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1.
Clin Exp Rheumatol ; 37 Suppl 119(4): 102-107, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31587695

RESUMO

OBJECTIVES: To retrospectively study nailfold videocapillaroscopy (NVC) changes in mixed connective tissue disease (MCTD) patients and to compare the capillary morphological abnormalities between patients affected by MCTD and systemic sclerosis (SSc) over time. METHODS: Ten MCTD patients on whom NVC had been performed, with a follow-up of three years, were selected. In addition, ten patients affected by SSc with similar age and disease duration of MCTD patients were enrolled to compare NVC abnormalities at baseline (T0). RESULTS: Seven out of ten patients with MCTD showed a "scleroderma-like pattern" at first NVC. No statistically significant variation of the detected NVC parameters was observed during the 3-year follow-up, and no statistically significant correlation was observed between capillary parameters and MCTD clinical aspects at first visit and during the follow-up. The scores of enlarged capillaries, giant capillaries and microhaemorrhages were significantly lower (p<0.05) in MCTD versus SSc patients at T0, moreover, the absolute number of total capillaries and normal capillaries was found significantly higher (p<0.05) in MCTD versus SSc patients. CONCLUSIONS: This study suggests that nailfold microvascular damage does not seem to be significantly progressive in MCTD patients during a three-year follow-up. MCTD patients show significantly lower number of enlarged/giant capillaries, but higher number of total and normal capillaries than SSc patients at first nailfold capillaroscopy. The identification of a specific NVC pattern in MCTD patients is not yet possible.


Assuntos
Angioscopia Microscópica/métodos , Doença Mista do Tecido Conjuntivo , Unhas , Escleroderma Sistêmico , Capilares , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Doença Mista do Tecido Conjuntivo/diagnóstico por imagem , Unhas/irrigação sanguínea , Unhas/diagnóstico por imagem , Estudos Retrospectivos , Escleroderma Sistêmico/diagnóstico por imagem
2.
Artigo em Inglês | MEDLINE | ID: mdl-31586421

RESUMO

OBJECTIVES: Urinary tract involvement is a seldom-reported manifestation of SSc that could compromise patients' quality of life. This study compares lower urinary tract symptoms (LUTS) in SSc patients and in healthy subjects and their association with clinical and diagnostic parameters. METHODS: LUTS were assessed through self-reported questionnaires in 42 SSc patients and 50 matched healthy subjects. Statistical analyses were performed to explore LUTS in the two populations and their association with SSc variables, including nailfold videocapillaroscopy patterns, SSc-related antibodies and DXA parameters. RESULTS: SSc patients showed significantly higher prevalence and severity of urinary incontinence (UI) and overactive bladder (OAB) than healthy controls (P < 0.005, P < 0.01). SSc was a strong predictor of LUTS, independent of demographic data, comorbidities and treatments (odds ratio 5.57, 95% CI 1.64-18.88). In SSc patients OAB positively correlated with sarcopenia (P < 0.001), and both OAB and UI significantly correlated with reduced BMD (P < 0.05, P = 0.001). UI positively correlated with Scl70 antibodies (P < 0.05) and ciclosporin treatment (P = 0.001) and negatively with RNA polymerase III antibodies (P < 0.05); OAB positively correlated with calcinosis (P < 0.005) and negatively with methotrexate treatment (P < 0.05). Nailfold videocapillaroscopy 'active' and 'late' patterns were predominant among SSc patients presenting urinary symptoms, although no statistical correlation was found. CONCLUSION: For the first time urinary tract involvement was found to be significantly higher in SSc patients than in healthy matched controls. In addition, sarcopenia, bone damage and calcinosis appeared significantly correlated with LUTS, suggesting a possible interplay.

