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1.
Rheumatol Int ; 2023 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-37925382

RESUMO

Rheumatoid arthritis is a chronic autoimmune disease that can affect different organs beyond the joints. Ocular involvement includes keratoconjunctivitis sicca, peripheral ulcerative keratitis (PUK), episcleritis, scleritis, anterior uveitis, and corneal impairment. The most severe form of scleritis, scleromalacia perforans, is an aggressive ophthalmic manifestation that can potentially lead to blindness, usually occurring in late stages of disease. We report a case of an elderly woman in which this severe ocular manifestation occurred early on disease onset, differing from most of the previously reported cases of scleromalacia perforans. Ocular symptoms started concomitantly with the polyarthritis and other extra-articular manifestations, including rheumatoid nodules and vasculitic skin lesions. Ocular disease progressed due to patient's loss to follow-up, requiring pulse therapy with methylprednisolone. However, despite treatment, right eye enucleation was required due to melting of the corneal patch with uveal exposition. The patient was then treated with rituximab with improvement of systemic disease. The present case reinforces that, although rare, this complication is severe and must be promptly diagnosed and aggressively treated to improve prognosis of ocular and systemic RA.

2.
Ann Rheum Dis ; 81(6): 889-897, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35193873

RESUMO

OBJECTIVE: To evaluate the effect on immunogenicity and safety of 2-week methotrexate (MTX) discontinuation after each dose of the Sinovac-CoronaVac vaccine versus MTX maintenance in patients with rheumatoid arthritis (RA). METHODS: This was a single-centre, prospective, randomised, investigator-blinded, intervention study (NCT04754698, CoronavRheum) including adult patients with RA (stable Clinical Disease Activity Index (CDAI) ≤10, prednisone ≤7.5 mg/day) randomised (1:1) to withdraw MTX (MTX-hold) for 2 weeks after each vaccine dose or maintain MTX (MTX-maintain), evaluated at day 0 (D0), D28 and D69. Coprimary outcomes were anti-SARS-CoV-2 S1/S2 IgG seroconversion (SC) and neutralising antibody (NAb) positivity at D69. Secondary outcomes were geometric mean titres (GMT) and flare rates. For immunogenicity analyses, we excluded patients with baseline positive IgG/NAb, and for safety reasons those who flared at D28 (CDAI >10) and did not withdraw MTX twice. RESULTS: Randomisation included 138 patients with 9 exclusions (5 COVID-19, 4 protocol violations). Safety evaluation included 60 patients in the MTX-hold and 69 patients in the MTX-maintain group. Further exclusions included 27 patients (13 (21.7%) vs 14 (20.3%), p=0.848) with positive baseline IgG/NAb and 10 patients (21.3%) in MTX-hold with CDAI >10 at D28. At D69, the MTX-hold group (n=37) had a higher rate of SC than the MTX-maintain group (n=55) (29 (78.4%) vs 30 (54.5%), p=0.019), with parallel augmentation in GMT (34.2 (25.2-46.4) vs 16.8 (11.9-23.6), p=0.006). No differences were observed for NAb positivity (23 (62.2%) vs 27 (49.1%), p=0.217). At D28 flare, the rates were comparable in both groups (CDAI, p=0.122; Disease Activity Score in 28 joints with C reactive protein, p=0.576), whereas CDAI >10 was more frequent in MTX-hold at D69 (p=0.024). CONCLUSION: We provided novel data that 2-week MTX withdrawal after each dose of the Sinovac-CoronaVac vaccine improves anti-SARS-CoV-2 IgG response. The increased flare rates after the second MTX withdrawal may be attributed to the short-term interval between vaccine doses. This strategy requires close surveillance and shared decision making due to the possibility of flares.


Assuntos
Artrite Reumatoide , Vacinas contra COVID-19 , COVID-19 , Metotrexato , Adulto , Anticorpos Neutralizantes , Anticorpos Antivirais , Artrite Reumatoide/tratamento farmacológico , COVID-19/prevenção & controle , Vacinas contra COVID-19/administração & dosagem , Humanos , Imunoglobulina G , Metotrexato/administração & dosagem , Metotrexato/uso terapêutico , Estudos Prospectivos , SARS-CoV-2 , Suspensão de Tratamento
3.
Ann Rheum Dis ; 81(5): 710-719, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35135832

