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1.
Sci Rep ; 9(1): 9468, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31263199

RESUMO

Quantitative high resolution computed tomography (HRCT) may objectively assess systemic sclerosis (SSc)-interstitial lung disease (ILD) extent, using three basic densitometric measures: mean lung attenuation (MLA), skewness, and kurtosis. This prospective study aimed to develop a composite index - computerized integrated index (CII) - that accounted for MLA, skewness, and kurtosis by means of Principal Component Analysis over HRCTs of 83 consecutive SSc subjects, thus eliminating redundancies. Correlations among CII, cardiopulmonary function and immune-inflammatory biomarkers (e.g. sIL-2Rα and CCL18 serum levels) were explored. ILD was detected in 47% of patients at visual HRCT assessment. These patients had worse CII values than patients without ILD. The CII correlated with lung function at both baseline and follow-up, and with sIL-2Rα and CCL18 serum levels. The best discriminating CII value for ILD was 0.1966 (AUC = 0.77; sensitivity = 0.81 [95%CI:0.68-0.92]; specificity = 0.66 [95%CI:0.52-0.80]). Thirty-four percent of patients without visual trace of ILD had a CII lower than 0.1966, and 67% of them had a diffusing lung capacity for CO <80% of predicted. We showed that this new composite CT index for SSc-ILD assessment correlates with both lung function and immune-inflammatory parameters and could be sufficiently sensitive for capturing early lung density changes in visually ILD-free patients.

2.
Arthritis Rheumatol ; 71(9): 1553-1570, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30969034

RESUMO

OBJECTIVE: Systemic sclerosis (SSc) is a heterogeneous connective tissue disease that is typically subdivided into limited cutaneous SSc (lcSSc) and diffuse cutaneous SSc (dcSSc) depending on the extent of skin involvement. This subclassification may not capture the entire variability of clinical phenotypes. The European Scleroderma Trials and Research (EUSTAR) database includes data on a prospective cohort of SSc patients from 122 European referral centers. This study was undertaken to perform a cluster analysis of EUSTAR data to distinguish and characterize homogeneous phenotypes without any a priori assumptions, and to examine survival among the clusters obtained. METHODS: A total of 11,318 patients were registered in the EUSTAR database, and 6,927 were included in the study. Twenty-four clinical and serologic variables were used for clustering. RESULTS: Clustering analyses provided a first delineation of 2 clusters showing moderate stability. In an exploratory attempt, we further characterized 6 homogeneous groups that differed with regard to their clinical features, autoantibody profile, and mortality. Some groups resembled usual dcSSc or lcSSc prototypes, but others exhibited unique features, such as a majority of lcSSc patients with a high rate of visceral damage and antitopoisomerase antibodies. Prognosis varied among groups and the presence of organ damage markedly impacted survival regardless of cutaneous involvement. CONCLUSION: Our findings suggest that restricting subsets of SSc patients to only those based on cutaneous involvement may not capture the complete heterogeneity of the disease. Organ damage and antibody profile should be taken into consideration when individuating homogeneous groups of patients with a distinct prognosis.

3.
Ann Rheum Dis ; 78(7): 979-987, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30967395

RESUMO

OBJECTIVE: To assess the safety and efficacy of rituximab in systemic sclerosis (SSc) in clinical practice. METHODS: We performed a prospective study including patients with SSc from the European Scleroderma Trials and Research (EUSTAR) network treated with rituximab and matched with untreated patients with SSc. The main outcomes measures were adverse events, skin fibrosis improvement, lung fibrosis worsening and steroids use among propensity score-matched patients treated or not with rituximab. RESULTS: 254 patients were treated with rituximab, in 58% for lung and in 32% for skin involvement. After a median follow-up of 2 years, about 70% of the patients had no side effect. Comparison of treated patients with 9575 propensity-score matched patients showed that patients treated with rituximab were more likely to have skin fibrosis improvement (22.7 vs 14.03 events per 100 person-years; OR: 2.79 [1.47-5.32]; p=0.002). Treated patients did not have significantly different rates of decrease in forced vital capacity (FVC)>10% (OR: 1.03 [0.55-1.94]; p=0.93) nor in carbon monoxide diffusing capacity (DLCO) decrease. Patients having received rituximab were more prone to stop or decrease steroids (OR: 2.34 [1.56-3.53], p<0.0001). Patients treated concomitantly with mycophenolate mofetil had a trend for better outcomes as compared with patients receiving rituximab alone (delta FVC: 5.22 [0.83-9.62]; p=0.019 as compared with controls vs 3 [0.66-5.35]; p=0.012). CONCLUSION: Rituximab use was associated with a good safety profile in this large SSc-cohort. Significant change was observed on skin fibrosis, but not on lung. However, the limitation is the observational design. The potential stabilisation of lung fibrosis by rituximab has to be addressed by a randomised trial.

