Table of Contents
Overview
Definition and Types
Scleroderma is a rare autoimmune condition characterized by the hardening of the skin and can also affect various internal organs due to excessive collagen production and fibrosis.[2.1] This long-lasting disease primarily impacts the skin and connective tissues, but its manifestations can extend to internal organs, significantly influencing a patient's quality of life.[3.1] Scleroderma is classified into two main types: localized scleroderma and systemic scleroderma. Localized scleroderma is confined to the skin and underlying structures, whereas systemic scleroderma, also known as systemic sclerosis, is more severe and can affect multiple body systems, including blood vessels and vital organs such as the heart, lungs, and kidneys.[6.1] The systemic form poses greater health risks and complications compared to its localized counterpart.[2.1] The etiology of scleroderma is believed to involve a combination of genetic predisposition, immune system dysfunction, and environmental factors, with some cases potentially triggered by exposure to certain viruses or medications.[4.1] Symptoms can vary widely, affecting different tissues throughout the body, and may include joint pain, stiffness, and skin thickening, particularly around the fingers and toes.[5.1]Symptoms and Diagnosis
Scleroderma presents in two primary forms: localized scleroderma and systemic sclerosis (SSc). Localized scleroderma is confined to the skin, leading to inflammation and collagen-induced thickening, manifesting as various subtypes like plaque morphea and linear scleroderma.[22.1] Systemic sclerosis, however, extends beyond the skin to affect major organs such as the heart and lungs, posing significant health risks.[24.1] The prevalence of localized scleroderma is higher, with approximately 200,000 cases, compared to 100,000 for systemic scleroderma, both predominantly affecting women.[25.1] Notably, localized scleroderma does not evolve into systemic sclerosis but can impact underlying structures like muscles and bones.[26.1] Diagnosing scleroderma, especially systemic sclerosis, remains challenging due to its diverse symptoms. The VEDOSS criteria have enhanced early detection, yet distinguishing between forms remains complex, often delaying diagnosis until organ damage occurs.[41.1] Efforts to refine diagnostic criteria continue, including expert-driven initiatives to identify early indicators of systemic sclerosis.[44.1] Despite advancements, the intricacies of scleroderma's presentation necessitate ongoing research to improve diagnostic precision and patient outcomes.[43.1]History
Early Descriptions and Understanding
The earliest known account of scleroderma can be traced back to Hippocrates, who described a patient in Athens with skin that could not be raised in folds due to its hardness, a condition he referred to as "thickened skin".[48.1] However, it was not until the mid-18th century that a more detailed description of the disease emerged. Italian physician Carlo Curzio is credited with the first comprehensive account of scleroderma in 1753, documenting the case of a 17-year-old girl exhibiting severe skin changes.[52.1] Despite this early recognition, the diagnosis attributed to Curzio has been debated, with some suggesting that the symptoms he described may have been more consistent with scleroedema rather than true scleroderma.[49.1] The understanding of scleroderma evolved significantly over the centuries, particularly in the 20th century when it began to be recognized as a multisystem disease. This shift in perception was accompanied by a growing body of knowledge regarding autoimmune diseases and their systemic implications.[50.1] The term "scleroderma," derived from the Greek words "sclero" (hard) and "derma" (skin), reflects the primary symptom of the disease, which is characterized by skin hardening and thickening.[48.1] As the medical community's understanding of scleroderma progressed, it became evident that the disease could manifest in various forms, leading to the classification of two major subsets: systemic sclerosis (SSc) and localized scleroderma (LoS).[65.1] Systemic sclerosis is a complex autoimmune disorder that affects not only the skin but also multiple internal organs, while localized scleroderma is primarily confined to the skin and subcutaneous tissues.[65.1] This differentiation has been crucial in shaping diagnostic criteria and treatment approaches, as systemic sclerosis is often more severe and progressive compared to localized forms of the disease.[64.1]Key Figures and Milestones in Research
Key figures and milestones in the research of scleroderma have significantly shaped the understanding and treatment of this complex autoimmune disease. The Scleroderma Research Foundation (SRF) has played a pivotal role in advancing research and awareness, particularly through initiatives like the annual Scleroderma Awareness Month, which includes events such as the "Collaborating for a Cure" online patient forum. This forum, first held on June 1, 2022, aims to connect patients with leaders in the medical and scientific community, fostering education and support for those affected by scleroderma.[57.1] The evolution of patient advocacy has also been crucial in the history of scleroderma research. The Scleroderma Foundation has established an advocacy committee that focuses on educating the public and influencing legislation to support individuals with scleroderma. This advocacy has been essential in addressing the barriers faced by patients, particularly regarding the lack of knowledge about juvenile scleroderma within the medical community.[61.1] Recent advancements in research have been marked by significant findings, such as the FDA's clearance of the Investigational New Drug application for the CONQUEST clinical trial platform, which aims to enroll patients for new treatment strategies.[67.1] Additionally, the updated 2023 EULAR recommendations for the treatment of systemic sclerosis reflect ongoing efforts to improve clinical practices and patient outcomes.[68.1] Observational studies, like the EUSTAR study, have highlighted the importance of monitoring skin fibrosis as a predictor of lung function decline and survival, underscoring the need for continuous research in this area.[69.1] Furthermore, innovative treatment approaches, including cell-based therapies and myeloablative autologous hematopoietic stem cell transplantation, are being explored to reset the immune system in patients with systemic sclerosis, indicating a promising direction for future therapies.[70.1] These milestones and figures in scleroderma research illustrate a dynamic and evolving landscape, driven by advocacy, community engagement, and scientific inquiry.In this section:
Recent Advancements
Emerging Therapies and Clinical Trials
