RESUMO
OBJECTIVES: To explore the immunosuppressive effect and mechanism of action of intraperitoneal (ip) and intra-articular (ia) mesenchymal stem cell (MSC) injection in proteoglycan induced arthritis (PGIA). METHODS: MSC were administered ip or ia after establishment of arthritis. We used serial bioluminescence imaging (BLI) to trace luciferase-transfected MSC. Mice were sacrificed at different time points to examine immunomodulatory changes in blood and secondary lymphoid organs. RESULTS: Both ip and local ia MSC injection resulted in a beneficial clinical and histological effect on established PGIA. BLI showed that MSC ip and ia in arthritic mice are largely retained for several weeks in the peritoneal cavity or injected joint respectively, without signs of migration. Following MSC treatment pathogenic PG-specific IgG2a antibodies in serum decreased. The Th2 cytokine IL-4 was only upregulated in PG-stimulated lymphocytes from spleens in ip treated mice and in lymphocytes from draining lymph nodes in ia treated mice. An increase in production of IL-10 was seen with equal distribution. Although IFN-γ was also elevated, the IFN-γ/IL-4 ratio in MSC treated mice was opposite to the ratio in (untreated) active PGIA. CONCLUSIONS: MSC treatment, both ip and ia, suppresses PGIA, a non-collagen induced arthritis model. MSC are largely retained for weeks in the injection region. MSC treatment induced at the region of injection a deviation of PG-specific immune responses, suggesting a more regulatory phenotype with production of IL-4 and IL-10, but also of IFN-γ, and a systemic decrease of pathogenic PG-specific IgG2a antibodies. These findings underpin the potential of MSC treatment in resistant arthritis.
Assuntos
Artrite Experimental/terapia , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/imunologia , Animais , Anticorpos/imunologia , Artrite Experimental/induzido quimicamente , Feminino , Tolerância Imunológica/imunologia , Imunoglobulina G/imunologia , Injeções Intra-Articulares , Injeções Intraperitoneais , Interferon gama/imunologia , Interleucina-4/imunologia , Medições Luminescentes , Células-Tronco Mesenquimais/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Proteoglicanas/imunologia , Proteoglicanas/toxicidade , Baço/citologia , Baço/imunologiaRESUMO
Clinical response to methotrexate (MTX) treatment for children with juvenile idiopathic arthritis (JIA) displays considerable heterogeneity. Currently, there are no reliable predictors to identify non-responders: earlier identification could lead to a targeted treatment. We genotyped 759 JIA cases from the UK, the Netherlands and Czech Republic. Clinical variables were measured at baseline and 6 months after start of the treatment. In Phase I analysis, samples were analysed for the association with MTX response using ordinal regression of ACR-pedi categories and linear regression of change in clinical variables, and identified 31 genetic regions (P<0.001). Phase II analysis increased SNP density in the most strongly associated regions, identifying 14 regions (P<1 × 10(-5)): three contain genes of particular biological interest (ZMIZ1, TGIF1 and CFTR). These data suggest a role for novel pathways in MTX response and further investigations within associated regions will help to reach our goal of predicting response to MTX in JIA.
Assuntos
Artrite Juvenil/tratamento farmacológico , Metotrexato/uso terapêutico , Artrite Juvenil/genética , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Masculino , Polimorfismo de Nucleotídeo ÚnicoRESUMO
Griscelli syndrome (GS, MIM 214450), a rare, autosomal recessive disorder, results in pigmentary dilution of the skin and the hair, the presence of large clumps of pigment in hair shafts and an accumulation of melanosomes in melanocytes. Most patients also develop an uncontrolled T-lymphocyte and macrophage activation syndrome (known as haemophagocytic syndrome, HS), leading to death in the absence of bone-marrow transplantation. In contrast, early in life some GS patients show a severe neurological impairment without apparent immune abnormalities. We previously mapped the GS locus to chromosome 15q21 and found a mutation in a gene (MYO5A) encoding a molecular motor in two patients. Further linkage analysis suggested a second gene associated with GS was in the same chromosomal region. Homozygosity mapping in additional families narrowed the candidate region to a 3.1-cM interval between D15S1003 and D15S962. We detected mutations in RAB27A, which lies within this interval, in 16 patients with GS. Unlike MYO5A, the GTP-binding protein RAB27A appears to be involved in the control of the immune system, as all patients with RAB27A mutations, but none with the MYO5A mutation, developed HS. In addition, RAB27A-deficient T cells exhibited reduced cytotoxicity and cytolytic granule exocytosis, whereas MYO5A-defective T cells did not. RAB27A appears to be a key effector of cytotoxic granule exocytosis, a pathway essential for immune homeostasis.
