OBJECTIVES:Glucocorticoids (GCs) are widely used as first-line therapy in rheumatoid arthritis (RA) due to their rapid onset of action and strong efficacy. However, inappropriate use is associated with significant adverse effects. Long-term treatment with low doses has been considered relatively safe for most RA patients, although its cardiovascular (CV) impact remains controversial. METHODS:A systematic literature review was conducted using PubMed to evaluate the CV effects of long-term (≥12 months) low-dose GC therapy (<7.5 mg/day prednisone equivalent) in RA patients. Studies published between 2010 and 15 March 2026 were screened independently by two reviewers. Study quality was assessed using the Newcastle-Ottawa Scale for observational studies and the Cochrane Risk of Bias 2 tool for randomised controlled trials. A meta-analysis was performed to estimate pooled hazard ratios (HRs) with 95% confidence intervals. RESULTS:Ten studies were included in the review, of which five provided adjusted HRs suitable for meta-analysis. Long-term GC exposure even to low doses was associated with an increased risk of CV events (pooled HR 1.37; 95%CI 1.03-1.81; p=0.01). Substantial heterogeneity was observed among studies. Egger's test did not indicate significant publication bias. CONCLUSIONS:Current evidence suggests that while short-term low-dose GC therapy may be relatively safe in selected RA patients, prolonged use and higher cumulative doses are associated with a slight increased CV risk, particularly in individuals with existing risk factors or comorbidities.

OBJECTIVES:In clinical practice, standardised reporting of nailfold videocapillaroscopy (NVC) findings is lacking, making the interpretation and comparison of results difficult. We aimed to achieve a national consensus on how to describe NVC findings in routine clinical practice. METHODS:A web-based Delphi consensus study was conducted among members of the Study Group on Capillaroscopy and Microcirculation in Rheumatic Diseases of the Italian Society of Rheumatology (CAPSIR). The study was based on items derived from a previous systematic review and international consensus by the EULAR Study Group on Microcirculation in Rheumatic Diseases (SG_MC/RD). RESULTS:A total of 40 items were proposed during the Delphi process, which was completed by 52 participants from different Italian regions. An agreement was reached on 23 items covering different aspects of the NVC examination: general aspects (2 items), description of the fingers examined (3 items), possible confounding factors (2 items), device description (2 items), image quality (1 item) and details of the NVC examination (13 items). Sixteen of these were considered mandatory for inclusion in the NVC practice report, and 7 were considered optional. CONCLUSIONS:The proposed NVC checklist covers 23 relevant issues in clinical practice, including 16 mandatory items grouped into five categories. This national consensus will improve the reproducibility and generalisability of NVC reporting in daily clinical practice. Furthermore, the outcomes of this NVC consensus process will inform the next European web-based Delphi consensus study, to be conducted among the member countries of the EULAR SG_MC/RD.

Background:Endothelial and microvascular damage is a hallmark of systemic sclerosis (SSc), an autoimmune connective tissue disease characterized by progressive skin and organ fibrosis. Aminaphtone (3-Methyl-1,4-dioxo-1,4-dihydro-naphthalen-2-yl-amino-benzoate) is a synthetic molecule used to treat microvascular disorders. Nailfold videocapillaroscopy (NVC) is the most reliable non-invasive method for assessing microvascular status and disease progression in SSc patients. Aim:To evaluate long-term safety and potential beneficial effects of aminaphtone on microcirculation in SSc. Methods:Seventy-six SSc patients (68 females, 8 males; mean age 69 ± 15 years) fulfilling the 2013 ACR/EULAR criteria and presenting Raynaud's phenomenon received aminaphtone (75 mg twice daily) in addition to stable standard therapy (ST). Forty age- and sex-matched SSc patients treated with ST alone served as controls. Side effects were monitored every six months. NVC was performed at baseline and after 1 and 4 years, using the Cutolo classification ("Early", "Active", "Late" patterns) to evaluate microvascular damage progression. Results:Aminaphtone showed a high long-term retention rate (89.5%) over four years. Eight of 76 patients (10.5%) discontinued treatment due to mild transient intolerance or poor compliance; no serious adverse events were reported. NVC patterns remained stable in 91% of treated patients. Compared with controls, aminaphtone-treated patients showed a slower transition from "Active" to "Late" NVC pattern (120 ± 64 vs 50 ± 26 months, p = 0.05). Linear mixed-effects modelling showed a significantly slower capillary density decline in the aminaphtone group over 48 months (p < 0.05) in both "Early" and "Active" scleroderma pattern subgroups. On multivariate linear regression, this effect was independent of age, disease phenotype, and concomitant therapies. Conclusion:Aminaphtone appears safe and well tolerated during long-term treatment in SSc patients with secondary Raynaud's phenomenon. The stability of NVC scleroderma patterns and the independent protective effect on capillary loss suggest a potential adjunctive role of aminaphtone in limiting microvascular damage progression when added to ST in SSc.

