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Vulval involvement in Crohn’s disease (CD) is rare, particularly in children. The clinical features include erythema, edema, ulceration, and labial skin tags. The authors present two cases of children with vulval CD. In both cases, marked labial edema was the presenting feature. In one patient the immunomodulator tacrolimus ointment 0.03% was used with success. In the second patient control was achieved with intralesional triamcinolone in combination with systemic metronidazole.

Crohn's disease (CD) is a chronic illness and radiographic evaluation is frequently used. Consequently, pediatric patients with CD who are diagnosed in childhood are at risk for high levels of radiation exposure during their lifetimes. We sought to evaluate the impact of magnetic resonance enterography (MRE) in management of pediatric patients with known or suspected Crohn's disease. A retrospective review of patients with known or suspected CD who underwent MRE for new onset of symptoms was conducted. All demographic data, clinical history, and results of all radiographic, endoscopic, and pathology studies were recorded. Twenty-eight patients with known or suspected CD underwent 31 MRE examinations. MRE showed active disease in 16 (52%), fistula or abscess in seven (22%), and no evidence of active disease in eight (26%). Sixty-five per cent of patients underwent MRE with no other radiation-based imaging used. Surgical intervention was deemed necessary after the MRE in 16 per cent. In all cases, surgical findings were consistent with MRE results. Nearly 60 per cent of patients with CD are managed based on the findings of MRE without additional radiographic evaluation. Based on the results of this retrospective study, we propose a clinical pathway for use of MRE in patients with known or suspected CD with new onset of symptoms.

BACKGROUND Children with Crohn's disease (CD) may report abdominal pain despite clinical remission, suggesting that functional abdominal pain (FAP) may be playing a role. The aim of this study was to explore the presence and impact of FAP in children with CD in remission. METHODS Children, aged 9 to 17 years, with CD were enrolled. Demographic information, the Pediatric Crohn's Disease Activity Index, and the Children's Depression Inventory were obtained. Disease remission was defined by physician global assessment, normal laboratories findings, absence of 3 or more stools a day, nocturnal stooling, bloody diarrhea, concurrent steroid therapy, strictures, or disease flare within 6 months. FAP was defined as patients with abdominal pain and CD remission. Rates of depression (Children's Depression Inventory >9) were compared. RESULTS Of 307 children, 139 reported abdominal pain. Of this group, 18 of 139 (13%) children met the criteria for FAP. Despite clinical remission, 8 of 18 patients with CD having FAP were classified with active disease by Pediatric Crohn's Disease Activity Index. These patients had a higher rate of depression than patients with CD in remission with no abdominal pain (55.6% versus 29.9%; P = 0.03), similar to patients with abdominal pain from active CD (55.6% versus 44.8%; P = 0.62). CONCLUSIONS A proportion of children with CD in remission have FAP. These children are at significant risk of depression. Future studies are needed to determine whether depression contributes to functional pain development or if pain itself leads to depression. Especially given that functional pain may exaggerate disease activity, clinicians caring for children with CD and FAP should consider evaluating for depressive disorders before escalating therapy.

In Crohn's disease, mild gastrointestinal bleeding often occurs; however massive gastrointestinal hemorrhage, which can have a dramatic effect on a patient's vital sign, is rare. This could result in potentially life-threatening complications, which can lead to death. Massive hemorrhagic Crohn's disease is not well known and for this reason, they are a diagnostic and therapeutic challenge. Various diagnostic and therapeutic methods are currently being developed and used. The surgical method is often used only as a last measure since this approach has the risk of serious complications that may endanger patients. However, if massive bleeding continues even after all therapeutic methods are used, the surgical method must be implemented. In this case, all therapeutic methods were found to be ineffective; therefore, surgery was used as a last option. Ultimately, the surgical method was found to be successfully used to treat life-threatening hemorrhagic Crohn's disease.