Recent advancements in scleroderma research have led to the development of innovative therapies and clinical trial platforms aimed at improving treatment outcomes for patients. A significant milestone was achieved with the Scleroderma Research Foundation's (SRF) announcement that the FDA cleared its Investigational New Drug application (IND) for the CONQUEST clinical trial platform, which is designed to facilitate the rapid advancement of new scleroderma treatments. This platform will involve contributions from pharmaceutical partners Sanofi and Boehringer Ingelheim, marking a collaborative effort to enhance the clinical development of scleroderma therapies.[92.1] The CONQUEST platform specifically targets systemic sclerosis-associated interstitial lung disease (SSc-ILD), a severe complication of scleroderma. Its design aims to streamline patient recruitment and improve data collection methodologies, addressing challenges faced in previous research efforts.[99.1] This innovative approach is expected to accelerate the evaluation of promising treatments, thereby potentially transforming the therapeutic landscape for scleroderma patients.[99.1] In addition to the CONQUEST initiative, recent studies have identified mycophenolate mofetil as an effective alternative treatment for systemic scleroderma with interstitial lung disease, suggesting possible long-term benefits for patients.[90.1] Furthermore, researchers are exploring advanced treatment options such as stem cell transplants and anti-fibrosis drugs, which may offer new avenues for managing this complex disease.[91.1] The ongoing collaboration between pharmaceutical companies and research foundations, exemplified by the CONQUEST trial, reflects a growing trend towards integrating diverse expertise in rheumatology and pulmonology to foster innovation in scleroderma treatment.[97.1] This collaborative model is anticipated to enhance the development of novel therapies and improve patient outcomes in the coming years.[96.1]In this section:
Pathophysiology
Mechanisms of Disease
Systemic sclerosis (scleroderma) is characterized by a complex interplay of immunological abnormalities, vascular injury, and excessive deposition of extracellular matrix proteins, particularly collagen, in the skin and various internal organs. The pathophysiology of scleroderma involves early endothelial damage, an inflammatory infiltrate, and a subsequent fibrotic reaction, which collectively contribute to the disease's progression and severity.[129.1] The disease manifests in various clinical forms, ranging from limited cutaneous systemic sclerosis, which primarily affects the skin, to diffuse cutaneous systemic sclerosis, which can lead to severe internal organ involvement and a more aggressive disease course.[130.1] The most common cause of mortality in patients with systemic sclerosis is pulmonary involvement, such as interstitial lung disease and pulmonary arterial hypertension.[130.1] Recent research has highlighted the role of immune dysregulation as a proximal cause of systemic sclerosis. This dysregulation is increasingly viewed as a unifying explanation for the fibrotic, vasculopathic, and inflammatory manifestations of the disease.[132.1] Specifically, cytokines such as Interleukin-13 (IL-13) have been implicated in the pathogenesis of scleroderma. IL-13, a T helper type 2 (Th2) cytokine, is a major inducer of fibrosis and has been shown to influence the progression of the disease by promoting fibrotic and vascular changes.[135.1] Dysregulated production of IL-13 by effector CD8+ T cells has been associated with more severe forms of cutaneous disease, indicating a critical role for this cytokine in the disease's severity.[135.1] Moreover, the Th2-oriented immune response is evident during both the inflammatory and fibrotic phases of systemic sclerosis, with elevated levels of IL-4, IL-13, and other related cytokines observed in the serum of affected patients compared to healthy controls.[136.1] This cytokine dysregulation not only contributes to the fibrotic process but also poses challenges for therapeutic interventions, as current treatments have not proven effective in modifying the disease course.[133.1] Understanding these mechanisms is essential for developing targeted therapies aimed at mitigating the effects of systemic sclerosis and improving patient outcomes.Impact on Internal Organs
Scleroderma is characterized by two main forms: systemic sclerosis and localized scleroderma, each impacting internal organs differently. Systemic sclerosis, or systemic scleroderma, typically affects not only the skin but also various internal organs, including the gastrointestinal tract, heart, lungs, and kidneys. This form is associated with systemic manifestations and can lead to increased mortality due to its extensive organ involvement.[141.1] In contrast, localized scleroderma primarily affects the skin and subcutaneous tissue, with minimal or no involvement of internal organs. Individuals with localized scleroderma rarely develop systemic scleroderma, and laboratory abnormalities commonly seen in systemic forms are often absent in localized cases.[141.1] Among the systemic manifestations, interstitial lung disease is particularly notable, manifesting as bibasilar pulmonary fibrosis, which is more prevalent and severe in patients with diffuse cutaneous systemic sclerosis. This subtype is characterized by rapid progression and aggressive skin involvement, leading to complications such as scleroderma renal crisis and pericardial effusion.[141.1] The clinical features of systemic scleroderma can include joint contractures, tendon friction rubs, and inflammatory arthritis, which further complicate the disease's impact on the patient's overall health.[141.1] Thus, the pathophysiology of scleroderma reveals significant differences in how each form affects internal organs, with systemic sclerosis posing a greater risk for severe complications and mortality compared to localized scleroderma.In this section:
Coping Strategies
Patient Perspectives and Challenges
Patients with scleroderma face significant psychological challenges due to the disease's impact on their daily functioning and overall quality of life. The distress associated with scleroderma is compounded by its physical manifestations, such as skin fibrosis and digital ulceration, which can lead to psychological trauma and a diminished perception of health.[186.1] To navigate these challenges, patients employ a variety of coping strategies that can be categorized into problem-focused, emotion-focused, and meaning-focused approaches. Problem-focused coping strategies include seeking professional help and gathering disease-related information, which empower patients to manage their condition more effectively.[182.1] Emotion-focused strategies often involve seeking social support from friends, family, and support groups, as well as utilizing adaptive distraction techniques to alleviate emotional distress.[182.1] Additionally, meaning-focused strategies, such as benefit finding and goal reappraisal, help patients reframe their experiences and maintain a sense of purpose despite their illness.[182.1] The importance of support systems cannot be overstated. Patients who successfully cope with scleroderma often report having discovered inner strengths and hope, as well as finding supportive individuals and groups that assist them in their journey.[184.1] Engaging with scleroderma organizations and educating others about the disease also contributes to a sense of empowerment and community involvement, which can enhance coping mechanisms.[184.1] Despite these strategies, patients often encounter barriers to effective coping, primarily due to a lack of access to healthcare-related resources and support services compared to those available for other chronic diseases.[183.1] This underscores the necessity for integrating knowledge, coping resources, and problem-solving skills into the daily routines of scleroderma patients to improve their mental and physical well-being.[183.1] To further aid in self-management, tools such as the SPIN Self-Management (SPIN-SELF) toolkit have been developed. This resource provides essential knowledge and coping skills across various aspects of living with scleroderma, including pain management, fatigue, and sleep issues, thereby equipping patients with practical techniques to implement at home.[185.1] Overall, while the psychological impact of scleroderma is profound, the combination of effective coping strategies and supportive networks can significantly enhance patients' resilience and quality of life.Support Networks and Self-Management Programs
