Characteristic Endoscopic Findings

Several SBCE findings are frequently associated with CD: aphthous lesions, serpiginous, linear or deep ulcerations, and mucosal edema (see Fig. 1 ). However, these findings are neither pathognomonic nor specific to CD. Some minor small-bowel lesions may be found in up to 10% of normal subjects, but the most common mimickers of small-bowel CD are nonsteroidal anti-inflammatory medication (NSAID)-induced enteropathy, which may appear after a short exposure Avoidance of NSAIDs for at least 1 month before SBCE examination is, therefore, mandatory for patients undergoing SBCE for suspected CD.

Endoscopic/Diagnostic Scores

Several diagnostic criteria were used for diagnosis of CD on SBCE ( Table 1 ). Earlier studies by Mow and colleagues required detection of ≥3 ulcers to fulfill the criteria of definite diagnosis of CD. This definition was replaced by more stringent criteria. Two endoscopic inflammatory scores are currently available for diagnosis and monitoring of CD or other small-bowel inflammation. The Lewis score was designed for quantification of small-bowel inflammation. This score divides the small bowel into 3 tertiles (identified by truncation of the small-bowel transit time) and assigns points to various findings (mucosal edema, ulcers, strictures) characteristic for CD in each of the tertiles, correcting for severity and extent of the findings. The Lewis score is incorporated in the software of the Medtronic/Given Imaging device (the RAPID software). A score less than 135 designates a normal small bowel, a score of 135 to 790 is considered mild to moderate inflammation, and a score ≥790 defines moderate-to-severe inflammation. An additional score known as Capsule Endoscopy Crohn’s Disease Activity Index (CECDAI) is also available. This score divides the small bowel in 2 segments and incorporates the degree of inflammation, extent of disease, and strictures in both. A significant correlation between the Lewis score and CECDAI was reported. Both of these scores have been validated. The Lewis score is easy and user friendly as it is incorporated in the software and was also found to have better correlation with fecal calprotectin.

Small-Bowel Capsule Endoscopy Versus Other Modalities for the Diagnosis of Crohn’s Disease

SBCE has been repeatedly compared with other diagnostic modalities for detection of CD, such as small-bowel follow-through, computed tomography enterography (CTE), and magnetic resonance enterography (MRE). The superiority of SBCE diagnostic yield over small-bowel follow-through, CTE, and ileocolonoscopy was repeatedly demonstrated. Despite the overall comparable accuracy of SBCE and MRE for detection of CD, there are several distinctive advantages and weaknesses to each modality. MRE is naturally superior for detection of penetrating and other extraluminal complications. However, its sensitivity for detection of mild mucosal inflammation is significantly inferior to that of SBCE. Moreover, the accuracy of MRE for detection of proximal small-bowel disease is poor. Jensen and colleagues reported that proximal small-bowel CD was detected in 18 of 93 patients by SBCE compared with 2 and 6 patients using MRE or CTE, respectively ( P <.05). Moreover, the acceptability and willingness of patients to repeat the procedure is significantly higher for SBCE compared with MRE, as bowel preparation for SBCE is not mandatory.

Small-Bowel Capsule Endoscopy in Established Crohn’s Disease

There are several potential applications for SBCE in patients with established CD. The main applications of capsule endoscopy in established CD include the following:

• •
  

  Assessment of disease extent, severity and, thus, prognosis

  
  
• •
  

  Evaluation of mucosal healing

  
  
• •
  

  Evaluation of postoperative recurrence

Disease Reclassification and Prognosis

Disease phenotype (both location and behavior) impacts the long-term prognosis and the treatment strategy. Patients with extensive/proximal small-bowel disease relapse sooner and are more prone to have surgery. The importance of proximal small-bowel disease is reflected in the recently published pediatric Paris classification of CD ; however, a similar change was not yet adopted in the adult Montreal classification. SBCE is capable of detecting active disease in previously unknown locations. Although MRE was not sensitive for detection of jejunal and proximal ileal CD, capsule endoscopy detected proximal lesions in more than 50% of patients with established small-bowel CD. In patients with a diagnosis of exclusively colonic CD, small-bowel involvement was diagnosed in 25.6% of patients in a recent large retrospective study. Phenotype changes can also be detected by SBCE. Although patients with severe fibrostenotic phenotype are usually not given an SBCE or they undergo a patency capsule procedure or cross-sectional imaging to rule out stricturing disease before an SBCE, previously unknown fibrostenotic disease can still be detected via SBCE in up to 11% of the patients.

