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Advances in Rheumatology, Volume: 62, Publicado: 2022
  • Musculoskeletal ultrasound as a screening-tool for rheumatoid arthritis: results of the “Rheuma-Truck” screening and awareness initiative Research

    Lautwein, Alexander; Ostendorf, Benedikt; Vordenbäumen, Stefan; Liedmann, Aiko; Brinks, Ralph; Giulini, Mario; Ohrndorf, Sarah; Backhaus, Marina; Acar, Hasan; Sander, Oliver; Richter, Jutta G.; Schneider, Matthias; Sewerin, Philipp

    Resumo em Inglês:

    Abstract Objective: To evaluate musculoskeletal ultrasound (MSUS) as a screening tool for rheumatoid arthritis (RA) and osteoarthritis (OA) patients in a rheumatology-screening program. Patients and methods: To raise awareness for rheumatic diseases, a mobile rheumatology office was deployed in different cities of Germany (“Rheuma-Truck”). Standardized questionnaire assessment, testing for rheumatoid factor and citrullinated peptide antibodies and medical student driven MSUS of the clinically dominant hand/foot including wrist, MCP-II, -III, -V, PIP-II, -III, MTP-II and -V were offered free of charge to the population. In case of suspicious results, a rheumatologist was consulted. Results: In MSUS, 192 of 560 selected volunteers (aged 18–89, mean 52.7 years; 72.9% female) had suspicious findings including synovitis or erosions primarily affecting the MTP-II (11.8%), dorsal wrist (8.9%), and MCP-II (7%). 354 of the 560 volunteers further visited a rheumatologist of whom 76 were diagnosed with RA. According to the ‘US7 Score’, a sum scores ≥ 5 was significantly predictive for RA (odds ratio (OR) 5.06; confidence interval (CI) 0.83–35.32). 313 volunteers displayed signs of OA including osteophytes, while MCP-II (36.2%), MCP-III (14.8%), and the wrist (10.5%) were mostly affected. Diagnosis of RA was favoured over OA if the wrist (OR 4.2; CI 1.28–13.95), MTP-II (OR 1.62; CI 1.0–2.6), and MCP-V (OR 2.0; CI 1.0–3.8) were involved. Conclusion: Medical student driven MSUS by the ‘US7 Score’ can facilitate diagnosis of RA in rheumatology-screening programs due to the level of the score and the affected joints. A high rate of unknown OA signs was detected by MSUS. A mobile rheumatology office displays an opportunity to screen patients for RA and OA.
  • Proteinuria and serum creatinine after 12 months of treatment for lupus nephritis as predictors of long-term renal outcome: a case–control study Research

    Braga, Fernanda Nogueira Holanda Ferreira; Medeiros, Marta Maria das Chagas; Viana Junior, Antonio Brazil; Lima, Matheus Eugênio de Sousa; Barros, Levi Coelho Maia; Pontes, Marcelo Ximenes; Lima, Allysson Wosley de Sousa; Fernandes, Paula Frassinetti Castelo Branco Camurça

    Resumo em Inglês:

    Abstract Background: Lupus nephritis (LN) is a major source of morbidity and mortality in patients with systemic lupus erythematosus (SLE), with 10–25% of patients progressing to end-stage renal disease (ESRD). Objective: This study aims to elucidate the predictive capabilities of 24-h proteinuria (24PTU) and serum creatinine (sCr) after 12 months of treatment with respect to long-term renal outcomes in LN in a single-center cohort of LN patients. Methods: A retrospective analysis was performed on 214 patients diagnosed with LN followed in our center. Values of 24PTU and sCr were assessed at baseline and after 3, 6 and 12 months, and after 5 years and/or the last evaluation. Chronic kidney disease (CKD) was defined as an estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2 for 3 months or longer. End-stage renal disease (ESRD) was defined as the need for permanent dialysis. Receiver operating characteristics curves (ROC) were used to test the best cut-off value of 24PTU and sCr at 12 months who predict bad long-term renal outcomes. Results: The mean follow-up period was 11.2 ± 7.2 years. The best cut-off values for 24PTU and sCr as predictor of CKD were, respectively, 0.9 g/24 h and 0.9 mg/dL. ROC curve for 24PTU had a slightly lower performance than ROC curve for sCr as predictor for CKD (PTU AUC = 0.68; sCr AUC = 0.70), but sensitivity and specificity were better for 24PTU (24PTU: sensitivity = 63.5%, specificity = 71.2%; sCr: sensitivity = 54.8%, specificity = 75.3%). When the outcome was ESRD the best cut-off points were 0.9 g/24hs and 1.3 mg/dL for 24PTU and sCr, respectively, and the curve performance was better for 24PTU (PTU AUC = 0.72; sCr AUC = 0.61). Conclusions: In this ethnically diverse population with LN followed for a long time (> 10 years), levels of 24PTU > 0.9/day at 12 months was a good predictor of bad long-term renal outcome. The serum creatinine > 0.9 mg/dL and > 1.3 mg/dL at 12 months were also good predictors of CKD and ESRD, respectively. Patients with 24PTU < 0.9 g/day and sCr < 1.3 mg/dL at 12 months are not likely to develop ESRD because of the high negative predictive values (NPV) (93.2% and 82%). 24PTU and sCr are relevant as components for a treat-to-target strategy for LN treatment, since their high NPV corroborates their importance as good predictors of long-term renal outcome.
  • Statin indication according to the 2019 World Health Organization cardiovascular disease risk charts and carotid ultrasound in Mexican mestizo rheumatoid arthritis patients Research

    Galarza-Delgado, Dionicio A.; Colunga-Pedraza, Iris J.; Azpiri-Lopez, Jose R.; Guajardo-Jauregui, Natalia; Rodriguez-Romero, Alejandra B.; Loya-Acosta, Julieta; Meza-Garza, Alejandro; Cardenas-de la Garza, Jesus A.; Lugo-Perez, Salvador; Castillo-Treviño, Jessica N.

    Resumo em Inglês:

    Abstract Background: We aimed to assess the concordance of recommendation for initiating statin therapy according to the 2019 World Health Organization (WHO) cardiovascular disease (CVD) risk charts and to the presence of carotid plaque (CP) identified with carotid ultrasound in Mexican mestizo rheumatoid arthritis (RA) patients, and to determine the proportion of patients reclassified to a high cardiovascular risk after the carotid ultrasound was performed. Methods: This was a cross-sectional study nested of a RA patients’ cohort. A total of 157 Mexican mestizo RA patients were included. The cardiovascular evaluation was performed using the 2019 WHO CVD risk charts (laboratory-based model) for the Central Latin America region. A carotid ultrasound was performed in all patients. The indication to start statin therapy was considered if the patient was classified as high risk, moderate risk if > 40 years with total cholesterol (TC) > 200 mg/dl or LDL-C > 120 mg/dl, and low risk if > 40 years with TC > 300 mg/dl, according to the WHO CVD risk chart or if the patient had carotid plaque (CP). Cohen’s kappa (k) coefficient was used to evaluate the concordance between statin therapy initiation. Results: Initiation of statin therapy was considered in 49 (31.2%) patients according to the 2019 WHO CVD risk charts and 49 (31.2%) patients by the presence of CP. Cardiovascular risk reclassification by the presence of CP was observed in 29 (18.9%) patients. A slight agreement (k = 0.140) was observed when comparing statin therapy recommendations between 2019 WHO CVD risk charts and the presence of CP. Conclusion: The WHO CVD risk charts failed to identify a large proportion of patients with subclinical atherosclerosis detected by the carotid ultrasound and the concordance between both methods was poor. Therefore, carotid ultra-sound should be considered in the cardiovascular evaluation of RA patients.
  • The effect of initiation of urate-lowering treatment during a gout flare on the current episode: a meta-analysis of randomized controlled trials Research

    Jia, Ertao; Yao, Xiaoling; Geng, Hongling; Zhong, Li; Xie, Jingjing; Xiao, Yuya; Jiang, Yubao; Qiu, Xia; Xiao, Min; Zhang, Yanying; Tang, Dabin; Wei, Jiaxin; Zhang, Jianyong

    Resumo em Inglês:

    Abstract Objective: The objective was to evaluate whether initiation of urate-lowering treatment (ULT) during an acute gout flare prolonged the current episode. Methods: A comprehensive search of MEDLINE and Web of Science databases was conducted from their inception to 15 March 2021. Five randomized controlled trials (RCTs) with 381 patients met the inclusion criteria. Standardized mean difference (SMD), odds ratio (OR), and 95% confidence interval (CI) were used for estimating the clinical efficacy of ULT in acute gout. Results: There was no statistical difference in days to resolution (intent-to-treat analysis) (SMD, 0.68; 95% CI — 0.42 to 1.78; I2, 49%; p = 0.22), the pain visual analogue score (VAS) by day 10 (SMD, — 0.07; 95% CI — 0.30 to 0.16; I2, 0%; p = 0.53), C-reactive protein (CRP) from day 7 to 10 (SMD, — 1.14; 95% CI — 5.63 to 3.36; I2, 55%; p = 0.62), erythrocyte sedimentation rate (ESR) from day 7 to 10 (SMD, — 2.51; 95% CI — 5.46 to 0.45; I2, 0%; p = 0.10) and the recurrence of gout flares within 28-30 days (OR 0.78; 95% CI 0.29 to 2.09; I2, 0%; p = 0.62). Conclusion: Initiation of ULT during an acute gout flare did not prolong the duration of the flare. However, larger sample size studies are needed to confirm this finding. Trial registration number PROSPERO (CRD42021234581).
  • Paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS): a Brazilian cohort Research

