correlations and non-parametric tests. Results: The 13 enrolled patients presented a cutaneous subset distribution of dcSSc/lcSSc = 6/7, with a mean age of 56.5 ± 23.6 years. Older age was significantly associated with poorer oral health (r=0.79, p=0.002) and greater functional disability (r=0.83, p=0.0008). Patients with interstitial lung disease (ILD) exhibited a significant reduction in mouth opening (p=0.019). A strong positive correlation was also observed between plaque accumulation and disability index (r=0.72, p=0.006). Other non-significant trends suggested a possible association between limited cutaneous subset and reduced salivary flow. Conclusions: In our experience, orofacial involvement in SSc—particularly in older patients and those with ILD—adversely affects oral function and quality of life. Regular oral health monitoring and early implementation of preventive and supportive strategies should be encouraged in the management of SSc patients. Further studies in larger cohorts are warranted to confirm these promising preliminary findings and to guide targeted interventions.
PO:34:217 | Possible role of phosphodiesterase type 5 inhibitors in the prevention of digital ulcers and videocapillaroscopic changes in patients with systemic sclerosis
Background. In systemic sclerosis (SSc), phosphodiesterase type 5 inhibitors (PDE5i) are currently used in the treatment of pulmonary hypertension and in the management of refractory Raynaud’s phenomenon, and they appear to play a role in the healing of digital ulcers. However, the impact of these drugs on ulcer prevention and on nailfold videocapillaroscopy (NVC) findings remains poorly investigated. Materials and Methods. In this single-center retrospective study, 17 patients diagnosed with SSc according to the 2013 ACR/EULAR criteria and treated with PDE5i for at least 12 months were enrolled. Clinical, serological, and capillaroscopic data were collected. Based on the occurrence of new digital ulcers (DU) after starting therapy, patients were divided into two groups (DU+ and DU–). NVC images before and after treatment were analyzed qualitatively and quantitatively. Capillaroscopic data were unavailable for five patients. Results. Of the 17 patients enrolled, 14 (82%) were female, with a median age of 60 years (IQR 50–68). Twelve (70%) had a history of digital ulcers. Based on the occurrence of new DU during therapy, two groups were identified: DU+ (n=7, 41%) and DU– (n=10, 59%), as shown in Table 1. The groups were comparable in terms of age, disease duration, and duration of PDE5i exposure. Patients with recurrent DU more frequently had diffuse cutaneous disease, a history of previous DU, positivity for anti-Scl70 antibodies, and greater use of prostanoid therapy. Regarding capillaroscopy performed at a median interval of 3 years (IQR 2–5), no statistically significant differences were found between groups in terms of NVC pattern. Quantitative analysis of NVC showed that, although not statistically significant, in the DU+ group the absolute number of capillaries/mm decreased during therapy, while in the DU– group it remained stable. Conversely, the number of megacapillaries/mm remained stable in the DU+ group but decreased in the DU– group. The overall results are presented in Table 1. Conclusions. Our data confirm the known association between DU recurrence and both anti-Scl70 positivity and the diffuse cutaneous form of SSc. From our pilot study, PDE5 inhibitors emerged as a valid therapeutic alternative in patients with DU, thanks to their ability to reduce the recurrence rate, which in our cohort was 59%. In patients treated with PDE5i, we observed a trend toward stabilization of specific SSc-related capillaroscopic abnormalities, associated with the absence of new DU. These findings need to be confirmed in larger cohorts and with a more accurate evaluation of concomitant therapies.
PO:35:219 | Real-world effectiveness of mepolizumab on gastrointestinal involvement in eosinophilic granulomatosis with polyangiitis and hypereosinophilic syndrome: a multicentre retrospective study
Background. Eosinophilic gastrointestinal disorders are characterized by marked eosinophilic infiltration of the gastrointestinal (GI) tract causing organ dysfunction and the onset of GI symptoms. They may present in isolation or as part of systemic diseases including eosinophilic granulomatosis with polyangiitis (EGPA) and hypereosinophilic syndrome (HES). Mepolizumab (MEPO), an anti-interleukin-5 monoclonal antibody, is approved for both conditions; however, data are limited regarding its effectiveness in managing GI involvement. This study aims to evaluate MEPO’s effectiveness on EGPA and HES-related GI involvement. Materials and Methods. This was a retrospective cohort study conducted among centres referring to the European EGPA Study Group. Inclusion criteria: age >18 years; EGPA or HES diagnosis; GI manifestations confirmed by histology or imaging; start of MEPO any dosage (100 or 300 mg/month sc, 750 mg/month iv) for uncontrolled GI manifestations. Data were collected from disease onset until MEPO start (t0), at 1 (t1), 3 (t3), 6 (t6), 12 (t12), 24 (t24) months, and during flares (exacerbations of GI symptoms requiring therapeutic escalation). Outcomes included symptom improvement, absolute eosinophil count (AEC) reduction, flare occurrence, and corticosteroid (CS)-sparing effect. Data are presented as n (%) or median (IQR). Wilcoxon or McNemar tests were used as appropriate. Flare rates (flares/patient-month) pre- and post-MEPO were compared using incidence rate ratio (IRR) with 95% CI (p<.05). Results. Forty-eight patients were included. At baseline, all the patients had active GI involvement, with median peak AEC 3857 (1593-9743) cells/mm3. Forty-six patients (96%) had a history of CS use prior to MEPO. Median time from diagnosis to MEPO start was 5 (1-49) months (Table 1). Median AEC decreased by t1 [t0: 805 (482-1805) cells/mm3; t1: 115 (60–223); p<.001] and remained low through t24 [70 (23–108) cells/mm3; p<.001]. By t24, active GI symptoms decreased from 65% to 12% (p<.001) and oral CS (OCS) use from 85% to 46% (p=.001). Median prednisone-equivalent daily dose decreased from 11.3 (5-25) mg/day at t0 to 0 (0-2.5) mg/day at t24 (p<.001) (Table 2). During follow up, 8 patients experienced a GI relapse. All of them were on a stable MEPO dose, with 3 also using OCS (2 tapering) and 1 MMF. Only 1 case of increased AEC was documented. All flares were managed by adjusting CS therapy; MEPO dose was increased from 100 mg to 300 mg/month in 2 cases and immunosuppressive therapy was added in 2 others (Table 3). The flare rate decreased from 0.021 to 0.0049 flares per patient-month after MEPO (IRR 0.23, 95% CI 0.11–0.49, p=.0001), indicating 77% reduction in flare incidence. Conclusions. MEPO effectively controlled GI symptoms in EGPA and HES patients and reduced CS use.
PO:35:220 | IgG anti-pentraxin 3 autoantibodies distinguish eosinophilic granulomatosis with polyangiitis from severe eosinophilic asthma and chronic rhinosinusitis with nasal polyps
Background. Eosinophilic granulomatosis with polyangiitis (EGPA) typically presents with severe eosinophilic asthma (SEA) and chronic rhinosinusitis with nasal polyps (CRSwNP), often preceding systemic vasculitis by years. Early identification of patients likely to develop EGPA among those with asthma and sinusitis is therefore crucial. Circulating IgG autoantibodies against Pentraxin-3 (PTX3) have recently been reported in EGPA, raising the possibility that they could help distinguish EGPA from related airway disorders. The objective of the study was to determine the prevalence of anti-PTX3 autoantibodies in patients with EGPA, SEA and CRSwNP, and to evaluate their utility as a biomarker for differentiating EGPA from these conditions. Materials and Methods. We performed a single-center study including consecutive patients diagnosed with EGPA, and patients with SEA or CRSwNP. Serum anti-PTX3 IgG levels were measured using a standardized, in-house ELISA (positivity cut-off: optical density > 0.234 at 405 nm), as previously described. Liquid-phase inhibition assays were performed to evaluate potential assay interferences. Categorical variables were compared with ² tests; continuous variables with the Mann–Whitney U test. Results. We included 120 patients diagnosed with EGPA (56.7% female, median age 61), 60 with SEA (68.3% female, median age 59), and 63 with CRSwNP (44.4% female, median age 58). Anti-PTX3 autoantibodies were detected in 35% EGPA patients, compared to 8.3% in asthma and 7.9% in CRSwNP (p<0.001 for EGPA vs each comparator). Median OD values were higher in EGPA (0.175) than in asthma (0.11, p=0.014) and CRSwNP patients (0.07, p=0.001). PTX3 inhibited anti-PTX3 binding in a dose-dependent manner. No associations were found with ANCA status or clinical features at diagnosis. At the time of sample collection, 10% (12/120) of patients were characterized by active disease, while 90% (108/120) experienced remission. No statistically significant differences in the median OD of anti-PTX3 were found based on clinical activity. Conclusions. IgG anti-PTX3 autoantibodies are significantly more common in EGPA than in SEA or CRSwNP and represent a promising biomarker for early diagnosis. Their detection is independent of ANCA status, and they could help bridge the diagnostic gap in patients with overlapping features.
PO:35:221 | Cryofibrinogen: a cold case. Characteristics and clinical outcomes from a cryofibrinogen positive cohort
Background. Cryofibrinogen (CF) is a protein tangle mainly made of fibrinogen, fibrin and fibronectin that precipitates when exposed to cold temperatures. Unlike cryoglobulins (CG), CF significance is still poorly understood. Objective: to characterize patient with CF positivity and to define its clinical impact and therapeutic outcomes. Materials and Methods. We retrospectively collected data focusing on 46 CF positive patients. Demographic, clinical and therapeutic features were assessed at baseline (To), after the first determination (T1) and at each CF finding. Standard descriptive statistics were employed for our analysis. Results. 20 patients (43.5%) presented with CF alone, whilst 26 (56.5%) showed CF + CG. Female sex was prevalent (76.1%) with an average age of 54.1 (±14.6) years. 41.3% of patients were diagnosed with vasculitis, 14 of which cryoglobulinaemic, 13% arthritis, 23.9% connectivitis, 21.7% had no defined diagnosis. Clinical involvement ranged from neurological (58.2%), to cutaneous (purpuric rash 48.9%, skin ulcers 20%), inflammatory arthralgias (34.8%), cardiovascular (13%) and renal (6.5%). We then provided a statistical analysis dividing patients into two subgroups depending on CF positivity alone or CF + CG positivity. Groups were homogeneous for demographic, therapeutic, clinical features and outcomes (Figura 1.a). We then performed a comparison between patients who experienced a resolution of the symptomatology (responders) and those who haven’t (non-responders). Non-responders showed a significantly more frequent CG positivity (72.7% vs 41.7%, p=0.04) and a similar trend for ANA positivity (57.1 vs 29.2, p=0.07). On the other hand, a significant lower baseline employment rate of csDMARD was observed among responders 12.5% vs 36.4%, p=0.05), being hydroxychloroquine the most frequent among non-responders (55.1% vs 0%). More responders were administered corticosteroids at T1 (83.3% vs 59.1) even if statistical significance wasn’t achieved, whilst other medication didn’t differ between groups. Finally, skin affection was more frequent among responders, specifically purpuric lesions (73.9% vs 22.7%) and cutaneous ulcers (34.8% vs 4.5%) with a statistical significance of respectively p=0.001 and p=0.02 (Figura 1.b). When confronted, patients that didn’t experience cutaneous affection, showed higher rates of ANA (57.9% vs 30,8%, p=0.06) and anti-ENA (47.4% vs 11.5%, p=0.07) positivity, csDMARD intake at T0 (40% vs 11.5%, p=0.04) and fewer overall T1 corticosteroid employment (55% vs 84.6%, p=0.03). Moreover, a 76.9% rate of clinical improvement was observed among subjects with skin involvement (vs 20%, p=0.0001). CF serum levels were more frequently reducing (37.5% vs 10%, p=0.36) in skin affected patients, whilst only 8.3% (vs 35%, p=0.05) showed stability (Figura 1.c), not such differences were observed in responders vs non-responders. Conclusions. CF positivity alone showed with important clinical implications. Our analysis suggests a more profound immunological disruption in those patients who experienced worse clinical outcomes. Skin affection and corticosteroid intake seemed positively predict for better outcomes.
