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To develop response criteria for juvenile dermatomyositis (DM). We analysed the performance of 312 definitions that used core set measures from either the International Myositis Assessment and Clinical Studies Group (IMACS) or the Paediatric Rheumatology International Trials Organisation (PRINTO) and were derived from natural history data and a conjoint analysis survey. They were further validated using data from the PRINTO trial of prednisone alone compared to prednisone with methotrexate or cyclosporine and the Rituximab in Myositis (RIM) trial. At a consensus conference, experts considered 14 top candidate criteria based on their performance characteristics and clinical face validity, using nominal group technique. Consensus was reached for a conjoint analysis-based continuous model with a total improvement score of 0-100, using absolute per cent change in core set measures of minimal (≥30), moderate (≥45), and major (≥70) improvement. The same criteria were chosen for adult DM/polymyositis, with differing thresholds for improvement. The sensitivity and specificity were 89% and 91-98% for minimal improvement, 92-94% and 94-99% for moderate improvement, and 91-98% and 85-86% for major improvement, respectively, in juvenile DM patient cohorts using the IMACS and PRINTO core set measures. These criteria were validated in the PRINTO trial for differentiating between treatment arms for minimal and moderate improvement (p=0.009-0.057) and in the RIM trial for significantly differentiating the physician's rating for improvement (p<0.006). The response criteria for juvenile DM consisted of a conjoint analysis-based model using a continuous improvement score based on absolute per cent change in core set measures, with thresholds for minimal, moderate, and major improvement.
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Dermatomiosite/terapia , Avaliação de Resultados em Cuidados de Saúde/normas , Índice de Gravidade de Doença , Adolescente , Adulto , Criança , Pré-Escolar , Consenso , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Sensibilidade e EspecificidadeRESUMO
Despite more than a decade of studying pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection (PANDAS), it is still not possible to confirm its existence and whether it is a poststreptococcal autoimmune disorder. Many controversies remain: the diagnostic criteria have not been validated, evidence of autoimmunity remains inconclusive, evidence of a genetic predisposition is weak, and streptococcal infections are common in childhood and could represent only a trigger of exacerbations of tics and obsessive-compulsive disorder. Patients who fit the PANDAS criteria appear to represent a subgroup of children with chronic tic disorder and/or obsessive-compulsive disorder who may experience symptom exacerbations after group A ß-hemolytic streptococci infections; however, those infections are not the sole or even the most common antecedent of exacerbations. There is not enough evidence to support PANDAS as a unique clinical entity.
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BACKGROUND: Concerns about the safety and efficacy of vaccines in patients with autoimmune diseases (AID) have led to contradictions and low vaccination coverage in this population, who are at a higher risk of infections, including by human papillomavirus (HPV). Although HPV vaccines have been recommended for immunocompromised patients, there is still a lack of data to support its use for AID patients, such as juvenile dermatomyositis (JDM) patients. The aim of this study was to assess the safety and immunogenicity of the quadrivalent HPV (qHPV) vaccine in a cohort of JDM patients. METHODS: JDM patients aged from 9 to 20 years and healthy controls (HC) were enrolled to receive a 3-dose schedule of qHPV vaccine from March/2014 to March/2016. Study visits were performed before the first dose, 1 month after the second and third doses, and 6 months after the third dose. Participants completed a diary of possible adverse events for 14 days following each dose of vaccination (AEFV). Disease activity and current therapy were analyzed at each visit for JDM patients. In addition, serum samples from all participants were collected to test antibody concentrations against HPV16 and 18 at each visit. Participant recruitment was conducted in ten Brazilian centres. From 47 eligible JDM patients and 41 HC, 42 and 35, respectively, completed the 3-dose schedule of the vaccine, given that five JDM patients and two HC had received doses prior to their inclusion in the study. RESULTS: The AEFVs presented by the participants were mild and in general did not differ between JDM and HC groups. No severe AEFVs were related to the vaccination. Disease activity was stable, or even improved during the follow-up. One month after the third dose of the vaccine the JDM group presented seropositivity of 100% for HPV16 and 97% for HPV18, similarly to the HC group, who presented 100% for both serotypes (p = 1.000). Six months after the third dose the seropositivity for the patient group was 94% for both HPV types. CONCLUSIONS: The HPV vaccination in this cohort of JDM patients was safe and immunogenic. Since the seropositivity against HPV16 and 18 was very high after the 3-dose schedule, this regimen should be recommended for JDM patients. TRIAL REGISTRATION: Brazilian Clinical Trials Registry, number: RBR-9ypbtf . Registered 20 March 2018 - Retrospectively registered.