Assuntos
Mutação/genética , Miosina Tipo I , Transtornos da Pigmentação/genética , Proteínas de Saccharomyces cerevisiae , Proteínas rab de Ligação ao GTP/genética , Linfócitos B/imunologia , Linfócitos B/metabolismo , Células Cultivadas , Criança , Pré-Escolar , Cromossomos Humanos Par 15/genética , Grânulos Citoplasmáticos/metabolismo , Análise Mutacional de DNA , Éxons/genética , Feminino , Proteínas Fúngicas/genética , Ligação Genética/genética , Homozigoto , Humanos , Lactente , Íntrons/genética , Ativação Linfocitária/imunologia , Masculino , Dados de Sequência Molecular , Miosinas/genética , Transtornos da Pigmentação/imunologia , Transtornos da Pigmentação/patologia , Síndrome , Linfócitos T Citotóxicos/imunologia , Linfócitos T Citotóxicos/metabolismo , Proteínas rab de Ligação ao GTP/metabolismo , Proteínas rab27 de Ligação ao GTPRESUMO
Evidence-based recommendations for vaccination of paediatric patients with rheumatic diseases (PaedRD) were developed by following the EULAR standardised procedures for guideline development. The EULAR task force consisted of (paediatric) rheumatologists/immunologists, one expert in vaccine evaluation, one expert in public health and infectious disease control, and one epidemiologist. A systematic literature review was conducted in MEDLINE, EMBASE, and abstracts of the EULAR and American College of Rheumatology meetings of 2008/9. The level of evidence and strength of recommendation were based on customary scoring systems. Delphi voting was applied to assess the level of agreement between task force members. 107 papers and eight abstracts were used. The majority of papers considered seasonal influenza (41) or pneumococcal (23) vaccination. 26 studies were performed specifically in paediatric patients, and the majority in adult rheumatoid arthritis and systemic lupus erythematosus patients. Fifteen recommendations were developed with an overall agreement of 91.7%. More research is needed on the safety and immunogenicity of (live-attenuated) vaccination in PaedRD, particularly in those using biologicals, and the effect of vaccination on prevention of infections.
Assuntos
Infecções Oportunistas/prevenção & controle , Doenças Reumáticas/imunologia , Vacinação/normas , Antirreumáticos/efeitos adversos , Criança , Contraindicações , Medicina Baseada em Evidências/métodos , Humanos , Hospedeiro Imunocomprometido , Infecções Oportunistas/complicações , Infecções Oportunistas/imunologia , Doenças Reumáticas/complicações , Doenças Reumáticas/terapia , Vacinação/efeitos adversos , Vacinação/métodos , Vacinas Atenuadas/efeitos adversos , Vacinas Atenuadas/imunologia , Vacinas Conjugadas/efeitos adversos , Vacinas Conjugadas/imunologiaRESUMO
OBJECTIVES: To develop evidence-based European League Against Rheumatism (EULAR) recommendations for vaccination in patients with autoimmune inflammatory rheumatic diseases (AIIRD). METHODS: A EULAR task force was composed of experts representing 11 European countries, consisting of eight rheumatologists, four clinical immunologists, one rheumatologist/clinical immunologist, one infectious disease physician, one nephrologist, one paediatrician/rheumatologist and one clinical epidemiologist. Key questions were formulated and the eligible spectrum of AIIRD, immunosuppressive drugs and vaccines were defined in order to perform a systematic literature review. A search was made of Medline from 1966 to October 2009 as well as abstracts from the EULAR meetings of 2008 and 2009 and the American College of Rheumatology (ACR) meetings of 2007 and 2008. Evidence was graded in categories I-IV, the strength of recommendations was graded in categories A-D and Delphi voting was applied to determine the level of agreement between the experts of the task force. RESULTS: Eight key questions and 13 recommendations addressing vaccination in patients with AIIRD were formulated. The strength of each recommendation was determined. Delphi voting revealed a very high level of agreement with the recommendations among the experts of the task force. Finally, a research agenda was proposed. CONCLUSION: Recommendations for vaccination in patients with AIIRD based on the currently available evidence and expert opinion were formulated. More research is needed, particularly regarding the incidence of vaccine-preventable infectious diseases and the safety of vaccination in patients with AIIRD.
