Treating Children and Adolescents

For the most part, the treatment approaches for children with IBD are based on adult experience. Children require individualized treatment that takes numerous factors into account: the specific disease manifestations (location of inflammation in the intestines, duration, prior response to therapy), the psychosocial adaptation of the child and family, and the child's age and size. Drug dosages also must be tailored, based upon the child's weight.

Children and adolescents are moving through a period of physical and emotional growth and development. Special consideration must be given to potential side effects and to issues of compliance with the prescribed treatment regimen. Regrettably, few well-designed clinical trials have generated data that specifically address the effectiveness of standard medications in children. However, the safety profile of these drugs has been supported by many years of use in pediatric clinical practice. Recently, the FDA mandated that the safety and effectiveness of new drugs be established in children and adolescents. Therefore, we anticipate that the number of studies of medications in the pediatric population will be dramatically increasing.

All of the medications used for adults with IBD are also used for children, and the indications and contraindications are similar. This section attempts to address the special considerations when the medications described above are prescribed for children and teenagers.

Aminosalicylates

For treating mild-to-moderate, active ulcerative colitis and Crohn's colitis in children, 5-aminosalicylate (5-ASA) compounds remain the initial therapy in most cases. Although sulfasalazine clearly is effective, its use has generally declined in favor of mesalamine and olsalazine products, which have fewer side effects. Side effects from sulfasalazine may include headache, sun sensitivity rash, or other signs of sulfa allergy.

5-ASA may be taken rectally or orally. The dosages for a child are extrapolated on a per-kilogram basis from data in adults. The number of pills required (as many as 10-16 per day), and the frequency of administration for effectiveness (3-4 times per day) makes compliance with Asacol,® Colazal,™ or Pentasa® difficult for young patients. The dosage schedule will have to be carefully considered in light of the child's schedule: Should a dose be included or excluded during the school day? Parents may want to involve the child in this decision to aid compliance.

Special consideration must be given to the younger child who is unable to swallow tablets or capsules. Although a commercially available form of liquid sulfasalazine is no longer available, many pharmacies will formulate one if requested. Additionally, Pentasa capsules may be opened and the contents placed in yogurt or peanut butter.

For the child or adolescent with left-sided colonic inflammation, topical therapy with a 5-ASA suppository or enema often helps and has minimal potential side effects. Enema therapy may be a daunting prospect at first, but with education, support, and guidance, many patients and families adapt readily to this treatment.

Corticosteroids

• Topical treatment
  In the child with mild-to-moderate, active ulcerative colitis with symptoms predominantly of left-sided colitis (tenesmus, a persistent urge to empty the bowel; urgency), rectal preparations of corticosteroids (foam, enema) are often prescribed, along with oral 5-ASA compounds. When tenesmus and urgency are particularly severe, foam may be tolerated better than cortisone enema preparations.
  
  
• Oral and parenteral treatment
  When mild-to-moderate, active ulcerative colitis or Crohn's disease do not improve, oral corticosteroids are prescribed on an outpatient basis. Dosages are determined on a per-kilogram basis. Often, sulfasalazine or mesalamine will be continued, in addition to steroids. Once again, the indications and dosages of corticosteroids for children who are more significantly ill and admitted to the hospital are similar to those in adults. Intravenous corticosteroids are administered at the hospital. Once remission is induced, the corticosteroid dosage is tapered gradually, with the goal of discontinuing this therapy altogether. Less commonly, with "steroid-dependent" disease (symptoms that respond only to steroid therapy), small dosages are given daily or every other day.
  
  
• Side effects
  The cosmetic side effects of corticosteroids may be disturbing to the child and overwhelming to the adolescent, and may lead to poor compliance. Unwelcome side effects may include facial swelling, excessive weight gain, hair growth, and acne. Fortunately, these are temporary conditions that disappear when the dose is lowered or the medication discontinued. Less commonly, high-dose steroid therapy may produce "stretch marks." The puffiness that accompanies steroid therapy can be reduced to some degree by lowering the child's salt intake.