Support networks and self-management programs play a crucial role in enhancing the coping strategies of individuals living with scleroderma. Patients often face significant challenges due to the rarity of the disease, which can limit their access to disease-specific educational resources and support systems. This lack of support can make coping with the physical and psychological implications of scleroderma more difficult compared to other chronic diseases.[169.1] To address these challenges, tailored self-management programs have been proposed as effective interventions. Such programs can provide patients with the necessary tools to manage their condition better and improve their overall quality of life.[173.1] These programs should focus on enhancing both problem-focused and emotion-focused coping strategies, which are essential for managing the unique difficulties associated with scleroderma.[174.1] Moreover, social support is vital for individuals coping with scleroderma. Patients report that they often struggle with accessing information and knowledgeable healthcare providers, which can exacerbate feelings of isolation and anxiety.[175.1] Therefore, fostering strong support networks can help mitigate these feelings and provide emotional reinforcement, enabling patients to navigate their challenges more effectively.[176.1]In this section:
Future Directions
Personalized Medicine Approaches
Significant advances in genetic research have enhanced the understanding of systemic sclerosis (scleroderma), leading to the identification of genetic susceptibility loci and various genes associated with different disease manifestations. These discoveries are pivotal for the development of personalized monitoring and treatment strategies tailored to individual patients.[220.1] Ongoing research into molecular and epigenetic pathways is crucial for offering new perspectives on disease phenotypes, which can further inform personalized treatment approaches.[221.1] Recent findings have also revealed cancer-like genetic mutations in the affected cells of individuals with scleroderma, suggesting potential new therapeutic avenues for this debilitating condition.[222.1] The field of systemic sclerosis therapeutics has undergone a remarkable transformation, characterized by the emergence of novel targeted therapies and a growing emphasis on precision medicine and personalized patient care.[223.1] In addition to genetic insights, the integration of biomarkers into clinical practice is essential for tailoring treatment plans for scleroderma patients. Biomarkers can serve multiple purposes, including disease diagnosis, staging, prognostication, and measuring treatment response.[241.1] They are particularly valuable for stratifying outcomes in systemic sclerosis, as they can indicate differential disease outcomes and help identify patients at risk for negative clinical events.[242.1] The heterogeneity of scleroderma necessitates the identification of easily measurable biomarkers that reflect ongoing disease activity or treatment response.[243.1] Recent advances have improved the ability to classify patient subgroups with similar prognoses, enhancing risk stratification and enriching clinical trials with patients likely to benefit from specific interventions.[244.1] Moreover, studies have demonstrated that specific gene expression signatures can predict treatment responses in scleroderma patients. For instance, higher baseline expression of a senescence-associated secretory phenotype gene signature has been associated with improved outcomes during treatment with dasatinib.[245.1] These findings underscore the potential of personalized medicine approaches in optimizing treatment strategies for individuals with scleroderma, ultimately aiming to improve patient outcomes through tailored therapies.Ongoing Research and Trials
Ongoing research in scleroderma (Systemic Sclerosis, SSc) is focused on understanding the disease's complex etiology and improving treatment options through better classification and personalization of therapies. As knowledge of the underlying mechanisms of scleroderma advances, there is a concerted effort to enhance early diagnosis, which is crucial for improving clinical trial designs and patient outcomes before significant organ damage occurs.[211.1] Current clinical trials are exploring various second-line therapies for patients who do not respond to first-line treatments. Options such as UVA-1 phototherapy, intravenous immunoglobulin (IVIG), and rituximab are being evaluated for their efficacy in managing refractory cases.[212.1] Additionally, the combination of rituximab and belimumab is under investigation as an add-on therapy with mycophenolate mofetil (MMF) in patients with early diffuse scleroderma.[213.1] Research is also examining the role of novel therapeutic agents, including Bruton’s tyrosine kinase (BTK) inhibitors and Janus kinase (JAK) inhibitors, which may target specific inflammatory and fibrotic pathways implicated in scleroderma.[213.1] Furthermore, studies funded by the National Institutes of Health (NIH) are investigating the potential of stem cell transplants for patients with severe scleroderma, showing promising long-term benefits.[214.1] Despite these advancements, drug development for scleroderma faces significant challenges, including the variability in patient responses to treatment and the lack of validated outcome measures and biomarkers for clinical trials.[219.1] This variability complicates the assessment of treatment efficacy and necessitates tailored approaches to individual patient care.[216.1]In this section:
References
[2] Understanding Scleroderma - National Scleroderma Foundation — Scleroderma is a rare rheumatic disease that causes excessive collagen production and fibrosis in the skin or internal organs. Learn about the different forms, symptoms, diagnosis, and treatment of scleroderma from this website.
[3] Scleroderma: Causes, Symptoms, and Treatment - WebMD — Scleroderma is a long-lasting autoimmune condition that can affect your skin, connective tissues, and internal organs. Learn about the different types, causes, and treatments of scleroderma and how it can impact your quality of life.
