Guidelines for the Management of Inflammatory Bowel Disease in Children in the United Kingdom

Abstract

1.0 INTRODUCTION (1) Inflammatory bowel disease (IBD) encompasses 2 related but distinct disorders of as yet unknown aetiology. Crohn disease (CD) is a chronic, idiopathic, transmural inflammation that can affect 1 or several segments of the digestive tract. Ulcerative colitis (UC) is a chronic idiopathic inflammation of the rectum extending continuously over a variable length of the colon from the distal end to the proximal end. Indeterminate colitis (IC) is reserved for cases of colitis for which findings are not sufficient to allow differentiation between CD and UC (1). 1.1 Development of Guidelines (2–4) These guidelines are the work of the IBD Working Group of the British Society of Paediatric Gastroenterology, Hepatology, and Nutrition (BSPGHAN) and are for use by clinicians and allied professionals caring for children with IBD in the United Kingdom. There is a paucity of paediatric trials of high methodological quality to provide a comprehensive evidence-based document. Thus, these clinical guidelines have had to be consensus based, informed by the best-available evidence from the paediatric literature and high-quality data from the adult IBD literature, together with the clinical expertise and multidisciplinary experience of IBD experts comprising paediatric gastroenterologists represented by BSPGHAN. They provide an evidence- and consensus-based document describing good clinical practice for the investigation and treatment of IBD in children, which will promote consistency of the management of such conditions. Individual cases must be managed on the basis of all of the clinical data available for that child. Parent and patient preferences must be sought and joint decisions made. These guidelines will be published on the BSPGHAN Web site (www.bspghan.org.uk), which will allow simple and regular updating in the future and easy access for society members and others. The IBD Working Group of BSPGHAN performed a comprehensive literature search of treatment modalities in paediatric IBD intervention studies using electronic databases (MEDLINE, PubMed, Cochrane, and Ovid). Evidence was graded using the Scottish Intercollegiate Guidelines Network (2). Methodology and detailed evaluation of evidence are published in a separate article in this issue. The British Society of Gastroenterology (BSG) produced evidence-based guidelines for the management of IBD in adults (3) for which a comprehensive literature search was also performed using electronic databases (MEDLINE, PubMed, and Ovid; key words: “inflammatory bowel disease,” “ulcerative colitis,” and “Crohn's disease”). The format of the paediatric guidelines is based on the BSG guidelines but uses, where available, paediatric data and practice. Where there are no or little paediatric data or there is controversy, the evidence-based evaluation by the authors of the BSG guidelines for adults with IBD has been used together with the European Crohn's and Colitis Organisation consensus document (4). 2.0 INFLAMMATORY BOWEL DISEASE 2.1 Definitions (1,4,5) UC is characterised by diffuse mucosal inflammation limited to the colon. Disease extent can be divided into distal or more extensive disease. “Distal” disease refers to colitis confined to the rectum (proctitis) or rectum and sigmoid colon (proctosigmoiditis). More extensive disease includes “left-sided colitis” (up to the splenic flexure), “extensive colitis” (up to the hepatic flexure), and “pancolitis” (affecting the whole colon). CD is characterised by patchy, transmural inflammation, which may affect any part of the gastrointestinal (GI) tract. It may be defined by location (terminal ileal, colonic, ileocolic, upper GI), or by pattern of disease (inflammatory, fistulating, or stricturing). These variables have been combined in the Montreal classification (5). About 10% of children with IBD affecting the colon are unclassifiable after considering clinical, radiological, endoscopic, and pathological criteria because they have some features of both conditions. This is termed indeterminate colitis (IC). 2.2 Epidemiology The only prospective national survey of IBD in children younger than 16 years in the United Kingdom (6) showed the incidence to be 5.2/100,000 individuals per year (60% CD, 28% UC, and 12% IC). It is slightly more common in boys and there is a slightly higher rate of UC in Asian children than in other ethnic groups. The mean age at diagnosis was 11.9 years. For CD there were approximately equal proportions of ileitis, colitis, and ileocolitis, and for UC almost 90% of children had a pancolitis (7). A systematic review of the epidemiological studies in North American cohorts estimates the incidence at 3 to 4/100,000 individuals per year (8). UC and CD are diseases of young people with a peak incidence between the ages of 10 and 40 years. Data from Scotland and Wales suggest that the incidence has risen during the last 20 years (9,10), with 25% of all cases presenting in children and young people. The incidence of CD may now have plateaued and that of UC may be increasing (11), so there is a need to determine current incidence trends again across the United Kingdom. IBD can affect any age; of the children presenting with IBD, 5% are younger than 5 years (7) and only 15% of adults are older than 60 years at diagnosis. Projected estimates suggest that up to 240,000 people are affected by IBD in the United Kingdom (12). 