Níveis de complemento em crianças brasileiras durante e após meningite meningocócica

PURPOSE: To evaluate the functional activity of the classical and alternative pathways of the complement system and the levels of C3, C4, and factor B during the first episode of meningococcal infection and during the convalescence period. PATIENTS AND METHODS: Ten Brazilian children ranging in age from 8 months to 8 years, admitted from 1991 to 1993 with a clinical-laboratory diagnosis of meningococcal meningitis, were studied during acute infection (up to 7 days from diagnosis) and during the convalescence period (1 to 6 months after the acute episode). C3, C4, and Factor B were measured using nephelometry, and the lytic activity of classical and alternative pathways were evaluated by a kinetic method and expressed as the time needed to lyse 50% of an erythrocyte suspension (T1/2, expressed in seconds). Low T1/2 values for classical and alternative pathways correlate with high activities of the classical and alternative complement pathways, respectively. RESULTS: A significant difference was observed between the alternative pathway lytic activity during infection and the convalescence period (282 vs 238 seconds, respectively, P = .01). No differences were detected in the other complement parameters analyzed. CONCLUSIONS: In the presence of meningococcal meningitis, the alternative pathway is preferentially activated. This is probably due to the greater ability of the meningococcal endotoxin to activate this pathway in vivo.OBJETIVO: Avaliar a atividade funcional das vias clássica e alternativa do sistema complemento e os níveis de C3, C4 e fator B durante o primeiro episódio de infecção meningocócica e durante a convalescença. PACIENTES E MÉTODOS: Dez crianças brasileiras com idades entre 8 meses e 8 anos, admitidas de 1991 a 1993, com diagnóstico clínico-laboratorial de meningite meningocócica, foram estudadas durante infecção aguda (até 7 dias do diagnóstico) e no período de convalescença (entre 1 e 6 meses após). C3, C4 e fator B foram quantificados por nefelometria e a atividade lítica das vias clássica e alternativa foi avaliada por método cinético e expressa como tempo necessário para lisar 50% de uma suspensão de eritrócitos (T1/2, expresso em segundos). Baixos valores de T1/2 das vias clássica e alternativa se correlacionam com elevadas atividades de via clássica e via alternativa, respectivamente. RESULTADOS: Observaram-se diferenças significativas entre a atividade lítica da via alternativa durante a infecção e no período de convalescença (282 e 238 segundos, respectivamente, P= .01). Nenhuma diferença foi detectada nos outros parâmetros analisados. CONCLUSÕES: Na presença de meningite meningocócica a via alternativa é preferencialmente ativada, provavelmente devido à maior capacidade da endotoxina meningocócica para ativar esta via, in vivo