PO:35:227 | Long-term renal and survival outcomes in microscopic polyangiitis: data from an observational monocentric cohort
Background. Microscopic polyangiitis (MPA) is an ANCA-associated small-vessel vasculitis, often causing severe renal involvement that may lead to dialysis or transplantation. While ANCA-associated vasculitides have been extensively studied, data focusing specifically on MPA remain limited. Materials and Methods. MPA patients fulfilling the 2022 ACR/EULAR criteria, who were followed at our centre between May 2004 and May 2025, were analysed retrospectively. Clinical and laboratory data as well as information regarding induction and maintenance therapy, were collected at diagnosis, during relapses, and at last follow-up. Furthermore, variables potentially associated with death, renal outcomes and relapse were investigated. Results. Of the 71 MPA patients included (median age 66 years; 54.5% female), 98.6% were ANCA-positive, mostly MPO-ANCA (91.5%). At diagnosis 94.4% had renal involvement. Induction therapy consisted of glucocorticoids alone (16.9%) or with immunosuppressants (83.1%), mainly cyclophosphamide (31%) and rituximab (19.7%), while mycophenolate mofetil (21.4%) was the most used for maintenance. Over a median follow-up of 55 months, 90% achieved remission, 18.3% died, 26.8% experienced at least one relapse and 26.8% progressed to end-stage kidney disease (ESKD). Among those, 18.3% required dialysis and 7% underwent kidney transplantation. Baseline characteristics are summarized in Table 1. Survival, based on Kaplan-Meier curves, was significantly lower in patients aged >65 years (p=0.0019), with rapidly progressive nephritis (p=0.0263), arterial hypertension (p=0.0251), or dialysis at onset (p=0.0445). No significant differences in survival were observed based on induction with rituximab (p=0.5597), cyclophosphamide (p=0.227), or maintenance immunosuppressants (p=0.058). Neither VDI >5 nor ANCA Renal Risk Score (ARRS) >8 were associated with increased mortality. In multivariate analysis, faster ANCA negativity was independently associated with better survival (HR 0.76, 95% CI 0.59–0.96, p=0.022), indicating a protective effect while hypertension was independently associated with lower risk of relapse (HR 0.18, 95% CI 0.04–0.72, p=0.016). Other univariate predictors of relapse included lower baseline prednisone (p=0.038) and disease progression before remission (p=0.046). Progression to ESKD was significantly associated with higher BVAS (p=0.002), higher FFS (p=0.003), nephrotic-range proteinuria (p=0.007), elevated serum creatinine and lower eGFR at diagnosis (both p<0.001). However, no variables retained significance in multivariate analysis for ESKD due to excessive covariate interaction. Conclusions. In this MPA cohort, renal involvement was common and often severe, frequently progressing to ESKD. Advanced age, rapidly progressive nephritis, and need for dialysis at onset were associated with reduced survival, while faster ANCA negativity emerged as a protective factor. Although remission was achieved in most patients, relapse and long-term renal damage were frequent. No specific induction or maintenance regimen showed significant prognostic impact, whereas baseline hypertension was independently associated with a lower risk of relapse.
PO:35:228 | Polymyalgia rheumatica and giant cell arteritis induced by immune checkpoint inhibitors for cancer treatment: a systematic review and meta-analysis highlighting differences from the idiopathic forms
Background. Immune checkpoint inhibitors (ICIs), widely used in cancer immunotherapy, can trigger immune-related adverse events, including polymyalgia rheumatica (PMR) and giant cell arteritis (GCA), likely through mechanisms involving altered immune tolerance. We conducted a systematic review (SLR) and meta-analysis to characterize these conditions and explore potential differences from the idiopathic forms. Materials and Methods. The SLR analyzed Medline and EMBASE databases up to July 2024, comparing ICI-induced PMR and GCA to their primary forms. Where direct comparisons with idiopathic forms were unavailable, we referred to data from prior meta-analyses and large observational cohorts to qualitatively explore potential differences. Results. From 1,237 abstracts, 46 were included, yielding 358 patients (314 with ICI-PMR and 44 with ICI-GCA). ICI-PMR had a pooled prevalence of 0.3% [95% CI: 0.1%–1.2%] among ICI recipients. Patients were predominantly males (64% [95% CI: 54%–73%]), with a mean age of 71 years [95% CI: 68–74]. PD1/PDL1 blockers were used in 85% [95% CI: 80%–89%] of cases. Inflammatory pain in the girdles was universal (100%), however pelvic girdle involvement was explicitly reported in only 3 studies. Peripheral arthritis in ICI-PMR was present in 26% [95% CI: 9%–54%], and normal inflammatory markers were detected in 26% [95% CI: 15%–40%]. Glucocorticoids (GCs) completely improved symptoms in 83% of patients [95% CI: 66%–92%], with 13% [95% CI: 12%–34%] requiring DMARDs and 18% [95% CI: 9%–33%] experiencing relapses (Figure 1). Two comparative case-control studies showed significant differences between ICI-induced and primary PMR. ICI-PMR patients had milder symptoms, lower C-reactive protein levels, and required lower median prednisone dosages. ICI-GCA prevalence was 0.06% among ICI recipients. Male patients comprised 51% [95% CI: 36%–66%], with a mean age of 71 years [95% CI: 68–74]. About 50% [95% CI: 23%–77%] received anti-CTLA4 blockers (alone or with PD1 blockers), while the rest received PD1/PDL1 blockers. Clinical features included cephalic symptoms (85% [95% CI: 70%–93%]), permanent visual loss (23% [95% CI: 12%–39%]), and large-vessel involvement (62% [95% CI: 40%–80%]). No comparative studies between ICI-GCA vs primary GCA were retrieved. High-dose GCs permitted remission in 95% [95% CI: 73%–99%], though 19% [95% CI: 7%–41%] experienced relapses and 10% [2% - 31%] required DMARDs (Figure 1). Conclusions. ICI-induced PMR and GCA may differ from idiopathic forms, potentially presenting with milder symptoms and more favorable treatment responses. Large observational data and meta-analyses on primary forms suggest higher relapse rates and prolonged GC use [1,2], yet further robust comparative studies are needed to validate whether ICI-induced syndromes truly represent a distinct and less severe clinical entity.
PO:36:238 | Clinical, functional, and radiological similarities between interstitial lung disease–anti–myeloperoxidase and idiopathic pulmonary fibrosis
Background. An association between interstitial lung disease (ILD) and anti–myeloperoxidase (MPO) antibody positivity is well established. This condition does not necessarily overlap with ANCA-associated vasculitis but in 60–70% of cases presents as an isolated pulmonary disease. Previous observations suggested that this fibrosing disorder (MPO-ILD) shares several clinical features with idiopathic pulmonary fibrosis (IPF). Radiologically, small case series reported the presence of honeycomb-like lesions in the anterior segment of the upper lobe and a possible larger size of honeycombing cysts, as suggested by expert radiologists. Based on these findings, we conducted an exploratory comparative study between MPO-ILD and IPF aimed at identifying potential clinical, functional, and radiological differences. Materials and Methods. We retrospectively enrolled patients followed at the tertiary referral clinics for interstitial lung disease and rheumatology, diagnosed with IPF or MPO-ILD. Clinical data (demographics, comorbidities, treatments, environmental exposures), laboratory findings (autoantibody profiles, CRP, baseline neutrophil count, creatinine), and pulmonary function parameters (FVC, TLC, DLCO) were collected. High-resolution CT (HRCT) scans at diagnosis and after 24 months were reviewed by an expert thoracic radiologist using a structured evaluation grid. A specific index was developed to assess honeycombing cyst size, based on the mean diameter of three cysts per lung side. Results. A total of 27 IPF and 5 MPO-ILD patients were included; two MPO-ILD patients developed vasculitis after the ILD diagnosis. Demographic, exposure, and comorbidity profiles were comparable between groups. Compared to IPF, MPO-ILD patients more frequently reported arthralgia and ENT symptoms (p = 0.009 and 0.008, respectively). At baseline, MPO-ILD patients had higher serum creatinine (p = 0.012) and neutrophil counts (p = 0.012). Low-titer ANA positivity was more frequent in MPO-ILD (18.5% in IPF vs 80% in MPO-ILD, p = 0.015). No relevant differences were observed in FVC or TLC between groups; however, an improvement in DLCO was noted in MPO-ILD patients during the first 12 months (p = 0.047). All MPO-ILD patients received corticosteroids, 4/5 received immunosuppressive therapy, 3/5 were treated with nintedanib, and 1/5 with pirfenidone. At chest CT review, most patients exhibited a definite or probable UIP pattern (81% IPF and 80% MPO-ILD at 24 months). No radiological item significantly differed between groups, either at baseline or after 24 months. Conclusions. MPO-ILD is a progressive fibrosing lung disease showing clinical and radiological features largely overlapping with IPF and not invariably associated with vasculitis. A transient improvement in DLCO may reflect the effect of corticosteroid or immunosuppressive therapy during the first 12 months; however, the subsequent decline appears similar to that observed in IPF.
PO:36:242 | Bilateral central retinal artery occlusion as the first manifestation of eosinophilic granulomatosis with polyangiitis during benralizumab therapy
Background. Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare systemic vasculitis characterized by an initial prodromal phase with eosinophil-driven manifestations such as asthma, nasal polyposis, and rhinitis, followed by an antineutrophil cytoplasmic antibody (ANCA)-associated vasculitic phase. Ocular involvement is possible but uncommon (approximately 15% of cases), and central retinal artery occlusion (CRAO) represents an exceedingly rare event. Although benralizumab, a monoclonal antibody targeting the IL-5 receptor, has proven effective in managing eosinophilic manifestations such as asthma and nasal polyposis, its ability to prevent vasculitic damage remains uncertain. We report a case of EGPA complicated by bilateral CRAO occurring during benralizumab therapy. Case report. A 61-year-old man with a history of adult-onset chronic rhinosinusitis and severe asthma, treated with benralizumab since 2022, presented to the emergency department in June 2024 with sudden bilateral blindness preceded by transient amaurosis episodes, without systemic symptoms or ocular pain. Ophthalmologic examination revealed markedly reduced visual acuity in both eyes (hand motion only) and a relative afferent pupillary defect. Fundus examination showed pale optic discs with central cherry-red spots. Optical coherence tomography (OCT) demonstrated inner retinal layer edema and hyperreflectivity (Figure 1a–c), while fluorescein angiography confirmed delayed retinal arteriolar filling (Figure 1d), findings consistent with CRAO. Laboratory tests revealed elevated inflammatory markers and high-titer myeloperoxidase (MPO)-ANCA positivity (134 IU/mL; positive >3 IU/mL) in the absence of peripheral eosinophilia, likely due to benralizumab therapy. Based on clinical and serological findings, a diagnosis of EGPA was established. High-dose corticosteroids and combined rituximab–cyclophosphamide therapy were initiated according to KDIGO and PEXIVAS recommendations. After an initial improvement, disease relapse occurred with increased MPO-ANCA levels, requiring steroid escalation and two additional cyclophosphamide infusions (cumulative dose: 4 g). Within six months, inflammatory markers and antibody titers normalized; however, visual loss persisted with only partial recovery (finger counting at 1 meter OD, 2/10 OS). Maintenance therapy with rituximab 500 mg every six months was started. Conclusions. This is the first reported case of EGPA complicated by bilateral CRAO occurring during benralizumab treatment. Suppression of eosinophilia did not prevent the development of a severe ANCA-mediated complication, suggesting distinct pathogenic pathways for eosinophilic and vasculitic damage. This case highlights the limitations of IL-5R inhibition in preventing systemic vasculitis and underscores the importance of early and aggressive immunosuppression to avoid irreversible outcomes.
