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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.
Adv Ther ; 36(12): 3494-3502, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31654331

RESUMO

INTRODUCTION: Rheumatoid arthritis (RA) is a chronic systemic auto-immune disease associated with a prothrombotic state. Tocilizumab, an interleukin-6 receptor inhibitor, is highly effective in controlling disease activity and thrombotic risk. Factor XIII (FXIII), involved in thrombotic complications, has been reported to be reduced in RA patients during maintenance treatment with tocilizumab, but no data are available before and after the drug administration. Thus, we investigated the effects of tocilizumab on FXIII, thrombin generation and inflammation in patients with RA naïve for the drug. METHODS: We studied 15 consecutive adult patients with RA at baseline and 4 weeks after the onset of parenteral administration of tocilizumab, measuring disease activity and plasma levels of C-reactive protein (CRP), FXIII, and prothrombin fragments F1+2 by immunoenzymatic methods. Fifteen healthy subjects, sex-and age-matched with patients, served as normal controls for laboratory measurements. RESULTS: At baseline, patients with established RA had a median DAS28 of 4.8 (3.2-8.3) and, compared to healthy controls, had higher plasma levels of CRP (p < 0.0001), FXIII (p = 0.017) and F1+2 (p < 0.0001). Four weeks after starting treatment with tocilizumab, based on the EULAR response criteria, eight patients were classifiable as responders and seven as non-responders. In responders, we observed a statistically significant reduction not only of the values of DAS28 and CRP (p = 0.012 for both), ut also of plasma levels of FXIII (p = 0.05) and F1+2 (p = 0.025). In non-responders, all the studied parameters were unchanged. CONCLUSION: The decrease of FXIII and F1+2 levels after tocilizumab treatment observed only in those patients who responded to the drug indicates that the effect of tocilizumab on the prothrombotic state is linked to the control of inflammation and disease activity and not to a direct effect of the drug, thus contributing to the reduction of the cardiovascular risk.

3.
Autoimmun Rev ; 18(11): 102394, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31520797

RESUMO

OBJECTIVES: This study was designed to propose a simple "Fast Track algorithm" for capillaroscopists of any level of experience to differentiate "scleroderma patterns" from "non-scleroderma patterns" on capillaroscopy and to assess its inter-rater reliability. METHODS: Based on existing definitions to categorise capillaroscopic images as "scleroderma patterns" and taking into account the real life variability of capillaroscopic images described standardly according to the European League Against Rheumatism (EULAR) Study Group on Microcirculation in Rheumatic Diseases, a fast track decision tree, the "Fast Track algorithm" was created by the principal expert (VS) to facilitate swift categorisation of an image as "non-scleroderma pattern (category 1)" or "scleroderma pattern (category 2)". Mean inter-rater reliability between all raters (experts/attendees) of the 8th EULAR course on capillaroscopy in Rheumatic Diseases (Genoa, 2018) and, as external validation, of the 8th European Scleroderma Trials and Research group (EUSTAR) course on systemic sclerosis (SSc) (Nijmegen, 2019) versus the principal expert, as well as reliability between the rater pairs themselves was assessed by mean Cohen's and Light's kappa coefficients. RESULTS: Mean Cohen's kappa was 1/0.96 (95% CI 0.95-0.98) for the 6 experts/135 attendees of the 8th EULAR capillaroscopy course and 1/0.94 (95% CI 0.92-0.96) for the 3 experts/85 attendees of the 8th EUSTAR SSc course. Light's kappa was 1/0.92 at the 8th EULAR capillaroscopy course, and 1/0.87 at the 8th EUSTAR SSc course. CONCLUSION: For the first time, a clinical expert based fast track decision algorithm has been developed to differentiate a "non-scleroderma" from a "scleroderma pattern" on capillaroscopic images, demonstrating excellent reliability when applied by capillaroscopists with varying levels of expertise versus the principal expert and corroborated with external validation.


