Residency · Residency · Pediatrics

Inflammatory Bowel Disease in Children and Adolescents

Overview

Inflammatory bowel disease (IBD) encompasses Crohn disease (CD) and ulcerative colitis (UC). Approximately 25% of IBD patients are diagnosed before age 20, and the incidence in pediatrics is rising. Pediatric IBD tends to be more extensive and aggressive than adult-onset disease. Growth failure is a hallmark of pediatric IBD and may precede gastrointestinal symptoms by years. Inflammatory bowel disease-unclassified (IBD-U) accounts for roughly 10-15% of pediatric cases.

Crohn Disease vs. Ulcerative Colitis

Crohn Disease

Crohn disease can affect any part of the GI tract from mouth to anus, though it most commonly involves the terminal ileum and colon. The inflammation is transmural and characterized by skip lesions, with granulomas present in 30-50% of biopsies. Complications include strictures, fistulas (perianal, enteroenteric, enterovesical), and abscesses. Perianal disease, including skin tags, fissures, and fistulas, is common and may be the presenting feature. Pediatric CD more often demonstrates ileocolonic involvement (L3) and upper GI involvement (L4) compared to adult CD.

Ulcerative Colitis

Ulcerative colitis is limited to the colon, with continuous inflammation starting from the rectum and extending proximally. The inflammation is mucosal and submucosal rather than transmural. Pediatric UC is more often pancolitis (60-80%) compared to adult UC, which is more frequently left-sided. Complications include toxic megacolon, massive hemorrhage, and increased colorectal cancer risk. "Backwash ileitis" may involve the terminal ileum but is superficial.

IBD-Unclassified

IBD-unclassified has features of both CD and UC that cannot be definitively classified. It is more common in pediatric than adult IBD and may declare itself over time. Management typically follows UC guidelines.

Clinical Presentation

GI Symptoms

Children with IBD present with chronic or recurrent abdominal pain and diarrhea (bloody in UC; may be non-bloody in CD). Urgency and tenesmus are characteristic of UC. Perianal disease (tags, fissures, fistulas) and oral ulcers (aphthous stomatitis) suggest CD. Nausea, vomiting, and anorexia are common in both forms.

Extraintestinal Manifestations

Growth failure and pubertal delay may be the only presenting feature, with up to 40% of pediatric CD patients having growth impairment at diagnosis. Arthritis or arthralgia (peripheral or axial) is the most common extraintestinal manifestation. Skin findings include erythema nodosum and pyoderma gangrenosum. Ocular involvement includes uveitis and episcleritis. Primary sclerosing cholangitis is more common in UC. Other manifestations include iron deficiency anemia, osteopenia or osteoporosis, and fever of unknown origin.

<image>Anatomic comparison of Crohn disease (transmural inflammation, skip lesions, terminal ileum and any GI segment involvement, perianal disease) versus ulcerative colitis (mucosal inflammation, continuous from rectum, colon only), with key histologic and endoscopic features of each</image>

Diagnostic Workup

Initial Laboratory Studies

A CBC may reveal anemia (iron deficiency), thrombocytosis, or leukocytosis. ESR and CRP are elevated in active disease, though CRP may be normal in UC. Albumin is low in severe disease from protein-losing enteropathy. Fecal calprotectin is a neutrophil-derived protein and an excellent screening marker: levels above 250 mcg/g are strongly suggestive of IBD, with a sensitivity of approximately 95% for mucosal inflammation. A normal fecal calprotectin essentially excludes active IBD. It is important to note that fecal calprotectin is normally elevated in infants and less reliable in children under age 4.

Serologic Markers

pANCA is positive in roughly 60-70% of UC cases, and ASCA is positive in approximately 50-60% of CD cases. These markers are adjunctive and do not replace endoscopy for diagnosis.

