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

• DOI: 10.1097/mpg.0b013e3181c92c53
• Publication Date: 2010-01-15T07:32:59Z
• Authors: Bhupinder K Sandhu; John ME Fell; R Mark Beattie; Sally G Mitton; David C Wilson; Huw Jenkins
• Keywords: Pediatric gastroenterology; Etiology

1.0 INTRODUCTION (1) Inflammatory bowel disease (IBD) encompasses 2 related but distinct disorders of as yet unknown aetiology. Crohn (CD) is a chronic, idiopathic, transmural inflammation that can affect 1 or several segments the digestive tract. Ulcerative colitis (UC) chronic idiopathic rectum extending continuously over variable length colon from distal end to proximal end. Indeterminate (IC) reserved for cases which findings are not sufficient allow differentiation between CD and UC (1). 1.1 Development Guidelines (2–4) These guidelines work IBD Working Group British Society Paediatric Gastroenterology, Hepatology, Nutrition (BSPGHAN) use by clinicians allied professionals caring children with in United Kingdom. There paucity paediatric trials high methodological quality provide comprehensive evidence-based document. Thus, these clinical have had be consensus based, informed best-available evidence literature high-quality data adult literature, together expertise multidisciplinary experience experts comprising gastroenterologists represented BSPGHAN. They an evidence- consensus-based document describing good practice investigation treatment children, will promote consistency management such conditions. Individual must managed on basis all available child. Parent patient preferences sought joint decisions made. published BSPGHAN Web site (www.bspghan.org.uk), simple regular updating future easy access society members others. The performed search modalities intervention studies using electronic databases (MEDLINE, PubMed, Cochrane, Ovid). Evidence was graded Scottish Intercollegiate Network (2). Methodology detailed evaluation separate article this issue. Gastroenterology (BSG) produced adults (3) also Ovid; key words: "inflammatory disease," "ulcerative colitis," "Crohn's disease"). format based BSG uses, where available, practice. Where there no little controversy, authors has been used European Crohn's Colitis Organisation (4). 2.0 INFLAMMATORY BOWEL DISEASE 2.1 Definitions (1,4,5) characterised diffuse mucosal limited colon. Disease extent divided into more extensive disease. "Distal" refers confined (proctitis) sigmoid (proctosigmoiditis). More includes "left-sided colitis" (up splenic flexure), "extensive hepatic "pancolitis" (affecting whole colon). patchy, inflammation, may any part gastrointestinal (GI) It defined location (terminal ileal, colonic, ileocolic, upper GI), pattern (inflammatory, fistulating, stricturing). variables combined Montreal classification (5). About 10% affecting unclassifiable after considering clinical, radiological, endoscopic, pathological criteria because they some features both This termed indeterminate (IC). 2.2 Epidemiology only prospective national survey younger than 16 years Kingdom (6) showed incidence 5.2/100,000 individuals per year (60% CD, 28% UC, 12% IC). slightly common boys higher rate Asian other ethnic groups. mean age at diagnosis 11.9 years. For were approximately equal proportions ileitis, colitis, ileocolitis, almost 90% pancolitis (7). A systematic review epidemiological North American cohorts estimates 3 4/100,000 (8). diseases young people peak ages 10 40 Data Scotland Wales suggest risen during last 20 (9,10), 25% presenting people. now plateaued increasing (11), so need determine current trends again across age; IBD, 5% 5 (7) 15% older 60 diagnosis. Projected up 240,000 affected (12). 2.3 Pathogenesis etiologies remain unknown. probably response environmental triggers (infection, drugs, agents) genetically susceptible individuals. genetic component stronger UC. Smoking increases risk decreases through mechanisms (13). Theories pathogenetic too complex considered broad areas examined epidemiology, gut/environmental interface, inflammatory process, genetics each Epidemiological diet, drug, vaccination history; seasonal variation; water supply; social circumstances. interface luminal bacteria, biofilms, epithelial glycocalyx mucus, barrier function, remodeling, immune/epithelial interactions. process cell signalling pathways, cytokine profiles, eicosanoid mediators, lymphocyte trafficking, surface molecules, interactions stromal immune cells, neuroimmune communication. Researchers susceptibility adopted candidate gene approach, genome-wide screening microsatellite markers, and, most recently, association scans functional expression. Mutations (CARD15/ NOD2), located chromosome 16, associated small intestinal white (but Asian) populations link innate immunity bacterial population gut. Recent implicated new pathways: T regulation IL-23 pathway via IL23R autophagy, controls intracellular genes ATG16L1 IRGM. Other identified, although their existence strongly suggested replicated linkage number chromosomes. 