Risk factors for mortality in 1528 Brazilian childhood-onset systemic lupus erythematosus patients.

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.

Patient-Reported Outcomes Among Patients Ages Two to Seventeen Years With Polyarticular-Course Juvenile Idiopathic Arthritis Treated With Subcutaneous Abatacept: Two-Year Results From an International Phase III Study.

OBJECTIVE: To describe longitudinal changes in patient-reported outcomes (PROs) in children with polyarticular-course juvenile idiopathic arthritis (pJIA) treated with subcutaneous abatacept. METHODS: Secondary analysis of a single-arm, open-label 24-month study of patients ages 6-17 years and 2-5 years. PROs included Childhood Health Assessment Questionnaire-Disability Index (CHAQ-DI), parent global assessment of child well-being (PaGA), pain assessment, and Activity Limitation Questionnaire (ALQ). Clinical outcomes included 50% or greater improvement in JIA American College of Rheumatology (ACR) criteria, clinically inactive disease, and Juvenile Arthritis Disease Activity Score. RESULTS: For the 6- to 17-year-old (n = 173) and 2- to 5-year-old (n = 46) cohorts, respectively, median (Q1, Q3) changes from baseline in CHAQ-DI at months 4 and 24 were -0.3 (-0.8, 0.0) and -0.5 (-1.0, -0.1), and -0.4 (-0.8, 0.0) and -0.5 (-1.0--0.1). Median pain scores were below cutoff threshold for clinically relevant pain (<35 mm) by month 1 (6 to 17 years, 32.3 mm; 2 to 5 years, 25.7 mm), reaching a nadir at month 24 (6 to 17 years, 6.0 mm; 2 to 5 years, 2.0 mm). For the 6- to 17-year-old and 2- to 5-year-old cohorts, respectively, median PaGA scores were 47.8 (n = 172) and 42.1 (n = 46) at baseline and 6.3 (n = 107) and 2.0 (n = 37) at month 24. In both cohorts, ALQ components improved from baseline to month 4 and were largely maintained to month 24. Clinical outcomes improved through to month 24. CONCLUSION: Early and sustained PRO improvements were reported in this phase III, open-label trial of subcutaneous abatacept in patients with pJIA.

Chronic kidney disease in patients with childhood-onset systemic lupus erythematosus.

BACKGROUND: Lupus nephritis (LN) is a frequent manifestation of childhood-onset systemic lupus erythematosus (cSLE) with a potential risk for kidney failure and poor outcomes. This study aimed to evaluate stages III, IV, and V of chronic kidney disease (CKD) and investigate risk factors for CKD in cSLE patients. METHODS: We performed a nationwide observational cohort study in 27 pediatric rheumatology centers, including medical charts of 1528 cSLE patients. Data were collected at cSLE diagnosis, during follow-up, and at last visit or death, between September 2016 and May 2019. RESULTS: Of 1077 patients with LN, 59 (5.4%) presented with CKD, 36/59 (61%) needed dialysis, and 7/59 (11.8%) were submitted for kidney transplantation. After Bonferroni's correction for multiple comparisons (p < 0.0013), determinants associated with CKD were higher age at last visit, urinary biomarker abnormalities, neuropsychiatric involvement, higher scores of disease activity at last visit and damage index, and more frequent use of methylprednisolone, cyclosporine, cyclophosphamide, and rituximab. In the regression model analysis, arterial hypertension (HR = 15.42, 95% CI = 6.12-38.83, p ≤ 0.001) and biopsy-proven proliferative nephritis (HR = 2.83, 95%CI = 1.70-4.72, p ≤ 0.001) increased the risk of CKD, while children using antimalarials had 71.0% lower CKD risk ((1.00-0.29) × 100%) than children not using them. The Kaplan-Meier comparison showed lower survival in cSLE patients with biopsy-proven proliferative nephritis (p = 0.02) and CKD (p ≤ 0.001). CONCLUSIONS: A small number of patients manifested CKD; however, frequencies of dialysis and kidney transplantation were relevant. This study reveals that patients with cSLE with hypertension, proliferative nephritis, and absence of use of antimalarials exhibited higher hazard rates of progression to CKD. A higher resolution version of the Graphical abstract is available as Supplementary information.

Childhood-onset systemic lupus erythematosus-related antiphospholipid syndrome: A multicenter study with 1519 patients.

OBJECTIVE: To assess childhood-onset systemic lupus erythematosus-related antiphospholipid syndrome(cSLE-APS) in a large Brazilian population. METHODS: A retrospective observational cohort study was carried-out in 27 Pediatric Rheumatology university centers, including 1519 cSLE patients. RESULTS: 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. CONCLUSIONS: 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.

