AUTHOR AND EDITOR INFORMATION

Section 1 of 11  

• Authors and Editors
• Introduction
• Differentials
• Radiograph
• CT SCAN
• Mri
• Ultrasound
• Nuclear Medicine
• Intervention
• Multimedia
• References

INTRODUCTION

Section 2 of 11  

• Authors and Editors
• Introduction
• Differentials
• Radiograph
• CT SCAN
• Mri
• Ultrasound
• Nuclear Medicine
• Intervention
• Multimedia
• References

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.

Clinical Details

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.

DIFFERENTIALS

Section 3 of 11  

• Authors and Editors
• Introduction
• Differentials
• Radiograph
• CT SCAN
• Mri
• Ultrasound
• Nuclear Medicine
• Intervention
• Multimedia
• References

Other Problems to be Considered

Infectious enteritis
Infectious colitis

RADIOGRAPH

Section 4 of 11  

• Authors and Editors
• Introduction
• Differentials
• Radiograph
• CT SCAN
• Mri
• Ultrasound
• Nuclear Medicine
• Intervention
• Multimedia
• References

Findings

The role of plain radiography is fairly limited. The 2 major purposes that it serves are (1) to assess the presence of intestinal obstruction and (2) to evaluate pneumoperitoneum prior to further radiological workup. Additional extraintestinal findings of sacroiliitis or oxalate kidney stones may be present. These further support the diagnosis of Crohn disease.

Double-contrast barium enema study is useful for diagnosing inflammatory bowel disease and for differentiating Crohn disease from ulcerative colitis, especially in the early phase of the disease. On double-contrast studies, early Crohn disease is characterized by discrete aphthoid ulcers, which are seen as punctate or slitlike collections of barium surrounded by radiolucent mounds of edema. The aphthoid ulcers are often separated by normal bowel and present as skip lesions.

On the contrary, ulcerative colitis extends proximally at various degrees from the rectum as a continuous area of disease that eventually leads to pancolitis. Early ulcerative colitis is characterized by a granular appearance on double-contrast examination as a result of edema and hyperemia of the mucosa. Thus, the 2 diseases can be differentiated on basis of radiographic findings.

As more severe Crohn disease develops, the small ulcers become enlarged and deeper, and they connect to one another, forming stellate, serpiginous, and linear ulcers. These ulcers are found most frequently in terminal ileum along the mesenteric border. These are pathognomonic of Crohn disease. On small-bowel series or enteroclysis, a mesenteric border ulcer appears as a long 1- to 2-mm barium collection that parallels a short, straight mesenteric border. A radiolucent collar usually parallels the linear barium collection at the margin of the ulcer. The antimesenteric border of the bowel is usually uninvolved and pulled into the ulcer collar, creating radiating folds.

As inflammation penetrates the submucosa and muscularis layers, deep knife like linear cleft form the basis of "cobblestoning" and fissure or fistula formation. They appear as a barium-filled reticular network of grooves that surround round or ovoid radiolucent island of mucosa. Eventually, transmural inflammation leads to decreased luminal diameter and limited distensibility. This leads to radiographic string sign that represents long areas of circumferential inflammation and fibrosis resulting in long segments of luminal narrowing.

Chronic inflammation in the lamina propria of the small intestine results in enlarged villi radiographically manifested as 0.5- to 2-mm, round or polygonal nodules. This fine mucosal nodularity occurs in the small intestine and should not be confused with the mucosal granularity seen in the colon of patients with ulcerative colitis.

Degree of Confidence

Aphthoid ulcers are detected on barium studies in 25-50% of patients with Crohn disease. These are identified in as many as 75% of surgical specimens with Crohn disease. Endoscopy is slightly superior to barium studies in the demonstration of isolated or a few aphthoid ulcers.