OBJECTIVE:Hand disability is a major musculoskeletal functional impairment in systemic sclerosis (SSc), but its objective assessment remains challenging. The validated Hand Test System (HTS) engineered glove has provided quantitative dexterity data in rheumatic diseases. The primary objective was to evaluate the applicability of the HTS glove in patients with SSc by comparing its parameters (touch duration [TD], intertapping interval [ITI], and movement rate [MR]) with healthy controls (HCs). The assumptions were that HTS parameters would be significantly impaired in patients with SSc and would correlate with clinical, imaging, and patient-reported outcome measures (PROMs). METHODS:A cross-sectional study was conducted enrolling 25 patients with SSc (fulfilling 2013 American College of Rheumatology/EULAR criteria) and 25 matched HCs. The main outcome variables were the HTS glove parameters. All participants also underwent grip strength measurement and an assessment of PROMs (Scleroderma Health Assessment Questionnaire and Duruöz Hand Index), together with a performance-based evaluation of hand mobility using the Hand Mobility in Scleroderma test. Clinical and imaging data were collected for patients with SSc including the modified Rodnan skin score (mRSS) and high-frequency skin ultrasonography (HFSU) to measure hand and total body dermal thickness. RESULTS:Patients with SSc performed finger movements significantly more slowly and less efficiently than HCs, demonstrated by prolonged mean TD and ITI and reduced MR (P < 0.05 for all). In patients with SSc, HTS parameters significantly correlated with poorer PROMs (0.39 < r < 0.65, all P < 0.01 for all). Notably, both mean TD and ITI directly correlated with the mRSS (0.40 < r < 0.48, all P < 0.05). Furthermore, the mean TD showed a significant direct correlation with HFSU-measured dermal thickness of the dorsum of the hands and with total body dermal thickness (P < 0.05 for all). No significant differences in HTS parameters were detected based on nailfold videocapillaroscopy findings or organ involvement. CONCLUSION:The HTS glove provides objective measures of the impaired hand dexterity in SSc. The significant correlations between HTS parameters, PROMs, mRSS, and HFSU-measured dermal thickness suggest a significant relationship between skin fibrosis and functional hand disability. The HTS glove seems a promising tool for objectively monitoring SSc hand outcomes, and studies to explore its utility in monitoring therapeutic responses are in progression.

Purpose Patients with acromegaly have increased skeletal fragility. To date, dual-energy X-ray absorptiometry (DXA) and vertebral morphometry are the recommended examinations to evaluate bone health in these patients, despite known limita-tion. Calcaneal quantitative ultrasound (cQUS) is a less expensive and less invasive method to evaluate bone status com-pared to DXA. We aimed to investigate bone status by cQUS in a cohort of patients with acromegaly and to evaluate its ability to detect bone impairment. Methods Observational cohort study including 56 patients with acromegaly (acromegaly group, AG) and 59 healthy sub-jects matched for age, sex and BMI (control group, CG). DXA and cQUS assessment were performed in both AG and CG; detailed clinical data were collected for the AG. Results All cQUS parameters showed a good correlation with the DXA-derived T-score values (p < 0.001) in both AG and CG. The cQUS-derived T-score was not significantly different in the AG compared to the CG (AG: 0.40 [IQR -1.60 to 1.50]; CG:-1,30 [IQR-1.65 to 0.95], p = 0.068 ) The cQUS-derived T-score showed a good discriminatory ability for the presence of osteopenia in the AG (AUC 0.833 [CI 0.721-0.945]). This discriminatory ability of the cQUS-derived T-score was similar between the AG and the CG (p = 0.325) Conclusions CQUS parameters showed a good correlation with DXA evaluation in patients with acromegaly, comparable to the observation in the general population. cQUS-derived T-score can accurately discriminate osteopenia in patients with acromegaly.