Assuntos
Algoritmos , Esclerodermia Localizada/diagnóstico , Escleroderma Sistêmico/diagnóstico , Humanos , Angioscopia Microscópica/métodos , Reprodutibilidade dos Testes
4.
J Rheumatol ; 46(9): 1164-1167, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30824644

RESUMO

OBJECTIVE: This is an update from the Outcome Measures in Rheumatology (OMERACT) Core Outcomes in Longterm Observational Studies Special Interest Group with a focus on rheumatoid arthritis. METHODS: Preliminary data and proposed next steps were outlined and discussed by participants. RESULTS: Domains identified after initial steps (systematic review and qualitative research) were pain, physical functioning, participation (i.e., work, social), longterm symptoms, fertility/family planning, emotional well-being, coping, financial status, and adverse events including death. CONCLUSION: The group agreed conceptually that short-term core outcomes could be different from longer term ones. Participants emphasized the importance of analyzing the need for core domains specifically for longterm longitudinal observational studies.

5.
Rheumatology (Oxford) ; 58(9): 1547-1555, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-30770717

RESUMO

OBJECTIVE: Lysyl oxidase (LOX) is an extracellular enzyme that cross-links collagen fibrils. LOX was found to be increased in serum of SSc patients and was suggested to be related to skin fibrosis, yet a vascular source of LOX has been demonstrated in idiopathic pulmonary arterial hypertension (iPAH). We aimed to validate elevated LOX serum levels in SSc and to study its correlation with clinical characteristics and investigate its main source at the tissue level. METHODS: A total of 86 established SSc patients were compared with 86 patients with very early diagnosis of systemic sclerosis (VEDOSS), 110 patients with primary RP (PRP) and 80 healthy controls. LOX serum levels were determined by ELISA. Five lung and 12 skin biopsies from SSc patients were stained for LOX and compared with controls. RESULTS: Serum levels of LOX in SSc were significantly higher than in VEDOSS, PRP and healthy controls (P < 0.001). LOX inversely correlated with the diffusing capacity of the lung for carbon monoxide diffusing capacity (DLCO) in diffuse SSc (r = -0.376, P = 0.02). Patients with moderate to severe estimated systolic PAH had higher LOX levels (P < 0.01). Lung biopsies demonstrated intense LOX staining in SSc patients with PAH that was predominantly located in the endothelium of the remodelled pulmonary vessels. CONCLUSION: Serum LOX levels are increased in established SSc and inversely correlate with the DLCO. LOX is elevated in patients with moderate to severe PAH and is located in the proliferating endothelium in lung arterioles, suggesting a possible role for LOX in SSc-associated PAH.

6.
Semin Arthritis Rheum ; 48(4): 686-693, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29706243

RESUMO

BACKGROUND: Systemic sclerosis (SSc) is an autoimmune chronic disease characterized by vascular impairment, immune dysfunction and collagen deposition. Raynaud's phenomenon (RP) and digital ulcers (DU) are prominent features of SSc. Intravenous (IV) iloprost (ILO), according to the recently updated EULAR recommendations, is indicated for RP after failure of oral therapy. Moreover, IV ILO could be useful in DU healing. IV ILO is currently available mainly on the European market approved for RP secondary to SSc with 3-5 days infusion cycle. Unfortunately, data published varies regarding regimen (dosage, duration and frequency). Up to now, ILO has been studied in small cohorts of patients and in few randomized controlled trials. METHODS: A systematic review of studies on IV ILO in patients with SSc complicated by DU and RP was performed. Insufficient data were available to perform a meta-analysis according to the GRADE system. We performed a three-stage internet-based Delphi consensus exercise. RESULTS: Three major indications were identified for IV ILO usage in SSc: RP non-responsive to oral therapy, DU healing, and DU prevention. IV ILO should be administered between 0.5 and 2.0ng/kg/min according to patient tolerability with a frequency depending on the indication. CONCLUSIONS: Although these suggestions are supported by this expert group to be used in clinical setting, it will be necessary to formally validate the present suggestions in future clinical trials.


