Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 59
Filtrar
1.
Artigo em Inglês | MEDLINE | ID: mdl-31444859

RESUMO

BACKGROUND: Chronic uveitis is a common manifestation of pediatric rheumatologic conditions and may result in irreversible blindness and long-term disability. While chronic anterior uveitis is the most commonly encountered ocular manifestation of rheumatic disease, little is known about the clinical presentation, management and long term outcome of more complex eye conditions such as pars planitis (PP), panuveitis (PU) and Vogt-Koyanagi-Harada disease (VKH). METHODS: We retrospectively reviewed a cohort of 75 children and adolescents with idiopathic PP (50), PU (12) and VKH (14) followed by the Pediatric Rheumatology Core at Children's Hospital Los Angeles and evaluated referral patterns, clinical presentation, treatment response and long term clinical outcome. RESULTS: Patients were followed for an average of 52 months. Their mean age at disease onset was 10 years. Bilateral eye involvement was seen in 87% of the patients. At first presentation to an ophthalmologist, glaucoma was noted in 21%, vision loss (<20/40) in 87% and legal blindness (<20/200 or less in the better-seeing eye) was diagnosed in 18/75 (24%) of the patients (PP 22%, PU 36%, VKH 21%). The average referral time to a pediatric rheumatologist was 13 months (range 1-96 months). Topical steroids were used in all patients, but 98% of the patients required additional DMARDs and 73% required therapy with biologics. After a mean of 52 months, 35% of patients across all disease groups had significant vision loss or were blind, and only 28% were in clinical remission off medications. The worst outcome was observed in children with panuveitis. Using regression analysis, young age at onset, delayed referral to a pediatric rheumatologist and chronic disease were strong predictors for the risk of long-term blindness. CONCLUSION: PP, PU and VKH have a high risk of permanent vision loss and should be managed by a skilled rheumatologist as early and as aggressive as possible. This article is protected by copyright. All rights reserved.

2.
J. pediatr. (Rio J.) ; 95(2): 180-187, Mar.-Apr. 2019. tab
Artigo em Inglês | LILACS-Express | ID: biblio-1002455

RESUMO

Abstract Objective: To translate and validate the Brazilian Portuguese version of the Transition Readiness Assessment Questionnaire in a population of adolescents and young adults with chronic rheumatologic disorders. This questionnaire evaluates the patient's readiness for making the transition from the pediatric health service to adult care. Methods: The four-phase methodology for the translation and validation of generic questionnaires was followed, including translation, back-translation, pilot testing and clinical validation of the final tool. The confirmatory factor analysis was used for clinical validation and the Cronbach's alpha coefficient was used to assess the overall internal consistency of the final tool. Results: A total of 150 patients with a mean age of 17.0 years (SD = 2.2 years, range 14-21 years) were enrolled for the final tool validation. Of those, 71 patients had juvenile systemic lupus erythematosus (47.3%), 64 had juvenile idiopathic arthritis (42.7%), and 15 had juvenile dermatomyositis (10%). During the confirmatory factor analysis, the dimension "Talking with providers" consisting of two questions, was considered as not fitting the translated questionnaire due to a very high ceiling effect and was therefore excluded. All other translated items favorably contributed to the overall consistency of the final tool; removing that dimension did not result in a substantial increase in Cronbach's alpha, which was 0.776. Conclusions: The Brazilian Portuguese version of the Transition Readiness Assessment Questionnaire was validated in a population of transitional patients with chronic rheumatologic disorders, after one dimension from the original questionnaire was excluded. It is a non-specific disease questionnaire; thus, it can be used to evaluate the transition readiness of Brazilian patients with other chronic diseases.


Resumo Objetivo: Traduzir para o português brasileiro e validar o Questionário de Avaliação do Preparo para a Transição em uma população de adolescentes e adultos jovens com doenças reumáticas crônicas. Este questionário avalia o preparo do paciente para realizar a transição do serviço de saúde pediátrico para a assistência ao adulto. Métodos: Seguimos a metodologia de quatro etapas para a tradução e validação de questionários genéricos que inclui tradução, retrotradução, teste piloto e validação clínica do instrumento final. Utilizamos Análise Fatorial Confirmatória e Coeficiente Alfa de Cronbach para testar a validade do instrumento e sua consistência interna. Resultados: Responderam ao questionário traduzido e adaptado 150 pacientes. A média de idade foi de 17,0 anos (DP = 2,2 anos, variação 14-21 anos). Tinham o diagnóstico de lúpus eritematoso sistêmico juvenil 71 pacientes (47,3%), 64 (42,7%) artrite idiopática juvenil e 15 (10%) dermatomiosite juvenil. Durante a análise fatorial confirmatória, a dimensão "Falando com a Equipe Médica" contendo duas questões teve que ser removida devido à presença de expressivo efeito teto. Todas as outras questões restantes contribuíram favoravelmente para aumentar a consistência interna do questionário, obteve-se um Coeficiente Alfa de Cronbach de 0,776. Conclusões: O Questionário de Avaliação do Preparo para a Transição na sua versão em português brasileiro pode ser validado em uma população de pacientes com doenças reumáticas crônicas em transição, com a exclusão de uma dimensão do questionário original. Por ser um questionário não específico para doenças reumáticas, poderá ser utilizado para avaliar o preparo para a transição de outros pacientes brasileiros com doenças crônicas.

