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Update on Gastrointestinal Disorders in Paediatrics

NPPG 18 th ANNUAL CONFERENCE AND EXHIBITION. Update on Gastrointestinal Disorders in Paediatrics. Dr Krish Venkatesh Consultant Paediatric Gastroenterologist Alder Hey Children’s Hospital Liverpool. Inflammatory bowel disease.

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Update on Gastrointestinal Disorders in Paediatrics

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  1. NPPG 18thANNUAL CONFERENCE AND EXHIBITION Update on Gastrointestinal Disorders in Paediatrics Dr Krish Venkatesh Consultant Paediatric Gastroenterologist Alder Hey Children’s Hospital Liverpool

  2. Inflammatory bowel disease • chronic inflammatory condition of GI tract • progressive • Remission and relapses • Ulcerative colitis (UC) and Crohn’s disease (CD). • Etiology unknown

  3. AETIOLOGY Trigger (?Infection) Genetic (Environ.,diet) Gut Microflora Abnormal Mucosal Immune Response Lack IR IR Intestinal Inflammation Normal Homeostasis Chronic IBD

  4. CLINICAL PRESENTATION

  5. Endoscopy

  6. Pathology

  7. Radiology

  8. COMPLICATIONS • Malnutrition and growth impairment Suboptimal intake Stool losses Increased nutritional needs Corticosteroid therapy Disease activity • Perianal disease • Fistulas, perforation, abscesses etc.. • Extraintestinal. • Quality of life • Cancer and mortality risk

  9. INVESTIGATIONS • Serology: “Fe-deficiency anaemia, unless explained by abnormal menstrual losses, reflects GI blood loss until proven otherwise”, B12, Viscosity, Inflammatory markers, albumin. Antibodies (ANCA, ASCA). • Stool (microscopy, proteins, C and S) • Radiology • Endoscopy

  10. DIAGNOSIS & TREATMENT • Goals of therapy: Clinical & lab. control of inflammation. Appropriate growth & development. Good quality of life. • Disease activity scores. (PCDAI, PUCAI)

  11. Anti-inflammatory Therapy • 5-Aminosalicylic acid compounds. • Antibiotics. • Nutritional therapy.

  12. Immunosuppressive therapy • Azathioprine. • 6 M-P. • Cyclosporine A • Methotrexate.

  13. Both • Corticosteroid therapy.

  14. Corticosteroids and IBD • used for the treatment of IBD since the 1950s • down regulate production of inflammatory cytokines such as interleukin (IL)-1, IL-6, and tumour necrosis factor (TNF)-alpha • inhibit protein synthesis • associated with significant adverse effects

  15. Enteral Nutrition and Crohn’s Disease • first used in 1973 • elemental (amino acid-based) • semi-elemental (oligopeptide) • polymeric (whole protein) • 15 trials so far comparing different formulations of EN • meta-analysis of 10 trials (334 patients) show no difference in efficacy between elemental and polymeric

  16. Azathioprine Indications for use in IBD • Steroid dependent • Refractory to steroids • Fistulating and perianal Crohn’s disease • Disease remission maintenance

  17. Metabolism of Azathioprine AZA 6-MP TPMT XO HGPRT TIMP 6-MeMP 6-TU 6-TGN

  18. Metabolism of Azathioprine AZA 6-MP TPMT XO HGPRT X TIMP 6-MeMP 6-TU 6-TGN

  19. Infliximab • IFX is a chimericmAb, • Binds to TNFα • mediates programmed cell death. • production of human anti-mouse Abs potentially limits therapeutic efficacy . • administered by intravenous (i.v.) infusion • Induction 0, 2 and 6 weeks • Maintenance 5-8 weeks

  20. Safety • Serious infections • Allergic reactions • Malignancy risk (HS T-cell lymphoma) • Drug-induced lupus • Demyelination • Cardiac failure

  21. Adalimumab • A fully human IgG1 monoclonal antibody. • CLASSIC I (Gastro 2006) Induction in IFX-naive (at W4: 36% Vs 12%) • CLASSIC II (Gut 2007) Maintenance: W56: 79% (2w), 83% (w), 44% • CHARM (Gastro 2007) At W 26: 40-47% Vs 19% At W 56: 36-41% Vs 12%

