Outcomes and factors associated with tolerance in infants with non-IgE-mediated cow's milk allergy with gastrointestinal manifestations.

OBJECTIVES: To evaluate outcomes of oral food challenge (OFC) test to assess tolerance in infants with non-IgE-mediated cow's milk allergy (CMA) with gastrointestinal manifestations and explore clinical data predictive of these outcomes. METHODS: Single-center retrospective study including infants (age < 12 months) who were referred for CMA between 2000 and 2018 and underwent OFC on follow-up. A univariate logistic regression test was performed to evaluate variables associated with the outcomes of the follow-up OFC test. RESULTS: Eighty-two patients were included, 50% were male. Eighteen patients had a positive OFC test (22%). Most patients had presented with hematochezia (77%). The median age of symptom onset was 30 days. Two-thirds of the patients were on appropriate infant formula (extensively hydrolyzed or amino acid-based formula), exclusively or in association with breastfeeding. The median time on an elimination diet before the OFC test was 8 months (Q1 6 - Q3 11 months). All cases with positive follow-up OFC tests (n = 18) had been exposed to cow's milk-based formula before the first clinical manifestation of CMA. Five out of eight cases with Food Protein-Induced Enterocolitis Syndrome (FPIES) had positive OFC tests. Exposure to cow's milk-based formula before diagnosis, a history of other food allergies, hematochezia and diarrhea were predictors of a positive OFC test. CONCLUSIONS: In infants with non-IgE-mediated CMPA with gastrointestinal manifestations, the use of cow's milk-based formula, a history of other food allergies, and hematochezia and diarrhea upon initial presentation were associated factors for the later achievement of tolerance.

Outcomes and factors associated with tolerance in infants with non-IgE-mediated cow's milk allergy with gastrointestinal manifestations

Abstract Objectives To evaluate outcomes of oral food challenge (OFC) test to assess tolerance in infants with non-IgE-mediated cow's milk allergy (CMA) with gastrointestinal manifestations and explore clinical data predictive of these outcomes. Methods Single-center retrospective study including infants (age < 12 months) who were referred for CMA between 2000 and 2018 and underwent OFC on follow-up. A univariate logistic regression test was performed to evaluate variables associated with the outcomes of the follow-up OFC test. Results Eighty-two patients were included, 50% were male. Eighteen patients had a positive OFC test (22%). Most patients had presented with hematochezia (77%). The median age of symptom onset was 30 days. Two-thirds of the patients were on appropriate infant formula (extensively hydrolyzed or amino acid-based formula), exclusively or in association with breastfeeding. The median time on an elimination diet before the OFC test was 8 months (Q1 6 - Q3 11 months). All cases with positive follow-up OFC tests (n= 18) had been exposed to cow's milk-based formula before the first clinical manifestation of CMA. Five out of eight cases with Food Protein-Induced Enterocolitis Syndrome (FPIES) had positive OFC tests. Exposure to cow's milk-based formula before diagnosis, a history of other food allergies, hematochezia and diarrhea were predictors of a positive OFC test. Conclusions In infants with non-IgE-mediated CMPA with gastrointestinal manifestations, the use of cow's milk-based formula, a history of other food allergies, and hematochezia and diarrhea upon initial presentation were associated factors for the later achievement of tolerance.

Combined multi-channel intraluminal impedance measurement and pHmetry in the detection of gastroesophageal reflux disease in children with cystic fibrosis

Abstract Objective To assess the prevalence of GERD exclusively by means of multichannel intraluminal impedanciometry associated with pH monitoring (MIIpH) and compare it with respiratory symptoms in children with CF. To compare MIIpH with pHmetry alone to perform GERD diagnosis. Methods An analytical cross-sectional study was conducted with children diagnosed with CF who underwent MIIpH. Clinical and laboratory markers, including respiratory and digestive symptoms, were used for comparative analyses. High-resolution chest computed tomography was performed on patients with symptoms of chronic lung disease. Severity was classified according to the Bhalla score. Results A total of 29 children < 10 yo (18 girls) were evaluated; 19 of whom with physiological GER and 10 with GERD. Of the children with GERD, seven had predominantly acid GER, two acid+non-acid GER, and one non-acid GER. Three patients had GERD diagnosed only by MIIpH. Bhalla scores ranged from seven to 17.75 with no significant relationship with GERD. The number of pulmonary exacerbations was associated with a decrease in esophageal clearance regardless of the position in pHmetry and MIIpH. Conclusions The prevalence of GERD was 34% in children with CF. There was no association between respiratory disease severity and GER types. MIIpH detected 30% more patients with GERD than pHmetry.

BRAZILIAN CONSENSUS ON THE MANAGEMENT OF INFLAMMATORY BOWEL DISEASES IN PEDIATRIC PATIENTS: A CONSENSUS OF THE BRAZILIAN ORGANIZATION FOR CROHN'S DISEASE AND COLITIS (GEDIIB).

BACKGROUND: Approximately 25% of patients with inflammatory bowel disease (IBD) develop the disease during childhood or adolescence and treatment aims to control active symptoms and prevent long-term complications. The management of Crohn's disease (CD) and ulcerative colitis (UC) can be especially challenging in children and adolescents, related to particularities that may affect growth, development, and puberty. OBJECTIVE: This consensus aims to provide guidance on the most effective medical and surgical management of pediatric patients with CD or UC. METHODS: Experts in Pediatric IBD representing Brazilian gastroenterologists (Brazilian Organization for Crohn's Disease and Colitis [GEDIIB]) developed this consensus. A rapid review was performed to support the recommendations/statements. Medical and surgical recommendations were structured and mapped according to the disease type, disease activity, and indications and contraindications for medical and surgical treatment. After structuring the statements, the modified Delphi Panel methodology was used to conduct the voting. The process took place in three rounds: two using a personalized and anonymous online voting platform and one face-to-face. Whenever participants did not agree with a specific recommendation, an option to explain why was offered to enable free-text responses and provide the opportunity for the experts to elaborate or explain disagreement. The consensus of recommendations in each round was accepted when reached ≥80% agreement. RESULTS AND CONCLUSION: The recommendations are presented according to the stage of treatment and severity of the disease in three domains: management and treatment (drug and surgical interventions), criteria for evaluating the effectiveness of medical treatment, and follow-up/ patient monitoring after initial treatment, follow-up/ patient monitoring after initial treatment. Surgical recommendations were grouped according to disease type and recommended surgery. The target audience for this consensus was general practitioners, gastroenterologists, and surgeons interested in the treatment and management of pediatric CD and UC. Additionally, the consensus aimed to support the decision-making of health insurance companies, regulatory agencies, and health institutional leaders and/or administrators.

