Reverse-engineered exclusive enteral nutrition in pediatric Crohn's disease: A pilot trial.

BACKGROUND: In pediatric Crohn's disease (CD), commercial formulas used as exclusive enteral nutrition (EEN) are effective at inducing remission. This study aims to assess the impact of a whole-food blended smoothie as EEN on CD activity and the intestinal microbiome. METHODS: A 4-week prospective trial assessed the impact of EEN with a whole-food smoothie on newly diagnosed mild-to-moderate active pediatric CD. The smoothie with a multivitamin were developed to meet age-appropriate nutritional requirements. Assessment over 4 weeks included Pediatric Crohn's Disease Activity Index (PCDAI), serum laboratories, fecal calprotectin (FCP), and stool collection for metagenomic shotgun sequencing and microbiota composition analysis. Clinical remission was defined as PCDAI ≤ 10 at week 4. RESULTS: Ten participants were enrolled with median age 14.5 years, and 8 completed the trial. Baseline mean PCDAI was 26.3 ± 9.1 and mean FCP 1149 ± 718 µg/g. At week 4, 80% of participants achieved clinical remission. FCP decreased by over half in 60% of participants, with FCP below 250 µg/g in 60% and below 100 µg/g in 40%. Microbiome analysis showed a significant increase in species richness over 4 weeks (p = 0.01). Compared to baseline, the relative abundance at week 2 and at week 4 was significantly increased for Bifidobacterium and Streptococcus and decreased for Blautia (p < 0.05 for all). CONCLUSION: A whole-food blended smoothie was effective for inducing clinical remission and decreasing FCP in pediatric CD similar to commercial EEN formulas. Further research may give insight into data-driven whole-food dietary approaches for CD management. CLINICALTRIALS: gov NCT03508193.

A Clinician's Guide to Gluten Challenge.

Gluten challenge is an essential clinical tool that involves reintroducing or increasing the amount of gluten in the diet to facilitate diagnostic testing in celiac disease (CD). Nevertheless, there is no consensus regarding the applications of gluten timing, dosing, and duration in children. This review aims to summarize the current evidence, discuss practical considerations, and proposes a clinical algorithm to help guide testing in pediatric patients. Childhood development, social circumstances, and long-term health concerns must be considered when identifying a candidate for gluten challenge. Based on previous studies, the authors suggest baseline serology followed by a minimum of 3-6 grams of gluten per day for over 12 weeks to optimize diagnostic accuracy for evaluation of CD. A formal provider check-in at 4-6 weeks is essential so the provider and family can adjust dosing or duration as needed. Increasing the dose of gluten further may improve diagnostic yield if tolerated, although in select cases a lower dose and shorter course (6-12 weeks) may be sufficient. There is consensus that mild elevations in celiac serology (<10 times the upper limit of normal) or symptoms, while supportive are not diagnostic for CD. Current North American Society for Pediatric Gastroenterology, Hepatology and Nutrition guidelines recommend histologic findings of intraepithelial lymphocytosis, crypt hyperplasia, and villous atrophy as the accurate and most appropriate endpoint for gluten challenge.

Children With Celiac Disease Consume Specific Food Additives More Frequently Compared to Children Without Celiac Disease.

BACKGROUND: Gluten-free foods often contain food additives to improve palatability, but the long-term effects on the human gastrointestinal tract are not well known. AIMS: This study aimed to quantify frequency of food additive exposure in children with and without celiac disease (CD). METHODS: Children with and without CD were enrolled and demographic data and three-day diet records were obtained. Foods were classified as gluten-free products (GFP) and "processed food", and were evaluated for presence of select food additives: polysorbate 80, carboxymethylcellulose, xanthan gum, guar gum, soy lecithin, titanium dioxide, carrageenan, maltodextrin, and aluminosilicates. The frequency of exposure was described. RESULTS: Twenty-eight participants were included in final analysis. Children with CD had a higher number of daily exposures to xanthan gum (5.3 ± 3.1 vs 2.3 ± 2.4; p = 0.009), but similar exposures to the other additives. GFP contributed 29% of total calories in the GF diet. Both groups had similar intake of processed foods. Comparing GFP and gluten-containing processed foods, 68% vs. 25% contained at least one food additive of interest (p < 0.0001); in the celiac group, those with higher consumption of GFP tended to have a higher frequency of exposure to food additives (p = 0.09). CONCLUSION: A gluten-free diet and consumption of GFP may contribute to differences in food additive intake; quantifying food additive exposures and their effect on humans requires further study.

