eMedicine Specialties > Pediatrics: General Medicine > Gastroenterology

Ulcerative Colitis: Treatment & Medication

Author: Jonathan E Markowitz, MD, Associate Professor of Clinical Pediatrics, University of South Carolina School of Medicine; Attending Pediatric Gastroenterologist, Associate Director of Pediatric Residency Program, Greenville Hospital System
Coauthor(s): Petar Mamula, MD, Assistant Professor, Department of Pediatrics, Division of Gastroenterology and Nutrition, The Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine; Robert Baldassano, MD, Director, Center for Pediatric Inflammatory Bowel Disease, Division of Gastroenterology and Nutrition, Associate Professor, Department of Pediatrics, The Children's Hospital of Philadelphia, University of Pennsylvania; David A Piccoli, MD, Chief of Pediatric Gastroenterology, Hepatology and Nutrition, The Children's Hospital of Philadelphia; Professor, University of Pennsylvania School of Medicine; Liz D Dancel, MD, Resident, Department of Pediatrics, Greenville Hospital System University Medical Center
Contributor Information and Disclosures

Updated: Sep 11, 2009

Treatment

Medical Care

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 the least adverse effects while permitting the patient to function as normally as possible.

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

• 5-Aminosalicylate (5-ASA)
  • The mainstay of outpatient management is anti-inflammatory therapy with 5-ASA preparations.²
  • Sulfasalazine (Azulfidine) was the first 5-ASA preparation available for the treatment of UC.
  • More recently, mesalamine (Pentasa, Asacol) was introduced. Mesalamine may have fewer adverse effects than sulfasalazine because the sulfa component has been removed. However, mesalamine is not available in a pediatric preparation.
  • Asacol tablets must be swallowed whole, which limits its use in young children.
  • 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 GI tract not affected in UC.
  • Balsalazide (Colazal) is another form of 5-ASA that is active in only the colon.
• Probiotics
  • 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; however, whether they are effective treatments remains controversial.
  • A recent trial of a specific probiotic preparation has shown promise in the treatment of children with UC. In a randomized, placebo-controlled trial, subjects in the treatment group achieved a 93% remission rate versus 36% in the control group, with a lower relapse rate at one year seen in the treatment group as well (21% vs 73%).³  
  • Probiotics may represent an appealing adjunct to other treatments given their low propensity for side effects.
• Corticosteroids
  • Corticosteroids (eg, prednisone) are effective in controlling acute flares of disease but less effective at maintaining long-term remission, and numerous adverse effects make their long-term use undesirable.
  • Corticosteroids are known to cause linear growth failure, which can be a clinically significant problem in the patient with IBD. Corticosteroids cause osteoporosis, which can also be a problem, 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 patient with UC demonstrates signs of steroid dependence, other treatments should be used to limit the patient's steroid exposure.
• 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 IBD who are steroid dependent or whose disease is refractory to steroid treatment. These medications take approximately 3 months to have 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 so later on.
• Intravenous corticosteroids
  • 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.
• Cyclosporine
  • Cyclosporine (cyclosporin A) is a potent inhibitor of the inflammatory cascade that primarily acts by inhibiting interleukin (IL)-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 (CMV) 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, only physicians who are experienced in its administration should use cyclosporine. In addition, for patients with UC, 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 patients with UC.
  • A recent review of 18 pediatric patients with UC reported that 17 had a response to tacrolimus, although 11 patients still ultimately required colectomy.⁴
  • Toxicities such as nephrotoxicity, bone marrow suppression, and neurologic symptoms make tacrolimus use for UC controversial. It should only be considered for select patients in whom other options are not possible or not effective.
• Infliximab
  • 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 recently received attention and indications for use in UC.⁵
  • The drug is given as an intravenous infusion, typically in an induction regimen of 2 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, 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.⁶ 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; however, the concurrent use of 6-mercaptopurine and infliximab has become more controversial following reports of hepatosplenic T-cell lymphoma in patients with IBD receiving both medications.

