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1.
Medicine (Baltimore) ; 99(43): e22443, 2020 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-33120739

RESUMO

The objectives of this study were to describe the prevalence and characteristics of radiographic lesions of the hands, and calcifications of the spine on computer tomography scans (CT-scans), and to investigate the relationships between radiographic and CT-scan abnormalities and clinical features in a population of patients with systemic sclerosis (SSc).Subjects underwent X-ray examination of the hands, and thoracic or thoraco-abdominal and pelvic CT scan or lumbar CT scan in the year. Structural lesions on hand X ray was scored and spinal calcifications were evaluated in the anterior, intracanal and posterior segments. Intra and inter-reliability was tested for radiography and CT- scan. Prognostic factors considered were interstitial pulmonary lesions on the CT scan, pulmonary arterial hypertension (PAH) and death.This study involved 77 SSc patients, 58 (75%) with limited cutaneous SSc (lcSSc) and 19 (25%) with diffuse SSc (dSSc). The prevalences of radiographic lesions of the hand were 28.6% for periarticular calcifications and 26% for calcinosis. On CT scan, 64 (83%) patients exhibited at least 1 calcification. Spine calcifications were depicted in 80.5%, 27.3%, and 35.1% at the anterior, intracanal and posterior segments respectively. Calcifications were mainly localized on thoracic spine. Inter reader reliabilities were good for hands and moderate for spine respectively. Spine calcifications and periarticular calcifications in the hands were associated (P = .012). Calcinosis in the hands was related to PAH (P = .02). Posterior calcification segment and foraminal calcifications were associated with interstitial lung disease (ILD) (P = .029) and death (P = .001).More than 80% of systemic sclerosis patients presented spine calcifications. A significant association between hands and spinal calcifications were confirmed and some localization in the posterior segment considered as a bad prognostic factor.


Assuntos
Calcinose/diagnóstico por imagem , Ossos da Mão/diagnóstico por imagem , Escleroderma Sistêmico/complicações , Doenças da Coluna Vertebral/diagnóstico por imagem , Coluna Vertebral/diagnóstico por imagem , Fatores Etários , Feminino , Humanos , Hipertensão Pulmonar/complicações , Doenças Pulmonares Intersticiais/complicações , Masculino , Pessoa de Meia-Idade , Prognóstico , Radiografia , Reprodutibilidade dos Testes , Estudos Retrospectivos , Escleroderma Sistêmico/mortalidade , Tomografia Computadorizada por Raios X
2.
Medicine (Baltimore) ; 99(41): e22582, 2020 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-33031308

RESUMO

RATIONALE: Systemic sclerosis (SSc) is a serious multisystem connective tissue disease. When SSc is accompanied by systemic lupus erythematosus (SLE), called SSc-SLE overlap syndrome. SSc associated thrombotic microangiopathy (SSc-TMA) can lead to scleroderma renal crisis, it mainly manifests hypertension or even malignant hypertension, acute kidney injury, and higher mortality. The case of SSc-SLE overlap syndrome combined with SSc-TMA has rarely been reported. PATIENT CONCERNS: We report the case of an elderly male with SSc-SLE overlap syndrome combined with scleroderma renal crisis and SSc-TMA. DIAGNOSES: The patient has typical of SSc on the face and hands, combined with pulmonary artery hypertension, interstitial lung disease, heart failure and malignant hypertension, as well as SLE, lupus nephritis class V, and TMA, which were definitively diagnosed by clinical laboratory examination and renal histopathology. INTERVENTIONS: The patient was treated with prednisone, cyclophosphamid, renin-angiotensin system inhibitors, diuretics, and acetylcysteine. OUTCOMES: The patient died suddenly of heart failure on the 35th day after discharge. LESSONS: The occurrence of TMA leads to the deterioration of the prognosis of SSC-SLE overlap syndrome. The diagnosis of SSC-TMA in SSc-SLE overlap syndrome depends on clinical laboratory examination and renal histopathology.


