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1.
Clin Exp Rheumatol ; 2019 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-31498071

RESUMO

OBJECTIVES: To analyse the frequency and predictors of new-onset cardiovascular (CV) risk factors in patients with anti-neutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV) and giant cell arteritis (GCA). METHODS: We analysed the frequency and predictors of new-onset hypertension and/or diabetes mellitus (HTN/DM) amongst patients with AAV or GCA recruited in the Diagnostic and Classification of Vasculitis (DCVAS) study. Patients with pre-existing HTN/DM were excluded. RESULTS: We included 873 patients with AAV (506 GPA, 183 MPA, 184 EGPA), and 443 with GCA. Patients with GCA were more likely female (68% vs. 52%; p<0.001) and older (71.33±8.65 vs. 52.80±16.48; p<0.001) compared to patients with AAV. HTN/DM developed within 6 months of diagnosis in 9% of patients with AAV (6% in GPA, 21% in MPA, 3% in EGPA) and 6% of patients with GCA, p=0.15. Rise in creatinine/reduced glomerular filtration rate and/or anaemia (OR 3.98, 95% CI 2.09-7.59, p<0.001) and diagnosis (MPA: OR 2.42, 95%CI 1.52-3.83, p<0.001 and GCA: OR 2.12, 95%CI 1.34-3.38, p=0.001 vs. GPA) were significantly associated with the occurrence of HTN/DM after adjusting for age, sex, ethnicity, and smoking status. We developed and validated a predictive score to discriminate patients according to the risk of developing HTN/DM within 6 months from diagnosis. CONCLUSIONS: Despite different epidemiological and clinical characteristics, new CV risk factors occur equally in the early stages of AAV and GCA. Renal function and type of diagnosis are associated with the occurrence of HTN/DM. We developed a simple predictive score for the risk-stratification of patients.

2.
J Control Release ; 310: 198-208, 2019 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-31430501

RESUMO

Interstitial lung involvement in Systemic Sclerosis (SSc-ILD) is a complication with high morbidity and mortality. Specifically, engineered gold nanoparticles (GNPs) are proposed as targeted delivery system increasing efficacy of drugs with antifibrotic effect, such as tyrosine kinases. We aimed to test in vitro and in vivo the activity of targeted Imatinib (Im)-loaded GNP on SSc-ILD patients derived cells and in experimental model of lung fibrosis. GNPs functionalized with anti-CD44 and loaded with Im (GNP-HCIm) were synthesized. Lung fibroblasts (LFs) and alveolar macrophages from bronchoalveolar lavage fluids of SSc-ILD patients were cultured in presence of nanoparticles. GNP-HCIm significantly inhibited proliferation and viability inducing apoptosis of LFs and effectively reduced IL-8 release, viability and M2 polarization in alveolar macrophages. Anti-fibrotic effect of tracheal instilled GNP-HCIm was evaluated on bleomycin lung fibrosis mouse model comparing effect with common route of Im administration. GNP-HCIm were able to reduce significantly lung fibrotic changes and collagen deposition. Finally, electron microscopy revealed the presence of GNPs inside alveolar macrophages. These data support the use of GNPs locally administered in the development of new therapeutic approaches to SSc-ILD.

3.
J Immunol Res ; 2019: 4236503, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30906789

RESUMO

Systemic lupus erythematosus (SLE) is an autoimmune disease with a complex etiology. Opportunistic viral pathogens, such as human cytomegalovirus (HCMV) and Epstein-Barr virus (EBV), are particularly relevant. The role of the T cell response in SLE has not been deeply studied; we investigated the role of HCMV- and EBV-specific T cell responses in SLE patients also in relation to their pharmacological immunosuppressive status. PBMCs from 70 SLE patients and 50 healthy controls were stimulated with EBV- and HCMV-specific antigens, and IFN-γ-secreting T cells were quantified. We observed that both EBV- and HCMV-specific T cell responses were significantly lower in SLE patients compared with healthy subjects. We reported decreased EBV- and HCMV-specific T cell responses among medium-high immunosuppressed patients compared to low immunosuppressed patients. Immunosuppressive level could exert a role in the control of herpesviruses reactivation, even if the immunosuppressive condition of SLE remains the driving cause of skewed virus-specific T cell response.


