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Kazuhiko Takehara - One of the best experts on this subject based on the ideXlab platform.
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diagnostic criteria severity classification and guidelines of Localized Scleroderma
Journal of Dermatology, 2018Co-Authors: Yoshihide Asano, Kazuhiko Takehara, Shinichi Sato, Minoru Hasegawa, Manabu Fujimoto, Masatoshi Jinnin, Osamu Ishikawa, Toshiyuki YamamotoAbstract:: We established diagnostic criteria and severity classification of Localized Scleroderma because there is no established diagnostic criteria or widely accepted severity classification of the disease. Also, there has been no clinical guideline for Localized Scleroderma, so we established its clinical guideline ahead of all over the world. In particular, the clinical guideline was established by clinical questions based on evidence-based medicine according to the New Minds Clinical Practice Guideline Creation Manual (version 1.0). We aimed to make the guideline easy to use and reliable based on the newest evidence, and to present guidance as specific as possible for various clinical problems in treatment of Localized Scleroderma.
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Localized Scleroderma is an autoimmune disorder
Rheumatology (Oxford England), 2004Co-Authors: Kazuhiko Takehara, Shinichi SatoAbstract:OBJECTIVES There have been many studies suggesting that Localized Scleroderma has a strong autoimmune background, although the lesions are usually limited to the skin and subcutaneous tissue. Here we summarize previous data on the autoimmunity of Localized Scleroderma, mostly published in the last two decades, because there has not been a review paper summarizing autoimmunity in this disorder. METHODS We classified the previous reports into three categories: antinuclear antibodies; cytokine and soluble receptors; and cell adhesion molecules and cell surface molecules. In each category, we introduce the important investigations. RESULTS High frequencies of antinuclear antibodies, detected by the indirect immunofluorescence method using cultured cells, are confirmed by many groups. The major autoantigens have been revealed to be histones. Recently, anti-topoisomerase II alpha antibody has been found to be detected highly frequently in Localized Scleroderma, while anti-topoisomerase I antibody, which is highly specific for systemic sclerosis, has not been detected in any case of Localized Scleroderma. In other studies, elevated serum cytokines and cell adhesion molecules suggest the immunoactivation of Localized Scleroderma. CONCLUSIONS Many previous studies conclude that Localized Scleroderma involves autoimmune abnormalities and is one of the organ-specific autoimmune disorders targeting mainly skin, although the types of autoimmune abnormality are different from systemic sclerosis.
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Anti-DNA topoisomerase IIα autoantibodies in Localized Scleroderma
Arthritis and rheumatism, 2004Co-Authors: Ikuko Hayakawa, Kazuhiko Takehara, Minoru Hasegawa, Shinichi SatoAbstract:Objective To determine the prevalence and clinical correlation of anti-DNA topoisomerase IIα (anti–topo IIα) antibody in patients with Localized Scleroderma. Methods Anti–topo IIα antibodies or anti-DNA topoisomerase I (topo I) antibodies were determined by enzyme-linked immunosorbent assay (ELISA) and immunoblotting. Inhibition of topo IIα enzymatic activity by the antibodies was evaluated by decatenation assays using kinetoplast DNA as a substrate. Results IgG or IgM anti–topo IIα antibody was detected in 76% (35 of 46) of patients with Localized Scleroderma, and in 85% (11 of 13) of patients with generalized morphea, the severest form of Localized Scleroderma. This prevalence of the antibody in patients with Localized Scleroderma was much higher than that found in patients with systemic sclerosis (SSc) (5 of 37 [14%]), systemic lupus erythematosus (2 of 26 [8%]), dermatomyositis (2 of 20 [10%]), and in healthy controls (3 of 42 [7%]). Immunoblotting confirmed the presence of IgG anti–topo IIα antibody in sera from patients with Localized Scleroderma and showed no cross-reactivity of anti–topo IIα antibody with topo I. Anti–topo I antibody was not detected by ELISA in any sera from patients with Localized Scleroderma. In addition, anti–topo I antibody from SSc patients did not cross-react with topo IIα. The presence of anti–topo IIα antibody was associated with a greater total number of sclerotic lesions and number of plaque lesions in patients with Localized Scleroderma. Furthermore, anti–topo IIα antibody was able to inhibit topo IIα enzymatic activity. Conclusion The results of the present study indicate that anti–topo IIα is a major autoantibody in Localized Scleroderma, and is distinct from anti–topo I antibody in SSc.