Purpose Vitamin D deficiency is common in Crohn disease (CD). The aim of the study was to examine the prevalence of vitamin D deficiency and evaluate the association between vitamin D status and growth outcome in Korean pediatric CD patients. Methods In this retrospective study, 17 children younger than 18 years old diagnosed with CD were enrolled and their serum 25-hydroxy vitamin D (25[OH]D) was checked between 2011 and 2015. We categorized the patients into two groups, Group 1 and Group 2. Group 1 included patients with serum 25(OH)D levels below 10 ng/mL, and Group 2 was for patients with a 25(OH)D serum levels between 10 ng/mL and 30 ng/mL. The z-scores for height (Htz), weight (Wtz), and body mass index (BMIz) were measured at baseline, 6 months, and 12 months. Results The mean serum 25(OH)D levels of the total 65 CD patients and 17 enrolled patients were 15.64±6.9 ng/mL and 13.1±5.1 ng/mL, respectively. There was no correlation at the beginning of the study between vitamin D level and growth parameters (Htz, Wtz, BMIz) or other variables including laboratory data and Pediatric Crohn Disease Activity Index. The Htz, Wtz, and BMIz in Group 1 showed no significant improvement at 6 months and 12 months follow-up. In Group 2, Wtz and BMIz showed significant improvements sustained until 12 months of follow-up. Htz showed no significant improvement at 6 months but there was significant improvement at 12 months. Conclusion It seems that baseline vitamin D status affects growth outcome in pediatric CD.

Il est admis que la maladie de Crohn (MC) résulte de facteurs immunologiques, environnementaux et génétiques. SIGIRR, un récepteur anti-inflammatoire, n’a jamais été étudié dans le contexte de la MC, et de nombreuses découvertes à son sujet ont mené plusieurs à s’intéresser quant à son utilité dans l’atténuation de maladies inflammatoires. Récemment, l’IL-37 a été identifié comme ligand d’un complexe formé de SIGIRR-IL-18Rα. SIGIRR et l’IL-37 pourraient alors être des acteurs de la dérégulation de l’inflammation retrouvée chez la MC. Nous les avons étudiés dans le contexte de la MC pédiatrique, afin d’y caractériser leurs effets. Nous avons identifié une diminution de l’expression de SIGIRR sur certains types de cellules immunitaires. De plus, les personnes atteintes de la MC ont des concentrations de protéines altérées, soit SIGIRR soluble, l’IL-37, l’IL-18BP, et l’IL-18, et tendent à revenir à la normale lorsque l’inflammation est contrôlée par médication. De plus, la concentration de l’IL-18 libre suit le même patron. Par analyse de régression linéaire de SIGIRR soluble et l’IL-37, de l’IL-18BP et l’IL-18, ainsi que l’IL-37 et l’IL-18, des tendances divergentes ont été identifiées entre les patients non traités aux contrôles et patients traités. Nos résultats suggèrent que le système IL-37-SIGIRR est compromis chez les patients de la MC. Étant donné que ce système est un facteur crucial dans la régulation négative de l’inflammation, il sera intéressant de déterminer si SIGIRR et l’IL-37 peuvent constituer des cibles thérapeutiques importantes dans l’atténuation et la résolution de l’inflammation chez les patients atteints de la MC., It is recognized that the Crohn's disease (CD) is the result of immunological, genetic and environmental factors. SIGIRR, an anti-inflammatory receptor, has never been studied in the context of the CD, and many discoveries about it led many to focus on its usefulness in mitigating inflammatory disease. Moreover, IL-37 has been recently identified as a ligand of SIGIRR-IL-18Rα complex. Thus, we supposed that SIGIRR and IL-37 might be inflammatory actors deregulated in CD. We have studied them in the context of pediatric CD, in order to characterize their effects. We have identified a decrease in the expression of SIGIRR on certain types of immune cells. In addition, our results showed that CD patients possess an altered protein expression of soluble SIGIRR, IL-37, IL-18BP and IL-18 which tends to return to normal when the inflammation is controlled by medication. In addition, the concentration of free IL-18 follows the same pattern. By linear regression analysis of soluble SIGIRR and IL-37, IL-18BP and IL-18 and IL-37 and IL-18, diverging trends were found between patients non-treated and controls or patients treated. Our results suggest that IL-37-SIGIRR system is compromised in patients with CD. Since this system is a crucial factor in the negative regulation of inflammation, it will be interesting to determine whether SIGIRR and IL-37 may be important therapeutic targets in the attenuation and resolution of inflammation in patients with CD.

