International Latin American Survey on Pediatric Intestinal Failure Team.

There is little data on the experience of managing pediatric Intestinal Failure (IF) in Latin America. This study aimed to identify and describe the current organization and practices of the IF teams in Latin America and the Caribbean. An online survey was sent to inquire about the existence of IF teams that managed children on home parenteral nutrition (HPN). Our questionnaire was based on a previously published European study with a similar goal. Twenty-four centers with pediatric IF teams in eight countries completed the survey, representing a total number of 316 children on HPN. The median number of children on parenteral nutrition (PN) at home per team was 5.5 (range 1-50). Teams consisted of the following members: pediatric gastroenterologist and a pediatric surgeon in all teams, dietician (95.8%), nurse (91.7%), social worker (79.2%), pharmacist (70.8%), oral therapist (62.5%), psychologist (58.3%), and physiotherapist (45.8%). The majority of the centers followed international standards of care on vascular access, parenteral and enteral nutrition, and IF medical and surgical management, but a significant percentage reported inability to monitor micronutrients, like vitamins A (37.5%), E (41.7%), B1 (66.7%), B2 (62.5%), B6 (62.5%), active B12 (58.3%); and trace elements-including zinc (29.2%), aluminum (75%), copper (37.5%), chromium (58.3%), selenium (58.3%), and manganese (58.3%). Conclusion: There is wide variation in how IF teams are structured in Latin America-while many countries have well-established Intestinal rehabilitation programs, a few do not follow international standards. Many countries did not report having an IF team managing pediatric patients on HPN.

mTOR inhibitors reduce enteropathy, intestinal bleeding and colectomy rate in patients with juvenile polyposis of infancy with PTEN-BMPR1A deletion.

Ultra-rare genetic disorders can provide proof of concept for efficacy of targeted therapeutics and reveal pathogenic mechanisms relevant to more common conditions. Juvenile polyposis of infancy (JPI) is caused by microdeletions in chromosome 10 that result in haploinsufficiency of two tumor suppressor genes: phosphatase and tensin homolog deleted on chromosome 10 (PTEN) and bone morphogenetic protein receptor type IA (BMPR1A). Loss of PTEN and BMPR1A results in a much more severe phenotype than deletion of either gene alone, with infantile onset pan-enteric polyposis and a high mortality rate. No effective pharmacological therapy exists. A multi-center cohort analysis was performed to characterize phenotype and investigate the therapeutic effect of mammalian target of rapamycin (mTOR) inhibition (adverse events, disease progression, time to colectomy and mortality) in patients with JPI. Among 25 JPI patients identified (mean age of onset 13 months), seven received mTOR inhibitors (everolimus, n = 2; or sirolimus, n = 5). Treatment with an mTOR inhibitor reduced the risk of colectomy (hazard ratio = 0.27, 95% confidence interval = 0.07-0.954, P = 0.042) and resulted in significant improvements in the serum albumin level (mean increase = 16.3 g/l, P = 0.0003) and hemoglobin (mean increase = 2.68 g/dl, P = 0.0077). Long-term mTOR inhibitor treatment was well tolerated over an accumulated follow-up time of 29.8 patient years. No serious adverse events were reported. Early therapy with mTOR inhibitors offers effective, pathway-specific and personalized treatment for patients with JPI. Inhibition of the phosphoinositol-3-kinase-AKT-mTOR pathway mitigates the detrimental synergistic effects of combined PTEN-BMPR1A deletion. This is the first effective pharmacological treatment identified for a hamartomatous polyposis syndrome.

Successful Treatment of Juvenile Polyposis of Infancy With Sirolimus.

Juvenile polyposis syndrome is a rare autosomal dominant condition characterized by multiple hamartomatous polyps throughout the gastrointestinal tract. Juvenile polyposis of infancy is a generalized severe form of juvenile polyposis syndrome associated with a poor prognosis. A 47-month-old female infant presented initially with gastrointestinal bleeding and protein-losing enteropathy at 4 months of age. At the age of 12 months, the condition worsened, requiring albumin infusions every 24 to 48 hours and red blood cell transfusions every 15 days. Upper gastrointestinal endoscopy, colonoscopy, and small-bowel enteroscopy revealed diffuse polyposis that was treated with multiple endoscopic polypectomies. Despite subtotal colectomy with ileorectal anastomosis, protein-losing enteropathy and bleeding persisted, requiring continued blood transfusions and albumin infusions. A chromosomal microarray revealed a single allele deletion in chromosome 10q23, involving both the PTEN and BMPR1A genes. Loss of PTEN function is associated with an increased activation of the protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway involved in cell proliferation. Treatment with sirolimus, an mTOR inhibitor, was initiated with the aim of inhibiting polyp growth. Soon after initiation of treatment with sirolimus, blood and albumin infusions were no longer needed and resulted in improved patient growth and quality of life. This case represents the first detailed report of successful drug therapy for life-threatening juvenile polyposis of infancy.

IBD-Like Features in Syndromic Diarrhea/Trichohepatoenteric Syndrome.