3.
Autoimmun Rev ; : 102397, 2019 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-31520798

RESUMO

BACKGROUND AND AIM: Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease; the clinical manifestations are correlated with continuum multiarticular synovitis, cartilage and bone damage, and defeat of joint function, that causes disability. Involvement of internal organs is also frequent. Between the inflammatory cells involved in RA, macrophages play a key role. These cells can polarize in different phenotype and mediate the immune/inflammatory reaction as well as the reparatory phase when possible. The properties of these cells are mediate by the body's environmental factors. In this systematic review, all English-speaking articles concerning the role of M1 (pro-inflammatory) or M2 (anti-inflammatory) macrophages in RA were systematically reviewed and categorized according to their polarized-function in RA, especially in the synovial tissue. Analyses of the endogenous molecules and the drugs that could modulate M1 and M2 activity in RA were achieved. METHODS: A sensitive search was developed in Pubmed, Web of Science, Ovid Med-Line, Embase Database and Science Direct Database (la both from Elsevier) to identify articles to increase the highlighting on the role of macrophages M1 and M2 in RA using the following terms: ((M1 AND M2) AND Rheumatoid Arthritis). All selected papers were read and discussed by two independent reviewers. The selection process was based on title, abstract and full text level. Relevant data were extracted and analyzed using a standardized template designed for this review. RESULTS: In total 39 resulting articles were selected and categorized according to description of M1/M2's role in RA. Data from humans, mice and rats were subcategorized, thus in every section were highlighted the contribute, in peripheral blood and synovial tissue, of both polarized macrophages; section for endogenous molecules and drugs that favor the switch from M1 to M2 macrophages were carried out. The most evinced relevant results, were that in RA blood and in the synovial tissue, there isn't a clear distinction phase with M1 or M2 macrophages (by membrane marker analysis); rather there is M1 and M2 subset disequilibrium and by deeply analyses of mRNA gene and cytokine produced, it emerged that a non-coherent expression inner marker match with membrane molecules, and also the tissue section can define the marker expressed. CONCLUSION: This systematic review emphasizes that the rigid classical subdivision of M1 and M2 macrophages, as well as the different samples' results comparison, might be questionable. In addition, it is suggested, when taking samples from RA patients, to carefully consider their therapies in order to analyze the M1 and M2 macrophages behavior without drug influence. In line with the advances in M1 and M2 knowledge, and the progression in the single-cell methodologies by identification of individual cell molecular markers, therapeutic approaches seem possible to favor the anti-inflammatory macrophage response in RA (e.g. M2 polarization).

4.
Artigo em Inglês | MEDLINE | ID: mdl-31526595

RESUMO

OBJECTIVES: To investigate the validation status of laser Doppler flowmetry (LDF) in systemic sclerosis (SSc) according to the 'Outcome Measures in Rheumatologic Clinical Trials' (OMERACT) filter. METHODS: The literature was systematically reviewed to identify all reports assessing the microcirculatory flow in SSc patients. The OMERACT filter -including the domains of truth, discrimination and feasibility- was applied and a quality assessment was done by the 'Good Methods Checklist'. To ease the comparison between studies the results were grouped per dynamic test situation: basal, cold/heat challenge and occlusion. RESULTS: The literature search resulted in 4332 hits. Based on title and abstract screening 243 hits were retained and of these, 52 full texts described an assessment by LDF in SSc patients. Finally, 18 studies passed the quality assessment and form the object of this review. The review reveals that expert consensus is lacking on the face and content validity of LDF in SSc. The construct validity of LDF, on the other hand is partially validated. Conflicting results exist on the discriminant capacity of LDF in distinguishing healthy from diseased patients, primary from secondary Raynaud's phenomenon and in differentiating between disease subsets. Yet, complementing an LDF-measurement with a heat challenge, as well as the evaluation of the post-occlusive hyperaemic response, has the potential to elicit a difference between healthy and diseased patients. Lastly, data on the feasibility of LDF in SSc is lacking in the identified literature. CONCLUSION: This systematic review emphasizes the very preliminary validation status of LDF in the assessment of the microcirculatory flow in SSc.