[4] Scleroderma - Symptoms and causes - Mayo Clinic — Scleroderma - Symptoms and causes - Mayo Clinic About Mayo Clinic Research & Education at Mayo Clinic Research at Mayo Clinic About Mayo Clinic Research & Education at Mayo Clinic Research at Mayo Clinic Scleroderma If you are a Mayo Clinic patient, this could include protected health information. Most likely, scleroderma is caused by a combination of factors, including immune system problems, genetics and environmental triggers. Research suggests that in some people, scleroderma symptoms may be triggered by exposure to certain viruses, medicines or drugs. Connect with others like you for support and answers to your questions in the Transplants support group on Mayo Clinic Connect, a patient community. Mayo Clinic. Clinical manifestations and diagnosis of systemic sclerosis (scleroderma) in adults. Scleroderma Scleroderma Scleroderma About Mayo Clinic
[5] Scleroderma: Symptoms, Causes & Treatment Options - Cleveland Clinic — Scleroderma can cause lots of symptoms and affect tissue throughout your body. Scleroderma usually affects your skin, but can cause symptoms in any tissue throughout your body. Visit a healthcare provider if you’re experiencing symptoms like pain and stiffness in your joints, especially if you notice thickened skin around your fingers and toes. What are scleroderma symptoms? This means your provider will probably use a few tests to determine what’s causing your symptoms before ruling out other conditions and diagnosing you with scleroderma. Talk to your provider if you feel like your scleroderma treatments aren’t working as well or if your symptoms are changing or getting worse — especially if they affect your ability to breathe or swallow.
[6] Scleroderma Basics: Overview, Symptoms, and Causes — Localized scleroderma only affects the skin and the structures directly under the skin. Systemic scleroderma, also called systemic sclerosis, affects many parts of the body. This is the more serious type of scleroderma and can damage your blood vessels and internal organs, such as the heart, lungs, and kidneys.
[22] Localized and systemic scleroderma - PubMed — Scleroderma is a broad term encompassing both localized and systemic sclerosis. Localized scleroderma is a cutaneous limited fibrosis that manifests as plaque morphea, generalized morphea, linear scleroderma, and deep morphea. Systemic scleroderma (sclerosis) can manifest as either limited or diffuse disease.
[24] Scleroderma > Fact Sheets - Yale Medicine — (Around 200,000 people have localized scleroderma, while about 100,000 have systemic scleroderma.) Both localized and systemic scleroderma are more common in women than in men. Both forms of the disease can affect people of any age, but systemic scleroderma is most commonly diagnosed in people between ages 20 and 50 and rarely occurs in children.
[25] Scleroderma and Kids - National Scleroderma Foundation — An Overview of Scleroderma and the Differences Between Localized Scleroderma and Systemic Sclerosis: Scleroderma translates to "hard skin." The cause and cure of scleroderma are unknown, but it is treatable. There are two main forms of scleroderma: Localized scleroderma (LS), also referred to as Morphea (primarily by dermatologists)
[26] Scleroderma and Systemic Sclerosis (SSc): An Overview — Localized scleroderma does NOT evolve into systemic scleroderma. Localized scleroderma is seen in all age groups, but is somewhat more common in children. This can affect the growth and development of underlying structures, including muscle and bones. Treatment for this condition includes steroid and vitamin D creams, light (UVA1 or UVB
[41] Very Early Diagnosis of Systemic Sclerosis - SAGE Journals — Scleroderma and Related Disorders The early diagnosis of systemic sclerosis (SSc) has been a major challenge for the scleroderma community in the past 50 years. 1 The recent publication of the predictive value of the VEDOSS (Very Early Diagnosis of Systemic Sclerosis) criteria in the Lancet Rheumatology in December 2021 has
[43] Early diagnosis of systemic sclerosis, where do we stand today? — Therefore, the clinical use of the new 2013 ACR/EULAR classification criteria may lead to a possible late recognition of SSc when organ damage is already established [Citation 18], not allowing a very early diagnosis. It is important to remark that the classification criteria ensure the enrollment of homogenous groups of patients in clinical
[44] Preliminary criteria for the very early diagnosis of systemic sclerosis ... — Objective: To identify a core set of preliminary items considered as important for the very early diagnosis of systemic sclerosis (SSc). Methods: A list of items provided by European League Against Rheumatism (EULAR) Scleroderma Trial and Research(EUSTAR) centres were subjected to a Delphi exercise among 110 experts in the field of SSc.
[48] The History of Scleroderma — MORE: Learn more about common scleroderma symptoms. The term scleroderma comes from the greek word, "sclero" which means hard, or hardening and "derma" meaning skin. According to sclero.org, Hippocrates was the first to describe the illness as "thickened skin." The first detailed description of the disease was by an Italian doctor named Carlo Curzio in the mid 1700s.
[49] Historical Perspective of Scleroderma | SpringerLink — It is often considered that the first description of the systemic disease that we recognize as scleroderma was in 1753 by Cario Curzio (Naples Italy) (Fig. 1.1).However, a careful review of the reported case suggests the diagnosis may, in reality, have been scleroedema because of the distribution of the skin changes and due to an apparent improvement in the 17-year-old female patient after a
[50] Historical Perspective of Scleroderma - Semantic Scholar — The history of scleroderma reflects the temporal context as well as a growth in knowledge and understanding about multisystem and autoimmune disease. There are key historic events that are relevant, but it was not until the twentieth century that scleroderma emerged as a concept for multisystem disease. This chapter reviews key aspects of early
[52] Scleroderma History - News-Medical.net — An Italian doctor from Naples, Carlo Curzio, wrote the first detailed description of the health condition in the mid-1700s, approximately 1752 or 1753. ... Scleroderma History. News-Medical
[57] Scleroderma Research Foundation Will Host Its Inaugural Virtual Patient ... — SAN FRANCISCO (May 9, 2022) - The Scleroderma Research Foundation (SRF) will host its inaugural Virtual Patient Forum, Collaborating for a Cure, on Wednesday, June 1, 2022, to kick off Scleroderma Awareness Month.Designed for those living with scleroderma and the people who care about them, the half-day patient forum will bring together leaders from the scientific and medical community so
[61] Advocacy and Awareness - National Scleroderma Foundation — Advocacy and Awareness Advocating for changes in public policy contributes to the relentless force in finding a cure and improving the lives of people affected by scleroderma. Each individual in the scleroderma community can make an incredible difference by reaching out to their elected officials to encourage them to support legislation for people affected by scleroderma. Our chapter will
[64] Systemic Sclerosis vs. Localized Scleroderma: What's the Difference? — Unlike systemic sclerosis, localized scleroderma does not typically affect internal organs. In summary, systemic sclerosis affects both the skin and internal organs, while localized scleroderma primarily affects the skin. Systemic sclerosis is more severe and progressive, whereas localized scleroderma is usually milder and less likely to involve internal organs. Systemic sclerosis, also known as systemic scleroderma, is a chronic autoimmune disease that affects the connective tissues in the body. While the primary symptoms of systemic sclerosis involve skin thickening and hardening, the condition can also lead to various complications that affect different organs and systems. Unlike systemic sclerosis, which can affect multiple organs, localized scleroderma is limited to specific areas of the body.
