CLOVIS ARTUR ALMEIDA DA SILVA
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Pediatria, Faculdade de Medicina - Docente
Instituto da Criança, Hospital das Clínicas, Faculdade de Medicina
LIM/36 - Laboratório de Pediatria Clínica, Hospital das Clínicas, Faculdade de Medicina - Líder
Instituto da Criança, Hospital das Clínicas, Faculdade de Medicina
LIM/36 - Laboratório de Pediatria Clínica, Hospital das Clínicas, Faculdade de Medicina - Líder
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conferenceObject Behcet's Disease Activity: An Important Factor For Immunogenicity Of Unadjuvanted Influenza A/H1N1 Vaccine(2013) PRADO, Leandro L.; SAAD, Carla G. S.; MORAES, Julio C. B.; RIBEIRO, Ana Cristina Medeiros; AIKAWA, Nadia E.; SILVA, Clovis A.; SCHAINBERG, Claudia G.; SAMPAIO-BARROS, Percival D.; PRECIOSO, Alexander R.; ISHIDA, Maria A.; BONFA, Eloisa; GONCALVES, CelioconferenceObject Yellow Fever Vaccination in Brazil: Short-Term Safety in Pediatric Autoimmune Rheumatic Diseases(2018) AIKAWA, Nadia E.; BALBI, Verena A.; TONACIO, Adriana C.; SALLUM, Adriana M. E.; CAMPOS, Lucia M. A.; KOZU, Katia T.; VENDRAMINI, Margarete B.; FONTOURA, Nicole; SARTORI, Ana M. C.; ANTONANGELO, Leila; SILVA, Clovis A.; BONFA, Eloisa- Risk factors for mortality in 1528 Brazilian childhood-onset systemic lupus erythematosus patients(2023) SAKAMOTO, Ana P.; SILVA, Clovis A.; PITA, Ana C.; TRINDADE, Vitor C.; ISLABAO, Aline G.; FIOROT, Fernanda J.; LOPES, Sandra R. M.; PEREIRA, Rosa M. R.; SAAD-MAGALHAES, Claudia; RUSSO, Gleice C. S.; LEN, Claudio A.; PRADO, Rogerio do; CAMPOS, Lucia M. A.; AIKAWA, Nadia E.; APPENZELLER, Simone; FERRIANI, Virginia P. L.; SILVA, Marco F.; FELIX, Marta; FONSECA, Adriana R.; ASSAD, Ana P. L.; SZTAJNBOK, Flavio R.; SANTOS, Maria C.; BICA, Blanca E.; SENA, Evaldo G.; MORAES, Ana J.; FRAGA, Melissa M.; ROBAZZI, Teresa C.; SPELLING, Paulo F.; SCHEIBEL, Iloite M.; CAVALCANTI, Andre S.; MATOS, Erica N.; GUIMARAES, Luciano J.; SANTOS, Flavia P.; MOTA, Licia M. H.; BONFA, Eloisa; TERRERI, Maria T.Objectives: To identify associations between mortality in cSLE patients and their characteristics: clinical and laboratory features, disease activity and damage scores, and treatment; to evaluate risk factors associated with mortality in cSLE; and to determine the most frequent causes of death in this group of patients.Methods: We performed a multicenter retrospective cohort using data from 1,528 cSLE patients followed in 27 pediatric rheumatology tertiary centers in Brazil. Patients' medical records were reviewed according to a standardized protocol, in which information regarding demographic and clinical features, disease activity and damage scores, and treatment were collected and compared between deceased cSLE patients and survivors. Univariate and multivariate analyses by Cox regression model were used to calculate risk factors for mortality, whereas survival rates were analyzed by Kaplan-Meier plots.Results: A total of 63/1,528 (4.1%) patients deceased, 53/63 were female (84.1%), median age at death was 11.9 (9.4-13.1) years and median time interval between cSLE diagnosis and death was 3.2 (0.5-5.3) years. Sepsis was the main cause of death in 27/63 (42.8%) patients, followed by opportunistic infections in 7/63 (11.1%), and alveolar hemorrhage in 6/63 (9.5%) patients. The regression models resulted in neuropsychiatric lupus (NP-SLE) (HR = 2.56, 95% CI = 1.48-4.42) and chronic kidney disease (CKD) (HR = 4.33, 95% CI = 2.33-4.72), as risk factors significantly associated with mortality. Overall patient survival after cSLE diagnosis at 5, 10, and 15 years were 97%, 95.4%, and 93.8%, respectively.Conclusions: This study confirmed that the recent mortality rate in cSLE in Brazil is low, but still of concern. NP-SLE and CKD were the main risk factors for mortality, indicating that the magnitude of these manifestations was significantly high.