3.
J Allergy Clin Immunol Pract ; 7(6): 1970-1985.e4, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30877075

RESUMO

BACKGROUND: Although autoimmunity and hyperinflammation secondary to recombination activating gene (RAG) deficiency have been associated with delayed diagnosis and even death, our current understanding is limited primarily to small case series. OBJECTIVE: Understand the frequency, severity, and treatment responsiveness of autoimmunity and hyperinflammation in RAG deficiency. METHODS: In reviewing the literature and our own database, we identified 85 patients with RAG deficiency, reported between 2001 and 2016, and compiled the largest case series to date of 63 patients with prominent autoimmune and/or hyperinflammatory pathology. RESULTS: Diagnosis of RAG deficiency was delayed a median of 5 years from the first clinical signs of immune dysregulation. Most patients (55.6%) presented with more than 1 autoimmune or hyperinflammatory complication, with the most common etiologies being cytopenias (84.1%), granulomas (23.8%), and inflammatory skin disorders (19.0%). Infections, including live viral vaccinations, closely preceded the onset of autoimmunity in 28.6% of cases. Autoimmune cytopenias had early onset (median, 1.9, 2.1, and 2.6 years for autoimmune hemolytic anemia, immune thrombocytopenia, and autoimmune neutropenia, respectively) and were refractory to intravenous immunoglobulin, steroids, and rituximab in most cases (64.7%, 73.7%, and 71.4% for autoimmune hemolytic anemia, immune thrombocytopenia, and autoimmune neutropenia, respectively). Evans syndrome specifically was associated with lack of response to first-line therapy. Treatment-refractory autoimmunity/hyperinflammation prompted hematopoietic stem cell transplantation in 20 patients. CONCLUSIONS: Autoimmunity/hyperinflammation can be a presenting sign of RAG deficiency and should prompt further evaluation. Multilineage cytopenias are often refractory to immunosuppressive treatment and may require hematopoietic cell transplantation for definitive management.

4.
J Pediatr (Rio J) ; 95(2): 180-187, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-29457995

RESUMO

OBJECTIVE: To translate and validate the Brazilian Portuguese version of the Transition Readiness Assessment Questionnaire in a population of adolescents and young adults with chronic rheumatologic disorders. This questionnaire evaluates the patient's readiness for making the transition from the pediatric health service to adult care. METHODS: The four-phase methodology for the translation and validation of generic questionnaires was followed, including translation, back-translation, pilot testing and clinical validation of the final tool. The confirmatory factor analysis was used for clinical validation and the Cronbach's alpha coefficient was used to assess the overall internal consistency of the final tool. RESULTS: A total of 150 patients with a mean age of 17.0 years (SD=2.2 years, range 14-21 years) were enrolled for the final tool validation. Of those, 71 patients had juvenile systemic lupus erythematosus (47.3%), 64 had juvenile idiopathic arthritis (42.7%), and 15 had juvenile dermatomyositis (10%). During the confirmatory factor analysis, the dimension "Talking with providers" consisting of two questions, was considered as not fitting the translated questionnaire due to a very high ceiling effect and was therefore excluded. All other translated items favorably contributed to the overall consistency of the final tool; removing that dimension did not result in a substantial increase in Cronbach's alpha, which was 0.776. CONCLUSIONS: The Brazilian Portuguese version of the Transition Readiness Assessment Questionnaire was validated in a population of transitional patients with chronic rheumatologic disorders, after one dimension from the original questionnaire was excluded. It is a non-specific disease questionnaire; thus, it can be used to evaluate the transition readiness of Brazilian patients with other chronic diseases.


Assuntos
Doenças Reumáticas/terapia , Inquéritos e Questionários , Transição para Assistência do Adulto , Adolescente , Brasil , Doença Crônica , Características Culturais , Feminino , Humanos , Masculino , Psicometria , Reprodutibilidade dos Testes , Fatores Socioeconômicos , Traduções , Adulto Jovem
5.
Arthritis Res Ther ; 20(1): 14, 2018 01 30.
Artigo em Inglês | MEDLINE | ID: mdl-29382366

RESUMO

BACKGROUND: Prior studies have demonstrated abnormalities in the composition of the gastrointestinal microbiota in pediatric and adult patients with spondyloarthritis (SpA). In particular, diminished fecal abundance of Faecalibacterium prausnitzii and abnormalities in both directions in the abundance of the Bacteroides genus have been identified. METHODS: We obtained fecal specimens from 30 children with treatment-naïve enthesitis-related arthritis (ERA) and 19 healthy controls, as well as specimens from 11 adult patients with longstanding SpA and 10 adult healthy controls. All of the samples underwent sequencing of the 16S ribosomal DNA. A subset of the pediatric fecal samples was subjected to shotgun metagenomics sequencing. RESULTS: ERA patients had decreased abundance of the anti-inflammatory F. prausnitzii A2-165 strain (41 ± 28% versus 54 ± 20% of all sequences matching F. prausnitzii, p = 0.084) and an increased abundance of the control F. prausnitzii L2/6 strain (28 ± 28% versus 15 ± 15%, p = 0.038). Similar trends were observed in adults with longstanding SpA (n = 11) and controls (n = 10). In contrast, the fecal abundance of Bacteroides fragilis was increased in ERA subjects (2.0 ± 4.0% versus 0.45 ± 0.7% of all sequences, p = 0.045), yet was diminished in adult subjects (0.2 ± % versus 1.0 ± % of all sequences, p = 0.106). Shotgun metagenomics sequencing of the fecal DNA in the pediatric subjects revealed diminished coverage of the butanoate pathway (abundance normalized to controls of 1 ± 0.48 versus 0.72 ± 0.33 in ERA, p = 0.037). CONCLUSIONS: The anti-inflammatory F. prausnitzii A2-165 strain appears to be depleted in both pediatric and adult SpA. In contrast, B. fragilis may be depleted in adult disease yet abundant in pediatric SpA, suggesting developmental effects on the immune system.