5.
Autoimmun Rev ; : 102394, 2019 Sep 11.
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.

7.
Clin Exp Rheumatol ; 37 Suppl 119(4): 69-75, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31365333

RESUMO

OBJECTIVES: Relaxin is a potent anti-fibrotic hormone that has been tested to ameliorate fibrosis in systemic sclerosis (SSc), but with controversial results. The aim of the study is to sequence relaxin receptor gene RXFP1 and to assess its mRNA expression and protein levels in the skin of SSc patients and healthy subjects. METHODS: Fibroblasts were isolated from unaffected/affected skin samples of (n=16) limited-cutaneous-SSc-(LcSSc) and from affected ones of (n=4) diffuse-cutaneous-SSc-(DcSSc) patients. Fibroblasts from healthy subjects were used as controls. Sequencing of exonic target regions of interest for RXFP1 gene was performed, coupled with mRNA transcript variant analysis. RXFP1 mRNA and protein levels were assessed by quantitative-real-time-PCR-(qRT-PCR) and by immunocytochemistry-(ICC). Alpha-smooth-muscle-actin-(α-SMA) synthesis induced by transforming-growth-factor-beta-1-(TGF-ß1) stimulation was investigated in all fibroblasts with and without pre-treatment with serelaxin (a recombinant form of human relaxin-2 targeting the receptor RXFP1). RESULTS: Sequencing of RXFP1 gene showed no relevant mutations in all fibroblast populations. The analysis of mRNA transcripts revealed the presence of 13 different mRNA isoforms of RXFP1 (7 coding and 6 non-coding) upregulated in LcSSc/DcSSc-affected samples and not in LcSSc-unaffected and in healthy ones. On the contrary, ICC demonstrated the absence of RXFP1 in LcSSc/DcSSc-affected fibroblasts and the presence in LcSSc-unaffected and in healthy ones. To prove these findings, serelaxin pre-incubation was unable to counteract TGF-ß1-driven upregulation of α-SMA in LcSSc/DcSSc-affected fibroblasts only, but not in LcSSc-unaffected and healthy ones. CONCLUSIONS: The absence/altered expression of relaxin receptor RXFP1 in the affected fibroblasts of SSc patients could explain the inefficacy of relaxin-based anti-fibrotic treatments in the disease.


Assuntos
Fibroblastos/metabolismo , Relaxina , Esclerodermia Difusa , Escleroderma Sistêmico , Idoso , Feminino , Fibroblastos/patologia , Fibrose/metabolismo , Fibrose/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Receptores Acoplados a Proteínas-G/metabolismo , Receptores de Peptídeos/metabolismo , Proteínas Recombinantes , Relaxina/metabolismo , Esclerodermia Difusa/metabolismo , Esclerodermia Difusa/patologia , Escleroderma Sistêmico/metabolismo , Escleroderma Sistêmico/patologia
8.
J Rheumatol ; 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31416927

RESUMO

OBJECTIVE: Pulmonary arterial hypertension (PAH) is one of the leading causes of death in systemic sclerosis (SSc). Current screening algorithms are hampered by low positive predictive values. Outcome measures that could futurely add to performance characteristics would be very welcome. Against this background, we aim to evaluate the role of nailfold videocapillaroscopy (NVC) using standardized definitions, in SSc related PAH (SSc-PAH). METHODS: A systematic review to identify original research papers documenting an association between NVC and right heart catheterisation defined SSc-PAH was performed according to the PRISMA guidelines. Subsequently, NVC parameters were subdivided into quantitative (capillary density, dimension, morphology, and haemorrhages), semi-quantitative and qualitative assessment (NVC pattern), according to the definitions of the EULAR Study Group on Microcirculation in Rheumatic Diseases. RESULTS: The systematic search identified 316 unique search results, of which 5 were included in the final qualitative analysis. The occurrence of incident SSc-PAH unequivocally associated in 2 longitudinal studies with progressive capillary loss (p=0.04 and p=0.033) and the progression to a severe (active/late) NVC pattern (p=0.05/0.01 and HR=5.12, 95%CI: 1.23- 21.27). In 3 cross-sectional studies, SSc-PAH was found to be unequivocally inversely associated with capillary density (p=0.001 and p<0.05) and associated with the presence of a severe NVC pattern (p=0.03 and p<0.05). CONCLUSION: This is the first systematic literature review investigating the role of NVC in SSc-PAH using standardized description. Unequivocal associations were found between (incident) SSc-PAH and capillary density and NVC pattern. Integration of NVC into current screening algorithms to boost their performance may be a future step.

