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1.
Pediatr Rheumatol Online J ; 16(1): 74, 2018 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-30466444

RESUMO

OBJECTIVE: To understand the demographics, clinical features and treatment outcomes of Chronic Non-bacterial Osteitis (CNO) from three tertiary paediatric rheumatology services in the United Kingdom. METHODS: Children less than 18 years of age diagnosed with CNO between 2001 to 2016 from one tertiary service and between 2001 to 2017 from two tertiary services were included. Clinical notes were reviewed and all pertinent data were collected on a pre-defined proforma. One hundred and thirty one patients were included in the study. The Bristol diagnostic criteria were applied retrospectively. RESULTS: Retrospective analysis of the data showed that the disease was more common in girls than boys (2.5:1), median age at onset of symptoms was 9.5 years (IQR 8 to 11 years). Bone pain was the predominant symptom in 118/129 (91.4%) followed by swelling in 50/102 (49.01%). Raised inflammatory markers were present in 39.68% of the patients. Whole body Magnetic Resonance Imaging (MRI) was a useful diagnostic tool. Metaphyses of long bones were most often involved and the distal tibial metaphyses 65/131 (49.6%) was the most common site. Non-steroidal anti-inflammatory drugs were used as first line (81.67%) followed by bisphosphonates (61.79%). Treatment was escalated to a TNF blocker when response to bisphosphonates was suboptimal. The disease was in remission in 82.4% of the patients during the last follow up. CONCLUSION: Our multicentre study describes features and outcomes of CNO in a large number of patients in the United Kingdom. SIGNIFICANCE AND INNOVATION: Raised inflammatory markers were present in 39.68% of our patients. Whole body MRI is useful for diagnosis and also determining response to treatment. A greater number of lesions were detected on radiological imaging compared to clinical assessment. Metaphyses of long bones were most often involved and the distal tibial metaphyses (49.6%) were the most common site. Non-steroidal anti-inflammatory drugs were used as first line (81.67%) followed by bisphosphonates (61.79%). There was no difference in number of medications used for management in unifocal versus multifocal disease. TNF blockers were used with good effect in our cohort.

2.
Front Pediatr ; 6: 284, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30356795

RESUMO

Juvenile dermatomyositis (JDM) is a rare autoimmune disease mainly characterized by muscle and skin involvement. Vasculopathy is considered central to the pathogenesis of the disease. The exact nature of vasculopathy is not yet understood but it is a complex process with both an inflammatory and a non-inflammatory, occlusive component. Impaired function of JDM vasculature includes immune complex deposition, altered expression of cell adhesion molecules predominantly inducing Th17 cell infiltration, and endothelial cell dysfunction. Development of vasculopathy is associated with the severe extra-muscular manifestations of JDM, such as gastrointestinal and cardiac manifestations, interstitial lung disease, ulcerative skin disease or development of calcinosis, and portends a poor prognosis. Correlation of histopathological findings, autoantibodies, and extensive diagnostic workup represent key elements to the early detection of vasculopathic features and early aggressive treatment. Monitoring of vasculopathy remains challenging due to the lack of non-invasive biomarkers. Current treatment approaches provide variable benefit, but better understanding of the essential pathogenic mechanisms should help lead to improved outcomes. Whilst acknowledging that evidence is limited, this review aims to describe the vasculopathy of JDM in the context of pathophysiology, clinical features, and treatment of disease.

