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1.
Lancet Respir Med ; 8(10): 963-974, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32866440

RESUMO

BACKGROUND: A phase 2 trial of tocilizumab showed preliminary evidence of efficacy in systemic sclerosis. We assessed skin fibrosis and systemic sclerosis-associated interstitial lung disease (SSc-ILD) in a phase 3 trial to investigate the safety and efficacy of tocilizumab, an anti-interleukin-6 receptor antibody, in the treatment of systemic sclerosis. METHODS: In this multicentre, randomised, double-blind, placebo-controlled, phase 3 trial, participants were recruited from 75 sites in 20 countries across Europe, North America, Latin America, and Japan. Adults with diffuse cutaneous systemic sclerosis for 60 months or less and a modified Rodnan skin score (mRSS) of 10-35 at screening were randomly assigned (1:1) with a voice-web-response system to receive subcutaneous tocilizumab 162 mg or placebo weekly for 48 weeks, stratified by IL-6 levels; participants and investigators were masked to treatment group. The primary endpoint was the difference in change from baseline to week 48 in mRSS. Percentage of predicted forced vital capacity (FVC% predicted) at week 48, time to treatment failure, and patient-reported and physician-reported outcomes were secondary endpoints. This trial is registered with ClinicalTrials.gov (number NCT02453256) and is closed to accrual. FINDINGS: Between Nov 20, 2015, and Feb 14, 2017, 210 individuals were randomly assigned to receive tocilizumab (n=104) or placebo (n=106). In the intention-to-treat population, least squares mean [LSM] change from baseline to week 48 in mRSS was -6·14 for tocilizumab and -4·41 for placebo (adjusted difference -1·73 [95% CI -3·78 to 0·32]; p=0·10). The shift in distribution of change from baseline in FVC% predicted at week 48 favoured tocilizumab (van Elteren nominal p=0·002 vs placebo), with a difference in LSM of 4·2 (95% CI 2·0-6·4; nominal p=0·0002), as did time to treatment failure (hazard ratio 0·63 [95% CI 0·37-1·06]; nominal p=0·08). Change in LSM from baseline to week 48 in Health Assessment Questionnaire-Disability Index and in patient-global and physician-global visual analogue scale assessments did not differ between tocilizumab and placebo. In the safety set, infections were the most common adverse events (54 [52%] of 104 participants in the tocilizumab group, 53 [50%] of 106 in the placebo group). Serious adverse events were reported in 13 participants treated with tocilizumab and 18 with placebo, primarily infections (three events, eight events) and cardiac events (two events, seven events). INTERPRETATION: The primary skin fibrosis endpoint was not met. Findings for the secondary endpoint of FVC% predicted indicate that tocilizumab might preserve lung function in people with early SSc-ILD and elevated acute-phase reactants. Safety was consistent with the known profile of tocilizumab. FUNDING: F Hoffmann-La Roche Ltd.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Escleroderma Sistêmico/tratamento farmacológico , Adulto , Estudos de Coortes , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Escleroderma Sistêmico/diagnóstico , Escleroderma Sistêmico/fisiopatologia , Fatores de Tempo , Resultado do Tratamento , Capacidade Vital
2.
J Am Acad Orthop Surg ; 28(16): e686-e695, 2020 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-32769717

RESUMO

Scleroderma is derived from Latin meaning hard skin. It is an uncommon, noninflammatory connective tissue disorder characterized by increased fibrosis of the skin and in certain variants, multiple other organ systems. Scleroderma involves a spectrum of pathologic changes and anatomic involvement. It can be divided into localized and systemic scleroderma. Hand involvement is common and can include calcium deposits within the soft tissues, digital ischemia, and joint contracture. Nonsurgical management consists of lifestyle modifications, biofeedback, therapy for digital stiffness/contracture, and various pharmacologic medications. When nonsurgical measures are unsuccessful, certain surgical options may be indicated, each with their inherent advantages and pitfalls. Patients with scleroderma who are undergoing surgical intervention pose unique difficulties because of their poorly vascularized tissue and deficient soft-tissue envelopes, thus increasing their susceptibility to wound healing complications and infection. Some subgroups of patients are frequently systemically ill, and specific perioperative measures should be considered to reduce their surgical risk. The spectrum of hand manifestations seen in patients with scleroderma will be reviewed with the focus on evaluation and management.