- Pancreatitis Subtypes Survey in 852 Childhood-Onset Systemic Lupus Erythematosus Patients(2016) MARQUES, Victor L. S.; GORMEZANO, Natali W. S.; BONFA, Eloisa; AIKAWA, Nadia E.; TERRERI, Maria T.; PEREIRA, Rosa M.; MAGALHAES, Claudia S.; GUARIENTO, Andressa; APPENZELLER, Simone; FERRIANI, Virginia P.; BARBOSA, Cassia M.; RAMOS, Valeria C.; LOTUFO, Simone; SILVA, Clovis A.Objective:Pancreatitis is a rare and a life-threatening systemic lupus erythematosus (SLE) manifestation in childhood-onset SLE (cSLE). The objective of this study was to systematically classify pancreatitis in cSLE according to the International Study Group of Pediatric Pancreatitis and determine the overall prevalence, clinical features, laboratory, and first episode outcomes.Methods:A multicenter cohort study in 10 pediatric rheumatology centers, including 852 patients with cSLE.Results:Pancreatitis was diagnosed in 22 of 852 (2.6%) patients with cSLE. It was classified as acute pancreatitis in 20 (91%), acute recurrent pancreatitis in 2 (9%), and none of them had chronic pancreatitis. None of them had gallstones, traumatic pancreatitis, or reported alcohol/tobacco use. The comparison of patients with pancreatitis (first episode) and without this complication revealed a shorter disease duration (1 [0-10] vs 4 [0-23] years, P<0.0001) and higher median of Systemic Lupus Erythematosus Disease Activity Index 2000 (21 [0-41] vs 2 [0-45], P<0.0001). The frequencies of fever (P<0.0001), weight loss (P<0.0001), serositis (P<0.0001), nephritis (P<0.0001), arterial hypertension (P<0.0001), acute renal failure (P<0.0001), macrophage activation syndrome (P<0.0001), and death (P=0.001) were also higher in patients with pancreatitis. The frequencies of intravenous methylprednisolone use (P<0.0001) and the median of prednisone dose (55 [15-60] vs 11 [1-90] mg/day, P<0.0001) were significantly higher in patients with pancreatitis. Of note, the 2 patients with acute recurrent pancreatitis had 2 episodes, with pain-free interval of 1 and 4 years.Conclusions:This was the first study characterizing pancreatitis using the International Study Group of Pediatric Pancreatitis standardized definitions in patients with cSLE showing that the predominant form is acute pancreatitis seen in association with glucocorticoid treatment and active severe disease.