Personalized Research on Diet in Ulcerative Colitis and Crohn's Disease: A Series of N-of-1 Diet Trials.

INTRODUCTION: Evidence about specific carbohydrate diet (SCD) for inflammatory bowel disease (IBD) is limited. We conducted 54 single-subject, double-crossover N-of-1 trials comparing SCD with a modified SCD (MSCD) and comparing each with the participant's baseline, usual diet (UD). METHODS: Across 19 sites, we recruited patients aged 7-18 years with IBD and active inflammation. Following a 2-week baseline (UD), patients were randomized to 1 of 2 sequences of 4 alternating 8-week SCD and MSCD periods. Outcomes included fecal calprotectin and patient-reported symptoms. We report posterior probabilities from Bayesian models comparing diets. RESULTS: Twenty-one (39%) participants completed the trial, 9 (17%) completed a single crossover, and 24 (44%) withdrew. Withdrawal or early completion occurred commonly (lack of response [n = 11], adverse events [n = 11], and not desiring to continue [n = 6]). SCD and MSCD performed similarly for most individuals. On average, there was <1% probability of a clinically meaningful difference in IBD symptoms between SCD and MSCD. The average treatment difference was -0.3 (95% credible interval -1.2, 0.75). There was no significant difference in the ratio of fecal calprotectin geometric means comparing SCD and MSCD (0.77, 95% credible interval 0.51, 1.10). Some individuals had improvement in symptoms and fecal calprotectin compared with their UD, whereas others did not. DISCUSSION: SCD and MSCD did not consistently improve symptoms or inflammation, although some individuals may have benefited. However, there are inherent difficulties in examining dietary changes that complicate study design and ultimately conclusions regarding effectiveness.

Drivers of Variation in Diagnosis and Management of Eosinophilic Esophagitis: A Survey of Pediatric Gastroenterologists.

BACKGROUND: Widespread variation in the diagnosis and treatment of eosinophilic esophagitis (EoE) has previously been reported among adult gastroenterologists; however, variation in EoE practice in among pediatric populations is poorly characterized. The study objectives were to describe guideline adherence and understand reasons for variation in EoE practice among pediatric gastroenterologists following publication of the updated 2018 international EoE guidelines. METHODS: We developed and administered a 28-item survey to pediatric gastroenterologists via an email listserv using the PEDGI Bulletin Board from 03/2019 to 04/2019. The survey was developed using evidence-based review, expert validation, and cognitive interviews. Survey domains included respondent knowledge of and adherence to published guidelines, diagnostic and management approach and rationale, and participant demographics. Analysis included descriptive statistics and tests for association. RESULTS: A total of 288 pediatric gastroenterologists completed the survey, most of whom practiced in an academic center (73%). More than half (63%) reported knowledge of the 2018 updated guidelines; however, only 52% agreed with them and 50% reported adherence. Respondents who reported not agreeing with updated guidelines cited concerns regarding increasing number of endoscopies (72%), misdiagnosing eosinophilia from reflux (56%), and insufficient data (23%). The most common drivers of decision making with respect to therapy choice were patient/family preference, evidence/guidelines, and symptom burden. CONCLUSIONS: Many physicians are not adherent to current guidelines for reasons which include lack of knowledge of updated guidelines and concern regarding the strength of the supporting evidence. This study elucidates several areas to enhance education regarding these guidelines to promote widespread adherence.

Mutations in 3ß-hydroxysteroid-δ8, δ7-isomerase paradoxically benefit epidermal permeability barrier homeostasis in mice.