Combined multi-channel intraluminal impedance measurement and pHmetry in the detection of gastroesophageal reflux disease in children with cystic fibrosis.

OBJECTIVE: To assess the prevalence of GERD exclusively by means of multichannel intraluminal impedanciometry associated with pH monitoring (MIIpH) and compare it with respiratory symptoms in children with CF. To compare MIIpH with pHmetry alone to perform GERD diagnosis. METHODS: An analytical cross-sectional study was conducted with children diagnosed with CF who underwent MIIpH. Clinical and laboratory markers, including respiratory and digestive symptoms, were used for comparative analyses. High-resolution chest computed tomography was performed on patients with symptoms of chronic lung disease. Severity was classified according to the Bhalla score. RESULTS: A total of 29 children < 10 yo (18 girls) were evaluated; 19 of whom with physiological GER and 10 with GERD. Of the children with GERD, seven had predominantly acid GER, two acid+non-acid GER, and one non-acid GER. Three patients had GERD diagnosed only by MIIpH. Bhalla scores ranged from seven to 17.75 with no significant relationship with GERD. The number of pulmonary exacerbations was associated with a decrease in esophageal clearance regardless of the position in pHmetry and MIIpH. CONCLUSIONS: The prevalence of GERD was 34% in children with CF. There was no association between respiratory disease severity and GER types. MIIpH detected 30% more patients with GERD than pHmetry.

INDUCED PROCTOCOLITIS - ORAL FOOD CHALLENGE SHOULD BE DONE TO CONFIRM THE DIAGNOSIS OF COW'S MILK ALLERGY IN NEONATES?

BACKGROUND: Suspicion of food protein-induced proctocolitis based on empirical understanding of rectal bleeding can lead to misdiagnosis. OBJECTIVE: to verify clinical and evaluative characteristics of patients who presented neonatal rectal bleeding and were on a restricted cow's milk diet. METHODS: A cross-sectional retrospective study included patients followed up in a tertiary care center, who presented rectal bleeding in the neonatal period. The analyzed data included gender, gestational age, type of delivery, use of antibiotics during the last trimester of pregnancy, use of parenteral nutrition before the first manifestation, use of mechanical ventilation, initial clinical manifestations associated with rectal bleeding, diet before the first manifestation, period of elimination diet, oral food challenge (OFC) results and symptoms presented in cases of positive OFC. Fisher's exact test and Mann-Whitney test were used to analyze the data. The level of significance was set to 5%. RESULTS: Forty-two patients were selected: 30 preterm infants, 34 cesarean deliveries, 10 exclusively breastfed patients before rectal bleeding. Median age at OFC was 6.3 months old. Median of length of the elimination period before OFC was 5.9 months. OFC was negative in 33/42 (79%) patients and positive in 9/42 (21%). There was no association between OFC results and the evaluated data. The main symptom observed in patients with positive OFC was blood in stools. CONCLUSION: OFC was negative in most cases of suspected cow's milk allergy due to rectal bleeding in neonates, most of them with a history of prematurity.

Proctocolite induzida por proteína alimentar - teste de provocação oral deve ser realizado para confirmar o diagnóstico de alergia ao leite de vaca em neonatos? / Induced proctocolitis - oral food challenge should be done to confirm the diagnosis of cow's milk allergy in neonates?

ABSTRACT Background: Suspicion of food protein-induced proctocolitis based on empirical understanding of rectal bleeding can lead to misdiagnosis. Objective: to verify clinical and evaluative characteristics of patients who presented neonatal rectal bleeding and were on a restricted cow's milk diet. Methods: A cross-sectional retrospective study included patients followed up in a tertiary care center, who presented rectal bleeding in the neonatal period. The analyzed data included gender, gestational age, type of delivery, use of antibiotics during the last trimester of pregnancy, use of parenteral nutrition before the first manifestation, use of mechanical ventilation, initial clinical manifestations associated with rectal bleeding, diet before the first manifestation, period of elimination diet, oral food challenge (OFC) results and symptoms presented in cases of positive OFC. Fisher's exact test and Mann-Whitney test were used to analyze the data. The level of significance was set to 5%. Results: Forty-two patients were selected: 30 preterm infants, 34 cesarean deliveries, 10 exclusively breastfed patients before rectal bleeding. Median age at OFC was 6.3 months old. Median of length of the elimination period before OFC was 5.9 months. OFC was negative in 33/42 (79%) patients and positive in 9/42 (21%). There was no association between OFC results and the evaluated data. The main symptom observed in patients with positive OFC was blood in stools. Conclusion: OFC was negative in most cases of suspected cow's milk allergy due to rectal bleeding in neonates, most of them with a history of prematurity.

