Ulcerative Colitis in Children Treatment & Management

Updated: Jul 26, 2019
  • Author: Judith R Kelsen, MD; Chief Editor: Carmen Cuffari, MD  more...
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Treatment

Approach Considerations

The general goals for managing inflammatory bowel disease (IBD) in children are to achieve the best possible clinical and laboratory control of the disease with minimal adverse effects while permitting the patient to function as normally as possible. [15]

Most patients with ulcerative colitis (UC) can be treated on an outpatient basis. Nevertheless, hospitalization is necessary when maximal outpatient therapy is unsuccessful or when patients develop severe disease.

For more information on the general treatment of ulcerative colitis, see Ulcerative Colitis.

See also the Guidelines section for recommendations by the American College of Gastroenterology and the American Gastroenterological Association.

Consultations

For patients presenting with the symptoms of ulcerative colitis, consultations are indicated with a pediatric gastroenterologist and, in more severe cases, a pediatric surgeon.

Long-term monitoring

In children who have chronic inflammatory changes in the pouch reservoir, annual screening endoscopy should be performed. If no inflammation is present, screening endoscopy may be performed every 2 years. [16]

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Treatment of Mild Disease

Mild ulcerative colitis (UC) in the pediatric population can be treated with pharmacotherapy, most commonly anti-inflammatory agents.

5-Aminosalicylic acid

The mainstay of outpatient management is anti-inflammatory therapy with 5-aminosalicylic acid (5-ASA) preparations. [17] Sulfasalazine (Azulfidine) was the first such preparation available for the treatment of UC. More recently, mesalamine (Pentasa, Asacol, Lialda) was introduced. Mesalamine may have fewer adverse effects than sulfasalazine because the sulfa component has been removed; it is not available in a pediatric preparation, however.

Asacol tablets must be swallowed whole, which limits its use in young children. However, Asacol is the only oral product that is approved for children aged 5 years or older.

Asacol's efficacy was evaluated in a 6-week treatment study of two dose levels in 82 pediatric patients aged 5-17 years with mildly to moderately active ulcerative colitis. All patients were divided by weight category (17 to < 33 kg, 33 to < 54 kg, and 54 to 90 kg) and randomly assigned to receive a low dose (1.2, 2.0, and 2.4 g/day for the respective weight category) or a high dose (2.0, 3.6, and 4.8 g/day). Baseline and screening visits were followed by a treatment period of 6 weeks. The high dose was not more effective than the low dose and is not an approved dosage. At week 6, 73.2% of the patients in the low dose group, and 70.0% of the patients in the high dose group achieved success based on the TM-Mayo; 34.1% of the patients in the low dose group and 42.5% of the patients in the high dose group achieved complete response. [18]

Pentasa capsules may be opened so that the granules can be swallowed from a spoon (eg, mixed with applesauce), but this exposes the medicine to degradation high in the gastrointestinal tract—an area that is not affected in UC. Balsalazide (Colazal) is another form of 5-ASA that is active in only the colon.

Lialda uses a multimatrix (MMX) release system, is pH dependent, and includes an expedient that further slows the release of 5-ASA throughout the entire colon.

Rectal therapy may be helpful. Many symptoms of UC, such as urgency and tenesmus, are secondary to rectal disease or left-sided colitis. 5-ASA suppositories alone for ulcerative proctitis and distal proctosigmoiditis are useful in inducing remission, with reported rates as high as 70-80%.

Probiotics as potential treatment

Probiotics are defined as live microbial food products that have beneficial effects on the host. Probiotics have been suggested as potential treatments for numerous digestive disorders; whether they are effective treatments remains controversial, however.

In an investigation of a specific probiotic preparation, subjects in the treatment group achieved a 93% remission rate versus 36% in the control group, with a lower relapse rate at 1 year seen in the treatment group as well (21% vs 73%). [19]

Probiotics may represent an appealing adjunct to other treatments, given their low propensity for side effects.

Probiotics may have a more important role with pouchitis in patients with ulcerative colitis.