Assuntos
Doenças Autoimunes/complicações , Infecções Oportunistas/complicações , Infecções Oportunistas/prevenção & controle , Doenças Reumáticas/complicações , Vacinação , Doenças Autoimunes/tratamento farmacológico , Técnica Delphi , Medicina Baseada em Evidências/métodos , Humanos , Imunossupressores/efeitos adversos , Doenças Reumáticas/tratamento farmacológicoRESUMO
BACKGROUND: Non-infective cutaneous granulomas with unknown pathogenesis occur in various primary immunodeficiencies (PIDs) including ataxia telangiectasia (A-T). OBJECTIVE: To find a common immunological denominator in these cutaneous granulomas. METHODS: The dermatological and immunological features of 4 patients with A-T and cutaneous granulomas were described. The literature on skin granulomas in A-T and in other PIDs is reviewed. RESULTS: All 4 A-T patients had progressive granulomas on their limbs and showed decreased IgG and IgA concentrations with normal IgM levels. They had a marked decrease in B cells and naïve T cells coinciding with the appearance of the cutaneous granulomas. Similar B- and T-cell abnormalities were described in patients with other PIDs with skin granulomas. CONCLUSIONS: We hypothesize that the pathogenesis of these skin granulomas is related to immune dysregulation of macrophages due to the absence of naïve T cells with an appropriate T-cell receptor repertoire and the unopposed activity of γδ T cells and/or natural killer cells.
Assuntos
Ataxia Telangiectasia/imunologia , Granuloma/imunologia , Dermatopatias/imunologia , Ataxia Telangiectasia/complicações , Linfócitos B/imunologia , Criança , Pré-Escolar , Feminino , Granuloma/complicações , Humanos , Imunoglobulina A/metabolismo , Imunoglobulina G/metabolismo , Síndromes de Imunodeficiência/complicações , Síndromes de Imunodeficiência/imunologia , Lactente , Dermatoses da Perna/imunologia , Masculino , Dermatopatias/complicações , Linfócitos T/imunologiaAssuntos
Dermatomiosite/terapia , Transplante de Células-Tronco , Adolescente , Quimiocina CXCL10/imunologia , Criança , Citocinas/imunologia , Dermatomiosite/imunologia , Feminino , Galectinas/imunologia , Humanos , Inflamação/imunologia , Receptores Tipo II do Fator de Necrose Tumoral/imunologia , Índice de Gravidade de Doença , Transplante Autólogo , Resultado do TratamentoRESUMO
Juvenile dermatomyositis (JDM) is a chronic inflammatory disorder of unknown aetiology that affects muscle and skin. We report on two patients with severe progressive JDM who developed contractures and were wheelchair dependent despite therapy including methotrexate (MTX), steroids, immunoglobulins, cyclosporin A, and rituximab. On account of the refractory disease, autologous stem cell transplantation (ASCT) was performed using a CD3/CD19-depleted graft after immunoablative conditioning with fludarabine, cyclophosphamide, and anti-thymocyte globulin. This induced a dramatic improvement and sustained remission of the disease in both patients. We demonstrate that ASCT is a therapeutic option with low toxicity for patients with severe, refractory JDM.
