KATIA TOMIE KOZU
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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- 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.
- Anti-ribosomal P antibody: a multicenter study in childhood-onset systemic lupus erythematosus patients(2017) VALOES, C. C. M.; MOLINARI, B. C.; PITTA, A. C. G.; GORMEZANO, N. W. S.; FARHAT, S. C. L.; KOZU, K.; SALLUM, A. M. E.; APPENZELLER, S.; SAKAMOTO, A. P.; TERRERI, M. T.; PEREIRA, R. M. R.; MAGALHAES, C. S.; FERREIRA, J. C. O. A.; BARBOSA, C. M.; GOMES, F. H.; BONFA, E.; SILVA, C. A.Objectives: Anti-ribosomal P protein (anti-P) autoantibodies are highly specific for systemic lupus erythematosus (SLE). However, the evaluation of this autoantibody in childhood-onset SLE (cSLE) populations has been limited to a few small series, hampering the interpretation of the clinical and laboratorial associations. Therefore, the objective of this multicenter cohort study was to evaluate demographic, clinical/laboratorial features, and disease damage score in cSLE patients with and without the presence of anti-P antibody. Methods: This was a retrospective multicenter study performed in 10 pediatric rheumatology services of Sao Paulo state, Brazil. Anti-P antibodies were measured by ELISA in 228 cSLE patients. Results: Anti-P antibodies were observed in 61/228 (27%) cSLE patients. Frequencies of cumulative lymphadenopathy (29% vs. 15%, p = 0.014), acute confusional state (13% vs. 5%, p = 0.041), mood disorder (18% vs. 8%, p = 0.041), autoimmune hemolytic anemia (34% vs. 15%, p = 0.001), as well as presence of anti-Sm (67% vs. 40%, p = 0.001), anti-RNP (39% vs. 21%, p = 0.012) and anti-Ro/SSA antibodies (43% vs. 25%, p = 0.016) were significantly higher in cSLE patients with anti-P antibodies compared to those without these autoantibodies. A multiple regression model revealed that anti-P antibodies were associated with autoimmune hemolytic anemia (odds ratio (OR) = 2.758, 95% confidence interval (CI): 1.304-5.833, p = 0.008) and anti-Sm antibody (OR = 2.719, 95% CI: 1.365-5.418, p = 0.004). The SLICC/ACR damage index was comparable in patients with and without anti-P antibodies (p = 0.780). Conclusions: The novel association of anti-P antibodies and autoimmune hemolytic anemia was evidenced in cSLE patients and further studies are necessary to determine if anti-P titers may vary with this hematological manifestation.
conferenceObject Distinct Clinical Correlates of Immune Thrombocytopenic Purpura at Diagnosis of Childhood-Onset and Adult SLE(2016) ESTEVES, Gladys; GORMEZANO, Natali W.; PEREIRA, Oriany; KERN, David; KOZU, Katia T.; PEREIRA, Rosa M. R.; SILVA, Clovis A.; BONFA, Eloisa; AIKAWA, Nadia E.- Symptomatic polyautoimmunity at diagnosis of 1463 childhood-onset lupus: A Brazilian multicenter study(2018) SETOUE, Debora N.; PITTA, Ana C.; FIOROT, Fernanda J.; NASTRI, Mariana M.; NOVAK, Glaucia V.; MOLINARI, Beatriz C.; OLIVEIRA, Juliana C.; GORMEZANO, Natali W.; SAKAMOTO, Ana P.; TERRERI, Maria T.; PEREIRA, Rosa M.; SAAD-MAGALHAES, Claudia; SALLUM, Adriana M.; KOZU, Katia; FRAGA, Melissa M.; PIOTTO, Daniela P.; CLEMENTE, Gleice; MARINI, Roberto; GOMES, Hugo R.; RABELO-JUNIOR, Carlos N.; FELIX, Marta M.; RIBEIRO, Maria C.; ALMEIDA, Rozana G.; ASSAD, Ana P.; SACCHETTI, Silvana B.; BARROS, Leandra C.; BONFA, Eloisa; SILVA, Clovis A.Objective: To evaluate symptomatic polyautoimmunity (PA) at childhood-onset systemic lupus erythematosus (cSLE) diagnosis, and its association with demographic data, disease activity, clinical manifestations and laboratorial abnormalities in a large Brazilian cSLE population. Methods: A multicenter retrospective