4.
Autoimmun Rev ; 2018 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-30408582

RESUMO

Autoimmune rheumatic diseases are characterised by an abnormal immune system response, complement activation, cytokines dysregulation and inflammation. In last years, despite many progresses in managing these patients, it has been shown that clinical remission is reached in less than 50% of patients and a personalised and tailored therapeutic approach is still lacking resulting in a significant gap between guidelines and real-world practice. In this context, the need for biomarkers facilitating early diagnosis and profiling those individuals at the highest risk for a poor outcome has become of crucial interest. A biomarker generally refers to a measured characteristic which may be used as an indicator of some biological state or condition. Three different types of medical biomarkers has been suggested: i. mechanistic markers; ii. clinical disease markers; iii. therapeutic markers. A combination of biomarkers from these different groups could be used for an ideal more accurate diagnosis and treatment. However, although a growing body of evidence is focused on improving biomarkers, a significant amount of this information is not integrated on standard clinical care. The overarching aim of this work was to clarify the meaning of specific biomarkers during autoimmune diseases; their possible role in confirming diagnosis, predicting outcome and suggesting specific treatments.

5.
Clin Exp Rheumatol ; 36 Suppl 113(4): 68-75, 2018 Jul-Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30277860

RESUMO

OBJECTIVES: To describe differences in clinical presentation between men and women in a large group of patients with early (<3 years' duration) systemic sclerosis (SSc) according to disease subsets. METHODS: A cross-sectional analysis of the prospective EULAR Scleroderma Trial and Research database (EUSTAR) was performed. Patients fulfilling preliminary ACR 1980 classification criteria for SSc, with less than 3 years from the first non-Raynaud's symptom at first entry, were selected. A group of patients with less than 3 years from the first SSc symptom, including Raynaud's phenomenon, was also analysed. SSc related variables, including antibodies, SSc subsets, disease activity and organ involvement were included. Descriptive and bivariate analyses were performed. RESULTS: A total of 1,027 patients were included, 90% Caucasian, 80% women, and 40% with diffuse cutaneous disease. In early stages of SSc, men showed more frequently than women active disease, diffuse cutaneous subset, anti-Scl-70 antibodies, elevated acute phase reactants, muscular and pulmonary involvement. Differences between men and women were confirmed in the limited, but not in the diffuse SSc subset. The results were similar when 650 patients with less than three years from the first SSc symptom, including Raynaud's phenomenon, were analysed. CONCLUSIONS: In early stages of SSc, men present signs and symptoms of more severe disease. In the limited disease subset, men might appear with clinical features and organ involvement similar to those of the diffuse subgroup. In clinical practice, the identification of such differences might help to select the appropriate management for each particular patient.

6.
Clin Rheumatol ; 37(5): 1239-1247, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29442260

RESUMO

This study aims to investigate pre-clinical esophageal involvement in systemic sclerosis (SSc) by high-resolution impedance manometry (HRiM), its associations with disease features including lung involvement, and its predictivity of esophageal symptoms overtime. Charts of 45 asymptomatic (no heartburn/regurgitation/dysphagia) SSc patients (96% females; mean age 46 years) with at least one follow-up (FU) visit and complete clinical, serological, functional, and radiological assessment, including high-resolution computed tomography (HRCT) of the chest and lung function tests, that had undergone esophageal HRiM were retrospectively evaluated. Esophagogastric junction-contractile integral (EGJ-CI) and esophageal body motility, as evaluated by mean distal contractile integral (DCI), were assessed. SSc patients had a normal esophageal motility in 7/45 cases, a defective EGJ-CI in 28, an ineffective esophageal motility (IEM) in 17, and aperistalsis in 12. Defective EGJ-CI was associated with IEM/aperistalsis in 20 cases, while 9 patients had isolated IEM. Defective EGJ-CI and/or IEM/aperistalsis were associated with a diffusing lung capacity for CO < 80% of predicted value (all p < 0.05), while defective EGJ-CI was also associated with interstitial lung disease on HRCT (p = 0.03). Prevalence of any HRiM abnormality was higher in anti-centromere antibody negative patients (all p < 0.05). IEM/aperistalsis independently increased the risk of esophageal symptoms by 2.3-fold (95% CI 1.1-5.7) and was associated with their higher cumulative incidence with respect to patients with other HRiM patterns at FU (χ2 = 4.63; p = 0.03). SSc patients asymptomatic for esophageal involvement can have HRiM abnormalities in up to 84% of cases. A baseline-impaired motility is a risk factor for symptomatic esophageal disease.