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Corticosteroides/uso terapêutico , Dermatomiosite , Imunogenicidade da Vacina/imunologia , Infecções por Papillomavirus , Vacinas contra Papillomavirus , Alphapapillomavirus/imunologia , Brasil/epidemiologia , Criança , Dermatomiosite/epidemiologia , Dermatomiosite/imunologia , Dermatomiosite/terapia , Feminino , Humanos , Hospedeiro Imunocomprometido/efeitos dos fármacos , Avaliação de Processos e Resultados em Cuidados de Saúde , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/prevenção & controle , Vacinas contra Papillomavirus/administração & dosagem , Vacinas contra Papillomavirus/efeitos adversos , Adulto JovemRESUMO
OBJECTIVE: To establish the diagnostic criteria for PANDAS and to analyze the existing evidence regarding its etiopathogenesis, treatment and prophylaxis. SOURCES: Review of the scientific literature through a MEDLINE search carried out between 1989 and 2006. SUMMARY OF THE FINDINGS: The diagnostic criteria for PANDAS were established nearly 10 years ago, but a lot of controversy still exists over the actual existence of this new pediatric disease. The name of this new disease, supposedly of poststreptococcal etiology, derives from an acronym that stands for pediatric autoimmune neuropsychiatric disease associated with streptococcal infection. Tics and obsessive-compulsive symptoms are the major clinical signs of the disease, which develop after streptococcal infections, probably through autoimmune mechanisms. Even though these neuropsychiatric symptoms are common in rheumatic chorea, whose etiology is also poststreptococcal, the classic choreiform movements and other symptoms of rheumatic fevers are absent in PANDAS. The use of antimicrobial and immunologic therapy has been investigated and considered feasible in some cases. CONCLUSIONS: Further research is still necessary in order to answer the question posed in the title of this article. In the meantime, the identification of tic disorders and obsessive-compulsive disorders in children should include the possibility of PANDAS, seeking to provide evidence of previous streptococcal infection.
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Doenças Autoimunes , Transtorno Obsessivo-Compulsivo , Infecções Estreptocócicas , Tiques , Abreviaturas como Assunto , Doenças Autoimunes/tratamento farmacológico , Doenças Autoimunes/microbiologia , Doenças Autoimunes/prevenção & controle , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Transtorno Obsessivo-Compulsivo/tratamento farmacológico , Transtorno Obsessivo-Compulsivo/microbiologia , Transtorno Obsessivo-Compulsivo/prevenção & controle , Infecções Estreptocócicas/tratamento farmacológico , Infecções Estreptocócicas/prevenção & controle , Infecções Estreptocócicas/psicologia , Tiques/tratamento farmacológico , Tiques/microbiologia , Tiques/prevenção & controleRESUMO
OBJECTIVE: To develop response criteria for juvenile dermatomyositis (DM). METHODS: We analyzed the performance of 312 definitions that used core set measures from either the International Myositis Assessment and Clinical Studies Group (IMACS) or the Paediatric Rheumatology International Trials Organisation (PRINTO) and were derived from natural history data and a conjoint analysis survey. They were further validated using data from the PRINTO trial of prednisone alone compared to prednisone with methotrexate or cyclosporine and the Rituximab in Myositis (RIM) trial. At a consensus conference, experts considered 14 top candidate criteria based on their performance characteristics and clinical face validity, using nominal group technique. RESULTS: Consensus was reached for a conjoint analysis-based continuous model with a total improvement score of 0-100, using absolute percent change in core set measures of minimal (≥30), moderate (≥45), and major (≥70) improvement. The same criteria were chosen for adult DM/polymyositis, with differing thresholds for improvement. The sensitivity and specificity were 89% and 91-98% for minimal improvement, 92-94% and 94-99% for moderate improvement, and 91-98% and 85-86% for major improvement, respectively, in juvenile DM patient cohorts using the IMACS and PRINTO core set measures. These criteria were validated in the PRINTO trial for differentiating between treatment arms for minimal and moderate improvement (P = 0.009-0.057) and in the RIM trial for significantly differentiating the physician's rating for improvement (P < 0.006). CONCLUSION: The response criteria for juvenile DM consisted of a conjoint analysis-based model using a continuous improvement score based on absolute percent change in core set measures, with thresholds for minimal, moderate, and major improvement.
