Fecal microbial transplant for the treatment of pediatric inflammatory bowel disease

The role of fecal microbial transplant(FMT) in the treatment of pediatric gastrointestinal disease has become increasingly popular among pediatric practitioners, patients, and parents. The success of FMT for the treatment of recurrent Clostridium difficile infection(RCDI) has bolstered interest in its potential application to other disease states, such as inflammatory bowel disease(IBD). FMT has particular interest in pediatrics, given the concerns of patients and parents about rates of adverse events with existing therapeutic options, and the greater cumulative medication burden associated with childhoodonset disease. Published literature on the use of FMT in pediatrics is sparse. Only 45 pediatric patients treated for RCDI have been reported, and only 27 pediatric patients with pediatric IBD. The pediatric microbiome may uniquely respond to microbial-based therapies. This review will provide a comprehensive overview of fecal microbial transplant and its potential role in the treatment of pediatric inflammatory bowel disease. We will discuss the microbiome in pediatric inflammatory bowel disease, existing adult and pediatric literature on the use of FMT in IBD treatment, and pediatric FMT trials that are currently recruiting patients. This review will also discuss features of the microbiome that may be associated with host response in fecal transplant, and potential challenges and opportunities for the future of FMT in pediatric IBD treatment.     

Special issues in pediatric inflammatory bowel disease

The incidence of pediatric inflammatory bowel disease （IBD） is rising and recent advances in diagnostics and therapeutics have improved the care provided to these children. There are distinguishing features worth noting between early onset and adult onset IBD. Physical and psychosocial development remains a critical target for the comprehensive management of pediatric IBD. Children are not just little adults and consideration must be given to the stages of development and how these stages impact disease presentation and management. The final stage will be the transition from pediatric care to that of adult oriented care and special consideration must be given to make this a successful process. This review highlights special considerations in the management of the child with IBD.     

Magnetic resonance imaging of the perineum in pediatric patients with inflammatory bowel disease

Magnetic resonance imaging (MRI) has profoundly changed and improved the investigation of abdominal and pelvic inflammatory bowel disease (IBD) in pediatrics. Using an imaging modality without ionizing radiation is of particular advantage because the pediatric IBD population is young and often requires repeat evaluation. MRI of the pelvis has become the imaging gold standard for detecting and monitoring perianal disease while bowel-directed imaging techniques (eg, enterography, enteroclysis and colonography) can accurately evaluate bowel inflammation in IBD. With recent technological innovations leading to faster and higher resolution, the role of MRI in IBD will likely continue to expand. The present article focuses on MRI of the perineum in pediatric IBD.     

Pediatric inflammatory bowel disease: clinical and molecular genetics

Pediatric-onset inflammatory bowel disease (IBD) is characterized by distinct phenotypic differences compared to adult-onset IBD. This raises the question whether early (pediatric) onset IBD represents the same disease process occurring in adults but merely at an earlier age or does IBD in children have a very different etiology and pathogenesis but with the same clinical presentation as adults. The use of techniques such as whole genome association studies to perform broad, unbiased screening for the contributions of common genetic variations to complex disease has rapidly assisted in the identification of several novel susceptibility loci associated with pediatric-onset Crohn's disease such as IL23R and ATG16L1. These genes join the already confirmed IBD susceptibility genes such as NOD2/CARD15, IBD5, and DLG5. Therefore, there is hope that advances in the field of clinical and molecular genetics will assist in answering the fundamental question of whether pediatric IBD has a different etiology and pathogenesis compared to adult IBD. This review examines the current status of clinical and molecular genetics of pediatric IBD, and highlights the differences between pediatric and adult IBD in disease phenotypes and genotypes. Finally, the future directions of genetic investigations in pediatric IBD are discussed.     