RESUMO Contexto: A suspeita de proctocolite induzida por proteína alimentar (PCIPA) com base na compreensão empírica de sangramento retal pode levar a diagnósticos equivocados. Objetivo Verificar as características clínicas e evolutivas de pacientes que apresentavam sangramento retal neonatal e faziam uso de dieta restrita com leite de vaca. Métodos: Estudo transversal retrospectivo com pacientes acompanhados em um centro terciário, que apresentaram sangramento retal no período neonatal. Os dados analisados incluíram: sexo, idade gestacional, tipo de parto, uso de antibióticos no último trimestre da gravidez, uso de nutrição parenteral antes da primeira manifestação, uso de ventilação mecânica, manifestações clínicas iniciais associadas ao sangramento retal, dieta antes da primeira manifestação, período de dieta de eliminação, resultados do teste de provocação oral (TPO) e sintomas apresentados em casos de TPO positivo. O teste exato de Fisher e o teste de Mann-Whitney foram usados para analisar os dados. O nível de significância adotado foi de 5%. Resultados: Quarenta e dois pacientes foram selecionados: 30 prematuros, 34 partos cesáreos, 10 pacientes amamentadas exclusivamente antes do sangramento retal. A idade média na ocasião do TPO foi de 6,3 meses. A mediana da duração do período da dieta de eliminação antes do TPO foi de 5,9 meses. O TPO foi negativo em 33/42 (79%) pacientes e positivo em 9/42 (21%). Não houve associação entre os resultados do TPO e os dados avaliados. O principal sintoma observado em pacientes com TPO positivo foi sangue nas fezes. Conclusão: O TPO foi negativo na maioria dos casos de suspeita de alergia ao leite de vaca devido a sangramento retal em neonatos, a maioria deles com história de prematuridade.

Management of children with functional constipation referred to tertiary care

Abstract Objectives: To describe the management, to compare treatment at initial referral vs. during specialized follow-up, and to describe outcomes of children with functional constipation (FC) referred to a Brazilian tertiary care center. Methods: Retrospective study, including children (4-18 years) with FC followed at a single center from 2006 to 2019. Demographics, treatments, time of follow-up, and outcomes were analyzed. The management of FC followed an institutional protocol. Results: 104 patients were identified, 79 were eligible and included in the analysis: 59% male, mean age at referral was 6.4 years, and mean duration of symptoms was 4.4 years. There were significant changes in the therapy(ies) used at the time of referral compared to during follow-up, with a noticeable increase in the frequency of the use of polyethylene glycol, enemas, magnesium hydroxide, and bisacodyl; 5.1% received trans-anal irrigation, and 3.8% underwent surgery. Outcomes were favorable in more than half of the cases: 31% improved; 19.5% had complete resolution and 2.5% were transferred back to primary care. Symptoms remained unchanged in 30.4%, and no patients experienced worsening of symptoms. The mean duration of follow-up was 2.8 years. When comparing patients with favorable vs. unfavorable outcomes, the authors did not identify significant differences in gender, age, therapies used, duration of symptoms, or length of follow-up. Conclusions: Children with FC are often referred to specialized care not receiving optimal therapy. Many patients whose FC was labeled "refractory" may be treated successfully with a well-established plan of care, and do not truly present intractable constipation.

FUNCTIONAL ABDOMINAL PAIN IS THE MAIN ETIOLOGY AMONG CHILDREN REFERRED TO TERTIARY CARE LEVEL FOR CHRONIC ABDOMINAL PAIN.

BACKGROUND: Chronic abdominal pain (CAP) carries a significant burden of disease. The last edition of the Rome Criteria (Rome IV) allows the diagnosis of functional gastrointestinal disorders (FGIDs) according to symptoms-based criteria; however, patients continue to experience a delay in their diagnosis and to be submitted to different interventions before the establishment of a positive diagnosis. OBJECTIVE: We aimed to characterize etiology, clinical features, and interventions in a pediatric cohort of patients with CAP secondary to FGIDs, who were referred to our tertiary care university-affiliated hospital, in Brazil. METHODS: A retrospective descriptive study of children and adolescents (aged 20 years and younger) referred to our institution, from January/2013 to December/2018, for CAP, and who fulfilled criteria for FGIDs classified according to Rome IV criteria. RESULTS: Three hundred twenty-eight patients with CAP were screened, of which 67.9% (223 patients) fulfilled the criteria for FGIDs and were included in the study. Sixty percent were female, with a mean age of 8.3 years. At the time of referral, the mean duration of symptoms was 2.8 years. Length/height for age and weight for age mean z-scores were -0.08±1.87 and -0.38±1.62, respectively. Functional abdominal pain not otherwise specified was overall the most common diagnosis (70.4%). Before establishing the diagnosis of FGIDs, multiple pharmacological interventions were described, while after, the mainstay of therapy was education/reassurance and dietary interventions. Thirty-two percent of patients did not further require specialized follow-up. CONCLUSION: Even at the tertiary care level, FGIDs were still the most common etiology of chronic abdominal pain, particularly functional abdominal pain not otherwise specified. Despite the relatively long duration of symptoms at referral, cessation of specialized care follow-up was possible in approximately a third of the cases.

Dor abdominal funcional é a principal etiologia em crianças encaminhadas ao nível de atenção terciária por dor abdominal crônica / Functional abdominal pain is the main etiology among children referred to tertiary care level for chronic abdominal pain

ABSTRACT Background Chronic abdominal pain (CAP) carries a significant burden of disease. The last edition of the Rome Criteria (Rome IV) allows the diagnosis of functional gastrointestinal disorders (FGIDs) according to symptoms-based criteria; however, patients continue to experience a delay in their diagnosis and to be submitted to different interventions before the establishment of a positive diagnosis. Objective We aimed to characterize etiology, clinical features, and interventions in a pediatric cohort of patients with CAP secondary to FGIDs, who were referred to our tertiary care university-affiliated hospital, in Brazil. Methods A retrospective descriptive study of children and adolescents (aged 20 years and younger) referred to our institution, from January/2013 to December/2018, for CAP, and who fulfilled criteria for FGIDs classified according to Rome IV criteria. Results Three hundred twenty-eight patients with CAP were screened, of which 67.9% (223 patients) fulfilled the criteria for FGIDs and were included in the study. Sixty percent were female, with a mean age of 8.3 years. At the time of referral, the mean duration of symptoms was 2.8 years. Length/height for age and weight for age mean z-scores were -0.08±1.87 and -0.38±1.62, respectively. Functional abdominal pain not otherwise specified was overall the most common diagnosis (70.4%). Before establishing the diagnosis of FGIDs, multiple pharmacological interventions were described, while after, the mainstay of therapy was education/reassurance and dietary interventions. Thirty-two percent of patients did not further require specialized follow-up. Conclusion Even at the tertiary care level, FGIDs were still the most common etiology of chronic abdominal pain, particularly functional abdominal pain not otherwise specified. Despite the relatively long duration of symptoms at referral, cessation of specialized care follow-up was possible in approximately a third of the cases.