Purpose: To characterize fast and slow diffusion components in diffusion-weighted magnetic resonance imaging (DW-MRI) of pediatric Crohn's disease (CD). Overall diffusivity reduction as measured by the apparent diffusion coefficient (ADC) in patients with CD has been previously demonstrated. However, the ADC reduction may be due to changes in either fast or slow diffusion components. In this study we distinguished between the fast and slow diffusion components in the DW-MRI signal decay of pediatric CD. Materials and Methods: We acquired MRI from 24 patients, including MR enterography (MRE) and DW-MRI with 8 b-values (0–800 s/mm2). We characterized fast and slow diffusivity by intravoxel incoherent motion (IVIM) model parameters (f, D*, D), and overall diffusivity by ADC values. We determined which model best described the DW-MRI signal decay. We assessed the influence of the IVIM model parameters on the ADC. We evaluated differences in model parameter values between the enhancing and nonenhancing groups. Results: The IVIM model described the observed data significantly better than the ADC model (P = 0.0088). The ADC was correlated with f (r = 0.67, P = 0.0003), but not with D (r = 0.39, P = 0.062) and D* (r = −0.39, P = 0.057). f values were significantly lower (P < 0.003) and D* values were significantly higher (P = 0.03) in the enhancing segments, while D values were not significantly different between the groups (P = 0.14). Conclusion: For this study population the IVIM model provides a better description of the DW-MRI signal decay than the ADC model. The reduced ADC is related to changes in the fast diffusion rather than to changes in the slow diffusion. J. Magn. Reson. Imaging 2013;37:156–163. © 2012 Wiley Periodicals, Inc.

This article reviews MR enterography (MRE), contrasts MRE to other available tests and provides recommendations for optimal use of MRE in the clinical management of Crohn’s disease. A review of Crohn’s disease and diagnostic approaches is introduced. MRE is described from a historical perspective, and a technical approach with key essential elements vital to optimal diagnostic yield is described. MRE is contrasted to disease activity index, capsule and optical endoscopy, small bowel follow-through or enteroclysis, and CT enterography. Key patterns of findings on MRE in correlation with pathological relationships are summarized. Recommendations for clinical use of MRE are then provided, including how to use MRE to direct therapeutic management.