Assuntos
Linfócitos T CD8-Positivos/imunologia , Infecções por Citomegalovirus/imunologia , Citomegalovirus/imunologia , Infecções por Vírus Epstein-Barr/imunologia , Herpesvirus Humano 4/imunologia , Lúpus Eritematoso Sistêmico/imunologia , Adulto , Antígenos Virais/imunologia , Células Cultivadas , ELISPOT , Feminino , Humanos , Interferon gama/metabolismo , Ativação Linfocitária , Masculino , Pessoa de Meia-Idade , Especificidade do Receptor de Antígeno de Linfócitos T , Adulto Jovem
4.
J Autoimmun ; 99: 81-97, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30777378

RESUMO

The mechanisms whereby autoreactive T cells escape peripheral tolerance establishing thus autoimmune diseases in humans remain an unresolved question. Here, we demonstrate that autoreactive polyfunctional CD8+ T cells recognizing self-antigens (i.e., vimentin, actin cytoplasmic 1, or non-muscle myosin heavy chain 9 epitopes) with high avidity, counter-regulate Tregs by killing them, in a consistent percentage of rheumatoid arthritis (RA) patients. Indeed, these CD8+ T cells express a phenotype and gene profile of effector (eff) cells and, upon antigen-specific activation, kill Tregs indirectly in an NKG2D-dependent bystander fashion in vitro. This data provides a mechanistic basis for the finding showing that AE-specific (CD107a+) CD8+ T killer cells correlate, directly with the disease activity score, and inversely with the percentage of activated Tregs, in both steady state and follow-up studies in vivo. In addition, multiplex immunofluorescence imaging analyses of inflamed synovial tissues in vivo show that a remarkable number of CD8+ T cells express granzyme-B and selectively contact FOXP3+ Tregs, some of which are in an apoptotic state, validating hence the possibility that CD8+ Teff cells can counteract neighboring Tregs within inflamed tissues, by killing them. Alternatively, the disease activity score of a different subset of patients is correlated with the expansion of a peculiar subpopulation of autoreactive low avidity, partially-activated (pa)CD8+ T cells that, despite they conserve the conventional naïve (N) phenotype, produce high levels of tumor necrosis factor (TNF)-α and exhibit a gene expression signature of a progressive activation state. Tregs directly correlate with the expansion of this autoreactive (low avidity) paCD8+ TN cell subset in vivo, and efficiently control their differentiation rather their proliferation in vitro. Interestingly, autoreactive high avidity CD8+ Teff cells or low avidity paCD8+ TN cells are significantly expanded in RA patients who would become non-responders or patients who would become responders to TNF-α inhibitor therapy, respectively. These data provide evidence of a previously undescribed role of such mechanisms in the progression and therapy of RA.

5.
J Rheumatol ; 46(1): 3-4, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30600234
6.
Joint Bone Spine ; 86(4): 475-481, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30579917

RESUMO

OBJECTIVE: The reproductive choices of women affected by rheumatic diseases (RD) can be influenced by several factors, including the quality of physician-patient communication. We conducted a survey on reproductive issues aiming at exploring the unmet needs of women with RD during childbearing age. METHODS: We administered 65 multiple-choice and 12 open-answer questions about pregnancy counselling, contraception, use of drugs during pregnancy and other women reproductive issues to 477 consecutive women with RD aged 18-55 years followed-up in 24 rheumatology centres in Italy. Analysis was restricted to 398 patients who received their diagnosis of RD before the age of 45. According to the RD diagnosis, patients were subdivided into 2 groups: connective tissue diseases (n = 249) and chronic arthritis (n = 149). RESULTS: At the time of interview, women in both groups had a mean age of 40 years. Nearly one third of patients in each group declared not to have received any counselling about either pregnancy desire nor contraception. A smaller family size than desired was reported by nearly 37% of patients, because of concerns related to maternal disease in one fourth of the cases. A "Disease Knowledge Index" (DKI) was created to investigate the degree of patients' information about the implications of their RD on reproductive issues. Having received counselling was associated with higher DKI values and with a positive impact on family planning. CONCLUSION: Italian women of childbearing age affected by RD reported several unmet needs in their knowledge about reproductive issues. Strategies are needed to implement and facilitate physician-patient communication.