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Treatment of Moderate-to-Severe Disease

Acute flares of moderate to severe ulcerative colitis (UC) in the pediatric population tend to respond well to corticosteroids, but numerous adverse effects limit long-term use. Immunomodulatory agents, such as 6-mercaptopurine, are useful in patients who are steroid-dependent or who have disease that is refractory to steroid treatment. These drugs can take up to 3-months to take effect, however, severely limiting their usefulness in acute exacerbations of disease.

Corticosteroids

Corticosteroids (eg, prednisone) are effective in controlling acute flares of disease but long-term use is not desirable owing to numerous adverse effects.

Corticosteroids are known to cause linear growth failure, which may already be a clinically significant problem in the young patient with inflammatory bowel disease. Corticosteroids also cause osteoporosis, which leads to compression fractures of the spine. The many undesirable cosmetic effects of corticosteroids include weight gain, acne, and cushingoid appearance. Steroids may cause agitation and restlessness, as well as personality changes, such as irritability or emotional lability.

Despite the undesirable adverse effects, some patients depend on steroids to keep their disease under control. In other patients, the disease does not respond well to steroids. When a UC patient demonstrates signs of steroid dependence, other treatments should be used to limit the patient's steroid exposure.

Intravenous corticosteroids (eg, methylprednisolone) may be effective in inducing remission when oral steroids are ineffective. Significantly increased efficacy does not appear to occur with doses above 2 mg/kg/d (not to exceed 48 mg/d). High-dose intravenous steroids have the adverse effects of oral steroids and increase the likelihood of hyperglycemia and hypertension.

Immunomodulatory Agents

Immunomodulatory agents are purine analogs that inhibit purine ribonucleotide synthesis and cell proliferation. Immunosuppressive agents also inhibit the immune response of natural killer cells and cytotoxic T cells.

Use immunomodulatory agents, such as 6-mercaptopurine (Purinethol) and azathioprine (Imuran), in patients with inflammatory bowel disorder who are steroid-dependent or whose disease is refractory to steroid treatment. These medications take approximately 3 months to take full effect and, therefore, are not useful in acute exacerbations of disease.

Although immunomodulatory agents are usually well tolerated, they do have the potential adverse effects of pancreatitis, hepatitis, and bone marrow suppression. The pancreatitis is usually an idiosyncratic reaction that is not dose related and that resolves on removal of the drug. The hepatitis appears to be related to the buildup of a metabolite of the medication and may resolve when the dose is adjusted. Bone-marrow suppression is dose related and may have delayed onset.

Monitor patients for leukopenia on a frequent basis early in the course of therapy and then less frequently in the months that follow.

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Treatment of Fulminant Disease

Treatments for fulminant ulcerative colitis (UC) include cyclosporine, tacrolimus, and infliximab.

Cyclosporine

Cyclosporine (cyclosporin A) is a potent inhibitor of the inflammatory cascade that primarily acts by inhibiting interleukin-2 production, though it also decreases the recruitment of cytotoxic T cells and blocks other inflammatory cytokines.

In refractory fulminant UC, cyclosporine has effectively induced remission, obviating immediate surgery. Because cyclosporine is such a potent immunosuppressive agent, the physician must be absolutely certain that an infection is not contributing to the colitis. The patient must also be considered susceptible to opportunistic infections, such as those due to cytomegalovirus and Pneumocystis carinii.

Cyclosporine is nephrotoxic and may cause irreversible renal insufficiency. In addition, cyclosporine is epileptogenic and may precipitate seizures in patients, especially those with low cholesterol or magnesium levels.

Because of its many potential toxicities, cyclosporine should be used only by physicians who are experienced in its administration. In addition, for UC patients, strongly consider surgical colectomy to treat fulminant disease because of the long-term risk of cancer and the curative nature of the surgery.

Tacrolimus

Tacrolimus is a potent inhibitor of T-lymphocyte function, although the exact mechanism is poorly understood. Tacrolimus is primarily used to prolong the survival of transplant grafts. Tacrolimus has shown some anecdotal success in inducing remission and preventing colectomy among UC patients. A review of 18 pediatric patients with UC reported that 17 had a response to tacrolimus, although 11 patients still ultimately required colectomy. [20]

Toxicities such as nephrotoxicity, bone marrow suppression, and neurologic symptoms make tacrolimus use for UC patients controversial. It should only be considered for select patients in whom other options are not possible or not effective.