    Cavalcanti, André; Islabão, Aline; Magalhães, Cristina; Veloso, Sarah; Lopes, Marlon; Prado, Rogério do; Aquilante, Bruna; Terrazas, Ana Maria; Rezende, Maria Fernanda; Clemente, Gleice; Terreri, Maria Teresa

    Resumo em Inglês:

    Abstract Background: Paediatric inflammatory multisystem syndrome (PIMS) associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been described since mid-April 2020 with the first reports coming from Europe. Our objective was to describe the characteristics of patients among the Brazilian population. Methods: A multicenter retrospective study was conducted with the participation of five pediatric rheumatology centers in Brazil during the period from March to November 2020. Children and adolescents with PIMS temporally associated with SARS-CoV-2 (TS) who met the definition criteria for the disease according to the Royal College of Paediatrics and Child Health were included. Demographic, clinical, laboratory, therapeutic characteristics and molecular and serological diagnosis of SARS-CoV-2 infection were described. Results: Fifty-seven children and adolescents with PIMS-TS were evaluated, 54% female, with a median age of 8 (3–11) years. Most (86%) were previously healthy, with asthma being the main comorbidity, present in 10% of the patients. Fever was the main manifestation, present in all patients, followed by mucocutaneous and gastrointestinal features, present in 89% and 81% of the patients, respectively. Myocarditis occurred in 21% of the patients and in 68% of them required intensive care. The Kawasaki disease phenotype occurred in most patients (77%). All patients had elevated inflammatory markers, with elevated CRP being the most found (98%). Anemia and lymphopenia were present in 79% and 72%, respectively. Laboratory evidence of SARS-CoV-2 was found in 77% of the patients, with 39% positive RT-PCR and 84% positive serology for SARS-CoV-2. An immunomodulatory treatment was performed in 91% of the patients, with 67% receiving intravenous immunoglobulin (IVIG) associated with glucocorticoid, 21% receiving IVIG, and 3.5% receiving glucocorticoid. The median length of hospitalization was 10 days. Conclusions: This study showed a high morbidity of PIMS-TS in Brazilian children, with a prolonged length of hospitalization and a high rate of admission to pediatric intensive care unit. Multicenter prospective studies are needed to assess the morbidity of the disease in the medium and long term.
  • Evaluation of peripheral neuropathy in lower limbs of patients with rheumatoid arthritis and its relation to fall risk Research

    Pereira, Fabio de Araújo; Lourenço, Mariana de Almeida; Assis, Marcos Renato de

    Resumo em Inglês:

    Abstract Background: Rheumatoid Arthritis (RA) is a chronic disabling systemic disease characterized by joint inflammation, and extra-articular manifestations, including peripheral neuropathy, a condition that can be associated with changes in muscle strength, proprioception and postural balance contributing for the risk of falls. The objective of this study is to analyze the incidence of peripheral neuropathy in patients with RA and its association with the occurrence of falls. Methods: Patients were assessed by an electroneuromyography (ENMG) exam and by a questionnaire on accidental falls occurrence in the previous 12 months. They were also assessed on balance by the Short Physical Performance Battery (SPPB), functionality by the Health Assessment Questionnaire (HAQ), disease activity by the Disease Activity Score (DAS-28), neuropathic pain by the Questionnaire for the Diagnosis of Neuropathic Pain (DN4), and cutaneous sensitivity of the feet by the monofilament testing of Semmes–Weinstein. Monthly calls on falls were made in the subsequent six months. Data analysis was performed using the Shapiro–Wilk test for normality and Spearman, Chi-square, and T-student correlation tests, with a significant P level ≤0.05. Results: A sample of 33 patients were evaluated. The incidence of peripheral neuropathy was 48.5%, of which 68.7% were axonal and 31.3% myelinic. The sensorimotor type was present in 64.7%, motor in 17.6%, and sensorial in 11.7% of the cases. Neuropathy was associated to balance (P = 0.026), neuropathic pain (P =0.016), deep tendon reflexes absence (P =0,049), altered skin sensitivity of the feet (P =0.029) and fear of falling (P =0.001). No association was found between peripheral neuropathy and age, gender, disease activity, or functionality. No significant association was found between peripheral neuropathy and occurrence of falls, in a 12-month retrospective and 6-month prospective evaluation. Conclusion: Peripheral neuropathy has a high incidence in patients with RA, and is related to neuropathic pain, altered postural balance, but not to the occurrence of falls.
  • Increased risk of mortality in systemic sclerosis-associated pulmonary hypertension: a systemic review and meta-analysis Research

    Xiong, Anij; Liu, Qingting; Zhong, Jiaxun; Cao, Yuzi; Xiang, Qilang; Hu, Ziyi; Zhou, Shifeng; Song, Zhuoyao; Chen, Huini; Zhang, Yan; Cui, Hongxu; Shuai, Shiquan

    Resumo em Inglês:

    Abstract Background: Pulmonary hypertension (PH) is a frequent complication of systemic sclerosis (SSc) and is currently one of the primary causes of death in patients with this disease. We conducted a systematic review and meta-analysis to assess the association between PH and mortality in patients with SSc to verify trends in mortality in patients with SSc-associated PH. Methods: We searched the PubMed and Embase databases for published studies on SSc-associated PH from inception to May 2021. All cohort studies in which mortality and/or survival for SSc-associated PH were reported were included in the analysis. The outcome parameters were pooled and analyzed using a random-effects model via generic inverse-variance weighting in conventional and cumulative meta-analysis. Results: The literature search identified 1161 citations, and the full texts of 54 studies were examined. Sixteen articles, with a total of 7857 patients with SSc and 1140 patients with SSc-associated PH, were included in the metaanalysis. Patients with SSc-associated PH had a higher pooled risk of mortality than patients with SSc without PH (risk ratio = 3.12; 95% confidence interval: [2.44, 3.98]). Conclusions: This meta-analysis revealed a higher mortality in patients with SSc-associated PH. PH was a significant predictor of death in patients with SSc. Thus, early diagnosis and treatment of PH are important in patients with SSc.
  • Factors associated with hospitalizations for Covid-19 in patients with rheumatoid arthritis: data from the Reumacov Brazil registry Research

    Gomides, Ana Paula Monteiro; Albuquerque, Cleandro Pires de; Mota, Licia Maria Henrique da; Devidé, Guilherme; Dias, Laiza Hombre; Duarte, Angela Luzia Branco Pinto; Giovelli, Raquel Altoé; Karnopp, Thais Evelyn; Lima, Hugo Deleon de; Marinho, Adriana; Oliveira, Marianne Schrader de; Omura, Felipe; Ranzolin, Aline; Resende, Gustavo; Ribeiro, Francinne Machado; Ribeiro, Sandra Lúcia Euzébio; Sacilotto, Nathália de Carvalho; Santos, Wander Gonzaga dos; Shinjo, Samuel Katsuyuki; Studart, Samia Araujo de Sousa; Teixeira, Flávia Patricia Sena; Yazbek, Michel Alexandre; Ferreira, Gilda Aparecida; Monticielo, Odirlei A.; Paiva, Eduardo; Pileggi, Gecilmara Cristina Salviato; Reis Neto, Edgard Torres dos; Pinheiro, Marcelo de Medeiros; Marques, Claudia D. L.

    Resumo em Inglês:

    Abstract Background: Patients using immunosuppressive drugs may have unfavorable results after infections. However, there is a lack of information regarding COVID 19 in these patients, especially in patients with rheumatoid arthritis (RA). Therefore, the aim of this study was to evaluate the risk factors associated with COVID 19 hospitalizations in patients with RA. Methods: This multicenter, prospective cohort study is within the ReumaCoV Brazil registry and included 489 patients with RA. In this context, 269 patients who tested positive for COVID 19 were compared to 220 patients who tested negative for COVID 19 (control group). All patient data were collected from the Research Electronic Data Capture database. Results: The participants were predominantly female (90.6%) with a mean age of 53 ±12 years. Of the patients with COVID 19, 54 (20.1%) required hospitalization. After multiple adjustments, the final regression model showed that heart disease (OR =4.61, 95% CI 1.06–20.02. P < 0.001) and current use of glucocorticoids (OR =20.66, 95% CI 3.09–138. P < 0.002) were the risk factors associated with hospitalization. In addition, anosmia was associated with a lower chance of hospitalization (OR =0.26; 95% CI 0.10–0.67, P < 0.005). Conclusion: Our results demonstrated that heart disease and the use of glucocorticoids were associated with a higher number of hospital admissions for COVID 19 in patients with RA. Trial registration: Brazilian Registry of Clinical Trials RBR 33YTQC.
  • Reference range of serum uric acid and prevalence of hyperuricemia: a cross-sectional study from baseline data of ELSA-Brasil cohort Research

    Dório, Murillo; Benseñor, Isabela M.; Lotufo, Paulo; Santos, Itamar S.; Fuller, Ricardo

    Resumo em Inglês:

    Abstract Background: Most of the few studies that have established reference ranges for serum uric acid (SUA) have not taken into account factors which may interfere with its levels and followed rigorous laboratory quality standards. The aim of this study was to establish reference ranges for SUA and determine the prevalence of hyperuricemia. Method: Cross-sectional study including 15,100 participants (all sample) aged 35 to 74 years from baseline data of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil), a multicentric cohort of volunteer civil servants from five universities and one research institute located in different regions of Brazil. It was established a reference sample excluding participants with factors that directly influence SUA levels: glomerular filtration rate lower than 60 ml/min, excessive alcohol intake, use of diuretics, aspirin, estrogen or urate-lowering therapy. SUA was measured using the uricase method and following rigorous international quality standards. Reference ranges were defined as values between percentiles 2.5 (P2.5) and 97.5 (P97.5) of SUA distribution in the reference sample, stratified by sex. Hyperuricemia was defined as SUA ≥ 7 mg/100 ml in the all sample. Results: The reference sample was composed of 10,340 individuals (55.3% women, median age 50 years). Reference ranges (P2.5 to P97.5) for SUA were: 4.0 to 9.2 mg/100 ml for men and 2.8 to 6.9 mg/100 ml for women. Sex was a major determinant for SUA levels (median [IQR], mg/100 ml: 6.1 [5.3–7.0] for men versus 4.5 [3.9–5.3] for women, p < 0.001). Higher levels of SUA were found in patients with higher BMI. Higher age had (a modest) influence only for women. The prevalence of hyperuricemia for all sample (N = 15,100) was 31.9% (95% confidence interval [CI] 30.8– 33.0%) in men and 4.8% (95% CI 4.3–5.3%) in women. Conclusion: SUA reference ranges were 4.0 to 9.2 mg/100 ml for men and 2.8 to 6.9 mg/100 ml for women. Prevalence of hyperuricemia was 31.9% in men and 4.8% in women. Updated SUA reference ranges and prevalence of hyperuricemia are higher nowadays and might be used to guide laboratories and the screening for diseases related to SUA.
  • Effect of biological disease-modifying antirheumatic drugs on body composition in patients with rheumatoid arthritis: a systematic review and meta-analysis Research

    Souza, Mariana Peixoto Guimarães Ubirajara e Silva de; Guimarães, Nathalia Sernizon; Guimarães, Maria Fernanda Brandão de Resende; Souza, Viviane Angelina de; Kakehasi, Adriana Maria

    Resumo em Inglês:

    Abstract Background: Rheumatoid arthritis (RA) generates an inflammatory profile that predisposes to total and visceral fatty accumulation and reduced fat free mass (FFM). This metabolic disorder contributes to poor functionality, increased cardiovascular risk and higher mortality. This study aimed to address a systematic review with meta-analysis to determine the effect of biological and targeted synthetic disease-modifying antirheumatic drugs (bDMARDs and tsDMARDs) on body composition (BC) of patients with RA. Methods: The search was conducted at the electronic databases PubMed, Cochrane Library, Embase, Lilacs and grey literature. This investigation was carried until July 2021. Outcomes of interest were total weight, body mass index (BMI), fat mass (FM) and FFM. A meta-analysis comparing these outcomes in RA patients under bDMARD treatment versus controls was performed. Results: Out of 137 studies reviewed, 18 were selected: fifteen prospective cohorts, two retrospective cohorts, and one cross-sectional study. The studies comprised 1221 patients, 778 on bDMARD treatment and 443 controls, which included RA patients under conventional synthetic DMARD (csDMARD). No study addressing BC analysis in patients using tsDMARD was found. The mean age and duration of the disease was 56.7 years and 6.77 years, respectively. Ten studies demonstrated a significant increase of total weight in 88.2% of patients and 42.3% for BMI. In studies that analyzed BC by double X-ray absorptiometry (DXA), the increase in total weight and BMI correlated positively to the increase in FFM. The meta-analysis carried out in five studies showed no significant difference of the mean difference for total weight 0.12 kg (95% CI − 5.58, 5.82), BMI 0.08 kg/m2 (95% CI − 1.76, 1.92), FM − 0.08 kg (95% IC − 5.31, 5.14), and FFM − 2.08 kg (95% CI − 7.37, 3.21). Conclusion: This systematic review suggests a possible impact of bDMARDs on BC of RA patients, even though, the meta-analysis carried out in a small part of these studies was not able to confirm significant variation in BC components. Trial registration: PROSPERO code: CRD42020206949.
  • Fibronectin extra domain A as a drug delivery targeting epitope for rheumatoid arthritis Research

    Sun, Victor Z.; Melim, Terry L.; Mitra, Soumya; Erickson, Jamie E.; Bryant, Shaughn H.; Farnham, Avery; Westmoreland, Susan; Knight, Heather; Zhang, Liang; Ritacco, Wendy; Homan, Kristoff; Benatuil, Lorenzo; Sterman, Annette J. Schwartz; Goodearl, Andrew D.

    Resumo em Inglês:

    Abstract Objectives: To assess the ability of monoclonal antibodies (mAbs) specific for fibronectin extra-domain A (FnEDA) to target diseased tissues of mouse collagen induced arthritis (mCIA) models. To explore the parameters of the targeting exhibited by anti-FnEDA mAbs including timing and location. Methods: Targeting capabilities of anti-FnEDA mAbs were demonstrated by biodistribution study where i.v. injected antibodies were detected by conjugated near-infrared (NIR) fluorophore, 125I label and immunohistochemistry (IHC) of the injected antibody. Location of FnEDA expression in both mCIA and human RA tissue were mapped by IHC. Quantification of anti-FnEDA mAbs targeted to disease tissue was measured by whole-body autoradiography (WBA). Timing of the targeting was interrogated with fluorescent and confocal microscopy using anti-FnEDA mAbs labeled with different fluorophores and injected at different times. Results: Anti-FnEDA mAbs show specific targeting to diseased paws of mCIA animal. The targeting was focused on inflamed synovium which is consistent with FnEDA expression profile in both mCIA and human RA tissues. Anti-FnEDA mAbs accumulated in diseased tissue at pharmacologically relevant concentrations, the targeting was sustained for up to 14 days and FnEDA was able to support targeting of multiple doses of anti-FnEDA mAbs given 5 days apart. Conclusion: FnEDA is specifically upregulated in the inflamed tissues of mCIA. Antibodies specific for FnEDA can be useful as molecular delivery vehicles for disease specific targeting of payloads to inflamed joint tissue.
  • Primary Sjögren syndrome and development of another autoimmune rheumatic disease during the follow-up Research

    Rodríguez, María Florencia; Asnal, Cecilia; Gobbi, Carla Andrea; Pellet, Antonio Carlos Catalán; Herscovich, Natalia; Amitrano, Cristina; Demarchi, Julia; Noé, Damián Duartes; Segura, Carolina; Caeiro, Francisco; Riscanevo, Nadia; Saurit, Verónica; Papasidero, Silvia; Alba, Paula B.; Raiti, Laura; Cruzat, Vanesa; Santiago, María Lida; Vélez, Sofía; Salvatierra, Gabriela; Juárez, Vicente; Secco, Anastasia

    Resumo em Inglês:

    Abstract Background: Primary Sjögren syndrome (pSS) is a chronic autoimmune disease with its main target being exocrine glands, and is the connective tissue disease more frequently associated with other autoimmune diseases. The aim of this study was to assess the frequency of another autoimmune rheumatic disease (ARD) developed in primary Sjögren syndrome (pSS) patients and to describe it’s clinical, serological and histologic characteristics. Materials and methods: This is a retrospective cohort study. Data of patients with pSS diagnosis (American-European criteria 2002), included in the GESSAR database (Grupo de Estudio Síndrome de Sjögren, Sociedad Argentina de Reumatología) were analyzed. The development of a second ARD was registered during the follow up. Results: 681 patients were included, 94.8% female. The mean age was 54 (SD 14) years and mean age at diagnosis of 50 (SD 13) years. The mean follow-up was 4.7 (SD 4.9) years; 30 patients (4.41%, CI 95%: 3.1–5.7) developed a second ARD during the follow up, incidence rate was 9.1/1000 patients-year (IR 95%: 5.8–12.4/1000 patients-year), the most frequent being rheumatoid arthritis (RA). 96% out of these 30 patients had xerophthalmia, 86.2% xerostomia, 92% positive Schirmer test, 88.24% positive Rosa Bengala test, lisamine green or Ocular Staining Score, 81.2% positive unstimulated salivary flow, 82.1% Ro(+) and 33.33% La(+). Minor salivary gland biopsy had been performed in 14 of the 30 patients, 12 with positive results. There were no statistically significant differences respect baseline characteristics when comparing the patients who developed another ARD to the ones that did not. Conclusions: Of all the patients analyzed, 4.4% presented another ARD during their follow-up. It is important to be aware of this, to make an early and proper diagnosis and treatment of our patients. Key points Patients with primary Sjögren’s Syndrome may develop another connective tissue disease during follow-up. The most frequently connective tissue disease developed during follow-up in the population of patients with primary Sjogren’s Syndrome studied was rheumatoid arthritis. It is important to be aware of this to make an early and proper diagnosis.
  • Spotlight on latent tuberculosis infection screening for juvenile idiopathic arthritis in two countries, comparing high and low risk patients Research

