Introduction
Background
Crohn disease is not a distinct histopathologic entity. Although described and named after its author in 1932, Crohn disease was not clinically, histologically, or radiographically distinguished from ulcerative colitis until 1959.
Currently, the diagnosis of Crohn disease entails an analysis of clinical, radiologic, endoscopic, pathologic, and stool specimen results. Contrast-enhanced radiography is used to localize the extent, severity, and contiguity of disease. CT scanning provides cross-sectional images for assessing mural and extramural involvement. Endoscopy enables direct visualization of the mucosa and provides ability to obtain a biopsy specimen for histopathologic correlation. Ultrasonography and MRI are both adjuncts that provide alternative cross-sectional images in populations in whom radiation exposure is a concern.
For excellent patient education resources, visit eMedicine's Crohn Disease Center and Esophagus, Stomach, and Intestine Center. Also, see eMedicine's patient education articles, Inflammatory Bowel Disease, Crohn Disease, and Crohn Disease FAQs.
Pathophysiology
Etiology
The etiology of Crohn disease is largely unknown. Genetic, infectious, immunologic and psychological factors have all been implicated in influencing the development of the disease. The disease is characterized by chronic inflammation extending through all layers of the intestinal wall and involving mesentery as well as regional lymph nodes.
Early mucosal involvement consists of longitudinal and transverse aphthous ulcerations, which are responsible for cobblestone appearance. As the disease progress, deep fissures, sinuses and fistulas develop. Eventually, communication between diseased bowel segments, the abdominal wall, retroperitoneal structures, and the urinary tract occurs.
Because of the transmural nature of the disease, mesenteric and perianal manifestations are fairly common and because of the inflammation strictures resulting from edema, inflammation, and ultimately fibrosis and scaring are frequent. Crohn disease is pervasive. The basic pathologic process of disease can occur at any segment of the alimentary tract.
Risk factors
Risk factors include the following: family history, smoking, use of oral contraceptives, diet, and ethnicity.
In multiple studies, Crohn disease is associated with HLA-DR1 and DQw5 genes. Some results have suggested genetic anticipation whereby children of parents with Crohn disease tend to have earlier onset of the disease. Interestingly, although smokers have a decreased risk for ulcerative colitis, they have an increased risk of Crohn disease.
The risk ratio of developing Crohn disease is 2 to 1 with use of oral contraceptives; the risk is proportional to the duration of use. Diet has often been implicated as a risk factor in Crohn disease, but findings of current studies are inconclusive. However, ethnicity and race play integral parts in development of Crohn disease. Several investigators have suggested that the rate of inflammatory bowel disease is 2- to 4-fold higher in Jewish populations than in other ethnic groups. According to hospital census data from admissions in the United States, the rates are highest among Caucasians, followed by those in African Americans and Asians.
Histology
Crohn disease and ulcerative colitis share similar inflammatory changes. Cryptitis and subsequent crypt abscesses consisting of polymorphonuclear cells are identical for both diseases. However, during the inflammatory flare-ups, Crohn disease involves increases in the number of cells containing immunoglobulin G2 (IgG2), and ulcerative colitis involves a predominant increase in immunoglobulin G1 (IgG1) and immunoglobulin G3 (IgG3) cell types.
The inflammatory infiltrate of lamina propria in Crohn disease leads to loose aggregations of macrophages and they organized into noncaseating granuloma, which involve all layers of the bowel wall from mucosa to serosa. Occasionally, they can be seen on laparoscopy as miliary nodules, and they function as contiguous spread of the disease from the intestine. With chronic inflammation, the bowel walls become thickened, fibrotic, and stenotic in Crohn disease, extension of inflammation and fistula formation often occurs or as a result of a transmural fissure.
In ulcerative colitis, hemorrhagic and ulcerative inflammation is mostly limited to the mucosa, with recurrence leading to atrophic mucosa. Ulcers often have irregular borders, giving rise to a collar-stud effect. In recurrent disease, inflammatory polyps develop from exuberant epithelial regeneration. When inflammation infiltrate extends into submucosa and muscularis propria, it does so in a diffuse pattern, in contrast to Crohn disease in which they appear as lymphoid aggregates. Why Crohn disease has a skip distribution as opposed to that seen in ulcerative colitis is uncertain.
Frequency
United States
Findings from studies in the United States and Western Europe indicate that the incidence of Crohn disease is 2 cases per 100,000 population. The prevalence is estimated to be 20-40 cases per 100,000 population. Many have suggested that the prevalence of Crohn disease has been increasing.
International
Recent data show that, at least in Europe, rates in southern countries are catching up to those in their northern neighbors.
