Publications by authors named "Manoel B Bertolo"

32 Publications

Safety of the Methotrexate-leflunomide Combination in Rheumatoid Arthritis: Results of a Multicentric, Registry-based, Cohort Study (BiobadaBrasil).

J Rheumatol 2021 May 1. Epub 2021 May 1.

This study is supported by funds from the Brazilian Society of Rheumatology, with funds from the different pharmaceutical companies marketing biological compounds in Brazil (www.reumatologia.org.br/institucional). The sponsor or any pharmaceutical company had no role in the design or conduct of the study, in the preparation or review of the manuscript, or in the decision to publish it. M. Bredemeier, MD, PhD, Hospital Nossa Senhora da Conceição, Grupo Hospitalar Conceição, Porto Alegre; R. Ranza, MD, PhD, Universidade Federal de Uberlândia, Uberlândia; A.M. Kakehasi, MD, PhD, Hospital das Clínicas da Universidade Federal de Minas Gerais, Belo Horizonte; A. Ranzolin, MD, PhD, A.L. Duarte, MD, PhD, Universidade Federal de Pernambuco (UFPE), Recife; I.G. da Silveira, MD, PhD, Hospital São Lucas, Faculdade de Medicina da PUCRS, Porto Algere; A.C. Ribeiro, MD, PhD, Hospital das Clínicas da Faculdade de Medicina da USP (HCFMUSP), São Paulo; D.C. Titton, MD, Universidade Federal do Paraná, Curitiba; A.L. Hayata, MD, PhD, Clínica de Reumatologia, Osasco; H.M. Carvalho, MD, Hospital de Base do Distrito Federal, Brasília; B.S. Kahlow, MD, Hospital Universitário Evangélico de Curitiba, Curitiba; V. Fernandes, MD, PhD, Hospital Geral Universitário de Cuiabá, Cuiabá; P. Louzada Jr., MD, PhD, Faculdade de Medicina USP, Ribeirão Preto; M. Bértolo, MD, PhD, Universidade Estadual de Campinas, Campinas; J.C. Macieira, MD, Universidade Federal de Sergipe, Aracajú; J.R. Miranda, MD, Artrocenter Clínica Médica de Taubaté, Taubaté; G.R. Pinheiro, MD, PhD, Universidade Estadual do Rio de Janeiro, Rio de Janeiro; R.B. Teodoro, MD, Hospital da Universidade Federal do Triângulo Mineiro, Uberaba; M.M. Pinheiro, MD, PhD, Universidade Federal de São Paulo, São Paulo; V. Valim, MD, PhD, Universidade Federal do Espírito Santo, Vitória; I.A. Pereira, MD, PhD, Hospital Universitário da Universidade Federal de Santa Catarina, Florianópolis; M.F. Sauma, MD, PhD, Universidade Federal do Pará, Belém; G.R. de Castro, MD, Hospital Governador Celso Ramos, Florianópolis; L.F. da Rocha Jr., MD, PhD, Instituto de Medicina Integral Prof. Fernando Figueira (IMIP), Recife; S.A. Studart, MD, Hospital Geral de Fortaleza, Fortaleza; M.O. Gazzeta, MD, Santa Casa de Misericórdia do Rio de Janeiro, Rio de Janeiro; L.G. da Silveira, MS, Universidade Federal do Rio Grande do Sul/Hospital de Clínicas de Porto Alegre, Porto Alegre; C.M. Lupo, MD, Faculdade de Medicina de São José do Rio Preto, São José do Rio Preto; I.M. Laurindo, MD, PhD, Faculdade de Medicina da Universidade Nove de Julho, São Paulo, Brazil. The authors declare no conflicts of interest relevant to this article. Address correspondence to Dr. M. Bredemeier, Serviço de Reumatologia do Hospital Nossa Senhora da Conceição, Avenida Francisco Trein, 596, Bloco H, 3o andar, Porto Alegre, RS, 91350-200, Brazil. Email: Accepted for publication April 20, 2021. {"mode":"full","isActive":false}.

Objective: To evaluate the safety of the methotrexate (MTX)-leflunomide (LEF) combination in rheumatoid arthritis (RA), comparing it with other therapeutic schemes involving conventional synthetic (cs-) and biologic (b-) disease-modifying antirheumatic drugs (DMARDs) or Janus kinase inhibitors ( JAKi).

Methods: Patients with RA starting a treatment course with a csDMARD (without previous use of bDMARD or JAKi) or their first bDMARD/JAKi were followed up in a registry-based, multicentric cohort study in Brazil (BiobadaBrasil). The primary outcome was the incidence of serious adverse events (SAEs); secondary outcomes included serious infections. Multivariate Cox proportional hazards models and propensity score matching analysis (PSMA) were used for statistical comparisons.

Results: In total, 1671 patients (5349 patient-years [PY]) were enrolled; 452 patients (1537 PY) received MTX + LEF. The overall incidence of SAEs was 5.6 per 100 PY. The hazard of SAEs for MTX + LEF was not higher than for MTX or LEF (adjusted HR [aHR] 1.00, 95% CI 0.76-1.31, = 0.98). MTX + LEF presented a lower hazard of SAEs (aHR 0.56, 95% CI 0.36-0.88, = 0.01) and infectious SAEs (aHR 0.48, 95% CI 0.25-0.94, = 0.03) than bDMARDs/JAKi with MTX or LEF. MTX + LEF presented lower hazard of SAEs than MTX + sulfasalazine (SSZ; aHR 0.33, 95% CI 0.16-0.65, = 0.002). Analysis using PSMA confirmed the results obtained with traditional multivariate Cox analysis.

Conclusion: In our study, MTX + LEF presented a relatively good overall safety profile in comparison to MTX + SSZ and schemes involving advanced therapies in RA.
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http://dx.doi.org/10.3899/jrheum.201248DOI Listing
May 2021

Effects of Anti-TNF alpha Therapy on Blood Pressure in Resistant Hypertensive Subjects: A Randomized, Double-Blind, Placebo-Controlled Pilot Study.

Arq Bras Cardiol 2021 03;116(3):443-451

Universidade Estadual de Campinas, Campinas, SP - Brasil.

Background: The cytokine tumor necrosis factor-alpha (TNF-α) is elevated in resistant hypertension (RH), but the effects of a TNF-α inhibitor in this population is unknown.

Objective: The aim of this trial was to evaluate whether a single dose of infliximab controlled by placebo acutely reduces blood pressure (BP) in RH subjects.

Methods: A double-blind, placebo-controlled, crossover trial was conducted, and randomized RH subjects received either infliximab or placebo. The primary endpoint was the change in mean BP levels relative to the baseline immediately after the infusion obtained by continuously beat-to-beat non-invasive hemodynamic assessment. Secondary endpoints included changes in office, ambulatory and central BP measurements; endothelial function; and inflammatory biomarkers after 7 days. The level of significance accepted was alpha=0.05.

