Endoscopic diagnosis of inflammatory bowel disease

Endoscopic diagnosis of inflammatory bowel disease
[size=16]James B McGee, MD

Numerous studies support the use of endoscopic evaluation of the colon and terminal ileum for the diagnosis of inflammatory bowel disease (IBD) [1-5]. Colonoscopy with ileoscopy and biopsy can usually differentiate among ulcerative colitis, Crohn's disease, and other disorders that mimic IBD. It also plays an important role in the evaluation of strictures, surveillance for neoplasms, and preoperative assessment, particularly in Crohn's disease.

The current challenge is to select patients who will benefit diagnostically or therapeutically from endoscopy, and to decide when to use other diagnostic modalities either in combination with or instead of colonoscopy. This card will review the diagnostic accuracy of colonoscopy and ileoscopy in comparison to radiography, the technique for performing endoscopy, and the major endoscopic findings that may be seen in patients with IBD. The clinical manifestations and treatment of the different forms of this disorder are discussed separately.

COMPARISON TO RADIOGRAPHY – Ulcerative colitis (UC) and Crohn's disease were previously diagnosed using clinical characteristics, radiologic studies, and rectosigmoidoscopy. However, radiographic studies are now considered an adjunctive rather than a primary diagnostic tool due to the nearly universal availability of colonoscopy.

Barium studies – Correlation between the endoscopic and radiographic diagnosis of IBD varies from 50 to 90 percent [2,6,7]; this wide range may reflect the varying technical skill of radiologic personnel. The presence and extent of disease tend to be underestimated when radiographic studies are compared to direct endoscopic visualization, since subtle mucosal abnormalities, color changes, and the presence of friability can only be detected with colonoscopy [8,9]. The addition of biopsy adds even more to the sensitivity and specificity of colonoscopy.

In Crohn's disease, colonoscopy offers the following advantages over double contrast barium studies:

• Visualization and biopsy of the terminal ileum can be routinely accomplished by an experienced endoscopist in nearly all patients (80 to 97 percent) [10,11]. While this area may also be visualized by barium enema, colonoscopy with ileoscopy has improved accuracy. As an example, in one study of 110 patients with suspected Crohn's disease based upon involvement of the terminal ileum on barium examination, only 48 (44 percent) had a final diagnosis of Crohn's disease [3]. The positive predictive value of ileoscopy was 96 percent; there was only one false positive result on colonoscopy (due to Y. enterocolitica infection).

• Infection (usually tuberculosis and Y. enterocolitica), lymphoid hyperplasia (a common normal finding of the terminal ileum), backwash ileitis, irradiation, neoplasia, and lymphangiectasia can all give a false positive barium study; each of these disorders can usually accurately diagnosed with colonoscopy and biopsy of the suspected area (see Infectious colitis below) [3].

• Radiography can miss endoscopically evident nodular mucosal changes, pseudopolyps, or ulcers, even when the radiologist is aware of the endoscopic findings [12].

Despite the shortcomings of air contrast barium enema for the diagnosis of colitis, small bowel radiography remains a commonly employed tool in Crohn's disease. It is the diagnostic procedure of choice in patients with small bowel involvement above the terminal ileum, or when ileoscopy is not possible [13]. In the pediatric population, small bowel barium studies have been shown to be 90 percent specific for IBD in general, and as high as 96 percent if only Crohn's disease is present. In the same group of patients, endoscopic visualization of the terminal ileum combined with biopsy was diagnostic in 100 percent of cases [6].

In ulcerative colitis, barium enema may confirm the diagnosis and help to determine the extent of involvement in patients with ulcerative colitis. However, there are two limitations to barium enema in this setting: it may be normal in mild forms of disease; and it should be avoided in those who are severely ill since it may precipitate ileus with toxic megacolon.

Other radiologic tests – Other radiologic tests have been used in the diagnosis of IBD. A prospective study of 39 children with suspected IBD, for example, compared barium enema, technetium-99 labeled white blood cell scanning, and colonoscopy. Agreement in all three was found in 21 of 39 cases; the sensitivity of the technetium-99 scan was 90 percent, colonoscopy 87 percent, and barium enema only 42 percent [7].

Computed tomography (CT) of the colon and small bowel can be used to delineate areas of involvement and the severity of IBD. A prospective study of 32 patients showed CT to have a 71 percent sensitivity and 98 percent specificity when compared to colonoscopy and surgery. Specific lesions such as abscesses (100 percent sensitivity and specificity) and fistulas (80 percent sensitivity and 100 percent specificity) were particularly well seen with this modality [14].

COLONOSCOPY IN PATIENTS WITH IBD – For the reasons noted above, colonoscopy is the initial procedure of choice for most patients with suspected IBD.

Bowel preparation – A typical colonoscopy bowel preparation may be too aggressive for patients with active IBD, leading to increased diarrhea and bleeding. The preparation should be tailored to the individual patient. Clear liquids by mouth for several days and gentle tap water enemas, for example, may be all that is necessary in acutely ill patients [4]. Some experts recommend limited colonoscopy without preparation in this setting.

