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Open research questions in Systemic Sclerosis and Related Diseases

125 gap statements mined from Systemic Sclerosis and Related Diseases papers in our 4.5M-paper local library, which holds 676 papers on the topic — drawn mostly from each paper's own stated research gap, future-work, challenge and limitation notes, and its abstract. The ones listed below are a selection still marked open; each names the study that raised it, with a DOI link where the paper has one.

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What the literature leaves open

  • With respect to ILD, results were mixed: the DESIRES showed improved FVC values at week 24 in the RTX group compared to placebo, while the Leiden trial failed to show any difference in terms of spirometric or radiographic progression between the two groups [4,17]. Despite growing evidence supporting both TCZ and RTX in SSc treatment, real-world data remain limited, especially for patients w

    Tocilizumab and Rituximab in Systemic Sclerosis: A Real-Life Retrospective Observational Study Across Different Clinical Phenotypes · 2026 · DOI

  • Future studies could investigate the effects of various stressors, such as inflammatory cytokines and autoanti- bodies, on endothelial cell senescence. First, current 3D cul- ture technologies remain at a relatively early stage, often involving high costs and a lack of standardized, univer- sally accepted protocols for cell culture and harvest.

    3D-Mesenchymal stromal cells derived VASH2 alleviates oxidative stress-induced endothelial senescence by mediating α-tubulin detyrosination in systemic sclerosis · 2026 · DOI

  • The present case contributes to the limited literature on late-onset disease and highlights the importance of considering ECDS in adults presenting with progressive craniofacial atrophy.

    Late-Onset En Coup de Sabre: A Rare Presentation of Linear Scleroderma in an Elderly Woman · 2026 · DOI

  • late into meaningful improvements in symptoms, functional capacity, or long-term clinical outcomes remains uncertain and SUPPLEMENTARY DATA cannot be determined from the present study.

    Intravenous immunoglobulin for cardiac involvement in systemic sclerosis: insights from echocardiography and cardiac magnetic resonance imaging in a retrospective cohort · 2026 · DOI

  • These observations expand the limited evidence base on systemic inflammation in morphea and support CBC-derived indices, particularly PIV, as pragmatic, low-cost adjunct biomarkers for disease discrimination in daily practice.

    Pan-immune-inflammation value and other CBC-derived indices reveal a systemic inflammatory signature in morphea · 2026 · DOI

  • should be done, in considerations particular, because the normal limits and physiologic correlates of TAPSE are not well known, even in healthy subjects. Our study is in keeping with the few studies on the potential role of TAPSE/PAPs ratio in predicting worse outcomes in SSc- PH patients (22–25).

    The predictive role of the TAPSE/sPAP ratio for cardiovascular events and mortality in systemic sclerosis with pulmonary hypertension · 2024 · DOI

  • As limitations of the present study, we can mention: (i) the small sample size of the studies; (ii) the absence of control groups; (iii) the lack of important information and ho- mogenization in the descriptions of the reports; (iv) the sample formed by reports/series of cases, which leads to the inability to generalize; and (v) the absence of randomized controlled trials (RCTs), which prevents meta-analyses from being carried out.

    Raynaud’s Phenomenon of the Nipple: Epidemiological, Clinical, Pathophysiological, and Therapeutic Characterization · 2024 · DOI

  • To the best of our knowledge, similar cases have not been previously reported. Treatment remains challenging, as no standardized therapeutic approach has been established.

    Nodular Scleroderma in a Patient With Anti–RNA Polymerase III–Antibody Positive Systemic Sclerosis: A Case Report and Literature Review · 2026 · DOI

  • Future research should focus on identifying barriers to guideline imple- mentation and evaluating the impact of standardised practices on patient outcomes.

    Screening and management of systemic sclerosis-associated pulmonary complications in Iraq: insights from a national survey of rheumatologists and pulmonologists · 2026 · DOI

  • Many proposed macrophage-associated biomarkers remain insufficiently standardized, and most macrophage-directed strategies are still preclinical or exploratory in SSc.

    Macrophage programming in systemic sclerosis: Niches, networks, and translational horizons · 2026 · DOI

  • Our findings need to be replicated on larger longitudinal cohorts to verify the role of EVs as biomarkers in paving the road to new therapeutic avenues.

    Circulating extracellular vesicles as predictive biomarkers of progressive interstitial lung disease in systemic sclerosis—a prospective cohort study · 2025 · DOI

  • The follow-up period was rela- tively short, and the long-term durability of ASCs-medi- ated benefits remains to be determined.