Mortality/Morbidity
Crohn disease is associated with higher rate of mortality, as compared with that of the general population, independent of the GI tract is involved. The excess mortality is most pronounced in the first few years after diagnosis. This observation has been attributed to complications of Crohn disease, which include abscesses, fistulas, intestinal obstructions and perforations, and colorectal cancer.
Approximately 15% of the cases of Crohn disease appear in those older than 50 years. In the older population, Crohn disease tends to involve the colon, and more obstructive and inflammatory complications tend to develop. However, despite this fact, older patients have been shown to tolerate medical and surgical therapy as well as young patients.
Abscesses develop in approximately 15-20% of patients with Crohn disease as a result of sinus track formation or as a complication of surgery. Abscess can be found in the mesentery, peritoneal cavity, or retroperitoneum, or in an extraperitoneal location. The most common sites of retroperitoneal abscesses are the ischiorectal fossa, the presacral space, and the iliopsoas region. The terminal ileum is the most common site of origin of abscesses. It is one of leading cause of mortality in Crohn disease.
Obstruction occurs in 20-30% of patients during the course of the disease. Early in the disease, it appears as reversible intermittent postprandial obstruction due to edema and bowel spasm. Over several years, this persistent inflammation gradually progresses to fibrostenotic narrowing and stricture, which may require regional resection.
Fistula formation is a frequent complication of Crohn disease of the colon. Fistulas can be categorized into 3 groups: benign, nuisance, and intractable. Benign fistula simple includes ileoileal, ileocecal, and ileosigmoid fistulas, which might produce only mild or moderate diarrhea. They may even remain asymptomatic for years without any treatment. Nuisance fistulas must be closed because of annoying symptoms or troublesome pathophysiologic consequences, but neither the complications nor the underlying bowel disease is severe enough to require surgery. This intermediate group includes enterovesicular, enterocutaneous, cologastric, and coloduodenal fistulas.
Complicated fistulas with abscesses or severe underlying bowel disease (either ulcerating inflammation or distal obstruction) are the most difficult to manage. They occur in 50% of patients with Crohn disease. The role of medical therapy is simply to control the obstructing, inflammatory, or suppurative processes before definitive surgery is performed. The operation is aimed at evacuation of the abscess and, if not contraindicated by associated sepsis, resection of the diseased bowel. This form of fistula often leads to spontaneous intestinal perforation in 1-2% of patients.
GI cancer has been the leading cause of mortality in Crohn disease. Adenocarcinoma usually arises in areas of chronic disease. The cancer risk is higher in both the small intestine and the colon, as compared with that of general population. The relative risk for adenocarcinoma of ileum is at least 100-fold greater in age- and sex-matched controls. Small-bowel cancers typically arise at sites of macroscopic disease after mean age of 18 years.
Unfortunately, most cancers related to Crohn disease are not detected until advanced stages and have poor prognosis. Mounting evidence from studies indicates that Crohn disease has a cancer risk equal to that of ulcerative colitis. Some extraintestinal cancers (eg, squamous cell cancer in patients with chronic perianal, vulvar, or rectal disease) and Hodgkin or non-Hodgkin lymphomas have been also shown to be more common in patients with Crohn disease.
Race
In the early 1960s, the incidence rate for Crohn disease among African Americans was approximately one fifth that of whites. The difference in incidence rates between these populations narrowed in the late 1970s. Because the data were based on hospital admissions, some authors have argued that bias was introduced because of unequal access to medical services.
In contrast, in a study of the hospital records from the Kaiser-Permanente medical care program in northern California, the rates of hospital admissions for inflammatory bowel disease in African Americans and in whites were equal between 1970 and 1982, whereas the rate among Asians was found to be much lower.
Studies of the incidence of inflammatory bowel disease in populations that emigrate to high-risk geographic areas suggest that the incidence rate increases in these groups.
Findings from several studies have suggested that, within specified geographic areas, the incidence rate of inflammatory bowel disease is 2- to 4-fold higher in Jewish populations than in other ethnic groups.
Sex
Studies consistently reveal a greater incidence in women than in men, with a female-to-male ratio of 1.1-1.8:1. Many believe that this distribution corresponds to the autoimmune process in Crohn disease.
Age
Crohn disease has a bimodal distribution. One early peak occurs in those aged 18-25 years. A smaller peak is observed in those aged 60-80 years.
In patients younger than 20 years, the percentage of cases in which Crohn disease involves the small intestine is 88.7%, as compared with 57.5% in those older than 40 years. A significantly greater frequency of colonic disease is found in patients older than 40 years, as compared with those younger than 20 years. The reasons for the differences are not clear.