RESUMO

OBJECTIVES: To evaluate the distinct impact of disease modifying antirheumatic drugs (DMARD) combination and monotherapy in immune response to an inactivated SARS-CoV-2 vaccine in patients with rheumatoid arthritis (RA). METHODS: This phase 4 prospective study analysed seroconversion (SC) of anti-SARS-CoV-2 immunoglobulin G (IgG) and neutralising antibodies (NAb) induced by the inactivated vaccine (CoronaVac) in patients with RA in comparison to controls (CG). Disease activity and treatment were also assessed. Only participants with baseline negative IgG/NAb were included. RESULTS: Patients with RA (N=260) and CG (N=104) had comparable median ages (59 years (50-65 years) vs 58 years (49.8-64 years), p=0.483). Patients with RA had moderate but lower SC (61.8% vs 94.2%, p<0.001) and NAb positivity (45% vs 78.6%, p<0.001) in comparison to CG after full vaccination. Baseline disease activity did not influence immunogenicity (p>0.05). After multivariate analyses, factors independently related to reduced SC were: older age (OR=0.79 (0.70-0.89) for each 5-year interval, p<0.001), methotrexate (OR=0.54 (0.29-0.98), p=0.044), abatacept (OR=0.37 (0.19-0.73), p=0.004) and number of DMARD (OR=0.55 (0.33-0.90), p=0.018). Regarding NAb, age (OR=0.87 (0.78-0.96) for each 5-year interval, p=0.007) and prednisone >7.5 mg/day (OR=0.38 (0.19-0.74), p=0.004) were negatively related to the presence of NAb. Further comparison of SC/NAb positivity among RA treatment subgroups and CG revealed that methotrexate/tofacitinib/abatacept/tocilizumab use, in monotherapy or in combination, resulted in lower responses (p<0.05), while tumour necrosis factor inhibitor and other conventional synthetic DMARD interfered solely when combined with other therapies. CONCLUSIONS: Patients with RA under DMARD have a moderate immunogenicity to CoronaVac. We identified that nearly all DMARD combinations have a deleterious effect in immunogenicity, whereas a more restricted number of drugs (methotrexate/tofacitinib/abatacept/tocilizumab) also hampered this response as monotherapy. These findings reinforce the need of a broader approach, not limited to specific drugs, to improve vaccine response for this population. TRIAL REGISTRATION DETAILS: NCT04754698.


Assuntos
Antirreumáticos , Artrite Reumatoide , COVID-19 , Abatacepte/uso terapêutico , Idoso , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , COVID-19/prevenção & controle , Vacinas contra COVID-19 , Quimioterapia Combinada , Humanos , Imunoglobulina G/uso terapêutico , Metotrexato/uso terapêutico , Pessoa de Meia-Idade , Estudos Prospectivos , SARS-CoV-2 , Resultado do Tratamento , Vacinas de Produtos Inativados
4.
Arch Osteoporos ; 19(1): 40, 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38773042