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Novel Autoantibody to Cu/Zn Superoxide Dismutase in Patients with Localized Scleroderma
The Journal of investigative dermatology, 2004Co-Authors: Masaki Nagai, Kazuhiko Takehara, Minoru Hasegawa, Shinichi SatoAbstract:Abnormal production of reactive oxygen species (ROS) induces tissue damage and superoxide dismutase (SOD) that converts superoxide radicals to hydrogen peroxide functions as defense against ROS. Cu/Zn SOD administration has been shown to be effective for various fibrotic conditions by inhibiting the fibrogenic effects of ROS. We hypothesized that autoimmune background in Localized Scleroderma induced anti-Cu/Zn SOD autoantibodies that inhibited SOD activity and thereby contributed to fibrosis by increasing ROS. ELISA using human purified Cu/Zn SOD revealed that IgG or IgM anti-Cu/Zn SOD Ab was detected in the serum of 89% of Localized Scleroderma patients, especially 100% of patients with generalized morphea, the severest form of Localized Scleroderma, but was positive only in the serum of less than 15% of patients with other autoimmune disorders, including systemic sclerosis, systemic lupus erythematosus, dermatomyositis, and autoimmune bullous disorders. The immunoblotting analysis confirmed the presence of IgG anti-Cu/Zn SOD Ab in sera from Localized Scleroderma patients. Remarkably, anti-Cu/Zn SOD autoantibody could inhibit Cu/Zn SOD enzymatic activity. Collectively, these results indicate that anti-Cu/Zn SOD Ab is a novel, major autoantibody in Localized Scleroderma, and also suggest that the autoantibody may play a role in the development of fibrosis by directly inhibiting SOD activity.
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Serum levels of soluble interleukin 6 receptor and soluble gp130 are elevated in patients with Localized Scleroderma.
The Journal of rheumatology, 2000Co-Authors: Tetsuya Nagaoka, Hironobu Ihn, Shinichi Sato, Minoru Hasegawa, Kazuhiko TakeharaAbstract:Objective. To investigate the clinical relevance of serum soluble interleukin 6 receptor (sIL-6R) and soluble gp130 (sgp130) in Localized Scleroderma. Methods. Serum levels of sIL-6R and sgp130 were examined by ELISA in 45 patients with Localized Scleroderma. Twenty patients with systemic sclerosis (SSc) and 20 healthy individuals served as controls, Results. Serum levels of both sIL-6R and sgp130 were significantly elevated in patients with Localized Scleroderma compared with healthy controls. Moreover, serum sgp130 levels in patients with Localized Scleroderma were significantly higher than in patients with SSc. In patients with Localized Scleroderma, elevated sIL-6R levels significantly correlated with levels of IgM antihistone antibodies, the presence of rheumatoid factor, the number of linear lesions, and the number of body areas involved. Elevated sgpl30 levels were significantly associated with levels of IgG antihistone antibodies, the number of plaque lesions, the total number of lesions, and the number of body areas involved. Conclusion. These results suggest that elevated serum sIL-6R and sgp130 may reflect activation of the IL-6 system that may be associated with the development of sclerotic lesions and autoantibody production in Localized Scleroderma.
Shinichi Sato - One of the best experts on this subject based on the ideXlab platform.
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diagnostic criteria severity classification and guidelines of Localized Scleroderma
Journal of Dermatology, 2018Co-Authors: Yoshihide Asano, Kazuhiko Takehara, Shinichi Sato, Minoru Hasegawa, Manabu Fujimoto, Masatoshi Jinnin, Osamu Ishikawa, Toshiyuki YamamotoAbstract:: We established diagnostic criteria and severity classification of Localized Scleroderma because there is no established diagnostic criteria or widely accepted severity classification of the disease. Also, there has been no clinical guideline for Localized Scleroderma, so we established its clinical guideline ahead of all over the world. In particular, the clinical guideline was established by clinical questions based on evidence-based medicine according to the New Minds Clinical Practice Guideline Creation Manual (version 1.0). We aimed to make the guideline easy to use and reliable based on the newest evidence, and to present guidance as specific as possible for various clinical problems in treatment of Localized Scleroderma.
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Case of Localized Scleroderma associated with osteomyelitis.