Wstęp: Nieswoiste choroby zapalne jelit (inflammatory bowel diseases - IBD), zwłaszcza choroba Leśniowskiego-Crohna (Crohn’s disease - CD), są narastającym problemem w gastroenterologii pediatrycznej. Dostępne dane dotyczące klinicznych i demograficznych aspektów choroby w Polsce są ograniczone. Cel: Zebranie rzetelnych danych o klinicznych i demograficznych aspektach choroby Leśniowskiego-Crohna u dzieci w Polsce na podstawie utworzonego internetowo prospektywnego rejestru choroby mających pomóc w opracowaniu najbardziej optymalnych strategii terapeutycznych dla tej grupy pacjentów. Materiał i metody: We wrześniu 2005 roku został utworzony w Internecie ogólnopolski rejestr pacjentów z chorobą Leśniowskiego-Crohna. Do projektu włączono 10 jednostek szpitalnych (9 szpitali akademickich, 1 rejonowy szpital referencyjny). W celu zebrania danych demograficznych i klinicznych zastosowano dostępny internetowo kwestionariusz, który następnie przesyłano do centralnego rejestru do prospektywnej analizy. Ocenie poddano następujące dane: demografia, historia rodzinna, lokalizacja i postać choroby, objawy pozajelitowe, choroby współistniejące, diagnostyka oraz leczenie (włączając w to interwencje chirurgiczne). Wyniki: Przez 4 lata 320 pacjentów (płeć męska : płeć żeńska - 191 : 129) w wieku poniżej 16 lat ze zdiagnozowaną CD (średni wiek w momencie postawienia diagnozy: 9,2 ±6,8 roku) zostało zarejestrowanych w bazie danych. Tak zwany wczesny początek choroby (wiek przy rozpoznaniu poniżej 5 lat) stwierdzono u 68 dzieci (21,25%). Rodzinne występowanie (obciążony wywiad rodzinny) odnotowano u 16 pacjentów (5%). Główne miejsce zmian chorobowych (według Klasyfikacji montrealskiej: L1 - jelito cienkie, L2 - jelito grube, L3 - ileocolon, L4 - górny odcinek przewodu pokarmowego) stanowiła lokalizacja krętniczo-kątnicza (L3) - 217 (67,8,%). Postać niepenetrująca bez zwężeń była przeważającą postacią choroby - 225 (70,32%) pacjentów. Objawy pozajelitowe zaobserwowano u 20 chorych (6,25%). Wnioski: Badanie dostarcza pełnych informacji dotyczących aspektów demograficznych i klinicznych choroby Leśniowskiego-Crohna w Polsce. Uzyskane dane są zgodne z doniesieniami z innych krajów. Wnioski z badania są następujące: zbierane informacje muszą być dobrze zdefiniowane i określone już na samym początku badania, weryfikowane oraz aktualizowane systematycznie w trakcie jego trwania, aby usprawnić pracę i uzyskać jak najbardziej wiarygodne wyniki. Introduction: Inflammatory bowel disease, particularly Crohn’s disease (CD), is a rising problem in pediatric gastroenterology. Limited information is available on demographic and clinical aspects of pediatric CD in Poland. Aim: Preliminary data on demographic and clinical characteristic of pediatric CD in Poland based on the web-based prospective registry in order to gather reliable information to identify appropriate treatment strategies. Material and methods: In September 2005 a web-based prospective registry of CD patients was initiated in Poland. Ten institutes (9 academic centers, 1 referred regional hospital) took part in the project with the object of obtaining the demographic and clinical data of pediatric CD patients across the country. With this end in view, a computerized questionnaire was used and the collected data were sent prospectively to a central registry for analysis. The following data were analyzed: demographics, family history, location and behavior of disease, extraintestinal manifestation, coexisting diseases, diagnostic work-up, and medical treatment including surgical intervention. Results: Through the period of 4 years, 320 patients (male : female - 191 : 129) aged below 16 years with CD diagnosed at the mean age of 9.2 ±6.8 years were incorporated in the registry. Early onset of disease (age at diagnosis below 5 years) was recorded in 68 children (21.25%). Positive family history was reported for 16 patients (5%). The predominant localization of lesions described using the Montreal classification (L1 for small intestine, L2 for colon, L3 for ileocolon, and L4 for the upper gastrointestinal tract) was ileocolon (L3) - 217 patients (67.8%). The predominant behavior of disease was non-stricturing and non-penetrating - 225 patients (70.32%). Extraintestinal manifestation was reported in 20 patients (6.25%). Coexisting diseases occurred in 35 patients (10.93%). The predominant initial therapy was mesalazine (227 patients - 70.1%). Seventeen patients (5.31%) required a surgical intervention. Conclusions: This study provides comprehensive information on demographic and clinical aspects of pediatric CD in Poland. Our results are consistent with the previously published reports from other countries in terms of age of onset and male predominance in pediatric CD patients. Our conclusions are as follows: information needs to be well defined, validated at entry, and updated at every visit, which facilitates our work and makes the data more reliable.

Objective The increasing incidence of pediatric Crohn's disease (CD) is well known in Western countries in the last two decades. This study was conducted to delineate the trends of incidence during this period and clinical patterns of pediatric CD in Taiwan. Methods All children admitted to National Taiwan University Hospital between 1990 and 2009 who met the Porto Criteria for CD were included. Annual enrollment and clinical characteristics were retrospectively reviewed. The incidence was calculated by dividing the number of index cases by total hospitalized pediatric cases to minimize the bias caused by the growing number of hospitalized patients there. We quoted data and statistics from the Department of Health, Executive Yuan, Taiwan, and Accounting and Statistics, Executive Yuan, Taiwan, to present the social-economic changes in Taiwan in the recent decades. Results The cumulative hospital-based incidence of CD rose from 13.2 per 100,000 to 25.4 per 100,000 children admitted to this hospital in the past two decades. The median age of diagnosis in the first decade of this study was less than that of the second decade. The other study parameters, including gender, disease activity at diagnosis, duration from disease onset to diagnosis, anatomic location and disease behavior, and symptoms at diagnosis, were not different. Conclusions This study showed that the hospital-based incidence of pediatric CD has been increasing in Taiwan in recent decades. Factors contributing to such an increase could be physicians' awareness of the disease, easier access to health care, and environmental factors.

