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1.
Autoimmun Rev ; : 102458, 2020 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-31927087

RESUMO

Capillaroscopy is a non-invasive and safe tool which allows the evaluation of the morphology of the microcirculation. Since its recent incorporation in the 2013 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria for systemic sclerosis together with its assessed role to monitor disease progression, capillaroscopy became a 'mainstream' investigation for rheumatologists. Given its increasing use by a variety of physicians internationally both in daily practice to differentiate primary from secondary Raynaud's phenomenon, as well as in research context to predict disease progression and monitor treatment effects, standardisation in capillaroscopic image acquisition and analysis seems paramount. To step forward to this need, experts in the field of capillaroscopy/microcirculation provide in this very consensus paper their view on image acquisition and analysis, different capillaroscopic techniques, normal and abnormal capillaroscopic characteristics and their meaning, scoring systems and reliability of image acquisition and interpretation.

2.
Artigo em Inglês | MEDLINE | ID: mdl-31680161

RESUMO

OBJECTIVES: Racial factors play a significant role in SSc. We evaluated differences in SSc presentations between white patients (WP), Asian patients (AP) and black patients (BP) and analysed the effects of geographical locations. METHODS: SSc characteristics of patients from the EUSTAR cohort were cross-sectionally compared across racial groups using survival and multiple logistic regression analyses. RESULTS: The study included 9162 WP, 341 AP and 181 BP. AP developed the first non-RP feature faster than WP but slower than BP. AP were less frequently anti-centromere (ACA; odds ratio (OR) = 0.4, P < 0.001) and more frequently anti-topoisomerase-I autoantibodies (ATA) positive (OR = 1.2, P = 0.068), while BP were less likely to be ACA and ATA positive than were WP [OR(ACA) = 0.3, P < 0.001; OR(ATA) = 0.5, P = 0.020]. AP had less often (OR = 0.7, P = 0.06) and BP more often (OR = 2.7, P < 0.001) diffuse skin involvement than had WP. AP and BP were more likely to have pulmonary hypertension [OR(AP) = 2.6, P < 0.001; OR(BP) = 2.7, P = 0.03 vs WP] and a reduced forced vital capacity [OR(AP) = 2.5, P < 0.001; OR(BP) = 2.4, P < 0.004] than were WP. AP more often had an impaired diffusing capacity of the lung than had BP and WP [OR(AP vs BP) = 1.9, P = 0.038; OR(AP vs WP) = 2.4, P < 0.001]. After RP onset, AP and BP had a higher hazard to die than had WP [hazard ratio (HR) (AP) = 1.6, P = 0.011; HR(BP) = 2.1, P < 0.001]. CONCLUSION: Compared with WP, and mostly independent of geographical location, AP have a faster and earlier disease onset with high prevalences of ATA, pulmonary hypertension and forced vital capacity impairment and higher mortality. BP had the fastest disease onset, a high prevalence of diffuse skin involvement and nominally the highest mortality.

3.
Artigo em Inglês | MEDLINE | ID: mdl-31665474

RESUMO

OBJECTIVE: High frequency ultrasound allows visualization of epidermis, dermis and hypodermis, precise measurement of skin thickness, as well as assessment of skin oedema, fibrosis and atrophy. The aim of this pilot cross-sectional observational study was to assess the performance and multiobserver variability of ultra-high-frequency (UHF) (50 MHz) ultrasound (US) in measuring skin thickness as well as the capacity of UHF-derived skin features to differentiate SSc patients from healthy controls. METHODS: Twenty-one SSc patients (16 limited and five diffuse SSc) and six healthy controls were enrolled. All subjects underwent US evaluation by three experts at three anatomical sites (forearm, hand and finger). Dermal thickness was measured and two rectangular regions of interest, one in dermis and one in hypodermis, were established for texture feature analysis. RESULTS: UHF-US allowed a precise identification and measurement of the thickness of the dermis. The dermal thickness in the finger was significantly higher in patients than in controls (P < 0.05), while in the forearm it was significantly lower in patients than in controls (P < 0.001). Interobserver variability for dermal thickness was good to excellent [forearm intraclass correlation coefficient (ICC) = 0.754; finger ICC = 0.699; hand ICC = 0.602]. Texture computed analysis of dermis and hypodermis was able to discriminate between SSc and healthy subjects (area under the curve >0.7). CONCLUSION: These preliminary data show that skin UHF-US allows a very detailed imaging of skin layers, a reliable measurement of dermal thickness, and a discriminative capacity between dermis and hypodermis texture features in SSc and healthy subjects.

