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The Kaohsiung Journal of Medical... Mar 2022Systemic sclerosis (scleroderma) is an autoimmune-triggered chronic fibrosing disease that affects the skin and many other organs. Its pathophysiology is complex and... (Review)
Review
Systemic sclerosis (scleroderma) is an autoimmune-triggered chronic fibrosing disease that affects the skin and many other organs. Its pathophysiology is complex and involves an early endothelial damage, an inflammatory infiltrate and a resulting fibrotic reaction. Based on a predisposing genetic background, an altered balance of the acquired and the innate immune system leads to the release of many cytokines and chemokines as well as autoantibodies, which induce the activation of fibroblasts with the formation of myofibroblasts and the deposition of a stiff and rigid connective tissue. A curative treatment is still not available but remarkable progress has been made in the management of organ complications. In addition, several breakthroughs in the pathophysiology have led to new therapeutic concepts. Based on these, many new compounds have been developed during the last years, which target these different pathways and offer specific therapeutic approaches.
Topics: Adaptive Immunity; Environment; Fibrosis; Genetic Predisposition to Disease; Humans; Immunity, Innate; Scleroderma, Systemic
PubMed: 35234358
DOI: 10.1002/kjm2.12505 -
Advances in Clinical and Experimental... Aug 2017Systemic sclerosis is a rare generalized disease with scleroderma, i.e. skin thickening as one of the most common symptoms. The disease has 2 main subsets, diffuse and... (Review)
Review
Systemic sclerosis is a rare generalized disease with scleroderma, i.e. skin thickening as one of the most common symptoms. The disease has 2 main subsets, diffuse and limited forms. The subset known as systemic sclerosis sine scleroderma (ssSSc) is a very rare subset characterized by the total or partial absence of cutaneous manifestations of systemic sclerosis with the occurrence of internal organ involvement and serologic abnormalities. The classification of ssSSc into 3 groups was proposed. Type I (complete) is characterized by the lack of any cutaneous changes typical for the disease at least until systemic sclerosis-related insufficiency of any internal organ occurs. Type II (incomplete) is characterized by the absence of sclerodactyly, but other cutaneous involvements (e.g. calcifications, telangiectasies, pitting scars) can be found. Type III (delayed) is characterized by clinical internal organ involvement typical for systemic sclerosis that has appeared before skin changes (complete or incomplete). In general, the demographic and clinical characteristics of the ssSSc patients suggest that they are similar to those with diffuse or limited form of the disease. Diagnosis of ssSSc still remains difficult and this disease form should be considered in all cases of unexplained fibrotic involvement of the internal organs.
Topics: Disease Progression; Fibrosis; Humans; Prevalence; Prognosis; Scleroderma, Systemic; Severity of Illness Index; Terminology as Topic
PubMed: 29068586
DOI: 10.17219/acem/64334 -
Lancet (London, England) Oct 2017Systemic sclerosis, also called scleroderma, is an immune-mediated rheumatic disease that is characterised by fibrosis of the skin and internal organs and vasculopathy.... (Review)
Review
Systemic sclerosis, also called scleroderma, is an immune-mediated rheumatic disease that is characterised by fibrosis of the skin and internal organs and vasculopathy. Although systemic sclerosis is uncommon, it has a high morbidity and mortality. Improved understanding of systemic sclerosis has allowed better management of the disease, including improved classification and more systematic assessment and follow-up. Additionally, treatments for specific complications have emerged and a growing evidence base supports the use of immune suppression for the treatment of skin and lung fibrosis. Some manifestations of the disease, such as scleroderma renal crisis, pulmonary arterial hypertension, digital ulceration, and gastro-oesophageal reflux, are now treatable. However, the burden of non-lethal complications associated with systemic sclerosis is substantial and is likely to become more of a challenge. Here, we review the clinical features of systemic sclerosis and describe the best practice approaches for its management. Furthermore, we identify future areas for development.