- Heart function in juvenile idiopathic arthritis patients: A biventricular two-dimensional speckle-tracking echocardiography study(2022) LIANZA, Alessandro C.; LEAL, Gabriela N.; AIKAWA, Nadia E.; KOZU, Katia T.; DINIZ, Maria De Fatima R.; SAWAMURA, Karen S. S.; MENEZES, Carolina R. B.; MARTINS, Camila Lino; CAMPOS, Lucia M.; ELIAS, Adriana M.; SILVA, Clovis A.Objectives We evaluated cardiac function in juvenile idiopathic arthritis (JIA) patients by 2D speckle-tracking echocardiography (2DSTE) and to assess possible associations with clinical, laboratorial, and treatment data. Methods A group of 42 JIA patients and 42 healthy controls were evaluated using both conventional echocardiography and 2DSTE. JIA patients underwent clinical and laboratory assessment. Results Conventional echocardiography data demonstrated normal left ventricular (LV) ejection fraction in both groups (71 vs. 71%; p = .69). 2DSTE analysis demonstrated that JIA patients presented significantly lower LV global systolic longitudinal strain (LVGLS) (-18.76 vs. -22%; p < .0001), LV systolic strain rate (LVSSR) (1.06 vs. 1.32 s(-1); p < .0001), LV diastolic strain rate (LVDSR) (1.58 vs. 1.8 s(-1); p < .0137), right ventricular global systolic strain (RVGLS) (-24.1% vs. -27.7%; p = .0002), and right ventricular systolic strain rate (RVSSR) (1.4 vs. 1.8 s(-1); p = .0035). JIA patients under biological agents presented higher LVGLS (p = .02) and RVLS (p = .01). We also detected an association between LVGLS and C-reactive protein [CRP; -20% in normal CRP (10/42) vs. -18% in elevated CRP patients (32/42), p = .03]. Conclusions JIA patients present different echocardiographic status from healthy patients. Moreover, our data suggest that JIA patients under biological agents present association with better cardiac function as shown by strain analysis.
conferenceObject NUTRITIONAL ASSESSMENT, BODY COMPOSITION AND PHASE ANGLE IN JUVENILE DERMATOMYOSITIS PATIENTS(2023) PUGLIESE, Camila; KOZU, Katia T.; CAMPOS, Lucia M. A.; AIKAWA, Nadia E.; SILVA, Clovis A. A.; ELIAS, Adriana M.- Chronic arthritis in systemic lupus erythematosus: distinct features in 336 paediatric and 1830 adult patients(2016) GORMEZANO, Natali W. S.; SILVA, Clovis A.; AIKAWA, Nadia E.; BARROS, Diego L.; SILVA, Mariana A. da; OTSUZI, Carini I.; KOZU, Katia; SEGURO, Luciana Parente; PEREIRA, Rosa M. R.; BONFA, EloisaThe objectives of this study are to assess the frequency of chronic arthritis and compare the clinical and laboratory features in a large population of childhood-onset systemic lupus erythematosus (cSLE) and adult-onset (aSLE) patients. This historical study evaluated 336 cSLE and 1830 aSLE patients. Chronic arthritis was defined as synovitis of at least 6 weeks of duration. Rhupus was characterised as the association of SLE and chronic inflammatory arthritis with erosion and positive rheumatoid factor. Jaccoud's arthropathy is a non-erosive subluxation leading to severe deformity of the hands and feet. Data were compared using Student's t test or the Mann-Whitney test for continuous variables. For categorical variables, differences were assessed by Fisher's exact test and Pearson chi-square. Frequencies of chronic arthritis were similar in cSLE and aSLE (2.4 vs. 3.8 %, p=0.261). The median time from disease onset to appearance of chronic arthritis was shorter in cSLE (0 vs. 10 years, p<0.001), and the median of age at chronic arthritis diagnosis was [10.8 (4.2-14.6) vs. 40 (21-67), p<0.001]. The children presented with more chronic polyarthritis than the adults (75 vs. 32 %, p=0.024), a higher median number of joints with arthritis [8.5 (118) vs. 3 (1-9), p=0.017] and a higher number of joints with limitation [1.5(0-24) vs. 0(0-4), p=0.004]. The chronic arthritis diagnosis frequencies of hepatomegaly (25 vs. 0 %, p=0.009), splenomegaly (25 vs. 0 %, p=0.009), pericarditis (25 vs. 0 %, p=0.009), nephritis (37 vs. 3 %, p=0.006), haematuria (37 vs. 1.4 %, p=0.002), lupus anticoagulant (40 vs. 1.6 %, p=0.012), anticardiolipin IgM (40 vs. 1.5 %, p=0.012) and median Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) [10.5(1-20) vs. 6(4-16), p=0.029] were higher in cSLE. Frequency of rhupus, (12 vs. 17 %, p=1.0), Jaccoud's arthropathy (0 vs. 17 %, p=0.343) and treatments were similar in cSLE and aSLE. We determined that chronic arthritis in SLE has distinct features in children, with very early onset, polyarticular involvement and association with active disease. We further demonstrated in this series that a proportion of chronic arthritis involvement in SLE is manifested as rhupus and Jaccoud's arthropathy.
