ADRIANA MALUF ELIAS SALLUM
Projetos de Pesquisa
Unidades Organizacionais
Instituto da Criança, Hospital das Clínicas, Faculdade de Medicina - Médico
LIM/36 - Laboratório de Pediatria Clínica, Hospital das Clínicas, Faculdade de Medicina
LIM/36 - Laboratório de Pediatria Clínica, Hospital das Clínicas, Faculdade de Medicina
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- Exposure to Air Pollutants and Disease Activity in Juvenile-Onset Systemic Lupus Erythematosus Patients(2015) FERNANDES, Elisabeth C.; SILVA, Clovis A.; BRAGA, Alfesio L. F.; SALLUM, Adriana M. E.; CAMPOS, Lucia M. A.; FARHAT, Sylvia C. L.ObjectiveTo investigate the association between exposure to air pollutants in the Sao Paulo metropolitan area and disease activity in juvenile-onset systemic lupus erythematosus (SLE) patients. MethodsA longitudinal panel study based on 409 consecutive visits of juvenile-onset SLE patients living in the Sao Paulo metropolitan area was carried out. Disease activity was evaluated in accordance with the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K), and the patients were divided into 2 groups: those with SLEDAI scores 8 and those with SLEDAI scores >8. Daily concentrations of inhaled particulate matter (PM10), sulfur dioxide, nitrogen dioxide (NO2), ozone, and carbon monoxide (CO) were evaluated on the 21 days preceding the medical visits. A generalized estimation equation model was used to assess the impact of these measurements on SLEDAI-2K scores, considering the fixed effects for repetitive measurements. The models were adjusted for erythrocyte sedimentation rate, corticosteroid use (daily and cumulative doses), antimalarial use, the use of immunosuppressive agents, the presence of infection 20 days preceding the medical appointment, and the minimum temperature and relative humidity outdoors. ResultsPM(10), NO2, and CO were risk factors for juvenile-onset SLE disease activity (SLEDAI-2K score >8) approximately 2 weeks after exposure. A 13.4 g/m(3) increase in the PM10 moving average (from lag 12 to lag 15) was associated with a 34% increase (95% confidence interval 7.0-68.0) in the risk of a SLEDAI-2K score >8. ConclusionThis is the first study to show that exposure to inhaled pollutants may increase the risk of disease activity in children with juvenile-onset SLE in a large urban center.
- Vasculite digital inicial em uma grande coorte multicêntrica de pacientes com lúpus eritematoso sistêmico de início na infância(2017) SAKAMOTO, Ana Paula; SILVA, Clovis Artur; SILVA, Marco Felipe Castro da; LOPES, Anandreia Simoes; RUSSO, Gleice Clemente Souza; SALLUM, Adriana Maluf Elias; KOZU, Katia; BONFA, Eloisa; SAAD-MAGALHAES, Claudia; PEREIRA, Rosa Maria Rodrigues; LEN, Claudio Arnaldo; TERRERI, Maria TeresaObjectives: To assess clinical digital vasculitis (DV) as an initial manifestation of childhood onset systemic lupus erythematosus (cSLE) within a large population. Methods: Multicenter cross-sectional study including 852 cSLE patients (ACR criteria) followed in ten Pediatric Rheumatology centers in Sao Paulo State, Brazil. Results: DV was observed in 25/852 (3%) cSLE patients. Periungual hemorrhage was diagnosed in 12 (48%), periungual infarction in 7 (28%), tip finger ulceration in 4 (16%), painful nodules in 1 (4%) and gangrene in 1 (4%). A poor outcome, with digital resorption, occurred in 5 (20%). Comparison of patients with and without DV revealed higher frequency of malar rash (80% vs. 53%, p = 0.008), discoid rash (16% vs. 4%, p = 0.017), photosensitivity (76% vs. 45%, p = 0.002) and other cutaneous vasculitides (80% vs. 19%, p <0.0001), whereas the frequency of overall constitutional features (32% vs. 61%, p = 0.003), fever (32% vs. 56%, p = 0.020) and hepatomegaly (4% vs. 23%, p = 0.026) were lower in these patients. Frequency of female gender, severe multi-organ involvement, autoantibodies profile and low complement were alike in both groups (p >0.05). SLEDAI-2K median, DV descriptor excluded, was significantly lower in patients with DV compared to those without this manifestation [10 (0-28) vs. 14 (0-58), p = 0.004]. Visceral vasculitis or death were not observed in this cSLE cohort. The frequency of cyclophosphamide use (0% vs. 18%, p = 0.014) was significantly lower in the DV group. Conclusion: Our large multicenter study identified clinical DV as one of the rare initial manifestation of active cSLE associated with a mild multisystemic disease, in spite of digital resorption in some of these patients. (C) 2017 Published by Elsevier Editora Ltda.