PO:36:243 | Drug survival, discontinuation reasons and disease activity in patients with Behçet's disease treated with infliximab - a real-life study
Background. Behçet's Disease (BD) is a rare multisystemic vasculitis that can result in life-threatening manifestations when involving the central nervous system or vascular system. Infliximab (IFX) is an immunosuppressive drug widely used for the treatment of BD with major organ involvement or refractory to therapies. The objective of the study was to evaluate the drug survival, discontinuation reasons, safety profile and disease activity of a cohort of patients diagnosed with BD receiving IFX. Materials and Methods. We conducted a retrospective observational study examining all the patients affected by BD according to ISG criteria treated with Infliximab. Patient demographics and background data were collected. Disease activity was assessed using the BDCAF (Behçet’s Disease Current Activity Form 2006) index, and clinical remission was evaluated with a score <= 2 points; the safety outcomes were the incidence of adverse drug reactions (ADRs). IFX 5 mg/kg was administered as an intravenous infusion at weeks 0, 2, and 6, and at 6-8 week intervals thereafter. We performed statistical analysis using descriptive statistics (mean ± standard deviation), median (interquartile range IQR), Odds Ratio, Chi-square test, Student’s t-test or Mann Whitney test, statistical significance was assessed for p < 0.05. Results. A total of 60 BD patients (56.7% female, 43.3% male) were treated with IFX from 2003 to 2025. Their mean age of disease onset was 30.9 years (range 8-63), with a mean age at the introduction of Infliximab of 41.6 years. The main cumulative reasons for starting therapy were: oral and genital recurrent aphthae (71.7% and 35%), cutaneous manifestations (35%), articular involvement (inflammatory arthralgias in 23.3% and arthritis in 23.3%), ocular involvement was found in 28% and SNC involvement in 15%. Analyzing the duration of treatment, it was observed that therapy is currently being followed by 27 patients (drug survival 45%) with a median treatment duration of 37 months (IQR 17-72); drug survival at one year is 78%, at two years of 63.3%, and at five years of 35%. The main causes of discontinuation of therapy were allergic reactions (13%), loss of efficacy (13%), inefficacy (13%), and de novo manifestations (12%) mainly because of recurrent aphthous manifestation. Analyzing the BDCAF index, it emerged that 92.6% of patients currently undergoing treatment with IFX show an improvement in BDCAF, as well as 89.3% of patients who discontinued treatment, with an average reduction of this index by 4 points. Conclusions. This study showed that IFX is associated with low rates of discontinuation due to adverse events in patients with BD. Notably, 12% of patients experienced de novo organ manifestations. Drug survival was 45%, with a median treatment duration of 37 months. The drug led to a significant reduction in the BDCAF index in the analyzed patients, demonstrating a good safety profile and effectiveness in real life.
PO:36:244 | Early diagnosis in eosinophilic granulomatosis with polyangiitis: a multidisciplinary approach
Background. Early diagnosis of Eosinophilic Granulomatosis with Polyangiitis (EGPA) remains one of the major unmet needs in clinical practice due to the non-specific nature of prodromal symptoms and the lack of specific biomarkers, particularly in patients who are anti-neutrophil cytoplasmic antibody (ANCA)-negative. The involvement of a multidisciplinary team may improve clinical management and the diagnostic-therapeutic process. The study objectives were: 1. To identify factors that may suggest an early diagnosis of EGPA by comparing patients referred to the rheumatologist through a multidisciplinary team, who do or do not receive an EGPA diagnosis. 2. To evaluate whether clinical features differ between EGPA patients referred through a multidisciplinary team and those referred through conventional pathways. Materials and Methods. A retrospective study was conducted on consecutive patients between December 2023 and May 2025, categorized into three groups: 1. Patients with suspected EGPA evaluated through the multidisciplinary eosinophilic diseases pathway at our university hospital, who received a confirmed diagnosis (EGPA-MDT); 2. Patients evaluated through the same pathway who did not receive an EGPA diagnosis (nEGPA); 3. Patients referred through conventional channels who were diagnosed with EGPA (EGPA-CR). Demographic, clinical, laboratory, and instrumental data were compared. Non-parametric tests (Kruskal-Wallis, Mann-Whitney, and Chi-square) were used for statistical analysis. A p-value < 0.05 was considered statistically significant. Results. A total of 85 patients were enrolled: 21 EGPA-MDT, 26 nEGPA, and 38 EGPA-CR. Demographic data are shown in Table 1. Compared to nEGPA patients, EGPA-MDT patients had a higher prevalence of systemic manifestations (81% vs 26.9%; p = 0.001) and more severe nasal disease (Nasal Polyp Score 4.0±2.3 vs 2.6±2.3; p = 0.05), as well as higher mean eosinophil counts (absolute mean values 4283.6±6131.6 cells/µL vs 644.4±537.4 cells/µL; p < 0.001), erythrocyte sedimentation rate (ESR, 49.3±31.1 mm/h vs 17.1±21.7 mm/h; p = 0.001), and C-reactive protein (CRP, 39.9±34.0 mg/L vs 2.0±3.5 mg/L; p < 0.001). Furthermore, EGPA-MDT patients showed greater steroid dependence (76.2% vs 15.4%; p < 0.001) and a higher rate of hospitalization at the time of first rheumatologic referral (61.9% vs 19.2%; p = 0.003) compared to nEGPA patients. When comparing clinical indices, EGPA-CR patients had higher mean BVAS scores (15.5±5.2 vs 11.6±5.6; p = 0.01) and VDI scores (4.7±1.0 vs 3.5±1.5; p = 0.006) than EGPA-MDT patients. Conclusions. Constitutional symptoms, steroid dependence, and greater severity of sinonasal manifestations emerged as possible red flags for early EGPA diagnosis in patients within a multidisciplinary pathway. EGPA-CR patients, by contrast, displayed more severe systemic symptoms and higher disease activity, often eluding early diagnosis. Our data suggest that a multidisciplinary approach facilitates referral and early diagnosis, enabling phenotype-specific treatments that may improve the clinical course and quality of life of patients with EGPA.
PO:36:245 | Uncovering clinical and demographic differences in major organ involvement versus benign Behçet’s disease: insights from a single-centre study
Background. Behçet’s disease (BD) is a rare chronic inflammatory disease with a multi-systemic clinical presentation. Mucosal ulcerations and skin lesions are the most common features, typically indicating a benign disease course. In contrast, major organ involvement (MOI) defines a severe disease due to the organ-threatening potential. Patients with MOI often require immunosuppressive treatment to achieve sustained remission and prevent organ damage. Identifying factors associated with the development of a MOI subset is crucial for understanding disease progression and guiding therapeutic strategies. The aim of this analysis was to describe and compare the clinical and demographic characteristics of patients with MOI BD and benign subset. Materials and Methods. We retrospectively analyzed 186 BD patients with a minimum of 5 -year follow-up. Patients were classified into the MOI subset if they had a history of ocular, vascular or neurological involvement; those without MOI were classified as having benign disease. Descriptive statistics was performed (mean ± standard deviation, median with interquartile range). Categorical variables were compared using Chi-square test or Fisher's exact test when appropriate. Continuous variables were compared using Student's t-test for normally distributed data or Mann-Whitney U test for non-parametric data. Statistical significance was set at p < 0.05. Results. The benign group included 80 patients (43.2%) while the MOI group consisted of 105 patients (56.8%). In both groups patients were mainly females (67.5% in benign group versus 64.8% in MOI group). The mean age at disease onset was 31.2 years (median:35) for benign group and 28.1 years (median:30) for MOI group, whereas the mean age at diagnosis was 38.1 years (median: 39) and 37.3 years (median: 38), respectively. The median diagnostic delay amounted to 3 years in benign group and 5 years in MOI group. However, no statistically significant differences were found regarding gender and age distribution. Oral ulcers (98.8%), genital ulcers (68.8%) and pseudo-folliculitis (46.3%) were the most common cumulative clinical features in patients with benign disease, while MOI patients most frequently showed ocular manifestations (74%), followed by neurological (21%) and vascular (24%) lesions. Differences in prevalence of arthritis, erythema nodosum and gastrointestinal involvement were less pronounced among the two groups. Conclusions. This monocentric cohort highlights distinct organ involvements in patients with benign and MOI BD subset, consistent with previous evidence. Patients with MOI BD showed earlier disease onset and longer diagnostic delay compared to benign patients. These findings suggest that in addition to MOI, also prolonged disease duration before diagnosis may contribute to disease severity. Further studies including also etiopathogenetic variables are needed to identify potential predictive factors of severe disease, aiming to facilitate earlier diagnosis and timely treatment to reduce organ damage and clinical burden.
PO:36:246 | Early real-world outcomes with benralizumab in eosinophilic granulomatosis with polyangiitis: a monocentric retrospective
Background. Eosinophilic Granulomatosis with Polyangiitis (EGPA) is a rare small-vessel vasculitis driven by eosinophilic inflammation. Benralizumab, an IL-5 receptor antagonist, has recently been introduced for EGPA treatment, although data from real-life clinical practice following its European approval remain limited. This study aimed to assess the early effectiveness and safety of Benralizumab in patients with EGPA during the first 6 months of therapy. Materials and Methods. Patients with EGPA were enrolled according to the 2022 American College of Rheumatology/European Alliance of Associations for Rheumatology Classification Criteria. Blood eosinophil counts and clinical manifestations were recorded at baseline, after three months (T3), and at six months (T6). Changes in continuous variables were analyzed using the Wilcoxon signed-rank test. Results. Thirteen patients (F: 66.7%) were included. No relapses were observed during the 6-month follow-up (mean relapse count: 0.0). The mean blood eosinophil count significantly decreased from baseline to T3 and T6 (mean reduction: 984.2 cells/mm³; p < 0.001; figure 1). Clinical improvement was observed across several domains. ENT symptoms, present at baseline, resolved in all affected patients. Renal involvement showed improvement (p = 0.0316), while neurological involvement remained unchanged (p = 0.157). No adverse events or treatment discontinuations were reported. Conclusions. In this early monocentric real-world experience, Benralizumab was associated with a favorable safety profile, significant eosinophil depletion, and clinical improvement—particularly in ENT and renal involvement. Although limited by small sample size and short follow-up, these preliminary findings support the potential role of Benralizumab as a therapeutic option in EGPA, especially in patients with prominent eosinophilic or upper airway manifestations.
