Alberto Sulli

Objective. Nailfold videocapillaroscopy (NVC) is a key imaging technique for assessing microcirculation in patients with Raynaud’s phenomenon and is essential for the diagnosis of scleroderma-related diseases and monitoring of systemic sclerosis. Few studies have evaluated structured NVC training programs, and none have investigated their impact on medical residents. This study aimed to assess skill acquisition during the First Residential NVC Course promoted by the Italian Society of Rheumatology for first-year rheumatology trainees, held in Rome on May 29-30, 2025. Methods. Trainees from 14 Italian regions participated in a 2-day program. Day 1 consisted of frontal lectures, while day 2 focused on hands-on training and interactive image interpretation. All participants completed a theoretical test and a self-evaluation of competence before and after the course. On the second day, trainees undertook an image interpretation test and filled out a satisfaction questionnaire. Results. A total of 82 trainees attended the course; 86.6% reported no prior theoretical knowledge of NVC, whereas 62.2% had performed at least one examination. Significant improvements were found in 13 of the 15 theoretical questions. Self-perceived competence increased, with 62.2% of participants reporting an improvement from ‘poor’ to ‘adequate’. The mean score on the image interpretation test was 89.3%, and overall satisfaction was high (mean rating of 3.77/4). Conclusions. This intensive residential course enhanced theoretical knowledge, self-perceived competence, and practical interpretation skills among first-year trainees. Given the central role of NVC in current rheumatology training standards, early structured exposure should be considered an essential component of postgraduate education.

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: Increasing number of epigenetic variations have been characterized in rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE).Aim: The aim of this pilot study was to prospectively evaluate pregnancy and postpartum-related epigenetic, hormonal and immunologic modifications in RA/SLE patients, versus healthy women (HS).Methods: A total of 46 pregnant (15 HS, 13 RA, 18 SLE) and 50 non-pregnant women (15 HS, 16 RA, 19 SLE) were enrolled in 4 Centres (Genoa, Brescia, Milan, Ghent). Clinical data collection, hormonal (human chorionic gonadotropin (hCG), estradiol, progesterone, prolactin), interleukin (IL)-10 dosages and epigenetic analyses (DNA methylation, chromatin accessibility/ ATAC-seq) were performed at each trimester and postpartum. DNA methylation data were used to estimate the deconvoluted distribution of different immune cells.Findings: Estradiol and progesterone serum levels showed a statistically significant increase during pregnancy in all study groups, whereas prolactin levels were significantly higher in HS and SLE pregnant vs non-pregnant women (p<0.001 and p<0.01, respectively). Pregnancy induced most differences in chromatin accessibility in the post-partum period, also in HS also in the first trimester. In HS, changes in DNA methylation occurred mainly in the first and second trimesters, with gradual normalization over the course of pregnancy. In RA, pregnancy induced fewer differentially methylated sites compared to non-pregnant, with most changes occurring after delivery. SLE pregnancies showed the lowest amount of DNA methylation changes among all groups, with most changes occurring after delivery. Differently to RA, in SLE patients changes were shifted toward hypomethylation compared to non-pregnant patients. Interpretation: This is the first study to prospectively report pregnancy-related epigenetic changes in RA and SLE patients compared to HS, suggesting a coordinated, disease-specific pattern, potentially involved in hormonal-immune modulation of pregnancy outcomes.

Background: Fibromyalgia (FM) is a chronic condition with complex etiology, characterized by widespread pain and associated symptoms that significantly impact quality of life. In Italy, organizational heterogeneity and the absence of standardized care pathways hinder uniform management. The RF-2019-12369647 project was launched to develop a national strategy for integrated and multidisciplinary care. Methods: A nationwide mapping of clinical centers dedicated to FM was conducted through online reconnaissance and validation by Regional Health Departments. A structured survey was administered to 131 identified centers to collect data on organizational models, clinical workload, and care practices. In addition, a systematic literature review of diagnostic and therapeutic guidelines was performed, and a digital repository was developed to support information sharing. Results: A total of 131 centers were mapped, and 56 completed the survey (42.7% response rate). Centers managed an average of 485 patients annually, supported by multidisciplinary teams dominated by rheumatologists (91%). Despite territorial coverage, only 16% of centers were part of regional networks, and 21% reported not using any formal care protocol. Critical issues included lack of standardized pathways, insufficient training, and limited multidisciplinary integration. A cloud-based repository and web portal were developed to facilitate knowledge dissemination. Conclusions: The findings highlight wide regional disparities, fragmented care models, and insufficient adoption of guidelines for FM management in Italy. These results support the urgent need for a coordinated national strategy to ensure equitable, standardized, and multidisciplinary care pathways for patients with fibromyalgia.