  22. Surgical Therapy • Curative?? • Indication??

  23. GORD N. Vakil, S.V. van Zanten, P. Kahrilas, J. Dent and R. Jones, Global consensus group. The Montreal definition and classification of gastroesophageal reflux disease: a global evidence-based consensus, Am J Gastroenterol101 (8) (2006 Aug), pp. 1900–1920

  24. Burden of disease... • Commonest GI diagnosis in outpatient visits in US • 8.2 million prescriptions for PPI • $10 billion in sales • Omeprazole is the most commonly prescribed GI generic compound and most common purchased OTC agent Shaheen NJ, Hansen RA et al. The burden of Gastrointestinal and liver diseases, 2006;101:2128-38

  25. General GER symptoms • Faltering growth • Anaemia • Irritability • Occasional stricture-related symptoms

  26. Extra-oesophageal symptoms Tolia V, Vandenplas Y. Systematic Review: the extra-oesophageal symptoms of GERD in children. Alim Pharm Ther. 2009; 29: 258-72

  27. Extra-oesophageal manifestations

  28. Diagnosing GOR/LPR • ultrasound • fluoroscopy • scintigraphy • pH metry • endoscopy "gold standard"

  29. pH metry • acid (< 4) and alkaline (> 7.5) GOR • physiological oesophageal pH 5 - 6.8:concealed • hypoacidic postprandial phase:concealed

  30. The Impedance Catheter 1 pH sensor 1 2 2 Impedance electrode 3 3 Impedance channels 4 4 5 5 6 pH sensor 6 7

  31. air impedance

  32. fluid impedance

  33. Classification of Oesophagitis Nayar DS, Vaezi MF. Classifications of esophagitis: who needs them. Gastrointest Endosc 2004; 60:253-57

  34. Chronic Oesophagitis Grade 4

  35. Candidial oesophagitis

  36. Eosinophillic oesophagitis

  37. NPPG 18thANNUAL CONFERENCE AND EXHIBITION Consensus ESPGHAN-NASPGN Guidelines on Gastroesophageal Reflux2009

  38. Treatment

  39. Consider a 2 to 4 week trial of an extensive protein hydrolysate or AA if formula fed Thickened formula decreases visible regurgitation Supine positioning during sleep is generally recommended LIFESTYLE CHANGES IN INFANTS Evidence A

  40. Left side positioning and elevation of the head of the bed decrease GOR symptoms No support for dietary restrictions In adults obesity and late night eating are associated with GOR. LIFESTYLE CHANGES IN OLDER CHILDREN AND ADOLESCENTS Evidence A

  41. Making the diagnosis Evidence A • H2RAs: relief of symptoms and mucosal healing. PPIs are superior to H2RAs • Insufficient support for routine use of metoclopramide, erythromycin, bethanechol or domperidone for GERD Evidence B Chronic therapy for GERD with antacids, alginate and sucralfate is not recommended.

  42. Currently, there is insufficient evidence to justify the routine use of cisapride, metoclopramide, erythromycin, bethanecol, domperidone or baclofen in the routine treatment of GERD Potential side effects of each prokinetic agent outweigh the benefits PROKINETIC THERAPY Evidence A

  43. ANTI-REFLUX SURGERY: INDICATIONS In infants: who have life-threatening complications In children: who have failed optimal medical therapy who are dependent on medical therapy over a long period of time who are non-compliant with medical therapy who have life-threatening complications Rule out non-GERD causes prior to surgery

  44. Chronic heartburn in older children and adolescents: Lifestyle changes with 4 week PPI trial If symptoms resolve, continue PPI for 3 months If symptoms persist, refer the patient to a paediatric gastroenterologist for further investigations

  45. In the infant or child with reflux oesophagitis: Initial treatment consists of lifestyle changes and PPI therapy. In most cases, efficacy of therapy can be monitored by the degree of symptoms relief (evidence A) PPIs not to be stopped abruptly Relapses: 10-50%

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