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Antirreumáticos/uso terapêutico , Dermatomiosite/tratamento farmacológico , Glucocorticoides/uso terapêutico , Adolescente , Alanina Transaminase/metabolismo , Aspartato Aminotransferases/metabolismo , Criança , Creatina Quinase/metabolismo , Ciclosporina/uso terapêutico , Dermatomiosite/metabolismo , Dermatomiosite/fisiopatologia , Europa (Continente) , Frutose-Bifosfato Aldolase/metabolismo , Humanos , L-Lactato Desidrogenase/metabolismo , Modelos Logísticos , Metotrexato/uso terapêutico , Força Muscular , Avaliação de Resultados em Cuidados de Saúde , Medidas de Resultados Relatados pelo Paciente , Prednisona/uso terapêutico , Reprodutibilidade dos Testes , Reumatologia , Rituximab/uso terapêutico , Sociedades Médicas , Inquéritos e Questionários , Resultado do Tratamento , Estados UnidosRESUMO
OBJECTIVE: To establish guidelines based on scientific evidence for the management of familial Mediterranean fever. DESCRIPTION OF THE EVIDENCE COLLECTION METHOD: The Guideline was prepared from 5 clinical questions that were structured through PICO (Patient, Intervention or indicator, Comparison and Outcome), to search 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. RESULTS: 10,341 articles were retrieved and evaluated by title and abstract; from these, 46 articles were selected to support the recommendations. RECOMMENDATIONS: 1. The diagnosis of FMF is based on clinical manifestations, characterized by recurrent febrile episodes associated with abdominal pain, chest or arthritis of large joints. 2. FMF is a genetic disease presenting an autosomal recessive trait, caused by mutation in the MEFV gene. 3. Laboratory tests are not specific, demonstrating high serum levels of inflammatory proteins in the acute phase of the disease, but also often showing high levels even between attacks. SAA serum levels may be especially useful in monitoring the effectiveness of treatment. 4. The therapy of choice is colchicine; this drug has proven its effectiveness in preventing acute inflammatory episodes and progression toward amyloidosis in adults. 5. Based on the available information, the use of biological drugs appears to be an alternative for patients with FMF who do not respond or are intolerant to therapy with colchicine.
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Amiloidose Familiar/prevenção & controle , Colchicina/uso terapêutico , Febre Familiar do Mediterrâneo/diagnóstico , Febre Familiar do Mediterrâneo/terapia , Guias de Prática Clínica como Assunto , Pirina/genética , Amiloidose Familiar/genética , Medicina Baseada em Evidências , Febre Familiar do Mediterrâneo/genética , Humanos , Fenótipo , SíndromeRESUMO
OBJECTIVE: To establish guidelines based on cientific evidences for the management of cryopyrin associated periodic syndromes. DESCRIPTION OF THE EVIDENCE COLLECTION METHOD: The 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. RESULTS: 1215 articles were retrieved and evaluated by title and abstract; from these, 42 articles were selected to support the recommendations. RECOMMENDATIONS: 1. 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-1ß inhibitors prevents progression of bone lesions.