RESUMO Contexto A dor abdominal crônica (DAC) pode acarretar importante morbidade. A última edição dos Critérios de Roma (Roma IV) permite o diagnóstico de distúrbios gastrointestinais funcionais (DGIFs) de acordo com critérios baseados em sintomas; no entanto, esses pacientes continuam a apresentar atraso no diagnóstico e a serem submetidos a diferentes intervenções antes do estabelecimento de um diagnóstico. Objetivo Caracterizar a etiologia, características clínicas e intervenções de crianças com DAC que não são mantidas na atenção primária e que foram encaminhadas ao nosso hospital universitário de nível terciário, no Brasil. Métodos Estudo retrospectivo descritivo de crianças e adolescentes (com idade igual ou inferior a 20 anos) encaminhados a nossa instituição, entre janeiro/2013 e dezembro/2018, por DAC e que preenchiam os critérios para DGIFs conforme o consenso de Roma IV. Resultados Trezentos e vinte e oito pacientes com DAC foram triados, 67,9% (223 pacientes) preencheram os critérios para DGIFs e foram analisados. Sessenta por cento do sexo feminino, com idade média de 8,3 anos. A duração média dos sintomas no encaminhamento era de 2,8 anos. Os escores z médios de estatura para idade e peso para idade foram -0,08±1,87 e -0,38±1,62, respectivamente. Dor abdominal funcional sem outra especificação foi o diagnóstico mais comum (70,4%). Antes do diagnóstico de DGIFs, múltiplas intervenções farmacológicas foram descritas, enquanto depois, a base da terapia foi a educação, passar segurança à família e intervenções dietéticas. Trinta e dois por cento dos pacientes apresentaram resolução dos sintomas e receberam alta do acompanhamento especializado. Conclusão Mesmo no nível terciário, as desordens gastrointestinais funcionais ainda constituem a etiologia mais comum da DAC, particularmente a dor abdominal funcional não especificada. Apesar da duração longa dos sintomas, alta do serviço especializados foi possível em aproximadamente um terço dos casos.

Management of children with functional constipation referred to tertiary care.

OBJECTIVES: To describe the management, to compare treatment at initial referral vs. during specialized follow-up, and to describe outcomes of children with functional constipation (FC) referred to a Brazilian tertiary care center. METHODS: Retrospective study, including children (4-18 years) with FC followed at a single center from 2006 to 2019. Demographics, treatments, time of follow-up, and outcomes were analyzed. The management of FC followed an institutional protocol. RESULTS: 104 patients were identified, 79 were eligible and included in the analysis: 59% male, mean age at referral was 6.4 years, and mean duration of symptoms was 4.4 years. There were significant changes in the therapy(ies) used at the time of referral compared to during follow-up, with a noticeable increase in the frequency of the use of polyethylene glycol, enemas, magnesium hydroxide, and bisacodyl; 5.1% received trans-anal irrigation, and 3.8% underwent surgery. Outcomes were favorable in more than half of the cases: 31% improved; 19.5% had complete resolution and 2.5% were transferred back to primary care. Symptoms remained unchanged in 30.4%, and no patients experienced worsening of symptoms. The mean duration of follow-up was 2.8 years. When comparing patients with favorable vs. unfavorable outcomes, the authors did not identify significant differences in gender, age, therapies used, duration of symptoms, or length of follow-up. CONCLUSIONS: Children with FC are often referred to specialized care not receiving optimal therapy. Many patients whose FC was labeled "refractory" may be treated successfully with a well-established plan of care, and do not truly present intractable constipation.

Consenso brasileiro de manejo das doenças inflamatórias intestinais em pacientes pediátricos: Consenso da Organização Brasileira para doença de Crohn e colite (GEDIIB) / Brazilian consensus on the management of inflammatory bowel diseases in pediatric patients: a consensus of the brazilian organization for crohn's disease and colitis (gediib)

ABSTRACT Background: Approximately 25% of patients with inflammatory bowel disease (IBD) develop the disease during childhood or adolescence and treatment aims to control active symptoms and prevent long-term complications. The management of Crohn's disease (CD) and ulcerative colitis (UC) can be especially challenging in children and adolescents, related to particularities that may affect growth, development, and puberty. Objective: This consensus aims to provide guidance on the most effective medical and surgical management of pediatric patients with CD or UC. Methods: Experts in Pediatric IBD representing Brazilian gastroenterologists (Brazilian Organization for Crohn's Disease and Colitis [GEDIIB]) developed this consensus. A rapid review was performed to support the recommendations/statements. Medical and surgical recommendations were structured and mapped according to the disease type, disease activity, and indications and contraindications for medical and surgical treatment. After structuring the statements, the modified Delphi Panel methodology was used to conduct the voting. The process took place in three rounds: two using a personalized and anonymous online voting platform and one face-to-face. Whenever participants did not agree with a specific recommendation, an option to explain why was offered to enable free-text responses and provide the opportunity for the experts to elaborate or explain disagreement. The consensus of recommendations in each round was accepted when reached ≥80% agreement. Results and conclusion: The recommendations are presented according to the stage of treatment and severity of the disease in three domains: management and treatment (drug and surgical interventions), criteria for evaluating the effectiveness of medical treatment, and follow-up/ patient monitoring after initial treatment, follow-up/ patient monitoring after initial treatment. Surgical recommendations were grouped according to disease type and recommended surgery. The target audience for this consensus was general practitioners, gastroenterologists, and surgeons interested in the treatment and management of pediatric CD and UC. Additionally, the consensus aimed to support the decision-making of health insurance companies, regulatory agencies, and health institutional leaders and/or administrators.