PO:36:251 | Rheumatoid factor predicts vasculitis relapse in eosinophilic granulomatosis with polyangiitis: a machine learning approach
Background. The present study was conducted with the objective of evaluating the frequency and prognostic significance of rheumatoid factor (RF) in patients diagnosed with eosinophilic granulomatosis with polyangiitis (EGPA). A particular emphasis was placed on the potential role of RF in predicting vasculitis relapses. Materials and Methods. A retrospective cohort study was conducted, encompassing patients diagnosed with EGPA who underwent RF testing (immunoturbidimetric assay/nephelometric assay/enzyme-linked immunosorbent assay) at the time of diagnosis. Clinical and laboratory data were prospectively collected starting from diagnosis and throughout the following 60 months. Relapse was defined as the new onset, recurrence, or worsening of systemic signs or symptoms (excluding asthma and nasal polyps exacerbations) associated with a BVASv3 > 0, requiring the modification of systemic therapy. Kaplan-Meier curves were used to assess relapse-free survival. A Random Forest machine learning model was developed to identify relapse predictors, with support from SHAP analysis. Results. A total of 83 patients diagnosed with EGPA were included in the present study, 45.8% of whom (38/83) were found to have positive RF. During follow-up, 19.3% (16/83) of patients experienced at least one relapse. Patients with a positive RF test had a significantly higher relapse rate than those with a negative RF test (39.5% vs. 2.2%, p=0.003). The median time to relapse was 29 [11.8-71.8] months. The overall relapse rate at 12, 24 and 60 months were 4.8%, 9.1% and 26.2%, respectively. As illustrated in Figure, the Kaplan-Meier analysis demonstrated a significant lower 5-year relapse-free survival in RF-positive patients compared to RF-negative patients (log-rank test, p < 0.001). Furthermore, patients with a positive RF test had a higher frequency of mononeuritis multiplex (52.6% vs. 13.3%, p = 0.011) and elevated C-reactive protein levels (49.1 mg/L vs. 11.0 mg/L, p = 0.007) compared to RF-negative patients. The Random Forest model identified RF positivity as the strongest relapse predictor (VIMP 0.2031, 95%CI -0.012 to 0.307), outperforming established variables such as ANCA positivity and age at disease onset. Subsequent SHAP analysis confirmed that negative RF was associated with a greater relapse-free probability (phi +0.1469). Conclusions. RF is a prevalent and clinically significant biomarker in EGPA. In our cohort, it is associated with increased systemic relapse risk. These findings suggest that RF may define a distinct immunopathogenic subset of EGPA, characterised by increased systemic inflammation and vasculitic phenotype. The integration of RF into future prognostic models has the potential to enhance patient stratification and guide personalized treatment approaches.
PO:36:253 | Lifestyle and Behçet's syndrome: a preliminary study on gender differences
Background. Behçet’s syndrome (BS) is a chronic, relapsing autoinflammatory disease characterised by various clinical manifestations, including oral and genital ulcers, skin lesions, ocular inflammation, and neurological, vascular, and gastrointestinal involvement. Both genetic and environmental factors contribute to susceptibility and disease phenotype. A previous study investigating the clinical phenotype across gender differences revealed that the disease is more frequent and more severe in male subjects [1]. Emerging literature evidences support the role of a healthy lifestyle as an environmental factor able to modulate disease activity, disease severity, and quality of life [2, 3]. The purpose of this preliminary study is to evaluate gender differences in the main lifestyle-related aspects within a cohort of patients with BS. Materials and Methods. An anonymous questionnaire was administered to a cohort of consecutive patients with BS, who provided information on the following items: age, sex, dietary habits, physical activity, smoking habits, alcohol consumption, impact of the disease on work, and sleep habits/hygiene. Results. Table 1 reports the results of the survey related to the 39 recruited patients (24M:15F). Statistically significant differences were found in case of: 1) fruit consumption: women consumed more abundant weekly portions compared to men (16-29 weekly portions in 8.3% of males vs 33.3% of females); 2) consumption of sugary drinks: the weekly frequency was zero in a significantly higher number of females compared to males (73.3% F vs 16.7% M); 3) the impact on work, which was reported as null for 10.7% of males compared to 46.7% of females. Conclusions. Our study highlights a greater consumption of pro-inflammatory dietary components (sugars) and a lower consumption of anti-inflammatory foods (fruit) in men. Among the modifiable lifestyle factors, nutrition plays an essential role for human health: a diet rich in anti-inflammatory foods, such as fruit and vegetables, omega-3 fatty acids, combined with a reduction in processed foods, represents a significant factor in modulating inflammation, with a positive impact on disease activity and quality of life. Although our data need to be validated in a larger cohort of subjects, also including a population of healthy subjects, the present study emphasizes the importance of a personalised and holistic approach for BS management, also considering the wide disease heterogeneity. References p]:pt-0 [&>p]:mb-2 [&>p]:my-0"> Leccese P, et al. Behçet's syndrome: one year in review 2022. Clin Exp Rheumatol. 2022;40(6):945-958. p]:pt-0 [&>p]:mb-2 [&>p]:my-0"> Di Cianni F, Sulis A, Italiano N. The impact of environmental factors on aetiopathogenesis and clinical manifestations of Behçet's syndrome. Clin Exp Rheumatol. 2024;42(1):15-21.
PO:37:256 | Spontaneous renal artery dissection: a subtle presentation of a “vasculitis-mimicker”
Background. Medium- and large-vessel vasculitides represent a diagnostic challenge. The case described here highlights the importance of an accurate differential diagnosis, as non-inflammatory vascular diseases can mimic vasculitic patterns, with significant therapeutic implications. Materials and Methods. A 42-year-old man presented to the emergency department with subacute onset of temporal headache, low-grade fever, left flank pain, and hypertension (BP 170/100 mmHg). Rheumatologic history was unremarkable and physical examination was normal. Abdominal CT, performed for suspected ureterolithiasis, showed a hypodense area in the mid and upper third of the left kidney compatible with parenchymal ischemia, and a sleeve-like thickening with filiform stenosis of the ipsilateral renal artery, initially suggestive of vasculitis (renal arteritis). The patient was admitted to the Rheumatology Unit. Laboratory tests revealed inflammatory activity (CRP 3.7 mg/dL, ESR 51 mm/h). Intravenous methylprednisolone pulses (250 mg for 3 days) were started, followed by oral prednisone (1 mg/kg) and antihypertensive therapy. Given the suspicion of vasculitis, PET imaging was performed, showing no evidence of vascular inflammation, as well as duplex ultrasound of the four limbs and supra-aortic trunks, which revealed no stenotic or occlusive lesions. Considering the abrupt onset of symptoms, negative autoimmunity, negative PET findings, and absence of additional clinical or instrumental abnormalities, a renal arteriography was performed. It revealed a dissection of the left renal artery with thrombosis of the false lumen and parenchymal ischemia, allowing a final diagnosis of spontaneous left renal artery dissection complicated by renal infarction and renovascular hypertension. Results. The case was discussed with the Radiologist and Vascular Surgeon. Given the complete thrombosis of the false lumen, endovascular revascularization was excluded, and a conservative approach was adopted with antihypertensive and antiplatelet therapy, along with progressive steroid tapering, with no clinical relapse. A follow-up contrast-enhanced CT after 15 days confirmed stability of the renal ischemic lesion and improved parenchymal perfusion (Figure 1). Conclusions. Spontaneous renal artery dissection is a rare clinical entity with elusive etiology, accounting for only 1–2% of all arterial dissections. To date, approximately 200 cases have been reported in the medical literature. Our case emphasizes the importance of considering non-inflammatory vascular conditions, such as spontaneous dissection, in all instances where first-line imaging raises a generic suspicion of medium- or large-vessel vasculitis, particularly in cases of isolated vascular involvement and absence of systemic symptoms. A high index of suspicion is required in clinical practice, especially in atypical or subtle presentations, to promptly achieve the correct diagnosis.
PO:37:257 | Giant cell arteritis debuting with aortic involvement: the importance of integrated diagnostics in fever of unknown origin
Background: giant cell arteritis (GCA) is the most frequent large vessel vasculitis, affecting both male and female patients older than 50 years old. Opposite to the cranic involvement (common carotid arteries and their branches) that may debut with headache and visus loss, the extra-cranic involvement (aorta and its branches) is more subtle, leading to a delayed diagnosis, causing the development of aneurisms and dissections [1-3]. Usually, these are late disease complications (after 10 years) but can be found even at diagnosis [1-3]. Case report: a 68-year-old woman, ex-smoker, comes to visit because of a 4-month history of daily fever (up to 38.5°C) with shivers and night sweats, myalgias, fatigue and weight loss. Blood tests showed high neutrophil and platelet count, with persistent inflammation (CRP 35 mg/L). To rule out an occult infection, the patient had been thoroughly screened with blood cultures, urine cultures, treponemic tests, which all came back negative. Being affected by a fever of unknown origin (FUO), the patient was admitted to our Clinic to undergo further testing from which no sign of autoimmunity emerged. Given the development of a persistent frontal headache, even though no other arteritis symptoms were present, an ultrasonographic study of the temporal, axillary, and carotid arteries was performed, showing no halo sign. Because of the persistence of fever and inflammation without explanation, a PET-CT and an echocardiography (to rule out infective endocarditis) were performed and, since GCA was still highly suspected, a temporal artery biopsy was scheduled. PET-CT (Figure 1) showed an intense FDG avidity along the full length of the aortic wall and the carotid and axillary arteries while the echocardiography found a dilation of the aortic root with valve insufficiency and no sign of endocarditis. Granulomatous inflammation suggesting GCA was found in the biopsy specimen of the temporal artery. The aortic dilation was studied performing a CT angiography that confirmed the enlargement of the aortic root and arch and showed a focal dissection 4 cm wide (Figure 2). Glucocorticoid therapy was immediately started and tapered for 8 weeks, alongside tocilizumab, leading to the resolution of fever and inflammation. In the meantime, heart surgeons successfully performed a replacement of the aortic arch. Histological analysis of the aortic wall confirmed the GCA diagnosis (Figure 3). Conclusions. PET-CT and temporal artery biopsy should always be a part of the FUO diagnostic work-up, even when signs or symptoms suggesting GCA are absent. They turn out to be crucial to timely diagnose the disease and may help early identify severe and potentially fatal complications like aneurisms and aortic dissections that, despite being more frequent in the late course of the disease, can also be found at its debut4. This has important therapeutic and prognostic implications.