Assuntos
Transtornos da Motilidade Esofágica/diagnóstico , Esôfago/fisiopatologia , Escleroderma Sistêmico/fisiopatologia , Adulto , Impedância Elétrica , Transtornos da Motilidade Esofágica/fisiopatologia , Feminino , Humanos , Masculino , Manometria , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Escleroderma Sistêmico/diagnóstico
8.
Rheumatology (Oxford) ; 57(3): 441-450, 2018 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-28499034

RESUMO

Objectives: The multisystem manifestations of SSc can greatly impact patients' quality of life. The aim of this study was to identify factors associated with disability in SSc. Methods: SSc patients from the prospective DeSScipher cohort who had completed the scleroderma health assessment questionnaire (SHAQ), a disability score that combines the health assessment questionnaire and five visual analogue scales, were included in this analysis. The effect of factors possibly associated with disability was analysed with multiple linear regressions. Results: The mean SHAQ and HAQ scores of the 944 patients included were 0.87 (s.d. = 0.66) and 0.92 (s.d. = 0.78); 59% of the patients were in the mild to moderate difficulty SHAQ category (0 ⩽ SHAQ < 1), 34% in the moderate to severe disability category (1 ⩽ SHAQ < 2) and 7% in the severe to very severe disability category (2 ⩽ SHAQ ⩽ 3). The means of the visual analogue scales scores were in order of magnitude: overall disease severity (37 mm), RP (31 mm), pulmonary symptoms (24 mm), gastrointestinal symptoms (20 mm) and digital ulcers (19 mm). In multiple regression, the main factors associated with high SHAQ scores were the presence of dyspnoea [modified New York Heart Association (NYHA) class IV (regression coefficient B = 0.62), modified NYHA class III (B = 0.53) and modified NYHA class II (B = 0.21; all vs modified NYHA class I)], FM (B = 0.37), muscle weakness (B = 0.27), digital ulcers (B = 0.20) and gastrointestinal symptoms (oesophageal symptoms, B = 0.16; stomach symptoms, B = 0.15; intestinal symptoms, B = 0.15). Conclusion: SSc patients perceive dyspnoea, pain, digital ulcers, muscle weakness and gastrointestinal symptoms as the main factors driving their level of disability, unlike physicians who emphasize objective measures of disability.


Assuntos
Atividades Cotidianas , Avaliação da Deficiência , Qualidade de Vida , Escleroderma Sistêmico/fisiopatologia , Perfil de Impacto da Doença , Europa (Continente) , Gastroenteropatias/etiologia , Gastroenteropatias/fisiopatologia , Humanos , Hipertensão Pulmonar/etiologia , Hipertensão Pulmonar/fisiopatologia , Estudos Longitudinais , Debilidade Muscular/etiologia , Debilidade Muscular/fisiopatologia , Medição da Dor , Estudos Prospectivos , Análise de Regressão , Fatores de Risco , Escleroderma Sistêmico/complicações , Escleroderma Sistêmico/psicologia , Índice de Gravidade de Doença , Úlcera Cutânea/etiologia , Úlcera Cutânea/fisiopatologia
9.
PLoS One ; 13(12): e0210023, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30596753

RESUMO

Carbamylation is a post-translational modification that mostly affects proteins with low turnover, such as dermal proteins. Carbamylated proteins accumulate in skin in an age-dependent manner, contributing to tissue alterations. As dermis is affected by systemic sclerosis (SSc) and anti-carbamylated protein antibodies (anti-CarP Ab) are found in SSc patients, we sought to evaluate the specificity of anti-CarP Ab and their relationship with clinical parameters reflecting skin involvement in SSc. This study investigated serum samples and clinical data from 124 patients with SSc. Anti-CarP Ab were affinity purified from pooled SSc sera, and their specificity was assessed by western blotting and ELISA with carbamylated proteins from two species (human and bovine albumin; human fibrinogen). Anti-CarP Ab were measured in SSc serum samples and in 41 healthy aged-matched individuals. Affinity-purified anti-CarP Ab recognized carbamylated epitopes irrespective of the protein type or species origin. Anti-CarP Ab levels inversely correlated with the modified Rodnan skin score (mRss) (Spearman's R = -0.32, p<0.001), independently of patients' age. Receiver operating characteristics (ROC) analysis identified anti-CarP Ab cut-offs that best discriminated dichotomized clinical variables related to skin involvement: the only clinical variables that were significantly different between groups were mRss (p = 0.001) and scleredema (p<0.001). Low anti-CarP Ab levels were associated with worse skin involvement. Future prospective studies are needed to assess their usefulness in the clinical setting.