Assuntos
Mãos , Procedimentos Ortopédicos/métodos , Esclerodermia Localizada/cirurgia , Escleroderma Sistêmico/cirurgia , Calcinose , Mãos/patologia , Mãos/cirurgia , Humanos , Comunicação Interdisciplinar , Equipe de Assistência ao Paciente , Esclerodermia Localizada/diagnóstico , Esclerodermia Localizada/patologia , Esclerodermia Localizada/terapia , Escleroderma Sistêmico/diagnóstico , Escleroderma Sistêmico/patologia , Escleroderma Sistêmico/terapia
3.
Methodist Debakey Cardiovasc J ; 16(2): 162-166, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32670478

RESUMO

Cardiac involvement of infiltrative disease, such as systemic sclerosis, carries significant morbidity and mortality. All parts of the heart may be affected, although the conduction system is less commonly involved. We report a rare case of systemic sclerosis causing third-degree atrioventricular block and the first known reported case to use cardiac magnetic resonance imaging (CMR) as a diagnostic and prognostic instrument. It is not known whether using cardiac CMR in systemic sclerosis with cardiac involvement could lead to earlier intervention with escalation of medical therapy or earlier referral for transplant evaluation.


Assuntos
Bloqueio Atrioventricular/diagnóstico por imagem , Cardiomiopatias/diagnóstico por imagem , Imagem por Ressonância Magnética , Escleroderma Sistêmico/complicações , Adulto , Bloqueio Atrioventricular/etiologia , Bloqueio Atrioventricular/fisiopatologia , Bloqueio Atrioventricular/terapia , Estimulação Cardíaca Artificial , Cardiomiopatias/etiologia , Cardiomiopatias/fisiopatologia , Cardiomiopatias/terapia , Progressão da Doença , Evolução Fatal , Glucocorticoides/uso terapêutico , Humanos , Imunossupressores/uso terapêutico , Masculino , Valor Preditivo dos Testes , Escleroderma Sistêmico/diagnóstico , Escleroderma Sistêmico/tratamento farmacológico , Resultado do Tratamento
4.
Autoimmun Rev ; 19(9): 102619, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32663627

RESUMO

OBJECTIVE: To investigate whether nailfold videocapillaroscopy (NVC), an increasingly worldwide used non-invasive tool to reliably evaluate the peripheral microcirculation, may be an outcome measure in future screening algorithms for systemic sclerosis related interstitial lung disease (SSc-ILD). METHODS: A systematic review to identify original research papers documenting an association between NVC and SSc-ILD was performed in 3 electronic databases according to the PRISMA guidelines. Subsequently, NVC parameters were subdivided according to the consented standardised capillaroscopic definitions of the EULAR Study Group on Microcirculation in Rheumatic Diseases / Scleroderma Clinical Trials Consortium on Capillaroscopy, into quantitative (capillary density, capillary dimension, capillary morphology and haemorrhages) and qualitative assessment (NVC pattern). RESULTS: The systematic search identified 310 unique search results, of which 2 cross-sectional and 1 longitudinal study were retained. In both cross-sectional studies, the presence of SSc-ILD was found to be inversely associated with capillary density (p = .008 and p = .005). The presence of a severe (active/late) NVC pattern was evaluated and associated with the presence of SSc-ILD in one of the cross-sectional studies. In the longitudinal study, incident SSc-ILD was associated with progressive capillary loss (p = .03) and the conversion to a worse (active/late) NVC pattern (p = .001/p = .003). CONCLUSIONS: This first systematic literature review investigating the role of NVC in SSc-ILD using standardised capillaroscopic definitions uncovered associations between NVC and (incident) SSc-ILD. If large prospective studies further corroborate and elucidate these findings, NVC might possibly be a candidate outcome measure to be integrated in screening algorithms for incident/progressive SSc-ILD.


