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1.
Isr Med Assoc J ; 22(2): 104-110, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32043328

RESUMO

BACKGROUND: Autologous hematological stem cell transplantation (HSCT) is a novel therapy for systemic sclerosis (SSc) that has been validated in three randomized controlled trials. OBJECTIVES: To report the first Israeli experience with HSCT for progressive SSc and review the current literature. METHODS: Five SSc patients who were evaluated in our department and were treated by HSCT were included. Medical records were evaluated retrospectively. Demographic, clinical, and laboratory data were recorded. Continuous data are presented as the mean ± standard deviation. Categorical variables are presented as frequencies and percentages. RESULTS: Five SSc patients were treated with HSCT. Four patients were adults (mean age 53 ± 12 years) and one was a 12-year-old pediatric patient. All patients were female. HSCT was initiated 1.4 ± 0.8 years after diagnosis. Two patients were RNA POLIII positive, two were anti-topoisomerase 1 positive, and one only antinuclear antibodies positive. All patients had skin and lung involvement. The mean modified Rodnan Skin Score was 29 ± 4.7 before HSCT, which improved to 10.4 ± 9.6 after HSCT. The forced vital capacity improved from 68 ± 13% to 90 ± 28%. Diffusing capacity of the lungs for carbon monoxide increased by 6%. Among severe adverse events were cyclophosphamide-related congestive heart failure, antithymocyte globulin-related capillary leak syndrome, and scleroderma renal crisis. All symptoms completely resolved with treatment without sequela. No treatment related mortality was recorded. CONCLUSIONS: HSCT is an important step in the treatment of progressive SSc in Israel. Careful patient selection reduces treatment related morbidity and mortality.


Assuntos
Ciclofosfamida , Transplante de Células-Tronco Hematopoéticas , Escleroderma Sistêmico , Adulto , Autoanticorpos/sangue , Autoanticorpos/classificação , Criança , Ciclofosfamida/administração & dosagem , Ciclofosfamida/efeitos adversos , Feminino , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Imunossupressores/administração & dosagem , Imunossupressores/efeitos adversos , Israel/epidemiologia , Pulmão/patologia , Monitorização Fisiológica/métodos , Testes de Função Respiratória/métodos , Estudos Retrospectivos , Escleroderma Sistêmico/diagnóstico , Escleroderma Sistêmico/epidemiologia , Escleroderma Sistêmico/imunologia , Escleroderma Sistêmico/terapia , Pele/patologia , Transplante Autólogo
2.
Internist (Berl) ; 60(12): 1251-1269, 2019 Dec.
Artigo em Alemão | MEDLINE | ID: mdl-31754753

RESUMO

Systemic sclerosis (SSc) is a rare fibrosing rheumatic multi-systemic disease involving many medical specialties. The mortality of SSc is determined by lung fibrosis, pulmonary arterial hypertension and cardiac involvement. With early and intensive treatment, the disease can be stabilized and symptoms relieved. This review summarizes insights into pathophysiology, disease classification, clinical manifestations and successful therapies, as well as recent studies on new immunosuppressant, biological and vasoactive therapies.


Assuntos
Hipertensão Pulmonar/fisiopatologia , Fibrose Pulmonar/fisiopatologia , Escleroderma Sistêmico/fisiopatologia , Humanos , Hipertensão Pulmonar/etiologia , Imunossupressores/uso terapêutico , Doenças Pulmonares Intersticiais/etiologia , Fibrose Pulmonar/etiologia , Escleroderma Sistêmico/complicações , Escleroderma Sistêmico/terapia
3.
Clin Exp Rheumatol ; 37 Suppl 119(4): 3-14, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31587697

RESUMO

Systemic sclerosis (SSc) is a complex disorder characterised by the involvement of small arteries, microvessels and connective tissue, with deposition of fibrotic tissue and microvascular obliteration in the skin and internal organs. Due to the multifaceted nature of the disease, several articles are published in the medical literature every year, aimed at exploring different aspects of the pathogenesis, internal organ involvement and clinical aspects, and possible therapeutic approaches. In this article we have reviewed the literature on SSc of the past year, with the aim of identifying novel approaches that may help the treating physician in the clinical management of patients.


