Search Results (7)

Background: Autoantibodies are central to the diagnosis and risk stratification of systemic sclerosis (SSc), but their prevalence and clinical associations may vary across populations. This study aimed to evaluate the prevalence and immuno-clinical associations of different autoantibodies in the Rheumatic Diseases Portuguese Register systemic sclerosis cohort. Methods: This was a multicentre observational registry-based study that used data from the Reuma.pt SSc module. Patients were divided according to autoantibody status, and associations between autoantibody expression and clinical data were assessed using appropriate statistical tests, with Bonferroni correction applied for multiple comparisons. Multivariable binary logistic regression was performed for clinically relevant outcomes, with adjustment for sex, age at diagnosis and disease duration. Results: A total of 1080 patients were included, 87.5% female, with a mean age at last evaluation of 60.2 ± 14.6 years and a mean disease duration of 12.4 ± 10.0 years. Limited cutaneous SSc was the most frequent clinical category (57.4%), followed by diffuse cutaneous SSc (17.7%), very early diagnosis of systemic sclerosis (VEDOSS; 12.3%), overlap syndromes (9.8%) and SSc sine scleroderma (2.8%). Antinuclear antibodies were present in 93.4% of patients. Anti-centromere antibodies (ACAs) were the most frequent SSc-specific autoantibodies (54.6%), followed by topoisomerase I antibodies (ATAs; 21.8%). ACA positivity was associated with limited cutaneous disease; older age at diagnosis; and lower frequency of interstitial lung disease (ILD), myositis and flexion contractures. ATA positivity was associated with diffuse cutaneous disease, male sex, higher modified Rodnan skin score (mRSS), digital ulcers, flexion contractures, oesophageal involvement and ILD. Among less frequent autoantibodies, anti-Pm/Scl antibodies were associated with myositis, joint involvement, calcinosis and ILD; anti-U1RNP antibodies with younger age, MCTD overlap, myositis and joint involvement; anti-RNA polymerase III antibodies (ARAs) with scleroderma renal crisis and higher mRSS; anti-U3RNP antibodies with diffuse cutaneous disease and renal involvement; and anti-Ku antibodies with overlap syndromes. Conclusions: In this large real-world SSc cohort, autoantibody status was strongly associated with distinct clinical phenotypes, confirming its value for disease stratification. While most established immuno-clinical associations were reproduced, some differences from international cohorts were observed, supporting the need for population-specific validation of autoantibody associations in SSc. Full article

Systemic sclerosis (SSc) is a heterogeneous autoimmune connective tissue disease characterized by immune activation, vasculopathy and progressive fibrosis of the skin and internal organs. Immunosuppressive treatment is commonly used in early inflammatory disease and in SSc-associated interstitial lung disease (SSc-ILD), yet the optimal first-line agent depends on the dominant clinical phenotype. Methotrexate (MTX) and mycophenolate mofetil (MMF) are two widely used conventional immunomodulatory options. This review summarizes the clinical trial evidence from the last four decades and places it into the context of contemporary guideline recommendations and real-world comparative effectiveness data. Two randomized placebo-controlled trials support a modest role for MTX in early diffuse cutaneous SSc, particularly for skin and musculoskeletal manifestations, but evidence for lung benefit is limited. MMF has stronger evidence for SSc-ILD, principally from the Scleroderma Lung Study II, a randomized double-blind trial showing comparable efficacy to oral cyclophosphamide with better tolerability, and from subsequent pilot, open-label, and real-world studies. Overall, the current evidence supports a phenotype-driven approach: MTX may be considered when skin or joint disease predominates without clinically relevant ILD, whereas MMF is generally preferred for SSc-ILD and systemic inflammatory disease. Direct head-to-head MTX versus MMF trials are lacking and remain an important research priority. Full article

Systemic scleroderma (SSc) is an autoimmune disease characterized by excessive collagen production and progressive fibrosis. As the disease advances, vascular injury leads to fibrosis of the skin and internal organs, among which interstitial lung disease (ILD) carries the worst prognosis. Recent advances in biomarkers, imaging techniques, and innovative therapies offer hope for improving outcomes and quality of life in patients with SSc and ILD. To evaluate the usefulness of disease biomarkers and the efficacy and safety of immunomodulatory therapies in SSc-associated ILD (SSc-ILD), a literature review was conducted using the PubMed database for studies published mainly over the last 5 years. After applying inclusion criteria, 53 clinical studies were analyzed. Treating SSc-ILD remains challenging, with therapeutic strategies aiming to suppress inflammation and limit fibrosis progression. Clinical studies have demonstrated moderate to good efficacy of immunosuppressants such as cyclophosphamide (CYC) and mycophenolate mofetil (MMF), showing improvements in lung function parameters, such as forced vital capacity (FVC), and slowing disease progression. Additionally, biological agents such as nintedanib and tocilizumab have shown promising results—nintedanib in reducing the annual rate of FVC decline and tocilizumab in decreasing inflammatory biomarkers and stabilizing pulmonary function. However, despite these therapeutic advances, many studies had small sample sizes, heterogeneous patient populations, and varying inclusion criteria. Given the challenges in diagnostics and the critical need to evaluate the efficacy alongside the safety of immunomodulatory and anti-fibrotic therapies in systemic sclerosis-associated interstitial lung disease (SSc-ILD), there remains a strong demand for large, well-designed, multicenter trials with clearly defined patient cohorts to reliably assess the long-term outcomes of agents such as tocilizumab and nintedanib. Full article

