IBD

Inflammatory bowel disease is a multifactorial disease characterized by chronic inflammation with periods of remission and exacerbation of the GI tract separated into two entities: Crohn’s disease (CD) and ulcerative colitis (UC). Table 1 lists the classic findings/differences found in CD and UC.

Epidemiology

-       Current incidence is ~5-11/100,000 in the US

-       20-25% of new IBD cases are diagnosed in children

-       There is acceleration in incidence in recent years with the most significant increases occurring in children < 9yrs.

-       M:F is 1.5:1 for pediatric CD vs 1:1 in adult CD

-       M:F is 1:1 for pediatric UC, similar to adult UC

-       The ratio of CD:UC is 2.8:1 compared to a ratio of 0.85:1 in adults.

-       Whites > non-whites

-       Jews from eastern Europe have a higher incidence

Etiology

-       The precise cause is unknown.

-       Risk factors include: FH, ethnicity, tobacco use, state of socioeconomic development.

-       Many theories include:

o   The hygiene hypothesis- low microbial exposure early in life leads to less capable immune system later in life, unable to eliminate offending agents causing chronic inflammation

o   Heritable disease- family history is a very strong risk factor for disease

o   Infectious cause- limited evidence, but an entero-adhesive/ invasive strain of E.Coli has been associated with ileal CD.

o   Impaired interaction with gut flora- there is enhanced reactivity against gut bacterial antigens in those with IBD, and some gene mutations associated with IBD code bacterial-sensing proteins.

Clinical Features

            - Intestinal symptoms: characterized by variable and overlapping symptoms

o   The classic triad for UC is abdominal pain, diarrhea and rectal bleeding

o   The classic triad for CD is abdominal pain (often localized to the RLQ), diarrhea and weight loss.

o   Other symptoms especially for UC include-

§  hematochezia

§  fecal urgency

§  low grade/intermittent fevers

§  anorexia

§  anemia,

§  hypoalbuminemia

o   Other symptoms for CD include-

§  growth failure

§   non-bloody to melanotic stool to frank blood in stool

§  recurrent apthous-stomatitis

§  anal disease including tags, fissures, fistulas or abscess

o   Growth Failure- more frequent in CD>UC, often precedes diagnosis

o   Other-

§  nausea/vomiting,

§  pain with defecation,

§  fever without localization

§  clubbing

-       Extra-intestinal manifestations:

o   Joint inflammation- peripheral joints or axial joints (ankylosing spondylitis and sacroiliitis)

o   Cutaneous manifestations- erythema nodusum and pyoderma gangrenosum

o   Ocular disease- episleritis and uveitis- more frequent in CD

o   Osteoporosis

o   Oral apthous stomatitis

o   Primary sclerosing cholangitis- in UC patients

o   Renal stones- classically oxalate stones

o   Pancreatitis

o   Neurologic symptoms include neuropathies, myelopathies, and myasthenia gravis

o   Clubbing

Differential Diagnosis

-       Bacterial enteritis

-       HSP

-       Ischemic bowel

-       Radiation colitis

-       HUS

-       Meckel’s diverticulum

-       Streptococcal infection can mimic peri-rectal disease

-       Mesenteric adenitis

-       Appendicitis

-       Ovarian cyst

-       Lymphoma

-       Gastrointestinal TB

-       Celiac disease

-       Extra-intestinal manifestation—SLE, JRA, collagen vascular disease, infectious etiologies

Diagnosis

1.     Lab studies: CBC with diff, ESR, CRP, LFTs

2.     Exclude infectious etiology with screening stool studies: culture for Salmonella, Shigella, E.coli, Campylobacter, Yersinia; examination for Giardia and Cryptosporidium; assay for C. diff; if history applicable check for Entamoeba histolytica.

3.     Fecal calprotectin (CP) and lactoferrin (FL)- noninvasive markers for gut inflammation

4.     Serology- not recommended for screening or isolated diagnostic tool. Most useful to differentiate UC vs CD in children with indeterminate colitis. Includes:

a.     ASCA( anti-Saccharomyces cerevisiae antibody)

b.     immunoglobin A and G

c.      ANCA (anti-neutrophil cytoplasmic antibody)

d.     histamine protein 1

e.      DNAase-specific

f.      Anti Omp C (outer membrane protein of E. coli) (see Table 1)

5.     Imaging- endoscopy both esophagogastroduodenoscopy and colonoscopy with biopsy sampling is the gold standard: differences seen in imaging and pathology are outlined in Table 1.