Results: Ten RH subjects were enrolled. The primary endpoint analysis showed an acute decrease in mean BP values (mean of differences ± standard deviation = -6.3 ± 7.2 mmHg, p=0.02) from baseline, after the application of infliximab compared with placebo. Diastolic BP levels (-4.9 ± 5.5 mmHg, p=0.02), but not systolic BP levels (-9.4 ± 19.7 mmHg, p=0.16), lowered after infliximab infusion. No further significant differences were identified in either the other hemodynamic parameters or in secondary endpoints, except for TNF-α levels, which increased continuously after infliximab infusion. No adverse events were reported during the protocol.

Conclusions: A single-dose of infliximab decreased the mean and diastolic BP levels immediately after its infusion, when compared to the placebo in RH. The anti-TNF-α therapy was found to be safe and well-tolerated. The results of this proof-of-concept are hypothesis-generating and need to be further investigated. (Arq Bras Cardiol. 2021; 116(3):443-451).
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http://dx.doi.org/10.36660/abc.202190703DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8159563PMC
March 2021

Sustained efficacy of a concise self-management programme for hands in systemic sclerosis: a longitudinal case-control observational study.

Rheumatology (Oxford) 2020 11;59(11):3330-3339

Department of Orthopedics and Rheumatology, University of Campinas-Unicamp, Campinas, SP, Brazil.

Objectives: In a longitudinal case-control observational study, we evaluated the benefits of a self-management programme for hands developed for patients with SSc.

Methods: Patients with SSc included in the intervention group (IG) received a concise self-management programme with emphasis on hand exercises and were evaluated during 24 weeks regarding hand pain, hand function, range of motion, grip and tip and key pinch strength. Results were compared with a control group (CG) with no intervention using an analysis of variance for repeated measures with variables transformed into ranks (P ≤ 0.05). Effect sizes were calculated using Cohen's test.

Results: Of 90 patients who were evaluated, seven were excluded at enrolment and 26 were excluded during the follow-up. Data from 57 subjects (IG 40, CG 17) were used for analysis. Groups were similar at baseline, except for the Scleroderma HAQ and tip and key pinch strength. Outcome improvements were noted only in the IG (P ≤ 0.05, large effect size). In the CG, variables did not change or had even worsened (hand grip strength and finger motion).

Conclusions: This self-management programme based on hand exercises for SSc resulted in pain reduction and hand function, strength and range of motion improvement. It can be a simple and useful intervention, especially when a regular rehabilitation programme is not available.
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http://dx.doi.org/10.1093/rheumatology/keaa140DOI Listing
November 2020

High Levels of Polypharmacy in Rheumatoid Arthritis-A Challenge Not Covered by Current Management Recommendations: Data From a Large Real-Life Study.

J Pharm Pract 2021 Jun 26;34(3):365-371. Epub 2019 Aug 26.

28130Universidade do Estado do Rio de Janeiro, Rio de Janeiro, Brazil.

Background: Rheumatoid arthritis (RA) is associated with high frequency of comorbidities and increased risk of polypharmacy. Although there is a great potential for complications, there is a gap in literature on polypharmacy in patients with rheumatic arthritis.

Objective: To evaluate the prevalence and factors associated with polypharmacy in a population in a real-life setting.

Methods: A cross-sectional multicenter study was conducted in Brazil. Patients underwent clinical evaluation and medical records analysis. Polypharmacy was considered as a dependent variable. To test independent variables, we used Poisson regression.

Results: We evaluated 792 patients (89% female, median age 56.6 years). Median duration of disease was 12.7 years, 78.73% had a positive rheumatoid factor. The median of disease activity score-28 was 3.5 (disease with mild activity), median of the clinical disease activity index score was 9, and median of health assessment questionnaire-disability index was 0.875; 47% used corticosteroids, 9.1% used nonsteroidal anti-inflammatory drugs, 90.9% used synthetic disease-modifying antirheumatic drugs, 35.7% used biologic disease-modifying antirheumatic drugs (DMARDs). In total, 537 (67.9%) patients used 5 or more drugs. Polypharmacy showed a relationship with a number of comorbidities and use of specific drugs (corticosteroids, methotrexate, and biological DMARDs).

Conclusion: We found a high prevalence of polypharmacy (67.9%) in RA. Solutions to management this problem should be stimulated.
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http://dx.doi.org/10.1177/0897190019869158DOI Listing
June 2021

Incidence of tuberculosis among patients with rheumatoid arthritis using TNF blockers in Brazil: data from the Brazilian Registry of Biological Therapies in Rheumatic Diseases (Registro Brasileiro de Monitoração de Terapias Biológicas - BiobadaBrasil).

Rev Bras Reumatol Engl Ed 2017;57 Suppl 2:477-483. Epub 2017 Jul 22.

Hospital Geral de Fortaleza (HGF), Fortaleza, CE, Brazil.

Objectives: To assess the incidence of tuberculosis and to screen for latent tuberculosis infection among Brazilians with rheumatoid arthritis using biologics in clinical practice.

Patients And Methods: This cohort study used data from the Brazilian Registry of Biological Therapies in Rheumatic Diseases (Registro Brasileiro de Monitoração de Terapias Biológicas - BiobadaBrasil), from 01/2009 to 05/2013, encompassing 1552 treatments, including 415 with only synthetic disease-modifying anti-rheumatic drugs, 942 synthetic DMARDs combined with anti-tumor necrosis factor (etanercept, infliximab, adalimumab) and 195 synthetic DMARDs combined with other biologics (abatacept, rituximab and tocilizumab). The occurrence of tuberculosis and the drug exposure time were assessed, and screening for tuberculosis was performed.

Statistical Analysis: Unpaired t-test and Fisher's two-tailed test; p<0.05.

Results: The exposure times were 981 patient-years in the controls, 1744 patient-years in the anti-TNF group (adalimumab=676, infliximab=547 and etanercept=521 patient-years) and 336 patient-years in the other biologics group. The incidence rates of tuberculosis were 1.01/1000 patient-years in the controls and 2.87 patient-years among anti-TNF users (adalimumab=4.43/1000 patient-years; etanercept=1.92/1000 patient-years and infliximab=1.82/1000 patient-years). No cases of tuberculosis occurred in the other biologics group. The mean drug exposure time until the occurrence of tuberculosis was 27(11) months for the anti-TNF group.

Conclusions: The incidence of tuberculosis was higher among users of synthetic DMARDs and anti-TNF than among users of synthetic DMARDs and synthetic DMARDs and non-anti-TNF biologics and also occurred later, suggesting infection during treatment and no screening failure.
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http://dx.doi.org/10.1016/j.rbre.2017.05.005DOI Listing
August 2019

Quality of life in spondyloarthritis: analysis of a large Brazilian cohort.

Rev Bras Reumatol Engl Ed 2016 Jan-Feb;56(1):22-7. Epub 2015 Sep 4.

Universidade Federal do Pará, Belém, PA, Brazil.

Objective: To analyze quality of life and demographic and clinical variables associated to its impairment in a large Brazilian cohort of patients with spondyloarthritis (SpA).

Methods: A common protocol of investigation was applied to 1465 Brazilian patients classified as SpA according to the European Spondyloarthropaties Study Group (ESSG) criteria, attended at 29 reference centers for Rheumatology in Brazil. Clinical and demographic variables were recorded. Quality of life was analyzed through the Ankylosing Spondylitis Quality of Life (ASQoL) questionnaire.