Assuntos
Artrite Juvenil/microbiologia , Fezes/microbiologia , Microbioma Gastrointestinal/fisiologia , Espondilartrite/microbiologia , Adolescente , Adulto , Fatores Etários , Bactérias/classificação , Bactérias/genética , Criança , DNA Bacteriano/química , DNA Bacteriano/genética , Feminino , Microbioma Gastrointestinal/genética , Humanos , Masculino , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Especificidade da Espécie
6.
Ann Rheum Dis ; 77(1): 21-29, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28507219

RESUMO

OBJECTIVE: This report aims to determine the safety, pharmacokinetics (PK) and efficacy of subcutaneous golimumab in active polyarticular-course juvenile idiopathic arthritis (polyJIA). METHODS: In this three-part randomised double-blinded placebo-controlled withdrawal trial, all patients received open-label golimumab (30 mg/m2 of body surface area; maximum: 50 mg/dose) every 4 weeks together with weekly methotrexate during Part 1 (weeks 0-16). Patients with at least 30% improvement per American College of Rheumatology Criteria for JIA (JIA ACR30) in Part 1 entered the double-blinded Part 2 (weeks 16-48) after 1:1 randomisation to continue golimumab or start placebo. In Part 3, golimumab was continued or could be restarted as in Part 1. The primary outcome was JIA flares in Part 2; secondary outcomes included JIA ACR50/70/90 responses, clinical remission, PK and safety. RESULTS: Among 173 patients with polyJIA enrolled, 89.0% (154/173) had a JIA ACR30 response and 79.2%/65.9%/36.4% demonstrated JIA ACR50/70/90 responses in Part 1. At week 48, the primary endpoint was not met as treatment groups had comparable JIA flare rates (golimumab vs placebo: 32/78=41% vs 36/76=47%; p=0.41), and rates of clinical remission were comparable (golimumab vs placebo: 10/78=12.8% vs 9/76=11.8%). Adverse event and serious adverse event rates were similar in the treatment groups during Part 2. Injection site reactions occurred with <1% of all injections. PK analysis confirmed adequate golimumab dosing for polyJIA. CONCLUSION: Although the primary endpoint was not met, golimumab resulted in rapid, clinically meaningful, improvement in children with active polyJIA. Golimumab was well tolerated, and no unexpected safety events occurred. CLINICAL TRIAL REGISTRATION: NCT01230827; Results.


Assuntos
Anticorpos Monoclonais/administração & dosagem , Antirreumáticos/administração & dosagem , Artrite Juvenil/tratamento farmacológico , Artrite/tratamento farmacológico , Metotrexato/administração & dosagem , Adolescente , Artrite/patologia , Artrite Juvenil/patologia , Criança , Pré-Escolar , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Humanos , Injeções Subcutâneas , Masculino , Indução de Remissão , Exacerbação dos Sintomas , Resultado do Tratamento
7.
Pediatr Rheumatol Online J ; 15(1): 47, 2017 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-28558790

RESUMO

BACKGROUND: Transition guidelines and recommendations for developing countries are limited and best transition practices in young patients with chronic medical conditions have been poorly examined. This study evaluates transition practices from pediatric to adult rheumatology care in Brazil. METHODS: Practicing pediatric rheumatologists registered in the Brazilian Society of Rheumatology were e-surveyed with SurveyMonkey® using the Chira et al. questionnaire that had been used previously to evaluate transition practices of pediatric rheumatologists from the Childhood Arthritis and Rheumatology Research Alliance (CARRA) in the USA and Canada. The questionnaire was modified to better address specific issues pertaining to the Brazilian health care system. RESULTS: Seventy-six of 112 (68%) pediatric rheumatologists responded. Only 13% of the respondents reported that they had a well-established transition program and only 14% were satisfied with their current transition process. Eighty percent did not use any specific tools to assess transition readiness. While 43% of respondents considered 18 as the ideal transition age, only a third effectively transitioned their patients at that age while 48% did later. Major hurdles for a successful transition cited by the respondents included emotional attachment to the patients (95%) insufficient training in transition practice (87%), lack of devoted time for transition preparation and process (80%), lack of assistance by pediatric generalists, (77%), and lack of available adult subspecialists (75%). Sixty-seven percent of respondents stated that their program would need more tools/resources to facilitate transition and 59% believed that the development of specific guidelines would be useful to standardize and help with the transition process. CONCLUSIONS: Our study demonstrates that the identified challenges pertaining to transition in Brazilian patients are similar to those reported by pediatric rheumatologists in the United States and Canada. However, the current financial economic pressures affecting Brazil's health care system may force physicians to deprioritize non emergent care such as transition. A comprehensive understanding of transition issues specific to youth in developing countries and educating not only patients but also health care providers about the importance of a seamless transition process will support the development of transition guidelines and ensure better outcomes of pediatric subspecialty patients.