study was performed in 1463 cSLE(ACR criteria) patients from 27 Pediatric Rheumatology services. Symptomatic PA was defined according to the presence of more than one concomitant autoimmune disease(AD) and symptomatic multiple autoimmune syndrome(MAS) was defined as three or more AD. An investigator meeting was held to define the protocol. Demographic data, SLICC classification criteria and SLEDAI-2K were evaluated. Results: At cSLE diagnosis symptomatic PA was observed in 144/1463(9.8%) and symptomatic MAS occurred in solely 10/1463(0.7%). In the former group the more frequently observed associated AD were Hashimoto thyroiditis n = 42/144(29%), antiphospholipid syndrome n = 42/144(29%), autoimmune hepatitis n = 26/144(18%) and type 1 diabetes mellitus n = 23/144(15.9%). Further comparisons between cSLE patients with and without PA showed a higher median age(p = 0.016) and lower mean SLICC criteria (p = 0.039) in those with PA. Additionally, these cSLE patients had less renal involvement(35% vs. 44%, p = 0.038) and red blood cell cast(6% vs. 12%, p = 0.042) and more antiphospholipid antibodies(29% vs. 15%, p < 0.0001). Conclusions: Approximately 10% of cSLE had symptomatic PA at diagnosis, particularly endocrine autoimmune disorders and antiphospholipid syndrome. Lupus was characterized by a mild disease onset and MAS was infrequently evidenced. Further studies are necessary to determine if this subgroup of cSLE patients have a distinct genetic background with a less severe disease and a better long-term outcome.
conferenceObject Chronic Arthritis in Systemic Lupus Erythematosus: Distinct Features in 336 Pediatric and 1,830 Adult Patients(2015) GORMEZANO, Natali W.; SILVA, Clovis A.; AIKAWA, Nadia E.; BARROS, Diego L.; SILVA, Mariana A. da; OTSUZI, Carini I.; KOZU, Katia T.; SEGURO, Luciana; PEREIRA, Rosa M. R.; BONFA, Eloisa- Distinct clinical correlates of immune thrombocytopenic purpura at diagnosis of childhood-onset and adult SLE(2018) ESTEVES, Gladys Cherres Xavier; GORMEZANO, Natali Weniger Spelling; PEREIRA, Oriany L.; KERN, David; SILVA, Clovis Almeida; PEREIRA, Rosa Maria Rodrigues; KOZU, Katia Tomie; BONFA, Eloisa; AIKAWA, Nadia EmiObjectives: To compare clinical and laboratorial features between childhood-onset systemic lupus erythematosus (cSLE) and adult SLE (aSLE) at concomitant diagnosis of immune thrombocytopenic purpura (ITP).Methods: This study evaluated 56 cSLE and 73 aSLE patients regularly followed at Pediatric and Rheumatology Divisions of the same University hospital with ITP (platelets count <100,000/mm(3) in the absence of other causes) at lupus onset.Results: Median current age was 11.6 and 27.3 years in cSLE and aSLE, respectively. cSLE had a higher frequency of ITP compared to aSLE (17% vs. 4%, p<.0001) and the former group had more hemorrhagic manifestations (36% vs. 16%, p=.0143). Constitutional symptoms and reticuloendothelial manifestations (p<.05), as well as pericarditis (25% vs. 10%, p=.029) and central nervous system (CNS) involvement (30% vs. 14%, p=.029) were more common in cSLE. Conversely, in aSLE, ITP was solely associated with cutaneous and articular involvements (p<.05). Concerning treatment, intravenous methylprednisolone, intravenous immunoglobulin, blood transfusion and platelets transfusion were more frequently used in the cSLE population (p<.05).Conclusion: ITP at cSLE has distinct features compared to aSLE with a more severe presentation characterized by concomitant constitutional/reticuloendothelial manifestations, CNS involvement and hemorrhagic manifestation. These findings reinforce the need for a more aggressive treatment in this age group.
