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scleroderma and skin and treatment

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https://www.readbyqxmd.com/read/29336866/regulatory-mechanisms-of-collagen-expression-by-interleukin-22-signaling-in-scleroderma-fibroblasts
#1
Soichiro Sawamura, Masatoshi Jinnin, Kuniko Inoue, Keitaro Yamane, Noritoshi Honda, Ikko Kajihara, Takamitsu Makino, Shinichi Masuguchi, Satoshi Fukushima, Hironobu Ihn
BACKGROUND: Various cytokines have been indicated to be involved in the pathogenesis of systemic sclerosis (SSc). IL-22 is one of the member of IL-10 cytokine family, and several studies have implicated IL-22 signaling in the pathogenesis of autoimmune diseases. OBJECTIVES: To clarify the role of IL-22 in the regulatory mechanism of ECM expression and to determine the contribution of IL-22 to the phenotype of SSc. METHODS: The effect of IL-22 on ECM expression in normal fibroblasts was determined by using PCR array, real-time PCR and immunoblotting...
December 29, 2017: Journal of Dermatological Science
https://www.readbyqxmd.com/read/29324934/stem-cells-therapy-the-future-in-the-management-of-systemic-sclerosis-a-case-report
#2
Jung In Song, Silvanie Volz, Maria Eirini Liodaki, Peter Mailänder, Konstantinos Kalousis
OBJECTIVE: Systemic sclerosis (SSc) is a connective tissue disorder of unknown etiology, with heterogeneous clinical manifestations and chronic and often progressive course. The diffuse cutaneous form of SSc (dcSSc) is characterized by thickening of the skin (scleroderma) and distinctive involvement of multiple internal organs. Patients with limited cutaneous SSc (lcSSc) generally have long-standing Raynaud's phenomenon before other manifestations of SSc appear. Over the last decade the Interest of adipose-derived cell therapy in regenerative medicine has increased continuously...
September 2017: Hellenic Journal of Nuclear Medicine
https://www.readbyqxmd.com/read/29321259/plasmacytoid-dendritic-cells-promote-systemic-sclerosis-with-a-key-role-for-tlr8
#3
Marie Dominique Ah Kioon, Claudio Tripodo, David Fernandez, Kyriakos A Kirou, Robert F Spiera, Mary K Crow, Jessica K Gordon, Franck J Barrat
Systemic sclerosis (SSc) is a multisystem life-threatening fibrosing disorder that lacks effective treatment. The link between the inflammation observed in organs such as the skin and profibrotic mechanisms is not well understood. The plasmacytoid dendritic cell (pDC) is a key cell type mediating Toll-like receptor (TLR)-induced inflammation in autoimmune disease patients, including lupus and skin diseases with interface dermatitis. However, the role of pDCs in fibrosis is less clear. We show that pDCs infiltrate the skin of SSc patients and are chronically activated, leading to secretion of interferon-α (IFN-α) and CXCL4, which are both hallmarks of the disease...
January 10, 2018: Science Translational Medicine
https://www.readbyqxmd.com/read/29316366/impact-of-radiation-therapy-on-scleroderma-and-cancer-outcomes-in-scleroderma-patients-with-breast-cancer
#4
Dhaval J Shah, Ram Hirpara, Corrie L Poelman, Adrianne Woods, Laura K Hummers, Fredrick M Wigley, Jean L Wright, Arti Parekh, Virginia D Steen, Robyn T Domsic, Ami A Shah
OBJECTIVES: We examined SSc patients with breast cancer to 1) identify the prevalence of radiation complications and 2) examine SSc outcomes in SSc patients who received radiation therapy (RT) as part of their cancer treatment. METHODS: Patients with SSc and breast cancer were identified from the Johns Hopkins and University of Pittsburgh Scleroderma Center databases. We examined whether erythema, blistering, ulceration, or thickening of the skin developed in the RT port...