2.4 Clinical Features Pattern (7,14–20) In blood loss (84%), diarrhea (74%), abdominal pain (62%) Weight less (35%) (58%). symptoms include lethargy anorexia. reported extraintestinal symptom arthropathy (10%). Skin manifestations rare. Children IC predominantly colitic symptoms. With modern medical surgical management, slight excess mortality first subsequent difference non-IBD (14,15). severe attack still potentially life-threatening illness. course marked exacerbation remission. 50% patients relapse year. An appreciable minority frequently relapsing continuous moderate diagnosis, colectomy around severity predictive long-term outcome. Symptoms heterogeneous nonspecific delay Abdominal pain, diarrhoea, weight "classic triad" present way. presentation childhood decades changed. Hospital Sick Children, Toronto, 1980 1989, 80% presented classical triad (16), recent large population-based 1998 1999 found way Of 44% majority (72%) complain pain. Many vague complaints lethargy, anorexia, discomfort isolated growth failure. significant markedly impaired final height (17,18). Neglect record parameters, particularly those paediatrician, identified (7,17,20). fever, nausea, vomiting, delayed puberty, psychiatric disturbance, erythema nodosum exacerbations tends cause greater disability (Table 1).TABLE 1: Presenting signs UK (7)2.5 Diagnosis Investigations (1,21–24) diagnose tissue diagnoses distribution recognized 25 ago (22). To ensure receive optimal care, developed protocol confirmed combination biochemical, histological, nuclear medicine investigations (Fig. 1). made suspicion supported appropriate macroscopic colonoscopy, typical histological biopsy, negative stool examinations infectious agents. depends demonstrating focal lesions granuloma in, most, 40% 60%.Figure Porto (1).2.5.1 History Examination full history should travel, medication, dietary family history, frequency, consistency, urgency, presence blood, pus rectum. malaise, loss, (joint, cutaneous, eye) sought. General examination well-being, centiles, pubertal status Tanner staging, pulse rate, pressure, temperature, tenderness, distension, masses including inspection perianal area skin tags, fissures, ulcers, and/or oedema suggesting CD. 2.5.2 Initial Laboratory count (FBC), C-reactive protein (CRP), erythrocyte sedimentation liver function tests (especially albumin). Reduced levels haemoglobin, raised markers (CRP, platelets), reduced serum albumin suggestive IBD. however, typical. Stool cultures carried out exclude diarrhoea tested Clostridium difficile toxins B. Additional needed who traveled abroad. Identification pathogen, does necessarily episode documented enteric infection. tuberculosis (TB), excluded. Perinuclear anti-neutrophil cytoplasmic antibody positively anti-Saccharomyces cerevisiae diagnostic sensitivity serological ranges 60% 80%, use. noninvasive faecal calprotectin lactoferrin become increasingly important monitoring activity avoid invasive investigations. radiography essential assessment suspected colonic dilatation silent perforation. 2.5.3 Upper GI Endoscopy Colonoscopy Ideally, having lower endoscopy preferably intubation terminal ileum multiple biopsies (oesophagus, stomach, duodenum) tract (ileum, caecum, ascending colon, transverse descending sigmoid, rectum) barium meal follow-through evaluate involvement bowel. aid when pathognomic present. Histological 30% even absence Unlike adults, pancolitis, making colonoscopy advisable. Sigmoidoscopy role except perforation higher, flexible sigmoidoscopy safer option. defer until condition improves. behaves like few later diagnosed Once documented, chosen. Histology ileal help (eg, TB, Behcet syndrome, lymphoma, vasculitis) well assess sent TB culture. 2.5.4 Technetium scanning documents undertaken centres. safe, lack specificity helpful define extent. give false-negative result if child taking steroids show oesophageal pelvic inflammation. Ultrasound skilled hands sensitive identifying thickened loops identify abscesses free fluid peritoneum. Computed tomography increasingly, magnetic resonance imaging (MRI) pelvis, example, complications fistula). Due decreased radiation exposure, small-bowel MRI replacing Laparoscopy selected patients, possible. Capsule widely valuable intestine. cannot strictures it retained. 2.6 Histopathology Histopathological biopsy specimens according principles outlined (23). type clearly along coexistent dysplasia recorded. 2.7 Imaging desirable discuss radiologist unnecessary exposure ionizing (24). forum best results context planned. 3.0 TREATMENT OF Treatment consists bringing active remission followed prevention (Figs 3). Choice influenced type, distribution, short stature, status. that, much widespread, 9% 7% involvement, nearly gastroduodenal disease, 20% jejunal Not paediatric-onset rapid progression (25). Evaluation efficacy symptomatic improvement, gain, later, improved velocity, biochemical resolution abnormal markers), cases, re-evaluation confirm healing. randomised controlled drug children. medications unlicensed unavailable child-friendly formats tablets rather liquid form). choice medication child's cooperation parents' willingness administer treatment; accept enemas. Therapy rapidly evolving field, many biological agents under likely change therapeutic strategies radically next decade.Figure 2: treatment.Figure 3: treatment.3.1 Management benefits risks discussed openly family, relation immunomodulators. Factors potential immunosuppression, bone marrow suppression, malignancy discussion recorded case notes. expressed index Activity Index (26). 