Interstitial lung disease (ILD) is a severe complication of certain connective tissue diseases (CTDs) such as systemic sclerosis (SSc), mixed connective tissue disease (MCTD), idiopathic inflammatory myopathies (IIM), rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), and it is associated with nailfold videocapillaroscopy (NVC) changes and increased morbidity and mortality rates. Early diagnosis is crucial in order to prevent the progression of ILD, prevent respiratory failure and enhance the patient’s overall quality of life. The most common paraclinical investigations are high-resolution computed tomography (HRCT) and functional respiratory tests such as forced vital capacity (FVC) and the diffusing capacity of the lungs for carbon monoxide (DLCO). The most frequent CTD associated with both ILD and NVC changes is systemic sclerosis. The “late” scleroderma pattern was the most common abnormality identified in NVC results in SSc patients. Other autoimmune diseases were also correlated with ILD and NVC changes, especially when the Raynaud phenomenon was present. Low capillary density was associated with the presence and severity of ILD and a reduction in FVC and DLCO. NVC can also differentiate the capillaroscopic changes in some particular types of ILD, such as the usual interstitial pneumonia (UIP) pattern from the non-specific interstitial pneumonia (NSIP) pattern. Nevertheless, further extensive research is necessary in order to establish the diagnostic value of NVC in CTD-ILD in clinical practice. Full article

We previously found IQ motif containing GTPase activating protein (IQGAP1) to be consistently elevated in lung fibroblasts (LF) isolated from patients with scleroderma (systemic sclerosis, SSc)-associated interstitial lung disease (ILD) and reported that IQGAP1 contributed to SSc by regulating expression and organization of α-smooth muscle actin (SMA) in LF. The aim of this study was to compare the development of ILD in the presence and absence of IQGAP1. Pulmonary fibrosis was induced in IQGAP1 knockout (KO) and wild-type (WT) mice by a single-intratracheal instillation of bleomycin. Two and three weeks later, mice were euthanized and investigated. We observed that the IQGAP1 KO mouse was characterized by a reduced rate of actin polymerization with reduced accumulation of actin in the lung compared to the WT mouse. After exposure to bleomycin, the IQGAP1 KO mouse demonstrated decreased contractile activity of LF, reduced expression of SMA, TGFβ, and collagen, and lowered overall fibrosis scores compared to the WT mouse. The numbers of inflammatory cells and expression of pro-inflammatory cytokines in lung tissue were not significantly different between IQGAP1 KO and WT mice. We conclude that IQGAP1 plays an important role in the development of lung fibrosis induced by bleomycin, and the absence of IQGAP1 reduces the contractile activity of lung fibroblast and bleomycin-induced pulmonary fibrosis. Thus, IQGAP1 may be a potential target for novel anti-fibrotic therapies for lung fibrosis. Full article

Systemic sclerosis (also known as scleroderma) is a chronic fibrosing autoimmune disease with both skin and multisystem organ involvement. Scleroderma has the highest mortality among all rheumatic diseases. The pathophysiology mechanism of systemic sclerosis is a progressive self-amplifying process, which involves widespread microvascular damage, followed by a dysregulation of innate and adaptive immunity and inflammation and diffuse fibrosis of the skin and visceral organs. Fibrosis of internal organs is a hint for systemic sclerosis, moreover associated with interstitial lung disease (SSc-ILD) is a complex process. In order to correlate scientific data from the literature with clinical experience, we present the case of a 56-year-old woman who was diagnosed with systemic sclerosis 16 years ago. The association of numerous comorbidities characterized by a considerable level of seriousness characterizes this case: the highly extensive systemic damage, the cardiovascular impact of the illness, and the existence of severe pulmonary arterial hypertension. The systemic and clinical manifestations, respiratory functional tests, radiological features, and specific therapy are discussed. Full article

About 20% of patients with systemic sclerosis have symptoms of another connective tissue disease (CTD). Interstitial lung disease (ILD) is one of the most common organ manifestations in systemic sclerosis (SSc) as well as viral illnesses, such as COVID-19, and can lead not only to diffuse alveolar damage, but also trigger an exacerbation of fibrosis among patients with preexisting ILD. It is also associated with substantial morbidity and mortality. According to the World Scleroderma Foundation, SSc-ILD can mask or mimic early COVID-19 lesions and there are no available computed tomography guidelines on how to discern those two conditions. We present a case of systemic sclerosis exacerbation after COVID-19 in a patient with SSc-Lupus Overlap Syndrome. Full article