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Pediatric antiphospholipid syndrome (APS) is a rare acquired multisystem autoimmune thromboinflammatory condition characterized by thrombotic and non-thrombotic clinical manifestations. APS in children and adolescents typically presents with large-vessel thrombosis, thrombotic microangiopathy, and, rarely, obstetric morbidity. Non-thrombotic clinical manifestations are frequently seen in pediatric APS and may be present even before the vascular thrombotic events occur. We review insights into the pathogenesis of APS and discuss potential targets for therapy. The identification of multiple immunologic abnormalities in patients with APS reveals molecular targets for current or future treatment. Management strategies, especially for APS in adolescents, require screening for additional prothrombotic risk factors and consideration of counseling regarding contraceptive strategies, lifestyle recommendations, treatment adherence, and mental health issues associated with this autoimmune thrombophilia. The main goal of therapy in pediatric APS is the prevention of thrombosis. The management of acute thrombosis events in children and adolescents is the same as for primary APS, which involves isolated occurrences, and secondary APS, which is seen in association with another autoimmune disease, e.g., systemic lupus erythematosus. A pediatric hematologist should be consulted so other differential thrombophilic conditions can be eliminated. Therapy includes unfractionated heparin or low-molecular-weight heparin followed by vitamin K antagonists. Treatment of catastrophic APS involves triple therapy (anticoagulation, intravenous corticosteroid pulse therapy, and plasma exchange) and may include intravenous immunoglobulin for children and adolescents with this condition. New drugs such as eculizumab and sirolimus seem to be promising drugs for APS.

Made available in DSpace on 2022-04-29T08:46:03Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-01-01 Objective: To evaluate if the 2019-European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) criteria at diagnosis of childhood-onset systemic lupus erythematosus (cSLE) are associated with higher rates of early damage scored by Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) Damage Index (SDI). Methods: This retrospective multicenter study included 670 cSLE patients with ≤5 years of disease duration. All patients fulfilled both 2019-EULAR/ACR and 1997-ACR classification criteria. Total score of 2019-EULAR/ACR criteria and each of its specific domains were assessed at diagnosis as predictors of damage accrual at the last visit, according to the presence of any organ damage (defined by SDI ≥ 1). Results: Median disease duration was 2.8 (IQR 1.8–3.8) years and 200 (29.9%) patients had at least one organ damage (SDI ≥ 1). The most frequent domains were neuropsychiatric (12%), renal (7%), and musculoskeletal (6%). There was a higher frequency of renal (58% vs 43%, p = 0.0004) and neuropsychiatric domain (21% vs 7%, p < 0.0001) of 2019-EULAR/ACR criteria in patients with damage (SDI ≥ 1) compared to those without damage (SDI = 0). Patients scoring renal or neuropsychiatric domains of the 2019-EULAR/ACR criteria at diagnosis were associated with renal damage (odds ratio 9.701, 95% confidence interval 3.773–24.941, p < 0.001) or neuropsychiatric damage (OR 9.480, 95% CI 5.481–16.399, p25 was associated with more overall (SDI ≥ 1) (38% vs 25%, p = 0.0002) and renal damage (11% vs 5%, p = 0.023). Conclusions: The 2019-EULAR/ACR criteria at diagnosis were associated with a higher rate of early damage in cSLE patients, especially for renal and neuropsychiatric damage. Of note, damage was particularly associated with high disease activity at diagnosis and 2019-EULAR/ACR score >25. Pediatric Rheumatology Unit Children’s Institute Hospital das Clinicas HCFMUSP Faculdade de Medicina Universidade de Sao Paulo Division of Rheumatology Hospital das Clinicas HCFMUSP Faculdade de Medicina Universidade de Sao Paulo Pediatric Rheumatology Unit Universidade Federal de Sao Paulo Pediatric Rheumatology Division Sao Paulo State University (UNESP) Pediatric