Assuntos
Autoanticorpos/sangue , Carbamilação de Proteínas , Escleroderma Sistêmico/sangue , Pele/metabolismo , Adulto , Animais , Bovinos , Feminino , Fibrinogênio/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Escleroderma Sistêmico/patologia , Pele/patologia
10.
Ann Rheum Dis ; 76(11): 1897-1905, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-28835464

RESUMO

OBJECTIVES: To determine the causes of death and risk factors in systemic sclerosis (SSc). METHODS: Between 2000 and 2011, we examined the death certificates of all French patients with SSc to determine causes of death. Then we examined causes of death and developed a score associated with all-cause mortality from the international European Scleroderma Trials and Research (EUSTAR) database. Candidate prognostic factors were tested by Cox proportional hazards regression model by single variable analysis, followed by a multiple variable model stratified by centres. The bootstrapping technique was used for internal validation. RESULTS: We identified 2719 French certificates of deaths related to SSc, mainly from cardiac (31%) and respiratory (18%) causes, and an increase in SSc-specific mortality over time. Over a median follow-up of 2.3 years, 1072 (9.6%) of 11 193 patients from the EUSTAR sample died, from cardiac disease in 27% and respiratory causes in 17%. By multiple variable analysis, a risk score was developed, which accurately predicted the 3-year mortality, with an area under the curve of 0.82. The 3-year survival of patients in the upper quartile was 53%, in contrast with 98% in the first quartile. CONCLUSION: Combining two complementary and detailed databases enabled the collection of an unprecedented 3700 deaths, revealing the major contribution of the cardiopulmonary system to SSc mortality. We also developed a robust score to risk-stratify these patients and estimate their 3-year survival. With the emergence of new therapies, these important observations should help caregivers plan and refine the monitoring and management to prolong these patients' survival.


Assuntos
Escleroderma Sistêmico/mortalidade , Idoso , Causas de Morte , Bases de Dados Factuais , Atestado de Óbito , Feminino , França , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Fatores de Risco , Fatores de Tempo
11.
Clin Exp Rheumatol ; 35 Suppl 106(4): 114-121, 2017 Sep-Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28664832

RESUMO

OBJECTIVES: To explore the prevalence and clinical associations of elevated systolic pulmonary artery pressure (sPAP), measured by Transthoracic Doppler-echocardiography (TTE) in patients with early systemic sclerosis (SSc). METHODS: A cross-sectional analysis of the prospective EULAR Scleroderma Trial and Research (EUSTAR) database was performed. SSc patients with <3 years from the first non-Raynaud's phenomenon (RP) symptom at baseline EUSTAR visit, were selected. Elevated sPAP was defined as sPAP>40 mmHg on baseline TTE. First visit SSc related variables, including disease subsets, antibodies and visceral involvement, were examined. RESULTS: From 1,188 patients, 81% were women. Mean (SD) age at first non-RP symptom was 50 (14) years, 55% had limited cutaneous SSc (lcSSc) and 42% active disease. Elevated sPAP was found in 17% of patients, both lcSSc and diffuse cutaneous SSc (dcSSc). In lcSSc, older age at first non-RP symptom, ACA positivity, joint contractures, restrictive defect and lower DLCO, were independently associated with elevated sPAP. In dcSSc, older age at first non-RP symptom, longer time between RP onset and first non-RP symptom, digital ulcers, cardiac blocks, and proteinuria were associated with elevated sPAP. CONCLUSIONS: The prevalence of elevated sPAP on TTE in early SSc patients is considerable. Association with cardiac, lung and renal involvement suggests that, although some patients might have pulmonary arterial hypertension, others may present pulmonary hypertension secondary to lung or heart involvement. Our findings emphasize the need to consider right heart catheterisation in selected early SSc patients with PH suspicion, to clearly determine the cause of PH.