- Are prematurity and environmental factors determinants for developing childhood-onset systemic lupus erythematosus?(2018) CONDE, Paola G.; FARHAT, Luis C.; BRAGA, Alfesio L. F.; SALLUM, Adriana E. M.; FARHAT, Sylvia C. L.; SILVA, Clovis A.Objective: The objective of this study is to evaluate the influence of exposure to air pollutants and inhalable environmental elements during pregnancy and after birth until childhood-onset systemic lupus erythematosus(cSLE) diagnosis. Methods: This case-control study comprised 30 cSLE patients and 86 healthy controls living in the Sao Paulo metropolitan area. A structured and reliable questionnaire (kappa index for test-retest was 0.78) assessed demographic data, gestational and perinatal-related-factors, and exposure to inhalable particles and/or volatile vapor, and/or tobacco, as well as, the presence of industrial activities or gas stations near the home/work/daycare/school). Tropospheric pollutants included: particulate matter (PM10), sulfur dioxide (SO2), nitrogen dioxide (NO2), ozone (O-3) and carbon monoxide (CO). Results: The median current age was similar between cSLE patients and healthy controls [16.0 (5-21) versus 15.0 (4-21) years, p = .32], likewise the frequency of female gender (87% versus 78%, p = .43). The frequencies of prematurity (30% versus 6%, p = .001), maternal occupational exposure during pregnancy (59% versus 12%, p < .001), exposure to volatile vapor (48% versus 8%, p < .001) and fetal smoking (maternal and/or secondhand) (37% versus 19%, p = .008) were significantly higher in cSLE patients compared with controls. In a multivariate analysis regarding the gestation period, maternal occupational exposure (OR 13.5, 95% CI 2.5-72.4, p = .002), fetal smoking (OR 8.6, 95% CI 1.6-47, p = .013) and prematurity (OR 15.8, 95% CI 1.9-135.3, p = .012) remained risk factors for cSLE development. Furthermore, exposure to secondhand smoking during pregnancy and after birth (OR 9.1, 95% CI 1.8-42.1, p = .002) was also a risk factor for cSLE development. Conclusions: Prematurity and environmental factors were risk factors for developing cSLE.
- Influence of air pollution on renal activity in patients with childhood-onset systemic lupus erythematosus(2020) GOULART, Maria Fernanda Giacomin; ALVES, Andressa Guariento Ferreira; FARHAT, Juliana; BRAGA, Alfesio Luis Ferreira; PEREIRA, Luiz Alberto Amador; LICHTENFELS, Ana Julia de Faria Coimbra; CAMPOS, Lucia Maria de Arruda; SILVA, Clovis Artur Almeida da; ELIAS, Adriana Maluf; FARHAT, Sylvia Costa LimaBackground Childhood-onset systemic lupus erythematosus (cSLE) is an autoimmune and multifactorial disease that can affect the renal system. Exposure to air pollution can trigger systemic inflammation in cSLE patients and increase risk of disease activity. We evaluated effects of individual real-time exposure to air pollutants on renal activity in cSLE patients using the Systemic Lupus Erythematosus Disease Activity Index 2000. Methods Longitudinal panel study of 108 repetitive measures from 9 pediatric lupus patients. Over three consecutive weeks, daily individual levels of fine particulate matter (PM2.5) and nitrogen dioxide (NO2) were measured, as well as weekly clinical evaluation and laboratory tests. This was repeated every 10 weeks over a 1-year period. Specific generalized estimating equation models were used to evaluate the impact of these pollutants on risk of nephritis and anti-dsDNA > 20 UI/mL and on 24-h urine protein and serum complement (C3) levels. Results An interquartile range (IQR) increase of 18.12 mu g/m(3) in PM2.5 daily concentration was associated with increased risk of nephritis and positive results for anti-dsDNA. Moreover, increase in 24-h urine protein and decrease in C3 serum levels also associated with exposure to pollutants. An IQR increase in PM(2.5)7-day moving average was associated with increased risks of leukocyturia (3.4; 95% CI 2.6:4.3), positive anti-dsDNA (3.1; 95% CI 2.1:4.0), and 36.3-mg increase (95% IC 20.2:52.3) in 24-h urine protein. An IQR increase (63.1 mu g/m(3)) in 7-day cumulative NO2 levels was associated with decreased serum C3 levels. Conclusions This prospective study suggests exposure to air pollution can trigger renal activity in cSLE patients.
