BACKGROUND:The integration of artificial intelligence (AI) into healthcare has shown significant promise in addressing complex diagnostic and therapeutic challenges in rheumatology. This review examines the current state of AI applications across rheumatological practice. OBJECTIVE:To systematically evaluate AI applications in rheumatology, assess their clinical performance and identify future research directions. METHODS:We conducted a comprehensive literature review of AI applications in rheumatology, focusing on diagnostic imaging, clinical decision support and disease monitoring across major rheumatic conditions. RESULTS:AI demonstrates promising performance across multiple domains, with diagnostic accuracies frequently exceeding 80%-90% for imaging interpretation and disease classification. Applications span from automated radiographic scoring to real-time disease monitoring. CONCLUSIONS:While AI shows significant potential in rheumatology, successful clinical implementation requires addressing challenges related to data quality, algorithm transparency and clinical integration.

In the clinical context of the new medical concept of diseases related to the Major Histocompatibility Complex class I (MHC-I-opathy), contrasting data are available on the possible association among HLA-B*51, Behcet’s disease (BD), and spondyloarthritis (SpA). The aim of this retrospective study on a cohort of HLA-B*51-positive patients who were clinically observed for almost 5 years is primarily to evaluate which classification criteria they satisfy among BD, axial (ax) or peripheral (p) SpA, and psoriatic arthritis (PsA). Furthermore, we characterized the possible impact of different arthritis phenotypes on the most frequent extra-articular clinical manifestations in BD, ax-SpA, p-SpA, and PsA. A comparison with HLA-B*51-negative patients (matched with HLA-B*51-positive patients for age, gender, and diagnosis, by mean propensity score) was also performed to evaluate the true impact on clinical manifestations of HLA-B*51. We conducted a monocentric retrospective study from 2013 to 2025. The inclusion criteria were HLA-B*51 positivity, the availability of the entire MHC-I class test, and rheumatological clinical follow-up of at least 5 years. The exclusion criterion was positivity for clinically important MCH-I loci other than HLA-B*51. A total of 105 patients met the inclusion criteria in an average clinical observation period of 8.4 ± 2.9 years. All patients were Apulian and were HLA-B* 51 positive. During the follow-up, 32 patients (31%) met the BD criteria, 17 (16%) met the PsA criteria, 25 (24%) met the p-SpA criteria, and 13 (12%) met the ax-SpA criteria. Of note, 16% and 34% of BD patients met the ax-SpA and p-SpA ASAS criteria, respectively. Prevalent articular phenotypes in this HLA-B*51 cluster of patients are a polyarticular pattern and enthesis involvement in all disease groups. In BD patients, axial involvement was associated with a significantly higher percentage of neurological manifestations (40% vs. 7%, p = 0.043) and inflammatory bowel disease (IBD) (100% vs. 15%, p = 0.0001), compared to patients with exclusive peripheral joint involvement. This latest data on IBD remains significant, even in comparison with HLA-B*51 negative patients (33%; p = 0.035). In the p-SpA group, a significantly higher rate of uveitis (28%) was observed compared to both ax-SpA with HLA-B*51-positive (0%, p = 0.035) and p-SpA with HLA-B*51-negative patients (4%, p = 0.030). A high percentage of multi-drug failures was highlighted in patients with PsA (60%) and p-SpA (40%). This study provides new data on the association between HLA-B*51 and the onset of BD and/or SpA or PsA, and its possible impact on extra-articular manifestations. We confirm the higher prevalence of the peripheral articular phenotype in BD, but we also highlight a specific association between the rarer axial involvement and gastrointestinal involvement in HLA-B*51 patients. In SpA, the peripheral articular phenotype appears to be associated with a higher occurrence of uveitis in the presence of HLA-B*51.

Rhupus syndrome Rhupus syndrome, characterized by overlapping clinical features of rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), presents significant therapeutic challenges due to its complex pathogenesis and limited treatment options. This case report evaluates the efficacy of filgotinib, a selective JAK1 inhibitor, in a patient with refractory rhupus syndrome. Case presentation A 42-year-old male, initially diagnosed with SLE in 2013, presented with persistent polyarthritis, cutaneous manifestations, and constitutional symptoms. Conventional treatments including hydroxychloroquine, methotrexate, and belimumab failed to achieve adequate disease control. Diagnosis and treatment In October 2022, the diagnosis was revised to rhupus based on the evolution of clinical manifestations and laboratory findings, leading to the initiation of filgotinib, a JAK1 inhibitor. Disease activity was monitored over 24 months using standardized assessment tools. Results Significant clinical improvement was observed within weeks of filgotinib initiation, enabling prednisone dose reduction and maintaining low disease activity throughout the 24-month follow-up period. Conclusion This case highlights the therapeutic potential of filgotinib in managing rhupus syndrome but further research and larger clinical trials are necessary to establish filgotinib's therapeutic potential and safety profile in the management of SLE.