Results: The mean ASQoL score was 7.74 (+5.39). When analyzing the specific diseases in the SpA group, the ASQoL scores did not present statistical significance. Demographic data showed worse scores of ASQoL associated with female gender (p=0.014) and African-Brazilian ethnicity (p<0.001). The analysis of the clinical symptoms showed that buttock pain (p=0.032), cervical pain (p<0.001) and hip pain (p=0.001) were statistically associated with worse scores of ASQoL. Continuous use of nonsteroidal anti-inflammatory drugs (p<0.001) and biologic agents (p=0.044) were associated with higher scores of ASQoL, while the other medications did not interfere with the ASQoL scores.

Conclusion: In this large series of patients with SpA, female gender and African-Brazilian ethnicity, as well as predominant axial symptoms, were associated with impaired quality of life.
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http://dx.doi.org/10.1016/j.rbre.2015.07.013DOI Listing
October 2018

Drug survival and causes of discontinuation of the first anti-TNF in ankylosing spondylitis compared with rheumatoid arthritis: analysis from BIOBADABRASIL.

Clin Rheumatol 2015 May 8;34(5):921-7. Epub 2015 Apr 8.

Rheumatology Division, University Hospital Cassiano Antônio de Moraes, Medicine Department, Universidade Federal do Espírito Santo, Av. Marechal Campos, 1460, Departamento de Clínica Médica, CEP 29040-090, Vitória, Espírito Santo, Brazil.

Treatment survival with biological therapy may be influenced by many factors, and it seems to be different among various rheumatic diseases and biological agents. The goal of the study was to compare the drug survival and the causes of discontinuation of anti-tumoral necrosis factor (anti-TNF) therapy in ankylosing spondylitis (AS) with rheumatoid arthritis (RA). Study participants were a cohort from the Brazilian Registry of Biological Therapies in Rheumatic Diseases (BIOBADABRASIL) between 2008 and 2012. The observation time was up to 4 years following the introduction of the first treatment. Gender, age, disease duration, disease activity, comorbidities, and concomitant therapies were assessed. A total of 1303 patients were included: 372 had AS and 931 had RA in which 38.7 % (n = 504) used infliximab (IFX), 34.9 % (n = 455) used adalimumab (ADA), and 26.4 % (n = 344) used etanercept (ETA). The anti-TNF drug survival of patients with AS was 63.08 months (confidence interval (CI) 60.24, 65.92) and patients with RA was 47.5 months (CI 45.65, 49.36). It was significant higher in AS (log-rank; p ≤ 0.001). Patients with RA discontinued anti-TNF more than patients with AS when adjusted to gender and corticosteroid. The adjHR (95 % CI) was 1.6 (1.14, 2.31). Female patients who were also corticosteroid users, but not of advanced age, have shown lower survival for both diseases (log-rank, p ≤ 0.001). The discontinuation rate of IFX, but not of ADA or ETA, was significantly higher in RA than in SA; HR (95 % CI) was 2.49 (1.46, 4.24). The main causes of discontinuation were ineffectiveness and adverse event in both diseases. AS patients have better drug survival adjusted to gender, age, and corticosteroid. This results appear to be related to the disease mechanism.
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http://dx.doi.org/10.1007/s10067-015-2929-7DOI Listing
May 2015

[Evaluation of performance of BASDAI (Bath Ankylosing Spondylitis Disease Activity Index) in a Brazilian cohort of 1,492 patients with spondyloarthritis: data from the Brazilian Registry of Spondyloarthritides (RBE)].

Rev Bras Reumatol 2015 Jan-Feb;55(1):48-54. Epub 2014 Oct 16.

Universidade Federal do Pará, Belém, PA, Brasil.

Objective: To analyze the results of the application of the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) in a large series of Brazilian patients with the diagnosis of SpA and establish its correlations with specific variables into the group.

Methods: A common protocol of investigation was prospectively applied to 1492 Brazilian patients classified as SpA according to the European Spondyoarthropathies Study Group (ESSG), attended at 29 referral centers of Rheumatology in Brazil. Clinical and demographic variables, and disease indices (BASDAI, Basfi, Basri, Mases, ASQol) were applicated. The total values of BASDAI were compared to the presence of the different variables.

Results: The mean score of BASDAI was 4.20 ± 2.38. The mean scores of BASDAI were higher in patients with the combined (axial + peripheral + entheseal) (4.54 ± 2.38) clinical presentation, compared to the pure axial (3.78 ± 2.27) or pure peripheral (4.00 ± 2.38) clinical presentations (p<0.001). BASDAI also presented higher scores associated with the female gender (p<0.001) and patients who did not practice exercises (p < 0.001). Regarding the axial component, higher values of BASDAI were significantly associated with inflammatory low back pain (p<0.049), alternating buttock pain (p<0.001), cervical pain (p<0.001) and hip involvement (p<0.001). There was also statistical association between BASDAI scores and the peripheral involvement, related to the lower (p=0.004) and upper limbs (p=0.025). The presence of enthesitis was also associated to higher scores of BASDAI (p=0.040). Positive HLA-B27 and the presence of cutaneous psoriasis, inflammatory bowel disease, uveitis and urethritis were not correlated with the mean scores of BASDAI. Lower scores of BASDAI were associated with the use of biologic agents (p<0.001).

Conclusion: In this heterogeneous Brazilian series of SpA patients, BASDAI was able to demonstrate "disease activity" in patients with axial as well as peripheral disease.
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http://dx.doi.org/10.1016/j.rbr.2014.05.005DOI Listing
March 2017

[Epidemiologic profile of juvenile-onset compared to adult-onset spondyloarthritis in a large Brazilian cohort].

Rev Bras Reumatol 2014 Nov-Dec;54(6):424-30. Epub 2014 Sep 28.

Escola de Medicina e Saúde Pública, Salvador, BA, Brasil.

Objective: To analyze the clinical and epidemiologic characteristics of juvenile-onset spondyloarthritis (SpA) (< 16 years) and compare them with a group of adult-onset (≥ 16 years) SpA patients.

Patients And Methods: Prospective, observational and multicentric cohort with 1,424 patients with the diagnosis of SpA according to the European Spondyloarthropathy Study Group (ESSG) submitted to a common protocol of investigation and recruited in 29 reference centers participants of the Brazilian Registry of Spondyloarthritis (RBE - Registro Brasileiro de Espondiloartrites). Patients were divided in two groups: age at onset<16 years (JOSpA group) and age at onset ≥ 16 years (AOSpA group).

Results: Among the 1,424 patients, 235 presented disease onset before 16 years (16.5%). The clinical and epidemiologic variables associated with JOSpA were male gender (p<0.001), lower limb arthritis (p=0.001), enthesitis (p=0.008), anterior uveitis (p=0.041) and positive HLA-B27 (p=0.017), associated with lower scores of disease activity (Bath Ankylosing Spondylitis Disease Activity Index - BASDAI; p=0.007) and functionality (Bath Ankylosing Spondylitis Functional Index - BASFI; p=0.036). Cutaneous psoriasis (p<0.001), inflammatory bowel disease (p=0.023), dactylitis (p=0.024) and nail involvement (p=0.004) were more frequent in patients with adult-onset SpA.