- Increased Soluble Cytoplasmic Bcl-2 Protein Serum Levels and Expression and Decreased Fas Expression in Lymphocytes and Monocytes in Juvenile Dermatomyositis(2018) LIPHAUS, Bernadete L.; SALLUM, Adriana E. M.; AIKAWA, Nadia E.; KISS, Maria Helena B.; CARRASCO, Solange; PALMEIRA, Patricia; LIMA, Laila; SILVA, Clovis A.; GOLDENSTEIN-SCHAINBERG, Claudia; CARNEIRO-SAMPAIO, MagdaObjective. To evaluate soluble Fas antigen (sFas), sFas ligand (sFasL), soluble tumor necrosis factor-related apoptosis-inducing ligand, and soluble cytoplasmic Bcl-2 protein (sBcl-2) serum levels, Fas and Bcl-2 expressions in T and B lymphocytes and monocytes and relations with erythrocyte sedimentation rate, C-reactive protein (CRP), Childhood Myositis Assessment Scale, and manual muscle testing in juvenile dermatomyositis (JDM). Methods. Serum levels were determined by ELISA and peripheral cell expressions by flow cytometry for patients with JDM or juvenile idiopathic arthritis (JIA), and healthy controls. Results. Patients with JDM had increased sBcl-2, which correlated with CRP. Expression of Bcl-2 was increased and expression of Fas was decreased in CD3+, CD4+, and CD8+ T lymphocytes compared with JIA and/or healthy controls. Conclusion. Patients with JDM presented a unique apoptosis-related proteins profile, which may contribute to disease development.
- Lower genital tract infections in young female juvenile idiopathic arthritis patients(2019) V, Gabriela R. Ferreira; TOMIOKA, Renato B.; QUEIROZ, Ligia B.; KOZU, Katia; AIKAWA, Nadia E.; SALLUM, Adriana M. E.; SERAFINI, Paulo; TACLA, Maricy; BARACAT, Edmund C.; PEREIRA, Rosa M. R.; BONFA, Eloisa; SILVA, Clovis A.Background To evaluate human papillomavirus (HPV), Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) infections in juvenile idiopathic arthritis (JIA) patients. Methods After exclusion, 33 female adolescent and young JIA patients (ILAR criteria) and 28 healthy controls were selected for this study. Demographic data, gynecological, sexual function, cervical cytology and histological abnormalities were evaluated. JIA clinical/laboratorial parameters and treatment were also assessed. HPV-DNA, CT-DNA and NG-DNA testing in cervical specimens were performed by Hybrid Capture 2 assays. Results The mean current age was similar in JIA patients and controls (23.3 +/- 6.24 vs. 26.1 +/- 6.03 years, p = 0.09). The frequencies of sexual intercourse (76% vs. 89%, p = 0.201) and abnormal cervical cytology (24% vs. 11%, p = 0.201) were similar in JIA compared to controls. The higher frequency of HPV infection in JIA patients than controls (30% vs. 11%, p = 0.155) did not reach statistical significance. CT (0% vs. 7%, p = 0.207) and NG infections (0% vs. 4%, p = 0.459) were also alike in both groups. Further evaluation of JIA patients with abnormal and normal cervical cytology showed that the former group had a higher frequency of HPV infection (87% vs. 12%, p = 0.0002) with a low frequency of HPV vaccination (0% vs. 8%, p = 1.0). No differences were evidenced between these two JIA groups regarding demographic data, sexual function and clinical/laboratorial parameters. The frequencies of methotrexate (p = 0.206) and biological agent use (p = 0.238) were similar in both JIA groups. Conclusions To our knowledge, this was the first study to assess lower genital infections in JIA patients allowing the identification of HPV as main cause of cervical dysplasia. Methotrexate and biological agents do not seem to increase risk of lower genital tract infections in JIA patients.
