Colonoscopy is the overall preferred/standard screening procedure for the confirmation of either CD or UC in patients with clinical suspicion of IBD. Sigmoidoscopy is only a diagnostic choice in established UC to evaluate disease activity and in patients with established IBD in whom there is a suspicion of superimposed infection such as CMV and Clostridium difficile [2]. Moreover, apart from radiologic analyses of the small bowel in patients with CD, colonoscopy is the method of choice for re-evaluation of disease activity of UC and CD, and in cases where there is loss of response to therapy. Also, colonoscopy is recommended for the assessment of CD recurrence 6–12 months after resective surgery to adapt or modify medical therapy based on the endoscopic findings [3].

In adult patients in the absence of clinical signs for upper-GI involvement (e.g., epigastric pain), upper-GI endoscopy is usually not performed at the initial diagnostic evaluation for IBD. In contrast, in pediatric patients, CD often appears as a UC-like phenotype at colonoscopy; due to a relatively high percentage of upper-GI involvement in this age group an upper-endoscopy is always recommended as a staging procedure for suspected IBD in children [4].

In the US, a new strategy termed “Treatment to Target” is currently being passionately discussed [5, 6]. The aim of this strategy is the establishment of mucosal healing, using escalation of therapy in patients with persistent endoscopically visible inflammation until mucosal healing is achieved. There are no prospective studies that have proven such an approach, which requires frequent colonoscopies in patients with enduring endoscopic disease activity (every 3–6 months). In patients with small-bowel involvement this might consist of repeat radiological imaging procedures to re-evaluate the impact of therapeutic escalation.

For the initial assessment of small-bowel involvement in patients with IBD, one has to keep in mind that neither computer tomography (CT) nor magnetic resonance imaging (MRI) are able to visualize superficial ulcers in the small bowel. CE has been proven to be superior to both imaging modalities in patients with suspected CD [7–9]. However, due to the risk of concurrent strictures even in clinically asymptomatic patients, a radiological evaluation of the small intestine is always recommended before performing CE [10]. The main problem of diagnosing CD in patients with otherwise negative upper and lower endoscopy workup is (a) the lack of histological verification of the findings, which can be only achieved with a balloon enteroscopy, and (b) the lack of validated “diagnostic criteria for small-bowel involvement. This is illustrated by a 12-month follow-up study conducted in an American tertiary IBD center, in which 102 patients with suspected CD underwent CE after normal or equivocal findings on colonoscopy and radiological small-bowel imaging [11]. Only 13% of the patients who were found to have small-bowel ulcerations were subsequently diagnosed with CD based on endoscopic or radiographic re-evaluations. The overall sensitivity of CE (defined as any visualized small-bowel ulcers) for the diagnosis of CD (within 12 months of CE) was 85%, the specificity was 73%, the positive predictive value (PPV) was 31%, and the negative predictive value (NPV) was 97%. The PPV increased to 50% if >3 ulcers were used as a criterion for CD on the initial capsule study. Given the high NPV of a normal CE study, the real value is the exclusion of the diagnosis of CD in patients with suspected small-bowel inflammation and an otherwise negative previous workup.

As for patients with established CD, one retrospective single-center analysis which included 128 capsule endoscopies in patients with IBD reported a change in medication in 62% of the patients in the 3 months after the CE, with 40% commencing a new IBD medication based on the findings seen on CE [12].

SBE or DBE are available endoscopic modalities that can allow evaluation of the small bowel in patients with suspected or proven small-bowel CD. The advantages include the possibility to obtain biopsies and perform interventions such as dilation of strictures, which are sometimes not recognized by CT or MRI imaging [13, 14]. The disadvantages, compared to CE, are the need for sedation and the risk of perforation, which is estimated at around 1% in patients with IBD [10, 15, 16]. Also, DBE might be unsuccessful due to the presence of fixed bowel loops in the setting of previous surgery or inflammation. A recent retrospective analysis of five academic centers in the U.S. analyzed 98 DBE procedures performed over a 5-year period in 81 patients (47% known CD) [17]. In 17% of the patients, DBE was unsuccessful due to fixed bowel loops or inability to intubate the ileocecal valve. The overall diagnostic yield was 83%, which impacted the management in 79% of patients. Whereas the main indications for DBE in patients with established CD were abdominal pain (37%) and bleeding/anemia (39%), the indications in patients with suspected CD were abnormal radiologic imaging (44%) or abnormal CE (60%).