Assuntos
Lúpus Eritematoso Sistêmico/complicações , Esclerodermia Localizada/complicações , Escleroderma Sistêmico/complicações , Microangiopatias Trombóticas/complicações , Humanos , Masculino , Pessoa de Meia-Idade
4.
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
5.
Medicine (Baltimore) ; 99(33): e21734, 2020 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-32872058

RESUMO

To compare clinical characteristics and identify long-term outcomes of Chinese patients with systemic sclerosis (SSc) with and without muscle involvement.We retrospectively investigated the medical records, laboratory results, and computed tomography images of 204 consecutive SSc patients. Kaplan-Meier analysis was performed to determine survival rates. Patients were allocated into groups with and without myopathy.The prevalence of myopathy was 21.6%. The myopathy group was more likely to develop diffuse cutaneous involvement (90.9% vs 56%, P = .006), interstitial lung disease (90% vs 56%, P < .001), digestive system involvement (56.7% vs 29.3%, P = .001), pulmonary hypertension (29.5% vs 10.5%, P = .004), and pericardial effusion (25% vs. 10%, P = .019). Patients with myopathy had lower single-breath diffusing capacity of the lung for carbon oxide (46.5 ±â€Š11.1 vs 57.1 ±â€Š13.4, P < .001).Further, the myopathy group has similar results in interstitial lung disease associated higher resolution computed tomography score (186.8 ±â€Š64.5 vs 152.3 ±â€Š45.5, P = .037), Valentini score for disease activity (3.4 ±â€Š0.9 vs 2.0 ±â€Š0.9, P < .001) and modified Rodnan total skin score (19.4 ±â€Š6.1 vs 15.1 ±â€Š7.7, P = .002), compared with non-myopathy group. Kaplan-Meier survival analysis revealed decreased overall survival rate of the myopathy group (P = .028).SSc Patients with myopathy had more severe clinical manifestations and higher disease activity compared with those without, which affected survival rates and indicated worse prognosis.


Assuntos
Doenças Musculares/mortalidade , Escleroderma Sistêmico/mortalidade , Adulto , Idoso , China/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doenças Musculares/etiologia , Estudos Retrospectivos , Escleroderma Sistêmico/complicações
6.
Medicine (Baltimore) ; 99(38): e22239, 2020 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-32957368

RESUMO

BACKGROUND: Prolactin (PRL), an inflammatory hormone with cytokine properties, has long been considered to play a crucial role in the pathogenesis of autoimmune diseases, including systemic sclerosis (SSc). However, the plasma/serum levels of PRL in SSc were inconsistent in published studies. The aim of this study was to evaluate the plasma/serum levels of PRL in patients with SSc accurately. METHODS: Electronic databases, including PubMed, EMBASE, Cochrane Library, CNKI, VIP and WANFANG databases, were searched up to October 15, 2019. Pooled standard mean difference (SMD) with 95% confidence interval (CI) was calculated by fixed-effect or random-effects model analysis. All statistical analyses were conducted with STATA 12.0. RESULTS: Fifty three articles were obtained after searching databases, and 9 studies with 293 SSc patients and 282 controls were finally included. The meta-analysis showed that the plasma/serum PRL level in SSC patients was significantly increased compared with the healthy controls, with the SMD of 1.00 and 95% CI (0.56, 1.43). Subgroup analysis showed that female patients had higher plasma/serum PRL levels. However, no significant change in plasma/serum PRL levels was observed in male patients (P = .318). In subgroup analysis by detection type, electrochemiluminescence immunoassay (ECLIA) group and enzyme-linked immunosorbent assay (ELISA) group showed higher PRL levels among SSc patients. CONCLUSIONS: In summary, our meta-analysis showed a significantly higher plasma/serum PRL level in SSc patients than healthy controls, and it was associated with gender and detection method.


Assuntos
Prolactina/metabolismo , Escleroderma Sistêmico/sangue , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Medições Luminescentes , Masculino , Fatores Sexuais
8.
RMD Open ; 6(2)2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32878994