- Influence of air pollution on airway inflammation and disease activity in childhood-systemic lupus erythematosus(2018) ALVES, Andressa Guariento Ferreira; GIACOMIN, Maria Fernanda de Azevedo; BRAGA, Alfesio Luis Ferreira; SALLUM, Adriana Maluf Elias; PEREIRA, Luiz Alberto Amador; FARHAT, Luis Carlos; STRUFALDI, Fernando Louzada; LICHTENFELS, Ana Julia de Faria Coimbra; CARVALHO, Tomas de Santana; NAKAGAWA, Naomi Kondo; SILVA, Clovis Artur; FARHAT, Sylvia Costa LimaExposure to fine particles may trigger pulmonary inflammation/systemic inflammation. The objective of this study was to investigate the association between daily individual exposure to air pollutants and airway inflammation and disease activity in childhood-onset systemic lupus erythematosus (cSLE) patients. A longitudinal panel study was carried out in 108 consecutive appointments with cSLE patients without respiratory diseases. Over four consecutive weeks, daily individual measures of nitrogen dioxide (NO2), fine particulate matter (PM2.5), ambient temperature, and humidity were obtained. This cycle was repeated every 2.5 months along 1 year, and cytokines of exhaled breath condensate-EBC [interleukins (IL) 6, 8, 17 and tumoral necrose factor-alpha (TNF-alpha)], fractional exhaled NO (FeNO), and disease activity parameters were collected weekly. Specific generalized estimation equation models were used to assess the impact of these pollutants on the risk of Systemic Lupus Erythematous Disease Activity Index 2000 (SLEDAI-2K) ae 8, EBC cytokines, and FeNO, considering the fixed effects for repetitive measurements. The models were adjusted for inflammatory indicators, body mass index, infections, medication, and weather variables. An IQR increase in PM2.5 4-day moving average (18.12 mu g/m(3)) was associated with an increase of 0.05 pg/ml (95% CI 0.01; 0.09, p = 0.03) and 0.04 pg/ml (95% CI 0.02; 0.06, p = 0.01) in IL-17 and TNF-alpha EBC levels, respectively. Additionally, a short-term effect on FeNO was observed: the PM2.5 3-day moving average was associated with a 0.75 ppb increase (95% CI 0.38; 1.29, p = 0.03) in FeNO. Also, an increase of 1.47 (95% CI 1.10; 1.84) in the risk of SLEDAI-2K ae 8 was associated with PM2.5 7-day moving average. Exposure to inhalable fine particles increases airway inflammation/pulmonary and then systemic inflammation in cSLE patients.
article 24 Citação(ões) na Scopus Influenza A H1N1/2009 vaccine in juvenile dermatomyositis: reduced immunogenicity in patients under immunosuppressive therapy(2012) GUISSA, V. R.; PEREIRA, R. M. R.; SALLUM, A. M. E.; AIKAWA, N. E.; CAMPOS, L. M. A.; SILVA, C. A.; BONFA, E.Objectives The aim of the present paper is to assess the influence of demographic, muscle enzymes, JDM scores and treatment on non-adjuvanted influenza A H1N1/2009 vaccine immunogenicity in juvenile dermatomyositis (JDM) patients. Methods Thirty JDM patients and 81 healthy age-matched controls were vaccinated. All participants were evaluated pre- and 21 days post-vaccination and serology for anti-HI NI was performed by haemagglutination inhibition assay. Muscle enzymes, JDM scores and treatment were evaluated before and after vaccination. Adverse events were reported. Results After immunisation seroconversion rates were significantly lower in JDM patients compared to age-matched controls (86.7 vs. 97.5%, p=0.044), whereas seropmtection (p=0.121), geometric mean titres (GMT) (p=0.992) and factor increase (FI) in GMT (p=0.827) were similar in both groups. Clinical and labomtorial evaluations revealed that JDM scores and muscle enzymes remained stable throughout the study (p>0.05). A higher frequency of chronic course was observed in non-seroconverted compared to seroconverted (100% vs. 27%, p=0.012). Regarding treatment, a lower rate of seroconversion was observed in patients under prednisone>20mg/day (50% vs. 4%, p=0.039), and in those treated with a combination of prednisone, methotrexate and cyclosporine (50% vs. 4%, p=0.039). Local and systemic vaccine adverse events were mild and similar in patients and controls (p>0.05). Conclusion This study identified that chronic course and immunosuppressive therapy are the major factors hampering seroconversion was JDM, suggesting that a specific protocol may be required for this subgroup of patients. In spite of that, a single dose of non-adjuvanted influenza A/H1N1 2009 vaccine was generally seroprotective in this disease with no evident deleterious effect in disease itself (ClinicalTrials.gov, no. NCT01151644).