The Journal of dermatology, 2010Co-Authors: Eiji Muroi, Fumihide Ogawa, Toshifumi Yamaoka, Fumiko Sueyoshi, Shinichi SatoAbstract:We report a 4-year-old girl presenting with progressive linear Scleroderma affecting the right leg. Biopsy specimen disclosed typical histopathological findings of Localized Scleroderma. Right leg magnetic resonance imaging (MRI) showed high signal areas on T(2)-weighted images on the subcutaneous fatty tissue, muscles and bone marrow, suggesting that skin inflammation extended to the bone marrow. Oral corticosteroid therapy was instituted with improvement of both skin sclerosis and MRI findings. Our observations suggest that MRI examination should be considered in patients with Localized Scleroderma to evaluate the extension of the inflammation.
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Localized Scleroderma is an autoimmune disorder
Rheumatology (Oxford England), 2004Co-Authors: Kazuhiko Takehara, Shinichi SatoAbstract:OBJECTIVES There have been many studies suggesting that Localized Scleroderma has a strong autoimmune background, although the lesions are usually limited to the skin and subcutaneous tissue. Here we summarize previous data on the autoimmunity of Localized Scleroderma, mostly published in the last two decades, because there has not been a review paper summarizing autoimmunity in this disorder. METHODS We classified the previous reports into three categories: antinuclear antibodies; cytokine and soluble receptors; and cell adhesion molecules and cell surface molecules. In each category, we introduce the important investigations. RESULTS High frequencies of antinuclear antibodies, detected by the indirect immunofluorescence method using cultured cells, are confirmed by many groups. The major autoantigens have been revealed to be histones. Recently, anti-topoisomerase II alpha antibody has been found to be detected highly frequently in Localized Scleroderma, while anti-topoisomerase I antibody, which is highly specific for systemic sclerosis, has not been detected in any case of Localized Scleroderma. In other studies, elevated serum cytokines and cell adhesion molecules suggest the immunoactivation of Localized Scleroderma. CONCLUSIONS Many previous studies conclude that Localized Scleroderma involves autoimmune abnormalities and is one of the organ-specific autoimmune disorders targeting mainly skin, although the types of autoimmune abnormality are different from systemic sclerosis.
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Anti-DNA topoisomerase IIα autoantibodies in Localized Scleroderma
Arthritis and rheumatism, 2004Co-Authors: Ikuko Hayakawa, Kazuhiko Takehara, Minoru Hasegawa, Shinichi SatoAbstract:Objective To determine the prevalence and clinical correlation of anti-DNA topoisomerase IIα (anti–topo IIα) antibody in patients with Localized Scleroderma. Methods Anti–topo IIα antibodies or anti-DNA topoisomerase I (topo I) antibodies were determined by enzyme-linked immunosorbent assay (ELISA) and immunoblotting. Inhibition of topo IIα enzymatic activity by the antibodies was evaluated by decatenation assays using kinetoplast DNA as a substrate. Results IgG or IgM anti–topo IIα antibody was detected in 76% (35 of 46) of patients with Localized Scleroderma, and in 85% (11 of 13) of patients with generalized morphea, the severest form of Localized Scleroderma. This prevalence of the antibody in patients with Localized Scleroderma was much higher than that found in patients with systemic sclerosis (SSc) (5 of 37 [14%]), systemic lupus erythematosus (2 of 26 [8%]), dermatomyositis (2 of 20 [10%]), and in healthy controls (3 of 42 [7%]). Immunoblotting confirmed the presence of IgG anti–topo IIα antibody in sera from patients with Localized Scleroderma and showed no cross-reactivity of anti–topo IIα antibody with topo I. Anti–topo I antibody was not detected by ELISA in any sera from patients with Localized Scleroderma. In addition, anti–topo I antibody from SSc patients did not cross-react with topo IIα. The presence of anti–topo IIα antibody was associated with a greater total number of sclerotic lesions and number of plaque lesions in patients with Localized Scleroderma. Furthermore, anti–topo IIα antibody was able to inhibit topo IIα enzymatic activity. Conclusion The results of the present study indicate that anti–topo IIα is a major autoantibody in Localized Scleroderma, and is distinct from anti–topo I antibody in SSc.