RESUMO

OBJECTIVES: Patients with inflammatory rheumatic diseases (IRD) infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may be at risk to develop a severe course of COVID-19. The influence of immunomodulating drugs on the course of COVID-19 is unknown. To gather knowledge about SARS-CoV-2 infections in patients with IRD, we established a registry shortly after the beginning of the pandemic in Germany. METHODS: Using an online questionnaire (www.COVID19-rheuma.de), a nationwide database was launched on 30 March 2020, with appropriate ethical and data protection approval to collect data of patients with IRD infected with SARS-CoV-2. In this registry, key clinical and epidemiological parameters-for example, diagnosis of IRD, antirheumatic therapies, comorbidities and course of the infection-are documented. RESULTS: Until 25 April 2020, data from 104 patients with IRD infected with SARS-CoV-2 were reported (40 males; 63 females; 1 diverse). Most of them (45%) were diagnosed with rheumatoid arthritis, 59% had one or more comorbidities and 42% were treated with biological disease-modifying antirheumatic drugs. Hospitalisation was reported in 32% of the patients. Two-thirds of the patients already recovered. Unfortunately, 6 patients had a fatal course. CONCLUSIONS: In a short time, a national registry for SARS-CoV2-infected patients with IRD was established. Within 4 weeks, 104 cases were documented. The registry enables to generate data rapidly in this emerging situation and to gain a better understanding of the course of SARS-CoV2-infection in patients with IRD, with a distinct focus on their immunomodulatory therapies. This knowledge is valuable for timely information of physicians and patients with IRD, and shall also serve for the development of guidance for the management of patients with IRD during this pandemic.


Assuntos
Antirreumáticos/uso terapêutico , Produtos Biológicos/uso terapêutico , Infecções por Coronavirus/fisiopatologia , Pneumonia Viral/fisiopatologia , Sistema de Registros , Doenças Reumáticas/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Artrite Psoriásica/complicações , Artrite Psoriásica/tratamento farmacológico , Artrite Reumatoide/complicações , Artrite Reumatoide/tratamento farmacológico , Betacoronavirus , Infecções por Coronavirus/complicações , Infecções por Coronavirus/mortalidade , Feminino , Alemanha , Granulomatose com Poliangiite/complicações , Granulomatose com Poliangiite/tratamento farmacológico , Hospitalização , Humanos , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/mortalidade , Polimialgia Reumática/complicações , Polimialgia Reumática/tratamento farmacológico , Prognóstico , Doenças Reumáticas/complicações , Escleroderma Sistêmico/complicações , Escleroderma Sistêmico/tratamento farmacológico , Índice de Gravidade de Doença , Espondilite Anquilosante/complicações , Espondilite Anquilosante/tratamento farmacológico , Adulto Jovem
9.
Clin Exp Rheumatol ; 38 Suppl 125(3): 98-105, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32865165

RESUMO

OBJECTIVES: We aimed to investigate patients with early diffuse cutaneous systemic sclerosis (dcSSc) with regard to: 1. the association between skin thickness progression rate (STPR) at baseline visit and incidence rate of cardiopulmonary complications; 2. comparison of the mortality rate between patients with skin improvers and those with skin non-improvers. METHODS: An inception cohort of early dcSSc patients seen at the Rheumatology Clinic, Maharaj Nakorn Chiang Mai Hospital, Thailand, was selected. All patients were assessed for clinical manifestations, and modified Rodnan skin score (mRSS) and underwent echocardiography, and HRCT at study entry and then annually. RESULTS: One hundred and four dcSSc patients (57 of whom were females and 91 anti-topoisomerase I-positive) with a mean disease duration of 11.1±8.6 months were enrolled. Forty-two patients had rapid STPR [RPsp], 38 intermediate STPR [IMsp] and 24 slow STPR [SLsp]. At enrolment, the RPsp group had a significantly shorter disease duration, more prevalent anti-topoisomerase-I-positive, higher mRSS, more prevalent creatine kinase≥500 IU/L and higher NT-proBNP levels compared to the IMSp and SLsp groups. During a mean observation period of 4.5±2.0 years, the RPsp group had a significantly higher incidence rate of LVEF< 50% (6.06 vs. 0 per 100 person- years, p=<0.01) and interstitial lung disease (ILD) (69.69 vs. 34.66 per 100 person-years, p=0.012) than the SLsp group. Skin non-improvers had a signif- icantly higher mortality rate than skin improvers (28.6% vs. 5.8 %, p= 0.004). CONCLUSIONS: In this early dcSSc study cohort it was found that skin change determined by STPR at the baseline visit was a useful surrogate marker for cardiac and ILD complications. It was also found that skin improvers assessed 1-year later were a useful surrogate marker of mortality.