SBCE is useful in establishment of the final diagnosis in patients with undetermined inflammatory bowel disease (IBD). Colonic inflammatory bowel disease cannot be classified as CD or ulcerative colitis using current ileocolonoscopic and pathologic criteria in 10% to 15% of the patients and thus is named IBD unclassified . However, up to 30% of disease will be reclassified as CD during the course of the follow-up. Ascertainment of the diagnosis is especially important in severe cases requiring a surgical intervention, as rates of chronic pouchitis and pouch failure after ileal pouch-anal anastomosis are significantly higher in patients with CD. Mow and colleagues have described 22 patients with either isolated colitis or chronic symptoms following ileal pouch-anal anastomosis that had prior unremarkable small-bowel radiography. Multiple ulcerations (3 or more) were identified in 59% of these patients. Mehdizadeh and colleagues described 120 patients with a history of ulcerative colitis or IBD unclassified who underwent SBCE. Findings consistent with small-bowel CD were seen in 15.8% of the patients.

Evaluation of Mucosal Healing

The leading treatment paradigm in IBD has shifted in the last years from merely controlling symptoms to reversing the underlying inflammation. The concept of deep or stable remission, defined as a combination of clinical remission and mucosal healing, is an emerging treatment goal in clinical trials. However, most current knowledge pertains to mucosal healing in the colon and the terminal ileum that does not necessarily correlate with the degree of inflammation in the proximal small bowel. Determining what actually constitutes “small-bowel mucosal healing” is a crucial issue if this goal is to be adapted in future clinical trials or routine clinical practice. Recently, the Lewis score, originally developed to distinguish inflammatory from noninflammatory findings, was validated for monitoring of small-bowel mucosal healing in CD. A cutoff value of 135, consistent with the original value representing normal small bowel, was confirmed as a reasonable definition of mucosal healing in this large-scale Portuguese study. Since then, several other studies adopted this definition. The alternative diagnostic score (CECDAI) does not address a specific definition of mucosal healing; however, in a recent study that evaluated a correlation between the scores, the Lewis score value of 135 was consistent with a CECDAI of 3.8.

To date, only some studies addressed monitoring of mucosal healing by SBCE in CD, and some additional studies are ongoing. A small prospective study evaluated monitoring of mucosal healing with SBCE performed before and after treatment for acute CD flare-up. Forty patients with CD flares were included in the study, and all responded within 4 to 8 weeks of treatment. A significant improvement was seen in a subgroup of patients treated with corticosteroids combined with immunomodulators or biologics.

Two recent studies evaluated mucosal healing in CD patients taking immunomodulators or biologics after 12 or 52 weeks of therapy, respectively. The investigators used the CECDAI score and defined complete mucosal healing as absence of ulcers, whereas mild disease was defined as CECDAI less than 3.5 and moderate-to-severe disease as CECDAI ≥5.8. The study cohort included 37 patients with established CD, 84% of who were started on adalimumab and the rest on azathioprine treatment. In the initial assessment, moderate-to-severe disease activity was detected in 67% of the patients and mild-to-moderate disease in 33%. After 12 weeks, clinical remission was achieved by 54% of the patients, and a significant decrease in both C-reactive protein (CRP) and fecal calprotectin was achieved as well. However, the mucosal response was significantly more modest; significant CECDAI improvement was seen in only 27% of the patients, whereas none achieved complete mucosal healing. By week 52, 42% of the patients achieved complete mucosal healing that was also paralleled by clinical and biochemical remission.

A recent prospective study evaluated the prevalence of small-bowel mucosal healing using SBCE in patients with established small-bowel disease. Small-bowel mucosal healing was seen in 8 of 52 (15.4%) patients in clinical remission. Moderate-to-severe small-bowel inflammation was seen in 11 of 52 (21.1%) patients in clinical remission and in 1 of 21 (4.7%) of patients in clinical and biomarker remission. Only 7 of 52 (13.5%) patients were in deep remission. The long-term impact of a low-grade (Lewis score, 135–790) small-bowel inflammation on the long-term prognosis and the risk of complications are still to be determined.

To date, a single industry–funded, small-scale, phase 2 study from Israel that used serial SBCE follow-up within the setup of a clinical trial was published. No correlation between the Lewis score and clinical parameters (CDAI, Inflammatory Bowel Disease Questionnaire) or biomarkers was seen in this small study; the procedure itself was safe and well tolerated. These data suggest that SBCE may be used as a less-invasive yet accurate way to look at mucosal healing in small-bowel CD, especially when the proximal small intestine is involved.