In a comparison of 23 patients with ulcerative colitis with 27 with Crohn disease, Laufer et al established the differentiating features the conditions using barium study. They found that ulcerative colitis involves granular mucosa, diffuse rectal involvement, and continuous inflammatory changes in the bowel with sparing of the terminal ileum. Crohn disease involves patchy rectal involvement with punched-out ulcers, ulcers on normal mucosa, and discontinuous bowel inflammation typically with involvement of the terminal ileum. These criteria are distinguishing in 95% of patients. The difficulty in differentiating the 2 illnesses reported occurs at later chronic stages, during which numerous remissions and exacerbations can result in discontinuous ulcerative colitis has become. Despite this difficulty, careful examination of the mucosal surface with barium study enables the distinction.

False Positives/Negatives

Mucosal nodularity or granularity in a small-bowel series is a nonspecific finding that can be seen in diseases that infiltrate or inflame the lamina propria, such as amyloidosis or radiation enteritis.

Small-bowel follow-though examination is limited by the speed of barium passage through the pylorus. If too slow, incomplete distention in the lumen of the bowel can cause short skip lesions, masses, or obstructing lesions in the small bowel to be missed.

In general, 18-20% of findings are false-negative on barium study, as compared with endoscopic detection. However, barium enema has a 95% accuracy rate in distinguishing Crohn disease from ulcerative colitis.

CT SCAN

Section 5 of 11  

• Authors and Editors
• Introduction
• Differentials
• Radiograph
• CT SCAN
• Mri
• Ultrasound
• Nuclear Medicine
• Intervention
• Multimedia
• References

Findings

The role of CT in the evaluation of Crohn disease is well accepted. The ability of CT to depict bowel involvement and extraluminal pathology (eg, abscess, obstruction, fistula) makes it an essential imaging tool for patient care. The earliest CT finding of Crohn disease is bowel wall thickening, which usually involves the distal small bowel and colon, although any segment of GI tract can be affected. Typically, the luminal thickening is 5-15 mm.

Ulcerations in the mucosa can be detected on thin-section CT, although small-bowel series or enteroclysis is more sensitive to the early mucosal changes of Crohn disease. In addition, mesenteric stranding, increase in mesenteric fat, local adenopathy, fistula, and abscess are readily and commonly identified on CT scans.

Edema or mild inflammation of the mesenteric fat results in fat of increased attenuation, the so-called hazy fat on CT. Greater inflammation or fibrosis of fat results on CT in attenuating linear bands of soft tissue coursing through the mesentery. On CT, an ill-defined inflamed mass of mixed attenuation may represent a phlegmon or early abscess formation. Enlarged lymph nodes are usually seen in proximity to the bowel wall along the mesenteric course of the vascular bundle.

On CT scans, abscesses appear as well-defined, round or oval masses of fluid attenuation, and they are often multilocular. Pockets or bubbles of gas usually result from fistulous communication with bowel or, less likely, from infection by gas-producing organisms.

One limitation of CT has been in the area of delineating active versus inactive disease. The presence of mesenteric stranding does not reliably signify active disease because residual mesenteric thickening can remain during remission.

The introduction of multidetector-row CT scanners with thinner collimation and faster intravenous injections of contrast material have allowed more detailed evaluation of the bowel. The enhancement of the bowel wall after intravenous contrast enhancement is correlated with the enlargement of the feeding vessel and hyperemia during active disease. In an article by Del Campo et al, patients with active disease had a bowel wall attenuation of 95 HU, as compared with 65 HU in patients with disease in remission. The ability to measure bowel wall enhancement may prove valuable in treating patients with Crohn disease.

Degree of Confidence

CT should be the first radiologic procedure performed in patients with acute symptoms and suspected or known Crohn disease. The ability to directly demonstrate the bowel wall, adjacent abdominal organs, mesentery and retroperitoneum makes CT superior to barium studies in diagnosing the complications of Crohn disease. CT directly demonstrates bowel wall thickening, mesenteric edema and lymphadenopathy as well as phlegmon and abscess.

Although barium is more sensitive in demonstrating the presence of fissures and fistulas, CT is superior in demonstrating the sequelae of these tracks (eg, air in the urinary bladder in enterovesical fistula).