Assuntos
Ecocardiografia Doppler/métodos , Ecocardiografia/métodos , Artéria Pulmonar/fisiopatologia , Escleroderma Sistêmico/fisiopatologia , Sístole/fisiologia , Adulto , Idoso , Estudos Transversais , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Escleroderma Sistêmico/diagnóstico por imagem
12.
Autoimmun Rev ; 16(9): 911-924, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28705780

RESUMO

Autoimmune diseases are a complex set of diseases characterized by immune system activation and, although many progresses have been done in the last 15years, several unmet needs in the management of these patients may be still identified. Recently, a panel of international Experts, divided in different working groups according to their clinical and scientific expertise, were asked to identify, debate and formulate a list of key unmet needs within the field of rheumatology, serving as a roadmap for research as well as support for clinicians. After a systematic review of the literature, the results and the discussions from each working group were summarised in different statements. Due to the differences among the diseases and their heterogeneity, a large number of statements was produced and voted by the Experts to reach a consensus in a plenary session. At all the steps of this process, including the initial discussions by the steering committee, the identification of the unmet needs, the expansion of the working group and finally the development of statements, a large agreement was attained. This work confirmed that several unmet needs may be identified and despite the development of new therapeutic strategies as well as a better understanding of the effects of existing therapies, many open questions still remain in this field, suggesting a research agenda for the future and specific clinical suggestions which may allow physicians to better manage those clinical conditions still lacking of scientific clarity.


Assuntos
Doenças Autoimunes/diagnóstico , Doenças Reumáticas/diagnóstico , Doenças Autoimunes/imunologia , Doenças Autoimunes/terapia , Ensaios Clínicos como Assunto , Gerenciamento Clínico , Humanos , Melhoria de Qualidade , Doenças Reumáticas/imunologia , Doenças Reumáticas/terapia
13.
Arthritis Res Ther ; 19(1): 133, 2017 06 13.
Artigo em Inglês | MEDLINE | ID: mdl-28610600

RESUMO

BACKGROUND: Some abnormalities in nailfold videocapillaroscopy (NVC), such as the presence of micro-haemorrhages (MHEs), micro-thromboses (MTs), giant capillaries (GCs) and reduction in the number of capillaries (nCs), suggest a disease activity (DA) phase in systemic sclerosis (SSc). In a previous paper, we showed that the number of micro-haemorrhages and micro-thromboses (the so-called NEMO score) was the NVC feature more closely associated with DA. The present study was aimed at validating the NEMO score as a measure of DA in patients with SSc. METHODS: Two cohorts of 122 and 97 patients with SSc who were referred to two different rheumatology units, one in Milan and one in Naples, respectively, constituted the validation cohorts. The NEMO score, the total number of GCs and the mean nCs per digit were the parameters defined in each patient by eight-finger NVC. An expert operator analysed the NVCs in each of the participating units. The European Scleroderma Study Group (ESSG) index was used to define the DA level in each patient at the time of NVC examination. RESULTS: The NEMO score was the NVC parameter more strictly correlated with the ESSG score in both the Milan and Naples cohorts (p < 0.0001), and it was the only one among the NVC variables that gave a significant contribution in a logistic model where the ESSG score represented the dependent variable. ROC curve analysis confirmed that the NEMO score had the best performance in measuring DA. The AUC of the NEMO score was significantly greater than the AUCs obtained by plotting the sensitivity and specificity of the number of GCs and the mean nCs (p < 0.0001 in all cases). The NEMO score values that showed the best sensitivity-specificity balance in capturing patients with a relevant DA level were slightly higher in the Naples cohort than in the Milan cohort. CONCLUSIONS: This study confirms that the presence of a certain number of MHEs and MTs in NVC may be considered a strong warning signal of a current phase of DA in patients with SSc.


Assuntos
Hemorragia/fisiopatologia , Angioscopia Microscópica/métodos , Escleroderma Sistêmico/fisiopatologia , Trombose/fisiopatologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Dedos/irrigação sanguínea , Hemorragia/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Unhas/irrigação sanguínea , Reprodutibilidade dos Testes , Escleroderma Sistêmico/patologia , Trombose/patologia , Adulto Jovem
14.
Artigo em Inglês | MEDLINE | ID: mdl-28203114

RESUMO

INTRODUCTION/OBJECTIVES: To prospectively assess the quality of life (QoL) of patients affected by undifferentiated connective tissue diseases (UCTDs) and to identify factors associated with changes over time. PATIENTS AND METHODS: A total of 46 consecutive UCTD patients completed the Short-Form 36 (SF-36) questionnaire at presentation and then yearly. At each 6-month visit, all patients underwent a detailed history taking and a laboratory and physical assessment, in order to follow the evolution of the disease over time and to assess the the co-existence of fibromyalgia. RESULTS: At presentation, scores lower than the average of the general population were detected in 34 (74%) and 41 (89%) patients in the physical and mental domains, respectively. No difference between patients with and without Raynaud's phenomenon was detected. Fibromyalgia was the only independent variable associated with an impaired physical component summary score (p = 0.0009). No patient feature was found to be associated with the basal mental component summary score. During 24 months of follow-up, a significant improvement (ie, a change ≥5 from baseline) in physical component summary and mental component summary scores was observed in 14 (33.3%) and 20 (43.4%) patients, respectively. Patients who significantly improved in the physical domain more frequently had a history of glucocorticoids intake (p<0.001), while those who improved in the mental component more frequently had a history of either glucocorticoids (p = 0.043) or immunosuppressors (p = 0.037) intake during follow-up. CONCLUSION: UCTD patients perceive a worse QoL, regardless of Raynaud's phenomenon Fibromyalgia is one of the major contributors of physical QoL, whereas no factor influencing mental component has been identified. An improvement in QoL can be observed in less than half of patients over a 2-year follow-up. Larger studies are needed to identify factors influencing QoL and to define the role of pharmacological treatments.