Background/Objectives: Polymyalgia rheumatica (PMR) is a relatively common inflammatory rheumatic disease of the elderly. The role of vitamin D remains unclear in this condition. The endpoints of this study were to assess 25-hydroxyvitamin D [25(OH)D] serum concentrations in PMR patients with active disease compared to elderly controls and to determine if baseline levels or changes following supplementation [delta 25-hydroxyvitamin D, Δ25(OH)D] were associated with improved clinical outcomes. Methods: In this retrospective, case–control study, 29 PMR patients (55% males, 75.24 ± 9.6 years old, disease duration of 3.8 ± 3 months) were included, meeting the 2012 EULAR/ACR classification criteria, with 29 age- and sex-matched controls without systemic inflammatory rheumatic diseases. We assessed demographic, clinical and laboratory features for PMR patients, including baseline 25(OH)D serum concentrations, disease activity (polymyalgia rheumatica activity score), and serum inflammatory biomarkers. A subgroup of them (n = 25) was followed longitudinally, for an average period of 21.1 ± 17.7 months, to evaluate the association between Δ25(OH)D and clinical outcomes at follow-up using multivariate logistic regression. Results: Although lower than the normal reference values, baseline 25(OH)D concentrations did not differ significantly between PMR patients and controls (21.6 ± 9.2 vs. 22.7 ± 11.3 ng/mL, p = 0.66) and did not predict long-term clinical outcomes. However, after only 3 months of supplementation, the increase in 25(OH)D concentrations was significantly associated with a remission status, and patients in remission showed a significant increase in 25(OH)D compared to those with persistent disease activity (+22.02 vs. +1.33 ng/mL, respectively; p = 0.044). Notably, in the multivariate model, this Δ25(OH)D was the strongest independent predictor of remission (OR = 2.89; 95% CI [1.60–4.11]), an effect independent of prednisone dosage prescribed at first visit (p = 0.32) and glucocorticoid exposure at third month (p = 0.12). Conclusions: Individual’s response of PMR patients to supplementation of vitamin D seems to be a robust independent predictor of early clinical remission achievement. Interestingly, optimizing vitamin D supplementation based on individual responsiveness may represent a valuable adjunctive strategy in PMR management.

Introduction Juvenile dermatomyositis (jDM) is a systemic autoimmune disease mainly affecting the skeletal muscle and skin. The aim of our study was to investigate the possible correlations between nailfold videocapillaroscopy (NVC) findings with clinical and laboratory parameters in patients with jDM. Methods Twenty-eight jDM patients (mean age 7.1 ± 3 years, mean disease duration 3.1 ± 3 years), evaluated between 2019 and 2023, classified according to Bohan and Peter criteria, were age- and sex-matched with healthy controls. Clinical, laboratory, and NVC parameters were collected at first visit and after 1 year again in a subgroup of patients (n = 9). Results Positivity for myositis-specific autoantibodies (MSA) was associated with a lower mean capillary density (p = 0.02) in jDM patients. Additionally, the presence of giant capillaries was significantly more frequent in MSA-positive patients (p = 0.04). The skin component of the disease activity score (VAS and DAS skin score) showed a significant inverse correlation with capillary density (r = −0.53, p = 0.007) and was significantly higher in patients with giant capillaries (median 5.5 vs 1, p = 0.005). Periungual telangiectasias and Gottron’s papules were significantly associated with a reduction of the mean capillary count and with the presence of giant capillaries (all p-values < 0.05). Interestingly, no significant changes in NVC parameters were reported after 1 year of receiving immunosuppressive treatment. Conclusions Capillary loss and the presence of giant capillaries at NVC analysis were significantly associated with clinical and laboratory markers of skin disease activity in jDM. These findings suggest that NVC may serve as a promising non-invasive tool to support disease assessment, although further prospective studies are needed to confirm its role in clinical practice. Key Points • Nailfold videocapillaroscopy (NVC) abnormalities, particularly capillary loss and giant capillaries, correlate significantly with skin disease activity in juvenile dermatomyositis (jDM). • Myositis-specific antibodies (MSA), especially anti-TIF1γ, are associated with more severe microvascular damage, suggesting their potential role in patient stratification. • NVC parameters remained stable over 1 year of immunosuppressive treatment, highlighting the need for longer-term studies to evaluate microvascular change progressions in jDM. • NVC may represent a promising non-invasive biomarker to support the clinical assessment and follow-up of patients with jDM, but further validation in larger prospective studies is warranted.

