for learning purpose

1. Inflammatory bowel disease in children
Dr Pendo Chaula
Mmed 3

2. Layout
• Introduction
• Definition
• Classification
• Epidemiology
• Pathophysiology
• Risk factors
• Clinical features
• Investigations
• Diagnosis
• Diferretial diagnosis
• Treatment

3. • Inflammatory bowel disease (IBD) is an idiopathic disease caused by a
dysregulated immune response to host intestinal microflora
• There is a genetic predisposition for IBD, and patients with this condition are more
prone to the development of malignancy
• It comprised of two major disorders which are ulcerative colitis (UC) and Crohn
disease (CD)

4. • UC affects the colon and is characterized by inflammation of the mucosal
layer, whereas CD can involve any component of the gastrointestinal tract from
the mouth to the perianal area and is characterized by transmural inflammation
• Both have distinct pathologic findings although approximately 10%-15% of
patients cannot be classified definitively into either type (indeterminate colitis)
and their pathogenesis is poorly understood
• It may present at any age with a peak incidence in adolescents and young
adults also they have waxing and waning intensity and severity

5. Classification of IBD

8. Ulcerative colitis
• Is a chronic inflammatory condition characterized by relapsing and remitting
episodes of inflammation limited to the mucosal layer of the colon
• It almost invariably involves the rectum, and the extent often involves more
proximal portions of the colon in a continuous fashion
• It is classified according to severity as a mild, moderate, or severe disease but also
depending on the clinical parameters, practice guidelines stratify patients into
either a low- or high-risk category by assessing the inflammatory status

9. Crohn disease
• It is characterized by transmural inflammation and by skip areas of involvement
(ie, segments of normal-appearing bowel interrupted by areas of disease)
• Transmural inflammatory nature of Crohn disease may lead to fibrosis, strictures
and obstructive clinical presentations that are not typically seen in patients with
ulcerative colitis but also it can result in sinus tracts, giving rise to
microperforations and fistula formation
• Crohn disease most commonly involves the ileum and proximal colon; however,
any part of the gastrointestinal tract may be affected

11. Difference between crohn disease and
ulcerative colitis

12. Epidemiology
• Rare under the age of 5 years but have been reported as early as infancy
• IBD can present at any age, 5-10% of pts develop during childhood or adolescent
• UC m>f while CD f>m

13. Cont..
• Both are more common in Jewish compared with non-Jewish populations
• Incidence of IBD is lower in Hispanic populations and Black populations
compared with White populations
• Prevalence of IBD has been increasing globally with variations by geographic
region

14. Cont..
• The incidence of pediatric IBD has been rising
• Infants with IBD are more likely to have single gene defects that alter immune
function and often have more severe disease course
• Children with IBD have rapid clinical progression, present with extensive
intestinal involvement and are more likely to have family hx of IBD as compared
to adults

15. ETIOLOGY
• Deffective immune regulation
• Genetic mutations
• Exogeneous factors

16. RISK FACTORS
• Smoking
• Physical activity-Physical activity has been associated with a decrease in risk of
Crohn disease, but not ulcerative colitis
• Sleep duration — Sleep deprivation has been associated with an increased risk of
incident ulcerative colitis and of disease flares in patients with IBD

17. • Dietary factors
i. Fiber – High intake of dietary fiber, particularly from fruit and cruciferous
vegetables, has been associated with a decrease in risk of CD but not UC
ii. Fats – Increase intake total fat, animal fat, and polyunsaturated fatty acids has
been correlated with an increased incidence of UC and CD and relapse in
patients with UC though higher intake of omega-3 fatty acids and a lower intake
of omega-6 fatty acids has been associated with a lower risk of developing CD
iii. Vitamin D – Data suggest that vitamin D intake is inversely associated with risk
of CD and that vitamin D deficiency is common among patients with IBD

18. • Infection and the immune response
i. No specific pathogen has been identified to cause IBD
ii. Gastroenteritis-An increased risk of developing IBD was also found in a
population-based cohort study of 13,148 patients with documented Salmonella
or Campylobacter gastroenteritis when compared with a matched control group
(1.2 versus 0.5 percent),
iii. Other infectious pathogens are like mycobacteria, viruses and fungi