Conclusions: Patients with JOSpA in this large Brazilian cohort were characterized predominantly by male gender, peripheral involvement (arthritis and enthesitis), positive HLA-B27 and lower disease scores.
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http://dx.doi.org/10.1016/j.rbr.2014.06.005DOI Listing
December 2016

Assessment of fatigue in a large series of 1492 Brazilian patients with Spondyloarthritis.

Mod Rheumatol 2014 Nov 2;24(6):980-4. Epub 2014 Jun 2.

Santa Casa do Rio de Janeiro.

Background: The aim of the present study was to analyze the score of fatigue in a large cohort of Brazilian patients with SpA, comparing different disease patterns and its association with demographic and disease-specific variables.

Methods: A common protocol of investigation was prospectively applied to 1492 Brazilian patients classified as SpA according to the European Spondyloarthropathies Study Group (ESSG) criteria, attended at 29 reference centers. Clinical and demographic variables were recorded. Fatigue was evaluated using the first item of the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) questionnaire.

Results: The mean BASDAI fatigue score was 4.20 ± 2.99. There was no significant difference in the fatigue score between the different SpA. Fatigue was higher in female patients (p < 0.001), with mixed (axial + peripheral) involvement (p < 0.001) and in those who did not practice exercises (p < 0.001). Higher scores of fatigue were significantly associated with inflammatory low back pain (p = 0.013), alternating buttock pain (p = 0.001), cervical pain (p = 0.001), and hip involvement (p = 0.005). Fatigue presented a moderate positive statistical correlation with Bath Ankylosing Spondylitis Functional Index (BASFI) (0.469; p < 0.001) and Ankylosing Spondylitis Quality of Life (0.462; p < 0.001).

Conclusion: In this large series of Brazilian SpA patients, higher fatigue scores were associated with female gender, sedentary, worse functionality, and quality of life.
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http://dx.doi.org/10.3109/14397595.2014.906049DOI Listing
November 2014

Profile of the use of disease modifying drugs in the Brazilian Registry of Spondyloarthritides.

Rev Bras Reumatol 2014 Jan-Feb;54(1):33-7

Universidade Federal do Pará, Belém, PA, Brasil.

Introduction: Few studies have evaluated the profile of use of disease modifying drugs (DMD) in Brazilian patients with spondyloarthritis (SpA).

Methods: A common research protocol was applied prospectively in 1505 patients classified as SpA by criteria of the European Spondyloarthropathies Study Group (ESSG), followed at 29 referral centers in Rheumatology in Brazil. Demographic and clinical variables were obtained and evaluated, by analyzing their correlation with the use of DMDs methotrexate (MTX) and sulfasalazine (SSZ).

Results: At least one DMD was used by 73.6% of patients: MTX by 29.2% and SSZ by 21.7%, while 22.7% used both drugs. The use of MTX was significantly associated with peripheral involvement, and SSZ was associated with axial involvement, and the two drugs were more administered, separately or in combination, in the mixed involvement (p < 0.001). The use of a DMD was significantly associated with Caucasian ethnicity (MTX , p = 0.014), inflammatory back pain (SSZ, p = 0.002) , buttock pain (SSZ, p = 0.030), neck pain (MTX, p = 0.042), arthritis of the lower limbs (MTX, p < 0.001), arthritis of the upper limbs (MTX, p < 0.001), enthesitis (p = 0.007), dactylitis (MTX, p < 0.001), inflammatory bowel disease (SSZ, p < 0.001) and nail involvement (MTX, p < 0.001).

Conclusion: The use of at least one DMD was reported by more than 70% of patients in a large cohort of Brazilian patients with SpA, with MTX use more associated with peripheral involvement and the use of SSZ more associated with axial involvement.
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September 2015

Enteropathic arthritis in Brazil: data from the Brazilian Registry of Spondyloarthritis.

Rev Bras Reumatol 2013 Nov-Dec;53(6):452-9

Unlabelled: Inflammatory bowel diseases (Crohn's disease and ulcerative rectocolitis) have extraintestinal manifestations 25% of the patients, with the most common one being the enteropathic arthritis.

Methods: Prospective, observational, multicenter study with patients from 29 reference centers participating in the Brazilian Registry of Spondyloarthritis (RBE), which incorporates the RESPONDIA (Ibero-American Registry of Spondyloarthritis) group. Demographic and clinical data were collected from 1472 patients and standardized questionnaires for the assessment of axial mobility, quality of life, enthesitic involvement, disease activity and functional capacity were applied. Laboratory and radiographic examinations were performed. The aim of this study is to compare the clinical, epidemiological, genetic, imaging, treatment and prognosis characteristics of patients with enteropathic arthritis with other types of spondyloarthritis in a large Brazilian cohort.

Results: A total of 3.2% of patients were classified as having enteroarthritis, 2.5% had spondylitis and 0.7%, arthritis (peripheral predominance). The subgroup of individuals with enteroarthritis had a higher prevalence in women (P < 0.001), lower incidence of inflammatory axial pain (P < 0.001) and enthesitis (P = 0.004). HLA-B27 was less frequent in the group with enteroarthritis (P = 0.001), even when considering only those with the pure axial form. There was a lower prevalence of radiographic sacroiliitis (P = 0.009) and lower radiographic score (BASRI) (P = 0.006) when compared to patients with other types of spondyloarthritis. They also used more corticosteroids (P < 0.001) and sulfasalazine (P < 0.001) and less non-steroidal anti-inflammatory drugs (P < 0.001) and methotrexate (P = 0.001).

Conclusion: There were differences between patients with enteroarthritis and other types of spondyloarthritis, especially higher prevalence of females, lower frequency of HLA-B27, associated with less severe axial involvement.
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http://dx.doi.org/10.1016/j.rbr.2013.04.001DOI Listing
April 2015

Low prevalence of renal, cardiac, pulmonary, and neurological extra-articular clinical manifestations in spondyloarthritis: analysis of the Brazilian Registry of Spondyloarthritis.

Rev Bras Reumatol 2012 May-Jun;52(3):375-83

Universidade de Fortaleza.

Objective: To describe the extra-articular manifestations (cardiac, renal, pulmonary, and neurological), usually not related to spondyloarthritis (SpA), in a large cohort of Brazilian patients.

Materials And Methods: This retrospective study analyzed 1,472 patients diagnosed with SpA and cared for at 29 health care centers distributed in the five major geographic regions in the country, participating in the Brazilian Registry of Spondyloarthritis (BRS). All patients were assessed for the prevalence of major extra-articular manifestations (cardiac, renal, pulmonary, and neurological), classified according to the diagnosis [ankylosing spondylitis (AS), psoriatic arthritis (PsA), reactive arthritis (ReA), arthritis associated with inflammatory bowel disease (IBD), undifferentiated spondyloarthritis (uSpA), and juvenile SpA], and according to the clinical presentation (axial, peripheral, mixed, and enthesitis).

