Increases seen in frequency of pediatric inflammatory bowel disease

Although once considered rare in pediatrics, inflammatory bowel disease now is being recognized with increasing frequency in children of all ages. Epidemiologic studies suggest that the incidence rate of IBD has increased gradually worldwide^1-4. This same trend has been demonstrated in Wisconsin, where a recent population-based study found the incidence of IBD to be 7 per 100,000 in children younger than 18 years of age⁵. Despite the increasing incidence, the etiology of this potentially devastating disease remains elusive. Current thinking based on epidemiologic twin investigations⁶, family aggregation analyses^{7, 8} and clinical studies suggests that IBD is the result of a combination of genetic susceptibility and environmental interactions^{9, 10}.

Clinical presentation

Crohn's disease and ulcerative colitis, collectively known as IBD, are lifelong, idiopathic, inflammatory conditions of the gastrointestinal tract. Crohn's disease can involve any part of the digestive system from the mouth to the anus and results in transmural inflammation, while ulcerative colitis only affects the colon and is limited to mucosal involvement. In addition, the clinical presentation of Crohn's disease can differ with disease location, while the presentation of ulcerative colitis is more consistent. The common presenting clinical features are summarized in Table 1. Although most children present to the gastroenterologist with complaints of abdominal pain (with or without hematochezia and/or weight loss), evidence of growth failure, delays in sexual development, joint pain, iron deficiency anemia, skin rashes or even vague complaints of pain, fatigue or anorexia should be considered as possible presenting symptoms for IBD. As a result, a detailed history and physical examination remains the most important aspect in evaluating a child with suspected IBD. Table 2 lists several clinical indicators or red flags that should increase the clinician's suspicion for IBD in a child presenting with abdominal pain. The presence of these red flags together with recognition of the various clinical presentations and a high index of suspicion provides the basis of early diagnosis, therefore potentially avoiding the surgical interventions and associated complications of long-standing untreated disease.

Diagnosis

In addition to the presence of red flags on a child's history, a detailed physical exam also may be helpful in increasing a practitioner's index of suspicion. Although the abdominal exam is often nonspecific, a fullness or mass in the right lower quadrant may be indicative of Crohn's disease. Furthermore, rectal examination is important in identifying perianal disease such as fissures or fistulas as well as assessing for occult blood. Careful assessment of growth and development also should be documented and remains a vital part of the pediatric evaluation. Specifically, growth parameters such as height and weight, as well as the calculation of height and weight percentile for age, are important for assessing evidence of impaired growth velocity and/or failure to thrive. Based on the clinical index of suspicion, subsequent screening laboratories can further aid in determining if definitive endoscopic procedures should be performed. Specifically, the exclusion of common intestinal infections, which may precipitate abdominal pain with or without rectal bleeding, should be evaluated. Such pathogens would include Salmonella, Shigella, Campylobacter, Yersinia, Escherichia coli O157:H7 and Clostridium difficile. In addition, although laboratory data are in many cases nonspecific, a complete blood count may reveal evidence of hypochromic microcytic anemia, and a sedimentation rate may be beneficial as it has been documented to be elevated in more than 80 percent of patients with Crohn's disease. However, a normal sedimentation rate should not defer further investigation. Additional testing should include basic chemistries such as BUN, creatinine, albumin, total bilirubin, aspartate aminotransferase (AST), alanine transaminase (ALT) and alkaline phosphate, as well as assessment of micronutrient status such as folic acid, vitamin B12, serum iron, total iron binding capacity, calcium, 25-OH vitamin D, phosphorous and magnesium. Together these laboratories may identify underlying deficiencies or abnormalities indicative of IBD and prompt referral to a pediatric gastroenterologist for diagnostic testing such as endoscopic evaluation.

Treatment

Following endoscopy confirmation of IBD, management of this chronic relapsing disease requires a team approach. For the pediatric patient, this team includes the primary care provider, pediatric gastroenterologist, registered nurse, nutrition specialist, psychologist and/or social worker. Additional specialists who may be required include a dermatologist, ophthalmologist, endocrinologist and pediatric surgeon, depending on the disease, disease progression and extraintestinal manifestations. Each member of the team should have a firm understanding of the disease location (small bowel or upper tract involvement versus isolated large bowel for Crohn's disease; pancolitis versus limited colonic involvement for ulcerative colitis), the disease severity (mild, moderate or severe inflammation) and any complications or extraintestinal manifestations.