Assuntos
Dermatomiosite/cirurgia , Transplante de Células-Tronco Hematopoéticas/métodos , Condicionamento Pré-Transplante/métodos , Criança , Dermatomiosite/diagnóstico , Feminino , Seguimentos , Sobrevivência de Enxerto , Humanos , Imageamento por Ressonância Magnética , Medição da Dor , Medição de Risco , Índice de Gravidade de Doença , Fatores de Tempo , Transplante Autólogo , Resultado do TratamentoRESUMO
OBJECTIVES: Transition of care for adolescents includes a transfer from paediatric to adult health care. This requires a transfer of specific measurements, which evaluate disease profiles such as functional ability. One of the most common measurements is the Health Assessment Questionnaire (HAQ). METHODS: Results of the Childhood HAQ (CHAQ) and HAQ were compared among adolescents diagnosed with rheumatic diseases involving the musculoskeletal system. All adolescents had recently dealt with or would in the near future be dealing with transition. RESULTS: Overall results of both questionnaires were comparable; intra-class correlation for consistency (ICC) was 0.95 (95% confidence interval 0.93-0.97). For a smooth transfer from CHAQ to HAQ, both correlation and agreement are required. Agreement between both questionnaires was not found. Described by limits of agreement, results of HAQ can differ from CHAQ as much as 0.95. CONCLUSIONS: Despite strong correlations for consistency, lack of agreement was found in the results of CHAQ and HAQ. If correlation persists over time, this study suggests evaluating both the childhood and adult version of the HAQ during the transition period. When transfer into adulthood is completed, comparison to earlier tests at younger age is available and reliable.
Assuntos
Artrite Juvenil/fisiopatologia , Artrite Juvenil/terapia , Continuidade da Assistência ao Paciente/normas , Avaliação da Deficiência , Nível de Saúde , Inquéritos e Questionários/normas , Adolescente , Adulto , Feminino , Humanos , Masculino , Reprodutibilidade dos Testes , Reumatologia , Adulto JovemRESUMO
UNLABELLED: Henoch Schönlein Purpura (HSP) is usually mild and self-limiting, but it may be accompanied by severe complications such as bullous lesions. We describe the use of systemic prednisone in two patients with bullous lesions in HSP. The first patient presented with progressive bullous lesions distributed on the limbs that evolved into painful ulcers and necrosis. These were further complicated by a secondary skin infection. He then received 1 mg/kg/day prednisone after 9 days. Patient 2, a 10-year-old boy, presented with HSP and bullous lesions and received intravenous prednisone 1 mg/kg/day within 48 h after appearance of the bullous lesions. He recovered rapidly without any complications. CONCLUSION: To reduce the severity of HSP related bullous lesions and their sequelae, we would propose starting prednisone (1 mg/kg/day) as soon as the bullae appear. In addition to prednisone, analgesics and specialist skin care for bullae should be started.
Assuntos
Vesícula/tratamento farmacológico , Vasculite por IgA/tratamento farmacológico , Prednisona/administração & dosagem , Dor Abdominal/etiologia , Vesícula/etiologia , Criança , Esquema de Medicação , Humanos , Vasculite por IgA/complicações , Masculino , Índice de Gravidade de Doença , Pele/patologia , Resultado do TratamentoRESUMO
Work in the past years has led to a refined phenotypical description of functionally distinct T- and B-cell subsets. Since both lymphocyte compartments are established and undergo dramatic changes during childhood, redefined pediatric reference values of both compartments are needed. In a cohort of 145 healthy children, aged 0-18 years, the relative and absolute numbers of the various T- and B-cell subsets were determined. In addition, we found that besides thymic output, naive (CD27(+)CD45RO(-)) T-cell proliferation contributed significantly to the establishment of the naive T-cell compartment. At birth, regulatory (CD25(+)CD127(-)CD4(+)) T cells (Tregs) mainly had a naive (CD27(+)CD45RO(-)) phenotype whereas 'memory or effector-like' (CD45RO(+)) Tregs accumulated slowly during childhood. Besides the CD27(+)IgM(+)IgD(+) memory B-cell population, the recently identified CD27(-)IgG(+) and CD27(-)IgA(+) memory B-cell populations were already present at birth. These data provide reference values of the T- and B-cell compartments during childhood for studies of immunological disorders or immune reconstitution in children.