Assuntos
Iloprosta/uso terapêutico , Doença de Raynaud/tratamento farmacológico , Escleroderma Sistêmico/complicações , Úlcera Cutânea/tratamento farmacológico , Vasodilatadores/uso terapêutico , Consenso , Dedos , Humanos , Iloprosta/administração & dosagem , Injeções Intravenosas , Úlcera Cutânea/etiologia , Vasodilatadores/administração & dosagem
7.
Microvasc Res ; 122: 125-130, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-29981761

RESUMO

OBJECTIVE: We aimed to study in SSc patients macrovascular involvement by using power Doppler ultrasound (PDUS) and microvascular one by PDUS and nailfold video-capillaroscopy (NVC) and to examine the association between history of digital ulcers (HDU) and imaging (PDUS and NVC) parameters. METHODS: NVC and PDUS were systematically performed in 106 consecutive SSc patients at the 3rd and 4th finger of the dominant hand after exclusion of ulnar artery occlusion (UAO). 22 MHz PDUS measurements included nailbed and fingertip qualitatively graded, and resistivity index (RI) of ulnar and radial proper digital arteries. Capillary number/mm was calculated by NVC on the same digits examined by PDUS. RESULTS: Vascularization at fingertip and nailbed showed a good correlation between them and to capillary number. RI, representative of macrovascular involvement, did not correlate to microvascular involvement as assessed by PDUS and NVC. RI and capillary number at NVC showed significant correlation to HDU while fingertip and nailbed vascularization as assessed by PDUS did not. As such, PDUS and NVC provide different and potentially complementary information on SSc-related peripheral macro- and micro-vascular involvement. CONCLUSION: Macro- and micro-vascular involvement in SSc patients are different processes and are not present at the same time in every patient. Thus, both these aspects should be carefully evaluated in SSc patients.


Assuntos
Capilares/diagnóstico por imagem , Microcirculação , Angioscopia Microscópica , Unhas/irrigação sanguínea , Artéria Radial/diagnóstico por imagem , Doença de Raynaud/diagnóstico por imagem , Escleroderma Sistêmico/diagnóstico por imagem , Úlcera Cutânea/diagnóstico por imagem , Artéria Ulnar/diagnóstico por imagem , Ultrassonografia Doppler , Capilares/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Imagem Multimodal , Valor Preditivo dos Testes , Prognóstico , Estudos Prospectivos , Artéria Radial/fisiopatologia , Doença de Raynaud/etiologia , Doença de Raynaud/fisiopatologia , Fluxo Sanguíneo Regional , Escleroderma Sistêmico/complicações , Escleroderma Sistêmico/fisiopatologia , Úlcera Cutânea/etiologia , Úlcera Cutânea/fisiopatologia , Artéria Ulnar/fisiopatologia
8.
Rheumatology (Oxford) ; 58(1): 18-26, 2019 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-29538754

RESUMO

RP is the most common manifestation of SSc and a major cause of disease-related morbidity. This review provides a detailed appraisal of the patient experience of SSc-RP and potential implications for disease classification, patient-reported outcome instrument development and SSc-RP clinical trial design. The review explores the clinical features of SSc-RP, the severity and burden of SSc-RP symptoms and the impact of SSc-RP on function, work and social participation, body image dissatisfaction and health-related quality of life in SSc. Where management of SSc-RP is concerned, the review focuses on the 'patient experience' of interventions for SSc-RP, examining geographic variation in clinical practice and potential barriers to the adoption of treatment recommendations concerning best-practice management of SSc-RP. Knowledge gaps are highlighted that could form the focus of future research. A more thorough understanding of the patient experience could support the development of novel reported outcome instruments for assessing SSc-RP.