False Positives/Negatives

The sensitivity of CT for Crohn disease is estimated to be 71%, with lower detection of early mucosal disease as compared with barium studies. A recent study by Philpotts et al has shown that the CT findings of Crohn disease considerably overlap with those of infectious, radiation, ulcerative, and ischemic colitides.

However, certain distinguishing features including differences in wall thickness and attenuation; the distribution of colonic wall involvement; the presence or absence of abscesses, fistulas, small-bowel disease, and mesenteric fibrofatty proliferation have all been cited in delineating Crohn disease from other forms of enterocolitis. In using the mentioned features, CT can attain positive predictive value above 90% and a diagnostic accuracy as high as 93%.

There is considerable overlap between CT findings of ulcerative colitis and Crohn disease. Despite this fact, certain defining features of each disease have been characterized. Ulcerative colitis is predominantly a mucosal disease. However, with progression of illness, there is hypertrophy of the muscularis often by 40 fold, increase submucosa fatty deposition, and thickening of the lamina propria from round cell infiltration which all leads to bowel wall thickening. On average, thickening of the luminal wall is 7.8 mm in ulcerative colitis, which is less than the amount of wall thickening typically seen with Crohn disease.

Submucosal fat as mentioned is a prominent finding in chronic ulcerative colitis and is one of the defining features of the mural stratification seen in ulcerative colitis. In comparison, Crohn disease has transmural involvement that over time leads to replacement of submucosal fat with fibrosis and loss of mural stratification. In distinction to ulcerative colitis, Crohn disease also has several extraluminal CT findings including mesenteric fibrofatty proliferation and abscess.

MRI

Section 6 of 11  

• Authors and Editors
• Introduction
• Differentials
• Radiograph
• CT SCAN
• Mri
• Ultrasound
• Nuclear Medicine
• Intervention
• Multimedia
• References

Findings

Traditionally, MRI has had a well-defined role in evaluation of anorectal complications of Crohn disease. With a regular fast spin-echo technique, the pathologic entities of a fistula, a sinus tract, and an abscess can be detected in the static anorectal region by using MRI.

Sinus tracts and fistulas often appear hyperintense on T1-weighted images and hyperintense on T2-weighted images because of their fluid content. With fat suppression, the fluid signal is further intensified and easily seen as being hyperintense on T2-weighted images. An abscess often appears as an isolated collection of high-signal-intensity areas on the T2-weighted image, especially in ischioanal fossa. Defining whether abscess, fistula, or sinus tract is above or below the levator ani muscle is important for drainage, because any part of the abscess above the levator ani muscle will not drain adequately in the inferior direction, and vice versa.

Recently, the development of faster pulse sequences (eg, single-shot fast spin-echo and gradient-echo sequences) and higher-gradient systems has made T1- and T2-weighted breath-hold imaging possible. This breath-hold imaging has been a major breakthrough in overcoming physiologic motion artifacts in abdominal imaging. It has made routine abdominal MRI feasible. Because of a decrease in cumulative radiation exposure and because of the possibility of attaining high-quality coronal images correlating with barium studies, MRI is currently being investigated for monitoring disease activity in Crohn disease.

The parameters of active disease from multiple investigations have included wall thickening, fibrofatty proliferation, and bowel wall enhancement with gadolinium-based contrast agents. During active inflammation, gadolinium enhancement of the bowel wall can be seen on T2-weighted images, and it is easily differentiated from normal adjacent bowel. The enhancement pattern described by Koh et al is "layered" and specific to Crohn disease.

Wall thickening has been variable in active disease, as described in many reports. The general consensus is that concentric bowel wall thickening greater than 4 mm is suggestive of active disease. In study by Maccioni et al, active disease is characterized by a thickened bowel wall with gadolinium enhancement, but inactive disease is not. Fibrofatty proliferation is hyperintense on T2-weighted images and related to regional mesenteritis or edema and dilatation of local vessels in both active and nonactive disease.

Fat-suppressed T2-weighted images can also be used for differentiation because they fat-suppressed show high signal intensity in active disease and low or absent signal intensity in nonactive disease. Madsen et al evaluated the use of T2-weighted gadolinium-enhanced imaging in assessing wall thickening in response to treatment.