Inherited or acquired blockade of distal steps in the cholesterol synthetic pathway results in ichthyosis, due to reduced cholesterol production and/or the accumulation of toxic metabolic precursors, while inhibition of epidermal cholesterol synthesis compromises epidermal permeability barrier homeostasis. We showed here that 3ß-hydroxysteroid-δ8, δ7-isomerase-deficient mice (TD), an analog for CHILD syndrome in humans, exhibited not only lower basal transepidermal water loss rates, but also accelerated permeability barrier recovery despite the lower expression levels of mRNA for epidermal differentiation marker-related proteins and lipid synthetic enzymes. Moreover, TD mice displayed low skin surface pH, paralleled by increased expression levels of mRNA for sodium/hydrogen exchanger 1 (NHE1) and increased antimicrobial peptide expression, compared with wild-type (WT) mice, which may compensate for the decreased differentiation and lipid synthesis. Additionally, in comparison with WT controls, TD mice showed a significant reduction in ear thickness following challenges with either phorbol ester or oxazolone. However, TD mice exhibited growth retardation. Together, these results demonstrate that 3ß-hydroxysteroid-δ8, δ7-isomerase deficiency does not compromise epidermal permeability barrier in mice, suggesting that alterations in epidermal function depend on which step of the cholesterol synthetic pathway is interrupted. But whether these findings in mice could be mirrored in humans remains to be determined.

Is Endoscopic Assessment of the Esophagus and Stomach Enough to Determine the Need for Biopsy at These Sites in Pediatric Patients Undergoing Endoscopy for Elevated TTG?

OBJECTIVES: The goal of our study was to determine whether visual assessment of the esophagus and stomach could predict abnormal histology and determine the frequency of interventions based on biopsies in patients undergoing endoscopy for elevated tissue transglutaminase immunoglobulin A antibody (TTG). METHODS: Pathology records were searched for patients with biopsy performed for elevated TTG. Pathology report, endoscopy report, and follow-up were obtained and slides from the duodenum reviewed. Pathology was considered gold standard for sensitivity and specificity calculations. RESULTS: 240 patients were included. 215 patients had esophageal biopsies performed. Esophageal endoscopic visual assessment had sensitivity of 47% and specificity of 93% for abnormal histology. 16(7%) patients had therapy or referral related to results and, of these, 6(38%) had visually normal endoscopy. 237 biopsies were performed of stomach. Gastric endoscopic visual assessment had a sensitivity and specificity of 20% and 87%. 24(10%) patients had therapy based on findings and, of these, 12 (50%) had visually normal endoscopy. CONCLUSIONS: Endoscopic assessment of esophagus and stomach has low sensitivity and high specificity for pathologic abnormalities when indication for endoscopy is elevated TTG. When endoscopy is visually normal clinical interventions based on biopsy are rare, and foregoing biopsy may be considered.

Inducible nitric oxide synthase is required for epidermal permeability barrier homeostasis in mice.

Nitric oxide (NO) regulates a variety of epidermal functions, including epidermal proliferation, differentiation and cutaneous wound healing. However, whether nitric oxide (NO) and its synthetic enzymes regulate epidermal permeability barrier homeostasis is not clear. In the present study, we employed inducible nitric oxide synthase (iNOS) KO mice to explore the role of iNOS in epidermal permeability barrier homeostasis. Our results showed that iNOS mice displayed a comparable levels of basal transepidermal water loss rates, stratum corneum hydration and skin surface pH to their wild-type mice, but epidermal permeability barrier recovery was significantly delayed both 2 and 4 hours after acute barrier disruption by tape stripping. In parallel, expression levels of mRNA for epidermal differentiation-related proteins and lipid synthetic enzymes were lower in iNOS KO mice versus wild-type controls. Topical applications of two structurally unrelated NO donors to iNOS KO mice improved permeability barrier recovery kinetics and upregulated expression levels of mRNA for epidermal differentiation-related proteins and lipid synthetic enzymes. Together, these results indicate that iNOS and its product regulate epidermal permeability barrier homeostasis in mice.

Do Histologic Features Help Predict Colectomy in Pediatric Patients Presenting With Acute Severe Colitis?