Systemic sclerosis (SSc) is a rare systemic disease characterised by progressive fibrosis, vasculopathy, and immune dysregulation, resulting in multiorgan damage. Independently of pulmonary arterial hypertension, cardiac involvement, encompassing myocardial fibrosis, coronary microvascular dysfunction, arrhythmias, conduction disorders, pericardial and valvular disease, and heart failure, represents a frequently underestimated cause of morbidity and mortality. Clinically manifest cardiac disease is observed in 15 to 35% of patients, while subclinical dysfunction is detectable in approximately 70% when advanced screening tools are employed. The annual incidence of sudden cardiac death is estimated at between 1.0% and 3.3%, exceeding the general-population risk by more than tenfold. The pathophysiological framework rests on coronary microvascular dysfunction driven by endothelial injury, ischaemia-reperfusion cycles, and TGF-β-mediated replacement fibrosis, potentiated by autonomic nervous system imbalance and activation of the renin-angiotensin-aldosterone system. Electrocardiographic abnormalities, detectable in 25 to 85% of patients, are independent predictors of mortality, while diastolic dysfunction, present in 18 to 62% of cases, constitutes a robust prognostic marker. Cardiac magnetic resonance imaging has transformed subclinical detection, revealing late gadolinium enhancement fibrosis in the majority of screened patients without a prior cardiovascular diagnosis. Management requires a multidisciplinary approach, integrating SSc-specific adaptation of guideline-directed heart failure therapies, immunosuppression targeting inflammatory and fibrotic pathways, arrhythmia management with implantable devices, and EULAR-recommended cardiovascular risk reduction. This narrative review synthesises current evidence on the epidemiology, pathogenesis, diagnostic evaluation, and therapeutic strategies of cardiac involvement in SSc, highlighting the need for early, systematic, risk-stratified screening and the establishment of dedicated multidisciplinary cardiac teams.

To evaluate the “real-life” effectiveness and safety of Janus kinase inhibitors (JAKis) in patients with rheumatoid arthritis (RA) and to analyze the impact of cardiometabolic comorbidities on these outcomes. Patients with RA treated with JAKis were evaluated for disease activity scores, patient-reported outcomes (PROs), and safety in a 12‑month multicenter observational study conducted within the GIRRCS (Gruppo Italiano di Ricerca in Reumatologia Clinica e Sperimentale). Patients were grouped and compared according to the presence of type 2 diabetes (T2D), cardiometabolic multimorbidity (defined as the simultaneous presence of two or more among high blood pressure, T2D, and/or dyslipidaemia), and age ≥ 65 years. 440 patients treated with JAKis were included (82.9

OBJECTIVE:Some concerns remain about the safety of nintedanib in patients with rheumatoid arthritis-related interstitial lung disease (RA-ILD), such as in the presence of comorbidities or in combination with biologic, targeted synthetic, and/or conventional synthetic disease-modifying antirheumatic drugs (DMARDs). In this multicenter study, we retrospectively evaluated the safety of nintedanib in a real-world population of patients with RA-ILD from the Italian Group for the Study of Early Arthritis (GISEA) registry and the possible role of comorbidities and DMARDs on drug safety and withdrawal. Our secondary aim was to investigate the causes of nintedanib discontinuation. METHODS:Sixty-five patients treated with nintedanib in accordance with the current therapeutic indications were enrolled in the study. Nintedanib was prescribed in combination with DMARDs and/or steroids in 62 patients (95.4%). RESULTS:The 12-month retention rate of nintedanib was 76.7% and the drug was effective in about 80% of patients with ≥ 6 months of follow-up. Adverse events (AEs) were recorded in 36 subjects (55.3%), and these were mainly gastroenteric. Thirty-one subjects required a reduction of the nintedanib dose; among them, a transient or permanent reduction of the daily dose of nintedanib allowed the continuation of the treatment in 22, whereas 15 (23.1%) withdrew from the drug. All reductions and discontinuations were owing to treatment-related AEs. Comorbidities were significantly associated with side effects in multivariate analysis, whereas AEs due to nintedanib were the main cause of discontinuation. CONCLUSION:Combination therapy with DMARDs did not reduce the safety and effectiveness of nintedanib, and AEs were the main cause of drug withdrawal or dose reduction, mainly owing to comorbidities.