Background: Osteoprotegerin (OPG) may have proinflammatory roles in addition to its contribution to the maintenance of bone mass. Exclusive enteral nutrition (EEN) is an established therapy for the induction of remission in Crohn's disease (CD). The aims of this study were to ascertain serum, fecal, and mucosal expression of OPG in children with CD and to investigate the effects of EEN on OPG expression. Methods: OPG was measured by enzyme-linked immunosorbent assay in serum, mucosal, and fecal samples collected from children with CD and controls. Fecal and Serum OPG was measured prior to and following 6–8 weeks of EEN therapy. Results: Children with CD (n = 82) and controls (n = 45) were included. Mucosal and fecal OPG levels were elevated in CD compared to controls (P = 0.018 and P < 0.0001, respectively). Serum OPG was elevated in children with severe CD (P = 0.005). Serum and fecal OPG levels dropped significantly following EEN therapy (P = 0.0001 and P = 0.002, respectively). Conclusions: Increased serum and fecal OPG are seen in active CD and likely originate from the inflamed gut. Fecal and serum OPG decrease following EEN therapy. Further investigation of OPG and related proteins in the setting of IBD is now required. (Inflamm Bowel Dis 2011;)

Our data indicate that genetic influences due to stature-associated and possibly CD risk alleles may predispose CD patients to alterations in linear growth. This is the first report of a link between a stature-associated locus and growth impairment in CD.

The Pediatric Crohn's Disease Activity Index (PCDAI) is the outcome measure of choice in clinical trials of pediatric Crohn's disease. The aim of this study was to provide knowledge on its performance and accuracy of different cutoff scores.Longitudinal data prospectively generated from four sources were used, including the REACH and budesonide trials, a North-American inflammatory bowel diseases (IBD) registry, and a cohort aimed at evaluating growth. Cutoff values of disease activity were determined by physician global assessment from the pooled cohort using serial receiver operator characteristic curves and area under the curve (AUC) as well as comparing the overall accuracy. Test-retest reliability and responsiveness were ascertained by comparing the baseline and follow-up scores, using an external anchor.A total of 437 children were included (268 (61%) males, mean age 12.9+/-2.6 years). To define remission, a composite definition of10 points or7.5 points without the height item had the highest accuracy; this addressed the limitation that height is not a responsive item. The best cutoff of 10-27.5 was determined for mild disease, 30-37.5 for moderate disease, 40-100 for severe disease, and a change of12.5 points for response (AUC 0.8-0.9; P0.001). Ninety children whose disease remained unchanged showed fair test-retest reliability (intraclass correlation coefficient=0.74-0.8; P0.001). The PCDAI showed good responsiveness, as reflected from the correlational (r=0.7; P0.001), distributional (Guyatt's responsiveness statistics=0.9), and diagnostic utility analysis (AUC 0.85 (95% confidence interval 0.81-0.88).The clinimetric properties of the PCDAI are sufficient to support its use in clinical research. Cutoff values suggested by this study differ slightly from those previously published on much smaller cohorts.

Crohn's disease is characterized by chronic inflammation involving any portion of the gastrointestinal tract. Treating Crohn's disease is a major challenge for clinicians, as no curative therapy currently exists. Pediatric Crohn's disease is characterized by frequent relapses, a wide extent of disease, a high prevalence of extraintestinal manifestations, and a severe clinical course. The classic therapeutic approach is known as the 'step-up' strategy, and follows a progressive course of treatment intensification as disease severity increases. Although this approach is usually effective for symptom control, many patients become either resistant to or dependent on corticosteroids. The efficacy of infliximab suggests that, rather than a progressive course of treatment, early intense induction may reduce complications associated with conventional treatment and improve quality of life. Intensive early therapy with infliximab is known as the 'top-down' strategy. Such therapy offers the potential for altering the natural history of Crohn's disease, and is changing treatment paradigms. However, the relatively new concept of an early aggressive or 'top-down' treatment approach is not yet widely accepted, especially in pediatric patients. The results of our current study demonstrate that early and intensive treatment of pediatric Crohn's disease patients with infliximab, at initial diagnosis, was more effective for maintaining remission and reducing flares.