Assuntos
Microvasos/patologia , Escleroderma Sistêmico , Vasos Sanguíneos/patologia , Fibrose , Humanos , Escleroderma Sistêmico/fisiopatologia , Escleroderma Sistêmico/terapia , Pele
4.
Lakartidningen ; 1162019 Sep 26.
Artigo em Sueco | MEDLINE | ID: mdl-31573670

RESUMO

Systemic sclerosis is an autoimmune systemic disease with an annual incidence in Sweden of only 20 cases per million and a standardised mortality rate of 3-4. Disease onset is usually preceded by a period with Raynaud's phenomenon, combined with structurally abnormal nailbed capillaries and accompanied by presence of scleroderma related autoantibodies. The presenting symptoms are skin thickness, puffy fingers, digital ulcers, dysphagia, joint stiffness and pain, and pruritus. Optimal management involves a number of specialists including allied health professionals. Early recognition, diagnosis and treatment are important. The dominating causes of death are cardiopulmonary.


Assuntos
Escleroderma Sistêmico , Autoanticorpos/imunologia , Humanos , Atenção Primária à Saúde , Doenças Raras/complicações , Doenças Raras/diagnóstico , Doenças Raras/patologia , Doenças Raras/terapia , Doença de Raynaud/etiologia , Encaminhamento e Consulta , Escleroderma Sistêmico/complicações , Escleroderma Sistêmico/diagnóstico , Escleroderma Sistêmico/patologia , Escleroderma Sistêmico/terapia
5.
Int J Mol Sci ; 20(18)2019 09 04.
Artigo em Inglês | MEDLINE | ID: mdl-31487964

RESUMO

: Systemic sclerosis (SSc) is a rare autoimmune disease, characterized by vasculopathy and fibrosis of the skin and internal organs. This disease is still considered incurable and is associated with a high risk of mortality, which is related to fibrotic events. An early diagnosis is useful for preventing complications, and targeted therapies reduce disease progression and ameliorate patients' quality of life. Nevertheless, there are no validated biomarkers for early diagnosis with predictive prognostic value. Exosomes are membrane vesicles, transporting proteins and nucleic acids that may be delivered to target cells, which influences cellular behavior. They play important roles in cell-cell communication, both in physiological and pathological conditions, and may be useful as circulating biomarkers. Recent evidences suggest a role for these microvesicles in the three main aspects related to the pathogenesis of SSc (immunity, vascular damage, and fibrosis). Moreover, exosomes are of particular interest in the field of nano-delivery and are used as biological carriers. In this review, we report the latest information concerning SSc pathogenesis, clinical aspects of SSc, and current approaches to the treatment of SSc. Furthermore, we indicate a possible role of exosomes in SSc pathogenesis and suggest their potential use as diagnostic and prognostic biomarkers, as well as therapeutic tools.


Assuntos
Exossomos/metabolismo , Escleroderma Sistêmico/metabolismo , Animais , Exossomos/genética , Fibroblastos/metabolismo , Fibroblastos/patologia , Humanos , Linfócitos/imunologia , MicroRNAs/genética , MicroRNAs/metabolismo , Escleroderma Sistêmico/imunologia , Escleroderma Sistêmico/patologia , Escleroderma Sistêmico/terapia , Transdução de Sinais
6.
Hautarzt ; 70(9): 723-741, 2019 Sep.
Artigo em Alemão | MEDLINE | ID: mdl-31384958

RESUMO

Systemic sclerosis is a rare rheumatologic disease that is characterised by skin and organ fibrosis as well as vascular changes and the occurrence of specific autoantibodies. It has a high morbidity and mortality while its manifestations show significant heterogeneity in patients. Thus, diagnosis and follow-up of patients with systemic sclerosis has to be extensive, the more so because treatment must be adapted to organ manifestations. Although specific therapies for gastrointestinal, pulmonary or vascular complications exist, patients respond only partly to these and new therapeutic approaches are still needed.


Assuntos
Escleroderma Sistêmico , Autoanticorpos , Fibrose , Humanos , Escleroderma Sistêmico/diagnóstico , Escleroderma Sistêmico/terapia , Pele
7.
BioDrugs ; 33(4): 401-409, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31302863

RESUMO

Three prospective controlled clinical trials and numerous small series and case reports have confirmed that durable, drug-free remission in systemic sclerosis is possible via an autologous hematopoietic stem cell transplantation. Similar results have been seen in other autoimmune diseases. The exact mechanism by which this immune "reset" was achieved in some but not all cases remains elusive, but includes major reduction of autoreactive immune competent cells, re-establishment of T- and B cell regulatory networks and normalization of tissue niche function, particularly vascular. Some aspects regarding mobilization, conditioning and graft manipulation still remain open, but clearly a significant toxicity is associated with all effective regimens at present, and therefore patient selection remains a key issue. In the hematology/oncology arena, major efforts are being made to reduce genotoxic and other collateral toxicity induced by current mobilization and conditioning protocols, which may also translate to autoimmune disease. These include developments in rapid mobilization and antibody drug conjugate conditioning technology. If effective, such low-toxicity regimens might be applied to autoimmune disease at an earlier stage before chronicity of autoimmunity has been established, thus changing the therapeutic paradigm.


