Crohn’s disease is characterized by transmural inflammation that may involve any segment of the intestinal tract from the mouth to the anus. Disease presentation is primarily determined by the location and extent of involvement. In children, the most common presenting distribution is ileocolonic disease (Figure 110-1) followed by small bowel disease alone and then colonic disease alone. Gastroduodenal disease is found in 30% of children with Crohn’s disease. Patients with ileocecal disease often present with right lower quadrant abdominal pain and diarrhea. In such patients, loops of bowel or fullness may be palpable in the right lower quadrant. Bloody stool is more common in colonic disease. Epigastric pain may occur with gastroduodenal disease. Dysphagia can be seen with esophageal involvement. Many children with Crohn’s disease have diarrhea, nocturnal defecation, low-grade intermittent fever, oral ulcers, weight loss, and decelerated growth velocity.

Figure 110-1 Ileocolonic Crohn’s disease.

Crohn’s disease is categorized into three subtypes: inflammatory, stricturing, and fistulizing. Inflammatory disease is that described above. Stricturing disease involves luminal narrowing, which may be accompanied by prestenotic dilatation or signs of intestinal obstruction. This most commonly occurs in the small bowel but may involve the colon. Perianal or perirectal fistulae and abscesses or intraabdominal fistulae, phlegmon, or abscesses characterize fistulizing disease (Figure 110-2).

Figure 110-2 Types of fistulae in Crohn’s disease.

Extraintestinal Manifestations

About a third of patients with IBD also have extraintestinal manifestations involving rheumatologic, cutaneous, ocular, vascular, hepatobiliary, renal, and skeletal systems (Figure 110-3). Arthralgia and arthritis are the most common extraintestinal symptoms and may involve both axial and peripheral joints. Joint manifestations may precede GI tract disease, so IBD should be in the differential diagnosis of isolated arthralgia or arthritis. Juvenile rheumatoid arthritis and ankylosing spondylitis are associated with IBD.

Figure 110-3 Extraintestinal manifestations of inflammatory bowel disease.

Skin manifestations of IBD are common in the pediatric population and include erythema nodosum and pyoderma gangrenosum. Red, raised, tender nodules located along the anterior shins characterize erythema nodosum. Its course correlates with the severity of GI tract inflammation. Deep necrotic ulcers (often on the legs) characterize pyoderma gangrenosum, with a course that is not related to intestinal disease.

The most common hepatobiliary diseases associated with IBD are primary sclerosing cholangitis and autoimmune hepatitis. Primary sclerosing cholangitis is more commonly associated with UC but can also be found in patients with Crohn’s disease. Its activity is not associated with intestinal disease activity, and its onset may occur years before or after IBD diagnosis. Other associated hepatobiliary disorders include hepatic abscess, hepatic granuloma, cholelithiasis, and cholecystitis. Cholelithiasis in IBD is caused by terminal ileal inflammation or resection, which leads to interrupted enterohepatic circulation of bile acids, causing lithogenic bile. Patients with ileal disease also have increased risk of kidney stones because of malabsorption of fat, which binds calcium and leaves oxalate to be absorbed and excreted in the urine.

Ocular findings associated with IBD include episcleritis, uveitis, and iritis. They are more common in Crohn’s disease patients compared with those with UC. Uveitis may be asymptomatic, so patients should have routine ophthalmologic examinations.

There is an increased incidence of thromboembolic disease in both Crohn’s disease and UC patients compared with the general population. This hypercoagulable state is likely attributable to chronic inflammation and may result in deep venous thrombosis, pulmonary embolism, and cerebrovascular disease.

IBD-associated osteopenia is multifactorial with contributions from malabsorption, malnutrition, inadequate calcium and vitamin D intake, chronic steroid use, inactivity, and chronic inflammation.

Evaluation And Management

A thorough history, including family history, is very important in the evaluation process. Review of potential extraintestinal symptoms should be carefully conducted. Review of the growth chart may reveal subtle growth failure. A careful physical examination may reveal fullness in the right lower quadrant, skin findings, clubbing, or stomatitis. Inspection of the perianal area and perineum for skin tags and fistulae and a digital rectal examination with stool guaiac are necessary.