Assuntos
Doenças Reumáticas , Transição para Assistência do Adulto , Adolescente , Adulto , Atitude do Pessoal de Saúde , Brasil/epidemiologia , Feminino , Humanos , Masculino , Determinação de Necessidades de Cuidados de Saúde , Pediatria/métodos , Pediatria/normas , Guias de Prática Clínica como Assunto , Padrões de Prática Médica/estatística & dados numéricos , Doenças Reumáticas/epidemiologia , Doenças Reumáticas/terapia , Reumatologia/métodos , Reumatologia/normas , Transição para Assistência do Adulto/organização & administração , Transição para Assistência do Adulto/normas
8.
Arthritis Rheumatol ; 68(10): 2514-26, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27111558

RESUMO

OBJECTIVE: To uniquely classify children with microscopic polyangiitis (MPA), to describe their demographic characteristics, presenting clinical features, and initial treatments in comparison to patients with granulomatosis with polyangiitis (Wegener's) (GPA). METHODS: The European Medicines Agency (EMA) classification algorithm was applied by computation to categorical data from patients recruited to the ARChiVe (A Registry for Childhood Vasculitis: e-entry) cohort, with the data censored to November 2015. The EMA algorithm was used to uniquely distinguish children with MPA from children with GPA, whose diagnoses had been classified according to both adult- and pediatric-specific criteria. Descriptive statistics were used for comparisons. RESULTS: In total, 231 of 440 patients (64% female) fulfilled the classification criteria for either MPA (n = 48) or GPA (n = 183). The median time to diagnosis was 1.6 months in the MPA group and 2.1 months in the GPA group (ranging to 39 and 73 months, respectively). Patients with MPA were significantly younger than those with GPA (median age 11 years versus 14 years). Constitutional features were equally common between the groups. In patients with MPA compared to those with GPA, pulmonary manifestations were less frequent (44% versus 74%) and less severe (primarily, hemorrhage, requirement for supplemental oxygen, and pulmonary failure). Renal pathologic features were frequently found in both groups (75% of patients with MPA versus 83% of patients with GPA) but tended toward greater severity in those with MPA (primarily, nephrotic-range proteinuria, requirement for dialysis, and end-stage renal disease). Airway/eye involvement was absent among patients with MPA, because these GPA-defining features preclude a diagnosis of MPA within the EMA algorithm. Similar proportions of patients with MPA and those with GPA received combination therapy with corticosteroids plus cyclophosphamide (69% and 78%, respectively) or both drugs in combination with plasmapheresis (19% and 22%, respectively). Other treatments administered, ranging in decreasing frequency from 13% to 3%, were rituximab, methotrexate, azathioprine, and mycophenolate mofetil. CONCLUSION: Younger age at disease onset and, perhaps, both gastrointestinal manifestations and more severe kidney disease seem to characterize the clinical profile in children with MPA compared to those with GPA. Delay in diagnosis suggests that recognition of these systemic vasculitides is suboptimal. Compared with adults, initial treatment regimens in children were comparable, but the complete reversal of female-to-male disease prevalence ratios is a provocative finding.


Assuntos
Granulomatose com Poliangiite/fisiopatologia , Hemorragia/fisiopatologia , Falência Renal Crônica/fisiopatologia , Pneumopatias/fisiopatologia , Poliangiite Microscópica/fisiopatologia , Síndrome Nefrótica/fisiopatologia , Insuficiência Respiratória/fisiopatologia , Adolescente , Corticosteroides/uso terapêutico , Distribuição por Idade , Anticorpos Anticitoplasma de Neutrófilos , Ásia/epidemiologia , Azatioprina/uso terapêutico , Canadá/epidemiologia , Criança , Pré-Escolar , Estudos de Coortes , Ciclofosfamida/uso terapêutico , Quimioterapia Combinada , Europa (Continente)/epidemiologia , Feminino , Granulomatose com Poliangiite/complicações , Granulomatose com Poliangiite/epidemiologia , Granulomatose com Poliangiite/terapia , Hemorragia/etiologia , Humanos , Imunossupressores/uso terapêutico , Lactente , Falência Renal Crônica/etiologia , Falência Renal Crônica/terapia , Pneumopatias/etiologia , Masculino , Metotrexato/uso terapêutico , Poliangiite Microscópica/complicações , Poliangiite Microscópica/epidemiologia , Poliangiite Microscópica/terapia , Ácido Micofenólico/uso terapêutico , Síndrome Nefrótica/etiologia , Oxigenoterapia , Plasmaferese , Proteinúria/etiologia , Diálise Renal , Insuficiência Respiratória/etiologia , Insuficiência Respiratória/terapia , Rituximab/uso terapêutico , Estados Unidos/epidemiologia
9.
Arthritis Care Res (Hoboken) ; 67(11): 1521-8, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25939495