Endoscopy and Histology

Both esophagogastroduodenoscopy (EGD) and ileocolonoscopy with biopsies are required for diagnosis. Pediatric IBD guidelines recommend upper and lower endoscopy at diagnosis regardless of symptoms, given the high rate of upper GI involvement in pediatric CD. Biopsies should be taken from multiple segments, including normal-appearing mucosa. CD is characterized by granulomas and focal or patchy inflammation with transmural features. UC shows continuous crypt distortion, crypt abscesses, and diffuse mucosal inflammation.

Imaging

MR enterography (MRE) is the preferred modality for small bowel evaluation, detecting strictures, fistulas, and active inflammation without radiation exposure. Capsule endoscopy is used for suspected small bowel CD when MRE is inconclusive, with a patency capsule first to assess for stricture. Ultrasound has an emerging role for assessing bowel wall thickening and monitoring disease. CT should be avoided when possible due to radiation exposure concerns in children.

<image>Diagnostic algorithm for pediatric IBD showing initial screening (fecal calprotectin, CBC, CRP, albumin), followed by endoscopic evaluation (EGD and ileocolonoscopy with biopsies), small bowel imaging (MR enterography), and classification into Crohn disease, ulcerative colitis, or IBD-unclassified using Paris classification</image>

Classification

The Paris classification is a pediatric modification of the Montreal classification that categorizes IBD by age, location, behavior (stricturing, penetrating, perianal), growth, and disease extent. It is important for standardized communication and treatment decisions.

Treatment

Induction of Remission

Crohn Disease

Exclusive enteral nutrition (EEN) uses polymeric formula as the sole nutrition for 6-8 weeks. Its efficacy equals that of corticosteroids for inducing remission (approximately 80%) but is superior for mucosal healing and avoids steroid side effects. ECCO/ESPGHAN guidelines prefer EEN as first-line induction in pediatric CD. The main challenge is adherence and palatability, often requiring a nasogastric tube. Corticosteroids (prednisone 1-2 mg/kg/day, maximum 40-60 mg, with taper; budesonide for ileocecal disease) are effective for symptom control but not for mucosal healing and are not appropriate for maintenance due to steroid dependency and growth suppression. Early biologic therapy is increasingly used as first-line induction for moderate-to-severe or high-risk CD.

Ulcerative Colitis

5-ASA (mesalamine) is first-line for mild-to-moderate UC, given orally and/or rectally. Corticosteroids are used for moderate-to-severe UC, with IV methylprednisolone for acute severe colitis (PUCAI score of 65 or greater). Infliximab serves as rescue therapy for steroid-refractory acute severe UC.

Maintenance Therapy

Crohn Disease

Thiopurines (azathioprine 2-2.5 mg/kg/day or 6-mercaptopurine 1-1.5 mg/kg/day) require TPMT/NUDT15 genotyping before initiation due to myelosuppression risk. There is a rare but serious risk of hepatosplenic T-cell lymphoma, especially in young males on combination thiopurine and anti-TNF therapy. Methotrexate (15 mg/m2/week subcutaneously) is an alternative to thiopurines but is teratogenic, requiring mandatory contraception counseling. Anti-TNF biologics (infliximab 5 mg/kg IV every 8 weeks, adalimumab subcutaneously) are highly effective for moderate-to-severe CD and promote mucosal healing. Therapeutic drug monitoring with trough levels and anti-drug antibodies guides dose optimization. Vedolizumab (anti-integrin), a gut-selective agent, is second-line for anti-TNF failure. Ustekinumab (anti-IL-12/23) is approved for adolescents aged 12 years and older with CD.

Ulcerative Colitis

5-ASA is the maintenance therapy for mild-to-moderate UC. Thiopurines are used for steroid-dependent or 5-ASA-refractory disease. Anti-TNF biologics and vedolizumab are options for moderate-to-severe UC. Tofacitinib (a JAK inhibitor) is approved for adults with UC, with pediatric data emerging. Colectomy with ileal pouch-anal anastomosis (J-pouch) is curative for UC and indicated for refractory disease, dysplasia, or fulminant colitis.

