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.

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.

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.

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.

COVID-19 and pediatric inflammatory bowel disease: How to manage it?

Pediatric gastroenterologists, family members, and caregivers of patients with inflammatory bowel disease (IBD) are on alert; they are all focused on implementing prophylactic measures to prevent infection by severe acute respiratory syndrome coronavirus 2, evaluating the risks in each patient, guiding them in their treatment, and keeping IBD in remission. To face the current issues of the coronavirus disease pandemic, we have developed a synthesis of the main recommendations of the literature directed at pediatric gastroenterologists in control of patients with pediatric IBD and adapted to the national reality.

COVID-19 and pediatric inflammatory bowel disease: How to manage it?

Pediatric gastroenterologists, family members, and caregivers of patients with inflammatory bowel disease (IBD) are on alert; they are all focused on implementing prophylactic measures to prevent infection by severe acute respiratory syndrome coronavirus 2, evaluating the risks in each patient, guiding them in their treatment, and keeping IBD in remission. To face the current issues of the coronavirus disease pandemic, we have developed a synthesis of the main recommendations of the literature directed at pediatric gastroenterologists in control of patients with pediatric IBD and adapted to the national reality.

Correction to: Rate and determinants of non-adherence to a gluten-free diet and nutritional status assessment in children and adolescents with celiac disease in a tertiary Brazilian referral center: a cross-sectional and retrospective study.

CORRECTION: Unfortunately, after publication of this article [1], it was noticed that the names of the second and third authors were incorrectly displayed, respectively, as Glauce Hiromi Yonaminez and Carla Aline Satiro. The correct names are Glauce Hiromi Yonamine and Carla Aline Fernandes Satiro and can be seen in the corrected author list above. The original article has also been updated to correct this error.

Rate and determinants of non-adherence to a gluten-free diet and nutritional status assessment in children and adolescents with celiac disease in a tertiary Brazilian referral center: a cross-sectional and retrospective study.

BACKGROUND: Compliance with a gluten-free diet (GFD) is difficult at all ages but particularly for teenagers due to social, cultural, economic, and practical pressures. The multidisciplinary team responsible for the treatment of patients with celiac disease and give support to their parents plays a special role on strengthening GFD and assessing the nutritional and physical health. METHODS: A cross-sectional and retrospective study including patients under 20 years of age, with biopsy-confirmed CD, followed regularly at the Department of Pediatrics, Division of Gastroenterology, Hospital das Clínicas, University of Sao Paulo, School of Medicine, Sao Paulo, Brazil, were surveyed using a questionnaire and serologic test applied between November 2011 and February 2012. A retrospective chart review of these patients was performed to collect the anthropometric data along with the results of the serologic test performed at the time of diagnosis and after at least 1 year of treatment with a GFD. RESULTS: We evaluated 35 patients aged between 2.4 and 19.9 years. Of these 68.6% were female, 88.6% had the typical form of the disease and 51.4% had other comorbidities. The mean age at diagnosis was 5.4 years. Despite dietary guidance, 20% reported non-adherence to the diet. Most children recovered the weight and height deficit after 5 years of treatment, and in some children, excessive weight gain became a concern. CONCLUSION: The majority of transgressions occurred intentionally at home or at parties. There was a risk of excessive weight gain, especially in the first two years of treatment. More alternatives and easier access to low cost gluten-free foods, increasing the discussion about the benefits of adhering to a GFD among patients, families, and the general population, besides the acquisition of self-management skills, are crucial to fostering independent children and adolescents who have the knowledge and tools to manage life with CD.

Relative cost-effectiveness of using an extensively hydrolyzed casein formula in managing infants with cow's milk allergy in Brazil.