    Piotto, Daniela; Nicacio, Aline; Neto, Agna; Mourão, Ana Filipa; Oliveira-Ramos, Filipa; Campanilho-Marques, Raquel; Guedes, Margarida; Cabral, Marta; Santos, Maria José; Fonseca, João Eurico; Canhão, Helena; Aikawa, Nádia Emi; Oliveira, Sheila K. F.; Ferriani, Virginia P. L.; Pileggi, Gecilmara C. S.; Magalhães, Claudia S.; Silva, Clovis Artur; Terreri, Maria Teresa

    Resumo em Inglês:

    Abstract Background: Rheumatic diseases are associated with an increase in overall risks of tuberculosis (TB). The aim of this study was to evaluate the frequency of TB and the frequency of latent TB infection (LTBI), in clinical practice, for juvenile idiopathic arthritis (JIA) patients from high and low risk of TB incidence endemic countries. Methods: This is an international, multicenter, cross-sectional, observational study of data collection from Brazil and Registry of Portugal at REUMA.PT. The inclusion criteria were patients with Juvenile Idiopathic Arthritis (JIA) with age ≤ 18 years who underwent screening for Mycobacterium tuberculosis infection [tuberculin skin test (TST) and/or interferon gamma release assay (IGRA)]. Chest X-rays and history of exposure to TB were also assessed. Results: 292 JIA patients were included; mean age 14.3 years, mean disease duration 7.5 years, 194 patients (66.4%) performed only TST, 14 (4.8%) only IGRA and 84 (28.8%) both. The frequency of LTBI (10.6%) and TB was similar between the two countries. The reasons for TB screening were different; in Brazil it was performed more often at JIA onset while in Portugal it was performed when starting Disease Modified Anti-Rheumatic Drugs (DMARD) treatment (p < 0.001). Isoniazid therapy was prescribed in 40 (13.7%) patients (31 with LTBI and 9 with epidemiologic risks and/or due to contact with sick people). Only three patients (1%) developed active TB. Conclusion: We found nearly 10% of patients with LTBI, a small percentage of patients with treatment due to epide-miologic risks and only 1% with active TB. Distinct reasons and screening methods for LTBI were observed between the two countries.
  • Syndecan-4 is correlated with disease activity and serological characteristic of rheumatoid arthritis Research

    Zhao, Juan; Ye, Xia; Zhang, Zhuoli

    Resumo em Inglês:

    Abstract Objectives: To describe the feature of expression of syndecan-4 in serum, synovial fluid (SF) and synovium in rheumatoid arthritis (RA) patients, and to analyze the correlation of syndecan-4 with disease activity and serological characteristic of RA. Methods: Syndecan-4 in sera of 60 RA patients, 20 osteoarthritis (OA) patients, 20 healthy controls, and in SF of 25 RA patients and 25 OA patients were tested by enzyme linked immunosorbant assay. The expressions of syndecan-4 in synovium of RA and OA patients were detected by immunohistochemistry. The expression of syndecan-4 on synovial fibroblasts from RA and OA patients were detected by immunofluorescence. The correlation between serum synde-can-4 concentration and disease activity were analyzed in RA patients. Results: The serum syndedcan-4 concentration was significantly higher in RA patients than in OA patients and healthy controls, and was higher in rheumatoid factor (RF)-positive RA patients than in RF-negative ones. Syndecan-4 concentration in SF of RA patients was comparable with OA patients. Syndecan-4 expression in synovial tissue was similar between RA and OA patients. The syndecan-4 concentration was significantly lower in SF than in serum of RA and OA patients. Syndecan-4 concentration in both serum and SF was positively correlated with disease activity of RA patients. Conclusion: The serum syndecan-4 concentration was higher in RA patients than in OA patients, and significantly higher in RF-positive RA patients than in RF-negative ones. Syndecan-4 concentration in both serum and SF was positively correlated with disease activity of RA patients.
  • Effects of medications on incidence and risk of knee and hip joint replacement in patients with osteoarthritis: a systematic review and meta-analysis Research

    Cui, Beibei; Chen, Yuehong; Tian, Yunru; Liu, Huan; Huang, Yupeng; Yin, Geng; Xie, Qibing

    Resumo em Inglês:

    Abstract Background: This systematic review and meta-analysis aimed to investigate the incidence and risk of knee and hip replacement in patients with osteoarthritis (OA) treated with different medications. Methods: OVID MEDLINE, OVID EMBASE, Cochrane and Web of Science electronic databases were searched from inception to May 4th, 2022. Clinical trials, including randomized controlled trials, cohort studies and case–control studies, were selected. The meta-analysis effect size was estimated using either incidence with 95% confidence intervals (CIs) or odds ratio (OR)/relative risk (RR) with 95% CIs. The risk of bias and heterogeneity among studies were assessed and analyzed. Results: Forty studies were included, involving 6,041,254 participants. The incidence of joint replacement in patients with OA varied according to the study design and treatments. The incidence of knee arthroplasty varied from 0 to 70.88%, while the incidence of hip arthroplasty varied from 11.71 to 96.43%. Compared to non-users, bisphosphonate users had a reduced risk of knee replacement (RR = 0.71, 95% CI: 0.66–0.77; adjusted hazard ratio [aHR] = 0.76, 95% CI: 0.70–0.83). Compared to intra-articular corticosteroid users, hyaluronic acid (HA) users had a higher risk of knee arthroplasty (RR = 1.76, 95% CI: 1.38–2.25). No publication bias was observed. Conclusion: Bisphosphonate treatment is associated with a reduced risk of knee replacement. More studies are needed to validate our results due to the limited number of eligible studies and high heterogeneity among studies.
  • The effect of systemic lupus erythematosus on sexual function in women: an updated meta-analysis based on cross-sectional studies Research

    Liu, Maoyu; Dou, Jianguo; Wang, Qianqian

    Resumo em Inglês:

    Abstract Background: Systemic lupus erythematosus (SLE), a chronic systemic autoimmune disease, often affects different organs and tissues. It can be effectively managed using drugs; however, attention should be paid to the patient's quality of life. This study aimed to evaluate the effect of SLE on female sexual function based on current literature. Methods: The PubMed, Embase, and Cochrane Library databases were searched for eligible studies published up to November 9, 2021. This review included all English studies that compared the sexual function between women with SLE and healthy women. A meta-analysis was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Results: A total of 367 records were retrieved from 3 electronic databases. Five studies that involved 710 women with SLE and 2059 healthy women were finally included in this meta-analysis. The result indicated a significant decrease (mean difference =−1.74, 95% confidence interval −3.14 to −0.34, p =0.02) in the total scores of the Female Sexual Function Index in women with SLE, implying that healthy women had better sexual function than those with SLE. Conclusion: The results of our study indicated that SLE could negatively affect the quality of sexual life in terms of desire, arousal, and pain. Thus, close attention should be paid to the sexual function of women with SLE. Trial registration: This study was registered in the International Prospective Register of Systematic Reviews (registration number: CRD42021290439).
  • PLCL1 regulates fibroblast-like synoviocytes inflammation via NLRP3 inflammasomes in rheumatoid arthritis Research

    Luo, Shuai; Li, Xiao-Feng; Yang, Ying-Li; Song, Biao; Wu, Sha; Niu, Xue-Ni; Wu, Yuan-Yuan; Shi, Wen; Huang, Cheng; Li, Jun

    Resumo em Inglês:

    Abstract Background: Phospholipase C-like 1 (PLCL1), a protein that lacks catalytic activity, has similar structures to the PLC family. The aim of this research was to find the function and underlying mechanisms of PLCL1 in fibroblast-like synoviocyte (FLS) of rheumatoid arthritis (RA). Methods: In this study, we first analyzed the expression of PLCL1 in the synovial tissue of RA patients and K/BxN mice by immunohistochemical staining. Then silencing or overexpressing PLCL1 in FLS before stimulating by TNF-α. The levels of IL-6, IL-1β and CXCL8 in FLS and supernatants were detected by Western Blot (WB), Real-Time Quantitative PCR and Enzyme Linked Immunosorbent Assay. We used INF39 to specifically inhibit the activation of NLRP3 inflammasomes, and detected the expression of NLRP3, Cleaved Caspase-1, IL-6 and IL-1β in FLS by WB. Result: When PLCL1 was silenced, the level of IL-6, IL-1β and CXCL8 were down-regulated. When PLCL1 was overexpressed, the level of IL-6, IL-1β and CXCL8 were unregulated. The previous results demonstrated that the mechanism of PLCL1 regulating inflammation in FLS was related to NLRP3 inflammasomes. INF39 could counteract the release of inflammatory cytokines caused by overexpression of PLCL1. Conclusion: Result showed that the function of PLCL1 in RA FLS might be related to the NLRP3 inflammasomes. We finally confirmed our hypothesis with the NLRP3 inhibitor INF39. Our results suggested that PLCL1 might promote the inflammatory response of RA FLS by regulating the NLRP3 inflammasomes.
  • Vitamin D supplementation modulates autophagy in the pristane-induced lupus model Research

    Santos, Manuela dos; Silva, Jordana Miranda de Souza; Bartikoski, Bárbara Jonson; Freitas, Eduarda Correa; Busatto, Amanda; Santo, Rafaela Cavalheiro do Espírito; Monticielo, Odirlei Andre; Xavier, Ricardo Machado

