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Mayo Clinic Proceedings Apr 2013Systemic sclerosis (scleroderma) is unique among the rheumatic diseases because it presents the challenge of managing a chronic multisystem autoimmune disease with a... (Review)
Review
Systemic sclerosis (scleroderma) is unique among the rheumatic diseases because it presents the challenge of managing a chronic multisystem autoimmune disease with a widespread obliterative vasculopathy of small arteries that is associated with varying degrees of tissue fibrosis. The hallmark of scleroderma is clinical heterogeneity with subsets that vary in the degree of disease expression, organ involvement, and ultimate prognosis. Thus, the term scleroderma is used to describe patients who have common manifestations that link them together, whereas a highly variable clinical course exists that spans from mild and subtle findings to aggressive, life-threatening multisystem disease. The physician needs to carefully characterize each patient to understand the specific manifestations and level of disease activity to decide appropriate treatment. This is particularly important in treating a patient with scleroderma because there is no treatment that has been proven to modify the overall disease course, although therapy that targets specific organ involvement early before irreversible damage occurs improves both quality of life and survival. This review describes our approach as defined by evidence, expert opinion, and our experience treating patients. Scleroderma is a multisystem disease with variable expression; thus, any treatment plan must be holistic, yet at the same time focus on the dominant organ disease. The goal of therapy is to improve quality of life by minimizing specific organ involvement and subsequent life-threatening disease. At the same time the many factors that alter daily function need to be addressed, including nutrition, pain, deconditioning, musculoskeletal disuse, comorbid conditions, and the emotional aspects of the disease, such as fear, depression, and the social withdrawal caused by disfigurement.
Topics: Combined Modality Therapy; Early Diagnosis; Humans; Phenotype; Quality of Life; Scleroderma, Systemic
PubMed: 23541012
DOI: 10.1016/j.mayocp.2013.01.018 -
Clinical and Experimental Immunology Jul 2020
Topics: Humans; Immunity, Innate; Scleroderma, Systemic
PubMed: 32458451
DOI: 10.1111/cei.13452 -
Pediatric Clinics of North America Apr 2012Pediatric scleroderma includes 2 major groups of clinical entities, systemic sclerosis (SSc) and localized scleroderma (LS). Although both share a common... (Review)
Review
Pediatric scleroderma includes 2 major groups of clinical entities, systemic sclerosis (SSc) and localized scleroderma (LS). Although both share a common pathophysiology, their clinical manifestations differ. LS is typically confined to the skin and underlying subcutis, with up to a quarter of patients showing extracutaneous disease manifestations such as arthritis and uveitis. Vascular, cutaneous, gastrointestinal, pulmonary, and musculoskeletal involvement are most commonly seen in children with SSc. Treatment of both forms targets the active inflammatory stage and halts disease progression; however, progress needs to be made toward the development of more effective antifibrotic therapy to help reverse disease damage.
Topics: Anti-Inflammatory Agents; Child; Dermatologic Agents; Humans; Immunosuppressive Agents; Prognosis; Scleroderma, Localized; Scleroderma, Systemic; Treatment Outcome; Ultraviolet Therapy
PubMed: 22560576
DOI: 10.1016/j.pcl.2012.03.011 -
Postgraduate Medical Journal Feb 1988Difficulty in the diagnosis of the disease scleroderma may occur at the early stage prior to the development of obvious skin sclerosis. A presumptive diagnosis may be... (Review)
Review
Difficulty in the diagnosis of the disease scleroderma may occur at the early stage prior to the development of obvious skin sclerosis. A presumptive diagnosis may be made if Raynaud's phenomenon is accompanied by a positive 'neck test', 'scleroderma' capillary changes in the nailfolds or antinuclear antibodies. Definitive diagnosis may have to be delayed for several years from the onset of Raynaud's phenomenon until definite characteristic skin changes are seen. Ten cases in which an earlier diagnosis of scleroderma was not substantiated are listed. The earlier incorrect diagnosis would have been avoided by use of the methods described in this paper. Various terms have been used to denote subdivisions of scleroderma. These include acrosclerosis, diffuse scleroderma and CREST. We have used the terms Type 1, Type 2 and Type 3 based on the early extent of the skin sclerosis where Type 1 (limited extent) indicates sclerodactyly only, Type 2 (moderate extent) indicates sclerosis proximal to the metacarpophalangeal joints but excluding the trunk and Type 3 (extensive) indicates diffuse skin sclerosis including the trunk. The clinical value of this simple classification is reviewed and contrasted to other classifications which appear to be poorly defined and of limited use.
Topics: Adult; Female; Humans; Male; Scleroderma, Systemic
PubMed: 3050937
DOI: 10.1136/pgmj.64.748.121 -
Matrix Biology : Journal of the... Apr 2024The largest mammalian organ, skin, consisting of a dermal connective tissue layer that underlies and supports the epidermis, acts as a protective barrier that excludes... (Review)
Review
The largest mammalian organ, skin, consisting of a dermal connective tissue layer that underlies and supports the epidermis, acts as a protective barrier that excludes external pathogens and disseminates sensory signals emanating from the local microenvironment. Dermal connective tissue is comprised of a collagen-rich extracellular matrix (ECM) that is produced by connective tissue fibroblasts resident within the dermis. When wounded, a tissue repair program is induced whereby fibroblasts, in response to alterations in the microenvironment, produce new ECM components, resulting in the formation of a scar. Failure to terminate the normal tissue repair program causes fibrotic conditions including: hypertrophic scars, keloids, and the systemic autoimmune connective tissue disease scleroderma (systemic sclerosis, SSc). Histological and single-cell RNA sequencing (scRNAseq) studies have revealed that fibroblasts are heterogeneous and highly plastic. Understanding how this diversity contributes to dermal homeostasis, wounding, fibrosis, and cancer may ultimately result in novel anti-fibrotic therapies and personalized medicine. This review summarizes studies supporting this concept.