7.
Patient Prefer Adherence ; 12: 2153-2168, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30410311

RESUMO

Objective: To estimate preferences in relevant treatment characteristics evaluated by different groups involved in the management of patients with rheumatic diseases. Subjects and methods: We surveyed patients with rheumatic diseases, and rheumatologists, nurses, and pharmacists with experience in treatment with/provision of biologic drugs for these patients. Through a discrete choice experiment, participants evaluated 16 possible scenarios in which pairs of similarly efficacious treatments were described with six characteristics: 1) frequency of administration; 2) mode and place of administration; 3) manner, helpfulness, efficiency, and courtesy of health personnel; 4) frequency of reactions at the site of drug administration; 5) severity of generalized undesired/allergic reactions; and 6) additional cost. The direction and strength of preferences toward each characteristic level and the relative importance of each characteristic were estimated through a random-effects conditional logistic regression model. Results: In total, 513 patients, 110 rheumatologists, 51 nurses, and 46 pharmacists from 30 centers in Italy participated. Characteristics 3, 4, and 6 were the most important for every subgroup; 1 was least important for patients and rheumatologists, 2 was least important for pharmacists, and 2 and 5 were least important for nurses. For characteristic 2, pharmacists preferred subcutaneous self-injection with a syringe; nurses preferred assisted infusion at an infusion center close to the patient's home; patients and rheumatologists preferred subcutaneous self-injection with a pen. Conclusion: The different preferences for some characteristics shown by the different groups can play an important role, together with purely clinical aspects, in the choice and consequent benefit of treatments, contributing also to a more satisfactory use of resources.

8.
Drugs Aging ; 2018 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-30484240

RESUMO

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) usually affect adults and older populations. The well recognized clinical (i.e., granulomatosis with polyangiitis [GPA], microscopic polyangiitis, and eosinophilic GPA) and serological phenotypes (i.e., anti-MPO-ANCA, anti-PR3-ANCA and ANCA negative) within AAV differ substantially for clinical, demographic, and epidemiological features, including age at presentation. Whether and how aging could contribute to the clinical expression of these disease phenotypes is intriguing and still overlooked. In addition, despite being predominantly a disease of the elderly, most of the studies analyzing drug interventions and the clinical trials on AAV explicitly excluded older patients, limiting the understanding of the disease in this subset of patients. In elderly patients induced with cyclophosphamide, a lower dose of treatment for patients aged 60 years or older and with reduced renal function has been recommended. Giant cell arteritis (GCA) and Takayasu's arteritis (TAK) are two primary systemic vasculitides involving large vessels that differ in age at presentation, with GCA patients being at least 10 years older than TAK patients. Different treatment approaches are effective in these conditions. However, a few authors have suggested that they might be considered expressions of the same clinical syndrome, rather than two different diseases. Novel insights into the role of senescence-related immunological and vascular processes might help to interpret the link between these two conditions. Overall, the impact of aging on all these vasculitides is complex and not easy to analyze. So far, few studies focusing on this topic have been published. We reviewed data on the clinical presentation, epidemiology, therapy, and disease- and treatment-related complications in patients affected by these vasculitides, highlighting the differences in young versus elderly subjects.