Nephrolithiasis as an extra-intestinal presentation of pediatric inflammatory bowel disease unclassified

Urolithiasis is quite rare in pediatric inflammatory bowel disease (IBD) compared with the incidence at 9–18% in adult cases. The diagnosis and treatment of pediatric IBD is challenging. Indeterminate colitis (IC), originally proposed as a subgroup of fulminant IBD, has also been used for patients when the diagnosis of either UC or CD cannot be made with certainty. Such patients should be diagnosed as having “IBD unclassified” based on evidence including mucosal biopsy samples. We report herewith a 9-year-old boy with isolated colitis that reached a diagnosis of IBD unclassified. Infliximab therapy led to a successful remission after the refractory course. However, urolithiases were impacted in the urethral valves and vesico-ureteral junction. Microhematuria was noticed from the onset of colitis. Renal calculi were detected on the X-ray films during the first line treatment. Transurethrally crushed stones consisted of calcium oxalate. Renal calculi are more closely associated with CD than ulcerative colitis in adult patients for the ileal involvement. The oxalate stones and treatment response indicated a CD-like pathophysiology. Nephrolithiasis might be a rare but noticeable extra-intestinal presentation of pediatric IBD. Infliximab therapy could be an option in pediatric refractory colitis to change the critical steroid dependency.     

Inflammatory bowel disease in pediatric and adolescent patients:A biomolecular and histopathological review

Crohn’s disease(CD)and ulcerative colitis(UC)are the two main forms of inflammatory bowel disease(IBD)with both overlapping and distinct clinical,pathological and biomolecular features.It has been suggested that pediatric IBD is a distinct disease entity,with probably different disease subtypes.The aim of this study is to review and summarize the evolution of the current concept of pediatric IBD.The results of this review reinforce the idea that pediatric CD and UC may be further classified in various clinicopathologic entities.For clinicians and pathologists convenience,practical algorithms for the distinction of the various subphenotypes of pediatric IBD are also provided.     

Transitioning the adolescent inflammatory bowel disease patient: guidelines for the adult and pediatric gastroenterologist

Twenty percent of inflammatory bowel disease (IBD) patients present in the pediatric years, with recent reports suggesting a rising incidence in the pediatric age group. This highlights the need for both pediatric and adult gastroenterologists to better understand issues related to the process of transition from pediatric to adult care. Research from other disciplines outside of IBD provide evidence that the transition period can be associated with poorer health outcomes and that a structured transition program may improve patient compliance and disease control. Recent data from the IBD literature support a need for transition clinics. The ideal model of a transition program has not been established. Controlled trials are not available to measure the impact of a structured transition program on clinically relevant endpoints such as disease control and hospital admissions. As local resources and availability of staffing and funding are highly variable, we have summarized some practical guidelines for the adult and pediatric gastroenterologist that can be used as an aid to help adolescents through the transition process even without the support of an established transition clinic.     

Transition of pediatric to adult care in inflammatory bowel disease: Is it as easy as 1, 2, 3?

Inflammatory bowel disease(IBD)is a heterogeneous group of chronic diseases with a rising prevalence in the pediatric population,and up to 25%of IBD patients are diagnosed before 18 years of age.Adolescents with IBD tend to have more severe and extensive disease and eventually require graduation from pediatric care toadult services.The transition of patients from pediatric to adult gastroenterologists requires careful preparation and coordination,with involvement of all key players to ensure proper collaboration of care and avoid interruption in care.This can be challenging and associated with gaps in delivery of care.The pediatric and adult health paradigms have inherent differences between health care models,as well as health care priorities in IBD.The readiness of the young adult also influences this transition of care,with often times other overlaps in life events,such as school,financial independence and moving away from home.These patients are therefore at higher risk for poorer clinical disease outcomes.The aim of this paper is to review concepts pertinent to transition of care of young adults with IBD to adult care,and provides resources appropriate for an IBD pediatric to adult transition of care model.     

Antitumor necrosis factor treatment for pediatric inflammatory bowel disease

Infliximab, adalimumab, and certolizumab are monoclonal antibodies against tumor necrosis factor-α (TNFα), a proinflammatory cytokine with an increased expression in the inflamed tissues of inflammatory bowel disease (IBD) patients. Currently, infliximab is the only anti-TNF drug that has been approved for use in refractory pediatric Crohn's disease (CD). Nevertheless, adalimumab and certolizumab have been used off-label to treat refractory pediatric IBD. Over the past 10 years, anti-TNF treatment has been of great benefit to many pediatric IBD patients, but their use is not without risks (infections, autoimmune diseases, malignancies). Despite the growing experience with these drugs in children with IBD, optimal treatment strategies still need to be determined. The purpose of this review is to summarize the current knowledge on the use of anti-TNF drugs in pediatric IBD and to discuss the yet-unsolved issues.     

