Andrea Lo Monaco

Background/Objectives: Systemic sclerosis (SSc) patients frequently develop osteoporosis; however, vertebral fracture risk factors remain poorly characterized. This study identifies general and SSc-specific predictors of vertebral fractures in SSc patients undergoing osteoporosis evaluation. Methods: This multicenter cross-sectional study enrolled consecutive SSc patients meeting ACR/EULAR 2013 criteria with suspected osteoporosis. Data included demographics, disease characteristics, bone density (DXA), and vertebral imaging. Stepwise logistic regression analyzed fracture associations (p ≤ 0.05 significant). Results: The majority of 103 enrolled patients were female and all were post-menopausal. The prevalence of osteoporosis was 52.4%, that of vertebral fractures was 38.8%, and that of osteopenia was 28.1%. General risk factor analysis identified family history of fragility fractures (OR 11.8, p = 0.008) and vertebral T-scores (OR 0.6, p = 0.049) as significant predictors. When adding SSc-specific factors, only family history (OR 13.8, p = 0.03) and gastrointestinal (GI) involvement (OR 4.8, p = 0.05) remained significant. Conclusions: Vertebral fractures in SSc patients are strongly linked to a family history of fractures. The suggestive association with GI involvement may imply a significant role for malabsorption-related metabolic impairment. Prioritizing bone density screening in SSc patients with GI symptoms may enable earlier intervention and reduce fracture risk.

Objective. In the absence of national and European guidelines on the treatment of rheumatoid arthritis (RA) with interstitial lung disease (ILD), the Italian Society of Rheumatology decided to develop national clinical practice guidelines on the management of patients with RA-ILD in accordance with the requirements of the National Guideline System of the National Institute of Health. Methods. The development process included a systematic review of the available evidence and its adaptability to the Italian context, followed by a consultation with experts in rheumatology, respiratory diseases, radiology, and representatives of the health professions and patients. Results. The panel decided to develop recommendations in three main scenarios. The first section of recommendations is focused on drugs indicated for RA to assess their safety and efficacy in RA-ILD. The second set of recommendations covered the drugs indicated for the treatment of ILD in patients with RA-ILD (to assess their efficacy and safety in patients with RA). The third part of these guidelines dealt with drugs indicated for the treatment of RA-ILD upon first-line failure. Moreover, the lack or absence of scientific evidence in literature on certain topics, such as the value of a multidisciplinary treatment approach and lung transplantation, led to the decision to proceed through expert consensus to develop good clinical practice guidelines. Conclusions. These guidelines represent a fundamental step towards improving the health management of patients with rheumatological diseases in Italy by providing specific and evidence-based guidelines for the management of RA-ILD. Their use is intended to promote health and reduce the burden of morbidity and mortality in this vulnerable population.

Introduction: Dermatomyositis (DM) is a rare autoimmune disorder, with the anti-melanoma differentiation-associated gene 5 (anti-MDA5) antibody positive subtype associated with severe complications such as rapidly progressive interstitial lung disease (RP-ILD) and, more rarely, spontaneous pneumomediastinum (SPM). This case highlights the challenges of managing a patient with such complex condition, particularly in the context of multiple comorbidities, including a history of cancer and recurrent infections.Case description: A 45-year-old woman with an history of vulvar squamous cell carcinoma (July 2022) presented with classic features of DM, including Gottron’s papules, proximal muscle weakness, dysphagia, severe cutaneous vasculitis and lymphopenia. She was then diagnosed with anti-MDA5-positive DM in October 2023. High-resolution CT (HRCT) of the lung performed in January 2024, in the absence of respiratory symptoms, revealed early interstitial changes with ground-glass opacities. Initial corticosteroid therapy yielded partial improvement. A Listeria monocytogenes meningitis in July 2024, coupled with her history of cancer, delayed the start of aggressive immunosuppressive therapy, even though the onset of dyspnea and imaging in June 2024 had already revealed worsening interstitial lung disease (ILD). In the meantime she received two cycles of intravenous immunoglobulin (IVIg). By October 2024, clinical decline with cutaneous ulcers and severe lymphopenia prompted cyclosporine (CyA) initiation. Concurrently, imaging revealed progressing ILD with new-onset pneumomediastinum and subcutaneous emphysema, culminating in massive emphysema requiring hospitalization and bilateral thoracic drainage. A multidisciplinary team approved the escalation to rituximab, which, in combination with her existing regimen, led to clinical stabilization and the resolution of her pulmonary and cutaneous symptoms.Conclusion: This case emphasizes the complexity of managing anti-MDA5-positive DM with severe pulmonary complications. Early recognition, a multidisciplinary approach, and personalized treatment are crucial to improving outcomes.