4.
Ann Rheum Dis ; 78(11): 1472-1479, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31427438

RESUMO

OBJECTIVES: To describe and explore differences in formal regulations around sick leave and work disability (WD) for patients with rheumatoid arthritis (RA), as well as perceptions by rheumatologists and patients on the system's performance, across European countries. METHODS: We conducted three cross-sectional surveys in 50 European countries: one on work (re-)integration and social security (SS) system arrangements in case of sick leave and long-term WD due to RA (one rheumatologist per country), and two among approximately 15 rheumatologists and 15 patients per country on perceptions regarding SS arrangements on work participation. Differences in regulations and perceptions were compared across categories defined by gross domestic product (GDP), type of social welfare regime, European Union (EU) membership and country RA WD rates. RESULTS: Forty-four (88%) countries provided data on regulations, 33 (75%) on perceptions of rheumatologists (n=539) and 34 (77%) on perceptions of patients (n=719). While large variation was observed across all regulations across countries, no relationship was found between most of regulations or income compensation and GDP, type of SS system or rates of WD. Regarding perceptions, rheumatologists in high GDP and EU-member countries felt less confident in their role in the decision process towards WD (ß=-0.5 (95% CI -0.9 to -0.2) and ß=-0.5 (95% CI -1.0 to -0.1), respectively). The Scandinavian and Bismarckian system scored best on patients' and rheumatologists' perceptions of regulations and system performance. CONCLUSIONS: There is large heterogeneity in rules and regulations of SS systems across Europe in relation to WD of patients with RA, and it cannot be explained by existing welfare regimes, EU membership or country's wealth.

5.
Rheumatol Int ; 39(9): 1595-1605, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31309294

RESUMO

To assess prevalence and change of depression/anxiety symptoms in spondyloarthritis patients and feasibility of depression/anxiety questionnaires. 43 Patients with axial spondyloarthritis (axSpA) and 27 patients with psoriatic arthritis (PsA) were consecutively recruited. There were 34 patients on biologics and 36 patients on nonbiologics. Patients were not previously treated for depression. The demographic variables, pain, patient global assessment, laboratory, clinical findings, diseases activity scores, Beck Depression Inventory (BDI) and Depression Anxiety and Stress Scale-short version (DASS-21) were collected. The study visits were at the beginning, after 1 month, after 3 and after 6 months. In axSpA and PsA patients on biologics, BDI and DASS-21 were significantly lower compared to nonbiologics group during time. The axSpA patients on biologics had significantly lower BDI and depression severity by BDI at each time point and lower DASS-21 after 1, 3 and 6 months. BDI in PsA patients who received biological therapy was significantly lower after 3 and 6 months. In biologics groups, BDI significantly decreased after 3 months in axSpA patients and after 1 month in PsA patients. In axSpA patients, there was a medium correlation between BDI and axial pain, patient global assessment and disease activity scores. The biological therapy significantly affected the depression/anxiety symptoms in axSpA and PsA during time. BDI moderately correlated with pain and disease activity in axSpA. BDI and DASS-21 are easy to use in daily practice.

6.
Lancet ; 393(10188): 2303-2311, 2019 06 08.
Artigo em Inglês | MEDLINE | ID: mdl-31130260

RESUMO

BACKGROUND: Upadacitinib, an oral Janus kinase (JAK)1-selective inhibitor, showed efficacy in combination with stable background conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) in patients with rheumatoid arthritis who had an inadequate response to DMARDs. We aimed to evaluate the safety and efficacy of upadacitinib monotherapy after switching from methotrexate versus continuing methotrexate in patients with inadequate response to methotrexate. METHODS: SELECT-MONOTHERAPY was conducted at 138 sites in 24 countries. The study enrolled adults (≥18 years) who fulfilled the 2010 American College of Rheumatology (ACR)-European League Against Rheumatism (EULAR) classification criteria for rheumatoid arthritis. Patients with active rheumatoid arthritis despite stable methotrexate were randomly assigned 2:2:1:1 to switch to once-daily monotherapy of of upadacitinib or to continue methotrexate at their existing dose as blinded study drug; starting from week 14, patients assigned to continue methotrexate were switched to 15 mg or 30 mg once-daily upadacitinib per prespecified random assignment at baseline. The primary endpoints in this report are proportion of patients achieving 20% improvement in the ACR criteria (ACR20) at week 14, and proportion achieving low disease activity defined as 28-joint Disease Activity Score using C-reactive protein (DAS28[CRP]) of 3·2 or lower, both with non-responder imputation at week 14. Outcomes were assessed in patients who received at least one dose of study drug. This study is active but not recruiting and is registered with ClinicalTrials.gov, number NCT02706951. FINDINGS: Patients were screened between Feb 23, 2016, and May 19, 2017 and 648 were randomly assigned to treatment. 598 (92%) completed week 14. At week 14, an ACR20 response was achieved by 89 (41%) of 216 patients (95% CI 35-48) in the continued methotrexate group, 147 (68%) of 217 patients (62-74) receiving upadacitinib 15 mg, and 153 (71%) of 215 patients (65-77) receiving upadacitinib 30 mg (p<0·0001 for both doses vs continued methotrexate). DAS28(CRP) 3·2 or lower was met by 42 (19%) of 216 (95% CI 14-25) in the continued methotrexate group, 97 (45%) of 217 (38-51) receiving upadacitinib 15 mg, and 114 (53%) of 215 (46-60) receiving upadacitinib 30 mg (p<0·0001 for both doses vs continued methotrexate). Adverse events were reported in 102 patients (47%) on continued methotrexate, 103 (47%) on upadacitinib 15 mg, and 105 (49%) on upadacitinib 30 mg. Herpes zoster was reported by one (<1%) patient on continued methotrexate, three (1%) on upadacitinib 15 mg, and six (3%) on upadacitinib 30 mg. Three malignancies (one [<1%] on continued methotrexate, two [1%] on upadacitinib 15 mg), three adjudicated major adverse cardiovascular events (one [<1%] on upadacitinib 15 mg, two [<1%] on upadacitinib 30 mg), one adjudicated pulmonary embolism (<1%; upadacitinib 15 mg), and one death (<1%; upadacitinib 15 mg, haemorrhagic stroke [ruptured aneurysm]) were reported in the study. INTERPRETATION: Upadacitinib monotherapy showed statistically significant improvements in clinical and functional outcomes versus continuing methotrexate in this methotrexate inadequate-responder population. Safety observations were similar to those in previous upadacitinib rheumatoid arthritis studies. FUNDING: AbbVie Inc, USA.