Characteristics of Pediatric Inflammatory Bowel Disease in Korea: Comparison with EUROKIDS Data

Background/Aims

Pediatric inflammatory bowel disease (IBD) has been increasing worldwide. The characteristics of pediatric-onset IBD have mainly been reported in Western countries. We investigated the clinical characteristics of pediatric IBD in Korea and compared these with the data from the 5-year European multicenter study of children with new-onset IBD (EUROKIDS registry).

Methods

Children who were diagnosed with IBD between July 1987 and January 2012 were investigated at five Korean university hospitals. Their clinical characteristics were retrospectively evaluated by medical record review. The results were compared with the EUROKIDS data.

Results

A total of 30 children with Crohn’s disease (CD) and 33 children with ulcerative colitis (UC) were enrolled. In comparison with the EUROKIDS group, Korean pediatric IBD patients showed a male predominance (86.7% vs 59.2%, p=0.002 in CD; 75.8% vs 50%, p=0.003 in UC). Korean pediatric CD patients had a higher prevalence of terminal ileal disease (36.7% vs 16.3%, p=0.004) and perianal disease (33.3% vs 8.2%, p<0.001) than patients in the EUROKIDS group. Korean pediatric UC patients had a higher prevalence of proctitis than patients in the EUROKIDS group.

Conclusions

Our results suggest that the characteristics of Korean pediatric IBD patients and European pediatric IBD patients may be different.     

Recent advances in the diagnosis and treatment of pediatric inflammatory bowel disease

The diagnosis and management of inflammatory bowel disease (IBD) in children and adolescents is a challenge to patients, their families, and to the healthcare team. This review highlights recent advances in the epidemiology, diagnosis, and management of pediatric IBD. Among the most prominent advances are the new diagnostic serologic assays that can help screen for IBD in the absence of physical signs of disease and help discriminate between ulcerative and Crohn's colitis. Other tests have been identified as potential noninvasive markers of disease activity, including color Doppler abdominal ultrasound and sugar permeability tests. Recent advances in pharmacogenetics afford clinicians the ability to optimize and individualize therapy using azathioprine or 6-mercaptopurine. Finally, bone health has come forth as a major issue in the complete management of pediatric IBD.     

Lamina propria and circulating interleukin-6 in newly diagnosed pediatric inflammatory bowel disease patients

OBJECTIVES: Understanding cytokine production patterns in early mucosal lesions of pediatric patients newly diagnosed with inflammatory bowel disease (IBD) may be critical to understanding IBD pathogenesis. Interleukin-6 (IL-6) has a central role in a multitude of immune system reactions; however, inconsistent lamina propria and serum IL-6 has been reported in IBD patients. Newly diagnosed pediatric IBD patients have not previously been evaluated for lamina propria or serum IL-6. METHODS: Serum and intestinal lamina propria biopsy whole organ culture supernatants were evaluated by ELISA for IL-6 obtained from newly diagnosed IBD patients, before initiation of immunomodulatory therapies. RESULTS: Levels of lamina propria IL-6 demonstrated significant correlation with graded severity of histological inflammation (p < 0.001). Log-transformed serum and organ culture IL-6 levels demonstrated significant correlation (p < 0.0001, R2 = 0.6226). Assigning a demarcation level of >400 pg/ml, serum IL-6 concentrations were a superior marker for the presence of microscopic intestinal inflammation than erythrocyte sedimentation rate (ESR), with a sensitivity of 82%, specificity of 100%, positive predictive value of 100%, and negative predictive value of 82%. When evaluating subtypes of IBD, serum IL-6 levels were correlated more significantly with active disease in ulcerative colitis patients (p = 0.01, R2 = 0.74) than in Crohn's disease patients (p = 0.21, R2 = 0.33). CONCLUSIONS: This study outlines graded production of IL-6 in intestinal lamina propria and serum of newly diagnosed pediatric IBD patients, confirming the presence of IL-6 in early IBD patients. In addition, serum IL-6 may be a good predictor of IBD in pediatric patients with suspected or newly diagnosed IBD.     