- Immunogenicity and safety of the 2009 non-adjuvanted influenza A/H1N1 vaccine in a large cohort of autoimmune rheumatic diseases(2011) SAAD, Carla G. S.; BORBA, Eduardo F.; AIKAWA, Nadia E.; SILVA, Clovis A.; PEREIRA, Rosa M. R.; CALICH, Ana Luisa; MORAES, Julio C. B.; RIBEIRO, Ana C. M.; VIANA, Vilma S. T.; PASOTO, Sandra G.; CARVALHO, Jozelio F.; FRANCA, Ivan L. A.; GUEDES, Lissiane K. N.; SHINJO, Samuel K.; SAMPAIO-BARROS, Percival D.; CALEIRO, Maria T.; GONCALVES, Celio R.; FULLER, Ricardo; LEVY-NETO, Mauricio; TIMENETSKY, Maria do Carmo S.; PRECIOSO, Alexander R.; BONFA, EloisaBackground Despite the WHO recommendation that the 2010-2011 trivalent seasonal flu vaccine must contain A/California/7/2009/H1N1-like virus there is no consistent data regarding its immunogenicity and safety in a large autoimmune rheumatic disease (ARD) population. Methods 1668 ARD patients (systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), ankylosing spondylitis (AS), systemic sclerosis, psoriatic arthritis (PsA), Behcet's disease (BD), mixed connective tissue disease, primary antiphospholipid syndrome (PAPS), dermatomyositis (DM), primary Sjogren's syndrome, Takayasu's arteritis, polymyositis and Granulomatosis with polyangiitis (Wegener's) (GPA)) and 234 healthy controls were vaccinated with a non-adjuvanted influenza A/California/7/2009(H1N1) virus-like strain flu. Subjects were evaluated before vaccination and 21 days post-vaccination. The percentage of seroprotection, seroconversion and the factor increase in geometric mean titre (GMT) were calculated. Results After immunisation, seroprotection rates (68.5% vs 82.9% p < 0.0001), seroconversion rates (63.4% vs 76.9%, p < 0.001) and the factor increase in GMT (8.9 vs 13.2 p < 0.0001) were significantly lower in ARD than controls. Analysis of specific diseases revealed that seroprotection significantly reduced in SLE (p < 0.0001), RA (p < 0.0001), PsA (p=0.0006), AS (p=0.04), BD (p=0.04) and DM (p=0.04) patients than controls. The seroconversion rates in SLE (p < 0.0001), RA (p < 0.0001) and PsA (p=0.0006) patients and the increase in GMTs in SLE (p < 0.0001), RA (p < 0.0001) and PsA (p < 0.0001) patients were also reduced compared with controls. Moderate and severe side effects were not reported. Conclusions The novel recognition of a diverse vaccine immunogenicity profile in distinct ARDs supports the notion that a booster dose may be recommended for diseases with suboptimal immune responses. This large study also settles the issue of vaccine safety. (ClinicalTrials.gov #NCT01151644)
- 2019-EULAR/ACR classification criteria domains at diagnosis: predictive factors of long-term damage in systemic lupus erythematosus(2022) INSFRAN, Carlos E.; AIKAWA, Nadia E.; PASOTO, Sandra G.; FILHO, Dilson M. N.; FORMIGA, Francisco F. C.; PITTA, Ana C.; BORBA, Eduardo F.; RIBEIRO, Carolina T.; SILVA, Clovis A.; BONFA, EloisaThe objective of this study is to assess the role of the 2019-European League Against Rheumatism/American College of Rheumatology (2019-EULAR/ACR) classification criteria at diagnosis and its domains in predicting long-term damage in systemic lupus erythematosus(SLE). We performed a retrospective analysis using an electronic chart database utilized in routine clinical care of SLE patients and established in 2000 in a tertiary hospital. Two hundred and nine consecutive SLE patients with disease onset >= 18 years old and long disease duration were included. Cumulative damage at the last visit was scored using the SLICC/ACR-Damage Index (SDI). The median age at SLE diagnosis was 28 years (18-63), disease duration was 14 years (8-25), and 88% were females. Damage (SDI >= 1) was observed in 