conferenceObject ANTI-RO/SSA and/or ANTI-La/SSB Antibodies: Association with Mild LUPUS Manifestations in 645 Childhood-Onset Systemic LUPUS Erythematosus(2016) NOVAK, Glaucia V.; MARQUES, Mariana; BALBI, Verena; GORMEZANO, Natali W.; KOZU, Katia T.; SAKAMOTO, Ana Paula; PEREIRA, Rosa M. R.; TERRERI, Maria Teresa; MAGALHAES, Claudia S.; SR., Silvana B. Sacchetti; SALLUM, Adriana M. E.; SR., Roberto Marini; FERRIANI, Virginia; BARBOSA, Cassia M.; CASTRO, Tania C. M.; RAMOS, Valeria C.; BONFA, Eloisa; SILVA, Clovis A.- Anti-RO/SSA and anti-La/SSB antibodies: Association with mild lupus manifestations in 645 childhood-onset systemic lupus erythematosus(2017) NOVAK, Glaucia V.; MARQUES, Mariana; BALBI, Verena; GORMEZANO, Natali W. S.; KOZU, Katia; SAKAMOTO, Ana P.; PEREIRA, Rosa M. R.; TERRERI, Maria T.; MAGALHAES, Claudia S.; GUARIENTO, Andressa; SALLUM, Adriana M. E.; MARINI, Roberto; FERRIANI, Virginia Paes Leme; BARBOSA, Cassia Maria; CASTRO, Tania Caroline Monteiro de; RAMOS, Valeria C.; BONFA, Eloisa; SILVA, Clovis A.Background: To our knowledge there are no studies assessing anti-Ro/SSA and anti-La/SSB autoantibodies in a large population of childhood-systemic lupus erythematosus (cSLE) patients. Methods: This was a retrospective multicenter cohort study performed in 10 Pediatric Rheumatology services, Sao Paulo state, Brazil. Anti-Ro/SSA and anti-La/SSB antibodies were measured by enzyme linked immunosorbent assay (ELISA) in 645 cSLE patients. Results: Anti-Ro/SSA and anti-La/SSB antibodies were evidenced in 209/645 (32%) and 102/645 (16%) of cSLE patients, respectively. Analysis of cSLE patients with and without anti-Ro/SSA antibodies revealed higher frequencies of malar rash (79% vs. 71%, p = 0.032), photosensitivity (73% vs. 65%, p = 0.035), cutaneous vasculitis (43% vs. 35%, p = 0.046) and musculoskeletal involvement (82% vs. 75%, p = 0.046) in spite of long and comparable disease duration in both groups (4.25 vs. 4.58 years, p = 0.973). Secondary Sjogren syndrome was observed in only five patients with this antibody (2.5% vs. 0%, p = 0.0035), two of them with concomitant anti-La/SSB. The presence of associated autoantibodies: anti-Sm (50% vs. 30%, p < 0.0001), anti-RNP (39% vs. 21%, p < 0.0001) and anti-ribossomal P protein (46% vs. 21%, p = 0.002) was also significantly higher in patients with anti-Ro/SAA antibodies. Further evaluation of cSLE patients with the presence of anti-La/SSB antibodies compared to those without these autoantibodies showed that the frequency of alopecia (70% vs. 51%, p = 0.0005), anti-Sm (59% vs. 31%, p < 0.0001) and anti-RNP (42% vs. 23%, p < 0.0001) were significantly higher in the former group. Conclusions: Our large multicenter cohort study provided novel evidence in cSLE that anti-Ro/SSA and/or anti-La/SSB antibodies were associated with mild manifestations, particularly cutaneous and musculoskeletal. Secondary Sjogren syndrome was rarely observed in these patients, in spite of comparable frequencies of anti-Ro/SSA and/or anti-La/SSB reported for adult SLE.