Treatments:

-       Steroids- used for induction of remission with a taper given over 2 mo.; budesonide which has significant first pass metabolism is delivered more to distal ileum and proximal colon and has less efficacy in CD and little efficacy for UC compared to other conventional steroids.

-       Nutritional therapy- uses specific elemental or polymeric formulas as primary treatment to induce remission. Has been shown to produce short term remission in 80% of children with CD. May be considered as first line agent in pediatric population with CD, but difficult adherence.

-       5-Aminosalicylates- well tolerated in children with few side effects, but possibly little efficacy compared to placebo in CD for induction of remission. Mild to moderate effect for remission and maintenance in UC.

-       6-MP and azathioprine (AZA)- slow onset of action (3-6mo), used for maintenance of remission in both UC and CD.

-       Methotrexate- often used for induction and maintenance in CD, especially if refractive to 6-MP class or steroids. May be helpful for maintenance in UC if steroid dependent or refractory to other treatments. Subcutaneous injections are more efficacious than oral medication.

-       Cyclosporine- only used as a rescue therapy in severe, refractory UC.

-       Biologics- Infliximab is the first TNF-alpha blocker to be approved for pediatric IBD. It is a chimeric monoclonal IgG antibody that binds TNF-alpha. It shows efficacy for induction and maintenance in both CD and UC, often use is reserved for moderate-severe disease. There have been cases of hepatosplenic T-cell lymphoma often in young males patients taking both infliximab and 6-MP/AZA. Therefore infliximab is not currently used in conjunction with immunomodulators.

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-       Antibiotics- metronidazole and ciprofloxacin are often used for fistula or pouchitis treatment.

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-       Surgery- indications include fulminant colitis, perforation, stricture, absess, fistula, toxic megacolon, failure of medical therapy or steroid dependency, dysplasia, pediatric growth failure or pubertal delay

References:

1. Markowitz, James. Inflammatory bowel disease: The pediatrician's role. Contemporary Pediatrics. May 1996; 25-46.

2. Hanauer, S. Drug Therapy: Inflammatory Bowel Disease. N Engl J Med. 1996; 334: 841-48.

2. Galbraith S et al. Asymptomatic Inflammatory Bowel Disease Presenting With Mucocutaneous Findings. Pediatrics. 2005; 116: e439-e444.

4. Hyams, Jeffrey. Inflammatory Bowel Disease. Pediatrics in Review. 2005; 26: 314–20.

5. Glick S and Carvalho R. Inflammatory bowel disease. Pediatrics in Review. 2011; 32:14-25.

6. Shikhare G and Kugathasan S. Inflammatory bowel disease in children: current trends. J Gastroenterol. 2010; 45:673-82.

7. Sauer C and Kugathasan S. Pediatric Inflammatory bowel disease: highlighting pediatric differences in IBD. Gastroenterol Clin N Am. 2009; 38:611-28.

8. Hanauer, S. Inflammatory Bowel Disease. NEJM Vol. 334, No. 13 March 28, 1996

9. Podolsky D.K. Inflammatory Bowel Disease. NEJM Vol. 347 No. 6 August 8, 2002

10. Sheila S. Galbraith, Beth A. Drolet, Subra Kugathasan, Amy S. Paller, and Nancy B. Esterly
Asymptomatic Inflammatory Bowel Disease Presenting With Mucocutaneous Findings
 Pediatrics 2005; 116: e439-e444
11. Hyams J. Inflammatory Bowel Disease Pediatrics in Review September 200512.

12.Colombo J et al. Getting current on the treatment of inflammatory bowel disease.  Contemporary Pediatrics Oct 2006
13. Mack et al. Laboratory Values for Children with Newly Diagnosis Inflammatory Bowel Disease. Pediatrics June 2007

TABLE 1. Classis findings in Crohn’s disease (CD) and Ulcerative colitis (UC).