Currently, gadolinium-enhanced spoiled gradient-echo MRI is the most useful study for depicting mural changes during active disease. Dilute barium sulfate and water can be used to distend the bowel and act as a negative contrast agent on fat-suppressed T2-weighted spoiled gradient-echo images.

Another possible imaging sequence in use has been the single-shot fast spin echo sequence, in which T2-weighted images are acquired by using half-Fourier transformation and a long echo train. Each image section is acquired independently in less than 1 second, and the method eliminates physiologic motion from bowel and the need for breath holds. Compared with gradient-echo techniques, this method is less sensitive to motion artifact. Both water and dilute 2% barium sulfate serve as positive intraluminal contrast agents in single-shot fast spin-echo sequences. Low et al and Marcos and Semelka have found gradient-echo imaging to be more sensitive than other methods in determining the severity of Crohn disease, and they favor the use of gadolinium-enhanced gradient-echo MRI.

Gadolinium-based contrast agents (gadopentetate dimeglumine [Magnevist], gadobenate dimeglumine [MultiHance], gadodiamide [Omniscan], gadoversetamide [OptiMARK], gadoteridol [ProHance]) have recently been linked to the development of nephrogenic systemic fibrosis (NSF) or nephrogenic fibrosing dermopathy (NFD). For more information, see the eMedicine topic Nephrogenic Fibrosing Dermopathy. The disease has occurred in patients with moderate to end-stage renal disease after being given a gadolinium-based contrast agent to enhance MRI or MRA scans.

As of late December 2006, the FDA had received reports of 90 such cases. Worldwide, over 200 cases have been reported, according to the FDA. NSF/NFD is a debilitating and sometimes fatal disease. Characteristics include red or dark patches on the skin; burning, itching, swelling, hardening, and tightening of the skin; yellow spots on the whites of the eyes; joint stiffness with troublemoving or straightening the arms, hands, legs, or feet; pain deep in the hip bones or ribs; and muscle weakness. For more information, see the FDA Public Health Advisory or Medscape.

Degree of Confidence

Gadolinium-enhanced spoiled gradient-echo MRI has reported sensitivity of 85-89%, a specificity of 96-94%, and an accuracy of 94-91% for active disease as compared with single-shot fast spin-echo MRI, which has a sensitivity of 51-52%, a specificity of 98-96%, and an accuracy of 83-84% (Low, 2002).

False Positives/Negatives

In general, most investigators currently favored the use of gadolinium-enhanced gradient-echo imaging for monitoring Crohn disease activity with MRI. In the gradient-echo sequence, active disease is best correlated with mural thickening, as shown with gadolinium enhancement.

False-positive findings most often occur when gadolinium enhancement is present without mural thickening. False-negative findings most often occur when distension of the bowel is suboptimal.

ULTRASOUND

Section 7 of 11  

• Authors and Editors
• Introduction
• Differentials
• Radiograph
• CT SCAN
• Mri
• Ultrasound
• Nuclear Medicine
• Intervention
• Multimedia
• References

Findings

Ultrasonography can be an alternative to CT in the evaluation of the intraluminal and extraluminal manifestations of Crohn disease. The normal GI wall appears as 5 concentric, alternating echogenic and hypoechoic layers; this appearance is known as the gut signature. The GI wall has an average thickness of less than 5 mm.

In the case of active Crohn disease, the wall thickness can range from 5 mm to 2 cm with either partial or total loss of layering, which reflects transmural edema, inflammation or fibrosis. With severe inflammation, the wall appears diffusely hypoechoic with a central hyper echoic line that corresponds to the narrowed lumen. Peristalsis is reduced or absent, and the diseased segment is noncompressible and rigid with a loss of haustra.

Ultrasonography can depict ballooning of the less involved segments, which is seen as focal sacculation or outpouching. These findings reflect the skip lesions found in Crohn disease. The accuracy of ultrasonography is further improved with the use of color Doppler imaging. The use of Doppler imaging is helpful in the detection of hyperemia of an inflamed bowel wall and adjacent fat during active disease.