Assuntos
Algoritmos , Doenças Pulmonares Intersticiais/diagnóstico , Angioscopia Microscópica , Escleroderma Sistêmico/diagnóstico , Capilares , Estudos Transversais , Humanos , Estudos Longitudinais , Unhas
5.
Clin Dermatol ; 38(2): 235-249, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32513403

RESUMO

Sclerodermalike syndromes (SLSs) comprise diseases with mucin deposition (eg, scleromyxedema, scleredema), with eosinophilia (eg, eosinophilic fasciitis), metabolic or biochemical abnormalities (eg, nephrogenic systemic fibrosis), or endocrine disorders (eg, POEMS syndrome, or polyneuropathy, organomegaly, endocrinopathy, monoclonal lymphoproliferative disorder, and hypothyroidism). Chronic graft-versus-host disease may also show sclerodermalike skin changes. Inherited progeria syndromes with early aging (eg, Werner syndrome) and a heterogeneous group of hereditary disorders with either skin thickening (eg, stiff skin syndrome) or atrophy and tightening (eg, acrogeria) can also imitate classic systemic sclerosis (SSc). In addition, SLSs can be provoked by several drugs, chemicals, or even physical injury (eg, trauma, vibration stress, radiation). In SLSs, the distribution of skin involvement seems to be atypical compared with SSc. The acral skin involvement is usually missing, and lack of Raynaud phenomenon, scleroderma-specific antinuclear antibodies, the absence of scleroderma capillary pattern, and internal organ manifestations indicate the presence of an SLS. Skin involvement is sometimes nodular, and the underlying tissues can also be affected. For the differential diagnosis, a skin biopsy of the deeper layers including fascia and muscle is required. Histology does not always allow differentiation between SSc and SLSs; therefore, the diagnosis is often based on the distribution, quality of cutaneous involvement, and other accompanying clinical features.


Assuntos
Escleroderma Sistêmico/diagnóstico , Escleroderma Sistêmico/patologia , Pele/patologia , Biópsia/métodos , Diagnóstico Diferencial , Humanos , Escleroderma Sistêmico/etiologia , Síndrome
7.
Clin Rheumatol ; 39(7): 2025-2029, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: covidwho-272596

RESUMO

The coronavirus disease 2019 (COVID-19), the result of an infection with the new virus, SARS-CoV-2, is rapidly spreading worldwide. It is largely unknown whether the occurrence of COVID-19 in patients with rheumatic immune diseases has some specific manifestations, or makes them more prone to rapidly progress into severe COVID-19. In this case report, we describe the clinical features of 5 rheumatic immune disease patients with the concomitant presence of COVID-19. Amongst these patients, 4 had rheumatoid arthritis (RA) and 1 had systemic sclerosis (SSc). Two patients had a history of close contact with a COVID-19 patient. The age of the patients ranged between 51 and 79 years. Fever (80%), cough (80%), dyspnea (40%), and fatigue (20%) were the most common presenting symptoms. Laboratory investigations revealed leukopenia and lymphopenia in 2 patients. In all the patients, chest computerized tomography (CT) revealed patchy ground glass opacities in the lungs. During the hospital stay, the condition of two patients remained the same (i.e., mild COVID-19), two patients progressed to the severe COVID-19, and one patient worsened to the critically ill COVID-19. These patients were treated with antiviral agents for COVID-19, antibiotics for secondary bacterial infections, and immunomodulatory agents for rheumatic immune diseases. All the patients responded well, were cured of COVID-19, and subsequently discharged.


Assuntos
Antivirais/uso terapêutico , Artrite Reumatoide , Infecções por Coronavirus , Imunomodulação , Pandemias , Pneumonia Viral , Escleroderma Sistêmico , Idoso , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/epidemiologia , Artrite Reumatoide/terapia , Betacoronavirus/isolamento & purificação , Contagem de Células Sanguíneas/métodos , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/terapia , Estado Terminal/terapia , Progressão da Doença , Feminino , Humanos , Pulmão/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Pneumonia Viral/diagnóstico , Pneumonia Viral/epidemiologia , Pneumonia Viral/imunologia , Pneumonia Viral/terapia , Escleroderma Sistêmico/diagnóstico , Escleroderma Sistêmico/epidemiologia , Escleroderma Sistêmico/terapia , Avaliação de Sintomas/métodos , Tomografia Computadorizada por Raios X/métodos , Resultado do Tratamento
8.
Clin Rheumatol ; 39(7): 2025-2029, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32406001