Assuntos
Doença Enxerto-Hospedeiro/prevenção & controle , Transplante de Células-Tronco Hematopoéticas/métodos , Imunoconjugados/uso terapêutico , Escleroderma Sistêmico/terapia , Condicionamento Pré-Transplante/métodos , Ensaios Clínicos Controlados como Assunto , Doença Enxerto-Hospedeiro/imunologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Estudos Prospectivos , Escleroderma Sistêmico/imunologia , Transplante Autólogo/efeitos adversos , Transplante Autólogo/métodos , Transplante Homólogo/efeitos adversos , Transplante Homólogo/métodos , Resultado do Tratamento
8.
Medicine (Baltimore) ; 98(26): e16086, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31261523

RESUMO

Pleuroparenchymal fibroelastosis (PPFE) is a rare new interstitial lung disease (ILD) characterized by the fibrotic thickening of the visceral pleura and subadjacent parenchymal areas of the upper lobes This study reveals that patients with ILD-SSc associated with chest HRCT evidence of PPFE require close and recurrent follow-up with periodic evaluation of lung function parameters, DLCO and chest HRCT. Rheumatologists should be aware of this new radiological finding which is accompanied by a negative prognosis, especially when associated with a progressive course. Patients with this radiological pattern need to be monitored with particular attention.


Assuntos
Doenças Pulmonares Intersticiais/complicações , Doenças Pulmonares Intersticiais/diagnóstico por imagem , Doenças Pleurais/complicações , Doenças Pleurais/diagnóstico por imagem , Escleroderma Sistêmico/complicações , Escleroderma Sistêmico/diagnóstico por imagem , Idoso , Feminino , Seguimentos , Humanos , Pulmão/diagnóstico por imagem , Doenças Pulmonares Intersticiais/terapia , Masculino , Doenças Pleurais/terapia , Prognóstico , Fibrose Pulmonar/complicações , Fibrose Pulmonar/diagnóstico por imagem , Fibrose Pulmonar/terapia , Estudos Retrospectivos , Reumatologistas , Escleroderma Sistêmico/terapia
9.
BMJ Case Rep ; 12(2)2019 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-30824467

RESUMO

Sudden respiratory distress in association with severe weight loss are unusual features of systemic sclerosis (SSc). We report the case of a 56-year-old Caucasian woman with a 9-year history of a diffuse form of SSc who presented with acute stridor due to vocal cord paralysis and required an emergency tracheostomy. She had sought medical attention only after 4 years of disease onset, presenting with a mask-like face, diffuse skin thickening, acro-osteolysis and severe interstitial lung disease. Even though skin tightness improved after immunosuppressive treatment, several spontaneous facial fractures and episodes of dysphagia and choking occurred in the years that followed. At the time of stridor, she was severely malnourished and a percutaneous endoscopic gastrostomy was required for feeding. Permanent vocal cord damage in combination with severe loco-regional bone resorption resulted in severe disability and impaired nutrition. We hereby highlight the features of SSc for which therapy remains challenging.


Assuntos
Reabsorção Óssea/etiologia , Reabsorção Óssea/patologia , Mandíbula/patologia , Escleroderma Sistêmico/complicações , Paralisia das Pregas Vocais/etiologia , Anticorpos Monoclonais Humanizados/uso terapêutico , Reabsorção Óssea/diagnóstico por imagem , Cálcio/uso terapêutico , Diagnóstico Diferencial , Suplementos Nutricionais , Feminino , Humanos , Desnutrição/diagnóstico , Desnutrição/etiologia , Desnutrição/terapia , Mandíbula/diagnóstico por imagem , Pessoa de Meia-Idade , Escleroderma Sistêmico/patologia , Escleroderma Sistêmico/terapia , Tomografia Computadorizada por Raios X , Traqueostomia , Vitamina D/uso terapêutico , Paralisia das Pregas Vocais/terapia
10.
Wounds ; 31(3): 81-84, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30830857