OBJECTIVE: To estimate the cost-effectiveness of three alternative dietetic strategies for cow's milk allergy in Brazil: 1) using an extensively hydrolyzed casein formula (eHCF; Nutramigen) as a first-line formula, but switching to an amino acid formula (AAF) if infants remain symptomatic; 2) using an AAF as a first-line formula and then switching to an eHCF after 4 weeks once infants are symptom-free, but switching back to an AAF if infants become symptomatic; and 3) using an AAF as a first-line formula and keeping all infants on that formula. The analysis was conducted from the perspective of the Brazilian public health care system, Sistema Único de Saude. METHODS: Decision modeling was used to estimate the probability of immunoglobulin E (IgE)-mediated and non-IgE-mediated allergic infants developing tolerance to cow's milk by 12 months from starting a formula. The models also estimated the Sistema Único de Saude cost (at 2013/2014 prices) of managing infants over 12 months after starting a formula, as well as the relative cost-effectiveness of each of the dietetic strategies. RESULTS: The probability of developing tolerance to cow's milk by 12 months from starting a formula was higher among infants with either IgE-mediated or non-IgE-mediated allergy who were initially fed with an eHCF, compared with those who were initially fed with an AAF. The total health care cost of initially feeding an eHCF to cow's milk allergic infants was less than that of initially feeding both IgE-mediated and non-IgE-mediated infants with an AAF. CONCLUSION: Within the study's limitations, using an eHCF instead of an AAF for the first-line management of newly-diagnosed infants with cow's milk allergy affords a cost-effective use of publicly funded resources, since it improves the outcome for less cost.

A snapshot of the nutritional status of Crohn's disease among adolescents in Brazil: a prospective cross-sectional study.

BACKGROUND: The relationship between nutrition and Crohn's disease (CD) is complex and involves several therapeutic possibilities including: nutrition treatment for malnourished patients, optimization of growth and development, prevention of osteoporosis, first-line therapy for active disease, and maintenance of disease remission. In children and adolescents with CD, malnutrition is a common problem that adversely affects the prognosis. In at-risk adolescent CD patients, it is important to assess body composition, food intake, energy expenditure, nutrient balance and serum levels of nutrients before planning interventions for this population. The aim of this study was to provide a snapshot of the nutritional status of adolescents with CD in Brazil. METHODS: We prospectively selected 22 patients with mildly to moderately active CD, 29 patients with inactive CD and 35 controls (first-degree relatives of and in the same age bracket as the CD patients). The age range of participants was between 13.2 and 19.4 years old. We collected anthropometric data including weight, height, and body mass index (BMI), which were expressed as Z scores: weight-for-age, height-for-age and BMI-for-age, respectively, as well as using bioimpedance to determine body composition and assessing the Tanner stage. We also assessed macronutrients and micronutrients (serum levels and dietary intake of both). We used the chi-square test to determine whether any of the studied variables were associated with inactive or active CD. The level of significance was set at 5 % (p < 0.05). We have written informed parental consent for participation for any minors and written informed consent for any participants that were adults. RESULTS: The mean values for lean body mass, Tanner stage, height-for-age Z score and BMI-for-age Z score were lower in the active CD group than in the inactive CD and control groups (p < 0.05 for both). Compared with the controls, the CD patients showed significant differences in terms of the quality of dietary intake (particularly in caloric intake, dietary protein intake, dietary fiber intake, and micronutrient intake), which were reflected in the serum levels of nutrients, mainly vitamins A and E (p < 0.05). CONCLUSIONS: Adolescents with CD (including those with mildly to moderately active or inactive disease) have a nutritional risk, which makes it important to conduct nutritional assessments in such patients.

Clinical manifestations, treatment, and outcomes of children and adolescents with eosinophilic esophagitis.

OBJECTIVE: This study aimed to describe the clinical, endoscopic, and histologic characteristics, as well as the response to conventional treatment of pediatric patients with the classical form of eosinophilic esophagitis (EoE). METHODS: Study of clinical, laboratory, endoscopic, and histologic data and response to conventional treatment of 43 previously followed pediatric patients with the classical form of EoE. RESULTS: A total of 43 patients diagnosed with EoE were included in the study, of which 37 were males (86%), with a mean age of 8.4 years. The most common symptoms were: nausea, vomiting, and abdominal pain (100%) in children younger than 7 years, and loss of appetite (60%), heartburn (52%), and food impaction (48%) in children older than 7 years and adolescents. Regarding the endoscopic findings, 12 (28%) patients had whitish plaques on the esophageal lining, 8 (18.5%) had longitudinal grooves, 2 (4.5%) had concentric rings, 3 (7%) had longitudinal grooves and whitish plaques, and the remaining 18 (42%) had esophageal mucosa with normal appearance. Despite the initial favorable response, 76.7% of patients required more than one course of corticosteroid therapy (systemic or aerosol) and diet (exclusion or elimination of food or elementary allergens). Persistence of eosinophil infiltration was found in some patients despite favorable clinical response. CONCLUSIONS: The classic form of EoE typically shows different symptoms according age range. A significant number of patients required more than one treatment cycle to show clinical remission. Endoscopic and histologic improvement was observed; however, eosinophilic infiltration persisted in some patients.