Inflammatory bowel disease in the South Asian pediatric population of British Columbia

BACKGROUND: Geographical differences, population migration, and changing demographics suggest an environmental role in prevalence, modulation, and phenotypic expression of inflammatory bowel disease (IBD). AIM: To determine the incidence of IBD and disease subtype in the pediatric South Asian population in British Columbia (BC) compared with non-South Asian IBD patients in the same geographic area. METHODS: Chart review with data collected for all patients 相似文献   

Current perspectives on pediatric inflammatory bowel disease focusing on transitional care management. What should we consider?

The prevalence of inflammatory bowel disease (IBD) continues to rise around the globe. Although the percentage of pediatric IBD patients seems to be increasing, rates are surprisingly heterogeneous among different populations. Although the pathogenesis of IBD is believed to be multifactorial, a genetic predisposition may be especially relevant in pediatric-onset IBD. Phenotypic characteristics can also be significantly different when comparing pediatric and adult-onset IBD. Patients that develop the disease at a younger age usually present with more extensive and more aggressive disease and develop complications faster when compared to those that develop it during adulthood. Children with IBD are found to have frequent mood disorders and have a higher risk of developing socio-economic hardship, failing to meet development milestones. Therefore, IBD management should always involve a multidisciplinary team that is not limited to medical providers. Most institutions do not have an established transition protocol and lack the resources and training for transition care. Although there is no consensus on an optimal timing to transition the patient's care to an adult team, it is usually accepted they should be eligible for adult care when most of the key transition points have been met. Management strategies should be tailored to each patient's developmental level and environment. A successful transition can improve the long-term outcomes such as sustained remission, medication adherence, mental health and social and academic performance, while decreasing healthcare utilization. Every institution that manages pediatric IBD patients should have a well-established transition protocol in order to make sure to maintain continuity of care.     

Differences between adults and children: genetics and beyond

Clinical observations and epidemiological studies have highlighted some important differences in disease course and phenotypes between pediatric inflammatory bowel disease (IBD) and adult-onset IBD. Also from a therapeutic angle, the approach to young-onset IBD is different with a more rapid introduction of azathioprine and a high threshold for long and systemic steroid use, which may affect bone mineral density and growth. The observed clinical differences have been an area of scientific research and genetic studies have been the focus of attention. Specific candidate gene studies as well as genome-wide association studies have been performed in pediatric IBD. With the exception of very early-onset IBD occurring before the age of 2 years; no overt differences in genetic susceptibility have been identified. In contrast, very early-onset IBD seems in particular to be a genetic disease with defects in the IL10 signaling pathway being the principal example. This review aims to answer some straightforward questions arising in this topic by giving concise information.     

Inflammatory bowel disease in pediatric and adolescent patients.

IBD is a chronic pediatric disease that needs to be treated by a team of experts consisting of pediatricians, pediatric gastroenterologists, psychologists, nutritionists, social workers, and nurses. A critical factor in successful management of this disease is the willingness of the patient to participate and cooperate with the team. Parents and patients must be educated and supported to treat these disorders effectively. Much further research is necessary to understand the specific causative and therapeutic issues unique to young patients with IBD.     