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Novel Autoantibody to Cu/Zn Superoxide Dismutase in Patients with Localized Scleroderma
The Journal of investigative dermatology, 2004Co-Authors: Masaki Nagai, Kazuhiko Takehara, Minoru Hasegawa, Shinichi SatoAbstract:Abnormal production of reactive oxygen species (ROS) induces tissue damage and superoxide dismutase (SOD) that converts superoxide radicals to hydrogen peroxide functions as defense against ROS. Cu/Zn SOD administration has been shown to be effective for various fibrotic conditions by inhibiting the fibrogenic effects of ROS. We hypothesized that autoimmune background in Localized Scleroderma induced anti-Cu/Zn SOD autoantibodies that inhibited SOD activity and thereby contributed to fibrosis by increasing ROS. ELISA using human purified Cu/Zn SOD revealed that IgG or IgM anti-Cu/Zn SOD Ab was detected in the serum of 89% of Localized Scleroderma patients, especially 100% of patients with generalized morphea, the severest form of Localized Scleroderma, but was positive only in the serum of less than 15% of patients with other autoimmune disorders, including systemic sclerosis, systemic lupus erythematosus, dermatomyositis, and autoimmune bullous disorders. The immunoblotting analysis confirmed the presence of IgG anti-Cu/Zn SOD Ab in sera from Localized Scleroderma patients. Remarkably, anti-Cu/Zn SOD autoantibody could inhibit Cu/Zn SOD enzymatic activity. Collectively, these results indicate that anti-Cu/Zn SOD Ab is a novel, major autoantibody in Localized Scleroderma, and also suggest that the autoantibody may play a role in the development of fibrosis by directly inhibiting SOD activity.
Hironobu Ihn - One of the best experts on this subject based on the ideXlab platform.
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Alternatively activated macrophages (M2 macrophages) in the skin of patient with Localized Scleroderma.
Experimental dermatology, 2009Co-Authors: Nobuyo Higashi-kuwata, Yuji Inoue, Takamitsu Makino, Motohiro Takeya, Hironobu IhnAbstract:Localized Scleroderma is a connective tissue disorder that is limited to the skin and subcutaneous tissue. Macrophages have been reported to be particularly activated in patients with skin disease including systemic sclerosis and are potentially important sources for fibrosis-inducing cytokines, such as transforming growth factor beta. To clarify the features of immunohistochemical characterization of the immune cell infiltrates in Localized Scleroderma focusing on macrophages, skin biopsy specimens were analysed by immunohistochemistry. The number of cells stained with monoclonal antibodies, CD68, CD163 and CD204, was calculated. An evident macrophage infiltrate and increased number of alternatively activated macrophages (M2 macrophages) in their fibrotic areas were observed along with their severity of inflammation. This study revealed that alternatively activated macrophages (M2 macrophages) may be a potential source of fibrosis-inducing cytokines in Localized Scleroderma, and may play a crucial role in the pathogenesis of Localized Scleroderma.
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Immunohistochemical characterization of the cellular infiltrate in Localized Scleroderma
International journal of dermatology, 2008Co-Authors: Yong Xie, Xiaoyong Zhang, Shoji Wakasugi, Takamitsu Makino, Yuji Inoue, Hironobu IhnAbstract:Background Localized Scleroderma is a connective tissue disorder with hardening of the skin and fibrosis of the affected tissue as the most prominent features. The etiology of Localized Scleroderma is still unknown, but immunologic factors may play an important role in the pathogenesis. This study was performed to determine the immunohistochemical features of the cellular infiltrate in Localized Scleroderma. Methods Skin samples were obtained from six patients by 6-mm punch biopsy. The samples were stained with monoclonal antibodies against CD1a, CD3, CD4, CD8, CD20, CD25, CD30, and CD57. The number of cells stained with each monoclonal antibody was calculated. Results There were more CD1a+, CD3+, CD4+, CD8+, CD20+, CD25+, and CD57+ cells in the dermal infiltrate in Localized Scleroderma relative to those in normal controls. The numbers of CD1a+, CD3+, CD4+, CD8+, and CD57+ cells in Localized Scleroderma were significantly greater than those in normal skin (P
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Anti‐agalactosyl immunoglobulin G antibodies in Localized Scleroderma
International journal of dermatology, 2005Co-Authors: Yoshihiro Mimra, Hironobu Ihn, Kenichi Yamane, Yoshihide Asano, Norihito Yazawa, Masatoshi Jinnin, Kunihiko TamakiAbstract:Background Anti-agalactosyl immunoglobulin G (IgG) antibodies (anti-AG IgG) have been reported to be detected and correlated with disease activity in some collagen diseases. Method Forty-seven serum samples from patients with Localized Scleroderma were examined using an enzyme-linked immunosorbent assay. Results Anti-AG IgG were positive in 19% of patients with Localized Scleroderma. The frequency of anti-AG IgG in generalized morphea was much higher than that in linear Scleroderma or that in morphea. There was a significant correlation between anti-AG IgG levels and the number of the sclerotic lesions and between anti-AG IgG levels and the number of involved areas. The levels of anti-AG IgG were significantly higher in patients with antinuclear antibody, antisingle-stranded DNA antibody or rheumatoid factor than in those without. Conclusion Anti-AG IgG can be an indicator of the severity of Localized Scleroderma.
