Crohn’s Disease

The earliest endoscopic lesions in Crohn’s disease are considered to be tiny punched-out ulcers in an otherwise normal-appearing mucosa. These tiny ulcers enlarge and aggregate to form larger surface ulcerations. Normal mucosa surrounds the ulcerations until late in the disease. Scanning electron microscopy has identified surface erosions of 100 to 200 µm surrounded by M cells, which may be the entry point for whatever the etiologic agent is found to be in Crohn’s disease.¹

Ulcerative Colitis

Ulcerative colitis triggers an increase in the surface blood flow, which causes the earliest lesions endoscopically to be diffuse erythema and vascular congestion. The mucosa looks like “wet sandpaper”; the edema produces a fine granular appearance and dulls the mucosal vascular architecture. The engorged mucosa bleeds readily when touched by the endoscope (termed mucosal friability), and as inflammation progresses, spontaneous bleeding occurs secondary to minute surface ulcerations that have been formed.

Crohn’s Disease

The Crohn’s Disease Activity Index (CDAI) was developed in 1976 by Best and coworkers³ as part of the National Cooperative Crohn’s Disease Study. It is the “gold standard” index for any Crohn’s disease clinical trial. A multivariant regression analysis was performed, and eight variables were identified as predictors of disease activity: number of stools, abdominal pain, general well-being, extraintestinal complications, antidiarrheal agents used in the previous 7 days, abdominal mass felt on palpation, hematocrit, and body weight (Table 21.1). CDAI scores range from 0 to 600. A score of less than 150 corresponds to relative disease quiescence (remission); 150 to 219, mildly active disease; 220 to 450, moderately active disease; and greater than 450, severe disease. A decrease in greater than 100 points indicates a clinically significant improvement in disease activity (termed clinical response). Older literature suggests that a clinical response is defined by a decrease in CDAI by greater than 70 points. The limitations of the CDAI include the complexity of the calculation needed by the physician, the weight placed on subjective complaints such as general well-being and abdominal pain, and the requirement of the patient to keep a diary for 7 days.

The Harvey-Bradshaw Index,⁴ or the Simple Index, is less complicated than the CDAI and uses five variables recorded on one occasion (Table 21.2). No diary and no laboratory values are required. The five variables are general well-being, abdominal pain, abdominal mass, number of liquid stools, and systemic complications. Each variable is weighted the same. Studies have found that the Harvey-Bradshaw Index correlates well with the CDAI.⁵

Table 21.2 Harvey-Bradshaw Index (Simple Index)

From Harvey RF, Bradshaw JM: A simple index of Crohn’s disease activity. Lancet 1:514, 1980.

The Crohn’s Disease Endoscopic Index of Severity (CDEIS)⁶ is a third index and the first to use endoscopic data in assessing disease severity. This prospectively developed index was established in 1989 by the French group Groupe d’Etudes Therapeutique des Affections Inflammatoires du Tube Digestif (GETAID). The CDEIS was validated in a large multicenter trial⁶ and is the “gold standard” for evaluation of endoscopic, rather than clinical, activity. The bowel is divided into five segments (rectum, sigmoid and left colon, transverse colon, right colon, and ileum), and a numerical score is assigned based on objective endoscopic criteria: the presence or absence of deep or superficial ulcerations and the extent of the surface involved by the disease (Table 21.3). Scores range from 0 to 44, with higher scores indicating more severe disease. The CDEIS is reproducible, but it is time-consuming for the physician to calculate a score, which hinders its use outside of clinical trials. It also has failed to correlate with patient symptoms or other indicators of clinical activity.⁷

The main goal of therapy in Crohn’s disease has been to achieve remission from disease symptoms rather than to achieve endoscopic remission. Endoscopic severity previously had not been shown to correlate reliably with prognosis or to predict a clinical response to therapy.⁸ However, more recent studies with infliximab treatment imply that there is a longer remission and fewer disease events in patients achieving endoscopic remission.^9,10 This finding may alter the role that endoscopy plays in the evaluation of the clinical course of Crohn’s disease.