3.
Artigo em Inglês | MEDLINE | ID: mdl-30358861

RESUMO

Objectives: Rituximab (RTX) may be a treatment option for children and young people with JIA, although it is not licensed for this indication. The aim of this study was to describe RTX use and outcomes among children with JIA. Methods: This analysis included all JIA patients within the UK Biologics for Children with Rheumatic Diseases study starting RTX. Disease activity was assessed at RTX start and at follow-up. The total number of courses each patient received was assessed. Serious infections and infusion reactions occurring following RTX were reported. Results: Forty-one JIA patients starting RTX were included, the majority with polyarthritis: polyarthritis RF negative [n = 14 (35%)], polyarthritis RF positive [n = 13 (33%)] and extended oligoarthritis [n = 9 (23%)]. Most were female (80%) with a median age of 15 years [interquartile range (IQR) 12-16] and a median disease duration of 9 years (IQR 5-11). The median improvement in the clinical Juvenile Arthritis Disease Activity Score (cJADAS; three-variable 71-joint JADAS) from RTX start was 9 units (n = 7; IQR -14-2). More than half reported more than one course of RTX. The median time between each course was 219 days (IQR 198-315). During follow-up, 17 (41%) patients reported switching to another biologic, including tocilizumab (n = 8), abatacept (n = 6) and TNF inhibitor (n = 3). Three patients (7%) reported a serious infection on RTX (rate of first serious infection 6.2/100 person-years). Four patients (10%) reported an infusion reaction. Conclusions: This real-world cohort of children with JIA, the majority with polyarticular or extended oligoarticular JIA, showed RTX may be an effective treatment option for children who do not respond to TNF inhibitor, with a low rate of serious infections on treatment.

5.
Ann Rheum Dis ; 77(2): 241-250, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29084729

RESUMO

OBJECTIVES: This study aimed to develop consensus on an internationally agreed dataset for juvenile dermatomyositis (JDM), designed for clinical use, to enhance collaborative research and allow integration of data between centres. METHODS: A prototype dataset was developed through a formal process that included analysing items within existing databases of patients with idiopathic inflammatory myopathies. This template was used to aid a structured multistage consensus process. Exploiting Delphi methodology, two web-based questionnaires were distributed to healthcare professionals caring for patients with JDM identified through email distribution lists of international paediatric rheumatology and myositis research groups. A separate questionnaire was sent to parents of children with JDM and patients with JDM, identified through established research networks and patient support groups. The results of these parallel processes informed a face-to-face nominal group consensus meeting of international myositis experts, tasked with defining the content of the dataset. This developed dataset was tested in routine clinical practice before review and finalisation. RESULTS: A dataset containing 123 items was formulated with an accompanying glossary. Demographic and diagnostic data are contained within form A collected at baseline visit only, disease activity measures are included within form B collected at every visit and disease damage items within form C collected at baseline and annual visits thereafter. CONCLUSIONS: Through a robust international process, a consensus dataset for JDM has been formulated that can capture disease activity and damage over time. This dataset can be incorporated into national and international collaborative efforts, including existing clinical research databases.

7.
Ann Rheum Dis ; 77(1): 30-39, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28855174

RESUMO

AIMS: The EuroMyositis Registry facilitates collaboration across the idiopathic inflammatory myopathy (IIM) research community. This inaugural report examines pooled Registry data. METHODS: Cross-sectional analysis of IIM cases from 11 countries was performed. Associations between clinical subtypes, extramuscular involvement, environmental exposures and medications were investigated. RESULTS: Of 3067 IIM cases, 69% were female. The most common IIM subtype was dermatomyositis (DM) (31%). Smoking was more frequent in connective tissue disease overlap cases (45%, OR 1.44, 95% CI 1.09 to 1.90, p=0.012). Smoking was associated with interstitial lung disease (ILD) (OR 1.32, 95% CI 1.06 to 1.65, p=0.013), dysphagia (OR 1.43, 95% CI 1.16 to 1.77, p=0.001), malignancy ever (OR 1.78, 95% CI 1.36 to 2.33, p<0.001) and cardiac involvement (OR 2.40, 95% CI 1.60 to 3.60, p<0.001).Dysphagia occurred in 39% and cardiac involvement in 9%; either occurrence was associated with higher Health Assessment Questionnaire (HAQ) scores (adjusted OR 1.79, 95% CI 1.43 to 2.23, p<0.001). HAQ scores were also higher in inclusion body myositis cases (adjusted OR 3.85, 95% CI 2.52 to 5.90, p<0.001). Malignancy (ever) occurred in 13%, most commonly in DM (20%, OR 2.06, 95% CI 1.65 to 2.57, p<0.001).ILD occurred in 30%, most frequently in antisynthetase syndrome (71%, OR 10.7, 95% CI 8.6 to 13.4, p<0.001). Rash characteristics differed between adult-onset and juvenile-onset DM cases ('V' sign: 56% DM vs 16% juvenile-DM, OR 0.16, 95% CI 0.07 to 0.36, p<0.001). Glucocorticoids were used in 98% of cases, methotrexate in 71% and azathioprine in 51%. CONCLUSION: This large multicentre cohort demonstrates the importance of extramuscular involvement in patients with IIM, its association with smoking and its influence on disease severity. Our findings emphasise that IIM is a multisystem inflammatory disease and will help inform prognosis and clinical management of patients.