Assuntos
Doenças Pulmonares Intersticiais , Esclerodermia Difusa , Escleroderma Sistêmico , Estudos de Coortes , Feminino , Humanos , Incidência , Pele , Tailândia
10.
Clin Exp Rheumatol ; 38 Suppl 125(3): 137-139, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32865166

RESUMO

OBJECTIVES: The assessment of digital ulcers (DUs) in systemic sclerosis (SSc) depends crucially on visual aspects. However, little is known about the differences in visual assessment of these wounds between experts and non-experts or medical lay persons (novices). To develop potential training recommendations for the visual assessment of digital ulcers in SSc, we analysed gaze pattern data during assessment of digital ulcers between assessors with different levels of expertise. METHODS: Gaze pattern data from 36 participants were collected with a mobile eye tracking device. 20 pictures from digital ulcers of SSc patients were presented to each participant. The analysis comprised the scan path, the dwell times (for areas of interest), fixation counts and the entry time for each picture and subject. RESULTS: Most significant differences were found between novices and medically educated groups. Dwell times in the wound area for novices differed statistically significantly from all medically educated groups (1.76s-3.1s less). Above all, novices had lower dwell times in wound margin and wound surrounding and spent more time in other areas (up to 1.92s longer). Correspondingly, they had less fixation points and longer overall scan paths in wound areas. Similar gaze pattern data were generated for medically educated groups. CONCLUSIONS: For the first time, we could analyse the visual assessment of digital ulcers in SSc and detected differences according to levels of medical education and expertise. Adequate training on proper interpretation of changes in all wound areas are warranted to improve wound assessment in digital ulcers.


Assuntos
Escleroderma Sistêmico , Úlcera Cutânea , Dedos , Humanos , Úlcera
11.
Clin Exp Rheumatol ; 38 Suppl 125(3): 73-84, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32865168

RESUMO

OBJECTIVES: Systemic sclerosis (SSc) is a rare multi-organ disorder with a prominent gastrointestinal (GI) involvement. Altered gut microbiota is now considered a pivotal factor associated with the development of immune-mediated and inflammatory diseases. We performed a 16S ribosomal RNA (rRNA) gene-sequencing analysis of fecal microbiota in a cohort of SSc patients and matched healthy controls (HCs), with the aim to obtain some hints about a possible role of dysbiosis in the onset, progression, and severity of the disease. METHODS: We analysed stool samples from 63 SSc patients with different disease duration, phenotype, and nutritional status and from 17 HCs through 16S ribosomal RNA (rRNA) gene-sequencing. RESULTS: Microbial richness was lower for patients with long-standing disease. A similar observation was made for patients with diffuse cutaneous SSc (dsSSc) compared to those with limited variant (lcSSc) and for patients who reported a recent weight loss. Consistent with previous reports, we noted a deviation of the intestinal microbial composition in patients with SSc compared to HCs, with a greater expression of Lactobacillus and Streptococcus and a depletion of Sutterella. Nutritional status, assessed using BMI as a surrogate, appeared to have a marked impact on the gut microbiota, with overweight patients showing lower richness compared both to underweight and normal-BMI patients. CONCLUSIONS: Our findings expand the current knowledge of gut microbiota in SSc and could be useful to identify patients who would most benefit from treatments aimed at restoring the eu-biosis.


Assuntos
Microbioma Gastrointestinal , Escleroderma Sistêmico , Disbiose , Fezes , Humanos , Estado Nutricional , RNA Ribossômico 16S
12.
Clin Exp Rheumatol ; 38 Suppl 125(3): 132-136, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32865167

RESUMO

OBJECTIVES: Nailfold videocapillaroscopy (NVC) is the current gold standard for detection and quantification of capillary abnormalities in Raynaud's phenomenon (RP). The objective of this study is to evaluate the role of dermatoscopy as a further screening tool in RP. METHODS: Nailfold capillaries of RP patients were examined by a hand-held non-contact polarised dermatoscope connected to the digital camera (D1) and connected to an iPad (D2). Both dermatoscopic images were marked with an arrowhead. NVC examination was evaluated at the arrowhead. Single blinded reader performed all examinations. NVC was graded as per standard of European League against Rheumatism (EULAR) study group on microcirculation in rheumatic diseases. Consensus evaluation of dermatoscopy characteristics/grade was determined and each dermatoscopic image was given a final impression of 'normal', 'non-specific' or 'scleroderma' pattern. The final interpretation by both techniques was compared after completion of the blinded reading. RESULTS: Classification of 100 consecutive dermatoscopic images resulted in 37 (wide view) 'non-interpretable', 2 'normal', 48 'non-specific' and 13 'scleroderma' pattern with D1; 23 'non-interpretable', 4 'normal', 52 'non-specific' and 21 'scleroderma' pattern by the experts with D2; 0 non-interpretable, 4 normal, 13 non-specific and 83 'scleroderma' pattern with NVC. CONCLUSIONS: Overall, 50% of dermatoscopic images were classified as non-specific and 30% were classified as non-interpretable in RP patients. However, all images classified by dermatoscopy as "normal" or as overt "scleroderma" pattern were confirmed by concomitant NVC analysis. These findings demonstrate tenuous promise for dermatoscopy as a tool for the initial screening of nailfold capillaries in RP. Further regular work up with NVC is needed to further clarify non-interpretable and non-specific findings possibly related to non-scleroderma patterns.