January 5, 2018: Arthritis Care & Research
https://www.readbyqxmd.com/read/29298160/myeloablative-autologous-stem-cell-transplantation-for-severe-scleroderma
#5
RANDOMIZED CONTROLLED TRIAL
Keith M Sullivan, Ellen A Goldmuntz, Lynette Keyes-Elstein, Peter A McSweeney, Ashley Pinckney, Beverly Welch, Maureen D Mayes, Richard A Nash, Leslie J Crofford, Barry Eggleston, Sharon Castina, Linda M Griffith, Julia S Goldstein, Dennis Wallace, Oana Craciunescu, Dinesh Khanna, Rodney J Folz, Jonathan Goldin, E William St Clair, James R Seibold, Kristine Phillips, Shin Mineishi, Robert W Simms, Karen Ballen, Mark H Wener, George E Georges, Shelly Heimfeld, Chitra Hosing, Stephen Forman, Suzanne Kafaja, Richard M Silver, Leroy Griffing, Jan Storek, Sharon LeClercq, Richard Brasington, Mary E Csuka, Christopher Bredeson, Carolyn Keever-Taylor, Robyn T Domsic, M Bashar Kahaleh, Thomas Medsger, Daniel E Furst
BACKGROUND: Despite current therapies, diffuse cutaneous systemic sclerosis (scleroderma) often has a devastating outcome. We compared myeloablative CD34+ selected autologous hematopoietic stem-cell transplantation with immunosuppression by means of 12 monthly infusions of cyclophosphamide in patients with scleroderma. METHODS: We randomly assigned adults (18 to 69 years of age) with severe scleroderma to undergo myeloablative autologous stem-cell transplantation (36 participants) or to receive cyclophosphamide (39 participants)...
January 4, 2018: New England Journal of Medicine
https://www.readbyqxmd.com/read/29297205/cyclophosphamide-for-connective-tissue-disease-associated-interstitial-lung-disease
#6
REVIEW
Hayley Barnes, Anne E Holland, Glen P Westall, Nicole Sl Goh, Ian N Glaspole
BACKGROUND: Approximately one-third of individuals with interstitial lung disease (ILD) have associated connective tissue disease (CTD). The connective tissue disorders most commonly associated with ILD include scleroderma/systemic sclerosis (SSc), rheumatoid arthritis, polymyositis/dermatomyositis, and Sjögren's syndrome. Although many people with CTD-ILD do not develop progressive lung disease, a significant proportion do progress, leading to reduced physical function, decreased quality of life, and death...
January 3, 2018: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/29248149/morphea-in-childhood-an-update
#7
B Aranegui, J Jiménez-Reyes
Morphea is an inflammatory, fibrosing skin disorder. When it occurs in childhood, it is also known as localized juvenile scleroderma. It is more common in girls and typically appears around the age of 5 to 7 years. According to a recent classification system, morphea is divided into 5 types: circumscribed (plaque), linear, generalized, pansclerotic, and mixed. Approximately 40% of patients present extracutaneous manifestations. Childhood morphea is treated with phototherapy, oral or topical calcitriol, topical tacrolimus 0...
December 13, 2017: Actas Dermo-sifiliográficas
https://www.readbyqxmd.com/read/29207307/systemic-sclerosis-clinical-manifestations-anesthetic-and-orthopedic-considerations-in-a-patient
#8
Obada Hasan, Muneeba Jessar, Muhammad Ashar, Shahryar Noordin, Tashfeen Ahmad
INTRODUCTION: Systemic sclerosis is a rare and progressive multisystem autoimmune disorder that is characterized pathologically by vascular abnormalities, connective tissue sclerosis and atrophy of skin and various internal organs (e.g., alimentary tract, lungs, heart, kidney, CNS), and autoantibodies. With an unknown etiology, Scleroderma is a complex polygenetic disease. A recent Genome Wide Association Study (GWAS) confirmed a strong association with the Major Histocompatibility Complex (MHC) and autoimmunity...