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Síndromes Periódicas Associadas à Criopirina/diagnóstico , Síndromes Periódicas Associadas à Criopirina/terapia , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Guias de Prática Clínica como Assunto , Idade de Início , Síndromes Periódicas Associadas à Criopirina/genética , Medicina Baseada em Evidências , Febre , Humanos , Inflamação/genética , Inflamação/imunologia , Interleucina-1beta , Mutação , Prognóstico , Índice de Gravidade de Doença , UrticáriaRESUMO
OBJECTIVE: To establish guidelines based on scientific evidence for the management of periodic fever, aphthous stomatitis, pharyngitis and adenitis (PFAPA) syndrome. DESCRIPTION OF THE EVIDENCE COLLECTION METHOD: The Guideline was prepared from 5 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. RESULTS: 806 articles were retrieved and evaluated by title and abstract; from these, 32 articles were selected to support the recommendations. RECOMMENDATIONS: 1. PFAPA is a diagnosis of exclusion established on clinical grounds, and one must suspect of this problem in children with recurrent and periodic febrile episodes of unknown origin, or with recurrent tonsillitis interspersed with asymptomatic periods, especially in children in good general condition and with preservation of weight and height development. 2. Laboratory findings are nonspecific. Additional tests do not reveal pathognomonic changes. 3. The evidence supporting an indication for surgical treatment (tonsillectomy with or without adenoidectomy), is based on two non-blinded randomized clinical trials with small numbers of patients. 4. The use of prednisone at the onset of fever in patients with PFAPA proved to be an effective strategy. There is still need for more qualified evidence to support its use in patients with PFAPA. 5. Despite promising results obtained in studies with IL-1ß inhibitors, such studies are limited to a few case reports.
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Febre/terapia , Linfadenite/terapia , Faringite/terapia , Guias de Prática Clínica como Assunto , Estomatite Aftosa/terapia , Adenoidectomia , Febre/diagnóstico , Febre/cirurgia , Humanos , Linfadenite/diagnóstico , Linfadenite/cirurgia , Faringite/diagnóstico , Faringite/cirurgia , Estomatite Aftosa/diagnóstico , Estomatite Aftosa/cirurgia , Síndrome , TonsilectomiaRESUMO
OBJECTIVE: To compare the capacity of the 2004 diagnostic guidelines for hemophagocytic lymphohistiocytosis (HLH-2004) with the capacity of the preliminary diagnostic guidelines for systemic juvenile idiopathic arthritis (JIA)-associated macrophage activation syndrome (MAS) to discriminate MAS complicating systemic JIA from 2 potentially confusable conditions, represented by active systemic JIA without MAS and systemic infection. METHODS: International pediatric rheumatologists and hemato-oncologists were asked to retrospectively collect clinical information from patients with systemic JIA-associated MAS and confusable conditions. The ability of the guidelines to differentiate MAS from the control diseases was evaluated by calculating the sensitivity and specificity of each set of guidelines and the kappa statistics for concordance with the physician's diagnosis. Owing to the fact that not all patients were assessed for hemophagocytosis on bone marrow aspirates and given the lack of data on natural killer cell activity and soluble CD25 levels, the HLH-2004 guidelines were adapted to enable the diagnosis of MAS when 3 of 5 of the remaining items (3/5-adapted) or 4 of 5 of the remaining items (4/5-adapted) were present. RESULTS: The study sample included 362 patients with systemic JIA and MAS, 404 patients with active systemic JIA without MAS, and 345 patients with systemic infection. The best capacity to differentiate MAS from systemic JIA without MAS was found when the preliminary MAS guidelines were applied. The 3/5-adapted HLH-2004 guidelines performed better than the 4/5-adapted guidelines in distinguishing MAS from active systemic JIA without MAS. The 3/5-adapted HLH-2004 guidelines and the preliminary MAS guidelines with the addition of ferritin levels ≥500 ng/ml discriminated best between MAS and systemic infections. CONCLUSION: The preliminary MAS guidelines showed the strongest ability to identify MAS in systemic JIA. The addition of hyperferritinemia enhanced their capacity to differentiate MAS from systemic infections. The HLH-2004 guidelines are likely not appropriate for identification of MAS in children with systemic JIA.
