Systemic Scleroderma (Systemic Sclerosis)

A chronic multi-system disorder of CONNECTIVE TISSUE. It is characterized by SCLEROSIS in the SKIN, the LUNGS, the HEART, the GASTROINTESTINAL TRACT, the KIDNEYS, and the MUSCULOSKELETAL SYSTEM. Other important features include diseased small BLOOD VESSELS and AUTOANTIBODIES. The disorder is named for its most prominent feature (hard skin), and classified into subsets by the extent of skin thickening: LIMITED SCLERODERMA and DIFFUSE SCLERODERMA.

Also Known As:

Networked: 7227 relevant articles (350 outcomes, 936 trials/studies)

Relationship Network

Disease Context: Research Results

Related Diseases

1.	Interstitial Lung Diseases (Interstitial Lung Disease)
2.	Fibrosis (Cirrhosis)
3.	digital ulcers
4.	Systemic Lupus Erythematosus (Libman-Sacks Disease)
5.	Rheumatoid Arthritis

Experts

1.	Sato, Shinichi: 143 articles (11/2022 - 06/2002)
2.	Distler, Oliver: 115 articles (12/2022 - 01/2002)
3.	Denton, Christopher P: 108 articles (11/2022 - 07/2003)
4.	Matucci-Cerinic, Marco: 97 articles (10/2022 - 01/2002)
5.	Asano, Yoshihide: 96 articles (01/2022 - 02/2003)
6.	Allanore, Yannick: 91 articles (11/2022 - 01/2003)
7.	Khanna, Dinesh: 84 articles (05/2022 - 02/2005)
8.	Distler, Jörg H W: 77 articles (01/2022 - 02/2004)
9.	Varga, John: 75 articles (06/2022 - 04/2003)
10.	Mayes, Maureen D: 74 articles (10/2022 - 09/2003)

Drugs and Biologics

Drugs and Important Biological Agents (IBA) related to Systemic Scleroderma:

1.	Cyclophosphamide (Cytoxan)FDA LinkGeneric 06/01/2021 - "This review has a focus on the evidence of efficacy of cyclophosphamide in different aspects of systemic sclerosis and its organ involvements, reviews its toxicity, and will answer the question whether there is still a role for cyclophosphamide in the treatment of systemic sclerosis, taking the evidence and current therapeutic options into account." 12/31/2007 - "Clinically modest short-term efficacy of cyclophosphamide treatment has been shown in systemic sclerosis, but was not maintained at 2 years." 01/01/2002 - "To evaluate, in a pilot study, the efficacy of a short term cyclophosphamide (CYC) pulse regimen on alveolitis in a cohort of patients with systemic sclerosis (SSc). " 05/01/2020 - "Both intravenous (IV) and oral (PO) cyclophosphamide (CYC) showed beneficial effects on skin and lung involvement in systemic sclerosis (SSc) in placebo-controlled randomised clinical trials and observational studies. " 01/01/2006 - "Low-dose intravenous cyclophosphamide in systemic sclerosis: an open prospective efficacy study in patients with early diffuse disease."
2.	Bosentan (Tracleer)FDA Link 10/01/2011 - "Bosentan is effective against digital ulcerations and hyperkeratosis in systemic sclerosis." 07/01/2015 - "Bosentan blocks the antiangiogenic effects of sera from systemic sclerosis patients: an in vitro study." 12/01/2006 - "Bosentan increases myocardial perfusion and function in systemic sclerosis: a magnetic resonance imaging and Tissue-Doppler echography study." 06/01/2023 - "Real-world effectiveness and safety of bosentan in Japanese patients with systemic sclerosis: A single-center retrospective study." 12/01/2021 - "Novel Use of Bosentan for Postoperative Wound Healing of the Foot in Systemic Sclerosis."
3.	Rituximab (Mabthera)FDA Link 01/01/2021 - "Is rituximab effective for systemic sclerosis? " 06/01/2020 - "Safety and efficacy of Rituximab in systemic sclerosis: A systematic review and meta-analysis." 01/01/2019 - "To assess the safety and efficacy of rituximab in systemic sclerosis (SSc) in clinical practice. " 06/01/2018 - "To describe safety and efficacy of rituximab in patients with systemic sclerosis. " 03/01/2012 - "To assess the safety and efficacy of long-term treatment with rituximab (RTX) in patients with systemic sclerosis (SSc). "
4.	nintedanibIBA 01/01/2022 - "The achievement of the Safety and Efficacy of Nintedanib in Systemic SClerosIS (SENSCIS) trial has led to the approval by drug agencies of the first antifibrotic drug for SSc-ILD. " 11/01/2017 - "Nintedanib inhibits macrophage activation and ameliorates vascular and fibrotic manifestations in the Fra2 mouse model of systemic sclerosis." 09/01/2023 - "We conducted a meta-analysis of randomized controlled trials (RCTs) examining nintedanib efficacy and safety in patients with ILD with or without systemic sclerosis (SSc). " 01/01/2021 - "In the randomized, double-blind, placebo-controlled SENSCIS trial, the efficacy and safety of nintedanib was investigated in patients with ILD associated with systemic sclerosis (SSc-ILD). " 06/01/2020 - "The adoption of nintedanib in systemic sclerosis: the SENSCIS study."
5.	tocilizumab (atlizumab)FDA Link 01/01/2018 - "We analyzed clinical data and gene expression in skin biopsy samples from 38 placebo-treated patients, part of the Roche Safety and Efficacy of Subcutaneous Tocilizumab in Adults with Systemic Sclerosis (FASSCINATE) phase II study of tocilizumab in SSc. " 01/01/2018 - "Data from the phase 2 Safety and Efficacy of Subcutaneous Tocilizumab in Adults with Systemic Sclerosis (faSScinate) trial were used, which compared tocilizumab (TCZ) vs placebo over 48 weeks followed by an open-label TCZ period to 96 weeks. " 01/01/2018 - "Safety and efficacy of subcutaneous tocilizumab in systemic sclerosis: results from the open-label period of a phase II randomised controlled trial (faSScinate)." 06/25/2016 - "Safety and efficacy of subcutaneous tocilizumab in adults with systemic sclerosis (faSScinate): a phase 2, randomised, controlled trial." 07/04/2023 - "The efficacy and safety of tocilizumab in patients with systemic sclerosis were consistent between the Japanese subpopulation and the global trial population."