With transmural inflammation, edema and fibrosis of the adjacent mesentery occurs, leading to fingerlike projections of mesenteric fat that creeps over the serosal surface of the bowel. This creeping fat eventually envelops the diseased bowel segment. On sonograms, this appears as a uniform hyperechoic mass, which is classically seen at the cephalic margin of the terminal ileum. With long-standing disease, this becomes more heterogeneous or even hypoechoic.

In active Crohn disease, reactive mesenteric nodes are enlarged and may coalesce to form a conglomerate mass. On sonograms, enlarged nodes can be seen as oval hypoechoic masses in the mesentery. With confluence, they become lobulated mass of various sizes.

Many complications of Crohn disease can also be seen in their ultrasonographic forms. Phlegmon appears as hypoechoic mass with irregular borders and no identifiable wall or fluid. Abscess appears as a fluid collection with thickened wall containing air or echogenic debris. Obstruction appears as dilated hyperperistaltic fluid filled segments. Perforation appears as bright echoes with distal acoustic shadows outside the boundaries of bowel loops.

Fistula, on the other hand, appears as a hypoechoic tract. If gas is present in the fistulous tract, it contains hyperechoic foci with acoustic shadowing. Palpation of diseased loops during sonography enables tract identification. In addition sonography should be able to identify gas bubbles in abnormal locations, eg, air in bladder or vaginal vault, retroperitoneum, subcutaneous tissue and urachal remnant.

Degree of Confidence

The detection of bowel wall thickening varies widely. Detection rates range from 22% to 89%. The large variation presumably reflects differences in technique, operator experience, and ultrasound equipment. Determination of the extent of the disease is not always possible, and correlation between wall thickening and the clinical activity of disease is poor.

False Positives/Negatives

The loss of gut signature and bowel wall thickening is a nonspecific finding. It is found in infectious, ischemic, neoplastic, and radiation-induced conditions. In addition, the detection of bowel wall changes in Crohn disease varies significantly because of operator dependence.

The literature states that the differentiation between hypoechoic foci from creeping fat versus from phlegmon or edema may be difficult or nearly impossible. Proponents of CT have also stated that the specificity of color Doppler imaging is still unknown. In general, the confidence level of the radiologist in interpreting the results is operator dependent, and it is often lower than that of CT. For these reasons, ultrasonography has not been the favored modality for imaging Crohn disease.

NUCLEAR MEDICINE

Section 8 of 11  

• Authors and Editors
• Introduction
• Differentials
• Radiograph
• CT SCAN
• Mri
• Ultrasound
• Nuclear Medicine
• Intervention
• Multimedia
• References

Findings

Leukocytes labeled with either technetium-99m-HMPAO or indium-111 can be used to assess for active bowel inflammation in inflammatory bowel disease. Compared to the ¹¹¹In label, the ^99mTc HMPAO label has better imaging characteristics and can be imaged much sooner after injection. However, imaging must typically be done within an hour after injection of ^99mTc HMPAO labeled leukocytes as there is normal excretion into the bowel after this time, unlike ¹¹¹-labeled leukocytes, which have no normal bowel excretion.

Degree of Confidence

Molnar et al found that ^99mTc HMPAO leukocyte scan in active Crohn disease had a sensitivity of 76.1% and specificity of 91.0% compared to CT sensitivity of 71.8% and specificity of 83.5%. While leukocyte scan may be better in the detection of segmental inflammatory activity, CT is superior for the detection of complications.

False Positives/Negatives

False-positive bowel activity can be seen with gastrointestinal bleeding, swallowed leukocytes (eg, from uptake related to sinusitis or nasogastric tubes), or activity related to indwelling enteric tubes. In addition, leukocyte uptake is not specific for Crohn disease and will be seen in most infectious or inflammatory bowel processes. As mentioned above, there is often normal bowel excretion of ^99m99m HMPAO leukocytes if imaged after the first hour of the injection.

