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Original Article

Ileoscopy reduces the need for small bowel imaging in suspected Crohn’s disease

Michael Dam Jensen1, Torben Nathan1, Søren Rafael Rafaelsen2 & Jens Kjeldsen3,

1. sep. 2012
15 min.

Faktaboks

Fakta

There is no single gold standard diagnostic test for Crohn’s disease (CD). Even today, CD remains a syndrome diagnosis based on symptoms, physical examination and findings at endoscopy, histology, radiology, biochemical testing and occasionally surgery [1].

CD can affect any region of the gastrointestinal tract – from the mouth to the anus, and often does so discontinuously. At the time of diagnosis, approximately one third of cases have isolated disease in the small intestine, one third colonic disease and one third ileocolonic disease [2, 3]. In approximately 90% of patients, small bowel CD involves the terminal ileum, and CD isolated in the upper small bowel without distal involvement is rare [3]. Ileocolonoscopy is the mainstay for obtaining the diagnosis and an accepted gold standard for assessing ileocolonic CD [1].

In expert hands, ileoscopy is achieved in 85-90% of patients [4]. If the colon is normal and terminal ileum intubation is not achieved during colonoscopy, small bowel imaging plays a central role for obtaining the diagnosis. Conversely, in patients with CD of the colon, the primary purpose of small bowel imaging is to map disease location beyond the reach of the colonoscope.

Current guidelines for diagnosing CD suggest ileocolonoscopy with multiple biopsies from the terminal ileum and each colonic segment as the first diagnostic examination [1]. However, irrespective of the findings at ileocolonoscopy, further investigation is recommended to examine the location and extent of any CD in the upper small bowel (evidence level 5, recommendation grade D). Magnetic resonance imaging enterography (MRE) and computed tomography enterography (CTE) are regarded first line imaging techniques and should generally precede capsule endoscopy [1].

MATERIAL AND METHODS

In this article, we bring together results from a prospective blinded diagnostic study of MRE, CTE, capsule endoscopy and faecal calprotectin (fCal) in patients undergoing their first diagnostic work-up for CD [5, 6]. Our data suggest that a diagnostic approach different to that described in the guidelines may be expedient.

Trial registration: The study was approved by the Ethics Committee of Southern Denmark (S-20070072) and the Danish Data Protection Agency (journal number: 2007-41-0675). ClinicalTrials.gov identifier: NCT01019460.

RESULTS

Our study population consisted of 93 patients with clinical, endoscopic and/or histological suspicion of CD. Inclusion criteria and patient characteristics are described elsewhere [5, 6]. One study compared sensitivities and specificities of MRE, CTE and capsule endoscopy for detection of CD in the terminal ileum with ileocolonoscopy as gold standard. The other study examined the diagnostic properties of fCal for detection of CD in the same population (only 83 patients provided a stool sample). Figure 1 shows the number of patients entering the study and completing diagnostic procedures.

Selecting patients for endoscopy

A non-invasive and easily applicable method for selection of patients to invasive procedures is desirable. No clinical index for the diagnosis of CD is available, and biochemical markers of inflammation (C-reactive protein (CRP), orosomucoid, and sedimentation ratio) are limited by inadequate sensitivities [6, 7]. Multiple studies have established fCal as a sensitive marker of intestinal inflammation and a useful tool to discriminate inflammatory bowel diseases from functional disorders [8]. Despite this evidence, fCal has a minor role in the current guidelines for diagnosing CD [1]. In previous studies, fCal was primarily evaluated against colonoscopy, and until recently there has been a lack of evidence regarding the diagnostic performance of fCal in small bowel CD [9, 10]. This aspect is critical because the majority of patients with newly diagnosed CD have small bowel involvement, and the utility of fCal as a screening tool before colonoscopy relies upon equally high sensitivities in all disease locations.

In our population counting 83 patients undergoing their first diagnostic work-up for CD, levels and sensitivities of fCal were equal in colonic and small bowel CD. With a 50 mg/kg cut-off, fCal had a 95% sensitivity for detection of CD and a negative predictive value of 92% (disease prevalence 48%). These performance measures make fCal an effective marker for ruling out CD and for selecting patients for ileocolonoscopy.