December 2, 2017: International Journal of Surgery Case Reports
https://www.readbyqxmd.com/read/29196283/ringed-telangiectasias-an-unusual-presentation-of-telangiectasia-macularis-eruptiva-perstans
#9
Laila Siddique, Hadjh Ahrns, Elizabeth Seiverling
Telangiectasia macularis eruptiva perstans (TMEP) is a rare form of cutaneous mastocytosis. While most cutaneous mastocytoses occur in children and are asymptomatic, TMEP occurs predominantly in adults and is associated with systemic manifestations, requiring medical management. TMEP is typically characterised by scattered red-brown macules on the trunk and extremities, but must be differentiated from other telangiectatic conditions such as scleroderma, hereditary haemorrhagic telangiectasia and telangiectasias secondary to cirrhosis...
November 30, 2017: BMJ Case Reports
https://www.readbyqxmd.com/read/29196241/scleroderma-skin-ulcers-definition-classification-and-treatment-strategies-our-experience-and-review-of-the-literature
#10
REVIEW
Dilia Giuggioli, Andreina Manfredi, Lumetti Federica, Colaci Michele, Clodoveo Ferri
BACKGROUND: Skin ulcers (SU) are one of the most frequent manifestations of systemic sclerosis (SSc). SSc-SU are very painful, often persistent and recurrent; they may lead to marked impairment of patient's activities and quality of life. Despite their severe impact on the whole SSc patient's management, the proposed definition, classification criteria, and therapeutic strategies of SSc-SU are still controversial. OBJECTIVE: The present study aimed to elaborate a comprehensive proposal of definition, classification, and therapeutic strategy of SSc-SU on the basis of our long-term single center experience along with a careful revision of the world literature on the same topic...
November 28, 2017: Autoimmunity Reviews
https://www.readbyqxmd.com/read/29151520/dropped-head-syndrome-and-the-presence-of-rimmed-vacuoles-in-a-muscle-biopsy-in-scleroderma-polymyositis-overlap-syndrome-associated-with-anti-ku-antibody
#11
Yoshida Takeshi, Yoshida Mai, Mitsuyo Kinjo, Jonosono Manabu, Higuchi Itsuro
A 66-year-old woman with a history of interstitial lung disease presented with a 3-month history of dropped head syndrome (DHS), followed by camptocormia and extremity weakness. A clinical examination revealed Raynaud phenomenon, arthralgia, distal skin sclerosis, and microbleeds in the nailfold capillaries. An anti-Ku antibody test was positive. A muscle biopsy revealed inflammatory myopathy with rimmed vacuoles (RVs). The diagnosis of scleroderma-polymyositis (SSc-PM) overlap syndrome was made. RVs on a muscle biopsy in a patient with inflammatory myositis involving axial muscles may be seen either in inclusion body myositis or SSc-PM overlap syndrome...
November 20, 2017: Internal Medicine
https://www.readbyqxmd.com/read/29121455/bench-to-bedside-and-back-again-finding-the-goldilocks-zone-within-the-scleroderma-universe
#12
EDITORIAL
Janet E Pope, Jason J Lee, Christopher P Denton
Systemic sclerosis (SSc) is a complex inflammatory connective tissue disease characterized by skin thickening, organ fibrosis and vasculopathy [1, 2]. The underlying disease mechanisms and pathophysiology are not fully understood. However, it appears to be, at least in part, driven by autoimmunity and inflammation associated with microvascular dysfunction ultimately resulting in excess extracellular matrix deposition in target organs [2-4]. Clinical heterogeneity coupled with our lack of understanding of the disease pathogenesis means that current treatment strategies are mostly organ based therapies using anti-rheumatic drugs that were originally approved for other indications [5]...