Assuntos
Pesquisa Biomédica/métodos , Cooperação Internacional , Miosite/epidemiologia , Sistema de Registros/estatística & dados numéricos , Estudos de Coortes , Estudos Transversais , Feminino , Nível de Saúde , Humanos , Masculino , Miosite/etiologia , Miosite/patologia , Prognóstico , Índice de Gravidade de Doença , Fumar/efeitos adversos , Inquéritos e Questionários
8.
Ann Rheum Dis ; 76(2): 329-340, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27515057

RESUMO

BACKGROUND: In 2012, a European initiative called Single Hub and Access point for pediatric Rheumatology in Europe (SHARE) was launched to optimise and disseminate diagnostic and management regimens in Europe for children and young adults with rheumatic diseases. Juvenile dermatomyositis (JDM) is a rare disease within the group of paediatric rheumatic diseases (PRDs) and can lead to significant morbidity. Evidence-based guidelines are sparse and management is mostly based on physicians' experience. Consequently, treatment regimens differ throughout Europe. OBJECTIVES: To provide recommendations for diagnosis and treatment of JDM. METHODS: Recommendations were developed by an evidence-informed consensus process using the European League Against Rheumatism standard operating procedures. A committee was constituted, consisting of 19 experienced paediatric rheumatologists and 2 experts in paediatric exercise physiology and physical therapy, mainly from Europe. Recommendations derived from a validated systematic literature review were evaluated by an online survey and subsequently discussed at two consensus meetings using nominal group technique. Recommendations were accepted if >80% agreement was reached. RESULTS: In total, 7 overarching principles, 33 recommendations on diagnosis and 19 recommendations on therapy were accepted with >80% agreement among experts. Topics covered include assessment of skin, muscle and major organ involvement and suggested treatment pathways. CONCLUSIONS: The SHARE initiative aims to identify best practices for treatment of patients suffering from PRD. Within this remit, recommendations for the diagnosis and treatment of JDM have been formulated by an evidence-informed consensus process to produce a standard of care for patients with JDM throughout Europe.


Assuntos
Dermatomiosite/terapia , Terapia por Exercício , Glucocorticoides/uso terapêutico , Imunossupressores/uso terapêutico , Guias de Prática Clínica como Assunto , Protetores Solares/uso terapêutico , Ciclosporina/uso terapêutico , Dermatomiosite/diagnóstico , Europa (Continente) , Medicina Baseada em Evidências , Humanos , Metotrexato/uso terapêutico , Ácido Micofenólico/uso terapêutico , Equipe de Assistência ao Paciente/organização & administração , Prednisolona/uso terapêutico , Rituximab/uso terapêutico , Sociedades Médicas
9.
Best Pract Res Clin Rheumatol ; 31(4): 535-557, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-29773272

RESUMO

Registries and biobanks for juvenile dermatomyositis (JDM) have generated statistical power to help understand pathogenesis and determine treatment and long-term outcomes in this rare and heterogeneous disease. Genotype, autoantibodies, muscle histology and early clinical features may predict prognosis and guide personalised treatment. While corticosteroids and disease-modifying anti-rheumatic drugs improve outcomes, there remain children who experience refractory disease. Ongoing research into the aberrant immune response and novel biological targets is necessary. Best practice guidelines promote prompt stepwise treatment, and there is growing appreciation of the role of exercise in improving prognosis. Validated tools standardise assessment of disease activity and damage in musculoskeletal, mucocutaneous, pulmonary, cardiac, gastrointestinal and endocrine systems. Recently, an internationally agreed dataset for JDM has been defined for clinical practice and incorporation into registries. In the future, with bigger datasets, statistical models may guide stratification for personalised medicine and discern the most relevant outcome markers for research.