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Rheumatoid factor isotypes in Localized Scleroderma.
Clinical and experimental dermatology, 2005Co-Authors: Yoshihiro Mimura, Hironobu Ihn, Kenichi Yamane, Yoshihide Asano, Masatoshi Jinnin, Kunihiko TamakiAbstract:Summary Localized sclerodema is a connective tissue disorder that is sometimes accompanied by various immunological abnormalities. In this study, we analysed serum levels of rheumatoid factor (RF) isotypes in patients with Localized Scleroderma and in normal controls to determine if any of these isotypes reflect the severity of the disease. IgM RF, IgG RF and IgA RF were positive in 30%, 21%, and 7% of the patients, respectively. The levels of IgM RF were significantly higher in the patients with generalized morphea (GM), the most severe form of Localized Scleroderma, than those with linear Scleroderma (LS) (P
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Anti-U1RNP antibodies in patients with Localized Scleroderma
Archives of dermatological research, 2001Co-Authors: Kenichi Yamane, Hironobu Ihn, Masahide Kubo, Masataka Kuwana, Yoshihide Asano, Norihito Yazawa, Kunihiko TamakiAbstract:Antibodies to U1 ribonucleoproteins (RNP) have been detected in serum from patients with various autoimmune diseases. However, the presence of anti-U1RNP antibodies in patients with Localized Scleroderma has not been reported. In this study, we examined the frequency of anti-U1RNP antibodies using immunoprecipitation of U small nuclear RNAs and determined the antigen specificity by immunoblotting. Of 70 serum samples from patients with Localized Scleroderma, 2 (3%) immunoprecipitated U1 small nuclear RNA. Indirect immunofluorescence using HEp-2 cells as substrate showed coarse speckled nuclear fluorescence without nucleolar staining in both of the samples positive for anti-U1RNP antibodies. In addition, the presence of anti-U1RNP antibodies in each serum sample was confirmed by immunodiffusion against HeLa cell extracts. Immunoblotting analysis showed anti-70 kDa antibodies in each serum sample. This reaction against 70 kDa protein in the patients with Localized Scleroderma was analogous to that in patients with systemic sclerosis or mixed connective tissue disease. Both patients with positive serum were diagnosed as having linear Scleroderma, but neither had evidence of Raynaud's phenomenon or sclerodactyly. These results indicate that the presence of anti-U1RNP antibodies is one of the serological abnormalities in Localized Scleroderma, and that the mechanism of induction of anti-U1RNP antibodies in patients with Localized Scleroderma might be similar to that in patients with systemic sclerosis and mixed connective tissue disease.
Francesco Zulian - One of the best experts on this subject based on the ideXlab platform.