RESUMO Contexto: Aproximadamente 25% dos pacientes desenvolvem doença inflamatória intestinal (DII) durante a infância ou adolescência, e o tratamento visa controlar os sintomas ativos e prevenir complicações a longo prazo. O tratamento da doença de Crohn (DC) e retocolite ulcerativa (RCU) pode ser especialmente desafiador em crianças e adolescentes, relacionado a particularidades que podem afetar o crescimento, o desenvolvimento e a puberdade. Objetivo: Este consenso visa fornecer orientações sobre o tratamento clínico e cirúrgico mais eficaz de pacientes pediátricos com DC ou RCU. Métodos: Gastroenterologistas brasileiros especialistas em DII Pediátrico membro da Organização Brasileira para Doença de Crohn e Colite (GEDIIB) desenvolveram este consenso. Uma revisão rápida foi realizada para apoiar as recomendações/declarações. As recomendações médicas e cirúrgicas foram estruturadas e mapeadas de acordo com o tipo de doença, atividade da doença e indicações e contraindicações para tratamento médico e cirúrgico. Após a estruturação das declarações, foi utilizada a metodologia modificada do Painel Delphi para conduzir a votação. O processo ocorreu em três rodadas: duas por meio de uma plataforma de votação online personalizada e anônima e uma presencial. Sempre que os participantes não concordavam com a recomendação específica, uma opção para explicar o motivo era oferecida para permitir respostas em texto livre e dar a oportunidade para os especialistas elaborarem ou explicarem a discordância. O consenso das recomendações em cada rodada foi aceito quando houve concordância ≥80%. Resultados e conclusão: As recomendações são apresentadas de acordo com o estágio de tratamento e gravidade da doença em três domínios: manejo e tratamento (intervenções medicamentosas e cirúrgicas), critérios para avaliar a eficácia do tratamento médico, acompanhamento/monitoramento do paciente após tratamento. As recomendações cirúrgicas foram agrupadas de acordo com o tipo de doença e cirurgia recomendada. O público-alvo deste consenso foram clínicos gerais, gastroenterologistas e cirurgiões interessados no tratamento e manejo da RCU e DC pediátrica. Além disso, o consenso visava apoiar a tomada de decisão das operadoras de planos de saúde, agências reguladoras e líderes e/ou administradores de instituições de saúde.

Elevated IgA and IL-10 levels in very-early-onset inflammatory bowel disease secondary to IL-10 receptor deficiency / Níveis elevados de IgA e IL-10 na doença inflamatória intestinal de início muito precoce secundária à deficiência do receptor de IL-10

ABSTRACT Objective: To report two patients with very-early-onset inflammatory bowel disease (VEOIBD) secondary to interleukin-10 receptor (IL-10R) mutations, explore immunophenotyping data and plasma cytokine profile on these cases compared to healthy controls, and describe the phenotype of IL-10/IL-10R mutations based on a literature review. Case description: We report on two female infants referred to our tertiary center at the age of ten months, with severe colonic and perianal disease, as well as significant malnutrition, who had shown limited response to usual inflammatory bowel disease (IBD) therapy agents. In the first case, whole-exome sequencing (WES) revealed a homozygous (c.537G>A/p.T179T) mutation in exon 4 of the IL-10RA gene, while in the second patient, compound heterozygosity was identified, also in the IL-10RA gene (chr11:117.859.199 variant A>G/p.Tyr57Cys and chr11: 117.860.335 variant G>T/p.Val123Leu). Both patients underwent hematopoietic cell transplantation (HCT). Immunological work-up of these patients revealed increased IL-10 plasma levels and increased IgA. Comments: Our case reports disclose novel findings on plasma cytokine profile in IL-10R deficiency, and we describe the severe phenotype of IL-10/IL-10R deficiency that should be recognized by physicians.

RESUMO Objetivo: Relatar os casos de duas pacientes com doença inflamatória intestinal de início muito precoce (em inglês VEOIBD) secundária a mutações do receptor de interleucina 10 (IL-10R), explorar dados de imunofenotipagem e perfil de citocinas plasmáticas nesses casos em comparação com indivíduos saudáveis e descrever o fenótipo de mutações IL-10/IL-10R com base em uma revisão da literatura. Descrição do caso: Duas lactentes do sexo feminino foram encaminhadas ao nosso centro terciário, ambas com dez meses no momento do encaminhamento, com doença colônica e perianal grave, bem como desnutrição significativa, tendo uma resposta limitada aos agentes de terapia usuais de doença inflamatória intestinal (DII). No primeiro caso, o sequenciamento completo do exoma revelou mutação homozigótica (c. 537G>A/p.T179T) no exon 4 do gene IL-10RA, enquanto no segundo caso heterozigosidade composta foi identificada também no gene IL-10RA [chr11: 117.859.199 - variante A>G/p.Tyr57Cys e chr11: 117.860.335 - variante G>T/ p.Val123Leu]. Ambas as pacientes foram submetidas a Transplante de Células-Tronco Hematopoiéticas. A investigação imunológica das pacientes revelou aumento dos níveis plasmáticos de IL-10 e aumento da IgA. Comentários: Nossos relatos de casos descrevem novos achados no perfil de citocinas plasmáticas na deficiência de IL-10R, e relatamos o fenótipo grave da deficiência de IL-10/IL-10R que deve ser reconhecido pelos médicos.

GASTROESOPHAGEAL REFLUX DISEASE IN INFANTS WHO PRESENTED BRIEF RESOLVED UNEXPLAINED EVENT (BRUE).

