Inflammatory Bowel Disease Workup

Updated: Apr 10, 2020
  • Author: William A Rowe, MD; Chief Editor: BS Anand, MD  more...
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Workup

Approach Considerations

Several laboratory studies are of value in assisting with the management of inflammatory bowel disease (IBD) and provide supporting information. However, no laboratory test is specific enough to adequately and definitively establish the diagnosis of IBD. Laboratory values may be used as surrogate markers for inflammation and nutritional status and to look for deficiencies of necessary vitamins and minerals. Serologic studies have been proposed to help diagnose IBD and to differentiate Crohn disease from ulcerative colitis, but such studies are not recommended for routine diagnosis of Crohn disease or ulcerative colitis.

In individuals who are immunosuppressed, are from third world countries, or have a history of travel, intestinal tuberculosis (TB) may need to be excluded. In such cases, tuberculin purified protein derivative (PPD) or interferon-gamma assays (eg, QuantiFERON-TB, T-SPOT, TB test) may be indicated, as well as culture for amebiasis, giardiasis, Strongyloides infection, and studies for histoplasmosis and coccidioidomycosis. [1] Chest radiography may exclude pulmonary TB, but this imaging modality does not exclude extrapulmonary TB. [1]

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Laboratory Studies

Hematologic tests

Complete blood cell count

The components of the complete blood cell (CBC) count can be useful indicators of disease activity and iron or vitamin deficiency. An elevated white blood cell (WBC) count is common in patients with active inflammatory disease and does not necessarily indicate infection.

Anemia is common and may be either an anemia of chronic disease (usually normal mean corpuscular volume [MCV]) or an iron deficiency anemia (MCV is often low). Anemia may result from acute or chronic blood loss, malabsorption (iron, folate, and vitamin B12) or may reflect the chronic disease state. Note that the MCV can be elevated in patients taking azathioprine (Imuran) or 6-mercaptopurine (6-MP). Generally, the platelet count is normal, or it may be elevated in the setting of active inflammation.

Nutritional evaluation: Vitamin B12 evaluation, iron studies, RBC folate, nutritional markers

Vitamin B12 deficiency can occur in patients with Crohn disease who have significant terminal ileum disease or in patients who have had terminal ileum resection. The standard replacement dose of vitamin B12 is 1000 mg subcutaneously (SC) every month, because oral replacement is often insufficient.

Serum iron studies should be obtained at the time of diagnosis, because active IBD is a source for GI blood loss, making iron deficiency common. A microcytic hypochromic anemia suggests iron deficiency; if confirmed with serum iron/total iron-binding capacity (TIBC), iron should be replaced either enterally or parenterally. For parenteral replacement, intravenous (IV) iron sucrose can be used, and dosing is based on the table in the package insert, with a maximum of 30 mL (1500 mg) at once.

Although folate deficiency is not common in persons with IBD, several concerns have been raised regarding this vitamin. Sulfasalazine (Azulfidine) is a folate reductase inhibitor and may inhibit normal uptake of folate; thus, many practitioners commonly administer folate supplements in patients taking sulfasalazine. Folate supplements are indicated in all women who are pregnant to help prevent neural tube defects; this is particularly true for patients with IBD, and supplementation with 2 mg/day or more (rather than the usual 1 mg/day) should be considered in those on sulfasalazine.

Nutritional status can be assessed by serum albumin, prealbumin, and transferrin levels. However, note that transferrin is an acute-phase reactant that can be falsely elevated in persons with active IBD. Hypoalbuminemia may reflect malnutrition because of poor oral intake or because of protein-losing enteropathy that can coexist with active IBD.

ESR and CRP levels

The erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) level are often used as serologic markers for inflammation, but they are not specific for IBD. However, measuring such inflammatory markers also aids in monitoring disease activity and response to treatment. A small but significant number of patients with Crohn disease or ulcerative colitis may not have elevated ESR or CRP levels even in the setting of significant active inflammation. In addition, inflammatory markers may be elevated in the setting of superimposed intestinal or extraintestinal infections.