[65] Clinical Treatment Options in Scleroderma: Recommendations and ... — There are two major clinical subsets of scleroderma: (i) systemic sclerosis (SSc) is a complex systemic autoimmune disorder characterized by inflammation, vasculopathy, and excessive fibrosis of the skin and multiple internal organs and (ii) localized scleroderma (LoS), also known as morphea, is confined to the skin and/or subcutaneous tissues resulting in collagen deposition and subsequent
[67] The Scleroderma Research Foundation Launches CONQUEST — SAN FRANCISCO, December 19, 2023 — The Scleroderma Research Foundation (SRF), the nation's largest non-profit funder of scleroderma research, today announced that the FDA has cleared its Investigational New Drug application (IND) to launch the CONQUEST clinical trial platform and begin enrolling patients. ... and as such they are the first
[68] Systemic sclerosis - Latest research and news - Nature — Latest Research and Reviews. ... The updated 2023 EULAR recommendations for treatment of systemic sclerosis bring notable changes to recommendations for skin, peripheral vascular disease
[69] Improving outcomes in scleroderma: recent progress of cell-based ... — Indeed, the European Scleroderma Trials and Research (EUSTAR) observational study of 1021 SSc patients found that progressive skin fibrosis within 1 year, indicated by higher mRSS scores, was associated with worsening lung function and decreased survival during follow-up , and thus monitoring skin fibrosis may help clinicians to identify
[70] Improving outcomes in scleroderma: recent progress of cell-based ... — Improving outcomes in scleroderma: recent progress of cell-based therapies - PubMed Silverchair Information Systems Free PMC article Search in PubMed Search in PubMed Scleroderma is a rare, potentially fatal, clinically heterogeneous, systemic autoimmune connective tissue disorder that is characterized by progressive fibrosis of the skin and visceral organs, vasculopathy and immune dysregulation. [Contribution of mesenchymal stromal cell transplantation in systemic scleroderma]. Myeloablative autologous haematopoietic stem cell transplantation resets the B cell repertoire to a more naïve state in patients with systemic sclerosis. Zhao M, et al. Systemic sclerosis – multidisciplinary disease: clinical features and treatment. Search in PubMed Search in PubMed Search in PubMed Search in PubMed Search in PubMed Search in PubMed Search in PubMed Search in PubMed Search in PubMed Search in PubMed Silverchair Information Systems Free PMC article
[90] From the Expert: New Advances in Treatment of Systemic Scleroderma — A recent study found that mycophenolate mofetil is an effective alternative for the treatment of systemic scleroderma with interstitial lung disease, resulting in possible long-term improvement. According to Aryeh Fischer, MD, this new research points to the future expansion of treatment options
[91] What's new on the horizon for scleroderma? - NIH MedlinePlus Magazine — Researchers working with the National Institute of Arthritis and Musculoskeletal and Skin Diseases are exploring new ways of helping patients with scleroderma, including stem cell transplants and anti-fibrosis drugs.
[92] The Scleroderma Research Foundation Launches CONQUEST — SAN FRANCISCO, December 19, 2023 — The Scleroderma Research Foundation (SRF), the nation’s largest non-profit funder of scleroderma research, today announced that the FDA has cleared its Investigational New Drug application (IND) to launch the CONQUEST clinical trial platform and begin enrolling patients. Sanofi and Boehringer Ingelheim will each contribute an experimental agent to CONQUEST, and as such they are the first pharma partners to commit to this protocol designed to efficiently advance new scleroderma treatments through clinical development. Luke Evnin, Ph.D., Chairman of the Scleroderma Research Foundation, commented, “Both Sanofi and Boehringer Ingelheim have a rich history of innovation in the immunologic and fibrotic disease arena, and they are bringing their considerable expertise to CONQUEST.
[96] The Scleroderma Research Foundation Launches CONQUEST — SAN FRANCISCO, December 19, 2023 — The Scleroderma Research Foundation (SRF), the nation’s largest non-profit funder of scleroderma research, today announced that the FDA has cleared its Investigational New Drug application (IND) to launch the CONQUEST clinical trial platform and begin enrolling patients. Sanofi and Boehringer Ingelheim will each contribute an experimental agent to CONQUEST, and as such they are the first pharma partners to commit to this protocol designed to efficiently advance new scleroderma treatments through clinical development. Luke Evnin, Ph.D., Chairman of the Scleroderma Research Foundation, commented, “Both Sanofi and Boehringer Ingelheim have a rich history of innovation in the immunologic and fibrotic disease arena, and they are bringing their considerable expertise to CONQUEST.