In 2002, a second severity index based on endoscopic findings was proposed: the Simple Endoscopic Score for Crohn’s Disease (SES-CD).¹¹ Because endoscopic remission has become one of the goals for monitoring treatment in clinical trials, a simpler endoscopic activity assessment than the CDEIS is needed. The bowel is divided into the same five segments as in the CDEIS, and a score of 0 to 3 is assigned based on endoscopic criteria—presence of ulcers, degree of ulcerated surface, degree of affected surface, presence of narrowings, and number of affected segments (Table 21.4). This index is easier and faster to calculate than the CDEIS. The reproducibility of the SES-CD was as good as the CDEIS, and it reliably correlated with the CDEIS, the present “gold standard.” However, similar to the CDEIS, the correlation of SES-CD results with clinically active disease was weak.

The role of endoscopic assessment of severity of disease in clinical practice is still being developed. It is currently well accepted that if a patient with Crohn’s disease has symptoms of active disease it is appropriate to assess if there is mucosal inflammation because numerous other factors may cause patients to have similar symptoms, including bacterial overgrowth; intestinal fistulas; infectious diseases including Clostridium difficile, cytomegalovirus (CMV), and enteric infections; and other conditions, such as intestinal fibrotic strictures. It has not yet become the standard of practice to reassess the intestinal mucosa if a patient enters remission from a specific medical therapy.

Ulcerative Colitis

The first qualitative grading system for ulcerative colitis was developed by Truelove and Witts¹² in 1955. This classification system divides patients into mild, moderate, or severe disease categories based on five criteria: temperature, heart rate, hemoglobin, erythrocyte sedimentation rate, and diarrheal symptoms (Table 21.5). When this index was initially described, only definitions for patients with mild and severe disease were provided. This index is simple, quick, and easily applied and can identify rapidly the sickest patients with ulcerative colitis. Powell-Tuck and coworkers¹³ developed a scoring system to be used in their clinical trial that incorporated clinical data and endoscopic criteria. This scoring system includes a wider range of symptoms than the Truelove and Witts scoring system and includes examination for abdominal tenderness and a sigmoidoscopic scoring system. Assessment of the macroscopic sigmoidoscopic appearance is subjective, and studies have found poor correlation between the colonoscopic findings and the Powell-Tuck Activity Score.¹⁴ This finding suggests that sigmoidoscopy is not the most accurate method of assessing disease activity once the diagnosis of ulcerative colitis has been established.

Table 21.5 Truelove and Witts’ Classification of Severity in Ulcerative Colitis

ESR, erythrocyte sedimentation rate.

From Truelove SC, Witts LJ: Cortisone in ulcerative colitis: Final report on a therapeutic trial. BMJ 2:1041–1048, 1955.

The Simple Colitis Activity Index¹⁵ was developed to aid in the initial evaluation of exacerbations of ulcerative colitis by outpatient physicians. It was compared with the established Powell-Tuck Activity Score, and the authors found good correlation between the two indices (P < .0001). This simpler index includes six clinical criteria: bowel frequency during the day, bowel frequency during the night, urgency of defecation, blood in stool, general well-being, and extracolonic manifestations (Table 21.6). Because this index does not employ endoscopic or laboratory data, it may be used as an initial assessment in the outpatient setting and possibly by patients themselves as a guide to modifying treatment and the need to seek further medical advice.

Table 21.6 Simple Colitis Activity Index

From Walmsley RS, Ayres RC, Pounder RE, et al: A simple clinical colitis activity index. Gut 43:29–32, 1998.

The Ulcerative Colitis Disease Activity Index (UCDAI) was designed in 1987 by Sutherland and coworkers¹⁶ to provide an objective basis for assessing drug efficacy. Four variables are measured, with each receiving a numerical value of 0 (normal) to 3 (most severe); a total value of 12 indicates the most severe disease. The four variables are stool frequency, amount of blood in stool, endoscopic appearance of colonic mucosa, and physician’s assessment of disease severity. A potential strength of this index is its incorporation of endoscopic appearance. A clinical response to therapy is defined as a reduction in the UCDAI score by 2 or more points. This index is very similar to another well-accepted index, often called the “Mayo score,” developed by investigators at the Mayo Clinic.¹⁷ None of the aforementioned indices that have been described for patients with ulcerative colitis has been validated. They have been accepted as being appropriate without proper formal validation.