    Resumo em Inglês:

    Abstract Introduction/objectives: Clinical evidence of skeletal muscle involvement is not uncommon in systemic lupus erythematosus (SLE). Because of the poor understanding of signaling pathways involved in SLE muscle wasting, the aim of this study was to evaluate the effects of vitamin D supplementation on skeletal muscle in mice with pristane-induced lupus. Methods: Balb/c mice with lupus-like disease induced by pristane injection were randomized into three groups: pristane-induced lupus (PIL; n = 10), pristane-induced lupus + vitamin D supplementation (PIL + VD; n = 10) and healthy controls (CO; n = 8). Physical function was evaluated on days 0, 60, 120 and 180. The tibialis anterior and gastrocnemius muscles were collected to evaluate myofiber cross-sectional area (CSA) and protein expression. Results: The PIL + VD group showed lower muscle strength compared to the CO and PIL groups at different time points. PIL mice showed similar myofiber CSA compared to CO and PIL + VD groups. LC3-II expression was higher in PIL compared to CO and PIL + VD groups. MyoD expression was higher in PIL mice compared to PIL + VD, while myostatin expression was higher in PIL + VD than PIL group. Myogenin expression levels were decreased in the PIL + VD group compared with the CO group. The Akt, p62 and MuRF expressions and mobility assessment showed no significance. Conclusions: Changes in skeletal muscle in PIL model happen before CSA reduction, possibly due to autophagy degradation, and treatment with Vitamin D has a impact on physical function by decreasing muscle strength and time of fatigue.. Vitamin D supplementation has a potential role modulating physical parameters and signaling pathways in muscle during pristane-induced lupus model.
  • Does [18F]F-FDG-PET/MRI add metabolic information to magnetic resonance image in childhood-onset Takayasu’s arteritis patients? A multicenter case series Research

    Clemente, Gleice; Souza, Alexandre W. de; Leão Filho, Hilton; Coelho, Fernando M. A.; Buchpiguel, Carlos; Lima, Marcos; Carneiro, Camila; Pereira, Rosa M. R.; Aikawa, Nadia; Silva, Clovis A.; Campos, Lucia M. A.; Alves, Gabriel; Astley, Camilla; Gualano, Bruno; Terreri, Maria Teresa

    Resumo em Inglês:

    Abstract Background: The observation that 2-deoxy-2[18F]fluoro-D-glucose-positron emission tomography/magnetic resonance imaging ([18F]F-FDG-PET/MRI) revealed high-grade arterial wall FDG uptake, without arterial wall thickening with contrast-enhancement, in a considerable number of c-TA patients in our previous study, encouraged us to compare patients with both PET and MR angiography (MRA) positives, with those with PET positive but MRA negative. Our aim was to evaluate the relevance of these two imaging modalities together. Methods: A three-center cross-sectional study with 17 patients who fulfilled the EULAR/PRINTO/PReS criteria for c-TA and who underwent [18F]F-FDG-PET/MRI was previously performed. Herein we compared patients/vessels with positive PET (arterial wall 18F-FDG uptake higher than liver) and positive MRA (arterial wall thickening with contrast-enhancement)—group 1, with those with positive PET but negative MRA—group 2. Results: Median disease duration of 17 c-TA patients was 10.4 years. Nine patients were classified as group 1 and six as group 2. Median of metabolic inflammatory volume (MIV) of all arterial segments was significantly higher in group 1 (2346 vs. 1177 cm3; p = 0.036). Fifty-four (19%) from 284 available arterial segments presented positive findings in vessel wall in one or both images. Positive findings were concordant between PET and MRA in only 13% arterial segments (group 1); most changes (28–59.6%) that were discordant between both images, were positive in PET and negative in MRA (group 2). Conclusions: Our study demonstrated that [18F]F-FDG-PET/MRI added information about inflammation in vessel wall of c-TA patients. Prospective multicenter studies are needed in order to get solid data to guide immunosuppressive tapering and withdrawal.
  • Ultrasound joint examination by an automated system versus by a rheumatologist: from a patient perspective Research

    Frederiksen, Bill Aplin; Schousboe, Maja; Terslev, Lene; Iversen, Nikolaj; Lindegaard, Hanne; Savarimuthu, Thiusius Rajeeth; Just, Søren Andreas

    Resumo em Inglês:

    Abstract Background: The Arthritis Ultrasound Robot (ARTHUR) is an automated system for ultrasound scanning of the joints of both hands and wrists, with subsequent disease activity scoring using artificial intelligence. The objective was to describe the patient’s perspective of being examined by ARTHUR, compared to an ultrasound examination by a rheumatologist. Further, to register any safety issues with the use of ARTHUR. Methods: Twenty-five patients with rheumatoid arthritis (RA) had both hands and wrists examined by ultrasound, first by a rheumatologist and subsequently by ARTHUR. Patient-reported outcomes (PROs) were obtained after the examination by the rheumatologist and by ARTHUR. PROs regarding pain, discomfort and overall experience were collected, including willingness to be examined again by ARTHUR as part of future clinical follow-up. All ARTHUR examinations were observed for safety issues. Results: There was no difference in pain or discomfort between the examination by a rheumatologist and by ARTHUR ( p =0.29 and p =0.20, respectively). The overall experience of ARTHUR was described as very good or good by 92% (n =23), with no difference compared to the examination by the rheumatologist ( p =0.50). All (n =25) patients were willing to be examined by ARTHUR again, and 92% (n =23) would accept ARTHUR as a regular part of their RA clinical follow up. No safety issues were registered. Conclusion: Joint ultrasound examination by ARTHUR was safe and well-received, with no difference in PRO components compared to ultrasound examination by a rheumatologist. Fully automated systems for RA disease activity assessment could be important in future strategies for managing RA patients. Trial registration: The study was evaluated by the regional ethics committee (ID: S-20200145), which ruled it was not a clinical trial necessary for their approval. It was a quality assessment project, as there was no intervention to the patient. The study was hereafter submitted and registered to Odense University Hospital, Region of Southern Denmark as a quality assessment project and approved (ID: 20/55294).
  • Radiographic aspects in individuals infected by human T-lymphotropic virus type 1 (HTLV-1) with joint pain Research

    Carvalho, João Marcos da Silva; Campos, Eugênia Maria Teixeira de Araújo; Ferreira, José Luiz Nunes; Carvalho, Huliana Mourão; Carneiro Neto, José Abraão; Carneiro, Tássila de Oliveira; Carvalho, Edgar Marcelino

    Resumo em Inglês:

    Abstract Background: Joint pain in the absence or with little synovitis is observed in a large percentage of HTLV-1 infected subjects. As the virus infect CD4 +and CD8 +positive, macrophages and B cells an exaggerated production of pro-inflammatory cytokines is detected in these patients. However, the possible association of HTLV-1 infection with autoimmune diseases has not been documented definitively and the clinical characteristics of HTLV-1 associated arthropathy has not been defined. The objective this study is to describe clinic and radiographic features in HTLV-1-infected individuals with complaints of joint pain. Methods: Cross-sectional study enrolling HTLV-1-infected individuals with chronic joint pain, aged up to 75 years, both genders and seronegative controls with osteoarthritis. All participants underwent conventional radiography of the hips, knees and ankles. Results: Eighty-one HTLV-1 infected patients and 30 subjects with osteoarthritis participated in the study. Polyarticular and symmetrical arthritis prevailed in the HTLV-1 positive group (54%), while oligoarticular and asymmetrical (44%) were more common in controls ( p < 0.05). The frequency of enthesophytes (90%) in HTLV-1-infected patients was greater than in the control group (73%) ( p < 0.05). Radiographic features were similar in HTLV-1 carriers and in patients with probable or definite HTLV-1 associated myelopathy. The presence of enthesophytes in the absence of joint space reduction or osteophytes was only observed in HTLV-1-infected individuals ( p < 0.001). Magnetic resonance imaging of the ankles of five HTLV-1-infected patients and five controls demonstrated a higher frequency of enthesitis, bursitis and osteitis in the HTLV-1 infected group. Conclusion: HTLV-1-associated arthropathy is clinically characterized by symmetrical polyarthralgia and the main radiological finding is the presence of enthesophytes in the absence of osteophytes and joint space narrowing.
  • The influence of demography and referral medical specialty on the detection of autoantibodies to HEP-2 cells in a large sample of patients Research

    Santos, Wilton Ferreira Silva; Cantuária, Ana Paula de Castro; Félix, Daniele de Castro; Nardes, Leandro Kegler; Melo, Igor Cabral Santos de

    Resumo em Inglês:

    Abstract Background: The prevalence of anti-cell autoantibodies detected by indirect immunofluorescence assay on HEp-2 cells (HEp-2-IIFA) increases with age and is higher in female sex. The number of medical specialties that use HEp-2-IIFA in the investigation of autoimmune diseases has increased lately. This study aimed to determine the prevalence and patterns of autoantibodies on HEp-2-IIFA according to demographics variables and referring medical specialties. Methods: A retrospective analysis of the HEp-2-IIFA carried out between January and June of 2017 was performed. The International Consensus on Antinuclear Antibodies Patterns (ICAP) and the Brazilian Consensus on Autoantibodies were used for patterns definition on visual reading of the slides. Anti-cell (AC) codes from ICAP and Brazilian AC codes (BAC) were used for patterns classification. Results: From 54,990 samples referred for HEp-2-IIF testing, 20.9% were positive at titer ≥ 1/80. HEp-2-IIFA positivity in females and males was 24% and 12%, respectively ( p < 0.0001). The proportion of positive results in the 4 age groups analyzed: 0–19, 20–39, 40–59, and ≥ 60 years was 23.3, 20.2, 20.1, and 22.8%, respectively ( p < 0.0001). Considering all positive sera (n = 11,478), AC-4 nuclear fine speckled (37.7%), AC-2 nuclear dense fine speckled (21.3%), BAC-3 nuclear quasi -homogeneous (10%) and mixed/composite patterns (8.8%) were the most prevalent patterns. The specialties that most requested HEp-2-IIFA were general practitioner (20.1%), dermatology (15%), gynecology (9.9%), rheumatology (8.5%), and cardiology (5.8%). HEp-2-IIFA positivity was higher in patients referred by rheumatologists (35.7% vs. 19.6%) ( p < 0.0001). Moderate (46.4%) and high (10.8%) titers were more observed in patients referred by rheumatologists ( p < 0.0001). We observed a high proportion of mixed and cytoplasmic patterns in samples referred by oncologists and a high proportion of BAC-3 (nuclear quasi -homogeneous) pattern in samples referred by pneumologists. Conclusions: One-fifth of the patients studied were HEp-2-IIFA-positive. The age groups with more positive results were 0–19 and ≥ 60 years. AC-4, AC-2, BAC-3 and mixed/composite patterns were the most frequent patterns observed. Rheumatologists requested only 8.5% of HEp-2-IIFA. Positive results and moderate to high titers of autoanti-bodies were more frequent in patients referred by rheumatologists.
  • Graft versus host disease-related eosinophilic fasciitis: cohort description and literature review Research

    Calleja, Cristina Hidalgo; Hidalgo, Daniel Martín; Curto, Concepción Román; López, Lourdes Vázquez; López, Estefanía Pérez; Calvo, Mónica Cabrero; López, Ana África Martín; Barrigón, María Dolores Caballero; Lopez-Corral, Lucía

    Resumo em Inglês:

    Abstract Background: Chronic graft versus host disease (cGVHD) simulating eosinophilic fasciitis (EF) is an underdiagnosed and challenging complication due to the lack of knowledge about its pathogenesis, refractoriness to traditional immunosuppressive agents and their negative impact on the physical function and quality of life. The aim of this study is to describe the clinical-biological characteristics and response to treatment of a case series and to provide a comprehensive literature review on cGVHD related EF involvement. Methods: Prospective observational study to describe the clinical and diagnostic evaluation characteristics of patients with EF-like follow-up as part of our multidisciplinary cGVHD consultations. In addition, the literature on joint and/or fascial musculoskeletal manifestations due to cGVHD was comprehensively reviewed. Results: 118 patients were evaluated in multidisciplinary cGVHD consultations, 39 of whom (33%) developed fasciitis. Notably, 11 patients had isolated joint contractures without sclerotic skin. After a median of three lines of treatment, the vast majority of patients achieved some degree of response. 94 potentially eligible articles were identified by the search strategy, with 17 of them, the majority isolated case reports, making the final selection. The validated staging scales used for the assessment were the Joint and Fascial Score and the Photographic Range of Motion. Conclusion: Fascial/articular involvement needs to be recognized and evaluated early. To our knowledge, our cohort is the second largest series to have been reported. Literature addressing fascial/joints complications related to cGVHD is scarce. The search for new biomarkers, the use of advanced imaging techniques and multidisciplinary approach may help improve the prognosis of patients with cGVHD.
  • Serum MMP-9, SP-D, and VEGF levels reflect the severity of connective tissue disease-associated interstitial lung diseases Research

    Lv, Chengna; Zhang, Qipan; Tang, Pan; Guo, Lun; Ding, Qunli

    Resumo em Inglês:

    Abstract Background: Interstitial lung disease (ILD) is a common pulmonary complication of connective tissue disease (CTD). This study aims to evaluate the clinical diagnostic value of matrix metalloproteinase-9 (MMP-9), surfactant protein-D (SP-D), and vascular endothelial growth factor (VEGF) as potential biomarkers for CTD-ILD. Methods: This research included 33 CTD-ILD patients, 31 CTD patients without ILD, and 24 healthy control subjects. Then, the value of biomarkers for the diagnosis and evaluation of CTD-ILD was assessed through high-resolution computed tomography (HRCT) findings and pulmonary function test (PFT) parameters. Results: The serum MMP-9, SP-D, and VEGF levels in the CTD-ILD group were higher than those in the CTD-NILD group and healthy group. The ROC curve indicates that VEGF has good to excellent diagnostic performance in diagnosing CTD-ILD, the cut-off that best optimizes sensitivity and specificity in diagnosing CTD-ILD is 277.60 pg/ml (sensitivity, 87.9%; specificity, 83.6%), with an area under the curve (AUC) of 0.905 (95% confidence interval (CI) 0.842–0.968); The ROC curve for MMP-9 suggests this biomarker is fair for diagnosis of CTD-ILD(sensitivity, 81.8%; specificity, 81.8%), with an AUC of 0.867 (95% CI 0.784–0.950), but SP-D only provided lower specificity with higher sensitivity in diagnosing CTD-ILD(sensitivity, 90.9%; specificity, 40.0%). The different serum biomarkers are more specific and sensitive when combined to diagnose ILD. The semiquantitative score for the degree of ILD severity on HRCT was positively correlated with SP-D and VEGF levels ( r = 0.461, P = 0.007; r = 0.362, P = 0.039), and serum MMP-9 levels were elevated in the UIP subgroup compared to the non-UIP subgroup. The percentage of diffusing capacity of the lung for carbon monoxide (DLco) (% predicted) had a negative correlation with the SP-D level ( r = − 0.407, P = 0.044) and a statistically negative correlation between MMP-9 and the forced vital capacity (FVC) ( r = − 0.451, P = 0.024). Conclusions: Serum MMP-9, SP-D, and VEGF levels may have clinical value in screening and evaluating the severity of CTD-ILD. Key points Serum MMP-9, SP-D, and VEGF levels were increased in patients with CTD-ILD and they may have clinical value in screening and evaluating the severity of CTD-ILD. Serum SP-D and VEGF levels had a positive correlation with ILD severity as measured using semiquantitative HRCT scores. Serum MMP-9 levels were elevated in the UIP subgroup compared to the non-UIP subgroup. Therefore, further research is required to determine the role of serum MMP-9 levels in the preliminary determination of the ILD subtype. Serum MMP-9 levels had a negative correlation with DLco, and serum SP-D levels had a negative correlation with FVC.
  • Maintained activity in ankylosing spondylitis patients treated with TNFi and/or NSAID for at least 12 weeks: a cross-sectional study in Brazil Research

    Toledo, Ricardo Acayaba de; Grizzo, Felipe Merchan Ferraz; Fernandes, Vander; Calheiros, Renato; Russo, Ricardo T.; Rosal, Gustavo; Marchese, Luiz Roberto Delboni; Tunala, Roberto; Watanabe, Renato; Birck, Marina Gabriela; Julian, Guilherme Silva; Forestiero, Francisco Jose

    Resumo em Inglês:

    Abstract Background The aim of this study was to evaluate disease activity among patients with axial spondyloarthritis (AS) treated with tumor necrosis factor inhibitors (TNFi) and/or nonsteroidal anti-inflammatory drugs (NSAIDs) for at least 12 weeks in private outpatient settings in Brazil. Methods This was a cross-sectional, real-world study conducted in 17 Brazilian private health care institutes. Patients were selected if diagnosed with AS or axial radiographic spondyloarthritis (AxSpA) and treated with NSAIDs or TNFi for at least 12 weeks within the last 26 weeks prior to enrollment. The data were collected from interviewed-based and self-administered questionnaires from patients and physicians. Disease activity was defined as active (≥ 4), low /suboptimal (≥ 2 and < 4) and inactive (< 4) by Bath AS Disease Activity Index (BASDAI) and/or very high (≥ 3.5), high (≥ 2.1 to < 3.5), low (≥ 1.3 to < 2.1), and inactive (< 1.3) by AS Disease Activity Score (ASDAS-CRP). Both patients and physicians’ perceptions of disease control were assessed using a numeric rating scale (NRS; 0—inactive to 10—very active disease). Results The cohort included 378 patients with a mean age of 46 years, and the median time since diagnosis until enrollment was 5.4 years (interquartile range 2.7–10.5). Most patients were treated with TNFi alone (74%), followed by TNFi in combination with NSAID (15%), and NSAID alone (11%). About half AS patients showed active disease and 24% of patients showed low activity/suboptimal disease control despite having been treated for at least 12 weeks. Although TNFi showed better disease control than NSAID, inactive disease was experienced by few patients. The NRS (mean [standard deviation]) score for disease perception was 4.24 (3.3) and 2.85 (2.6) for patients and physicians, respectively. Conclusion This real-world study showed that most AS patients on TNFi and/or NSAID had not achieved an adequate disease control, as almost 75% of them exhibited active disease or low activity/suboptimal disease control. There remains a need for improved disease management among patients with AS.
  • Measurement properties of the Brazilian online version of the Fibromyalgia Rapid Screening Tool (FiRST) Research

