AUTHOR AND EDITOR INFORMATION

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• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
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INTRODUCTION

Section 2 of 11  

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• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
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Background

Crohn disease (CD) is a chronic inflammatory bowel disease. Once considered rare in the pediatric population, CD is recognized with increasing frequency among children of all ages. Approximately 20-30% of all patients with CD present when they are younger than 20 years. With its increasing recognition, CD has become one of the most important chronic diseases that affect children and adolescents.

In addition to the common GI symptoms of diarrhea, rectal bleeding, and abdominal pain, children often experience growth failure, malnutrition, pubertal delay, and bone demineralization. Other problems unique to the pediatric population include the paucity of controlled clinical trials and the psychological issues that occur in children and adolescents with CD. The unique problems encountered in the pediatric population necessitate a medical approach that promotes clinical improvement and reverses growth failure with minimal toxicity.

Pathophysiology

The pathogenesis of CD is multifactorial. After a triggering event occurs in a genetically susceptible individual, an altered immune response leads to chronic inflammation of the intestine. Although the etiology of the precipitating event is unknown, luminal bacteria or specific antigens are thought to be involved.

Chronic inflammation from T-cell activation leading to tissue injury is implicated. After activation by antigen presentation, unrestrained responses of helper lymphocytes type 1 (Th1) predominate in CD because of defective regulation. Th1 cytokines, such as interleukin (IL)-12 and tumor necrosis factor (TNF)-alpha stimulate the inflammatory response. Inflammatory cells recruited by these cytokines release nonspecific inflammatory substances, including arachidonic acid metabolites, proteases, platelet activating factor, and free radicals, which result in direct injury to the intestine.

The macroscopic findings at the time of endoscopy and/or colonoscopy or surgery include various degrees of edema, erythema, ulceration, friability, thickening of the bowel wall and mesentery, and extension of fat over the serosal surface of the intestine (see Media file 1). Skipped areas of inflammation anywhere in the upper or lower GI tract are characteristic of CD, in contrast to the continuous diffuse colonic inflammation found with ulcerative colitis (UC). Microscopic findings on intestinal mucosal biopsy consist of chronic inflammation with architectural distortion (see Media file 2). Granulomas (see Media file 3) are sometimes noted on biopsy findings in CD but never in UC; their presence can be useful in distinguishing between these 2 entities.

Frequency

United States

Over the past few decades, the incidence of inflammatory bowel disease (CD in particular) has greatly increased. The age-specific rate in North America for children aged 10-19 years is estimated to be approximately 3.5 cases per 100,000 population. The only prospective pediatric epidemiologic study from North America showed that the rate of CD in Wisconsin was 4.56 cases per 100,000 population, or twice that of UC.¹

International

The rate of CD in Europe and Canada is 2.1-3.7 cases per 100,000 population, and rates are somewhat higher in northern regions than southern regions. CD is rare in Africa, Asia, and South America.

Mortality/Morbidity

• Death from CD is extremely rare in children and adolescents.
• Severe and complicated CD may result in prolonged hospitalizations, surgeries, growth failure, malnutrition, pubertal delay, and poor quality of life.

Race

CD is more common in whites than in blacks and is rare in Asian and Hispanic children. Rates are higher in people of Jewish descent, particularly Ashkenazi Jews and Jews of middle European origin compared with Sephardic or eastern European Jews.

Sex

• The rate of CD in women is 1.1-1.8 times higher than that in men.
• There is a reverse pattern with pediatric inflammatory bowel disease, with a higher rate in boys than in girls. In the United States, the pediatric male-to-female ratio in 2003 was 1.6:1.

Age

• The rate of CD reaches its first peak in the second and third decade of life. The second, smaller peak occurs in adults aged 60-80 years.
• Approximately 25% of all cases of inflammatory bowel disease are diagnosed before age 20 years.

CLINICAL

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History

Patients with suspected Crohn disease (CD) should initially be evaluated by their primary care physician. The patients' symptoms should be elicited in detail. A medical history, detailed review of systems, and family history should be obtained, and growth parameters should be documented.

In a large series of pediatric patients with CD from the Hospital for Sick Children in Toronto (n = 386), the distribution of presenting symptoms was as follows: abdominal pain in 86%, weight loss in 80%, diarrhea in 78%, blood in the stool in 49%, perianal lesions in 44%, and fever in 38%.²

The location and extent of the disease primarily determines the patient's clinical presentation. The terminal ileum is involved in 50-70% of children. More than half of these patients also have inflammation in various segments of the colon, usually the ascending colon. Overall, children seem to be more likely than adults to have colonic involvement; approximately 10-20% have isolated colonic disease. Gastric inflammation, duodenal inflammation, or both may be observed in as many as 30-40% of children with CD.

• CD of the small intestine: Children with CD of the small intestine usually present with evidence of malabsorption, including diarrhea, abdominal pain, growth deceleration, weight loss, and anorexia. Initially, these symptoms may be quite subtle. The onset of growth failure is usually insidious, and any child or adolescent with persistent alterations in growth should undergo appropriate diagnostic evaluation for CD. Growth failure may precede GI symptoms by years.
• Colonic CD: This may be clinically indistinguishable from ulcerative colitis (UC), with symptoms of bloody mucopurulent diarrhea, cramping abdominal pain, and urgency to defecate.
• Perianal CD: Perianal involvement includes simple skin tags, fissures, abscesses, and fistulae. Symptoms of painful defecation, bright red rectal bleeding, and perirectal pain, erythema, or discharge may signal perianal disease and may occur without symptomatic involvement in any other area of the GI tract. The perineum should be inspected in all patients who present with signs and symptoms of CD because abnormalities detectable in this region substantially increase the clinical suspicion of inflammatory bowel disease.
• Upper GI CD: Patients with this condition may experience nausea, vomiting, and abdominal pain as dominating presenting symptoms.
  
  Characteristics Differentiating CD and UC

  Characteristic
  	CD	UC
  Distribution	Entire GI tract	Colon only, although gastritis recognized
  	Skip lesions	Continuous involvement proximally from rectum
  Pathology	Full thickness	Mucosa only
  	Granulomas (30%)	No granulomas
  Radiology	Entire GI tract	Colon only
  	Skip lesions	Continuous involvement proximally from rectum
  	Fistulas, abscesses, fibrotic strictures	Mucosal disease only
  Cancer risk	Increased	Estimated 1% per year starting 10 years after diagnosis
  Presentation
  	CD	UC
  Bleeding	Common	Very common
  Obstruction	Common	Uncommon
  Fistula	Common	None
  Weight loss	Common	Uncommon
  Perianal disease	Common	Rare

Physical

Findings on physical examination depend on the duration and extent of the disease and on the extraintestinal manifestations.

A careful assessment of growth and development is an important part of evaluating the pediatric patient. Growth abnormalities may be detected by evaluating several parameters: height and weight, percentage height and weight for the patient's age and percentage weight for the patient's height, growth velocity, body composition on anthropometry, and skeletal bone age. The most sensitive indicator of growth abnormalities is a decrease in growth velocity, which may be observed before the major percentile lines on standard growth curves are crossed.

• Vital signs are usually normal, although tachycardia may be present with anemic patients. Chronic intermittent fever is a common presenting sign.
• Body weight and height may reveal weight loss and growth delay.
• Abdominal findings may vary from normal to those of an acute abdomen. Diffuse abdominal tenderness is often present. Fullness or a discrete mass may be appreciated, typically in the right lower quadrant of the abdomen, which may represent a palpable thickened loop of bowel.
• Perianal disease (eg, skin tags, abscesses, fistulae, fissures) is present in approximately 45% of patients.
• Pubertal delay may precede the onset of intestinal symptoms, and accurate Tanner staging should be a part of routine physical examination.
• The most common cutaneous manifestations of CD are erythema nodosum and pyoderma gangrenosum. Skin examination may also reveal pallor in patients with anemia or jaundice in those with concomitant liver disease.
• Eye examination may reveal episcleritis. For the diagnosis of uveitis, a slit lamp examination by an experienced physician is necessary.
• The most common extraintestinal manifestations of CD are arthritis and arthralgia. The large joints (eg, hips, knees, ankles) are typically involved.

Causes

The etiology of CD is multifactorial. An interaction between the predisposing genetic factors, environmental factors, host factors, and triggering event is necessary for the disease to develop.

A high rate of concordance for CD between monozygotic twins (44.4%) compared with dizygotic twins (3.8%) was reported in a Swedish study of an unselected twin registry.³ Because monozygotic twins share identical genomic material and yet may be discordant for CD, the genetic component is necessary but not sufficient, as in all multifactorial diseases. About 30% of patients whose disease is diagnosed when they are younger than 20 years have a positive family history. The percentage decreases to 18% for patients whose disease is diagnosed at age 20-39 years and to 13% after age 40 years.

The first and best described disease-associated mutations for CD were found on the NOD2/CARD15 gene, which is found on chromosome 16 and regulates intracellular immune response to bacterial products. Stricturing disease requiring early surgery, ileal involvement, and younger age at diagnosis are phenotypic characteristics that have been associated with recognized CARD15 mutations. Approximately 25% of white children have a CARD15 mutation compared with only 2% of black and Hispanic children.

Multiple additional genes associated with CD have been recently discovered. An association between mutations in the IL23R gene and inflammatory bowel disease has recently been confirmed, suggesting a major protective effect on susceptibility to CD. A predisposition to CD, specifically with ileal involvement, has been associated with a single nucleotide polymorphism (SNP) in the ATG16L1 gene, which is involved in autophagocytosis, an essential component of the innate immune response targeted towards pathogen-derived proteins.

DIFFERENTIALS

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Other Problems to be Considered

Infection
Celiac disease
Immunodeficiency
Chronic granulomatous disease
Radiation enteritis
Ischemic enterocolitis

WORKUP

Section 5 of 11  

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Lab Studies

• Laboratory data are nonspecific.
• The CBC count may reveal evidence of hypochromic microcytic anemia due to the iron deficiency anemia secondary to GI blood loss, or it may reveal normocytic anemia due to the anemia of chronic disease.
• levels of acute-phase reactants, the erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) levels are often elevated in patients with Crohn disease (CD). However, a normal ESR or CRP level should not deter further evaluation in a suspicious case.
• Hypoalbuminemia is a common laboratory finding in patients with CD. Additional common deficiencies include iron and micronutrients (eg, folic acid, vitamin B-12, serum iron, total iron binding capacity, calcium, magnesium).
• Stool studies should be obtained to rule out bacterial or parasitic infection.
• Serologic testing for inflammatory bowel disease is available. Immunoglobulin A (IgA) and immunoglobulin G (IgG) antibodies to anti-Saccharomyces cerevisiae (ASCA) have been associated with CD, whereas perinuclear antineutrophil cytoplasmic antibody (p-ANCA) has been associated with ulcerative colitis (UC). Although these tests might assist in differentiating between CD and UC, they are not good screening tests. A retrospective review reported that serologic screening that included ASCA, perinuclear antineutrophil cytoplasmic antibody (pANCA), and antibody to Escherichia coli outer membrane porin (anti-OmpC) demonstrated a sensitivity of 60%, a specificity of 91%, and a positive predictive value of 60%.⁴
• Excretion of fecal calprotectin, a protein derived from neutrophils, is increased with colorectal inflammation. Enzyme-linked immunosorbent assay for fecal calprotectin is available; the cutoff level is more than 50 mcg/g feces.

Imaging Studies

• A single-contrast upper-GI tract radiologic series with small-bowel follow-through (SBFT) can be used to evaluate the small intestine, which cannot be reached during endoscopy (see Media file 4).
• In older children, double-contrast radiography (enteroclysis) is used to examine fine mucosal details. CT scanning is useful in the assessment of abscess and phlegmon.
• Radionuclide-tagged WBC scanning can be helpful. However, upper-GI involvement cannot be assessed with WBC scanning, and agreement with endoscopic findings is poor for topographic localization of lower-GI disease.
• MRI is becoming a standard diagnostic tool for the detection of inflammation in the intestine. MRI is especially useful in the evaluation of pelvic and perianal disease (see Media files 5-6).
• Abdominal ultrasonography can be used to investigate intestinal disease and to rule out gallbladder and kidney stones.
• Positron emission tomography is an experimental diagnostic tool.

Procedures

• The development of flexible, small-caliber endoscopes has allowed for colonoscopic evaluation of pediatric patients of all ages, including infants.
• • Colonoscopy with several colonic and terminal ileal biopsies is invaluable and considered a standard in the diagnosis of CD.
  • Upper endoscopy, or esophagogastroduodenoscopy (EGD), should be part of the first-line investigation in all new cases of suspected CD. It is useful in planning therapy and in differentiating between CD and UC, especially if granulomas are present. Clinically significant upper-tract inflammation can be present in the absence of upper-GI symptoms.
• Video capsule endoscopy is being increasingly used to evaluate for small-bowel CD in children. A dissolvable patency capsule or upper GI with SBFT should be performed first to ensure that no area of narrowing at which the capsule could obstruct is present.

Histologic Findings

The microscopic findings of intestinal biopsy samples consist of edema, inflammation (mononuclear and polymorphonuclear), cryptitis and crypt abscesses, architectural crypt changes, and transmural extension of the inflammation (see Media file 2). The presence of granulomas may be helpful in differentiating between UC and CD, but granulomas are present in only about 30% of biopsy specimens obtained from patients with CD. See Media file 3.

Staging

Multiple scoring systems incorporating the patient's history, physical findings, and laboratory data have been developed to assess disease activity in adults with CD. The Pediatric Crohn Disease Activity Index (PCDAI) was developed and validated in 1990. Its results are correlated with the physician's global assessment and with the modified Harvey-Bradshaw index, and it has significant interobserver reliability. The important difference between this index and the Crohn Disease Activity Index (CDAI), which was developed for use in adults with CD, is the inclusion of growth parameters in the score.

TREATMENT

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Medical Care

The general goals of treatment for children with CD are (1) to achieve the best possible clinical, laboratory, and histologic control of the inflammatory disease with the least adverse effects from medication; (2) to promote growth with adequate nutrition; and (3) to permit the patient to function as normally as possible (eg, in terms of school attendance, participation in activities). Treatment has changed over the past few years, reflecting the development of new agents that can target specific locations in the GI tract and specific cytokines.

Typically, therapy for pediatric CD is administered in a step-up approach. Patients with mild disease are treated with preparations of 5-aminosalicylic acid (5-ASA), antibiotics, and nutritional therapy. If no response occurs or if disease is more severe than initially thought, corticosteroid and immunomodulatory therapy with 6-mercaptopurine (6-MP) or methotrexate (MTX) is attempted. Finally, biologic and surgical therapies, at the tip of the treatment pyramid, are used.

• 5-ASA preparations
• • Although commonly used, recent adult meta-analyses have suggested that oral 5-ASA preparations do not demonstrate clinically important treatment effect for active Crohn disease (CD) and are not superior to placebo for the maintenance of remission in CD.⁵
  • Topical 5-ASA therapy is available in suppository and enema forms for the treatment of distal colitis.
• Nutritional therapy
• • Nutritional therapy is another important modality for the treatment of disease, malnutrition, and growth failure observed in CD. A dramatic reversal of malnutrition and a change in growth velocity can be expected in all children treated with adequate nutrition in conjunction with medical therapy to control symptoms of CD. Additionally, exclusive enteral nutrition has been shown to be as effective as corticosteroids for the induction of remission and might promote better GI tract mucosal healing.
  • Because most patients have appetite suppression, overnight nasogastric feeds are often used. Although the exact mechanism of action is unknown, beneficial effects could be due to alteration of the intestinal flora, decrease in the antigen load, and decrease in inflammatory cytokine levels.
• Corticosteroids
• • These are the mainstay of therapy for acute exacerbations because they suppress acute inflammation, thereby providing rapid symptomatic relief. 
  • Systemic corticosteroids are not indicated for maintenance therapy.
  • Enteric coated ileal-release preparations have been developed for the treatment of ileal and cecal CD with decreased systemic effects.
• Immunomodulators
• • Immunomodulators have been used to induce and maintain long-term remission in chronically active, steroid-dependent or steroid-refractory, moderate-to-severe pediatric CD. 
  • 6-mercaptopurine (6-MP) and its prodrug, azathioprine, are effective for the induction and maintenance of remission and reduction of corticosteroid exposure in pediatric CD. Three months is often required to achieve therapeutic efficacy, although the onset of action varies. 
  • Thiopurine methyltransferase (TPMT) activity should be measured prior to initiation of therapy to identify patients predisposed to altered drug metabolism, increasing the risk of leukopenia. 
  • Measurement of 6-thioguanine nucleotide (6-TG) metabolites are helpful in assessing compliance and adjusting therapy.
  • Methotrexate (MTX) is effective in inducing and maintaining remission in chronic CD in adults, and retrospective studies have suggested good efficacy and safety profile in pediatrics.⁶ The onset of action is shorter for MTX than for 6-MP, and the once-weekly dosing is sometimes preferred. Whether oral therapy is as effective as parenteral administration is unclear
• Antibodies to TNF-alpha
• • Infliximab, a chimeric monoclonal antibody to TNF-alpha, is effective in patients who have an inadequate response to conventional therapy and for the treatment of fistulizing CD. Infliximab has been approved for the treatment of pediatric CD. Current clinical practice is to use it as an intravenous (IV) infusion of 5 mg/kg at 0, 2, and 6 weeks, followed by maintenance IV infusions every 8 weeks.
  • The most common adverse events to infliximab therapy are acute and delayed infusion reactions, associated with the formation of antibodies to infliximab (ATI), occurring in 16-39% of children. Premedication does not seem to prevent infusion reactions; however, after an infusion reaction occurs, premedication may be indicated to prevent subsequent infusion reactions. 
  • Adalimumab, a fully humanized anti-TNF-alpha antibody, is a safe and effective substitute for patients who are allergic to infliximab or develop high titers of human antichimeric antibodies (HACA).
• Antibiotics: A few, small studies have shown the usefulness of antibiotic therapy in the treatment of CD. Metronidazole, as well as the combination of metronidazole and ciprofloxacin, is useful in both the management of perianal disease and small bowel and colonic disease.
• Alternative and complimentary therapies: Patients and their families frequently use alternative and complimentary therapies. A potential beneficial effect has been observed with omega-3 fatty acids found in fish oil. Probiotics might provide some treatment benefit, although studies have provided inconsistent results.

Surgical Care

Surgery is considered when medical therapy fails. Indications include intractable disease with growth failure, obstruction or severe stenosis, abscess requiring drainage, perianal fistulae, intractable hemorrhage, and perforation. Recurrence of disease at the anastomotic site is common after resection. Surgical treatment for CD, unlike that for ulcerative colitis (UC), is not curative. Laparoscopic techniques have shown promising results in children with CD, speeding recovery and shortening hospital stays.

Consultations

CD is a chronic disease that needs to be treated by a team of experts consisting of pediatricians, pediatric gastroenterologists, psychologists, nutritionists, social workers, and nurses. A critical factor in successful management of this disease is the willingness of the patient to participate and cooperate with the team. Parents and patients must be educated and receive support to effectively treat this disorder.

Diet

Patients are advised to avoid food that is difficult to digest because it is rich in insoluble fiber (eg, uncooked vegetables, popcorn, seeds, nuts) in order to prevent intestinal obstruction. The obstruction may be due to narrowing or stricture secondary to the inflammation in the small intestine. No other empiric dietary restrictions are recommended, although patients are advised to avoid any foods that tend to exacerbate their disease. 

Nutritional therapies are used for treatment of mild and moderate-to-severe disease, maintenance of remission, and nutritional rehabilitation. In addition to the beneficial nutritional effect, the formula is thought to have anti-inflammatory properties.

Activity

The goal of the therapy is to allow normal unrestricted activity. Patients with osteoporosis secondary to prolonged corticosteroid therapy should avoid high speed and high impact contact sports to minimize the risk of fracture.

MEDICATION

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The goals of pharmacotherapy are to reduce morbidity and prevent complications.

Drug Category: 5-aminosalicylic Acid Derivative

These agents are used to treat mild-to-moderate disease and to maintain remission.

Drug Category: Corticosteroids

These agents are used to treat active moderate-to-severe disease. They are not indicated for maintenance therapy. Budesonide is available in ileal controlled-release form and is used for the treatment of ileal and/or right-sided colonic disease.

Drug Category: Immunosuppressive agents

These agents are used to treat moderate-to-severe disease, to treat steroid-dependent or steroid-refractory disease, and to maintain remission.

Drug Category: Biologic therapy

These agents are used in the treatment of active disease or fistulizing disease unresponsive to other medical therapy.

Drug Category: Antibiotics

These agents are used in the treatment of mild-to-moderate disease, fistulizing, and perianal disease. Antibiotics may change the microbial flora of the intestine and have a potential effect on cell-mediated immune system.

FOLLOW-UP

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Further Inpatient Care

• Most patients with presumed Crohn disease (CD) can undergo outpatient diagnostic evaluation.
• Patients with an exacerbation of CD can be treated on an outpatient basis; however, if concern a serious complication of CD (eg, obstruction, perforation, abscess, hemorrhage) is a concern or if the patient fails outpatient treatment, IV therapy (eg, corticosteroids, antibiotics, total parenteral nutrition) may be required and hospitalization is warranted.

Further Outpatient Care

• Patients should be examined on a regular basis. The frequency depends on the severity and activity of their disease.
• Follow-up laboratory workup should be performed regularly to monitor the safety and success of therapy.

Complications

• The major intestinal complications of CD are due to the transmural nature of the disease. This leads to the formation of abscesses, fistulae, sinus tracts (incomplete fistulae ending in a "cul de sac"), strictures, and adhesions, which may also contribute to obstruction.
• • Frank perforation is one of the most serious complications of CD. Perforation typically occurs into other segments of bowel, leading to fistulae, or to areas such as the retroperitoneum, resulting in abscess formation. The presenting features of frank perforation are those of classic peritonitis, although high-dose corticosteroid therapy may mask these features.
  • Fistula and abscess formation is common in CD and is due to transmural bowel perforation. Perianal and perirectal fistulization are most common. Proper evaluation of perianal disease requires a combination of 2 of the following: pelvic MRI, examination under anesthesia, or endoscopic ultrasonography. Other complications of fistulizing disease include enterovesical and enterocutaneous fistulas.
• Colonic malignancy is a clinically significant complication of CD in patients with pancolitis beginning in childhood.
• • Although the risk of malignancy in CD is not as high as that in ulcerative colitis (UC), the risk of adenocarcinoma of the colon in Crohn colitis is 4-20 times that of the general population. Small intestinal carcinoma is 50-100 times more likely to develop in patients with small intestinal CD but is still rare. The risk for children with an onset of disease in the first decade is unknown, but children who develop colitis when younger than 10 years should undergo colonoscopic screening during adolescence.
  • Epithelial dysplasia generally precedes carcinoma; therefore, yearly surveillance colonoscopy is recommended for patients with this condition, who are at high risk.
• Approximately 25-35% of patients with CD have at least one extraintestinal manifestation, which may be diagnosed before, when, or after CD is diagnosed. Extraintestinal manifestations may carry prognostic importance and include the following:
• • Dermatologic manifestations
  • • Erythema nodosum
    • Pyoderma gangrenosum
    • Orofacial granulomatosis
    • Angular and aphthous stomatitis
    • Acrodermatitis enteropathica
    • Alopecia
    • Metastatic CD
    • CD of the vulva and penis
  • Ophthalmologic manifestations
  • • Episcleritis
    • Uveitis, iritis
    • Conjunctivitis
  • Musculoskeletal manifestations
  • • Arthralgia
    • Arthritis
    • Ankylosing spondylitis
    • Sacroiliitis
  • Bone metabolic disorders
  • • Osteopenia
    • Osteoporosis
  • Hematologic manifestations
  • • Iron deficiency anemia
    • Vitamin B12 deficiency anemia
    • Folate deficiency anemia
    • Anemia of chronic disease
    • Autoimmune hemolytic anemia
    • Thrombocytosis
    • Anemia due to GI bleed
    • Thrombosis
  • Hepatobiliary manifestations
  • • Primary sclerosing cholangitis
    • Autoimmune hepatitis
    • Granulomatous hepatitis
    • Cholelithiasis
    • Portal vein thrombosis
  • Genitourinary manifestations
  • • Nephrolithiasis
    • Obstructive uropathy
    • Fistulas (enterovesical)
    • Glomerulonephritis
    • Amyloidosis
  • Pancreatic manifestations - Pancreatitis
  • Pulmonary manifestations
  • • Granulomatous lung disease
    • Fibrosing alveolitis
    • Pulmonary vasculitis
  • Cardiovascular manifestations
  • • Pericarditis
    • Myocarditis
    • Vasculitis
• Growth failure and delayed sexual development are common in adolescents and children with CD. From studies of the growth of children with CD, impairment of linear growth was common before diagnosis and in subsequent years. Decrease in height velocity before the onset of intestinal symptoms can be observed in as many as 46% of patients with Tanner stage 1 or 2. Height at maturity is often compromised. The etiology of growth failure is multifactorial, with nutritional, hormonal, and disease-related factors all contributing.
• The most common extraintestinal manifestation in children and adolescents is arthritis (7-25% of pediatric patients). The arthritis is usually transient, nondeforming, asymmetric in distribution, and involves the large joints of the lower extremities. In adults, the arthritis occurs when the disease is active, but in children, the arthritis may occur years before any GI symptoms develop.
• Skin manifestations include the following:
• • The most common skin manifestation of CD is erythema nodosum. Erythema nodosum is more common in CD than in UC and usually follows the course of the disease. Erythema nodosum affects 3% of pediatric patients with CD, less frequent than in adults. Approximately 75% of patients with erythema nodosum ultimately develop arthritis. The lesions of erythema nodosum are raised, red, tender nodules that appear primarily on the anterior surfaces of the lower leg.
  • Pyoderma gangrenosum is another skin manifestation, though it is uncommon in CD. Pyoderma gangrenosum is often an indolent chronic ulcer, which may occur even when the disease is in remission. Therefore, medical therapy for the underlying bowel disease is not always successful.
• Aphthous ulceration in the mouth is the most common oral manifestation of CD. This ulceration is commonly associated with skin and joint lesions. Oral lesions appear to parallel intestinal disease in most cases, but they may also occur before any GI symptoms occur.
• In CD, ophthalmologic manifestations most frequently occur when the disease is active. The rate is 4% in the adult population but is lower in children and adolescents. The most common ocular findings are episcleritis and anterior uveitis. The uveitis is usually symptomatic, causing pain or decreased visual acuity. Increased intraocular pressure and cataracts may be observed in children who receive corticosteroid therapy. All patients with CD require ophthalmologic examination at regular intervals.
• Urologic manifestations of CD include nephrolithiasis, hydronephrosis, and enterovesical fistulae. Nephrolithiasis occurs in less than 5% of children with CD. Nephrolithiasis is usually the result of fat malabsorption that occurs with small bowel CD. Dietary calcium binds to malabsorbed fatty acids in the colonic lumen; therefore, free oxalate is absorbed. The absorption of free oxalate results in hyperoxaluria and oxalate stones. In patients with an ileostomy, increased fluid and electrolyte losses may lead to concentrated acidic urine and the formation of uric acid stones. External compression of the ureter by an inflammatory mass or abscess may lead to hydronephrosis. Enterovesical fistulae may present with recurrent urinary tract infections or pneumaturia.
• Hepatobiliary disease is one of the most common extraintestinal manifestations of CD and its therapies.
• • Abnormal serum aminotransferases are common during the course of CD in children. Most aminotransferase elevations are transient and appear to relate to medications or disease activity. Persistent aminotransferase elevations (>6 mo) should be investigated because the likelihood of serious liver disease is increased.
  • Both intrahepatic and extrahepatic manifestations of liver disease occur in children with CD. Intrahepatic manifestations include chronic active hepatitis, granulomatous hepatitis, amyloidosis, fatty liver, and pericholangitis. Extrahepatic manifestations include cholelithiasis and obstruction.
  • Chronic active hepatitis and sclerosing cholangitis develops in fewer than 1% of children with CD.
• Thromboembolic disease is considered the result of a hypercoagulable state that parallels disease activity and is manifested by thrombocytosis, elevated plasma fibrinogen, factor V, factor VIII, and decreased plasma antithrombin III. This may lead to deep vein thrombosis, pulmonary emboli, and neurovascular disease.

Prognosis

• CD may largely affect the life of a child or adolescent.
• With appropriate treatment and support, the prognosis is good, and the risk of a fatal outcome is extremely low.

Patient Education

• Education of patients and their families is encouraged and extremely important in the treatment process. Useful education materials can be obtained by contacting the Crohn's and Colitis Foundation of America.
• For excellent patient education resources, visit eMedicine's Crohn Disease Center and Esophagus, Stomach, and Intestine Center. Also, see eMedicine's patient education articles, Crohn Disease in Children and Teens, Crohn Disease, Inflammatory Bowel Disease, and Irritable Bowel Syndrome.

MISCELLANEOUS

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Special Concerns

• Balsalazide (5-ASA derivative) or sulfasalazine may be used in young children who cannot swallow tablets.

MULTIMEDIA

Section 10 of 11  

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Media file 1:  Colonoscopic image of a large ulcer and inflammation of the descending colon in a 12-year-old boy with Crohn disease.
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Media file 2:  Histologic features of chronic colitis with crypt atrophy and branching, and lymphocytic infiltrate. Hematoxylin-eosin staining. Courtesy of Dr E. Ruchelli.
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Media file 3:  Colonic granuloma in a patient with Crohn disease. Hematoxylin-eosin staining. Courtesy of Dr E. Ruchelli.
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Media file 4:  Image obtained during upper GI series with a small-bowel follow-through shows narrowing and irregularity in the distal ileum in a 16-year-old male adolescent with Crohn disease.
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Media file 5:  MRI of an inflamed terminal ileum in a 10-year-old girl with Crohn disease.
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Media file 6:  MRI of a small abscess on the right side of the anal sphincter in a 9-year-old boy with Crohn disease.
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Media type:  MRI

REFERENCES

Section 11 of 11

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

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