PO:37:258 | Neutrophil and eosinophil extracellular traps in eosinophilic granulomatosis with polyangiitis: phenotype-based characterization and response to mepolizumab
Background. EGPA presents eosinophil (EOS)-related and vasculitic features. Introduction of mepolizumab (MEP) revolutionized the treatment of EOS manifestations. However, efficacy of MEP also in vasculitic phenotypes suggests direct interactions between EOS and neutrophilic inflammation in EGPA. Neutrophil extracellular traps (NETs) are an important innate immune response involved in ANCA-associated vasculitis pathogenesis. Similarly, EOS produce extracellular traps (EETs), recently detected in EGPA patients. Our study aims to analyse NETs and EETs in different disease phenotypes and in response to MEP therapy. Materials and Methods. EGPA patients classified according to MIRRA trial and/or ACR/EULAR 2022 criteria and eligible for MEP therapy were consecutively enrolled. Clinical and routine blood chemistry data were collected before (T0) and after 6 (T1) and 12 (T2) months of treatment with MEP 300mg/4weeks. Oral steroid was tapered according to clinical judgement. Therapy with immunosuppressant, if taken, was unchanged during the study. In parallel, we evaluated NETs and EETs on peripheral blood by immunofluorescence staining (Petretto et al.,2019). NETs and EETs were expressed as percentage of total area of cells in the fields. Patients were stratified by disease phenotype according to presence/absence of MPO-ANCA, asthma, nasal polyposis (CRSwNP) and organ involvement. Results. 17 patients were enrolled (53% female (9/17)). MPO-ANCA were detected in 29.4% of patients (5/17). 88% (15/17) were asthmatic, 60% had severe asthma. 53% (9/17) were atopic and 82% had CRSwNP. At T0 94% (16/17) were administered oral prednisone (5.83±4.18mg, mean dose). Figure 1 reports distribution of organ involvement. Following MEP introduction, EOS blood count reduced from T0 to T1 (p=0.036) but not from T1 to T2, while neutrophils did not vary in any period. Steroid dosage was reduced to 1.04±2.59mg at T2 (p=0.003). 10 patients (58.8%) were steroid-free. No relapse was observed. At T0, NETs and EETs levels did not vary by ANCA status, organ involvement, EOS peak count, asthma or CRSwNP presence/severity. NETs levels were negatively correlated to total IgE titre (r=-0.52, p=0.05). EETs values are higher in atopic patients (p=0.017) regardless of steroid dosage and EOS blood count. In response to MEP, NETs and EETs decreased at T1 (respectively p=0.001, p=0.014) but were stable between T1 and T2 in the overall group (Figure 2). After stratification by ANCA status, NETs significantly decreased only in ANCA positive patients at T1 (p=0.01), whereas EETs only in ANCA negative patients at T1 (p=0.025), with no differences observed between T1 and T2. No difference was found according to asthma and CRSwNP presence. Conclusions. In a representative cohort of EGPA patients, NETs and EETs vary by atopic status but not by ANCA status or organ involvement. After 6 months of therapy, MEP influences NETs and EETs formation according to ANCA profile, suggesting utility of NETs and EETs assessment in disease phenotyping.
PO:37:259 | Is there a seasonal pattern in giant cell arteritis? Revisiting the evidence in a large monocentric cohort of 1203 patients
Background. Whether the disease onset in giant cell arteritis (GCA) exhibits a seasonal pattern remains unclear. Previous studies have yielded conflicting evidence: some report no seasonality, while others suggest seasonal variation, though findings are inconsistent and difficult to compare, especially due to methodological limitations, including small cohort sizes and reliance on diagnosis or biopsy dates rather than symptoms onset. We aimed to clarify whether a seasonal pattern exists by analyzing a large cohort using the date of symptom onset as the temporal reference. Materials and Methods. Consecutive patients from a large monocentric GCA (1994–2024) with a documented date of symptom onset were included. To ensure balanced seasonal representation, patients with symptom onset outside the period of December 1, 1994, to November 30, 2023, were excluded. Meteorological seasons were used for the analysis (spring: Mar–May; summer: Jun–Aug; autumn: Sep–Nov; winter: Dec–Feb). To assess whether symptom onsets were equally distributed across seasons (25% per season), we applied an exact multinomial test using the “ExactMultinom” package in R. Sensitivity analyses were performed for subgroups by sex and clinical phenotype (cranial vs extracranial involvement), with Bonferroni-Holm correction for multiple testing. Results. Of 1203 patients in the full cohort, 1149 fulfilled the inclusion criteria and were included in the main analysis (population’s characteristics are reported in Table 1). The overall seasonal distribution of symptom onset was: spring 292 (25.4%), summer 276 (24.0%), autumn 271 (23.6%), winter 310 (27.0%) (p = 0.36). Figure 1 illustrates the seasonal distribution of symptom onset stratified by years across the study period. Subgroup analyses revealed no overall significant seasonal variation as shown in Table 2. Conclusions. This large, single-center cohort study using symptom onset data found no evidence of a significant seasonal pattern in the disease onset of GCA patients.
PO:37:260 | Mepolizumab in the treatment of patients with eosinophilic granulomatosis with polyangiitis: real-life experience from a single-center cohort
Background. Mepolizumab is an anti-interleukin-5 (IL-5) monoclonal antibody approved for the treatment of eosinophilic granulomatosis with polyangiitis (EGPA) at a dose of 300 mg every 4 weeks, with the goal of both achieving and maintaining disease remission besides reducing the dose of glucocorticoids (GCs). The objective of this study is to evaluate the characteristics of patients with EGPA treated with mepolizumab at our center, their response to treatment, and the steroid-sparing effect. Materials and methods. Twenty-one patients (12 men) were enrolled, mean age 64.5 ± 9 years, median disease duration 4 years (IQR 1.6-7.25). Nine patients (43%) were positive for MPO (myeloperoxidase) antibodies, 2 (10%) for PR3 (proteinase 3). The mean duration of treatment with mepolizumab was 2.3 ± 1.7 years. In 6 patients (29%) mepolizumab was used as first-line, one patient had previously been treated with rituximab, 5 patients with cyclophosphamide, 9 patients with methotrexate/azathioprine or both. Results. The clinical description of patients with disease manifestations before starting mepolizumab therapy is reported in Table 1. All patients had an excellent response, with a reduction in the number of asthma flares, normalization of eosinophil counts, resolution of cutaneous vasculitis, improvement in nasal polyps, neuropathy, gastrointestinal and myocardial involvement. During follow-up, 13 patients (62%) were able to discontinue GCs, and in the remaining 8 cases, a dose of ≤5 mg/day was achieved. No adverse events leading to drug discontinuation occurred. Conclusions. In our cohort of patients with EGPA, mepolizumab confirmed its efficacy in reducing disease activity, its excellent safety profile and its steroid-sparing effect, allowing us to interrupt GCs in more than 60% of patients, and to reduce the daily dosage below 5 mg in the rest of the case series.
PO:37:263 | First non invasive visualization of vasculitis in the retinal arteries by high resolution optical coherence tomography in a patient with giant cell arteritis
Background. Giant cell arteritis (GCA) is an idiopathic vasculitis affecting the large- and medium-sized arteries of the elderly. GCA is characterized by systemic inflammation and patchy arterial inflammation resulting in arterial wall thickening and potential remodelling with stenosis/occlusion or aneurysms. Accordingly, GCA may be complicated by end-organ ischemia, especially in the eye, due to arteritic ischemic optic neuropathy, occlusion of central retinal artery (CRAO) or of one of its branches. Optical coherence tomography (OCT) is an imaging technique that exploits interferometry with short-coherence-length light to characterize the tissues on the micron scale, allowing to visualize retinal features and thickness. High resolution OCT (HR-OCT) is an evolution of OCT not yet available on the market. It has a higher spatial resolution tha traditional OCT. Being potentially able to characterize the arterial walls of the branches of the central retinal artery, HR-OCT is being developed to study retinal vasculopathies. Here we present the first case of GCA with visual involvement (specifically CRAO), evaluated with HR-OCT. Case Report. An 80 year old woman with history of hypertension, dyslipidemia, diverticolitis, and crhonic headache, present to the emergency room in March 2024 for visual loss. She refers that her chronic headhace had changed since the spring of 2023, affecting the temporal area bilaterally and being more prevalent in the morning. The patient also reported astenia for 6-12 months, worsening exertional dyspnea for 5-6 months and blurred vision for 2-3 months, for which she had a diagnosis of cataract. On the 21st of February 2024 the patient experienced loss of vision from the left eye for which she went to the ER of another hospital, and was diagnosed with CRAO. The patient was discharged with prescription of blood test which showed an ESR of 39 mm/h and a CRP of 76 mg/L. On the 4th of March 2024 GCA was suspected and the patient was referred to our center. The diagnosis was confirmed and she was treated with intravenous methylprednisone 1000 mg for three days, followed by oral prednisone 50 mg which was gradually tapered. High resolution-OCT was performed four days after the initial presentation showed a recanalization of the left retinal artery, with a thickened arterial wall as compared to the controlateral eye. Follow-up after one week showed an improvement in the arterial wall thickening. Conclusions. A novel semeiologic sign of GCA involvement in the branches of the retinal artery by HR-OCT is reported for the first time. This non-invasive finding is promising for its much higher spatial accuracy as compared to temporal artery ultrasonography or angio-CT/MR. However, the technique is not yet standardized and more data are required to assess its clinical relevance.
PO:37:267 | Mimickers of polyarteritis nodosa: a case of segmental arteriolar mediolysis
Background. The diagnosis of medium-vessel vasculitis often requires a thorough differential diagnosis to exclude non-inflammatory vasculopathies. We describe a case of Segmental Arteriolar Mediolysis (SAM), a non-inflammatory arteriopathy that can mimic medium-vessel vasculitis. Materials and Methods. A 54-year-old woman presented to the Emergency Department with acute abdominal pain radiating posteriorly. Laboratory tests showed CRP 21.7 mg/dl and ESR 106 mm/h. Abdominal CT angiography revealed dissection of the superior mesenteric artery and partial occlusion of the inferior mesenteric artery at the proximal and mid-distal segments. A positive urine culture for Klebsiella pneumoniae confirmed a urinary tract infection, treated with targeted antibiotics. A week later, a second abdominal CT angiography showed celiac trunk ectasia, circumferential thickening of the inferior mesenteric artery (reported by the radiologist to be suggestive of vasculitis, see Figure 1), and reduced caliber of the left hypogastric artery, with thrombotic appositions in the right internal mammary, inferior mesenteric, and segmental renal arteries. Further investigations revealed negative ANA and ANCA, equivocal lupus anticoagulant (not confirmed on repeat testing), and negative anticardiolipin and anti-beta2-glycoprotein antibodies. CRP measured approximately 10 days after antibiotic therapy was 0.9 mg/dL. Given the suspicion of medium-vessel vasculitis, high-dose corticosteroids were started, later combined with methotrexate. At the 4-month follow-up, methotrexate had been discontinued due to elevated liver enzymes, and the patient was on low-dose prednisone (5 mg/day). She was asymptomatic, with persistently normal inflammatory markers. The normalization of CRP before corticosteroid initiation, the absence of vascular lesions typical of polyarteritis nodosa, and full clinical and laboratory remission without maintenance therapy raised suspicion for SAM. A new abdominal CT angiography showed near-complete resolution of the circumferential thickening of the inferior mesenteric artery and full resolution of thrombotic appositions. After multidisciplinary discussion with radiologists and vascular surgeons, a diagnosis of SAM was confirmed. Conclusions. Segmental dissections of the celiac, mesenteric, and/or renal arteries are the key distinguishing feature of SAM (figure 2). This rare condition typically affects individuals aged 40–60 years, with a slight male predominance, and carries a high mortality rate (up to 50%) in cases of aneurysmal rupture. There are no established guidelines for treatment or follow-up, but optimal blood pressure control is essential to prevent vascular complications. The differential diagnosis from vasculitic diseases is challenging and relies on radiological, clinical, and laboratory assessment [1,2]. Correct identification of SAM, excluding vasculitic processes, has major implications for prognosis, treatment, and follow-up.