RESUMO

INTRODUCTION: Evidence of the role of hyaluronic acid (HA) in the tissue repair process is extensive. Hyaluronic acid produces a positive effect on skin ulcer healing, so many companies produce it in various topical applications. OBJECTIVE: This retrospective, observational study examined the use of different HA-based products in patients with chronic skin ulcers of various etiologies (vascular, scleroderma, postoperative) to assess the indication, effectiveness, and possible adverse reactions. MATERIALS AND METHODS: A retrospective case review was conducted on 79 patients presenting to the Department of Dermatology of the Spedali Civili (Brescia, Italy) with multiple chronic skin ulcers of the legs of various etiologies. The authors counted a total of 106 chronic wounds with granulating appearance but not responsive to common wound dressings; for this reason, these wounds were treated with a HA-based product. The efficacy of the treatment was evaluated by dividing the population into 2 groups: sclerodermic (41 ulcers) and nonsclerodermic (65 ulcers). RESULTS: Initial results confirmed HA-based products were effective for healing chronic skin wounds. However, when wounds are grouped by etiology, it was evident that patients with sclerodermic ulcers showed a rapid inflammatory response that led to a clinical deterioration and worsening of skin ulcers (92.7%). In contrast, patients with noninflammatory ulcers (vascular, postoperative) had the severe inflammatory event reduced to 1.5%, with a recovery of 98.5%. CONCLUSIONS: The negative effects of HA-based products on a patient with scleroderma could be explained by the fact that HA can produce a proinflammatory effect causing keratinocyte migration.


Assuntos
Ácido Hialurônico/efeitos adversos , Inflamação/induzido quimicamente , Escleroderma Sistêmico/patologia , Úlcera Cutânea/patologia , Cicatrização/efeitos dos fármacos , Adulto , Idoso , Idoso de 80 Anos ou mais , Movimento Celular/efeitos dos fármacos , Contraindicações de Medicamentos , Feminino , Humanos , Ácido Hialurônico/farmacologia , Queratinócitos/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Escleroderma Sistêmico/terapia , Úlcera Cutânea/terapia , Cicatrização/fisiologia
11.
Rheumatol Int ; 39(5): 933-941, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30838436

RESUMO

Disabling pansclerotic morphea of childhood (DPMC) is a rare subtype of juvenile localized scleroderma (JLS) characterized by pansclerosis mainly affecting children under the age of 14. This aggressive disease has a poor prognosis due to the rapid progression of deep musculoskeletal atrophy resulting in cutaneous ulceration and severe joint contractures. We describe the challenges in treating a previously well 5-year-old male who has refractory symptoms of DPMC. Over the 29 months, since his initial presentation, we trialed over ten therapies. There was subjective improvement with prednisolone and mycophenolate mofetil (MMF). However, other therapies including biologics and tyrosine kinase inhibitors (TKI) were ineffective. The patient has been referred for hematopoietic stem cell transplant given ongoing disease progression. We conducted a literature search focusing on English articles with keywords including DPMC. Publications with limited information or describing cases aged 20 and above were excluded. Thirty-seven case reports were identified and the reported treatments were evaluated. Methotrexate and corticosteroids have been the most commonly utilized. MMF has been anecdotally effective. Biologics, TKI, and Janus kinase inhibitors lack evidence in DPMC, but have had demonstrated efficacy in similar pathologies including systemic sclerosis, and, thus, have been used for DPMC. Phototherapy has been documented to be reducing skin thickness and stiffness of plaques. Eventually, most children require multi-modal and high-dose immunosuppressive therapies to reduce the inflammation inflicted by the disease. Long-term antibiotics and nutritional support are important in the ongoing care of these patients.


Assuntos
Esclerodermia Localizada/terapia , Escleroderma Sistêmico/terapia , Antirreumáticos/uso terapêutico , Produtos Biológicos/uso terapêutico , Biópsia , Pré-Escolar , Contratura/fisiopatologia , Edema/fisiopatologia , Transplante de Células-Tronco Hematopoéticas , Humanos , Hidroxicloroquina/uso terapêutico , Imunoglobulinas Intravenosas/uso terapêutico , Fatores Imunológicos/uso terapêutico , Imunossupressores/uso terapêutico , Inibidores de Janus Quinases/uso terapêutico , Masculino , Metilprednisolona/uso terapêutico , Ácido Micofenólico/uso terapêutico , Prednisolona/uso terapêutico , Inibidores de Proteínas Quinases/uso terapêutico , Esclerodermia Localizada/diagnóstico , Esclerodermia Localizada/patologia , Esclerodermia Localizada/fisiopatologia , Escleroderma Sistêmico/diagnóstico , Escleroderma Sistêmico/patologia , Escleroderma Sistêmico/fisiopatologia , Pele/patologia , Sinovite/fisiopatologia , Falha de Tratamento , Resultado do Tratamento
12.
PLoS One ; 14(3): e0213444, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30861018