RESUMO

The coronavirus disease 2019 (COVID-19), the result of an infection with the new virus, SARS-CoV-2, is rapidly spreading worldwide. It is largely unknown whether the occurrence of COVID-19 in patients with rheumatic immune diseases has some specific manifestations, or makes them more prone to rapidly progress into severe COVID-19. In this case report, we describe the clinical features of 5 rheumatic immune disease patients with the concomitant presence of COVID-19. Amongst these patients, 4 had rheumatoid arthritis (RA) and 1 had systemic sclerosis (SSc). Two patients had a history of close contact with a COVID-19 patient. The age of the patients ranged between 51 and 79 years. Fever (80%), cough (80%), dyspnea (40%), and fatigue (20%) were the most common presenting symptoms. Laboratory investigations revealed leukopenia and lymphopenia in 2 patients. In all the patients, chest computerized tomography (CT) revealed patchy ground glass opacities in the lungs. During the hospital stay, the condition of two patients remained the same (i.e., mild COVID-19), two patients progressed to the severe COVID-19, and one patient worsened to the critically ill COVID-19. These patients were treated with antiviral agents for COVID-19, antibiotics for secondary bacterial infections, and immunomodulatory agents for rheumatic immune diseases. All the patients responded well, were cured of COVID-19, and subsequently discharged.


Assuntos
Antivirais/uso terapêutico , Artrite Reumatoide , Infecções por Coronavirus , Imunomodulação , Pandemias , Pneumonia Viral , Escleroderma Sistêmico , Idoso , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/epidemiologia , Artrite Reumatoide/terapia , Betacoronavirus/isolamento & purificação , Contagem de Células Sanguíneas/métodos , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/terapia , Estado Terminal/terapia , Progressão da Doença , Feminino , Humanos , Pulmão/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Pneumonia Viral/diagnóstico , Pneumonia Viral/epidemiologia , Pneumonia Viral/imunologia , Pneumonia Viral/terapia , Escleroderma Sistêmico/diagnóstico , Escleroderma Sistêmico/epidemiologia , Escleroderma Sistêmico/terapia , Avaliação de Sintomas/métodos , Tomografia Computadorizada por Raios X/métodos , Resultado do Tratamento
9.
Clin Exp Dermatol ; 45(6): 679-684, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32449205

RESUMO

Paediatric morphoea is a debilitating fibrosing disorder of uncertain aetiology, affecting the skin and subcutaneous tissues. Defining optimum management strategies in paediatric morphoea remains an ongoing challenge, owing to the varied presentations and a relative paucity of paediatric-specific studies. We performed a literature search on PubMed, MEDLINE and Google Scholar, using keywords such as 'pediatric morphea', 'juvenile localised scleroderma' and 'juvenile systemic sclerosis'. Relevant studies, including randomized trials, reviews of standard current guidelines and original research articles, were selected and results analysed before summarizing them. In Part 1 of this review, we described the epidemiology, aetiopathogenesis and clinical classification; in this part, we discuss the diagnosis, markers of disease activity, management and natural history in paediatric morphoea.


Assuntos
Corticosteroides/uso terapêutico , Fototerapia , Esclerodermia Localizada/diagnóstico , Esclerodermia Localizada/terapia , Biomarcadores , Criança , Humanos , Metotrexato/uso terapêutico , Ácido Micofenólico/uso terapêutico , Esclerodermia Localizada/patologia , Escleroderma Sistêmico/diagnóstico , Escleroderma Sistêmico/terapia
10.
Rev Mal Respir ; 37(4): 341-345, 2020 Apr.
Artigo em Francês | MEDLINE | ID: mdl-32284205

RESUMO

In systemic sclerosis, the presence of an anti-RNA polymerase III antibody (ARNpol3) is associated with an increased risk of cancer. The characteristic picture of this serotype includes severe diffuse cutaneous involvement, a high risk of renal scleroderma crisis and a 10 year survival of only around 30%. Pulmonary involvement is less common. We report the case of a woman initially treated for drug-induced acute interstitial lung disease revealing chronic interstitial pneumonia with autoimmune features. The disease evolved in three stages with the occurrence of a rapidly progressive diffuse skin sclerosis with anti-ARNPol3 antibodies in the context of ovarian cancer remission.