15.
Ann Rheum Dis ; 76(1): 270-276, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27621285

RESUMO

BACKGROUND: Validity of European Scleroderma Study Group (EScSG) activity indexes currently used to assess disease activity in systemic sclerosis (SSc) has been criticised. METHODS: Three investigators assigned an activity score on a 0-10 scale for 97 clinical charts. The median score served as gold standard. Two other investigators labelled the disease as inactive/moderately active or active/very active. Univariate-multivariate linear regression analyses were used to define variables predicting the 'gold standard', their weight and derive an activity index. The cut-off point of the index best separating active/very active from inactive/moderately active disease was identified by a receiver-operating curve analysis. The index was validated on a second set of 60 charts assessed by three different investigators on a 0-10 scale and defined as inactive/moderately active or active/very active by other two investigators. One hundred and twenty-three were investigated for changes over time in the index and their relationships with those in the summed Medsger severity score (MSS). RESULTS: A weighted 10-point activity index was identified and validated: Δ-skin=1.5 (Δ=patient assessed worsening during the previous month), modified Rodnan skin score (mRss) >18=1.5, digital ulcers=1.5, tendon friction rubs=2.25, C-reactive protein >1 mg/dL=2.25 and diffusing capacity of the lung for CO (DLCO) % predicted <70%=1.0. A cut-off ≥2.5 was found to identify patients with active disease. Changes in the index paralleled those of MSS (p=0.0001). CONCLUSIONS: A preliminarily revised SSc activity index has been developed and validated, providing a valuable tool for clinical practice and observational studies.


Assuntos
Escleroderma Sistêmico/diagnóstico , Índice de Gravidade de Doença , Adulto , Idoso , Idoso de 80 Anos ou mais , Europa (Continente)/epidemiologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Curva ROC , Reprodutibilidade dos Testes , Escleroderma Sistêmico/complicações , Escleroderma Sistêmico/epidemiologia , Sensibilidade e Especificidade , Adulto Jovem
16.
Clin Exp Med ; 17(3): 411-414, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27650429

RESUMO

The aim of the study was to evaluate CXCL4 levels in undifferentiated connective tissue disease at risk for SSc (UCTD-SSc-risk) and confirm its increase and investigate its prognostic value. Serum CXCL4 levels were measured in 45 patients and 24 controls. CXCL4 was significantly higher in UCTD-SSc-risk patients than in controls. It resulted higher in patients with a shorter disease duration and in those lacking capillaroscopic alterations. We confirm that CXCL4 levels are increased in UCTD-risk-SSc patients. Further studies are needed to investigate the role of CXCL4 assessment in UCTD-risk-SSc.


Assuntos
Fator Plaquetário 4/sangue , Escleroderma Sistêmico/diagnóstico , Escleroderma Sistêmico/patologia , Doenças do Tecido Conjuntivo Indiferenciado/complicações , Doenças do Tecido Conjuntivo Indiferenciado/patologia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Doenças do Tecido Conjuntivo Indiferenciado/diagnóstico
17.
PLoS One ; 11(10): e0163894, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27706206