[97] Sanofi is first to join CONQUEST platform trial for scleroderma — Toby Maher, MD, a co-principal investigator at CONQUEST, says the platform trial will bring together pharmaceutical companies, academia, and other experts in rheumatology and pulmonology. ... 'Cool Comedy' raises over $1.2M for Scleroderma Research Foundation. August 11, 2022 News by Mary Chapman 'Cool Comedy, Hot Cuisine' 2022
[99] CONQUEST Platform Clinical Trial | Scleroderma Research Foundation — CONQUEST Platform Clinical Trial | Scleroderma Research Foundation CONQUEST CONQUEST About CONQUEST CONQUEST is a global, perpetual, platform clinical trial developed by the Scleroderma Research Foundation (SRF) in coordination with partner biopharmaceutical companies to accelerate the clinical development of agents for scleroderma. In the initial stages, the primary objective of CONQUEST is to accelerate the evaluation of the treatments for SSc-ILD (interstitial lung disease secondary to scleroderma). Consider enrolling in the CONQUEST study, a scleroderma clinical trial for people with systemic sclerosis-associated interstitial lung disease (SSc-ILD). About CONQUEST Learn more about how CONQUEST impacts scleroderma patients. CONQUEST CONQUEST CONQUEST About CONQUEST The Scleroderma Research Foundation provides access to these sites as a service to srfcure.org visitors and is not responsible or liable for the content and information presented within any non- Scleroderma Research Foundation external site.
[129] Scleroderma--pathophysiology - PubMed — Scleroderma is a fibrotic condition characterized by immunological abnormalities, vascular injury and increased accumulation of extracellular matrix proteins in the skin. Although the etiology of scleroderma has not yet been fully elucidated, a growing body of evidence suggests that extracellular ma …
[130] Scleroderma: Practice Essentials, Background, Pathophysiology — The term systemic sclerosis is used to describe a systemic autoimmune disease of unknown origin characterized by excessive deposition of collagen and other connective tissue macromolecules in skin and multiple internal organs, prominent and often severe fibroproliferative alterations in the microvasculature, and numerous humoral and cellular immunologic abnormalities. Systemic sclerosis is a complex and heterogeneous disease with clinical forms ranging from limited skin involvement (limited cutaneous systemic sclerosis) to forms with diffuse skin sclerosis and severe and often progressive internal organ involvement (diffuse cutaneous systemic sclerosis), and occasionally a fulminant course (fulminant systemic sclerosis). In contrast, pulmonary involvement (interstitial lung disease and/or pulmonary arterial hypertension) has become the most common cause of death in patients with systemic sclerosis.
[132] The Immune Pathogenesis of Scleroderma: Context Is Everything — Despite the co-occurrence of these seemingly disparate forms of pathology in SSc, accumulating evidence, such as the discovery of strong HLA associations with disease risk and direct observation of histologic and molecular immunopathology, increasingly suggest that immune dysregulation is a proximal cause of SSc. From this perspective, immune dysregulation is poised to emerge as a unifying explanation for the fibrotic, vasculopathic and inflammatory manifestations of SSc. Here, we review recent progress in the understanding of the immunopathogenesis of SSc, focusing on pathways that link inflammation with pro-fibrotic signaling and potentially the vasculopathy observed in SSc. We consider Interleukin-13 (IL13), and its upstream inducer IL33, in detail as examples of immune system-derived mediators that connects to fibrotic and vascular pathology.
[133] Role of IL-13 in systemic sclerosis - ScienceDirect — Abstract Systemic sclerosis (SSc) has the highest fatality rate among connective tissue diseases and is characterized by vascular damage, inflammation and fibrosis. Currently, no therapy has proven effective in modifying the course of SSc, a reflection of its complex pathogenesis. T cell-derived cytokines have been implicated in the induction of fibrosis. The role of the pro-fibrotic type 2
[135] Role of IL-13 in systemic sclerosis - ScienceDirect — Recent work has shown that dysregulated production of IL-13 by effector CD8+ T cells is critical for predisposing patients to more severe forms of cutaneous disease and that this dysregulation is associated with defects in the molecular control of IL-13 production, such as increased expression of the transcription factor GATA-3. Systemic sclerosis (SSc, scleroderma) is an autoimmune disease of connective tissue characterized by vascular damage, inflammation and progressive fibrosis of the skin and other internal organs . The IL1-like cytokine IL33 and its receptor ST2 are abnormally expressed in the affected skin and visceral organs of patients with systemic sclerosis Production of type 2 cytokines by CD8+ lung cells is associated with greater decline in pulmonary function in patients with systemic sclerosis
[136] Interleukin-4 and interleukin-13 as possible therapeutic targets in ... — Numerous evidences support the role of a Th2-oriented immune response during both the inflammatory and the fibrotic phase of SSc. Levels of IL-4, IL-13 and CXCL4 are higher in the serum of SSc patients compared to healthy controls. ... Interleukin-13 / blood* ... Scleroderma, Systemic / immunology
[141] Systemic Sclerosis (Scleroderma) - StatPearls - NCBI Bookshelf — Localized scleroderma primarily affects the skin and subcutaneous tissue, whereas systemic sclerosis is associated with systemic manifestations and internal organ involvement, leading to increased mortality. Interstitial lung disease manifests as bibasilar pulmonary fibrosis and is notably more prevalent and severe in diffuse cutaneous systemic sclerosis, African Americans, males, and individuals with anti–topoisomerase I antibodies. They are particularly associated with diffuse cutaneous systemic sclerosis and are linked to rapidly progressing and aggressive diffuse skin involvement, poor cutaneous outcomes, and scleroderma renal crisis. Diffuse cutaneous systemic sclerosis: Diffuse skin disease, large joint inflammatory arthritis, tendon friction rubs, joint contractures, distal bone osteolysis, scleroderma renal crisis, interstitial lung disease, and pericardial effusion.
[169] Challenges and strategies for coping with scleroderma: implications for ... — Challenges and strategies for coping with scleroderma: implications for a scleroderma-specific self-management program - PubMed Conclusion: When faced with significant challenges while coping with scleroderma, patients develop strategies to manage better and improve their quality of life. To help them cope, patients would benefit from easier access to supportive interventions, including tailored scleroderma self-management programs. Implications for Rehabilitation People living with rare diseases, including the rare autoimmune disease scleroderma, face unique challenges and often do not have access to disease-specific educational or other support resources. People with scleroderma report that they face challenges in accessing information, including knowledgeable healthcare providers; managing difficult social interactions and negative emotions; and accessing resources. Keywords: Scleroderma; coping; health care professional perspectives; patient perspectives; self-management programs; systemic sclerosis.