Assuntos
Dermatomiosite , Antirreumáticos/uso terapêutico , Autoanticorpos/imunologia , Biomarcadores , Criança , Dermatomiosite/tratamento farmacológico , Dermatomiosite/imunologia , Humanos , Prognóstico
10.
Indian J Pediatr ; 83(2): 163-71, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26489640

RESUMO

Juvenile dermatomyositis and juvenile scleroderma are rare multisystem autoimmune disorders. Although they share some pathognomonic hallmarks with adult onset myositis or scleroderma, there are significant differences in presentation, characteristics and associated features when the diseases present in childhood. In view of this, and the rarity of the conditions, it is important for care to be led by teams with expertise in pediatric rheumatology conditions. Prognosis has improved significantly in the West; likely due to early diagnosis and aggressive treatment with immunosuppressive medications. However, this trend is not replicated in the developing world. Early recognition of these diseases is crucial to achieve rapid and sustained remission and prevent disease or medication associated complications. This article aims to provide a practical overview for recognition, diagnosis and treatment of these conditions.


Assuntos
Dermatomiosite , Esclerodermia Localizada , Escleroderma Sistêmico , Criança , Dermatomiosite/sangue , Dermatomiosite/diagnóstico , Dermatomiosite/fisiopatologia , Dermatomiosite/terapia , Gerenciamento Clínico , Diagnóstico Precoce , Humanos , Esclerodermia Localizada/sangue , Esclerodermia Localizada/diagnóstico , Esclerodermia Localizada/fisiopatologia , Esclerodermia Localizada/terapia , Escleroderma Sistêmico/sangue , Escleroderma Sistêmico/diagnóstico , Escleroderma Sistêmico/fisiopatologia , Escleroderma Sistêmico/terapia
11.
Trials ; 16: 268, 2015 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-26063230

RESUMO

BACKGROUND: Juvenile dermatomyositis (JDM) is a rare autoimmune inflammatory disorder associated with significant morbidity and mortality. International collaboration is necessary to better understand the pathogenesis of the disease, response to treatment and long-term outcome. To aid international collaboration, it is essential to have a core set of data that all researchers and clinicians collect in a standardised way for clinical purposes and for research. This should include demographic details, diagnostic data and measures of disease activity, investigations and treatment. Variables in existing clinical registries have been compared to produce a provisional data set for JDM. We now aim to develop this into a consensus-approved minimum core dataset, tested in a wider setting, with the objective of achieving international agreement. METHODS/DESIGN: A two-stage bespoke Delphi-process will engage the opinion of a large number of key stakeholders through Email distribution via established international paediatric rheumatology and myositis organisations. This, together with a formalised patient/parent participation process will help inform a consensus meeting of international experts that will utilise a nominal group technique (NGT). The resulting proposed minimal dataset will be tested for feasibility within existing database infrastructures. The developed minimal dataset will be sent to all internationally representative collaborators for final comment. The participants of the expert consensus group will be asked to draw together these comments, ratify and 'sign off' the final minimal dataset. DISCUSSION: An internationally agreed minimal dataset has the potential to significantly enhance collaboration, allow effective communication between groups, provide a minimal standard of care and enable analysis of the largest possible number of JDM patients to provide a greater understanding of this disease. The final approved minimum core dataset could be rapidly incorporated into national and international collaborative efforts, including existing prospective databases, and be available for use in randomised controlled trials and for treatment/protocol comparisons in cohort studies.