OBJECTIVES:Patients with systemic sclerosis (SSc) exhibit systemic and more pronounced micro- and macro-architectural bone damage compared to healthy subjects (HS). The extent of the microvascular damage in SSc may be associated with the severity of compromised systemic bone integrity. The aim of this study is to investigate and score the status of the hand bone mineral density (BMD) in patients with SSc, using a new dedicated hand software and to score the microvascular status of the same hands by using nailfold videocapillaroscopy (NVC). METHODS:Bone mineral density (BMD/g/cm2) and bone mineral content (BMC/g) of left and right hand using a new hand dedicated software (enCore, GE Lunar Prodigy Bone Densitometer, BMD hand software, USA), as well total BMD of the skeleton (GE Lunar Prodigy Bone Densitometer), were measured in 32 SSc patients classified according to the 2013 ACR/EULAR criteria (mean age 61±14 years, 94% women, 47% (n=13) dcSSc and in 27 age-matched HS. Quality of peripheral microvascular involvement (NVC patterns) was evaluated via standardised NVC analysis including capillary number scoring. SSc organ involvement was evaluated according to the 2023 EULAR recommendations. Statistical analysis included non-parametric and multivariable regression analyses to explore the relationship between capillary density and hand bone status. RESULTS:A multiple regression analysis demonstrated that left- and right-hand BMD was significantly associated with capillary loss after adjustment for age, sex, BMI, osteoporosis history, grip strength, immunosuppressive therapy and bone-specific treatments (p=0.02 and p=0.03). Interestingly, BMD values were found positively correlated with the absolute number of capillaries per linear millimetre (left hand r=0.6893, p<0.001; right hand r=0.45, p=0.03). A significant negative correlation was also found between left hand BMD (r=-0.5752, p=0.001) with the presence of "late" NVC scleroderma pattern. A significant negative correlation was finally observed between left hand BMD and the presence of dcSSc (r=-0.3836, p=0.036) and the modified Rodnan skin score (r=-0.5811, p=0.002). Moreover, SSc patients exhibited significantly lower hand BMD compared to HS even adjusted for age, sex, BMI and history of osteoporosis. CONCLUSIONS:For the first time, hand local bone status was found significantly associated with hand/fingers NVC microvascular damage in SSc patients, emphasising the effects of capillary loss/local hypoxia on the observed bone loss. At the same time, the results of the regression model reinforced the role of capillary loss as a potential predictor of hand bone quality in SSc patients.

Polymyalgia rheumatica (PMR) is a clinically heterogeneous disease with variable trajectories. Although glucocorticoids (GCs) are effective, prolonged exposure carries significant toxicity risks. This study was aimed at exploring whether baseline frailty phenotypes (stratified by age and comorbidity burden) and treatment exposure influenced relapse patterns and the occurrence of glucocorticoid-related adverse events (GC-related AEs). Fifty-eight patients with isolated PMR were retrospectively analyzed over a 12-month follow-up. Unsupervised hierarchical clustering incorporating baseline and follow-up data was performed to identify distinct longitudinal clinical trajectories. Longitudinal outcomes related to disease activity (remission/relapses) were assessed using generalized estimating equation models. Safety dynamics were evaluated, determining the cumulative prednisone dosage at the first adverse event and using multivariable Cox proportional hazards regression to identify independent predictors of GC-related AEs, accounting for time-varying exposure patterns. Two clusters were identified: Cluster 1 (“frail”: older, multimorbid, n = 22) and Cluster 2 (“robust”: younger, fewer comorbidities, n = 36). Cluster membership was not associated with longitudinal disease activity (p = 0.129); relapse risk was instead associated with markers of treatment intensification, including DMARD requirement (OR 2.94, 95