Indications for small bowel imaging after ileocolonoscopy

Approximately two thirds of patients with newly diagnosed CD have small bowel involvement [2], but the number of patients with CD isolated to the upper small bowel without distal involvement is low [3]. Hence, it is relevant to question the benefit of additional small bowel imaging after ileocolonoscopy. A total of 40 patients were diagnosed with CD based on symptoms, clinical and biochemical findings, and the result of ileocolonoscopy with biopsies. Additional imaging yielded the following results (Table 1):

– Normal ileocolonoscopy (n = 43): A total of three patients (7%; 95% confidence interval (CI): 2-20%) were diagnosed with small bowel CD after additional imaging. However, only one patient (2%; CI: 0.1-14%) had CD located proximal to the terminal ileum and beyond the reach of the colonoscope (i.e. false negative ileocolonoscopy in two patients).

– CD detected at ileocolonoscopy (n = 31): A total of 20 patients were diagnosed with CD in the terminal ileum; small bowel imaging confirmed the finding in all patients. Capsule endoscopy (performed in 16/20) suggested disease extension beyond the reach of the colonoscope in 69% (CI: 41-88%). In 11 patients with CD in colon but a normal ileoscopy, CE added no diagnostic information.

– Colonoscopy without intubation of the terminal ileum (n = 18): Among patients with a normal colonoscopy or newly diagnosed CD in the colon in whom terminal ileum intubation was not achieved, additional imaging detected small bowel CD in four (22%; CI: 7-48%).

DISCUSSION

These findings suggest that in patients in whom ileocolonoscopy shows a normal terminal ileum, small bowel imaging adds little information irrespective of the colonic findings. In our study, CE added no diagnostic information in patients with CD in the colon and a normal terminal ileum.

In patients with non-complicated CD in the terminal ileum, CE adds no diagnostic information, but can be used to map disease extension beyond the reach of the colonoscope. Furthermore, in the present study, ileoscopy was sufficient to determine the severity of small bowel inflammation. According to current guidelines, extensive small bowel CD should be treated with thiopurines or methotrexate (evidence level 5, recommendation grade D) [11]. To the best of our knowledge, no study has proven that mapping of CD extension at the time of diagnosis – with immunomodulators in extensive disease – benefits clinical outcome compared to ileocolonoscopy alone.

If terminal ileum intubation is not achieved, additional imaging helps diagnose unacknowledged CD located in the small bowel after a normal colonoscopy or map CD in patients with newly diagnosed CD in the colon.

Which small bowel imaging modality?

Previous studies comparing MRE and CTE found similar sensitivities and specificities for detection of small bowel CD [12, 13], and a meta-analysis concluded that the diagnostic yield of capsule endoscopy was significantly higher than that of CTE in patients with suspected CD [14].

No previous studies have compared the diagnostic sensitivity and specificity of MRE, CTE and capsule endoscopy in patients undergoing their first diagnostic work-up for CD. We concluded that the sensitivity and specificity of capsule endoscopy for detection of CD in the terminal ileum is superior to that of cross-sectional imaging. MRE and CTE are complimentary examinations with moderate sensitivities and specificities. The diagnostic yield for CD located proximal to the terminal ileum is significantly higher with capsule endoscopy than with MRE and CTE.

An advantage of MRE and CTE is their ability to visualize the intestinal wall and extra-intestinal surroundings [15]. In our study, cross sectional imaging rarely detected extra-intestinal complications. At the time of diagnosis, intra-abdominal fistulas or abscesses are uncommon, and the ability to look beyond the mucosa is of little relevance in this group of patients; unless clinical suspicion exists.

Risk of capsule retention

Our data suggest capsule endoscopy as first line diagnostic modality for visualization of the small bowel in patients with suspected CD, but the risk of capsule retention is a concern. However, the reported risk of capsule retention in patients with suspected CD is low (1.4%), and a preceding small bowel radiological assessment does not rule out capsule retention [16].