Fator reumatóide-imunoglobulina E na artrite reumatóide juvenil

OBJECTIVES: To determine the presence of immunoglobulin E-rheumatoid factor in patients with juvenile rheumatoid arthritis and to correlate it with clinical and laboratory parameters. METHODS: A multicenter prospective study was carried out from January 1993 to January 1999 with the enrollment of 3 centers of pediatric rheumatology. Ninety-one children with juvenile rheumatoid arthritis diagnosed according to the American College of Rheumatology criteria were studied: 38 (42%) with systemic, 28 (31%) with pauciarticular, and 25 (27%) with polyarticular onset. Ages ranged from 2.1 years to 22.6 years (mean 10.5 ± 4.7), with 59 (65%) girls. The control group consisted of 45 healthy children. The detection of immunoglobulin E-rheumatoid factor was carried out utilizing an enzyme-linked immunosorbent assay. Associations of immunoglobulin E-rheumatoid factor with immunoglobulin M-rheumatoid factor (latex agglutination test), total serum immunoglobulin E, erythrocyte sedimentation rate, antinuclear antibody, and functional and radiological classes III or IV were analyzed. RESULTS: Positive immunoglobulin E-rheumatoid factor was found in 15 (16.5%) of the 91 children with juvenile rheumatoid arthritis: 7 (18.5%) with systemic, 5 (18%) with pauciarticular, and 3 (12%) with polyarticular onset. A significant correlation was observed between immunoglobulin E-rheumatoid factor and total serum immunoglobulin E in the juvenile rheumatoid arthritis patients. No correlation was found between immunoglobulin E-rheumatoid factor and positive latex agglutination slide test, erythrocyte sedimentation rate, antinuclear antibody, or the functional and radiological classes III or IV in any disease onset group. In 4 out of 45 control children (8.9%), immunoglobulin E-rheumatoid factor was positive but with no correlation with total serum immunoglobulin E levels. CONCLUSIONS: Immunoglobulin E-rheumatoid factor could be detected in 16.5% of juvenile rheumatoid arthritis patients, particularly in those with high levels of total serum immunoglobulin E, and immunoglobulin E-rheumatoid factor appears not to be associated with disease activity or severity.OBJETIVOS: Determinar os níveis séricos do fator reumatóide-imunoglobulina E na artrite reumatóide juvenil e correlacioná-los com parâmetros clínicos e laboratoriais. MÉTODOS: Estudo multicêntrico prospectivo, realizado entre janeiro de 1993 a janeiro de 1999 com participação de três centros de reumatologia pediátrica. Estudaram-se 91 crianças com o diagnóstico de artrite reumatóide juvenil de acordo com os critérios do Colégio Americano de Reumatologia: 38 (42%) com a forma de início sistêmica, 28 (31%) pauciarticular e 25 (27%) poliarticular. A idade variou de 2,1 a 22,6 anos (média de 10,5 ± 4,7 anos) e 59 (65%) crianças eram do sexo feminino. O grupo controle constituiu-se de 45 crianças sadias. A detecção do fator reumatóide-imunoglobulina E foi realizada através de um ensaio imunoenzimático. Associações do fator reumatóide-imunoglobulina E com: fator reumatóide-imunoglobulina M (látex), imunoglobulina E sérica total, VHS, FAN, classe funcional e radiológica III ou IV foram analisadas. RESULTADOS: Das 91 crianças com artrite reumatóide juvenil, quinze (16,5%) apresentaram fator reumatóide-imunoglobulina E positivo. Destas, 7(18,5%) na forma sistêmica, 5 (18%) na pauciarticular e 3 (12%) na poliarticular. Observou-se correlação estatisticamente significativa entre o fator reumatóide-imunoglobulina E e a média geométrica da imunoglobulina E sérica total no total dos pacientes com artrite reumatóide juvenil; não foi observada correlação estatística entre o fator reumatóide-imunoglobulina E e positividade para o Látex, VHS, FAN e classe funcional e radiológica 3 ou 4 em nenhuma das formas de início da doença. Dos 45 controles, 4 (8,9%) também apresentaram fator reumatóide-imunoglobulina E positivo, mas não houve correlação com a imunoglobulina E sérica total. CONCLUSÕES: O fator reumatóide-imunoglobulina E pode ser detectado em 16,5% dos pacientes com artrite reumatóide juvenil, especialmente naqueles com níveis elevados de imunoglobulina E sérica total. O fator reumatóide-imunoglobulina E parece não se associar com atividade ou gravidade da artrite reumatóide juvenil

Guidelines for the management and treatment of periodic fever syndromes Cryopyrin-associated periodic syndromes (cryopyrinopathies – CAPS)

AbstractObjectiveTo establish guidelines based on cientific evidences for the management of cryopyrin associated periodic syndromes.Description of the evidence collection methodThe Guideline was prepared from 4 clinical questions that were structured through PICO (Patient, Intervention or indicator, Comparison and Outcome), to search in key primary scientific information databases. After defining the potential studies to support the recommendations, these were graduated considering their strength of evidence and grade of recommendation.Results1215 articles were retrieved and evaluated by title and abstract; from these, 42 articles were selected to support the recommendations.Recommendations1. The diagnosis of CAPS is based on clinical history and clinical manifestations, and later confirmed by genetic study. CAPS may manifest itself in three phenotypes: FCAS (mild form), MWS (intermediate form) and CINCA (severe form). Neurological, ophthalmic, otorhinolaryngological and radiological assessments may be highly valuable in distinguishing between syndromes; 2. The genetic diagnosis with NLRP3 gene analysis must be conducted in suspected cases of CAPS, i.e., individuals presenting before 20 years of age, recurrent episodes of inflammation expressed by a mild fever and urticaria; 3. Laboratory abnormalities include leukocytosis and elevated serum levels of inflammatory proteins; and 4. Targeted therapies directed against interleukin-1 lead to rapid remission of symptoms in most patients. However, there are important limitations on the long-term safety. None of the three anti-IL-1β inhibitors prevents progression of bone lesions

Complement levels in Brazilian children during and after meningococcal meningitis