Fecal calprotectin levels

Fecal calprotectin has been proposed as a noninvasive surrogate marker of intestinal inflammation in IBD. [57] As colorectal neoplasia and gastrointestinal infection also increase fecal calprotectin, this marker is not in widespread use. Note that relatives of patients with IBD may also have elevated levels of fecal calprotectin (with unknown degrees of inflammation). [57]

A study by Henderson et al indicated that fecal calprotectin has a high sensitivity and modest specificity for diagnosing IBD in children. The researchers conducted a systematic review and meta-analysis of 8 studies including 394 pediatric IBD cases and 321 non-IBD controls. [58, 59] The use of fecal calprotectin during the investigation of suspected pediatric IBD was associated with a pooled sensitivity of 97.8%, a pooled specificity of 68.2%, a positive likelihood ratio of 3.07, and a negative likelihood ratio of 0.03.

Metabolite/enzyme levels

Many experts routinely check levels of thiopurine methyltransferase (TPMT) prior to initiation of treatment with mercaptopurine and azathioprine. Individuals who have low enzyme activity or are homozygous deficient in the TPMT mutation are at risk of very severe leukopenia, with potential septic complications, and they may not be good candidates for therapy with these drugs. [60]

Biologic drug and biologic drug antibody levels

The measurement of biologic drug levels and antibodies to the biologic drugs are most useful in patients who are not responding as expected to these agents.

  • If a nonresponding patient has a low or undetectable drug level, then the presence of an antibody suggests that using a different biologic in the same class may be effective.
  • If there is an undetectable or low drug level and no antibody, then increasing the dose of the same drug may be effective.
  • If the drug level is normal or high and antibody is absent, then a primary nonresponse indicates that switching to a different class of biologics would be in order.
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Serologic Studies

pANCA and ASCA tests

Perinuclear antineutrophil cytoplasmic antibodies (pANCA) have been identified in some patients with ulcerative colitis, and anti-Saccharomyces cerevisiae antibodies (ASCA) have been found in patients with Crohn disease. The combination of positive pANCA and negative ASCA has high specificity for ulcerative colitis, whereas the inverse pattern—positive ASCA, negative pANCA—is more specific for Crohn disease. [1] However, false-positive (and false-negative) results are not uncommon; therefore, at this time, serologic markers cannot be used to definitively rule in or exclude inflammatory bowel disease (IBD).

Note that a variant of Crohn disease particularly involving the colon may result in a positive pANCA test, which may complicate the diagnosis. Serum response to anti-CBir1, an antibody associated with the presence of IBD, has been shown to differentiate pANCA-positive results in ulcerative colitis versus ulcerative colitis–like Crohn disease. [61]

Patients with Crohn disease who have a greater number of positive ASCA may be at a greater risk for complications such as strictures and fistulas, and they may also be at a higher risk for surgery. However, serologic markers do not appear to predict response to medical therapy, and there is currently insufficient evidence to recommend the use of antibody testing to predict responses to medical treatment or surgery in patients with IBD. [61]

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Stool Studies

Before making a definitive diagnosis of idiopathic inflammatory bowel disease (IBD), perform a stool culture, ova and parasite studies, bacterial pathogens culture, and evaluation for Clostridium difficile infection. [3] At a minimum, a C difficile toxin assay should be performed on any patient hospitalized with a flare of colitis, or in any patient not responding to appropriate medical intervention, because pseudomembranous colitis is commonly superimposed on IBD colitis. Note that the level of the inflammatory marker calprotectin in feces correlates significantly with colonic inflammation in both ulcerative colitis and Crohn disease. [62]

Assessment for Cytomegalovirus colitis should be performed in cases refractory to steroids. [1] Amebiasis can be difficult to identify from the stool; therefore, consider serologic testing.

As many as 50%-80% of cases of acute terminal ileitis may be due to Yersinia enterocolitis infections. This produces a picture of pseudoappendicitis. As with IBD, yersiniosis has a high frequency of secondary manifestations, such as erythema nodosum and monoarticular arthritis. Thus, in the right clinical setting, a suspicion for Yersinia should be considered.