Lower Flexible Gastrointestinal Endoscopy (Colonoscopy and Flexible Sigmoidoscopy)

The quality of colonoscopy or flexible sigmoidoscopy depends on the effectiveness of the bowel preparation. Bowel cleansing should leave no residual fecal material and only very little fluid. An inadequate bowel preparation has many repercussions: It impairs visualization and colonoscopic diagnosis; it may require the procedure to be rescheduled; and it prolongs insertion time, which not only adds to patient discomfort¹⁸ but also increases the cost of the procedure.¹⁹

In a study comparing GoLYTELY, NuLytely, and Fleet Phospho-soda, Ell and colleagues²⁰ showed a statistically significant benefit to using GoLYTELY over the other two preparations in achieving effective cleansing of the entire colon before colonoscopy. There was no difference in patient satisfaction between the three preparations. In this study, the patients ate a regular breakfast on the day before the examination and thereafter had only clear fluids; they were not to eat anything on the day of the colonoscopy. The bowel cleansing regimen occurred in two stages, with divided doses the day before and on the morning of the procedure. A short interval between bowel preparation and colonoscopy has yielded better cleansing results.²¹ The GoLYTELY preparation in the past had been considered to be the “gold standard” for bowel cleansing before colonoscopy. None of these studies were performed in patients with IBD, and Fleet Phospho-soda enemas have been implicated in the development of an acute colitis.

For flexible sigmoidoscopy, patient studies have not shown a clearly superior method for bowel preparation. The addition of magnesium citrate to the regimen seems to improve the quality of the study over enemas alone.^22,23 Patients may consider a completely oral regimen more easily tolerated than one that includes enemas,²⁴ but the best preparation probably would be one that includes both oral magnesium citrate and one to two Fleet enemas.²⁵ These have yet to be adequately assessed in blinded controlled trials for patients with IBD.

Upper Endoscopy

No preparation is required for a patient to undergo an upper gastrointestinal (GI) endoscopy. Patients should ingest no solids for at least 6 hours before the procedure and no liquids for at least 4 hours. If a patient has a gastric emptying disorder, a longer period of fasting may be required.

Lower Flexible Gastrointestinal Endoscopy

Endoscopy plays a key role not only in the diagnosis of Crohn’s disease but also in its management. Although other radiologic modalities often are complementary to the diagnosis and treatment of Crohn’s disease, endoscopy is the only method that allows for biopsy specimens to be taken. Box 21.1 lists indications for colonoscopy in IBD. Colonoscopy is usually performed during the initial evaluation of ulcerative colitis and Crohn’s disease to confirm the diagnosis, assess disease severity, and determine the extent of the disease. It also plays an important role in assessing the disease response to therapy and is important in performing endoscopic surveillance for dysplasia or cancer. Colonoscopy and flexible sigmoidoscopy are contraindicated in patients with known or suspected peritonitis, bowel perforation, or colonic necrosis.²⁶ Severe coagulopathy, thrombocytopenia, and neutropenia also are contraindications for the procedure. In addition, toxic megacolon and fulminant colitis generally are relative contraindications for the procedure secondary to their increased risk of colonic perforation.

Upper Gastrointestinal Endoscopy

Upper GI endoscopy is used to evaluate upper GI symptoms in patients with IBD. Biopsy specimens of normal gastric mucosa in patients with indeterminate colitis may aid in the diagnosis of Crohn’s colitis. In patients with known Crohn’s disease, upper GI endoscopy allows for the diagnosis of Crohn’s disease of the esophagus, stomach, and duodenum. It also can treat strictures or upper GI bleeding.