116/209 (55%). Patients with (SDI >= 1, n=116) and without damage (SDI=0, n=93) had similar median disease duration [14 (8-25) vs. 12 (8-25) years, p=0.090[ and age at diagnosis [23 (18-55) vs. 23 (18-56) years, p=0.998[. No correlation was observed between total 2019-EULAR/ACR score at diagnosis and SDI at last visit (r=0.007, p=0.913). Presence of renal domain at diagnosis was associated with renal damage at last visit (OR=3.6, 95%CI 1.2-10.4, p=0.017) and antiphospholipid antibodies domain predicted neuropsychiatric damage (OR=3.0, 95%CI 1.2-7.6, p=0.015). A ROC analysis identified that a cut-off >24 in 2019-EULAR/ACR score could predict a trend for renal damage (p=0.077) with a lower renal survival (Kaplan-Meier curve) for patients above this limit (p=0.029). A multivariate logistic regression analysis revealed that 2019-EULAR/ACR score >24 at diagnosis (OR 4.583, 95%CI 1.052-19.962, p=0.043) was independently associated with renal damage. Specific domains in the 2019-EULAR/ACR criteria at diagnosis were associated with long-term organspecific damage, particularly renal and neuropsychiatric harm. A 2019-EULAR/ACR score >24 predicted worse renal survival.
- High Disease Activity: An Independent Factor for Reduced Immunogenicity of the Pandemic Influenza A Vaccine in Patients With Juvenile Systemic Lupus Erythematosus(2013) CAMPOS, Lucia M. A.; SILVA, Clovis A.; AIKAWA, Nadia E.; JESUS, Adriana A.; MORAES, Julio C. B.; MIRAGLIA, Joao; ISHIDA, Maria A.; BUENO, Cleonice; PEREIRA, Rosa M. R.; BONFA, EloisaObjectiveRecent findings demonstrated a reduced immunogenicity of the influenza A H1N1/2009 vaccine in juvenile rheumatic diseases. However, a point of concern is whether the vaccine could induce disease flares. The aim of this study was to assess the disease safety of and the possible influence of disease parameters and therapy on nonadjuvant influenza A H1N1 vaccine response of juvenile systemic lupus erythematosus (SLE) patients. MethodsOne hundred eighteen juvenile SLE patients and 102 healthy controls of a comparable age were vaccinated. Seroprotection rate, seroconversion rate, and factor increase in geometric mean titer (GMT) were calculated and effective immune response was defined by the Food and Drug Administration and the European Committee for Proprietary Medicinal Products vaccine immunologic standards. Disease parameters, treatment, and adverse events were evaluated. ResultsAge was comparable in juvenile SLE patients and controls (mean +/- SD 16.0 +/- 3.5 versus 15.9 +/- 4.5 years; P = 0.26). Three weeks after immunization, seroprotection rate (73.7% versus 95.1%; P < 0.001), seroconversion rate (63.6% versus 91.2%; P < 0.001), GMT (90.8 versus 273.3; P < 0.001), and factor increase in GMT (8.1 versus 19.9; P < 0.001) were significantly lower in juvenile SLE patients versus controls. Nonseroconversion was associated with a higher frequency of patients with a Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score 8 (48.8% versus 24%; P = 0.008) and a higher mean +/- SD current glucocorticoid dosage (18 +/- 21.4 versus 10.5 +/- 12.5 mg/day; P = 0.018). Multivariate logistic regression including a SLEDAI-2K score 8 revealed that only the SLEDAI-2K remained a significant factor for nonseroconversion (odds ratio 0.42, 95% confidence interval 0.18-0.98; P = 0.045). Disease parameters remained stable throughout the study and no severe vaccine adverse events were observed. ConclusionThe present study demonstrated adequate disease safety and is the first to discriminate that high disease activity impairs influenza A H1N1/2009 vaccine antibody production in juvenile SLE, in spite of an overall immune response within recommended levels.