Assuntos
Artrite Reumatoide/tratamento farmacológico , Compostos Heterocíclicos com 3 Anéis/administração & dosagem , Inibidores de Janus Quinases/administração & dosagem , Adulto , Idoso , Antirreumáticos/administração & dosagem , Antirreumáticos/efeitos adversos , Proteína C-Reativa/efeitos dos fármacos , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Compostos Heterocíclicos com 3 Anéis/efeitos adversos , Humanos , Inibidores de Janus Quinases/efeitos adversos , Masculino , Metotrexato/administração & dosagem , Metotrexato/efeitos adversos , Pessoa de Meia-Idade , Indução de Remissão , Resultado do Tratamento
7.
RMD Open ; 5(1): e000795, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30997148

RESUMO

Objective: To evaluate the level of agreement on ultrasonographic (US) lesions among highly experienced sonographers as well as the intraobserver and interobserver reliability of inflammatory and structural US lesions in patients with osteoarthritis (OA) of the foot. Methods: After a systematic literature review, a Delphi survey was performed to test definitions of US lesions in OA of the foot, including inflammatory lesions (ie, synovial hypertrophy [SH], joint effusion [JE], power Doppler signal [PD]), and structural abnormalities (ie, cartilage damage [CD] and osteophytes). Subsequently, the reliability of US in assessing the aforementioned lesions was tested on static images as well as during a live exercise. Reliability was assessed by kappa analyses and prevalence-adjusted bias-adjusted kappa (PABAK) on a dichotomous and an ordinal scale. Results: Intraobserver and interobserver reliability for SH and JE evaluated by binary scoring was good for both components, while the intraobserver reliability for semiquantitative scoring of SH ranged from moderate in the web-based exercise (PABAK 0.49) to good (PABAK 0.8) in the live exercise. Reliability for CD and PD assessments were respectively good and excellent in all exercises (ranged from PABAK 0.61 to 0.79 for CD and 0.88 to 0.95 for PD). The interobserver reliability for the semiquantitative scoring of osteophytes was fair in the live exercise (PABAK 0.36) and moderate in the static exercise (PABAK 0.60). Conclusions: Consensual US definitions were found to be reliable for assessing inflammatory lesions in OA of the foot, while the use of US to assess structural damage requires further studies.

8.
Rheumatology (Oxford) ; 58(10): 1802-1811, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31034077

RESUMO

OBJECTIVES: To develop and test the reliability of a new semiquantitative scoring system for the assessment of cartilage changes by ultrasound in a web-based exercise as well as a patient exercise of patients with RA. METHODS: A taskforce of the Outcome Measures in Rheumatology Ultrasound Working Group performed a systematic literature review on the US assessment of cartilage in RA, followed by a Delphi survey on cartilage changes and a new semiquantitative US scoring system, and finally a web-based exercise as well as a patient exercise. For the web-based exercise, taskforce members scored a dataset of anonymized static images of MCP joints in RA patients and healthy controls, which also contained duplicate images. Subsequently, 12 taskforce members used the same US to score cartilage in MCP and proximal interphalangeal joints of six patients with RA in in a patient reliability exercise. Percentage agreement and prevalence of lesions were calculated, as intrareader reliability was assessed by weighted kappa and interreader reliability by Light's kappa. RESULTS: The three-grade semiquantitative scoring system demonstrated excellent intrareader reliability (kappa: 0.87 and 0.83) in the web-based exercise and the patient exercise, respectively. Interreader reliability was good in the web-based exercise (kappa: 0.64) and moderate (kappa: 0.48) in the patient exercise. CONCLUSION: Our study demonstrates that ultrasound is a reliable tool for evaluating cartilage changes in the MCP joints of patients with RA and supports further development of a new reliable semiquantitative ultrasound scoring system for evaluating cartilage involvement in RA.