Assuntos
Doença de Raynaud/psicologia , Escleroderma Sistêmico/complicações , Adulto , Imagem Corporal/psicologia , Feminino , Humanos , Masculino , Qualidade de Vida , Doença de Raynaud/etiologia , Participação Social/psicologia
9.
Best Pract Res Clin Rheumatol ; 32(2): 223-240, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-30527428

RESUMO

Systemic sclerosis (SSc) is a chronic immune-mediated connective tissue disease with heterogeneous organ involvement. New classification criteria were developed allowing disease identification even before the onset of its hallmark, skin fibrosis. Incidence and prevalence vary among reports and are influenced by methodology. Despite earlier diagnosis, mortality of SSc is still considerable, mainly because of cardiopulmonary causes. Genetic predisposition is entangled and implies genes of the major histocompatibility complex and also other loci related to immune regulation. Known environmental risk factor is exposure to organic solvents and silica, but no single risk factor has emerged. Disease outcome measures including patient-reported outcomes have been proposed and validated, and their use is expected to contribute to measure treatment response in clinical trials. Because of the low frequencies and the high heterogeneity of the disease, large multicenter research collaborations are envisaged to achieve advancement in SSc management.


Assuntos
Escleroderma Sistêmico/epidemiologia , Escleroderma Sistêmico/etiologia , Humanos , Fatores de Risco
10.
Arthritis Res Ther ; 20(1): 187, 2018 08 29.
Artigo em Inglês | MEDLINE | ID: mdl-30157947

RESUMO

BACKGROUND: In systemic sclerosis (SSc), autoantibodies provide the most accurate tool to predict the disease subset and pattern of organ involvement. Scleroderma autoantibodies target nucleic acids or DNA/RNA-binding proteins, thus SSc immune complexes (ICs) can embed nucleic acids. Our working hypothesis envisaged that ICs containing scleroderma-specific autoantibodies might elicit proinflammatory and profibrotic effects in skin fibroblasts. METHODS: Fibroblasts were isolated from skin biopsies obtained from healthy subjects and patients with diffuse cutaneous SSc (dcSSc). ICs were purified by polyethylene-glycol precipitation from sera of SSc patients bearing different autoantibodies. ICs from patients with systemic lupus erythematosus (SLE) and primary anti-phospholipid syndrome (PAPS) and from normal healthy subjects (NHS) were used as controls. After incubation with ICs, fibroblasts were evaluated for ICAM-1 expression, interleukin (IL)-6, IL-8, monocyte chemoattractant protein (MCP)-1, matrix metalloproteinase (MMP)-2, tumor growth factor (TGF)-ß1 and Pro-CollagenIα1 secretion, collagen (col)Iα1, mmp-1, toll-like receptor (tlr)2, tlr3, tlr4, tlr7, tlr8, tlr9, interferon (ifn)-α, ifn-ß and endothelin-1 mRNA, and NFκB, p38MAPK and SAPK-JNK activation rate. Experiments were also performed after pretreatment with DNase I/RNase and NFκB/p38MAPK inhibitors. RESULTS: The antigenic reactivity for each SSc-IC mirrored the corresponding serum autoantibody specificity, while no positivity was observed in NHS-ICs or sera. SSc-ICs but not NHS-ICs increased ICAM-1 expression, stimulated IL-6, IL-8, MMP-2, MCP-1, TGF-ß1 and Pro-CollagenIα1 secretion, upregulated et-1, ifn-α, ifn-ß, tlr2, tlr3 and tlr4, and activated NFκB, p38MAPK and SAPK-JNK. tlr9 was significantly upregulated by ARA-ICs, mmp-1 was significantly induced by ACA-ICs whereas colIα1 was not modulated by any SSc-ICs. SLE-ICs and PAPS-ICs significantly upregulated MMP-2 and activated NFκB, p38MAPK and SAPK-JNK. SLE-ICs and PAPS-ICs did not affect colIα1, mmp-1 and Pro-CollagenIα1. DNase I and RNase treatment significantly reduced the upregulation of study mediators induced by SSc-ICs. Pretreatment with NFκB/p38MAPK inhibitors suggested that response to anti-Th/To-ICs was preferentially mediated by p38MAPK whereas ATA-ICs, ACA-ICs and ARA-ICs engaged both mediators. In dcSSc fibroblasts, stimulation with SSc-ICs and NHS-ICs upregulated IL-6 and IL-8. CONCLUSIONS: These data provide the first demonstration of the proinflammatory and profibrotic effects of SSc-ICs on fibroblasts, suggesting the potential pathogenicity of SSc autoantibodies. These effects might be mediated by Toll-like receptors via the interaction with nucleic acid fragments embedded in SSc-ICs.