Assuntos
Doença de Raynaud , Doenças Reumáticas , Escleroderma Sistêmico , Capilares , Consenso , Dermoscopia , Europa (Continente) , Humanos , Microcirculação , Angioscopia Microscópica , Unhas
13.
Clin Exp Rheumatol ; 38 Suppl 125(3): 161-168, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32865169

RESUMO

OBJECTIVES: Both intravenous (IV) and oral (PO) cyclophosphamide (CYC) showed beneficial effects on skin and lung involvement in systemic sclerosis (SSc) in placebo-controlled randomised clinical trials and observational studies. Our goal was to compare the relative efficacy and safety of PO- versus IV-CYC for treating interstitial lung disease and/or skin involvement in SSc. METHODS: Patients were derived from the EUSTAR centres and the Scleroderma Lung Studies I and II. A minimum of 6 months of CYC treatment and 12 months follow-up were required. Serious (SAEs) and non-serious adverse events and efficacy data (change in FVC%, DLCO%, mRSS) were analysed at the end of CYC treatment (EoT) and at follow-up (FU). Analysis included descriptive statistics and linear regressions. RESULTS: Differences in ethnicity, previous DMARD exposure, previous and concomitant steroid exposure/dosage were observed in the PO (n=149) and IV (n=153) CYC groups. Adjusted and unadjusted changes in FVC%, DLCO% and mRSS were similar irrespective of mode of administration. PO patients had more leukopenia (p<0.001), haemorrhagic cystitis (p=0.011) and alopecia (p<0.001) at the EoT visit, while the IV group had more SAEs (p=0.025) and need for oxygen supplementation at FU (p=0.049). CONCLUSIONS: In a comparison of PO- to IV-CYC for SSc, we found no differences in lung function or cutaneous sclerosis after one year. Some differences in side effects were seen. The results need to be considered as preliminary; however, because we needed to use a combination of RCT and registry data, with some differences in demographics and concomitant medications, well-controlled studies are warranted.


Assuntos
Imunossupressores , Escleroderma Sistêmico , Ciclofosfamida , Fibrose , Humanos , Pulmão , Resultado do Tratamento
14.
Clin Exp Rheumatol ; 38 Suppl 125(3): 92-97, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32865170

RESUMO

OBJECTIVES: The purpose of this study was to evaluate homocysteine (Hcy) serum levels in women with systemic sclerosis (SSc) compared with healthy controls and to examine possible associations between Hcy and markers of arterial stiffness. METHODS: A cross-sectional study was performed at a single hospital between November 2017 and May 2019: 62 women with SSc and 62 age- and sex-matched healthy controls were enrolled. Pulse wave velocity (PWV) was measured non-invasively along the carotid-femoral arterial segment. Serum Hcy was analysed using immunonephelo-metric method. RESULTS: There was a significant difference in Hcy serum levels between SSc female patients and healthy controls (11.9±3.3 vs. 10.3±2.3 µmol/ml, p=0.002). Serum levels of Hcy were positively correlated with PWV (r=0.28, p<0.05), brain natriuretic peptide (BNP) (r=0.36, p<0.05) and disease duration (r=0.38, p<0.05), within the SSc group. In addition, in the linear regression model, higher Hcy concentrations were associated with higher PWV [ß=0.74 95% CI (0.085, 1.394); p=0.027], BNP [ß=0.04 95% CI (0.014, 0.072); p=0.004] and disease duration [ß=0.18 95% CI (0.070, 0.300); p=0.002]. In multiple linear regression model adjusting for covariants, Hcy remained positively related to the PWV [ß=0.033 95% CI (0.003, 0.062); p=0.031]. CONCLUSIONS: Our findings revealed a positive correlation between Hcy serum levels and PWV, which indicates that high levels of Hcy may predispose to the development of vascular stiffness in patients with SSc.