Assuntos
Pesquisa Biomédica/métodos , Comportamento Cooperativo , Conjuntos de Dados como Assunto , Dermatomiosite , Comunicação Interdisciplinar , Cooperação Internacional , Projetos de Pesquisa , Consenso , Conferências de Consenso como Assunto , Técnica Delfos , Dermatomiosite/diagnóstico , Dermatomiosite/fisiopatologia , Dermatomiosite/psicologia , Dermatomiosite/terapia , Correio Eletrônico , Humanos , Internet , Pais/psicologia , Pacientes/psicologia , Desenvolvimento de Programas , Inquéritos e Questionários
12.
Artigo em Inglês | MEDLINE | ID: mdl-25075205

RESUMO

BACKGROUND: Juvenile dermatomyositis (JDM) is a rare but severe autoimmune inflammatory myositis of childhood. International collaboration is essential in order to undertake clinical trials, understand the disease and improve long-term outcome. The aim of this study was to propose from existing collaborative initiatives a preliminary minimal dataset for JDM. This will form the basis of the future development of an international consensus-approved minimum core dataset to be used both in clinical care and inform research, allowing integration of data between centres. METHODS: A working group of internationally-representative JDM experts was formed to develop a provisional minimal dataset. Clinical and laboratory variables contained within current national and international collaborative databases of patients with idiopathic inflammatory myopathies were scrutinised. Judgements were informed by published literature and a more detailed analysis of the Juvenile Dermatomyositis Cohort Biomarker Study and Repository, UK and Ireland. RESULTS: A provisional minimal JDM dataset has been produced, with an associated glossary of definitions. The provisional minimal dataset will request information at time of patient diagnosis and during on-going prospective follow up. At time of patient diagnosis, information will be requested on patient demographics, diagnostic criteria and treatments given prior to diagnosis. During on-going prospective follow-up, variables will include the presence of active muscle or skin disease, major organ involvement or constitutional symptoms, investigations, treatment, physician global assessments and patient reported outcome measures. CONCLUSIONS: An internationally agreed minimal dataset has the potential to significantly enhance collaboration, allow effective communication between groups, provide a minimal standard of care and enable analysis of the largest possible number of JDM patients to provide a greater understanding of this disease. This preliminary dataset can now be developed into a consensus-approved minimum core dataset and tested in a wider setting with the aim of achieving international agreement.


Assuntos
Dermatomiosite , Gerenciamento Clínico , Biomarcadores/análise , Canadá , Criança , Dermatomiosite/classificação , Dermatomiosite/diagnóstico , Dermatomiosite/fisiopatologia , Dermatomiosite/terapia , Progressão da Doença , Feminino , Humanos , Cooperação Internacional , Irlanda , Itália , Masculino , Avaliação de Resultados (Cuidados de Saúde) , Gravidade do Paciente , Reino Unido
13.
Rheumatology (Oxford) ; 53(8): 1504-12, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24692572

RESUMO

OBJECTIVE: To determine whether mucocutaneous manifestations are associated with major organ involvement in a UK national cohort of juvenile-onset SLE (JSLE) patients. METHODS: JSLE patients (n = 241) from 15 different centres whose diagnosis fulfilled four or more of the ACR criteria were divided into two groups: those with at least one ACR mucocutaneous criterion (ACR skin feature positive) and those without (ACR skin feature negative) at diagnosis. The relative frequency of skin involvement was described by the paediatric adaptation of the 2004 British Isles Lupus Assessment Group (pBILAG-2004) index. RESULTS: One hundred and seventy-nine patients (74%) had ACR-defined skin involvement with no significant demographic differences compared with those without. ACR skin feature negative patients showed greater haematological (84% vs 67%), renal (43% vs 26%) (P < 0.05) and neurological (16% vs 4%) involvement (P = 0.001). Forty-two per cent of ACR skin feature negative patients had skin involvement using pBILAG-2004, which included maculopapular rash (17%), non-scaring alopecia (15%), cutaneous vasculitis (12%) and RP (12%). ACR skin feature negative patients with moderate to severe skin involvement by pBILAG-2004 showed greater renal and haematological involvement at diagnosis and over the follow-up period (P < 0.05). Higher immunosuppressive drug use in the skin feature negative group was demonstrated. CONCLUSION: Patients who fulfil the ACR criteria but without any of the mucocutaneous criteria at diagnosis have an increased risk of major organ involvement. The pBILAG-2004 index has shown that other skin lesions may go undetected using the ACR criteria alone, and these lesions show a strong correlation with disease severity and major organ involvement.