9.
PLoS One ; 14(1): e0210466, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30653543

RESUMO

OBJECTIVE: Patients with primary Sjögren's Syndrome (pSS) have diminished health quality and fatigue, arthralgia along with dryness of the mouth and eyes have major impact on their psychological and social aspects of life. The purpose of this study was to determine psychological features of patients with pSS. We analyzed personality, depression and anxiety of patients with primary Sjögren's Syndrome (pSS) in comparison with patients with rheumatoid arthritis (RA) and healthy controls (HC) and assessed their association with sociodemographic factors and comorbidity. METHODS: In 105 pSS patients (mean age 51.34 years, mean disease duration 5.98 years), 52 RA patients (mean age 51.37 years, mean disease duration 8.10 years) and 54 HC (mean age 51.35 years) clinical and sociodemographic characteristics were determined and results analyzed. At enrollment patients and controls completed the Revisited NEO Personality Inventory Five-Factor model (NEO-PI-R), the Zung Self-Rating Depression Scale and the Zung Self-Rating Anxiety Scale. Statistical analyses were performed using SPSS [Version 16.0]. The relative size of the effect was assessed based on standardized estimates of effect size (d). RESULTS: Patients with pSS, similarly to RA patients had higher scores of Neuroticism (d = 0.46, p = 0.007) and lower scores of Extraversion (d = 0.51, p = 0.001) and Openness for experience (d = 0.65, p = 0.013) compared to HC. There was no significant differences between pSS group and HC in the depression (d = 0.171, p>0.05). However, patients with pSS had higher anxiety in comparison to HC (p<0.0001). In multivariate models, education and satisfaction with family relationships were significant predictors for psychological characteristics of patients, independently of clinical diagnosis. CONCLUSIONS: Our study is the first to show that patients with pSS scored high on neuroticism and anxiety and low on sociability. Education and satisfaction with family relationships predisposed to their psychological profile. Psychological assessment of patients with pSS may improve understanding and treatment of this clinical condition.


Assuntos
Transtornos de Ansiedade/psicologia , Artrite Reumatoide/psicologia , Transtorno Depressivo/psicologia , Personalidade , Síndrome de Sjogren/psicologia , Adulto , Transtornos de Ansiedade/epidemiologia , Artrite Reumatoide/epidemiologia , Artrite Reumatoide/fisiopatologia , Comorbidade , Transtorno Depressivo/epidemiologia , Fadiga/epidemiologia , Fadiga/psicologia , Feminino , Humanos , Pessoa de Meia-Idade , Qualidade de Vida , Sérvia/epidemiologia , Síndrome de Sjogren/epidemiologia , Síndrome de Sjogren/fisiopatologia , Inquéritos e Questionários
10.
Expert Opin Drug Metab Toxicol ; 15(3): 253-257, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30583708

RESUMO

BACKGROUND: Methotrexate (MTX), a folate analogue, is the most commonly used disease-modifying drug in the treatment of rheumatoid arthritis (RA). However, high interindividual differences in drug response are present among RA patients. RESEARCH DESIGN AND METHODS: In a group of 234 RA patients treated with MTX, we investigated whether rs1650697 polymorphism in DHFR gene may have an impact on MTX efficacy and/or adverse drug effects (ADEs). Relative DAS28 values (rDAS28) were used for the estimation of MTX therapy and all ADEs were recorded. Patients were genotyped for selected polymorphism by real-time PCR method. RESULTS: According to the European League Against Rheumatism criteria after 6 months of MTX therapy, 196 patients (83.8%) were classified as responders (25 (10.7%) were good and 171 (73.1%) were moderate) and 38 patients (16.2%) as nonresponders. ADEs were observed in 55 patients (23.5%). CONCLUSIONS: Our results showed that the presence of T allele might be protective against MTX hepatotoxicity measured by transaminase levels (p = 0.05). Furthermore, among patients who also received low-dose corticosteroids, we have found a lower rDAS value in patients with CC genotype (p = 0.039).


Assuntos
Antirreumáticos/efeitos adversos , Artrite Reumatoide/tratamento farmacológico , Metotrexato/efeitos adversos , Tetra-Hidrofolato Desidrogenase/genética , Corticosteroides/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Alelos , Antirreumáticos/uso terapêutico , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Doença Hepática Induzida por Substâncias e Drogas/genética , Feminino , Genótipo , Humanos , Masculino , Metotrexato/uso terapêutico , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Reação em Cadeia da Polimerase em Tempo Real , Resultado do Tratamento , Adulto Jovem
11.
PLoS One ; 14(12): e0226498, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31891590