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Sarcopenia in juvenile Localized Scleroderma: new insights on deep involvement
European radiology, 2020Co-Authors: Silvia Karem Janet Flores Quispe, Francesco Zulian, Annachiara Cavaliere, Michael Weber, Roberto Stramare, M Zuliani, Emilio Quaia, Chiara GiraudoAbstract:Juvenile Localized Scleroderma (JLS) is a rare chronic autoimmune disease which can also affect bones and muscles. Nevertheless, muscle loss was not previously investigated in patients with JLS. Thus, the aim of this study was to retrospectively evaluate deep involvement and assess and quantify sarcopenia in JLS patients using magnetic resonance imaging (MRI). Fourteen children with JLS (nine females, mean age ± SD, 7.1 ± 3.6 years) referring to our tertiary center from January 2012 to January 2018 who underwent at least one MRI examination including axial T1-weighted and short tau inversion recovery images were included. Two readers assessed in consensus superficial and deep involvement. Muscle edema, muscle fatty infiltration, and sarcopenia were independently scored (absent, moderate, or severe) and the Cohen’s kappa coefficient computed. Skin perimeter, subcutaneous area, muscle area, and muscle volume were independently measured using the contralateral unaffected extremity as reference (paired Student’s t test, p 0.750, each). Patients with JLS can be affected by sarcopenia and quantitative analyses allow a robust characterization of such finding. • Deep involvement in juvenile Localized Scleroderma is frequently characterized by sarcopenia. • In juvenile Localized Scleroderma, muscle edema and sarcopenia are mostly moderate while fatty infiltration, even if rare, can be severe. • Sarcopenia can be reliably quantified in children with juvenile Localized Scleroderma using MRI.
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Localized Scleroderma of the Face
Skin Manifestations in Rheumatic Disease, 2013Co-Authors: Francesco Zulian, Sabina Trainito, Anna Belloni-fortinaAbstract:Localized Scleroderma (LS), also known as morphea, is the most frequent form of Scleroderma in childhood and is grouped into five subtypes: circumscribed morphea, linear Scleroderma, generalized morphea, pansclerotic morphea, and a mixed subtype, where a combination of two or more of the previous subtypes is present. Linear Scleroderma is the most frequent subtype in childhood, and when it involves the face (LSF), it may cause aesthetic and functional abnormalities, sometimes complicated by hemifacial atrophy.
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Juvenile Localized Scleroderma
Scleroderma, 2011Co-Authors: Francesco ZulianAbstract:Juvenile Localized Scleroderma (JLS), known as morphea, comprises a group of conditions which involve essentially the skin and subcutaneous tissues. They have various features and range from very small plaques to extensive fibrotic lesions which may cause significant functional changes and cosmetic deformities.
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Chapter 8 Localized Scleroderma in Children
Handbook of Systemic Autoimmune Diseases, 2007Co-Authors: Francesco ZulianAbstract:Publisher Summary This chapter discusses the epidemiology, pathogenesis, clinical manifestations, diagnostic investigations, and treatments of Localized Scleroderma in children. Juvenile Localized Scleroderma (JLS), also known as morphea, comprises a group of distinct conditions involving the skin and subcutaneous tissues. They range from very small plaques involving only the skin, to full thickness lesions, which may cause significant functional and cosmetic deformity, with a variety of extracutaneous features. The etiology and pathogenesis of JLS are unknown. The descriptions of clinical manifestations of JLS in children, highlighting the possibility of extracutaneous manifestations are also included. The disregulation of fibroblast production of collagen and immunologic abnormalities is focused. New approaches to the treatment of JLS, including methotrexate, corticosteroids, phototherapy, and other immunosuppressive agents are developed. However, multicenter randomized controlled trials are needed to evaluate their real efficacy by using uniform classification criteria and validated outcome measures.
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Congenital Localized Scleroderma.
The Journal of pediatrics, 2006Co-Authors: Francesco Zulian, Cristina Vallongo, S Oliveira, Marilynn Punaro, Joan Ros, Henryka Mazur-zielinska, Paul Galea, Liviana Da Dalt, Lawrence F. EichenfieldAbstract:Objectives Juvenile Localized Scleroderma (JLS) usually has its onset during later childhood. This report describes the clinical and serologic features of six children with congenital Localized Scleroderma (CLS). Study design A large, multinational study was conducted among pediatric rheumatology and dermatology centers by collecting information on demographics, family history, triggering environmental factors, clinical features, laboratory reports, and treatment of patients with JLS. Patients with onset at birth were carefully examined. Results Among 750 patients with JLS, 6 patients (0.8%) had Scleroderma-related lesions at birth. Female-to-male ratio was 2:1. All patients had linear Scleroderma, in four involving the face with en coup de sabre appearance. Two patients were misdiagnosed as having skin infection, one nevus, one salmon patch, and two undefined skin lesions. The mean diagnostic delay was 3.9 years. In comparison with the group of 733 patients with late-onset JLS, CLS presented a significantly more prolonged disease duration at diagnosis and a higher frequency of en coup de sabre subtypes. Conclusions Congenital Localized Scleroderma is a rare and probably underestimated condition in neonates. The linear subtype was the exclusive manifestation of the disease. CLS should be included in the differential diagnosis of infants with cutaneous erythematous fibrotic lesions to avoid functional and aesthetic sequelae and to allow prompt therapy.