    Intralesional Adipose-Derived Stem Cells Reverse Established Dermal Fibrosis and Modulate Angiogenesis-Related Readouts in a Murine Systemic Sclerosis Model · 2026 · DOI

  • The retrospective cross-sectional design precludes conclusions about causality or prognosis; prospective studies incorporating concurrent functional diaphragm assessment are warranted.

    Diaphragmatic Muscle Thickness: A Complementary Tool in Assessing Lung Involvement in Patients with Systemic Sclerosis · 2026 · DOI

  • Diaphragmatic muscle impairment, which may contribute to respiratory dysfunction, is underexplored in SSc.

    Diaphragmatic Muscle Thickness: A Complementary Tool in Assessing Lung Involvement in Patients with Systemic Sclerosis · 2026 · DOI

  • However, in patients with short disease duration, the extent to which pulmonary function impairment reflects early right-heart involvement remains incompletely understood.

    Reduced DLCO flags early right-heart strain in systemic sclerosis despite short disease duration · 2026 · DOI

  • However, whether predictive factors differ between systemic sclerosis (SSc) and non-SSc CTD remains unclear.

    Differential predictors of mPAP progression in Systemic Sclerosis and Non-SSc connective tissue disease patients · 2026 · DOI

  • In particular, the frequency of the non-dipper pattern (lack of nighttime BP reduction) in SSc patients has not been adequately investigated.

    Increased Frequency of the Non-Dipper Blood Pressure Pattern in Patients with Systemic Sclerosis: Insights from 24-Hour Ambulatory Monitoring · 2025 · DOI

  • Sodium-glucose cotransporter 2 inhibitors (SGLT2i) have shown cardio-renal benefits in diverse populations with cardio-renal dysfunction, but their impact on outcomes in patients with systemic sclerosis has not been described.

    Sodium Glucose Co-Transporter-2 inhibitors in patients with systemic sclerosis with or without heart failure · 2025 · DOI

  • Further investigation of these miRNAs may enhance our understanding of the underlying mechanisms of SSc.

    miRNA profiles in early systemic sclerosis, organ complications, and treatment response · 2025 · DOI

  • However, existing studies on serum miRNA expression in SSc are limited by the number of detected miRNAs, size of the SSc patient cohort, and a lack of information on miRNA profiles after treatment.

    miRNA profiles in early systemic sclerosis, organ complications, and treatment response · 2025 · DOI

  • To date, a non-invasive monitoring tool, to capture chronic graft changes among VCA recipients, has not been established.

    37. Skin Viscoelasticity: A Potential Surrogate Marker for Facial Allograft Skin Fibrosis – A Case Series · 2025 · DOI

  • AIMS: Although certain autoimmune diseases (AIDs) have been associated with an increased rate of heart failure (HF), data on the long-term rate of HF across the spectrum of AIDs are lacking.

    Long-Term Rate of Heart Failure in Patients with Autoimmune Disease: A Nationwide Cohort Study · 2024 · DOI

  • Nonetheless, the mechanism of cellular interactions and the precise spatial distribution of these cellular events within the fibrotic tissues remain elusive, highlighting a critical gap in our comprehensive understanding of scleroderma's pathogenesis.

    Spatial transcriptomic analysis deciphers adipocyte-to-fibroblast transformation in bleomycin-induced murine skin fibrosis · 2024 · DOI

  • [1] The exact prevalence of rheumatoid arthritis-associated interstitial lung disease (RA-ILD) remains uncertain, ranging from 1% to 58% based on different study methodologies.

    Efficacy and safety of JAK inhibitors in connective tissue disease-associated interstitial lung disease · 2024 · DOI

  • The reported prevalence of ILD varies widely across studies owing to differences in inclusion criteria, research methodologies, and follow-up durations.

    Efficacy and safety of JAK inhibitors in connective tissue disease-associated interstitial lung disease · 2024 · DOI

Most-cited papers in Systemic Sclerosis and Related Diseases

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125 gap statements have been mined from Systemic Sclerosis and Related Diseases papers in our 4.5M-paper local library, which holds 676 papers on the topic; the gaps come from whichever of those papers state one. They are mostly the research gaps the authors state and the papers' abstracts, plus future-work, limitations and challenges passages. The ones listed below are a selection still marked open; each names the study that raised it, with a DOI link where the paper has one, so you can read the original claim in context.

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