Contraindications – In addition to the usual contraindications (such as a perforated viscus, recent myocardial infarction, and severe diverticulitis), patients with severe colitis, toxic megacolon, or an inability to undergo adequate bowel preparation are not candidates for colonoscopy. Examining the distal colon with a flexible sigmoidoscope, particularly in suspected UC, may provide sufficient diagnostic information with considerably less risk than a full colonoscopy [4].

Biopsy – Obtaining biopsies at the time of colonoscopy adds little to the risk or duration of the procedure and should always be performed. Biopsies should be obtained at multiple levels, even if the mucosa appears normal, since up to 40 percent of specimens obtained from grossly normal appearing tissue in patients with suspected IBD show inflammation on microscopic evaluation. The specimens should be labeled according to segments, since an intermittent pattern of inflammation can be helpful in differentiating Crohn's disease from ulcerative colitis [9]. Biopsy of the terminal ileum further increases the diagnostic accuracy [3]. Abnormal appearing tissue, polyps and masses should also be sampled to rule out concomitant neoplastic changes, and brushings and stool samples should be obtained if an infectious etiology is suspected.

Biopsy of microulcers (less than 5 mm in size) have the highest diagnostic yield, followed by the edge of larger ulcers [12]. Findings of chronic inflammation support the diagnosis of IBD. Granulomas are highly suggestive of Crohn's disease, but are found in only 5 to 24 percent of biopsy specimens [3,12].

Histology from a rectal biopsy is useful for differentiating IBD from self-limited (infectious) colitis. Crypt distortion with forked glands, crypt atrophy, and a villiform surface appearance support the diagnosis of IBD and are not usually seen with infectious colitis [15]. A mixed inflammatory infiltrate in the lamina propria is also associated with IBD, but can be more subjective than crypt distortion. Changes in crypt architecture occur early in the course of the disease, being seen as soon as seven days after the onset of symptoms in patients with acute onset IBD [16].

Utility of biopsy – A number of endoscopic features are common to both Crohn's disease and ulcerative colitis, including pseudopolyps, loss of haustral folds, fibrotic strictures, and linear superficial scars (see below) [9]. The ability of histologic examination to differentiate these two inflammatory lesions is somewhat limited since the mucosa is only able to respond to inflammation in a limited number of ways [9].

Nevertheless, the following findings illustrate the potential utility of colonoscopy in patients with acute colitis:

• One study prospectively evaluated 114 patients with acute hemorrhagic colitis [17]. The initial colonoscopic diagnosis was compared to the final diagnosis (using clinical, microbiological, endoscopic, and histologic data) 30 months later. Ulcerative colitis was confirmed in all 40 patients in whom it was initially suspected by endoscopic appearance. Hemorrhagic infectious colitis was the initial diagnosis in 70 patients; this was confirmed in all but two patients during follow-up. The distinguishing features of ulcerative colitis were bleeding, mucosal friability, granularity, and ulceration (see below). Patients with infectious colitis had mucosal edema, erythema, hemorrhagic spots, microaphthoid ulcers, and luminal exudates. Only four patients had Crohn's disease.

• Colonoscopy during an attack of acute ulcerative colitis can predict the need for surgery. In one report, the presence of severe ulceration (with deep, long, or serpiginous lesions) on colonoscopy predicted surgical intervention due to lack of response to medical therapy in 43 of 46 (93 percent) patients [18]. Conversely, 30 of 39 patients (77 percent) with mild endoscopic disease went into clinical remission. There was only one complication, colonic dilation, among the 85 colonoscopies that were performed.

• Repeat colonoscopy can confirm the initial diagnosis of either Crohn's disease or ulcerative colitis in the majority of cases. In one large series, repeat colonoscopy one to two years after the initial diagnosis (527 with ulcerative colitis and 228 Crohn's disease) resulted in reclassification of the diagnosis in 10 percent [19].

ENDOSCOPIC FINDINGS IN CROHN'S DISEASE – There are three major endoscopic findings that are specific for the diagnosis of Crohn's disease and help to distinguish it from UC; aphthous ulcers; cobblestoning; and discontinuous lesions [1]:

• Small discreet aphthous ulcers can be seen in early lesions (show endoscopy 1) [9]. Deeper ulcers involve the entire wall of the colon, in contrast to the ulcers in patients with UC which involve only the mucosa.

• Serpiginous and linear ulcers can course for several centimeters along the longitudinal axis of the colon in Crohn's disease (show endoscopy 2) [4]. This type of ulceration results in the typical cobblestoning lesions; the deep linear ulcers are the "cracks" between the stones, while areas of inflamed or normal tissue form the "stones."

• Crohn's disease lesions are typically discontinuous. They can be adjacent to normal tissue, resulting in "skip areas" (show endoscopy 3). In contrast, UC tends to be continuous and taper out gradually. If a biopsy taken from endoscopically normal tissue adjacent to an ulcer shows normal histology, the ulcer is probably due to Crohn's disease [4].