BACKGROUND: Very early onset inflammatory bowel disease (VEOIBD) (inflammatory bowel disease [IBD] before 6 years of age) may manifest as a monogenic disease affecting the gastrointestinal tract. Syndromic diarrhea/trichohepatoenteric syndrome (SD/THE), a rare disorder caused by alteration of a complex involved in RNA degradation, has been reported to present with some degree of colitis and in some cases an IBD-like presentation. METHODS: We reviewed clinical and biological data of 4 previously published cases and added detailed data of 2 new cases of SD/THE with an IBD-like presentation. RESULTS: All the 6 patients presented with typical intractable diarrhea and hair abnormalities. The colon was affected in all of the patients: 1 had ileitis, 2 had panenteritis, and 2 presented with perianal disease. Fecal calprotectin level and erythrosedimentation rate were elevated in 2 cases each. All the therapeutic classes of IBD treatment (mesalazine, steroids, immunomodulators, and biological therapy) were used in the 6 cases. In 2 patients, treatment had no effect. Three showed a partial effect, and 1 patient sustained only a transient effect. CONCLUSIONS: SD/THE can have a similar presentation as VEOIBD, often as pancolitis. IBD treatments appear to have little efficacy for SD/THE, suggesting a different pathogenesis for the IBD-like features in SD/THE compared with classical IBD.

[Eosinophilic gastroenteropathy: a pediatric series]. / Gastroenteropatía eosinofílica: una serie pediátrica.

Eosinophilic gastroenteropathy (EoG) is an uncommon disease characterized by eosinophilic infiltration of the gastrointestinal (GI) mucosa. A chart review was performed searching for patients diagnosed between 2000 and 2010. EoG was diagnosed based on mucosal infiltration of 20 or more eosinophils/HPF in upper GI tract and more than 60 eosinophils/HPF in lower GI tract. Ten patients [median age: 10 mo. (r 2 mo.- 10 yr.)], 9 males, were diagnosed. Four presented with severe protracted diarrhea and weight loss, 2/10 abdominal distention and weight loss and 4/10 protein-losing enteropathy. Exclusive elemental or hypoallergenic diets were administered depending on the age of presentation with remission achieved in 4/10. Six required methylprednisolone to induce remission, 5 are still on budesonide. Due to the emergence of many cases of EoG in the last decade, we should increase our level of suspicion. Multicenter studies could contribute to define the best therapeutic approach for these patients.

Gastroenteropatía eosinofílica: una seriepediátrica / Eosinophilic gastroenteropathy: a pediatric series

La gastroenteropatía eosinofílica es una entidad inusual caracterizada por infiltración eosinofílica de la mucosa gastrointestinal.Efectuamos un análisis retrospectivo de 10 pacientes diagnosticados como gastroenteropatía eosinofílica entre 2000 y 2010. El diagnóstico histológico se confirmó por infiltración de 20 o máseosinófilos/campo de gran aumento en tracto digestivo superior y/o más de 60 en tracto digestivo inferior. Diez pacientes [edad mediana 10 meses (r 2 meses -10 años)] con predominio masculino (9:1), fueron diagnosticados como gastroenteropatía eosinofílica.La presentación clínica fue: diarrea y deterioro ponderal (4/10); distensión abdominal y deterioro ponderal (2/10) y edema e hipoalbuminemia (4/10). Se administró dieta elemental/hipoalergénicasegún edad de presentación clínica, con remisión sintomática en 4/10. Seis requirieron inducción con corticoides, 5 realizan mantenimiento con budesonide. Dado el incremento de casos de gastroenteropatía eosinofílica en laúltima década, debemos agudizar la sospecha diagnóstica. Un estudio multicéntrico podría colaborar en la definición del mejor enfoque terapéuticoen estos pacientes.

[Cow's milk proteín allergy: proposed guidelines for the management of children with cow's milk protein allergy]. / Alergia a la proteína de la leche de vaca: propuesta de Guía para el manejo de los niños con alergia a la proteína de la leche de vaca.

Cow's milk allergy is a growing concern in the practice of pediatrics. The impression of an increasing incidence, similar to what has been reported in other latitudes, has determined the need for guidelines to help in the diagnosis and treatment of this disease. A group of pediatric specialists met to discuss the "state of the art" and propose local guidelines to deal with cow's milk allergy. The aim has been to contribute in the understanding of the pathophysiology, environmental factors, and clinical expressions of this problem, and help pediatricians in the overall management.

Alergia a la proteína de la leche de vaca: propuesta de Guía para el manejo de los niños con alergia a la proteína de la leche de vaca / Cow’s milk protein allergy: proposed guidelines for the management of children with cow’s milk protein allergy

El diagnóstico y manejo de la alergia a la proteína de leche de vaca es un verdadero desafío en la práctica pediátrica. Como se trata de una patología que pareciera estar aumentando en nuestro medio, de un modo similar a lo comunicado en otras latitudes, hemos considerado conveniente proponer una normalización de la nomenclatura y de la metodología diagnóstica. Un grupo de pediatras especialistas se ha reunido para realizar una Propuesta de Guía para el manejo de los niños con alergia a la proteína de la leche de vaca. El objetivo ha sido difundir el conocimiento actual de la fisiopatología, factores ambientales y sus manifestaciones clínicas, para colaborar con el pediatra mediante algoritmos que faciliten su manejo integral.

Cow’s milk allergy is a growing concern in the practice of pediatrics. The impression of an increasing incidence, similar to what has been reported in other latitudes, has determined the need for guidelines to help in the diagnosis and treatment of this disease. A group of pediatric specialists met to discuss the “state of the art” and propose local guidelines to deal with cow’s milk allergy. The aim has been to contribute in the understanding of the pathophysiology, environmental factors, and clinical expressions of this problem, and help pediatricians in the overall management.