    Sousa, Ana Paula de; Arruda, Guilherme Tavares de; Pontes-Silva, André; Souza, Marcelo Cardoso de; Driusso, Patricia; Avila, Mariana Arias

    Resumo em Inglês:

    Abstract Objective The Fibromyalgia Rapid Screening Tool (FiRST) was developed to screen people with chronic pain for Fibromyalgia (FM), especially in primary health care settings. This study aimed to translate the FiRST into Brazilian Portuguese and evaluate its measurement properties for an online application. Methods After the process of translation and backtranslation, the FiRST was applied online in 483 adults with chronic pain (FM group n = 395; Chronic pain group n = 88), along with the Numerical Rating Scale for pain and fatigue, the Brief Pain Inventory, and the Fibromyalgia Impact Questionnaire-Revised. A Receiver Operating Characteristics (ROC) curve was computed and the area under the curve (AUC) was used to determine the sensibility, specificity, and cutoff score for the FiRST. The Mann-Whitney test was used for quantitative variables and the Chi-square and the Fisher’s exact test, for the categorical variables with level of significance of 5%. Fleiss’ Kappa, Gwet’s AC1 and percentage of agreement were also calculated between test and retest. Results For all the questionnaires, the FM group presented higher scores, which mean a worst condition. The FiRST presented a sensitivity of 92.3%, and a specificity of 61.6% with 5 as the cut-off score. AUC, Fleiss’ Kappa, Gwet’s AC1 and percentage of agreement were, respectively, 0.82, 0.38, 0.63 and 71.8%. Conclusion The FiRST was translated into Brazilian Portuguese and the online version presented a good content validity and adequate measurement errors that allow FM patients to be screened among people with chronic pain.
  • Knee osteoarthritis pre-screening questionnaire (KOPS): cross-cultural adaptation and measurement properties of the brazilian version—KOPS Brazilian version Research

    Trombini-Souza, Francis; Macedo, Ingrid; Yázigi, Flávia; Veiga, Diogo; Carnide, Filomena; Espanha, Margarida; Oliveira, George; Goldenstein-Schainberg, Claudia; Fuller, Ricardo

    Resumo em Inglês:

    Abstract Background: Despite the criteria already established for the classification of knee osteoarthritis (OA), a radiographic and/or clinical knee OA diagnosis usually occurs in cases of fully manifest or more advanced disease, which can make health promotion, prevention, and functional rehabilitation in more advanced stages of the disease less effective. In addition, radiographic knee OA can generate more financial costs for health services. Therefore, developing and validating screening instruments to assess the probability of development and progression of knee OA would be of great value for both clinical practice and science. Objective: To cross-culturally adapt and investigate the measurement properties of the Knee OA Pre-screening Questionnaire Brazilian version. Methods: A total of 250 individuals of both sexes aged between 35 and 92 years [(mean (standard deviation): 63 (11) years old; 74.1 (15.1) kg; 1.59 (0.09) m; 29.38 (5.44) kg/m2] participated in this study. The cross-cultural adaptation and analyses of the measurement properties of the KOPS Brazilian version included: (1) assessment of conceptual and item equivalence; (2) assessment of semantic equivalence; (3) assessment of operational equivalence; and (4) assessment of measurement equivalence, reliability, and validity. Results: Cronbach's alpha for the internal consistency among the six components of the KOPS Brazilian version was 0.71. The test-retest 72 h apart for each component resulted in a coefficient correlation intraclass ranging from 0.74 to 1.00. The probability of an individual randomly chosen from the population having KL ≥ 1 and KOPS Brazilian version ≥ 21 points was 0.74 (area under the curve of the Receiver Operating Characteristic – AUC of ROC); furthermore, the AUC for KL ≥ 2 and the KOPS Brazilian version ≥ 23 points was 0.77. Conclusion: The KOPS Brazilian version is a reliable and valid instrument for early screening of knee OA in individuals aged 35 years and over in the Brazilian context.
  • Guidelines on COVID-19 vaccination in patients with immune-mediated rheumatic diseases: a Brazilian Society of Rheumatology task force Position Article And Guidelines

    Tavares, Anna Carolina Faria Moreira Gomes; Melo, Ana Karla Guedes de; Cruz, Vítor Alves; Souza, Viviane Angelina de; Carvalho, Joana Starling de; Machado, Ketty Lysie Libardi Lira; Valadares, Lilian David de Azevedo; Reis Neto, Edgard Torres dos; Rezende, Rodrigo Poubel Vieira de; Guimarães, Maria Fernanda Brandão de Resende; Ferreira, Gilda Aparecida; Braz, Alessandra de Sousa; Vieira, Rejane Maria Rodrigues de Abreu; Pinheiro, Marcelo de Medeiros; Ribeiro, Sandra Lúcia Euzébio; Bica, Blanca Elena Gomes Rios; Baptista, Kátia Lino; Costa, Izaias Pereira da; Marques, Claudia Diniz Lopes; Lopes, Maria Lúcia Lemos; Martinez, José Eduardo; Giorgi, Rina Dalva Neubarth; Mota, Lícia Maria Henrique da; Loures, Marcos Antônio Araújo da Rocha; Paiva, Eduardo dos Santos; Monticielo, Odirlei André; Xavier, Ricardo Machado; Kakehasi, Adriana Maria; Pileggi, Gecilmara Cristina Salviato

    Resumo em Inglês:

    Abstract Objective: To provide guidelines on the coronavirus disease 2019 (COVID-19) vaccination in patients with immune-mediated rheumatic diseases (IMRD) to rheumatologists considering specific scenarios of the daily practice based on the shared-making decision (SMD) process. Methods: A task force was constituted by 24 rheumatologists (panel members), with clinical and research expertise in immunizations and infectious diseases in immunocompromised patients, endorsed by the Brazilian Society of Rheumatology (BSR), to develop guidelines for COVID-19 vaccination in patients with IMRD. A consensus was built through the Delphi method and involved four rounds of anonymous voting, where five options were used to determine the level of agreement (LOA), based on the Likert Scale: (1) strongly disagree; (2) disagree, (3) neither agree nor disagree (neutral); (4) agree; and (5) strongly agree. Nineteen questions were addressed and discussed via teleconference to formulate the answers. In order to identify the relevant data on COVID-19 vaccines, a search with standardized descriptors and synonyms was performed on September 10th, 2021, of the MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, and LILACS to identify studies of interest. We used the Newcastle–Ottawa Scale to assess the quality of nonrandomized studies. Results: All the nineteen questions-answers (Q&A) were approved by the BSR Task Force with more than 80% of panelists voting options 4—agree—and 5—strongly agree—, and a consensus was reached. These Guidelines were focused in SMD on the most appropriate timing for IMRD patients to get vaccinated to reach the adequate covid-19 vaccination response. Conclusion: These guidelines were developed by a BSR Task Force with a high LOA among panelists, based on the literature review of published studies and expert opinion for COVID-19 vaccination in IMRD patients. Noteworthy, in the pandemic period, up to the time of the review and the consensus process for this document, high-quality evidence was scarce. Thus, it is not a substitute for clinical judgment.
  • Official position of the Brazilian Association of Bone Assessment and Metabolism (ABRASSO) on the evaluation of body composition by densitometry: part I (technical aspects)— general concepts, indications, acquisition, and analysis Position Article And Guidelines

    Maeda, Sergio Setsuo; Peters, Barbara Santarosa Emo; Martini, Lígia Araújo; Antunes, Hannah Karen Moreira; Gonzalez, Maria Cristina; Arantes, Henrique Pierotti; Prado, Carla M.; Pinto, Camila Lemos; Araújo, Iana Mizumukai de; Paula, Francisco José Albuquerque de; Borges, Joao Lindolfo Cunha; Albergaria, Ben-Hur; Ushida, Marcela; Souza, Guilherme Cardenaz de; Mendonça, Laura Maria Carvalho de; Prado, Mirley do; Pinheiro, Marcelo de Medeiros

    Resumo em Inglês:

    Abstract Objective: To review the technical aspects of body composition assessment by dual-energy X-ray absorptiometry (DXA) and other methods based on the most recent scientific evidence. Materials and methods: This Official Position is a result of efforts by the Scientific Committee of the Brazilian Association of Bone Assessment and Metabolism (Associação Brasileira de Avaliação Óssea e Osteometabolismo, ABRASSO) and health care professionals with expertise in body composition assessment who were invited to contribute to the preparation of this document. The authors searched current databases for relevant publications. In this first part of the Official Position, the authors discuss the different methods and parameters used for body composition assessment, general principles of DXA, and aspects of the acquisition and analysis of DXA scans. Conclusion: Considering aspects of accuracy, precision, cost, duration, and ability to evaluate all three compartments, DXA is considered the gold-standard method for body composition assessment, particularly for the evaluation of fat mass. In order to ensure reliable, adequate, and reproducible DXA reports, great attention is required regarding quality control procedures, preparation, removal of external artifacts, imaging acquisition, and data analysis and interpretation.
  • Official Position of the Brazilian Association of Bone Assessment and Metabolism (ABRASSO) on the evaluation of body composition by densitometry—part II (clinical aspects): interpretation, reporting, and special situations Position Article And Guidelines