Topics: Evidence-Based Medicine; Humans; Immunosuppression Therapy; Scleroderma, Systemic; Survival Analysis
PubMed: 28413064
DOI: 10.1016/S0140-6736(17)30933-9 -
Journal of the American Academy of... Nov 2022Systemic sclerosis (SSc), also referred to as systemic scleroderma or scleroderma, is a rare, complex immune-mediated connective tissue disease characterized by... (Review)
Review
Systemic sclerosis (SSc), also referred to as systemic scleroderma or scleroderma, is a rare, complex immune-mediated connective tissue disease characterized by progressive skin fibrosis and other clinically heterogenous features. The etiopathogenesis of SSc involves vasculopathy and immune system dysregulation occurring on a permissive genetic and epigenetic background, ultimately leading to fibrosis. Recent developments in our understanding of disease-specific autoantibodies and bioinformatic analyses has led to a reconsideration of the purely clinical classification of diffuse and limited cutaneous SSc subgroups. Autoantibody profiles are predictive of skin and internal organ involvement and disease course. Early diagnosis of SSc, with commencement of disease-modifying treatment, has the potential to improve patient outcomes. In SSc, many of the clinical manifestations that present early signs of disease progression and activity are cutaneous, meaning dermatologists can and should play a key role in the diagnosis and management of this significant condition. The first article in this continuing medical education series discusses the epidemiology, clinical characteristics, and pathogenesis of SSc in adults, with an emphasis on skin manifestations, the important role of dermatologists in recognizing these, and their correlation with systemic features and disease course.
Topics: Adult; Autoantibodies; Connective Tissue Diseases; Disease Progression; Fibrosis; Humans; Scleroderma, Localized; Scleroderma, Systemic
PubMed: 35131402
DOI: 10.1016/j.jaad.2021.10.065 -
The Lancet. Respiratory Medicine Mar 2020Systemic sclerosis is an autoimmune connective tissue disease, which is characterised by immune dysregulation and progressive fibrosis that typically affects the skin,... (Review)
Review
Systemic sclerosis is an autoimmune connective tissue disease, which is characterised by immune dysregulation and progressive fibrosis that typically affects the skin, with variable internal organ involvement. It is a rare condition that affects mostly young and middle-aged women, resulting in disproportionate morbidity and mortality. Currently, interstitial lung disease is the most common cause of death among patients with systemic sclerosis, with a prevalence of up to 30% and a 10-year mortality of up to 40%. Interstitial lung disease is more common among African Americans and in people with the diffuse cutaneous form of systemic sclerosis or anti-topoisomerase 1 antibodies. Systemic sclerosis-associated interstitial lung disease most commonly presents with dyspnoea, cough, and a non-specific interstitial pneumonia pattern on CT scan, with a minority of cases fulfilling the criteria for usual interstitial pneumonia. The standard therapy has traditionally been combinations of immunosuppressants, particularly mycophenolate mofetil or cyclophosphamide. These immunosuppressants can be supplemented by targeted biological and antifibrotic therapies, whereas autologous haematopoietic stem-cell transplantation and lung transplantation are reserved for refractory cases.
Topics: Disease Progression; Female; Humans; Lung Diseases, Interstitial; Male; Scleroderma, Systemic
PubMed: 32113575
DOI: 10.1016/S2213-2600(19)30480-1 -
The Medical Clinics of North America Sep 1989Scleroderma encompasses a wide variety of diseases, including localized scleroderma, overlap syndromes, sclerodermoid conditions, and systemic scleroderma. This article... (Review)
Review
Scleroderma encompasses a wide variety of diseases, including localized scleroderma, overlap syndromes, sclerodermoid conditions, and systemic scleroderma. This article emphasizes the systemic scleroderma.
Topics: Humans; Scleroderma, Systemic; Skin
PubMed: 2671539
DOI: 10.1016/s0025-7125(16)30626-5 -
Dermatology Online Journal Jun 2002Systemic sclerosis is a clinically heterogeneous, systemic disorder which affects the connective tissue of the skin, internal organs and the walls of blood vessels. It... (Review)
Review
Systemic sclerosis is a clinically heterogeneous, systemic disorder which affects the connective tissue of the skin, internal organs and the walls of blood vessels. It is characterized by alterations of the microvasculature, disturbances of the immune system and by massive deposition of collagen and other matrix substances in the connective tissue. This review discusses epidemiology and survival, clinical features including subsets and internal organ involvement, pathophysiology and genetics, microvasculature, immunobiology, fibroblasts and connective tissue metabolism and environmental factors. Early diagnosis and individually tailored therapy help to manage this disorder, which is treatable, but not curable. Therapy involves immunomodulation as well as the targeting of blood vessel mechanics and fibrosis. Physical therapy and psychotherapy are also important adjunctive therapies in this multifactorial disease.