BACKGROUND: Multiple prior studies have looked at clinical and laboratory parameters in ulcerative colitis to predict prognosis, but individual histologic features of inflammation and their prognostic significance have not been well studied. The purpose of our study was to determine whether histologic features at presentation with acute severe colitis predict colectomy in pediatric patients. METHODS: Patients were identified retrospectively through the gastroenterology and pathology databases. Demographic information, duration of disease, laboratory data, endoscopic appearance at scope, and histologic features of inflammation were reviewed along with medical therapies. Patients who underwent surgery within 90 days of hospitalization were compared to those who did not. RESULTS: Fifty patients with acute severe colitis, defined as Pediatric Ulcerative Colitis Activity Index ≥65, were included. Sixteen patients had colectomies performed within 90 days of presentation. No statistically significant difference was found between the surgery and no-surgery groups for patient age, albumin, hemoglobin, or C-reactive protein, though hemoglobin trended toward significance, P = .05. The endoscopic Mayo score and histologic features of inflammation (architectural changes, chronic inflammation, eosinophils, neutrophils within the lamina propria, neutrophils in epithelium, crypt destruction, and ulceration) were similar between groups. CONCLUSION: In pediatric patients presenting for hospitalization with acute severe colitis, no histologic features of inflammation predicted colectomy within 90 days.

The association between serum chloride levels and chronic kidney disease progression: a cohort study.

BACKGROUND: Limited data suggest serum chloride levels associate with mortality in heart failure, chronic kidney disease (CKD), and pulmonary arterial hypertension. Randomized trials have also shown that administration of crystalloid intravenous fluids with lower chloride concentration may have better renal outcomes. However, chloride has not been studied longitudinally for CKD progression. METHODS: We used a prospective cohort of subjects with stage 3 and 4 CKD recruited from a nephrology clinic at a single medical center. Linear regression, linear regression with generalized estimating equations, and Cox proportional hazards models were created for outcomes of overall change in estimated glomerular filtration rate (eGFR), longitudinal changes in eGFR, and time to > 30% decline in eGFR, respectively. Baseline chloride was modeled continuously and categorically, and models were adjusted for potential confounders. RESULTS: Median follow-up was 1.7 years. Baseline median age was 72 years and median eGFR was 35.7 mL/min/1.73m2. In multivariable analysis, higher serum chloride associated with worsened eGFR decline. Every 1 mEq/L increase in chloride associated with an overall eGFR decline of 0.32 mL/min/1.73m2 (p = 0.003), while the difference in eGFR decline in the highest quartile of chloride was 3.4 mL/min/1.73m2 compared to the lowest quartile (p = 0.004). No association between serum chloride and time to 30% decline in eGFR was observed in multivariable analysis (hazard ratio 1.05 per 1 mEq/L increase in serum chloride, p = 0.103). CONCLUSIONS: In CKD patients, higher serum chloride associated with a modestly steeper rate of eGFR decline, and may be a useful biomarker to predict CKD progression. Further studies are needed to determine causality.

Dietary therapy for clostridium difficile colonization: A case series.

Clostridium difficile (C. difficile) is an important nosocomial pathogen in adults and children. Roughly 4-5% of non hospitalized healthy adults carry the organism in their intestinal flora while adults in long term care facilities have asymptomatic carriage rates estimated at 20-50%. C. difficile colonization results in a spectrum of clinical conditions from asymptomatic carrier state to fulminant colitis. Changes in the fecal microbiome are central in the development of C. difficile colonization and disease pathogenesis. C. difficile infection has been shown to be associated with reduced biodiversity of the gut microbiome and intestinal dysbiosis. With the importance of the intestinal microbiota in development of CDI and with the known impact of diet on the intestinal microbiota, we report the first known case of C. difficile colonization/recurrence successful treated by dietary modification.

Clinical and Fecal Microbial Changes With Diet Therapy in Active Inflammatory Bowel Disease.

