Due to its ability to detect disease activity in the small bowel, capsule endoscopy (CE) can play an essential role in ensuring that patients with Crohn’s disease (CD) are receiving adequate treatment. Mucosal healing can be confirmed by this technology by verifying that inflammation is managed throughout areas of potential involvement. The marker of mucosal healing is now considered an important goal in the effort to achieve sustained disease control and prevent progressive bowel damage.1 Recent data have correlated complete mucosal healing with a significantly higher likelihood of persistent steroid-free remission.2

Of patients with CD, the majority experience discomfort in the small bowel,3 which is an area where damage can be difficult to detect with conventional endoscopy. Computed tomography enterography (CTE) is a sensitive test for detecting CD when inflammation penetrates the bowel wall, but may be less effective for evaluating mucosal healing when compared with CE.3,4

In adults with CD, CTE and magnetic resonance enterography (MRE) are the preferred tools for the initial diagnosis and evaluation of CD largely because they can rule out stricture or narrowing of the small bowel that may impede the capsule endoscope from descending. Studies have reported capsule retention rates in the range of 1% to 1.7% in adults.5 In children, CE may be used relatively early or even as an initial imaging tool when small-bowel involvement is suspected. “In children of ages 11 or 12 years, which is the average age of CD diagnosis, the time interval from disease onset to diagnosis is usually shorter, making the presence of stricture less likely. In addition, CE is clinically very helpful to establish the extent of mucosal inflammation,” said Joel Rosh, MD, director of the Division of Pediatric Gastroenterology and Nutrition at Goryeb Children’s Hospital, Atlantic Health, in Morristown, New Jersey.

Dr. Rosh does not perform CE in all children suspected of CD, and he emphasized that images from this tool must be interpreted in the context of other clinical information, particularly patient history and inflammatory biomarkers. However, Dr. Rosh noted that no imaging tool outside of CE is more sensitive when small-bowel involvement is suspected. “Symptoms particularly are unreliable for reflecting disease activity in the small bowel,” Dr. Rosh said. “CTE is most useful when rapid evaluation is required, but controlled studies have demonstrated that CE is more sensitive than any other single imaging tool for disease beyond the reach of the endoscope.”

In a blinded study conducted in adults with CD, the sensitivity of CE for CD in the terminal ileum was 100% versus 81% for MRE and 76% for CTE (Table).6 The study authors concluded that CE should be the first-line modality for detection of small-bowel CD in the absence of stenosis.6 “In a patient where stricture has been ruled out, CE can be essential for understanding disease activity when there are disparities in symptoms or biomarkers,” said Douglas C. Wolf, MD, Director of IBD Research at Atlanta Gastroenterology Associates, in Atlanta, Georgia. “Often, we continue to see upregulated markers of inflammation or anemia even when symptoms are controlled and colonoscopy is normal. Activity in the small bowel may be the reason.”

Relative to CTE, CE and MRE share a relative freedom from radiation exposure, which is a substantial advantage for the repeat imaging studies likely in a chronic disease with periodic flares. Data also have shown that patients report a preference for CE over standard ileoscopy and MRE,7,8 which could lead to improved follow-up and more frequent imaging using CE.

Table. Accuracy of CE, MRE, and CTE for the Diagnosis Of CD in the Terminal Ileuma

CE (n=69) MRE (n=72) CTE (n=73)
Sensitivity (%) 100 (79-100) 81 (58-95) 76 (53-92)
Specificity (%) 91 (79-97) 86 (74-94) 85 (72-93)
PPV (%) 76 (53-92) 71 (49-87) 67 (45-84)
NPV (%) 100 (93-100) 92 (80-98) 90 (78-97)
a In patients examined with CE, MRE, and CTE, assessment of the terminal ileum using ileoscopy was obtained in 69, 72, and 73 patients, respectively. 95% CIs in parentheses.
CD, Crohn’s disease; CE, capsule endoscopy; CTE, computed tomography enterography; MRE, magnetic resonance enterography; NPV, negative predictive value; PPV, positive predictive value Adapted from reference 6.

