Ulcerative Colitis: Hildebrand H

Oliva-Hemker M, Escher JC, Moore D, Dubinksy M, Hildebrand H, Koda YK, Murch S, Sandhu B, Seo JK, Tanzi MN, Warner B, Anonymous00097. · Division of Pediatric Gastroenterology and Nutrition, Johns Hopkins University School of Medicine, Baltimore, MD 21287-2631, USA. · J Pediatr Gastroenterol Nutr. · Pubmed #18664886 No free full text.

This publication has no abstract.

Cucchiara S, Escher JC, Hildebrand H, Amil-Dias J, Stronati L, Ruemmele FM. · Pediatric Gastroenterology Unit, University of Rome La Sapienza, University Hospital Umberto I, Rome, Italy. · J Pediatr Gastroenterol Nutr. · Pubmed #19274777 No free full text.

Abstract: Inflammatory bowel diseases (IBDs) are lifelong inflammatory gastrointestinal diseases starting in about one third of patients during childhood. Treatment strategies aim to control this chronic inflammatory process. Owing to recent advances in the understanding of IBD, immunosuppressive agents (mainly against TNFalpha directed) as well as biological drugs are more and more often used. This therapeutic approach clearly improved the clinical condition of the majority of patients with IBD. However, with this more aggressive treatment strategy, safety concerns clearly arise. Recently, the description of a series of a particularly severe form of T cell lymphoma in pediatric and young adult patients with IBD under immunomodulator and biological combination therapy raised the question of the risks of treatment-induced side effects or complications. As reviewed in the present article, there is a slightly increased risk of not only lymphoma development in IBD patients, potentially related to the inflammatory process, but also to the use of immunosuppressive therapies. On the basis of the literature data, were analyzed current treatment strategies for children with moderate-to-severe IBD, who are candidates to receive immunomodulator and/or biological agents potentially accelerating the risk of lymphoma development. Comparative clinical studies in IBD are still missing; however, it is prudent to think about adapting immunosuppressive therapies to the inflammatory process of the underlying disorder and if possible to reduce them to monotherapy. Alternative treatment strategies for heavy immunosuppression exist (eg, enteral nutrition in Crohn disease or colectomy in patients with ulcerative colitis) and should be considered whenever appropriate. There is a major need for comparative studies before evidence-based guidelines can be established for safest and best treatment strategies of pediatric patients with IBD.

Heuschkel R, Salvestrini C, Beattie RM, Hildebrand H, Walters T, Griffiths A. · Royal Free Hampstead NHS Trust, Centre for Paediatric Gastroenterology, Hampstead, London, UK. · Inflamm Bowel Dis. · Pubmed #18266237 links to  free full text

Abstract: Around 1 in 4 patients with inflammatory bowel disease (IBD) present in childhood, the majority around the time of their pubertal growth spurt. This presents challenges over and above those of managing IBD in adults as this period is a time of dramatic psychological and physical transition for a child. Growth and nutrition are key priorities in the management of adolescents and young adults with IBD. Growth failure in IBD is characterized by delayed skeletal maturation and a delayed onset of puberty, and is best described in terms of height-for-age standard deviation score (Z score) or by variations in growth velocity over a period of 3-4 months. Growth failure is common at presentation in Crohn's disease (CD), but less common in ulcerative colitis (UC). The etiology of growth failure is multifactorial. Principal determinants, however, include the inflammatory process per se, with proinflammatory cytokines (e.g., IL-1beta, IL-6) being directly implicated. Furthermore, poor nutrition and the consequences of prolonged corticosteroid use also contribute to the significant reduction in final adult height of almost 1 in 5 children. Initially a prompt, where possible steroid-free, induction of remission is indicated. The ideal is then to sustain a relapse-free remission until growth is complete, which is often not until early adulthood. These goals can often be achieved with a combination of exclusive enteral nutrition (EEN) and early use of immunosuppressants. The advent of potent and efficacious biological agents considerably improves the range of growth-sparing interventions available to children around puberty, although well-timed surgery remains another highly effective means of achieving remission and significant catch-up growth. We carried out a systematic review of publications to identify the best available evidence for managing growth failure in children with IBD. Despite the paucity of high-quality publications, sufficient data were available in the literature to allow practical, evidence-based where possible, management guidelines to be formulated. Although there is clear evidence that exclusive enteral nutrition achieves mucosal healing, its effect on growth has only been assessed at 6 months. In contrast to corticosteroids, EEN has no negative effect on growth. Corticosteroids remain the key therapy responsible for medication-induced growth impairment, although the use of budesonide in selected patients may minimize the steroid effect on dividing growth plates. Immunosuppressants have become a mainstay of treatment in children with IBD, and are being used earlier in the disease course than ever before. However, there are currently no long-term data reporting better growth outcome if these agents are introduced very soon after diagnosis. In comparison, recent data from a large prospective trial of infliximab in children with moderate to severe CD suggested significant catch-up growth during the first year of regular infusions. The only other intervention that has documented clear catch-up growth has been surgical resection. Resection of localized CD, in otherwise treatment-resistant children, early in the disease process achieves clear catch-up growth within the next 6 months. There are no data available that growth hormone improves final adult height in children with CD. In conjunction with expert endocrinological support, pubertal delay, more common in boys, may be treated with parenteral testosterone if causing significant psychological problems. The optimal management of children and adolescents requires a multidisciplinary approach frequently available within the pediatric healthcare setting. Dedicated dietetic support, along with nurse-specialist, child psychologist, and with closely linked medical and surgical care will likely achieve the best possible start for children facing a lifetime of chronic gut disease.