19. • Medications
i. Antibiotics —antibiotic exposure was associated with an increased risk of CD
but not UC
ii. NSAIDs —Cyclooxygenase-mediated disruption of the intestinal epithelial
barrier associated with NSAID use can affect the interaction between the gut
microbiome and immune cells in the intestine lining, NSAIDs alter platelet
aggregation, the release of inflammatory mediators, and
microvascular response to stress
iii. Isotretinoin

20. • Other factors
i. Appendectomy — The relationship between appendectomy and IBD depends on
whether the diagnosis is Crohn disease or ulcerative colitis
ii. Psychological factors –stress
iii. Obesity –accumulation of intra-abdominal fat may contribute to mucosal
inflammation, thereby affecting the clinical course in patients with established
IBD

21. Pathophysiology of IBD
• Full understanding of IBD pathogenesis is unclear, It involves;
i. Immune response dysregulation (Th17-IL17,TNF)
ii. Abnormal gut microbiota
iii. Environmental factors
iv. Genetic factors

25. Clinical presentations
• GI symptoms-diarrhea, bloody stools, abdominal pain, or tenesmus.
• Growth failure (C D)
• Systemic symptoms – Fever and fatigue are common at presentation
and during flares of disease
• Colitis-usually presents as a subacute illness (diarrhea that almost
always contains blood, fatigue, anemia, and sometimes weight loss)

26. Physical examination
• Physical findings – Abdominal tenderness and/or mass (especially in the right
lower quadrant), perianal disease (fistulae, anal skin tags, or fissures, or occult
blood in stool)
• Extraintestinal manifestations – Oral ulcerations (eg, aphthous stomatitis),
clubbing, rash (erythema nodosum or pyoderma gangrenosum), eye inflammation
(uveitis), jaundice or hepatomegaly, or arthritis
• Growth failure

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

28. Diagnosis
• Diagnostic evaluation of IBD involves 5 steps (first 2 G. pedi, 3Ped
gastro)
• Clinical suspicission of the illness based upon clinical symptoms,
screening laboratory data
• Exclussion of other illnesses that have similar presentation
• Differentiation between CD and UC
• Localization of the region of the disease
• Indentification of extraintestinal manifestations

29. Laboratory investigation
Blood tests
• FBP-Anemia (Hb <11g/dl), increased white blood cell, and platelet count
• Elevated erythrocyte sedimentation rate (ESR) (65-75% pts at dx) or C-
reactive protein (CRP) (85% at dx)
These markers are somewhat more sensitive for detecting CD than UC
CRP is more sensitive than ESR
• Depressed albumin level – (approx 40% pts with IBD)

30. 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 percent of
children with UC and 9 percent of children with CD

31. Stool tests
Gross or occult blood – Bloody stool is a presenting feature in at least 80 percent of
patients with UC and 40 percent of those with CD
If IBD is suspected but there is no history of gross rectal bleeding, a stool guaiac test
may be useful
Fecal calprotectin – elevated in inflammatory intestinal diseases and may be useful
for distinguishing inflammatory gastrointestinal disease including IBD from
noninflammatory causes of chronic diarrhea (such as functional abdominal pain)

32. However, the test characteristics vary depending on the prevalence of IBD in the
study population
High prevalence of IBD, such as a gastroenterology clinic, elevated fecal
calprotectin (eg, >200 mcg/g) is useful for identifying patients 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

33. By contrast, in settings with a low prevalence of IBD, such as a primary care setting,
fecal calprotectin is more useful to rule out IBD (ie, if fecal calprotectin is normal
[eg, <50 mcg/g], then IBD is unlikely)
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
Fecal lactoferrin

34. Fecal lactoferrin – Fecal lactoferrin has also been utilized to differentiate IBD from
non-inflammatory gastrointestinal conditions
Fecal leukocytes – Compared with fecal calprotectin and lactoferrin, fecal
leukocytes have considerably lower specificity and sensitivity for detecting
inflammatory diarrhea