Results: Of the patients with SpA assessed, 963 had AS, 271 PsA, 49 ReA, 48 arthritis associated with IBD, 98 uSpA, and 43 juvenile SpA. Cardiac involvement was reported in 44 patients (3.0%), pulmonary involvement in 19 (1.3%), renal involvement in 17 (1.2%), and neurological involvement in 13 patients (0.9%). Most patients with visceral involvement had AS or PsA, and the mixed (axial + peripheral) and/or predominantly axial clinical form.

Conclusion: Cardiac, renal, pulmonary, and neurological extra-articular manifestations are quite infrequent in SpA, ranging from 0.9% to 3% in this large Brazilian cohort, and affected predominantly patients with AS and PsA.
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October 2012

Gender characterization in a large series of Brazilian patients with spondyloarthritis.

Clin Rheumatol 2012 Apr 28;31(4):687-95. Epub 2011 Dec 28.

Hospital de Base do Distrito Federal, Unidade de Reumatologia, Brasília, DF, CEP 70330-000, Brazil.

An increasing number of women have been diagnosed with spondyloarthritis (SpA) in recent decades. While a few studies have analyzed gender as a prognostic factor of the disease, no studies have addressed this matter with a large number of patients in South America, which is a peculiar region due to its genetic heterogeneity. The aim of the present study was to analyze the influence of gender on disease patterns in a large cohort of Brazilian patients with SpA. A prospective study was carried out involving 1,505 patients [1,090 males (72.4%) and 415 females (27.6%)] classified as SpA according to the European Spondyloarthropaties Study Group criteria who attended at 29 reference centers for rheumatology in Brazil. Clinical and demographic variables were recorded and the following disease indices were administered: Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), Bath Ankylosing Spondylitis Radiologic Index (BASRI), Maastricht Ankylosing Spondylitis Enthesitis Score (MASES), and Ankylosing Spondylitis Quality of Life (ASQoL). Ankylosing spondylitis (AS) was the most frequent disease in the group (65.4%), followed by psoriatic arthritis (18.4%), undifferentiated SpA (6.7%), reactive arthritis (3.3%), arthritis associated to inflammatory bowel disease (3.2%), and juvenile SpA (2.9%). The male-to-female ratio was 2.6:1 for the whole group and 3.6:1 for AS. The females were older (p < 0.001) and reported shorter disease duration (p = 0.002) than the male patients. The female gender was positively associated to peripheral SpA (p < 0.001), upper limb arthritis (p < 0.001), dactylitis (p = 0.011), psoriasis (p < 0.001), nail involvement (p < 0.001), and family history of SpA (p = 0.045) and negatively associated to pure axial involvement (p < 0.001), lumbar inflammatory pain (p = 0.042), radiographic sacroiliitis (p < 0.001), and positive HLA-B27 (p = 0.001). The number of painful (p < 0.001) and swollen (p = 0.006) joints was significantly higher in the female gender, who also achieved higher BASDAI (p < 0.001), BASFI (p = 0.073, trend), MASES (p = 0.019), ASQoL (p = 0.014), and patient's global assessment (p = 0.003) scores, whereas the use of nonsteroidal anti-inflammatory drugs (p < 0.001) and biological agents (p = 0.003) was less frequent in the female gender. Moreover, BASRI values were significantly lower in females (p < 0.001). The female gender comprised one third of SpA patients in this large cohort and exhibited more significant peripheral involvement and less functional disability, despite higher values in disease indices.
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http://dx.doi.org/10.1007/s10067-011-1890-3DOI Listing
April 2012

Ethnic influence in clinical and functional measures of Brazilian patients with spondyloarthritis.

J Rheumatol 2012 Jan 1;39(1):141-7. Epub 2011 Nov 1.

Disciplina de Reumatologia, Faculdade de Medicina, Universidade de São Paulo, Av. Dr. Arnaldo, 455-3, Andar, Cerqueira César, São Paulo SP, Brasil, CEP 01246-903.

Objective: Spondyloarthritides (SpA) can present different disease spectra according to ethnic background. The Brazilian Registry of Spondyloarthritis (RBE) is a nationwide registry that comprises a large databank on clinical, functional, and treatment data on Brazilian patients with SpA. The aim of our study was to analyze the influence of ethnic background in SpA disease patterns in a large series of Brazilian patients.

Methods: A common protocol of investigation was prospectively applied to 1318 SpA patients in 29 centers distributed through the main geographical regions in Brazil. The group comprised whites (65%), African Brazilians (31.3%), and people of mixed origins (3.7%). Clinical and demographic variables and various disease index scores were compiled. Ankylosing spondylitis (AS) was the most frequent disease in the group (65.1%); others were psoriatic arthritis (18.3%), undifferentiated SpA (6.8%), enteropathic arthritis (3.7%), and reactive arthritis (3.4%).

Results: White patients were significantly associated with psoriasis (p = 0.002), positive HLA-B27 (p = 0.014), and use of corticosteroids (p < 0.0001). Hip involvement (p = 0.02), axial inflammatory pain (p = 0.04), and radiographic sacroiliitis (p = 0.025) were associated with African Brazilian descent. Sex distribution, family history, and presence of peripheral arthritis, uveitis, dactylitis, urethritis, and inflammatory bowel disease were similar in the 3 groups, as well as age at disease onset, time from first symptom until diagnosis, and use of anti-tumor necrosis factor-α agents (p > 0.05). Schober test and thoracic expansion were similar in the 3 groups, whereas African Brazilians had higher Maastricht Ankylosing Spondylitis Enthesitis Scores (p = 0.005) and decreased lateral lumbar flexion (p = 0.003), while whites had a higher occiput-to-wall distance (p = 0.02). African Brazilians reported a worse patient global assessment of disease (p = 0.011). Other index scores and prevalence of work incapacity were similar in the 3 groups, although African Brazilians had worse performance in the Ankylosing Spondylitis Quality of Life questionnaire (p < 0.001).

Conclusion: Ethnic background is associated with distinct clinical aspects of SpA in Brazilian patients. African Brazilian patients with SpA have a poorer quality of life and report worse disease compared to whites.
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http://dx.doi.org/10.3899/jrheum.110372DOI Listing
January 2012

Schistosoma mansoni infection: an immune complex disease presenting with polyarthritis.

Rheumatol Int 2013 May 13;33(5):1341-3. Epub 2011 Jan 13.

Rheumatology Unit, Department of Medicine, Faculty of Medical Sciences, State University of Campinas, Campinas, Brazil.

Schistosomiasis or bilharzia is a parasitic disease found in tropical countries. Most infections are subclinical but may progress to chronic form characterized most frequently by the presence of liver involvement and portal hypertension. We report a patient that presented chronic polyarthritis with positive rheumatoid factor. During investigation, increased liver enzymes, negative hepatitis serologies and signs of portal hypertension on an ultrasound examination raised suspicion of S. mansoni infection. We will discuss pathophysiology and clinical manifestations of S. mansoni infection with special attention to articular involvement.
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http://dx.doi.org/10.1007/s00296-010-1562-7DOI Listing
May 2013

Undifferentiated spondyloarthritis: a longterm followup.

J Rheumatol 2010 Jun 1;37(6):1195-9. Epub 2010 May 1.