As in adults, the list of potential side effects of long-term steroid usage in children is extensive. Some of the complications—such as mood swings or personality change and high blood pressure—are most likely related to the higher dosages prescribed. (These complications probably are more common in, although not exclusive to, adults.) In children, failure to grow and a decreased supply of the necessary minerals used to build strong bones (bone mineralization) are difficult problems that occur with long-term steroid therapy. If the disease is severe enough to require long-term steroid therapy, alternate-day therapy appears to lessen the impact on growth.

To minimize the risk of osteoporosis, it is important to ensure adequate calcium intake in all IBD patients. For patients on chronic steroid therapy or those with chronically active IBD, physicians may recommend a DEXA scan (a special X-ray) to evaluate bone mineral density. Osteonecrosis (bone deterioration) of the hip, although a recognized complication of steroid therapy in adults, is seldom a problem in children or adolescents.

One possible complication of steroid (or other immunosuppressive) therapy is seldom mentioned. This is the risk of overwhelming varicella (chicken pox) infection. If a "varicella-naïve" child (one who has not had chicken pox and has not been vaccinated) is taking steroids or 6-MP and is exposed to chicken pox, the child's physician should be notified immediately. In this case, an injection of varicella zoster immune globulin (VZIG) would be recommended to limit the potential severity of chicken pox. A full discussion of your child's immunization history with your doctor may help to minimize the risk of this complication.

Steroids do not make children with IBD more prone to develop colds or other infections. Similarly, children who have been on steroids do not appear to be at higher risk for adrenal insufficiency if they develop routine viral or bacterial illnesses soon after steroid treatment is discontinued. (Adrenal insufficiency refers to the impaired production of various hormones that the body needs in order to function properly.) However, stress doses of steroids should be considered before general anesthesia for surgery and during the ensuing 24 to 48 hours, to protect against potential adrenal insufficiency during the "stress" of surgery.

Antibiotics

Specific antimicrobial agents may be beneficial in treating IBD, particularly distal (left-sided) colitis or perianal disease.

Metronidazole is used in children and adolescents with perianal Crohn's disease. It is also used as an alternative, or in addition, to sulfasalazine or steroids for Crohn's colitis. The dosage prescribed depends on the weight of the child and is conveniently given with meals. Teenagers should be told that alcohol and metronidazole do not mix and may result in severe nausea and vomiting. Long-term therapy may lead to reversible peripheral neuropathy (nerve damage); if this occurs, the drug must be stopped.

Ciprofloxacin has been shown to be effective for treating adults with colitis, and is used as an alternative to metronidazole for perianal Crohn's disease. In the past, ciprofloxacin was not recommended for pre-pubescent children. However, prior concerns have not been validated in clinical use in children with cystic fibrosis or IBD, and the drug's safety profile is quite positive.

Immunomodulators

The indications, contraindications, and adverse side effects of the immunomodulators—such as 6-MP and azathioprine—are not significantly different in children, when compared with adults. Azathioprine and 6-MP have been widely prescribed as maintenance therapy for children with Crohn's disease and ulcerative colitis who do not respond to standard medications. It has been shown that 6-MP is effective in children for controlling active disease, for steroid-dependent disease, and for perianal disease. In addition, a newer study suggests that 6-MP may be effective in preventing the relapse of Crohn's disease after surgery. The risks and benefits of antimetabolite therapy with 6-MP or azathioprine should be discussed at length with the prescribing physician. However, these drugs should not necessarily be withheld from children based upon age alone. The steroid-sparing effects of this therapy, as well as its ability to control inflammation, may benefit children with IBD greatly. These treatments can minimize symptoms and optimize growth.

Limited information is available on the use of methotrexate in children with IBD. Its effectiveness in treating active Crohn's disease, as well as its potential as a maintenance drug for Crohn's, has been suggested in the adult and pediatric experience. Given the extensive use of this drug in children with rheumatoid arthritis, it would suggest relative safety. The significant potential side effect—scarring in the lungs or liver—appears to be quite uncommon in children. The principal side effects include nausea, vomiting, or headache following administration. A benefit of this drug is that only one dose per week is required. However, since the preferred administration is by injection, it may not appeal to young patients.