This study aims to evaluate the impact of pain catastrophizing (PC) on disease activity in patients with rheumatoid arthritis (RA) and to explore, in the same participants, if this association is related or not with anxiety and depression, which have been related to catastrophization in patients with chronic pain. A multi-center, observational study has been conducted on 158 RA patients from six Rheumatology Clinics. Participants were assessed using the Clinical Disease Activity Index (CDAI) and Simple Disease Activity Index (SDAI) and Disease Activity Score on 28 joints- C reactive protein (DAS28-CRP). Pain Catastrophizing, with its domains of Helplessness, Rumination and Magnification, was analyzed through Pain Catastrophizing Scale (PCS). Statistical analyses included univariable and multivariable regressions, to identify associations between disease activity and PC. Results revealed that higher PCS scores were significantly associated with increased CDAI, SDAI and DAS28-CRP values, indicating higher disease activity. Specifically, the domains of Rumination and Helplessness showed a strong correlation with disease activity, while Magnification did not. These associations persisted independently of anxiety and depression mood, as shown by multivariable regression analysis. Pain catastrophizing, particularly the domains of Rumination and Helplessness, significantly influences disease activity in RA patients, independent of mood disorders. These findings underscore the importance of addressing maladaptive cognitive perceptions of pain in the management of RA, to improve patient outcomes and facilitate disease remission.

Systemic sclerosis is a rare rheumatic disease characterized by immune cell activation, tissue fibrosis, and endothelial dysfunction. Extracellular matrix synthesis disorder causes widespread fibrosis, primarily in skin and internal organs. Various factors such as TGFβ, VEGF, Galectin-3, and signaling pathways like Wnt/β-catenin are involved in pathophysiological processes. Treatment lacks a unified approach but combines diverse modalities tailored to disease subtype and progression. Current therapeutic strategies include biologics, JAK inhibitors, and IL-6 pathway modulators. Monoclonal antibodies and hypomethylating agents demonstrate potential in fibrosis inhibition. This review focuses on emerging therapeutic evidence regarding drugs targeting collagen, cytokines, and cell surface molecules in systemic sclerosis, aiming to provide insight into potential innovative treatment strategies.

Background: Fibromyalgia syndrome (FS) is one of the most common causes of chronic generalised pain and often complicates the therapeutic management of inflammatory chronic arthritis (ICA), negatively impacting both the real assessment of disease activity and the perception of response. Our study aims to evaluate in a group of patients with ICA, multi-resistant to biologic/target synthetic disease-modifying antirheumatic drugs (b/ts-DMARDs), both the impact of FS on the possibility of achieving low disease activity (LDA) or remission (REM) and the possible improvement in the severity of FS symptoms, after starting b/ts-DMARDs with different a mechanism of action (MoA). Methods: A prospective study was conducted, from January 2023 to December 2024, on patients who fulfil the classification criteria for psoriatic arthritis (PsA) or fulfil the 2010 American College of Rheumatology criteria for RA. Results: Sixty-four Caucasian patients with ICA, of which 47 with FS, were enrolled in the study. At the baseline visit, FS patients had a significantly shorter ICA disease duration, worse fibromyalgia symptom-related indices (such as Fibromyalgia Severity Scale (FSS), Widespread Pain Index (WPI), and Symptom Severity Scale (SSS)) and functional and disability scores (such as health assessment questionnaire (HAQ) and Functional Assessment of Chronic Illness Therapy (FACIT)), and a higher basal value of Disease Activity in Psoriatic Arthritis (DAPSA) score compared to patients without FS. After 6 months of starting b/ts-DMARDs, no differences in severity of arthritis clinimetric indices (disease activity score (DAS) 28 (erythrocyte sedimentation (ESR)) and DAPSA) and Visual Analogue Scale (VAS) pain were found between the patients with FS compared to those without. At the follow-up visit, 36% of the whole group of patients were in LDA (36% ICA patients with FS vs. 35% of ICA patients without FS; p = 0.080), while 17% of patients reached REM (11% ICA with FS vs. 35% ICA without FS patients; p = 0.031). The FS presence appeared to be a factor associated with failure to reach REM (OR 4.5 (95%CI: 1.1-17.8), p = 0.028), but not for achieving LDA (OR 2.7 (95%CI: 0.8-8.9), p = 0.099). The overall retention rate at 6 months was 79%; in particular, 11 patients discontinued treatment with b/ts-DMARD, 69% of whom belonged to the FS group (p = 0.489). Among the group of patients with ICA and FS, patients in LDA/REM presented an important improvement in FSS, SSS, and VAS pain, with the best percentage variation from the baseline of these indices compared to patients who did not achieve the LDA/REM. Of note, sixteen patients with FS at the baseline no longer met the diagnostic criteria for FS after 6 months of follow-up. Conclusions: The presence of FS seems to negatively impact the achievement of REM, but not LDA, in both RA and PsA patients, even in b/ts-DMARDs patients with multi-failure of at least two different MOAs. Only a cluster of patients with FS, presumably those with FS triggered and/or amplified by the chronic joint inflammatory process, appear to improve their perception of FS severity by achieving ICA LDA/REM. However, these findings require further supporting data for more accurate validation.