Disciplina de Reumatologia, Faculdade de Medicina, Universidade de São Paulo, São Paulo SP, Brasil CEP 01246-903.

Objective: To analyze the longterm followup of a series of Brazilian patients with undifferentiated spondyloarthritis (uSpA).

Methods: Prospective study analyzing a group of 111 patients with the diagnosis of uSpA, fulfilling the European Spondylarthropathy Study Group and the Amor criteria, who were followed for 5 to 10 years in a single university referral center. Patients had their outcome analyzed at 5, 7, and 10 years.

Results: There was a predominance of men (81.1%), white ethnicity (78.4%), and positive HLA-B27 (61.3%), with a mean age at onset of 27.2 years. Twenty-seven patients presented development to ankylosing spondylitis (AS; 24.3%) and 3 to psoriatic arthritis (PsA; 2.7%), while 25 patients (22.5%) went into remission during the followup. Univariate logistic regression analysis revealed that ethnicity, HLA-B27, buttock pain, inflammatory low back pain, ankle involvement, grade I sacroiliitis at the beginning of the study, and the use of sulfasalazine were statistically associated with progression to AS. Multivariate logistic regression analysis revealed that HLA-B27 (p = 0.035, OR 6.720, 95% CI 11.45-39.43) and buttock pain (p = 0.009, OR 6.211, 95% CI 1.591-24.25) were statistically associated with progression to AS.

Conclusion: In a longterm followup of 111 Brazilian patients with uSpA, HLA-B27 and buttock pain were significant predictors of progression to a definite disease.
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http://dx.doi.org/10.3899/jrheum.090625DOI Listing
June 2010

Systemic lupus erythematosus associated with vasculitic syndrome (Takayasu's arteritis).

Rheumatol Int 2010 Nov 30;30(12):1669-72. Epub 2009 Sep 30.

Rheumatology Unit, Department of Internal Medicine, Faculty of Medical Sciences, State University of Campinas, UNICAMP, Campinas, SP, 13083-970, Brazil.

A 43-year-old woman reported pain in the right hypochondrium, which had started 3 years before and had been worsening for the past few days. Claudication in the superior and inferior limbs, diffuse myalgia, dyspnea, precordialgia followed by dizziness and visual turbidity were added to the clinical picture. In the physical examination bilateral carotid bruit was observed, abdominal aorta murmur and the decrease of the right radial and left pedis pulses and arterial hypertension with difference in the diastolic pressure between limbs >10 mmHg was also observed. On cardiac catheterisation with aortography, right coronary with proximal parietal irregularities, slight pressure increase in right chambers and pulmonary artery, preserved left ventricle contractility, competent valves, carotid and subclavian partial obstruction, severe narrowing of the abdominal aorta below the diaphragm (80%) and right renal artery significant stenosis were observed. Takayasu's arteritis (TA) diagnosis was established according to the ACR criteria based on the clinical symptomatology, on physical and image test findings. Two years later she presented malar rash, photosensitivity, nephropathy, leukopenia, lymphopenia and hemolytic anemia confirming the systemic lupus erythematosus (SLE) diagnosis. TA coexisting with SLE has rarely been reported.
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http://dx.doi.org/10.1007/s00296-009-1133-yDOI Listing
November 2010

Frequency of HLA-B27 alleles in Brazilian patients with psoriatic arthritis.

Clin Rheumatol 2008 Jun 3;27(6):709-12. Epub 2007 Nov 3.

Unit of Rheumatology-Department of Internal Medicine, State University of Campinas Faculty of Medical Sciences (FCM/UNICAMP), Barão Geraldo, Campinas-SP, CEP: 13081-970 Mail box 611, Brazil.

This prospective study analyzed the frequency of HLA-B27 and its alleles in 102 Brazilian patients with psoriatic arthritis (PsA). The association of the HLA-B27 alleles with these variants was compared to a control healthy HLA-B27 positive group of 111 individuals. There was a predominance of male gender (59.8%), Caucasian race (89.2%), and negative HLA-B27 (79.4%) patients. Asymmetric oligoarthritis (62.7%) was the most frequently observed clinical PsA subgroup, followed by spondylitis (16.7%), and polyarthritis (15.7%). Male gender and the spondylitis subgroup were statistically associated to the positive HLA-B27, and the oligoarthritis subgroup was associated to the negative HLA-B27. Among the 21 HLA-B27-positive PsA patients, there was a significant prevalence of the HLA-B*2705 allele (90.5%), similar to that observed in the control group (80.2%); HLA-B*2703 and HLA-B*2707 were statistically associated to the control group.
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http://dx.doi.org/10.1007/s10067-007-0770-3DOI Listing
June 2008

Infliximab reverses steatosis and improves insulin signal transduction in liver of rats fed a high-fat diet.

J Endocrinol 2007 Sep;194(3):539-50

Department of Internal Medicine and Gastrocentro, State University of Campinas, Campinas, SP 13083-970, Brazil.

Non-alcoholic fatty liver disease, induced by nutritional factors, is one of the leading causes of hepatic dysfunction in the modern world. The activation of proinflammatory signaling in the liver, which is induced by systemic and locally produced cytokines, and the development of hepatic insulin resistance are two important factors associated with the progression from steatosis to steatohepatitis, a pre-cirrhotic condition. The objective of the present study was to evaluate the effect of inhibition of tumour necrosis factor (TNF)-alpha , using the monoclonal antibody infliximab, on the expression of cytokines, induction of steatosis and fibrosis, and insulin signal transduction in the liver of Wistar rats fed a high-fat diet. Ten days of treatment with infliximab significantly reduced the expression of the proinflammatory markers, TNF-alpha , IL-6, IL-1beta , and SOCS-3, in the liver of rats fed a high-fat diet. This was accompanied by reduced fat deposition and fibrosis and by improved insulin signal transduction through insulin receptor (IR)/IR substrate/Akt/FOXO1 and JAK2/STAT3 pathways. In conclusion, short-term inhibition of TNF-alpha with infliximab reduces inflammation and steatosis/fibrosis, while improving insulin signal transduction in an animal model treated with a high-fat diet.
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http://dx.doi.org/10.1677/JOE-07-0234DOI Listing
September 2007

Infliximab restores glucose homeostasis in an animal model of diet-induced obesity and diabetes.

Endocrinology 2007 Dec 30;148(12):5991-7. Epub 2007 Aug 30.

Departamento de Clínica Médica, Faculdade de Ciências Médicas, Universidade Estadual de Campinas, Sao Paulo 13083-970, Brazil.