Assuntos
Subpopulações de Linfócitos B/imunologia , Doenças do Sistema Imunitário/sangue , Subpopulações de Linfócitos T/imunologia , Adolescente , Criança , Pré-Escolar , Estudos de Coortes , Sangue Fetal/imunologia , Humanos , Lactente , Recém-Nascido , Contagem de Linfócitos , Valores de ReferênciaAssuntos
Artrite Juvenil/imunologia , Papillomavirus Humano 16/imunologia , Infecções por Papillomavirus/prevenção & controle , Vacinas contra Papillomavirus/administração & dosagem , Vacinas contra Papillomavirus/efeitos adversos , Neoplasias do Colo do Útero/prevenção & controle , Feminino , HumanosRESUMO
Lysosomal storage disorders (LSDs), a heterogeneous group of inborn metabolic disorders, are far more common than most doctors presume. Although patients with a severe LSD subtype are often readily diagnosed, the more attenuated subtypes are frequently missed or diagnosis is significantly delayed. The presenting manifestations often involve the bones and/or joints and therefore these patients are frequently under specialist care by (paediatric) rheumatologists, receiving inadequate treatment. Since effective disease-specific treatments, including enzyme replacement therapy and stem cell transplantation, have become available for certain LSDs and timely initiation of these treatments is necessary to prevent the development of severe, disabling and irreversible manifestations, early diagnosis has become essential. The challenge is to raise awareness for better recognition of the presenting signs and symptoms of LSDs by all doctors who may encounter these patients, including rheumatologists.
Assuntos
Doenças por Armazenamento dos Lisossomos/complicações , Doenças Musculoesqueléticas/etiologia , Diagnóstico Diferencial , Humanos , Doenças por Armazenamento dos Lisossomos/diagnóstico , Doenças por Armazenamento dos Lisossomos/terapia , Mucopolissacaridoses/complicações , Mucopolissacaridoses/diagnóstico , Mucopolissacaridoses/terapia , Esfingolipidoses/complicações , Esfingolipidoses/diagnóstico , Esfingolipidoses/terapiaRESUMO
OBJECTIVE: We undertook an observational study to obtain a complete overview of the long-term effectiveness and safety of etanercept in patients with different juvenile idiopathic arthritis (JIA) subtypes. METHODS: At baseline we collected patient and disease characteristics of all Dutch patients with JIA who started treatment with etanercept. Disease activity was evaluated (at start of the study, after 3 months and then yearly) according to the JIA core set of the American College of Rheumatology paediatric definition for 30, 50 and 70% improvement (ACR Pedi 30, 50 and 70). Use of etanercept and concomitant drugs was monitored. Adverse events were recorded. RESULTS: We included 146 patients with JIA with a median follow-up of 2.5 years per patient (range 0.3-7.3). JIA subtypes represented: 27% systemic, 8% polyarticular rheumatoid factor positive, 38% polyarticular rheumatoid factor negative, 19% oligoarticular extended, 3% enthesitis-related and 5% psoriatica. Most patients (77%) met the criteria of the ACR Pedi 30 in the first 3 months of treatment. For the majority of patients this improvement was sustained; 53 (36%) of all patients met the remission criteria. No other second-line agents were needed in 43 patients. Although patients with systemic JIA responded initially less to etanercept therapy than patients from other subtypes, those who did respond showed equal effectiveness in the long term. Serious adverse events rate was low (0.029 per patient year). CONCLUSIONS: Etanercept is effective and safe in JIA, even for a large proportion of the patients with systemic JIA. The greatest improvement occurred in the first 3 months of treatment, and was sustained for a long time in most patients (up to 75 months).
