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1.
Artigo em Inglês | MEDLINE | ID: mdl-32044838

RESUMO

OBJECTIVES: neurologic adverse effects (NAE) induced by biotherapies have been reported in the literature mainly in adult patients with inflammatory bowel disease (IBD), rheumatic diseases or psoriasis. There are scant data in children. Aims of this study are to report and describe non-infective NAE associated with anti-TNFα antibodies in pediatric IBD, and to evaluate their incidence. METHODS: we retrospectively collected all reports of NAE in pediatric IBD treated with anti-TNFα antibodies recorded in the French Pharmacovigilance Database. To estimate the national incidence of NAEs, we extrapolated data from the French regional Inception population-based cohort EPIMAD. RESULTS: between 2000 and 2018, 231 adverse events in pediatric IBD exposed to anti-TNFα antibodies were reported to this Database. 17 NAE (7.36%) were collected: 8 severe NAE (one demyelinating neuropathy, one optic neuritis, one acute transverse myelitis, one polyradiculoneuritis, one sensorineural hearing loss, one seizure, one stroke, and one glioma), 7 moderate NAE (headaches), and 2 neuropsychic events. The median delay between anti-TNFα start and NAE occurrence was 6 months (range: 13 days to 26 months). In 10/17 patients, anti-TNFα antibodies were stopped. 9/17 patients had a complete resolution (including 2 severe NAE) and 8/17 a partial resolution (including 6 severe NAE). We estimate the incidence of severe NAE in pediatric IBD treated with anti-TNFα antibodies at 1 case for 10 000 patients-year in France. CONCLUSIONS: NAE associated with anti-TNFα antibodies in pediatric IBD are rare. In severe NAE, we recommend to discontinuate anti-TNFα therapy and to consider alternative treatment.

2.
Clin Gastroenterol Hepatol ; 18(1): 133-140.e1, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30981008

RESUMO

BACKGROUND & AIMS: Mucosal healing (MH) has become a goal of therapy for Crohn's disease (CD), but frequent endoscopies are not feasible. We aimed to develop and validate a non-invasive index to assess mucosal inflammation in children with CD. METHODS: We collected data from the multi-center prospective ImageKids study, in which children with CD underwent ileocolonoscopy with magnetic resonance enterography. We investigated the association of pediatric CD activity index (PCDAI) items and laboratory test results with the simple endoscopic score for CD (SESCD). We used these data in a blended mathematical judgmental clinimetric approach to develop a weighted categorized index to identify children with CD who have MH, which we called the MINI index. We validated the index using data from 3 independent patient cohorts. The derivation and validation cohorts included 154 and 168 children, respectively (age 14.1 ± 2.5 years and 14.2 ± 3.9 years), of whom 16% and 36% had MH (defined as SESCD<3). RESULTS: In multivariable models, the stooling item of the PCDAI, erythrocyte sedimentation rate, and level of fecal calprotectin were associated with SESCD (all P < .05). We added data on level of C-reactive protein to develop the MINI index. MINI scores below 8 identified children with MH with 88% sensitivity and 85% specificity in the derivation cohort and with 84% sensitivity and 87% specificity in the validation cohorts. Ninety percent of the patients in the validation cohort with scores of 8 or more had active mucosal inflammation, yet 78% of patients with scores below 8 had MH. Scores below 6 increase the positive predictive value to 86%. CONCLUSIONS: We developed an index to non-invasively assess mucosal inflammation in children with CD. This index, identifies children with MH with high sensitivity and specificity. The added benefit of MINI over measurement of fecal calprotectin was small but significant, especially for patients with concentrations of fecal calprotectin from 100 to 599 µg/g. ClinicalTrials.gov no: NCT01881490.

3.
Gut ; 69(1): 32-41, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-30979718

RESUMO

INTRODUCTION: The optimal trial design for assessing novel therapies in paediatric IBD (PIBD) is a subject of intense ongoing global discussions and debate among the different stakeholders. However, there is a consensus that the current situation in which most medications used in children with IBD are prescribed as off-label without sufficient paediatric data is unacceptable. Shortening the time lag between adult and paediatric approval of drugs is of the upmost importance. In this position paper we aimed to provide guidance from the global clinical research network (Pediatric Inflammatory Bowel Disease Network, PIBDnet) for designing clinical trials in PIBD in order to facilitate drug approval for children. METHODS: A writing group has been established by PIBDnet and topics were assigned to different members. After an iterative process of revisions among the writing group and one face-to-face meeting, all statements have reached consensus of >80% as defined a priori. Next, all core members of PIBDnet voted on the statements, reaching consensus of >80% on all statements. Comments from the members were incorporated in the text. RESULTS: The commentary includes 18 statements for guiding data extrapolation from adults, eligibility criteria to PIBD trials, use of placebo, dosing, endpoints and recommendations for feasible trials. Controversial issues have been highlighted in the text. CONCLUSION: The viewpoints expressed in this paper could assist planning clinical trials in PIBD which are both of high quality and ethical, while remaining pragmatic.


Assuntos
Ensaios Clínicos como Assunto/métodos , Fármacos Gastrointestinais/uso terapêutico , Doenças Inflamatórias Intestinais/tratamento farmacológico , Fatores Etários , Produtos Biológicos/administração & dosagem , Produtos Biológicos/uso terapêutico , Criança , Ensaios Clínicos como Assunto/normas , Relação Dose-Resposta a Droga , Aprovação de Drogas/métodos , Fármacos Gastrointestinais/administração & dosagem , Humanos , Seleção de Pacientes , Projetos de Pesquisa , Índice de Gravidade de Doença , Resultado do Tratamento
4.
Therap Adv Gastroenterol ; 12: 1756284819890534, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31803252

RESUMO

Environmental factors, particularly diet, are the focus of current research as potential triggers of inflammatory bowel disease (IBD). Epidemiological cohort data showing a rapid increase of IBD in western countries and the emergence of IBD in developing countries paralleling the introduction of a western diet are indirect arguments linking food and food behaviour to intestinal inflammation. The successful use of exclusive enteral nutrition (EEN), now considered as first-line induction therapy for paediatric Crohn's disease (CD), is the strongest argument for a link between diet and IBD. Mechanistic studies revealed that EEN impacts intestinal microbiota composition and together with the exclusion of potentially harmful food ingredients this allows the control of intestinal inflammation and induces mucosal healing. However, the exclusivity character of EEN is a major drawback. Based on the data of EEN, the search for more tolerable and still effective diets has begun. Recent reports on the new CD exclusion diet (CDED), CD-TREAT, as well as the specific carbohydrate diet (SCD) provide the first promising results, further underlining the potential of diet to control inflammation in patients with CD by excluding certain food components. Ongoing research is trying to combine nutritional interventions with analyses of intestinal microbiota and their metabolic functions with the aim of correcting the intestinal dysbiosis that characterizes IBD. This research is promising and gives new hope to patients that have been looking for decades for nutritional interventions with the aim of stabilizing their disease course. There might even be potential for disease prevention in high-risk patients by excluding potentially harmful food components.

6.
J Pediatr Gastroenterol Nutr ; 68(5): 676-683, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30664566

RESUMO

OBJECTIVES: Despite existence of international guidelines for diagnosis and management of inflammatory bowel diseases (IBD) in children, there might be differences in the clinical approach. METHODS: A survey on clinical practice in paediatric IBD was performed among members of the ESPGHAN Porto IBD working group and interest group, PIBD-NET, and IBD networks in Canada and German-speaking countries (CIDsCANN, GPGE), using a web-based questionnaire. Responses to 63 questions from 106 paediatric IBD centres were collected. RESULTS: Eighty-four percentage of centres reported to fulfil the revised Porto criteria in the majority of patients. In luminal Crohn disease (CD), exclusive enteral nutrition is used as a first-line induction therapy and immunomodulators (IMM) are used since diagnosis in the majority of patients. Infliximab (IFX) is mostly considered as first-line biological. Sixty percentage of centres have experience with vedolizumab and/or ustekinumab and 40% use biosimilars. In the majority of ulcerative colitis (UC) patients 5-aminosalicylates are continued as concomitant therapy to IMM (usually azathioprine [AZA]/6-MP). After ileocaecal resection (ICR) in CD patients without postoperative residual disease, AZA monotherapy is the preferred treatment. CONCLUSIONS: A majority of centres follows both the Porto diagnostic criteria as well as paediatric (ESPGHAN/ECCO) guidelines on medical and surgical IBD management. This reflects the value of international societal guidelines. However, potentially desirable answers might have been given instead of what is true daily practice, and the most highly motivated people might have answered, leading to some bias.

7.
Aliment Pharmacol Ther ; 49(2): 155-164, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30506693

RESUMO

BACKGROUND: In the IMAgINE 1 study, adalimumab induced and maintained remission of moderate-to-severe Crohn's disease in children. AIM: To assess the efficacy, pharmacokinetics, immunogenicity and safety of immunomodulator and adalimumab combination therapy vs adalimumab monotherapy in paediatric patients with Crohn's disease. METHODS: Patients 6-17 years old with moderate-to-severe Crohn's disease (n = 192) received weight-based adalimumab induction at baseline and week 2. At week 4, 188 patients were randomised to high-dose or low-dose adalimumab. Patients receiving immunomodulators (investigator's decision) at baseline maintained a stable dose until week 26; patients could then discontinue immunomodulators. Adalimumab serum concentrations were measured at weeks 4, 26 and 52. Safety was evaluated at each study visit. Data were analysed using non-responder imputation (NRI; week 4) or modified NRI (weeks 26; 52). RESULTS: At week 4, patients with (n = 117) and without (n = 71) baseline immunomodulator use had similar response (79%; 87%; P = 0.235) and remission (26%; 30%; P = 0.737) rates. At week 26, patients with and without baseline immunomodulators had no significant difference in response (68%; 55%; P = 0.086) or remission (41%; 30%; P = 0.122). At week 52, patients with (n = 82) and without (n = 106) immunomodulator use had no significant difference in response (56%; 46%; P = 0.189) or remission (38%; 33%; P = 0.539). Adalimumab serum trough concentrations and serious infection rates (7%; 6%) were not significantly different between groups. CONCLUSIONS: Analyses found no statistically significant difference in response or remission between patients receiving adalimumab monotherapy vs immunomodulator and adalimumab combination therapy. Serious and infectious adverse event rates were similar between groups.


Assuntos
Adalimumab/administração & dosagem , Anti-Inflamatórios/administração & dosagem , Doença de Crohn/diagnóstico , Doença de Crohn/tratamento farmacológico , Fatores Imunológicos/administração & dosagem , Adalimumab/efeitos adversos , Adalimumab/farmacocinética , Adolescente , Anti-Inflamatórios/efeitos adversos , Anti-Inflamatórios/farmacocinética , Doença Hepática Induzida por Substâncias e Drogas/diagnóstico , Criança , Doença de Crohn/metabolismo , Quimioterapia Combinada , Feminino , Humanos , Fatores Imunológicos/efeitos adversos , Fatores Imunológicos/farmacocinética , /diagnóstico , Masculino , Resultado do Tratamento
8.
J Crohns Colitis ; 13(7): 846-855, 2019 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-30541015

RESUMO

AIMS: Exclusive enteral nutrition [EEN] is as efficacious as corticosteroids [CS] to induce remission in Crohn's disease [CD], without their adverse effects. EEN seems to be more efficient than steroids to induce mucosal healing, but the underlying molecular mechanisms are only sparsely understood. We aimed in the present work to study the anti-inflammatory effects of EEN with Modulen IBD® vs CS in active paediatric CD, and to assess its modulatory effects on the intestinal microbiota as compared with steroids. MATERIALS AND METHODS: Nineteen patients with new-onset active CD (Harvey-Bradshaw index [HBI] >5), aged from 6 to 17 years, were included in this prospective randomised induction trial with CS [n = 6] or EEN [n = 13]. Patients were assessed at Weeks 0 and 8 using clinical parameters HBI, endoscopic findings (Crohn's Disease Endoscopic Index of Severity [CDEIS] score) and analysis of faecal microbiota composition. RESULTS: At 8 weeks, clinical remission [HBI <5] was achieved in 13/13 patients on EEN and 5/6 patients on steroids; the mucosal healing rate was significantly higher in the EEN [89%] compared with steroid group [17%]. There were no significant differences between groups regarding biological markers, but the intestinal microbiota profiles shifted upon EEN-induced remission to a higher proportion of Ruminococcus bacteria compared with steroid-induced remission [p = 0.049], and with higher proportions of bacteria belonging to Clostridium in EEN-treated patients. CONCLUSIONS: Both steroid and EEN induced clinical remission. However, patients with EEN-induced remission showed a higher rate of mucosal healing and this was associated with a different gut microbiota compositional shift in these children.


Assuntos
Corticosteroides/uso terapêutico , Doença de Crohn/terapia , Nutrição Enteral , Adolescente , Criança , Impressões Digitais de DNA , Feminino , Microbioma Gastrointestinal , Humanos , Masculino , Membrana Mucosa/patologia , Indução de Remissão
9.
PLoS One ; 13(10): e0205826, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30365510

RESUMO

Mutations in interleukin-10 receptor (IL-10R) genes are one cause of very early-onset inflammatory bowel disease with perianal lesions, which can be cured by hematopoietic stem cell transplantation. Using a functional test, which assesses responsiveness of peripheral monocytes to IL-10, we identified three unrelated Portuguese patients carrying two novel IL-10RB mutations. In the three patients, sequencing of genomic DNA identified the same large deletion of exon 3 which precluded protein expression. This mutation was homozygous in two patients born from consanguineous families and heterozygous in the third patient born from unrelated parents. Microsatellite analysis of the IL10RB genomic region revealed a common haplotype in the three Portuguese families pointing to a founder deletion inherited from a common ancestor 400 years ago. In the third patient, surface expression of IL-10R was normal but signaling in response to IL-10 was impaired. Complementary DNA sequencing and next-generation sequencing of IL10RB locus with custom-made probes revealed a ≈ 6 Kb duplication encompassing the exon 6 which leads to a frameshift mutation and a loss of the TYK2-interacting Box 2 motif. Altogether, we describe two novel copy number variations in IL10RB, one with founder effect and one preserving cell surface expression but abolishing signaling.


Assuntos
Variações do Número de Cópias de DNA , Subunidade beta de Receptor de Interleucina-10/deficiência , Subunidade beta de Receptor de Interleucina-10/genética , Alelos , Motivos de Aminoácidos , DNA Complementar/genética , Éxons , Saúde da Família , Feminino , Efeito Fundador , Genoma Humano , Haplótipos , Heterozigoto , Homozigoto , Humanos , Lactente , Leucócitos Mononucleares/citologia , Masculino , Repetições de Microssatélites , Mutação , Portugal , Transdução de Sinais
10.
J Pediatr Gastroenterol Nutr ; 67(2): 257-291, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-30044357

RESUMO

BACKGROUND: The contemporary management of ambulatory ulcerative colitis (UC) continues to be challenging with ∼20% of children needing a colectomy within childhood years. We thus aimed to standardize daily treatment of pediatric UC and inflammatory bowel diseases (IBD)-unclassified through detailed recommendations and practice points. METHODS: These guidelines are a joint effort of the European Crohn's and Colitis Organization (ECCO) and the Paediatric IBD Porto group of European Society of Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN). An extensive literature search with subsequent evidence appraisal using robust methodology was performed before 2 face-to-face meetings. All 40 included recommendations and 86 practice points were endorsed by 43 experts in Paediatric IBD with at least an 88% consensus rate. RESULTS: These guidelines discuss how to optimize the use of mesalamine (including topical), systemic and locally active steroids, thiopurines and, for more severe disease, biologics. The use of other emerging therapies and the role of surgery are also covered. Algorithms are provided to aid therapeutic decision-making based on clinical assessment and the Paediatric UC Activity Index (PUCAI). Advice on contemporary therapeutic targets incorporating the use of calprotectin and the role of therapeutic drug monitoring are presented, as well as other management considerations around pouchitis, extraintestinal manifestations, nutrition, growth, psychology, and transition. A brief section on disease classification using the PIBD-classes criteria and IBD-unclassified is also part of these guidelines. CONCLUSIONS: These guidelines provide a guide to clinicians managing children with UC and IBD-unclassified management to provide modern management strategies while maintaining vigilance around appropriate outcomes and safety issues.


Assuntos
Assistência Ambulatorial/normas , Colite Ulcerativa/diagnóstico , Criança , Fenômenos Fisiológicos da Nutrição Infantil , Colite Ulcerativa/terapia , Europa (Continente) , Feminino , Humanos , Masculino , Sociedades Médicas
11.
J Pediatr Gastroenterol Nutr ; 67(2): 292-310, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-30044358

RESUMO

BACKGROUND AND AIM: Acute severe colitis (ASC) is one of the few emergencies in pediatric gastroenterology. Tight monitoring and timely medical and surgical interventions may improve outcomes and minimize morbidity and mortality. We aimed to standardize daily treatment of ASC in children through detailed recommendations and practice points which are based on a systematic review of the literature and consensus of experts. METHODS: These guidelines are a joint effort of the European Crohn's and Colitis Organization (ECCO) and the European Society of Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN). Fifteen predefined questions were addressed by working subgroups. An iterative consensus process, including 2 face-to-face meetings, was followed by voting of the national representatives of ECCO and all members of the Paediatric Inflammatory Bowel Disease (IBD) Porto group of ESPGHAN (43 voting experts). RESULTS: A total of 24 recommendations and 43 practice points were endorsed with a consensus rate of at least 91% regarding diagnosis, monitoring, and management of ASC in children. A summary flowchart is presented based on daily scoring of the Paediatric Ulcerative Colitis Activity Index. Several topics have been altered since the previous 2011 guidelines and from those published in adults. DISCUSSION: These guidelines standardize the management of ASC in children in an attempt to optimize outcomes of this intensive clinical scenario.


Assuntos
Colite Ulcerativa/diagnóstico , Criança , Fenômenos Fisiológicos da Nutrição Infantil , Colite Ulcerativa/terapia , Europa (Continente) , Feminino , Humanos , Masculino , Índice de Gravidade de Doença , Sociedades Médicas
12.
J Crohns Colitis ; 12(10): 1249-1254, 2018 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-29939254

RESUMO

Background and Aims: Adalimumab has been shown to be more effective than placebo in healing fistulae in adults with moderately to severely active Crohn's disease. The efficacy and safety of adalimumab in healing fistulae in children/adolescents with Crohn's disease from the 52-week IMAgINE 1 clinical trial, and its open-label extension IMAgINE 2, are reported. Methods: Children/adolescents with perianal fistulae at baseline of IMAgINE 1 were assessed for fistula closure and improvement during IMAgINE 1 [Weeks 0-52] and from Week 0 of IMAgINE 2 [Week 52 of IMAgINE 1] through to Week 240 of IMAgINE 2 using non-responder imputation. Results: A total of 36 children/adolescents had fistulae at baseline of IMAgINE 1 and were included in the analysis. Fistula closure and improvement were observed in 44.4% and 52.8%, respectively, at Week 12. Rates of closure and improvement were maintained throughout the analysis period to Week 292. No new safety signals were identified. Conclusions: In children/adolescents with moderately to severely active, fistulizing Crohn's disease, adalimumab induced perianal fistula closure and improvement within 12 weeks of treatment, with rates that were sustained for more than 5 years. The safety profile of adalimumab in patients with fistulae at baseline was similar to that of the overall population in IMAgINE 1/2. ClinicalTrials.gov identifiers: IMAgINE 1 (NCT00409682); IMAgINE 2 (NCT00686374).


Assuntos
Adalimumab , Doença de Crohn , Fístula Retal , Adalimumab/administração & dosagem , Adalimumab/efeitos adversos , Adolescente , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/efeitos adversos , Criança , Doença de Crohn/complicações , Doença de Crohn/diagnóstico , Doença de Crohn/tratamento farmacológico , Relação Dose-Resposta a Droga , Método Duplo-Cego , Monitoramento de Medicamentos/métodos , Feminino , Humanos , Masculino , Fístula Retal/diagnóstico , Fístula Retal/tratamento farmacológico , Fístula Retal/etiologia , Regeneração/efeitos dos fármacos , Índice de Gravidade de Doença , Resultado do Tratamento , Fator de Necrose Tumoral alfa/antagonistas & inibidores
13.
Artigo em Inglês | MEDLINE | ID: mdl-29851766

RESUMO

BACKGROUND: The contemporary management of ambulatory ulcerative colitis (UC) continues to be challenging with ∼20% of children needing a colectomy within childhood years. We thus aimed to standardize daily treatment of paediatric UC and inflammatory bowel diseases (IBD)-unclassified through detailed recommendations and practice points. METHODS: These guidelines are a joint effort of the European Crohn's and Colitis Organization (ECCO) and the Paediatric IBD Porto group of European Society of Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN). An extensive literature search with subsequent evidence appraisal using robust methodology was performed before two face-to-face meetings. All 40 included recommendations and 86 practice points, were endorsed by 43 experts in Paediatric IBD with at least an 88% consensus rate. RESULTS: These guidelines centre on initial use of mesalamine (including topical), before using steroids, thiopurines and, for more severe disease, anti-TNF. The use of other emerging therapies and the role of surgery are also covered. Algorithms are provided to aid therapeutic decision making based on clinical assessment and the paediatric UC activity index (PUCAI). Advice on contemporary therapeutic targets incorporating the use of calprotectin and the role of therapeutic drug monitoring are presented, as well as other management considerations around pouchitis, extraintestinal manifestations, nutrition, growth, psychology and transition. A brief section on disease classification using the PIBD-classes criteria and IBDU is also part of these guidelines. CONCLUSION: These guidelines provide a guide to clinicians managing children with UC and IBDU to provide modern management strategies while maintaining vigilance around appropriate outcomes and safety issues.

14.
Artigo em Inglês | MEDLINE | ID: mdl-29851767

RESUMO

BACKGROUND AND AIM: Acute severe colitis (ASC) is one of the few emergencies in paediatric gastroenterology. Tight monitoring and timely medical and surgical interventions may improve outcomes and minimize morbidity and mortality. We aimed to standardize daily treatment of ASC in children through detailed recommendations and practice points which are based on a systematic review of the literature and consensus of experts. METHODS: These guidelines are a joint effort of the European Crohn's and Colitis Organization (ECCO) and the European Society of Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN). Fifteen predefined questions were addressed by working subgroups. An iterative consensus process, including two face-to-face meetings, was followed by voting by the national representatives of ECCO and all members of the Paediatric Inflammatory Bowel Disease (IBD) Porto group of ESPGHAN (43 voting experts). RESULTS: A total of 24 recommendations and 43 practice points were endorsed with a consensus rate of at least 91% regarding diagnosis, monitoring and management of ASC in children. A summary flowchart is presented based on daily scoring of the Paediatric Ulcerative Colitis Activity Index (PUCAI). Several topics have been altered since the previous 2011 guidelines and from those published in adults. DISCUSSION: These guidelines standardize the management of ASC in children in an attempt to optimize outcomes of this intensive clinical scenario.

16.
J Allergy Clin Immunol ; 141(3): 1036-1049.e5, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29241729

RESUMO

BACKGROUND: Immunodysregulation polyendocrinopathy enteropathy x-linked (IPEX) syndrome is a monogenic autoimmune disease caused by FOXP3 mutations. Because it is a rare disease, the natural history and response to treatments, including allogeneic hematopoietic stem cell transplantation (HSCT) and immunosuppression (IS), have not been thoroughly examined. OBJECTIVE: This analysis sought to evaluate disease onset, progression, and long-term outcome of the 2 main treatments in long-term IPEX survivors. METHODS: Clinical histories of 96 patients with a genetically proven IPEX syndrome were collected from 38 institutions worldwide and retrospectively analyzed. To investigate possible factors suitable to predict the outcome, an organ involvement (OI) scoring system was developed. RESULTS: We confirm neonatal onset with enteropathy, type 1 diabetes, and eczema. In addition, we found less common manifestations in delayed onset patients or during disease evolution. There is no correlation between the site of mutation and the disease course or outcome, and the same genotype can present with variable phenotypes. HSCT patients (n = 58) had a median follow-up of 2.7 years (range, 1 week-15 years). Patients receiving chronic IS (n = 34) had a median follow-up of 4 years (range, 2 months-25 years). The overall survival after HSCT was 73.2% (95% CI, 59.4-83.0) and after IS was 65.1% (95% CI, 62.8-95.8). The pretreatment OI score was the only significant predictor of overall survival after transplant (P = .035) but not under IS. CONCLUSIONS: Patients receiving chronic IS were hampered by disease recurrence or complications, impacting long-term disease-free survival. When performed in patients with a low OI score, HSCT resulted in disease resolution with better quality of life, independent of age, donor source, or conditioning regimen.


Assuntos
Diabetes Mellitus Tipo 1/congênito , Diarreia , Fatores de Transcrição Forkhead , Doenças Genéticas Ligadas ao Cromossomo X , Transplante de Células-Tronco Hematopoéticas , Doenças do Sistema Imunitário/congênito , Imunossupressão , Mutação , Adolescente , Adulto , Aloenxertos , Criança , Pré-Escolar , Diabetes Mellitus Tipo 1/genética , Diabetes Mellitus Tipo 1/imunologia , Diabetes Mellitus Tipo 1/mortalidade , Diabetes Mellitus Tipo 1/terapia , Diarreia/genética , Diarreia/imunologia , Diarreia/mortalidade , Diarreia/terapia , Intervalo Livre de Doença , Feminino , Seguimentos , Fatores de Transcrição Forkhead/genética , Fatores de Transcrição Forkhead/imunologia , Doenças Genéticas Ligadas ao Cromossomo X/genética , Doenças Genéticas Ligadas ao Cromossomo X/imunologia , Doenças Genéticas Ligadas ao Cromossomo X/mortalidade , Doenças Genéticas Ligadas ao Cromossomo X/terapia , Humanos , Doenças do Sistema Imunitário/genética , Doenças do Sistema Imunitário/imunologia , Doenças do Sistema Imunitário/mortalidade , Doenças do Sistema Imunitário/terapia , Lactente , Masculino , Estudos Retrospectivos , Taxa de Sobrevida
17.
Ann Nutr Metab ; 73 Suppl 4: 39-46, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30783043

RESUMO

Several disorders related to the ingestion of gluten are well recognized despite overlapping clinical presentations: celiac disease, an autoimmune enteropathy triggered by gluten ingestions in susceptible individuals, allergy to wheat, and more recently non-celiac gluten sensitivity (NCGS). While celiac disease and wheat allergy are well-known disorders with a clear-cut diagnosis based on clinical tests and biological parameters, NCGS is a more difficult diagnosis, especially in children with functional gastrointestinal (GI) complaints. NCGS is considered a syndrome of intestinal but also extraintestinal symptoms occurring within hours, but sometimes even after several days of gluten ingestion. In children, the leading symptoms of NCGS are abdominal pain and diarrhea, while extraintestinal symptoms are rare, in contrast to adult patients. No precise diagnostic test nor specific biomarkers exist, except a rather cumbersome three-phase gluten-exposure, gluten-free diet, followed by a blinded placebo-controlled gluten challenge with crossover to provoke symptoms elicited by gluten in a reproducible manner that disappear on gluten-free alimentation. Recent data indicate that the peptide part of wheat proteins is not necessarily the sole trigger of clinical symptoms. Mono- or oligosaccharides, such as fructan and other constituents of wheat, were able to provoke GI symptoms in clinical trials. These new findings indicate that the term gluten sensitivity is probably too restrictive. The incidence of NCGS was reported in the range of 1-10% in the general population and to increase steadily; however, most data are based on patients' self-reported gluten intolerance or avoidance without a medically confirmed diagnosis. Treatment consists of gluten avoidance for at least several weeks or months. Patients with NCGS require regular reassessment for gluten tolerance allowing with time the reintroduction of increasing amounts of gluten.


Assuntos
Dor Abdominal/etiologia , Intolerância Alimentar/diagnóstico , Glutens/efeitos adversos , Síndromes de Malabsorção/diagnóstico , Doença Celíaca , Criança , Intolerância Alimentar/complicações , Intolerância Alimentar/terapia , Humanos , Síndromes de Malabsorção/complicações , Síndromes de Malabsorção/terapia , Triticum
18.
Ann Nutr Metab ; 73 Suppl 4: 38, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30783046
20.
J Crohns Colitis ; 11(8): 981-987, 2017 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-28789473

RESUMO

Background: The importance of a holistic approach with a comprehensive multidisciplinary team, including nutritional and psychosocial support, is becoming well recognised as a key contributor to optimal care in paediatric inflammatory bowel disease [IBD]. The Paediatric committee of ECCO [P-ECCO] aimed to determine important components that would contribute to quality of care in a paediatric IBD centre [henceforth 'quality items']. Methods: First, a list of items has been generated by a Delphi group of 111 international paediatric IBD experts. Through an iterative process, the group graded and ranked the items according to their perceived relative contribution to quality care. We then surveyed 101 paediatric IBD centres affiliated with the Porto and Interest groups of ESPGHAN in Europe and with the ImproveCareNow registry in North America, exploring the availability of the retained items in their centres. Results: A total of 68 items were generated and reduced to a list of 60 ranked order items, grouped in six domains: Facility, Personnel, Management, Supportive Services, Patient Support and Accessibility, and Academia and Communications. Of the retained items, 52 [88%] were present in most of the 101 high-performing paediatric IBD centres, and there was a trend for increased availability with increased patient volume at the centres. Conclusion: In this P-ECCO study, we attempted to tabulate, for the first time in paediatrics, 60 quality items that paediatric IBD referral centres may wish to include.


Assuntos
Instituições de Assistência Ambulatorial/organização & administração , Doenças Inflamatórias Intestinais/terapia , Instituições de Assistência Ambulatorial/normas , Criança , Técnica Delfos , Europa (Continente) , Humanos , Equipe de Assistência ao Paciente/organização & administração , Qualidade da Assistência à Saúde/normas , Sistema de Registros , Recursos Humanos
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