2.3 Pathogenesis The etiologies of both UC and CD remain unknown. The consensus is that both diseases are probably a response to environmental triggers (infection, drugs, or other agents) in genetically susceptible individuals. The genetic component is stronger in CD than in UC. Smoking increases the risk of CD but decreases the risk of UC through unknown mechanisms (13). Theories and evidence for pathogenetic mechanisms are too complex to be considered in this document. The broad areas examined are epidemiology, the gut/environmental interface, the inflammatory process, and genetics of each disease. Epidemiological studies have considered diet, drug, and vaccination history; seasonal variation; water supply; and social circumstances. The gut/environmental interface includes work on luminal bacteria, biofilms, the epithelial glycocalyx and mucus, epithelial barrier function, epithelial remodeling, and immune/epithelial interactions. The inflammatory process has been examined through cell signalling pathways, cytokine profiles, eicosanoid and other inflammatory mediators, lymphocyte trafficking, cell surface molecules, interactions between stromal and immune cells, and neuroimmune communication. Researchers in genetic susceptibility to IBD have adopted a candidate gene approach, genome-wide screening through microsatellite markers, and, most recently, both genome-wide association scans and studies on functional gene expression. Mutations of 1 gene (CARD15/ NOD2), located on chromosome 16, have been associated with small intestinal CD in white (but not Asian) populations and link innate immunity and the bacterial population of the gut. Recent genome-wide association scans have implicated 2 new pathways: T cell regulation by the IL-23 pathway via the gene IL23R and the process of autophagy, which controls intracellular bacteria, by the genes ATG16L1 and IRGM. Other genes have yet to be identified, although their existence is strongly suggested by replicated linkage to a number of chromosomes. 2.4 Clinical Features and Pattern of Disease (7,14–20) In children with UC, blood loss (84%), diarrhea (74%), and abdominal pain (62%) are common (7). Weight loss is less common in UC (35%) than CD (58%). Other symptoms include lethargy and anorexia. The most common reported extraintestinal symptom is arthropathy (10%). Skin manifestations are rare. Children with IC have predominantly colitic symptoms. With modern medical and surgical management, the disease now has a slight excess of mortality in the first 2 years after diagnosis but little subsequent difference from the non-IBD population (14,15). A severe attack of UC is still a potentially life-threatening illness. The clinical course of UC is marked by exacerbation and remission. About 50% of patients with UC have a relapse in any year. An appreciable minority has frequently relapsing or chronic, continuous disease. In children with moderate to severe disease at diagnosis, the colectomy rate is around 25% at 5 years. Disease severity at diagnosis is predictive of long-term outcome. Symptoms of CD are more heterogeneous and the nonspecific symptoms in children with CD may delay diagnosis. Abdominal pain, diarrhoea, and weight loss were considered to be the “classic triad” of CD, but now only a minority present in this way. The clinical presentation of childhood CD during the last 2 decades has changed. Data from the Hospital for Sick Children, Toronto, during 1980 to 1989, showed that 80% of children with CD presented with the classical triad (16), but a more recent large population-based survey of childhood IBD in the United Kingdom during 1998 and 1999 found only 25% presented in this way (7). Of patients with CD, 44% have no diarrhoea, but the majority (72%) complain of abdominal pain. Many children with CD present with vague complaints such as lethargy, anorexia, and abdominal discomfort or with isolated growth failure. A significant minority have markedly impaired final adult height (17,18). Neglect to record growth parameters, particularly for those not presenting to a paediatrician, has been identified Other symptoms may include and (7). The clinical course of CD is characterised by and remission. CD to than UC symptoms and of children in the with CD and The need to children with IBD in a systematic way to provide and disease was more than years all children members of the IBD Working Group of the European Society of Paediatric Gastroenterology, Hepatology, and Nutrition have a consensus for investigation of these children (1). The diagnosis of IBD is by clinical evaluation and a of endoscopic, radiological, or The diagnosis of UC is on clinical by findings on findings on and for For CD, the diagnosis on with transmural inflammation and at to criteria for diagnosis of inflammatory bowel disease in children and A include recent and and a detailed bowel with and of mucus, or per Abdominal pain, weight and symptoms of extraintestinal manifestations of IBD and be includes weight and height using blood abdominal for of for (1) include blood and of inflammatory and and are of In some patients with UC, the may be be to and for A and may be for patients have of the not a diagnosis of IBD because a first of IBD may present after In children from populations at risk for this be is associated with UC and with CD, but the of these only between and so they are of limited clinical The of and may both for screening and disease to more Abdominal is for of patients with severe colitis to and and (1) all children of IBD have upper and with of and from all of the segments in the upper and intestinal and for diagnosis. A and be performed in all