[173] Challenges and strategies for coping with scleroderma: implications for ... — Challenges and strategies for coping with scleroderma: implications for a scleroderma-specific self-management program - PubMed Conclusion: When faced with significant challenges while coping with scleroderma, patients develop strategies to manage better and improve their quality of life. To help them cope, patients would benefit from easier access to supportive interventions, including tailored scleroderma self-management programs. Implications for Rehabilitation People living with rare diseases, including the rare autoimmune disease scleroderma, face unique challenges and often do not have access to disease-specific educational or other support resources. People with scleroderma report that they face challenges in accessing information, including knowledgeable healthcare providers; managing difficult social interactions and negative emotions; and accessing resources. Keywords: Scleroderma; coping; health care professional perspectives; patient perspectives; self-management programs; systemic sclerosis.
[174] Understanding coping strategies among people living with scleroderma: a ... — Scleroderma patients use similar coping strategies as patients with more common diseases, but they may not have access to the same level of support services. Accessible interventions, including self-management programs, aimed at improving problem- and emotion-focused coping are needed. Further, incr …
[175] Scleroderma patient perspectives on social support from close social ... — Purpose: People with rare diseases must cope with many physical and psychological challenges; an endeavor that can be difficult to carry out without external support. The purpose of this study was to understand how patients with scleroderma perceive the social support they need and receive from close relationships to better manage their disease.
[176] PDF — Psychological Impact of Scleroderma . Chapter 6 - 2 Chapter Highlights 1. Depression: Managing Intense Negative Feelings ... to depression in patients with Scleroderma. These include: 1. Fear, anxiety or uncertainty about the future. ... Social support is an important part of managing depression. Volunteer
[182] Understanding coping strategies among people living with scleroderma: a ... — Understanding coping strategies among people living with scleroderma: a focus group study - PubMed Understanding coping strategies among people living with scleroderma: a focus group study 10 j Department of Psychology , McGill University , Montréal , Canada. Understanding coping strategies among people living with scleroderma: a focus group study Results: Participants reported using a combination of problem-focused (e.g., professional help; seeking disease-related information), emotion-focused (e.g., social support; adaptive distraction techniques), and meaning-focused coping strategies (e.g., benefit finding; goal reappraisal) to help them to cope with and manage their disease. Conclusions: Scleroderma patients use similar coping strategies as patients with more common diseases, but they may not have access to the same level of support services.
[183] PDF — (Benrud-Larson, 2002) Therefore, due to scleroderma being a highly distressing disorder that ultimately affects the daily function and quality of life of these patients, it is important for them to have coping strategies that enhance their physical and mental well-being. (Pilch, 2016) Scleroderma Mental Health Social Life Physical Health Personal Life Health-Care Related Support/Resources Health care-related barriers exist with scleroderma, and this most likely makes coping with the disease more difficult than other chronic diseases. Scleroderma may not have the same level of support as other chronic diseases do, so including knowledge, coping resources, and problem-solving skills should be incorporated into each patient’s daily routine. (2013) Health-related quality of life, optimism, and coping strategies in persons suffering from localized scleroderma, Psychology, Health & Medicine, 18:6, 654-663, DOI: 10.1080/13548506.2013.764461 10.
[184] PDF — It’s during this time that patients typically do the following: • Find and join support groups • Seek out a physician who knows how to treat scleroderma • Search libraries and the Internet for information they feel might be helpful Depression can slow people down. Patients who cope well with their disease have these things in common: • They have discovered the hope and strengths they have inside • Have found people to help them along their way (friends, relatives, loved ones, healthcare providers, scleroderma support groups, counselors, or faith groups) • Have learned to help others by getting involved in scleroderma organizations, educating their friends and the public and helping other patients through difficult times The most important underlying factor seems to be that patients who successfully cope with scleroderma have discovered that their lives are worth the fight.
[185] TOOLKITS | Spin — The SPIN Self-Management (SPIN-SELF) toolkit provides essential knowledge and coping skills to help better manage day-to-day problems in scleroderma. Each of the 9 modules provides information about a different area (pain, fatigue, sleep, etc.) and teaches self-management techniques that you can implement at home.
[186] OP0305 Psychological Profile of Scleroderma Patients Described by ... — Background Scleroderma is a systemic multiorgan autoimmune disease with high mortality and morbidity rates. In serious disease with organ manifestation, quality of life and perception of health is deeply influenced in these patients. The face changes and fibrosis of skin, digital ulceration contribute to the psychological trauma of these patients. Only little is known about the objective
[211] Current and future direction in the management of scleroderma - Springer — Scleroderma is a heterogeneous disease with a complex etiology. As more information is gained about the underlying mechanisms and the improved classifications of scleroderma subtypes, treatments can be better personalized. Improving scleroderma patients' early diagnosis before end organ manifestations occur should improve clinical trial design and outcomes. Two recently FDA-approved
[212] Emerging treatments for scleroderma/systemic sclerosis - PMC — Second-line therapies, including UVA-1 phototherapy, IVIG, or rituximab, can be considered in patients with disease refractory to first-line treatments. Providers should assess extracutaneous involvement and use evidence-based recommendations to select the most appropriate therapy for patients with SSc. Keywords: Systemic Sclerosis, Scleroderma In one randomized controlled trial, 29 SSc patients with early progressive skin disease received either 15 mg methotrexate weekly (n = 17) or placebo (n = 12). MMF is a preferred option for treatment of SSc-related skin disease, particularly for patients with ILD or those with progressive skin disease who are unable to tolerate methotrexate. Although methotrexate remains the most commonly used therapy in treatment of scleroderma-related cutaneous disease, studies investigating the utility and efficacy of other therapeutics, including MMF, IVIG, and UVA-1 phototherapy, are promising.
