Systemic sclerosis: current views of its pathogenesis (original) (raw)
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Systemic Sclerosis: From Pathophysiology to Novel Therapeutic Approaches
Biomedicines, 2022
Systemic sclerosis (SSc) is a systemic, immune-mediated chronic disorder characterized by small vessel alterations and progressive fibrosis of the skin and internal organs. The combination of a predisposing genetic background and triggering factors that causes a persistent activation of immune system at microvascular and tissue level is thought to be the pathogenetic driver of SSc. Endothelial alterations with subsequent myofibroblast activation, excessive extracellular matrix (ECM) deposition, and unrestrained tissue fibrosis are the pathogenetic steps responsible for the clinical manifestations of this disease, which can be highly heterogeneous according to the different entity of each pathogenic step in individual subjects. Although substantial progress has been made in the management of SSc in recent years, disease-modifying therapies are still lacking. Several molecular pathways involved in SSc pathogenesis are currently under evaluation as possible therapeutic targets in clini...
Systemic sclerosis – the dermatological perspective
JDDG: Journal der Deutschen Dermatologischen Gesellschaft, 2019
Systemic scleroderma/systemic sclerosis (SSc) is an inflammatory connective tissue disease clinically characterized by two major subtypes: limited and diffuse SSc. While both conditions present with Raynaud's phenomenon (paroxysmal digital ischemia), diffuse SSc is associated with rapid disease progression and early-prognostically relevant-involvement of internal organs. Treatment is challenging. In addition to general lifestyle modifications, measures include treatments aimed at improving circulation as well as immunosuppressive and immunomodulatory drugs. However, these agents are effective only in terms of slowing disease progression.
Systemic Sclerosis: A Case Report and Review of Current Advances in Treatment
Journal of pharmaceutical research international, 2022
Systemic sclerosis (SSc) is a chronic multisystem disease characterized by excess deposition of connective tissue in skin and internal organs, associated with microvasculature changes and immunologic abnormalities. We hereby report a case of scleroderma in a 52 year old female with classical clinical and histopathological findings. The latter part of this article discusses and reviews existing and novel emerging therapies for the treatment of SSc, with an emphasis on recent trials targeting the cutaneous and pulmonary manifestations of this disease.
Systemic sclerosis: assessment and treatment : tight control in a tight disease
Bulletin of The Polish Academy of Sciences Mathematics, 2008
Systemic sclerosis(SSc) is a systemic auto immune disease, resulting in a decreased life expectancy in all, but especially in patients with diffuse cutaneous SSc. The major causes of death are pulmonary fibrosis and pulmonary hypertension. In this thesis the epidemiology of SSc and its pulmonary complications are described. Also, it offers a protocol for the diagnostic and therapeutic approach for
Current perspectives on the immunopathogenesis of systemic sclerosis
ImmunoTargets and Therapy, 2016
Systemic sclerosis (SSc or scleroderma) is a progressive and highly debilitating autoimmune disorder characterized by inflammation, vasculopathy, and extensive fibrosis. SSc is highly heterogeneous in its clinical presentation, extent and severity of skin and internal organ involvement, and clinical course and has the highest fatality rate among connective tissue diseases. While clinical outcomes have improved in recent years, no current therapy is able to reverse or slow the natural progression of SSc, a reflection of its complex pathogenesis. Although activation of the immune system has long been recognized, the mechanisms responsible for the initiation of autoimmunity and the role of immune effector pathways in the pathogenesis of SSc remain incompletely understood. This review summarizes recent progress in disease pathogenesis with particular focus on the immunopathogenetic mechanisms of SSc.
Clinical reviews in allergy & immunology, 2017
Systemic sclerosis (SSc) is a highly heterogeneous disease caused by a complex molecular circuitry. For decades, clinical and molecular research focused on understanding the primary process of fibrosis. More recently, the inflammatory, immunological and vascular components that precede the actual onset of fibrosis, have become a matter of increasing scientific scrutiny. As a consequence, the field has started to realize that the early identification of this syndrome is crucial for optimal clinical care as well as for understanding its pathology. The cause of SSc cannot be appointed to a single molecular pathway but to a multitude of molecular aberrances in a spatial and temporal matter and on the backbone of the patient's genetic predisposition. These alterations underlie the plethora of signs and symptoms which patients experience and clinicians look for, ultimately culminating in fibrotic features. To solve this complexity, a close interaction among the patient throughout its ...
Rheumatology Forum, 2023
Systemic sclerosis (SSc, scleroderma) is a chronic systemic connective tissue disease with a complex pathogenesis that is still not fully understood, in the course of which attention is increasingly drawn to the dynamic, sequential pathogenetic mechanisms according to disease stage. An increasing understanding of the diversity of mechanisms underlying this disease, as well as the prevalence of certain pathogenetic elements that depend i.a. on disease stage, will enable more effective therapeutic interventions in the future. Systemic sclerosis can thus be seen as a complex process, where the main players are immune cells, endothelial cells and fibroblasts, and the focal point is probably impaired function and subsequent damage to endothelial cells. Systemic sclerosis is also the final stage of a certain continuum of events, starting with a state of susceptibility to the development of the disease (dependent on genetic conditions and environmental influences), followed by disruption of homeostasis and initiation of pathological processes (e.g. as a result of viral infections), progression of pathological responses (inflammation, endothelial damage, fibrosis) and consequently organ damage. According to most authors, the key event and focal point of the cascade of phenomena is endothelial cell damage, and the mechanisms that lead to this damage are related to the activation of the immune system. There is growing acceptance of the thesis of an autoimmune origin of the disease involving mechanisms of innate and acquired immunity, both cellular and humoral.
Paraclinical Aspects in Systemic Sclerosis
International Journal of General Medicine
Systemic sclerosis (SSc) is a chronic inflammatory disease with an autoimmune substrate that affects the skin and a large number of internal organs. The chronic inflammatory process is sustained by a wide range of cytokines and chemokines, which are discharged by inflammatory cells, with fibrosis and nail bed vascular changes (disorganized vasculature architecture with microhemorrhages, megacapillaries and areas without capillaries). Confocal microscopy contributes to the understanding of the molecular mechanism involved in chronic inflammation and mainly targets the field of research. Coherent optical tomography, capillaroscopy, and skin biopsy are useful for the differential diagnosis of SSc with other sclerodermoid syndromes. The immunological profile is a classification criterion for SSc and directs the diagnosis to the two subsets of the disease. Multisystemic damage requires evaluation with the help of a set of investigations specific to each affected organ, such as: diffusing capacity for carbon monoxide, forced vital capacity, 6-minute walk test, high-resolution computed tomography standard and reduced sequential, cardiac ultrasound and right cardiac catheterization. The current possibilities of diagnosis, treatment and monitoring are permanently adapting to new medical discoveries.
Clinical Reviews in Allergy & Immunology, 2022
Systemic sclerosis (SSc) is a rare systemic autoimmune disease, characterized by the presence of three main actors: vasculopathy, immune activation, and fibrosis. This pathologic process is then translated in a clinical picture with great variability among different patients in terms of type of organ involvement, disease severity and prognosis. This heterogeneity is a main feature of SSc, which, in addition to the presence of early phases of the disease characterized by mild symptoms, can explain the high difficulty in establishing classification criteria, and in defining patients’ subsets and disease outcomes. The definition of disease outcomes is particularly relevant in the setting of clinical trials, where the aim is to provide reliable endpoints, able to measure the magnitude of the efficacy of a certain drug or intervention. For this reason, in the last years, increasing efforts have been done to design measures of disease activity, damage, severity, and response to treatment,...