Crohn’s disease is a chronic inflammatory disorder of the GI tract that often presents during childhood and adolescence. Children with Crohn’s disease are often subjected to repeated radiologic examinations throughout the course of their illness, thereby raising great concern over the potential harm of cumulative radiation exposure. Magnetic resonance enterography is a new modality that provides detailed images of the GI tract without exposure to ionizing radiation. This article reviews past methods of bowel imaging, the scope of the problem with regard to radiation exposure, as well as the technical aspects, indications, and current evidence for magnetic resonance enterography in children with Crohn’s disease. Various examples of inflammatory, stricturing and penetrating disease activity are provided.

Background: Improving granulocyte function may represent an effective therapy for Crohn's disease (CD). We performed a Phase I-2 trial of sargramostim (SRG) in children with CD. Methods: This was multicenter, open-label study in 6–16-year-old patients with moderate to severely active CD. Patients received either 4 or 6 μg/kg SRG subcutaneously daily for 8 weeks, with and without concomitant corticosteroids (CS). The primary endpoint was identification of a safe and tolerable dose in children. The secondary endpoint was establishment of the pharmacokinetics (PK). Efficacy, a tertiary endpoint, was measured by the Pediatric CD Activity Index (PCDAI). Response was defined as a decrease from baseline of ≥12.5 points and remission as absolute PCDAI of ≤10. Results: In all, 22 patients were enrolled: 12 and 10 received 4 and 6 mg/kg, respectively; 19 completed the course. Both doses were found to be safe and well tolerated. Mild injection-site reactions occurred in 90% of patients. Three patients required dose reductions due to elevated absolute neutrophil counts. Following 4 μg/kg the mean area under the curve (AUC) was 2.64 and 2.80 ngh/mL for the 6–11- and 12–16-year-old groups, respectively. The mean half-life (t1/2) was 1.22 and 1.59 hours, respectively. Following 6 μg/kg, the mean AUC was 5.01 ngh/mL for the 12–16-year-old group, a 1.8-fold increase. A total of 16/18 patients (88%) achieved remission or response. Conclusions: Sargramostim at both 4 and 6 mg/kg was well tolerated. PK analysis suggested dose proportionality unaffected by CS exposure. Remission and response data are encouraging, but further trials are needed to assess efficacy. (Inflamm Bowel Dis 2010)

Kalyan Ray Parashette1, Raghavendra Charan Makam2, Carmen Cuffari31Department of Pediatrics, University of Illinois at Chicago, Chicago, IL, USA; 2Department of Internal Medicine, Berkshire Medical Center, Pittsfield, MA, USA; 3Division of Pediatric Gastroenterology, The Johns Hopkins Children’s Center, Baltimore, MD, USAAbstract: Anti-tumor necrosis factor alpha (TNF-α) therapy has re-defined our treatment paradigms in managing patients with Crohn’s disease (CD) and ulcerative colitis. Although the ACCENT studies showed proven efficacy in the induction and maintenance of disease remission in adult patients with moderate to severe CD, the pediatric experience was instrumental in bringing forth the notion of “top-down” therapy to improve overall clinical response while reducing the risk of complications resulting from long-standing active disease. Infliximab has proven efficacy in the induction and maintenance of disease remission in children and adolescents with CD. In an open-labeled study of 112 pediatric patients with moderate to severe CD, 58% achieved clinical remission on induction of infliximab (5 mg/kg) therapy. Among those patients who achieved disease remission, 56% maintained disease remission on maintenance (5 mg/kg every 8 weeks) therapy. Longitudinal follow-up studies have also shown that responsiveness to infliximab therapy also correlates well with reduced rates of hospitalization, and surgery for complication of long-standing active disease, including stricture and fistulae formation. Moreover, these children have also been shown to improve overall growth while maintaining an effective disease remission. The pediatric experience has been instructive in suggesting that the early introduction of anti-TNF-α therapy may perhaps alter the natural history of CD in children, an observation that has stimulated a great deal of interest among gastroenterologists who care for adult patients with CD.Keywords: Crohn’s disease, infliximab, pediatric

