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      Localized scleroderma: clinical spectrum and therapeutic update *

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          Abstract

          Scleroderma is a rare connective tissue disease that is manifested by cutaneous sclerosis and variable systemic involvement. Two categories of scleroderma are known: systemic sclerosis, characterized by cutaneous sclerosis and visceral involvement, and localized scleroderma or morphea which classically presents benign and self-limited evolution and is confined to the skin and/or underlying tissues. Localized scleroderma is a rare disease of unknown etiology. Recent studies show that the localized form may affect internal organs and have variable morbidity. Treatment should be started very early, before complications occur due to the high morbidity of localized scleroderma. In this review, we report the most important aspects and particularities in the treatment of patients diagnosed with localized scleroderma.

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          Inter and intraobserver variability of total skin thickness score (modified Rodnan TSS) in systemic sclerosis.

          Assessment of the inter and intraobserver variability of the modified Rodnan (m-Rodnan) total skin thickness score by clinical palpation [a commonly used outcome measure in trials of systemic sclerosis (SSc)]. Skin thickness was assessed by clinical palpation of 17 body areas on 0 to 3 scale (normal, mild, moderate, severe). The m-Rodnan total skin thickness score was derived by summation of the scores from all 17 body areas. Using the m-Rodnan, 6-7 investigators assessed skin thickness in 5-6 patients with SSc (22 patients and 23 examiners total) at each of 4 sessions for the determination of interobserver variability (accuracy). In addition 21 of the investigators then assessed m-Rodnan in 2-3 patients each (60 patients total) 3 times over a 2-8 week period to quantitate intraobserver variability (reliability). Interobserver and intraobserver mean +/- within patient standard deviations (SD) for the m-Rodnan were found to be 17.7 +/- 4.6 and 20.7 +/- 2.45, respectively. The m-Rodnan total skin thickness score is at least as reliable for measuring skin thickness in SSc as are the ARA and Ritchie joint tenderness counts for assessing joint disease in rheumatoid arthritis. These data are useful for the determination of sample size and for the definitions of clinically meaningful response. Assessment of skin score is sufficiently reproducible to include as a measure of disease outcome, especially if patients are serially evaluated by the same investigator.
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            The pathogenesis of systemic sclerosis.

            Systemic sclerosis (SSc), also known as scleroderma, is a rare connective tissue disease characterized by vascular and immune dysfunction, leading to fibrosis that can damage multiple organs. Its pathogenesis is complex and poorly understood. Two major clinical subtypes are the limited and diffuse forms. Research into SSc has been hampered by its rarity, its clinical heterogeneity, and the lack of mouse models that accurately recapitulate the disease. Clinical and basic studies have yielded some mechanistic clues regarding pathogenesis. Recent insights gained through the use of microarrays have revealed distinctive subsets of SSc within and beyond the limited and diffuse subsets. In this review, we discuss potential mechanisms underlying the vascular, autoimmune, and fibrotic points of dysregulation. Proper categorization of SSc patients for research studies by use of microarrays or other biomarkers is critical, as disease heterogeneity may explain some of the inconsistencies of prior studies.
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              Analysis of systemic sclerosis in twins reveals low concordance for disease and high concordance for the presence of antinuclear antibodies.

              To examine concordance for systemic sclerosis (SSc) in monozygotic (MZ) and dizygotic (DZ) twins. MZ and DZ twins were recruited nationwide. Zygosity was confirmed by DNA fingerprint analysis. The presence of antinuclear antibodies (ANAs) was determined using indirect immunofluorescence with HEp-2 cells as substrate. Identification of SSc-associated serum autoantibodies was performed by immunoprecipitation and double immunodiffusion. Major histocompatibility complex class II alleles were identified by polymerase chain reaction-restriction fragment length polymorphism analysis. Concordance for SSc was found to be similar in MZ and DZ twins. Overall concordance for SSc was low in the twins (4.7%). Concordance for the presence of ANAs was significantly higher in MZ twins compared with DZ twins. SSc-associated serum autoantibodies occurred exclusively in patients with SSc. The distribution of SSc-associated serum autoantibodies was similar to that observed in our large database of SSc patients. Increased HLA allele sharing was detected in DZ twins, irrespective of disease concordance. These results indicate that inherited genetic factors are not sufficient to explain the development of SSc. Rather, these data indicate that inheritance may play a role in the development of serum autoantibodies in the "healthy" twin sibling of an SSc patient.
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                Author and article information

                Journal
                An Bras Dermatol
                An Bras Dermatol
                Anais Brasileiros de Dermatologia
                Sociedade Brasileira de Dermatologia
                0365-0596
                1806-4841
                Jan-Feb 2015
                Jan-Feb 2015
                : 90
                : 1
                : 62-73
                Affiliations
                [1 ]University of São Paulo (USP) – São Paulo (SP), Brazil.
                Author notes
                MAILING ADDRESS: Mariana Figueiroa Careta, Rua Barão de Teffe 1000 sala 13 - Jardim Ana Maria, 13208-765 - Jundiai - SP, Brazil. E-mail: mfcareta@ 123456yahoo.com.br
                Article
                10.1590/abd1806-4841.20152890
                4323700
                25672301
                ab12213f-bd23-4cd8-bd9c-730c17d7483f
                ©2015 by Anais Brasileiros de Dermatologia

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 24 June 2013
                : 11 October 2013
                Funding
                Funded by: CNPq (National Council for Scientific and Technological Development)
                Award ID: 141992/2011-5
                Financial Support: CNPq (National Council for Scientific and Technological Development), No.: 141992/2011-5.
                Categories
                Review

                autoimmune diseases,collagen diseases,immune system diseases,epidemiology,localized scleroderma,signs and symptoms

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