10.
Artigo em Inglês | MEDLINE | ID: mdl-31230071

RESUMO

OBJECTIVE: The pathological changes in SSc include immune system dysregulation and microvascular damage. However, the association of immune cell phenotype heterogeneity and microvascular abnormalities is unclear. The aim of this study is to elucidate this association in SSc. METHODS: Peripheral blood mononuclear cells obtained from 150 SSc patients were used for comprehensive flow cytometric analysis based on the Human Immunology Project. Hierarchical cluster analysis was used to classify SSc patients into subgroups and their association with microvascular abnormalities, as assessed by nailfold videocapillaroscopy (i.e. 'early', 'active' and 'late' patterns), was analysed. RESULTS: The proportions of activated CD4+ T cells, T cells re-expressing CD45RA, activated Th1 and Th17 cells and IgD-CD27- B cells were higher in SSc patients than in healthy individuals. Hierarchical cluster analysis stratified SSc patients into three groups: patients with few immune abnormalities (fewer abnormalities group), patients with high proportions of activated T and Treg cells (Treg-dominant group) and patients with high proportions of Tfh and plasmablasts (Tfh-dominant group). Age and disease duration were comparable among the groups. On the other hand, microvascular abnormalities, especially the 'late' nailfold videocapillaroscopy pattern, correlated with internal organ involvement. Among the groups stratified according to immune cell phenotype, the progression to the 'late' nailfold videocapillaroscopy pattern was more frequent in the Tfh-dominant group. CONCLUSION: Our study confirmed the presence of immunophenotypic abnormalities in SSc. Immunological abnormalities were not uniform but rather limited to subpopulations, particularly the Tfh-dominant group, where they were highly associated with microvascular abnormalities and organ involvement.

11.
Arthritis Res Ther ; 21(1): 152, 2019 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-31234888

RESUMO

BACKGROUND: The importance of systemic sclerosis (SSc) autoantibodies for diagnosis has become recognized by their incorporation into the 2013 ACR/EULAR classification criteria. Clear prognostic and phenotypic associations with cutaneous subtype and internal organ involvement have been also described. However, little is known about the potential of autoantibodies to exert a direct pathogenic role in SSc. The aim of the study is to assess the pathogenic capacity of anti-DNA-topoisomerase I (anti-Topo-I) and anti-centromeric protein B (anti-Cenp-B) autoantibodies to induce pro-fibrotic markers in dermal fibroblasts. METHODS: Dermal fibroblasts were isolated from unaffected and affected skin samples of (n = 10) limited cutaneous SSc (LcSSc) patients, from affected skin samples of diffuse cutaneous (DcSSc) patients (n = 10) and from healthy subjects (n = 20). Fibroblasts were stimulated with anti-Topo-I, anti-Cenp-B IgGs, and control IgGs in ratios 1:100 and 1:200 for 24 h. Cells were also incubated with 10% SSc anti-Topo-I+ and anti-Cenp-B+ whole serum and with 10% control serum for 24 h. Viability was assessed by MTT test, while apoptosis was assessed by flow cytometry. Activation of pro-fibrotic genes ACTA2, COL1A1, and TAGLN was evaluated by quantitative real-time PCR (qPCR), while the respective protein levels alpha-smooth-muscle actin (α-SMA), type-I-collagen (Col-I), and transgelin (SM22) were assessed by immunocytochemistry (ICC). RESULTS: MTT showed that anti-Cenp-B/anti-Topo-I IgGs and anti-Cenp-B+/anti-Topo-I+ sera reduced viability (in a dilution-dependent manner for IgGs) for all the fibroblast populations. Apoptosis is induced in unaffected LcSSc and control fibroblasts, while affected LcSSc/DcSSc fibroblasts showed apoptosis resistance. Basal mRNA (ACTA2, COL1A1, and TAGLN) and protein (α-SMA, Col-1, and SM22) levels were higher in affected LcSSc/DcSSc fibroblasts compared to LcSSc unaffected and to control ones. Stimulation with anti-Cenp-B/anti-Topo-I IgGs and with anti-Cenp-B+/anti-Topo-I+ sera showed a better induction in unaffected LcSSc and control fibroblasts. However, a statistically significant increase of all pro-fibrotic markers is reported also in affected LcSSc/DcSSc fibroblasts upon stimulation with both IgGs and sera. CONCLUSIONS: This study suggests a pathogenic role of SSc-specific autoantibodies to directly induce pro-fibrotic activation in human dermal fibroblasts. Therefore, besides the diagnostic and prognostic use of those autoantibodies, these data might further justify the importance of immunosuppressive drugs in the early stages of the autoimmune disease, including SSc.