Infliximab, a murine monoclonal antibody directed against TNF-α, has been approved for the induction and maintenance of remission in moderate-to-severe pediatric Crohn’s disease that is unresponsive to conventional therapy. Infliximab is administered intravenously and can be infused over 2–3 h. The recommended induction dosing schedule consists of a series of three 5 mg/kg doses of infliximab delivered at weeks 0, 2 and 6. Regularly scheduled maintenance therapy is recommended to be given every 8 weeks. While initially it was believed that the administration of concomitant immunomodulators would significantly enhance the clinical efficacy of infliximab, recent data and safety concerns have called the benefit of such a strategy into question. Currently, clinical research on the use of infliximab in pediatric Crohn’s disease has focused on the unmet need of being able to identify which patients could benefit most from infliximab therapy.

Improvements in insulin resistance after anti-TNF-alpha therapy have been reported in inflammatory conditions, although no changes were noted in adult patients with Crohn's disease. There is no information concerning insulin resistance and substrate metabolism in children with Crohn's disease after anti-TNF-alpha therapy. Our aim was to describe changes in carbohydrate and lipid metabolism in children with active Crohn's disease after their initial dose of infliximab. Children with active Crohn's disease underwent measurement of plasma insulin and glucose just before and 2 wk after their initial infusion of infliximab, an anti-TNF-alpha antibody. In addition, resting energy expenditure, with determination of both carbohydrate and lipid oxidation rates, was determined. Measurements were conducted in both fasting and parenterally fed states. Despite no changes in resting energy expenditure, a significant reduction (p0.05) in RQ (5%) and carbohydrate oxidation rate (24%), with a corresponding increase in lipid oxidation rate (42%) was found during parenteral nutrition infusion. No differences in plasma insulin, glucose, and insulin resistance were noted when comparing pre- and postinfliximab measurements.

The relationship between the age at diagnosis and disease course is poorly defined in children with Crohn's disease (CD). We examined the presentation and course of disease in patients 0-5 compared to 6-17 yr of age at diagnosis.We analyzed uniform data from 989 consecutive CD patients collected between January 2000 and November 2003, and stored in the Pediatric IBD Consortium Registry. The statistical tests account for the length of follow-up of each patient.In total, 98 patients (9.9%) were of 0-5 yr of age at diagnosis. The mean follow-up time was 5.6 +/- 5.0 yr in the younger group and 3.3 +/- 2.8 yr in the older group (P0.001). Race/ethnicity differed by the age group (P= 0.015); a larger proportion of the younger group was Asian/Pacific Islander or Hispanic, and a larger proportion of the older group was African American. The initial classification as ulcerative colitis or indeterminate colitis was more common among the 0-5 yr of age group (P0.001). The 6-17 yr of age patients presented with more abdominal pain (P0.001), weight loss (P= 0.001), or fever (P= 0.07), while the 0-5 yr of age patients presented with more rectal bleeding (P= 0.008). The 6-17 yr of age patients were more likely to be treated with antibiotics (P0.001), 6-mercaptopurine/azathioprine (P0.001), infliximab (P= 0.001), or corticosteroids (P= 0.0006). The 6-17 yr of age patients had a higher cumulative incidence of treatment with 5-aminosalicylates (P= 0.009) or methotrexate (P= 0.04). The risk for developing an abscess (P= 0.001), a fistula (P= 0.02), a stricture (P= 0.05), or a perianal fissure (P= 0.06) was greater in the 6-17 yr of age patients.The 6-17 yr of age patients with CD appear to have a more complicated disease course compared to 0-5 yr of age children. The 0-5 yr of age group may represent a unique disease phenotype and benefit from different approaches to management. Long-term prospective studies are required to validate these findings.