RESUMO

This study compared the bone parameters of adolescents with persistent cow's milk allergy (CMA) with those of healthy adolescents. Adolescents with CMA had compromised bone parameters (lower bone mineral density, impaired trabecular microarchitecture, and lower bone strength). Partial exclusion diet was associated with better bone parameters than total exclusion diet. BACKGROUND: Persistent immunoglobulin E (IgE)-mediated cow's milk allergy (CMA) may impair bone parameters and increase the risk of fractures. High-resolution peripheral quantitative computed tomography (HR-pQCT) is a novel methodology that not only assesses trabecular and cortical bone compartments and volumetric density measurements, but also evaluates bone microarchitecture and estimates biomechanical properties through finite element analysis (FEA). Both HR-pQCT and bone strength parameters derived from FEA have shown a strong correlation with fracture risk. PURPOSE: To assess the bone density, microarchitecture, and bone strength of adolescents with persistent IgE-mediated CMA (IgE-CMA). METHODS: This was an observational, cross-sectional study with female adolescents with persistent IgE-CMA and healthy control participants matched by female sex and sexual maturation. Bone parameters were assessed by areal bone mineral density (aBMD) through dual-energy X-ray absorptiometry (DXA), bone microarchitecture by HR-pQCT at the radius and tibia, and laboratory markers related to bone metabolism. RESULTS: The median age of adolescents with persistent IgE-CMA (n = 26) was 13.0 years (interquartile range (IQR) 11.4-14.7) and of healthy control participants (n = 28) was 13.6 years (IQR 11.9-14.9). Adolescents with IgE-CMA ingested 27.4% less calcium (p = 0.012) and 28.8% less phosphorus (p = 0.009) than controls. Adolescents with IgE-CMA had lower bone mineral content (BMC) (38.83 g vs. 44.50 g) and aBMD (0.796 g/cm2 vs. 0.872 g/cm2) at lumbar spine, and lower BMC (1.11 kg vs. 1.27 kg) and aBMD (0.823 g/cm2 vs. 0.877 g/cm2) at total body less head (TBLH) (p < 0.05). However, Z-scores BMC and Z-scores aBMD at lumbar spine and TBLH, when adjusted for Z-score height/age, were not significantly different between the groups. Moreover, CMA adolescents had lower bone strength at the distal tibia (S 169 kN/mm vs. 194 kN/mm; F Load 8030 N vs. 9223 N) (p < 0.05). Pairing of groups by the presence of menarche showed compromised parameters at the tibia-lower total volumetric BMD (Tt.vBMD) (293.9 mg HA/cm3 vs. 325.9 mg HA/cm3) and trabecular vBMD (Tb.vBMD) (170.8 mg HA/cm3 vs. 192.2 mg HA/cm3), along with lower cortical thickness (Ct.th) (1.02 mm vs. 1.16 mm) and bone strength (S 174 kN vs. 210 kN; F Load 8301 N vs. 9950 N)-and at the radius (S 61 kN/mm vs. 71 kN/mm; F Load 2920 N vs. 3398 N) (p < 0.05) among adolescents with IgE-CMA. Adolescents with IgE-CMA on a total exclusion diet (n = 12) showed greater impairment of bone features than those on a partial exclusion diet (n = 14), with lower lumbar spine Z-score BMC (- 0.65 vs. 0.18; p = 0.013), lumbar spine trabecular bone score (TBS) (1.268 vs. 1.383; p = 0.005), Z-score TBS (0.03 vs. 1.14; p = 0.020), TBLH Z-score BMC (- 1.17 vs. - 0.35; p = 0.012), TBLH Z-score aBMD (- 1.13 vs. - 0.33; p = 0.027), Tt.vBMD at the tibia (259.0 mg HA/cm3 vs. 298.7 mg HA/cm3; p = 0.021), Ct.th at the tibia (0.77 mm vs. 1.04 mm; p = 0.015) and Ct.th at the radius (0.16 mm vs. 0.56 mm; p = 0.033). CONCLUSION: Adolescents with persistent IgE-CMA had lower aBMD and compromised microarchitecture (impaired trabecular microarchitecture and lower bone strength). Adolescents on a partial exclusion diet had better bone parameters than those on a total exclusion diet.


Assuntos
Densidade Óssea , Imunoglobulina E , Hipersensibilidade a Leite , Humanos , Feminino , Adolescente , Imunoglobulina E/sangue , Estudos Transversais , Hipersensibilidade a Leite/fisiopatologia , Hipersensibilidade a Leite/imunologia , Hipersensibilidade a Leite/diagnóstico por imagem , Criança , Tomografia Computadorizada por Raios X , Absorciometria de Fóton , Estudos de Casos e Controles , Animais , Tíbia/diagnóstico por imagem , Tíbia/fisiopatologia
5.
Arch Osteoporos ; 19(1): 59, 2024 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-38990403

RESUMO

The SPAH study is a population-based prospective cohort of Brazilian community-dwelling elderlies with higher fracture risk than observed in the studies used to construct the Brazilian FRAX model. In this study, the FRAX tool was a good fracture predictor within this high-risk elderly cohort, especially when calculated without bone density. PURPOSE: To determine the performances of FRAX and age-dependent intervention thresholds according to National Osteoporosis Guideline Group (NOGG) guidelines with and without bone mineral density (BMD) regarding fracture prediction in community-dwelling elderly Brazilians. METHODS: Seven hundred and five older adults (447 women; 258 men) were followed for 4.3 ± 0.8 years. FRAX risk for hip and major osteoporotic fractures with and without BMD was calculated at baseline. The bivariate analysis investigated the associations between the absolute probability of fracture (FRAX), as well as the age-dependent intervention thresholds (NOGG), and the incidence of vertebral fracture (VF), non-vertebral fracture (NVF), and major osteoporotic fractures (MOF), segregated by sex. Age-adjusted Poisson's multiple regression and ROC curves were constructed to determine FRAX and NOGG's accuracies as fracture predictors. RESULTS: Fractures occurred in 22% of women and 15% of men. FRAX with and without BMD was higher in women with all types of fractures (p < 0.001). Only NOGG risk classification without BMD was associated with NVF (p = 0.047) and MOF (p = 0.024). FRAX was associated with NVF in the multiple regression, regardless of BMD. ROC curves of FRAX with and without BMD had AUCs of 0.74, 0.64, and 0.61 for NVF, VF, and MOF, respectively. The most accurate risk cutoffs for FRAX were 8% for MOF and 3% for hip fractures. No statistically significant associations were found in men. CONCLUSION: FRAX predicted NVF more accurately than VF or MOF in elderlies, regardless of BMD. These results reiterate that FRAX may be used without BMD, even considering that Brazilian elderlies have known higher fracture risk.