9.
J Rheumatol ; 2018 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-30442823

RESUMO

OBJECTIVE: To describe nailfold videocapillaroscopy (NVC) features of patients with antisynthetase syndrome (AS) and to investigate possible correlations with clinical and serological features of the disease. METHODS: We retrospectively analyzed NVC images of 190 patients with AS [females/males 3.63, mean age 49.7 ± 12.8 yrs, median disease duration 53.7 mos (interquartile range 82), 133 anti-Jo1 and 57 non-anti-Jo1-positive patients]. For each patient, we examined number of capillaries, giant capillaries, microhemorrhages, avascular areas, ramified capillaries, and the presence of systemic sclerosis (SSc)-like pattern. Finally, we correlated NVC features with clinical and serological findings of patients with AS. Concomitantly, a historical cohort of 75 patients with antinuclear antibody-negative primary Raynaud phenomenon (RP) and longterm followup was used as a control group (female/male ratio 4.13/1, mean age 53.9 ± 17.6 yrs) for NVC measures. RESULTS: NVC abnormalities were observed in 62.1% of AS patients compared with 29.3% of primary RP group (p < 0.001). An SSc-like pattern was detected in 67 patients (35.3%) and it was associated with anti-Jo1 antibodies (p = 0.002) and also with a longer disease duration (p = 0.004). Interestingly, there was no significant correlation between the presence of SSc-like pattern and RP, and only 47% of patients with SSc-like pattern had RP. CONCLUSION: NVC abnormalities are commonly observed in AS, independently from the occurrence of RP. The presence of an SSc-like pattern could allow identification of a more defined AS subtype, and prospective studies could confirm the association with clinical and serological features of AS.

10.
J Rheumatol ; 2018 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-30442833

RESUMO

OBJECTIVE: To date, "healed/non-healed" and clinical judgment are the only available assessment tools for digital ulcers (DU) in patients with systemic sclerosis (SSc). The aim of our study is to examine a preliminary composite DU clinical assessment score (DUCAS) for SSc for face, content, and construct validity. METHODS: Patients with SSc presenting at least 1 finger DU were enrolled and assessed with the Health Assessment Questionnaire-Disability Index, Cochin scale, visual analog scale (VAS) for DU-related pain, patient global DU status, and global assessment as patient-reported outcomes (PRO), and physician VAS for DU status (phyGDU) as an SSc-DU expert physician/nurse measure. The DUCAS included 7 DU-related variables selected by a committee of SSc DU experts and weighted on a clinical basis. Face validity was examined by consensus and partial construct validity was tested through convergent correlation with other measures of hand function, using Spearman's correlations. A range of patients with SSc was examined. A linear regression model with backward stepwise analysis was used to determine the relationship of individual variables with the primary clinical parameter, phyGDU. RESULTS: Forty-four patients with SSc (9 males, mean age 55 ± 15 yrs, mean disease duration 9.9 ± 5.8 yrs) were enrolled in the study. Overall DUCAS showed significant positive correlations with all abovementioned PRO (r > 0.4, p < 0.01). When all scores and scales were modeled, only DUCAS significantly predicted phyGDU (r = 0.59, R² = 0.354, Akaike information criterion = 385.4). CONCLUSION: Preliminarily, we suggest that the DUCAS may be a new clinical score for SSc-related DU, having face and content validity and convergent/divergent correlations (construct validity). These early data suggest that this score deserves further evaluation.

