Pediatric Crohn Disease
- Author: Andrew B Grossman, MD; Chief Editor: Carmen Cuffari, MD more...
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.
Essential update: FDA approves adalimumab for pediatric patients with Crohn's
The FDA has approved an additional indication for the tumor necrosis factor-alpha inhibitor adalimumab (Humira) for the treatment of pediatric patients 6 years of age and older with moderately to severely active Crohn's disease who have had an inadequate response to corticosteroids or immunomodulators. Approval was based on a prospective multicenter study in children with Pediatric Crohn's Disease Activity Index (PCDAI) scores >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.[1, 2]
Adalimumab drug is already approved for the treatment of moderately to severely active Crohn's disease in adults.
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:
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
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.
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  ; on ELISA, the cutoff level is 50 µg/g feces.
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
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
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 
See Workup for more detail.
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)
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 
Adalimumab is a safe and effective substitute for patients who are allergic to infliximab or develop high titers of human antichimeric antibodies (HACA) 
Surgery is considered when medical therapy fails 
Indications for surgery include the following:
Intractable disease with growth failure
Obstruction or severe stenosis
Abscess requiring drainage
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 
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.
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.
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. 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. 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.
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.
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.
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.
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.
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.
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|Crohn Disease||Ulcerative Colitis|
|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|
|GI = gastrointestinal.|