Rheumatology Unit Janeiro Federal University (IPPMG-UFRJ) Pediatric Rheumatology Unit Hospital da Criança de Brasília Jose Alencar Post-graduation Program in Medical Science and Rheumatology Unit University of Brasilia Pediatric Rheumatology Unit Ribeirao Preto Medical School University of Sao Paulo Pediatric Rheumatology Unit Hospital Geral de Fortaleza Pediatric Rheumatology Unit University of Campinas (UNICAMP) Pediatric Rheumatology Unit Pedro Ernesto University Hospital Pediatric Rheumatology Unit Irmandade da Santa Casa de Misericórdia de Sao Paulo Rheumatology Division - Universidade Federal do Rio de Janeiro Hospital Universitário Clementino Fraga Filho Pediatric Rheumatology Unit Federal University of Pará Pediatric Rheumatology Unit Federal University of Bahia Pediatric Rheumatology Unit Hospital Menino Jesus Pediatric Rheumatology Unit Federal University of Pernambuco Pediatric Rheumatology Unit Federal University of Mato Grosso do Sul Pediatric Rheumatology Division Sao Paulo State University (UNESP)

Made available in DSpace on 2020-12-10T20:01:32Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-06-05 Objective This study aimed to assess the safety and immunogenicity of the quadrivalent human papillomavirus (qHPV) vaccination in childhood-onset systemic lupus erythematosus (cSLE) patients. Methods Volunteer cSLE patients aged 9-20 years and healthy controls (HC) were enrolled to receive a two- or three-dose qHPV vaccination schedule from March 2014 to March 2016. Study visits were performed before the first dose, one month after the second and third doses and one year after the first dose. In each study visit, disease activity and adverse events following vaccination were analyzed, and a serum sample was collected for testing antibody concentrations. Participant recruitment was conducted in 15 Brazilian paediatric rheumatology units. Of the 256 cSLE patients included, 210 completed the two- or three-dose schedules; 15 had previously received one dose, and 18 had received two doses of the vaccine. The analysis was based on intention-to-treat so that participants who did not complete the entire study protocol were also included. Results No severe adverse events were related to the vaccination. Disease activity was generally low and remained stable or even improved. The HC presented 100% seropositivity to HPV16 and HPV18, whereas the two- and three-dose cSLE groups presented 93% and 83% versus 97% and 91%, respectively. One year after the first dose, seropositivity of the three-dose cSLE group was 91% to HPV16 and 84% to HPV18. Conclusions HPV vaccination in cSLE patients is safe and immunogenic. Since the seropositivity to HPV16 and HPV18 was higher for the three-dose schedule group, this regimen should be recommended for cSLE patients. Univ Med Ctr Utrecht, Wilhelmina Childrens Hosp, Dept Paediat Immunol & Rheumatol, Utrecht, Netherlands Univ Fed Parana, Hosp Clin, Dept Paediat, Curitiba, Parana, Brazil Univ Sao Paulo, Dept Paediat, Fac Med Ribeirao Preto, Sao Paulo, Brazil Univ Estado Rio De Janeiro, Dept Paediat Rheumatol, Rio De Janeiro, Brazil Univ Sao Paulo, Hosp Clin, Inst Crianca, Dept Paediat Rheumatol,Fac Med, Sao Paulo, Brazil Hosp Infantil Albert Sabin, Dept Paediat Rheumatol, Fortaleza, Ceara, Brazil Univ Florida, Coll Med, Dept Paediat Immunol & Rheumatol, Gainesville, FL USA Univ Estadual Campinas, Dept Paediat Rheumatol, Sao Paulo, Brazil Hosp Crianca Brasilia Jose Alencar, Dept Paediat Rheumatol, Brasilia, DF, Brazil Univ Estadual Paulista, Dept Paediat Rheumatol, Botucatu, SP, Brazil Univ Fed Rio de Janeiro, Inst Puericultura & Pediat Martagao Gesteira IPPM, Dept Paediat Rheumatol, Rio De Janeiro, Brazil Univ Fed Rio de Janeiro, Dept Paediat Rheumatol, Rio De Janeiro, Brazil Hosp Infantil Darcy Vargas, Dept Paediat Rheumatol, Sao Paulo, Brazil Hosp Estadual Infantil Nossa Senhora da Gloria, Dept Paediat Rheumatol, Vitoria, ES, Brazil Santa Casa Sao Paulo, Dept Paediat Rheumatol, Sao Paulo, Brazil Univ Fed Bahia, Dept Paediat Rheumatol, Fac Med, Salvador, BA, Brazil Univ Fed Sao Paulo, Dept Paediat Rheumatol, Sao Paulo, Brazil Hosp Pequeno Principe, Dept Paediat Rheumatol, Curitiba, Parana, Brazil Natl Inst Publ Hlth & Environm RIVM, Ctr Infect Dis Control, Bilthoven, Netherlands Fac Med Barretos FACISB, Dept Paediat Rheumatol, Barretos, Brazil Univ Estadual Paulista, Dept Paediat Rheumatol, Botucatu, SP, Brazil