Assuntos
Complexo Antígeno-Anticorpo/imunologia , Autoanticorpos/imunologia , Fibroblastos/imunologia , Escleroderma Sistêmico/imunologia , Colágeno Tipo I/genética , Colágeno Tipo I/imunologia , Colágeno Tipo I/metabolismo , Citocinas/genética , Citocinas/imunologia , Citocinas/metabolismo , Fibroblastos/metabolismo , Fibroblastos/patologia , Fibrose/imunologia , Expressão Gênica/imunologia , Humanos , Inflamação/genética , Inflamação/imunologia , Molécula 1 de Adesão Intercelular/genética , Molécula 1 de Adesão Intercelular/imunologia , Molécula 1 de Adesão Intercelular/metabolismo , Fenótipo , Escleroderma Sistêmico/genética , Escleroderma Sistêmico/patologia , Pele/imunologia , Pele/metabolismo , Pele/patologia , Receptores Toll-Like/genética , Receptores Toll-Like/imunologia , Receptores Toll-Like/metabolismo
11.
Inflammation ; 41(5): 1648-1660, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29804189

RESUMO

Somatostatin and its analogues are known to have modulatory effects on immune response and their anti-proliferative, anti-angiogenic, and analgesic properties make them attractive candidates for a therapeutic use in immune-mediated diseases, such as rheumatoid arthritis. Here, we demonstrate the ability of the somatostatin analogue octreotide to inhibit interleukin-15 and to increase interleukin-10 production by rheumatoid arthritis fibroblast-like synovial cells maintained in a chronic inflammatory state. We also prove that the inhibitory effect of octreotide on interleukin-15 and tumor necrosis factor-α production depended on the increase in interleukin-10, since neutralizing anti-interleukin-10 antibody was able to partially reverse this inhibition. In addition, our observations suggest an octreotide control on purinergic signaling, with an inhibitory effect on purinergic P2X and P2Y receptors activation. This would have great implications, considering the roles of P2 receptors in the onset of inflammation. Data here reported extend knowledge on the biological action of octreotide and underline its multiple effects on immune response, which could make octreotide an attractive and valid support for the therapy of diseases where several inflammatory mediators are involved, such as rheumatoid arthritis, and in which the simultaneous action on different aspects can be a successful strategy.


Assuntos
Artrite Reumatoide/tratamento farmacológico , Inflamação/tratamento farmacológico , Octreotida/farmacologia , Somatostatina/análogos & derivados , Sinoviócitos/patologia , Artrite Reumatoide/patologia , Humanos , Interleucina-10/agonistas , Interleucina-15/antagonistas & inibidores , Octreotida/uso terapêutico , Purinérgicos , Sinoviócitos/efeitos dos fármacos , Fator de Necrose Tumoral alfa/biossíntese
12.
Rheumatology (Oxford) ; 57(8): 1408-1416, 2018 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-29733400

RESUMO

Objectives: I.v. iloprost (ILO) may be used in the treatment of refractory RP and digital ulcers. We aim to evaluate the acute and chronic effects of two different ILO regimens by power Doppler US (PDUS) and nailfold videocapillaroscopy. Methods: In this 3-month single-centre pragmatic non-randomized trial, 96 SSc patients were included and stratified according to ILO treatment as: no ILO (group A), ILO once monthly (group B) and ILO for five consecutive days (group C). Resistivity index (RI), finger pulp blood flow and periungual vascularization by PDUS, and sum of capillaries apex width in 1 mm by nailfold videocapillaroscopy were evaluated. Results were adjusted for the average outdoor temperature at the place of residence. Results: An acute ILO effect was observed for only finger pulp blood flow in groups B and C (P < 0.001 and P < 0.005, respectively). An acute effect was observed for RI and periungual vascularization only in group B. A progressive increase was observed for other parameters without statistical difference. ILO effects were not observed any longer before the following infusion. Some parameters (finger pulp blood flow in group B and RI in group C) showed a statistically higher increase the lower the outdoor temperature was. Conclusion: ILO had an acute effect as assessed by PDUS, especially in group B. By contrast, an ILO chronic effect was not detectable before the following infusion in both treatment groups. More studies are needed to define how often ILO should be administered.