Assuntos
Escleroderma Sistêmico , Rigidez Vascular , Biomarcadores , Estudos Transversais , Feminino , Homocisteína , Humanos , Análise de Onda de Pulso
16.
Clin Exp Rheumatol ; 38 Suppl 125(3): 140-147, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32865172

RESUMO

OBJECTIVES: To evaluate the diagnostic value of hand ultrasound (US) in systemic sclerosis (SSc) and to explore its relevance within a combined diagnostic approach. METHODS: 224 patients with suspected SSc were consecutively included. They all had US evaluation assessing the presence of fibrotic tenosynovitis (fibrotic TS) and ulnar artery occlusion (UAO). The final diagnosis of SSc was based on the clinical evaluation of a board of experts independently of any pre-established classification criteria. RESULTS: 166 patients were finally diagnosed as SSc according to the experts as reference standard. 62 SSc and 8 non-SSc patients had UAO (uni or bilateral) (p=0.001). 23 SSc patients and 1 non-SSc patient had US fibrotic TS (p=0.007). A US SSc-pattern (presence of UAO and/or fibrotic TS) was reported in 73 SSc patients and 9 non-SSc patients (p<0.001). UAO had an area under ROC curve (AUC) for the diagnosis of SSc of 0.618 (95%CI 0.539- 0.697); with Se=0.373 (0.304-0.449) and Sp=0.862 (0.751-0.928). Fibrotic TS had an AUC of 0.561 (0.480-0.643); with Se=0.139 (0.094-0.199) and Sp=0.983 (0.909-0.997). The US-SSc pattern had a AUC of 0.641 (0.563- 0.695), with Se=0.440 (0.367-0.516) and Sp=0.845 (0.731-0.916). A scoring system including these US parameters and items from ACR/EULAR classification criteria had an AUC of 0.979 (0.962-0.996)) and allows the substitution of capillaroscopy by US parameters with similar performances. CONCLUSIONS: The use of hand US parameters may help to refine the diagnostic strategy of SSc and their inclusion in a combined diagnostic approach could be discussed.


Assuntos
Esclerodermia Localizada , Escleroderma Sistêmico , Humanos , Angioscopia Microscópica , Artéria Ulnar , Ultrassonografia
17.
Clin Exp Rheumatol ; 38 Suppl 125(3): 85-91, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32865173

RESUMO

OBJECTIVES: Major vascular complication, such as digital ulcers (DUs), pulmonary arterial hypertension (PAH) and scleroderma renal crisis (SRC) are hallmarks of systemic sclerosis (SSc). Interstitial lung disease (ILD) is the major cause of mortality in SSc. The aim of study is to identify cardiopulmonary exercise testing (CPET) variables that predict MVC and mortality for ILD in SSc patients. METHODS: In this cohort study, 45 SSc patients underwent clinical evaluation, echocardiography, pulmonary function tests (PFTs), high resolution computerised tomography (HRCT) and CPET. PFTs and echocardiography were performed annually for a 5-year follow-up. RESULTS: 16 (35.6%) SSc patients had MVC: 14 new DUs (31.1%), 1 PAH (2.2%) and 1 SRC (2.2%). At univariate regression analysis, mRss [HR 1.099 (1.008-1.199), p<0.05], NVC patterns (active and late) [HR 0.032 (0.004-0.250), p<0.001], V'E/V'CO2 slope [HR 1.123 (1.052-1.198), p<0.001] were predictive of new onset of MVC. In multivariate analysis, NVC patterns (active and late) (HR 0.044 (0.004-0.486), p<0.05), V'E/V'CO2 (HR 1.094 (1.020-1.198), p<0.05) were predictive of new onset of MVC. The 5-year mortality for ILD is 8.9%. In univariate analysis, DLco [(HR 0.927(CI 0.874- 0.983), p<0.05], V'E/V'CO2 slope and lung parenchymal with radiological patterns of ILD [(1.2.02 (CI 1.018-1.419), p<0.05], represent risk factors for 5-year mortality for ILD [HR 1.142 (1.030-1.267), p<0.05]. In multivariate analysis, only V'E/V'CO2 slope [1.268 (CI 1.003-1.602), p<0.05] represents a risk factor for 5-year mortality for ILD. CONCLUSIONS: V' E/V' CO2 slope is a prognostic marker of MVC and five-year mortality for ILD.