RESUMO

OBJECTIVE: Transition from pediatric to adult care is a complex process and can negatively impact patients with chronic disease. We describe the transition experience of patients with pediatric-onset systemic lupus erythematosus (SLE) and its associated outcomes in adulthood. METHODS: A telephone survey of 41 pediatric-onset SLE patients was conducted following their transition to adult care. Data on medical and social outcomes during and after the transition were collected. Health status was compared to retrospectively collected baseline data at pediatric discharge. RESULTS: The mean ± SD followup interval was 5 ± 3.7 years; the mean ± SD age at followup was 24 ± 4.2 years. More than half of patients (22 of 41) experienced transition difficulties, primarily due to loss of insurance and emotional readjustment, which were associated with poor symptom control (P = 0.03) and multiple organ system involvement (P = 0.05) at followup. After the transition, most patients (35 of 41) were followed by an adult-care rheumatologist, and the majority (37 of 41) reported recent symptoms of active disease; 41% (13 of 29) had developed symptoms suggestive of new renal manifestations following transition. One-third (15 of 41) reported new or ongoing neuropsychiatric symptoms. Both renal and neuropsychiatric manifestations were associated with unemployment (P < 0.05). Direct referral by a pediatric rheumatologist was associated with fewer hospitalizations following transition (P = 0.04). CONCLUSION: The majority of patients transitioned successfully to adult rheumatologic care. Major challenges were loss of insurance and attachment to pediatric providers, highlighting the importance of a structured transition process that focuses on providing emotional and financial guidance. Disease activity in pediatric-onset SLE remains high throughout adulthood, with morbidity primarily related to renal and neuropsychiatric manifestations.


Assuntos
Nível de Saúde , Inquéritos Epidemiológicos , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/terapia , Transição para Assistência do Adulto/tendências , Adulto , Idade de Início , Feminino , Seguimentos , Inquéritos Epidemiológicos/métodos , Humanos , Entrevistas como Assunto/métodos , Masculino , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
10.
Arthritis Rheumatol ; 67(5): 1377-85, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25676588

RESUMO

OBJECTIVE: To determine the dose of triptorelin that is sufficient to maintain complete ovarian suppression in female patients with childhood-onset systemic lupus erythematosus (SLE) who require cyclophosphamide therapy, to determine the length of time needed to achieve ovarian suppression after initiation of triptorelin treatment, and to investigate the safety of triptorelin. METHODS: In this randomized, double-blind, placebo-controlled, dose-escalation study, female patients ages <21 years were randomized 4:1 to receive triptorelin (n = 25) or placebo (n = 6). The starting doses of triptorelin were 25, 50, 75, and 100 µg/kg, and the dose was escalated until complete ovarian suppression was maintained. The primary outcome was the weight-adjusted dose of triptorelin that provided complete ovarian suppression in at least 90% of the patients, as determined by gonadotropin-releasing hormone agonist stimulation testing. The secondary outcome was the period of time required to achieve ovarian suppression, as measured by unstimulated follicle-stimulating hormone and luteinizing hormone levels after the initiation of triptorelin treatment. RESULTS: Treatment with triptorelin at a weight-adjusted dose of 120 µg/kg body weight provided sustained complete ovarian suppression in 90% of the patients. After administration of the initial dose of triptorelin, 22 days were required to achieve complete ovarian suppression. The rates of adverse events (AEs) and serious adverse events (SAEs) per 100 patient-months of followup were not higher in the triptorelin group compared with the placebo group (for AEs, 189 versus 362; for SAEs, 2.1 versus 8.5). CONCLUSION: High doses of triptorelin are needed to achieve and maintain complete ovarian suppression, but such doses appear to be well tolerated in adolescent female patients with childhood-onset SLE. Our data suggest that a lag time of 22 days after initiation of triptorelin treatment is required before cyclophosphamide therapy is started or continued.


Assuntos
Antirreumáticos/efeitos adversos , Ciclofosfamida/efeitos adversos , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Luteolíticos/administração & dosagem , Inibição da Ovulação , Insuficiência Ovariana Primária/prevenção & controle , Pamoato de Triptorrelina/administração & dosagem , Adolescente , Método Duplo-Cego , Feminino , Hormônio Foliculoestimulante/metabolismo , Humanos , Hormônio Luteinizante/metabolismo , Insuficiência Ovariana Primária/induzido quimicamente , Fatores de Tempo , Adulto Jovem
11.
Arthritis Care Res (Hoboken) ; 67(5): 658-66, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25220674

RESUMO

OBJECTIVE: To determine whether order of medication withdrawal in children with juvenile idiopathic arthritis (JIA) taking methotrexate (MTX) and tumor necrosis factor inhibitor (TNFi) combination therapy (CBT) affects flare-free survival (FFS). METHODS: This retrospective observational study of 335 patients with polyarticular JIA or enthesitis-related arthritis analyzed FFS off medications in 4 withdrawal arms: 1) TNFi plus MTX, off MTX first, 2) TNFi plus MTX, off TNFi first, 3) MTX monotherapy, or 4) TNFi monotherapy. Outcomes were evaluated based on order of medication withdrawal, clinical presentation, serologic parameters, and duration of clinically inactive disease (CID) while taking medications. RESULTS: Sixty-four percent of all patients achieved CID. However, 89% of patients on CBT who withdrew TNFi first flared within 12 months despite continuing MTX, compared to 12% of those who withdrew MTX and continued TNFi (P < 0.0005). Twenty-seven percent of patients discontinued all medications, but 63% flared within 12 months, and only 49% of these regained CID within 12 months of restarting therapy. Patients on MTX monotherapy had the best FFS after medication withdrawal. FFS was independent of disease subtype, rheumatoid factor status, initial erythrocyte sedimentation rate, initial joint count, corticosteroid exposure, time in CID, and method of medication discontinuation. CONCLUSION: This study confirms that flare rates in JIA are high, and discontinuing medications is challenging. Withdrawal of TNFi from CBT first carries a significantly higher risk of disease flare than withdrawing MTX first. The high relapse rate after discontinuation of TNFi suggests that these medications may not modify the underlying disease process.