11.
Clin Exp Rheumatol ; 2018 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-30299248

RESUMO

OBJECTIVES: We aimed to evaluate the correlation between serum calprotectin and clinical and ultrasonographic (US) variables in early-onset psoriatic arthritis (PsA) and controls with rheumatoid arthritis (RA). METHODS: In a retrospective cross-sectional study, including PsA and matched RA patients, 44 joint counts (TJC, SJC), calprotectin, ESR and CRP were measured. US of wrists and MCPs 1-5 was performed, with grey-scale (GS) and power Doppler (PD) scored 0-3 at each site, summed in a total score. The correlation between calprotectin, clinical and US variables was evaluated by Spearman's coefficient, the predictivity by calprotectin of US by regression. Secondary analyses separating polyarticular PsA and using different US definitions (GS>1, PD>1) were performed. RESULTS: 78 PsA and 78 RA were included (PsA male 32%; mean age 51.7 (13.5)). Calprotectin did not significantly differ in PsA and RA. In PsA, calprotectin correlated with GS score (ρ=0.340, p=0.008), PD score (ρ=0.292, p=0.023) and the presence of PD (ρ=0.263, p=0.042); in RA there were no significant correlations. In polyarticular PsA, a significant correlation between calprotectin and GS (ρ=0.369, p=0.019) and PD scores (ρ=0.363, p=0.021) was confirmed. In both PsA and RA, calprotectin and CRP significantly correlated, while SJC and TJC did not. In the regression analysis, calprotectin did not predict US variables in PsA. Similar results were achieved in RA. CONCLUSIONS: In early PsA, serum calprotectin correlates with US measures of disease activity. Our results provide preliminary evidence for the application of this biomarker in early PsA.

12.
Rheumatology (Oxford) ; 57(57 Suppl 7): vii5-vii10, 2018 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-30289535

RESUMO

TNF inhibitors are biologic DMARDs approved for the treatment of active RA in mid-1990s. They still represent a valuable therapeutic option to control the activity, disability and radiographic progression of the disease. In the context of TNF inhibitors, there are currently several molecules and different administration routes that provide optimal treatment personalization, allowing us to respond to a patient's needs in the best possible way. The increasing use of TNF inhibitors has not only improved the management of RA, but it has also helped in our understanding of the pathogenetic mechanisms of the disease. This review focuses on the basis of this targeted therapy and on the knowledge gained from their use about therapeutic effects and adverse events. Effectiveness analysed from drug registries and safety issues are presented together with recent data on infections (in particular, Mycobacterium tuberculosis and hepatitis B), cancer (lymphoma, skin cancers) and cardiovascular risk.


Assuntos
Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Produtos Biológicos/uso terapêutico , Previsões , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Artrite Reumatoide/diagnóstico , Progressão da Doença , Humanos
13.
Rheumatology (Oxford) ; 57(57 Suppl 7): vii23-vii31, 2018 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-30289540

RESUMO

Objectives: To review the available evidence concerning the possibility of discontinuing and/or tapering the dosage of TNF inhibitors (TNFi) in RA patients experiencing clinical remission or low disease activity. Methods: A systematic review of the literature concerning the low dosage and discontinuation of TNFi in disease-controlled RA patients was performed by evaluation of reports published in indexed international journals (Medline via PubMed, EMBASE), in the time frame from 8 April 2013 to 15 January 2016. Results: We analysed the literature evaluating the efficacy and the safety of two different strategies using TNFi, decreasing dosage or discontinuation, in patients experiencing clinical remission or low disease activity. After the analysis of online databases, 25 references were considered potentially relevant and 16 references were selected. The majority of data concerned etanercept and adalimumab. Results suggested the induction of stable clinical remission or low disease activity by using TNFi followed by a dosage tapering and/or discontinuation of such drugs may be associated with the maintenance of a good clinical response in a subset of patients affected by early disease. Conclusion: RA patients treated early with TNFi and achieving their therapeutic clinical targets seem to maintain their clinical response after tapering or discontinuing TNFi. These data may allow physicians a more dynamic and tailored management of RA patients.