November 9, 2017: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/29120857/the-safety-and-efficacy-of-light-emitting-diodes-based-ultraviolet-a1-phototherapy-in-bleomycin-induced-scleroderma-in-mice
#13
Diana Karpec, Romualdas Rudys, Laima Leonaviciene, Zygmunt Mackiewicz, Ruta Bradunaite, Gailute Kirdaite, Algirdas Venalis
PURPOSE: To define the efficacy and safety of narrowband ultraviolet A1 (UVA1) for the treatment of dermal fibrosis in bleomycin-induced mouse model of scleroderma. MATERIALS AND METHODS: 42 DBA/2 strain mice were included in the study: healthy mice and mice with established scleroderma, treated with high or medium dose of UVA1. Non-treated groups served as control. The equipment emitting 365±5nm UVA1 radiation was used in the study. The average cumulative doses were 1200J/cm2 for high and 600J/cm2 for medium dose course...
November 6, 2017: Advances in Medical Sciences
https://www.readbyqxmd.com/read/29104809/mycobacterium-intracellulare-infection-mimicking-progression-of-scleroderma
#14
Simon Krabbe, Merete Engelhart, Sören Thybo, Søren Jacobsen
This case report describes a patient with scleroderma who developed Mycobacterium intracellulare infection, which for more than a year mimicked worsening of her connective tissue disorder. The patient was diagnosed with scleroderma based on puffy fingers that developed into sclerodactyly, abnormal nail fold capillaries, interstitial lung disease, Raynaud's phenomenon, esophageal dysmotility, and positivity for rheumatoid factor and anti-SSA antibodies. She developed massive inflammatory changes of the cutis, the subcutis, and the muscle fasciae of the right leg, that after several failed attempts of immunosuppressive treatments were found to be caused by Mycobacterium intracellulare...
2017: Case Reports in Rheumatology
https://www.readbyqxmd.com/read/29093152/pomalidomide-in-patients-with-interstitial-lung-disease-due-to-systemic-sclerosis-a-phase-ii-multicenter-randomized-double-blind-placebo-controlled-parallel-group-study
#15
Vivien M Hsu, Christopher P Denton, Robyn T Domsic, Daniel E Furst, Maureen Rischmueller, Marina Stanislav, Virginia D Steen, Jörg H W Distler, Shimon Korish, Alyse Cooper, Suktae Choi, Peter H Schafer, Gerald Horan, Douglas R Hough
OBJECTIVE: To evaluate the safety and efficacy of pomalidomide (POM) on forced vital capacity (FVC), modified Rodnan skin score (mRSS), and gastrointestinal (GI) symptomatology over 52 weeks of treatment in patients with interstitial lung disease due to systemic sclerosis (SSc). METHODS: Twenty-three adult patients diagnosed with SSc were randomized 1:1 POM:placebo (PBO). RESULTS: Mean change at Week 52 from baseline in predicted FVC% -5.2 and -2...
November 1, 2017: Journal of Rheumatology
https://www.readbyqxmd.com/read/29065190/discovery-and-pharmacological-characterization-of-a-new-class-of-prolyl-trna-synthetase-inhibitor-for-anti-fibrosis-therapy
#16
Akira Shibata, Masako Kuno, Ryutaro Adachi, Yosuke Sato, Harumi Hattori, Atsushi Matsuda, Yuumi Okuzono, Keiko Igaki, Yusuke Tominari, Terufumi Takagi, Masato Yabuki, Masanori Okaniwa
Scleroderma has clinical characteristics including skin and other tissue fibrosis, but there is an unmet need for anti-fibrotic therapy. Halofuginone (HF) is a well-known anti-fibrosis agent in preclinical and clinical studies which exerts its effect via inhibition of TGF-β/Smad3 signaling pathway. Recently, prolyl-tRNA synthetase (PRS) was elucidated as a target protein for HF that binds to the proline binding site of the catalytic domain of PRS. Here, we characterized a new class of PRS inhibitor (T-3833261) that is carefully designed in a way that binds to the ATP site of the catalytic domain and does not disrupt binding of proline...