TNF-alpha plays an important role in obesity-linked insulin resistance and diabetes mellitus by activating at least two serine kinases capable of promoting negative regulation of key elements of the insulin signaling pathway. Pharmacological inhibition of TNF-alpha is currently in use for the treatment of rheumatoid and psoriatic arthritis, and some case reports have shown clinical improvement of diabetes in patients treated with the TNF-alpha blocking monoclonal antibody infliximab. The objective of this study was to evaluate the effect of infliximab on glucose homeostasis and insulin signal transduction in an animal model of diabetes. Diabetes was induced in Swiss mice by a fat-rich diet. Glucose and insulin homeostasis were evaluated by glucose and insulin tolerance tests and by the hyperinsulinemic-euglycemic clamp. Signal transduction was evaluated by immunoprecipitation and immunoblotting assays. Short-term treatment with infliximab rapidly reduced blood glucose and insulin levels and glucose and insulin areas under the curve during a glucose tolerance test. Furthermore, infliximab increased the glucose decay constant during an insulin tolerance test and promoted a significant increase in glucose infusion rate during a hyperinsulinemic-euglycemic clamp. In addition, the clinical outcomes were accompanied by improved insulin signal transduction in muscle, liver, and hypothalamus, as determined by the evaluation of insulin-induced insulin receptor, insulin receptor substrate-1, and receptor substrate-2 tyrosine phosphorylation and Akt and forkhead box protein O1 serine phosphorylation. Thus, pharmacological inhibition of TNF-alpha may be an attractive approach to treat severely insulin-resistant patients with type 2 diabetes mellitus.
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http://dx.doi.org/10.1210/en.2007-0132DOI Listing
December 2007

Frequency of HLA-B27 and its alleles in patients with Reiter syndrome: comparison with the frequency in other spondyloarthropathies and a healthy control population.

Rheumatol Int 2008 Mar 24;28(5):483-6. Epub 2007 Aug 24.

Unit of Rheumatology, Department of Internal Medicine, State University of Campinas Faculty of Medical Sciences (FCM/UNICAMP), Barão Geraldo, CEP: 13081-970, Campinas, SP, Brazil.

This retrospective study analyzed the HLA-B 27 alleles in a group of 20 consecutive patients with the diagnosis of Reiter syndrome (RS) followed in a tertiary referral university hospital in Brazil, during the period 1990-2006, and compared the data with that observed in other patients with spondyloarthropathies followed at the same institution. Eight cases were associated to gastrointestinal infection, eight cases to previous urethritis, and four cases presented no established preceding infection. HLA-B 27 alleles were typed by polymerase chain reaction-amplified DNA hybridized with sequence-specific oligonucleotide probes (HLA-B 2,701 to HLA-B 2,721). They were compared to a group of 108 patients with ankylosing spondylitis (AS), 40 with undifferentiated spondyloarthropathy (uSpA) and 111 healthy controls. Among the 20 patients, 17 were HLA-B 27 positive (85%). Two HLA-B 27 alleles were observed: HLA-B 2,705 (65%) and HLA-B 2,702 (35%). In the other spondyloarthropathies, the observed alleles were HLA-B 2,705 (90% in AS and 92.5% in uSpA), HLA-B 2,702 (8% in AS and 5% in uSpA), HLA-B 2,704 (1% in AS and 2.5% in uSpA) and HLA-B 2,713 (1% in AS). Among the 111 healthy controls, 80% presented HLA-B 2,705, followed by HLA-B 2,702 in 10%, HLA-B 2,703 in 6%, HLA-B 2,707 in 3% and HLA-B 2,713 in 1%. Concluding, in the HLA-B 27 positive patients with RS in this study there was predominance of HLA-B 2,705 allele, in a lower frequency than that observed in patients with other spondyloarthropathies and healthy controls.
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http://dx.doi.org/10.1007/s00296-007-0441-3DOI Listing
March 2008

Characterization and outcome of uveitis in 350 patients with spondyloarthropathies.

Rheumatol Int 2006 Oct 7;26(12):1143-6. Epub 2006 Sep 7.

Unit of Rheumatology, Department of Internal Medicine, State University of Campinas, Faculty of Medical Sciences FCM/UNICAMP, Barão Geraldo, CEP 13081-970 Campinas, SP, Brazil.

This retrospective study analyzed 350 patients with the diagnosis of spondyloarthropathies (SPA) (207 with ankylosing spondylitis (AS), 80 with undifferentiated spondyloarthropathies (USPA) and 63 with psoriatic arthritis (PsA)) attended at a tertiary referral hospital for a minimum period of 5 years. All the patients presented complete clinical (axial and peripheral involvement, heel enthesopathies, extra-articular manifestations) and radiologic (sacroiliac, lumbar, dorsal and cervical spine) evaluation. HLA-B27 and respective alleles were searched. These data were compared with the occurrence of uveitis during the follow-up of the SPA patients. Thirty AS patients (14.5%) presented 55 episodes of acute anterior uveitis; there was statistical association between uveitis and juvenile-onset AS (P = 0.0094) and achillean (P = 0.0003) and plantar (P = 0.0067) enthesopathies; one AS patient presented a single episode of posterior uveitis, associated to tuberculosis. Seven USPA patients (8.8%) presented 13 episodes of acute anterior uveitis; it was not observed statistical association with any variable; one patient presented a single episode of posterior uveitis, associated to toxoplasmosis. Five HLA-B27 positive PsA patients (8%) presented 13 episodes of acute anterior uveitis. All the 26 positive HLA-B27 SPA patients with anterior uveitis tested for the HLA-B27 alleles were HLA-B*2705. No patient presented ophthalmologic severe sequelae of the anterior uveitis. Concluding, anterior uveitis was associated to the juvenile onset of the disease and to the enthesophatic involvement of the lower limbs in AS patients. The HLA-B*2705 allele was predominant in the anterior uveitis patients, whilst posterior uveitis was rare and associated to infectious disease.
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http://dx.doi.org/10.1007/s00296-006-0203-7DOI Listing
October 2006

Tumor necrosis factor-alpha activates signal transduction in hypothalamus and modulates the expression of pro-inflammatory proteins and orexigenic/anorexigenic neurotransmitters.

J Neurochem 2006 Jul 21;98(1):203-12. Epub 2006 Apr 21.

Department of Internal Medicine, State University of Campinas, Sao Paulo, Brazil.

Tumor necrosis factor-alpha (TNF-alpha) is known to participate in the wastage syndrome that accompanies cancer and severe infectious diseases. More recently, a role for TNF-alpha in the pathogenesis of type 2 diabetes mellitus and obesity has been shown. Much of the regulatory action exerted by TNF-alpha upon the control of energy stores depends on its action on the hypothalamus. In this study, we show that TNF-alpha activates canonical pro-inflammatory signal transduction pathways in the hypothalamus of rats. These signaling events lead to the transcriptional activation of an early responsive gene and to the induction of expression of cytokines and a cytokine responsive protein such as interleukin-1beta, interleukin-6, interleukin-10 and suppressor of cytokine signalling-3, respectively. In addition, TNF-alpha induces the expression of neurotransmitters involved in the control of feeding and thermogenesis. Thus, TNF-alpha may act directly in the hypothalamus inducing a pro-inflammatory response and the modulation of expression of neurotransmitters involved in energy homeostasis.
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http://dx.doi.org/10.1111/j.1471-4159.2006.03857.xDOI Listing
July 2006

Adult-onset Still disease in southeast Brazil.

J Clin Rheumatol 2005 Apr;11(2):76-80

Department of Internal Medicine, State University of Campinas (UNICAMP), CEP 13081-970 Campinas, São Paulo, Brazil.

Background: Adult-onset Still disease (AOSD) has been described all over the world. Clinical presentations and prognosis have varied in different studies.