Biologic Therapies

New biologic therapies are emerging to treat Crohn's disease. Infliximab (Remicade®, an anti-tumor necrosis factor antibody) has been studied in a limited number of pediatric patients. The majority of children and adolescents with refractory Crohn's disease appear to respond to infliximab therapy, whether the drug is used to treat inflammatory or fistulizing disease. The limiting factors appear similar to the adult experience: lack of a maintained response, potential allergic reaction, and the fact that long-term side effects (if any) from this drug have not yet been established.

Nutrition as Therapy

Obviously, adequate nutrition is vital for all children who are actively developing and growing. In children with IBD, it may be crucial for the healing of inflammation. Therefore, a high-calorie, well-balanced diet is encouraged as part of the general health maintenance for the young IBD patient, but may be quite difficult to achieve. If there is no clear history of lactose (milk sugar) intolerance, eliminating dairy products from the diet is seldom suggested. These foods often constitute a major source of the child's daily caloric intake, and are important sources of dietary calcium; eliminating them may result in malnutrition. Oral nutritional supplements may be quite beneficial, but are often poorly tolerated for long periods of time. Children may complain about the unacceptable taste or refuse to take the amount needed to achieve the stated caloric goals. Consultation with a nutritionist is advised, as is involving the young person in ways to make sure that nutritional goals are achieved.

There has been significant evidence to support the use of an elemental diet as therapy for patients with Crohn's disease. An elemental diet is one in which the protein constituents are broken down into their smallest building blocks. Studies suggest that this type of diet may induce remission in pediatric patients with Crohn's disease, particularly newly diagnosed patients, and patients whose disease affects the small intestine. This form of therapy is very safe. However, the unpleasant taste and the alternative of exclusive elemental tube feedings make this therapy unpopular with young children and adolescents.

Nutritional therapy may be of paramount importance in children who experience growth failure. For the child with significant problems with weight gain and linear growth, increased calories can be provided at night, either by nasogastric tube (placed through the nose down into the stomach), gastrostomy tube (placed through the skin into the stomach), or intravenously (via a central veinous catheter). Data suggest that supplemental feeding with either regular or elemental formulas is effective in promoting growth in children and adolescents with Crohn's disease. These are special circumstances that require excellent communication between the patient, family, and health care personnel to achieve the most effective method of treatment.

Other Drug Issues

• Antidiarrheal agents
  Many pediatric gastroenterologists support the use of loperamide (Imodium®) to alleviate the diarrhea of IBD if severe abdominal pain or profuse bleeding are absent. Anticholinergic drugs, codeine sulfate, or diphenoxylate hydrochloride with atropine sulfate (Lomotil®), are not recommended since they may result in significant side effects.
  
  

• Acne medications
  Acne, a common problem among adolescents, may affect young people with IBD even more severely.  It is often triggered or aggravated by steroid therapy. Isotretinoin (Accutane®) is commonly prescribed for severe acne that does not respond to other treatments. However, the safety of isotretinoin in people with IBD has not been clearly established. There are reports of its use without any complications, but there also are anecdotal reports of patients who experienced flare-ups of their disease while on this medication.
  
  Isotretinoin may occasionally trigger colitis-like symptoms, such as bleeding and diarrhea -- a condition called drug-induced hypersensitivity colitis. Rarely, isotretinoin has been linked to the appearance of chronic symptoms that mimic full-blown ulcerative colitis. However, there is no evidence that the medication actually causes IBD. Potential drug interactions may occur, most notably when isotretinoin is used with 6-MP.
  
  Because of these concerns, initial therapy for acne in people with IBD should include topical treatment with cleansing agents or antibiotics, followed by oral antimicrobial agents. Isotretinoin should be used with caution and in consultation with all the physicians involved (e.g., the gastroenterologist as well as the dermatologist). Ideally, steroid-induced acne will improve by gradually tapering the steroid dose.

Treatment of IBD in the pediatric patient continues to improve, thanks to advances in therapy and clinical trials of new agents that are being conducted in children and teenagers. We hope that the information provided here will be helpful when patients and their physicians consult to determine the most effective course of treatment for each individual case.