Growth and Nutrition

Optimizing nutrition requires caloric supplementation and monitoring of iron, vitamin D, calcium, zinc, and folate. Growth velocity should be assessed at every visit, with bone age assessment if growth failure is present. Achieving mucosal healing and disease control is the most effective strategy for growth recovery. Corticosteroids suppress growth and should be minimized.

<image>Treatment approach for pediatric Crohn disease showing induction options (exclusive enteral nutrition as preferred first-line, corticosteroids, early biologic therapy for high-risk patients) and maintenance options (thiopurines, methotrexate, anti-TNF biologics, vedolizumab, ustekinumab) with emphasis on steroid-free remission and mucosal healing as treatment targets</image>

Monitoring

Standardized disease activity scores include the Pediatric Crohn Disease Activity Index (PCDAI) and Pediatric Ulcerative Colitis Activity Index (PUCAI). Fecal calprotectin correlates with mucosal inflammation and is useful for non-invasive monitoring. Endoscopic reassessment is recommended within 6-12 months to confirm mucosal healing. Therapeutic drug monitoring for biologics (trough levels and anti-drug antibodies) guides dose optimization. Cancer surveillance colonoscopy should begin 8-10 years after diagnosis for pancolitis.

Clinical Pearls

Growth failure may be the only presenting sign of Crohn disease in a child, so growth curves should always be plotted and IBD considered in any child with unexplained weight loss or linear growth deceleration. Fecal calprotectin is an excellent non-invasive screening test, and a normal value essentially rules out active IBD. Exclusive enteral nutrition is as effective as steroids for inducing remission in pediatric CD with fewer side effects and should be the first-line induction therapy. Perianal disease (tags, fissures, fistulas) in a child or adolescent should prompt evaluation for Crohn disease. Steroid-free remission and mucosal healing are the treatment targets, not just symptom control. TPMT/NUDT15 genotyping must be performed before starting thiopurines to avoid life-threatening myelosuppression.

Key Controversy: Early Top-Down Biologic Therapy vs. Step-Up

The traditional step-up approach starts with 5-ASA or thiopurines and escalates to biologics only if refractory. The top-down approach initiates early biologic therapy (anti-TNF) at diagnosis for moderate-to-severe or high-risk disease. Evidence from the REACT and CALM trials in adults shows that early combined immunosuppression leads to higher remission rates, better mucosal healing, and fewer complications. Growing pediatric data support early biologic therapy, especially for patients with high-risk features such as deep ulcers, extensive disease, perianal disease, and growth failure. Counterarguments include cost, infection risk, rare malignancy (hepatosplenic T-cell lymphoma with thiopurine plus anti-TNF), and the fact that some patients do well with conventional therapy. The current trend in pediatric IBD is moving toward earlier biologic use, personalized risk stratification, and therapeutic drug monitoring to optimize outcomes.

References

• Rosen MJ, et al. Inflammatory Bowel Disease in Children and Adolescents. JAMA Pediatr. 2015;169(11):1053-1060.
• Ruemmele FM, et al. Consensus Guidelines of ECCO/ESPGHAN on the Medical Management of Pediatric Crohn's Disease. J Crohns Colitis. 2014;8(10):1179-1207.
• Turner D, et al. Management of Paediatric Ulcerative Colitis (ECCO/ESPGHAN Guidelines). J Pediatr Gastroenterol Nutr. 2018;67(2):257-291.
• Colombel JF, et al. Effect of Tight Control Management on Crohn's Disease (CALM Study). Lancet. 2018;390(10114):2779-2789.
• Hyams JS, et al. Clinical Outcome of Infliximab in Pediatric Crohn's Disease (REACH Trial). Inflamm Bowel Dis. 2007;13(12):1534-1540.
• Levine A, et al. Pediatric Modification of the Montreal Classification for IBD: The Paris Classification. Inflamm Bowel Dis. 2011;17(6):1314-1321.

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