Manifestações clínicas, terapêutica e evolução de crianças e adolescentes com esofagite eosinofílica / Clinical manifestations, treatment, and outcomes of children and adolescents with eosinophilic esophagitis

OBJECTIVE: This study aimed to describe the clinical, endoscopic, and histologic characteristics, as well as the response to conventional treatment of pediatric patients with the classical form of eosinophilic esophagitis (EoE). METHODS: Study of clinical, laboratory, endoscopic, and histologic data and response to conventional treatment of 43 previously followed pediatric patients with the classical form of EoE. RESULTS: A total of 43 patients diagnosed with EoE were included in the study, of which 37 were males (86%), with a mean age of 8.4 years. The most common symptoms were: nausea, vomiting, and abdominal pain (100%) in children younger than 7 years, and loss of appetite (60%), heartburn (52%), and food impaction (48%) in children older than 7 years and adolescents. Regarding the endoscopic findings, 12 (28%) patients had whitish plaques on the esophageal lining, 8 (18.5%) had longitudinal grooves, 2 (4.5%) had concentric rings, 3 (7%) had longitudinal grooves and whitish plaques, and the remaining 18 (42%) had esophageal mucosa with normal appearance. Despite the initial favorable response, 76.7% of patients required more than one course of corticosteroid therapy (systemic or aerosol) and diet (exclusion or elimination of food or elementary allergens). Persistence of eosinophil infiltration was found in some patients despite favorable clinical response. CONCLUSIONS: The classic form of EoE typically shows different symptoms according age range. A significant number of patients required more than one treatment cycle to show clinical remission. Endoscopic and histologic improvement was observed; however, eosinophilic infiltration persisted in some patients.

OBJETIVO: O objetivo deste estudo foi descrever as características clínicas, endoscópicas e histológicas, assim como a resposta ao tratamento convencional de pacientes pediátricos com a forma clássica de esofagite eosinofílica (EEo). MÉTODOS: Levantamento de dados clínicos, laboratoriais, endoscópicos, histológicos e da resposta ao tratamento convencional de 43 pacientes pediátricos acompanhados previamente com a forma clássica de EEo. RESULTADOS: Foram incluídos 43 pacientes com diagnóstico de EEo, sendo 37 do sexo masculino (86%), com idade média de 8,4 anos. Os sintomas mais encontrados foram: náusea, vômito e dor abdominal (100%) em crianças menores de sete anos; e inapetência (60%), queimação retroesternal (52%) e impactação alimentar (48%) em crianças maiores de sete anos e adolescentes. Em relação aos achados endoscópicos, 12 (28%) pacientes apresentavam placas esbranquiçadas na mucosa do esôfago, oito (18,5%) sulcos longitudinais, dois (4,5%) anéis concêntricos, três (7%) sulcos longitudinais e placas esbranquiçadas, e os outros 18 (42%) apresentavam aparência normal da mucosa esofágica. Apesar da resposta favorável inicial, 76,7% dos pacientes necessitaram realizar mais de um ciclo terapêutico com corticoterapia (aerossol ou sistêmica) e dieta (de exclusão ou eliminação dos alérgenos alimentares ou elementares). Persistência do infiltrado eosinofílico foi encontrada em uma parcela dos pacientes, a despeito da resposta clínica favorável. CONCLUSÕES: A forma clássica da EEo apresenta sintomas diferentes segundo a faixa etária. Parcela expressiva dos pacientes necessitou de mais de um ciclo terapêutico para apresentar remissão clínica. Observou-se melhora endoscópica e histológica; no entanto, a infiltração eosinofílica persistiu em parcela dos pacientes.