Assuntos
Cistadenocarcinoma Seroso/complicações , Flecainida/efeitos adversos , Doenças Pulmonares Intersticiais/induzido quimicamente , Neoplasias Ovarianas/complicações , Escleroderma Sistêmico/complicações , Escleroderma Sistêmico/diagnóstico , Idoso , Autoanticorpos/sangue , Cistadenocarcinoma Seroso/patologia , Cistadenocarcinoma Seroso/terapia , Feminino , Humanos , Doenças Pulmonares Intersticiais/complicações , Doenças Pulmonares Intersticiais/imunologia , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/terapia , RNA Polimerase III/imunologia , Indução de Remissão , Escleroderma Sistêmico/sangue
11.
Best Pract Res Clin Rheumatol ; 34(1): 101489, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-32147386

RESUMO

Systemic sclerosis is a severe immune-mediated rheumatic disease by virtue of its clinical impact and mortality. There are a number of other sclerosing skin diseases that should be considered in the differential diagnosis and these are important because they may require specialist investigation and management. In addition, long-term follow up of the different conditions should reflect the risk of associated complications and anticipated duration of therapy. This article reviews the clinical features of potential mimics of scleroderma (systemic sclerosis) including localised forms of scleroderma (morphoea) and other conditions that lead to skin thickening and connective tissue fibrosis or scarring.


Assuntos
Doença de Raynaud , Doenças Reumáticas , Esclerodermia Localizada , Escleroderma Sistêmico , Diagnóstico Diferencial , Humanos , Doença de Raynaud/diagnóstico , Esclerodermia Localizada/diagnóstico , Esclerodermia Localizada/terapia , Escleroderma Sistêmico/diagnóstico , Escleroderma Sistêmico/terapia
12.
Ann Rheum Dis ; 79(5): 626-634, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32161055

RESUMO

OBJECTIVES: To evaluate initial combination therapy with ambrisentan plus tadalafil (COMB) compared with monotherapy of either agent (MONO), and the utility of baseline characteristics and risk stratification in predicting outcomes, in patients with connective tissue disease-associated pulmonary arterial hypertension (CTD-PAH) and the systemic sclerosis (SSc)-pulmonary arterial hypertension (PAH) subpopulation. METHODS: This post hoc analysis of the Ambrisentan and Tadalafil in Patients with Pulmonary Arterial Hypertension (AMBITION) study included patients with CTD-PAH from the modified intention-to-treat population. Time to clinical failure (TtCF) was assessed by baseline characteristics, treatment assignment and risk group (low, intermediate and high) at baseline and week 16. TtCF was compared between groups using Kaplan-Meier curves and Cox proportional hazards regression modelling. RESULTS: The analysis included 216 patients (COMB, n=117; MONO, n=99). The risk of clinical failure was lower with COMB versus MONO (risk reduction: CTD-PAH 51.7%, SSc-PAH 53.7%), particularly in patients with haemodynamic parameters characteristic of typical PAH without features of left heart disease and/or restrictive lung disease at baseline. The risk of clinical failure was lower with COMB versus MONO in the baseline low-risk group (HR not calculated due to no events in COMB), baseline intermediate-risk group (HR 0.519, 95% CI 0.297 to 0.905) and in the week 16 low-risk group (HR 0.069, 95% CI 0.009 to 0.548). CONCLUSIONS: The benefit of COMB over MONO was demonstrated in patients with CTD-PAH, particularly in those with typical PAH haemodynamic characteristics at baseline. COMB is appropriate for patients categorised as low risk and intermediate risk at baseline and low risk at follow-up. TRIAL REGISTRATION NUMBER: NCT01178073.


Assuntos
Fenilpropionatos/administração & dosagem , Hipertensão Arterial Pulmonar/tratamento farmacológico , Hipertensão Arterial Pulmonar/epidemiologia , Piridazinas/administração & dosagem , Escleroderma Sistêmico/tratamento farmacológico , Escleroderma Sistêmico/epidemiologia , Tadalafila/administração & dosagem , Adulto , Comorbidade , Doenças do Tecido Conjuntivo/diagnóstico , Doenças do Tecido Conjuntivo/tratamento farmacológico , Doenças do Tecido Conjuntivo/epidemiologia , Relação Dose-Resposta a Droga , Método Duplo-Cego , Esquema de Medicação , Quimioterapia Combinada , Feminino , Seguimentos , Humanos , Análise de Intenção de Tratamento , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Hipertensão Arterial Pulmonar/diagnóstico , Medição de Risco , Escleroderma Sistêmico/diagnóstico , Resultado do Tratamento , Vasodilatadores/administração & dosagem
13.
Ann Biol Clin (Paris) ; 78(2): 126-133, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-32175889