RESUMO

OBJECTIVES: To assess the association between salivary ultrasonography (sUS) findings and disease activity and damage in patients with primary Sjogren's syndrome (pSS). We investigated the potential prognostic role of sUS as a tool in the assessment of disease activity. METHODS: In 303 pSS patients, disease activity was assessed by the European League Against Rheumatism (EULAR) Sjogren's Syndrome Disease Activity Index (ESSDAI), the EULAR Sjogren's Syndrome Patient Reported Index (ESSPRI), the Sjogren's Syndrome Disease Activity Index (SSDAI) and the Sjogren's Syndrome Disease Damage Index (SSDDI). The sUS parenchymal inhomogeneity (de Vita scoring system) was assessed in 303 pSS patients and 111 heathy controls. A receiver operating characteristic (ROC) curve was used to determine the cut-off value of the pathological sUS score. Logistic regression analysis was performed to assess risk factors for moderate and high disease activity. RESULTS: A pathological sUS score ≥ 2 was recorded in 271 (89.7%) patients and 8 (8.6%) healthy controls. Patients with moderate and high ESSDAI and SSDAI scores had significantly higher US activity in comparison to that of pSS patients with low disease activity (p = 0.006; p = 0.01, respectively). Additionally, pSS patients with moderate and high SSDDI scores had higher US activity (p = 0.031). Pathological sUS correlated with the glandular domain within the ESSDAI and SSDDI (p<0.001). The patients with a severe US score (5-6) had a 3.5 times greater chance of having moderate or high disease activity. The specificity of the severe de Vita sUS score for ESSDAI and SSDAI was 85.1% and 85.2%, respectively. In contrast, the sensitivity of a severe de Vita sUS score for ESSDAI was low, at 29.2%, while the sensitivity for the SSDAI was higher, 42.3%. In the analysis of disease activity, a de Vita score ≥ 5 could be used as a risk factor for moderate and high ESSDAI (p = 0.042) and SSDAI (p = 0.006). CONCLUSIONS: Pathological salivary gland ultrasonography is associated with high disease activity and damage in pSS. Consequently, sUS abnormalities might be surrogate items for glandular domains in the assessment of disease activity and damage. Thus, ultrasonography of the salivary gland combined with clinical and serological markers might be part of the next prognostic and therapeutic algorithm in the near future.

12.
Immunol Lett ; 204: 1-8, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30308218

RESUMO

Systemic sclerosis (SSc) is a heterogeneous multisystem autoimmune disease with unknown etiology. Numerous studies have indicated that the disease heterogeneity implies various genetic abnormalities. Considering that SSc is characterized by a strong sex bias and that the position of IRAK1 gene is on the X chromosome, we assume that variations in IRAK1 gene could explain female predominance of SSc. It was previously described that miR-146a has a role in 'fine-tuning' regulation of the TLR/NF-kB signaling pathway through down-regulation of IRAK1 gene. The aim of the present study was to analyze both variants and expression level of IRAK1 and miR-146a genes in terms of susceptibility to SSc and clinical presentation of SSc patients. We analyzed variants IRAK1 rs3027898 C > A and miR-146a rs2910164 C > G in 102 SSc patients and 66 healthy subjects. Genotyping was performed by Sanger sequencing. Expression level of IRAK1 mRNA and miR-146a in PBMCs was performed in subset of 50 patients and 13 healthy controls by RT-qPCR. Our results showed that there was no association between IRAK1 rs3027898 and the risk of SSc in women. However, the analysis of genotype distribution of the mir-146a rs2910164 C > G variant indicated that CC genotype shows strong association with lung fibrosis and active form of the disease. When expression level of IRAK1 gene was analyzed, we detected significant downregulation of IRAK1 mRNA in SSc patients compared to controls, as well as in male compared to female patients, in patients with ACAs autoantibodies and in patients with severe skin involvement. Regarding the expression level of miR-146a, we have found significantly reduced expression in SSc patients, in patients with skin involvement and in male SSc patients. The results from this study indicate that expression of IRAK1 gene could explain phenotypic heterogeneity of SSc and may be involved in the pathogenesis of SSc due to its differential expression in certain subgroups. Our results also suggested that miR-146a rs2910164 CC genotype may be predisposing factor for development lung fibrosis and more progressive form of SSc. Results from relative expression analysis of miR-146a demonstrated that changes in the level of this miRNA may have an impact on development and clinical course of SSc.


Assuntos
Genes Ligados ao Cromossomo X , Estudos de Associação Genética , Predisposição Genética para Doença , Variação Genética , Quinases Associadas a Receptores de Interleucina-1/genética , MicroRNAs/genética , Escleroderma Sistêmico/diagnóstico , Escleroderma Sistêmico/genética , Idoso , Alelos , Biomarcadores , Estudos de Casos e Controles , Feminino , Expressão Gênica , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Fenótipo , Escleroderma Sistêmico/metabolismo
13.
Clin Exp Rheumatol ; 36 Suppl 113(4): 68-75, 2018.
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.


Assuntos
Disparidades nos Níveis de Saúde , Esclerodermia Difusa/diagnóstico , Esclerodermia Limitada/diagnóstico , Proteínas da Fase Aguda/análise , Autoanticorpos/sangue , Biomarcadores/sangue , Estudos Transversais , Bases de Dados Factuais , Progressão da Doença , Feminino , Humanos , Pneumopatias/diagnóstico , Pneumopatias/etiologia , Masculino , Proteínas Nucleares/imunologia , Prognóstico , Doença de Raynaud/diagnóstico , Doença de Raynaud/etiologia , Fatores de Risco , Esclerodermia Difusa/sangue , Esclerodermia Difusa/complicações , Esclerodermia Difusa/imunologia , Esclerodermia Limitada/sangue , Esclerodermia Limitada/complicações , Esclerodermia Limitada/imunologia , Índice de Gravidade de Doença , Fatores Sexuais
14.
Med Ultrason ; 20(3): 335-341, 2018 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-30167587