Background and Objectives: Vitamin D is a secosteroid hormone essential for calcium homeostasis and skeletal health, but established evidence highlights its significant roles also in muscle health and in the modulation of immune response. This review aims to explore the impact of impaired vitamin D status on outcomes of muscle function and involvement in inflammatory and autoimmune rheumatic diseases damaging the skeletal muscle efficiency both with direct immune-mediated mechanisms and indirect processes such as sarcopenia. Methods: A comprehensive literature search was conducted on PubMed and Medline using Medical Subject Headings (MeSH) terms: “vitamin D, muscle, rheumatic diseases.” Additionally, conference abstracts from The European Alliance of Associations for Rheumatology (EULAR) and the American College of Rheumatology (ACR) (2020–2023) were reviewed, and reference lists of included papers were scanned. The review emphasizes the evidence published in the last five years, while also incorporating significant studies from earlier years, structured by the extent of evidence linking vitamin D to muscle health in the most commonly inflammatory and autoimmune rheumatic diseases encountered in clinical practice. Results: Observational studies indicate a high prevalence of vitamin D serum deficiency (mean serum concentrations < 10 ng/mL) or insufficiency (<30 ng/mL) in patients with idiopathic inflammatory myopathies (IIMs) and polymyalgia rheumatica, as well as other autoimmune connective tissue diseases such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and systemic sclerosis (SSc). Of note, vitamin D insufficiency may be associated with reduced muscle strength (2 studies on RA, 2 in SLE and 1 in SSc), increased pain (1 study on SLE), fatigue (2 studies on SLE), and higher disease activity (3 studies on IIMs and 1 on SLE) although there is much heterogeneity in the quality of evidence and different associations for the different investigated diseases. Therefore, linked to the multilevel biological intervention exerted by vitamin D, several translational and clinical studies suggest that active metabolites of this secosteroid hormone, play a role both in reducing inflammation, but also in enhancing muscle regeneration, intra-cellular metabolism and mitochondrial function, although interventional studies are limited. Conclusions: Altered serum vitamin D status is commonly observed in inflammatory and autoimmune rheumatic diseases and seems to be associated with adverse muscle health outcomes. While maintaining adequate serum vitamin D concentrations may confer muscle-protective effects, further research is needed to confirm these findings and establish optimal supplementation strategies to obtain a safe and efficient serum threshold.

Introduction: Juvenile Sjögren’s disease (jSjD) is a rare autoimmune disease characterized by exocrine gland involvement and systemic manifestations, including small vessel vasculitis and Raynaud’s phenomenon (RP). We aimed to investigate the microvascular status in jSjD patients by nailfold videocapillaroscopy (NVC) and the potential correlations with clinical and serological features. Methods: Clinical data from thirteen consecutive jSjD patients (11 females and 2 males), with a mean age of 16 ± 4 years, diagnosed before 16 years of age (mean age at diagnosis 12 ± 3) according to the 2016 American College of Rheumatology/EULAR criteria for adult SjD, were collected including age- and sex-matched healthy controls (HCs). Clinical, laboratory, and instrumental data were collected, together with NVC examination. Non-specific and specific NVC parameters were investigated, such as capillary density, capillary dilations, giant capillaries, microhaemorrhages and abnormal shapes. Associations between NVC findings and clinical/serological features were explored and analysed using parametrical and non-parametrical tests. Results: Capillary density reduction correlated significantly with articular involvement (arthralgias) (p = 0.024). Microhaemorrhages correlated with lower C3 levels (p = 0.034). No specific NVC pattern for jSjD was identified, whereas abnormal capillary shapes were significantly higher in jSjD patients than HCs (p = 0.005). NVC abnormalities were not associated with SjD-specific instrumental tests (biopsy, imaging, Schirmer’s test). RP was present in 8% of jSjD patients. Conclusions: The reduction of capillary density, as well as microhaemorrhages at NVC analysis, are significantly associated with some clinical aspects like articular involvement and serum biomarkers (C3 reduction). The NVC is suggested as safe and further analysis in jSjD patients. Key Points• Juvenile Sjögren’s disease (jSjD) exhibits a higher rate of abnormal shapes at nailfold videocapillaroscopy (NVC) compared to matched healthy controls.• Articular involvement in jSjD is significantly associated with a lower capillary number at NVC.• Microhaemorrhages on NVC are associated with lower C3 levels, prompting this finding as a putative novel negative biomarker/prognostic factor for jSjD.