RESUMO

AIM: To describe the autoantibody profile in a cohort of Algerian patients with systemic sclerosis (SSc) and to determine clinical associations between SSc-related autoantibodies, disease subtypes and specific clinical features. METHODS: Consecutive Algerian patients with SSc were included in the present study. In addition to clinical characterization, all subjects underwent autoantibody testing using indirect immunofluorescence, immunoenzymatic, and line immunoblot assays. RESULTS: A total of 150 patients were included in this study, 103 (68.7%) had limited cutaneous SSc (lcSSc), 42 (28%) had diffuse cutaneous SSc (dcSSc) and 5 (3.3%) had sine cutaneous scleroderma. One hundred thirty-five (90.0%) patients were positive for SSc-related autoantibodies, including 63 (42%) with more than one autoantibody. The two most frequent autoantibodies were anti-topoisomerase I (ATA) (76; 50.7%) and anti-SSA/Ro (49; 32.7%). Only 23 (15.3%) patients were positive for anticentromere; 9 (6%) were positive for anti RNA polymerase III; 5 (3.3%) for anti-U3 RNP; 3 (2%) for anti Th/To; 25 (16.7%) for anti-U1 RNP; 11 (7.3%) for anti-PM/Scl and 4 (2.7%) for anti-Ku. Anti-topoisomerase I was associated with dcSSc (p <0.0001), interstitial lung disease (ILD) (p <0.0001) and digital ulcers (p <0.0001). Anti-U3 RNP was associated with pulmonary arterial hypertension (PAH) (p=0.031). CONCLUSION: Notable similarities and differences in the prevalence of SSc-related autoantibodies were found in our population when compared to other ethnic groups. ATA and anti-U3 RNP may be a reliable biomarker for ILD and PAH. Further studies should be conducted to better understand the ethnic influence on disease expression and autoantibody production.


Assuntos
Autoanticorpos/sangue , Escleroderma Sistêmico/sangue , Escleroderma Sistêmico/epidemiologia , Adulto , Argélia/epidemiologia , Autoanticorpos/análise , Biomarcadores/análise , Biomarcadores/sangue , Estudos de Coortes , Feminino , Imunofluorescência , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Prognóstico , Escleroderma Sistêmico/diagnóstico
14.
Lancet Respir Med ; 8(3): 304-320, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32113575

RESUMO

Systemic sclerosis is an autoimmune connective tissue disease, which is characterised by immune dysregulation and progressive fibrosis that typically affects the skin, with variable internal organ involvement. It is a rare condition that affects mostly young and middle-aged women, resulting in disproportionate morbidity and mortality. Currently, interstitial lung disease is the most common cause of death among patients with systemic sclerosis, with a prevalence of up to 30% and a 10-year mortality of up to 40%. Interstitial lung disease is more common among African Americans and in people with the diffuse cutaneous form of systemic sclerosis or anti-topoisomerase 1 antibodies. Systemic sclerosis-associated interstitial lung disease most commonly presents with dyspnoea, cough, and a non-specific interstitial pneumonia pattern on CT scan, with a minority of cases fulfilling the criteria for usual interstitial pneumonia. The standard therapy has traditionally been combinations of immunosuppressants, particularly mycophenolate mofetil or cyclophosphamide. These immunosuppressants can be supplemented by targeted biological and antifibrotic therapies, whereas autologous haematopoietic stem-cell transplantation and lung transplantation are reserved for refractory cases.


Assuntos
Doenças Pulmonares Intersticiais/etiologia , Escleroderma Sistêmico/complicações , Progressão da Doença , Feminino , Humanos , Doenças Pulmonares Intersticiais/diagnóstico , Doenças Pulmonares Intersticiais/patologia , Doenças Pulmonares Intersticiais/terapia , Masculino , Escleroderma Sistêmico/diagnóstico , Escleroderma Sistêmico/patologia , Escleroderma Sistêmico/terapia
15.
Autoimmun Rev ; 19(5): 102515, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32173517

