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1.
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
2.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 35(8): 707-713, 2019 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-31638568

RESUMO

Objective To investigate the relationship between mitochondria and systemic sclerosis (SSc) by analyzing the expression of mitochondrial function-related genes in skin biopsy samples from patients with SSc. Methods Gene chip expression profile of SSc skin biopsy in Gene Expression Omnibus (GEO) database was used, and differently expressed genes (DEGs) related to mitochondrial function were identified by t test and fold change (FC). What's more, functional annotation, functional enrichment and protein interaction network analysis were performed. Results A total of 422 significant DEGs were identified between the SSc group and the normal group. Among them, 23 DEGs were mitochondrial function-related genes. Functional annotation and enrichment analysis of 23 DEGs revealed that abnormally expressed mitochondrial function-related genes mainly affected several biological processes, such as mitochondrial energy supply and cell metabolism. Conclusion The dysregulation of mitochondrial function-related genes in SSc patients affects the function of mitochondria, suggesting that the abnormality of mitochondrial function may be associated with the development of SSc.


Assuntos
Biologia Computacional , Regulação da Expressão Gênica , Redes Reguladoras de Genes , Mitocôndrias , Escleroderma Sistêmico , Perfilação da Expressão Gênica , Humanos , Mitocôndrias/genética , Mitocôndrias/patologia , Escleroderma Sistêmico/genética , Escleroderma Sistêmico/fisiopatologia , Transcriptoma
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.
Clin Exp Rheumatol ; 37 Suppl 119(4): 97-101, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31573479

RESUMO

OBJECTIVES: The fingers, toes, and tips of the nose and ears have specialised structural and functional features for thermoregulation, and are the most common areas of Raynaud's phenomenon in systemic sclerosis. Digital thermal monitoring (DTM) of vascular reactivity assesses Doppler ultrasound hyperemic, low frequency, blood velocity of radial artery and fingertip vascular function. Flow mediated dilation (FMD) is an indirect measure of endothelial function, perfusion, and vasodilator ability. In this study, we investigated the cross-sectional correlation of FMD and DTM variables to inform an optimised noninvasive study of SSc endothelial function. A student's T-test was used to compare means of DTM across binary variables. METHODS: Consented SSc registry patients were included in this analysis. The subjects were prepared for FMD and DTM per standardised guidelines. The SSc clinical features were recorded. Spearman's Rank Correlation was used to assess the strength of a relationship FMD and DTM variables. RESULTS: Thirty-four SSc subjects had FMD and DTM performed on the same day. Relative (0.42, p=<0.02), absolute FMD (0.41, p<0.02), and shear rate (0.32, p<0.07) were weakly, but significantly correlated with the DTM. Reactive hyperemia (-0.44, p=0.000) was weakly inversely, but significantly related with DTM. Baseline diameter and flow were not significantly related to the DTM. CONCLUSIONS: This non-invasive study of SSc endothelial function suggests that macrocirculation (including relative and absolute FMD, shear rate, and peak hyperemia) and microcirculatory thermoregulation (characterised by DTM) are significantly correlated, thus warrants further prospective study.


Assuntos
Microcirculação/fisiologia , Fluxo Sanguíneo Regional/fisiologia , Escleroderma Sistêmico , Pele/irrigação sanguínea , Artéria Braquial , Estudos Transversais , Dilatação , Endotélio Vascular , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Escleroderma Sistêmico/fisiopatologia , Vasodilatação
5.
Isr Med Assoc J ; 21(7): 471-474, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31507123

RESUMO

BACKGROUND: Microvascular damage, clinically expressed by Raynaud's phenomenon, is generally the first symptom of the disease and the injured vascular cells, both endothelial and perivascular, may transdifferentiate to myofibroblasts, thus leading to collagen deposition in the tissue and consequent fibrosis. Systemic sclerosis (SSc, scleroderma) is complex disease characterized by autoimmunity, vasculopathy, and fibrosis. It has been shown that microvascular damage may be the first symptom of SSc. Injured endothelial cells and pericytes may transdifferentiate into myofibroblasts, the cells responsible for fibrosis and collagen deposition in the tissue. Based on these factors, the process of myofibroblast generation may link two pivotal events of SSc: microvascular damage and fibrosis. Understanding the development, differentiation, and function of myofibroblasts is therefore crucial to individuate early pathogenetic events and develop new therapeutic target for SSc, a condition in which no disease-modifying agents are available. The aim of this review was to discuss the possible origins of myofibroblasts in SSc, highlighting the process of endothelial mesenchymal transition and pericytes to myofibroblast transition and to show how these events may contribute to pathogenesis of the disease.