Objective. Interstitial lung disease (ILD) is rare, but it is one of the most frequent extra-articular manifestations and a relevant cause of morbidity and mortality in rheumatoid arthritis (RA). Over the past few years, Janus kinase inhibitors (JAKis) have been reported to have promising efficacy in the treatment of active RA, but recent concerns have been raised about their safety profile, namely, malignancy and cardiovascular disease, limiting their use to certain patient categories. Methods. The objective of this narrative review is to summarize the current evidence of the efficacy and safety of JAKis in RA-ILD management, investigating a possible emerging role for this drug class in such a subset of patients. Results. Current studies focusing on JAKis in RA-ILD are scarce, but they globally report an overall stabilization of respiratory symptoms, functional data, and radiographic extension of ILD. In some cohorts, JAKis determined even an encouraging improvement in lung disease, and few reports presented good tolerability of JAKis in combination with antifibrotics. Concerning the safety profile, no significant increased risk of pulmonary infection has been reported. Conclusions. Thus far, evidence regarding the role of JAKis in the treatment of RA-ILD remains relatively limited, and additional prospective studies are needed to better understand the place of JAKis, if any, in preventing/stabilizing ILD in RA patients.

Iloprost is recommend worldwide for the treatment of RP and the healing of DUs. The aim of this study is to report the regimens of Iloprost administered in different rheumatological centers within the same regional Health System Methods: A questionnaire exploring different items related to the use of Iloprost was developed and reviewed by three expert rheumatologists. The questionnaire was distributed as an online survey to all local SSc referral centers in Emilia-Romagna (Italy). Data are reported as percentage or median with interquartile range (IQR), as appropriate. An updated review of world literature on this topic was also carried out. All the invited centers completed the survey. There were both local (8) and university hospitals (4). The majority (58%) had a rheumatologist as head physician. All centers used Iloprost: a single monthly administration was the most common treatment (75%). The cycle lasted 1 [IQR 1-2] days with a 0.5-2.0 ng/Kg/min dose according to the drug tolerance of the patients. There were overall 68 spots (beds, reclining armchair, or simple armchair); 2.0 [1.5-4.0] patients were able to receive Iloprost at the same time. University Hospitals had more physicians at their disposal than local hospitals but less paramedic personnel (respectively: 1.8 vs 1.2 physicians, 1.5 vs 2.1 nurses). These observations were in line with the majority of previous studies reporting different regimens, comparing similar (but not identical) dose and schedule administration, however, despite differences being at times substantial, no standard infusion method is yet available.