Tratamento da retocolite ulcerativa inespecífica em crianças com enemas contendo butirato: relato de caso / Treatment of ulcerative colitis in child with enemas containing butyrate. Case report

Objetivo - Chamar a atenção para uma promissora alternativa terapêutica no tratamento de retocolite ulcerativa inespecífica em criança. Método - É descrito o caso de uma criança com diagnóstico de retocolite ulcerativa inespecífica, com forma evolutiva crônica contínua, refratária ao tratamento convencional e que foi tratada com enemas contendo butirato. Revisão de literatura pertinente ao caso foi realizada. Resultados - Paciente de 4 anos, feminina, parda, com diagnóstico de retocolite ulcerativa inespecífica desde 1 ano de idade e evolução refratária ao tratamento com corticóide (via oral e retal) e imunossupressor (6-mercaptopurina). Respondeu de modo satisfatório com melhora do quadro clínico, laboratorial, endoscópico e histológico, após o uso de enemas com butirato semelhante às descrições da literatura internacional. Conclusão - Embora sem estar esclarecido o mecanismo de ação do butirato na retocolite ulcerativa inespecífica, melhora significante foi observada neste caso, acenando como possibilidade terapêutica segura nos casos de retocolite ulcerativa inespecífica confinados a segmentos distais.

Estudos imunohistoquímicos dos macrófagos na mucosa colônica em crianças na doença de Crohn e na retocolite ulcerativa inespecífica / Immunohistochemical study of macrophages in the colonic mucosa of children with Crohn's disease and ulcerative colitis

Sao quantificadas e analisadas as características histológicas dos macrófagos na mucosa colônica na doença de Crohn e na retocolite ulcerativa inespecífica. Foram estudados 12 pacientes com doença de Crohn 19 com retocolite ulcerativa inespecífica e 10 espécimes de mucosa retal representando o grupo controle, de acordo com o seguinte modelo: período I (PI) = pré-tratamento; período II (PII)= até dois anos de evoluçao e período III (PIII)= mais de dois anos de evoluçao. Os macrófagos foram identificados em mucosa colônica pelo monoclonal CD68 através do método de imunoperoxidase. A quantificaçao dos macrófagos foi feita através de análise de imagem computadorizada cromática, que expressa em porcentagem a área (mm2) ocupada pelas células CD68 positivas. A porcentagem da área ocupada pelos macrófagos se apresentava aumentada em ambas as doenças, em todos os períodos estudados, quando comparada com o grupo controle, porém sem diferença estatisticamente significante. A distribuiçao dos macrófagos dentro da mucosa do grupo controle foi subepitelial, enquanto na dos doentes atingiu toda a altura da mucosa, concentrando-se nas bases das úlceras e ao longo das fissuras. Na doença de Crohn as células CD68 positivas facilitaram a identificaçao dos microgranulomas, eventualmente despercebidos na coloraçao de hematoxilina-eosina. Embora nao houvesse diferença entre pacientes e controles quanto à área ocupada pelos macrófagos, a distribuiçao diferente pode sugerir a participaçao dos macrófagos na lesao destas duas doenças, embora nao permitam diagnóstico diferencial, possivelmente pela variabilidade dos valores. O CD68 nao identificou os diferentes estados funcionais dos macrófagos, mas a sua posiçao na mucosa sugere que com as fissuras e úlceras, sua funçao principal seria a fagocitose, e nos demais sítios a de célula apresentadora de antígenos e recrutadora de outras células inflamatórias.

Estudo imunohistológico do linfócito T (total e auxiliador) e do linfócito B da mucosa colónica de crianças portadoras de doença de Crohn e retocolite ulcerativa inespecífica / Immunohistological study of the T-lymphocyte (total and helper) and the B-lymphocyte of the colonic mucous in children with Crohn's disease and unspecific ulcerative colitis

