Pediatric Crohn Disease 

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.^[1] 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.^[2]

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.^[3]

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.

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.