- Exercise Training in Juvenile Dermatomyositis(2012) OMORI, Clarissa Harumi; SILVA, Clovis Artur Almeida; SALLUM, Adriana Maluf Elias; PEREIRA, Rosa Maria Rodrigues; PINTO, Ana Lucia de Sa; ROSCHEL, Hamilton; GUALANO, BrunoObjective. To investigate the effects of a supervised exercise training program on health parameters, physical capacity, and health-related quality of life in patients with mild and chronic juvenile dermatomyositis (DM). Methods. This was a prospective longitudinal study following 10 children with mild and chronic juvenile DM (disease duration >1 year). The exercise program consisted of twice-a-week aerobic and resistance training. At baseline and after the 12-week intervention, we assessed muscle strength and function, aerobic conditioning, body composition, juvenile DM scores, and health-related quality of life. Results. Child self-report and parent proxy-report Pediatric Quality of Life Inventory scores were improved after the intervention (-40.3%; P = 0.001 and -48.2%; P = 0.049, respectively). Importantly, after exercise, the Disease Activity Score was reduced (-26.9%; P = 0.026) and the Childhood Muscle Assessment Scale was improved (+2.5%; P = 0.009), whereas the Manual Muscle Test presented a trend toward statistical significance (+2.2%; P = 0.081). The peak oxygen consumption and time-to-exhaustion were increased by 13.3% (P = 0.001) and 18.2% (P = 0.003), respectively, whereas resting heart rate was decreased by 14.7% (P = 0.006), indicating important cardiovascular adaptations to the exercise program. Upper and lower extremity muscle strength and muscle function were also significantly improved after the exercise training (P < 0.05). Both the whole-body and the lumbar spine bone mineral apparent density were significantly increased after training (1.44%; P = 0.044 and 2.85%; P = 0.008, respectively). Conclusion. We showed for the first time that a 12-week supervised exercise program is safe and can improve muscle strength and function, aerobic conditioning, bone mass, disease activity, and health-related quality of life in patients with active and nonactive mild and chronic juvenile DM with near normal physical function and quality of life.
- Physical (in)activity and its influence on disease-related features, physical capacity, and health-related quality of life in a cohort of chronic juvenile dermatomyositis patients(2016) PINTO, Ana Jessica; SOLIS, Marina Yazigi; PINTO, Ana Lucia de Sa; SILVA, Clovis Artur; SALLUM, Adriana Maluf Elias; ROSCHEL, Hamilton; GUALANO, BrunoObjectives: To objectively measure physical activity levels in a cohort of juvenile dermatomyositis (JDM) patients; to compare physical capacity and health-related quality of life in JDM patients and their healthy controls (CTRL) matched by physical activity levels; and to associate physical activity variables with disease-related parameters, physical capacity, and health-related quality of life. Methods: This was a cross-sectional study in which 19 JDM patients and 19 CTRL matched by physical activity levels, age, sex, and body mass index were compared. Physical activity was objectively measured using accelerometers. Results: In our cohort, only one of the 19 JDM patients (5%) achieved the minimum recommended moderate-to-vigorous physical activity levels (MVPA) (i.e., minimum of 60 min/day). JDM showed lower aerobic condition (e.g., VO2peak), muscle function (e.g., timed-stands test), and health-related quality of life in comparison to CTRL (p < 0.05). Sedentary time was positively correlated with disease duration (r = 0.649; p = 0.003), and negatively with VO2peak (r = -0.459; p = 0.048). Moreover, MVPA was negatively associated with disease duration (r = -0.509; p = 0.026), and positively associated with VO2peak (r = 0.797; p < 0.001), and current use of corticoid (r = 0.748; p < 0.001). Conclusion: Physical capacity and health-related quality of life were reduced in JDM patients when compared with CTRL matched by physical activity levels, suggesting that the disease itself and/or glucocorticoid use may adversely affect overall health in JDM, despite an apparently well-controlled disease. Physical (in)activity correlated with important disease-related and physical capacity parameters, suggesting that sedentary lifestyle may be an important, but preventable, factor associated with poor overall health in JDM.