To assess childhood-onset systemic lupus erythematosus-related antiphospholipid syndrome(cSLE-APS) in a large Brazilian population.A retrospective observational cohort study was carried-out in 27 Pediatric Rheumatology university centers, including 1519 cSLE patients.cSLE-APS was observed in 67/1519 (4%) and was diagnosed at disease onset in 39/67 (58%). The median disease duration was 4.9 (0-17) years. Thrombosis recurrences were evidenced in 18/67 (27%) cSLE-APS patients. The most frequent thrombosis sites in cSLE-APS patients were: venous thrombosis in 40/67 (60%), especially deep vein thrombosis in 29/40 (72%); arterial thrombosis in 35/67 (52%), particularly stroke; small vessels thrombosis in 9/67 (13%) and mixed thrombosis in 3/67 (4%). Pregnancy morbidity was observed in 1/67 (1%). Non-thrombotic manifestation associated to cSLE-APS occurred in 21/67 (31%), mainly livedo reticularis in 14/67 (21%), valvar thickening in 4/67 (6%) and valvar vegetations not related to infections in 2/67 (3%). None of them had catastrophic APS. Further analysis demonstrated that the median of SLICC/ACR-DI [1(0-5) vs. 0(0-7),p 0.0001] was significantly higher in cSLE-APS patients compared to cSLE without APS. The frequencies of cerebrovascular disease (40% vs. 1%,p 0.0001), polyneuropathy (9% vs. 1%,p 0.0001), SLICC/ACR-DI ≥1 (57% vs. 27%, p 0.0001) and intravenous cyclophosphamide use (59% vs. 37%, p 0.0001) were significantly higher in the former group.Our large multicenter study demonstrated that cSLE-APS was a rare condition, occurring during disease course with a high accrual damage. Central and peripheral neuropsychiatric involvements were distinctive features of this autoimmune thrombosis.

Background: Concerns about the safety and efficacy of vaccinations in patients with pediatric rheumatic diseases, such as juvenile dermatomyositis, have led to contradictions and low vaccination coverage in this group, who are at a higher risk of infections, including by human papillomavirus (HPV). Although HPV vaccine should be recommended for all juvenile dermatomyositis patients, there is a lack of data to support the safety of this vaccine. The aim of this study was to assess the safety and immunogenicity of the quadrivalent HPV vaccination in juvenile dermatomyositis patients.Methods: Juvenile dermatomyositis patients aged from 9-20 years and healthy controls were enrolled to receive a 3-dose schedule of quadrivalent HPV vaccination from March/2014 until March/2016. Study visits were performed before the first dose, one month after the second and third doses and one year after the first dose. Participants completed a diary of possible adverse events following each dose, and disease activity was measured. At each visit, serum samples was collected for testing antibody concentrations. Participants recruitment was conducted in ten Brazilian centers. From 48 eligible patients, 42 completed the 3 doses schedule of the vaccine (5 patients had received doses previously). The McNemar test and the Kappa concordance coefficient were applied to compare the disease activity scores used for juvenile dermatomyositis patients between quadrivalent HPV vaccine doses and before the vaccination. The software used was SAS 9.4.Results: No severe adverse events were related to the vaccination. The disease activity scores were usually low, and remained stable, or even improved during the follow-up. After three vaccine doses the juvenile dermatomyositis group presented seropositivity of 100% for HPV16 and 97% for HPV18, similarly to the control group who presented 100% for both. One year after the first dose the seropositivity for the patients group was 94% for both HPV types.Conclusions: The HPV vaccination in juvenile dermatomyositis patients is safe and immunogenic. Since the seropositivity against HPV16 and HPV18 was very high after the 3-dose schedule, this regimen should be recommended for juvenile dermatomyositis patients.