OBJECTIVE:To determine whether multimodal imaging tools can detect dermal and microvascular abnormalities in pre-systemic sclerosis (pre-SSc) patients compared with matched healthy controls (HC). METHODS:Non-selected pre-SSc patients (n = 20, fulfilling LeRoy's criteria) from the Ghent University (hospital) Raynaud's clinic and age-, sex-, and BMI-matched HC (n = 20) were evaluated. Dermal thickness (DT) was measured using high-frequency ultrasound (HFUS, 18 MHz) at 17 sites. Nailfold videocapillaroscopy (NVC, 200x magnification) was assessed using standardized consensus. Peripheral blood perfusion (PBP) was quantified using laser speckle contrast analysis (LASCA). Group differences were analysed using generalised linear mixed models with group, location and their interaction as fixed effects, accounting for matching and within-subject clustering. RESULTS:HFUS showed an effect of group on mean DT (p = 0.011). Significant locations included the right and left fingers (0.80 ± 0.04 vs 0.68 ± 0.04 mm, p = 0.012; 0.81 ± 0.04 vs 0.67 ± 0.04 mm, p = 0.015) and left forearm (1.02 ± 0.05 vs 0.88 ± 0.05 mm, p = 0.035). LASCA demonstrated reduced (volar) fingertip PBP in pre-SSc (139 ± 12 vs 200 ± 12 perfusion units; mean difference = 61, 95% CI: 38-85; p < 0.001). NVC revealed lower capillary density (7.8 vs 9.8/mm, p < 0.001), increased microhaemorrhages (18%vs 7.4%, p = 0.032), and exclusivity of giant capillaries and scleroderma pattern. CONCLUSION:Dermal, functional and structural microvascular abnormalities are detectable in pre-SSc in the absence of clinical skin thickening or overt organ involvement. Future multicentric longitudinal studies are required to confirm multimodal differentiative value.

Large vessel vasculitis (LVV) comprises inflammatory disorders that primarily affect large arteries, most notably Takayasu arteritis (TAK) and giant cell arteritis (GCA). GCA frequently coexists with polymyalgia rheumatica (PMR), reflecting a shared disease spectrum. [18F]FDG-PET/CT is an established imaging modality and has become integral to the evaluation of these conditions. When performed alone or combined with CT angiography ([18F]FDG-PET/CT(A)), it enables visualization of metabolic activity in inflamed arterial walls as well as characteristic periarticular involvement. Since publication of the previous procedural recommendations, substantial new evidence has emerged, prompting an update of guidance. This joint guideline, developed by EANM, SNMMI, ASNC, CANM, CSNM and ANZSNM, provides updated evidence-based recommendations and expert consensus on the use of [18F]FDG-PET/CT(A) in LVV and PMR. It addresses patient preparation, tracer administration, image acquisition, interpretation, reporting, and radiation considerations, with a strong emphasis on standardization to improve diagnostic accuracy and reproducibility. The guideline highlights the impact of glucocorticoid therapy on PET sensitivity and provides disease-specific interpretation criteria for large-vessel (lvGCA) and cranial GCA (cGCA), TAK, and PMR, including validated visual grading systems and composite scores. Systematic reviews and meta-analyses demonstrate moderate to high diagnostic accuracy of [18F]FDG-PET/CT in LVV and PMR. Current evidence does not support routine PET imaging for treatment monitoring or relapse prediction. However, [18F]FDG-PET/CT is valuable for identifying vascular territories at risk of future structural damage. The guideline also reviews emerging developments, including PET/MRI, long axial field-of-view PET/CT systems, and novel radiotracers, and underscores the importance of training and harmonized practice. Overall, these updated procedural recommendations aim to strengthen international harmonization and establish robust standards for [18F]FDG-PET/CT(A) imaging in LVV and PMR, supporting clinical decision-making and guiding future research.