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Radiography

Upright chest and abdominal radiography

Abdominal radiography may allow for assessment of the kidneys, ureters, and bladder for nephrolithiasis and the vertebral bodies for osteopenia or osteoporosis and sacroileitis. If severe fulminant colitis is present, abdominal radiography may reveal an edematous, irregular colon with thumbprinting (see the first image below). Occasionally, pneumatosis coli (air in the colonic wall) may be present. Free air and evidence of toxic megacolon, which appears as a long continuous segment of air-filled colon greater than 6 cm in diameter, indicates a surgical emergency. (See the images below.)

Inflammatory bowel disease. Plain abdominal radiog Inflammatory bowel disease. Plain abdominal radiograph of a patient with known ulcerative colitis who presented with an acute exacerbation of his symptoms. This image shows thumbprinting in the region of the splenic flexure of the colon.
Inflammatory bowel disease. Plain abdominal radiog Inflammatory bowel disease. Plain abdominal radiograph in a 26-year-old with a 10-year history of ulcerative colitis shows a long stricture/spasm of the ascending colon/cecum (<i>arrow</i>). Note the pseudopolyposis in the descending colon.
Inflammatory bowel disease. Toxic megacolon. Court Inflammatory bowel disease. Toxic megacolon. Courtesy of Dr. Pauline Chu.

Toxic megacolon is a life-threatening complication of ulcerative colitis and requires urgent surgical intervention. This condition occurs predominantly in the transverse colon, probably because air collects there in the supine position. The transverse colon is dilated, usually more than 8 cm (dilation more than 6 cm is considered abnormal). A colectomy is required if no improvement occurs within 24-48 hours. Repeat radiographs are required at 12- to 24-hour intervals to monitor the course of dilatation and to assess the need for emergency colectomy.

Barium enema double-contrast radiographic studies

The barium enema imaging technique was one of the first studies that allowed characterization of the typical findings associated with inflammatory bowel disease (IBD). Barium enemas may be useful in cases of limited or no access to endoscopy, in cases of incomplete colonoscopy, or to measure stricture length. [1]

Several terms have been used to describe abnormalities found after barium studies of the colon, including the following:

  • A lead-pipe or stove-pipe appearance suggests chronic ulcerative colitis that has resulted in a loss of colonic haustra due to the colon becoming a rigid foreshortened tube (see the following image)

    Inflammatory bowel disease. Double-contrast barium Inflammatory bowel disease. Double-contrast barium enema study shows pseudopolyposis of the descending colon in a patient with ulcerative colitis.
  • Rectal sparing suggests Crohn colitis in the presence of inflammatory changes in other portions of the colon (see the image below)

    Inflammatory bowel disease. Double-contrast barium Inflammatory bowel disease. Double-contrast barium enema study demonstrates marked ulceration, inflammatory changes, and narrowing of the right colon in a patient with Crohn colitis.
  • Thumbprinting indicates mucosal inflammation (which can also be seen frequently on the abdominal flat plate) (see the following image)

    Inflammatory bowel disease. Plain abdominal radiog Inflammatory bowel disease. Plain abdominal radiograph of a patient with known ulcerative colitis who presented with an acute exacerbation of his symptoms. This image shows thumbprinting in the region of the splenic flexure of the colon.
  • Skip lesions indicate areas of inflammation alternating with normal-appearing areas, again suggesting Crohn colitis

Barium can be refluxed into the terminal ileum in many cases (see the first image below), which can assist in the diagnosis of Crohn disease. The string sign (a narrow band of barium flowing through an inflamed or scarred area) in the terminal ileum is typical of one form of ileal Crohn disease observed on radiographs (see the first image below). Barium enema is contraindicated in patients with moderate to severe colitis, because it risks perforation or precipitation of a toxic megacolon (see the second image below).

Inflammatory bowel disease. Crohn disease involvin Inflammatory bowel disease. Crohn disease involving the terminal ileum. Note the "string sign" in the right lower quadrant (viewer's left).
Inflammatory bowel disease. Toxic megacolon. Court Inflammatory bowel disease. Toxic megacolon. Courtesy of Dr. Pauline Chu.

In Crohn disease, areas of segmental narrowing with loss of normal mucosa, fistula formation, and the string sign (a narrow band of barium flowing through an inflamed or scarred area) in the terminal ileum are typically observed on radiographs (see the images below). Some patients with ulcerative colitis also demonstrate inflammatory changes in the terminal ileum (ileitis), but these findings lack the skip pattern that is characteristic of Crohn disease.

