Pediatric Crohn Disease Treatment & Management

The general goals of treatment for children with Crohn disease are as follows:

• To achieve the best possible clinical, laboratory, and histologic control of the inflammatory disease with the least adverse effects from medication
• To promote growth with adequate nutrition
• To permit the patient to function as normally as possible (eg, in terms of school attendance and participation in activities)

Treatment has changed over the past few years, reflecting the development of new agents that can target specific locations in the gastrointestinal (GI) tract and specific cytokines.

Step-up approach

Typically, therapy for pediatric Crohn disease is administered in a step-up approach. Patients with mild disease are treated with preparations of 5-aminosalicylic acid (5-ASA), antibiotics, and nutritional therapy. If no response occurs or if the disease is more severe than was initially thought, corticosteroid and immunomodulatory therapy with 6-mercaptopurine (6-MP) or methotrexate (MTX) is attempted. Finally, biologic and surgical therapies, at the tip of the treatment pyramid, are used.

Some adult data support the use of biologic therapy earlier in the course of disease (ie, a top-down approach) as a more effective treatment method.^[10] A small, retrospective pediatric trial also supported the use of a top-down approach, but prospective pediatric data are needed.^[11]

Patients and their families frequently use alternative and complimentary therapies. A potential beneficial effect has been observed with the omega-3 fatty acids found in fish oil. Probiotics might provide some treatment benefit, although studies have yielded inconsistent results.

5-Acetylsalicylic acid

Although oral 5-ASA preparations are commonly used, adult meta-analyses suggest that these preparations do not have a clinically important treatment effect on active Crohn disease and are not superior to placebo for the maintenance of remission in Crohn disease.^[12] Topical 5-ASA therapy is available in suppository and enema forms for the treatment of distal colitis.

Antibiotics

A few small studies have shown the usefulness of antibiotic therapy in the treatment of Crohn disease. Metronidazole, as well as the combination of metronidazole and ciprofloxacin, is useful in the management of perianal disease and of small bowel and colonic disease.

Nutritional therapy

Nutritional therapy is another important modality for the treatment of disease, malnutrition, and growth failure in Crohn disease.^[13] A dramatic reversal of malnutrition and a change in growth velocity can be expected in all children treated with adequate nutrition in conjunction with medical therapy to control symptoms of Crohn disease. Additionally, exclusive enteral nutrition has been shown to be as effective as corticosteroids for the induction of remission and might promote better GI tract mucosal healing.^[14]

Because most patients have appetite suppression, overnight nasogastric feedings are often used. Although the exact mechanism of action is unknown, the beneficial effects of this approach could be due to alteration of the intestinal flora, a decrease in the antigen load, and reductions in inflammatory cytokine levels.

Corticosteroids

Corticosteroids are the mainstay of therapy for acute exacerbations because they suppress acute inflammation, thereby providing rapid symptomatic relief. Systemic corticosteroids are not indicated for maintenance therapy. Enteric coated ileal-release preparations have been developed for the treatment of ileal and cecal Crohn disease; systemic effects are decreased with these formulations.

Immunomodulators

Immunomodulators have been used to induce and maintain long-term remission in chronically active, steroid-dependent or steroid-refractory, moderate-to-severe pediatric Crohn disease.

6-Mercaptopurine (6-MP) and its prodrug, azathioprine, are effective for the induction and maintenance of remission and the reduction of corticosteroid exposure in pediatric Crohn disease. Three months is often required to achieve therapeutic efficacy, although the onset of action varies.

Thiopurine methyltransferase (TPMT) activity should be measured before the initiation of therapy to identify patients predisposed to altered drug metabolism (which increases the risk of leukopenia). Measurement of 6-thioguanine nucleotide (6-TG) metabolites is helpful in assessing compliance and adjusting therapy.

