Jul 2026· International Journal of Innovative Technologies in Social Science· Vol 1· 0 citations· 65 references
TL;DR
Despite substantial progress in understanding disease mechanisms and expanding therapeutic options, systemic sclerosis remains a clinically heterogeneous disorder requiring early diagnosis, multidisciplinary management, and individualized treatment to optimize survival and quality of life.
Abstract
Systemic sclerosis is a rare autoimmune connective tissue disorder marked by immunological dysregulation, vasculopathy, and progressive fibrosis of the skin and internal organs, resulting in considerable morbidity and mortality. The disease results from a complex interaction between genetic susceptibility, epigenetic modifications, environmental triggers, endothelial dysfunction, and aberrant immune responses. These mechanisms promote persistent inflammation, stimulation of fibroblasts and abundant extracellular matrix deposition, eventually causing irreversible tissue fibrosis and organ dysfunction. The diagnosis is based on clinical manifestations, supported by specific antibodies detection, capillaroscopy, and appropriate functional and imaging tests. To facilitate diagnosis, the American College of Rheumatology/European League Against Rheumatism issued guidelines in 2013, enabling earlier diagnosis and more accurate prognostic assessment. Although no curative therapy is currently available, treatment has advanced considerably and focuses on suppressing disease activity, slowing fibrosis, and preventing organ complications. Current therapeutic strategies include immunosuppressive agents, biologic therapies, antifibrotic drugs, and targeted vasodilator treatments tailored to individual organ involvement. Emerging approaches, such as JAK-STAT pathway inhibitors, CAR-T cell therapy, and stem cell transplantation, may further improve long-term outcomes in selected patients. Despite substantial progress in understanding disease mechanisms and expanding therapeutic options, systemic sclerosis remains a clinically heterogeneous disorder requiring early diagnosis, multidisciplinary management, and individualized treatment to optimize survival and quality of life.
Multiple Sclerosis (MS) is a chronic immune-mediated neurodegenerative disorder of the Central Nervous System (CNS) that affects more than 2.8 million people worldwide. It is recognized as one of the leading causes of non-traumatic neurological disability among young adults. It is an inflammatory demyelination disease with axonal damage and progressive neurological disability, which creates high personal, social, and economic costs. The development of neuroimaging, immunobiology, and molecular biology has significantly enhanced the accuracy of diagnosis, disease monitoring, and therapeutic development, enabling earlier intervention and better relapse management with disease-modifying therapeutic agents. These innovations have improved clinical training, retention, and optimization of treatment for relapsing forms of the disease. The Pathophysiology of MS is complex, and the factors that lead to the condition are a complicated interplay of genetic risk, environmental exposure (Epstein-Barr virus, vitamin D deficiency, and smoking), and impaired immunological responses. Despite these gains, there are some significant limitations. There are limited therapeutic interventions that are effective against progressive multiple sclerosis; remyelination failure still plays a role in irreversible disability. Predicting treatment response in this disorder is yet to be identified. The existing literature has identified gaps in understanding immune dysregulation, neurodegeneration, and new modulators, including viral exposures, the gut microbiota, and cell signalling pathways. These unaddressed gaps impede the design of individual and neuroprotective therapeutic approaches that can modify the disease course over the long term. This review critically examines the recent developments and current issues in multiple sclerosis, including etiology and Pathophysiology and diagnostic and therapeutic interventions, with a particular focus on highlighting critical areas of knowledge gaps as well as future research directions that may be used in support of multidisciplinary and integrative approaches to enhance the quality of life and multiple sclerosis clinical outcomes in patients.