Para melhor compreensao dos mecanismos imunológicos envolvidos na mucosa colônica da retocolite ulcerativa inespecífica e da doença de Crohn, foram estudadas as mucosas colônicas de 19 crianças com retocolite ulcerativa inespecífica, 12 crianças com doença de Crohn e um grupo controle representado por 10 espécimes de mucosa retal de pacientes com obstipaçao intestinal crônica inespecífica. As mucosas foram coradas com a técnica de imunoperoxidase, e os linfócitos T (total e auxiliador) e B foram identificados com marcadores específicos - para os linfócitos T total, CD3, linfócitos T auxiliador, CD4 e para o B, CD20 - e quantificadas na lâmina própria através de análise de imagem computadorizada cromática em diferentes períodos evolutivos da doença: PI (antes do tratamento), PH (até dois anos de evoluçao) e PIII (com mais de dois anos de evoluçao). No epitélio superficial foi quantificado apenas o linfócito T total, através de contagem linear. O marcador CD3, do linfócito T total, esteve aumentado no epitélio (superficial e glandular) e na lâmina própria das mucosas doentes em relaçao às do controle. Na mucosa dos pacientes, esteve distribuído difusamente, concentrando-se ao redor dos microgranulomas, no interior dos nódulos linfóides e nas áreas lesadas em proximidade aos macrófagos. Na doença de Crohn, PI, sua média na lâmina própria diferiu significantememte em relaçao ao controle. Comportamento semelhante ocorreu com o marcador CD20 do linfócito B nas mucosas doentes, cujas médias foram superiores aos do controle, embora apenas no PI da doença de Crohn essa diferença tenha sido significativa. O marcador CD4 do linfócito T auxiliador também apresentou nas mucosas doentes médias elevadas em relaçao à mucosa controle, mas sem significaçao estatística. As células CD4+ distribuíram-se difusamente por toda altura da mucosa doente, concentrando-se ao redor dos nódulos linfóides e dos microgranulomas. De modo geral, todos os marcadores estudados neste trabalho apresentaram médias superiores aos do grupo controle com diferentes graus de significância nos diferentes períodos estudados. Esses resultados confirmam a participaçao desses elementos na patogênese da retocolite ulcerativa inespecífica e da doença de Crohn. Os achados de correlaçao positiva entre os marcadores CD4 e CD20 na retocolite ulcerativa inespecífica e CD3 e CD20...

Estudo imunohistoquímico da expressäo HLA-DR no epitélio superficial e na lâmina própria da mucosa colônica de crianças portadoras de doença de Crohn e retocolite ulcerativa inespecífica / Immunohistochemical study of the HLA-DR expression in the superficial epithelium and in the lamina propria of the colonic mucosa in children with Crohn's disease and nonspecific ulcerative colitis

Alguns estudos têm realçado a importância da expressao HLA-DR no epitélio superficial e na lâmina própria da mucosa dos pacientes portadores de retocolite ulcerativa inespecífica e doença de Crohn. Neste estudo foram quantificadas e analisadas as características histológicas da expressao HLA-DR na mucosa colônica nestas duas doenças. Foram estudados 12 pacientes em doença de Crohn, 19 com retocolite ulcerativa inespecífica e 10 espécimes de mucosa retal representando o grupo controle, de acordo com o seguinte modelo: período I = pé-tratamento; período II = até dois anos de evoluçao e período III = mais de dois anos de evoluçao. A expressao HLA-DR foi identificada pelo monoclonal HLA-DR (DAKO) em espécimes de mucosa colônica pelo método de imunoperoxidase. A quantificaçao da expressao HLA-DR na lâmina própria foi feita através de análise de imagem computadorizada cromática, que expressa em porcentagem a área (mum2) ocupada pelas células HLA-DR positivas e no epitélio superficial quantificada por uma avaliaçao semi-quantitativa. Na lâmina própria da mucosa dos doentes a expressao HLA-DR esteve aumentada em todos osperíodos estudados, quando comparada com o grupo controle, porém sem diferença estatística. A distribuiçao da expressao HLA-DR na lâmina própria foi em localizaçoes correspondentes aos macrófagos e aos linfócitos B. O epitélio colônico superficial dos pacientes com retocolite ulcerativa inespecífica e com retocolite ulcerativa inespecífica e com doença de Crohn foi HLA-DR positivo em 86,95 por cento e 80,96 por cento, respectivamente, nos três períodos estudados. O epitélio superficial de todas as mucosas retais do grupo controle nao mostraram a expressao HLA-DR. A presença da expressao HLA-DR no epitélio colônico superficial dos pacientes com retocolite ulcerativa inespecífica e doença de Crohn e sua ausência no epitélio do grupo controle foi um achado de grande importância neste estudo. É consenso entre os diversos autores que a expressao HLA-DR representa uma intensa açao local das citocinas indutoras desta expressao na mucosa colônica dos pacientes com retocolite ulcerativa inespecífica e donça de Crohn, representando a sua ativaçao em resposta ao antígeno invasor da mucosa intestinal. O estudo da expressao HLA-DR na lâmina própria nao foi conclusivo, pois o resultado nao representou diferença significativa em relaçao ao controle.