Inflammatory bowel disease. Enteroenteric fistula Inflammatory bowel disease. Enteroenteric fistula noted on a small bowel series of x-ray films in a patient with inflammatory bowel disease. The narrow-appearing segments filled out relatively normally on subsequent films. Note that barium is just starting to enter the cecum in the right lower quadrant (viewer's left), but the barium has also started to enter the sigmoid colon toward the bottom of the picture, thus indicating the presence of a fistula from the small bowel to the sigmoid colon.

The small bowel series, or small bowel follow-through (see the image below), can reveal inflammation, can assist in the assessment of stricture length and severity, and can help determine the most appropriate surgical approach. Fistulas may be demonstrated on films from a small bowel series, even if they are not suggested on the basis of the clinical evaluation.

Inflammatory bowel disease. Cobblestoning in Crohn Inflammatory bowel disease. Cobblestoning in Crohn disease. Spot views 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.

Although radiologists may remark on the abnormalities suggested in the cecum or ascending colon when the barium from a small bowel series enters the colon, independent confirmation must be sought because the presence of stool and dilution of the barium may make proper interpretation of colon findings difficult.

The small bowel series is usually sufficient for the evaluation of small intestine Crohn disease; however, in rare cases, it may not provide an adequate view of the terminal ileum, necessitating an enteroclysis.

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Small Bowel Enteroclysis and Fistulography

Small bowel enteroclysis differs from a small bowel series in that a nasoenteric or oroenteric tube is placed and contrast material is instilled directly into the small intestine. This is usually performed when fine detail of the intestinal mucosa is required or the distal small intestine is not adequately seen on the small bowel series owing to dilution of the contrast agent as it passes through the (usually dilated) small bowel. This has been supplanted for the most part by computed tomography (CT) enterography.

In fistulographic studies, contrast can also be inserted directly into an enterocutaneous fistula in order to help determine the course of the fistula in anticipation of surgical correction and to assist in guiding the surgical approach.

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Ultrasonography

Ultrasonography (US) is a non-invasive technique in diagnosing Crohn disease. Although this technique has a sensitivity of 84% and a specificity of 92%, it has less accuracy when disease is located proximal to the terminal ilium. [63] Ultrasonography, magnetic resonance imaging (MRI), and computed tomography (CT) scanning have similar accuracy for the entire bowel and are reliable in identifying fistulas, abscesses, and stenosis; however, US may lead to false positives for abscesses. US and MRI are often preferred over CT scanning because of the lack of radiation risk, especially in younger patients. [63]

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CT Scanning and MRI

Findings on computed tomography (CT) scanning of the abdomen and pelvis may be very suggestive of inflammatory bowel disease (IBD). Bowel wall thickening on CT scans is nonspecific and may occur from smooth muscle contraction alone, especially in the absence of other extraintestinal inflammatory changes; however, the presence of inflammatory changes (eg, mesenteric fat stranding, wall enhancement, increased vascularity ["comb sign"]) significantly increases the predictive value of the CT scan.

CT scanning is the ideal study to determine if the patient has abscesses, and it can be used to guide percutaneous drainage of these abscesses. Fistulas may also be detected on CT scans. CT scanning is best for demonstrating intra-abdominal abscesses, mesenteric inflammation, and fistulas. (See the following images.)

Inflammatory bowel disease. This computed tomograp Inflammatory bowel disease. This computed tomography scan from a patient with terminal ileal Crohn disease shows an enteroenteral fistula (arrow) between loops of diseased small intestine.
Inflammatory bowel disease. A teenage patient with Inflammatory bowel disease. A teenage patient with Crohn disease underwent a contrast-enhanced upper gastrointestinal computed tomography study with small-bowel follow-through. Several loops of small bowel are in the pelvis. Note there is a loop of distal bowel with a thickened wall (solid arrow), which is contrasted with a less involved loop of bowel in which the intestinal wall is not thickened at all (dotted arrow).
Inflammatory bowel disease. Computed tomography sc Inflammatory bowel disease. Computed tomography scan depicting Crohn disease in the fundus of the stomach.