2017: PloS One
https://www.readbyqxmd.com/read/29058626/combined-platelet-rich-plasma-and-lipofilling-treatment-provides-great-improvement-in-facial-skin-induced-lesion-regeneration-for-scleroderma-patients
#17
Francesco Virzì, Paola Bianca, Alessandro Giammona, Tiziana Apuzzo, Simone Di Franco, Laura Rosa Mangiapane, Maria Luisa Colorito, Dario Catalano, Emanuela Scavo, Annalisa Nicotra, Antonina Benfante, Giuseppe Pistone, Valentina Caputo, Francesco Dieli, Roberto Pirrello, Giorgio Stassi
BACKGROUND: The use of stem cells, including mesenchymal stem cells (MSCs), for regenerative medicine is gaining interest for the clinical benefits so far obtained in patients. This study investigates the use of adipose autologous tissue in combination with platelet-rich plasma (PRP) to improve the clinical outcome of patients affected by systemic sclerosis (SSc). METHODS: Adipose-derived mesenchymal stem cells (AD-MSCs) and PRPs were purified from healthy donors and SSc patients...
October 23, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28980909/tocilizumab-in-two-children-with-pansclerotic-morphoea-a-hopeful-therapy-for-refractory-cases
#18
Giorgia Martini, Simona Campus, Bernd Raffeiner, Gianluca Boscarol, Alessandra Meneghel, Francesco Zulian
Pansclerotic morphoea (PM) is a subtype of juvenile localised scleroderma characterised by severe course with generalised full-thickness skin involvement and possible growth and functional impairment. PM treatment comprises a combination of immunosuppressive agents such as corticosteroids, methotrexate, mycophenolate mofetil, PUVA and antithymocyte globulin and biological agents used in off-label. A possible role of IL-6 in the regulation of firoblast differentiation and stimulation of collagen synthesis has been suggested and in patients with systemic sclerosis (SSc) the treatment with tocilizumab (TCZ) was associated to improvement of skin thickness and joint motion...
September 2017: Clinical and Experimental Rheumatology
https://www.readbyqxmd.com/read/28980901/long-term-treatment-of-scleroderma-related-digital-ulcers-with-iloprost-a-cohort-study
#19
Michele Colaci, Federica Lumetti, Dilia Giuggioli, Serena Guiducci, Silvia Bellando-Randone, Ginevra Fiori, Marco Matucci-Cerinic, Clodoveo Ferri
OBJECTIVES: Raynaud's phenomenon and chronic/recurrent digital ulcers (DU) are main features of systemic sclerosis (SSc). Their treatment includes both systemic (i.e., iloprost) and local therapies. We report the therapeutic effects of iloprost in a cohort of SSc patients during a long-lasting follow-up period. METHODS: Fifty consecutive SSc patients (M/F 7/43, age at SSc diagnosis 43.5±12.7SD years) received iloprost infusions for 10±4.2SD years. Iloprost schedule consisted in monthly infusion at 0...
September 2017: Clinical and Experimental Rheumatology
https://www.readbyqxmd.com/read/28955239/searching-novel-therapeutic-targets-for-scleroderma-p2x7-receptor-is-up-regulated-and-promotes-a-fibrogenic-phenotype-in-systemic-sclerosis-fibroblasts
#20
Daniela Gentile, Pietro E Lazzerini, Alessandra Gamberucci, Mariarita Natale, Enrico Selvi, Francesca Vanni, Alessandra Alì, Paolo Taddeucci, Silvia Del-Ry, Manuela Cabiati, Veronica Della-Latta, David J Abraham, Maria A Morales, Rosella Fulceri, Franco Laghi-Pasini, Pier L Capecchi
Objectives: Systemic sclerosis (SSc) is a connective tissue disorder presenting fibrosis of the skin and internal organs, for which no effective treatments are currently available. Increasing evidence indicates that the P2X7 receptor (P2X7R), a nucleotide-gated ionotropic channel primarily involved in the inflammatory response, may also have a key role in the development of tissue fibrosis in different body districts. This study was aimed at investigating P2X7R expression and function in promoting a fibrogenic phenotype in dermal fibroblasts from SSc patients, also analyzing putative underlying mechanistic pathways...
2017: Frontiers in Pharmacology
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