“CE is not required in every Crohn’s patient, but it is a sensitive tool for detecting disease activity in the small bowel, and the information it provides may lead to a change in management,” said David Hudesman, MD, director of the inflammatory bowel disease (IBD) program at NYU Langone Medical Center/Tisch Hospital, in New York, New York. Dr. Hudesman also suggested that a change in management on the basis of visualization of the small bowel could lead either to intensification or de-escalation of therapy.

The value of CE in this situation has been documented: In a series of 907 CEs performed for a variety of conditions—including persistent symptoms inconsistent with disease activity on colonoscopy—the majority of patients underwent a change in management that was based on images from this technology. Specifically, 61.6% had a change in medication within 3 months of having CE performed. In 39.5%, a new medication was added. In 12.8% of patients, surgery was performed.9

In some cases, CE changes fundamental assumptions about disease status, according to Dr. Wolf. “In one case, we ordered CE in a patient referred to me with ulcerative colitis,” he said. “We were concerned about inadequately controlled symptoms and persistently elevated C-reactive protein levels, although mucosal lesions in the large intestine were modest. On the basis of ulcers clearly observed in the small bowel, we changed the diagnosis to CD and immediately initiated treatment to bring the relatively severe small-bowel involvement under control.”

Both Dr. Hudesman and Dr. Rosh recounted similar cases when activity in the small bowel on CE deviated from symptoms of CD, biomarker surrogates of activity, or both. However, Dr. Hudesman cautioned that the images provided by CE, although more sensitive for CD than alternative imaging tools, are not definitive. “This is an imaging tool, so we still do not have tissue to examine histologically,” Dr. Hudesman noted. “If the goal is to evaluate small-bowel CD activity in a patient with a flare, the best imaging tool is generally the tool that was employed previously because this is the easiest way to detect change in disease activity. However, CE, by providing images of the surface mucosa, may have an advantage when the goal is to confirm healing as it is defined most strictly.”

Strict definition of healing is relevant to the deep remissions that appear to be important for reducing the risk for flares. The meaning of tight control still is being debated. In CD patients with small-bowel involvement, scheduled imaging—as opposed to imaging only when there is concern that active disease is being missed—may allow escalation of therapy at the early signs of inflammation. This concept remains theoretical. “The risk of conducting an imaging study of the small bowel at routine intervals, such as every 6 months, is that it could lead to overtreatment,” Dr. Rosh said. “The potential benefit is that it may provide opportunities to preserve deep remissions. Based on the debate about the value of deep remissions for improving long-term outcome, this may be a study worth doing.”

References

  1. Kopylov U, et al. Detection of small bowel mucosal healing and deep remission in patients with known small bowel Crohn’s disease using biomarkers, capsule endoscopy, and imaging. Am J Gastroenterol. 2015;110(9):1316-1323.
  2. Baert F, et al. Mucosal healing predicts sustained clinical remission in patients with early-stage Crohn’s disease. Gastroenterology. 2010;138(2):463-468.
  3. Wilkins T, et al. Diagnosis and management of Crohn’s disease. Am Fam Physician. 2011;84(12):1365-1375.
  4. Horsthuis K, et al. Inflammatory bowel disease diagnosed with US, MR, scintigraphy, and CT: meta-analysis of prospective studies. Radiology. 2008;247(1):64-79.
  5. Liao Z, et al. Indications and detection, completion, and retention rates of small-bowel capsule endoscopy: a systematic review. Gastrointest Endosc. 2010;71(2):280-286.
  6. Jensen MD, et al. Diagnostic accuracy of capsule endoscopy for small bowel Crohn’s disease is superior to that of MR enterography or CT enterography. Clin Gastroenterol Hepatol. 2011;9(2):124-129.
  7. Pons Beltrán V, et al. Evaluation of postsurgical recurrence in Crohn’s disease: a new indication for capsule endoscopy? Gastrointest Endosc. 2007;66(3):533-540.
  8. Wiarda BM, et al. Patient burden and patient preference: comparing magnetic resonance enteroclysis, capsule endoscopy and balloon-assisted enteroscopy. J Gastroenterol Hepatol. 2013;28(3):464-471.
  9. Long MD, et al. Impact of capsule endoscopy on management of inflammatory bowel disease: a single tertiary care center experience. Inflamm Bowel Dis. 2011;17(9):1855-1862.