Systemic sclerosis (SSc) is a rare autoimmune connective tissue disease characterized by a widespread accumulation of extracellular matrix components leading to fibrosis of the skin and internal organs. Vascular changes occur in all involved tissues and are responsible for several distinctive clinical manifestations of the disease. This review focuses on the usefulness of various diagnostic tools in clinical practice for the early identification of clinical, functional, and/or structural RV impairment in SSc patients at risk of PH. It aims to identify specific causes of RV dysfunction, describe potential differences in outcome measures, and, ultimately, determine different cut-off values compared to subjects with PH not related to SSc.

Pulmonary involvement is a common and serious complication of rheumatic diseases, significantly contributing to morbidity and mortality. Beyond the well-characterized interstitial lung disease and pulmonary arterial hypertension, patients may develop less common but clinically important respiratory manifestations, including pleural disease, airway disorders, alveolar hemorrhage, and thromboembolism. These conditions are often challenging to recognize due to their variable presentations and overlap with more typical complications. This review provides a current and comprehensive overview of respiratory symptoms in patients with autoimmune rheumatic diseases, excluding pulmonary arterial hypertension and interstitial lung disease, with a focus on less common but clinically significant entities. We discuss diagnostic approaches, including high-resolution imaging, pulmonary function tests, serological biomarkers, and, when necessary, tissue biopsy, that enable accurate identification of these rare complications. Increasing clinician awareness and adopting multidisciplinary care models are essential to optimize diagnosis and management. Recognizing these uncommon respiratory manifestations facilitates tailored interventions, helps preserve lung function, and improves overall prognosis. This review aims to serve as a practical guide for clinicians, ensuring that patients with systemic rheumatic diseases receive timely, thorough, and effective respiratory care.

Background/Objectives: Psoriatic arthritis (PsA) is a chronic inflammatory condition that primarily affects the musculoskeletal system and skin. While biologic and targeted synthetic DMARDs have improved treatment, many patients still fail to achieve remission. Combining conventional synthetic disease modifying anti-rheumatic drugs (csDMARDs) with biologic (b) DMARDs or targeted synthetic (ts) DMARDs shows no added benefit over monotherapy with IL-17, IL-23 inhibitors, or JAK inhibitors, unlike TNFi, which benefit from csDMARD co-administration. Guselkumab (GUS) and risankizumab (RKZ) target IL-23 with high specificity. RCTs (DISCOVER 1 and 2, COSMOS) have confirmed GUS efficacy regardless of methotrexate (MTX) use, though liver toxicity was higher with MTX. Real-world data on GUS remain limited, with gaps in understanding its long-term effectiveness and drug survival. The aim of this study is to assess the following three points within a multicenter Italian real-life cohort of PsA patients treated with guselkumab (GUS) and followed for 12 months: (1) effectiveness and safety of GUS; (2) drug retention rate (DRR) and reasons for discontinuation; (3) impact of comorbidities on achieving minimal disease activity (MDA). Methods: This study utilized data from the GISEA registry, which includes centers in different parts of Italy (north, center, south, and islands), and included patients aged 18 and older diagnosed with PsA according to the CASPAR criteria. Results: Data on 170 PsA patients treated with GUS were collected. In the first 6 months, a prompt mean percentage improvement in all clinimetric indexes was observed compared to the baseline. At 6-month follow-up, ACR 20 was reached by 60% of patients, ACR 50 by 30%, ACR 70 by 15%, MDA by 28%, and DAPSA < 14 by 50% of patients in the overall group. Significant differences were found in the rate of ACR 50 in the bDMARD-naive group (50%) compared to one bDMARDs non-responder (NR) (8%) (p = 0.021). At 12-month follow-up, a notable gap was observed in the rate of patients reaching MDA between bDMARD-naive (60%) and one bDMARDs NR (22%) (p = 0.035) and between bDMARD-naive (60%) and ≥2 bDMARDs NRs (22%) (p = 0.024). By using multivariate binary logistic analysis, the predictors of reaching MDA at 12-month follow-up were naive bDMARDs (OR: 7.9, 95% CI: 1.3-44.8, p = 0.019) and a higher value of pGA at baseline (OR: 1.1, 95% CI: 1-1.5; p = 0.046). The presence of comorbidities, including fibromyalgia and obesity, did not seem to affect the reaching of MDA. At 12-month follow-up, the GUS retention rate was 76%, with a mean survival time of 10.5 months ± 0.2 (95% CI: 10-10.9). No significant differences in GUS survival time were found among bDMARD-naive, one bDMARDs NR, and ≥2 bDMARDs NR patients (in the latter, regardless of the previous mechanism of action: TNFi or other mechanism), as well as between patients treated with GUS in monotherapy and those treated in combination with csDMARDs. A low rate (17%) of discontinuation was found due to both primary NR and secondary NR. The high safety of GUS was recorded. In fact, discontinuation due to adverse events (all definable as minor) was observed in just 4% of patients. By using COX regression multivariate analysis, the factors associated with higher GUS discontinuation risk were a more severe baseline PASI (HR: 1.05, 95% CI: 1-1.1, p = 0.038) and higher baseline ESR (HR:1.06, 95% CI: 1-1.03, p = 0.05). Conclusions: Good performance of GUS was observed in both biologic-naive patients and those with failure of previous bDMARDs (regardless of the mechanism of action of the previous drug: TNFi or non-TNFi), presenting good persistence in therapy even when used as a third mechanism of action. Its high safety profile allows the use of GUS even in particularly complex patients.