children may have CD to the of the small Disease may be to diagnosis features are not evidence of CD in the upper can be present in up to of cases in the of upper symptoms. more than 90% of children with UC have a not have a in severe UC where the risk of bowel is a It may be to the clinical The majority of IC UC, but a are as diagnosis and disease are treatment can be of may to other as as the extent of IBD, and in children from a population at high risk for be for Other white cell areas of inflammation and is in several It is a investigation that may but can be to disease It may a the is and also may not or in is a and way of small bowel in CD and may or in the and, of the for may clinicians to and of disease to is small bowel in some may be in for intestinal is is not used in children at present but may in the diagnosis of disease of the small be used in the of because may be of be to the by the BSG The of IBD be defined with other or and the or of It is that clinicians with an to to A multidisciplinary is to review the of in the of the clinical so that management can be INFLAMMATORY BOWEL DISEASE of IBD of disease into by of relapse 2 and of treatment is by disease and associated presenting features such as weight and Recent data (7) suggest in CD, of the is more with only of children isolated small bowel disease and isolated disease. The majority have both and small bowel 50% have and have disease. only is IBD characterised by extensive intestinal at diagnosis but also the majority of children of disease of treatment includes of weight and height of blood inflammatory and, in some of disease by to mucosal There are trials in Many are for use in children and are in large than The of on the and the to for a with distal colitis may not treatment with for IBD is a with new investigation that are to in the Crohn disease Ulcerative colitis of Crohn Disease The and of any treatment be with patients and their particularly in to and such as the risk of and must be and the in the Disease can be using a disease such as the Paediatric Crohn's Disease of at or Disease The of treatment in most cases is between and This is with the BSG which also that there is evidence to the use of other some have using at diagnosis for those with severe disease. but is not at 3 after the Nutrition Evidence to and is an for small and large bowel in to 80% of that the use of include patient and of and in of and The is between IBD, or There to be no significant difference in between the are available in and has been suggested that may be more via a or is an of is children need approximately of to be to and is may be during the course of 1 to 3 on patient symptoms the and 1 to 2 40 is an for small and large bowel disease. be at for 2 to review at 2 in or via clinical and of the for to on the of and and with may be in the of Other at for disease in high or 3 can to may be in disease. is in to moderate blood of and is less than as for isolated but has 2 or 2 60 be to children with severe disease at may be are in those with severe but at 3 to be for after to extent of disease may be as for patients with severe disease. or CD in has to at diagnosis or during subsequent relapse are defined as CD may be defined as disease an 20 and 2 of patients be considered for treatment with is not an or after that are Of the patients are to up to 50% will but may be after 16 is of to is a issue. is not an patients can to there is no significant small bowel which may with 5 at and can be in patients are or to in with and in is There be a at the for using with the length of course defined 3 and be and may have a the patient and or be a the of and be Guidelines for use in adults have been produced by the for Clinical be for isolated or and for those in medical treatment has between gastroenterologists and a in paediatric IBD is In CD, is not and management is at the of disease. of patients in the first 10 years of the disease and approximately to 80% will in their Other Disease CD can be managed with and and may be considered for disease used with may symptoms. and for at is treatment for simple disease. or may be an treatment for and but there is a delay in of 3 of 5 each at and may be an treatment for and but be reserved for patients are to other A be to any and to and may be particularly with of in CD There is no for for patients with CD in remission. For patients are must be to other or be as in individuals relapse in less than relapse 2 or more per year and in all also be for fistulating, or extensive disease. be treatment and is probably at diagnosis. In may be to to determine they are or not to is There is some evidence that more than of all adults will relapse 3 years of and the practice of at years may not be This be with the patient and and also adult as part of the not be at key during growth and most the of to adult or is or with 5 after each to any and must be 2 for the first per may the risk of relapse and may growth and little in but may be of limited in high as for disease. is with with may be It may be to to a higher for loss of and to for subsequent first to and bacterial after be considered are data of risk with which may or may not be related to of or with at to can be patient to these symptoms may be or with a of Other in patients to or can be considered by 40 other and, Other there is little evidence for a of and to in of Ulcerative Colitis of UC on disease and Disease can be using a clinical on evaluation the disease is the patient to be to a paediatric for the disease is the patient an abdominal to and joint and The majority of