Anatomy
Although Crohn disease can involve any segment of the alimentary tract, 3 primary clinical and anatomic presentations are recognized. They are small-bowel involvement only (30%), distal small-bowel and colonic involvement (45%), and colonic involvement only (25%). Superficially, 30% of cases of Crohn disease occur with rectal disease, and 33-50% occur with perianal disease such as anal fissures, perianal abscesses, and fistulas.
Presentation
General clinical features of Crohn disease are fever, abdominal pain, diarrhea, and fatigability. Weight loss is also associated. Diarrhea and pain are the most common symptoms of colonic involvement. Rectal bleeding is less common. Anorectal complications are fistulas, fissures, and perirectal abscess. Involvement of the small intestine can lead to steady and localized right lower quadrant pain; ileitis is fairly common. Physical examination may reveal right lower quadrant tenderness with an associated fullness or mass. Patients may also have mild anemia, leukocytosis, and an increased erythrocyte sedimentation rate.
Intestinal obstruction is a frequent complication. In the initial stage, obstruction from edema and inflammation commonly in the ileum are reversible. As disease progresses, fibrosis develops, leading to decreasing diarrhea and more constipation and intractable obstruction from fixed luminal narrowing.
Fistula formation is common and can cause indolent abscess, malabsorption, cutaneous fistula, persistent urinary tract infection, or pneumaturia. Although uncommon, free intestinal perforation can occur as a result of transmural involvement of the disease.
Extraintestinal manifestation of Crohn disease includes oral aphthous ulcer, erythema nodosum, osteomalacia, and anemia due to chronic malabsorption; osteonecrosis due to chronic steroid therapy; gallstone formation due to ileal involvement of disease leading to poor bile salt reabsorption; oxalate kidney stones due to colonic disease; pancreatitis due to sulfasalazine, mesalamine, azathioprine, or 6-mercaptopurine therapy; bacteria overgrowth due to surgical resection; and miscellaneous manifestations such as amyloidosis, thromboembolic complications, hepatobiliary disease, and primary sclerosing cholangitis.
Preferred Examination
The preferred examinations are plain radiography, double-contrast barium enema examination, single-contrast upper GI series with small-bowel follow-though or enteroclysis with CT and double-contrast evaluation of the small bowel. Ultrasonography and MRI can be used as adjuncts if radiation exposure is an issue in monitoring disease activity.
Currently, no specific laboratory test is useful in the diagnosis of Crohn disease or in correlating the findings with the clinical activity.
Limitations of Techniques
Abdominal radiographic findings are not specific for Crohn disease. Radiography is useful in evaluation of bowel-loop distention and pneumoperitoneum.
In general, barium contrast studies are limited in the evaluation of transluminal inflammation in Crohn disease. Distention of small bowel with contrast material is required for proper evaluation. Slow passage of the contrast agent through the pylorus can result in nonvisualization of small-bowel lesions in small bowel series. Enteroclysis is one way to circumvent the dilemma by passing a catheter to the duodenal jejunal junction.
CT has is not as sensitive in delineating fissure or fistula as barium studies, but it is superior to barium studies in showing the extraluminal sequelae of Crohn disease. Residual contrast material from barium studies leads to severe streak artifact on CT scans due to hyperattenuating contrast suspension used in barium studies. On the other hand, CT contrast residue does not preclude a barium study. Thus, in general, clinician should select CT first in evaluation of Crohn disease.
Sonographic findings have high variability because of operator dependence in detection of the bowel-wall changes seen in Crohn disease. Transmission of ultrasound waves through fatty tissues is limited, and detection may be severely limited by the patient's body habitus.
Traditionally, MRI had been limited to the evaluation of the abdomen because of motion artifact. With stronger gradients, breath-hold imaging is possible and MRI of the abdomen and pelvis can be readily performed in most patients.
In addition, optimal imaging with MRI often requires the use of large volumes of positive or negative contrast agents given either orally or via nasojejunal or rectal tube. However, acutely ill patients may not be able to tolerate a large oral fluid load. If suboptimal distension occurs, detection of inflamed segments of bowel may be limited. Air in the colon can be a substantial susceptibility artifact with some sequences, especially gradient-echo sequences.
Differential Diagnoses
Cholangitis, Primary Sclerosing
Colitis, Ischemic
Colitis, Pseudomembranous
Colon, Diverticulitis
Tuberculosis, Gastrointestinal
Ulcerative Colitis
Other Problems to Be Considered
Infectious enteritis
Infectious colitis
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References
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Further Reading
Keywords
Crohn's disease, regional enteritis, inflammatory bowel disease, HLA-DR1 gene, DQw5 gene
