RESUMO
OBJECTIVE: Juvenile localized scleroderma (JLS) includes a number of conditions often grouped together. With the long-term goal of developing uniform classification criteria, we studied the epidemiological, clinical and immunological features of children with JLS followed by paediatric rheumatology and dermatology centres. METHODS: A large, multicentre, multinational study was conducted by collecting information on the demographics, family history, triggering environmental factors, clinical and laboratory features, and treatment of patients with JLS. RESULTS: Seven hundred and fifty patients with JLS from 70 centres were enrolled into the study. The disease duration at diagnosis was 18 months. Linear scleroderma (LS) was the most frequent subtype (65%), followed by plaque morphea (PM) (26%), generalized morphea (GM) (7%) and deep morphea (DM) (2%). As many as 15% of patients had a mixed subtype. Ninety-one patients (12%) had a positive family history for rheumatic or autoimmune diseases; 100 (13.3%) reported environmental events as possible trigger. ANA was positive in 42.3% of the patients, with a higher prevalence in the LS-DM subtype than in the PM-GM subtype. Scl70 was detected in the sera of 3% of the patients, anticentromere antibody in 2%, anti-double-stranded DNA in 4%, anti-cardiolipin antibody in 13% and rheumatoid factor in 16%. Methotrexate was the drug most frequently used, especially during the last 5 yr. CONCLUSION: This study represents the largest collection of patients with JLS ever reported. The insidious onset of the disease, the delay in diagnosis, the recognition of mixed subtype and the better definition of the other subtypes should influence our efforts in educating trainees and practitioners and help in developing a comprehensive classification system for this syndrome.
Assuntos
Esclerodermia Localizada/diagnóstico , Adolescente , Idade de Início , Autoanticorpos/sangue , Doenças Autoimunes/genética , Criança , Pré-Escolar , Meio Ambiente , Feminino , Predisposição Genética para Doença , Humanos , Imunossupressores/uso terapêutico , Lactente , Recém-Nascido , Cooperação Internacional , Masculino , Metotrexato/uso terapêutico , Doenças Reumáticas/genética , Fatores de Risco , Esclerodermia Localizada/tratamento farmacológico , Esclerodermia Localizada/epidemiologia , Esclerodermia Localizada/etiologiaRESUMO
BACKGROUND: Rice bodies can occur in the joints in many rheumatic conditions, but they are most common in rheumatoid arthritis. They are generally believed to occur rarely in patients with osteoarthritis, but one study reported rice bodies with apatite crystals. OBJECTIVE: To report on a series of joint fluids with rice bodies containing apatite clumps and examine their clinical pictures. METHODS: All synovial fluid analysis reports for 10 years were reviewed for rice bodies and eight patients were reported on. A series of patients with a variety of diseases with synovial fluid rice bodies found to contain calcific material is described. All were examined by compensated polarised light and alizarin red stain, and four were examined by electron microscopy. RESULTS: The eight patients all had alizarin red S chunks embedded throughout the rice body. Transmission electron microscopy disclosed the presence of a matrix of collagen, fibrin, and amorphous materials containing typical apatite crystals. Clinical diagnoses, radiographic findings, and leucocyte counts varied, but six of the eight patients had had previous repeated corticosteroid injections into the joints. CONCLUSION: Aggregates of apatites may be more common than previously recognised in rice bodies as they are not routinely sought. Whether they are a result of joint damage or depot steroid injections and whether that might contribute to further joint injury now needs to be investigated.
Assuntos
Apatitas/análise , Artrite Reumatoide/metabolismo , Líquido Sinovial/química , Antraquinonas , Artrite Reumatoide/tratamento farmacológico , Cálcio , Pré-Escolar , Feminino , Glucocorticoides/efeitos adversos , Humanos , Injeções Intra-Articulares , Articulação do Joelho , Masculino , Microscopia Eletrônica , Pessoa de Meia-IdadeRESUMO
We describe our experience with tamoxifen in a prepubertal girl with retroperitoneal fibrosis who had failed treatment with high dose corticosteroid therapy. Her response was excellent.