Lower Gastrointestinal Endoscopy

Colonoscopy is performed in the initial diagnosis of Crohn’s disease to confirm the diagnosis and assess the extent of the disease. Intubation of the terminal ileum should be attempted in all patients; there is an 80% to 97% success rate of insertion of the colonoscope into the distal ileum.^27,28 Biopsy specimens of the terminal ileum should be taken because Crohn’s ileitis can appear macroscopically normal. Endoscopic involvement of the ileum is usually associated with Crohn’s disease, but patients with pancolonic involvement who have ulcerative colitis can have backwash ileitis, a patchy inflammation without ulceration that extends a few centimeters into the terminal ileum. Biopsy specimens are required to differentiate the two diagnoses.

Flexible sigmoidoscopy may be appropriate to perform when a colonoscopy was recently performed or when the inflammation is known to be limited to the left side of the colon.²⁹ In patients with severe disease activity, colonoscopy may be contraindicated secondary to the severe degree of inflammation, whereas flexible sigmoidoscopy can be useful to confirm that a patient’s symptoms are related to Crohn’s disease and not to an infectious or other form of colitis. Flexible sigmoidoscopy can also be used to confirm a diagnosis of irritable bowel syndrome (IBS) by excluding other inflammatory or neoplastic disorders. In IBS, there is normal colonic anatomy, but there may be nonspecific findings of increased colonic mucus, mural spasm, and increased sensitivity to painful stimuli during flexible sigmoidoscopy.³⁰

Colonic perforation is the most common major complication of diagnostic colonoscopy, with a risk of approximately 0.25%.^31,32 In patients with severe colitis, a suspected abscess, toxic megacolon, or signs or symptoms of a bowel obstruction, colonoscopy is generally not recommended because the risk of perforation is greatly increased. A very small scope (6-mm outer diameter) can be used to assess the rectum and sigmoid; this technique practically eliminates the risk of colonic perforation. The proximal extent of disease can be evaluated by computed tomography (CT) scan. The most common reason to abort a colonoscopy in patients with Crohn’s disease is related to the presence of severe inflammation with large, deep ulcerations, which carry an increased risk of perforation.

The endoscopic appearance of IBD usually is not specific enough to make the definitive diagnosis of ulcerative colitis versus Crohn’s disease; the accuracy of colonoscopy in differentiating between the two forms of inflammatory colitis is 85% to 90%.³³ Some features favor one diagnosis over the other (Table 21.7). Endoscopically, Crohn’s disease tends to vary with disease duration and severity. The rectum is typically spared, with the most severe involvement occurring in the cecum and right colon; the most common patterns of disease distribution are ileocolitis in 40% to 50%, ileitis in 30% to 40%, and colitis in 15% to 25%. Classically, the disease is discontinuous, forming skip areas—areas of disease that are separated by normal mucosa. In early Crohn’s disease, small punched-out aphthous ulcers are typically seen on the background of normal mucosa (Fig. 21.1). Aphthous ulcers are a result of submucosal lymphoid follicle expansion and penetration through the mucosa. As the disease progresses, these superficial ulcerations enlarge and coalesce to become long and linear and may take on the appearance of a star (“stellate ulcers”) (Fig. 21.2). These ulcerations can deepen throughout the bowel wall to lead to abscess and fistula formation. With increasing chronicity, submucosal edema and injury results in a cobblestoning appearance, which practically is pathognomonic for Crohn’s disease; cobblestoning consists of uniform nodulations that are low in height with a broad base.

Table 21.7 Endoscopic Appearance of Crohn’s Disease and Ulcerative Colitis

Fig. 21.1 A and B, Multiple aphthous ulcers seen in recurrent Crohn’s disease in the neoterminal ileum of ileocolic anastomosis 3 months after resection.

Fig. 21.2 Stellate colonic ulcers in a patient with Crohn’s disease.