6.	Endothelin Receptor AntagonistsIBA 12/11/2012 - "Endothelin receptor antagonists: effects on extracellular matrix synthesis in primary cultures of skin fibroblasts from systemic sclerosis patients." 02/01/2011 - "Endothelin receptor antagonists as disease modifiers in systemic sclerosis." 01/01/2005 - "Accordingly, new class of drugs, endothelin receptor antagonists have been introduced for treatment of patients with systemic sclerosis. " 01/01/2011 - "The purpose of this paper is to summarize the published studies and case reports evaluating the efficacy of endothelin receptor antagonists in the treatment of Raynaud's phenomenon and digital ulcers associated with systemic sclerosis." 06/01/2011 - "diabetes mellitus, systemic sclerosis) and the use of endothelin antagonists in these patient groups may yield improved outcomes."
7.	Iloprost (Ventavis)FDA Link 05/01/2006 - "Hepatic perfusion significantly improved after Iloprost administration, suggesting that such treatment might be useful in preventing vascular complications in patients with systemic sclerosis. " 09/01/1998 - "The results on the daily duration of Raynaud's attacks suggest that both 50 and 100 microg oral iloprost twice daily may be effective in the treatment of Raynaud's phenomenon secondary to systemic sclerosis. " 01/01/2001 - "[Tolerability, safety and efficacy of Iloprost infusion without peristaltic pump in systemic sclerosis]" 08/01/2019 - "Iloprost use and medical management of systemic sclerosis-related vasculopathy in Italian tertiary referral centers: results from the PROSIT study." 08/01/2018 - "Acute and chronic effects of two different intravenous iloprost regimens in systemic sclerosis: a pragmatic non-randomized trial."
8.	AntibodiesIBA 02/01/2021 - "Recent developments in systemic sclerosis-gastrointestinal research efforts have revealed promising treatment targets, including specific auto-antibodies and microbiota alterations. " 06/01/2022 - "This study aims to compare the utility of nailfold capillaroscopy for the early diagnosis of the scleroderma-spectrum of diseases in patients who present with Raynaud's phenomenon, undifferentiated non-Raynaud's phenomenon features and positive systemic sclerosis-associated antibodies without scleroderma-spectrum of disease features. " 01/01/2020 - "The aim of this study was to evaluate the role of single nucleotide polymorphisms (SNPs) of NOTCH3 and TP53 genes and serum anti-TP53 antibodies with the susceptibility, clinical subset of systemic sclerosis (SSc), and clinical profile of SSc patient, particularly with lung involvement and disease activity. " 08/01/2017 - "A recent study also found a positive association of aPL antibodies with ILD and PH in patients with systemic sclerosis. " 01/01/2017 - "To examine the clinical correlates and survival in patients with antifibrillarin antibodies (AFA) in a large international study population consisting of well-characterized systemic sclerosis (SSc) cohorts from Canada, Australia, and the United States. "
9.	Sildenafil Citrate (Viagra)FDA Link 12/01/2005 - "We describe a patient with limited cutaneous systemic sclerosis who presented with severe nonhealing finger ulcerations despite conventional management, who showed marked improvement with oral sildenafil." 07/01/2005 - "Improvement in digital flexibility and dexterity following ingestion of sildenafil citrate (viagra) in limited systemic sclerosis." 09/01/2017 - "Evaluation of the effect of sildenafil on the microvascular blood flow in patients with systemic sclerosis: a randomised, double-blind, placebo-controlled study." 12/01/2015 - "Sildenafil attenuates the fibrotic phenotype of skin fibroblasts in patients with systemic sclerosis." 01/01/2013 - "To retrospectively analyze the efficacy and safety of sildenafil (Sf) in patients with systemic sclerosis (SS). "
10.	Methotrexate (Mexate)FDA LinkGeneric 01/01/2000 - "Methotrexate (MTX) has been shown to be effective in the treatment of systemic sclerosis. " 08/01/1998 - "Low-dose methotrexate (MTX) has been shown to be effective in the treatment of systemic sclerosis. " 01/27/2017 - "Workup revealed limited cutaneous systemic sclerosis, and the patient improved with methotrexate. " 02/01/2009 - "The medical community often labels trials with p values > 0.05 as "negative." Our study demonstrates how Bayesian analysis conveys more relevant information to clinicians - using the example of methotrexate (MTX) in systemic sclerosis (SSc). " 01/01/2005 - "Placebo controlled trial of methotrexate in systemic sclerosis."