Assuntos
Antirreumáticos/administração & dosagem , Artrite Reumatoide/tratamento farmacológico , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Relação Dose-Resposta a Droga , Humanos , Indução de Remissão
14.
Rheumatol Int ; 2018 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-30074077

RESUMO

Diffuse alveolar haemorrhage (DAH) secondary to anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) is a rare life-threatening condition presenting with severe respiratory failure. The management of AAV-related DAH consists of remission induction immunosuppressive therapy, which requires time to be effective, with significant fatality rates despite appropriate treatment. Extracorporeal membrane oxygenation (ECMO) can support gas exchanges providing the time necessary for immunosuppressive treatment to control the underlying disease in cases refractory to the conventional ventilation techniques. Despite severe preexisting bleeding has been considered a relative contraindication, ECMO has proven to be life-saving in several cases of respiratory failure associated with pulmonary haemorrhage due to various causes, including AAV. We reviewed the clinical presentation and course of two patients affected by AAV-related DAH treated at our Institution between 2012 and 2017, whose management required the use of veno-venous ECMO. We reviewed the current literature on the role of ECMO in the support of these patients. In both patients, ECMO provided life support and allowed disease control, in combination with immunosuppressive treatment. Despite systemic anticoagulation, clinical improvement was achieved without exacerbation of the pulmonary bleeding. We performed a literature review, and summarized available data confirming the effectiveness and safety of ECMO in AAV-related DAH. ECMO has a life-saving role in the management of patients with severe respiratory failure due to ANCA-associated pulmonary capillaritis.

15.
Arthritis Rheumatol ; 70(5): 702-710, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29409140

RESUMO

OBJECTIVE: To evaluate whether the choice of synovial biopsy technique (arthroscopy, blind needle [BN] biopsy, ultrasound [US]-guided portal and forceps [P&F], or US-guided needle biopsy [NB]) translates to significant variation in synovial tissue quality and quantity, with the aim of informing recommendations for the choice of synovial sampling technique within clinical trials. METHODS: In total, 159 procedures from 5 academic rheumatology centers were evaluated. Hematoxylin and eosin-stained, paraffin-embedded synovial tissue sections from patients with inflammatory arthritis were assessed in order to determine the proportion of graded synovial fragments, total area of graded synovial tissue, and synovitis score per procedure. RNA quantity (µg of RNA) and quality (RNA integrity number) per procedure were also assessed in the synovial samples. RESULTS: In this study, 84 of the 159 procedures performed on large joints at baseline (25 arthroscopic, 35 US-P&F, 11 US-NB, and 13 BN biopsies), 41 of the 159 procedures performed on small joints at baseline (11 US-P&F, 20 US-NB, and 10 BN biopsies), and 34 sequential biopsy procedures were evaluated. Compared to all other techniques evaluated in the small and large joints, fewer small joint BN biopsies and a significantly lower proportion of large joint BN biopsies yielded graded synovial tissue. No significant difference in either the proportion of graded tissue samples or total graded synovial tissue area between the US-NB and arthroscopic large joint procedures was demonstrated. Among the sequential biopsy procedures evaluated (small joint US-NB, large joint arthroscopy, US-P&F biopsy, and BN biopsy), no significant difference in the proportion of graded synovial tissue or total graded synovial tissue area was demonstrated. All procedures yielded RNA of significant quality and quantity for subsequent transcriptomic analysis. CONCLUSION: These data support the integration of US-guided methods along with arthroscopic biopsy for clinical trial protocols in which sequential sampling of synovium from the large and small joints is needed for both histologic and molecular analysis. BN biopsy may be considered if graded synovial tissue is not required for subsequent analyses.

16.
Autoimmun Rev ; 17(1): 24-28, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29108829

RESUMO

The advent of anti-tumour necrosis factor (TNF) drugs for rheumatoid arthritis (RA) or spondyloarthritis (SpA) has revolutionised the approach to patients with active disease who do not respond to conventional therapy. Although there are differences in their structure, morphology, pharmacokinetic properties and activity, all anti-TNF drugs ultimately neutralise the TNFα pathway of inflammation. However, despite their similar clinical efficacy, there are disagreements concerning drug survival and safety, with systematic reviews and meta-analyses confirming one result or the other. The fact that 20-30% of patients fail to respond to TNFα inhibitors indicates the possibility of primary resistance or the development of an immune response to the drugs themselves, which may act as antigens. The overall benefit of switching to another anti-TNF drug or a biological agent with a different mechanism of action, may be a valuable option in individual patients. There are few data concerning the use of anti-TNF drugs in patients with SpA but it seems that there are fewer adverse advents and higher drug survival in comparison with patients with RA.