Kanako Kikuchi - One of the best experts on this subject based on the ideXlab platform.
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Soluble CD4 and CD8 in serum from patients with Localized Scleroderma
Archives of Dermatological Research, 1996Co-Authors: Shinichi Sato, Hironobu Ihn, Kanako Kikuchi, Manabu Fujimoto, Kunihiko Tamaki, Kazuhiko TakeharaAbstract:Localized Scleroderma has been shown to be accompanied by various immunologic abnormalities. To obtain functional information on activated CD4+ or CD8+ T cells, we studied the levels of soluble CD4 (sCD4) and soluble CD8 (sCD8) in serum from patients with Localized Scleroderma. Serum samples were examined by enzyme-linked immunosorbent assay. The samples were obtained from 49 patients in the following three subgroups: 15 patients with generalized morphea, 22 with linear Scleroderma, and 12 with morphea. The levels of sCD4 and sCD8 were significantly elevated in patients with generalized morphea. Furthermore, these patients showed significantly higher levels of sCD4 than those with systemic sclerosis (SSc). The frequency of positivity for IgG anti-single-stranded DNA (ssDNA) antibody was significantly higher in Localized Scleroderma patients with elevated sCD4 levels than in patients with normal sCD4 levels. The frequency of positivity for antinuclear antibodies, IgM antihistone antibodies, IgG anti-ssDNA antibody and rheumatoid factor, and elevated sCD23 levels were significantly higher in Localized Scleroderma patients with elevated sCD8 levels than in patients with normal sCD8 levels. Our findings suggest that both CD4+ and CD8+ T cells are activated in vivo in generalized morphea and that the immunologic events in generalized morphea are different from those in SSc.
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Elevated soluble CD23 levels in the sera from patients with Localized Scleroderma.
Archives of dermatological research, 1996Co-Authors: Shinichi Sato, Hironobu Ihn, Kanako Kikuchi, Manabu Fujimoto, Kunihiko Tamaki, Kazuhiko TakeharaAbstract:Soluble CD23 (sCD23) is closely related to B-cell activation and elevated serum levels of sCD23 have been reported in several autoimmune disorders. This study investigated the serum levels of sCD23 and determined the correlation of sCD23 with other immunologic abnormalities and clinical features in Localized Scleroderma. We examined 49 serum samples by an enzyme-linked immunosorbent assay in the following three subgroups: 15 patients with generalized morphoea, 22 with linear Scleroderma, and 12 with morphoea. The serum levels of sCD23 were significantly elevated in patients with Localized Scleroderma, compared with those in healthy individuals. Of the three subgroups of Localized Scleroderma, patients with generalized morphoea had the highest levels of serum sCD23. The frequency of IgM antihistone antibody (AHA) and IgM rheumatoid factor (RF), the number of linear lesions, and the frequency of muscle involvement were significantly higher in patients with elevated sCD23 levels than in those with normal levels of sCD23. A significant correlation between the serum sCD23 level and the number of involved areas of the body was observed. Our data suggest that the activation of virgin B cells, which is reflected by elevated sCD23 levels, is closely associated with the production of IgM autoantibodies in Localized Scleroderma and furthermore that the serum levels of sCD23 are a new serological indicator of the severity of Localized Scleroderma.