RESUMO

Systemic sclerosis (SSc) is an autoimmune disease which is characterized by vasculopathy, tissue fibrosis and activation of the innate and adaptive immune system. Clinical features of the disease consists of skin thickening and internal organ involvement. Due to the heterogeneous nature of the disease it is difficult to predict disease progression and complications. Despite the discovery of novel autoantibodies associated with SSc, there is an unmet need for biomarkers for diagnosis, disease progression and response to treatment. To date, the use of single (surrogate) biomarkers for these purposes has been unsuccessful. Combining multiple biomarkers in to predictive panels or ultimately algorithms could be more precise. Given the limited therapeutic options and poor prognosis of many SSc patients, a better understanding of the immune-pathofysiological profiles might aid to an adjusted therapeutic approach. Therefore, we set out to explore immunological fingerprints in various clinically defined forms of SSc. We used multilayer profiling to identify unique immune profiles underlying distinct autoantibody signatures. These immune profiles could fill the unmet need for prognosis and response to therapy in SSc. Here, we present 3 pathophysiological fingerprints in SSc based on the expression of circulating antibodies, vascular markers and immunomodulatory mediators.


Assuntos
Medicina de Precisão , Escleroderma Sistêmico/diagnóstico , Escleroderma Sistêmico/fisiopatologia , Autoanticorpos/imunologia , Biomarcadores/análise , Feminino , Fibrose/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Escleroderma Sistêmico/imunologia , Escleroderma Sistêmico/patologia
16.
Autoimmun Rev ; 19(5): 102507, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32194200

RESUMO

A few scores predicting the short-term risk of mortality in Systemic sclerosis (SSc) have been reported to date. Our study aimed to create a predictive 15-year all-cause mortality score at the time of the diagnosis of SSc. The study was based on the Spanish Scleroderma Registry (RESCLE). The cohort was split up in derivation (DC) and validation cohort (VC). A multivariate analysis to detect variables related to all-cause mortality within the first 15 years from SSc diagnosis was performed, assigning points to the rounded beta values to create the score (RESCLESCORE). 1935 SSc patients were included. The variables in the final model were as follows: age at diagnosis (+2 points > 65 years-old), male gender (+1 point), lcSSc subset (-1 point), mode of onset other than Raynaud's (+1 point), cancer (+1 point) and visceral involvement, such as ILD (+1 point), PAH (+1 point), heart (+1 point) and renal involvement (+2 points). Autoantibodies did not achieve statistical significance in the multivariate analysis. The 3 categories of risk to predict 15-year all-cause mortality at the time of diagnosis were as follows: low risk (5% vs. 7%, p = .189), intermediate risk (26.5% vs. 25.5%, p = .911) and high risk (47.8% vs. 59%, p = .316). The AUC was 0.799 (DC) vs. 0.778 (VC) (p = .530). In conclusion, the RESCLESCORE demonstrated an excellent ability to categorize SSc patients at the time of diagnosis in separate 15-year all-cause mortality risk strata at the time of diagnosis.


Assuntos
Causas de Morte , Escleroderma Sistêmico/diagnóstico , Escleroderma Sistêmico/mortalidade , Idoso , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Doença de Raynaud/diagnóstico , Doença de Raynaud/mortalidade , Sistema de Registros , Reprodutibilidade dos Testes , Espanha/epidemiologia
17.
Surg Pathol Clin ; 13(1): 165-188, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32005430

RESUMO

Patients with connective tissue diseases may have pulmonary involvement, including interstitial lung disease. Various patterns of interstitial lung disease have been classically described in certain connective tissue diseases. It is now recognized that there is significant overlap between patterns of interstitial lung disease observed in the various connective tissue diseases. Differentiating idiopathic from connective tissue disease-related interstitial lung disease is challenging but of clinical importance. New concepts in the diagnosis of connective tissue disease related interstitial lung disease may prove useful in making the diagnosis.


Assuntos
Doenças do Tecido Conjuntivo/diagnóstico , Doenças Pulmonares Intersticiais/diagnóstico , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/patologia , Doenças do Tecido Conjuntivo/patologia , Dermatomiosite/diagnóstico , Dermatomiosite/patologia , Diagnóstico Diferencial , Humanos , Pulmão/patologia , Doenças Pulmonares Intersticiais/patologia , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/patologia , Doença Mista do Tecido Conjuntivo/diagnóstico , Doença Mista do Tecido Conjuntivo/patologia , Polimiosite/diagnóstico , Polimiosite/patologia , Escleroderma Sistêmico/diagnóstico , Escleroderma Sistêmico/patologia , Síndrome de Sjogren/diagnóstico , Síndrome de Sjogren/patologia
18.
Int J Cardiovasc Imaging ; 36(5): 883-888, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32060775