35. Other tests
• Stool testing for enteric pathogens (ova, parasite testing, clostridium difficile and
culture)
• Tuberculosis screening (interferon gamma testing or tuberculin skin test)
• Titres for varicella and measles
• HBV serologies
• HIV
• Lactose/glucose hydrogen breath test for lactose intolerance

36. Endocopic studies
• Upper endoscopy (including ileoscopy) with biopsies
• Colonoscopy
We suggest both colonoscopy and upper endoscopy for patients with suspected IBD,
even in the absence of clear lower gastrointestinal symptoms such as bloody
diarrhea

37. Radiographic studies
For localization of small bowel disease, one of the following:
• Magnetic resonance enterography (MRE) – MRE is the preferred small bowel
imaging modality in children,
-sensitivity of 83 percent and a specificity of 93 percent
-It aslso provides information about extraintestinal findings (eg, intraabdominal or
perianal fistula or abscess, liver disorders, renal problems, and bone disease)
• Computed tomography enterography (CTE) – CTE (CT of the abdomen with oral
contrast

38. • Ultrasonography — used for small bowel imaging of IBD at some centers
Sensitivity 76%, specificity 92% are highly dependent on the experience of the
operator

39. • 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%-*0% of pts with CD)
• Have reasonably high sensitivities for detecting IBD (>90% in populations with
symptoms) but their ability to distinguish between UC and CD is not well
validated

40. Diagnosis
There are no specific diagnostic criteria for IBD
The diagnosis of IBD is usually established by the combination of clinical features,
with or without 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 symptoms,
and usually can distinguish between UC and CD

41. Very early-onset inflammatory bowel disease
IBD that becomes symptomatic or is diagnosed before six years of age
Infantile IBD occurs before two years of age and are more likely to have monogenic
IBD and often have a more severe disease course
Clinical features that raise suspicion for monogenic IBD include;
Young age of onset (eg, <6yrs particularly < 2yrs)
Family history of IBD and/or immunodeficiency in multiple family members,
particularly with male predominance, or consanguinity

42. Recurrent infections or unexplained fever
Associated features of autoimmunity (eg, arthritis, sclerosing cholangitis, anemia,
or endocrine dysfunction)
Very severe IBD, complex fistulizing disease, and/or resistance to conventional
therapies for IBD

43. Symptoms or signs suggesting hemophagocytic lymphohistiocytosis (hepatomegaly,
fever, cytopenias, high ferritin) (see "Clinical features and diagnosis of
hemophagocytic lymphohistiocytosis")
Lesions of the skin, nails, or hair
Current or past history of cancer in the patient
Endoscopic biopsies with tissue eosinophilia, villous flattening (without evidence of
celiac disease)

44. Infants or young children presenting with these features warrant careful evaluation
for monogenic IBD and consultation with an immunologist
Genetic sequencing is recommended for every child with IBD onset under age two
years and also suggested for children under age six
Important causes of monogenic IBD include defects in interleukin-10 (IL-10)
signaling, atypical severe combined immunodeficiency, common variable
immunodeficiency, chronic granulomatous disease and other neutrophil defects,
Wiskott-Aldrich syndrome, agammaglobulinemia, hyperimmunoglobulin M
syndrome, familial hemophagocytic lymphohistiocytosis, and IPEX (immune
dysregulation, polyendocrinopathy, enteropathy, X-linked) or other autoimmune
enteropathy

45. Differential diagnosis
Rectal bleeding Rectal bleeding and other symptoms
• Anal fissures or hemorrhoids
• Polyps
• Meckel’s diverticulum
• Milk protein-induced proctocolitis
• Enteric pathogens;
Include Salmonella, Shigella, Yersinis, E coli,
Amoeba, C difficile
• CMV; ass/c high rate of steroid resistance
• Intussusception
• Immunoglobulin A
• Vasculitis (IgAV)
• Familial Mediterranean fever

46. Management
• Management option depends 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