Stool studies for bacterial pathogens, parasites, Clostridium difficile, Cryptosporidium spp., and Giardia spp. are indicated to differentiate infectious diarrhea from IBD. In addition, patients with IBD have an increased incidence of C. difficile infection. On routine laboratory studies, patients may have anemia, elevated erythrocyte sedimentation rate, elevated C-reactive protein, hypoalbuminemia, and thrombocytosis. If toxic megacolon is present, studies may demonstrate leukocytosis with bandemia. Anti-neutrophil cytoplasmic antibody (pANCA) and anti–Saccharomyces cerevisiae antibody (ASCA) have low positive and negative predictive values and thus are of limited use in diagnosing IBD.

The most important diagnostic tests for IBD are upper endoscopy and colonoscopy. Findings of erythema, aphthous ulcers, cobblestone appearance, pseudopolyps, and mucosal friability are all consistent with IBD (Figure 110-4). In UC, there will be signs of inflammation starting in the rectum, extending proximally in a continuous fashion. In Crohn’s disease, rectal sparing and skip lesions are often noted. Microscopically, inflammatory infiltrates with crypt distortion and crypt abscesses consistent with chronic active inflammation are diagnostic for IBD. Occasionally, granulomas, which are consistent with Crohn’s disease and not with UC, may be noted.

Figure 110-4 Findings typical of ulcerative colitis on colonoscopy and fluoroscopy study.

In addition to upper endoscopy and colonoscopy, an upper GI series with small bowel follow-through is routinely used to evaluate for small bowel disease. In Crohn’s disease, there may be nodularity and thickened bowel loops in the terminal ileum. Occasionally, fistulous tracts and luminal narrowing can be seen. Computed tomography is often used in the emergency department to evaluate patients presenting with severe abdominal pain for a surgical abdomen, such as acute appendicitis (see Chapter 5). This may reveal thickened bowel loops, fistulous tracts, and intraabdominal abscesses in patients with IBD. Abdominal ultrasound may reveal thickening or vascular congestion within the bowel wall or intraabdominal abscess, raising suspicion for IBD. Magnetic resonance imaging is especially valuable in the context of perirectal disease and may help delineate the extent of perirectal fistulae and abscesses.

Recently, wireless capsule endoscopy, in which a pill capsule containing a camera is swallowed by the patient, has become widely available and may be useful to visually assess for small bowel ulcers in patients suspected of Crohn’s disease when conventional studies have been unrevealing. It is crucial that the small intestine is already known to be patent (most often by using small bowel follow-through imaging) before the patient undergoes a capsule study. This large capsule is typically swallowed but can be placed endoscopically into the stomach or duodenum in a patient who cannot swallow it. The capsule study does not allow for tissue pathology because biopsies are not possible.

Treatment

Medical management of Crohn’s disease and UC are very similar with subtle differences. The aminosalicylates, including sulfasalazine and mesalamine, are frequently used in mild to moderate IBD and act locally in the GI tract with limited systemic absorption. They function by inhibiting the cyclooxygenase and lipoxygenase pathways of arachidonic acid metabolism, which alters mucosal prostaglandin production. The various preparations differ in their locations of action based on their release mechanism. In addition to the oral form, a rectal suppository and retention enema can be useful in distal colonic disease. The main side effects are headache, nausea, vomiting, diarrhea, abdominal pain, and rash. Less common side effects include hepatotoxicity, pancreatitis, nephritis, and pericarditis.

Systemic corticosteroids are typically effective in symptom control in all distributions of IBD and remain the mainstay of therapy for acute exacerbations. Oral prednisone is usually initiated at 1 to 2 mg/kg/d, with a maximum dose of 60 mg/d. Corticosteroid dependence, defined as recurrent symptoms when the dose is gradually tapered, is a common occurrence and may require an increased dose or additional therapy with immunomodulators (see below). Corticosteroid resistance may occur over time and together with the many side effects of corticosteroids make them inappropriate for long-term therapy.

Budesonide is a synthetic steroid that has extensive first-pass hepatic metabolism, resulting in fewer side effects and less adrenal suppression than prednisone. Entocort EC, budesonide formulated to release in the terminal ileum, is sometimes used in patients with terminal ileal or cecal disease for short-term therapy, typically less than 3 months.

Antibiotic therapy is sometimes used to treat complications of Crohn’s disease, such as C. difficile infection and perianal fistulae. It may also be used as part of a maintenance regimen. The most common antibiotics in IBD are metronidazole and ciprofloxacin, used separately or in combination. Side effects with long-term use include peripheral neuropathy associated with metronidazole and potential cartilage damage with ciprofloxacin.

There are several different classes of immunomodulators used to treat moderate to severe IBD. Six-mercaptopurine (6-MP) and its prodrug, azathioprine, are some of the most commonly used drugs in IBD. In active disease, these are often used in conjunction with corticosteroids to induce remission. They may be used as monotherapy for maintenance after the disease is in remission. The side effects of these medications include leucopenia, thrombocytopenia, hepatitis, infection, pancreatitis, and allergic reaction. There have also been cases of malignancy reported in patients taking these medications. 6-MP is metabolized by the enzyme thiopurine methyltransferase (TPMT), and the TPMT phenotype is commonly tested before initiating therapy. After therapy is initiated, patients should be monitored closely for toxicity. Furthermore, the therapeutic effect and its potential for toxicity can be measured with 6-MP metabolite levels.

Methotrexate is another class of immunomodulator that may be used long term to maintain remission. Limited data are available on the use of methotrexate in the pediatric IBD population. It can be given by the oral or subcutaneous route, although the oral form may have less bioavailability when there is small bowel inflammation and poor absorption. Common side effects include nausea, vomiting, diarrhea, alopecia, headache, hepatotoxicity, bone marrow suppression, and allergic reactions. Folic acid supplementation should be given concurrently to minimize side effects.

Infliximab is a humanized, chimeric, monoclonal anti–TNF-α antibody used to treat severe and fistulizing IBD. It is given as an infusion of 5 mg/kg at 0, 2, and 6 weeks for induction therapy and subsequently given approximately every 8 weeks. The dose can be increased to 10 mg/kg if needed. In the past, this medication was reserved for patients who failed immunomodulators in combination with corticosteroids. However, more recently, it has been used as first-line therapy in conjunction with corticosteroids for patients presenting with moderate to severe disease. Studies are underway to assess these different approaches in the use of biologic therapy. Adalimumab is a closely related, fully humanized, monoclonal anti–TNF-α antibody that is given as a subcutaneous injection every 2 weeks. It is often used in patients who have had an allergic reaction to infliximab. Both of these medications have side effects that include opportunistic infections, serum sickness, and rare cases of malignancy. Furthermore, infusion reaction may occur with infliximab, necessitating premedication with corticosteroids and diphenhydramine.

Nutritional therapy is an important part of medical management in patients with IBD with malnutrition. In children with growth failure and predominant small bowel Crohn’s disease, exclusive enteral nutrition therapy with special formulas can help patients achieve remission and decrease corticosteroid use. Formulas are best tolerated by nasogastric tube because most formulas are not very palatable. Bowel rest with total parenteral nutrition (TPN) may sometimes be required in patients with severe, steroid-refractory disease. However, it carries significant risks such as central venous line infection and TPN-associated liver disease.

Surgical therapy in IBD may be indicated when medical therapy fails. Surgical therapies are targeted toward the symptoms and may include small bowel resection, colectomy, abscess drainage, and seton placement in the case of perianal abscess (Figure 110-5). Indications for surgery include bowel stricture or obstruction, uncontrollable GI bleeding, intraabdominal abscess, perianal abscess, and fistula(e). Although surgical colectomy for UC is curative and eliminates the risk for future malignancy, surgery for Crohn’s disease often results in temporary relief of symptoms, and disease frequently recurs. Therefore, bowel resections should be considered carefully in Crohn’s disease patients. In addition, patients with indeterminate colitis or young patients with presumed UC require thorough repeat evaluations, including esophagogastroduodenoscopy, colonoscopy, and small bowel imaging before colectomy.