Assuntos
Densidade Óssea , Fraturas por Osteoporose , Humanos , Masculino , Feminino , Idoso , Brasil/epidemiologia , Medição de Risco/métodos , Fraturas por Osteoporose/epidemiologia , Idoso de 80 Anos ou mais , Estudos Prospectivos , Osteoporose/epidemiologia , Osteoporose/complicações , Vida Independente/estatística & dados numéricos , Fatores de Risco , Guias de Prática Clínica como Assunto , Fatores Etários
6.
Adv Rheumatol ; 64(1): 63, 2024 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-39187901

RESUMO

BACKGROUND: Patient management in rheumatoid arthritis (RA) has evolved to a "treat-to-target" (T2T) approach, which entails intensive treatment and regular follow-up with the goal of achieving low levels of disease activity or clinical remission. Even though a T2T approach is endorsed by professional organizations and yields superior outcomes, its implementation remains incomplete. EVEREST (EleVatE care in RhEumatoid arthritiS with Treat-to-target) is a quality-improvement initiative designed to improve the widespread implementation of a personalized T2T strategy and enable patients with RA to reach their full potential for remission. We describe the Brazilian results from the Global T2T Survey, first part of the EVEREST program. METHODS: Between June and September 2022, we conducted an online survey targeting rheumatologists in Brazil. Our objective was to evaluate the barriers and knowledge gaps hindering the effective implementation of T2T strategies. To achieve this, we employed a set of multiple-choice questions specifically crafted to elicit responses categorized in a structured order. RESULTS: 166 rheumatologists participated in the survey, 51% of them with more than 21 years of experience in rheumatology. Regarding the perceived challenges in the management of RA in clinical practice, the highest percentage of agreement/strong agreement among the participants was related to the contradictory results of disease activity measures (60%). In terms of the main barriers to assess the disease activity in clinical practice, the lack of adherence to treatment and contradictory assessments between patient-reported outcomes and composite measures were indicated by 75% and 59% of the participants, respectively, as a moderate/serious barrier. The most frequently knowledge and skill gaps related to the management of RA pointed out by the participants were on the difficulty to assess patients' health literacy (54% stated to have no more than intermediate knowledge on standardized methods to assess it and 43% no more than intermediate skills on determining the level of health literacy of the patients). In general, the use of tools to support the management of RA patients in clinical practice was indicated to be unusual by the participants. Self-reflection questionnaires, patient education materials and treatment consideration checklists were pointed out as the least frequently used tools (85%, 64% and 62% of the participants stated to use them never, rarely, or only sometimes, respectively). CONCLUSIONS: Our findings indicate a greater need for design, selection, and uptake of practical strategies to further improve communication between healthcare providers and patients with RA, as well as for promoting well-informed, collaborative decision-making in their care.


Assuntos
Artrite Reumatoide , Reumatologistas , Artrite Reumatoide/tratamento farmacológico , Humanos , Brasil , Antirreumáticos/uso terapêutico , Inquéritos e Questionários , Indução de Remissão , Melhoria de Qualidade , Masculino
7.
Front Immunol ; 15: 1400036, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38835762

RESUMO

Introduction: Polyarticular juvenile idiopathic arthritis (pJIA) is a childhood-onset autoimmune disease. Immune cells contribute to persistent inflammation observed in pJIA. Despite the crucial role of monocytes in arthritis, the precise involvement of classical monocytes in the pathogenesis of pJIA remains uncertain. Here, we aimed to uncover the transcriptomic patterns of classical monocytes in pJIA, focusing on their involvement in disease mechanism and heterogeneity. Methods: A total of 17 healthy subjects and 18 premenopausal women with pJIA according to ILAR criteria were included. Classical monocytes were isolated, and RNA sequencing was performed. Differential expression analysis was used to compare pJIA patients and healthy control group. Differentially expressed genes (DEGs) were identified, and gene set enrichment analysis (GSEA) was performed. Using unsupervised learning approach, patients were clustered in two groups based on their similarities at transcriptomic level. Subsequently, these clusters underwent a comparative analysis to reveal differences at the transcriptomic level. Results: We identified 440 DEGs in pJIA patients of which 360 were upregulated and 80 downregulated. GSEA highlighted TNF-α and IFN-γ response. Importantly, this analysis not only detected genes targeted by pJIA therapy but also identified new modulators of immuno-inflammation. PLAUR, IL1B, IL6, CDKN1A, PIM1, and ICAM1 were pointed as drivers of chronic hyperinflammation. Unsupervised learning approach revealed two clusters within pJIA, each exhibiting varying inflammation levels. Conclusion: These findings indicate the pivotal role of immuno-inflammation driven by classical monocytes in pJIA and reveals the existence of two subclusters within pJIA, regardless the positivity of rheumatoid factor and anti-CCP, paving the way to precision medicine.