Assuntos
Antineoplásicos Hormonais/uso terapêutico , Fibrose Retroperitoneal/tratamento farmacológico , Tamoxifeno/uso terapêutico , Criança , Feminino , Fibrose , Humanos , Mediastino/patologia , Fibrose Retroperitoneal/patologia , Tomografia Computadorizada por Raios XRESUMO
Mutations in the extracellular domain of the 55-kD tumor-necrosis factor (TNF) receptor (TNFRSF1A), a key regulator of inflammation, define a periodic-fever syndrome, TRAPS (TNF receptor-associated periodic syndrome [MIM 142680]), which is characterized by attacks of fever, sterile peritonitis, arthralgia, myalgia, skin rash, and/or conjunctivitis; some patients also develop systemic amyloidosis. Elsewhere we have described six disease-associated TNFRSF1A mutations, five of which disrupt extracellular cysteines involved in disulfide bonds; four other mutations have subsequently been reported. Among 150 additional patients with unexplained periodic fevers, we have identified four novel TNFRSF1A mutations (H22Y, C33G, S86P, and c.193-14 G-->A), one mutation (C30S) described by another group, and two substitutions (P46L and R92Q) present in approximately 1% of control chromosomes. The increased frequency of P46L and R92Q among patients with periodic fever, as well as functional studies of TNFRSF1A, argue that these are low-penetrance mutations rather than benign polymorphisms. The c.193-14 G-->A mutation creates a splice-acceptor site upstream of exon 3, resulting in a transcript encoding four additional extracellular amino acids. T50M and c.193-14 G-->A occur at CpG hotspots, and haplotype analysis is consistent with recurrent mutations at these sites. In contrast, although R92Q also arises at a CpG motif, we identified a common founder chromosome in unrelated individuals with this substitution. Genotype-phenotype studies identified, as carriers of cysteine mutations, 13 of 14 patients with TRAPS and amyloidosis and indicated a lower penetrance of TRAPS symptoms in individuals with noncysteine mutations. In two families with dominantly inherited disease and in 90 sporadic cases that presented with a compatible clinical history, we have not identified any TNFRSF1A mutation, despite comprehensive genomic sequencing of all of the exons, therefore suggesting further genetic heterogeneity of the periodic-fever syndromes.
Assuntos
Antígenos CD/genética , Febre Familiar do Mediterrâneo/genética , Heterogeneidade Genética , Mutação/genética , Receptores do Fator de Necrose Tumoral/genética , Processamento Alternativo/genética , Sequência de Aminoácidos , Amiloidose/genética , Antígenos CD/química , Sequência de Bases , Análise Mutacional de DNA , Etnicidade/genética , Éxons/genética , Feminino , Haplótipos/genética , Humanos , Íntrons/genética , Masculino , Repetições de Microssatélites/genética , Modelos Moleculares , Dados de Sequência Molecular , Linhagem , Penetrância , Polimorfismo de Nucleotídeo Único/genética , Estrutura Terciária de Proteína , Receptores do Fator de Necrose Tumoral/química , Receptores Tipo I de Fatores de Necrose TumoralRESUMO
OBJECTIVE: To determine the point prevalence and pattern of silent cardiac abnormalities and associations with suspected risk factors in a sample of children with systemic lupus erythematosus (SLE). METHODS: Cross-sectional analysis of 19 children with SLE from a referral-based rheumatology clinic at an urban children's hospital. Patients were eligible if they were 20 years of age or younger and classified with SLE using the revised criteria of the American College of Rheumatology. Each patient completed a survey, physical examination, standard 12-lead electrocardiogram (ECG), echocardiogram, and had laboratory determinations of complement, triglyceride, and cholesterol levels. RESULTS: Six patients (32%) had cardiac abnormalities on ECG or echocardiogram. In 3, the abnormalities were mild and considered within the normal range. In 5, the abnormalities were considered silent. These abnormalities included ischemic changes (3 patients), valvular insufficiency (3 patients), ventricular repolarization defects (2 patients), cardiac enlargement (1 patient), and ventricular dysfunction (1 patient). Only a recent history of palpitations was significantly associated with the presence of cardiac abnormalities (p = 0.04). CONCLUSIONS: Silent cardiac abnormalities can occur in children with SLE. A recent history of palpitations may be associated with cardiac abnormalities. Routine evaluation of children with SLE using ECG and echocardiogram may help screen for these abnormalities. However, future studies comprising larger sample sizes and longitudinal followup will be required to determine the natural history of cardiac abnormalities in children with SLE and to identify risk factors.