Assuntos
Dedos/irrigação sanguínea , Iloprosta/administração & dosagem , Fluxo Sanguíneo Regional/efeitos dos fármacos , Escleroderma Sistêmico/tratamento farmacológico , Administração Intravenosa , Adulto , Idoso , Idoso de 80 Anos ou mais , Relação Dose-Resposta a Droga , Feminino , Seguimentos , Humanos , Fluxometria por Laser-Doppler , Masculino , Angioscopia Microscópica , Pessoa de Meia-Idade , Estudos Retrospectivos , Escleroderma Sistêmico/diagnóstico , Escleroderma Sistêmico/fisiopatologia , Fatores de Tempo , Resultado do Tratamento , Vasodilatadores/administração & dosagem , Adulto Jovem
13.
Adv Ther ; 35(4): 439-456, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29556907

RESUMO

Patients with inflammatory rheumatic diseases often need orthopaedic surgery due to joint involvement. Total hip replacement and total knee replacement are frequent surgical procedures in these patients. Due to the complexity of the inflammatory rheumatic diseases, the perioperative management of these patients must envisage a multidisciplinary approach. The frequent association with extraarticular comorbidities must be considered when evaluating perioperative risk of the patient and should guide the clinician in the decision-making process. However, guidelines of different medical societies may vary and are sometimes contradictory. Orthopaedics should collaborate with rheumatologists, anaesthesiologists and, when needed, cardiologists and haematologists with the common aim of minimising perioperative risk in patients with inflammatory rheumatic diseases. The aim of this review is to provide the reader with simple practical recommendations regarding perioperative management of drugs such as disease-modifying anti-rheumatic drugs, corticosteroids, non-steroidal anti-inflammatory drugs and tools for a risk stratification for cardiovascular and thromboembolic risk based on current evidence for patients with inflammatory rheumatic diseases.


Assuntos
Relações Interprofissionais , Procedimentos Ortopédicos/métodos , Assistência Perioperatória/métodos , Doenças Reumáticas/cirurgia , Corticosteroides/uso terapêutico , Anestesiologistas , Anti-Inflamatórios não Esteroides/uso terapêutico , Antirreumáticos/uso terapêutico , Artroplastia de Quadril/métodos , Artroplastia do Joelho/métodos , Cardiologistas , Hematologia , Humanos , Equipe de Assistência ao Paciente/organização & administração , Doenças Reumáticas/tratamento farmacológico , Fatores de Risco
14.
Autoimmun Rev ; 17(4): 344-352, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29427827

RESUMO

Nailfold capillaroscopy is an easy, non-invasive technique to assess microvascular involvement in rheumatic diseases. Multiple studies describe capillaroscopic changes in systemic lupus erythematosus (SLE), including a wide range of non-specific findings. On behalf of the European League Against Rheumatism (EULAR) study group on microcirculation in rheumatic diseases, a systematic review was done to obtain all original research studies (in English) in which SLE patients had capillaroscopy. Forty such studies are identified. This article firstly provides a résumé of the results of these studies according to capillaroscopic parameters (density, dimensions, morphology, haemorrhages), semi-quantitative assessment and qualitative assessment of capillaroscopy in SLE patients. Secondly, the correlations between capillaroscopic parameters in SLE patients and clinical and laboratory parameters (including auto-immune parameters) are outlined. The following capillaroscopic parameters are found to be significantly more prevalent in SLE patients compared to healthy controls: tortuous capillaries, abnormal morphology and haemorrhages. Hairpin-shaped capillaries are significantly less prevalent than in healthy persons. The semi-quantitatively determined nailfold capillaroscopic score (NFC score) in SLE patients is also higher than in healthy controls. Several correlations between clinical and laboratory parameters and capillaroscopic parameters are identified in the review. Disease activity is correlated with NFC score in seven studies, with abnormal morphology (i.e. "meandering") in one study and with haemorrhages in one study. Frequent attacks of Raynaud's phenomenon (RP) and gangrene are significantly correlated with dilated capillaries. In two studies a possible correlation between anti-SSA antibodies and lower density of capillaries is withheld. About other immune parameters conflicting results are found. In one study a significant negative correlation is found between 24-hour proteinuria and abnormal morphology (i.e. "meandering"). For the first time, an overview of the nailfold capillaroscopic changes that have been described in SLE and their correlations with clinical and laboratory findings is given. Further large-scale research on the identification of capillaroscopic changes in SLE and their correlations with standardised clinical and laboratory parameters, is ongoing at the EULAR study group on microcirculation in rheumatic diseases.