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Artrite Juvenil/complicações , Linfo-Histiocitose Hemofagocítica/diagnóstico , Síndrome de Ativação Macrofágica/diagnóstico , Guias de Prática Clínica como Assunto , Criança , Pré-Escolar , Diagnóstico Diferencial , Feminino , Humanos , Técnicas In Vitro , Lactente , Síndrome de Ativação Macrofágica/complicações , Masculino , Estudos RetrospectivosRESUMO
INTRODUCTION: In children, vasculitis as a paraneoplastic syndrome has never been reported before. In this work we report a vasculitis syndrome as a neoplasm onset manifestation in a child and we discuss our case regarding the data from literature. CASE REPORT: A 7-year-old girl presented with hand and foot ulceration, fixed cyanosis and pallor. During investigation, a central nervous system (CNS) rhabdomyosarcoma with metastasis on multiple sites was diagnosed. DISCUSSION: Rhabdomyosarcomas represent 5 to 8% of child neoplasms, although the CNS seldom is the primary site. In the indexed English language literature there were no published cases of vasculitis associated with rhabdomyosarcoma as a paraneoplastic syndrome in childhood, which suggests that the described report is the first being published. Awareness of this possible coexistence could allow to an earlier diagnosis of neoplasms expressed by vasculitis, leading to an earlier treatment and a longer survival.
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Neoplasias Encefálicas/complicações , Neoplasias Encefálicas/diagnóstico , Síndromes Paraneoplásicas/diagnóstico , Rabdomiossarcoma/complicações , Rabdomiossarcoma/diagnóstico , Pele/irrigação sanguínea , Vasculite/etiologia , Criança , Feminino , HumanosRESUMO
OBJECTIVE: To report the efficacy and adverse events with the use of anti-TNFalpha agents in pediatric patients with rheumatic diseases. PATIENTS AND METHODS: Retrospective, observational clinical case series of patients with rheumatic diseases refractory to the conventional treatment. Infliximab and etanercept were the the drugs used. RESULTS: Thirty patients received anti-TNFalpha therapy: Juvenile Idiopathic Arthritis (18), chronic idiopathic anterior uveitis (2), juvenile dermatomyositis (4), Blau syndrome (1), relapsing polychondritis (2), CINCA syndrome (1), and microscopic polyangiitis (1). Twenty (66,6%) patients used infliximab exclusively, 2 (6,6%) etanercept and 8 (26,6%) both drugs. The response with infliximab was good in 9 patients, partial in 12 and poor in 5. Two patients were not evaluated for the short period of treatment. The response with etanercept was good in 7, partial in 2 and poor in 1. The best benefits were observed in JIA patients with polyarticular arthritis, psoriatic arthritis and enthesitis-related arthritis. Adverse effects occurred in 15 patients (50%). Suspension of the treatment due to adverse events occurred in 7. The most frequent infusion reactions with the infliximab were cough and nausea. Infectious complications occurred in 2 patients receiving etanercept and in 7 receiving infliximab (one death due to sepsis). No patients developed tuberculosis. CONCLUSION: Infliximab and etanercept are effective in some subtypes of juvenile idiopathic arthritis and other rheumatic diseases refractory to conventional therapy. Although frequent, adverse events could be controlled most of the time.