PO:37:268 | Antineutrophil cytoplasmic antibodies-associated vasculitis mimicking giant cell arteritis: a diagnostic dilemma
Background. Here we present a diagnostically challenging case of ANCA-associated vasculitis (AAV) that initially presented with clinical features highly suggestive of giant cell arteritis (GCA). Case Report. An 80-year-old woman, with a medical history notable only for prior COVID-19 pneumonitis and a diagnosis of polymyalgia rheumatica (PMR) in 2024, presented to the emergency department in February 2025 with a three-week history of worsening pelvic and scapular girdle pain. Routine laboratory tests revealed elevated inflammatory markers (ESR 76 mm/h, CRP 16.8 mg/dL) and findings consistent with a urinary tract infection (UTI), with preserved renal function (GFR >60 mL/min). A presumptive diagnosis of a PMR flare triggered by the UTI was made, and antibiotic therapy was initiated. Due to the persistence of symptoms, she was referred to the rheumatology unit. A positive history of recent unintentional weight loss and new-onset jaw claudication emerged. Given the high clinical suspicion of giant cell arteritis (GCA), corticosteroid therapy was promptly initiated. Subsequent vascular ultrasound revealed intima-media complex thickening and a positive compression sign in the left frontal artery, along with moderate intima-media thickening of the right facial artery. While suggestive of GCA, these findings were insufficient for a definitive diagnosis. Following an initial symptom remission, corticosteroid tapering led to a relapse of jaw claudication and the new onset of widespread livedo reticularis. Additionally, previously absent signs of acute kidney injury (AKI) emerged, prompting hospital admission for further diagnostic workup. Laboratory testing revealed persistently elevated ESR and CRP levels, significant renal impairment (creatinine 1.67 mg/dL, GFR 29 mL/min), and positive anti-MPO antibodies (37.0 UI/mL). Over the following days, renal function deteriorated rapidly (creatinine rising to 2.2 mg/dL). Given the progressive AKI and ANCA-MPO positivity, a diagnosis of ANCA-associated vasculitis (AAV) with glomerulonephritis was established. Treatment included three intravenous methylprednisolone pulses followed by two 1 g rituximab infusions administered two weeks apart. A PET-CT scan performed shortly after steroid initiation showed no evidence of large vessel involvement. Furthermore, chest X-ray and electromyography revealed no abnormalities suggestive of other organ manifestations of AAV. At one-month follow-up, renal function had sligthly improved (creatinine 1.5 mg/dL, GFR 33 mL/min), while inflammatory markers and anti-MPO titers (5 UI/mL) had significantly decreased. The coexistence or sequential development of GCA and AAV, though rare, has been documented [Tab 1]. In our case, the absence of a temporal artery biopsy prevents the definitive exclusion of GCA and raises the possibility of an overlap syndrome, rather than an atypical manifestation of AAV mimicking cranial vasculitis. Conclusions. This case highlights the importance of considering alternative diagnoses in patients with atypical GCA presentations, particularly when temporal artery biopsy is unavailable.
PO:37:269 | Intensive therapeutic plasma exchange in life-threatening ANCA-associated vasculitis
Background. In ANCA-associated vasculitis (AAV), despite the findings of the PEXIVAS trial, the usefulness of plasma exchange (PLEX) remains debated in selected clinical settings, such as diffuse alveolar hemorrhage (DAH). Methods. We report a case of life-threatening AAV successfully treated with an intensive, high-volume, and individualized PLEX protocol. Results. We describe a 40-year-old man with newly diagnosed AAV (c-ANCA/anti-PR3, high titer) who presented with rapidly progressive glomerulonephritis and severe respiratory failure (PaO2/FiO2 ratio < 200) secondary to DAH, requiring mechanical ventilation. In addition to induction therapy with methylprednisolone pulses (total 3000 mg) and weekly rituximab (375 mg/m²), we initiated an intensive PLEX regimen consisting of 20 sessions over 52 days (three consecutive at onset), with a mean plasma exchange volume of 1.0–1.5 times the plasma volume (mean exchanged volume per session: 4450 ± 705 mL; total exchanged volume: 89 L). From the third PLEX session, we observed a marked reduction in ANCA titer and inflammatory markers, followed by significant respiratory improvement after the sixth session (Figure 1). The last four sessions were performed after extubation. At 48 months of follow-up, under maintenance therapy with mycophenolate mofetil, no vasculitis flares were observed, although renal recovery was not achieved. This case highlights the potential benefit of an intensive, high-volume PLEX protocol in life-threatening AAV with DAH, supporting several considerations: the PEXIVAS trial, cornerstone of current guidelines, adopted a limited PLEX schedule (7 sessions) without escalation in refractory cases—possibly underestimating efficacy in severe disease phenotypes (our patient achieved pulmonary recovery after the 6th session). Moreover, only 61 patients (8.7%) in PEXIVAS had DAH, and subgroup analysis showed lower one-year mortality in PLEX-treated patients (19.4% vs. 33.3%). A post-hoc analysis of PLEXIVAS demonstrated improved eGFR recovery at 4–8 weeks and greater renal recovery at one year in patients receiving PLEX. Although these findings are not generalizable, they retain potential clinical significance in selected severe cases. The KDIGO 2024 guidelines currently support PLEX in patients with serum creatinine ≥ 300 µmol/L (3.4 mg/dL), suggesting a tailored, individualized approach. Conclusions. Intensive and personalized PLEX regimens deserve renewed consideration in life-threatening AAV—especially in patients with DAH, rapidly progressive renal involvement, or refractoriness to conventional therapy. The efficacy of PLEX in these settings cannot be fairly dismissed based on the PEXIVAS trial alone.
PO:37:270 | Efficacy of iloprost as a therapy for skin ulcers in cryofibrinogenemia and cryoglobulinemia: a complex case in a fragile patient
Background. We present the case of a 75-year-old patient with a past medical history of melanoma removed in 2020, type 2 diabetes mellitus, cognitive decline evolving into Lewy body dementia, and IgG-lambda MGUS (0.5 g/dL) under hematological follow-up. Case Report. Starting in 2020, the patient reported the recurrent appearance of small, subcentimeter ulcers on the fingers, which resolved spontaneously within a few weeks, and an isolated episode of frank purpura on the lower limbs, which subsequently evolved into dyschromic scars. In the rheumatological field, immunological and instrumental tests were performed (capillaroscopy, echocardiogram, ANA, ENA, ANCA, ACPA, antiphospholipids, RF, C3/C4, PCR, serologies for HBV and HCV, Bence Jones proteinuria), all of which were within normal limits. In this context, the presence of a 6% cryocrit was documented, composed of monoclonal IgM-lambda cryoglobulin (2%) and cryofibrinogen (4%). Subsequent hematological investigation with flow cytometry documented a circulating T-LGL population (30%), with no evidence of clonality on bone marrow biopsy, nor signs of myelodysplasia. In the absence of criteria for overt lymphoproliferative disease, there was no indication for specific treatment. In the following years, subcentimeter digital lesions continued to appear episodically, always self-limiting, without deep ulcerations or purpuric recurrences. However, in early 2025, following reported exposure to low temperatures, a sudden worsening was observed, with the appearance of crusted ulcers on the lower limbs, not consistent with vascular distribution. The major lesions were located on the lateral surface of both legs (up to 4 cm in diameter), on the heels, and on some toes. The patient initially reported home management without benefit. A lower extremity ECD was negative for occlusive changes. A skin biopsy of a lesion on the right heel showed partial epidermal ulcerative necrosis, hyperkeratosis, epidermal hyperplasia, and in the dermis, scar-like fibrosis, reactive vascular proliferation, and minimal lymphocytic inflammation, with no histological evidence of vasculitis. The patient arrived at the Difficult Wounds service of the Rheumatology unit in February 2025. Considering the comorbidities, the histological picture, and the high-titer cryofibrinogen, monthly therapy with Iloprost via continuous infusion was initiated, along with advanced local wound care. Progressive resolution of the lesions was observed by May 2025, with good tolerance to the therapy and no apparent clinical recurrences. Conclusions. Iloprost represents an effective and well-tolerated therapeutic option for the treatment of ulcers associated with cryofibrinogenemia, especially in fragile patients for whom the use of immunosuppressants is risky or contraindicated. In complex cases, multidisciplinary discussion is confirmed to be crucial for a correct diagnostic assessment and targeted management.
PO:38:278 | Cognitive behavioural therapy vs. physical therapy for chronic primary low back pain: a systematic review with meta-analysis of randomised controlled trials
Background. Over recent decades, chronic primary low back pain (CPLBP) has shown a consistent epidemiological increase worldwide. Although cognitive behavioural therapy (CBT) is not among the most commonly used interventions for this condition, several recent systematic reviews h ave demonstrated its efficacy. Given its limited implementation in clinical practice, this review aimed to assess the therapeutic validity of CBT by comparing it with physiotherapy (PT) interventions, designed according to the most recent clinical guidelin es for CPLBP. Materials and Methods: Randomised controlled trials (RCTs) comparing CBT and PT in adults with CPLBP were included. The databases PubMed, Cochrane CENTRAL, Embase, CINAHL, Scopus, and PEDro were searched from inception to March 3, 2025. Risk of bias was independently assessed by two reviewers using the Cochrane Risk of Bias 2.0 (RoB 2.0) tool. Based on extracted data, several meta analyses were conducted, grouping outcomes into early phase, acute phase, and late phase follow ups. The certainty of evidence was evaluated according to the GRADE approach. Results: Twelve RCTs were included, comprising a total of 1,762 participants. Meta analyses indicated very low certainty evidence that CBT is more effective than PT in reducing pain in the early p hase (n = 650, MD = −1.29, 95% CI = −2.00 to −0.59, p = 0.0003, I² = 83%), acute phase (n = 337, SMD = −0.16, 95% CI = −0.38 to +0.05, p = 0.14, I² = 0%), and late phase (n = 1108, SMD = −0.45, 95% CI = −0.87 to −0.03, p = 0.03, I² = 91%), as well as in de creasing disability in the early phase (n = 650, SMD = −1.00, 95% CI = −1.55 to −0.44, p = 0.0004, I² = 90%), acute phase (n = 337, MD = −0.27, 95% CI = −2.43 to +1.88, p = 0.80, I² = 75%), and late phase (n = 1108, SMD = −0.97, 95% CI = −1.52 to −0.41, p = 0.0007, I² = 95%). The results for early phase and late phase outcomes, for both pain and disability, were statistically significant. Conclusions: Although supported by very low certainty evidence, these findings suggest that cognitive behavioural therap y may be a valuable intervention to integrate into clinical practice to reduce pain and improve disability in individuals with chronic primary low back pain. Further high quality randomised controlled trials are needed to confirm these results and draw more robust conclusions.
PO:38:280 | Accuracy of generative artificial intelligence in risk of bias assessment using RoB 2.0 tool and extracting data in exercise therapy for chronic low back pain randomised controlled trials
Background. Systematic reviews are essential tools for evidence-based practice but are often time-consuming. Recent developments in artificial intelligence, including large language models such as ChatGPT-4o, offer potential to support and partially automate some processes. This study aimed to evaluate the performance of ChatGPT-4o in assessing Risk of Bias (RoB) using RoB 2.0 tool and in extracting data from randomised controlled trials (RCTs) on exercise therapy for chronic low back pain. Materials and Methods. This cross-sectional comparative study included 150 RCTs previously assessed by human reviewers. ChatGPT-4o was tested in two tasks: (1) RoB assessment using a single structured prompt, compared with expert ratings across five domains and overall judgement; (2) data extraction across 34 predefined variables using both simplified and detailed prompts. Human reviewers served as the reference standard. Statistical analysis focused on Cohen’s kappa and overall accuracy, alongside sensitivity, specificity, PPV, NPV, and F1-score. Results. Agreement between ChatGPT-4o and human reviewers for RoB assessment was low (Cohen’s κ = 0.14), with a tendency to underestimate bias. Sensitivity was 40%, while specificity and PPV were higher for low-risk classifications. For data extraction, ChatGPT-4o showed strong performance, with accuracy above 84% and F1-scores over 90% using both prompt types. Hallucinations were rare (<0.02%). Task duration was reduced from 30-50 minutes (human reviewers) to under 5 minutes with ChatGPT-4o. Conclusions. While ChatGPT-4o showed limited reliability for RoB assessment, likely due to the interpretative complexity of the task, it performed robustly in data extraction, particularly when guided by well-structured prompts. Its high precision, speed, and low hallucination rate suggest strong potential as a secondary reviewer in systematic review workflows. Nonetheless, its application to evaluative tasks requiring critical judgement remains premature. With further development and proper human oversight, LLMs like ChatGPT-4o may help streamline systematic review processes, especially for labour-intensive, structured data extraction.