Assuntos
Lúpus Eritematoso Sistêmico/imunologia , Angioscopia Microscópica/métodos , Unhas/irrigação sanguínea , Capilares , Feminino , Humanos , Masculino
15.
Arthritis Care Res (Hoboken) ; 70(9): 1373-1384, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29473715

RESUMO

OBJECTIVE: Raynaud's phenomenon (RP) is the most common manifestation of systemic sclerosis (SSc). RP is an episodic phenomenon, not easily assessed in the clinic, leading to reliance on self-report. A thorough understanding of the patient experience of SSc-RP is essential to ensuring that patient-reported outcome (PRO) instruments capture domains important to the target patient population. We report the findings of an international qualitative research study investigating the patient experience of SSc-RP. METHODS: Focus groups of SSc patients were conducted across 3 scleroderma centers in the US and UK, using a topic guide and a priori purposive sampling framework devised by qualitative researchers, SSc patients, and SSc experts. Focus groups were audio recorded, transcribed, anonymized, and analyzed using inductive thematic analysis. Focus groups were conducted until thematic saturation was achieved. RESULTS: Forty SSc patients participated in 6 focus groups conducted in Bath (UK), New Orleans (Louisiana), and Pittsburgh (Pennsylvania). Seven major themes were identified that encapsulate the patient experience of SSc-RP: physical symptoms, emotional impact, triggers and exacerbating factors, constant vigilance and self-management, impact on daily life, uncertainty, and adaptation. The interrelationship of the 7 constituent themes can be arranged within a conceptual map of SSc-RP. CONCLUSION: We have explored the patient experience of SSc-RP in a diverse and representative SSc cohort and identified a complex interplay of experiences that result in significant impact. Work to develop a novel PRO instrument for assessing the severity and impact of SSc-RP, comprising domains/items grounded in the patient experiences of SSc-RP identified in this study, is underway.


Assuntos
Doença de Raynaud/psicologia , Escleroderma Sistêmico/complicações , Adulto , Idoso , Feminino , Grupos Focais , Humanos , Masculino , Pessoa de Meia-Idade , Pesquisa Qualitativa , Doença de Raynaud/etiologia
17.
Curr Rheumatol Rev ; 14(1): 5-11, 2018 04 20.
Artigo em Inglês | MEDLINE | ID: mdl-28641553

RESUMO

BACKGROUND: Nailfold capillaroscopy is a safe and useful investigational tool that allows an early detection and a qualitative description of the microvascular abnormalities in patients with Raynaud's phenomenon secondary to scleroderma-spectrum disorders. Nowadays, the role of capillaroscopy in the diagnosis of systemic sclerosis is well known. Capillaroscopy has been included in the new 2013 classification criteria for systemic sclerosis and is considered a key investigation in the very early phases of the disease. CONCLUSION: Because of its potential value in monitoring disease progression and treatment response, nailfold capillaroscopy may also have a role in the management of overt systemic sclerosis. RESULTS: Its application in scleroderma-spectrum disorders in which a microvascular component is suspected may also provide new insights into their pathophysiology.