BACKGROUND: The term brief resolved unexplained events (BRUE) is a description of the acute event occurring in infants less than 1-year-old that includes at least one of the following characteristics: cyanosis or pallor; absent, decreased, or irregular breathing; marked change in tone or altered level of responsiveness. An investigative proceeding is required to identify the triggering phenomenon in those who are at high risk of complications. Prolonged esophageal pHmetry has been used as a tool in searching for gastroesophageal reflux disease (GERD) as one of the underlying etiologies. OBJECTIVE: The study aims to verify the frequency of GERD in infants up to 1-year-old, when pHmetry has been performed for investigating high-risk BRUE (HR-BRUE) and to analyze if clinical characteristics or any particular symptom related by caregivers during BRUE could be correlated to GERD. METHODS: It was performed a cross-sectional study. The data was collected retrospectively of patients less than 1-year-old, who had performed pHmetry in a tertiary hospital for investigating HR-BRUE between October 2008 and January 2018. For the analysis of medical records, a data collection protocol included: gender, age at the first HR-BRUE episode, age at the time of the pHmetry, gestational age, type of delivery (normal or caesarean) and birth weight and symptoms associated to HR-BRUE related by caregivers. Relation between variables were assessed using Fisher's exact test and Mann-Whitney test. The significance level was set at 0.05. RESULTS: A total of 54 infants were included (preterm 25, term 29), 62.9% males, median age at the HR-BRUE was 36 days, 53.7% HR-BRUE episodes had occurred during or right after feeding. According to pHmetry results: nine pHmetry results were considered inconclusive, physiological reflux (n=30) and GERD (n=15). The frequency of GERD diagnosed by pHmetry was 33%. GERD was not statistically related to gender (P-value=0.757), age at first HR-BRUE episode (P-value=0.960), age at the time of the pHmetry (P-value=0.720), prematurity (P-value=0.120) or type of delivery (P-value=0.738). GERD was statistically related to low birth weight (P-value=0.023). There was no association between symptoms reported by caregivers during HR-BRUE and GERD. CONCLUSION: GERD diagnosed by the pHmetry was found in one third of infants that experiencing a HR-BRUE, showing the importance of properly investigation. In half of infants BRUE occurred during or right after feeding. Besides low birth weight, it was not possible to select other data from the clinical history that suggest that these patients would be more likely to have GERD.

CLASSICAL SEROLOGICAL MARKERS IN PEDIATRIC INFLAMMATORY BOWEL DISEASE IN BRAZIL.

BACKGROUND: Perinuclear anti-neutrophil cytoplasmic antibodies (p-ANCA) and anti-Saccharomyces cerevisiae antibodies (ASCAs) have long been used to differentiate between Crohn's disease (CD) and ulcerative colitis (UC), more recently having been used as prognostic indicators. OBJECTIVE: To determine the diagnostic accuracy of serological markers in the identification of pediatric CD and UC in Sao Paulo, Brazil, as well as to correlate those markers with characteristics demographic and clinical of these two diseases. METHODS: Retrospective cross-sectional multi-center study involving pediatric patients with inflammatory bowel disease (IBD). We identified ASCAs serological markers and p-ANCA, correlating their presence with demographic and clinical data, not only in the patients with IBD but also in a group of age-matched gastrointestinal disease-free controls. RESULTS: A total of 122 patients, 74 with IBD (46% males), treated at four pediatric gastroenterology referral centers, the mean age of 13±7 years, 49 (66%) with CD, and 25 (34%) with UC. The control Group comprised 48 patients (54% males). The proportion of patients testing positive for p-ANCA was significantly higher in the UC group (69.9%) compared to the CD group (30.4%), as well as being significantly higher in the CD group versus the control Group (P<0.001 for both). The proportion of patients testing positive for ASCA IgA (76.2%) and ASCA IgG (94.4%) markers was also significantly higher in the CD group than in the control Group (P<0.001), and such positivity correlated significantly with the use of immunomodulatory medications such as azathioprine and anti-tumor necrosis factor agents (azathioprine 38.9%, anti-TNF 55.6%; P=0.002). In the CD group, the proportion of patients testing positive for the ASCA IgA was significantly higher among those who underwent surgery than among those who did not (26.86±17.99; P=0.032). CONCLUSION: In pediatric patients with IBD in Sao Paulo, Brazil, serological tests proving to be highly specific, although not very sensitive, for the diagnosis of IBD. However, the serological markers showed a positive correlation with the severity of the disease.

Elevated IgA and IL-10 levels in very-early-onset inflammatory bowel disease secondary to IL-10 receptor deficiency.

OBJECTIVE: To report two patients with very-early-onset inflammatory bowel disease (VEOIBD) secondary to interleukin-10 receptor (IL-10R) mutations, explore immunophenotyping data and plasma cytokine profile on these cases compared to healthy controls, and describe the phenotype of IL-10/IL-10R mutations based on a literature review. CASE DESCRIPTION: We report on two female infants referred to our tertiary center at the age of ten months, with severe colonic and perianal disease, as well as significant malnutrition, who had shown limited response to usual inflammatory bowel disease (IBD) therapy agents. In the first case, whole-exome sequencing (WES) revealed a homozygous (c.537G>A/p.T179T) mutation in exon 4 of the IL-10RA gene, while in the second patient, compound heterozygosity was identified, also in the IL-10RA gene (chr11:117.859.199 variant A>G/p.Tyr57Cys and chr11: 117.860.335 variant G>T/p.Val123Leu). Both patients underwent hematopoietic cell transplantation (HCT). Immunological work-up of these patients revealed increased IL-10 plasma levels and increased IgA. COMMENTS: Our case reports disclose novel findings on plasma cytokine profile in IL-10R deficiency, and we describe the severe phenotype of IL-10/IL-10R deficiency that should be recognized by physicians.