PO:38:281 | Therapeutic exercise in temporomandibular disorders: a scoping review of the literature
Background. Temporomandibular disorders (TMD) are musculoskeletal dysfunctions affecting the temporomandibular joint and related structures, leading to pain and functional limitations. The aim of this review is to map the available studies on therapeutic exercise for temporomandibular disorders in the adult population, analyzing rehabilitation strategies, their dosage, and clinical implications. Materials and Methods. A scoping review was conducted through a literature search in five databases: MEDLINE, EMBASE, CINAHL, PEDro and Cochrane. Primary studies (RCTs, prospective and retrospective studies, case series and case reports) conducted on adults diagnosed with TMD of non-traumatic, non-infectious, non-neoplastic or non-post-surgical origin who underwent therapeutic exercise interventions were included. Study selection and data extraction processes were carried out independently by two reviewers. Results. A total of 57 studies were included in the review, from which 267 exercises were extracted and organized into functionally homogeneous categories. 76% (204/267) of the identified exercises targeted the orofacial region, particularly mouth opening (50%), lateral movements (13%), and protrusion movements (7%). Motor-control strategies accounted for 20% of the interventions analyzed. Only 19% of the studies provided explicit instructions for pain management during exercise execution. The overall duration of rehabilitation protocols varied across studies, with 68% recommending daily exercises and 89% adopting a multi-session frequency. Conclusions. The analyzed data indicate that mouth-opening exercises and motor-control exercises are the most commonly used strategies for the rehabilitation of TMD. However, the lack of standardization in terminology and exercise prescription limits the clinical applicability of the findings, particularly regarding their impact on pain management. Future research should focus on developing shared therapeutic strategies to optimize rehabilitation protocols and improve their clinical effectiveness.
PO:38:283 | Accuracy of chatgpt 4 omni in providing clinical recommendations in musculoskeletal care: a valuable support for clinicians and patients?
Background. Generative artificial intelligence models, such as ChatGPT-4 omni, is gaining popularity in healthcare and could provide valuable support for the clinical management of widespread diseases in the population, such as osteoarthritis. However, its accuracy in providing up-to-date clinical recommendations remains underexplored, particularly in the context of osteoarthritis (OA), one of the most common conditions with a high socio-economic impact, where it is critical that recommendations are up-to-date, clear and consistent with scientific evidence. Objective: to evaluate the accuracy and consistency of the clinical recommendations generated by ChatGPT-4 omni in relation to the most recent international guidelines for osteoarthritis (NICE, EULAR, OARSI) and to compare them with the responses given by Italian physiotherapists. Materials and methods: cross-sectional study based on 24 clinical questions derived from OARSI, NICE and EULAR guidelines. The questions were presented to ChatGPT-4o in the form of ‘classic’ and ‘medical’ prompts, in Italian and English, for a total of nine administrations each. A complex clinical case was also evaluated. Accuracy, internal reliability (SD, CV%) and concordance (Cohen's K) were calculated. Results: ChatGPT-4o showed good internal consistency (CV < 25%) and moderate to high agreement between Italian and English (K up to 0.902). Accuracy ranged from 66.7% to 79.2%, higher in classical and English prompts. Agreement with Italian physiotherapist was low (K = 0.106). In the clinical case, the mean accuracy was 81.4%, but answers were only 38.2% complete. Conclusion: ChatGPT-4o proved to be potentially useful to support clinical practice in the musculoskeletal field. However, its efficacy in daily practice is contingent on its integration with human clinical reasoning and critical practitioner supervision. Keywords: Artificial Intelligence (AI), Deep Learning (DL), Large Language Model (LLM), Large Multimodal Model (LMM), Clinical Practice Guidelines (CPG), Osteoarthritis (OA), knee, hip.
PO:38:285 | Cross-sectional analysis: interpretation of nonstatistically significant results in randomised controlled clinical trials in rehabilitation
Objectives: to assess the prevalence of misinterpretation of non-statistically significant results, both in the abstract and in the article conclusions, in a sample of randomised controlled trials with nonstatistically significant primary outcomes published in rehabilitation journals and reporting of primary outcomes according to CONSORT guidelines. Methods: a cross-sectional analysis of all randomised controlled trials with non- statistically significant primary outcomes in 5 general rehabilitation journals with the highest Impact Factor published between 2019 and 2023 to determine the prevalence of trials in which non-significance was interpreted as absence of evidence, evidence of absence, or advice to use the intervention in clinical practice in the abstract and article conclusions, and the prevalence of trials that adhered to CONSORT guidelines for reporting the primary outcome. Results: at the end of the selection process, 31 trials were included. The most common interpretation of non-statistically significant results is the evidence of absence, both in the abstract (74.2%) and in the article (58.1%). Only 4 (12.9%) studies in the abstract and 5 (16.1%) in the article conclusions suggest the correct interpretation as absence of evidence. Adherence to CONSORT guidelines for reporting primary outcomes was moderate, with only 61.3% of trials reporting summaries of results for each arm, effect size and confidence interval. Conclusions: There is the need for increased rigor in reporting and interpreting non statistically significant results in rehabilitation trials. Evidence misinterpretations can adversely impact clinical decision-making and future research directions. Efforts should be made to promote accurate interpretation of statistical results, emphasize the importance of reporting and analysing effect sizes and confidence intervals, and develop educational interventions to improve statistical literacy.
S02:5 | Combined anti-IL-5/IL-5r and dupilumab therapy in eosinophilic granulomatosis with polyangiitis: a European retrospective study
Background. Eosinophilic granulomatosis with polyangiitis (EGPA) is a small-vessel vasculitis characterized by asthma, ear, nose, and throat (ENT) symptoms, eosinophilia, and systemic involvement. Despite the use of anti-interleukin (IL)-5/IL-5R therapies, asthma or primarily ENT symptoms may persist. Dupilumab (anti-IL-4R) is approved for severe asthma and chronic rhinosinusitis but has been associated with drug-induced eosinophilia and EGPA flares. Given their complementary mechanisms, the combination of anti-IL-5/IL-5R and dupilumab may improve disease control in patients with EGPA. We report the safety and efficacy of this off-label combination in relapsing/refractory EGPA. Materials and Methods. This European, multicenter, retrospective study included EGPA patients fulfilling 2022 ACR/EULAR classification criteria treated with anti-IL-5/IL-5R in combination with dupilumab for relapsed or refractory disease. Complete response (CR) was defined as BVAS=0 and prednisone dose (PDN) not exceeding 4 mg/day, partial response (PR) as BVAS=0 and PDN >4 mg/day. Failure was defined as inability to reduce PDN <7.5 mg/day due to persistently active disease, vasculitis relapse and/or worsening of asthma or ENT symptoms requiring treatment escalation. Results. Sixteen patients received the combination therapy, with mepolizumab or benralizumab in 8 cases each. Twelve patients (75%) received the addition of dupilumab to ongoing anti-IL-5/IL-5R, 6 for uncontrolled ENT symptoms, 5 for both uncontrolled ENT and asthma symptoms, and 1 for uncontrolled asthma. The remaining 4 patients (25%) received the addition of anti-IL-5/IL-5R to dupilumab for drug-induced eosinophilia associated with vasculitis relapse in 3 patients and for uncontrolled ENT symptoms/asthma in 3 cases. Thirteen patients [Figure 1] with at least 3 months of follow-up were analyzed for efficacy (median follow-up 6 (3-12) months). At the start of combination therapy, the median PDN dose was 5 mg/day (0-10), decreasing to 4.38 mg/day (0-6.25) at 3 months and 3.75 mg/day (1.25-5) at 6 months. In patients with dupilumab-induced eosinophilia, the addition of anti-IL-5/IL-5R reduced eosinophil counts from 1600/uL (1082-4000) to 170/uL (90-465) at 3 months and remained 170/uL (165-175) at 6 months. No eosinophilia occurred when dupilumab was added to anti-IL-5/IL-5R. At 3 months, 4/13 (31%) and 1/13 (8%) achieved CR and PR, respectively, while 3/13 (23%) had treatment failure. At 6 months (data available for 11 patients), 5/11 (45%) and 3/11 (27%) achieved CR and PR, respectively, and at 9 months, CR was achieved in all patients with available follow-up, except for the 3 patients with initial treatment failure [Figure 2]. Safety analysis showed no serious adverse events, only two patients reported mild-to-moderate adverse events. Conclusions. The combination of anti-IL-5/IL-5R and dupilumab in this case series was safe and appeared to be an effective option in EGPA patients with uncontrolled ENT manifestations while on anti-IL-5/IL-5R or in patients with dupilumab-induced hypereosinophilia and EGPA manifestations, with optimal response requiring at least 6 months of treatment.
S05:6 | Prevalence of osteoporosis and bone mineral metabolism disorders in an Italian cohort of patients with microcrystalline arthritis: results from the PREMIA observational study of the Italian Society of Rheumatology
Background. Rheumatologic diseases are frequently associated with osteoporosis (OP) and bone mineral metabolism disorders. Crystal-induced arthropathies, in particular, may involve alterations in calcium, phosphate and parathyroid hormone (PTH) that act as both pathogenic and predisposing factors. This study aimed to evaluate the prevalence of OP and related metabolic disturbances in patients enrolled in the PREMIA study, promoted by the Italian Society of Rheumatology’s Microcrystalline Arthritis Study Group (AMC). Methods. A total of 1,003 patients from Italian rheumatology centers participating in the PREMIA project were included. Each patient underwent a specialist rheumatologic evaluation, clinical data collection, and basic laboratory testing. Suspected OP or bone metabolism disorder was defined by at least one of the following: (a) history of fragility fracture, (b) pharmacologic treatment for OP, or (c) abnormal serum levels of calcium, phosphate, alkaline phosphatase, or PTH. Patients were stratified according to rheumatologic diagnosis and comorbidities. Results. Overall, 244 patients (24.3%; 95% CI: 21.7%–27.1%) met criteria for OP or bone metabolism disorder, with a predominance of women (62.3%) and a mean age of 69.4 years. Altered serum calcium was detected in 21.5% of cases, and 10.3% were receiving OP treatment (Fig. 1). Among rheumatologic comorbidities, rheumatoid arthritis (42.4%), osteoarthritis (36.7%), connective tissue diseases (34.5%), and systemic vasculitis (33.3%) showed the highest association with OP (Tab. 1). Notably, 32.6% of patients with chronic gout presented evidence of altered bone mineral metabolism. Discussion. Approximately one in four patients with microcrystalline arthritis exhibits osteoporosis or bone metabolism disturbances, with prevalence increasing to one in three among those with rheumatoid arthritis, osteoarthritis, or connective tissue disease. These findings indicate that bone fragility extends beyond traditional risk groups to include chronic crystal arthropathies. The association with age and post-menopausal status was confirmed, but the occurrence in younger patients with systemic diseases underscores the importance of bone health assessment across all age groups. Integrating clinical and biochemical parameters proved effective for early identification of at-risk patients, reflecting real-world rheumatology practice where osteoporosis risk is often underrecognized.