Background and Objectives: Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease in which persistent synovial inflammation and joint damage are influenced not only by immune dysregulation but also by environmental, genetic, and epigenetic factors. Vitamin D is a secosteroid hormone and has emerged as a key immunomodulatory hormone, with reported effects on innate and adaptive immune responses, with potential relevance to RA clinical activity and treatment. This narrative review synthesizes mechanistic and clinical evidence enlightening vitamin D's immunomodulatory role in RA pathogenesis and management. Methods: A comprehensive literature search was carried out on PubMed and MEDLINE databases using Medical Subject Headings (MeSH) terms: "Vitamin D", "Cholecalciferol", "Arthritis, Rheumatoid", "Seasons", "Epigenomics", "DNA Methylation", and "Therapy". The narrative review highlights evidence published mainly in the last 5 years on the link between vitamin D and RA, focusing on epigenetic interactions, circannual rhythms, and therapeutic implications. Results: Emerging data suggest that vitamin D-related epigenetic mechanisms (e.g., DNA methylation, histone acetylation, and microRNA regulation) and genetic polymorphisms have been associated with disease susceptibility and treatment outcomes. Latitude and seasonal fluctuations in serum 25-hydroxyvitamin D levels correlate with variations in RA disease activity, although results remain heterogeneous across studies. Overall, the available evidence supports an association between vitamin D deficiency and greater RA disease activity, while its adequate supplementation has been associated with improvements in inflammatory markers and selected clinical outcomes, especially when tailored to baseline status and individual risk factors, such as limited dietary intake and sunlight exposure. Conclusions: Current evidence emphasizes the need for further studies using standardized methods and larger, geographically diverse cohorts to define how best to leverage seasonal vitamin D variations in RA management, considering also the range of concomitant epigenetic modifiers that may influence the effects of vitamin D on the management of RA patients.

BACKGROUND:Early diagnosis is pivotal for guiding the intensity of clinical monitoring, optimizing therapeutic strategies and preventing organ damage in inflammatory and autoimmune rheumatic diseases (IARDs). This review summarizes current evidence on early diagnostic and therapeutic approaches of some IARDs, including rheumatoid arthritis (RA), systemic sclerosis (SSc) and detection of large-vessel vasculitis (LVV) in polymyalgia rheumatica (PMR), representing distinct pathophysiological mechanisms of joint synovitis, tissue fibrosis and vasculitis, respectively. METHODS:A comprehensive narrative literature review was conducted focusing on early recognition strategies, searching PubMed and Scopus databases with emphasis on studies from the past 5 years and recent EULAR/ACR conference abstracts (2023-2025). RESULTS:In RA, clinically suspect arthralgia with seropositivity for rheumatoid factor and anti-citrullinated peptide antibodies significantly increases progression risk to definite RA. Musculoskeletal ultrasound detects subclinical synovitis in 44%-51% of high-risk individuals, while MRI identifies bone marrow edema predicting erosive progression. Abatacept significantly reduces RA development in seropositive individuals at high risk of RA. In SSc, Raynaud's phenomenon combined with SSc-specific autoantibodies and abnormal nailfold capillaroscopy predicts progression to definite disease, with 79.5% developing SSc within 4.6 years. LeRoy's criteria, validated by Koenig, enables early identification, though evidence for disease-modifying interventions in preclinical stages remains limited. For PMR, imaging reveals subclinical LVV in 16%-23% of patients without cranial symptoms. Subclinical LVV associates with higher relapse rates in retrospective studies, though optimal management approaches require prospective validation. CONCLUSIONS:Advances in early IARD recognition through refined clinical criteria, enhanced biomarkers and imaging enable risk stratification and personalized management. While intervention strategies show promise, particularly in RA, optimal patient selection and treatment protocols require further research.