Background To our knowledge the influence of ethnic background in childhood-onset SLE (cSLE) presentation was not evaluated in a large population of Latin American country. Objectives To assess demographic data, clinical manifestations, laboratory abnormalities and disease activity score in cSLE patients according to ethnic groups at diagnosis Methods This multicenter study included cSLE patients(ACR criteria) followed in 27 Pediatric Rheumatology services of Brazil. Ethnicities were classified in four groups according to the parents’ and all four grandparents’ self-reported ethnicity. The statistical analysis was performed using the Bonferroni’s correction(p Results According to ethnic groups, 1,537 cSLE patients were classified in: Caucasian (n=786), African-Latin American(n=526), Asian(n=8) and others/unknown(n=217). Comparisons between 1,312 African-Latin American and Caucasian revealed similar median age at cSLE diagnosis[12.2(2.6-18) vs. 12.1(0.3-18) years,p=0.234], time interval to diagnosis[0.25(0-12) vs. 0.3(0-10) years,p=0.034] and SLEDAI-2K score[14(0-55) vs. 14(0-63),p=0.781] in both groups. The mean number of diagnostic criteria according to SLICC(6.47±1.911 vs. 5.81±1.631, p Conclusion Our study demonstrated that disease presentation severity of African-Latin American cSLE patients is comparable to Caucasian. Mucocutaneous manifestations and autoantibodies profile were the only distinctive features of the former group. The unique mixed background of Brazilian patients probably minimized race diversity spectrum of these patients. Disclosure of Interests None declared

Made available in DSpace on 2019-10-06T16:49:50Z (GMT). No. of bitstreams: 0 Previous issue date: 2019-01-01 Objective: To evaluate the influence of ethnicity in presentation of childhood-onset systemic lupus erythematosus (cSLE) patients. Methods: This multicenter study included cSLE patients (American College of Rheumatology criteria) followed in 27 Pediatric Rheumatology services of Brazil. Ethnicities were classified in four groups according to the parents’ and all four grandparents’ self-reported ethnicity. The statistical analysis was performed using the Bonferroni’s correction (p < 0.0027). Results: According to ethnic groups, 1537 cSLE patients were classified in Caucasian (n = 786), African-Latin American (n = 526), Asian (n = 8), and others/unknown (n = 217). Comparisons between 1312 African-Latin American and Caucasian revealed similar median age at cSLE diagnosis [12.2(2.6–18) vs. 12.1(0.3–18) years, p = 0.234], time interval to diagnosis [0.25(0–12) vs. 0.3(0–10) years, p = 0.034], and SLEDAI-2K score [14(0–55) vs. 14(0–63), p = 0.781] in both groups. The mean number of diagnostic criteria according to SLICC (6.47 ± 1.911 vs. 5.81 ± 1.631, p < 0.0001) and frequencies of maculopapular lupus rash (8% vs. 3%, p < 0.0001), palate oral ulcers (17% vs. 11%, p = 0.001), tongue oral ulcers (4% vs. 1%, p = 0.001), and nonscarring alopecia (29% vs. 16%, p < 0.0001) were significantly higher in African-Latin American, whereas malar rash (45% vs. 58%, p < 0.0001) was more frequent in Caucasian. The presence of anti-phospholipid antibody (23% vs. 12%, p < 0.0001), low complement levels (58% vs. 41%, p < 0.0001), and isolated direct Coombs test (10% vs. 5%, p = 0.001) was also significantly higher in the former group. Conclusions: Our study demonstrated that disease presentation severity of African-Latin American cSLE patients is comparable with Caucasian. Mucocutaneous manifestations and autoantibodies profile were the only distinctive features of the former group. The unique mixed background of Brazilian patients probably minimized race diversity spectrum of these patients.Key Points• Our study demonstrated that disease presentation severity of African-Latin American cSLE patients is comparable with Caucasian.• Mucocutaneous manifestations and autoantibodies profile were the only distinctive features of African-Latin American cSLE patients.• African-Latin American cSLE patients had more often anti-phospholipid antibodies and hypocomplementemia.