Assuntos
Miofibroblastos/citologia , Doença de Raynaud/fisiopatologia , Escleroderma Sistêmico/fisiopatologia , Diferenciação Celular/fisiologia , Células Endoteliais/citologia , Transição Epitelial-Mesenquimal/fisiologia , Fibrose/patologia , Humanos , Pericitos/citologia
7.
J Med Case Rep ; 13(1): 145, 2019 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-31084620

RESUMO

BACKGROUND: Scleredema is a rare sclerodermoid skin condition characterized by diffuse symmetrical thickening of the upper part of the body. Its association with monoclonal gammopathy and myeloma was recently described; very few cases have been reported to date. CASE PRESENTATION: A 66-year-old Sri Lankan woman who had been followed in a dermatology unit for 34 years with diffuse systemic sclerosis presented with an acute exacerbation of the skin disease. Absence of Raynaud's phenomenon; sclerodactyly; characteristic lung, gastrointestinal, and cardiac involvement of systemic sclerosis; and repeatedly negative antinuclear antibodies test results led to reevaluation for the possibility of scleredema. Skin biopsies from four body sites showed normal epidermis and thickened reticular dermis with swollen collagen bundles separated from one another by clear spaces, resulting in fenestration. The skin appendages were not atrophied or bound down. Alcian blue staining showed interstitial mucin deposition. Serum protein electrophoresis demonstrated an abnormal monoclonal band in the ß-region with a paraprotein level of 8.9 g/dl. Immunofixation showed an abnormal band in the γ-region consisting of immunoglobulin A and κ. Bone marrow biopsy revealed abnormal monoclonal plasma cells (15%) with multinuclearity. There was no evidence of end organ damage, and whole-body magnetic resonance imaging did not reveal any evidence of bone involvement. The patient's diagnosis was revised as scleredema type 2 associated with IgA-κ, and she was referred to a hemato-oncologist for chemotherapy, which led to significant improvement in the skin condition. CONCLUSIONS: Scleredema is a rare disorder that has an enigmatic, rare association with monoclonal gammopathy. Dermatologists should be aware of this rare but important association.


Assuntos
Imagem por Ressonância Magnética , Escleredema do Adulto/diagnóstico por imagem , Escleroderma Sistêmico/fisiopatologia , Mieloma Múltiplo Latente/diagnóstico por imagem , Imagem Corporal Total , Idoso , Antineoplásicos/administração & dosagem , Bortezomib/administração & dosagem , Progressão da Doença , Feminino , Humanos , Imunoglobulinas/administração & dosagem , Fatores Imunológicos/administração & dosagem , Escleredema do Adulto/tratamento farmacológico , Escleredema do Adulto/fisiopatologia , Escleroderma Sistêmico/complicações , Escleroderma Sistêmico/tratamento farmacológico , Mieloma Múltiplo Latente/tratamento farmacológico , Mieloma Múltiplo Latente/fisiopatologia , Resultado do Tratamento
8.
Int J Cardiovasc Imaging ; 35(10): 1795-1802, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31093897