Assuntos
Cardiopatias/epidemiologia , Cardiopatias/etiologia , Lúpus Eritematoso Sistêmico/complicações , Adolescente , Adulto , Criança , Estudos Transversais , Delaware , Ecocardiografia , Eletrocardiografia , Feminino , Cardiopatias/diagnóstico , Cardiopatias/fisiopatologia , Humanos , Masculino , Philadelphia , PrevalênciaRESUMO
OBJECTIVE: To compare a series of commercial ELISA tests with an indirect immunofluorescent antibody (IFA) test for the detection of antinuclear antibodies (ANA) in children with juvenile rheumatoid arthritis (JRA). METHODS: Sera from 178 patients with JRA (88 pauciarticular, 68 polyarticular, 22 systemic) were compared with 26 healthy pediatric subjects. Twenty-one samples from patients with systemic lupus erythematosus (SLE) were also tested. All samples were analyzed by IFA and by 3 commercial ELISA methods. Concordance of ELISA results with IFA results (selected standard) were used as a measure of performance. Sensitivity and specificity were calculated for each test and likelihood ratios (LR) were established for IFA and ELISA in pauciarticular and polyarticular JRA sera. The increment in pretest probability was then obtained for each test as an additional measure of test performance. RESULTS: IFA rendered positive results on 18-77% of the JRA sera depending upon the subset, 100% of SLE sera, and 15% of normal patient sera. Using IFA as the standard, correspondence with positive results among patients with JRA ranged from 0 to 74% for the 3 ELISA tests, while it ranged from 5 to 73% in IFA negative sera. IFA tests showed intermediate range likelihood ratios (0.3, 0.5, 3.5, and 5) and increments in pretest probability ranging from 25 to 45%. While one of the ELISA tests attained 50% of increment in pretest probability for the positive test, it showed 0% increment as a negative test. The other 2 ELISA tests incremented the pretest probability from 0 to 25%. CONCLUSION: Our findings indicate that in JRA, the lack of correspondence with the historic standard IFA precludes the use of ELISA tests for detection of ANA. In addition, IFA out-performs ELISA by a substantial degree when "clinical utility" analysis of test performance is utilized. Detection of ANA in children with JRA should either continue to rely on IFA or be based on a different set of antigens if an ELISA format is chosen.
Assuntos
Anticorpos Antinucleares/sangue , Artrite Juvenil/imunologia , Ensaio de Imunoadsorção Enzimática/métodos , Anticorpos Antinucleares/análise , Artrite Juvenil/sangue , Estudos de Avaliação como Assunto , Técnica Indireta de Fluorescência para Anticorpo , Humanos , Kit de Reagentes para Diagnóstico , Sensibilidade e EspecificidadeRESUMO
This article discusses the effects of sex steroids and anterior pituitary hormones on the immune system. Data from clinical and experimental studies on the effects of CRH, FSH, LH, and prolactin are reviewed. This is followed by a summary of results from our studies on the effects of FSH, LH, and prolactin on PBMC, CD4+ cells, and CD8+ cells in vitro.
Assuntos
Doenças Autoimunes/imunologia , Sistema Hipotálamo-Hipofisário/imunologia , Sistema Hipófise-Suprarrenal/imunologia , Doenças Reumáticas/imunologia , Adolescente , Artrite Juvenil/imunologia , Hormônio Liberador da Corticotropina/imunologia , Feminino , Hormônio Foliculoestimulante/imunologia , Humanos , Hormônio Luteinizante/imunologia , Masculino , Prolactina/imunologia , Puberdade/imunologia , Maturidade Sexual/imunologia , Subpopulações de Linfócitos T/efeitos dos fármacosRESUMO
OBJECTIVE: AI/RHEUM is a multimedia expert system developed originally to assist in the diagnosis of rheumatic diseases in adults. In the present study we evaluated the usefulness of a modified version of this diagnostic decision support system in diagnosing childhood rheumatic diseases. METHODOLOGY: AI/RHEUM was modified by the addition of 5 new diseases to the knowledge base of the system. Criteria tables for each of the diseases included in the knowledge base were modified to suit the needs of children. The modified system was tested on 94 consecutive children seen in a pediatric rheumatology clinic. RESULTS: AI/RHEUM made the correct diagnosis in 92% of the cases when the diagnosis was available in the knowledge base of the system. It was also shown to be effective in the education of pediatric trainees through its multimedia features. CONCLUSIONS: AI/RHEUM is an expert system that may be helpful to the nonspecialist as a diagnostic decision support system and as an educational tool.