Assuntos
Antirreumáticos/uso terapêutico , Artrite Juvenil/tratamento farmacológico , Imunoglobulina G/uso terapêutico , Receptores do Fator de Necrose Tumoral/uso terapêutico , Adolescente , Antirreumáticos/efeitos adversos , Criança , Etanercepte , Feminino , Seguimentos , Humanos , Imunoglobulina G/efeitos adversos , Masculino , Países Baixos , Sistema de Registros , Índice de Gravidade de Doença , Análise de Sobrevida , Resultado do TratamentoRESUMO
OBJECTIVES: To examine the change in health-related quality of life (HRQOL) and its determinants in children with juvenile idiopathic arthritis (JIA) treated with methotrexate (MTX). METHODS: Patients were extracted from the PRINTO clinical trial which aimed to evaluate the efficacy and safety profile of MTX administered in standard, intermediate or higher doses (10, 15 and 30 mg/m(2)/week respectively). Children with polyarticular-course JIA, who were less than 18 years and had a complete HRQOL assessment were included. RESULTS: A total of 521 children were included. At baseline, patients with JIA showed poorer HRQOL (p<0.01) than healthy children. In 207/412 (50%) and 63 (15%) children, HRQOL values were 2 standard deviations below the mean of healthy controls in the physical and psychosocial summary scale, respectively. After 6 months of treatment with standard dose MTX, there was a statistically significant improvement in all HRQOL health concepts, particularly the physical ones. Similar improvements were observed in those who did not respond to a standard dose of MTX and were subsequently randomised to a higher dose. The presence of marked disability at baseline was associated with a fivefold increased risk of retaining poor physical health after 6 months of active treatment with standard dose MTX. Other less important determinants of retaining poor physical well-being were the baseline level of systemic inflammation, pain intensity and an antinuclear-antibody-negative status. CONCLUSIONS: MTX treatment produces a significant improvement across a wide range of HRQOL components, particularly in the physical domains, in patients with JIA.
Assuntos
Antirreumáticos/uso terapêutico , Artrite Juvenil/tratamento farmacológico , Imunossupressores/uso terapêutico , Metotrexato/uso terapêutico , Qualidade de Vida , Adolescente , Artrite Juvenil/fisiopatologia , Artrite Juvenil/psicologia , Criança , Pré-Escolar , Avaliação da Deficiência , Relação Dose-Resposta a Droga , Feminino , Humanos , Masculino , Recuperação de Função Fisiológica , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
Children with juvenile idiopathic arthritis (JIA) often have significant physical impairment. A minority is unresponsive to combinations of medications, and a possible treatment of resistant JIA is intense immunosuppression followed by autologous hematopoietic SCT (ASCT). Children resistant to conventional therapy have a poor prognosis with regard to long-term outcome of joint function, exercise tolerance and quality of life. It has previously been shown that ASCT can induce long-term remissions in such children. The long-term effects of this treatment are still largely unknown. This retrospective study investigates the exercise tolerance and functional ability in children with JIA who have undergone ASCT compared to healthy subjects. Ten children with JIA who received ASCT between 1997 and 2003 participated in this study. Patients were tested during their regular clinical follow-up. Exercise tolerance was determined using a maximal exercise test. Functional ability was measured using the Childhood Health Assessment Questionnaire and joint status. The study group showed significantly reduced exercise tolerance compared to healthy subjects. Functional ability and joint status were also decreased in patients after ASCT. Children with JIA postASCT have impaired exercise tolerance even 9 years postASCT.