The use of magnetic resonance imaging (MRI) was validated in a prospective study that compared this imaging modality to the standard Crohn’s Disease Endoscopic Index of Severity (CDEIS). [64] MRI accurately assessed intestinal wall thickness, the presence and degree of edema, and ulcers in patients with Crohn disease. This study confirmed that through relative contrast enhancement (RCE), MRI can play an essential role in predicting disease activity and severity in Crohn disease. [64] In addition, pelvic MRI has a higher sensitivity for the diagnosis of perirectal complications of Crohn disease.

CT enterography

A newer CT technique (called CT enterography) is a contrast CT technique in which larger than normal amounts of oral contrast are ingested by the patient. This technique, which requires a skilled radiologist, allows for better visualization of the small bowel mucosa and is considered by some to be superior to the small bowel x-ray series because of its ability to identify extraintestinal lesions; for diagnosing intestinal disease, it compares favorably with capsule enterography, ileocolonoscopy, and small bowel follow-through x-ray. In situations where repeated studies are needed, MR enterography may be considered in order to avoid excess radiation exposure. [65, 66, 67]

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Colonoscopy and Flexible Sigmoidoscopy

Colonoscopy

Colonoscopy is one of the most valuable tools available to the physician for the diagnosis and treatment of inflammatory bowel disease (IBD), although its limitations must be recognized. Foremost, not all mucosal inflammation is idiopathic IBD. Infectious causes of inflammation must always be considered, as should diverticulitis and ischemia (which are far more common as new diagnoses in an elderly population than IBD, despite the similar colonoscopic and histologic appearance).

When used appropriately, colonoscopy can help determine the extent and severity of colitis, assist in guiding treatment, and provide tissue to assist in the diagnosis. In skilled hands, the colonoscope can frequently reach the terminal ileum and permit assessment of inflammation to assist in the diagnosis or exclusion of Crohn disease. Inflammation may occasionally occur in the terminal ileum in patients with ulcerative colitis; this is referred to as a backwash ileitis and is mild, is nonulcerating, and may occur when a widely patent ileocecal valve is present. (See the following images.)

Inflammatory bowel disease. Severe colitis noted d Inflammatory bowel disease. Severe colitis noted during colonoscopy in a patient with inflammatory bowel disease. The mucosa is grossly denuded, with active bleeding noted. The patient had her colon resected very shortly after this view was obtained.
Inflammatory bowel disease. Stricture in the termi Inflammatory bowel disease. Stricture in the terminal ileum noted during colonoscopy in a patient with inflammatory bowel disease. This image depicts a narrowed segment visible upon intubation of the terminal ileum with the colonoscope. Relatively little active inflammation is present, indicating that this is a cicatrix stricture.

Colonoscopy or sigmoidoscopy reveals that the rectum is almost always involved in ulcerative colitis, but it is frequently spared in Crohn disease. The disease can be limited to the rectum (proctitis); to the rectum, sigmoid, and descending colon (left-sided colitis); or to the entire colon (pancolitis). Ulcerative colitis does not involve any other segment of the GI tract. Colectomy is curative.

Colonoscopy with ileoscopy in the assessment of Crohn disease has a sensitivity of 74% and a specificity of 100%, leading to a positive predictive value of 100% as a diagnostic test. [68] When paired with small bowel follow-through, the sensitivity of this pair of diagnostic tests is increased to 78%, with a continued positive predictive value of 100%. [68]

Colonoscopy can also be used for therapeutic intervention in patients with IBD. The most common therapeutic use is stricture dilation in persons with Crohn disease. Colonic, anastomotic, and even small bowel strictures can often be dilated using pneumatic through-the-scope dilators. Intralesional injection of steroids (eg, triamcinolone at 5 mg in 4 quadrants) may help, but it is usually of transient value and has yet to be assessed in controlled trials.

Patients with IBD who are undergoing endoscopic procedures may have higher complication rates than the general population. The risks of colonoscopy apply (eg, reaction to medication, bleeding, perforation), and the risk of bleeding is increased in the presence of inflammation. The risk of perforation is also increased, particularly in patients taking high doses of steroids long term or who have severe colitis.