Objective: The objective of this study was to determine the clinical presentation and the evolution of AOSD at a tertiary referral center in southeast Brazil.

Methods: The clinical records of 16 patients were retrospectively studied to determine symptoms at diagnosis, follow up, and the medication prescribed.

Results: The mean age at onset was 30.8 years (range, 24-55 years; standard deviation [SD], 9.2 years) with a slight male prevalence (54.2%). All patients presented constitutional symptoms, fever, and skin rash. Liver involvement was observed in all cases, with hepatomegaly in 81.3%, increased liver enzymes in 50.0%, and hypergammaglobulinemia in 68.8%. Cardiac involvement was observed in 12.6%, pleuritis in 6.3%, and renal involvement in 25.0%. All patients presented leukocytosis with a predominance of neutrophils. Elevated ferritin levels were observed in 56.3%, and these levels were normalized after disease remission. Initial treatments included nonsteroidal antiinflammatory drugs and low-dosage corticosteroids in all patients; 43.8% also needed methotrexate. In 25.0% of cases, a monocyclic disease was observed; others had recurrent episodes. After a follow up of 6.9 years (SD, 1.2 years), carpal ankylosis was the main articular sequel, observed in 53.6% of the patients.

Conclusion: AOSD is rare in southeast Brazil. Although less severe systemic manifestations, like serositis and pneumonitis, were observed, reversible liver involvement was common; the frequency of recurrent disease and carpal ankylosis was higher than in previous studies.
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http://dx.doi.org/10.1097/01.rhu.0000158544.38663.0aDOI Listing
April 2005

Acute dermatomyositis with subcutaneous generalized edema.

Clin Rheumatol 2006 Nov 22;25(6):898-900. Epub 2006 Aug 22.

Rheumatology Unit, Department of Internal Medicine, Faculty of Medical Sciences, State University of Campinas, Distrito de Barão Geraldo, 13081-970, Campinas-SP, Brazil.

The authors report a 40-year-old Caucasian man with relapsing muscle and skin involvement of dermatomyositis treated with high-dose corticosteroids, taken orally, and methotrexate and human gamma globulin, both administered intravenously. After 4 months of aggressive treatment, he presented with generalized edema, considered secondary to dermatomyositis. Aggressive immunosuppression did not stop disease progression. The literature concerning anasarca due to inflammatory myopathies is revised.
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http://dx.doi.org/10.1007/s10067-005-0053-9DOI Listing
November 2006

Isolated pulmonary hypertension secondary to rheumatoid arthritis.

Clin Rheumatol 2006 Nov 25;25(6):901-3. Epub 2005 Nov 25.

Unit of Rheumatology, Department of Internal Medicine, State University of Campinas, Campinas, Brazil.

The authors report a case of a woman with pulmonary hypertension secondary to rheumatoid arthritis, whose treatment with azathioprine resulted in normalization of pulmonary artery pressure and resolution of clinical symptoms. Different etiologies for pulmonary hypertension are discussed and literature review is presented.
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http://dx.doi.org/10.1007/s10067-005-0089-xDOI Listing
November 2006

Camurati-Engelmann disease: failure of response to bisphosphonates: report of two cases.

Clin Rheumatol 2005 Aug 20;24(4):398-401. Epub 2005 Jan 20.

Departamento de Clínica Médica, Faculdade de Ciências Médicas/ UNICAMP, Campinas, SP, Brazil.

Camurati-Engelmann disease is a rare bone disorder characterized by cortical thickening of the diaphysis of tubular bones, with sparing of the epiphysis. It has variable degrees of penetrance and expression, but may be very disabling for the affected individuals who manifest the painful symptoms. The authors report on two women with typical presentation of severe Camurati-Engelmann disease whose treatment with bisphosphonates failed to add any improvement beyond that elicited by corticosteroids alone.
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http://dx.doi.org/10.1007/s10067-004-1056-7DOI Listing
August 2005

Protein-losing enteropathy associated with systemic lupus erythematosus: response to cyclophosphamide.

Rheumatol Int 2005 Mar 13;25(2):135-8. Epub 2004 Jul 13.

Rheumatology Unit, Department of Internal Medicine, Faculty of Medical Sciences, State University of Campinas, Campinas, Brazil.

Protein-losing enteropathy is a rare manifestation of systemic lupus erythematosus (SLE) leading to hypoalbuminemia and anasarca. We report the case of a woman with SLE who presented chronic hypoalbuminemia diagnosed as protein-losing enteropathy associated with SLE. She was refractory to prednisone and azathioprine administration but showed good response to cyclophosphamide. The diagnosis and management of hypoalbuminemia in lupus-associated enteropathy are discussed.
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http://dx.doi.org/10.1007/s00296-004-0483-8DOI Listing
March 2005

Undifferentiated spondyloarthropathies in Brazilians: importance of HLA-B27 and the B7-CREG alleles in characterization and disease progression.

J Rheumatol 2003 Dec;30(12):2632-7

Rheumatology Unit, Department of Internal Medicine, State University of Campinas, Barao Geraldo, Campinas SP, CEP 13081-970, Brazil.

Objective: To analyze the profile of the HLA-B27 and B7 cross-reactive group (CREG) alleles and the role of these markers in disease characterization and progression in patients with undifferentiated spondyloarthropathies (uSpA).

Methods: A total of 80 patients with a diagnosis of uSpA (40 HLA-B27 positive and 40 HLA-B27 negative) were prospectively studied for 2 years. The control group consisted of 66 HLA-B27 positive and 112 HLA-B27 negative individuals without a history of seronegative SpA. HLA-B alleles were typed at low (B7-CREG alleles, i.e., B*7, B*54, B*55, B*56, B*40, B*42) or high resolution (B*27 alleles) using polymerase chain reaction-amplified DNA hybridized with sequence-specific oligonucleotide probes.

Results: HLA-B*2705 was the most frequent allele, observed in 92.5% of the patients and in 77% of the controls, followed by the HLA-B*2702, observed in 5% of the patients and in 12% of the controls. HLA-B*2704 was observed in only one patient (2.5%), and was absent in the control population. HLA-B*2703 (6%) and HLA-B*2707 (5%) alleles were observed only in controls. No associations between HLA-B*27 alleles or B7-CREG alleles and any specific manifestation of uSpA were observed. HLA-B27 positive patients more frequently presented juvenile onset SpA (p = 0.002) and progression to ankylosing spondylitis (AS) (p = 0.03) than did HLA-B27 negative patients. The B7-CREG alleles were observed in 5% of the HLA-B27 positive uSpA group, in 25% of the HLA-B27 negative uSpA group, in 7% of the HLA-B27 positive controls, and in 13% of the HLA-B27 negative controls; a significant association was observed between the presence of the B7-CREG and the HLA-B27 negative uSpA group (p = 0.012).

Conclusion: The frequency of the HLA-B*2705 allele among the B27 positive uSpA patients of this series was closely similar to that reported for patients with ankylosing spondylitis (AS). The presence of HLA-B*27 alleles was associated with the progression to AS, and the presence of B7-CREG was associated with uSpA in the HLA-B27 negative group.
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December 2003
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