GOAL: To determine the effect of the specific carbohydrate diet (SCD) on active inflammatory bowel disease (IBD). BACKGROUND: IBD is a chronic idiopathic inflammatory intestinal disorder associated with fecal dysbiosis. Diet is a potential therapeutic option for IBD based on the hypothesis that changing the fecal dysbiosis could decrease intestinal inflammation. STUDY: Pediatric patients with mild to moderate IBD defined by pediatric Crohn's disease activity index (PCDAI 10-45) or pediatric ulcerative colitis activity index (PUCAI 10-65) were enrolled into a prospective study of the SCD. Patients started SCD with follow-up evaluations at 2, 4, 8, and 12 weeks. PCDAI/PUCAI, laboratory studies were assessed. RESULTS: Twelve patients, ages 10 to 17 years, were enrolled. Mean PCDAI decreased from 28.1±8.8 to 4.6±10.3 at 12 weeks. Mean PUCAI decreased from 28.3±23.1 to 6.7±11.6 at 12 weeks. Dietary therapy was ineffective for 2 patients while 2 individuals were unable to maintain the diet. Mean C-reactive protein decreased from 24.1±22.3 to 7.1±0.4 mg/L at 12 weeks in Seattle Cohort (nL<8.0 mg/L) and decreased from 20.7±10.9 to 4.8±4.5 mg/L at 12 weeks in Atlanta Cohort (nL<4.9 mg/L). Stool microbiome analysis showed a distinctive dysbiosis for each individual in most prediet microbiomes with significant changes in microbial composition after dietary change. CONCLUSIONS: SCD therapy in IBD is associated with clinical and laboratory improvements as well as concomitant changes in the fecal microbiome. Further prospective studies are required to fully assess the safety and efficacy of dietary therapy in patients with IBD.

Rectal Picking Masquerading as Inflammatory Bowel Disease in Prader-Willi Syndrome.

Prader-Willi syndrome (PWS) is a genetic syndrome in which individuals have multisystem medical challenges. Gastroenterological difficulties in the syndrome include decreased vomiting, constipation, delayed gastric emptying, delayed colonic transit, dysphagia, increased choking, and increased risk of gastric dilation and rupture. In addition, self-injurious behavior such as rectal picking may be present and severe enough to lead to rectal ulceration and bleeding. Many patients have extensive gastroenterological workup and treatment before their ultimate diagnosis of severe rectal picking. We describe 4 new cases of rectal picking in individuals with PWS leading to rectal bleeding and ulceration as well as a review of the literature of prior cases of severe rectal picking in PWS and potential treatment options. It is important to recognize these cases early in order to prevent unnecessary treatments and implement appropriate behavioral interventions.

Children with Crohn's Disease Frequently Consume Select Food Additives.

OBJECTIVE: Certain food additives may promote the pathogenesis of Crohn's disease (CD), but thus far the evaluation of food additive exposures in humans has been limited. The objective of this study was to quantify food additive exposures in children with CD. METHODS: In a trial for bone health in CD, children were followed over 24 months with evaluation of disease characteristics, dietary intake, and body composition. At baseline, participants completed three 24-h dietary recalls. Foods were categorized, and the ingredient list for each item was evaluated for the presence of select food additives: polysorbate-80, carboxymethylcellulose, xanthan gum, soy lecithin, titanium dioxide, carrageenan, maltodextrin, and aluminosilicates. The frequency of exposures to these food additives was described for study participants and for food categories. RESULTS: At study baseline, 138 participants, mean age 14.2 ± 2.8 years, 95% having inactive or mild disease, were enrolled and dietary recalls were collected. A total of 1325 unique foods were recorded. Mean exposures per day for xanthan gum was 0.96 ± 0.72, carrageenan 0.58 ± 0.63, maltodextrin 0.95 ± 0.77, and soy lecithin 0.90 ± 0.74. The other additives had less than 0.1 exposures per day. For the 8 examined food additives, participants were exposed to a mean (SD) of 3.6 ± 2.1 total additives per recall day and a mean (SD) of 2.4 ± 1.0 different additives per day. CONCLUSION: Children with CD frequently consume food additives, and the impact on disease course needs further study.

Administration of Antibiotics to Children Before Age 2 Years Increases Risk for Childhood Obesity.