RESUMO

AIMS: Autologous conditioned serum (ACS; marketed as Orthokine®) is an autologous blood product that has previously shown efficacy in treatment of joint osteoarthritis, spinal radiculopathy, tendon and muscle injuries in randomized controlled trials. In this 24-week, randomized, double-blind study, we compared the efficacy and safety of ACS with glucocorticoid (betamethasone) injections in chronic supraspinatus tendinopathy patients. MATERIAL AND METHODS: Thirty-two patients with chronic supraspinatus tendinopathy were enrolled in the study. The ACS group received four ACS injections once weekly over four weeks and the glucocorticoid group received three betamethasone injections once weekly over three weeks with a placebo (saline) injection at week 4 into the enthesis and paratenon of the supraspinatus tendon. Study endpoints were pain intensity (VAS) and Constant Shoulder Score (CSS) assessed at weeks 0, 4 and 24. RESULTS: Shoulder pain intensity improved after 4 weeks and significantly improved after 24 weeks in patients treated with ACS compared with those treated with glucocorticoids (pain intensity week 4: ACS=22.0, glucocorticoid=32.0; week 24: ACS=15.0, glucocorticoid=40.0). CSS improved to a similar extent in both groups after 4 weeks. After 24 weeks, ACS patients exhibited significantly greater CSS improvements than glucocorticoid patients. Adverse events (n=8) were reported in betamethasone patients. CONCLUSIONS: Compared with betamethasone, ACS therapy improved joint function and reduced shoulder pain more effectively after 4 weeks of treatment; these improvements were sustained to week 24. Combined with its favorable safety profile, ACS appears to be a more effective treatment than glucocorticoids and could enhance the quality of life in patients with chronic rotator cuff tendinopathy.


Assuntos
Dexametasona/administração & dosagem , Segurança do Paciente , Plasma Rico em Plaquetas , Dor de Ombro/diagnóstico por imagem , Dor de Ombro/terapia , Tendinopatia/complicações , Adulto , Idoso , Autoenxertos , Dor Crônica , Método Duplo-Cego , Feminino , Hospitais Universitários , Humanos , Injeções Intra-Articulares , Masculino , Pessoa de Meia-Idade , Medição da Dor , Prognóstico , Estudos Prospectivos , Amplitude de Movimento Articular/efeitos dos fármacos , Amplitude de Movimento Articular/fisiologia , Dor de Ombro/etiologia , Dor de Ombro/fisiopatologia , Estatísticas não Paramétricas , Tendinopatia/diagnóstico por imagem , Resultado do Tratamento , Ultrassonografia Doppler/métodos
15.
Clin Rheumatol ; 37(9): 2447-2454, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29948346

RESUMO

Genetic predisposition to systemic sclerosis (SSc) has still not been fully revealed. Interleukin-6 (IL-6) is a mediator of T cell proliferation and fibrotic events in SSc. Polymorphisms in the IL-6 are found to be important in susceptibility to development of SSc. We aimed to assess the frequency of -174 C/G of IL-6 gene polymorphism in SSc patients and healthy controls, as well as correlation with disease manifestations. In the case-control study, 102 patients with SSc and 93 controls were included. PCR-RFLP method was performed for genotyping promotor variants -174 C/G of IL-6 gene. The expression level of IL-6 was determined by qRT-PCR on subset of 50 patients and 13 healthy controls with different IL-6 genotypes. We used UCLA GIT 2.0 questionnaire to assess gastrointestinal involvement in SSc patients. The expression level of IL-6 gene was significantly higher in patients with SSc in comparison with healthy controls (p < 0.05). Carriers of C-allele of IL-6 gene compared to those with G allele, showed higher expression of IL-6 gene (95.8 vs. 41.2, p < 0.05), higher GIT total score (0.85 vs. 0.5, p < 0.05) and higher distension scale score (1.4 ± 0.9 vs. 0.78 ± 0.8, p = 0.05). No significant differences in genotype distribution and allele frequency were observed between patients and controls. The expression of IL6 gene varies significantly during the course of SSc. The IL-6 gene variant -174 C/G (presence of C-allele) is associated with higher IL-6 gene expression and greater GIT impairment in patients with SSc.


Assuntos
Gastroenteropatias/genética , Interleucina-6/genética , Polimorfismo de Nucleotídeo Único , Escleroderma Sistêmico/genética , Adulto , Idoso , Estudos de Casos e Controles , Estudos Transversais , Feminino , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Sérvia
16.
Med Princ Pract ; 27(4): 378-386, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29794470