12.
Rheumatol Int ; 39(8): 1369-1376, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31056725

RESUMO

The objective is to detect any possible correlation between the modified Rodnan skin score (mRSS) and dermal thickness (DT) measured by skin high-frequency ultrasound (US) and the percentage of circulating fibrocytes in patients with limited cutaneous systemic sclerosis (lcSSc). Eight lcSSc patients and five healthy subjects (control group, CNT) were enrolled. The skin involvement was evaluated by mRSS and US (18 and 22 MHz probes) in all 13 subjects in the 17 standard skin areas evaluated by mRss. Circulating fibrocytes were isolated from the peripheral blood mononuclear cells (PBMCs) of all lcSSc patients and the CNT group to analyze their percentage at baseline time (T0) when the experiments started with PBMCs' isolation and collection and after 8 days of culture (T8). Non-parametric tests were used for the statistical analysis. A positive correlation between the percentage of circulating fibrocytes at T0, mRSS (p = 0.04 r = 0.96), and DT-US, evaluated by the 22 MHz and the 18 MHz probes (p = 0.03, r = 0.66 and p = 0.05, r = 0.52, respectively), was observed in lcSSc patients. Conversely, at T8, there was no correlation (p > 0.05) between these parameters in lcSSc group. In the CNT group, no correlations between mRSS or DT-US and the percentage of circulating fibrocytes were observed both at T0 and T8. The study shows the presence of a significant relationship between the percentage of circulating fibrocytes and DT, as evidenced by both mRSS and US, in limited cutaneus SSc. This observation may well suggest the reasonable hypothesis of a crucial contribution of circulating fibrocytes to skin fibrosis progression, which might be considered as further biomarkers.

13.
Expert Rev Clin Immunol ; 15(7): 753-764, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31046487

RESUMO

Introduction: Systemic sclerosis (SSc) is a complex autoimmune connective tissue disease characterized by chronic and progressive tissue and organ fibrosis with broad patient-to-patient variability. Some risk factors are known and include combination of persistent Raynaud's phenomenon, steroid hormone imbalance, selected chemicals, thermal, or other injuries. Endogenous and/or exogenous environmental trigger/risk factors promote epigenetic mechanisms in genetically primed subjects. Disease pathogenesis presents early microvascular changes with endothelial cell dysfunction, followed by the activation of mechanisms promoting their transition into myofibroblasts. A complex autoimmune response, involving innate and adaptive immunity with specific/functional autoantibody production, characterizes the disease. Progressive fibrosis and ischemia involve skin and visceral organs resulting in their irreversible damage/failure. Progenitor circulating cells (monocytes, fibrocytes), together with growth factors and cytokines participate in disease diffusion and evolution. Epigenetic, vascular and immunologic mechanisms implicated in systemic fibrosis, represent major targets for incoming disease modifying therapeutic approaches. Areas covered: This review discusses current understanding and new insights of SSc pathogenesis, through an overview of the most relevant advancements to present aspects and mechanisms involved in disease pathogenesis. Expert opinion: Considering SSc intricacy/heterogeneity, early combination therapy with vasodilators, immunosuppressive and antifibrotic drugs should successfully downregulate the disease progression, especially if started from the beginning.