3.1.0 Induction Remission Relapse (27–72) exclusive enteral nutrition oral corticosteroids. concordant guidelines, state insufficient recommend outside trials/specialist Recently, centres started azathioprine Azathioprine prevents relapse, fully effective least months starting drug. 3.1.1 Exclusive Enteral (27–35) Levels (EL) 1+ 1-, 2-, 3, 4 first-line therapy inducing cases. influence parent choice, compliance, palatability, corticosteroid toxicity, terms nutritional growth. polymeric Modulen Alicalm) elemental EO28) feeds. appears 2. Both feeds different flavours palatable. Administration nasogastric tube gastrostomy Duration usually 6 weeks. Most 120% reference nutrient intake; this, needs tapered individual needs, dietetic support essential. Food reintroduced cautiously weeks, dependent whilst weaning feed. 3.1.2 Corticosteroids (35–40) EL1-, Prednisolone mg · kg−1 day−1 (maximum mg/day) dose weeks achieved (with every clinic telephone, remission) thereafter gradual reduction 8 depending response. Ensure adequate intake calcium vitamin D insufficient, consider supplement Calcichew D3 tablet daily). Gastric acid suppression proton pump inhibitors omeprazole) required gastritis. 3.1.3 Strategies (41–50) Antibiotics (EL3): metronidazole (7.5 dose−1 tds) ± ciprofloxacin (5 bd) Aminosalicylates (EL1-, 3) (mesalazine 50–100 day−1, maximum 3–4 g/day sulphasalazine 40–60 g/d, increase 100 tolerated): mild Topical mesalazine left-sided colitis. Regular renal functions Budesonide 9 mg/day 3): prednisolone ileocaecal fewer side effects Intravenous (iv) iv (hydrocortisone mg/kg qds, methylprednisolone od, maximum) given presentation. introduced immediately (after checking thiopurine methyltransferase [TPMT] satisfactory) takes effective. Surgery complication abscess/fistula) pelvis Parenteral (EL3) complicated 3.1.4 Refractory Nonresponsive (51–78) Patients whom standard induction therapy, high-dose intravenous steroids, failed induce either nonresponsive Steroid refractory despite (1–2 day−1; minimum duration (at weeks) steroid therapy. Such immunomodulators surgery immediate consideration. (2–2.5 day−1) 6-mercaptopurine (1–1.25 (EL3), TPMT satisfactory. intolerant azathioprine, tolerate 6-mercaptopurine. Methotrexate 15 mg/m2 once weekly subcutaneously. occurs within further improvement seen administration benefit nonadherence major If issue, then switch methotrexate, provided interfere absorption. Infliximab 0, 2, (EL2-, inappropriate. plan outset infliximab, doses reassessment). Before initiating sepsis excluded (chest x-ray/Mantoux test molecular quantification tests). already immunosuppressive drugs Mantoux. treatment, his her counseled about malignancy, written consent obtained. infliximab National Institute Excellence. considered, especially strictures, fistulae failed. Close collaboration surgeon experienced curative directed minimising impact At require 70% undergo lifetime. 3.1.5 Sites Oral: nutrition, exclusion diet (benzoate cinnamon free), topical intralesional injections. Azathioprine, thalidomide resistant (EL3). Gastroduodenal disease: inhibitors, reduce Fistulising Metronidazole (EL4) dose−1) enterocutaneous (check before treatment), onset action. Infliximab, intravenous: infusions treatments. scan abscess infliximab. Surgery: drainage, fistulotomy, seton insertion treatment. Image MRI. 3.1.6 Maintenance (77–97) maintenance dependent, effort find initiated months, times following initial successful steroid-dependent patients; administered postoperatively complex, checked done nonresponders useful check thioguanine nucleotides whether noncompliant absorbing. When stop controversial. half stopping hence usual valid. parents gastroenterology colleagues transition plan. Certainly, discontinued education, continue time transfer physicians. Methotrexate: subcutaneously 3), ineffective poorly tolerated, folic 24 hours ameliorate effects. FBC monitored month. (EL2-): supplementary improve 5-aminosalicylic acid, (EL4): maintaining remission, (50–100 tolerated) induced necessary intravenous, weekly). escalate (10 mg/kg) responsiveness successful, revert infusions. Consider reinvestigating ongoing sepsis, stricture, overgrowth. Stopping coexisting immunosuppression (there emerging lymphoma concomitant infliximab). Assess annually discontinued. develops hypersensitivity abolished ameliorated hydrocortisone antihistamine infusion. anti-TNF initially responsive intolerant, alternative adalimumab (subcutaneous) 80 stat week). Reassess endoscopically necessary, radiologically, second-line beneficial effect probiotics, fish oil, Trichuris (worm) maintain 3.2 distribution. (98–100). severe, admitted unit intensive intrav