Therapies and Procedures

1.	Therapeutics 03/01/2011 - "Treatment for gastrointestinal tract (GIT) disease in systemic sclerosis (SSc) is challenging as no immunosuppressive or anti-fibrotic therapy is available with clearly proven efficacy. " 10/15/2008 - "Although no disease-modifying therapy has been proven effective, complications of systemic sclerosis are treatable, and interventions for organ-specific manifestations have improved substantially. " 06/01/2020 - "Continuing elucidation of their potential mechanistic roles raises hope of a better understanding of systemic sclerosis pathogenesis leading to improved therapies." 09/01/2016 - "In patients with systemic sclerosis (SSc), local disability of the hands and face, due to the involvement of skin, subcutaneous tissues and musculoskeletal system, is scarcely improved by pharmacological therapy, but may be treated efficaciously with rehabilitation, which can prevent and reduce local disability, thus ameliorating global disability and impaired Quality of Life, related to changes in the hands and face. " 12/01/1991 - "All this activity in the therapy of systemic sclerosis will certainly lead to improvement in the overall management of disease."
2.	Stem Cell Transplantation 11/01/2013 - "Retrospective analyses of independent cohorts of systemic sclerosis patients treated with autologous stem cell transplantation showed significant improvement of skin thickening, lung function and quality of life, but at the expense of 6-17% treatment-related mortality. " 08/01/2004 - "To analyse the durability of the responses after haematopoietic stem cell transplantation (HSCT) for severe systemic sclerosis (SSc) and determine whether the high transplant related mortality (TRM) improved with experience. " 06/01/2023 - "Autologous haematopoietic stem cell transplantation is now well-established as an effective treatment for severe systemic sclerosis with clear demonstration of favourable end-organ and survival outcomes. " 02/01/2012 - "Autologous stem cell transplantation (aSCT) for systemic sclerosis (SSc) has been shown to be effective in recent reports. " 01/01/2021 - "This study confirms the efficacy of autologous stem cell transplantation in real-life practice for severe systemic sclerosis using non myeloablative conditioning. "
3.	Hematopoietic Stem Cell Transplantation 01/01/2021 - "Association of Autologous Hematopoietic Stem Cell Transplantation in Systemic Sclerosis With Marked Improvement in Health-Related Quality of Life." 08/01/2003 - "Hematopoietic stem cell transplantation for systemic sclerosis with rapid improvement in skin scores: is neoangiogenesis occurring?" 01/01/2021 - "Autologous hematopoietic stem cell transplantation (aHSCT) represents an effective treatment for systemic sclerosis (SSc), but it also can cause immunological adverse events (iAEs). " 08/01/2019 - "Three prospective controlled clinical trials and numerous small series and case reports have confirmed that durable, drug-free remission in systemic sclerosis is possible via an autologous hematopoietic stem cell transplantation. " 01/01/2021 - "Cardiac safe hematopoietic stem cell transplantation for systemic sclerosis with poor cardiac function: a pilot safety study that decreases neutropenic interval to 5 days."
4.	Transplantation 01/01/2021 - "Safety and efficacy of faecal microbiota transplantation by Anaerobic Cultivated Human Intestinal Microbiome (ACHIM) in patients with systemic sclerosis: study protocol for the randomised controlled phase II ReSScue trial." 01/01/2021 - "This European Society for Blood and Marrow Transplantation multi-center prospective non-interventional study was designed to further decipher efficacy and safety of this procedure for severe systemic sclerosis patients in real-life practice and to search for prognostic factors. " 01/01/2016 - "Improvement of Mouth Functional Disability in Systemic Sclerosis Patients over One Year in a Trial of Fat Transplantation versus Adipose-Derived Stromal Cells." 01/01/2023 - "Effects of faecal microbiota transplantation on the small intestinal mucosa in systemic sclerosis." 04/01/2022 - "[Contribution of mesenchymal stromal cell transplantation in systemic scleroderma]."
5.	Phototherapy (Light Therapy) 03/12/2003 - "Ultraviolet A1 (340-400 nm, UVA1) phototherapy is highly effective in sclerotic lesions of systemic sclerosis (SSc). " 06/01/2009 - "This study would suggest that UVA1 phototherapy is effective for scleroderma affecting proximal and acral sites in patients with systemic sclerosis." 10/01/2000 - "These studies indicate that UVA1 phototherapy is effective for patients with systemic sclerosis." 10/01/2000 - "Our purpose was to determine whether UVA1 phototherapy is effective for systemic sclerosis. " 03/01/2023 - "This is the first study to show the association between the AhR pathway and the anti-fibrotic mechanism of UVA1 phototherapy, which provides additional evidence of the role of AhR in the fibrotic mechanism of systemic scleroderma from different perspectives. "