Inflammatory bowel disease (ibd) in children

Inflammatory bowel disease in children both Ulcerative Colitis (UC)and Crohn's Disease (CD), based more on diagnosis and diagnostic investigations.

1. Inflammatory bowel disease (IBD ) in children Dr Joyce Mwatonoka 3 rd Year Resident Pediatric and Child Heath 2021

2. Introduction IBD is comprised of two major disorders: ulcerative colitis (UC) and Crohn disease ( CD) UC affects the colon and is characterized by inflammation of the mucosal layer CD can involve any component of the gastrointestinal tract from the oral cavity to the anus and is characterized by transmural inflammation

3. Cont… These disorders have distinct pathologic and clinical characteristics, but their pathogenesis remains poorly understood The diseases may present at any age, but peak incidence is in adolescents and young adults

4. Epidemiology Peak Incidence between 15 – 30yrs 5 – 10% of pts develop IBD during childhood or adolescence T he incidence of pediatric IBD appears to be increasing Rare under the age of 5 years What is the peak age for onset of IBD?Johnston RD, Logan RF  Inflamm Bowel Dis. 2008 Oct;14 Suppl 2:S4-5. 

5. Cont… IBD that becomes symptomatic or is diagnosed before 6 years of age is termed "very early-onset IBD" ( VEO-IBD) Compared with children whose IBD develops later in life, those with VEO-IBD, and particularly those with onset before 2 yrs of age (sometimes termed "infantile IBD") are more likely to have single gene defects that alter immune function or disturb epithelial barrier function, and often have a more severe disease course

6. Cont… Compared with adults, children with IBD; Are more likely to present with extensive intestinal involvement H ave rapid clinical progression A re more likely to have a family history of IBD Definition of phenotypic characteristics of childhood-onset inflammatory bowel disease. Van Limbergen J, et al Gastroenterology. 2008;135(4):1114. Epub 2008 Jul 3. 

7. Cont… Data from a multicenter pediatric IBD registry; Family hx (including both first-degree relatives and extended family) was positive for IBD in 29% of pts overall, and 44% of children with UC who were < 3 years Children with early-onset inflammatory bowel disease (IBD): analysis of a pediatric IBD consortium registry. Heyman MB, Kirschner BS, et al, Pediatr . 2005;146(1):35. 

8. Pathophysiology Full understanding of IBD pathogenesis is unclear. It involves; Immune response dysregulation (Th17 – IL 17, TNF) Abnormal gut microbiota Environmental factors Genetic factors

9. Clinical manifestations GI sxs ; loose stools or bloody diarrhea, abdominal pain, or tenesmus -UC ; bloody diarrhoea , abdominal pain around bowel movement, tenesmus -CD ; subtle; low gradeabdominal pain, weight loss, lack of appetite, diarrhoea c/ cout blood Systemic sxs ; fever, fatigue and anorexia

10. O/E Abdominal tenderness and/or mass (especially in the RLQ), perianal disease (fistulae, anal skin tags, or fissures, or occult blood in stool) Extraintestinal manifestations ; Oral ulcerations ( aphthous stomatitis ), clubbing, rash ( erythema nodosum or pyoderma gangrenosum ), eye inflammation ( uveitis ), jaundice or hepatomegaly , or arthritis Growth failure, delayed puberty

11. Clinical features that raise suspicion for monogenic IBD Young age of onset Family history of IBD and/or immunodeficiency in multiple family members Recurrent infections or unexplained fever Associated features of autoimmunity ( eg , arthritis, primary sclerosing cholangitis , anemia, or endocrine dysfunction) Very severe IBD and/or resistance to conventional therapies for IBD

12. Diagnosis The diagnostic evaluation of IBD involves five steps The first two typically are performed by the general pediatrician, while the last three are performed by the pediatric gastroenterologist

13. Cont… Clinical suspicion of the illness based upon clinical sxs , examination, and screening laboratory data Exclusion of other illnesses that have a similar presentation Differentiation between CD and UC Localization of the region of the disease Identification of extraintestinal manifestations

14. Suggestive laboratory features FBP ; anemia , leukocytosis , and lymphocytosis ; Approx 70% of pts have anemia at dxs of IBD Elevated ESR (in 65-75% pts)   or CRP (in 85%) - somewhat more sensitive for detecting CD than UC -no cut off point, an ESR >20 or >25 mm/hr and CRP >5 or >10 mg/L have been used Hypoalbuminemia (in 40% of pts)   Laboratory values for children with newly diagnosed inflammatory bowel disease. Mack DR, et al, Pediatric Inflammatory Bowel Disease Collaborative Research Group Pediatrics. 2007;119(6):1113. 

15. Cont… Normal laboratory tests do not exclude the diagnosis of IBD. In a study of more than 500 children who ultimately were diagnosed with IBD, the ESR, hemoglobin, platelet count, and albumin level were all normal in 19% of children with UC and 9% of children with CD  Laboratory values for children with newly diagnosed inflammatory bowel disease. Mack DR, et al, Pediatric Inflammatory Bowel Disease Collaborative Research Group Pediatrics. 2007;119(6):1113. 