Assuntos
Antirreumáticos/administração & dosagem , Artrite Juvenil/tratamento farmacológico , Produtos Biológicos/administração & dosagem , Metotrexato/administração & dosagem , Adolescente , Artrite Juvenil/diagnóstico , Artrite Juvenil/imunologia , Criança , Pré-Escolar , Intervalo Livre de Doença , Esquema de Medicação , Quimioterapia Combinada , Feminino , Humanos , Lactente , Estimativa de Kaplan-Meier , Los Angeles , Masculino , Recidiva , Indução de Remissão , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Fator de Necrose Tumoral alfa/antagonistas & inibidores
12.
Biomed Res Int ; 2014: 854842, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25147819

RESUMO

OBJECTIVE: To examine the effect of rilonacept on the health-related quality of life (HRQoL) in patients with poorly controlled familial Mediterranean fever (FMF). METHODS: As part of a randomized, double-blinded trial comparing rilonacept and placebo for the treatment of FMF, patients/parents completed the modified Child Health Questionnaire (CHQ) at baseline, and at the start and end of each of 4 treatment courses, 2 each with rilonacept and placebo. RESULTS: Fourteen subjects were randomized; mean age was 24.4 ± 11.8 years. At baseline the physical HRQoL score was significantly less (24.2 ± 49.5) but the psychosocial score was similar to the population norm (49.5 ± 10.0). There were significant improvements in most HRQoL concepts after rilonacept but not placebo. Significant differences between rilonacept and placebo were found in the physical (33.7 ± 16.4 versus 23.7 ± 14.5, P = 0.021) but not psychosocial scores (51.4 ± 10.3 versus 49.8 ± 12.4, P = 0.42). The physical HRQoL was significantly impacted by the treatment effect and patient global assessment. CONCLUSION: Treatment with rilonacept had a beneficial effect on the physical HRQoL in patients with poorly controlled FMF and was also significantly related to the patient global assessment. This trial is registered with ClinicalTrials.gov Identifier NCT00582907.


Assuntos
Febre Familiar do Mediterrâneo/tratamento farmacológico , Proteínas Recombinantes de Fusão/uso terapêutico , Adulto , Método Duplo-Cego , Feminino , Humanos , Masculino , Qualidade de Vida , Inquéritos e Questionários , Resultado do Tratamento , Adulto Jovem
13.
J Clin Rheumatol ; 20(4): 183-8, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24847743

RESUMO

BACKGROUND: Pediatric Takayasu arteritis (pTA) is difficult to treat and can lead to significant morbidity and mortality. OBJECTIVES: The objective of this study was to describe clinical characteristics for pTA and determine the safety and efficacy of cyclophosphamide (CYC) and infliximab (IFX) in pTA. METHODS: This was a retrospective analysis of 23 pTA patients seen at Children's Hospital Los Angeles and Universidade Federal de São Paulo-Brazil from 1990 to 2011. All patients fulfilled the 1990 American College of Rheumatology criteria for Takayasu arteritis. Disease activity was assessed using a modified National Institutes of Health score. RESULTS: Twenty-three patients (14 female and 9 male patients), mean age of 15.7 ± 6.0 years, were included. Cyclophosphamide was used before IFX treatment in 17 of 23 and IFX before CYC in 2 of 23 patients. The average time from disease onset to treatment initiation was 2.6 ± 2.4 years for CYC and 4.1 ± 2.4 years for IFX. Nine (60%) of 15 patients failed CYC, and of these 6 were changed to IFX with subsequent clinical stabilization in 5 (83%) of 6. Two patients initially treated with IFX were switched to CYC because of lack of appropriate response: 1 patient later worsened, and the other was lost to follow-up. Five opportunistic infections requiring hospitalization occurred in the CYC group, whereas none were observed in the IFX group. Patients in the IFX group were more likely to decrease or stop their corticosteroids when compared with the CYC patients. CONCLUSIONS: Cyclophosphamide is often used as initial treatment but has many adverse effects. In this retrospective case series, IFX was equivalent to CYC with fewer adverse effects, making IFX an alternative therapeutic option for pTA.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Antirreumáticos/uso terapêutico , Ciclofosfamida/uso terapêutico , Arterite de Takayasu/tratamento farmacológico , Adolescente , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/efeitos adversos , Antirreumáticos/administração & dosagem , Antirreumáticos/efeitos adversos , Brasil , Criança , Estudos de Coortes , Ciclofosfamida/administração & dosagem , Ciclofosfamida/efeitos adversos , Quimioterapia Combinada , Feminino , Humanos , Infliximab , Masculino , Indução de Remissão , Resultado do Tratamento , Estados Unidos
14.
Rheum Dis Clin North Am ; 39(4): 801-32, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24182856

RESUMO

Chronic inflammatory eye diseases are a common manifestation of pediatric rheumatologic diseases, potentially leading to lifelong vision impairment and disability. The mechanisms leading to the breach of the blood eye/brain barrier and the subsequent immune attack against a variety of intraocular mostly unidentified antigens remains poorly understood. Pediatric rheumatologists need to be familiar with the various inflammatory eye diseases because they are often responsible for selecting and supervising treatment in close collaboration with the ophthalmologist. This article provides an update of recent developments in the pathogenesis and treatment of the most relevant ocular diseases encountered in rheumatologic practice.