Topics: Animals; Humans; Risk Factors; Scleroderma, Systemic; Sex Factors
PubMed: 12165213
DOI: No ID Found -
British Journal of Hospital Medicine... Sep 2019Systemic sclerosis is a complex autoimmune connective tissue disease which carries a significant burden of disease-related morbidity including potentially... (Review)
Review
Systemic sclerosis is a complex autoimmune connective tissue disease which carries a significant burden of disease-related morbidity including potentially life-threatening complications. Systemic sclerosis can affect all the major organs and therefore, although the disease is uncommon, many hospital-based specialists are involved in patient care. Vascular disease (e.g. Raynaud's phenomenon) is an almost universal symptom in patients with systemic sclerosis and is often the earliest manifestation of the disease. Systemic sclerosis not uncommonly can overlap with other rheumatological conditions (e.g. rheumatoid arthritis and myositis). During the past few decades there have been major advances in understanding the pathogenesis of systemic sclerosis and these are driving advances in treatment. There are now a number of effective treatments to manage many of the different organ-based complications. Autologous haemopoietic stem cell transplantation is a potential treatment option in highly selected patients. This review updates the clinician about epidemiology, pathogenesis, differential diagnosis, the wide clinical spectrum of disease, and current and emerging treatments for systemic sclerosis.
Topics: Humans; Scleroderma, Systemic
PubMed: 31498665
DOI: 10.12968/hmed.2019.80.9.530 -
Clinics in Dermatology 2006Sclerosing conditions of the skin are manifested by a full spectrum of presentations that includes skin-limited forms as well as those which can involve internal organs... (Review)
Review
Sclerosing conditions of the skin are manifested by a full spectrum of presentations that includes skin-limited forms as well as those which can involve internal organs and result in death. At this point, we are just beginning to understand the mechanisms of tissue fibrosis, and it is likely that the fibrotic processes are a heterogeneous group of disorders in which perturbation of multiple molecular pathways, including vascular and immunologically mediated pathways, can lead to fibrosis. We now have some moderately effective therapies for vascular aspects of systemic sclerosis (eg, bosentan for pulmonary arterial hypertension, calcium-channel blockers for Raynaud's, or angiotensin-converting enzyme inhibitors for renal crisis). We also are beginning to find treatments interrupting the immunologic pathways that manifest as systemic sclerosis (eg, methotrexate for the skin or cyclophosphamide for the lungs). The basic process of fibrosis, however, awaits proven, effective therapy.
Topics: Antipruritics; Diagnosis, Differential; Fibrosis; Humans; Immunosuppressive Agents; Physical Therapy Modalities; Scleroderma, Localized; Scleroderma, Systemic; Skin; Skin Diseases
PubMed: 16966019
DOI: 10.1016/j.clindermatol.2006.07.004 -
Seminars in Cutaneous Medicine and... Mar 2001Scleroderma is a broad term encompassing both localized and systemic sclerosis. Localized scleroderma is a cutaneous limited fibrosis that manifests as plaque morphea,... (Review)
Review
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. Limited systemic sclerosis is typically preceded by Raynaud's phenomenon, involves cutaneous sclerosis distal to the elbows, with gastrointestinal and pulmonary fibrosis, and anticentromere antibody positivity. Diffuse systemic scleroderma is characterized by simultaneous Raynaud's phenomenon, cutaneous skin involvement proximal to the elbow with gastrointestinal, pulmonary, renal and cardiac fibrosis, and positive serology for antitopoisomerase and anti-RNAP III antibodies. This article discusses the classification, epidemiology, pathogenesis, clinical manifestations, treatment, and prognosis of the scleroderma.
Topics: Adult; Bone Marrow Transplantation; Calcium Channel Blockers; Child; Humans; Immunosuppression Therapy; Male; PUVA Therapy; Photopheresis; Prognosis; Prostaglandins; Relaxin; Scleroderma, Localized; Scleroderma, Systemic; Skin
PubMed: 11308134
DOI: 10.1053/sder.2001.23093