Assuntos
Artrite Juvenil , Perfilação da Expressão Gênica , Inflamação , Monócitos , Transcriptoma , Adulto , Criança , Feminino , Humanos , Anticorpos Antiproteína Citrulinada , Artrite Juvenil/classificação , Artrite Juvenil/genética , Artrite Juvenil/imunologia , Artrite Juvenil/patologia , Estudos de Casos e Controles , Doença Crônica , Análise por Conglomerados , Inflamação/genética , Inflamação/imunologia , Inflamação/patologia , Mediadores da Inflamação/imunologia , Interferon gama/imunologia , Monócitos/imunologia , Monócitos/metabolismo , Fenótipo , Medicina de Precisão , Pré-Menopausa , Ligação Proteica , Mapas de Interação de Proteínas , Fator Reumatoide , Análise de Sequência de RNA , Transcriptoma/genética , Fator de Necrose Tumoral alfa/imunologia , Aprendizado de Máquina não Supervisionado
8.
Adv Rheumatol ; 64(1): 43, 2024 05 28.
Artigo em Inglês | MEDLINE | ID: mdl-38807174

RESUMO

INTRODUCTION: Takayasu's arteritis (TAK) patients are at an elevated risk of metabolic syndrome and cardiovascular diseases (CVD). Currently, there are no well-validated biomarkers to assess this risk in this population. Previous research in different cohorts has linked serum levels of osteoprotegerin (OPG) and its polymorphisms to accelerated atherosclerosis and a marker of poor prognosis in CVD. Thus, we assessed this protein as a potential biomarker of CVD in TAK patients. OBJECTIVES: To evaluate the serum levels of OPG and its SNPs (single nucleotide polymorphisms) in TAK patients and healthy controls, and to associate these parameters with clinical data. METHODS: This bicentric cross-sectional study included TAK patients who were compared with healthy individuals (control group). The serum levels of OPG and the frequency of OPG SNPs [1181G > C (rs2073618), 245 A > C (rs3134069), 163T > C (rs3102735), and 209 C > T (rs3134070)] were compared between the both groups and associated with clinical data. RESULTS: In total, 101 TAK patients and 93 controls were included in the study. The serum levels of OPG (3.8 ± 1.9 vs. 4.3 ± 1.8pmol/L, respectively; P = 0.059), and its four polymorphisms were comparable between both groups. In an additional analysis of only TAK patients, serum OPG levels and its four genes were not associated with any CVD parameters, except for higher OPG levels among patients without dyslipidemia. CONCLUSION: No significant differences were observed in serum OPG levels or in the genotype frequencies of OPG SNPs between the patient and control groups. Similarly, no correlation was found between laboratory parameters and clinical data on CVD risk in TAK patients.


Assuntos
Biomarcadores , Osteoprotegerina , Polimorfismo de Nucleotídeo Único , Arterite de Takayasu , Humanos , Arterite de Takayasu/genética , Arterite de Takayasu/sangue , Osteoprotegerina/sangue , Osteoprotegerina/genética , Estudos Transversais , Feminino , Masculino , Adulto , Estudos de Casos e Controles , Biomarcadores/sangue , Pessoa de Meia-Idade
9.
Reumatol Clin (Engl Ed) ; 19(7): 374-378, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37661115

RESUMO

INTRODUCTION/OBJECTIVES: Coeliac disease (CD) and non-coeliac gluten sensitivity (NCGS) cause symptoms like those seen in patients with fibromyalgia (FM) and functional gastrointestinal disorders. There is no consistent data on frequency of these symptoms and no study performed duodenal biopsies to investigate CD/NCGS in Brazilian FM patients. Therefore, we sought to verify the prevalence of CD/NCGS in FM patients and the association between gastrointestinal manifestations and FM symptoms. MATERIAL AND METHODS: Sixty-two individuals with FM (ACR2010) were recruited from FM outpatient clinics of a tertiary hospital. Clinical evaluation included the Widespread Pain Index (WPI), Severity Symptom Scale (SS), Polysymptomatic Distress Scale (PDS), and Fibromyalgia Impact Questionnaire (FIQ). Subjects were screened for the presence of coeliac antibodies and upper gastrointestinal endoscopy (duodenal biopsies) was performed for diagnosis of CD/NCGS. RESULTS: 46 (74.2%) women reported at least one digestive symptom: constipation, abdominal distension, loss of weight/inappetence, and nausea/vomiting. Fourteen (31.8%) presented macroscopic duodenitis and 2(4.5%) had duodenal lymphocytic infiltrates, but none met CD criteria. In 1(1.6%) patient NCGS was confirmed. There was association between presence of any digestive symptom and WPI and SS (fatigue, waking up tired, cognition), but no difference on FIQ between patients with and without gastrointestinal symptoms. CONCLUSION: Gastrointestinal complaints were frequent and associated with increased degree of polysymptomatic distress in FM patients, but presence of these symptoms was not related to overall impact of FM over different dimensions of the patient's life. Moreover, the prevalence of CD/NCGS was very low. This suggests that screening for CD in Brazilian FM patients might not be cost-effective, since the frequency of CD/NCGS was very low.