Assuntos
Artrite Reumatoide/tratamento farmacológico , Espondilartrite/tratamento farmacológico , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Artrite Reumatoide/patologia , Humanos , Espondilartrite/patologia
17.
Clin Exp Rheumatol ; 36(1): 44-49, 2018 Jan-Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28770709

RESUMO

OBJECTIVES: To evaluate if the timing of appearance with respect to disease onset may influence the arthritis presentation pattern in antisynthetase syndrome (ASSD). METHODS: The patients were selected from a retrospective large international cohort of ASSD patients regularly followed-up in centres referring to AENEAS collaborative group. Patients were eligible if they had an antisynthetase antibody testing positive in at least two determinations along with arthritis occurring either at ASSD onset (Group 1) or during the course of the disease (Group 2). RESULTS: 445 (70%; 334 females, 110 males, 1 transsexual) out of the 636 ASSD we collected had arthritis, in the majority of cases (367, 83%) from disease onset (Group 1). Patients belonging to Group 1 with respect to Group 2 had an arthritis more commonly polyarticular and symmetrical (p=0.015), IgM-Rheumatoid factor positive (p=0.035), erosions at hands and feet plain x-rays (p=0.036) and more commonly satisfying the 1987 revised classification criteria for rheumatoid arthritis (RA) (p=0.004). Features such as Raynaud's phenomenon, mechanic's hands and fever (e.g. accompanying findings) were more frequently reported in Group 2 (p=0.005). CONCLUSIONS: In ASSD, the timing of appearance with respect to disease onset influences arthritis characteristics. In particular, RA features are more common when arthritis occurs from ASSD onset, suggesting an overlap between RA and ASSD in these patients. When arthritis appears during the follow-up, it is very close to a connective tissue disease-related arthritis. Also, the different prevalence of accompanying features between these two groups is in line with this possibility.


Assuntos
Artrite/epidemiologia , Miosite/epidemiologia , Adulto , Artrite/diagnóstico , Artrite/imunologia , Autoanticorpos/sangue , Biomarcadores/sangue , Europa (Continente)/epidemiologia , Feminino , Humanos , Masculino , México/epidemiologia , Pessoa de Meia-Idade , Miosite/diagnóstico , Miosite/imunologia , Fenótipo , Prevalência , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo
18.
Mod Rheumatol ; 28(3): 542-549, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-28880727

RESUMO

BACKGROUND: Treat to target (T2T), aiming at inactive disease (ID), has become the recommended strategy for axial-SpA (ax-SpA). Using the Ankylosing Spondylitis Disease Activity Score (ASDAS), we assessed the prevalence of ID in ax-SpA patients treated with TNFα inhibitors (TNFi). METHODS: A multicentric, cross-sectional study was performed assessing disease activity status (BASDAI and ASDAS) of consecutive patients with ax-SpA on stable treatment with TNFi for at least six months. We analyzed differences with nonradiographic axSpA (nr-ax-SpA) and the influence of population characteristics and comorbidities in reaching ID. ID was defined as ASDAS-CRP <1.3. RESULTS: A total of 218 patients were enrolled, 165 with AS and 53 with nr-ax-SpA. ASDAS-CRP ID was reached by 89 (40.8%) patients, while 163 (74.8%) of patients achieved good disease control with BASDAI. There were no significant differences between the two diagnostic groups. Multivariate logistic regression demonstrated a negative correlation of concomitant fibromyalgia, higher BASMI and current NSAIDs with the chances of reaching ASDAS-CRP ID or BASDAI <4. CONCLUSION: T2T represents a new challenge in the management of ax-SpA, with recently introduced disease activity measures being significantly more stringent. The prevalence of ID was affected by concomitant fibromyalgia, decreased spine mobility and concomitant NSAIDs.