Assuntos
Artrite Juvenil/fisiopatologia , Artrite Juvenil/terapia , Tolerância ao Exercício , Transplante de Células-Tronco Hematopoéticas , Articulações/fisiopatologia , Adolescente , Criança , Feminino , Seguimentos , Humanos , Masculino , Qualidade de Vida , Transplante AutólogoRESUMO
OBJECTIVE: The aims of this study are to examine in our juvenile idiopathic arthritis (JIA) population: 1) the prevalence and characteristics of uveitis, 2) the complications and outcome of uveitis, 3) prognostic factors, and 4) the adequacy of the current ophthalmologic screening guidelines. METHODS: Retrospective analysis of medical records. RESULTS: 1) Of the 153 JIA patients included, 27 developed asymptomatic anterior uveitis (17.6%) - 7 unilateral and 20 bilateral. The 27 uveitis patients were significantly younger at JIA presentation than the 126 JIA patients without uveitis. 2) The following uveitis complications were noticed: glaucoma, cataract, posterior synechiae, cystoid macular oedema and papillitis. A visual outcome was acquired in 25 patients - 21 patients had a known visual acuity of > or = 0.1. Four patients had a visual acuity of <0.05 - 3 unilateral and 1 bilateral. 3) Female gender could not be confirmed as an independent risk factor for uveitis, neither was Anti Nuclear Antibody (ANA) positivity. We did not find a significant relationship between the moment of clinical remission of arthritis and of uveitis. 4) When applying current uveitis screening guidelines to our JIA population, we found that the optimum screening regimen would consist of a combination of the higher screening frequency of Southwood (1) and the longer screening period of the American Academy of Pediatrics (2) (AAP) screening guidelines. CONCLUSIONS: Uveitis is often encountered in JIA patients. It is a serious cause of morbidity. The use of disease-modifying antirheumatic drugs (DMARDs) probably has a positive effect on the preservation of visual function. We recommend a uveitis screening regimen which combines the AAP and Southwood guidelines and which includes rheumatoid factor positivity (RF+) and systemic onset patients in the quarterly screening.
Assuntos
Artrite Juvenil/diagnóstico , Técnicas de Diagnóstico Oftalmológico/normas , Guias de Prática Clínica como Assunto/normas , Uveíte/diagnóstico , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Programas de Rastreamento/normas , Prognóstico , Estudos Retrospectivos , Reumatologia/normasRESUMO
In certain inborn errors of metabolism, an allogeneic stem cell transplantation is able to prevent disease progression. This is only possible when the stem cell transplantation (SCT) is performed early in life, before cerebral involvement has occurred. In addition to bone marrow and peripheral blood, unrelated umbilical cord blood appears to be an effective stem cell source as well. Important advantages of umbilical blood as stem cell source are: the time between diagnosis and SCT can be considerably reduced; there is a greater chance of finding a suitable donor and the risk of graft-versus-host disease and viral transmission is decreased. By far the most common disease in the group of inborn metabolic errors for which SCTs are performed is Hurler's disease. In these patients, the percentage of successful transplantations is considerably higher after the use ofunrelated cord blood than when bone marrow or peripheral blood is used as a stem cell source. In addition, donor chimerism occurred significantly more often in those patients who had received unrelated umbilical cord blood. There are also potential disadvantages attached to the use of umbilical blood as stem cell source: the possibility of only one donation per donor and less adaptive immunity following umbilical blood SCT with an increased risk of reactivation of a previous viral infection. However, these disadvantages are less applicable to young children with inborn errors of metabolism. The improvement of transplantation techniques and the availability of this new stem cell source could improve the success rate of this procedure and consequently the prognosis of these severely affected patients.