Assuntos
Antirreumáticos/uso terapêutico , Imunossupressores/uso terapêutico , Doenças Reumáticas/diagnóstico , Uveíte/diagnóstico , Síndrome de Behçet/diagnóstico , Síndrome de Behçet/tratamento farmacológico , Criança , Síndrome de Cogan/diagnóstico , Síndrome de Cogan/tratamento farmacológico , Oftalmopatias/diagnóstico , Oftalmopatias/tratamento farmacológico , Humanos , Nefrite Intersticial/diagnóstico , Nefrite Intersticial/tratamento farmacológico , Pars Planite/diagnóstico , Pars Planite/tratamento farmacológico , Doenças Reumáticas/tratamento farmacológico , Uveíte/tratamento farmacológico , Síndrome Uveomeningoencefálica/diagnóstico , Síndrome Uveomeningoencefálica/tratamento farmacológico
15.
16.
J Clin Immunol ; 33(8): 1289-92, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24122031

RESUMO

We describe a boy who developed autoinflammatory (chronic sterile multifocal osteomyelitis) and autoimmune (autoimmune cytopenias; vitiligo) phenotypes who subsequently developed disseminated granulomatous disease. Whole exome sequencing revealed homozygous RAG1 mutations thus expanding the spectrum of combined immunodeficiency with autoimmunity and granuloma that can occur with RAG deficiency.


Assuntos
Autoanticorpos/biossíntese , Exoma/genética , Exoma/imunologia , Doença Granulomatosa Crônica/imunologia , Proteínas de Homeodomínio/genética , Síndromes de Imunodeficiência/imunologia , Mutação/imunologia , Osteomielite/imunologia , Pré-Escolar , Doença Granulomatosa Crônica/genética , Homozigoto , Humanos , Síndromes de Imunodeficiência/genética , Masculino , Osteomielite/genética , Análise de Sequência de DNA
17.
Clin Immunol ; 149(1): 146-55, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23994768

RESUMO

Multi-center evaluations of pediatric patients with juvenile systemic sclerosis (jSSc) have suggested that the pathogenesis of jSSc may differ from that of systemic sclerosis (SSc) in adult patients. Therefore, we undertook to identify abnormalities in the T lymphocytes of jSSc patients and to determine if they differed from the abnormalities reported in the T lymphocytes of adult SSc patients. We identified decreases in the frequency of resting regulatory T lymphocytes and an increased frequency of CD45RA expressing effector memory (EMRA) CD4 T lymphocytes, which were characterized by an increased frequency of CCR7 protein expressing cells. Neither the increases in the EMRA subpopulation nor the increased CCR7 protein expression have been reported in adult SSc patients. The decrease in resting regulatory T lymphocytes in jSSc patients may permit the expansion of the disease initiating CD4 T lymphocytes present in the CCR7 expressing EMRA CD4 T lymphocyte subpopulation.


Assuntos
Linfócitos T CD4-Positivos/imunologia , Escleroderma Sistêmico/imunologia , Subpopulações de Linfócitos T/imunologia , Adolescente , Adulto , Criança , Feminino , Perfilação da Expressão Gênica , Humanos , Masculino , Análise de Sequência com Séries de Oligonucleotídeos , Receptores CCR7/genética , Escleroderma Sistêmico/genética , Adulto Jovem
18.
Arthritis Rheum ; 65(9): 2486-96, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23754188

RESUMO

OBJECTIVE: To determine the long-term safety and efficacy of rilonacept, an anti-interleukin-1 fusion protein, in patients with active systemic juvenile idiopathic arthritis (JIA). METHODS: In patients with systemic JIA, ages 4-20 years, the efficacy of rilonacept was evaluated using 30%, 50%, and 70% levels of improvement according to the adapted American College of Rheumatology (ACR) Pediatric 30, 50, and 70 response criteria, respectively. Efficacy and safety were evaluated during 23 months of open-label treatment (3 phases) after a 4-week, double-blind, placebo-controlled phase. Following double-blind treatment with 2.2 mg/kg or 4.4 mg/kg of rilonacept, patients were eligible to receive open-label treatment at their prior dose, with adjustments. Reductions in the median daily dose of oral prednisone and improvements in laboratory parameters of disease activity (i.e., decreased levels of D-dimer and myeloid-related proteins [MRPs]) were also evaluated. RESULTS: Twenty-four patients entered the double-blind study and 23 entered the open-label period. Patients were predominantly white and female, and had a median age of 14.0 years at baseline. No significant differences in efficacy were observed between the rilonacept- and placebo-treated patients during the double-blind phase, but fever and rash completely resolved by month 3 in all patients during the open-label treatment period and did not recur. Adapted ACR Pediatric 30, 50, and 70 response rates at 3 months from the start of the study were 78.3%, 60.9%, and 34.8%, respectively; these responses were generally maintained over the study duration. Levels of D-dimer and MRP-8/MRP-14 dramatically improved during the study, and in 22 of 23 patients, the prednisone dose was decreased or prednisone therapy was discontinued. No serious treatment-related adverse events were observed. CONCLUSION: Sustained improvements in clinical and laboratory measures of the articular and systemic manifestations of systemic JIA were achieved in >50% of rilonacept-treated patients over 2 years. Treatment with rilonacept had a substantial steroid-sparing effect and was generally well-tolerated.