Soluble urokinase plasminogen activator receptor suPAR as a marker for inflammation in pediatric inflammatory bowel disease

Abstract Objective. In inflammatory bowel disease (IBD), more means to monitor early therapeutic response are needed. In pediatric IBD, blood inflammatory markers erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP) may be low in 10 to 20% of patients with severe disease. Recently, soluble urokinase plasminogen activator receptor (suPAR) was described as a potential blood inflammatory marker in adult IBD. Methods. We tested the performance of suPAR by the start of therapy with glucocorticoids (n = 19) or TNF-α-antagonist (n = 16) in pediatric IBD (Crohn's disease n = 19, ulcerative colitis (UC) n = 16). Results. The levels of suPAR were low in both patient groups studied. There was no difference in the values regarding the presence of Crohn's disease or ulcerative colitis. Thus, all analyses were performed on the entire sample set. Glucocorticoid therapy, however, resulted in a significant decline in suPAR levels from a median of 3.06 to 2.54 ng/ml (p < 0.01). In contrast, TNF-α-antagonist had no effect. The suPAR levels did not associate with ESR or CRP or fecal calprotectin (FC). Conclusions. In pediatric IBD, the suPAR levels in blood are low and do not reflect the level of intestinal inflammation assessed with FC. The introduction of corticoids, however, results in a decline of suPAR levels in blood but not reflect therapeutic response to TNF-α-antagonist. Thus, suPAR is of limited value in assessing systemic inflammatory responses in pediatric IBD.     

Is pediatric IBD treatment different than in adults?

The incidence of pediatric inflammatory bowel disease (IBD) continues to rise in most countries. Approximately 20-25% of IBD patients present before the age of 20, and their management is associated with many unique challenges. These challenges stem both from the inherent differences between children and adults, and from the differences in the nature and course of the disease. Children with IBD are more likely than adults to present with extensive disease ? both in Crohn's disease (CD) and ulcerative colitis (UC). Diagnosis requires a high index of suspicion, as children may present with less typical signs such as poor growth and delayed puberty. In the very young patients with inflammatory bowel disease, the pediatric clinician must consider a broader range of immunological and allergic disorders. Optimal management requires recognition of pediatric patterns of presentation, efficacy and adverse-effect profiles, and understanding monitoring aspects unique to pediatrics. These aspects include pediatric disease-related psychological issues, adherence to therapy and transition to adult care. Inadequate attention to growth, puberty or bone health in childhood can result in long-term consequences, such as impaired adult height and increased risk of fractures. Management of pediatric IBD and prevention of adverse long-term consequences relies on a variety of therapies well-known to the adult practitioner, along with therapies that are not widespread in adults, most notably exclusive enteral nutrition (EEN). The latter is as effective as corticosteroids in achieving clinical remission in children, while achieving better results than corticosteroids with regard to mucosal healing and growth. This review discusses the broad variety of issues that form the basis for management of pediatric IBD.     

Coping is excellent in Swiss Children with inflammatory bowel disease: Results from the Swiss IBD cohort study

BackgroundInflammatory bowel disease (IBD) starting during childhood has been assumed to impair quality of life (QoL) of affected children. As this aspect is crucial for further personality development, the health-related quality of life (HRQOL) was assessed in a Swiss nationwide cohort to obtain detailed information on the fields of impairment.MethodsData were prospectively acquired from pediatric patients included in the Swiss IBD Cohort Study. IBD activity was evaluated by PCDAI and PUCAI. The age adapted KIDSCREEN questionnaire was evaluated for 110 children with IBD (64 with Crohn's disease 46 with ulcerative colitis). Data were analyzed with respect to established reference values of healthy controls.ResultsIn the KIDSCREEN index a moderate impairment was only found for physical wellbeing due to disease activity. In contrast, mental well-being and social support were even better as compared to control values. A subgroup analysis revealed that this observation was restricted to the children in the German speaking part of Switzerland, whereas there was no difference compared to controls in the French part of Switzerland. Furthermore, autonomy and school variables were significantly higher in the IBD patients as compared to controls.ConclusionsThe social support for children with IBD is excellent in this cohort. Only physical well-being was impaired due to disease activity, whereas all other KIDSCREEN parameters were better as compared to controls. This indicates that effective coping and support strategies may be able to compensate the burden of disease in pediatric IBD patients.     

Characteristics and Trends in the Incidence of Inflammatory Bowel Disease in Korean Children: A Single-Center Experience

Background  

Inflammatory bowel disease (IBD) is rare in Asian children and few reports on pediatric IBD have appeared.