In our study of MRE, CTE and capsule endoscopy, six out 93 patients were suspected of having a small bowel stenosis [5]. Ileocolonoscopy detected stenosis in the terminal ileum in three patients. None of these were demonstrated with MRE, whereas CTE detected stenosis in all patients. In two additional patients, CTE detected stenosis in the small bowel. Hence, after ileocolonoscopy with a persistent attempt to intubate the terminal ileum, additional stenoses were suspected in only 2% of patients, and it should be emphasized that not all strictures on imaging translate into a mechanically significant obstruction. Sensitivities of conventional small bowel radiography, MRE and CTE for detection of small bowel stenosis are not perfect, and some authors believe that a careful history is perhaps the best single method to determine the risk of capsule retention [17, 18].

In patients with suspected CD, small bowel stenoses are infrequent and capsule endoscopy can be used as first-line modality for detection of small bowel CD beyond the reach of the colonoscope. In selected patients with a clinical suspicion of small bowel stenosis, a preceding test with a patency capsule could be helpful.

Suggested diagnostic algorithm

The above mentioned results suggest a new diagnostic algorithm for diagnosing suspected CD (Figure 2). This diagnostic approach is valid for young patients referred to gastroenterology out-patient clinics because of clinical suspicion of CD. It should be emphasized that fCal has a poor sensitivity for detection of colorectal cancer [19] and colonoscopy should be considered in patients > 40 years of age with a recent change in bowel habits.

The diagnostic algorithm yields the following results when applied to our study population of 83 patients examined with fCal, ileocolonoscopy and small bowel imaging:

– fCal was ≤ 50 mg/kg in 26 patients (31%; CI: 22-43%); false negative in two patients.

– fCal was elevated in 57 patients (69%; CI: 57-78%).

– At subsequent colonoscopy, intubation of the terminal ileum was achieved in 46 patients (ileoscopy rate 81%). CD was diagnosed in 30 patients, and the terminal ileum was involved in 18. Ileoscopy detected a small bowel stenosis in two patients.

– In 11 patients, ileoscopy was not achieved. Additional imaging revealed small bowel CD in two patients.

In summary, using fCal as a marker to select patients for endoscopy reduces the number of colonoscopies by 31%. With an ileoscopy rate of 81%, additional small bowel imaging is needed in only 13% of patients. Capsule endoscopy can be performed in the majority of these patients. Additional small bowel imaging (or upper endoscopy) may be indicated in few patients with complicated disease or clinical suspicion of CD in the upper gastrointestinal tract without distal involvement.

Limitations

The place of new endoscopic and cross sectional imaging modalities in suspected CD remains to be fully determined. This brief article suggests a new diagnostic algorithm based on evidence provided by a single prospective study of MRE, CTE, capsule endoscopy, and fCal in patients undergoing their first diagnostic work-up for CD. It is not a systematic review of the literature.

Ultrasound is a non-invasive, patient friendly, radiation free and widely available modality for detection of small bowel CD and extra-intestinal complications. Our study did not include ultrasound as a fourth imaging modality. A recent systematic review concluded that ultrasound is an accurate technique for the initial diagnostic workout of patients with suspected CD [20]. Depending on local expertise, ultrasound can substitute MRE or CTE in the suggested diagnostic algorithm. However, the observer variability is significant, and achieving a high accuracy requires experienced radiologists. In patients with a high suspicion of CD, a negative ultrasound should be confirmed with other diagnostic techniques [20].

CONCLUSION

As a first line test in young patients with clinical suspicion of CD, fCal is useful to identify patients without need for colonoscopy or small bowel imaging. Patients with fCal > 50 mg/kg should undergo colonoscopy including a persistent attempt to intubate the terminal ileum, and small bowel imaging is primarily indicated if ileoscopy is not achieved. Capsule endoscopy is superior to MRE and CTE and is therefore recommended as first choice for small bowel imaging in this setting. If stenosis is suspected capsule endoscopy should be preceded by a patency capsule. MRE and CTE are complimentary modalities preferably used in patients with stenosis detected at ileocolonoscopy or suspicion of extra-intestinal disease complications.

Correspondence: Michael Dam Jensen , Afdeling for Intern Medicin, Gastroenterologisk Afdeling, Sygehus Lillebælt, Vejle Sygehus, Kabbeltoft 25, 7100 Vejle, Denmark. E-mail: michael.dam.jensen@slb.regionsyddanmark.dk

Accepted: June 13 2012

Conflicts of interest:Disclosure forms provided by the authors are available with the full text of this article at www.danmedj.dk

Referencer

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