K. Ravi, K. Arora· Current Neurovascular Resear...· 0 citations
Systemic sclerosis (SSc) is a heterogeneous autoimmune disease characterized by immune dysregulation, vasculopathy, and progressive fibrosis affecting the skin and internal organs. Although biologic therapies have expanded the therapeutic landscape of immune-mediated diseases, their impact in SSc has been uneven and remains difficult to interpret when viewed only on a drug-by-drug basis. This focused narrative review reappraises biologic therapies in SSc using a manifestation-based framework spanning cutaneous, pulmonary, vascular, gastrointestinal, musculoskeletal, and global or composite outcomes. Published evidence is most developed for selected cutaneous and pulmonary manifestations, particularly through B-cell depletion in selected cutaneous–pulmonary phenotypes and interleukin-6 blockade that attenuates pulmonary function decline in early inflammatory disease, whereas gastrointestinal and vascular manifestations have not yet shown comparable clinical evidence of benefit and remain insufficiently studied. We argue that this asymmetry not only reflects differences in trial design and endpoint selection, but also manifestation-specific pathobiology, disease stage, and the extent to which inflammatory, vascular, and fibrotic processes remain therapeutically modifiable. In particular, vasculopathy may represent an upstream pathogenic layer that constrains the disease-modifying capacity of biologics that primarily improve downstream inflammatory or fibrotic manifestations. We also highlight the relevance of Japanese contributions to the biologics literature in SSc and discuss future priorities, including manifestation-appropriate endpoint selection, early-disease enrichment, and biomarker-informed stratification. Overall, biologics have changed the treatment of SSc in a selective rather than global manner; embracing a manifestation-based view is now essential for both trial design and day-to-day therapeutic decision-making.
Souta Kobayashi, Y. Ikuno, Masahiro Yamada et al.· Sclerosis· 0 citations
Sjögren's disease (SjD) is a chronic systemic autoimmune disorder characterized by immune-mediated injury to exocrine glands and multiple extra-glandular organs, affecting millions of individuals worldwide. Despite its clinical burden, SjD remains challenging to diagnose in a timely manner due to the limited availability of objective diagnostic tools and the lack of knowledge in its pathogenic mechanisms, which also hinders the development of targeted therapy. Current therapeutic strategies include systemic immunosuppressive agents and corticosteroids, supplemented by symptomatic management; however, these approaches offer variable efficacy and induce systemic side effects. This review summarizes recent advances in the clinical diagnosis of SjD, emphasizing evolving diagnostic criteria and advanced diagnostic tools including ultrasound imaging, biopsies, as well as tear/salivary and hematological biomarkers; and discusses current concepts of SjD pathophysiology, focusing on immune dysregulation, inflammatory signaling, and tissue-specific pathological changes; Moreover, novel therapeutics targeting Pattern Recognition Receptors and lymphocytic activation was included.
Regina Liu, Eman Seyal, Yi Li et al.· American Journal of Patholog...· 0 citations
Background and objectives: Autoimmune and autoinflammatory diseases extend far beyond their primary organ manifestations. Systemic inflammation in these disorders disrupts metabolic homeostasis, driving insulin resistance, dyslipidemia, accelerated atherosclerosis, and altered body composition. Metabolic syndrome (MetS) affects approximately 30% of patients with rheumatoid arthritis, with similar or higher prevalence in systemic lupus erythematosus, psoriasis, and antiphospholipid syndrome, contributing substantially to cardiovascular morbidity and mortality yet remaining underrecognized and undermanaged in routine clinical practice. This review summarizes the mechanisms linking chronic inflammation to metabolic dysfunction and the clinical epidemiology of metabolic complications across different autoimmune and autoinflammatory diseases, with attention to the metabolic effects of common immunomodulatory treatments. Methods: This narrative review was based on a literature search of PubMed/MEDLINE, Scopus, and Web of Science (publications available up to March 2026), using search terms covering autoimmune and autoinflammatory diseases, metabolic syndrome, insulin resistance, dyslipidemia, cardiovascular risk, cytokines, adipokines, and immunomodulatory treatments. Results: proinflammatory cytokines, adipokines, and immune cell populations were found to mediate insulin resistance and dyslipidemia across diseases. Conventional disease-modifying antirheumatic drugs (DMARDs), glucocorticoids, and emerging targeted biologics can either ameliorate or worsen metabolic disturbances depending on the specific agent and disease context. Conclusions: Understanding the bidirectional inflammation–metabolism relationship, together with treatment-related metabolic effects, is essential for comprehensive disease management and may identify novel therapeutic targets to reduce cardiovascular burden in this population.