RESUMO

OBJECTIVE: Systemic sclerosis (SSc) is a rare and clinically heterogeneous autoimmune disorder characterised by fibrosis and microvascular obliteration of the skin and internal organs. Organ involvement mostly manifests after a variable period of the onset of Raynaud's phenomenon (RP). We aimed to map the incidence and predictors of pulmonary, cardiac, gastrointestinal (GI) and renal involvement in the early course of SSc. METHODS: In the EUSTAR cohort, patients with early SSc were identified as those who had a visit within the first year after RP onset. Incident SSc organ manifestations and their risk factors were assessed using Kaplan-Meier methods and Cox regression analysis. RESULTS: Of the 695 SSc patients who had a baseline visit within 1 year after RP onset, the incident non-RP manifestations (in order of frequency) were: skin sclerosis (75%) GI symptoms (71%), impaired diffusing capacity for monoxide<80% predicted (65%), DU (34%), cardiac involvement (32%), FVC<80% predicted (31%), increased PAPsys>40mmHg (14%), and renal crisis (3%). In the heart, incidence rates were highest for diastolic dysfunction, followed by conduction blocks and pericardial effusion. While the main baseline risk factor for a short timespan to develop FVC impairment was diffuse skin involvement, for PAPsys>40mmHg it was higher patient age. The main risk factors for incident cardiac manifestations were anti-topoisomerase autoantibody positivity and older age. Male sex, anti-RNA-polymerase-III positivity, and older age were risk factors associated with incident renal crisis. CONCLUSION: In SSc patients presenting early after RP onset, approximately half of all incident organ manifestations occur within 2 years and have a simultaneous rather than a sequential onset. These findings have implications for the design of new diagnostic and therapeutic strategies aimed to 'widen' the still very narrow 'window of opportunity'. They may also enable physicians to counsel and manage patients presenting early in the course of SSc more accurately.


Assuntos
Gastroenteropatias/epidemiologia , Cardiopatias/epidemiologia , Nefropatias/epidemiologia , Pneumopatias/epidemiologia , Doença de Raynaud/complicações , Escleroderma Sistêmico/complicações , Dermatopatias/epidemiologia , Adulto , Idoso , Autoanticorpos , Feminino , Humanos , Incidência , Estimativa de Kaplan-Meier , Estudos Longitudinais , Pneumopatias/fisiopatologia , Masculino , Pessoa de Meia-Idade , Doença de Raynaud/fisiopatologia , Análise de Regressão , Estudos Retrospectivos , Fatores de Risco , Escleroderma Sistêmico/fisiopatologia
18.
Clin Rheumatol ; 35(10): 2591-6, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27562035

RESUMO

CXCL4 is an antiangiogenic and immunomodulatory chemokine. We aimed to investigate serum levels of CXCL4 in primary Sjögren's syndrome (pSS), looking for associations with disease features. Thirty-nine consecutive pSS patients underwent clinical-serological assessment and nailfold videocapillaroscopy (NVC). Thirty-six patients and 30 controls affected by osteoarthritis were also investigated for serum levels of CXCL4 and soluble E-selectin (sE-selectin). CXCL4 was higher in pSS patients than in controls (1.79 [0.2-11.18] vs 1.023 ng/ml [0.02-14.45], p < 0.05), particularly in those without anti-La/SSB antibodies (2.89 [1.01-11.18] vs 1.69 ng/ml [0.2-2.72], p < 0.05), while it was lower in pSS patients with a focus score ≥1 at lip biopsy (1.44 [0.86-2.1] vs 2.24 ng/ml [1.64-3.25], p < 0.05) and clinically evident lymphadenopathy (1.53 [0.38-1.7] vs 2.08 ng/ml [1.45-3.03], p < 0.05). CXCL4 correlated with disease duration (r = 0.35, p < 0.05) and sE-selectin (r = 0.45, p < 0.01). Patients with Raynaud's phenomenon (RP) had more frequently abnormal CXCL4 levels than patients without RP (11/15 vs 3/21, p < 0.001), enlarged capillaries (14/16 vs 7/23, p < 0.001) and capillary loss at NVC (14/16 vs 6/23, p < 0.001). The hitherto unknown association of increased serum CXCL4 with features of microvascular impairment in pSS, along with the negative association with features of lymphocytic response (i.e., the absence of subset disease-specific autoantibodies, a low focus score, and the absence of lymphadenopathy) suggest clarifying the possible implication of this chemokine in pSS pathogenesis in larger studies.


Assuntos
Capilares/patologia , Linfonodos/patologia , Fator Plaquetário 4/sangue , Doença de Raynaud/sangue , Glândulas Salivares/patologia , Síndrome de Sjogren/sangue , Adulto , Idoso , Autoanticorpos/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doença de Raynaud/etiologia , Doença de Raynaud/patologia , Síndrome de Sjogren/complicações , Síndrome de Sjogren/patologia
19.
Int J Cardiol ; 223: 385-389, 2016 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-27543715