Patients with severe disease can have large linear ulcers (“bear claw” ulcers) and deep serpiginous ulcers (Figs. 21.3 and 21.4). Strictures can form in areas with transmural circumferential inflammation. Patients with moderate to severe disease activity may be endoscopically indistinguishable from patients with ulcerative colitis and many other similar diseases (Fig. 21.5). Histologically, there is transmural inflammation with predominantly lymphocytic infiltration. Granulomas are the hallmark of Crohn’s disease, although they are present in only 10% to 25% of biopsy specimens. They are more common in the early stages of the disease.³⁴ Granulomas can be found throughout the GI tract and in macroscopically normal areas. For this reason, it is recommended that upper GI endoscopy with mucosal biopsy be performed when the differentiation between ulcerative colitis and Crohn’s disease is unclear.

Fig. 21.3 Irregularly shaped ulcerations in a patient with Crohn’s disease.

Fig. 21.4 Multiple serpiginous ulcerations of the rectum in a patient with Crohn’s disease.

Fig. 21.5 Ulcers in the colon in patients with Behçet’s disease cannot be differentiated endoscopically from patients with Crohn’s disease.

Upper Gastrointestinal Endoscopy

A hallmark of Crohn’s disease is that it can affect the entire GI tract, from the mouth to the anus. The upper GI tract was previously thought to be an uncommon site of disease, with a prevalence of less than 4%.^35,36 Routine use of endoscopy has found a prevalence closer to 50% to 60%.³⁷ Dysphagia, odynophagia, epigastric pain, and stomatitis are the most common symptoms, although most patients are asymptomatic.^38–40

Endoscopic features of Crohn’s disease in the esophagus tend to be nonspecific and may include aphthous ulcers, cobblestoning, stricture formation, friability, and granularity. Huchzermeyer and coworkers⁴¹ described two different stages of esophageal involvement. The first stage is a milder and earlier form of the disease. Erythema and edema progress to aphthous ulcerations with intervening normal mucosa, resembling a cobblestoning appearance. In the second stage, esophageal strictures and stenosis occur. Histologically, it is rare to see a granuloma on a biopsy specimen of the esophagus; 75% of biopsy specimens show active chronic inflammation, and 30% show ulcerations.³⁸

The antrum and duodenum are the most common sites of involvement of the upper GI tract (Fig. 21.6). Gastroduodenal disease is contiguous in approximately 60% of patients, with only 40% having duodenal disease solely.⁴² In contrast to the round and oval ulcers seen in peptic ulcer disease, the ulcerations in gastroduodenal Crohn’s disease tend to be more serpiginous and longitudinal.³⁵ Mucosal erythema and nodularity, cobblestoning, and strictures have also been described.^36,42 The descending duodenum is often the most severely affected. The pathognomonic granulomas are found in approximately 40% of biopsy specimens taken from the duodenum.⁴²

Fig. 21.6 A, Duodenal active ulceration in a patient with Crohn’s disease. B, Duodenal bleeding in an active ulcer in the same patient with Crohn’s disease.

Lower Gastrointestinal Endoscopy

In ulcerative colitis, the inflammatory response is directed solely at the colon and is limited to the mucosa and submucosa. The disease starts in the rectum in 95% of cases, which should cause one to reconsider the diagnosis of ulcerative colitis in any patient with rectal sparing. The inflammation usually occurs in a circumferential, contiguous pattern.

Early in the disease, there is loss of the vascular pattern and congestion. The smooth and glistening appearance of normal colonic mucosa is replaced by a more granular-appearing mucosa caused by disruption of the normal light reflection. There is blunting of the normal, finely branched mucosal vascular pattern, blunting of the intrahaustral folds caused by mucosal edema, and diffuse mucosal erythema. At later stages, the edematous mucosa acquires a sandpaperlike appearance and becomes very friable; this leads to easy mucosal bleeding, even in response to being brushed lightly by the endoscope or a cotton swab. With severe disease, mucopus, a yellow-white exudate, may be present. The colonic mucosa is disrupted, and small shallow ulcers can develop and progress to large deep ulcerations. These large ulcerations can coalesce to form areas of completely destroyed mucosa; pseudopolyps or mucosal bridges can form from the congested mucosal remnants present in the denuded areas (Figs. 21.7 and 21.8).⁴³ Usually pseudopolyps are not clinically significant, but in patients with long-standing ulcerative colitis, biopsy of pseudopolyps is needed because they resemble adenomatous and malignant polyps (Fig. 21.9).