RESUMO

OBJECTIVE: To investigate the association of high baseline serum levels of metalloproteinases-3 (MMP-3) with structural damage to hand and feet joints, assessed by ultrasonography (US), in patients with early, treatment-naïve rheumatoid arthritis (RA), without initial X-ray-visible erosions, during 24 months follow-up. METHODS: Sixty-three early RA (European League Against Rheumatism/American College of Rheumatology 2010), disease-modifying anti-rheumatic drugs/glucocorticoid naïve patients (mean age 53.4 ± 14.1) with symptom duration ≤12 months, had baseline serum levels of MMP-3 tested. OMERACT US group definition was used to detect the presence, as well as longitudinal diameter of erosions by US at study entry and after 24 months, at the level of wrists, metacarpophalangeal (MCP2/MCP5) joints of both hands, and fifth metatarsophalangeal joints. RESULTS: Complete data were collected from 52 out of 63 patients. High baseline serum levels of MMP-3 (MMP-3-positive) were found in 46/63 patients. 122 bone erosions in total (1.9 bone erosions/patients) were detected by US at baseline visit and 213 erosions (4.3/patients) after 24 months. MMP-3 positive patients had significantly higher total number of erosions than MMP-3-negative (p = 0.039) and higher increase in size of bone erosions in the feet but not in the hand joints after follow-up (OR 4.82 [1.23-18.9], p = 0.024; OR 1.17 [0.320-4.26], p = 0.816 respectively). CONCLUSION: After 2 years of follow-up, US assessment showed a higher number of new bone erosions in MMP-3-positive compared to MMP-3-negative patients with early RA and no visible initial radiographic changes. High baseline levels of MMP-3 predict significantly higher structural damage progression at the level of feet, but not at the level of hand joints.


Assuntos
Artrite Reumatoide/sangue , Artrite Reumatoide/diagnóstico por imagem , Metaloproteinases da Matriz/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Progressão da Doença , Feminino , Pé/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Ultrassonografia , Articulação do Punho/fisiopatologia , Adulto Jovem
17.
Ann Rheum Dis ; 77(8): 1194-1199, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29535120

RESUMO

OBJECTIVES: To assess the reliability of the OMERACT ultrasound (US) definitions for the identification of calcium pyrophosphate deposition disease (CPPD) at the metacarpal-phalangeal, triangular fibrocartilage of the wrist (TFC), acromioclavicular (AC) and hip joints. METHODS: A web-based exercise and subsequent patient-based exercise were carried out. A panel of 30 OMERACT members, participated at the web-based exercise by evaluating twice a set of US images for the presence/absence of CPPD. Afterwards, 19 members of the panel met in Siena, Italy, for the patient-based exercise. During the exercise, all sonographers examined twice eight patients for the presence/absence of CPPD at the same joints. Intraoberserver and interobserver kappa values were calculated for both exercises. RESULTS: The web-based exercise yielded high kappa values both in intraobserver and interobserver evaluation for all sites, while in the patient-based exercise, inter-reader agreement was acceptable for the TFC and the AC. TFC reached high interobserver and intraobserver k values in both exercises, ranging from 0.75 to 0.87 (good to excellent agreement). AC reached moderate kappa values, from 0.51 to 0.85 (moderate to excellent agreement) and can readily be used for US CPPD identification. CONCLUSIONS: Based on the results of our exercise, the OMERACT US definitions for the identification of CPPD demonstrated to be reliable when applied to the TFC and AC. Other sites reached good kappa values in the web-based exercise but failed to achieve good reproducibility at the patient-based exercise, meaning the scanning method must be further refined.


Assuntos
Condrocalcinose/diagnóstico por imagem , Ultrassonografia/normas , Articulação Acromioclavicular/diagnóstico por imagem , Idoso , Feminino , Articulação do Quadril/diagnóstico por imagem , Humanos , Cooperação Internacional , Internet , Masculino , Articulação Metacarpofalângica/diagnóstico por imagem , Pessoa de Meia-Idade , Variações Dependentes do Observador , Sistemas de Informação em Radiologia , Reprodutibilidade dos Testes , Ultrassonografia/métodos , Articulação do Punho/diagnóstico por imagem
18.
Ann Rheum Dis ; 77(4): 563-570, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29306872

RESUMO

OBJECTIVES: Our aim was to use the opportunity provided by the European Scleroderma Observational Study to (1) identify and describe those patients with early diffuse cutaneous systemic sclerosis (dcSSc) with progressive skin thickness, and (2) derive prediction models for progression over 12 months, to inform future randomised controlled trials (RCTs). METHODS: The modified Rodnan skin score (mRSS) was recorded every 3 months in 326 patients. 'Progressors' were defined as those experiencing a 5-unit and 25% increase in mRSS score over 12 months (±3 months). Logistic models were fitted to predict progression and, using receiver operating characteristic (ROC) curves, were compared on the basis of the area under curve (AUC), accuracy and positive predictive value (PPV). RESULTS: 66 patients (22.5%) progressed, 227 (77.5%) did not (33 could not have their status assessed due to insufficient data). Progressors had shorter disease duration (median 8.1 vs 12.6 months, P=0.001) and lower mRSS (median 19 vs 21 units, P=0.030) than non-progressors. Skin score was highest, and peaked earliest, in the anti-RNA polymerase III (Pol3+) subgroup (n=50). A first predictive model (including mRSS, duration of skin thickening and their interaction) had an accuracy of 60.9%, AUC of 0.666 and PPV of 33.8%. By adding a variable for Pol3 positivity, the model reached an accuracy of 71%, AUC of 0.711 and PPV of 41%. CONCLUSIONS: Two prediction models for progressive skin thickening were derived, for use both in clinical practice and for cohort enrichment in RCTs. These models will inform recruitment into the many clinical trials of dcSSc projected for the coming years. TRIAL REGISTRATION NUMBER: NCT02339441.