S07:5 | Ankle ultrasound patterns may in the identification of Löfgren’s syndrome in patients with acute-onset erythema nodosum
Background. In this study, we performed ultrasound (US) evaluation of the ankles in patients with acute-onset erythema nodosum (EN) and joint symptoms to characterize the US features of this common manifestation and to assess whether these findings could help differentiate Löfgren’s syndrome (LS) from other conditions. Materials and Methods. Thirteen consecutive patients with acute onset of EN and mono- or bilateral ankle involvement (arthralgia/arthritis/swelling) were recruited at a single rheumatologic centre. All patients underwent specific diagnostic investigations aimed at identifying the cause of EN, separating those cases in which it was a manifestation of LS from those in which it was secondary to other causes (OC). An experienced operator in musculoskeletal US, blinded to the course of the diagnostic work-up, performed US examination of ankles bilaterally, investigating the presence of the following parameters: (a) Joint effusion/synovitis at tibiotalar joint (TT JEP); (b) Tenosynovitis (TS) at anterior (AC), lateral (LC) and medial compartment (MC) level; (c) Soft cutaneous tissue inflammation (SCTI) around the ankle. All parameters were initially scored according to OMERACT definition, both for grey scale (GS) and Power Doppler (PD), except for SCTI which were scored according to GLOUDAS definition. US features were classified as positive if their OMERACT parameters were GS>=2 and PD>=1 and if GLOUDAS GS and PD SCTI were >=1. Chi-square test was performed to assess the association between patients diagnosed with LS and US findings. Results. At the end of the diagnostic workup, 8 patients were diagnosed with LS; whereas the remaining patients received diagnosis of mediastinal lymphoma, Sweet's syndrome during pregnancy, EN secondary to Chron's disease, reactive manifestation during M. homini infectiction and one case remained idiopathic. Demographic and clinical details of the recruited cohort are reported in table 1. Mean time of the US examination was 5 minutes. The prevalence and comparison of US findings in the whole group, in LS group and in OC group are shown in table 2. In particular, within the comparison of LS vs OC, we found a higher prevalence of bilateral positive SCTI, MC and LC compartment TS in the LS group. At statystical analysis, bilateral TS of MC and bilateral SCTI were associated with LS (p<0.095 and p<0.001 respectively) while no statystical difference was found for TT JEP between the two groups. Conclusions. Despite widely considered as arthritis for its clinical appareance, our study shows how the typical ankle involvement in LS is characterised by a periarticular inflammation, tipically involving soft tissue and tendons without involving talo-navicular joint. Identifying those features with a rapid US ankles assessment in patients with new diagnosis of EN, may raise suspicion for LS, addressing diagnostic and therapeutic workup even during a outpatient visit.
S13:5 | Association between vasoactive-vasodilating therapy and reduced detection of pulmonary arterial hypertension in systemic sclerosis: evidence from a European Scleroderma Trials and Research study
Background. Vasoactive-vasodilating drugs (VVD) are the cornerstone of the treatment of pulmonary arterial hypertension (PAH), a form of precapillary pulmonary hypertension (pPH) that represents a complication of systemic sclerosis (SSc). VVD categories include endothelin receptor antagonists (ERAs), phosphodiesterase type 5 inhibitors (PDE5i) and prostanoids, which are commonly used to treat digital ulcers (DU) and Raynaud’s phenomenon. As protective effects remain unclear, we investigated the effectiveness of VVD on the primary prevention of pPH. Materials and Methods. SSc patients from the EUSTAR cohort who underwent right heart catheterization (RHC) were included; postcapillary PH cases (pulmonary wedge pressure – PWP >15 mmHg) were excluded. Multivariable logistic regression assessed the association between exposure to VVD and detection of pPH (mPAP>20 mmHg, PVR>2 WU and PWP<15 mmHg) and of PAH (pPH, ILD extent <20% and FVC >70%). Models 1 and 2 tested the exposure at the time of RHC ever and ongoing to VVD categories, models 3 and 4 tested the same for specific VVD molecules. The primary outcome was the diagnosis of precapillary PH; PAH was analyzed as sensitivity analyses. All models were adjusted for known confounders. Interaction terms between VVDs and current DU were also tested. Results. Among 944 eligible patients, 498 (53%) were diagnosed with pPH, of whom 367 (74%) had PAH (Table 1). For VVD classes, a statistically significant association was detected for the interaction of ERAs and current DU with the detection of pPH, in both logistic regression models 1 and 2 (Figure 1a and 1b). However, this finally resulted in a non-significant association between ERAs exposure in patients with current DU and PH detection when calculating marginal effects estimates (ERAs ongoing: OR 0.435, 95%CI 0.193-1.064; ERAs ever: OR 0.636, 95%CI 0.349-1.158). Additionally, both models showed lack of effectiveness of ERAs in patients without current DU, as well as for PDE5i or prostanoids overall. When focusing on specific VVD molecules, exposure “ever” to bosentan showed a significant protective association with pPH diagnosis, independently from the presence or absence of current DU (Figure 1c). Finally, we noted a statistically significant interaction between ongoing bosentan and current DU, which turned into a significant marginal effects estimate (OR 0.230, 95% CI 0.081 – 0.652) indicating protective effects of this medication towards the diagnosis of pPH in patients with current DU (Figure 1d). The protective effects of bosentan were confirmed in all sensitivity analyses targeting PAH detection. Conclusions. Our data show that bosentan is associated with less frequent diagnosis of PAH and precapillary PH, in particular when employed in patients with current DU at the time of RHC. Our results support further research to optimize the timing and patient selection for VVD therapy in SSc, aiming also at additional preventive effects at pulmonary level.
S13:6 | Investigating the intricate interplay between pulmonary functionality and advanced microangiopathy in very early diagnosis of systemic sclerosis
Background. Diffusing capacity of the lungs for carbon monoxide (DLCO) may correlate with major organ involvement, including Pulmonary Artery Hypertension (PAH), Interstitial lung Disease (ILD) and Left Ventricular Diastolic impairment in Systemic Sclerosis (SSc). Recently, the 2011 Very Early Diagnosis of Systemic Sclerosis (VEDOSS) preliminary classification criteria have been validated. Major features of VEDOSS that could predict progression toward definite SSc are represented by microvascular damage and SSc specific autoantibodies. However, Data concerning pulmonary function is still lacking in this population. The aim of our study was to detect differences between reduced versus normal values of DLCO% predicted (using a cut-off of DLCO of 80%), along with identifying several clinical predictors and to analyze the persistence of DLCO>80% in several intergroups. Materials and Methods. A cross-sectional retrospective study was conducted by analyzing Pulmonary function tests results across a cohort of VEDOSS. Patients were enrolled due to their fulfillment of 2021 VEDOSS validated criteria, while not meeting 2013 ACR/EULAR Classification Criteria for SSc. Enrollment period spanned from September to December 2024. Clinical and demographic data were obtained from medical records. DLCO values were collected from the last available assessment, as well as nail-fold videocapillaroscopic (NVC) patterns. Tricuspid Annular Plane Systolic Excursion (TAPSE) and systolic Pulmonary Arterial Pressure (sPAP) estimates were extracted from the last echocardiographic assessment. Chi-square or Fischer exact tests and T-student were used for intergroup analysis. General univariate regression model was used to define several clinically selected determinants of reduced DLCO, by including age, body mass index, late NVC pattern, SSc specific autoantibodies positivity. Kaplan-Meyer curves and long rank test were assessed using Raynaud’s phoenomenon duration as time interval to evaluate the persistence of DLCO>80%. Statistical p was sat at <0.05. Results. In this study, we compared clinical and demographic characteristics between patients with DLCO >80% (n=42) and DLCO<80% (n=23) [Table 1]. Patients exhibiting only Antinuclear antibody (ANA) positivity were more prevalent in the DLCO>80% group (p=0.03), while SSc-specific autoantibodies were more present in DLCO<80% group (p=0.04), as well as Gastrointestinal symptoms (p=0.03). Late NVC pattern was identified exclusively in the DLCO<80% group (p=0.01). Furthermore, notable differences were noticed also in TAPSE value, which were lower in the DLCO<80% (p<0.05) [Fig.1], no difference were reported regarding FVC% values, while FVC/DLCO% ratios were higher in DLCO reduced group. A general regression model confirmed the late NVC pattern as key predictor of reduced DLCO in VEDOSS population (p=0.013). Kaplan-Meyer analysis documented that, based on RP duration, late NVC patients presented a statistical reduced survival rate of DLCO>80% compared to early/active patients (log-rank test p<0.005) [Figure 1]. Conclusions. Reduced DLCO is also present in VEDOSS patients, and it is significantly associated with late NVC patterns and lower TAPSE values.
S14:5 | Erosive hand osteoarthritis: premenopausal onset and more severe disease progression
Background. Erosive hand osteoarthritis (EHOA) is a particularly aggressive and inflammatory subset of hand osteoarthritis (OA). It predominantly affects women and typically manifests after the age of 50, coinciding with the menopausal transition. However, recent evidence suggests that patients with EHOA, compared with those affected by non-erosive forms, may experience an earlier onset and a more severe clinical course with greater functional and radiographic impairment. The main objectives of our study were to: 1. Assess the prevalence of premenopausal onset among patients with EHOA; 2. Compare clinical, functional, and radiographic characteristics between patients with premenopausal and postmenopausal onset. Materials and Methods. A retrospective study was conducted on a cohort of 87 patients diagnosed with EHOA, followed at the Joint Pathology Outpatient Clinic of our Rheumatology Unit between January 2015 and February 2025. EHOA was diagnosed based on the presence of at least one central radiographic erosion involving a proximal or distal interphalangeal joint. Demographic, clinical, and laboratory data were collected, with particular attention to the age of symptom onset, menopausal status, and use of hormone replacement therapy (HRT). Joint function was assessed using validated AUSCAN and DREISER indices. Radiographic damage was evaluated using the Altman scoring system on bilateral hand radiographs. A total composite radiographic score was calculated by summing the individual joint scores for all assessed hand joints. Statistical analyses included Student’s t-test, and linear and logistic regression models, with statistical significance set at p < 0.05. Results. Eighty-seven patients with EHOA were retrospectively enrolled, with a mean age of 63.17 ± 8.85 years; 77 were women (88.5%). Among female patients, 71 (92.21%) were postmenopausal, and 17 (22.08%) had previously used or were currently using HRT. The mean disease duration was 13.75 ± 9 years. In 42.9% of women, symptom onset occurred before menopause: mean age at premenopausal onset was 44.91 ± 6.97 years versus 58.00 ± 6.96 years for postmenopausal onset. Functional assessment showed moderate-to-severe disability (AUSCAN: 30.90 ± 12.49 on 60; DREISER: 10.61 ± 6.26 on 30). Premenopausal disease onset was significantly associated with greater joint space narrowing on total radiographic scoring, confirmed by logistic regression adjusted for age and disease duration (p = 0.017) (Table 1). Conclusiuons. Premenopausal onset of EHOA was associated with more pronounced radiographic damage, suggesting a potential role of hormonal and genetic factors in the disease pathogenesis. These findings highlight the importance of a personalized management approach based on age at disease onset.