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Anticorpos Monoclonais/uso terapêutico , Antirreumáticos/uso terapêutico , Imunoglobulina G/uso terapêutico , Receptores do Fator de Necrose Tumoral/uso terapêutico , Doenças Reumáticas/tratamento farmacológico , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adolescente , Adulto , Anticorpos Monoclonais/efeitos adversos , Antirreumáticos/efeitos adversos , Criança , Pré-Escolar , Etanercepte , Feminino , Humanos , Imunoglobulina G/efeitos adversos , Infliximab , Masculino , Estudos RetrospectivosRESUMO
OBJECTIVE: To develop criteria for the classification of systemic sclerosis (SSc) in children (juvenile SSc). METHODS: The study consisted of 3 phases: 1) collection of data on the signs and symptoms of actual patients with juvenile SSc that are useful for defining involvement of a particular organ; 2) selection of the parameters essential for the classification of juvenile SSc and preparation of a set of provisional classification criteria (PCC) using 2 Delphi surveys; 3) consensus conference consisting of 2 steps: discussion and rating of clinical profiles of 160 patients with definite juvenile SSc, possible juvenile SSc, or other fibrosing diseases as "having or not having juvenile SSc," using nominal group technique, and defining those PCC with the best statistical performance and highest face validity by using the clinical profiles of patients with definite juvenile SSc as the gold standard. RESULTS: In phase 1, 55 centers submitted clinical data on 153 patients with juvenile SSc. A total of 48 signs and symptoms were derived from these patient data and were used to define 9 organ system categories (cutaneous, vascular, gastrointestinal, respiratory, renal, cardiac, neurologic, musculoskeletal, and serologic). During phase 2, these were reduced to 21 criteria (3 major criteria [Raynaud's phenomenon, proximal skin sclerosis/induration of the skin, and sclerodactyly] and 18 minor criteria) and combined to generate 86 different PCC. At the consensus conference, these 86 definitions were tested on the case profiles of 127 patients with juvenile SSc. The PCC with the highest ranking were proximal sclerosis/induration and at least 2 minor criteria. CONCLUSION: These provisional classification criteria for juvenile SSc will help standardize the conduct of clinical research, epidemiologic and outcome studies, and therapeutic trials.
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Pediatria/normas , Guias de Prática Clínica como Assunto , Reumatologia/normas , Escleroderma Sistêmico/classificação , Escleroderma Sistêmico/diagnóstico , Criança , Técnica Delphi , Humanos , Sociedades MédicasRESUMO
OBJECTIVES: Juvenile localized scleroderma (JLS) usually has its onset during later childhood. This report describes the clinical and serologic features of six children with congenital localized scleroderma (CLS). STUDY DESIGN: A large, multinational study was conducted among pediatric rheumatology and dermatology centers by collecting information on demographics, family history, triggering environmental factors, clinical features, laboratory reports, and treatment of patients with JLS. Patients with onset at birth were carefully examined. RESULTS: Among 750 patients with JLS, 6 patients (0.8%) had scleroderma-related lesions at birth. Female-to-male ratio was 2:1. All patients had linear scleroderma, in four involving the face with en coup de sabre appearance. Two patients were misdiagnosed as having skin infection, one nevus, one salmon patch, and two undefined skin lesions. The mean diagnostic delay was 3.9 years. In comparison with the group of 733 patients with late-onset JLS, CLS presented a significantly more prolonged disease duration at diagnosis and a higher frequency of en coup de sabre subtypes. CONCLUSIONS: Congenital localized scleroderma is a rare and probably underestimated condition in neonates. The linear subtype was the exclusive manifestation of the disease. CLS should be included in the differential diagnosis of infants with cutaneous erythematous fibrotic lesions to avoid functional and aesthetic sequelae and to allow prompt therapy.
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Esclerodermia Localizada/congênito , Esclerodermia Localizada/diagnóstico , Atrofia/patologia , Biópsia , Quelantes/uso terapêutico , Pré-Escolar , Feminino , Seguimentos , Humanos , Imunossupressores/uso terapêutico , Lactente , Recém-Nascido , Metotrexato/uso terapêutico , Penicilamina/uso terapêutico , Esclerodermia Localizada/tratamento farmacológico , Pele/patologiaRESUMO
OBJECTIVE: To determine the clinical and immunologic features of systemic sclerosis (SSc) in a large group of children and describe the clinical evolution of the disease and compare it with the adult form. METHODS: Data on 153 patients with juvenile SSc collected from 55 pediatric rheumatology centers in Europe, Asia, and South and North America were analyzed. Demographic, clinical, and immunologic characteristics of children with juvenile SSc at the onset, at diagnosis, and during the disease course were evaluated. RESULTS: Raynaud's phenomenon was the most frequent symptom, followed by skin induration in approximately 75% of patients. Musculoskeletal symptoms were present in one-third of patients, and the most frequently involved internal organs were respiratory and gastrointestinal, while involvement of renal, cerebral, and cardiovascular systems was extremely rare. Antinuclear antibodies were present in the sera of 81% of patients. Anti-topoisomerase I (Scl-70) and anticentromere antibodies were found to be positive in 34% and 7.1% of patients, respectively. Involvement of the respiratory, gastrointestinal, and cardiovascular systems was more frequent and occurred earlier in patients who died than in those who survived. Compared with the adult form, juvenile SSc appears to be less severe, with the involvement of fewer internal organs, particularly at the time of diagnosis, and has a less characterized immunologic profile. CONCLUSION: This study provides information on the largest collection of patients with juvenile SSc ever reported. Juvenile SSc appears to be less severe than in adults because children have less internal organ involvement, a less specific autoantibody profile, and a better long-term outcome.