Colonoscopy also plays an important role in surveillance for colorectal cancer in patients with IBD. The utility of endoscopic surveillance can be further optimized by autofluorescence plus high-resolution endoscopy, chromoendoscopy-guided confocal laser microscopy, and confocal laser microscopy in combination with narrow-band imaging and high-resolution endoscopy, as well as chromoendoscopy with methylene-blue dye and spray-targeted biopsies. [69]

Flexible sigmoidoscopy

Flexible sigmoidoscopy is useful for a preliminary diagnosis in patients with chronic diarrhea or rectal bleeding; however, because of the limited length of the scope (60 cm), it can only help diagnose distal ulcerative colitis or proctitis. Rarely, Crohn colitis can be diagnosed based on flexible sigmoidoscopy findings. Note that sigmoid inflammation, particularly in older patients, may be confused with diverticulitis or ischemia.

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Upper GI Endoscopy

Esophagogastroduodenoscopy (EGD) is used for the evaluation of upper gastrointestinal tract symptoms, particularly in patients with Crohn disease. Aphthous ulceration occurs in the stomach and duodenum in 5%-10% of patients with Crohn disease. The diagnosis of Crohn disease may be made after gastric or duodenal ulcers fail to heal with acid suppression alone but is usually accompanied by ileal or ileocolonic Crohn disease.

Guidelines on the use of endoscopy in the diagnosis and management of IBD are available from the American Society for Gastrointestinal Endoscopy. [70]

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Enteroscopy

Capsule enteroscopy

In capsule enteroscopy, the patient swallows an encapsulated video camera that transmits images to a receiver outside the patient. It is most commonly used for finding obscure sources of gastrointestinal (GI) blood loss, the images can find ulcerations associated with Crohn disease if upper endoscopy and colonoscopy are unrevealing. In one study, the detection rate of abnormalities was 70.5% for patients with suspected small bowel disease, and the diagnostic yield for patients with obscure GI bleeding was higher (85.7%) than that for patients with abdominal pain or diarrhea (53.3%). [71]

Capsule enteroscopy may also aid in the diagnosis of small bowel Crohn disease when the standard diagnostic workup with colonoscopy and upper endoscopy is negative. [1]

However, not all small intestinal ulcerations represent manifestations of Crohn disease. The major risk is the potential for the camera to become lodged at the point of a stricture, which may necessitate operative intervention for removal. The risk of the standard capsule can be avoided with a preliminary exam by using a patency capsule that disintegrates if a stricture is encountered or by performing an alternative small bowel imaging study to first exclude such strictures in patients with suspicious symptoms.

Double balloon enteroscopy

Double balloon enteroscopy, or deep small bowel enteroscopy, is a technique whereby a long enteroscope is passed into the intestine using an overtube. Both the endoscope and the overtube have balloons that can be inflated and deflated sequentially as the endoscope is advanced in an "inchworm" fashion. Successful evaluation of the entire small intestine with this technique is reported to be as high as 86% to as low as 23%. [72, 73, 74, 75] However, patients who have had previous surgery have a higher complication rate (perforation) with this technique relative to other small bowel imaging techniques.

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Histologic Findings

Ulcerative colitis

Ulcerative colitis is a superficial inflammation of the bowel wall almost entirely limited to the large bowel (when the cecum is involved, there may be some inflammation in the distal-most ileum, the so-called "backwash ileitis"). Only in complicated cases such as evolution into toxic megacolon are the deeper layers of the bowel wall involved with the inflammatory process.

Ulcerative colitis primarily involves the mucosa and the submucosa, with the formation of crypt abscesses and mucosal ulceration. The mucosa typically appears granular and friable. In more severe cases, pseudopolyps form, consisting of areas of hyperplastic growth with swollen mucosa surrounded by inflamed mucosa with shallow ulcers. In severe ulcerative colitis, inflammation and necrosis can extend below the lamina propria to involve the submucosa and the circular and longitudinal muscles.

Inflammation in ulcerative colitis almost always involves the rectum and is contiguous, regardless of the extent of the colon involved. The exception to this rule is that the initial inflammation may appear patchy during colonoscopy that is performed very early in the ulcerative colitis process, although biopsy specimens of the intervening normal-appearing mucosa often do reveal inflammation. The intestinal inflammation of ulcerative colitis only involves the colon. Biopsy specimens demonstrate neutrophilic infiltrate along with crypt abscesses and crypt distortion. Granulomas do not occur in ulcerative colitis. (See the following images.)