INTERVENTION

Section 9 of 11  

• Authors and Editors
• Introduction
• Differentials
• Radiograph
• CT SCAN
• Mri
• Ultrasound
• Nuclear Medicine
• Intervention
• Multimedia
• References

CT-guided therapy

CT has become the procedure of choice, not only in diagnosing Crohn disease but also in managing abscesses. A growing body of literature shows that CT-guided percutaneous abscess drainage may obviate surgery. In recent studies, CT percutaneous abscess drainage has shown great success either as a temporizing measure or as definitive therapy with a decreased rate of recurrence, as compared with that of surgery. Because about 70-90% of patients with regional enteritis eventually require surgery, avoiding an operation to treat an abscess is a tangible benefit of CT.

Medical therapy

The medical management of Crohn disease can be divided into the treatment of an acute exacerbation and the maintenance of remission. In acute exacerbation, triggers such as underlying infection, fistula, perforation, and other pathology must be ruled out prior to the intravenous administration of glucocorticoids.

Intravenous hydrocortisone or methylprednisolone is often used, in addition to metronidazole and bowel rest, as main acute therapy. The use of steroid therapy is limited for short burst response because of its various long-term adverse effects, including osteonecrosis, myopathy, osteoporosis, and growth retardation. A potent inhibitor of cell-mediated immunity, intravenous cyclosporine may be used for further immune modulation if the response to corticosteroids is poor. Many studies have established that cyclosporine is effective in the short term, but it fails as long-term therapy.

The goal of chronic therapy is the remission of bowel inflammation. Aminosalicylates has been the mainstay of therapy because of its anti-inflammatory activities. Several formulations have been introduced, each with a different carrier molecule for targeting a specific region of the bowel. Sulfasalazine and balsalazide are primarily released in the colon. Dipentum and Asacol are formulations for targeted release in the distal ileum and colon. Pentasa can be released in the duodenum to the distal colon, whereas Rowasa is specific for the rectum and distal colon.

Methotrexate, azathioprine, and 6-mercaptopurine are other nonsteroidal immune modulators that are well tolerated. Azathioprine, which is nonenzymatically converted in the body to 6-mercaptopurine, is metabolized to thioinosinic acid, which is a purine synthesis inhibitor. Adverse effects of azathioprine and 6-mercaptopurine are less common, as compared with those of steroids. Nevertheless, a 3% incidence of pancreatitis, allergic reactions, infections, and marrow toxicity is associated with their use. The main drawback to the use of azathioprine and 6-mercaptopurine is their slow onset of action. The effect of therapy is noted after 3-6 months of treatment.

Methotrexate, the long-standing folic acid antagonist, is effective in many patients with disease refractory to azathioprine and 6-mercaptopurine. It has the well-known adverse effects of leukopenia, GI upset, and hypersensitivity pneumonitis.

New therapies target tumor necrosis factor-alpha. Agents such as infliximab, Etanercept and CDP571 are becoming available and showing promising results, with an increased remission rate in 48% at 4 weeks and with complete fistula closure in 55% of patients at 80 days for infliximab. Other agents such as mycophenolate have been developed to inhibit guanine nucleotide synthesis and thereby inhibit B and T lymphocytes. Randomized clinical trials are underway to compare mycophenolate with azathioprine. So far, mycophenolate has shown a greater rate of improvement at 1 month.

Surgical therapy

More than 70% of patients with Crohn disease undergo surgery within 20 years of the diagnosis. Indications for surgery in Crohn disease include stricture, intractable or fulminant disease, anorectal disease and intra-abdominal abscess. The basic tenant in Crohn surgery is to limit small-bowel resection to grossly diseased segment. When stricture is present, the small bowel can often be preserved with stricturoplasty. This involves incising a stricture longitudinally and then suturing it transversely to widen the lumen.

The recurrence rate has been reported to be 34% at 7-year follow-up (Dietz, 2001), and it is comparable with that of surgical resection, namely, 25% at 5 years and 50% at 10 years. The procedure also has the additional benefit of preventing short-bowel syndrome. The morbidity rate of 18% and the lack of perioperative deaths with stricturoplasty are favorable features (Dietz, 2001), as compared with surgical resection. The site of recurrence in stricturoplasty is similar to that of resection, ie, perianastomotic, with the highest rate of recurrence in younger patients. Recurrence is often defined as detectable active disease, as depicted with radiography or endoscopy, with a return of symptoms.

