The diagnosis of IBD entails the documentation of the extent as well as severity of the inflammation affecting segments of the gastrointestinal tract, as well as the exclusion of other etiologies. There is no single test that is pathognomonic for ulcerative colitis (UC) or Crohn disease (CD). Bowel imaging techniques, whether endoscopic or radiological, are employed to support the diagnosis. The combination of ileocolonoscopy and EGD with multiple biopsies can usually differentiate between UC and CD based on the distribution and pattern of mucosal inflammation [2]. Endoscopic procedures provide invaluable information regarding the anatomic extent and severity of the mucosal inflammation. However, the vast majority of the small bowel is inaccessible to standard endoscopy or even enteroscopy. Over the past few years, several studies have established the utility of VCE to evaluate the small bowel in patients with IBD [6]. Whereas in adults, obscure bleeding is the most common indication for VCE, known or potential CD constitutes the majority (>60%) indication in children [13]. The potential uses of VCE in established or known IBD are summarized in Table 23.1, and discussed below.

Contrast small bowel radiography (SBR) and upper endoscopy (EGD and ileocolonoscopy) have long been the standard methods for evaluating known or suspected small bowel CD [2]. However, SBR has relatively low sensitivity for early and superficial lesions of CD in the small bowel [8, 11, 12]. Ileoscopy, when achieved, generally only affords examination of the distal and terminal ileum. Push enteroscopy can be employed to examine the proximal regions of the small bowel that cannot be examined by EGD. However, it too has a rather limited range. A recent Spanish consensus guideline recommends VCE as a far more promising tool for the evaluation of the small bowel in suspected IBD [14]. In cases where prior traditional investigations including EGD, ileocolonoscopy, and SBR were generally negative or nondiagnostic, VCE is vastly superior to establish, or exclude a diagnosis of “obscure” CD limited to the small bowel [6]. A meta-analysis reported a pooled odds ratio (OR) for VCE of 13.0 (95% confidence interval (CI) 3.2–16.3; p < 0.0001) compared with SBFT in detecting small-bowel abnormalities in patients with known or suspected CD [8]. The pooled OR for detecting lesions in known or suspected Crohn disease was 5.4 (95%CI 3.0–9.9) for VCE compared with enteroclysis. Another meta-analysis focused on 11 prospective comparative studies comparing VCE to other modalities for the diagnosis of established or suspected nonstricturing CD [15]. VCE was compared to multiple diagnostic modalities (ileoscopy, push enteroscopy, and small bowel radiography, including SBFT and enteroclysis, CT enterography, and small bowel MRI) in a total of 228 patients. The yield for VCE was significantly higher compared to barium small bowel radiography (63% vs. 23%, respectively). Similarly, the yield for VCE versus ileoscopy was 61% and 46%, whereas that for VCE versus CT was 69% and 30%, respectively. Subset analysis of patients with established CD showed that VCE had a higher yield compared to the other modalities. Ongoing issues include the lack of standardization between studies in terms of inclusion and exclusion criteria, as well as the widely variable capsule reading experience. Overall however, VCE is now established as more sensitive for small bowel mucosal lesions than other traditional imaging modalities. Moreover, a normal VCE examination has a very high negative predictive value, essentially ruling out small bowel CD.

Other techniques for small bowel imaging such as CT enterography (CTE) and MR enterography (MRE) are capable of evaluating bowel wall thickness and enhancement, supporting a diagnosis of CD. In addition, these techniques can also detect the presence of extraintestinal abnormalities, such as abscess formation. Also, CTE and MRE have been shown to correlate with disease activity. A small study compared VCE with MRE in 36 adults with known or suspected small bowel CD [17]. Among the 18 patients with known CD, VCE detected inflammatory lesions in the proximal and mid-small bowel (jejunum and ileum) in 12, compared to only one with MRI (p = 0.016). There was no significant difference in sensitivity between the two studies for terminal ileal involvement. The authors suggested that VCE is better to assess the severity and extent of small bowel inflammation. Another study compared MRE and VCE in 27 patients with established and 25 with suspected CD [10]. Among those with established CD, the yield for VCE was 93% compared to 79% with MRE. In those with suspected CD, VCE was more sensitive and specific (92%/100% vs. 77%/80%, respectively). Another small study (28 cases) used data analysis by consensus diagnosis, comparing VCE with CTE, SBFT, and ileocolonoscopy [11]. Although VCE had the highest sensitivity (83%) for CD, the specificity was lowest of the four modalities (53%).