Assuntos
Transplante de Células-Tronco de Sangue do Cordão Umbilical , Erros Inatos do Metabolismo/terapia , Mucopolissacaridose I/terapia , Doadores de Sangue , Intervalo Livre de Doença , Doença Enxerto-Hospedeiro , Humanos , Recém-Nascido , Resultado do TratamentoRESUMO
Hurler's syndrome (HS), the most severe form of mucopolysaccharidosis type-I, causes progressive deterioration of the central nervous system and death in childhood. Allogeneic stem cell transplantation (SCT) before the age of 2 years halts disease progression. Graft failure limits the success of SCT. We analyzed data on HS patients transplanted in Europe to identify the risk factors for graft failure. We compared outcomes in 146 HS patients transplanted with various conditioning regimens and grafts. Patients were transplanted between 1994 and 2004 and registered to the European Blood and Marrow Transplantation database. Risk factor analysis was performed using logistic regression. 'Survival' and 'alive and engrafted'-rate after first SCT was 85 and 56%, respectively. In multivariable analysis, T-cell depletion (odds ratio (OR) 0.18; 95% confidence interval (CI) 0.04-0.71; P=0.02) and reduced-intensity conditioning (OR 0.08; 95% CI 0.02-0.39; P=0.002) were the risk factors for graft failure. Busulfan targeting protected against graft failure (OR 5.76; 95% CI 1.20-27.54; P=0.028). No difference was noted between cell sources used (bone marrow, peripheral blood stem cells or cord blood (CB)); however, significantly more patients who received CB transplants had full-donor chimerism (OR 9.31; 95% CI 1.06-82.03; P=0.044). These outcomes may impact the safety/efficacy of SCT for 'inborn-errors of metabolism' at large. CB increased the likelihood of sustained engraftment associated with normal enzyme levels and could therefore be considered as a preferential cell source in SCT for 'inborn errors of metabolism'.
Assuntos
Rejeição de Enxerto/mortalidade , Transplante de Células-Tronco Hematopoéticas , Mucopolissacaridose I/mortalidade , Bussulfano/administração & dosagem , Criança , Pré-Escolar , Bases de Dados Factuais , Intervalo Livre de Doença , Europa (Continente) , Feminino , Rejeição de Enxerto/etiologia , Sobrevivência de Enxerto/efeitos dos fármacos , Humanos , Lactente , Recém-Nascido , Modelos Logísticos , Depleção Linfocítica/efeitos adversos , Masculino , Mucopolissacaridose I/terapia , Agonistas Mieloablativos/administração & dosagem , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida , Quimeras de Transplante , Condicionamento Pré-Transplante/efeitos adversos , Transplante HomólogoRESUMO
OBJECTIVE: To document the psychological side effects of methotrexate (MTX) treatment in children with juvenile idiopathic arthritis (JIA) and to explore the usefulness of psychological therapy to ameliorate these side effects. METHODS: The patients included in this study consisted of 29 patients with JIA using MTX. Of these, ten were referred to a pediatric psychologist because of MTX side effects, and had behavioural therapy to cope with these side effects with a strong behavioural component (anticipatory nausea, anxiety). The behavioural therapy was adapted to age and used systemic desensitization (distraction in a positive atmosphere) or cognitive behavioural therapy (relaxation and overruling negative thoughts by positive ones). The parents of the 29 children were interviewed about MTX treatment and the side effects their child had developed. Parents of children referred to the psychologist were also interviewed for their impression of the results of the behavioural therapy. RESULTS: Prior to the behavioural therapy, nine out of 10 children reported MTX related nausea. Six of these ten were nauseous even before the administration and developed anticipatory nausea. Nine out of ten patients also showed some sign of distress in anticipation of MTX treatment, either orally of via injections. The behavioural therapy they had fully abolished side effects in five children and decreased the severity of nausea and distress in two children. Of the remaining nineteen children, not referred to the pediatric psychologist, 11 reported nausea after MTX treatment and four of these developed anticipatory nausea. In addition, eight of these 18 developed behavioural distress in anticipation of the treatment. CONCLUSION: This study showed that children with JIA who receive MTX treatment frequently develop psychological side effects, such as anticipatory nausea and behavioural distress in anticipation of treatment. This is true for patients selected for reported MTX side effects, as well as for randomly chosen JIA patients using MTX. As MTX is still the first choice in the treatment of severe JIA, more attention should be given to the treatment and prevention of side effects. Psychological intervention can be of help, but further studies are needed on the nature of the side effects, as well as on the prerequisites and efficacy of behavioural therapy.