Disease presentation of 1312 childhood-onset systemic lupus erythematosus: influence of ethnicity.

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.

Screening for Attenuated Forms of Mucopolysaccharidoses in Patients with Osteoarticular Problems of Unknown Etiology.

INTRODUCTION: The mucopolysaccharidoses (MPS) are a group of 11 inborn errors of metabolism (IEM) which are part of the lysosomal storage diseases (LSDs). The MPS are multisystemic conditions that affect the entire body, with variations in the clinical presentation, having specific treatments available depending on the type of MPS. Nearly all MPS disorders compromise the osteoarticular system in different ways, and virtually all patients have abnormal urinary excretion of glycosaminoglycans (GAGs). MPS are rare diseases that are underdiagnosed due to health-care professionals' lack of awareness, to poor access to screening and diagnostic methods, and to their extensive clinical heterogeneity. Attenuated forms may occur, which can make diagnosis of MPS even more difficult. METHODS: This study was conducted prospectively from March 2012 to January 2014 and included 55 patients at rheumatology and/or orthopedic services in Porto Alegre, Brazil. The screened patients presented with articular manifestations with no defined etiology. These patients were screened by quantitative and qualitative assessment of urinary GAGs. RESULTS AND DISCUSSION: Among the 55 cases investigated, one 15-year-old patient exhibited increased urinary GAG excretion; this patient was subsequently diagnosed with an attenuated form of MPS II, which was previously undetected. CONCLUSION: Although the proportion of patients with MPS identified in the study sample was small (1/55), this study shows that these diseases are underdiagnosed and that systematic screening can help identify patients who may benefit from specific treatments already available for several MPS types.

Cobertura vacinal contra influenza e motivos da não vacinação em crianças com idade de risco internadas em hospital terciário / Immunization against influenza and the reasons for non-immunization in children under age of risk hospitalized in tertiary hospital

Introdução: As crianças menores de 2 anos de idade apresentam importante fator de risco para internação e mortalidade por Influenza A H1N1. Morte é um desfecho incomum, mas seu risco é maior nesta faixa etária, especialmente, se há comorbidades associadas. As complicações incluem pneumonia viral e infecção bacteriana secundária. A principal intervenção preventiva é a imunização. O objetivo deste estudo foi descrever o percentual pediátrico imunizado, em duas campanhas consecutivas, verificar o motivo da não vacinação e comparar a frequência vacinal nos anos de 2012 e 2013. Métodos: Estudo de série histórica, abrangendo crianças internadas na faixa etária de risco - seis meses a dois anos. Foram feitos a revisão da caderneta vacinal e o inquérito aos responsáveis pelo paciente para identificar quem havia indicado a vacinação e qual o motivo da não vacinação. Resultados: Foram estudadas 191 crianças em 2012, e 226 em 2013, que se encontravam na faixa etária de risco. Em 2012, 71,2% dos pacientes foram vacinados e em 2013, 79,5% (P=0,05). A campanha foi o maior estímulo para a vacinação em 69% dos casos, e as principais causas da não vacinação foram gripe (31,4%) e desinformação (22,5%). Conclusão: Comparando os dois anos, verificou-se não haver diferença entre as coberturas vacinais, embora ainda permaneçam aquém do resultado registrado nacionalmente. A perda da campanha ainda está relacionada à gripe, neste período, fato que não é contraindicação. No entanto, ainda permanece um fator importante de impedimento, inclusive dos centros de referência em vacinação, como as Unidades Básicas de Saúde (AU)

Introduction: Children under 2 years of age present a significant risk factor for hospitalization and mortality from influenza A, H1N1. Death is an unusual outcome, but the risk is higher in this age group, especially if there are associated comorbidities. Complications include viral pneumonia and secondary bacterial infection. The main preventive intervention is immunization. The aim of this study was to describe the percentage of immunized children in two consecutive campaigns, check the reason for non-vaccination and compare the vaccination rate in years 2012 and 2013. Methods: Historical series study, including hospitalized children in the age group of risk, i.e., from six months to two years. Vaccination records were reviewed and a survey was carried out with parents/caregivers to identify who had indicated vaccination and the reason for non-vaccination. Results: 191 children were studied in 2012 and 226 in 2013, who were in the age group of risk. In 2012, 71.2% of patients were vaccinated and in 2013, 79.5% (P = 0.05). The campaign was the greatest stimulus for vaccination in 69% of cases, and the main causes of non-vaccination were influenza A (31.4%) and lack of information (22.5%). Conclusion: Comparing the two years, no difference in vaccination coverage was found, although the vaccination rates still remained below the nationally reported outcomes. During this period, missing the campaign was still related to the flu, a condition that is not a contraindication. However, it still remains an important factor of non-vaccination, even in the referral centers for vaccination, such as Basic Health Units (AU)

An infant with acrodermatitis continua of Hallopeau: successful treatment with thalidomide and UVB therapy.