• The unique mixed background of Brazilian patients probably minimized race diversity spectrum of these patients. Pediatric Rheumatology Unit Children’s Institute Hospital das Clinicas HCFMUSP Faculdade de Medicina Universidade de Sao Paulo, Av. Dr. Eneas Carvalho Aguiar, 647 - Cerqueira César Pediatric Rheumatology Unit Hospital Jose Alencar Division of Rheumatology Hospital das Clinicas HCFMUSP Faculdade de Medicina Universidade de Sao Paulo Pediatric Rheumatology Unit Universidade Federal de Sao Paulo Pediatric Rheumatology Division Sao Paulo State University (UNESP) Pediatric Rheumatology Unit University of Campinas (UNICAMP) Pediatric Rheumatology Unit Ribeirao Preto Medical School – University of Sao Paulo Pediatric Rheumatology Unit Hospital Geral de Fortaleza Pediatric Rheumatology Unit Rio de Janeiro Federal University (IPPMG-UFRJ) Pediatric Rheumatology Unit Pedro Ernesto University Hospital Pediatric Rheumatology Unit Albert Sabin Children’s Hospital Pediatric Rheumatology Unit Hospital Darcy Vargas Pediatric Rheumatology Unit Irmandade da Santa Casa de Misericórdia de Sao Paulo Rheumatology Division - Universidade Federal do Rio de Janeiro Hospital Universitário Clementino Fraga Filho Pediatric Rheumatology Unit Lauro Vanderley University Hospital Pediatric Rheumatology Unit Federal University of Pará Pediatric Rheumatology Unit Obras Sociais Irmã Dulce Pediatric Rheumatology Unit Hospital Evangélico de Curitiba Pediatric Rheumatology Unit Hospital Criança Conceição Pediatric Rheumatology Unit Federal University of Pernambuco Pediatric Rheumatology Unit Federal University of Mato Grosso do Sul Pediatric Rheumatology Unit Federal University of Bahia Pediatric Rheumatology Unit University of Brasilia Pediatric Rheumatology Unit Federal University of Minas Gerais Pediatric Rheumatology Unit Pontifícia Catholic University of Sorocaba Pediatric Rheumatology Division Sao Paulo State University (UNESP)

Made available in DSpace on 2018-12-11T17:24:18Z (GMT). No. of bitstreams: 0 Previous issue date: 2018-09-01 Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Objective: The objective of this study was to compare demographic data, clinical/laboratorial features and disease activity at diagnosis in three different groups with distinct time intervals between onset of signs/symptoms and disease diagnosis. Methods: A multicenter study was performed in 1555 childhood-onset systemic lupus erythematosus (American College of Rheumatology criteria) patients from 27 pediatric rheumatology services. Patients were divided into three childhood-onset systemic lupus erythematosus groups: A: short time interval to diagnosis (500 mg/day (48% vs. 45% vs. 36%, P = 0.002) and low complement levels (81% vs. 81% vs. 71%, P < 0.0001) compared with groups A or B. Conclusions: Our large Brazilian multicenter study demonstrated that for most childhood-onset systemic lupus erythematosus patients, diagnosis is delayed probably due to mild disease onset. Conversely, the minority has a very short time interval to diagnosis and a presentation with a more severe and active multisystemic condition. Pediatric Rheumatology Unit Hospital das Clinicas HCFMUSP Faculdade de Medicina Universidade de Sao Paulo Pediatric Rheumatology Unit Universidade Federal de Sao Paulo Division of Rheumatology Hospital das Clinicas HCFMUSP Faculdade de Medicina Universidade de Sao Paulo Pediatric Rheumatology Division Sao Paulo State University (UNESP) Pediatric Rheumatology Unit University of Campinas (UNICAMP) Pediatric Rheumatology Unit University of Sao Paulo Pediatric Rheumatology Unit Hospital Geral de Fortaleza Pediatric Rheumatology Unit Rio de Janeiro Federal University (IPPMG-UFRJ) Pediatric Rheumatology Unit Hospital Jose Alencar Pediatric Rheumatology Unit Pedro Ernesto University Hospital Pediatric Rheumatology Unit Albert Sabin Children’s Hospital Pediatric Rheumatology Unit Hospital Darcy Vargas Pediatric Rheumatology Unit Irmandade da Santa Casa de Misericórdia de Sao Paulo Rheumatology Division Hospital Universitário Clementino Fraga Filho Pediatric Rheumatology Unit Lauro Vanderley University Hospital Pediatric Rheumatology Unit Federal University of Pará Pediatric Rheumatology Unit Obras Sociais Irmã Dulce Pediatric Rheumatology Unit Hospital Evangélico de Curitiba Pediatric Rheumatology Unit Hospital Criança Conceição Pediatric Rheumatology Unit Federal University of Pernambuco Pediatric Rheumatology Unit Federal University of Mato Grosso do Sul Pediatric Rheumatology Unit Federal University of Bahia Pediatric Rheumatology Unit University of Brasilia Pediatric Rheumatology Unit Federal University of Minas Gerais Pediatric Rheumatology Unit Hospital Municipal Piedade Pediatric Rheumatology Division Sao Paulo State University (UNESP) FAPESP: 03756-4