children with UC have than 10% have colitis, have disease confined to the rectum and have (7). of those pancolitis at presentation will to pancolitis be sought because this may with but in severe treatment with not be of at or Disease or UC or to a slightly in or are for to moderate colitis or isolated disease with or for distal disease is less than a of and or 3 can to is for 10 to and is particularly for UC or IC and for is available in and are to those and are and 1 to 2 40 for patients in agents) are to UC 1 to 2 40 at for 2 to at 2 in the or via clinical for to the during a Children with severe colitis be to for and of and a abdominal as a to for is surgical is and patient be managed between and 2 or 2 60 to by the need for of or colectomy abdominal only is or surgical review is also with a to colectomy there is evidence of colon in based on adult and in patients is for of can be considered in patients not to as a to and of may be an there is some evidence that be considered in severe UC. of with is for all but clinicians can in distal and disease in for years. to 3 be as and are in the United Kingdom for use in to 60 is an but may have It is the only available in It may be in patients with associated there is no for in the of remission. or be as in patients to or relapse in less than or relapse 2 or more per year with of and 3 is because or disease can In can be to determine they are or not with for their to is There is some evidence in adult patients that more than will relapse 3 years of and the practice of at years may not be This be with the patient and and also adult as part of the not be at key during growth and most the of to adult of Indeterminate Colitis patients with IC the as patients with UC. because the disease may to CD or UC. INFLAMMATORY BOWEL DISEASE Nutrition Nutrition is an part of the management of children with IBD, and be at presentation and at disease in children with be considered as an for any patient with CD or UC with can be is an of in children with chronic disease. of growth and and are at presentation and 3 to the course of the disease. may in IBD may be related more to disease than to IBD may also be by used and is 1 of the that may which is for Children with CD have growth were used to to those or for children with CD in may growth and remission. In children with CD with disease and growth are in growth has been of the with an in a joint is for children have growth failure. In children with CD, may be present at diagnosis. scans can be used to document but there is no for may The of and is and be considered in children with significant during the growth and during In severe the of an be patients long-term and severe pain may disease or that need to be identified management of pain is and some children regular must be with use in the the pain management is An of functional pain may with that to disease. 2 blood for the first the 2 3 for disease to the lymphocyte between and as an of be at of is and for In may or of vaccination and any and a patient is not no to be and It is not there is an mortality in children in the first years after diagnosis. In adults there is a rate but there is also a small in mortality for both UC and CD This is on age and of disease. data have that UC and, to a Crohn colitis are associated with an risk of of IBD on and Society 25% of individuals with IBD present the age of and diagnosis is in the and IBD in children can in growth and loss of Nutrition and growth are in paediatric IBD, particularly CD, the of treatment to and disease with on growth and The treatment is slightly from adult with not only symptom and quality of but also that disease is sufficient to growth and symptoms of UC or CD and and can significant such as or can such as weight and can be significant with such as in the are by children and and may their in IBD may be by future or intestinal and these be with the patient and The of IBD on children is high for the or or other and because presentation is at a young age with the to investigation and treatment be managed by a and with the and as part of a clinical For the has is and or may be with an adult in the management of with IBD, the is with the with a and are the for These patients at be with the paediatric to The of cases that and expertise are those in are between and particularly the is and clinical are of Colitis and Crohn's Disease of for and must be around the of the and with the the quality but as to as as part of a managed clinical It is that the are in any clinical between paediatric and are for It is to have a with an in an adult with an in young people with IBD, a paediatric and, a with the and can as part of a clinical be in a for and in the treatment of children with patients be managed in the there must be a multidisciplinary paediatric paediatric an IBD a with of IBD, a an a and a to upper and access in a for all children with symptoms of IBD access to and or in the of a relapse or and in and to the pattern of disease to allow and and to provide and access to for and and at and clinical a IBD for in and national must be an part of any with joint between adult and paediatric which young people can for as as is guidelines by BSPGHAN are now available from Crohn's in and the of Crohn's and Colitis with separate for and of or by clinical can be by other of but to be and to their The and other provide access to Crohn's in Web for Colitis and Crohn's Disease Web Crohn's and Colitis of Web 3 Web The authors the of all BSPGHAN members and the authors of the BSG adult IBD guidelines for their and were authors to this