RESUMO

This study examined the relationship between global longitudinal strain (GLS) and pulmonary function tests (PFT) in patients with systemic sclerosis (SS) and normal ejection fraction (EF) and pulmonary artery pressure (PAP) and healthy controls. Sixty patients in two groups underwent extensive screening, including echocardiography, physical examination, the modified Rodnan Skin Score, and pulmonary function tests. Pulmonary interstitial disease was diagnosed by the pulmonary function test and by CT scan in case of indication. GLS score was computed as the mean peak systolic strain for 17 segments. The mean GLS score was - 18.36 ± 2.1 in the case group and - 20.66 ± 1.6 in the control group (P value < 0.001). GLS scores had a significant inverse relationship with the forced expiratory volume in one second (FEV1) to forced vital capacity (FVC) ratio (P value = 0.049) and both FEV and FVC in patients younger than 35 years old (P = 0.046 and 0.049, respectively). GLS scores had no significant relationship with time elapsed since the onset of skin manifestations, and Raynaud phenomenon, Rodnan score, EF, systolic PAP, or the six-minute walk test results. The patients' six-minute walk test had a significant positive relationship with FVC and right ventricular end diastolic diameter (P value = 0.018 and 0.047, respectively). According to our findings, GLS is significantly lower in patients with SS (with normal EF & PAP) than in healthy individuals. It is also related with certain pulmonary function indices including FEV1/FVC. The reduction in GLS is associated with reduced pulmonary function strength.


Assuntos
Pressão Arterial , Doenças Pulmonares Intersticiais/etiologia , Pulmão/irrigação sanguínea , Contração Miocárdica , Hipertensão Arterial Pulmonar/etiologia , Artéria Pulmonar/fisiopatologia , Escleroderma Sistêmico/complicações , Disfunção Ventricular Esquerda/etiologia , Função Ventricular Esquerda , Adulto , Estudos de Casos e Controles , Tolerância ao Exercício , Feminino , Volume Expiratório Forçado , Humanos , Pulmão/fisiopatologia , Doenças Pulmonares Intersticiais/diagnóstico , Doenças Pulmonares Intersticiais/fisiopatologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Hipertensão Arterial Pulmonar/diagnóstico , Hipertensão Arterial Pulmonar/fisiopatologia , Fatores de Risco , Escleroderma Sistêmico/diagnóstico , Escleroderma Sistêmico/fisiopatologia , Disfunção Ventricular Esquerda/diagnóstico por imagem , Disfunção Ventricular Esquerda/fisiopatologia , Função Ventricular Direita , Capacidade Vital
19.
Clin Exp Immunol ; 201(1): 14-24, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32048277

RESUMO

Toll-like receptors (TLRs) are evolutionarily conserved receptors essential for the host defence against pathogens. Both immune and non-immune cells can express TLRs, although at different levels. Systemic sclerosis (SSc) is a chronic disease in which autoimmunity, dysregulated profibrotic mediator release and activation of fibroblasts lead to dysregulated collagen deposition and fibrosis. There is now increasing knowledge that the innate immune system and, in particular, TLRs take a part in SSc pathogenesis. The list of endogenous ligands that can stimulate TLRs in SSc is growing: these ligands represent specific danger-associated molecular patterns (DAMPs), involved either in the initiation or the perpetuation of inflammation, and in the release of factors that sustain the fibrotic process or directly stimulate the cells that produce collagen and the endothelial cells. This review reports evidences concerning TLR signalling involvement in SSc. We report the new DAMPs, as well as the TLR-linked pathways involved in disease, with emphasis on type I interferon signature in SSc, the role of plasmacytoid dendritic cells (pDCs) and platelets. The dissection of the contribution of all these pathways to disease, and their correlation with the disease status, as well as their values as prognostic tools, can help to plan timely intervention and design new drugs for more appropriate therapeutic strategies.


Assuntos
Plaquetas/imunologia , Células Dendríticas/imunologia , Plasmócitos/imunologia , Escleroderma Sistêmico/imunologia , Receptores Toll-Like/imunologia , Animais , Plaquetas/patologia , Células Dendríticas/patologia , Humanos , Plasmócitos/patologia , Escleroderma Sistêmico/diagnóstico , Escleroderma Sistêmico/patologia
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