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Inflammatory bowel diseases (IBD), including Crohn's disease (CD) and ulcerative colitis, are chronic relapsing and remitting diseases of the bowel, with an unknown etiology and appear to involve interaction between genetic susceptibility, environmental factors and the immune system. Although our knowledge and understanding of the pathogenesis and causes of IBD have improved significantly, the incidence in the pediatric population is still rising. In the last decade more drugs and treatment option have become available including 5-aminosalicylate, antibiotics, corticosteroids, immunomodulators and biological agents. Before the use of anti-tumor necrosis factor (TNF)-α became available to patients with IBD, the risk for surgery within five years of diagnosis was very high, however, with anti-TNF-α treatment the risk of surgery has decreased significantly. In the pediatric population a remission in disease can be achieved by exclusive enteral nutrition. Exclusive enteral nutrition also has an important role in the improvement of nutritional status and maintained growth. In this review we summarize the current therapeutic treatments in CD. The progress in the treatment options and the development of new drugs has led to optimized tactics for achieving the primary clinical goals of therapy - induction and maintenance of remission while improving the patient's growth and overall well-being.

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-α 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-α antibody recently approved for pediatric Crohn's disease not only in patients unresponsive to infliximab, but also as a first-line anti-TNF-α 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.

Nutritional concerns, linear growth deficiency, and delayed puberty are currently detected in up to 85% of patients with Crohn's disease (CD) diagnosed at childhood. To provide advice on how to assess and manage nutritional concerns in these patients, a Medline search was conducted using "pediatric inflammatory bowel disease", "pediatric Crohn's disease", "linear growth", "pubertal growth", "bone health", and "vitamin D" as key words. Clinical trials, systematic reviews, and meta-analyses published between 2008 and 2013 were selected to produce this narrative review. Studies referring to earlier periods were also considered if the data was relevant to our review. Although current treatment strategies for CD that include anti-tumor necrosis factor-α therapy have been shown to improve patients' growth rate, linear growth deficiencies are still common. In pediatric CD patients, prolonged diagnostic delay, high initial activity index, and stricturing/penetrating type of behavior may cause growth deficiencies (in weight and height) and delayed puberty, with several studies reporting that these patients may not reach an optimal bone mass. Glucocorticoids and inflammation inhibit bone formation, though their impact on skeletal modeling remains unclear. Long-term control of active inflammation and an adequate intake of nutrients are both fundamental in promoting normal puberty. Recent evidence suggests that recombinant growth factor therapy is effective in improving short-term linear growth in selected patients, but is of limited benefit for ameliorating mucosal disease and reducing clinical disease activity. The authors conclude that an intense initial treatment (taking a "top-down" approach, with the early introduction of immunomodulatory treatment) may be justified to induce and maintain remission so that the growth of children with CD can catch up, ideally before puberty. Exclusive enteral nutrition has a key role in inducing remission and improving patients' nutritional status.

Background & Aims: We examined the incidence of Crohn''s disease (CD)-related surgery in a multi-center, inception cohort of pediatric patients with CD. We also examined the effect of starting immunomodulator therapy within 30 days of diagnosis. Methods: Data from 854 children with CD from the Pediatric Inflammatory Bowel Disease Collaborative Research Group who were diagnosed with CD between 2002 and 2008 were analyzed. Results: Overall, 76 (9%) underwent a first CD-related surgery, 57 (7%) underwent a first bowel surgery (bowel resection, ostomy, strictureplasty, or appendectomy), and 19 (2%) underwent a first non-bowel surgery (abscess drainage or fistulotomy). The cumulative risks for bowel surgery, non-bowel surgery, and all CD-related surgeries were 3.4%, 1.4%, and 4.8%, respectively, at 1 year after diagnosis and 13.8%, 4.5%, and 17.7%, respectively, at 5 years after diagnosis. Older age at diagnosis, greater disease severity, and stricturing or penetrating disease increased the risk of bowel surgery. Disease between the transverse colon and rectum decreased the risk. Initiation of immunomodulator therapy within 30 days of diagnosis, sex, race, and family history of inflammatory bowel disease did not influence the risk of bowel surgery. Conclusions: In an analysis of pediatric patients with CD, the 5-year cumulative risk of bowel surgery was lower than that reported in recent studies of adult and pediatric patients but similar to that of a recent retrospective pediatric study. Initiation of immunomodulator therapy at diagnosis did not alter the risk of surgery within 5 years of diagnosis. [Copyright &y& Elsevier]

Background and Aims: Treatment of complex perianal fistulas associated with Crohn's disease is challenging. In adults, seton drainage combined with infliximab therapy has proven to be more effective than either one alone. Results following such treatment among pediatric patients have not been reported previously. The aim of this study was to describe outcomes after combined seton and infliximab treatment for complex perianal fistulas in adolescents with Crohn's disease., Methods: We performed a retrospective medical record review of all consecutive Crohn's disease patients treated for perianal fistulas with seton drainage and infliximab between 2007 and 2013 (n=13). A follow-up interview was conducted at median of two years., Results: Median age at fistula diagnosis was 14years. Following seton placement in fistula tracks, infliximab induction was administered at weeks 0, 2, and 6 and maintenance therapy at 8-week intervals. Over 90% responded to seton drainage and infliximab induction. Final fistula response was obtained at median of 8weeks, being complete in 77% and partial in 15%. Setons were kept in place for median of 8months. Fistulas recurred in 23% over a year after the final response. At last follow-up, 85% still had a response and 70% were free from perianal symptoms. Most were still on anti-TNF-α therapy, but one third had switched to adalimumab. Patients' anorectal function was well preserved and overall satisfaction with the treatment was high., Conclusions: The results suggest that combining seton drainage with infliximab therapy improves the perianal fistula response rates in pediatric patients., (Copyright © 2014 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.)

Purpose: To investigate the efficacy of early infliximab use and to follow the progress of pediatric cases of Crohn's disease for 3 years., Methods: We reviewed the medical records of 28 pediatric patients who had been treated with infliximab for Crohn's disease. Eighteen patients (the 'top-down' group) received infliximab and azathioprine for induction and maintenance therapy for the first year, and then were treated with azathioprine for 2 additional years. Ten patients who were refractory to conventional therapy were categorized in the 'step-up' group. All patients were followed for at least 36 months. Treatment efficacy was assessed by the relapse rate using the pediatric Crohn's disease activity index (PCDAI) score in each group at 12, 24, and 36 months. Blood samples were available from 10 patients, and were used to assess antibody to infliximab (ATI)., Results: The relapse rate in 'top-down' group was lower than that in 'step-up' group at 1, 2, and 3 years. But, just the relapse rate at the 2 years was significantly different. At 3 years, the relapse rate according to different characteristic variables (sex, age at diagnosis, involvement, PCDAI at diagnosis) was not significantly different. Only one patient treated with infliximab had an adverse event, consisting of dyspnea and tachycardia. ATI was not detected in the blood samples from 10 patients., Conclusion: Early induction with infliximab at diagnosis ('top-down' therapy) is effective for reducing the relapse rate compared to conventional therapies in pediatric Crohn's disease possibly for up to 3 years.