Monitoring of Postoperative Crohn’s Disease Recurrence

Endoscopic recurrence of small-bowel CD in the neo-terminal ileum after surgical resection is frequent without secondary preventive measures and is seen in 73% to 93% of the patients within 1 year of surgery. The current paradigm of postoperative surveillance and treatment is based on early and intensive endoscopic surveillance with aggressive treatment of high-risk patients SBCE may provide a comprehensive and safe alternative to repeated ileo-colonoscopies in these patients and may also reveal active disease in the proximal small bowel, potentially necessitating earlier and more aggressive intervention. The Rutgeerts score is frequently used to quantify postoperative small-bowel inflammatory findings; higher scores are associated with a rapid progression to clinical relapse. Bourreille and colleagues evaluated the accuracy of SBCE versus ileocolonoscopy for detection of postoperative recurrence. In this cohort, recurrence occurred in 68% of the patients enrolled within 32 months from surgery. The sensitivity of SBCE was 62% to 76% and the specificity was 90% to 100%. The severity of lesions as assessed by both methodologies correlated significantly ( P <.05). In an additional study that included 24 postoperative CD patients, neo-terminal ileum recurrence defined as Rutgeerts score greater than 2 was shown by ileocolonoscopy in 25% of patients and by capsule endoscopy in 62%. Capsule endoscopy detected proximal SB lesions inaccessible by ileocolonoscopy in 13 patients.

Correlation Between Endoscopic Findings and Inflammatory Biomarkers

Inflammatory biomarkers have a pivotal role in noninvasive management of CD. CRP is still probably the most available and used biomarker; however, almost 30% of CD patients with active disease do not have elevate CRP levels. Fecal calprotectin (FCP) is significantly more sensitive than CRP for detection of mucosal inflammation in CD. Because of cost considerations, it is tempting to use FCP as a triage tool guiding selection of patients for SBCE. However, it seems that the correlation of FCP levels with small-bowel inflammation as detected by SBCE in CD is not as strong as it is in the colon. A recent meta-analysis that pooled the results of 7 studies reporting on SBCE findings and calprotectin levels, found a strong correlation between the 2 for all evaluated cutoffs (50, 100, and 200 μg/g). For studies including patients with suspected CD only, the overall accuracy for FC cutoff of 50 μg/g was excellent (sensitivity, 0.89; specificity, 0.55; and a negative predictive value of 91.8%). In patients with established CD, the likelihood of detection of a low-degree mucosal inflammation (Lewis score, 135–790) was almost 62% when a cutoff value of 100 μg/g was used for FC; however, severe inflammation (Lewis score >790) was rare (4.7%).

Therapeutic Yield of Small-Bowel Capsule Endoscopy in Established Crohn’s Disease

In known CD patients, SBCE is usually performed in routine clinical practice when a clinical dilemma arises. The capsule’s results frequently lead to a change in therapy. In the largest case series of established CD patients evaluated with SBCE to date, a change in therapeutic management was suggested in 52.3% of 187 included patients, mainly escalation of anti-inflammatory therapy in 82.5% of the patients who required a change in therapy.

Safety Considerations

The main complication of SBCE is capsule retention, defined as a failure to excrete the capsule requiring directed medical, endoscopic, or surgical intervention ( Fig. 2 ). The risk of capsule retention is increased in patients with known small-bowel strictures, extensive small-bowel CD, history of small-bowel obstruction, and previous abdominal surgery ( Table 2 ). The risk of capsule retention in patients with established CD was reported to be as high as 13%, however, in more recent series that verified small-bowel patency before performing SBCE, the risk of retention was much lower (1.5%–7.5%). In the largest case series reported to date (406 patients), the rate of SBCE retention was 2.3%. Capsule retention is usually uneventful but may present with symptoms of partial or complete bowel obstruction. In approximately half of the cases, the capsule is excreted spontaneously or after a short course of corticosteroids; if this method fails, the capsule can be extracted by DAE or surgically. In rare cases, the capsule may remain in the small bowel or the colon without causing any symptoms for weeks or months. It is unclear whether these cases merit endoscopic or surgical procedures or what the optimal timing is of such intervention.

Only gold members can continue reading. Log In or Register to continue

Share this:

• Click to share on Twitter (Opens in new window)
• Click to share on Facebook (Opens in new window)

Related posts:

The First Endoscopy in Suspected Inflammatory Bowel Disease Role of Histologic Inflammation in the Natural History of Ulcerative Colitis Noninvasive Testing for Mucosal Inflammation in Inflammatory Bowel Disease The Gastroenterologist’s Role in Management of Perianal Fistula Motility Evaluation in the Patient with Inflammatory Bowel Disease Dilation of Strictures in Patients with Inflammatory Bowel Disease

Stay updated, free articles. Join our Telegram channel

Join