Inflammatory bowel disease. Chronic architectural Inflammatory bowel disease. Chronic architectural changes in ulcerative colitis. Note the crypt branching and irregularity of size and shape, with an increase in chronic inflammatory cells in the lamina propria.
Inflammatory bowel disease. Low-power image of a c Inflammatory bowel disease. Low-power image of a colon biopsy specimen in a patient with ulcerative colitis illustrates changes limited to the mucosa. These changes include chronic alterations of the crypt architecture and an increase in chronic inflammatory cells in the lamina propria.
Inflammatory bowel disease. Chronic architectural Inflammatory bowel disease. Chronic architectural changes in ulcerative colitis. Note the trifid crypt.

The typical histologic findings of ulcerative colitis include expansion of chronic inflammation in the mucosa and, in active cases, the presence of acute inflammation. In mildly active cases, there is an acute cryptitis that progresses to crypt abscesses in moderately active cases. In severe cases, mucosal ulcers develop as a result of the ongoing acute inflammatory process. Areas of relatively preserved mucosa between ulcerated areas may have a polypoid appearance grossly and are referred to as "pseudopolyps." In cases of many years’ duration, dysplasia of the large bowel mucosa may develop and signifies an increased risk for the development of colorectal adenocarcinoma. (See the images below.)

Inflammatory bowel disease. High-power view of a c Inflammatory bowel disease. High-power view of a crypt abscess in ulcerative colitis shows the crypt to be dilated and filled with neutrophils and debris.
Inflammatory bowel disease. This is an example of Inflammatory bowel disease. This is an example of low-grade glandular dysplasia in a patient with longstanding ulcerative colitis. Note the loss of mucin, nuclear hyperchromasia, and nuclear pseudostratification. See the next image.
Inflammatory bowel disease. High-grade dysplasia i Inflammatory bowel disease. High-grade dysplasia in the same patient as the previous image. There is significant cytologic atypia, with rounding of the nuclei and a greater degree of pseudostratification.
Inflammatory bowel disease. Histologic section fro Inflammatory bowel disease. Histologic section from another location in the same patient as described in the previous image. This field shows glands that are suspicious for invasive carcinoma.

Crohn disease

The entire intestinal wall is involved with inflammation in Crohn disease. Biopsy specimens may demonstrate granulomas (approximately 50% of the time). The presence of granulomas is often helpful in making the diagnosis but is not necessary.

Because biopsy specimens obtained at colonoscopy are generally superficial mucosal samples, the pathologist may have difficulty making a definitive diagnosis of ulcerative colitis or Crohn disease based on histologic findings alone. However, histology also helps rule out other causes of inflammation, including infectious colitis and ischemic colitis. The characteristic pattern of inflammation in Crohn disease is a transmural involvement of the bowel wall by lymphoid infiltrates that contains sarcoidlike granulomas in about half of the cases (most commonly in the submucosa). Also characteristic are proliferative changes in the muscularis mucosa and in the nerves scattered in the bowel wall and myenteric plexus. In the involved foci of the small and large bowel, Paneth cell hyperplasia is frequent and areas of pyloric metaplasia may be seen. In full-blown cases, long and deep fissurelike ulcers form. (See the following images.)

Inflammatory bowel disease. A deep knifelike, fiss Inflammatory bowel disease. A deep knifelike, fissuring, transmural ulcer in Crohn disease is shown in this histologic image.
Inflammatory bowel disease. Granuloma in the mucos Inflammatory bowel disease. Granuloma in the mucosa in a Crohn disease patient.
Inflammatory bowel disease. Colonic granuloma in a Inflammatory bowel disease. Colonic granuloma in a patient with Crohn disease (arrow). Hematoxylin-eosin staining. Courtesy of Dr E. Ruchelli.
Inflammatory bowel disease. A crypt abscess demons Inflammatory bowel disease. A crypt abscess demonstrating active, neutrophilic inflammation in Crohn disease.
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