Medical/Legal Pitfalls

• The oral administration of contrast material is to be avoided when moderate- or high-grade colonic obstruction is present.
• Double-contrast (air contrast) barium enema examination is contraindicated in patients with severe colitis because injection of air with contrast agent may precipitate toxic megacolon or colonic perforation.
• Barium studies are contraindicated when signs and symptoms of peritonitis or when radiographic signs of gas in the bowel wall or pneumoperitoneum are present.
• The intravenous injection of contrast material for CT studies should be avoided when chronic renal insufficiency, continued use of Glucophage, or signs and symptoms of acute renal failure are present.
• CT and barium studies use ionizing radiation, which may result in considerable radiation burden. This exposure is a relative contraindication in pregnancy and childhood. Sonography and MRI may prove to be useful alternative imaging modalities.

See also the Medscape topic Medical Malpractice and Legal Issues.

MULTIMEDIA

Section 10 of 11  

• Authors and Editors
• Introduction
• Differentials
• Radiograph
• CT SCAN
• Mri
• Ultrasound
• Nuclear Medicine
• Intervention
• Multimedia
• References

Media file 1:  Crohn disease. Aphthous ulcers. Double-contrast barium enema examination in Crohn colitis demonstrates numerous aphthous ulcers.
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Media file 2:  Crohn disease. Cobblestoning. Spot view of the terminal ileum from a small-bowel follow-through study demonstrates linear longitudinal and transverse ulcerations that create a cobblestone appearance. Also note the relatively greater involvement of the mesenteric side of the terminal ileum and the displacement of the involved loop away from the normal small bowel secondary to mesenteric inflammation and fibrofatty proliferation.
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Media file 3:  Crohn disease. Spot view of the terminal ileum from a small-bowel follow-through study demonstrates several narrowing and stricturing, consistent with the string sign. Also note a sinus tract originating from the medial wall of the terminal ileum and the involvement of the medial wall of the cecum.
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Media file 4:  Crohn disease of the terminal ileum with CT and sonographic correlation. Small-bowel follow-through study demonstrates the string sign in the terminal ileum. Also note pseudodiverticula of the antimesenteric wall of the terminal ileum, secondary to greater distensibility of this less-involved segment of the wall.
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Media file 5:  Crohn disease of the terminal ileum with CT and sonographic correlation. CT scan of the same patient as in Images 4-8. Note terminal ileal-wall thickening and adjacent mesenteric inflammatory stranding.
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Media file 6:  Crohn disease of the terminal ileum with CT and sonographic correlation. Sonogram in the same patient as in Images 4-8. Note hypoechoic wall thickening, loss of the gut signature, and the hyperechoic line representing the narrowed lumen.
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Media file 7:  Crohn disease of the terminal ileum with CT and sonographic correlation. Sonogram in the same patient as in Images 4-8. Note hypoechoic wall thickening, loss of the gut signature, and the hyperechoic line representing the narrowed lumen.
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Media file 8:  Crohn disease. Active small-bowel inflammation. CT scan demonstrates small-bowel wall thickening, mesenteric inflammatory stranding, and mesenteric adenopathy.
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Media file 9:  Crohn disease. Mesenteric inflammation. CT scan demonstrates inflammatory mass in the right lower quadrant associated with thickening of the wall and narrowing of the lumen of the terminal ileum.
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Media file 10:  Crohn disease. Mesenteric inflammation. CT scan in the same patient as in Image 9 demonstrates inflammatory mass in the right lower quadrant associated with thickening of the wall and narrowing of the lumen of the terminal ileum.
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Media file 11:  Crohn disease. Sonogram of a thickened bowel wall demonstrates the so-called pseudokidney appearance.
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Media file 12:  Crohn disease. Crohn colitis. Double-contrast barium enema study demonstrates marked ulceration, inflammatory changes, and narrowing of the right colon.
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Media file 13:  Crohn disease. Crohn colitis. CT scan in the same patient as in Image 12 demonstrates marked thickening of the wall of the right colon with inflammatory stranding in the adjacent mesenteric fat.