14.
Clin Rheumatol ; 2019 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-31127461

RESUMO

Rheumatic and musculoskeletal diseases (RMDs) encompass a spectrum of degenerative, inflammatory conditions predominantly affecting the joints. They are a leading cause of disability worldwide and an enormous socioeconomic burden. However, worldwide deficiencies in adult and paediatric RMD knowledge among medical school graduates and primary care physicians (PCPs) persist. In October 2017, the World Forum on Rheumatic and Musculoskeletal Diseases (WFRMD), an international think tank of RMD and related experts, met to discuss key challenges and opportunities in undergraduate RMD education. Topics included needs analysis, curriculum content, interprofessional education, teaching and learning methods, implementation, assessment and course evaluation and professional formation/career development, which formed a framework for this white paper. We highlight a need for all medical graduates to attain a basic level of RMD knowledge and competency to enable them to confidently diagnose, treat/manage or refer patients. The importance of attracting more medical students to a career in rheumatology, and the indisputable value of integrated, multidisciplinary and multiprofessional care are also discussed. We conclude that RMD teaching for the future will need to address what is being taught, but also where, why and to whom, to ensure that healthcare providers deliver the best patient care possible in their local setting.

15.
Microvasc Res ; 125: 103881, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31075243

RESUMO

INTRODUCTION AND AIM: Microangiopathy is a hallmark of systemic sclerosis (SSc). It is a progressive process from an early inflammatory and proangiogenic environment to insufficient microvascular repair with loss of microvessels. The exact underlying mechanisms remain ill-defined. Aim of the study was to investigate whether imbalanced angiopoietins/VEGF serum profile should be related in SSc to the altered microvascular reactivity characterized by aberrant angiogenesis and avascularity. MATERIALS AND METHODS: Serum levels of Angiopoietin-1 (Ang1), Angiopoietin-2 (Ang2) and VEGF were measured by ELISA in 47 SSc patients and 27 healthy controls. Microvascular alterations were assessed by nailfold videocapillaroscopy (NVC). RESULTS: Serum concentrations of Ang1 were significantly lower [mean (S.D.): 21516.04 (11,441.035) pg/ml], and Ang2 significantly increased [25,89.55 (934.225) pg/ml] in SSc as compared with the control group [Ang1: 28,457.08 (10,431.905) pg/ml; Ang2: 1556.23 (481.255) pg/ml, p < 0.01, respectively], whereas VEGF did not differ significantly. The ratios of Ang1/Ang2 and Ang1/VEGF were significantly lower in SSc patients (8.346 ±â€¯4.523 and 95.17 ±â€¯75.0, respectively) than in healthy subjects (17.612 ±â€¯6.731 p < 0.000001 and 183.11 ±â€¯137.73; p = 0.004]. Formation of giant capillaries with vascular leakage and collapse was associated with significant increase in VEGF and concomitant Ang1 deficiency. Capillary loss was related to significant increase in VEGF with respect to those with preserved capillary number (395.12 ±â€¯256.27 pg/mL vs. 254.80 ±â€¯213.61 pg/mL) whereas elevated Ang2 levels induced more advanced capillary damage as indicated by the presence of the "Late" NVC pattern. CONCLUSIONS: We found that serum levels of Ang1, Ang2 and VEGF are differentially expressed in SSc and altered Ang1/Ang2 profile might underlay the aberrant angiogenesis in SSc despite increase in VEGF. For the first time we identified that significant deficiency of Ang1 might be involved in early capillary enlargement, followed by collapse and lack of stable newly-formed vessels in VEGF-enriched environment, whereas Ang2 levels seem to increase later in disease progression and advanced microvascular damage ("Late" NVC pattern).