Crohn’s disease affects more than 500000 individuals in the United States, and about 25% of cases are diagnosed during the pediatric period. Imaging of the bowel has undergone dramatic changes in the past two decades. The endoscopy with biopsy is generally considered the diagnostic reference standard, this combination can evaluates only the mucosa, not inflammation or fibrosis in the mucosa. Actually, the only modalities that can visualize submucosal tissues throughout the small bowel are the computed tomography (CT) enterography (CTE) with the magnetic resonance enterography (MRE). CT generally is highly utilized, but there is growing concern over ionizing radiation and cancer risk; it is a very important aspect to keep in consideration in pediatric patients. In contrast to CTE, MRE does not subject patients to ionizing radiation and can be used to detect detailed morphologic information and functional data of bowel disease, to monitor the effects of medical therapy more accurately, to detect residual active disease even in patients showing apparent clinical resolution and to guide treatment more accurately.

BACKGROUND Pediatric Crohn's disease (CD) is a lifelong, debilitating, and costly disease. In previous studies, CD incidence increased with higher geographic latitude in the Northern Hemisphere. This may indicate a role for lower vitamin D status as a risk factor for CD. Analysis of worldwide incidence of pediatric CD has not been previously reported. METHODS We undertook a systematic review of population-based studies reporting incidence of pediatric CD and published between 2003 and 2013. Included studies had well-defined diagnostic criteria for CD, evidence of high case ascertainment, reported incidence according to age group, and provided a specific location. Average daily ambient ultraviolet radiation (UVR) for each location was derived from satellite data. Negative binomial regression was used to assess the association between pediatric CD incidence and latitude and ambient UVR, adjusting for the study year. RESULTS Twenty-eight articles provided 39 incidence data points. Incidence of pediatric CD increased with higher latitude, and in association with a greater number of months where the average daily UVR was lower than a previously published threshold of 1.488 kJ/m. Incidence of pediatric CD increased over calendar time. CONCLUSIONS After applying rigorous quality assessment criteria, and including only population-based studies, there was a modest increase in incidence of pediatric CD with higher latitude and greater number of months with low ambient UVR. Reporting using nonconsistent diagnostic criteria and age groups, with poorly defined geographic locations, makes it difficult to compare data across different studies.

Inflammatory bowel diseases are characterized by a chronic relapsing course, high morbidity and impaired quality of life. Their incidence is rising, and about 25% of cases are diagnosed in pediatric age. Anti-TNF-alpha antibodies, such as infliximab and adalimumab (ADA), are usually administered in patients refractory to conventional therapies. However, increasing evidence suggests that they can be introduced earlier in the course of the disease, especially in patients with aggressive and extensive disease since diagnosis. ADA is a fully human anti-TNF-alpha antibody recently approved for pediatric Crohn's disease not only in patients unresponsive to infliximab, but also as a first-line anti-TNF-alpha therapy. In this review, we aim to summarize the current knowledge on the use of ADA in pediatric Crohn's disease and to discuss open issues regarding safety as well as future perspectives.

Delayed growth is common in pediatric Crohn's disease (CD). Multiple factors have been shown to affect growth in this situation, the most prominent being the presence and severity of inflammation and inadequate nutritional intake. Inflammation, anorexia, and weight loss are all manifestations of circulating TNF-alpha, which is elevated in CD. The ability to secrete TNF-alpha may be affected by polymorphisms in the TNF-alpha promoter. The aim of our study was to determine whether growth retardation and disease severity in pediatric onset CD are affected by TNF promoter genotype.Genotyping for TNF-alpha and NOD2/CARD15 single nucleotide polymorphisms was performed in 87 patients with detailed growth records. Parameters including disease location and disease severity were recorded, and the effect of these polymorphisms on Z-scores for height and weight at disease onset and during follow-up were analyzed.Lower age of onset was linked to more height retardation, while the presence of colonic disease and the absence of ileal disease were more likely to predict the absence of growth retardation. The presence of two polymorphisms thought to decrease circulating TNF-alpha was associated with higher mean Z-scores for height and a trend toward less growth retardation. Two other polymorphisms were modestly associated with disease severity.Polymorphisms in the TNF-alpha promoter may independently modulate growth and disease severity in pediatric onset CD. The effect of these polymorphisms does not appear to be mediated via weight loss, and is relatively modest.