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Autoantibodies to mitochondrial 2-oxo-acid dehydrogenase complexes in Localized Scleroderma
Clinical & Experimental Immunology, 1996Co-Authors: Manabu Fujimoto, Shinichi Sato, Hironobu Ihn, T. Tamaki, Kanako Kikuchi, Yoshinao Soma, Kunihiko TamakiAbstract:Sera from patients with Localized Scleroderma frequently produce cytoplasmic staining by indirect immunofluorescence, although the antigen remains to be determined. We studied the prevalence, antigen specificity and associated clinical characteristics of anti-cytoplasmic antibodies in Localized Scleroderma. Serum samples from 60 patients with Localized Scleroderma were examined by indirect immunofluorescence analysis and immunoblotting. By immunofluorescence analysis on HEp-2 cell substrate, seven of 60 (12%) patients were shown to be positive for anti-cytoplasmic antibodies. Among these, six patients with generalized morphea had anti-mitochondrial antibodies as shown by immunoblotting: they showed reactivity with the E2 component of pyruvate dehydrogenase complex (PDC), with protein X, and with the E2 component of α-oxo-glutarate dehydrogenase complex, while two of them showed reactivity with PDC-E1α. One of these patients who was positive for anti-PDC-E1α antibody showed laboratory abnormalities, suggesting the presence of primary biliary cirrhosis. The age of disease onset was significantly higher in these six patients than in those without anti-mitochondrial antibodies. Furthermore, five of them were classified into generalized morphea with multiple plaque lesions but without linear lesions (multiple plaque type). These observations suggest that major antigens for anti-cytoplasmic antibodies in patients with Localized Scleroderma are mitochondrial enzymes, 2-oxo-acid dehydrogenase complexes. Patients with anti-mitochondrial antibodies may comprise a unique subset of Localized Scleroderma designated multiple plaque type of generalized morphea of older onset.
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ANTIGEN SPECIFICITY OF ANTIHISTONE ANTIBODIES IN Localized Scleroderma
Archives of dermatology, 1994Co-Authors: Shinichi Sato, Hironobu Ihn, Kanako Kikuchi, Manabu Fujimoto, Kazuhiko TakeharaAbstract:Background and Design: Recently, we detected antihistone antibodies (AHAs) in patients with Localized Scleroderma. However, the exact antigen specificity of AHAs in this disease is still unknown. Therefore, we determined the reactivity of AHAs with five individual histones and the correlation of AHAs with rheumatoid factor in Localized Scleroderma by means of enzyme-linked immunosorbent assay. Twenty patients with Localized Scleroderma who had IgG and/or IgM AHAs, as determined by enzyme-linked immunosorbent assay, were examined. These patients were classified into the following three subgroups: patients with generalized morphea (n=11), patients with linear Scleroderma (n=6), and patients with morphea (n=3). Results: In generalized morphea, IgG AHAs strongly reacted with histones H1, H2A, and H2B; and IgM AHAs strongly reacted with HI and H2B, as determined by means of enzyme-linked immunosorbent assay. The pattern of reactivity in linear Scleroderma and morphea was similar to that in generalized morphea. A homogeneous immunofluorescent pattern on HEp-2 cells, which was produced by Localized Scleroderma sera, was completely abolished by absorption with total histones. By employing a latex agglutination test, IgM rheumatoid factor was detected in 60% of the 20 patients with Localized Scleroderma and at a frequency of 82% in those with generalized morphea. However, an absorption test of rheumatoid factor activity with human IgG revealed no cross-reactivity of AHAs with rheumatoid factor. Conclusions: Our data suggest that AHAs in Localized Scleroderma are directed against native chromatin, since H1, H2A, and H2B occupy a relatively exposed portion of chromatin. (Arch Dermatol. 1994;130:1273-1277)
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Increased levels of circulating intercellular adhesion molecule-1 in patients with Localized Scleroderma
Journal of the American Academy of Dermatology, 1994Co-Authors: Hironobu Ihn, Shinichi Sato, Kanako Kikuchi, Manabu Fujimoto, Atsuyuki Igarashi, Yoshinao Soma, Kazuhiko TakeharaAbstract:Background: Intercellular adhesion molecule-1 (ICAM-1) is important in immune-mediated mechanisms, and its circulating form (cICAM-1) may be an indicator of immune activation. Localized Scleroderma is accompanied by various immunologic abnormalities. Objective: We investigated whether the serum level of cICAM-1 in patients with Localized Scleroderma was elevated and was correlated with the clinical or serologic features of this disease. Methods: Serum cICAM-1 levels were determined by an enzyme-linked immunosorbent assay in 48 patients with Localized Scleroderma, in 20 patients with systemic sclerosis, and in 20 healthy control subjects. Results: Serum levels of cICAM-1 were significantly higher in patients with Localized Scleroderma than in the healthy control subjects. These levels correlated with the number of lesions, the number of involved areas, levels of antihistone antibody IgM, and levels of soluble interleukin 2 receptor. Conclusion: The results suggest that immune activation may be a factor in Localized Scleroderma.