18.
Medicine (Baltimore) ; 98(13): e15052, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30921233

RESUMO

RATIONALE: Aromatase inhibitors (AIs) are a class of drugs widely used in the treatment of estrogen sensitive breast and ovarian cancer which convert testosterone to estradiol and androstenedione to estrogen. The AIs of third generation, including anastrazole, letrozole and exemestane, have actually become the standard of care of estrogen-receptor-positive breast cancer in menopausal women and are recommended as adjuvant treatment after surgery in place of/or following tamoxifen. Their main side-effects include reduction in bone mineral density, occurrence of menopausal manifestations and development of musculoskeletal symptoms which are, usually, transient, but sometimes evolve into a typical form of arthritis, such as rheumatoid arthritis (RA). Recently, a pathogenic linkage with other autoimmunity diseases, such as Sjogren syndrome (SjS), anti-synthetase antibody syndrome (ASAS), systemic sclerosis (SS) and subacute cutaneous lupus erythematosus (SCLE), was also described. PATIENT CONCERNS: Here, we report the first case of a patient with primary antiphospholipid syndrome (APS) developed during treatment with anastrazole. DIAGNOSIS: The patient developed a sudden onset of speech disturbance and disorientation, due to ischemic lesions, after 6 months of AIs therapy and the laboratory examination showed the positivity of anti-Cardiolipin antibodies, anti-ß2 Glycoprotein 1 antibodies and Lupus Anticoagulant, so a certain diagnosis of APS was achieved. INTERVENTIONS: The patient was treated with warfarin associated to hydroxychloroquine and monthly cycles of low doses intravenous immunoglobulins. OUTCOMES: A good control of the disease was obtained despite the continuation of anastrazole; the patient's clinical and laboratory situation remained not modified after AIs withdrawal. LESSONS: We discussed the possible role of anastrazole treatment in inducing APS in our patient, reporting the available literature data about the association between AIs treatment and autoimmune diseases. Furthermore, we analyzed the mechanism of action of estrogens in the pathophysiology of autoimmune rheumatic disorders.


Assuntos
Anastrozol/efeitos adversos , Antineoplásicos Hormonais/efeitos adversos , Síndrome Antifosfolipídica/induzido quimicamente , Inibidores da Aromatase/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Feminino , Humanos , Pessoa de Meia-Idade
19.
Ann Rheum Dis ; 78(9): 1160-1166, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30898837

RESUMO

Giant cell arteritis (GCA) represents the most common form of primary systemic vasculitis and is frequently associated with comorbidities related to the disease itself or induced by the treatment. Systematically collected data on disease course, treatment and outcomes of GCA remain scarce. The aim of this EULAR Task Force was to identify a core set of items which can easily be collected by experienced clinicians, in order to facilitate collaborative research into the course and outcomes of GCA. A multidisciplinary EULAR task force group of 20 experts including rheumatologists, internists, epidemiologists and patient representatives was assembled. During a 1-day meeting, breakout groups discussed items from a previously compiled collection of parameters describing GCA status and disease course. Feedback from breakout groups was further discussed. Final consensus was achieved by means of several rounds of email discussions after the meeting. A three-round Delphi survey was conducted to determine a core set of parameters including the level of agreement. 117 parameters were regarded as relevant. Potential items were subdivided into the following categories: General, demographics, GCA-related signs and symptoms, other medical conditions and treatment. Possible instruments and assessment intervals were proposed for documentation of each item. To facilitate implementation of the recommendations in clinical care and clinical research, a minimum core set of 50 parameters was agreed. This proposed core set intends to ensure that relevant items from different GCA registries and databases can be compared for the dual purposes of facilitating clinical research and improving clinical care.

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