Doença do refluxo gastroesofágico em lactentes que apresentaram Eventos Resolvidos Breves Não Explicados - Brief Resolved Unexplained Event (BRUE) / Gastroesophageal reflux disease in infants who presented brief resolved unexplained event (brue)

ABSTRACT BACKGROUND: The term brief resolved unexplained events (BRUE) is a description of the acute event occurring in infants less than 1-year-old that includes at least one of the following characteristics: cyanosis or pallor; absent, decreased, or irregular breathing; marked change in tone or altered level of responsiveness. An investigative proceeding is required to identify the triggering phenomenon in those who are at high risk of complications. Prolonged esophageal pHmetry has been used as a tool in searching for gastroesophageal reflux disease (GERD) as one of the underlying etiologies. OBJECTIVE: The study aims to verify the frequency of GERD in infants up to 1-year-old, when pHmetry has been performed for investigating high-risk BRUE (HR-BRUE) and to analyze if clinical characteristics or any particular symptom related by caregivers during BRUE could be correlated to GERD. METHODS: It was performed a cross-sectional study. The data was collected retrospectively of patients less than 1-year-old, who had performed pHmetry in a tertiary hospital for investigating HR-BRUE between October 2008 and January 2018. For the analysis of medical records, a data collection protocol included: gender, age at the first HR-BRUE episode, age at the time of the pHmetry, gestational age, type of delivery (normal or caesarean) and birth weight and symptoms associated to HR-BRUE related by caregivers. Relation between variables were assessed using Fisher's exact test and Mann-Whitney test. The significance level was set at 0.05. RESULTS: A total of 54 infants were included (preterm 25, term 29), 62.9% males, median age at the HR-BRUE was 36 days, 53.7% HR-BRUE episodes had occurred during or right after feeding. According to pHmetry results: nine pHmetry results were considered inconclusive, physiological reflux (n=30) and GERD (n=15). The frequency of GERD diagnosed by pHmetry was 33%. GERD was not statistically related to gender (P-value=0.757), age at first HR-BRUE episode (P-value=0.960), age at the time of the pHmetry (P-value=0.720), prematurity (P-value=0.120) or type of delivery (P-value=0.738). GERD was statistically related to low birth weight (P-value=0.023). There was no association between symptoms reported by caregivers during HR-BRUE and GERD. CONCLUSION: GERD diagnosed by the pHmetry was found in one third of infants that experiencing a HR-BRUE, showing the importance of properly investigation. In half of infants BRUE occurred during or right after feeding. Besides low birth weight, it was not possible to select other data from the clinical history that suggest that these patients would be more likely to have GERD.

RESUMO CONTEXTO: O termo Eventos Resolvidos Breves Não Explicados (Brief Resolved Unexplained Event - BRUE) é uma descrição do evento agudo que ocorre em lactentes menores de 1 ano de idade que inclui pelo menos uma das seguintes características: cianose ou palidez; respiração ausente, diminuída ou irregular, alteração acentuada no tônus ou nível alterado de responsividade. É necessário um procedimento investigativo para identificar o fenômeno desencadeante naqueles que apresentam alto risco de complicações. A pHmetria esofágica prolongada tem sido usada como uma ferramenta na pesquisa de doença do refluxo gastroesofágico (DRGE) como uma das etiologias subjacentes. OBJETIVO: Este estudo tem como objetivo verificar a frequência da DRGE em lactentes de até 1 ano de idade, quando a pHmetria foi realizada para investigação da BRUE de alto risco, e analisar se alguma característica clínica ou sintoma particular relatado pelos cuidadores durante a BRUE poderia estar correlacionado a DRGE. MÉTODOS: Foi realizado um estudo observacional, transversal, cujos dados foram coletados retrospectivamente de pacientes menores de 1 ano de idade, que realizaram pHmetria em hospital terciário para investigação de BRUE de alto risco de outubro de 2008 e janeiro de 2018. Para a análise dos prontuários, um protocolo de coleta de dados incluiu: sexo, idade no primeiro episódio de BRUE de alto risco, idade no momento da pHmetria, idade gestacional, tipo de parto (normal ou cesárea), peso ao nascer e sintomas associados a alto risco-BRUE relatado por cuidadores. A relação entre as variáveis foi avaliada por meio do teste exato de Fisher, qui-quadrado e teste de Mann-Whitney. O nível de significância foi estabelecido em 0,05. RESULTADOS: Foram incluídos 54 lactentes (pré-termo 25, termo 29), 62,9% do sexo masculino, idade mediana na BRUE de alto risco foi de 36 dias. De acordo com o relatório do cuidador, 53,7% dos episódios de BRUE de alto risco ocorreram durante ou logo após a alimentação. Resultados da pHmetria: nove resultados da pHmetria foram considerados inconclusivos, refluxo fisiológico (n=30) e DRGE (n=15). A frequência de DRGE diagnosticada por pHmetria foi de 33%. A DRGE não foi estatisticamente relacionada ao sexo (P=0,757), idade no primeiro episódio de BRUE de alto risco (P=0,96), idade no momento da pHmetria (P=0,72) prematuridade (P=0,321) ou tipo de parto (P=0,738). A DRGE foi estatisticamente relacionada ao baixo peso ao nascer (P=0,023). Não houve associação entre os sintomas relatados pelos cuidadores durante BRUE de alto risco e o diagnóstico de DRGE. CONCLUSÃO: A DRGE diagnosticada pela pHmetria foi encontrada em um terço dos lactentes que vivenciaram BRUE de alto risco, mostrando a importância da investigação adequada. Em metade das crianças, o evento ocorreu durante ou logo após a alimentação. Além do baixo peso ao nascer, não foi possível selecionar outros dados da história clínica que sugiram que esses pacientes terão maior probabilidade de apresentar DRGE.

Marcadores sorológicos clássicos na doença inflamatória intestinal pediátrica no Brasil / Classical serological markers in pediatric inflammatory bowel disease in brazil