Emmanuel Andrès, N. Lorenzo-Villalba, N. Dali-Youcef· Journal of Clinical Medicine· 0 citations
Psoriasis is a chronic, autoimmune skin disease driven by persistent inflammation and immune dysfunction that severely impairs quality of life and is associated with serious comorbidities, including psoriatic arthritis, cardiovascular diseases (CVDs), and depression. Emerging epidemiological evidence suggests an association between psoriasis and an increased risk of certain malignancies, such as breast cancer (BC) and non-Hodgkin’s lymphoma (NHL), although the strength and consistency of these associations vary across study designs, and the underlying thrombo-inflammatory mechanisms remain incompletely understood. Several therapeutic approaches, including topical therapies, conventional systemic drugs (e.g., methotrexate and cyclosporine), and biological agents have been investigated for their potential associations with malignancy risk. However, the available evidence is heterogeneous and influenced by disease severity, treatment duration, cumulative exposure, and patient-related confounding factors. While some epidemiological studies have reported associations between conventional therapies and selected skin or hematological malignancies, combined or sequential treatment regimens further complicate the interpretation of treatment-related cancer risk. Similarly, Janus kinase (JAK) inhibitors have been associated with higher reported rates of lymphoma and non-melanoma skin cancer than tumor necrosis factor α inhibitors (TNFi-α) in some observational studies. Recent studies also highlight the clinical utility of inflammatory markers, specifically the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte (PLR) ratio, and systemic immune-inflammation index (SII), for monitoring systemic inflammation and treatment response, while certain therapies may additionally influence CVD risk. Despite these advances, substantial heterogeneity across observational studies, meta-analyses, and Mendelian randomization analyses preclude definitive conclusions regarding causality. Overall, this review synthesizes the current epidemiological and mechanistic evidence linking psoriasis, chronic inflammation, therapeutic interventions, cancer risk, and cardiovascular comorbidities, while highlighting the need for large prospective studies and standardized analytical approaches.
Aikaterini Lymperi, Evgenia Lamprianidou, Theodora Adamantidi et al.· International Journal of Mol...· 0 citations
Autoinflammatory disorders arise from dysregulated innate immunity, most commonly involving inflammasome activation and excessive interleukin-1 (IL-1) signaling. Although rare, these conditions are increasingly recognized across age groups as genetic testing expands and phenotypic classification improves.
Therapeutic strategies focus on nonspecific immunosuppression of innate immune pathways. Corticosteroids remain effective for rapid suppression of acute inflammatory activity; however, their use is limited due to long-term toxicity. Colchicine is the first-line treatment for many autoinflammatory diseases, yet colchicine-resistant patients will require biologic therapy.
IL-1 blockade represents the major therapeutic breakthrough across autoinflammatory syndromes. Anakinra, canakinumab, and rilonacept rapidly control symptoms and reduce the usage of corticosteroids. These agents are effective in cryopyrin-associated periodic syndromes, tumor necrosis factor receptor–associated periodic syndrome (TRAPS), mevalonate kinase deficiency, colchicine-resistant familial Mediterranean fever, and adult-onset Still’s disease.
In selected phenotypes, alternative cytokine targeting is appropriate. Tumor necrosis factor inhibitors may benefit TRAPS, whereas IL-6 blockade is effective in Still’s disease–spectrum disorders. Increasing evidence supports the use of JAK inhibitors in interferon-mediated and complex autoinflammatory conditions that are resistant to other therapeutic agents.
A new generation of direct inhibitors of the Nod-like receptor pyrin domain-containing 3 (NLRP3) inflammasome is in clinical development. These small molecules aim to suppress upstream inflammasome activation.
Earlier diagnosis, rapid control of inflammation, improved quality of life, and prevention of long-term organ damage remain central goals. Guided therapy, cytokine profiling, and treat-to-target strategies using biomarkers together with long-acting biologics and oral inflammasome inhibitors are likely to be the mainstay of therapy over the coming decade.
The treatment landscape for autoinflammatory disorders has significantly advanced, with targeted modulation of innate immune pathways and IL-1 blockade forming the backbone of therapy. Promising inflammasome-directed therapies and precision medicine approaches are expected to enhance long-term patient outcomes.
A. Diamantopoulos· Journal of Human Immunity· 0 citations
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