Assuntos
Lúpus Eritematoso Sistêmico/complicações , Dermatopatias/complicações , Pele/patologia , Adolescente , Criança , Feminino , Humanos , Lúpus Eritematoso Sistêmico/patologia , Masculino , Índice de Gravidade de Doença , Dermatopatias/patologia
14.
J Clin Immunol ; 34(1): 42-8, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24217815

RESUMO

We report a child with short stature since birth who was otherwise well, presenting at 2.8 years with progressive granulomatous skin lesions when diagnosed with severe T cell immunodeficiency. When previously investigated for short stature, and at the time of current investigations, she had no radiological skeletal features characteristics for cartilage hair hypoplasia, but we found a disease causing RMRP (RNase mitochondrial RNA processing endoribonuclease) gene mutation. Whilst search for HLA matched unrelated donor for haematopoietic stem cell transplantation (HSCT) was underway, she developed rapidly progressive EBV-related lymphoproliferative disorder requiring laparotomy and small bowel resection, and was treated with anti-B cell monoclonal antibody and eventually curative allogeneic HSCT. Screening for RMRP gene mutations should be part of immunological evaluation of patients with 'severe and/or combined' T cell immunodeficiency of unknown origin, especially when associated with short stature and regardless of presence or absence of radiological skeletal features.


Assuntos
Cabelo/anormalidades , Doença de Hirschsprung/diagnóstico , Síndromes de Imunodeficiência/diagnóstico , Osteocondrodisplasias/congênito , Fenótipo , Osso e Ossos/diagnóstico por imagem , Pré-Escolar , Dermatite/patologia , Nanismo , Feminino , Granuloma/patologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Doença de Hirschsprung/genética , Doença de Hirschsprung/terapia , Humanos , Síndromes de Imunodeficiência/genética , Síndromes de Imunodeficiência/terapia , Imunofenotipagem , Osteocondrodisplasias/diagnóstico , Osteocondrodisplasias/genética , Osteocondrodisplasias/terapia , Radiografia , Receptores de Antígenos de Linfócitos T alfa-beta/metabolismo , Linfócitos T/metabolismo , Transplante Homólogo , Resultado do Tratamento
15.
Arthritis Rheum ; 64(7): 2356-65, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22294381

RESUMO

OBJECTIVE: The UK Juvenile-Onset Systemic Lupus Erythematosus (JSLE) Cohort Study is a multicenter collaborative network established with the aim of improving the understanding of juvenile SLE. The present study was undertaken to describe the clinical manifestations and disease course in patients with juvenile SLE from this large, national inception cohort. METHODS: Detailed data on clinical phenotype were collected at baseline and at regular clinic reviews and annual followup assessments in 232 patients from 14 centers across the UK over 4.5 years. Patients with SLE were identified according to the American College of Rheumatology (ACR) SLE classification criteria. The present cohort comprised children with juvenile SLE (n=198) whose diagnosis fulfilled ≥4 of the ACR criteria for SLE. RESULTS: Among patients with juvenile SLE, the female:male sex distribution was 5.6:1 and the median age at diagnosis was 12.6 years (interquartile range 10.4-14.5 years). Male patients were younger than female patients (P<0.01). Standardized ethnicity data demonstrated a greater risk of juvenile SLE in non-Caucasian UK patients (P<0.05). Scores on the pediatric adaptation of the 2004 British Isles Lupus Assessment Group disease activity index demonstrated significantly increased frequencies of musculoskeletal (82%), renal (80%), hematologic (91%), immunologic (54%), and neurologic (26%) involvement among the patients over time. A large proportion of the patients (93%) were taking steroids and 24% of the patients required treatment with cyclophosphamide. Disease damage was common, with 28% of the patients having a Systemic Lupus International Collaborating Clinics/ACR damage score of ≥1. CONCLUSION: The data on these patients from the UK JSLE Cohort Study, comprising one of the largest national inception cohorts of patients with juvenile SLE to date, indicate that severe organ involvement and significant disease activity are primary characteristics in children with juvenile SLE. In addition, accumulation of disease-associated damage could be seen.