Acrodermatitis Continua of Hallopeau is a rare, chronic, recurrent disorder classified as a form of pustular psoriasis, and most cases affect one or two digits. It tends to be resistant to both topical and systemic treatments for psoriasis. We present an infant with Acrodermatitis Continua of Hallopeau affecting nineteen nails, with an excellent response to the combination of thalidomide and ultraviolet B phototherapy.

Association of the HLA-G 14-bp insertion/deletion polymorphism with juvenile idiopathic arthritis and rheumatoid arthritis.

We tested the possible association of the 14-bp polymorphism of the HLA-G gene in the course of two inflammatory diseases, rheumatoid arthritis (RA) and juvenile idiopathic arthritis (JIA). Patients and controls were genotyped for the 14-bp polymorphism by polymerase chain reaction with specific primers for the exon 8 of the human leukocyte antigen (HLA)-G gene and the amplified fragment was visualized in a 6% polyacrylamide gel. A total of 106 JIA patients, 265 RA patients, 356 healthy adults and 85 healthy children were genotyped for the 14-bp polymorphism. Female JIA patients presented a higher frequency of the -14 bp allele when compared with female healthy children (0.743 and 0.500, corrected P=0.003), which reflected in the JIA group as a whole. This increased frequency of the -14-bp allele was observed in all JIA subtypes. In RA patients, no differences in allelic and genotypic frequencies were observed between patients and controls. No correlations were observed among genotype and disease severity or clinical manifestations. Our data suggest that the HLA-G -14 bp allele is probably a risk factor for JIA, mainly in females. Considering the differences observed in relation to gender, we suggest that hormonal differences can interfere with the development of JIA. Considering the RA patients, our data agree with results from the literature and highlight the differences in the etiology of RA and JIA.

The provisional Paediatric Rheumatology International Trials Organisation/American College of Rheumatology/European League Against Rheumatism Disease activity core set for the evaluation of response to therapy in juvenile dermatomyositis: a prospective validation study.

OBJECTIVE: To validate a core set of outcome measures for the evaluation of response to treatment in patients with juvenile dermatomyositis (DM). METHODS: In 2001, a preliminary consensus-derived core set for evaluating response to therapy in juvenile DM was established. In the present study, the core set was validated through an evidence-based, large-scale data collection that led to the enrollment of 294 patients from 36 countries. Consecutive patients with active disease were assessed at baseline and after 6 months. The validation procedures included assessment of feasibility, responsiveness, discriminant and construct ability, concordance in the evaluation of response to therapy between physicians and parents, redundancy, internal consistency, and ability to predict a therapeutic response. RESULTS: The following clinical measures were found to be feasible, and to have good construct validity, discriminative ability, and internal consistency; furthermore, they were not redundant, proved responsive to clinically important changes in disease activity, and were associated strongly with treatment outcome and thus were included in the final core set: 1) physician's global assessment of disease activity, 2) muscle strength, 3) global disease activity measure, 4) parent's global assessment of patient's well-being, 5) functional ability, and 6) health-related quality of life. CONCLUSION: The members of the Paediatric Rheumatology International Trials Organisation, with the endorsement of the American College of Rheumatology and the European League Against Rheumatism, propose a core set of criteria for the evaluation of response to therapy that is scientifically and clinically relevant and statistically validated. The core set will help standardize the conduct and reporting of clinical trials and assist practitioners in deciding whether a child with juvenile DM has responded adequately to therapy.

Lúpus eritematoso sistêmico juvenil: resultados do estudo multicêntrico nacional / Juvenile systemic lupus erythematosus: results of the multicentric national study