Surgical Care

If colectomy is not performed to control symptoms, the risk of death from colon cancer is about 8% 10-25 years after colitis is diagnosed. Therefore, surgical removal of the colon is a virtual necessity for most patients with UC. Because UC is limited to the colon, colectomy is considered a curative procedure.^7,8

• Approximately 5-10% of patients with UC require acute surgical intervention because of fulminant colitis refractory to medical therapy.
• 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.
• The most common procedure is the ileo-pouch anal anastomosis, in which an ileal pouch is connected to the anus to maintain continence.

Consultations

• Pediatric gastroenterologist
• Pediatric surgeon

Diet

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

Activity

The goal of therapy is to allow normal, unrestricted activity.

Medication

Anti-inflammatory agents

These drugs are used to maintain remission and to induce remission of mild flares of disease.

Mesalamine (Asacol, Pentasa, Rowasa)

DOC to maintain remission. Controlled-release cap (Pentasa) or enteric-coated tab (Asacol). Begin with low dose and increase if adverse effects (eg, headache, diarrhea) do not develop. Also available as enema or supp for rectal administration. The currently approved PO mesalamine products in the United States differ only in the mechanism of drug delivery. Asacol has mesalamine within a Eudragit-S coating that dissolves and releases the mesalamine at pH 7, which typically occurs in the terminal ileum. Pentasa is 5-ASA in ethylcellulose and has a time-release coating. Its release begins at the pylorus. Rectal dosage forms deliver high concentrations of mesalamine to the left colon as high as the splenic flexure (enema with 30 min retention) or to the rectum for use in proctitis (supp). Although effective, associated with relatively high relapse rate upon discontinuation.

Balsalazide (Colazal)

Prodrug converted into 5-aminosalicyclic acid through bacterial azoreduction. Metabolites of drug may decrease inflammation by blocking production of arachidonic acid metabolites in colon mucosa.

Immunosuppressive agents

These drugs are used in steroid-refractory or steroid-dependent patients.

6-Mercaptopurine (Purinethol)

Purine analog that inhibits purine ribonucleotide synthesis and cell proliferation. Alters immune response through effects on natural killer cells and cytotoxic T cells.

Azathioprine (Imuran)

Rapidly converted to 6-mercaptopurine in vivo. Antagonizes purine metabolism and inhibits synthesis of DNA, RNA, and proteins. May decrease proliferation of immune cells, which lowers autoimmune activity.

Cyclosporine (Sandimmune, Neoral)

Also called cyclosporin A. Used to treat severe colitis refractory to corticosteroids. Must strongly consider surgical colectomy. May cause irreversible nephrotoxicity, seizures, and opportunistic infections.

Corticosteroids

These drugs are used to induce the remission of acute exacerbations.

Prednisone (Deltasone, Orasone) or methylprednisolone (Solu-Medrol)

Used for short-term exacerbations. Direct effect on inflammation includes decreased release of inflammatory cytokines; inhibition of phospholipase, which, in turn, inhibits arachidonic acid liberation from membranes; and inhibition of neurofibromatosis (NF)–kappa-beta function.

TNF inhibitors

TNF is a cytokine; 2 forms with similar biologic properties have been identified. TNF-alpha, or cachectin, is produced predominantly by macrophages. TNF-beta, or lymphotoxin, is produced by lymphocytes. TNF is but one of many cytokines involved in the inflammatory cascade that may contribute to symptoms.

Infliximab (Remicade)

Neutralizes cytokine TNF-alpha and inhibits its binding to TNF-alpha receptor. Mix in 250 mL 0.9% NaCl and infuse IV over 2 h. Must use with low-protein-binding filter (1.2 µm or smaller). Indicated to reduce signs and symptoms, induce and maintain clinical remission and mucosal healing, and eliminate corticosteroid use in adults with moderate-to-severe active UC who have had an inadequate response to conventional therapy. Not yet FDA-approved for children with UC but approved in pediatrics for CD.

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