Assuntos
Doenças Pulmonares Intersticiais , Escleroderma Sistêmico , Estudos de Coortes , Teste de Esforço , Tolerância ao Exercício , Humanos
18.
Clin Exp Rheumatol ; 38 Suppl 125(3): 148-153, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32865175

RESUMO

OBJECTIVES: To evaluate the prevalence of skin ulcers (SUs) and their association with clinical phenotype in a monocentric cohort of patients affected with systemic sclerosis (SSc). METHODS: Patients affected with SSc (ACR/EULAR 2013 criteria) in regular follow-up at the Rheumatology Unit of Padova University Hospital, Italy, were considered and retrospectively evaluated. Demographic, clinical and laboratory data, organ involvement and therapy were recorded. We analysed the occurrence, timing (single episode, recurrent/chronic) and site of SUs. The association between SUs and demographic and clinical variables was assessed by logistic regression analysis. RESULTS: We evaluated 211 SSc patients, aged 60.8±12.4 years, 187 (89%) females, 147 (70%) affected with limited cutaneous SSc. During a median follow-up of 120 months (50-216), 105 (50%) patients experienced at least one episode of SU; among them, 66% had recurrent or persistent SUs. Patients with a history of SUs compared with those never affected were younger at SSc diagnosis (p=0.009), had more frequently a diffuse cutaneous form (p=0.001), chronic anaemia (p<0.001), systemic inflammation (p=0.001), lung (p=0.002) and cardiac (p=0.004) involvement, and calcinosis (p=0.001). At multivariate analysis a younger age at SSc diagnosis (p=0.031), articular involvement (p=0.005) and telangiectasia (p=0.003) were independently associated with SUs. Telangiectasia, articular involvement, chronic anaemia and inflammatory state were found to be associated with the recurrence/chronicisation of SUs. CONCLUSIONS: SUs represent a common complication in our cohort of patients with a long-term follow-up. The association of SUs with some clinical manifestations of SSc suggests a combined role of microcirculatory damage and inflammation in their origin.


Assuntos
Escleroderma Sistêmico , Úlcera Cutânea , Idoso , Feminino , Humanos , Itália , Microcirculação , Pessoa de Meia-Idade , Fenótipo , Estudos Retrospectivos
20.
Adv Exp Med Biol ; 1274: 137-176, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32894510

RESUMO

Lysophosphatidic acid (LPA) has major roles as a bioactive signaling molecule, with multiple physiological and pathological roles being described in almost every major organ system. In this review we discuss LPA signaling pathways as emerging drug targets for multiple conditions relevant to human health and disease. LPA signals through the six G protein-coupled receptors LPA1-6, and several of these receptors along with the LPA-producing enzyme including autotaxin (ATX) are now established as therapeutic targets with potential to treat various human diseases as exemplified by several LPA signaling targeting compounds now in clinical trials for idiopathic pulmonary fibrosis and systemic sclerosis. Several crystal structures of LPA receptors and ATX have been solved, which will accelerate development of highly selective and effective LPA signaling targeting compounds. We also review additional bioactive lysophospholipid (LPL) signaling molecules including lysophosphatidylserine and lysophosphatidylinositol, which represent the next wave of LPL druggable targets. An emerging theme in bioactive LPL signaling is that where the ligand is produced and how it is delivered to the cognate receptor are critical determinants of the biological responses. We will also discuss how connecting the production and function of bioactive LPLs will identify new therapeutic strategies to effectively target LPL signaling pathways.


Assuntos
Lisofosfolipídeos/metabolismo , Terapia de Alvo Molecular , Transdução de Sinais/efeitos dos fármacos , Humanos , Fibrose Pulmonar Idiopática/tratamento farmacológico , Fibrose Pulmonar Idiopática/metabolismo , Receptores de Ácidos Lisofosfatídicos/química , Receptores de Ácidos Lisofosfatídicos/metabolismo , Escleroderma Sistêmico/tratamento farmacológico , Escleroderma Sistêmico/metabolismo
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