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Bases de Dados Factuais , Cooperação Internacional , Escleroderma Sistêmico , Adolescente , Adulto , Idade de Início , Autoanticorpos/sangue , Doenças Autoimunes/etiologia , Doenças Autoimunes/imunologia , Doenças Autoimunes/fisiopatologia , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Doenças Musculoesqueléticas/etiologia , Doenças Musculoesqueléticas/imunologia , Doenças Musculoesqueléticas/fisiopatologia , Doença de Raynaud/etiologia , Doença de Raynaud/imunologia , Doença de Raynaud/fisiopatologia , Escleroderma Sistêmico/complicações , Escleroderma Sistêmico/imunologia , Escleroderma Sistêmico/mortalidade , Escleroderma Sistêmico/fisiopatologia , Taxa de SobrevidaAssuntos
Tornozelo/patologia , Policondrite Recidivante/patologia , Punho/patologia , Adolescente , Tornozelo/diagnóstico por imagem , Criança , Pré-Escolar , Feminino , Humanos , Imageamento por Ressonância Magnética , Policondrite Recidivante/diagnóstico por imagem , Radiografia , Punho/diagnóstico por imagemRESUMO
OBJECTIVE: To compare the safety and efficacy of parenteral methotrexate (MTX) at an intermediate dosage (15 mg/m(2)/week) versus a higher dosage (30 mg/m(2)/week) in patients with polyarticular-course juvenile idiopathic arthritis (JIA) who failed to improve while receiving standard dosages of MTX (8-12.5 mg/m(2)/week). METHODS: In the screening phase, 595 patients who were newly started on a standard dose of MTX were followed up for 6 months. Subsequently, the nonresponders, defined according to the American College of Rheumatology (ACR) pediatric 30% improvement criteria (pediatric 30), were randomized to receive an intermediate dose or higher dose of parenteral MTX for an additional 6 months. Improvement in the screening and randomization phase was defined by the ACR pediatric 30 response, as well as by the 50% and 70% response levels (ACR pediatric 50 and ACR pediatric 70, respectively). RESULTS: In the screening phase, after receiving standard doses of MTX, 430 patients (72%) improved according to the ACR pediatric 30, while 360 (61%) met the ACR pediatric 50 and 225 (38%) met the ACR pediatric 70; among these patients, 69 (12%) also met the definition of complete disease control. Of the 133 nonresponders, 80 were randomized to receive an intermediate dose or higher dose of MTX. In the randomization phase, the ACR pediatric 30 response rate was 25 of 40 children (62.5%) in the intermediate-dose group versus 23 of 40 children (57.5%) in the higher-dose group. An ACR pediatric 50 response rate was attained by 23 patients (57.5%) receiving an intermediate dose versus 22 (55%) in the higher-dose group. An ACR pediatric 70 response rate was seen in 18 children (45%) receiving an intermediate dose versus 19 (47.5%) receiving a higher dose. Five children (12.5%) in the intermediate-dose group versus 4 (10%) receiving the higher dose of MTX also met the definition of complete disease control. None of the intergroup differences in response rate were significant. There were no significant differences in the frequency of adverse events or laboratory abnormalities between the 2 randomized groups. CONCLUSION: This study shows that the plateau of efficacy of MTX in JIA is reached with parenteral administration of 15 mg/m(2)/week and that a further increase in dosage is not associated with any additional therapeutic benefit. MTX should be administered for up to 9-12 months to appreciate its full therapeutic effect.