Disease treatment is focused on a combination of short- and long-term goals. Short-term goals include inducing and maintaining remission with improvement in quality of life and prevention of complications. Long-term goals should include preventing relapses, optimizing growth and pubertal development, preventing bone loss and minimizing the need for surgical intervention.

Currently, medical therapy remains the mainstay of treatment. Corticosteroids are the initial treatment of choice for acute therapy in moderate to severe Crohn's disease and ulcerative colitis. In patients with active mucosal inflammation, both oral prednisone or intravenous Solu-Medrol® or hydrocortisone treatment induces rapid improvement by way of their potent anti-inflammatory activity. Despite this activity, there remains no evidence to suggest that corticosteroids heal the inflamed mucosa, and therefore corticosteroids should not be used as maintenance therapy. In addition, corticosteroids have a significantly negative side effect profile ranging from cosmetic issues such as acne and weight gain to more systemic affects such as growth retardation, cataracts and osteopenia. Consequently, the primary role for corticosteroids is in the acute setting to induce short-term remission, thus acting as a bridge while more slowly acting, more effective maintenance therapies take effect. Maintenance medications or steroid sparing medications therefore have been aggressively investigated in order to limit the patient's exposure to this potentially toxic medication.

Maintenance medications include the aminosalicylates, such as sulfasalazine or mesalamine, which are the first-line therapy of choice in mild to moderate ulcerative colitis, and the immune modulators such as 6-mercaptopurine and methotrexate, which have demonstrated benefit in moderate to severe disease. Biologic agents such as infliximab or adalizumab have been proved effective in treating patients with disease refractory to steroids and/or immune modulators. Treatment choice also should take into consideration the type of disease (Crohn's disease versus ulcerative colitis), disease location, disease severity and any complications or extraintestinal manifestations associated with the patient's disease. Each of these medications carries their own side effect profile and, therefore, the risks and potential benefits must be considered carefully when determining the most appropriate therapy for an individual patient.

References

1. Sandler R, Epidemiology of Inflammatory Bowel Disease, Baltimore: Williams & Wilkins; 1994.

2. Sonnenberg A, McCarty DJ, Jacobsen SJ, "Geographic variation of inflammatory bowel disease within the United States," Gastroenterology, Jan. 1991; 100(1):143-149.

3. Barton JR, Gillon S, Ferguson A, "Incidence of inflammatory bowel disease in Scottish children between 1968 and 1983: Marginal fall in ulcerative colitis, three-fold rise in Crohn's disease," Gut, May 1989; 30(5):618-622.

4. Calkins BM, Lilienfeld AM, Garland CF, Mendeloff AI, "Trends in incidence rates of ulcerative colitis and Crohn's disease," Dig Dis Sci, Oct. 1984; 29(10):913-920.

5. Kugathasan S, Judd RH, Hoffmann RG, et al, "Epidemiologic and clinical characteristics of children with newly diagnosed inflammatory bowel disease in Wisconsin: A statewide population-based study," J Pediatr, Oct. 2003; 143(4):525-531.

6. Orholm M, Binder V, Sorensen TI, Rasmussen LP, Kyvik KO, "Concordance of inflammatory bowel disease among Danish twins: Results of a nationwide study," Scand J Gastroenterol, Oct. 2000; 35(10):1075-1081.

7. Orholm M, Iselius L, Sorensen TI, Munkholm P, Langholz E, Binder V, "Investigation of inheritance of chronic inflammatory bowel diseases by complex segregation analysis," Bmj, Jan. 2, 1993; 306(6869):20-24.

8. Forabosco P, Collins A, Latiano A, et al, "Combined segregation and linkage analysis of inflammatory bowel disease in the IBD1 region using severity to characterize Crohn's disease and ulcerative colitis (on behalf of the GISC)," Eur J Hum Genet, Nov. 2000; 8(11):846-852.

9. Satsangi J, Morecroft J, Shah NB, Nimmo E, "Genetics of inflammatory bowel disease: Scientific and clinical implications," Best Pract Res Clin Gastroenterol, Feb. 2003; 17(1):3-18.

10. Bonen DK, Cho JH, "The genetics of inflammatory bowel disease," Gastroenterology, Feb. 2003; 124(2):521-536.

Vincent Biank, MD, is pediatric gastroenterologist at Children's Hospital of Wisconsin, an assistant professor of Pediatrics (Gastroenterology) at the Medical College of Wisconsin and a member of Children's Specialty Group.

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