[213] New promising drugs for the treatment of systemic sclerosis: Pathogenic ... — The drug was well-tolerated and additional studies are needed to better define the place of BAFF inhibition in the treatment of SSc. Clinical evidence for the relevance of BTK inhibitors in SSc are still needed, but ibrutinib showed promising results in a phase Ib/II trial in chronic GVHD (131), strengthening the relevance of evaluating this therapeutic option in SSc. A 52-week, single-center, randomized, double-blind, placebo-controlled phase II trial evaluating the combined effect of rituximab and belimumab as add-on therapy with MMF in patients with early dcSSc is currently ongoing (NCT03844061). Considering the recent demonstration that both M1 (pro-inflammatory) and M2 (pro-fibrotic) macrophages were over-activated in the skin of patients with diffuse SSc, JAK inhibition with pan-JAK inhibitors such as Tofacitinib (NCT03274076) or Ruxolitnib may be especially promising with potential impact on IL-6 (STAT-1/3 dependent) pro-inflammatory & profibrotic signaling, and IL-4/IL-13 (STAT6 dependent) pro-fibrotic & immunomodulatory signaling.
[214] What's new on the horizon for scleroderma? - NIH MedlinePlus Magazine — (right) work with NIH on scleroderma research. Both researchers work with NIH's National Institute of Arthritis and Musculoskeletal and Skin Diseases. There are major lung studies looking at drugs that can halt the development of thick scarring tissue, called fibrosis, that can occur in systemic scleroderma, as well as other lung diseases like asthma and chronic obstructive pulmonary disease, Dr. Feghali-Bostwick says. There is a lot of interest in a recent NIH-funded study that found that stem cell transplants for people with severe scleroderma could have long-term, beneficial results, says Dr. Varga. National Institute of Arthritis and Musculoskeletal and Skin Diseases: Scleroderma
[216] Current perspectives on the immunopathogenesis of systemic sclerosis — SSc exhibits an extensive patient-to-patient variability. Heterogeneity has been observed in its clinical manifestations, clinical course, response to treatment, ... Liakouli V, et al. Mesenchymal stem cells (MSCs) from scleroderma patients (SSc) preserve their immunomodulatory properties although senescent and normally induce T regulatory
[219] Clinical Trial Design Issues in Systemic Sclerosis: an Update — In the USA, there remains no FDA-approved therapy. As our understanding of SSc pathogenesis improves, targeted therapies interrupting key pathways and mediators will be studied in clinical trials. However, clinical trials in SSc are fraught with challenges. Validated clinical outcome measures do not exist for all disease manifestations.
[220] Genetics of scleroderma: implications for personalized medicine? — Significant advances have been made in understanding the genetic basis of systemic sclerosis (scleroderma) in recent years. Can these discoveries lead to individualized monitoring and treatment? Besides robustly replicated genetic susceptibility loci, several genes have been recently linked to various systemic sclerosis disease manifestations.
[221] Investigational drugs for the treatment of scleroderma: what's new ... — Ongoing significant research for new molecular and epigenetics pathways is of fundamental importance to offer new perspectives on disease phenotype and for the development of personalized treatment strategies.
[222] Researchers find gene mutations in scleroderma patients that could ... — Researchers have uncovered cancer-like genetic mutations in the affected cells of people with scleroderma, pointing the way to potential new ways to treat the debilitating and sometimes fatal skin and connective tissue disease.
[223] A Transformative Time in Research on Systemic Sclerosis Therapeutics — Recent years have witnessed a remarkable transformation in the field of systemic sclerosis (SSc) therapeutics, marked by the emergence of novel targeted therapies, precision medicine approaches, and a growing emphasis on personalized patient care. SSc, also known as scleroderma, is a complex autoimmune disorder characterized by progressive fibrosis of the skin and multiple organs, accompanied
[241] PDF — of Health Working Group on Biomarkers, is a measure that can be applied for purposes as varied as disease diagnosis, staging, prognostication, measuring or predicting treatment response, and even defining surrogate outcomes . Biomarkers have been examined in all of these contexts in scleroderma, though diagnosis and outcomes in scleroderma
[242] Biomarkers as an opportunity to stratify for outcome in systemic ... — Biomarkers are of crucial importance to stratify for outcome in SSc when assessing likely disease outcomes with treatment. Although prognostic biomarkers serve as indicators of differential disease outcomes (clinical event, disease recurrence, or progression) and can be useful to stratify the risk for negative clinical outcomes, and identify
[243] The current state of biomarkers in systemic sclerosis - PubMed — Scleroderma is a complex, multisystem autoimmune rheumatic disease with wide heterogeneity in phenotype and outcome. ... For these reasons, it is highly valuable to find easily measurable biomarkers that may represent ongoing disease activity or treatment response. This review examines the current state of biomarker development in systemic
[244] Biomarkers in Scleroderma: Progressing from Association to Clinical ... — Scleroderma is a heterogenous disease characterized by autoimmunity, a characteristic vasculopathy, and often widely varying extents of deep organ fibrosis. Recent advances in the understanding of scleroderma's evolution have improved the ability to identify subgroups of patients with similar prognosis in order to improve risk stratification, enrich clinical trials for patients likely to
[245] Biomarkers in systemic sclerosis - PMC - PubMed Central (PMC) — [29∎] SASP gene expression signature in skin SSc-ILD patients in single-arm trial of dasatinib Predictive High baseline SASP signature associated with greater Arthritis Rheumatol 2018; 70:912–919.∎ Using skin gene expression data from the placebo arm of the phase II trial of Tocilizumab for diffuse SSc, the investigators identified genes whose expression at baseline predicted subsequent mRSS progression. [Epub ahead of print] In a single-arm clinical trial of dasatinib for patients with SSc-interstitial lung disease (ILD), higher baseline skin expression of a senescence-associated secretory phenotype gene expression signature predicted mRSS improvement during dasatinib treatment.