BACKGROUND & AIMS: Childhood obesity is increasing and is associated with adult obesity. Antibiotics have been used to promote weight gain in livestock for several decades. Antibiotics are commonly prescribed for children, but it is not clear how exposure to antibiotics early in life affects risk for obesity. We performed a population-based cohort study to assess the association between antibiotic exposure before age 2 years and obesity at age 4 years. METHODS: We performed a retrospective cohort study of 21,714 children in The Health Improvement Network-a population-representative dataset of >10 million individuals derived from electronic medical records from 1995 through 2013 in the United Kingdom. Eligible subjects were registered within 3 months of birth with complete follow-up and height and weight were recorded within 12 months of their 4th birthday. Antibiotic exposure was assessed before age 2 years, and classified based on anti-anaerobic activity. The primary outcome was obesity at age 4 years. We performed logistic regression analyses, adjusting for maternal and sibling obesity, maternal diabetes, mode of delivery, socioeconomic status, year and country of birth, and urban dwelling. RESULTS: In the cohort, 1306 of the children (6.4%) were obese at 4 years of age. Antibiotic exposure was associated with an increased risk of obesity at 4 years (odds ratio [OR] = 1.21; 95% confidence interval [CI]: 1.07-1.38). ORs increased with repeated exposures: for 1-2 prescriptions, OR = 1.07 (95% CI, 0.91-1.23); for 3-5 prescriptions, OR = 1.41 (95% CI, 1.20-1.65); and for 6 or more prescriptions, OR = 1.47 (95% CI, 1.19-1.82). Antifungal agents were not associated with obesity (OR = 0.81; 95% CI, 0.59-1.11). CONCLUSIONS: Administration of 3 or more courses of antibiotics before children reach an age of 2 years is associated with an increased risk of early childhood obesity.

Nutritional Adequacy of the Specific Carbohydrate Diet in Pediatric Inflammatory Bowel Disease.

INTRODUCTION: The specific carbohydrate diet (SCD) is an exclusion diet used as a therapy in inflammatory bowel disease. The aim of this study was to evaluate the nutritional adequacy of the SCD. METHODS: Prospective dietary data for 12 weeks were analyzed for pediatric patients on the SCD. Intake of 20 key nutrients was compared to dietary recommended intake levels and nutrient intake data from similarly aged children from The National Health and Nutrition Examination Survey National Youth Fitness Survey in 2012. RESULTS: Nine patients enrolled, with 8 patients completing the study. Six of 8 individuals completing the study had gained weight, 1 individual had weight loss, and 1 had no change in weight. Energy intake was significantly greater than 100% of the recommended daily allowance (RDA)/adequate intake for 64% of daily intakes completed for this study. The majority of participants' daily intakes met or exceeded the RDA for vitamins B2, B3, B5, B6, B7, B12, C, A, and E. One hundred percent of participants' intakes were below the RDA for vitamin D. Seventy-five percent of daily intakes were less than the RDA for calcium. The upper limit was met or exceeded for magnesium in 42% of daily intakes. Average vitamin A intake was significantly greater than the upper limit (P = 0.01). CONCLUSIONS: Nutrient intake of pediatric inflammatory bowel disease patients on the SCD was adequate when compared with a healthy peer reference population, but adequacy was variable when compared with the dietary recommended intakes. Close monitoring with a multidisciplinary team for patients using the SCD as an alternative or adjunct therapy is recommend to ensure positive outcomes for overall patient health.

Lack of Mucosal Healing From Modified Specific Carbohydrate Diet in Pediatric Patients With Crohn Disease.

Exclusive enteral nutrition is effective in pediatric Crohn disease but challenging as maintenance therapy. There is interest in food-based therapies such as the specific carbohydrate diet (SCD) but paucity of data on efficacy and effect on mucosal healing, an evolving target of IBD therapy. We conducted a retrospective review of the mucosal healing effect of the SCD in pediatric Crohn disease (CD). The endoscopic findings for children younger than 18 years with CD treated exclusively with the SCD or modified SCD (mSCD; SCD + addition of "illegal foods") were reviewed before and after the diet. Ileocolonoscopic examinations were scored according to the Simple Endoscopic Score for CD and findings on upper endoscopy were described. Seven subjects were identified, all on mSCD. The average age at starting the SCD was 11 ±â€Š3.4 years and median duration of SCD/mSCD therapy was 26 months. All subjects reported no active symptoms before repeat endoscopic evaluation on mSCD, the majority had consistently normal C-reactive protein, albumin and hematocrit assessments, and mildly elevated fecal calprotectin (>50 µg/g, median 201, range 65-312) at any point within 3 months before the repeat endoscopy. One patient showed complete ileocolonic healing but persistent upper gastrointestinal tract ulceration. Complete macroscopic mucosal healing of both the ileocolon and upper gastrointestinal tract was not seen in any patient.