BACKGROUND: Digital ulcers (DU) affect 50% of systemic sclerosis (SSc) patients, representing a challenging clinical problem. Despite a high negative predictive value, capillaroscopic scores proposed to select patients at risk for DU show an inadequate positive predictive value, especially in patients without previous DU. AIM OF THIS STUDY: To increase the predictive value for DU development of capillaroscopy, through a predictive risk chart taking into account capillaroscopic, demographic, and clinico-serological parameters. PATIENTS AND METHODS: Two hundred and nineteen unselected SSc patients from 8 Italian Rheumatology Centers were consecutively enrolled during a 6-month period. Demographic, clinical, serological and instrumental data and capillaroscopy skin ulcers risk index (CSURI) were collected. RESULTS: A multivariate logistic regression analysis showed a significant positive association between DU appearance and male gender, DU history, altered CSURI, and ESR. A prediction risk chart of the development of DU within 6 months were built on the basis of the above parameters. According to the risk level, four risk classes were identified: low (≤19.3%); medium (>19.3%, ≤58.6%); high (>58.6%, ≤89.2%), and very high risk (>89.2%). CONCLUSIONS: The systematic evaluation of the above parameters can be helpful to identify patients at risk to develop DU optimizing preventive vasoactive therapy.

The prognosis for patients with rheumatoid arthritis or spondyloarthritides has improved dramatically due to earlier diagnosis, recognition of the need to treat early with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), alone or in combinations, the establishment of treatment targets, and the development of biological DMARDs (bDMARDs). Many patients are now able to achieve clinical remission or low disease activity with therapy, and reduce or eliminate systemic corticosteroid use. Guidelines recommend methotrexate as a first-line agent for the initial treatment of rheumatoid arthritis; however, a majority of patients will require a change of csDMARD or step up to combination therapy with the addition of another csDMARD or a bDMARD. However, treatment failure is common and switching to a different therapy may be required. The large number of available treatment options, combined with a lack of comparative data, makes the choice of a new therapy complex and often not evidence based. We summarize and discuss evidence to inform treatment decisions in patients who require a change in therapy, including baseline factors that may predict response to therapy.

Quiz Ref ID Systemic sclerosis is a heterogeneous autoimmune connective tissue disease characterized by vasculopathy, autoantibody formation, low-grade inflammation, and fibrosis in skin and internal organs, with varying geographical prevalence (50-300 per million persons per year) and incidence (2.3-22.8 per million persons per year).^1,2 Previous studies have shown that systemic sclerosis is amenable to treatment with autologous hematopoietic stem cell transplantation (HSCT).^3-9 Improvement of skin involvement and functional ability was consistently observed, although some studies showed that HSCT can also ameliorate vasculopathy, improve skin and lung involvement, and correct immune abnormalities.^10-13 The benefits of HSCT must be weighed against the risk of serious toxicities due to organ involvement in systemic sclerosis.¹⁴ It is still unclear whether HSCT prolongs survival in systemic sclerosis. We therefore conducted a randomized clinical trial called ASTIS (Autologous Stem Cell Transplantation International Scleroderma) to compare safety and efficacy of HSCT vs 12 successive monthly intravenous pulses of cyclophosphamide.

Digital ulcers (DU) occur in about 50% of systemic sclerosis (SSc) patients. Scleroderma DU are responsible for chronic pain and disability with the need of systemic and local treatments. Recently, capillaroscopic skin ulcer risk index (CSURI) has been validated as useful tool in predicting the appearance of new scleroderma ulcers and/or persistence of non-healing lesions, within 3 months from capillaroscopy evaluation. Since the image length of 1.57 mm might represent a critical factor for CSURI calculation, the present study aimed to evaluate the reliability of CSURI using three different videocapillaroscopy devices with distinct image widths. One hundred and seventy-six unselected SSc patients were consecutively enrolled for the study during a six-month period, using three different capillaroscopy devices (image widths of 1.33, 1.57, and 1.70 mm). After a three month-follow-up new DU or persisting non-healing ulcers were observed in 46/176 patients (26.1%). The receiver operating characteristic curve analysis for CSURI showed an area under curve respectively of 0.705 for the image width of 1.33 mm, 0.786 for the image of 1.70 mm, and 0.888 for the image width of 1.57 mm. The good sensitivity, specificity and positive predictive value of CSURI was confirmed in the whole patients' series, as well as in the three subgroups on different image widths obtained with various available devices. In addition, the negative predictive value of the capillaroscopic index remained very high regardless of the picture length adopted.