Assuntos
Doença Celíaca , Fibromialgia , Hipersensibilidade Alimentar , Humanos , Feminino , Masculino , Doença Celíaca/complicações , Doença Celíaca/epidemiologia , Doença Celíaca/diagnóstico , Glutens/efeitos adversos , Fibromialgia/epidemiologia , Fibromialgia/complicações , Prevalência , Brasil/epidemiologia , Hipersensibilidade Alimentar/complicações , Hipersensibilidade Alimentar/diagnóstico , Hipersensibilidade Alimentar/epidemiologia , Dieta Livre de Glúten
10.
Front Immunol ; 14: 1251034, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37868981

RESUMO

Introduction: Evidence-based data suggest that under inflammatory conditions, classical monocytes are the main source of osteoclasts and might be involved in bone erosion pathophysiology. Here, we analyze the transcriptomic profile of classical monocytes in erosive and non-erosive rheumatoid arthritis patients in order to better understand their contribution to bone erosion. Methods: Thirty-nine premenopausal RA patients were consecutively enrolled and divided into two groups based on the presence of bone erosions on hand joints. Classical monocytes were isolated from peripheral blood through negative selection, and RNA-seq was performed using a poly-A enrichment kit and Illumina® platform. Classical monocytes transcriptome from healthy age-matched women were also included to identify differentially expressed genes (DEGs). Therefore, gene sets analysis was performed to identify the enriched biological pathways. Results: RNA-seq analysis resulted in the identification of 1,140 DEGs of which 89 were up-regulated and 1,051 down-regulated in RA patients with bone erosion compared to those without bone erosions. Among up-regulated genes, there was a highlighted expression of IL18RAP and KLF14 related to the production of pro-inflammatory cytokines, innate and adaptive immune response. Genes related to collagen metabolism (LARP6) and bone formation process (PAPPA) were down-regulated in RA patients with erosions. Enriched pathways in patients with erosions were associated with greater activation of immune activation, and inflammation. Interestingly, pathways associated with osteoblast differentiation and regulation of Wnt signaling were less activated in RA patients with erosions. Conclusion: These findings suggest that alterations in expression of monocyte genes related to the inflammatory process and impairment of bone formation might have an important role in the pathophysiology of bone erosions in RA patients.


Assuntos
Artrite Reumatoide , Monócitos , Humanos , Feminino , Monócitos/metabolismo , Transcriptoma , Inflamação/genética , Inflamação/metabolismo , Perfilação da Expressão Gênica
11.
Adv Rheumatol ; 63(1): 34, 2023 07 26.
Artigo em Inglês | MEDLINE | ID: mdl-37496102

RESUMO

INTRODUCTION: Although Rheumatoid Arthritis (RA) extra-articular manifestations (ExtRA) occurrence has been decreasing over time, they are still a major mortality risk factor for patients. OBJECTIVE: To determine the prevalence of ExtRA in a large cohort, and its association with demographic and clinical variables. METHOD: Cross-sectional and observational study, based on a multi-centric database from a prospective cohort, in which 11 public rheumatology centres enrolled RA patients (1987 ARA or 2010 ACR-EULAR). Data collection began in 08-2015, using a single online electronic medical record. Continuous variables were compared using Mann-Whitney U-test, and Fisher's exact test or chi-square test, as appropriate, were used for categorical variables. The level of significance was set at 5% (p < 0.05). RESULTS: 1115 patients were included: 89% women, age [mean ± SD] 58.2 ± 11.5 years, disease duration 14.5 ± 12.2 years, positive Rheumatoid Factor (RF, n = 1108) in 77%, positive anti-cyclic citrullinated peptide (ACPA, n = 477) in 78%. Regarding ExtRA, 334 occurrences were registered in 261 patients, resulting in an overall prevalence of 23.4% in the cohort. The comparison among ExtRA and Non-ExtRA groups shows significant higher age (p < 0.001), disease duration (p < 0.001), RF high titers (p = 0.018), Clinical Disease Activity index (CDAI) (p < 0.001), Disease Activity Index 28 (DAS 28) (p < 0.001), and Health Assessment Questionnaire (HAQ) (p < 0.001) in ExtRA group. Treatment with Azathioprine (p = 0.002), Etanercept (p = 0.049) Glucocorticoids (GC) ('p = 0.002), and non-steroidal anti-inflammatory drugs (NSAIDs) (p < 0.001) were more frequent in ExtRA group. CONCLUSIONS: ExtRA manifestations still show an expressive occurrence that should not be underestimated. Our findings reinforce that long-term seropositive disease, associated with significant disability and persistent inflammatory activity are the key factors related to ExtRA development.