RESUMO

Heart failure with preserved ejection fraction (HFpEF) is common in systemic sclerosis (SSc) and implies a worse prognosis therefore non-invasive assessment of left ventricular (LV) filling pressure is pivotal. Besides E/e' the use of maximal left atrial volume (LA Vmax index) is recommended. LA reservoir strain was also reported to be useful. The utility of LA stiffness, however, was never investigated in SSc. Thus we aimed to compare the diagnostic power of LA Vmax index, reservoir strain and stiffness in predicting elevated LV filling pressure in SSc patients. 72 SSc patients (age: 57 ± 11 years) were investigated. LA stiffness was calculated as ratio of E/e' to LA reservoir strain. Elevated LV filling pressure was defined as NT-proBNP > 220 pg/ml. Receiver-operating characteristic (ROC) curves were used to estimate the diagnostic performance of the investigated parameters. Average NT-proBNP level was 181 ± 154 pg/ml. NT-proBNP > 220 pg/ml was found in 21 SSc patients. LA stiffness showed the highest diagnostic performance in predicting NT-pro-BNP > 220 pg/ml, with a cut off value of 0.314 (Area under the curve: 0.719, specificity: 89.4%, sensitivity: 42.1%). AUC values for LA reservoir strain and Vmax index were 0.595 and 0.521, respectively. LA stiffness was superior to Vmax index and reservoir strain in predicting elevated NT-proBNP levels in SSc patients. Although invasive validation studies on larger samples are required, our data suggest, that the use of LA stiffness may significantly contribute to diagnostic precision in populations with a high suspicion of HFpEF.


Assuntos
Função do Átrio Esquerdo , Ecocardiografia Doppler , Insuficiência Cardíaca/diagnóstico por imagem , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Escleroderma Sistêmico/diagnóstico por imagem , Adulto , Idoso , Biomarcadores/sangue , Feminino , Insuficiência Cardíaca/sangue , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Fatores de Risco , Escleroderma Sistêmico/sangue , Escleroderma Sistêmico/complicações , Escleroderma Sistêmico/fisiopatologia , Volume Sistólico , Regulação para Cima , Função Ventricular Esquerda
9.
Int J Rheum Dis ; 22(6): 1029-1035, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30989785

RESUMO

AIM: Autonomic dysfunction (AD) is an early feature of systemic sclerosis (SSc). A regular endothelial function is a prerequisite for normal response of the myocardial blood flow (MBF) to cold pressure test (CPT). The aim of the study was to evaluate the relation between MBF and AD at rest and after CPT in asymptomatic SSc patients. METHODS: Twenty SSc patients and 10 age-, sex- and body mass index-matched healthy controls underwent cardiac magnetic resonance at rest and after CPT. All subjects underwent 24 hours ambulatory 3-channel electrocardiogram Holter to evaluate AD by heart rate variability. RESULTS: We did not observe any significant difference in MBF (mL/g/min) at rest and after CPT between SSc patients and healthy controls. Delta of MBF (difference between MBF after CPT and rest MBF) was lower (P = 0.039) in SSc patients than healthy controls (0.28 [0.04-0.40] vs 0.33 [0.24-0.54]). The low frequency/high frequency (LF/HF) was higher (P = 0.002) in SSc patients than healthy controls (3 [1.7-6] vs 1.8 [1.1-2.8]). The high frequencies (HF), modulated mainly by paraympathetic system, was lower (P = 0.003) in SSc patients than healthy controls (30 [16-42] vs 36.5 [24-44]). Sympathetic hyperactivity, due to reduction of parasympathetic activity (HF), is present in SSc patients. A negative correlation was observed between Delta of MBF and LF/HF (r = -0.572, P = 0.0031). CONCLUSION: AD, characterized by sympathovagal imbalance due to a reduced parasympathetic tone with high LF/HF ratio, could be responsible for the reduced myocardial vasodilatory response after CPT.


Assuntos
Doenças do Sistema Nervoso Autônomo/etiologia , Sistema Nervoso Autônomo/fisiopatologia , Circulação Coronária , Cardiopatias/diagnóstico por imagem , Coração/diagnóstico por imagem , Coração/inervação , Imagem Cinética por Ressonância Magnética , Imagem de Perfusão do Miocárdio/métodos , Escleroderma Sistêmico/complicações , Adulto , Doenças do Sistema Nervoso Autônomo/diagnóstico , Doenças do Sistema Nervoso Autônomo/fisiopatologia , Estudos de Casos e Controles , Feminino , Cardiopatias/etiologia , Cardiopatias/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Fatores de Risco , Escleroderma Sistêmico/diagnóstico , Escleroderma Sistêmico/fisiopatologia , Vasodilatação , Adulto Jovem
10.
Clin Exp Rheumatol ; 37 Suppl 119(4): 133-140, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31025932