PURPOSE: To evaluate the functional activity of the classical and alternative pathways of the complement system and the levels of C3, C4, and factor B during the first episode of meningococcal infection and during the convalescence period. PATIENTS AND METHODS: Ten Brazilian children ranging in age from 8 months to 8 years, admitted from 1991 to 1993 with a clinical-laboratory diagnosis of meningococcal meningitis, were studied during acute infection (up to 7 days from diagnosis) and during the convalescence period (1 to 6 months after the acute episode). C3, C4, and Factor B were measured using nephelometry, and the lytic activity of classical and alternative pathways were evaluated by a kinetic method and expressed as the time needed to lyse 50% of an erythrocyte suspension (T1/2, expressed in seconds). Low T1/2 values for classical and alternative pathways correlate with high activities of the classical and alternative complement pathways, respectively. RESULTS: A significant difference was observed between the alternative pathway lytic activity during infection and the convalescence period (282 vs 238 seconds, respectively, P = .01). No differences were detected in the other complement parameters analyzed. CONCLUSIONS: In the presence of meningococcal meningitis, the alternative pathway is preferentially activated. This is probably due to the greater ability of the meningococcal endotoxin to activate this pathway in vivo

Signs and symptoms of rheumatic diseases as first manifestation of pediatric cancer: diagnosis and prognosis implications

ABSTRACT Objective: To assess the prevalence and describe the clinical, laboratory and radiological findings, treatment and outcome of children with cancer initially referred to a tertiary outpatient pediatric rheumatology clinic. Methods: Retrospective analysis of medical records from patients identified in a list of 250 new patients attending the tertiary Pediatric Rheumatology Clinic, Ribeirão Preto Medical School hospital, University of São Paulo, from July 2013 to July 2015, whose final diagnosis was cancer. Results: Of 250 patients seen during the study period, 5 (2%) had a cancer diagnosis. Among them, 80% had constitutional symptoms, especially weight loss and asthenia, and 60% had arthritis. Initially, all patients had at least one alteration in their blood count, lactate dehydrogenase was increased in 80% and a bone marrow smear was conclusive in 60% of patients. Bone and intestine biopsies were necessary for the diagnosis in 2 patients. JIA was the most common initial diagnosis. The definitive diagnosis was acute lymphoblastic leukemia (2 patients), M3 acute myeloid leukemia, lymphoma, and neuroblastoma (one case each). Of 5 patients studied, 3 (60%) are in remission and 2 (40%) died, one of them with prior use of steroids. Conclusion: The constitutional and musculoskeletal symptoms common to rheumatic and neoplastic diseases can delay the diagnosis and consequently worsen the prognosis of neoplasms. Initial blood count and bone marrow smear may be normal in the initial framework of neoplasms. Thus, the clinical follow-up of these cases becomes imperative and the treatment, mainly with corticosteroids, should be delayed until diagnostic definition

Diretrizes de conduta e tratamento de síndromes febris periódicas associadas a febre familiar do Mediterrâneo

Resumo Objetivo: Estabelecer diretrizes baseadas em evidências científicas para manejo da febre familiar do Mediterrâneo (FFM). Descrição do método de coleta de evidência: A diretriz foi elaborada a partir de 5 questões clínicas que foram estruturadas por meio do PICO (Paciente, Intervenção ou Indicador, Comparação e Outcome), com busca nas principais bases primárias de informação científica. Após definir os estudos potenciais para sustento das recomendações, esses foram graduados pela força da evidência e pelo grau de recomendação. Resultados: Foram recuperados, e avaliados pelo título e resumo, 10.341 trabalhos e selecionados 46 artigos para sustentar as recomendações. Recomendações: 1. O diagnóstico da FFM é baseado nas manifestações clínicas, caracterizadas por episódios febris recorrentes associados a dor abdominal, torácica ou artrite de grandes articulações; 2. A FFM é uma doença genética que apresenta traço autossômico recessivo ocasionada por mutação no gene MEFV; 3. Exames laboratoriais são inespecíficos e demonstram níveis séricos elevados de proteínas inflamatórias na fase aguda da doença, mas também, com frequência, níveis elevados mesmo entre os ataques. Níveis séricos de SAA podem ser especialmente úteis no monitoramento da eficácia do tratamento; 4. A colchicina é a terapia de escolha e demonstrou eficácia na prevenção dos episódios inflamatórios agudos e progressão para amiloidose em adultos; 5. Com base na informação disponível, o uso de medicamentos biológicos parece ser opção para pacientes com FFM que não respondem ou que são intolerantes à terapia com colchicina