Assuntos
Artrite Reumatoide , Humanos , Feminino , Pessoa de Meia-Idade , Idoso , Masculino , Estudos Prospectivos , Estudos Transversais , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/epidemiologia , Artrite Reumatoide/etiologia , Fator Reumatoide , Fatores de Risco
12.
Int J Rheum Dis ; 25(9): 1038-1045, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35766182

RESUMO

AIM: To evaluate hand function by hand grip test in rheumatoid arthritis (RA) patients, and its association with bone erosions and the estimated bone strength (finite element - FE analysis) through the analysis of the 2nd metacarpal head of the dominant hand using high resolution peripheral quantitative computed tomography (HR-pQCT). METHOD: Eighty-two female RA patients between 18-50 years old were selected. Demographic data, Health Questionnaire Assessment Disability Index (HAQ), Disease Activity Score of 28 joints (DAS)-28, simplified disease activity index (SDAI) and the hand grip test were set. The HR-pQCT scans of 2nd metacarpophalangeal joints of the dominant hand of all patients were performed according to SPECTRA group protocols. The images were used to assess bone erosions and FE analysis. The hand grip test was categorized in 2 groups and separately compared (< 18 vs ≥18 kgf). A logistic regression was performed using hand grip test <18 kgf as a dependent variable. RESULTS: A significant difference was found between the 2 groups regarding HAQ, inflammatory markers (erythrocyte sedimentation rate, C-reactive protein), DAS-28, SDAI, total volume of erosion and bone strength parameter (FE analysis - Failure Load [F.Load]). The logistic regression analysis showed that the risk factors associated with hand grip test <18 kgf were higher SDAI (odds ratio [OR] 0.912; 95% CI 0.837-0.993) and lower values of bone strength parameter (F.Load) (OR 1.007; 95% CI 1.002-1.012). CONCLUSION: Lower values of hand grip test were associated with higher disease activity score-SDAI and lower bone strength of 2nd metacarpal bone head of the dominant hand evaluated here through a FE analysis using HR-pQCT scan.


Assuntos
Artrite Reumatoide , Ossos Metacarpais , Adolescente , Adulto , Artrite Reumatoide/diagnóstico por imagem , Feminino , Análise de Elementos Finitos , Força da Mão , Humanos , Articulação Metacarpofalângica/diagnóstico por imagem , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios X/métodos , Adulto Jovem
13.
Adv Rheumatol ; 62(1): 11, 2022 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-35365246

RESUMO

OBJECTIVE: To present an updated and evidence-based guideline for the use of dual-energy x-ray absorptiometry (DXA) to assess body composition in clinical practice. MATERIALS AND METHODS: This Official Position was developed by the Scientific Committee of the Brazilian Association of Bone Assessment and Metabolism (Associação Brasileira de Avaliação Óssea e Osteometabolismo, ABRASSO) and experts in the field who were invited to contribute to the preparation of this document. The authors searched current databases for relevant publications in the area of body composition assessment. In this second part of the Official Position, the authors discuss the interpretation and reporting of body composition parameters assessed by DXA and the use of DXA for body composition evaluation in special situations, including evaluation of children, persons with HIV, and animals. CONCLUSION: This document offers recommendations for the use of DXA in body composition evaluation, including indications, interpretation, and applications, to serve as a guiding tool in clinical practice and research for health care professionals in Brazil.