Fig. 21.7 A and B, Pseudopolyps in a patient with ulcerative colitis.

Fig. 21.8 A, Pseudopolyps in a patient with severe ulcerative colitis. B and C, Pseudopolyps in the same patient after treatment.

Fig. 21.9 Large pseudopolyp in the rectum of a patient with long-standing ulcerative colitis.

Toxic megacolon is a dreaded complication of colitis; although seen more often in patients with ulcerative colitis, it is found in Crohn’s disease as well. In severe colitis, damage to the neural plexus and muscularis propria can lead to neuromuscular dysfunction. Progressive colonic dilation can result leading to a toxic megacolon. In chronic ulcerative colitis, the colon appears smooth, shortened, and noncompliant (rigid) on colonoscopy. There is loss of the haustral folds caused by thickening of the muscularis mucosae and submucosal fibrosis. The colon has a characteristic pipelike appearance. The terminal ileum can also be involved in 10% to 20% of patients with ulcerative pancolitis. There is erythema, an abnormal vascular pattern, and superficial erosions in the distal 5 cm of the terminal ileum secondary to backwash ileitis. This backwash ileitis is almost always found in the setting of a dilated and incompetent ileocecal valve. Although this ileitis does not cause any clinical symptoms, retrospective data suggest that backwash ileitis is associated with an increased risk of colorectal cancer (CRC).⁴⁴

Upper Gastrointestinal Endoscopy

Because ulcerative colitis, by definition, does not affect the upper GI tract, upper endoscopy would not be performed routinely. One of the few reasons to perform upper GI endoscopy is if the diagnosis of ulcerative colitis is in question; this test can look for evidence of inflammatory disease elsewhere in the GI tract to establish the diagnosis of Crohn’s disease.

Differentiating Malignant from Benign Strictures

The healing response to the chronic inflammation found in IBD is thought to result in intestinal strictures. It is believed that there is recruitment of fibroblasts and other structural components in healing, which promote fibrosis and luminal narrowing leading to strictures (Fig. 21.10).⁴⁵ The sheer number and diversity of cell types in the intestine make it difficult to identify a solitary cell responsible for the fibrosis seen in IBD. Stricture formation is found more often in patients with Crohn’s disease than in patients with ulcerative colitis because of the transmural nature of inflammation seen in Crohn’s disease (Figs. 21.11 and 21.12). The prevalence of colonic strictures in Crohn’s disease ranges from 4% to 5% in surgical series⁴⁶ to 8% to 9% in endoscopic series.⁴⁷ With all strictures, it is imperative to assess for any evidence of malignancy. Although strictures are found more often in patients with Crohn’s disease, the strictures that are associated with ulcerative colitis have a higher frequency of malignancy. The rate of malignancy in patients who have strictures is 7% to 11% in Crohn’s disease⁴⁸ compared with approximately 25% in ulcerative colitis.⁴⁹

Fig. 21.10 Multiple active ulcers in a patient with fibrostenotic Crohn’s disease.

Fig. 21.11 Crohn’s stricture at the anastomosis.

Fig. 21.12 Stricture at the ileocolic anastomosis.

Efforts should be made to exclude malignancy when performing a colonoscopy (Fig. 21.13). Such efforts include visualizing the entire length of the stricture and beyond and using a narrower pediatric colonoscope, push enteroscope, or gastroscope if necessary. Biopsy specimens should be obtained from the edge and the core of the stricture. Endoscopic features suggesting malignancy within a stricture are rigidity of the edge, an eccentric lumen, nodularity within the stricture, and an abrupt shelflike margin. Even if the biopsy specimen is negative for malignancy, these highly suspicious lesions should be treated as if they were malignant because carcinoma complicating IBD can extend submucosally. Surgery should be considered in all patients with biopsy-proven malignant strictures, patients with highly suspicious lesions based on gross endoscopic assessment, and patients in whom a colonoscope is unable to pass to survey the remainder of the colon.

Fig. 21.13

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