A recent prospective study [16] in a tertiary pediatric center compared MRE, small intestine contrast US, and VCE in a cohort of 25 pediatric cases of known or suspected CD. The performance of each method was compared blinded to a reference standard for the upper small bowel and ileocolonoscopy. The authors concluded that all three methods were effective in assessing the small bowel. They recommended an integrated approach using more than one tool to achieve a complete assessment of the small bowel in known or suspected pediatric CD. Major limitations to the study are the limited cohort size (n = 25), combining known and suspected cases and the use of a consensus reference to the upper small bowel.

Additional prospective studies are required to define the roles of VCE vs. CTE or MRE in the diagnostic algorithm for known and suspected CD [6]. A recommended approach, based on available data [12], is illustrated in Fig. 23.2. An economic analysis comparing VCE to the traditional modalities for diagnosing CD [17] concluded that VCE was a less costly strategy if its diagnostic yield was 64% or greater, based on average diagnostic yields in the literature of 70% for VCE and 54% for SBFT and colonoscopy/ileoscopy. The authors suggested that VCE may also be less costly as a first-line test in this situation.

The number of indications for VCE in established CD has been recently extensively reviewed [18]. Among them is to determine the presence of early postoperative recurrence of CD. Recurrence has been documented in the neo-terminal ileum in 73–93% of cases after resection [19]. A prospective comparison of VCE and ileocolonoscopy 6 months after surgery was carried out in 32 adult CD patients, 21 (68%) of whom had recurrent disease [20]. VCE was better able to identify proximal small bowel disease. However, ileocolonoscopy was more sensitive overall (90% vs. 62%). Other studies [19, 21] favored VCE or VCE and abdominal ultrasound. Overall, ileocolonoscopy remains the procedure of choice. However, in view of its noninvasive nature, VCE may be considered as an alternative approach in this clinical situation in the pediatric age group. VCE would be particularly helpful when the surgical anastomosis is not accessible by endoscopy [19].

Indeterminate colitis (IC), referred to as IBD of undetermined type (IBD-U), may be defined as a chronic inflammatory bowel disease limited to the colon, without clear endoscopic or pathologic features diagnostic for either CD or UC. Pilot studies [18, 22] reported that VCE led to a change in diagnosis in 29–40% of patients. In a study involving 120 cases of UC and IBD-U, VCE revealed findings compatible with CD in 19 cases (15.8%), whereas barium small bowel imaging found just one case [23]. In a pediatric study in 26 cases of IBD-U [24], small bowel lesions typical of Crohn disease were detected by imaging in 7 and by VCE in 16 (p < 0.05). Overall, VCE appears to have utility as a diagnostic tool for CD in patients with IBD-U, as over 30% will be reclassified as CD (G). Larger prospective studies are needed to confirm the usefulness of VCE in this setting.

Symptom assessment is a poor indicator of severity and extent of disease. Mucosal healing after treatment is predictive of reduced subsequent disease activity and decreased hospitalizations and surgery [25]. The high diagnostic precision of VCE can be useful to evaluate small bowel mucosal healing after treatment and thus impact upon disease management and clinical outcomes. Efthyemiou et al. [26] conducted a prospective, multicenter, case-series study. Forty patients with clinically active known or suspected CD were included, all with nonstricturing, nonpenetrating CD. All patients underwent VCE prior to the initiation of any treatment. Treatment was selected according to the treating physician. For the evaluation of mucosal healing, three endoscopic variables were collected: number of apthous ulcers, number of large ulcers, and period of time that any endoscopic lesion was visible (erythema, edema, ulcers). When patients achieved clinical response (after at least a month of treatment) they underwent a second VCE, with evaluation of the same parameters. The number of large ulcers before and after treatment were 8.3 ± 1.4 and 5 ± 0.8, respectively (mean ± SEM) (mean difference 3.3 ± 1.2, 95% confidence interval (CI) 0.8–5.9, p = 0.01).

