eMedicine Specialties > Pediatrics: General Medicine > Gastroenterology
Crohn Disease
Updated: Oct 8, 2009
Introduction
Background
Crohn disease (CD), or Crohn's disease, is a chronic inflammatory bowel disease. Once considered rare in the pediatric population, Crohn disease 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 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 Crohn disease. 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 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 in Crohn disease 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).
Colonoscopic image of a large ulcer and inflammation of the descending colon in a 12-year-old boy with Crohn disease.
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 (see Media file 2).
Histologic features of chronic colitis with crypt atrophy and branching, and lymphocytic infiltrate. Hematoxylin-eosin staining. Courtesy of Dr E. Ruchelli.
Granulomas (see Media file 3) are sometimes noted on biopsy findings in Crohn disease but never in UC; their presence can be useful in distinguishing between these 2 entities.
Colonic granuloma in a patient with Crohn disease. Hematoxylin-eosin staining. Courtesy of Dr E. Ruchelli.
Frequency
United States
Over the past few decades, the incidence of inflammatory bowel disease (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.1
International
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.
Mortality/Morbidity
Death from Crohn disease is extremely rare in children and adolescents. Severe and complicated Crohn disease may result in prolonged hospitalizations, surgeries, growth failure, malnutrition, pubertal delay, and poor quality of life.
Race
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.
Sex
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 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 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 inflammatory bowel disease are diagnosed before age 20 years.
Clinical
History
Patients with suspected Crohn disease (CD), or Crohn's disease, should initially be evaluated by their primary care team. 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 Crohn disease 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 Crohn disease.
- Crohn disease of the 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: This may be clinically indistinguishable from ulcerative colitis (UC), with symptoms of bloody mucopurulent diarrhea, cramping abdominal pain, and urgency to defecate.
- Perianal Crohn disease: 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 Crohn disease because abnormalities detectable in this region substantially increase the clinical suspicion of inflammatory bowel disease.
- Upper GI Crohn disease Crohn disease: Patients with this condition may experience nausea, vomiting, and abdominal pain as dominating presenting symptoms.
Characteristics Differentiating Crohn Disease and Ulcerative ColitisOpen table in new window
[ CLOSE WINDOW ]Table
Characteristic 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% per year starting 10 years after diagnosis Presentation Crohn Disease Ulcerative Colitis Bleeding Common Very common Obstruction Common Uncommon Fistula Common None Weight loss Common Uncommon Perianal disease Common Rare Characteristic 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% per year starting 10 years after diagnosis Presentation Crohn Disease Ulcerative Colitis 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 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.
Causes
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.3 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 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 Crohn disease 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 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.
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| References |
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Further Reading
Keywords
Crohn disease, CD, Crohn colitis, Crohn's disease, regional enteritis, granulomatous colitis, ileitis, terminal ileitis, inflammatory bowel disease, IBD, diarrhea, rectal bleeding, abdominal pain, growth failure, malnutrition, pubertal delay, bone demineralization, ulcerative colitis, UC, growth deceleration, anorexia, skin tags, fissures, abscesses, fistula, granuloma, erythema nodosum, pyoderma gangrenosum, orofacial granulomatosis, angular stomatitis, aphthous stomatitis, acrodermatitis enteropathica, alopecia, episcleritis, uveitis, iritis, conjunctivitis, arthralgia, arthritis
ankylosing spondylitis, sacroiliitis, osteopenia, osteoporosis, iron deficiency anemia, vitamin B12 deficiency anemia, folate deficiency anemia, autoimmune hemolytic anemia, thrombocytosis, thrombosis, primary sclerosing cholangitis, autoimmune hepatitis, granulomatous hepatitis, cholelithiasis, portal vein thrombosis, nephrolithiasis, obstructive uropathy, glomerulonephritis, amyloidosis, pancreatitis, granulomatous lung disease, fibrosing alveolitis, pulmonary vasculitis, pericarditis, myocarditis, vasculitis