RESUMO

OBJECTIVES: Cardiovascular involvement is a major contributor to mortality in systemic sclerosis (SSc). We examined whether N-terminal pro-brain natriuretic peptide (NT-proBNP) is a reliable predictor of mortality in SSc. METHODS AND RESULTS: This multicentre prospective cohort study included 523 patients presenting with SSc, whose mean age was 54±13years, mean disease duration 8±9years, and diffuse cutaneous form in 168. Plasma NT-proBNP was measured at baseline and the patients were followed yearly. Overall mortality was measured at 3years. At baseline, cardiovascular involvement was present in 37 patients, including 17 with pulmonary artery hypertension (PAH) and 20 with a left ventricular ejection fraction (LVEF) <55%. At 3years, 32 (7%) patients had died. The median [25th-75th percentile] NT-proBNP concentration was 203ng/l [129-514] in patients who died within 3years, versus 88ng/l [47-167] in survivors (P<0.001). NT-proBNP was an independent predictor of 3-years mortality in multivariate analysis (P=0.046). The optimal cut-off derived from the ROC curve was 129ng/l; sensitivity and specificity to predict 3y mortality were 78.1 and 66.7%. Using the previously recommended 125-ng/l concentration as threshold value, NT-proBNP reliably and independently predicted 3year mortality, with a sensitivity of 78.1 and a negative predictive value of 97.6%, respectively (P=0.006). The consideration of SSc patients without PAH or LVEF<55% at baseline yielded similar results. CONCLUSION: NT-proBNP appears as a reliable and independent predictor of mortality in patients with SSc.


Assuntos
Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Escleroderma Sistêmico/sangue , Escleroderma Sistêmico/mortalidade , Idoso , Biomarcadores/sangue , Feminino , Seguimentos , França/epidemiologia , Alemanha/epidemiologia , Humanos , Hungria/epidemiologia , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Estudos Prospectivos , Curva ROC , Taxa de Sobrevida/tendências , Fatores de Tempo
20.
Medicine (Baltimore) ; 95(25): e3931, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27336883

RESUMO

Patients with systemic sclerosis (SSc) who express autoantibodies to centromeric proteins (CENPs) are at risk of developing pulmonary vascular disease and pulmonary arterial hypertension without fibrosis. Currently no biomarkers are available to predict these complications. We previously characterized the fine specificity of anti-CENP-A antibodies in SSc by screening a phage display library (expressing random 12-mer peptides), and identified phage clones whose peptides were differentially recognized by patients' autoantibodies. Here, we examined if subgroups of SSc patients with different anti-CENP-A antibody subspecificities also differ clinically, and if serum reactivity to phage-displayed peptides can predict pulmonary vascular disease.Clinical data and serum samples were collected from 84 anti-CENP-A-positive SSc patients. Indirect ELISAs were used to test serum reactivity. Pulmonary vascular disease was defined as high systolic pulmonary arterial pressure (sPAP) and low diffusing lung capacity for carbon monoxide (DLCO; percent of predicted values).Sera were screened for reactivity to peptides expressed by phage clones pc4.2 and pc14.1, confirming our earlier observation of differential specificities. Linear regression showed that the levels of antibodies specific for the 2 phage clones were associated with clinical features of pulmonary vascular disease, but in opposite ways: anti-pc4.2 antibodies were positively associated with sPAP and inversely associated with DLCO, whereas anti-pc14.1 antibodies were inversely associated with sPAP and positively associated with DLCO. Anti-pc4.2 and anti-pc14.1 antibody levels predicted sPAP independently of DLCO. These associations were confirmed by logistic regression using antibodies as predictors and dichotomized sPAP (cutoff, 45 mm Hg) as outcome. The ratio of the 2 antibody levels was a useful marker in predicting high sPAP.This study demonstrates that some SSc clinical features associate with subspecificities of anti-CENP-A antibodies. Moreover, it shows that a simple, inexpensive phage-based assay can predict which SSc patients have high sPAP and low DLCO, hence who are at greater risk of developing pulmonary arterial hypertension. The ability to identify these at-risk patients can contribute to clinical efficiency and effectiveness. Further research into the peptides expressed by the phage clones may reveal the molecular mechanisms that put some anti-CENP-A-positive patients at greater risk than others for pulmonary vascular disease.


Assuntos
Autoanticorpos/imunologia , Autoantígenos/imunologia , Autoimunidade , Proteínas Cromossômicas não Histona/imunologia , Hipertensão Pulmonar/etiologia , Escleroderma Sistêmico/complicações , Autoanticorpos/sangue , Autoantígenos/sangue , Biomarcadores/sangue , Proteína Centromérica A , Proteínas Cromossômicas não Histona/sangue , Ensaio de Imunoadsorção Enzimática , Feminino , Seguimentos , Humanos , Hipertensão Pulmonar/diagnóstico , Hipertensão Pulmonar/imunologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Escleroderma Sistêmico/sangue , Escleroderma Sistêmico/imunologia
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