RESUMO

Systemic sclerosis (SSc) is a connective tissue disorder characterised by immune dysregulation, endothelial cell dysfunction followed by defective vascular repair and neovascularization and progressive tissue fibrosis of the skin and internal organs, whose pathophysiology remains to be fully elucidated. Perturbed neuroendothelial control mechanisms comprising either endothelial cell or peripheral nerve fiber impairment are supposed to play an important role in the onset of Raynaud's phenomenon and development of microvascular abnormalities which are the earliest events and key features of SSc. Such pathogenic neuroendothelial mechanisms may trigger both the early endothelial cell damage and the subsequent loss of peripheral microvascular integrity characterised by the lack of compensatory angiogenesis. Of note, the vascular and nervous systems have several anatomical similarities that extend to molecular level, and the molecular mechanisms of nerve regulation are shared by the vascular system. In this context, increasing evidence demonstrated that endothelial cells express receptors for axon guidance molecules, including Ephrin family receptor tyrosine kinases, Neuropilins, Plexins, Robos, and UNC5B that are able to respond to their soluble neuroendothelial trophic ligands, such as Semaphorins and Slits, to guide the sprouting of endothelial tip cells. Here, we first provide a historical view of neuroendothelial control mechanism alterations in the pathogenesis of SSc, and then discuss the emerging role of a class of molecules sharing neurogenic and angiogenic properties, such as members of Semaphorin/Plexin/Neuropilin and Slit/Roundabout families, in SSc-related peripheral microvasculopathy.


Assuntos
Neovascularização Patológica , Doenças Vasculares Periféricas/fisiopatologia , Doença de Raynaud , Escleroderma Sistêmico , Células Endoteliais , Humanos , Sistema Nervoso , Escleroderma Sistêmico/fisiopatologia
12.
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
14.
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
15.
Indian J Pathol Microbiol ; 62(1): 61-66, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30706861

RESUMO

Background: Juvenile idiopathic inflammatory myopathies (JIIM) are rare and heterogeneous. Subtype identification is important for treatment. Materials and Methods: Patients below 18 years diagnosed as idiopathic inflammatory myopathy (IIM) according to the Bohan and Peter criteria between January 2010 and May 2015 were evaluated with muscle biopsy in the four domains: muscle fiber, inflammation, connective tissue, and vascular, with basic panel of histochemical stains as per recommendations of the European Neuromuscular center (ENMC) workshop 2015. Immunohistochemistry with CD 31 was done to assess capillary density. Results: JIIM constituted 15.25% of IIM with juvenile dermatomyositis (JDM) being the most common subgroup (24/27) followed by juvenile overlap myositis (JOM) (3/27) in association with systemic lupus erythematosus (2) and systemic sclerosis (1). Muscle biopsy in JDM was characterized by perifascicular atrophy, necrosis, degeneration, and regeneration in all and the other features included perivascular inflammation (21), lymphoid aggregates (2), mitochondrial abnormalities (9), sarcoplasmic vacuoles (6), capillary dropout (5), capillary dilatation (6), and perimysial fibrosis (14). JOM was characterized by auto-antibodies and perivascular inflammation. Conclusion: JIIMs were rare and JDM was the most common subtype. Muscle biopsy evaluation as per ENMC criteria characterized the subgroups.


Assuntos
Músculos/patologia , Miosite/fisiopatologia , Adolescente , Corticosteroides/uso terapêutico , Doenças Autoimunes/fisiopatologia , Biópsia , Criança , Pré-Escolar , Dermatomiosite/fisiopatologia , Feminino , Humanos , Imuno-Histoquímica , Masculino , Metotrexato/uso terapêutico , Miosite/classificação , Miosite/diagnóstico , Molécula-1 de Adesão Celular Endotelial a Plaquetas/metabolismo , Estudos Retrospectivos , Escleroderma Sistêmico/fisiopatologia , Vasculite/fisiopatologia
16.
Medicine (Baltimore) ; 98(6): e14342, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30732161