Other endoscopic findings which support the diagnosis of Crohn's disease, but are not specific, include the following:

• A normal rectum supports the diagnosis of Crohn's disease, since UC always involves the rectum. On the other hand, involvement of the left side of the colon in general is less common in Crohn's disease than in ulcerative colitis.

• The presence of normal vasculature adjacent to affected tissue is seen in Crohn's disease, while loss of vascularity and friability is more typical of UC.

• Isolated involvement of the terminal ileum is highly suggestive of Crohn's disease. Terminal ileitis or "backwash ileitis" can occur in UC, but is only seen in the setting of pancolitis, allowing the distinction from Crohn's disease [3]. Ileoscopy should always be attempted in patients with suspected Crohn's disease; it adds little or no risk to a diagnostic colonoscopy [20].

The relationship between endoscopic and clinical severity is relatively weak, but statistically significant in Crohn's disease [21].

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ENDOSCOPIC FINDINGS IN ULCERATIVE COLITIS – Endoscopy in UC typically reveals the following findings:

• Erythema
• Loss of the usual fine vascular pattern
• Granularity of the mucosa
• Friability
• Edema

The granular appearance is manifested by changes in light reflection during colonoscopy. Instead of reflecting light in large patches, the granular mucosa reflects a multitude of small points of light, giving the appearance of "wet sandpaper" [4].

As noted above, the endoscopic findings in UC begin at the anal verge and extend proximally. The involvement is contiguous and circumferential, with inflammation beginning from the point of origin and continuing to a gradual transition to normal mucosa (show endoscopy 4) [4]. A progressive increase in chronic inflammation in a proximal to distal pattern supports the diagnosis of UC [9].

Pseudopolyps are not specific for UC but are more common in this disorder, occurring in approximately 20 percent of cases (show endoscopy 5). They can range from a few millimeters in diameter to a centimeter or more. They tend to be taller than they are wide and can mimic neoplasms; biopsy confirms that they are not neoplastic [4].

Pseudopolyps are associated with increased severity and more extensive involvement in UC. However, the outcome in patients with pseudopolyps is better than in those with similar disease extent and severity who do not have pseudopolyps [22].

ENDOSCOPIC MIMICS OF IBD – Several other types of colitis may mimic IBD endoscopically.

Infectious colitis – Several infectious agents can cause mucosal inflammation and look identical to either Crohn's disease or UC at colonoscopy (show table 1 and show endoscopy 6). In one study of patients with mucoid bloody diarrhea and suspected inflammatory bowel disease, 38 percent were found to have an infectious colitis [23]. As noted above, histologic findings may help to distinguish these disorders, with crypt distortion favoring the diagnosis of inflammatory bowel disease [15].

The self-limited nature of most episodes of infectious colitis often differentiate this disorder from IBD without the need for endoscopy. Examination of the stool for ova and parasites, culture, and anaerobic serology are required for confusing cases.

Tuberculosis of the terminal ileum and cecum can mimic Crohn's disease by producing a narrowed lumen and nodularity. The presence of caseating granulomas, positive culture, or acid fast bacilli on colonoscopic biopsy specimens establish the diagnosis of tuberculosis [24]. Other endoscopic findings suggestive of tuberculosis are grouped ulcers, nodules, and destruction of the ileocecal valve. It may be difficult to detect granulomas due to their deep location; thus, their absence does not rule out tuberculosis. Biopsies should be taken from the raised edematous margins and sent for histologic as well as bacteriologic tests [24].

Other infectious agents can cause terminal ileitis and confusion with Crohn's disease. In one prospective study, for example, 7 percent of 110 patients with suspected IBD based upon radiography had an eventual diagnosis of infectious colitis [3]. In addition to tuberculosis, other causative agents included Yersinia enterocolitica, Campylobacter, Shigella, and Salmonella caused ileitis (show table 1).

Pseudomembranous colitis – Pseudomembranous colitis may resemble IBD in some cases. Small groups of pseudomembranes can grossly look like the aphthous ulcers of Crohn's disease (show endoscopy 7A-7B). However, the pseudomembranes are present on top of the mucosa, and do not result in ulceration of the underlying tissue.

Radiation colitis – Radiation can cause mucosal inflammation that resembles ulcerative colitis. It tends to be continuous, friable, and left sided. A history of abdominal radiation, even if temporally distant, should differentiate the two diagnoses.

Ischemic colitis – Ischemic colitis tends to be continuous, left sided, and associated with mucosal friability, findings that resemble ulcerative colitis (show endoscopy Cool

. The keys to proper diagnosis are sparing of the rectum in ischemic colitis and the presence of risk factors for ischemic colitis (eg, atherosclerotic disease, congestive heart failure, recent hypotension). (See "Colonic ischemia").

References
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16. Surawicz, CM, Haggit, RC, Husseman, M, McFarland, LV. Mucosal biopsy diagnosis of colitis: Acute self-limited colitis and idiopathic inflammatory bowel disease. Gastroenterology 1994; 107:755.
17. Mantzaris, GJ, Hatzis, A, Archavlis, E, et al. The role of colonoscopy in the differential diagnosis of acute, severe hemorrhagic colitis. Endoscopy 1995; 27:9.
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