16. Cont; Stool tests Gross or occult blood; rectal bleeding is a presenting feature in at least 80% of pts with UC and 40% of those with CD -If IBD is suspected but there is no history of gross rectal bleeding, a stool guaiac (occult blood) test may be useful Epidemiologic and clinical characteristics of children with newly diagnosed inflammatory bowel disease in Wisconsin: a statewide population-based study. Kugathasan S, Judd RH, et al Wisconsin Pediatric Inflammatory Bowel Disease Alliance J Pediatr . 2003;143(4):525

17. Cont… Fecal calprotectin ; elevated in inflammatory intestinal diseases and may be useful for distinguishing inflammatory gastrointestinal disease including IBD from non-inflammatory causes of chronic diarrhea (such as functional abdominal pain)  Noninvasive Tests for Inflammatory Bowel Disease: A Meta-analysis. Holtman GA, Lisman -van Leeuwen Y, Reitsma JB, Berger MY Pediatrics. 2016;137(1) 

18. Cont… However, the test characteristics vary depending on the prevalence of IBD in the study population H igh prevalence of IBD, eg a gastroenterology clinic, elevated fecal calprotectin ( eg , >200 mcg/g) is useful for identifying pts with a high likelihood of having IBD In studies from referral centers for pediatric gastroenterology, fecal calprotectin had better performance characteristics for this purpose than ESR, CRP, or hypoalbuminemia

19. Cont… By contrast, in settings with a low prevalence of IBD, eg a primary care setting, it is more useful to rule out IBD ( ie , if fecal calprotectin is normal [ eg , <50 mcg/g], then IBD is unlikely ) Safely ruling out inflammatory bowel disease in children and teenagers without referral for endoscopy. Van de Vijver E, Schreuder AB, Cnossen WR, Muller Kobold AC, North Netherlands Pediatric IBD Consortium Arch Dis Child. 2012;97(12):1014. Epub 2012 Sep 27.  The diagnostic accuracy of fecal calprotectin during the investigation of suspected pediatric inflammatory bowel disease: a systematic review and meta-analysis. Henderson P, Anderson NH, Wilson DC Am J Gastroenterol . 2014;109(5):637. Epub 2013 May 14

20. Cont… Elevated levels of fecal calprotectin are also found in other causes of inflammatory diarrhea including bacterial and viral enteritis, intestinal lymphoma, celiac disease, food allergy, and immunodeficiency, and also in the setting of juvenile polyps Value of Fecal Calprotectin as a Biomarker for Juvenile Polyps in Children Investigated With Colonoscopy. Olafsdottir I, Nemeth A, Lörinc E, Toth E, Agardh D J Pediatr Gastroenterol Nutr . 2016 Jan;62(1):43-6

21. Cont… Fecal lactoferrin   Fecal leukocytes; Compared with fecal calprotectin , have considerably lower specificity and sensitivity for detecting inflammatory diarrhea

22. Other tests; Stool bacterial culture, ova and parasite testing, C. difficile testing Tuberculosis screening (interferon gamma testing or tuberculin skin test ) Titers for varicella and measles HBV serologies HIV Lactose/glucose hydrogen breath test for lactose intolerance

23. Radiographic studies For localization of small bowel disease, one of the following: MRE (Magnetic resonance enterography ) - sensitivity of 83% and a specificity of 93% Abdominal CT with oral contrast (CTE – computed enterography ) Diagnostic Performance of Magnetic Resonance Enterography for Detection of Active Inflammation in Children and Adolescents With Inflammatory Bowel Disease: A Systematic Review and Diagnostic Meta-analysis. Yoon HM, Suh CH, Kim JR, Lee JS, Jung AY, Kim KM, Cho YA JAMA Pediatr . 2017;171(12):1208. 

24. Endoscopic studies Colonoscopy (including ileoscopy ) with biopsies; -Colonoscopy should be performed in pts with suspected IBD, even in the absence of clear lower GI sxs such as bloody diarrhea Upper endoscopy with biopsies

25. Differentiation between CD and UC Usually is accomplished with the combination of endoscopy and imaging of the small bowel If the disease type remains uncertain after complete evaluation, it is provisionally termed IBD-unclassified (IBDU)

26. Cont… Antibody testing; commonest antibody tests are perinuclear antineutrophil cytoplasmic antibodies ( P-ANCA , 60-80% of those with UC compared with 10-27% of adults with CD ) and anti- saccharomyces cerevisiae antibodies ( ASCA, 40-80% of pts with CD )   Have reasonably high sensitivities for detecting IBD (> 90% in populations with sxs ), but their ability to distinguish between UC and CD is not well validated

27. Diagnosis ( Dx ) There are no specific diagnostic criteria for IBD The dx is usually established by the combination of clinical features, c/ cout laboratory abnormalities, coupled with characteristic findings on imaging and endoscopy, including histopathologic analysis Endoscopy and imaging also help to exclude some other causes of the sxs , and usually can distinguish between UC and CD

28. Differential diagnoses Rectal bleeding Rectal beeding + other sxs Anal fissures or hemorrhoids Polyps Meckel's diverticulum Milk protein-induced proctocolitis Enteric pathogens; include   Salmonella ,  Shigell ,   Yersinia ,   E coli ,  Amoeba ,   C. difficile CMV ; ass/c high rate of steroid resistance Intussusception Immunoglobulin A vasculitis   ( IgAV ) Familial Mediterranean fever

29. Management The treatment options depend on the disease location and severity and response to initial therapy 5- ASA ( aminosalicylate ; eg sulfasalazine ) based therapy – mild disease Glucocorticoids – acute attack Immunosupressants ; azathioprine , 6-MP, methotraxate Anti-TNF alpha Antibiotics