Assuntos
Angioscopia Microscópica/métodos , Escleroderma Sistêmico/diagnóstico por imagem , Humanos , Doença de Raynaud/diagnóstico por imagem , Esclerodermia Localizada/diagnóstico por imagem
18.
J Scleroderma Relat Disord ; 3(3): 249-252, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30705970

RESUMO

The episodic nature of Raynaud's phenomenon (RP) in systemic sclerosis (SSc) has led to a reliance on patient-reported outcome (PRO) instruments such as the Raynaud's Condition Score (RCS) diary. Little is known about the utilisation in routine clinical practice and health professional attitudes towards existing PRO instruments for assessing SSc-RP. Members of the Scleroderma Clinical Trials Consortium Vascular Working Group (SCTC-VWG, n=28) were invited to participate in a survey gauging attitudes towards the RCS diary and the perceived need for novel PRO instruments for assessing SSc-RP. Nineteen SCTC-VWG members (68% response rate) from academic units based in North America (n=9), Europe (n=8), South America (n=1) and Australasia (n=1) took part in the survey. There was broad consensus that RCS diary returns could be influenced by factors including seasonal variation in weather, efforts made by patients to avoid or ameliorate attacks of RP, habituation to RP symptoms, evolution of RP symptom characteristics with progressive obliterative microangiopathy, patient coping strategies, respondent burden and placebo effect. There was consensus that limitations of the RCS diary might be a barrier to drug development (79% of respondents agree/strongly agree) and that a novel PRO instrument for assessing SSc-RP should be developed with the input of both clinicians and patients (84% agree/strongly agree). Perceived potential limitations of the RCS diary have been identified along with concerns that such factors might impede drug development programs for SSc-RP. There is support within the systemic sclerosis community for the development of a novel PRO instrument for assessing SSc-RP.

19.
Drug Des Devel Ther ; 11: 2891-2904, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29042750

RESUMO

The steadily increasing knowledge regarding pathogenetic mechanisms in autoimmune rheumatic diseases has paved the way to different therapeutic approaches. In particular, the market entry of biologics has dramatically modified the natural history of rheumatic chronic inflammatory diseases with a meaningful impact on patients' quality of life. Among the wide spectrum of available biological treatments, rituximab (RTX), first used in the treatment of non-Hodgkin's lymphoma, was later approved for rheumatoid arthritis and anti-neutrophil cytoplasmic antibodies-associated vasculitis. Nowadays, in rheumatology, RTX is also used with off-label indications in patients with systemic sclerosis, Sjögren's syndrome and systemic lupus erythematosus. RTX is a monoclonal antibody directed to CD20 molecules expressed on the surfaces of pre-B and mature B lymphocytes. It acts by causing apoptosis of these cells with antibody- and complement-dependent cytotoxicity. As inflammatory responses to cell-associated immune complexes are key elements in the pathogenesis of several autoimmune rheumatic diseases, such an approach might be effective in these patients. In fact, RTX, by promoting the rapid and long-term depletion of circulating and lymphoid tissue-associated B cells, leads to a lower recruitment of these effector cells at sites of immune complex deposition, thus reducing inflammation and tissue damage. RTX is of the most interest to rheumatologists as it represents an important additional therapeutic approach. Thus, the advent in clinical practice of approved RTX biosimilars, such as CT-P10, may be of help in improving treatment access as well as in reducing costs.


Assuntos
Doenças Autoimunes/tratamento farmacológico , Doenças Reumáticas/tratamento farmacológico , Rituximab/uso terapêutico , Animais , Antígenos CD20/imunologia , Antirreumáticos/administração & dosagem , Antirreumáticos/farmacologia , Antirreumáticos/uso terapêutico , Doenças Autoimunes/imunologia , Doenças Autoimunes/fisiopatologia , Medicamentos Biossimilares/administração & dosagem , Humanos , Qualidade de Vida , Doenças Reumáticas/imunologia , Doenças Reumáticas/fisiopatologia , Rituximab/administração & dosagem , Rituximab/farmacologia
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