Another pilot study aimed to determine the efficacy of infliximab in treatment of chronic refractory pouchitis complicated by ileitis, using capsule endoscopy [27]. VCE was repeated at week 10 and the Pouchitis Disease Activity Index score was determined. Clinical remission was achieved in 9/10 patients. At VCE and pouch endoscopy, a complete recovery of lesions was observed in eight patients.

In an ongoing study, we are evaluating VCE to assess mucosal healing of the small bowel in a cohort of adult patients with moderate to severe jejunal and or ileal CD [28]. After 6 months of adalimumab monotherapy a second VCE was carried out blinded to the initial severity score, using the Lewis Index [29]. The evaluation of the first ten cases showed complete mucosal healing in five and partial healing in four others (Lewis score decrease >50 %). Although promising, further study of the use of VCE to determine mucosal healing of the small bowel after therapy is needed. This concept is particularly appealing for pediatric onset disease, given the noninvasive nature of VCE.

VCE was approved as a safe and beneficial in the pediatric population after the first trial [5]. Potential roles for VCE in suspected CD are substantiated by

An early study used VCE in 12 adolescent patients with a clinical suspicion of CD despite negative EGD and colonoscopy [30]. Ileoscopy, achieved in 50% of the patients, was normal in all. Lesions suggestive of CD were identified by VCE in 7/12 (58%) cases. In our comparative and prospective, self-controlled pediatric trial, 30 patients from 10 to 18 years of age were evaluated for obscure small bowel disease [5]. Lesions consistent with a diagnosis of CD were found only by VCE in 10/20 (50%) patients suspected of CD, whereas the diagnosis was formally ruled out in 8. Two remaining cases were found to have eosinophilic gastroenteropathy (by histopathology obtained via subsequent enteroscopic assessment), for an overall VCE diagnostic yield of 60%. Other reports suggest that VCE is potentially useful in the evaluation of possible CD among young patients presenting with a protein-losing enteropathy [31] and/or growth failure when other studies are negative.

No gold standard test exists for the diagnosis of CD. The diagnosis is based on a compilation of clinical, endoscopic, histological, radiological, and biochemical findings. There is a justifiable concern that normal variant capsule findings in the small bowel may be overinterpreted. In adults, up to 13% of normal, asymptomatic individuals can have mucosal breaks and other minor lesions of the small bowel detected by VCE. Therefore, VCE findings of minor mucosal lesions of the small bowel are alone not sufficient for a diagnosis of CD. Other causes to be considered include celiac disease, infectious, ischemic, autoimmune as well as immunodeficiency-related, allergic and drug-induced etiologies. Nonsteroidal anti-inflammatory drug (NSAID) induced enteropathy is common and should be excluded, as it is generally conceded that lesions detected by VCE in NSAID enteropathy cannot be reliably distinguished from those due to CD. The chronicity of the lesions may assist is the differential diagnosis of CD and NSAID induced enteropathy [32].

A standard terminology system has been developed along with a VCE scoring index for small bowel inflammatory lesions such as seen for CD [29]. The parameters that were found to have the necessary inter- and intraobserver consistency were villous edema, mucosal ulcerations and the presence of stenotic lesions. This “Lewis Score” [29] provides an aid to diagnosis and a validated measure of mucosal damage:

In the assessment of any diagnostic technology, a critical evaluation of the impact or added value of the test must be considered. A retrospective review of VCE in 83 children was reported by a single tertiary care center [35]. Among these approximately 60% were established CD, 20% IBD-U, and 20% suspected IBD. One year after VCE, patients with known CD had significant improvements in growth, higher body mass index, lower ESR and Harvey Bradshaw index. VCE also revealed more extensive disease extent in 43% of CD compared to other modalities used. The negative predictive value for suspected IBD was 94%. Moreover, 50% of IBD-U cases had their diagnosis changed to CD after VCE [35].