Assuntos
Esclerodermia Difusa/diagnóstico , Índice de Gravidade de Doença , Testes Cutâneos/estatística & dados numéricos , Adulto , Área Sob a Curva , Progressão da Doença , Diagnóstico Precoce , Feminino , Humanos , Modelos Logísticos , Masculino , Valor Preditivo dos Testes , Estudos Prospectivos , RNA Polimerase III/análise , Curva ROC , Esclerodermia Difusa/enzimologia , Esclerodermia Difusa/patologia , Pele/patologia
19.
J Clin Ultrasound ; 46(3): 188-194, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29064088

RESUMO

AIM: To evaluate the influence of systemic sclerosis (SSc) on right ventricular (RV) remodeling by two- and three-dimensional echocardiography (2DE and 3DE) and heart rate variability (HRV). METHODS: Forty-five SSc patients and 35 age- and gender-matched healthy controls underwent clinical examination, 24-h Holter monitoring, and comprehensive 2DE and 3DE. RESULTS: 2DE RV global and RV free wall longitudinal strains, as well as 2DE RV endocardial, mid-myocardial, and epicardial longitudinal strains were lower in SSc subjects, who exhibited greater 3DE RV volumes but lower 3DE RV ejection fraction than controls. HRV indices were impaired in SSc subjects. These differences in RV global and free wall longitudinal strain, layer-specific strains, and ejection fraction, were associated with HRV indices independently of demographic, clinical, and echocardiographic parameters. Modified Rodnan Skin Score, clinical indicator of skin involvement in SSc, was associated with HRV parameters, RV layer-specific mechanics, and RV ejection fraction. CONCLUSION: SSc affects RV function and mechanics of all myocardial layers, as well as cardiac autonomic nervous function. HRV indices are significantly associated with RV function, RV deformation, and skin involvement in SSc patients.


Assuntos
Sistema Nervoso Autônomo/fisiopatologia , Frequência Cardíaca/fisiologia , Escleroderma Sistêmico/fisiopatologia , Função Ventricular Direita/fisiologia , Remodelação Ventricular/fisiologia , Ecocardiografia/métodos , Ecocardiografia Tridimensional/métodos , Eletrocardiografia Ambulatorial/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
20.
Rheumatol Int ; 38(3): 383-391, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29238865

RESUMO

The objective of this study was to determine the construct validity and sensitivity to change of Belgrade Ultrasound Enthesitis Score (BUSES) in spondyloarthritis patients. Seventy-six spondyloarthritis patients with enthesitis were included in this pilot, prospective, double-blinded ultrasound study. Thirty-four patients received biological and forty-two patients received non-biological therapy. BUSES was determined at the beginning, after 1, 3, and 6 months. Spearman's correlation coefficient was calculated between BUSES and baseline characteristics. Brunner-Langer mixed non-parametric ANOVA was used to examine sensitivity to change of BUSES and effect of biological therapy on BUSES. Effect of time on the presence of each of the ultrasound enthesitis signs (increased thickness, hypoehogenicity, Power Doppler, enthesophytes, and erosions) was assessed using Cochran Q test. There was a weak, positive correlation between BUSES and disease duration, clinical enthesitis score, BASFI, BASDAI, and ASDAS-ESR/CRP. BUSES was higher at the beginning than after 1 month (p = 0.004), after 3 months (p < 0.001) and after 6 months (p < 0.001), as well as BUSES was higher after 1 month than after 3 months (p < 0.001) and after 6 months (p = 0.002). There is no difference in efficiency between non-biological and biological therapies on BUSES. Increased thickness, hypoechogenicity, and Power Doppler have decreased on Achilles tendon's and plantar fascia's enthesis over time. BUSES has a certain degree of construct validity because of the weak, positive correlation with parameters referring to severity of spondyloarthritis. BUSES demonstrated sensitivity to change over time due to decreasing of ultrasound acute enthesitis signs in treated spondyloarthritis patients. BUSES could be useful for monitoring the progression of enthesitis and effectiveness of the treatment.


Assuntos
Tendão do Calcâneo/diagnóstico por imagem , Entesopatia/diagnóstico por imagem , Espondilartrite/diagnóstico por imagem , Ultrassonografia Doppler em Cores , Tendão do Calcâneo/efeitos dos fármacos , Tendão do Calcâneo/fisiopatologia , Adulto , Antirreumáticos/uso terapêutico , Produtos Biológicos/uso terapêutico , Método Duplo-Cego , Entesopatia/tratamento farmacológico , Entesopatia/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Valor Preditivo dos Testes , Estudos Prospectivos , Reprodutibilidade dos Testes , Sérvia , Índice de Gravidade de Doença , Espondilartrite/tratamento farmacológico , Espondilartrite/fisiopatologia , Fatores de Tempo , Resultado do Tratamento
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