OBJECTIVE:A dysregulated immune response is involved in the pathogenesis of polymyalgia rheumatica (PMR) and giant cell arteritis (GCA). These diseases have been reported as immune-related adverse events in patients with cancer treated with immune checkpoints inhibitors. In this cross-sectional study, the relationship between soluble immune checkpoint molecules (sICMs) and clinical/imaging features of PMR and GCA was investigated. METHODS:Consecutive patients with PMR diagnosed according to the criteria by Bird et al were compared with age- and sex-matched healthy controls. Patients with PMR and overlapping GCA had to also satisfy the 1990 ACR classification criteria for GCA. All patients underwent standardized clinical, laboratory examination, and 18F-fluorodeoxyglucose positron emission tomography/computed tomography scans. The sICM anticytotoxic T Ly-4, the programmed cell death protein 1 (PD-1), and PD-1 ligands PD-L1 and PD-L2 were measured by enzyme-linked immunosorbent assay. RESULTS:Forty patients (80% women, mean age 76 years, and mean disease duration 88 days) were assessed. Of these, 30 had isolated PMR and 10 had PMR with GCA. Patients showed significantly higher concentrations of all sICMs compared with controls (P < 0.001). Conditional logistic regression revealed the strong discriminative capacity of these molecules between patients and healthy controls, with PD-1 showing complete separation among groups (effect size = 0.78) and PD-L1 (odds ratio [OR] 134.33, P < 0.001) and PD-L2 (OR 63.00, P < 0.001) demonstrating the strongest ability to distinguish patients from controls. Correlations between sICM levels and clinical features were generally weak or absent, with no significant differences based on disease phenotype or glucocorticoid exposure. Results were similar in glucocorticoid-naive patients. CONCLUSION:sICMs are significantly elevated in PMR and GCA and strongly differentiate patients from healthy controls. Although they do not correlate with clinical or imaging features, their consistent elevation in active disease might suggest a complex interplay between innate and adaptive immunity.

Objective Immune-mediated adverse events (irAEs) from immune checkpoint inhibitors (ICIs) often require high-dose glucocorticoids (GCs), which can promote cancer progression and counteract ICI benefits. This study evaluated the articular and oncologic clinical outcomes of ICI-induced arthritis treated with methotrexate (MTX) as a GC-sparing agent. Methods Adult patients with ICI-induced arthritis in 2023 were included. Arthritis was assessed using the disease activity score on 28 joints by C-reactive protein (DAS28-CRP), with follow-ups every 3 months. All patients received subcutaneous MTX, and oncologic outcomes were evaluated using RECIST 1.1 criteria after one year. Results Fourteen patients (median age 74.5 years) with melanoma (64.3%), colorectal cancer (14.3%), lung cancer (14.3%), or Hodgkins' lymphoma (7.1%) were treated with PD1 antagonists (92.9%) or combined with CTLA4 blockers (7.1%). Arthritis presentations included oligo-arthritis (36%), mono-arthritis (29%), polyarthritis (21%), and polymyalgia rheumatica-like syndrome (14.3%), with a mean onset of 4.7 +/- 3.7 months post-ICI. MTX was started for all at a mean dose of 9.5 +/- 1.5 mg weekly, beginning at the first rheumatology visit in 78.5% of patients. Over a mean follow-up of 12.8 +/- 4.6 months, DAS28-CRP scores improved significantly, and prednisone dosage was in all reduced (3.6 mg at V4 vs. 8.4 mg at V0, p=0.003). No major MTX-related toxicities were noted. Cancer responses at follow-up were complete (50%), partial (21.4%), stable disease (7.1%), and progression (21.5%). Conclusion The use of MTX in ICI-induced arthritis showed promising results in reducing GC dosages and managing the inflammatory articular activity, with no major toxicities observed over one year. These findings suggest that MTX may be a viable GC-sparing option in this context, but larger, controlled studies are needed to confirm these observations and better understand the impact on both articular and oncologic outcomes.