RESUMO

BACKGROUND: Pulmonary artery systolic pressure (PASP) is an important parameter for detecting pulmonary arterial hypertension (PAH). The difference between rest PASP and post-exercise PASP (ΔPASP) may play a role in predicting and screening resting PAH. The aim of this study is to analyze ΔPASP in systemic sclerosis (SSc) patients with PAH or non-PAH and suggest a cutoff value of ΔPASP for detection of PAH. METHODS: PubMed, Embase, and Web of Science were searched for relevant publications up to July 7, 2018. Characteristics of control, no PAH, exercise-induced PAH (EIPH) and PAH subgroups in SSc patients were extracted. R 3.5.0 with the "meta" package was used to conduct this meta-analysis. RESULTS: Twelve articles involving 1279 patients were included in this study. The subgroups meta-analysis showed pooled mean ΔPASP in different subgroups: control group (8.6 mmHg, 95% CI: 6.9-10.5), no PAH group (12.2 mmHg, 95% CI: 11.2-13.2), EIPH group (26.0 mmHg, 95% CI: 24.2-27.7) and PAH group (36.2 mmHg, 95% CI: 29.7-42.7). CONCLUSION: Combining the results of our study with the previous studies, an abnormal increase in PASP after exercise could indicate the development of PAH in SSc patients. In addition, if ΔPASP>29 mmHg, a high suspicion of PAH should be raised.


Assuntos
Exercício/fisiologia , Hipertensão Pulmonar/diagnóstico , Hipertensão Pulmonar/epidemiologia , Artéria Pulmonar/fisiopatologia , Escleroderma Sistêmico/epidemiologia , Pressão Sanguínea/fisiologia , Humanos , Hipertensão Pulmonar/fisiopatologia , Descanso/fisiologia , Escleroderma Sistêmico/fisiopatologia
17.
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
18.
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
19.
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
20.
Arthritis Rheumatol ; 71(5): 805-816, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30615302

RESUMO

OBJECTIVE: This prospective study was undertaken to evaluate right ventricular function and pulmonary arterial compliance (PAC; ratio of stroke volume to pulse pressure) at rest and during exercise in patients with systemic sclerosis (SSc) with normal mean pulmonary artery pressure (PAP), patients with SSc with mildly elevated mean PAP, and patients with SSc with manifest pulmonary hypertension (PH). METHODS: Patients with SSc (n = 112) underwent clinical assessment and right-sided heart catheterization at rest and during exercise and were divided into 3 groups according to their resting mean PAP values: normal mean PAP (≤20 mm Hg), mildly elevated mean PAP (21-24 mm Hg), and PH (mean PAP ≥25 mm Hg). Results were compared between groups by analysis of variance followed by post hoc Student's t-test. RESULTS: Compared to patients with normal mean PAP, patients with mildly elevated mean PAP had a lower 6-minute walking distance (P = 0.008), lower cardiac index (P = 0.027) and higher pulmonary vascular resistance (P = 0.0002) during exercise, and lower PAC at rest (P = 0.016) and different stages of exercise (P = 0.033 for 25W and P = 0.024 for 75W). CONCLUSION: The results of this study suggest that impaired 6-minute walking distance in SSc patients with mildly elevated mean PAP might be caused by reduced PAC during exercise and reduced right ventricular output reserve, presumably due to impaired coupling between the right ventricle and the pulmonary vasculature. These findings provide further evidence of the clinical relevance of mildly elevated mean PAP in patients with SSc.


Assuntos
Débito Cardíaco/fisiologia , Artéria Pulmonar/fisiopatologia , Escleroderma Sistêmico/fisiopatologia , Resistência Vascular/fisiologia , Disfunção Ventricular Direita/fisiopatologia , Adulto , Idoso , Pressão Sanguínea/fisiologia , Cateterismo Cardíaco , Estudos de Casos e Controles , Complacência (Medida de Distensibilidade) , Ecocardiografia Doppler , Teste de Esforço , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Volume Sistólico/fisiologia , Disfunção Ventricular Direita/diagnóstico por imagem , Teste de Caminhada
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