It is well known that rheumatic diseases are characterized by an increased infection risk, due to several factors, such as an intrinsically dysfunctional immune system, disease activity, and the use of immunosuppressive drugs. Glucocorticoids are widely used therapeutic agents for treating several chronic inflammatory and immune diseases, due to their anti-inflammatory and immunosuppressive effects. Their use is burdened by well-known side effects in dose- and duration of use-dependent manner. Physicians need to be aware of the mechanism of action of glucocorticoids, their side effects, particularly infectious side effects, and the significance of cumulative dose and duration of glucocorticoid treatment. Additionally, physicians shoultdleveld have knowledge of each patient and their comorbidities. They could use appropriate tools for assessing glucocorticoid-related toxicity and morbidity, particularly in the context of chronic glucocorticoid administration. This comprehensive understanding is crucial for ensuring the proper and safe use of these drugs, particularly in terms of minimizing infectious risks. The aim of this review is to focus on available data concerning the infectious risk associated to glucocorticoid treatment in rheumatic diseases, highlighting the role of the correct drug management in clinical practice and the role of the disease itself in the occurrence of this worthy side effect. We conducted a review of randomized controlled trials and observational studies about glucocorticoid use in autoimmune/rheumatic diseases, analyzing the infectious risk during glucocorticoid therapy, and its relationship with the used dose and duration of treatment.

OBJECTIVES:We aimed to investigate the effectiveness of tumour necrosis factor inhibitors (TNFi), anti-interleukin-17 or interleukin-12/23 monoclonal antibodies (anti-IL) on comorbidities in a cohort of patients with spondyloarthritis (SpA), using an average treatment effect (ATE) analysis. METHODS:SpA patients from the multicentre Italian GISEA Registry were divided into groups according to pharmacological exposure: no treatment (G0), TNFi (G1) and non-responders to TNFi switched to anti-IL (G2). In each group, we recorded the prevalence and incidence of infectious, cardiopulmonary, endocrinological, gastrointestinal, oncologic, renal and neurologic comorbidities. Each comorbidity was then fitted for ATE and baseline features were evaluated for importance. RESULTS:The main findings of this study comprising 4458 SpA patients relate to cancer, other gastrointestinal diseases (OGID) and fibromyalgia. ATE showed no increased risk of solid cancer in G1 (0.42 95% CI 0.20-0.85) and G2 (0.26 95% CI 0.08-0.71) vs. G0, with significantly higher incidence in G0 (14.07/1000 patient-years, p=0.0001). Conversely, a significantly higher risk of OGID and fibromyalgia was found in G1 (1.56 95% CI 1.06-2.33; 1.69 95% CI 1.05-2.68, respectively) and G2 (1.91 95% CI 1.05-3.24; 2.13 95% CI 1.14-3.41, respectively) vs. G0. No treatment risk reduction was observed in haematological malignancies, cardiovascular events and endocrinological comorbidities. CONCLUSIONS:Overall, our study confirms the safety of TNFi and anti-IL in SpA patients, albeit with some caveats pertaining to solid cancers, OGID and fibromyalgia. Furthermore, taking into consideration causality with observational data may yield more reliable and relevant clinical information.