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Media file 14:  Crohn disease. Fibrofatty proliferation. CT scan in a patient with Crohn colitis in the chronic phase demonstrates wall thickening of the right colon, an absence of adjacent mesenteric inflammatory stranding, and a large amount of fatty proliferation around the right colon separating the colon from the remainder of the gut, so-called creeping fat.
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Media file 15:  Crohn disease. Single-contrast barium enema study demonstrates stricturing of the caput cecum, the so-called coned cecum.
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Media file 16:  Crohn disease. Coned cecum. CT scan in the same patient as in Image 15 demonstrates wall thickening of the cecum with marked narrowing of the lumen.
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Media file 17:  Crohn disease. CT with MRI correlation. CT scan in a patient with chronic inactive Crohn disease demonstrates thickening of the wall of the right colon with intramural lucency. This was believed to represent intramural fat deposition.
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Media file 18:  Crohn disease. MRI with CT correlation. MRI in the same patient as in Image 17 demonstrates thickening of the wall of the right colon with intramural increased signal on a T1-weighted image. This was believed to represent intramural fat deposition.
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Media file 19:  Crohn disease. Perianal abscesses. CT scan demonstrates multiple fluid, contrast material, and air collections around the anorectum. Note the presence of a rectal tube.
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Media file 20:  Crohn disease. Perianal abscesses. CT scan in the same patient as in Image 19 demonstrates multiple fluid, contrast agent, and air collections around the anorectum. Note the presence of a rectal tube.
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Media file 21:  Crohn disease. Small-bowel obstruction in a patient with recurrence proximal to an anastomosis. CT scan in a patient with a prior ileocolectomy demonstrates small-bowel dilatation and wall thickening of the small bowel proximal to the anastomosis.
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Media file 22:  Crohn disease. Small-bowel obstruction in a patient with recurrence proximal to an anastomosis. CT scan in the same patient as in Image 21 demonstrates small-bowel dilatation and a transition zone at the anastomosis. Note the narrowed segment of bowel at the staple line in the right lower quadrant.
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Media file 23:  Crohn disease. Small-bowel obstruction in a patient with recurrence proximal to an anastomosis. Small-bowel follow-through in same patient as in Images 21-22 demonstrates mucosal changes of Crohn disease in the distal ileum proximal to the anastomosis and anastomotic stricture.
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Media file 24:  Crohn disease. Enteroenteric fistula. CT scan demonstrates the tract of an enteroenteric fistula.
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Media file 25:  Crohn disease. Enterocutaneous fistula. CT scan demonstrates enterocutaneous and colocutaneous fistula formation.
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Media file 26:  Crohn disease. Enterocolic fistula. Double-contrast barium enema study demonstrates multiple fistulous tracts between the terminal ileum and the right colon adjacent to the ileocecal valve, the so-called double-tracking of the ileocecal valve.
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Media file 27:  Crohn disease. Small-bowel follow-through study demonstrates narrowing of the lumen and multiple enteroenteric fistulae, but it fails to show the enterovesical fistula.
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Media file 28:  Crohn disease. Cystogram in the same patient as in Images 27-30 demonstrates a filling defect and inflammatory changes of the dome of the bladder, but it fails to demonstrate the enterovesical fistula.
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Media file 29:  Crohn disease. Enterovesical fistula. CT in the same patient as in Images 27-30 demonstrates an air-filled fistulous tract from the small bowel to the bladder.
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Media file 30:  Crohn disease. Enterovesical fistula. CT in the same patient as in Images 27-29 demonstrates focal thickening of the bladder dome and air in the urinary bladder.
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REFERENCES

Section 11 of 11

• Authors and Editors
• Introduction
• Differentials
• Radiograph
• CT SCAN
• Mri
• Ultrasound
• Nuclear Medicine
• Intervention
• Multimedia
• References

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