Assuntos
Espondilite Anquilosante/tratamento farmacológico , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adulto , Anti-Inflamatórios não Esteroides/uso terapêutico , Feminino , Fibromialgia/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Espondilite Anquilosante/epidemiologia , Espondilite Anquilosante/patologia
19.
Am J Reprod Immunol ; 78(6)2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28921728

RESUMO

Undifferentiated connective tissue diseases (UCTDs) are a heterogeneous group of disorders characterized by symptoms and signs suggestive of systemic autoimmune rheumatic disease (ARD), but which do not fulfill all the established criteria for definite diagnosis of a condition. Although a third of UCTDs can progress to a definite ARD within months or years, most UCTDs can remain stable for years with minimal disease activity. The annual incidence of UCTD in the general population ranges from 14 to 140 per 100 000 people. UCTDs are associated with the persistence of several circulating autoantibodies including antinuclear, antiphospholipid or antithyroid antibodies. Immunological evaluation of subjects with UCTDs suggests a proinflammatory state and dysregulation of the Th1/Th2 balance. Autoantibodies have well-known deleterious effects on placentation and have been associated with an increased risk of prematurity, fetal growth restriction (FGR), preeclampsia, and congenital atrioventricular heart block. Although epidemiological and biological data suggest a potential negative impact on reproductive outcomes, the relationship between UCTD and pregnancy outcomes has not been adequately studied. While awaiting definitive data from large studies, obstetricians should be aware that rheumatic disorders in their early, incomplete, or undifferentiated phases can adversely affect pregnancy outcomes, increasing the likelihood of pregnancy loss, FGR, preeclampsia, and prematurity.


Assuntos
Doenças Autoimunes/epidemiologia , Retardo do Crescimento Fetal/epidemiologia , Pré-Eclâmpsia/epidemiologia , Doenças Reumáticas/epidemiologia , Doenças do Tecido Conjuntivo Indiferenciado/epidemiologia , Adulto , Animais , Autoanticorpos/metabolismo , Feminino , Humanos , Incidência , Gravidez , Resultado da Gravidez , Risco , Equilíbrio Th1-Th2
20.
Curr Opin Rheumatol ; 29(6): 612-617, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28796005

RESUMO

PURPOSE OF REVIEW: To provide the most recent evidence on anti-Jo-1 syndrome. RECENT FINDINGS: Several new evidences on anti-Jo-1 syndrome have recently emerged. It has been clearly established that, at disease onset, the classic clinical triad (arthritis, myositis and interstitial lung disease - ILD) is only rarely observed. Indeed, disease onset with an isolated arthritis is common. Patients presenting with an isolated manifestation are at high risk for the subsequent occurrence of initially lacking triad findings. Moreover, the ex-novo occurrence of accompanying features such as Raynaud's phenomenon, mechanic's hands and fever during follow-up is a strong risk factor for the occurrence of overt antisynthetase syndrome (ASSD) with further triad manifestations. Several contributions on ILD involvement and prognosis have been published, as well as the distinctive muscle MRI characteristics compared with healthy controls, and a novel definition of a rare skin manifestation (hiker's feet). SUMMARY: Recent evidence has shed a light on the need for a better understanding of the clinical course, imaging modalities and prognosis of anti-Jo-1 syndrome, providing some relevant elements to allow early diagnosis of this often unrecognized disease.


Assuntos
Anticorpos Antinucleares , Artrite/diagnóstico , Doenças Autoimunes/diagnóstico , Histidina-tRNA Ligase/imunologia , Doenças Pulmonares Intersticiais/diagnóstico , Miosite/diagnóstico , Artrite/imunologia , Doenças Autoimunes/imunologia , Humanos , Doenças Pulmonares Intersticiais/imunologia , Miosite/imunologia , Prognóstico , Fatores de Risco , Avaliação de Sintomas , Síndrome
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