MTX is effective in inducing and maintaining remission in chronic Crohn disease in adults and has been shown to be effective and well tolerated for maintenance of remission in children.^{[15, 16, 17, 18]} MTX has a quicker onset of action than 6-MP does, and the once-weekly dosing is sometimes preferred. Whether oral therapy is as effective as parenteral administration is unclear.

Infliximab, a chimeric monoclonal antibody to tumor necrosis factor (TNF)-α, is effective in patients who have an inadequate response to conventional therapy and in patients who have fistulizing Crohn disease.^[19] It has been approved for the treatment of pediatric Crohn disease. Current clinical practice is to give infliximab in an intravenous (IV) infusion of 5 mg/kg at 0 weeks, 2 weeks, and 6 weeks, followed by maintenance IV infusions every 8 weeks.

The most common adverse events to infliximab therapy are acute and delayed infusion reactions associated with the formation of antibodies to infliximab (ATI), which occur in 16-39% of children. Premedication does not seem to prevent infusion reactions; however, after an infusion reaction occurs, premedication may be indicated to prevent subsequent infusion reactions.^[20]

Adalimumab, a fully humanized anti–TNF-α antibody, is a safe and effective substitute for patients who are allergic to infliximab or develop high titers of human antichimeric antibodies (HACA).^[21] One prospective multicenter study demonstrated that adalimumab is effective for induction and maintenance of remission for pediatric crohn disease, and is well tolerated by children.^[22]

One area of concern with the use of these medications is that multiple patients have been reported to develop a rare hepatosplenic T-cell lymphoma when treated with dual therapy consisting of 6-MP or azathioprine with a TNF-α inhibitor. Although this has been a rare complication, all reported cases have been in adolescents and young adults.

Surgery is considered when medical therapy fails.^[23] Indications include intractable disease with growth failure, obstruction or severe stenosis, abscess requiring drainage, perianal fistulae, intractable hemorrhage, and perforation.

Recurrence of disease at the anastomotic site is common after resection. Surgical treatment for Crohn disease, unlike that for ulcerative colitis (UC), is not curative. Laparoscopic techniques are becoming the standard of care for most inflammatory bowel disease (IBD) procedures, resulting in decreased recovery time.^[24]

Crohn disease is a chronic disease that must be treated by a team of experts consisting of pediatricians, pediatric gastroenterologists, psychologists, nutritionists, social workers, and nurses. A critical factor in successful management of this disease is the willingness of the patient to participate and cooperate with the team.

For effective treatment of this disorder, parents and patients must be appropriately educated (see Patient Education) and receive the necessary support.

To prevent intestinal obstruction, patients are advised to avoid food that is difficult to digest because it is rich in insoluble fiber (eg, uncooked vegetables, popcorn, seeds, and nuts). Such obstruction may be due to narrowing or stricture secondary to the inflammation in the small intestine. No other empiric dietary restrictions are recommended, though patients are generally advised to avoid any foods that tend to exacerbate their disease.

Besides being used for treatment of mild and moderate-to-severe disease and maintenance of remission, nutritional therapies are used for nutritional rehabilitation. In addition to the beneficial nutritional effects, the formula is thought to have anti-inflammatory properties.

A goal of therapy for Crohn disease is to allow normal unrestricted activity. Patients with osteoporosis secondary to prolonged corticosteroid therapy should avoid high speed and high impact contact sports to minimize the risk of fracture.

Most patients with presumed Crohn disease can undergo outpatient diagnostic evaluation. Patients should be examined on a regular basis. The frequency depends on the severity and activity of their disease. Follow-up laboratory workup should be performed regularly to monitor the safety and success of therapy.

Patients with an exacerbation of Crohn disease can be treated on an outpatient basis; however, if a serious complication of Crohn disease (eg, obstruction, perforation, abscess, or hemorrhage) becomes a concern or if the patient fails outpatient treatment, IV therapy (eg, with corticosteroids, antibiotics, or total parenteral nutrition) may be required and hospitalization warranted.