Assuntos
Antirreumáticos/uso terapêutico , Artrite Juvenil/tratamento farmacológico , Proteínas Recombinantes de Fusão/uso terapêutico , Adolescente , Antirreumáticos/efeitos adversos , Criança , Pré-Escolar , Método Duplo-Cego , Feminino , Humanos , Masculino , Proteínas Recombinantes de Fusão/efeitos adversos , Resultado do Tratamento , Adulto Jovem
19.
Pediatrics ; 130(5): e1190-7, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23071213

RESUMO

BACKGROUND AND OBJECTIVES: Little information is available concerning the natural history and optimal treatment of chronic nonbacterial osteomyelitis (CNO). We conducted a retrospective review to assess the clinical characteristics and treatment responses of a large cohort of pediatric CNO patients. METHODS: Children diagnosed with CNO at 3 tertiary care centers in the United States between 1985 and 2009 were identified. Their charts were reviewed, and clinical, laboratory, histopathologic, and radiologic data were extracted. RESULTS: Seventy children with CNO (67% female patients) were identified. Median age at onset was 9.6 years (range 3-17), and median follow-up was 1.8 years (range 0-13). Half of the patients had comorbid autoimmune diseases, and 49% had a family history of autoimmunity. Patients with comorbid autoimmune diseases had more bone lesions (P < .001), higher erythrocyte sedimentation rate (P < .05), and higher use of second line therapy (P = .02). Treatment response to nonsteroidal antiinflammatory drugs (NSAIDs), sulfasalazine, methotrexate, tumor necrosis factor α inhibitors, and corticosteroids was evaluated. The only significant predictor of a positive treatment response was the agent used (P < .0001). Estimated probability of response was 57% for NSAIDs, 66% for sulfasalazine, 91% for methotrexate, 91% for tumor necrosis factor α inhibitors, and 95% for corticosteroids. CONCLUSIONS: In a US cohort of 70 children with CNO, coexisting autoimmunity was a risk factor for multifocal involvement and treatment with immunosuppressive agents. Disease-modifying antirheumatic drugs and biologics were more likely to lead to clinical improvement than NSAIDs.


Assuntos
Osteomielite , Adolescente , Anti-Inflamatórios/uso terapêutico , Criança , Pré-Escolar , Doença Crônica , Feminino , Humanos , Imunossupressores/uso terapêutico , Masculino , Osteomielite/diagnóstico , Osteomielite/tratamento farmacológico , Osteomielite/imunologia , Estudos Retrospectivos
20.
Ann Intern Med ; 157(8): 533-41, 2012 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-23070486

RESUMO

BACKGROUND: Currently, there is no proven alternative therapy for patients with familial Mediterranean fever (FMF) that is resistant to or intolerant of colchicine. Interleukin-1 is a key proinflammatory cytokine in FMF. OBJECTIVE: To assess the efficacy and safety of rilonacept, an interleukin-1 decoy receptor, in treating patients with colchicine-resistant or -intolerant FMF. DESIGN: Randomized, double-blind, single-participant alternating treatment study. (ClinicalTrials.gov number: NCT00582907). SETTING: 6 U.S. sites. PATIENTS: Patients with FMF aged 4 years or older with 1 or more attacks per month. INTERVENTION: One of 4 treatment sequences that each included two 3-month courses of rilonacept, 2.2 mg/kg (maximum, 160 mg) by weekly subcutaneous injection, and two 3-month courses of placebo. MEASUREMENTS: Differences in the frequency of FMF attacks and adverse events between rilonacept and placebo. RESULTS: 8 males and 6 females with a mean age of 24.4 years (SD, 11.8) were randomly assigned. Among 12 participants who completed 2 or more treatment courses, the rilonacept-placebo attack risk ratio was 0.59 (SD, 0.12) (equal-tail 95% credible interval, 0.39 to 0.85). The median number of attacks per month was 0.77 (0.18 and 1.20 attacks in the first and third quartiles, respectively) with rilonacept versus 2.00 (0.90 and 2.40, respectively) with placebo (median difference, -1.74 [95% CI, -3.4 to -0.1]; P = 0.027). There were more treatment courses of rilonacept without attacks (29% vs. 0%; P = 0.004) and with a decrease in attacks of greater than 50% compared with the baseline rate during screening (75% vs. 35%; P = 0.006) than with placebo. However, the duration of attacks did not differ between placebo and rilonacept (median difference, 1.2 days [-0.5 and 2.4 days in the first and third quartiles, respectively]; P = 0.32). Injection site reactions were more frequent with rilonacept (median difference, 0 events per patient treatment month [medians of -4 and 0 in the first and third quartiles, respectively]; P = 0.047), but no differences were seen in other adverse events. LIMITATION: Small sample size, heterogeneity of FMF mutations, age, and participant indication (colchicine resistance or intolerance) were study limitations. CONCLUSION: Rilonacept reduces the frequency of FMF attacks and seems to be a treatment option for patients with colchicine-resistant or -intolerant FMF. PRIMARY FUNDING SOURCE: U.S. Food and Drug Administration, Office of Orphan Products Development.


Assuntos
Febre Familiar do Mediterrâneo/tratamento farmacológico , Receptores Tipo I de Interleucina-1/uso terapêutico , Proteínas Recombinantes de Fusão/uso terapêutico , Adolescente , Adulto , Criança , Pré-Escolar , Colchicina/efeitos adversos , Colchicina/uso terapêutico , Método Duplo-Cego , Resistência a Medicamentos , Feminino , Humanos , Masculino , Proteínas Recombinantes de Fusão/efeitos adversos , Resultado do Tratamento , Adulto Jovem
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA