Pediatric Crohn Disease 

Updated: Oct 23, 2018
Author: Andrew B Grossman, MD; Chief Editor: Carmen Cuffari, MD 

Overview

Practice Essentials

Crohn disease, a chronic inflammatory bowel disease (see the image below) that was once considered rare in the pediatric population, is currently recognized as one of the most important chronic diseases that affect children and adolescents. Approximately 20-30% of all patients with Crohn disease present when they are younger than 20 years. In addition to the common GI symptoms (diarrhea, rectal bleeding, and abdominal pain), children with Crohn disease often experience growth failure, malnutrition, pubertal delay, and bone demineralization.

Colonoscopic image of large ulcer and inflammation Colonoscopic image of large ulcer and inflammation of descending colon in 12-year-old boy with Crohn disease.

Signs and symptoms

The clinical presentation is primarily determined by the location and extent of the patient’s disease. With upper GI tract involvement, nausea, vomiting, and abdominal pain dominate as presenting symptoms.

Children with Crohn disease of the small intestine usually present with evidence of malabsorption, including the following:

  • Diarrhea

  • Abdominal pain

  • Growth deceleration

  • Weight loss

  • Anorexia

Initially, manifestations of malabsorption may be quite subtle. The onset of growth failure is usually insidious and may precede GI symptoms by years.

Colonic Crohn disease may be clinically indistinguishable from ulcerative colitis (UC), with manifestations that include the following:

  • Bloody mucopurulent diarrhea

  • Cramping abdominal pain

  • Urgency to defecate

Perianal involvement in Crohn disease may produce the following:

  • Simple skin tags, fissures, abscesses, and fistulae

  • Painful defecation

  • Bright-red rectal bleeding

  • Perirectal pain, erythema, or discharge

Physical examination findings

  • Vital signs are usually normal, although tachycardia may be present in anemic patients

  • Chronic intermittent fever is a common presenting sign

  • Body weight and height may reveal weight loss and growth delay

  • 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

  • Abdominal findings may vary from normal to those of an acute abdomen; diffuse abdominal tenderness is common; fullness or a discrete mass may be palpable, typically in the right lower quadrant

  • Perianal disease (eg, skin tags, abscesses, fistulae, fissures) is present in approximately 45% of patients

  • Tanner staging may indicate pubertal delay, which may precede the onset of intestinal symptoms

  • The most common cutaneous manifestations are erythema nodosum and pyoderma gangrenosum

  • Skin examination may also reveal pallor in patients with anemia or jaundice in those with concomitant liver disease

  • The most common ocular findings are episcleritis and anterior uveitis

  • The most common extraintestinal manifestations of Crohn disease are arthritis and arthralgia, typically involving the large joints (eg, hips, knees, ankles)

See Clinical Presentation for more detail.

Diagnosis

Laboratory data for Crohn disease are nonspecific, as follows:

  • The CBC may show hypochromic microcytic anemia, from iron deficiency due to GI blood loss, or normocytic anemia of chronic disease

  • levels of acute-phase reactants (ESR and CRP) are often elevated in patients with Crohn disease but may be normal

  • Hypoalbuminemia is common

  • Additional common deficiencies include iron and micronutrients (eg, folic acid, vitamin B-12, serum iron, total iron binding capacity, calcium, and magnesium)

  • Stool studies should be obtained to rule out bacterial or parasitic infection

  • Excretion of fecal calprotectin is increased with colorectal inflammation[1] ; on ELISA, the cutoff level is 50 µg/g feces.

Imaging studies

  • A single-contrast upper GI radiologic series with small-bowel follow-through (SBFT) can be used to evaluate the small intestine, which cannot be reached during endoscopy

  • Magnetic resonance enterography (MRE)[2] and computed tomography enterography (CTE) are as sensitive and specific as SBFT for detection of small bowel inflammation and may be more accurate for detection of extraenteric complications, including fistulae and abscesses[3]

  • MRI is especially useful in the evaluation of pelvic and perianal disease

  • Abdominal ultrasonography (US) can be used to investigate intestinal disease and to rule out gallbladder and kidney stones

Endoscopy

  • Colonoscopy with several colonic and terminal ileal biopsies is considered a standard diagnostic procedure

  • Upper endoscopy, or esophagogastroduodenoscopy (EGD), should be part of the first-line investigation

  • Video capsule endoscopy is increasingly being used to evaluate for small-bowel Crohn disease in children[4]

See Workup for more detail.

Management

The general goals of treatment for children with Crohn disease are as follows:

  • To achieve the best possible clinical, laboratory, and histologic control of the inflammatory disease with the least adverse effects from medication

  • To promote growth with adequate nutrition

  • To permit the patient to function as normally as possible (eg, in terms of school attendance and participation in activities)

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 the disease is more severe than was initially thought, corticosteroid and immunomodulatory therapy with 6-mercaptopurine (6-MP) or methotrexate (MTX) is attempted

  • Infliximab is effective in patients who have an inadequate response to conventional therapy and in patients who have fistulizing Crohn disease[5]

  • Adalimumab is a safe and effective substitute for patients who are allergic to infliximab or develop high titers of human antichimeric antibodies (HACA)[6]

  • Surgery is considered when medical therapy fails[7]

Surgical care

Indications for surgery include the following:

  • Intractable disease with growth failure

  • Obstruction or severe stenosis

  • Abscess requiring drainage

  • Perianal fistulae

  • Intractable hemorrhage

  • Perforation

Features of surgery are as follows:

  • Recurrence of disease at the anastomotic site is common after resection

  • Surgical treatment for Crohn disease is not curative

  • Laparoscopic techniques are becoming the standard of care[8]

See Treatment and Medication for more detail.

Background

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

In addition to the common gastrointestinal (GI) symptoms (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 Crohn disease. These problems necessitate a medical approach that promotes clinical improvement and reverses growth failure with minimal toxicity.

Pathophysiology

The pathogenesis of Crohn disease 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 because of defective regulation. Th1 cytokines (eg, interleukin [IL]–12 and tumor necrosis factor [TNF]-α) stimulate the inflammatory response. Inflammatory cells recruited by these cytokines release nonspecific inflammatory substances (eg, arachidonic acid metabolites, proteases, platelet activating factor, and free radicals), which directly injure the intestine.

The macroscopic findings at the time of endoscopy 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 the image below).

Skipped areas of inflammation anywhere in the upper or lower GI tract are characteristic of Crohn disease, 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. Granulomas are sometimes noted on biopsy findings in Crohn disease but never in UC; their presence can be useful in distinguishing between these 2 entities.

Etiology

The etiology of Crohn disease 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 Crohn disease between monozygotic twins (44.4%) compared with dizygotic twins (3.8%) was reported in a Swedish study of an unselected twin registry.[9] Because monozygotic twins share identical genomic material and yet may be discordant for Crohn disease, 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 Crohn disease were found on the NOD2/CARD15 gene, which is found on chromosome 16 and regulates intracellular immune response to bacterial products.[10] Stricturing disease necessitating 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.[11]

Additional genes associated with Crohn disease have been discovered. An association between mutations in the IL23R gene and inflammatory bowel disease (IBD) has been confirmed, suggesting a major protective effect on susceptibility to Crohn disease. A predisposition to Crohn disease, 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.

Epidemiology

United States statistics

Over the past few decades, the incidence of IBD (Crohn disease 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 Crohn disease in Wisconsin was 4.56 cases per 100,000 population, or twice that of UC.[12]

International statistics

The rate of Crohn disease 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. Crohn disease is rare in Africa, Asia, and South America.

Age-, sex-, and race-related demographics

The rate of Crohn disease 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 IBD are diagnosed before age 20 years.

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

Crohn disease 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.

Prognosis

Although Crohn disease may have a sizable effect on 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.

Death from Crohn disease is extremely rare in children and adolescents. Severe and complicated Crohn disease may result in prolonged hospitalizations, multiple surgical procedures, growth failure, malnutrition, pubertal delay, and poor quality of life.

 

 

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 patient education resources, see the Crohn Disease Center and the Esophagus, Stomach, and Intestine Center, as well as Crohn Disease in Children and Teens, Crohn Disease, Inflammatory Bowel Disease, and Irritable Bowel Syndrome.

 

Presentation

History

Patients with suspected Crohn disease should initially be evaluated by their primary care team. Symptoms should be elicited in detail. A medical history, a detailed review of systems, and a family history should be obtained, and growth parameters should be documented.

In a series of 386 pediatric patients with Crohn disease from the Hospital for Sick Children in Toronto, 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%.[13]

The clinical presentation is primarily determined by the location and extent of the patient’s disease. 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 Crohn disease.

Upper gastrointestinal Crohn disease

Patients with upper gastrointestinal (GI) Crohn disease condition may experience nausea, vomiting, and abdominal pain as dominating presenting symptoms.

Crohn disease of small intestine

Children with Crohn disease 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 Crohn disease. Growth failure may precede GI symptoms by years.

Colonic Crohn disease

Colonic Crohn disease may be clinically indistinguishable from ulcerative colitis (UC), with symptoms of bloody mucopurulent diarrhea, cramping abdominal pain, and urgency to defecate (see the Table below).

Table. Characteristics and Presentations Differentiating Crohn Disease From Ulcerative Colitis (Open Table in a new window)

 

Crohn Disease

Ulcerative Colitis

Characteristic

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%/y, starting 10 y after diagnosis

Presentation

Bleeding

Common

Very common

Obstruction

Common

Uncommon

Fistula

Common

None

Weight loss

Common

Uncommon

Perianal disease

Common

Rare

GI = gastrointestinal.

Perianal Crohn disease

Perianal involvement in Crohn disease includes simple skin tags, fissures, abscesses, and fistulae. 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 Crohn disease because abnormalities detectable in this region substantially increase the clinical suspicion of inflammatory bowel disease (IBD).

Physical Examination

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

Careful assessment of growth and development is an important part of evaluating the pediatric patient. Growth abnormalities may be detected by evaluating 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 Crohn disease 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 Crohn disease are arthritis and arthralgia. The large joints (eg, hips, knees, ankles) are typically involved.

Complications

The major intestinal complications of Crohn disease 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 Crohn disease. Perforation typically occurs into other segments of bowel, leading to fistulae, or into areas such as the retroperitoneum, resulting in abscess formation. The presenting features of frank perforation are those of classic peritonitis, though these features may be masked by high-dose corticosteroid therapy.

Fistula and abscess formation is common in Crohn disease 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 magnetic resonance imaging (MRI)

  • Examination under anesthesia

  • Endoscopic ultrasonography

Other complications of fistulizing disease include enterovesical and enterocutaneous fistulas.

A study by Herman et al aimed to assess phenotypic features at diagnosis and long-term disease-specific outcomes in 296 children perianal Crohn's disease reported that fistulizing and nonfistulizing perianal disease was associated with worse outcomes. The study also reported that the presence of nonfistulizing disease at diagnosis was a significant risk factor for the development of fistulizing perianal disease (HR 3.4, P = 0.002) and that females were more associated with perianal involvement (P = 0.01).[35]

Colonic malignancy is a clinically significant complication of Crohn disease in patients with pancolitis beginning in childhood. Although the risk of malignancy in Crohn disease is not as high as that in 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 Crohn disease 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.

Extraintestinal manifestations

Approximately 25-35% of patients with Crohn disease have at least 1 extraintestinal manifestation, which may be diagnosed before, when, or after Crohn disease is diagnosed. These manifestations may carry prognostic importance.

Dermatologic manifestations of Crohn disease include the following:

  • Erythema nodosum

  • Pyoderma gangrenosum

  • Orofacial granulomatosis[14]

  • Angular and aphthous stomatitis

  • Acrodermatitis enteropathica

  • Alopecia

  • Metastatic Crohn disease

  • Crohn disease of the vulva and penis

Erythema nodosum is the most common skin manifestation of Crohn disease. It is more common in Crohn disease than in UC and usually follows the course of the disease. Erythema nodosum affects 3% of pediatric patients with Crohn disease (a lower rate than that 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 may also develop in Crohn disease, though it is uncommon in this setting. 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 Crohn disease. 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.

Ophthalmologic manifestations of Crohn disease include the following:

  • Episcleritis

  • Uveitis, iritis

  • Conjunctivitis

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. Episcleritis and anterior uveitis are the most common ocular findings. 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 Crohn disease require ophthalmologic examination at regular intervals.

Musculoskeletal manifestations of Crohn disease include the following:

  • Arthralgia

  • Arthritis

  • Ankylosing spondylitis

  • Sacroiliitis

Arthritis is the most common extraintestinal manifestation in children and adolescents (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.

Bone metabolic disorders seen in Crohn disease include the following:

  • Osteopenia

  • Osteoporosis

Hematologic manifestations of Crohn disease include the following:

  • Iron deficiency anemia

  • Vitamin B-12 deficiency anemia

  • Folate deficiency anemia

  • Anemia of chronic disease

  • Autoimmune hemolytic anemia

  • Thrombocytosis

  • Anemia due to GI bleeding

  • Thrombosis

Hepatobiliary disease is one of the most common extraintestinal manifestations of Crohn disease and its therapies. Hepatobiliary manifestations include the following:

  • Primary sclerosing cholangitis

  • Autoimmune hepatitis

  • Granulomatous hepatitis

  • Cholelithiasis

  • Portal vein thrombosis

Abnormal serum aminotransferases are common during the course of Crohn disease in children. Most aminotransferase elevations are transient and appear to relate to medications or disease activity. Persistent aminotransferase elevations (>6 months) should be investigated because the likelihood of serious liver disease is increased.

Both intrahepatic and extrahepatic manifestations of liver disease occur in children with Crohn disease. 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 develop in fewer than 1% of children with Crohn disease.

Genitourinary manifestations of Crohn disease include the following:

  • Nephrolithiasis

  • Hydronephrosis

  • Enterovesical fistulae

  • Obstructive uropathy

  • Glomerulonephritis

  • Amyloidosis

Nephrolithiasis occurs in fewer than 5% of children with Crohn disease. It is usually the result of fat malabsorption that occurs with small bowel Crohn disease. 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.

In the pancreas, Crohn disease may be manifested as pancreatitis.

Pulmonary manifestations of Crohn disease include the following:

  • Granulomatous lung disease

  • Fibrosing alveolitis

  • Pulmonary vasculitis

Cardiovascular manifestations include the following:

  • Pericarditis

  • Myocarditis

  • Vasculitis

Growth failure and delayed sexual development are common in adolescents and children with Crohn disease. Studies of the growth of these children have found that impairment of linear growth is common before diagnosis and in subsequent years. Decreased 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.

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.

 

DDx

Diagnostic Considerations

In addition to the conditions listed in the differential diagnosis (see below), other problems to be considered include the following:

  • Infection

  • Celiac disease

  • Immunodeficiency

  • Chronic granulomatous disease

  • Radiation enteritis

  • Ischemic enterocolitis

Differential Diagnoses

 

Workup

Laboratory Studies

Laboratory data for Crohn disease are nonspecific. The complete blood count (CBC) may reveal evidence of hypochromic microcytic anemia due to the iron deficiency anemia secondary to gastrointestinal (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. 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 Crohn disease. Additional common deficiencies include iron and micronutrients (eg, folic acid, vitamin B-12, serum iron, total iron binding capacity, calcium, and magnesium).

Stool studies should be obtained to rule out bacterial or parasitic infection.

Serologic testing for inflammatory bowel disease (IBD) is available. Immunoglobulin A (IgA) and immunoglobulin G (IgG) antibodies to anti– Saccharomyces cerevisiae (ASCA) have been associated with Crohn disease, whereas perinuclear antineutrophil cytoplasmic antibody (p-ANCA) has been associated with ulcerative colitis (UC).

Although these tests might assist in differentiating between Crohn disease and UC, they are not good screening tests. In a retrospective review, serologic screening that included ASCA, 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%.[15]

Excretion of fecal calprotectin, a protein derived from neutrophils, is increased with colorectal inflammation.[1] Enzyme-linked immunosorbent assay (ELISA) for fecal calprotectin is available; the cutoff level is 50 µg/g feces.

Radiography, MRI, CT, US, and PET

A single-contrast upper GI radiologic series with small-bowel follow-through (SBFT) can be used to evaluate the small intestine, which cannot be reached during endoscopy (see the image below).

Image obtained during upper gastrointestinal serie Image obtained during upper gastrointestinal series with small-bowel follow-through shows narrowing and irregularity in distal ileum in 16-year-old male adolescent with Crohn disease.

Magnetic resonance enterography (MRE)[2] and computed tomography enterography (CTE) are increasingly being used for evaluation of the small bowel. Both modalities are as sensitive and specific as SBFT for detection of small bowel inflammation and may be more accurate for detection of extraenteric complications, including fistulae and abscesses.[3] MRE is a particularly attractive option because of the lack of radiation exposure.

Proximal small bowel Crohn disease is present in up to 35% of children with this chronic inflammatory bowel disorder. It is also regarded as a more severe clinical phenotype that is associated with significant morbidity, including poor growth. MRE has now become the radiological procedure of choice in identifying proximal small bowel disease in children with Crohn disease. Moreover, the increased sensitivity of MRE to detect early-onset disease may allow physicians to tailor therapy more effectively.[16]

MRI is especially useful in the evaluation of pelvic and perianal disease (see the images below). Abdominal ultrasonography (US) can be used to investigate intestinal disease and to rule out gallbladder and kidney stones. Positron emission tomography (PET) is an experimental diagnostic tool.

Inflamed terminal ileum in 10-year-old girl with C Inflamed terminal ileum in 10-year-old girl with Crohn disease.
Small abscess on right side of anal sphincter in 9 Small abscess on right side of anal sphincter in 9-year-old boy with Crohn disease.

Endoscopy

The development of flexible, small-caliber endoscopes has allowed 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 Crohn disease (see the image below).

Colonoscopic image of large ulcer and inflammation Colonoscopic image of large ulcer and inflammation of descending colon in 12-year-old boy with Crohn disease.

Upper endoscopy, or esophagogastroduodenoscopy (EGD), should be part of the first-line investigation in all new cases of suspected Crohn disease. It is useful in planning therapy and in differentiating between Crohn disease and UC, especially if granulomas are present. Clinically significant upper GI inflammation can be present in the absence of upper GI symptoms.

Video capsule endoscopy is increasingly being used to evaluate for small-bowel Crohn disease in children.[4] Before the procedure is initiated, a dissolvable patency capsule should be placed or small bowel imaging performed to ensure that there are no areas of narrowing or stricture where the video capsule might create an obstruction.

Histologic Findings

The microscopic findings in intestinal biopsy samples from pediatric patients with Crohn disease consist of edema, inflammation (mononuclear and polymorphonuclear), cryptitis and crypt abscesses, architectural crypt changes, and transmural extension of the inflammation (see the image below).

Histologic features of chronic colitis with crypt Histologic features of chronic colitis with crypt atrophy and branching and lymphocytic infiltrate. Hematoxylin-eosin staining. Image courtesy of Dr E Ruchelli.

The presence of granulomas may be helpful in differentiating between UC and Crohn disease (see the image below), but granulomas are present in only about 30% of biopsy specimens obtained from patients with Crohn disease.

Colonic granuloma in patient with Crohn disease. H Colonic granuloma in patient with Crohn disease. Hematoxylin-eosin staining. Image courtesy of Dr E Ruchelli.

Staging

Multiple scoring systems incorporating the patient’s history, physical findings, and laboratory data have been developed to assess disease activity in adults with Crohn disease.

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 Crohn disease, is the inclusion of growth parameters in the score.

 

Treatment

Approach Considerations

The general goals of treatment for children with Crohn disease are as follows:

  • To achieve the best possible clinical, laboratory, and histologic control of the inflammatory disease with the least adverse effects from medication

  • To promote growth with adequate nutrition

  • To permit the patient to function as normally as possible (eg, in terms of school attendance and participation in activities)

Treatment has changed over the past few years, reflecting the development of new agents that can target specific locations in the gastrointestinal (GI) tract and specific cytokines.

Step-up approach

Typically, therapy for pediatric Crohn disease 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 the disease is more severe than was 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.

Some adult data support the use of biologic therapy earlier in the course of disease (ie, a top-down approach) as a more effective treatment method.[17] A small, retrospective pediatric trial also supported the use of a top-down approach, but prospective pediatric data are needed.[18]

Patients and their families frequently use alternative and complimentary therapies. A potential beneficial effect has been observed with the omega-3 fatty acids found in fish oil. Probiotics might provide some treatment benefit, although studies have yielded inconsistent results.

Pharmacologic and Nutritional Therapy for Mild Disease

5-Acetylsalicylic acid

Although oral 5-ASA preparations are commonly used, adult meta-analyses suggest that these preparations do not have a clinically important treatment effect on active Crohn disease and are not superior to placebo for the maintenance of remission in Crohn disease.[19] Topical 5-ASA therapy is available in suppository and enema forms for the treatment of distal colitis.

Antibiotics

A few small studies have shown the usefulness of antibiotic therapy in the treatment of Crohn disease. Metronidazole, as well as the combination of metronidazole and ciprofloxacin, is useful in the management of perianal disease and of small bowel and colonic disease.

Nutritional therapy

Nutritional therapy is another important modality for the treatment of disease, malnutrition, and growth failure in Crohn disease.[20] 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 Crohn disease. 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.[21]

Because most patients have appetite suppression, overnight nasogastric feedings are often used. Although the exact mechanism of action is unknown, the beneficial effects of this approach could be due to alteration of the intestinal flora, a decrease in the antigen load, and reductions in inflammatory cytokine levels.

Corticosteroid and Immunomodulatory Therapy for More Severe Disease

Corticosteroids

Corticosteroids 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 Crohn disease; systemic effects are decreased with these formulations.

Immunomodulators

Immunomodulators have been used to induce and maintain long-term remission in chronically active, steroid-dependent or steroid-refractory, moderate-to-severe pediatric Crohn disease.

6-Mercaptopurine (6-MP) and its prodrug, azathioprine, are effective for the induction and maintenance of remission and the reduction of corticosteroid exposure in pediatric Crohn disease. Three months is often required to achieve therapeutic efficacy, although the onset of action varies.

Thiopurine methyltransferase (TPMT) activity should be measured before the initiation of therapy to identify patients predisposed to altered drug metabolism (which increases the risk of leukopenia). Measurement of 6-thioguanine nucleotide (6-TG) metabolites is helpful in assessing compliance and adjusting therapy.

MTX is effective in inducing and maintaining remission in chronic Crohn disease in adults and has been shown to be effective and well tolerated for maintenance of remission in children.[22, 23, 24, 25] MTX has a quicker onset of action than 6-MP does, and the once-weekly dosing is sometimes preferred. Whether oral therapy is as effective as parenteral administration is unclear.

Biologic Therapy for Unresponsive Disease

Infliximab (Remicade), a chimeric monoclonal antibody to tumor necrosis factor (TNF)-α, is effective in patients who have an inadequate response to conventional therapy and in patients who have fistulizing Crohn disease.[5] It has been approved for the treatment of pediatric Crohn disease. Current clinical practice is to give infliximab in an intravenous (IV) infusion of 5 mg/kg at 0 weeks, 2 weeks, 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), which occur 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.[26]

Adalimumab (Humira), a fully humanized anti–TNF-α antibody, was approved by the US Food and Drug Administration (FDA) in September 2014 for children aged 6 years or older with moderately to severely active Crohn disease who have had an inadequate response to corticosteroids or immunomodulators (eg, azathioprine, 6-mercaptopurine, methotrexate). It is also a safe and effective substitute for patients who are allergic to infliximab or who develop high titers of human antichimeric antibodies (HACA).[6] Its approval was based on a prospective multicenter study in children with a Pediatric Crohn's Disease Activity Index (PCDAI) score of more than 30 for whom conventional treatment was unsuccessful (n= 192). The study demonstrated that adalimumab is effective for induction and maintenance of remission for pediatric Crohn disease and is well tolerated by children.[27, 28]

Adalimumab drug is already approved for the treatment of moderately to severely active Crohn's disease in adults.

A study by Dziechciarz et al assessed the published evidence on the efficacy and safety of adalimumab for Crohn's disease in children. The study found that there was only low-quality evidence based mainly on case series that showed that approximately half of children with Crohn's disease on adalimumab therapy achieve remission during the first year of the therapy with reasonable safety profile.[29, 30]  

Another study by Horneff et al that included 577 pediatric patients reported a similar safety profile of adalimumab in pediatric patients with polyarticular juvenile idiopathic arthritis, enthesitis-related arthritis, psoriasis, and Crohn disease. The most common adverse events were infections which occurred in 76% of patients with Crohn disease.[41]

 

One area of concern with the use of these medications is that multiple patients have been reported to develop a rare hepatosplenic T-cell lymphoma when treated with dual therapy consisting of 6-MP or azathioprine with a TNF-α inhibitor. Although this has been a rare complication, all reported cases have been in adolescents and young adults.

Data from the observational RISK study has been published. The study included children from 28 pediatric gastroenterology centers in North America. Results showed that in newly diagnosed children with comparably severe Crohn disease, early monotherapy with and anti-TNF-alpha agents produced better overall clinical and growth outcomes at 1 year than early monotherapy with an immunomodulator. Further investigation is needed to identify which children are most likely to benefit from early anti-TNF-alpha therapy.[31]

A study examined changes in bone density and structure in children and adolescents with Crohn's disease following initiation of anti-tumor necrosis factor (TNF)-alpha inhibitors therapy. The study concluded that anti-TNF-α therapy was associated with improvements in trabecular bone mineral density and cortical structure. Improvements were greater in younger and growing participants, suggesting a window of opportunity for treatment of bone deficits.[32, 33]

Another study that included 75 pediatric patients with Crohn disease reported that after the initiation of anti-TNF-α therapy, short-term increases in insulinlike growth factor 1 z scores predicted recovery of bone and muscle outcomes.[40]

Surgical Treatment After Failed Medical Therapy

Surgery is considered when medical therapy fails.[7]  [34] 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 Crohn disease, unlike that for ulcerative colitis (UC), is not curative. Laparoscopic techniques are becoming the standard of care for most inflammatory bowel disease (IBD) procedures, resulting in decreased recovery time.[8]

Consultations

Crohn disease is a chronic disease that must 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.

For effective treatment of this disorder, parents and patients must be appropriately educated (see Patient Education) and receive the necessary support.

Diet and Activity

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

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

A goal of therapy for Crohn disease 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.

Long-Term Monitoring

Most patients with presumed Crohn disease can undergo outpatient diagnostic evaluation. 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.

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

 

Medication

Medication Summary

The goals of pharmacotherapy in Crohn disease are to reduce morbidity and prevent complications. Agent classes used include 5-aminosalicylic acid (5-ASA) derivatives, corticosteroids, immunosuppressive agents, biologic agents, and antibiotics.

5-Aminosalicylic Acid Derivatives

Class Summary

5-ASA derivatives are used to treat mild-to-moderate Crohn disease and to maintain remission.

Mesalamine (Asacol, Pentasa, Rowasa, Canasa)

Mesalamine inhibits leukotriene biosynthesis via the lipoxygenase pathway of arachidonic acid metabolism and interferes with myeloperoxidase activity and reactive oxygen species. The oral mesalamine products currently approved in the United States differ only with respect to the mechanism of drug delivery. Mesalamine is approved by the US Food and Drug Administration (FDA) for treatment of UC but is widely used off label for treatment of Crohn disease.

Mesalamine products have not been approved for use in children but are considered standard of care for inflammatory bowel disease (IBD) and are supported by numerous reports in the literature.

Asacol contains mesalamine within a Eudragit-S coating that dissolves and releases the mesalamine at pH 7, which typically occurs in the terminal ileum. Pentasa contains 5-ASA in ethylcellulose and has a time-release coating. Release of mesalamine from Pentasa begins at the pylorus; consequently, this drug is often used when proximal intestinal Crohn disease is suggested. Despite the drug's proximal release site, there are no convincing data to indicate that the site of release translates into clinical superiority.

Rectal dosage forms deliver high concentrations of mesalamine to the left colon as high as the splenic flexure (enema with 30 minutes retention) or to the rectum for use in proctitis (suppository). Although mesalamine is effective, it is associated with a relatively high relapse rate upon discontinuance. In many cases, widespread use of topical agents is limited by patient acceptance; often, patients with active rectal disease have difficulty holding in the enema.

Corticosteroids

Class Summary

Corticosteroids 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 or right-side colonic disease.

Prednisone

Prednisone exercises its anti-inflammatory effects through decreased capillary permeability, impaired neutrophil chemotaxis, release of anti-inflammatory cytokines, decreased production of eicosanoids, and stabilization of the lysosomal membrane.

Methylprednisolone (Medrol, Solu-Medrol)

Methylprednisolone exerts its anti-inflammatory effects by means of decreased capillary permeability, impaired neutrophil chemotaxis, release of anti-inflammatory cytokines, decreased production of eicosanoids, and stabilization of the lysosomal membrane.

Budesonide (Entocort EC)

Budesonide exerts its anti-inflammatory effects by means of decreased capillary permeability, impaired neutrophil chemotaxis, release of anti-inflammatory cytokines, decreased production of eicosanoids, and stabilization of the lysosomal membrane.

Hydrocortisone (Cortenema, Anusol-HC, Anucort HC, Anu-med HC, Proctosol-HC)

Hydrocortisone is a rectally administered corticosteroid similar to the intravenous (IV) and oral corticosteroids; significant amounts of corticosteroids can be absorbed systemically when these agents are administered via an enema or suppository. Various products containing hydrocortisone are available for rectal use. This agent is useful for treating distal colonic disease.

Immunosuppressants

Class Summary

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

6-Mercaptopurine (Purinethol)

6-Mercaptopurine (6-MP) and its prodrug, azathioprine, are purine analogues that interfere with protein synthesis and nucleic acid metabolism. 6-MP has a cytotoxic effect on lymphoid cells. The onset of action is delayed for 2-3 months.

Azathioprine (Imuran, Azasan)

Azathioprine antagonizes purine metabolism and inhibits synthesis of DNA, RNA, and proteins. It may decrease the proliferation of immune cells, which lowers autoimmune activity.

Methotrexate (Trexall, Rheumatrex)

Methotrexate impairs DNA synthesis, induces apoptosis, and reduces production of interleukin (IL)-1. It is used for treatment of moderate-to-severe disease and maintenance of remission. The onset of action is delayed.

Monoclonal Antibodies

Class Summary

Biologic agents are used in the treatment of active Crohn disease or fistulizing disease that is unresponsive to other medical therapy.

Infliximab (Inflectra, Remicade)

Infliximab is a chimeric immunoglobulin G1 kappa (IgG1κ) monoclonal antibody that neutralizes cytokine tumor necrosis factor (TNF)-α and inhibits its binding to TNF-α receptors. It reduces infiltration of inflammatory cells and TNF-α production in inflamed areas.

Adalimumab (Humira)

Adalimumab is a recombinant human IgG1 monoclonal antibody that is specific for human TNF. It binds specifically to TNF-α and blocks interaction with p55 and p75 cell-surface TNF receptors. It is indicated for children older than 6 years with moderately to severely active Crohn disease who have had an inadequate response to corticosteroids or immunomodulators (eg, azathioprine, 6-mercaptopurine, methotrexate).

Antibiotics, Other

Class Summary

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

Metronidazole (Flagyl)

Metronidazole is an imidazole ring-based antibiotic that is active against various anaerobic bacteria and protozoa.

Ciprofloxacin (Cipro)

Ciprofloxacin inhibits bacterial DNA synthesis and, consequently, growth.

 

Questions & Answers

Overview

What is pediatric Crohn disease?

What is the typical presentation of pediatric Crohn disease?

What is the presentation of pediatric Crohn disease of the small intestine?

What is the presentation of pediatric Crohn disease of the colon?

What is the presentation of perianal pediatric Crohn disease?

Which physical findings suggest pediatric Crohn disease?

Which lab test results indicate pediatric Crohn disease?

What is the role of imaging studies in the diagnosis of pediatric Crohn disease?

Which procedures are performed in the diagnosis of pediatric Crohn disease?

What are the goals of treatment for pediatric Crohn disease?

What is the step-up approach for the management of pediatric Crohn disease?

What is the role of surgery in the management of pediatric Crohn disease?

What is pediatric Crohn disease?

What are the effects of pediatric Crohn disease on a child’s development?

What is the pathogenesis of pediatric Crohn disease?

Which endoscopy or colonoscopy findings indicate pediatric Crohn disease?

How is pediatric Crohn disease differentiated from ulcerative colitis (UC)?

What is the etiology of pediatric Crohn disease?

What is the role of genetics in pediatric Crohn disease?

Which genetic mutations are associated with pediatric Crohn disease?

What is the incidence of pediatric Crohn disease in the US?

What is the global prevalence of pediatric Crohn disease?

What percentage of cases of irritable bowel disease (IBD) are pediatric?

Does pediatric Crohn disease have a gender predilection?

Does pediatric Crohn disease have a racial predilection?

What is the prognosis of pediatric Crohn disease?

What information should be provided to parents and children with pediatric Crohn disease?

Presentation

What is the initial evaluation for suspected pediatric Crohn disease?

What are common presenting symptoms of pediatric Crohn disease?

Which factors determine the clinical presentation of pediatric Crohn disease?

What are the signs and symptoms of upper GI pediatric Crohn disease?

What are the signs and symptoms of pediatric Crohn disease of the small intestine?

What are the symptoms of pediatric Crohn disease of the colon?

What are the symptoms of perianal pediatric Crohn disease?

How does pediatric Crohn disease affect growth and development?

Which vital signs findings indicate pediatric Crohn disease?

Which abdominal findings indicate pediatric Crohn disease?

What causes major intestinal complications of pediatric Crohn disease?

What are the symptoms of perforation in pediatric Crohn disease?

What are the possible complications of pediatric Crohn disease and how are they evaluated?

Are patients with pediatric Crohn disease at increased risk for developing GI malignancies?

Which patients with pediatric Crohn disease should undergo a yearly surveillance colonoscopy?

How common are extraintestinal symptoms of pediatric Crohn disease?

What are dermatologic manifestations of pediatric Crohn disease?

What is the prevalence of erythema nodosum in pediatric Crohn disease and how does it present?

What is the presentation of pyoderma gangrenosum in patients with pediatric Crohn disease?

When are aphthous ulcerations likely to appear in patients with pediatric Crohn disease?

What are ophthalmologic manifestations of pediatric Crohn disease?

How common are ophthalmologic complications of pediatric Crohn disease?

Which musculoskeletal disorders are possible complications of pediatric Crohn disease?

What are the symptoms of arthritis in patients with pediatric Crohn disease?

Which bone metabolic disorders are possible complications of pediatric Crohn disease?

What hematologic disorders are possible complications of pediatric Crohn disease?

Which hepatobiliary disorders are possible complications of pediatric Crohn disease?

What is the role of abnormal serum aminotransferases in patients with pediatric Crohn disease?

What is the presentation of liver disease in patients with pediatric Crohn disease?

Which genitourinary disorders are possible complications of pediatric Crohn disease?

What is the prevalence of nephrolithiasis in patients with pediatric Crohn disease?

What causes hydronephrosis in patients with pediatric Crohn disease?

Is pancreatitis a possible complication of pediatric Crohn disease?

Which pulmonary disorders are possible complications of pediatric Crohn disease?

Which cardiovascular disorders are possible complications of pediatric Crohn disease?

What is the prevalence of growth failure in patients with pediatric Crohn disease?

What causes thromboembolic disease in pediatric Crohn disease?

DDX

Which disorders should be included in the differential diagnosis of pediatric Crohn disease?

What are the differential diagnoses for Pediatric Crohn Disease?

Workup

What is the role of a complete blood count (CBC) in the diagnosis of pediatric Crohn disease?

What is the role of routine lab testing in the diagnosis of pediatric Crohn disease?

Which deficiencies in routine lab tests suggest pediatric Crohn disease?

What is the role of stool analysis in the diagnosis of pediatric Crohn disease?

What is the role of serologic testing in the diagnosis of pediatric Crohn disease?

What is the role of enzyme-linked immunosorbent assay (ELISA) in the diagnosis of pediatric Crohn disease?

Which radiological procedure can be used to evaluate the small intestine in patients with pediatric Crohn disease?

What radiological study is performed to evaluate the small bowel in patients with pediatric Crohn disease?

What is the imaging study of choice for the diagnosis of proximal small bowel pediatric Crohn disease?

What is the role of MRI, abdominal ultrasonography (US), and PET scanning in the diagnosis of pediatric Crohn disease?

Which procedure is the diagnostic standard in the diagnosis of pediatric Crohn disease?

What are the roles of upper endoscopy and esophagogastroduodenoscopy (EGD) in the diagnosis of pediatric Crohn disease?

What is the role of video capsule endoscopy in the diagnosis of pediatric Crohn disease?

Which intestinal biopsy findings indicate pediatric Crohn disease?

Which histologic findings may help differentiate ulcerative colitis (UC) from pediatric Crohn disease?

How is disease activity assessed in patients with Crohn disease?

What is the Pediatric Crohn Disease Activity Index (PCDAI)?

Treatment

What are the general goals of treatment for pediatric Crohn disease?

What is the step-up approach to therapy for pediatric Crohn disease?

What is the top-down approach to therapy for pediatric Crohn disease?

Which alternative and complimentary therapies may be beneficial for pediatric Crohn disease?

What is the efficacy of 5-acetylsalicylic acid (5-ASA) in the treatment of pediatric Crohn disease?

What is the efficacy of antibiotics in the treatment of pediatric Crohn disease?

What is the role of nutritional therapy in the management of pediatric Crohn disease treatment?

What is the role of corticosteroids in the management of pediatric Crohn disease?

What is the role of immunomodulators in the management of pediatric Crohn disease treatment?

What is the role of 6-Mercaptopurine (6-MP) and azathioprine in the treatment of pediatric Crohn disease?

What is the efficacy of methotrexate (MTX) in the treatment of pediatric Crohn disease?

When is infliximab (Remicade) indicated in the treatment of pediatric Crohn disease and what are the potential adverse events?

What is the role of adalimumab (Humira) in the treatment of pediatric Crohn disease?

What is the efficacy of adalimumab (Humira) in the treatment of pediatric Crohn disease?

What rare adverse effect has been reported in pediatric patients with Crohn disease receiving treatment with both anti-tumor necrosis factor (TNF)-alpha agents and an immunomodulator?

Are anti-tumor necrosis factor (TNF)-alpha agents more effective than an immunomodulator for the treatment of pediatric Crohn disease?

When is surgery indicated for the management of pediatric Crohn disease?

Is surgical resection a curative treatment for pediatric Crohn disease?

Which specialists should be consulted for the effective treatment of pediatric Crohn disease?

How is intestinal obstruction prevented in patients with pediatric Crohn disease?

What are the uses of nutritional therapy for pediatric Crohn disease?

Which activities should be restricted in patients with pediatric Crohn disease?

What is the long-term follow-up needed for children with Crohn disease?

When is hospitalization indicated in patients with pediatric Crohn disease?

Medications

What are the goals of pharmacotherapy in pediatric Crohn disease?

Which medications in the drug class Antibiotics, Other are used in the treatment of Pediatric Crohn Disease?

Which medications in the drug class Monoclonal Antibodies are used in the treatment of Pediatric Crohn Disease?

Which medications in the drug class Immunosuppressants are used in the treatment of Pediatric Crohn Disease?

Which medications in the drug class Corticosteroids are used in the treatment of Pediatric Crohn Disease?

Which medications in the drug class 5-Aminosalicylic Acid Derivatives are used in the treatment of Pediatric Crohn Disease?