Assuntos
Progressão da Doença , Lúpus Eritematoso Sistêmico/diagnóstico , Índice de Gravidade de Doença , Adolescente , Idade de Início , Criança , Estudos de Coortes , Ciclofosfamida/uso terapêutico , Grupos Étnicos , Feminino , Humanos , Imunossupressores/uso terapêutico , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Lúpus Eritematoso Sistêmico/etnologia , Lúpus Eritematoso Sistêmico/patologia , Masculino , Fatores Sexuais , Reino Unido , Adulto Jovem
16.
PLoS Genet ; 6(3): e1000874, 2010 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-20300641

RESUMO

We investigated eight families with a novel subtype of congenital generalized lipodystrophy (CGL4) of whom five members had died from sudden cardiac death during their teenage years. ECG studies revealed features of long-QT syndrome, bradycardia, as well as supraventricular and ventricular tachycardias. Further symptoms comprised myopathy with muscle rippling, skeletal as well as smooth-muscle hypertrophy, leading to impaired gastrointestinal motility and hypertrophic pyloric stenosis in some children. Additionally, we found impaired bone formation with osteopenia, osteoporosis, and atlanto-axial instability. Homozygosity mapping located the gene within 2 Mbp on chromosome 17. Prioritization of 74 candidate genes with GeneDistiller for high expression in muscle and adipocytes suggested PTRF-CAVIN (Polymerase I and transcript release factor/Cavin) as the most probable candidate leading to the detection of homozygous mutations (c.160delG, c.362dupT). PTRF-CAVIN is essential for caveolae biogenesis. These cholesterol-rich plasmalemmal vesicles are involved in signal-transduction and vesicular trafficking and reside primarily on adipocytes, myocytes, and osteoblasts. Absence of PTRF-CAVIN did not influence abundance of its binding partner caveolin-1 and caveolin-3. In patient fibroblasts, however, caveolin-1 failed to localize toward the cell surface and electron microscopy revealed reduction of caveolae to less than 3%. Transfection of full-length PTRF-CAVIN reestablished the presence of caveolae. The loss of caveolae was confirmed by Atomic Force Microscopy (AFM) in combination with fluorescent imaging. PTRF-CAVIN deficiency thus presents the phenotypic spectrum caused by a quintessential lack of functional caveolae.


Assuntos
Arritmias Cardíacas/complicações , Lipodistrofia Generalizada Congênita/complicações , Lipodistrofia Generalizada Congênita/genética , Síndrome do QT Longo/complicações , Mutação/genética , Proteínas de Ligação a RNA/genética , Tecido Adiposo/patologia , Adolescente , Arritmias Cardíacas/genética , Sequência de Bases , Cavéolas/patologia , Cavéolas/ultraestrutura , Criança , Análise Mutacional de DNA , Família , Evolução Fatal , Feminino , Fibroblastos/patologia , Fibroblastos/ultraestrutura , Homozigoto , Humanos , Recém-Nascido , Lipodistrofia Generalizada Congênita/patologia , Síndrome do QT Longo/genética , Masculino , Dados de Sequência Molecular , Músculos/patologia , Omã , Linhagem , Fenótipo
17.
Rheumatology (Oxford) ; 49(1): 123-7, 2010 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-19933594