Objetivo: estudar as características clínicas e demográficas de crianças e adolescentes brasileiros com lúpus eritematoso sistêmico juvenil (LESj), seguidos em centros de referência em Reumatologia Pediátrica. Métodos: o estudo foi multicêntrico retrospectivo (análise de prontuários) e envolveu 12 centros de São Paulo, Rio de Janeiro, Goiás, Rio Grande do Norte e Rio Grande do Sul. Foram analisados 280 prontuários de crianças e adolescentes com LESj dos quais 234 eram do sexo feminino (83,6%). A idade de início variou de 1 a 16 anos, com média de 11,4 anos. Foram analisados os dados clínicos e laboratoriais iniciais e de seguimento. Para o cálculo da taxa de mortalidade foram excluídos os pacientes que abandonaram o seguimento. Resultados: a presença de anticorpos antinucleares (AAN) foi descrita em 259 pacientes (93%). As manifestações iniciais mais freqüentes foram: artrite (73%), citopenia (67%), presença de anti-DNA (59%), fotossensibilidade (50%) e nefrite (45%). O comprometimento do sistema nervoso central foi observado em 15% dos pacientes, sendo que destes 50% apresentaram convulsões e 38% psicose lúpica. Vinte e sete pacientes (9,7%) abandonaram o acompanhamento médico. Quinze dos 253 pacientes restantes (5,9% evoluíram para óbito durante o seguimento, sendo as principais causas a infecção (73%) e a falência renal (33%), isoladas ou associadas. A mortalidade foi relativamente maior no sexo masculino (11:210 meninas [5,2%] e 4:43 meninos [9,3%]). Não se observou correlação entre a mortalidade e a idade de início da doença, o tempo de seguimento ou o número de critérios presentes na primeira consulta. Conclusão: as crianças e adolescentes brasileiros com LESj apresentam características clínicas semelhantes às observadas em outras populações. As infecções e a insuficiência renal são as principais causas de óbito.

Avaliaçäo da cobertura vacinal do esquema básico para o primeiro ano de vida / Assessment of immunization coverage for the basic schedule in children

Em 1991, avaliou-se a cobertura vacinal em crianças de 12 a 23 meses de idade no território de responsabilidade de um Posto de Atençäo Primária à Saúde, na periferia da Zona Norte de Porto Alegre, RS, Brasil, cinco anos após sua implantaçäo, com a finalidade de melhorar a qualidade das açöes de saúde desenvolvidas no serviço. Foram investigadas todas as crianças através de um inquérito domiciliar, observando-se a carteira de vacinas e as informaçöes da mäe. Em 1986, um inquérito inicial havia identificado uma cobertura vacinal inferior a 60 por cento para cada uma das vacinaas. A atual cobertura vacinal (doses comprovadas) para três doses de vacina DPT (Difteria, Pertussis e Tétano), três doses da Sabin (antipoliomielite), uma dose da anti-sarampo (VAS) e uma dose de BCG säo, respectivamente 87, 89, 88 e 79 por cento. Apesar das altas coberturas observadas por tipos de vacinas, quando se verificou para cada criança se o esquema básico do primeiro ano de vida estava completo (3 doses de DPT + 3 doses de Sabin + 1 dose de VAS + 1 dose de BCG) encontrou-se apenas 75 por cento das crianças, na citada situacäo. A cobertura vacinal é heterogênea dentro do território, sendo maior naquelas áreas caracterizadas por piores condiçöes socioeconômicas, onde a equipe de saúde havia intensificado esforços. A comparaçäo com o método administrativo de avaliaçäo de cobertura, realizado mensalmente, mostrou a näo-adequaçäo desse, que subestimava a cobertura vacinal. Avaliou-se a situaçäo vacinal das mäes, para vacina antitetânica, e apenas 49 por cento das crianças estavam protegidas contra o tétano neonatal. Os dados obtidos subsidiaram a imediata reestruturaçäo das açöes do programa, com vistas a atingir uma cobertura vacinal de 100 por cento, e melhorar a qualidade das açöes de saúde prestadas pela equipe

Polipose familiar colônica juvenil / Juvenile colonic familial polyposis

A investigaçäo de sangramento anal em crianças deve incluir um exame retal, por ser este sinal comum na presença de pólipos retais. A maioria säo pólipos únicos que freqüentemente auto-amputam-se, possivelmente por torçäo e necrose do pedículo, sendo o sangramentoe retal indolor a manifestaçäo clínica típica. Quando múltiplos, o comprometimento pode ser sistêmico, e também extra-colônico, dependendo da síndrome específica. Dentre estas, temos a polipose juvenil, uma das sídromes familiares de polipose hamartomatosa do trato gastro-intestinal, que deve ser histologicamente confirmada e diferenciada de outras poliposes do tubo digestivo, pois esta entidade, a princípio benigna, tem possibilidades de transformaçäo maligna se apresentar focos de tecido adenomatoso nos pólipos hamartomatosos. Neste trabalho, será relatado um caso de polipose juvenil em um paciente de 12 anos, com sinais e sintomas de malabsorçäo e hematoquesia, além de manifestaçöes extra-colônicas. Ao exame, comprometimento pancolônico, por inúmeros pólipos. A investigaçäo familiar, todos os irmäos apresentavam a síndrome, mas assintomáticos. Como o número de pólipos era reduzido, foram tratados com polipectomia por via endoscópica. O paciente evoluiu bem, após colectomia total e anastomose ileoretal