Ana Catarina Duarte

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.

Ana Catarina Duarte, M.D., Rodrigo Rei, M.D., Helena Donato, M.D., Tiago Alfaro, Ph.D., Maria José Santos, Ph.D.. J Rheum Dis -0001;0:. https://doi.org/10.4078/jrd.2025.0207

Eduardo Dourado, Carolina Mazeda, Raquel Freitas, Patrícia Martins, Ana Teresa Melo, Liliana Saraiva, Francisca Guimarães, Emanuel Costa, Diogo Esperança Almeid

Antineutrophil cytoplasmic antibodies (ANCA)–associated vasculitis (AAV) is a heterogeneous group of rare diseases characterized by necrotizing inflammation predominantly of small vessels and the presence of these circulating antibodies. AAV comprises three important diseases, namely granulomatosis with polyangiitis, microscopic polyangiitis, and eosinophilic granulomatosis with polyangiitis, which affect multiple organ systems, significantly affecting patients' quality of life and survival. The diagnosis is established according to the clinical manifestations, detectable ANCA, and histopathology findings. Primary treatment strategies are adapted to the severity of the disease and based on immunosuppression with corticosteroids and cyclophosphamide, with increasing adoption of new, less toxic agents aimed at sustained remission of the disease, such as rituximab, methotrexate, and mycophenolate mofetil. Several international medical organizations have proposed recommendations for diagnosing and managing these diseases to standardize the procedures. In this study, we provide an up-to-date European perspective on AAV management, compiling current and relevant information regarding its epidemiology, symptoms, diagnosis, treatment strategies, and prognosis.

Granulomatous with polyangiitis (GPA) is a necrotizing granulomatous vasculitis that mostly affects small-sized vessels. The disease can affect many organs, although renal and respiratory tract involvement are the most frequent and distinguishing features. Musculoskeletal manifestations have been reported in about 50% of patients and can occur as myalgia, oligoarthralgia/arthritis of large joints or polyarthralgia/arthritis of small joints. Infrequently musculoskeletal symptoms can be the first disease manifestation, and in this clinical scenario GPA diagnosis might be delayed or mistaken by other rheumatic diseases. The authors describe three patients with musculoskeletal symptoms as earliest GPA manifestations, illustrating the clinical challenge.

Patients’ objectives and experiences must be core to the study and management of chronic diseases, such as systemic sclerosis (SSc). Although patient-reported outcomes have attracted increasing attention, evaluation of the impact of disease on the overall subjective well-being, equivalent to ‘happiness’, is remarkably lacking. To examine the determinants of happiness and quality of life in patients with SSc, with emphasis on disease features and personality traits. Observational, cross-sectional multicentre study, including 142 patients, with complete data regarding disease activity, disease impact, personality, health-related quality of life (HR-QoL) and happiness. Structural equation modelling was used to evaluate the association between the variables. The results indicated an acceptable fit of the model to the data. Perceived disease impact had a significant negative direct relation with HR-QoL (β=-0.79, p < 0.001) and with happiness (β=-0.52, p < 0.001). Positive personality traits had a positive relation with happiness (β = 0.36, p = 0.002) and an important indirect association upon QoL (β = 0.43) and happiness (β = 0.23). Perceived disease impact is influenced by body image, fatigue, and SSc-related disability to a higher degree (β =  0.6–0.7) than by disease activity (β = 0.28) or form (β = 0.17). Impact of disease had a much stronger relation with HR-QoL than with happiness. The results suggest that treatment strategies targeting not only disease control but also the mitigation of relevant domains of disease impact (body image, fatigue, global disability) may be important to improve the patients’ experience of the disease. The reinforcement of resilience factors, such as positive psychological traits, may also play a contributory role towards better patient outcomes.