Hildebrand H, Finkel Y, Grahnquist L, Lindholm J, Ekbom A, Askling J. · Department of Women and Child Health, Astrid Lindgren Children's Hospital, Stockholm, Sweden. · Gut. · Pubmed #12970135 links to  free full text

Abstract: BACKGROUND: An increased incidence of paediatric Crohn's disease was reported recently by our group. AIMS: To assess the incidence and characteristics of inflammatory bowel disease (IBD) in northern Stockholm between 1990 and 2001. METHODS: All records of individuals 0-15 years of age with suspected IBD in the population based catchment area of 180000 individuals were scrutinised using defined diagnostic criteria. Patient files were searched for relatives with IBD, and for concomitant autoimmune diseases. RESULTS: A total of 152 children were diagnosed with IBD, corresponding to an overall incidence (per 100000) of IBD of 7.4. The incidence of Crohn's disease (CD) was 4.9, ulcerative colitis (UC) 2.2, and indeterminate colitis 0.2. Between 1990 and 2001, there was a marked increase in the incidence of CD while the incidence of UC was almost unchanged, leading to a net increase in the overall occurrence of IBD. There was a male dominance of CD. Fourteen per cent and 11% of patients with CD and UC, respectively, had a first or second degree relative with IBD. Eighteen per cent and 10% of patients with CD and UC, respectively, had a concomitant autoimmune disease. Ten patients with CD (10%) underwent surgery. CONCLUSIONS: The incidence of CD has increased in northern Stockholm. The current incidence is higher than that reported from other areas. Our results suggest a shift in presentation and diagnosis from UC towards CD, but also a net increase in IBD. Concomitant autoimmune disorders and family history are common in paediatric IBD.

Lindberg E, Lindquist B, Holmquist L, Hildebrand H. · Department of Paediatrics, Orebro Medical Centre Hospital, Sweden. · J Pediatr Gastroenterol Nutr. · Pubmed #10749408 No free full text.

Abstract: BACKGROUND: A prospective study of inflammatory bowel disease (IBD) in Sweden was performed to investigate whether the incidence and morbidity have changed from 1984 through 1995. METHODS: Children 15 years of age or less with IBD were included--i.e., those with a definite diagnosis of ulcerative colitis (UC) and Crohn's disease (CD) and those classified as having indeterminate colitis (IC) and probable Crohn's disease (PCD). The study covered 56.5% of the pediatric population of Sweden. RESULTS: The diagnosis of IBD was made in 639 children, which corresponds to a mean annual incidence of 5.8 per 100,000. The incidence increased from 4.6 per 100,000 per year from 1984 through 1986 to 7.0 from 1993 through 1995. It reflected an increase in UC from 1.4 to 3.2 per 100,000 per year, which is a significant yearly percentage of increase (8%; confidence interval, 2-14%; P < 0.05). In contrast, no change occurred in the incidence of CD (1.2-1.3 per 100,000). The incidence of IC and PCD also remained fairly stable. The percentages of children who underwent surgery decreased from 17.3% in the first 6 years to 4.6% in the last 6 years (P < 0.001). Surgery was performed in 27.7% of CD and 5.3% of UC cases. The median age at diagnosis was 12.2 years for UC, 13.0 years for CD, 11.2 for IC, and 11.2 for PCD. At diagnosis, 48 children (7.5%) were 5 years of age or less, whereas most of the patients were 11 years of age or more (398 children, 62.3%). CONCLUSIONS: In Sweden, the incidence of UC has increased, whereas that of CD remains the same. A significant number of children were classified with IC and PCD. In most children, IBD was diagnosed when they were 11 years old or more, but some cases were detected even in those below 6 years of age. A decrease in the frequency of surgery occurred during the study.