Assuntos
Densidade Óssea , Osteoporose , Absorciometria de Fóton , Composição Corporal , Brasil , Humanos , Osteoporose/diagnóstico por imagem , Sociedades Médicas
15.
Adv Rheumatol ; 63: 34, 2023. tab, graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1505590

RESUMO

Abstract Introduction Although Rheumatoid Arthritis (RA) extra-articular manifestations (ExtRA) occurrence has been decreasing over time, they are still a major mortality risk factor for patients. Objective To determine the prevalence of ExtRA in a large cohort, and its association with demographic and clinical variables. Method Cross-sectional and observational study, based on a multi-centric database from a prospective cohort, in which 11 public rheumatology centres enrolled RA patients (1987 ARA or 2010 ACR-EULAR). Data collection began in 08-2015, using a single online electronic medical record. Continuous variables were compared using Mann-Whit-ney U-test, and Fisher's exact test or chi-square test, as appropriate, were used for categorical variables. The level of significance was set at 5% (p < 0.05). Results 1115 patients were included: 89% women, age [mean ± SD] 58.2 ± 11.5 years, disease duration 14.5 ± 12.2 years, positive Rheumatoid Factor (RF, n = 1108) in 77%, positive anti-cyclic citrullinated peptide (ACPA, n = 477) in 78%. Regarding ExtRA, 334 occurrences were registered in 261 patients, resulting in an overall prevalence of 23.4% in the cohort. The comparison among ExtRA and Non-ExtRA groups shows significant higher age (p < 0.001), disease duration (p < 0.001), RF high titers (p = 0.018), Clinical Disease Activity index (CDAI) (p < 0.001), Disease Activity Index 28 (DAS 28) (p < 0.001), and Health Assessment Questionnaire (HAQ) (p < 0.001) in ExtRA group. Treatment with Azathioprine (p = 0.002), Etanercept (p = 0.049) Glucocorticoids (GC) ('p = 0.002), and non-steroidal anti-inflammatory drugs (NSAIDs) (p < 0.001) were more frequent in ExtRA group. Conclusions ExtRA manifestations still show an expressive occurrence that should not be underestimated. Our findings reinforce that long-term seropositive disease, associated with significant disability and persistent inflammatory activity are the key factors related to ExtRA development.

18.
Adv Rheumatol ; 62: 11, 2022. tab, graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1374210

RESUMO

Abstract Objective: To present an updated and evidence-based guideline for the use of dual-energy x-ray absorptiometry (DXA) to assess body composition in clinical practice. Materials and methods: This Official Position was developed by the Scientific Committee of the Brazilian Association of Bone Assessment and Metabolism ( Associação Brasileira de Avaliação Óssea e Osteometabolismo , ABRASSO) and experts in the field who were invited to contribute to the preparation of this document. The authors searched current databases for relevant publications in the area of body composition assessment. In this second part of the Official Position, the authors discuss the interpretation and reporting of body composition parameters assessed by DXA and the use of DXA for body composition evaluation in special situations, including evaluation of children, persons with HIV, and animals. Conclusion: This document offers recommendations for the use of DXA in body composition evaluation, including indications, interpretation, and applications, to serve as a guiding tool in clinical practice and research for health care professionals in Brazil.

20.
Clin Rheumatol ; 29(12): 1427-31, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-20473539

RESUMO

Hematological disturbances are common in systemic lupus erythematous (SLE). Specifically, autoimmune hemolytic anemia (AHA) may manifest in SLE patients at the time of diagnosis or within the first year of the disease. AHA is often associated with thrombocytopenia, lupus nephritis, and central nervous system activity. In this study we investigated these associations in Brazilian patients with SLE. Forty-four consecutive SLE patients who had a history of AHA were age, gender, and disease duration matched with 318 SLE patients without AHA who formed the control group. All patients fulfilled the revised American College of Rheumatology criteria for SLE and were followed-up within our Service. Clinical and laboratorial manifestations were similar in both groups, except for the predominance of leukopenia, thrombocytopenia, and anti-dsDNA on univariate analysis in the AHA group. The multivariate logistic regression model revealed risk only for thrombocytopenia in the AHA group compared to the control group (odds ratio, 2.70; 95% confidence interval, 1.32-5.50). Our results corroborate previous data that AHA in SLE increases the risk of thrombocytopenia in individuals with SLE. This association suggests a common mechanism in AHA and SLE pathophysiologies.


Assuntos
Anemia Hemolítica Autoimune/complicações , Lúpus Eritematoso Sistêmico/complicações , Trombocitopenia/complicações , Adulto , Anemia Hemolítica Autoimune/sangue , Anemia Hemolítica Autoimune/epidemiologia , Brasil/epidemiologia , Feminino , Humanos , Lúpus Eritematoso Sistêmico/sangue , Lúpus Eritematoso Sistêmico/epidemiologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Trombocitopenia/sangue , Trombocitopenia/epidemiologia
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