Infliximab

In September 2011, the US Food and Drug Administration (FDA) approved infliximab for the treatment of UC in children.

Infliximab is a monoclonal antibody against tumor necrosis factor (TNF)-alpha, a proinflammatory cytokine that occurs early in the inflammatory cascade. Infliximab is effective in treating Crohn disease (CD) and has received attention and indications for use in UC patients. [21, 22] The drug is given as an intravenous infusion, typically in an induction regimen of two infusions over 2 weeks. In several reports, refractory UC responded to infliximab, and emergency colectomy was avoided.

In a retrospective series of pediatric patients with UC, 100% of patients were short-term responders to infliximab, with 75% showing complete resolution of symptoms and the remaining 25% showing partial improvement after a median of 6 infusions; 67% were long-term responders after a median of 10.4 months. [23] A better response was noted in patients who were considered steroid-dependent rather than steroid-refractory.

A better response to infliximab infusions was also observed among patients concurrently taking 6-mercaptopurine; the concurrent use of 6-mercaptopurine and infliximab has become more controversial, however, following reports of hepatosplenic T-cell lymphoma in patients with inflammatory bowel disease receiving both medications. Dual therapy has not been proven to be better. Higher levels of infliximab are seen, but dual therapy is not necessarily better.

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Total Proctocolectomy

Historically, surgery has been viewed as definitive therapy for ulcerative colitis (UC). Ileo-pouch anal anastomosis, which is performed in one, two, or three stages, is often curative in patients with UC, alleviating symptoms and removing the risk of colonic adenocarcinoma, whereas surgery is palliative in patients with Crohn disease and pancolitis.

Prior to 1980, total proctocolectomy with end ileostomy or continent (or Koch) ileostomy was the mainstay of therapy. Yet, in the late 1970s, reports of continence-preserving procedures involving ileal pouch–anal anastomosis (IPAA) began to surface. [9, 24] As experience amassed, the procedure was refined, and the IPAA has become the most common operation for UC patients who choose to maintain anal continence.

If colectomy is not performed to control symptoms, the risk of death from colon cancer is about 8% at 10-25 years after colitis is diagnosed. Therefore, surgical removal of the colon is a virtual necessity for most patients with UC. Because the disease is limited to the colon, colectomy is considered a curative procedure. [25, 26]

Approximately 5-10% of patients with UC require acute surgical intervention because of fulminant colitis refractory to medical therapy. In addition, the presence of pancolitis is the strongest predictor of the need for surgery in children.

In a study of 41 children with medically refractory UC who underwent two-stage laparoscopic IPAA between 2004 and 2017 at a single institution, investigators found similar outcomes whether the patients were treated with the traditional approach (an initial total proctocolectomy and creation of an IPAA and diverting stoma, followed by ileostomy closure several weeks later) (TIPPA) or with an alternative approach in which a subtotal colectomy and end ileostomy is performed (NIPAA). [27]  However, children in NIPAA treatment group required significantly fewer prescriptions for antidiarrheal agents.

Contraindications to ileal pouch–anal procedures in children with UC are few. The only absolute contraindication is anal sphincter dysfunction. Preexisting incontinence due to neurologic impairment or other causes makes reservoir construction unnecessary, and it makes ileoanal pull-through inadvisable.

In children, elective colectomy is indicated when refractory disease significantly interferes with their growth and nutrition or with their ability to maintain a normal lifestyle (ie, attend school) or when dysplasia or malignancy is detected.

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Dietary Modifications

Patients with ulcerative colitis should avoid poorly digested foods, such as uncooked vegetables, seeds, nuts, and high roughage, especially patients with stricture or narrowing. Patients with fulminant disease, possible obstruction, or possible toxic megacolon should ingest nothing by mouth until their condition is stable.

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