    Maeda, Sergio Setsuo; Albergaria, Ben-Hur; Szejnfeld, Vera Lúcia; Lazaretti-Castro, Marise; Arantes, Henrique Pierotti; Ushida, Marcela; Domiciano, Diogo Souza; Pereira, Rosa Maria Rodrigues; Marin-Mio, Rosângela Villa; Oliveira, Mônica Longo de; Mendonça, Laura Maria Carvalho de; Prado, Mirley do; Souza, Guilherme Cardenaz de; Palchetti, Cecília Zanin; Sarni, Roseli Oselka Saccardo; Terreri, Maria Teresa; Castro, Luiz Claudio Gonçalves de; Artoni, Silvana Martinez Baraldi; Amoroso, Lizandra; Karcher, Débora Emy; Prado, Carla M.; Gonzalez, Maria Cristina; Pinheiro, Marcelo de Medeiros

    Resumo em Inglês:

    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.
  • Recommendations for evaluation and diagnosis of extra-glandular manifestations of primary sjogren syndrome: results of an epidemiologic systematic review/ meta-analysis and a consensus guideline from the Brazilian Society of Rheumatology (articular, pulmonary and renal) Position Article And Guidelines

    Trevisani, Virginia Fernandes Moça; Pugliesi, Alisson; Pasoto, Sandra Gofinet; Lopes, Maria Lucia Lemos; Guedes, Lissiane Karine Noronha; Miyamoto, Samira Tatiyama; Fernandes, Marilena Leal Mesquita Silvestre; Fialho, Sonia Cristina de Magalhães Souza; Pinheiro, Aysa César; Santos, Laura Caldas dos; Appenzeller, Simone; Fidelix, Tania; Ribeiro, Sandra Lúcia Euzébio; Brito, Danielle Christinne Soares Egypto de; Libório-Kimura, Tatiana Nayara; Santos, Maria Carmen Lopes Ferreira Silva; Cantali, Diego Ustárroz; Gennari, Juliana D’Agostino; Civile, Vinicius Tassoni; Pinto, Ana Carolina Pereira Nunes; Rocha-Filho, César Ramos; Oliveira, Fabiola Reis; Rocha, Aline Pereira da; Valim, Valeria

    Resumo em Inglês:

    Abstract Sjogren’s Syndrome (SS) is an autoimmune disease characterized by lymphocytic infiltration of the exocrine glands and other organs, associated with sicca syndrome but also with systemic involvement with varying degrees of severity. Despite their importance, these systemic manifestations are not routinely evaluated and there is no homogenous approach to their diagnosis or evaluation. To close this gap, a panel of experts from the Brazilian Society of Rheumatology conducted a systematic review and meta-analysis on the identification of epidemiologic and clinical features of these manifestations and made recommendations based on the findings. Agreement between the experts was achieved using the Delphi method. The first part of this guideline summarizes the most important topics, and 11 recommendations are provided for the articular, pulmonary, and renal care of SS patients.
  • VI Brazilian consensus guidelines for detection of anti-cell autoantibodies on HEp-2 cells Position Article And Guidelines

    Cruvinel, Wilson de Melo; Andrade, Luis Eduardo Coelho; Dellavance, Alessandra; Ximenes, Antônio Carlos; Bichara, Carlos David Araújo; Mangueira, Cristóvão Luis Pitangueira; Bonfá, Eloísa; Brito, Fabiano de Almeida; Mariz, Henrique Ataíde; Anjos, Lisiane Maria Enriconi dos; Pasoto, Sandra Gofinet; Valim, Valeria; Santos, Wilton Ferreira Silva dos; Gomes, Clayson Moura; Neves, Roberpaulo Anacleto; Francescantonio, Paulo Luiz Carvalho

    Resumo em Inglês:

    Abstract Background: The VI Brazilian Consensus on Autoantibodies against HEp-2 cells for determination of autoantibodies against cellular constituents on HEp-2 cells was held on September, 2019, in Fortaleza (CE, Brazil). The guidelines in this edition were formulated by the group of Brazilian experts discussing the classification of complex patterns, the classification of the nuclear discrete dots (few and multiple), the identification of the discrete fine speckled pattern (AC-4a) and improvements on the ANA report. Mainbody: Sixteen Brazilian researchers and experts from universities and clinical laboratories representing the various geographical regions of Brazil participated in the meeting. Four main topics were discussed: (1) How to classify patterns with fluorescence in more than one cell compartment considering three relevant categoris: composite patterns, mixed patterns and multiple patterns; (2) The splitting of the discrete nuclear dots pattern into the multiple discrete nuclear dots (AC-6) and few discrete nuclear dots (AC-7) patterns, respectively; (3) Inclusion of a novel nuclear pattern characterized by discrete fine speckled pattern highly associated with antibodies to SS-A/Ro60, classified as AC-4a. In addition, adjustments on the Brazilian Consensus nomenclature were implemented aiming to harmonize the designation of some patterns with the International Consensus on ANA Patterns (ICAP). Furthermore, the designations of the PCNA-like pattern (AC-13), CENP-F-like pattern (AC-14) and Topo I-like pattern (AC-29) were adjusted in accordance to ICAP. Finally, there was a recommendation for adjustment in the test report in order to address the status of nuclear envelope staining. For all topics, the aim was to establish specific guidelines for laboratories and clinicians. All recommendations were based on consensus among participants. All recommendations from the V Consensus were maintained and there was relevant progress in the BCA/HEp-2 guidelines and further harmonization with ICAP. Conclusion: The VI BCA/HEp-2 edition was successful in establishing important recommendations regarding the classification of complex patterns, in supporting the identification of a novel pattern within the AC-4 group and in the harmonization process with the ICAP terminology.
  • Recommendations for evaluation and diagnosis of extra-glandular manifestations of primary Sjögren syndrome: results of an epidemiologic systematic review/ meta-analysis and a consensus guideline from the Brazilian society of rheumatology (hepatic, gastrointestinal and pancreatic) Position Article And Guidelines

    Trevisani, Virginia Fernandes Moça; Pinheiro, Aysa César; Fialho, Sonia Cristina de Magalhães Souza; Fernandes, Marilena Leal Mesquita Silvestre; Pugliesi, Alisson; Pasoto, Sandra Gofinet; Lopes, Maria Lucia Lemos; Guedes, Lissiane Karine Noronha; Miyamoto, Samira Tatiyama; Santos, Laura Caldas dos; Appenzeller, Simone; Fidelix, Tania; Ribeiro, Sandra Lúcia Euzébio; Brito, Danielle Christinne Soares Egypto de; Libório-Kimura, Tatiana Nayara; Santos, Maria Carmen Lopes Ferreira Silva; Cantali, Diego Ustárroz; Gennari, Juliana D.’Agostino; Capobianco, Karina Gatz; Civile, Vinicius Tassoni; Pinto, Ana Carolina Pereira Nunes; Rocha, Aline Pereira da; Rocha Filho, César Ramos; Oliveira, Fabiola Reis; Valim, Valeria

    Resumo em Inglês:

    Abstract Sjogren's syndrome (SS) is an autoimmune disease characterized by lymphocytic infiltration of the exocrine glands and other organs, associated with sicca syndrome but also with systemic involvement with varying degrees of severity. Despite their importance, some systemic manifestations, mainly liver, gastrointestinal, and pancreatic are not routinely evaluated. To address these manifestations, the Sjögren's Syndrome Committee of the Brazilian Society of Rheumatology conducted a broad systematic review of the literature on studies investigating prevalence and diagnosis of these symptoms in Sjogren´s patients and made recommendations based on the findings. Agreement between the experts was achieved using the Delphi method. This is the second part of this guideline, providing 6 recommendations for liver, gastrointestinal, and pancreatic care of SS patients.
  • Psoriatic arthritis mutilans: a descriptive study from a Brazilian tertiary center Letter

    Cordeiro, Rafael Alves; Oliveira, Jobson Lopes de; Sampaio-Barros, Percival Degrava; Goldenstein-Schainberg, Claudia

    Resumo em Inglês:

    Abstract In this paper, we sought to determine the prevalence of arthritis mutilans in a single cohort of Brazilian psoriatic arthritis patients followed at a tertiary university reference center. Our study demonstrated a high prevalence of arthritis mutilans associated to comorbidities and biologic therapy. In addition, our data suggest that axial involvement may be an intriguing aspect of psoriatic arthritis mutilans and that rheumatologists should be aware of axial disease, even if the phenotype is marked by peripheral joint severity.
  • Update to “guidelines on COVID-19 vaccination in patients with immune-mediated rheumatic diseases: a Brazilian Society of Rheumatology task force” Letter

    Tavares, Anna Carolina Faria Moreira Gomes; Melo, Ana Karla Guedes de; Cruz, Vítor Alves; Valadares, Lilian David de Azevedo; Xavier, Ricardo Machado; Souza, Viviane Angelina de; Pileggi, Gecilmara Cristina Salviato
Sociedade Brasileira de Reumatologia Av. Brigadeiro Luís Antônio, 2466, Jardim Paulista, 01402-000 - São Paulo, SP, Tel.: +551132897165 - São Paulo - SP - Brazil
E-mail: rbreumatol@terra.com.br