RESUMO

OBJECTIVES: Adult studies have demonstrated that ultrasonography (US) is more sensitive at detecting synovitis than clinical examination. The detection of subclinical disease has implications for deciding which patients receive more aggressive therapy from the outset. This study aimed to determine whether children with clinically diagnosed oligoarticular juvenile idiopathic arthritis (JIA) had US-detectable subclinical synovitis. METHODS: This was a cross-sectional pilot study conducted in a tertiary paediatric rheumatology clinic. Seventeen children with a median age of 10 years (range 3-13 years) and with oligoarticular disease of duration <12 months (median 5 months) were recruited. All subjects were DMARD and oral/i.v. corticosteroid naïve. A core set of 40 joints was clinically examined for synovitis and then scanned by a rheumatologist trained in joint US and blinded to all clinical data, at the same appointment. RESULTS: In total, 680 joints were examined both clinically and by US. Twenty-three joints were found to have clinical synovitis, and of these only 17 had synovitis confirmed by US. A further 15 joints were found to have synovitis on US examination alone. Overall, subclinical synovitis was detected in 6/17 children, mostly in the hands and feet. One child was reclassified as having polyarticular disease. CONCLUSIONS: This pilot study has highlighted a discrepancy between clinical examination and ultrasound when assessing the joints of children with JIA. US is a feasible tool for examining multiple joints and identifying subclinical synovitis, particularly when considering the small joints of the hands and feet.


Assuntos
Artrite Juvenil/complicações , Sinovite/diagnóstico por imagem , Sinovite/etiologia , Adolescente , Criança , Pré-Escolar , Métodos Epidemiológicos , Feminino , Articulações do Pé/diagnóstico por imagem , Articulação da Mão/diagnóstico por imagem , Humanos , Masculino , Exame Físico , Sinovite/patologia , Ultrassonografia
18.
Rheumatology (Oxford) ; 49(2): 315-25, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19948753

RESUMO

OBJECTIVE: Joint hypermobility, common in childhood, can be associated with severe pain and significant morbidity. Physiotherapy, the mainstay of treatment, lacks a robust evidence base. This study is aimed at determining the best physiotherapy intervention in managing childhood hypermobility. METHODS: A prospective randomized comparative trial (RCT) compared a 6-week generalized programme, improving muscular strength and fitness, with a targeted programme aimed at correcting motion control of symptomatic joints. Patients were assessed on symptom scores (pain/global-impact), function, muscle strength and fitness. RESULTS: Fifty-seven children, aged 7-16 years with symptomatic hypermobility, were randomly assign to receive a targeted (T; n = 30) or generalized (G; n = 27) programme. Statistically significant improvements were demonstrated in both the children's and parental pain scores across both the randomized groups between baseline and follow-up assessments (P < 0.05). However, the difference in improvement between the groups was not statistically significant. Child's assessment of change in pain score: mean difference (95% CI) T - G, 3.97 (-15.59, 20.85) at the end of treatment and 9.41 at 3-month follow-up (-17.42, 36.24). At the end of treatment, parental assessment of change in pain score, T - G was: -0.27 (-15.05, 14.50) and at 3-month follow-up it was: -9.48 (-26.40, 7.43). Change in parental global assessment was statistically significant, in favour of targeted physiotherapy at final assessment: -21.29 (-40.03, -2.55). CONCLUSION: This is the first physiotherapy RCT for treating hypermobility. It demonstrated significant and sustained reduction in pain when both groups were combined, but did not detect any difference between the groups. This study provides normative and methodological data for future studies of hypermobility. TRIAL REGISTRATION: Current Controlled Trials, www.controlled-trials.com, ISRCTN58523390.


Assuntos
Terapia por Exercício/métodos , Instabilidade Articular/reabilitação , Adolescente , Artrometria Articular , Criança , Feminino , Humanos , Instabilidade Articular/fisiopatologia , Masculino , Força Muscular , Medição da Dor/métodos , Amplitude de Movimento Articular , Resultado do Tratamento
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