Assuntos
Diagnóstico por Computador , Sistemas Inteligentes , Doenças Reumáticas/diagnóstico , Criança , Humanos , Artropatias/diagnóstico , Multimídia , Tendinopatia/diagnóstico , Vasculite/diagnósticoRESUMO
OBJECTIVE: Turner's syndrome (TS) is a disorder associated with characteristic defects in the X chromosome. Autoimmune conditions such as thyroiditis, inflammatory bowel diseases and diabetes have been described in association with TS. METHODS: We have studied the association between TS and juvenile arthritis (JA) by using a survey in which 28 pediatric rheumatology centers (15 in the USA, 10 in Europe, and 3 in Canada) participated. RESULTS: Eighteen cases of TS in a population of approximately 15,000 JRA patients have been found. Two different patterns of arthritis were present: polyarticular (7) and oligoarticular (11). Children with polyarticular disease had early onset, seronegative, progressively deforming arthritis and growth retardation. Those with oligoarticular arthritis had a benign course and were ANA+ (8/11). The oligoarticular children had varying karyotypes whereas almost all of the polyarthritic patients shared the same 45X0 karyotype (6/7). The light and electron microscopic studies of synovium performed in two patients showed chronic inflammation and hyperplasia of the synovial lining cells, vascular proliferation and infiltration with lymphocytes, plasma cells and mononuclear phagocytes. CONCLUSION: Juvenile arthritis is a new autoimmune condition association with Turner's syndrome. The prevalence seems to be at least six times greater than would be expected if the two conditions were only randomly associated. This is the first description of the synovium in Turner's syndrome; no differences from other forms of juvenile rheumatoid arthritis were found.
Assuntos
Artrite Juvenil/complicações , Síndrome de Turner/complicações , Artrite Juvenil/epidemiologia , Artrite Juvenil/patologia , Criança , Pré-Escolar , Grânulos Citoplasmáticos/ultraestrutura , Feminino , Humanos , Lactente , Articulações/patologia , Cariotipagem , Prevalência , Membrana Sinovial/patologia , Sinovite/patologia , Síndrome de Turner/epidemiologia , Síndrome de Turner/patologiaRESUMO
There are many questions and no clear answers raised by these children. These syndromes, however, seem to be biologic experiments of nature and present unique opportunities to study the various elements involved in the pathogenesis of arthritis. Pediatric rheumatologists are in a unique position to study these syndromes.
Assuntos
Artrite/complicações , Adolescente , Artrite/patologia , Criança , Pré-Escolar , Diagnóstico Diferencial , Saúde da Família , Humanos , SíndromeRESUMO
OBJECTIVE: To determine, in a case-control study, if patients with new-onset juvenile dermatomyositis (juvenile DM) have increased symptoms prior to onset, exposure to certain environmental conditions, frequency of familial autoimmune diseases, or antibody titers, compared with 2 control groups. METHODS: A structured interview with the families of 80 children with juvenile DM, 40 children with juvenile rheumatoid arthritis (JRA), or 23 healthy children, from the same geographic area as the children with juvenile DM, was conducted. All children's sera were tested for antibody to Toxoplasma gondii, herpes simplex virus (HSV), or coxsackievirus B (CVB). RESULTS: A high proportion of children with juvenile DM had constitutional symptoms 3 months before the disease-onset date (P = 0.013 versus control children). Children with JRA had more relatives with rheumatoid arthritis (P = 0.0001) and pernicious anemia (P = 0.003) than did children with juvenile DM or healthy children. Among children < or =7 years of age, elevated enteroviral titers were more frequent in those with juvenile DM (81%) and in healthy controls (90%) than in those with JRA (64%), suggesting a common environmental exposure. Titers to T gondii, HSV, or CVB 1-6 were normal. CONCLUSION: Frequencies of familial autoimmune disease, exposure to environmental factors, or elevated antibody titers to T gondii, HSV, or CVB are not increased in juvenile DM. Children with juvenile DM do have symptoms of illness 3 months before the disease-onset date, and young patients have elevated enteroviral titers, as do young geographic controls.