ABSTRACT BACKGROUND: Perinuclear anti-neutrophil cytoplasmic antibodies (p-ANCA) and anti-Saccharomyces cerevisiae antibodies (ASCAs) have long been used to differentiate between Crohn's disease (CD) and ulcerative colitis (UC), more recently having been used as prognostic indicators. OBJECTIVE: To determine the diagnostic accuracy of serological markers in the identification of pediatric CD and UC in Sao Paulo, Brazil, as well as to correlate those markers with characteristics demographic and clinical of these two diseases. METHODS: Retrospective cross-sectional multi-center study involving pediatric patients with inflammatory bowel disease (IBD). We identified ASCAs serological markers and p-ANCA, correlating their presence with demographic and clinical data, not only in the patients with IBD but also in a group of age-matched gastrointestinal disease-free controls. RESULTS: A total of 122 patients, 74 with IBD (46% males), treated at four pediatric gastroenterology referral centers, the mean age of 13±7 years, 49 (66%) with CD, and 25 (34%) with UC. The control Group comprised 48 patients (54% males). The proportion of patients testing positive for p-ANCA was significantly higher in the UC group (69.9%) compared to the CD group (30.4%), as well as being significantly higher in the CD group versus the control Group (P<0.001 for both). The proportion of patients testing positive for ASCA IgA (76.2%) and ASCA IgG (94.4%) markers was also significantly higher in the CD group than in the control Group (P<0.001), and such positivity correlated significantly with the use of immunomodulatory medications such as azathioprine and anti-tumor necrosis factor agents (azathioprine 38.9%, anti-TNF 55.6%; P=0.002). In the CD group, the proportion of patients testing positive for the ASCA IgA was significantly higher among those who underwent surgery than among those who did not (26.86±17.99; P=0.032). CONCLUSION: In pediatric patients with IBD in Sao Paulo, Brazil, serological tests proving to be highly specific, although not very sensitive, for the diagnosis of IBD. However, the serological markers showed a positive correlation with the severity of the disease.

RESUMO CONTEXTO: Os anticorpos citoplasmáticos anti-neutrófilos perinuclear (p-ANCA) e anticorpos anti-Saccharomyces cereviciae (ASCAs) são utilizados para diferenciar a doença de Crohn (DC) da colite ulcerativa (CU) e mais recentemente para correlacioná-los com o prognóstico da doença. OBJETIVO: 1) Determinar a acurácia diagnóstica dos marcadores sorológicos na identificação de DC e CU pediátrica em São Paulo, Brasil. 2) Correlacioná-los com as características demográficas e clínicas destas duas doenças. MÉTODOS: Estudo multicêntrico transversal em pacientes com diagnóstico estabelecido de doença inflamatória intestinal (DII) determinando a presença dos marcadores sorológicos ASCAs e p-ANCA, correlacionando seus resultados com os dados demográficos e clínicos, e também em pacientes controles isentos de doenças gastrointestinal. RESULTADOS: 122 pacientes, 74 com DII (46% masculinos) em quatro centros de referência em Gastroenterologia Pediátrica, média de idade 13±7 anos, 49 (66%) com DC e 25 (34%) com CU e 48 controles (54% masculinos). O marcador p-ANCA apresenta maior porcentagem de detecção na CU (69,6%), mas também na DC (30,4%) quando comparado ao grupo controle (P<0,001). Os marcadores ASCA IgA (76,2%) e IgG (94,4%) apresentam maiores porcentagens de detecção na DC, quando comparada ao controle (P<0,001) e que a positividade do marcador esteve relacionada ao uso de medicações em pacientes portadores de DC que realizaram cirurgia (26,86±17,99; P=0,032). CONCLUSÃO: Os resultados dos testes sorológicos em crianças com DII em São Paulo, Brasil, foram altamente específicos, mas pouco sensíveis para auxiliar no diagnóstico, embora com correlação positiva com a gravidade da doença.

CASE-CONTROL STUDY ON VITAMIN D STATUS IN CHILDREN AND ADOLESCENTS WITH EOSINOPHILIC ESOPHAGITIS.

BACKGROUND: Vitamin D is an essential fat-soluble steroid hormone and vitamin D deficiency is a global public health problem especially among children and adolescents. Factors such as the low intake of vitamin D-rich food sources, poor absorption and less exposure to the sun influence this outcome. Vitamin D has an anti-inflammatory effect in the body by promoting regulatory T cell differentiation as well as recovering T helper 17 cell response and secretion of anti-inflammatory cytokines. Eosinophilic esophagitis (EoE) is a chronic disease, histologically characterized by predominantly eosinophilic inflammation. The most common therapeutic approaches are allergen-eliminating diets, such as excluding cow's milk, egg, soy, wheat, peanuts and seafood, or more specific dietary restrictions. OBJECTIVE: To verify the serum levels of vitamin D in children and adolescents with eosinophilic esophagitis on a restricted food diet and to analyze their association with nutritional status, consumption of different food sources, exposure to the sun and skin color. METHODS: Case-control study conducted in the city of Campinas-SP, Brazil, in which included patients were aged 2 to 18 years old, and those diagnosed with eosinophilic esophagitis was referred to as the case group (n=15), meanwhile a control group (n=17) was also formed. Epidemiological data, nutritional status, data on vitamin D intake (24-hour recall - performed only by EoE patients - and self-reported intake of vitamin D food sources: milk and dairy products, canned tuna and sardines, Bull's liver, chicken eggs - applied in both groups), and daily time of sun exposure (≥30 min or ≤30 min) were recorded. The samples were collected for serum levels of 25-hydroxy-vitamin D, where sufficiency levels >30 ng/mL were considered, insufficiency 21 to 30 ng/mL, deficiency <20 ng/mL. RESULTS: There was a higher frequency of vitamin D insufficiency/ deficiency in the Eosinophilic Esophagitis group (P=0.035), even with longer sun exposure (P= 0.035). Skin color was not associated with lower levels of vitamin D in both groups studied. No difference was found in nutritional status between the groups. CONCLUSION: The present study demonstrated a higher frequency of inadequate/ deficient levels of vitamin D in children and adolescents with EoE on a restricted diet. When necessary, serum levels should be investigated and correct exposure to the sun should be encouraged, with special attention to the recommended guidelines, time spent in the sun and the appropriate clothing for correct absorption. Since exposure for more than 30 minutes in the sun does not appear to have provided a protective effect in the EoE group, even in a region with high levels of solar radiation. There was a significant difference only in the consumption of cow's milk between the case and control groups, demonstrating the low adherence to the restriction diet by the case group. No association was found between serum 25 hydroxyvitamin D levels and nutritional status. Moreover, no association regarding the adequate or inadequate status of 25 hydroxyvitamin D and the consumption vitamin D-rich foods was identified. Multicentered studies with a larger number of cases should be performed to assess serum 25 hydroxyvitamin D levels and associated factors in pediatric patients with EoE.