Nutritional Therapy in Very Early-Onset Inflammatory Bowel Disease: A Case Report.

Inflammatory bowel disease (IBD) is a chronic inflammatory disease of the gastrointestinal tract caused by a dysregulated immune response to the fecal microbiota. Very early-onset inflammatory bowel disease (VEO-IBD) refers to a subgroup of pediatric patients with IBD diagnosed before 6 years of age. This subgroup is often characterized by increased severity, aggressive progression, strong family history of IBD, and often poor response to conventional treatments. Nutritional therapies have been utilized to treat IBD, but their role in VEO-IBD is unclear. Disease behavior in VEO-IBD is often different from disease in adolescents and adults, as it is often restricted to the colon and refractory to standard medical therapies. Up to 25% of VEO-IBD patients have an identified underlying immunodeficiency, which may impact response to therapy. While specific mutations in interleukin 10 (IL-10), the IL-10 receptor (IL-10R), and mutations in NCF2, XIAP, LRBA, and TTC7 have been identified in VEO-IBD, polymorphisms in these genes are also associated with increased risk of developing IBD in adolescence or adulthood. We describe two cases in which infants presenting with VEO-IBD achieved clinical remission using exclusive enteral nutrition, a formula-based diet which has been shown to induce remission in older children with active Crohn's disease.

Diet in the pathogenesis and treatment of inflammatory bowel diseases.

Some of the most common symptoms of the inflammatory bowel diseases (IBD, which include ulcerative colitis and Crohn's disease) are abdominal pain, diarrhea, and weight loss. It is therefore not surprising that clinicians and patients have wondered whether dietary patterns influence the onset or course of IBD. The question of what to eat is among the most commonly asked by patients, and among the most difficult to answer for clinicians. There are substantial variations in dietary behaviors of patients and recommendations for them, although clinicians do not routinely endorse specific diets for patients with IBD. Dietary clinical trials have been limited by their inability to include a placebo control, contamination of study groups, and inclusion of patients receiving medical therapies. Additional challenges include accuracy of information on dietary intake, complex interactions between foods consumed, and differences in food metabolism among individuals. We review the roles of diet in the etiology and management of IBD based on plausible mechanisms and clinical evidence. Researchers have learned much about the effects of diet on the mucosal immune system, epithelial function, and the intestinal microbiome; these findings could have significant practical implications. Controlled studies of patients receiving enteral nutrition and observations made from patients on exclusion diets have shown that components of whole foods can have deleterious effects for patients with IBD. Additionally, studies in animal models suggested that certain nutrients can reduce intestinal inflammation. In the future, engineered diets that restrict deleterious components but supplement beneficial nutrients could be used to modify the luminal intestinal environment of patients with IBD; these might be used alone or in combination with immunosuppressive agents, or as salvage therapy for patients who do not respond or lose responsiveness to medical therapies. Stricter diets might be required to induce remission, and more sustainable exclusion diets could be used to maintain long-term remission.

Ustekinumab in Pediatric Crohn Disease Patients.

OBJECTIVES: We describe the use of ustekinumab for 4 patients with pediatric Crohn disease treated at the Seattle Children's Hospital Inflammatory Bowel Disease Center. METHODS: A retrospective chart review was done to identify patients' clinical data, disease phenotype, treatment history, and laboratory and growth parameters before treatment with ustekinumab and at last follow-up. Adverse events while on ustekinumab were also recorded. RESULTS: Four adolescent patients with Crohn disease at our center received ustekinumab. All had previously received corticosteroids, methotrexate, azathioprine/6-mercaptopurine, and both infliximab and adalimumab. Patients had varying disease phenotypes. Ages at ustekinumab initiation were 12, 13, 16, and 17 years. Weight ranged from 40.5 to 57.8 kg, mean 49.5 kg. Two patients showed clinical response and remain on ustekinumab. Two patients discontinued therapy because of continued symptoms and disease complications and required multiple hospitalizations. CONCLUSIONS: Ustekinumab was used in 4 children with pediatric Crohn disease with 2 of 4 patients showing clinical response (1 with persistently elevated C-reactive protein). A prospective study is needed to define its efficacy, safety, and placement in managing pediatric Crohn disease in the future.