Topics: Animals; Cicatrix, Hypertrophic; Epidermis; Fibroblasts; Fibrosis; Mammals; Scleroderma, Systemic; Skin
PubMed: 38423396
DOI: 10.1016/j.matbio.2024.02.009 -
Rheumatic Diseases Clinics of North... Feb 2018Although classification criteria for systemic sclerosis (SSc) do not incorporate gastrointestinal tract (GIT) manifestations often present in this disease, the GIT is... (Review)
Review
Although classification criteria for systemic sclerosis (SSc) do not incorporate gastrointestinal tract (GIT) manifestations often present in this disease, the GIT is the most common internal organ involved. Pathophysiology of GIT involvement is thought to be similar to other organs in SSc with fibroproliferative vascular lesions of small arteries and arterioles, increased production of profibrotic growth factors, and alterations of innate, humoral, and cellular immunity. These processes result in neuropathy progressing to myopathy with eventual fibrosis. Proper diagnostics and therapeutics for SSc-GIT involvement require the treating physician to have an understanding of an integrated approach and potential medication adverse effects.
Topics: Gastrointestinal Diseases; Humans; Inflammation; Liver Diseases; Medication Therapy Management; Scleroderma, Systemic
PubMed: 29149923
DOI: 10.1016/j.rdc.2017.09.002 -
Medecine Sciences : M/S Feb 2016Systemic sclerosis (SSc) is an orphan disease affecting the connective tissue. The cause of SSc remains unknown but is likely to involve environmental factors in a... (Review)
Review
Systemic sclerosis (SSc) is an orphan disease affecting the connective tissue. The cause of SSc remains unknown but is likely to involve environmental factors in a genetically primed individual with SSc belonging to the multigenic disorders. Pathogenesis is dominated by early microvascular changes targeting endothelial cells and with the release of several mediators promoting an inflammatory response and vascular remodelling. Several lines of evidence position autoimmunity as a key perpetuating event with activation of both innate and adaptive immunity and with the production of distinct autoantibodies. The cascade ultimates with the fibrosis defined by accumulation of extra-cellular matrix through an imbalance between synthesis and degradation of several components and mesenchymal cell activation and differentiation controlled by a large number of autocrine and paracrine factors.
Topics: Animals; Autoantibodies; Autoimmunity; Endothelial Cells; Fibrosis; Humans; Immunity, Innate; Inflammation; Scleroderma, Systemic
PubMed: 26936176
DOI: 10.1051/medsci/20163202012 -
The Israel Medical Association Journal... Jul 2019
Topics: Humans; Microscopic Angioscopy; Nails; Raynaud Disease; Scleroderma, Systemic
PubMed: 31507129
DOI: No ID Found -
Current Opinion in Rheumatology Nov 2015Recent data suggest a paraneoplastic mechanism of scleroderma pathogenesis in unique subsets of scleroderma patients. In this article, we review these data, explore... (Review)
Review
PURPOSE OF REVIEW
Recent data suggest a paraneoplastic mechanism of scleroderma pathogenesis in unique subsets of scleroderma patients. In this article, we review these data, explore potential links between cancer and scleroderma, and propose an approach to malignancy screening in scleroderma.
RECENT FINDINGS
Emerging data have demonstrated that patients with scleroderma and RNA polymerase III autoantibodies have a significantly increased risk of cancer within a few years of scleroderma onset. Genetic alterations in the gene encoding RNA polymerase III (POLR3A) have been identified, and patients with somatic mutations in POLR3A have evidence of mutation specific T-cell immune responses with generation of cross-reactive RNA polymerase III autoantibodies. These data strongly suggest that scleroderma is a by-product of antitumor immune responses in some patients. Additional epidemiologic data demonstrate that patients developing scleroderma at older ages may also have a short cancer-scleroderma interval, suggestive of paraneoplastic disease.
SUMMARY
Scleroderma may be a paraneoplastic disease in unique patient subsets. Aggressive malignancy screening in these patients may aid in early cancer detection. Further study is required to determine whether cancer therapy could improve scleroderma outcomes in this patient population.
Topics: Early Detection of Cancer; Humans; Neoplasms; Paraneoplastic Syndromes; Scleroderma, Systemic
PubMed: 26352736
DOI: 10.1097/BOR.0000000000000222 -
International Journal of Molecular... Aug 2023Systemic sclerosis, also known as scleroderma or SSc, is a condition characterized by significant heterogeneity in clinical presentation, disease progression, and... (Review)
Review
Systemic sclerosis, also known as scleroderma or SSc, is a condition characterized by significant heterogeneity in clinical presentation, disease progression, and response to treatment. Consequently, the design of clinical trials to successfully identify effective therapeutic interventions poses a major challenge. Recent advancements in skin molecular profiling technologies and stratification techniques have enabled the identification of patient subgroups that may be relevant for personalized treatment approaches. This narrative review aims at providing an overview of the current status of skin gene expression analysis using computational biology approaches and highlights the benefits of stratifying patients upon their skin gene signatures. Such stratification has the potential to lead toward a precision medicine approach in the management of SSc.
Topics: Humans; Precision Medicine; Transcriptome; Skin; Scleroderma, Systemic; Gene Expression Profiling
PubMed: 37628728
DOI: 10.3390/ijms241612548