Assuntos
Dermatomiosite/etiologia , Animais , Anticorpos Antiprotozoários/análise , Anticorpos Antivirais/análise , Artrite Juvenil/etiologia , Artrite Juvenil/imunologia , Doenças Autoimunes/genética , Estudos de Casos e Controles , Criança , Pré-Escolar , Estudos de Coortes , Doenças do Tecido Conjuntivo/genética , Dermatomiosite/imunologia , Enterovirus/imunologia , Poluição Ambiental/efeitos adversos , Saúde da Família , Feminino , Humanos , Infertilidade Feminina/complicações , Mordeduras e Picadas de Insetos/complicações , Masculino , Simplexvirus/imunologia , Fatores Socioeconômicos , Toxoplasma/imunologiaRESUMO
OBJECTIVE: To investigate the association of polyarthritis and chromosome 22q11.2 deletions. METHODS: Eighty patients with chromosome 22q11.2 deletion syndrome followed up at The Children's Hospital of Philadelphia were examined for evidence of arthropathy or arthritis. Patients with chromosome 22q11.2 deletion syndrome and polyarthritis underwent laboratory evaluations of immunologic function to determine the relationship of their immunodeficiency to the polyarthritis. RESULTS: The prevalence of polyarthritis in patients with chromosome 22q11.2 deletion syndrome was markedly increased over the prevalence of polyarticular juvenile rheumatoid arthritis (JRA) in the general population. All 3 patients with polyarthritis had evidence of impaired T cell function. Two of the patients with polyarthritis also had IgA deficiency. CONCLUSION: The chromosome 22q11.2 deletion syndrome represents a primary T cell disorder which can be associated with a JRA-like polyarthritis. All 3 patients with polyarthritis had evidence of more extensive immunoregulatory derangements than those typically seen in patients with chromosome 22q11.2 deletion, and these derangements may have predisposed to the development of polyarthritis.
Assuntos
Artrite Juvenil/genética , Artrite/genética , Deleção Cromossômica , Cromossomos Humanos Par 22 , Síndrome de DiGeorge/genética , Linfócitos T CD8-Positivos/imunologia , Criança , Síndrome de DiGeorge/epidemiologia , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , PrevalênciaAssuntos
Acremonium , Estenose Esofágica/microbiologia , Esofagite/microbiologia , Micoses/diagnóstico , Acremonium/isolamento & purificação , Esôfago de Barrett/etiologia , Esôfago de Barrett/cirurgia , Pré-Escolar , Cimetidina/uso terapêutico , Doenças do Tecido Conjuntivo/complicações , Doenças do Tecido Conjuntivo/tratamento farmacológico , Feminino , Fundoplicatura , Humanos , Cetoconazol/uso terapêutico , Metoclopramida/uso terapêutico , Micoses/tratamento farmacológico , Micoses/etiologia , Prednisona/efeitos adversos , Prednisona/uso terapêuticoAssuntos
Medicina/estatística & dados numéricos , Padrões de Prática Médica/estatística & dados numéricos , Doenças Reumáticas/terapia , Reumatologia/estatística & dados numéricos , Especialização , Criança , Pré-Escolar , Inquéritos Epidemiológicos , Humanos , Pessoa de Meia-Idade , Sociedades Médicas , Estados UnidosRESUMO
OBJECTIVE: To evaluate the clinical features and outcome of antiphospholipid syndrome (APS) in children. STUDY DESIGN: Retrospective chart review of patients seen at the Children's Hospital of Philadelphia and Children's Seashore House Pediatric Rheumatology Center between 1988 and 1993. RESULTS: Nine patients with ages ranging from 8 months to 17 years are presented. Clinical features of five patients with primary APS, described in detail, were digital ischemia, stroke, chorea, Addison disease, and pulmonary vaso-occlusive disease. The four children with secondary APS had systemic lupus erythematosus. Clinical features of these patients include livedo reticularis, deep venous thrombosis, and pulmonary hypertension. Antiphospholipid titers, results of coagulation studies, and serologic findings did not predict outcome. CONCLUSION: APS in children has diverse clinical features similar to those in adults and should be considered in cases of unexplained vaso-occlusive disease.
Assuntos
Síndrome Antifosfolipídica/diagnóstico , Adolescente , Síndrome Antifosfolipídica/complicações , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Estudos RetrospectivosRESUMO
Our understanding of the pathogenesis of vasculitis has improved significantly in recent years. The study of cytokines, endothelium, and adhesion molecules in the initiation of inflammatory responses has opened new avenues of investigation and treatment of these disorders. The recognition of newer antibodies such as antineutrophil cytoplasmic antibody has given us newer classification of some of the vasculitides. In this paper, articles published in 1995 on childhood vasculitis with both clinical and research importance are reviewed.