RESUMO

OBJECTIVES: To evaluate interstitial lung disease associated with systemic sclerosis (SSc-ILD) and its changes during treatment by using quantitative analysis (QA) compared to semi-quantitative analysis (semiQA) of chest computed tomography (CT) scans. To assess the prognostic value of QA in predicting functional changes. MATERIALS AND METHODS: We retrospectively selected 35 consecutive patients with SSc-ILD with complete pulmonary functional evaluation, Doppler-echocardiography, immunological tests, and chest CT scan at both baseline and follow-up after immunosuppressive therapy. CT images were analyzed by two chest radiologists for semiQA and by a computational platform for texture analysis of ILD patterns (CALIPER) for QA. Concordance between semiQA and QA was tested. Traction bronchiectasis severity was scored. Analysis of ROC curves was performed. RESULTS: Seventy CT scans were analyzed and QA failed in 4/70 scans. Thus, the final population included 31/35 patients (51.3±12.1 years). QA had a weak-to-good concordance with semiQA (ICC reticular:0.275; ICC ground-glass:0.667) and QA correlated better than semiQA (r = -0.3 to -0.74 vs r = -0.3 to -0.4) with functional parameters. Both methods correlated with traction bronchiectases score and pulmonary artery diameter at CT. A pulmonary artery diameter ≥29mm distinguished patients with lower lung volumes and ILD extent greater than 39% (p<0.001). Changes in QA patterns during treatment were not accurate (AUC: 0.50 to 0.70; p>0.05) in predicting disease progression as assessed by functional parameters, whereas variation in total lung volume at QA accurately predicted changes in the composite functional respiratory endpoint with FVC% and DLco% (AUC = 0.74; 95%CI: 0.54 to 0.93; p = 0.03). CONCLUSIONS: Pulmonary QA of CT images can objectively quantify specific patterns of ILD changes during treatment in patients with SSc-ILD. Changes in QA patterns do not correlate with functional changes, but variation in total lung volume at QA accurately predicted changes in the composite functional respiratory endpoint with FVC% and DLco%. Pulmonary artery diameter at CT reflects the interstitial involvement, identifying patients with more severe prognosis.


Assuntos
Doenças Pulmonares Intersticiais/diagnóstico por imagem , Escleroderma Sistêmico/diagnóstico por imagem , Adulto , Bronquiectasia/diagnóstico por imagem , Feminino , Humanos , Estudos Longitudinais , Doenças Pulmonares Intersticiais/fisiopatologia , Doenças Pulmonares Intersticiais/terapia , Masculino , Pessoa de Meia-Idade , Prognóstico , Artéria Pulmonar/diagnóstico por imagem , Interpretação de Imagem Radiográfica Assistida por Computador , Testes de Função Respiratória , Estudos Retrospectivos , Rituximab/uso terapêutico , Escleroderma Sistêmico/fisiopatologia , Escleroderma Sistêmico/terapia , Tomografia Computadorizada por Raios X/estatística & dados numéricos
13.
Dtsch Med Wochenschr ; 144(3): 189-193, 2019 02.
Artigo em Alemão | MEDLINE | ID: mdl-30703839

RESUMO

This literature review summarizes the main findings in systemic sclerosis (SSc) made in the last few years. Accordingly, the disease pathogenesis is mainly driven by the adaptive immune system, which is proven by the effects of autologous stem cell transplantation. Particularly, autoantibodies can activate both adaptive as well as innate immune cells as identified for the anti-angiotensin receptor antibodies. In addition, major achievements come from the early recognition of organ complications, which mainly appear in the first years upon Raynaud`s phenomenon. This implicates screening for organ complications such as for pulmonary arterial hypertension (PAH) or interstitial lung disease (ILD) even without any clinical symptoms at the beginning. On the other hand, the presence of anti-polymerase III antibodies indicates a risk or the presence of malignant diseases, which should be identified. Several studies in the last years showed the high burden of the disease, which is often underscored by physicians. Pain, depressions, fatigue, and incontinence often determine quality of life and should be recognized and treated, if possible. Systemic sclerosis is a disease with the highest disease-related mortality among the rheumatic diseases. More than half of the SSc patients die from SSc manifestations particularly from cardiac and lung involvement such as PAH and ILD. Ventricular tachycardias should be recognized by Holter-ECG. Finally, intensive therapies such as autologous stem cell transplantation or combination therapies seem to be most successful in SSc as well as in SSc-related PAH. Currently, several studies are ongoing, which will hopefully change the outcome and quality of life.


Assuntos
Escleroderma Sistêmico , Humanos , Escleroderma Sistêmico/diagnóstico , Escleroderma Sistêmico/mortalidade , Escleroderma Sistêmico/terapia
14.
Biomed Res Int ; 2019: 4569826, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30809542

RESUMO

Systemic sclerosis (SSc) is a complex rheumatologic autoimmune disease in which inflammation, fibrosis, and vasculopathy share several pathogenic pathways that lead to skin and internal organ damage. Recent findings regarding the participation and interaction of the innate and acquired immune system have led to a better understanding of the pathogenesis of the disease and to the identification of new therapeutic targets, many of which have been tested in preclinical and clinical trials with varying results. In this manuscript, we review the state of the art of the pathogenesis of this disease and discuss the main therapeutic targets related to each pathogenic mechanism that have been discovered so far.


Assuntos
Doenças Autoimunes/terapia , Fibrose/terapia , Inflamação/terapia , Escleroderma Sistêmico/terapia , Doenças Autoimunes/patologia , Fibroblastos/patologia , Fibrose/patologia , Humanos , Inflamação/patologia , Escleroderma Sistêmico/patologia , Pele/patologia
15.
Expert Rev Gastroenterol Hepatol ; 13(3): 213-227, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30791766

RESUMO

INTRODUCTION: Systemic sclerosis (SSc) is a multisystem connective tissue disease, characterized by chronic inflammation and vascular changes that result in esophageal smooth muscle atrophy and fibrosis. Subsequent progressive loss of peristalsis in the distal esophagus and loss of lower esophageal sphincter function lead to problems with the protective barrier and exposure of sensitive tissues to the gastroduodenal contents, a disorder called reflux disease. Areas covered: Depending on the range, nature and symptoms of the disease, the term 'reflux disease' may refer to gastroesophageal reflux, laryngopharyngeal reflux, microaspiration into the airways and silent reflux. Despite the links between these visceral complications, this connection remains controversial. This is due to a lack of complete understanding, the asymptomatic nature of the disease and the limited diagnostic accuracy of tests, which can delay diagnosis. Such delays are problematic, given that the early detection of GERD in SSc patients, the timing of assessment, the treatment of the organs involved are critical aspects of patient prognosis and disease outcome. Expert commentary: This review summarizes the most recent knowledge about the pathophysiology, diagnosis and prospective treatment of GERD in SSc patients and highlights how innovative technologies applied through an integrative, interdisciplinary approach may soon lead to effective treatment strategies.


Assuntos
Esôfago/fisiopatologia , Refluxo Gastroesofágico , Refluxo Laringofaríngeo , Aspiração Respiratória , Sistema Respiratório/fisiopatologia , Escleroderma Sistêmico , Refluxo Gastroesofágico/diagnóstico , Refluxo Gastroesofágico/epidemiologia , Refluxo Gastroesofágico/fisiopatologia , Refluxo Gastroesofágico/terapia , Humanos , Refluxo Laringofaríngeo/diagnóstico , Refluxo Laringofaríngeo/epidemiologia , Refluxo Laringofaríngeo/fisiopatologia , Refluxo Laringofaríngeo/terapia , Laringe/fisiopatologia , Aspiração Respiratória/diagnóstico , Aspiração Respiratória/epidemiologia , Aspiração Respiratória/fisiopatologia , Fatores de Risco , Escleroderma Sistêmico/diagnóstico , Escleroderma Sistêmico/epidemiologia , Escleroderma Sistêmico/fisiopatologia , Escleroderma Sistêmico/terapia , Resultado do Tratamento
16.
Respir Res ; 20(1): 13, 2019 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-30658650

RESUMO

BACKGROUND: Systemic sclerosis (SSc) is a rare connective tissue disease with a heterogeneous clinical course. Interstitial lung disease (ILD) is a common manifestation of SSc and a leading cause of death. MAIN BODY: All patients newly diagnosed with SSc should receive a comprehensive clinical evaluation, including assessment of respiratory symptoms, a high-resolution computed tomography (HRCT) scan of the chest, and pulmonary function tests. ILD can develop in any patient with SSc, including those with pulmonary hypertension, but the risk is increased in those with diffuse (rather than limited) cutaneous SSc, those with anti-Scl-70/anti-topoisomerase I antibody, and in the absence of anti-centromere antibody. While it can occur at any time, the risk of developing ILD is greatest early in the course of SSc, so patients should be monitored closely in the first few years after diagnosis. An increased extent of lung fibrosis on HRCT and a low forced vital capacity (FVC) are predictors of early mortality. While not all patients will require treatment, current approaches to the treatment of progressive SSc-ILD focus on immunosuppressant therapies, including cyclophosphamide and mycophenolate mofetil. In patients with severe and/or rapidly progressive disease, both haematopoietic stem cell transplantation (HSCT) and lung transplantation have been successfully used. A number of medications, including the two drugs approved for the treatment of idiopathic pulmonary fibrosis (IPF), are under active investigation as potential new therapies for SSc-ILD. CONCLUSIONS: Physicians managing patients with SSc should maintain a high level of suspicion and regularly monitor for ILD, particularly in the first few years after diagnosis.


Assuntos
Doenças Pulmonares Intersticiais/fisiopatologia , Doenças Pulmonares Intersticiais/terapia , Escleroderma Sistêmico/fisiopatologia , Escleroderma Sistêmico/terapia , Anti-Inflamatórios/uso terapêutico , Transplante de Células-Tronco Hematopoéticas/métodos , Transplante de Células-Tronco Hematopoéticas/tendências , Humanos , Doenças Pulmonares Intersticiais/epidemiologia , Transplante de Pulmão/métodos , Transplante de Pulmão/tendências , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Escleroderma Sistêmico/epidemiologia
17.
Ann Rheum Dis ; 78(3): 391-398, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30612118

RESUMO

OBJECTIVE: The autologous stromal vascular fraction (SVF) from adipose tissue is an alternative to cultured adipose-derived stem cells for use in regenerative medicine and represents a promising therapy for vasculopathy and hand disability in systemic sclerosis (SSc). However, the bioactivity of autologous SVF is not documented in this disease context. This study aimed to compare the molecular and functional profiles of the SVF-based medicinal product obtained from SSc and healthy subjects. METHODS: Good manufacturing practice (GMP)-grade SVF from 24 patients with SSc and 12 healthy donors (HD) was analysed by flow cytometry to compare the distribution of the CD45- and CD45+ haematopoietic cell subsets. The ability of SVF to form a vascular network was assessed using Matrigel in vivo assay. The transcriptomic and secretory profiles of the SSc-SVF were assessed by RNA sequencing and multiplex analysis, respectively, and were compared with the HD-SVF. RESULTS: The distribution of the leucocyte, endothelial, stromal, pericyte and transitional cell subsets was similar for SSc-SVF and HD-SVF. SSc-SVF retained its vasculogenic capacity, but the density of neovessels formed in SVF-loaded Matrigel implanted in nude mice was slightly decreased compared with HD-SVF. SSc-SVF displayed a differential molecular signature reflecting deregulation of angiogenesis, endothelial activation and fibrosis. CONCLUSIONS: Our study provides the first evidence that SSc does not compromise the vascular repair capacity of SVF, supporting its use as an innovative autologous biotherapy. The characterisation of the specific SSc-SVF molecular profile provides new perspectives for delineating markers of the potency of SVF and its targets for the treatment of SSc.


Assuntos
Tecido Adiposo/citologia , Neovascularização Fisiológica/fisiologia , Escleroderma Sistêmico/fisiopatologia , Células Estromais/fisiologia , Tecido Adiposo/irrigação sanguínea , Feminino , Humanos , Masculino , Transplante de Células-Tronco Mesenquimais , Pessoa de Meia-Idade , Escleroderma Sistêmico/terapia
18.
J Dermatol Sci ; 93(1): 2-7, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30514664

RESUMO

B cells have moved to the center stage in many autoimmune diseases including autoantibody-mediated diseases and T cell-mediated autoimmune diseases such as rheumatoid arthritis and multiple sclerosis. B cells play an important role for immune response beyond antibody production through mechanisms like antigen presentation and cytokine production. However, not all B cells positively regulate immune responses. Regulatory B cells negatively regulate immune responses by production of anti-inflammatory cytokines such as IL-10, IL-35, and TGF-ß. Regulatory B cells have been found to be decreased and/or functionally impaired in various autoimmune diseases. In contrast, B cells also produce pro-inflammatory cytokines, such as IL-6, IFN-γ and GM - CSF. These effector B cells contribute to the pathogenesis of autoimmune diseases. Regulatory and effector B cell balance regulates immune response through the release of cytokines. Furthermore, a protocol that selectively depletes effector B cells while sparing regulatory B cells would represent a potent therapy for autoimmune diseases rather than pan-B cell depletion using anti-CD20 mAb.


Assuntos
Subpopulações de Linfócitos B/imunologia , Linfócitos B Reguladores/imunologia , Imunidade Celular , Lúpus Eritematoso Sistêmico/imunologia , Escleroderma Sistêmico/imunologia , Subpopulações de Linfócitos B/metabolismo , Linfócitos B Reguladores/metabolismo , Citocinas/metabolismo , Humanos , Imunoterapia/métodos , Mediadores da Inflamação/metabolismo , Lúpus Eritematoso Sistêmico/terapia , Escleroderma Sistêmico/terapia
19.
Mod Rheumatol ; 29(3): 484-490, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-29667474

RESUMO

OBJECTIVE: Severe skin sclerosis in patients with systemic sclerosis (SSc) can result in a loss of hand function. The aim of this study is to examine the long-term changes of finger passive range of motion (ROM) in Japanese SSc patients treated with self-administered stretching. METHODS: This is a single-center, retrospective, observational cohort study. Forty-three Japanese patients with SSc were given instructions on self-administered stretching. ROM was assessed using a goniometer on their first visit and after 1 year, 3 years, 5 years and 9 years. Hand function was assessed by the Health Assessment Questionnaire disability index (HAQ-DI) at their first visit and after 9 years. RESULTS: Total passive ROM significantly improved in each finger after 3 years of finger stretching. Most patients (37 of 43 patients, 86%) improved or maintained total passive ROM and hand function within 9 years after their first visit. However, significant improvement of total passive ROM was lost in 6 of 43 SSc patients (14%) 9 years after their first visit. The HAQ-DI also was increased in these six patients. Multivariable analyses revealed that re-elevation of modified Rodnan total skin thickness score during the clinical course (OR = 5.260e + 7, 95% CI 1.52e + 150-uncalculated p = .0096) was the independent factor associated with deterioration of total passive ROM at 9 years. CONCLUSION: Patients with progressive skin sclerosis during the clinical course need multimodality therapy to maintain finger joint motion, since the effect of self-administered stretching is limited in these patients.


Assuntos
Articulações dos Dedos/fisiopatologia , Exercícios de Alongamento Muscular/métodos , Amplitude de Movimento Articular , Escleroderma Sistêmico/terapia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Escleroderma Sistêmico/reabilitação
20.
Semin Arthritis Rheum ; 48(4): 694-700, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-29685482

RESUMO

BACKGROUND: To estimate patient acceptable symptom state (PASS) and minimal clinically important difference (MCID) for patient-reported outcomes in systemic sclerosis (SSc). METHODS: We conducted a secondary analysis of the SCLEREDUC trial, a 12-month randomized controlled trial comparing the efficacy of physical therapy to usual care in 220 SSc patients followed-up from September 2005 to October 2010. Self-rated state and change in patient health at 12 months were assessed by using 2 external anchors extracted from the Medical Outcomes Study 36-Item Short-Form. Patients who self-rated their health as "excellent", "very good" or "good" were the PASS group and those who self-rated their health change as "somewhat better" were the MCID group. Main outcomes were the estimates of PASS by using the 75th percentile method and of MCID by using the mean change in scores method for pain and activity limitation. RESULTS: PASS (95% confidence interval) and mean (SD) MCID estimates at 12 months were 53.75 (34.00 to 68.00) and -6.74 (32.02) for the joint-pain visual analog scale (range 0-100), 1.41 (1.13 to 1.63) and -0.21 (0.48) for the Health Assessment Questionnaire (HAQ, range 0-3), 1.27 (1.07 to 1.62) and -0.13 (0.45) for the scleroderma HAQ (range 0-3), 26.00 (17.00 to 37.00) and -3.38 (9.87) for the Cochin Hand Function Scale (range 0-90), and 19.40 (17.20 to 21.90) and -5.69 (6.79) for the McMaster-Toronto Arthritis Patient Preference Disability Questionnaire (range 0-30), respectively. CONCLUSIONS: We provide, for the first time, the PASS and MCID estimates for pain and activity limitation in SSc. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00318188. First Posted: April 26, 2006.


Assuntos
Modalidades de Fisioterapia , Escleroderma Sistêmico/terapia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Diferença Mínima Clinicamente Importante , Medidas de Resultados Relatados pelo Paciente , Satisfação do Paciente , Escleroderma Sistêmico/tratamento farmacológico
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