Comparison of Capsule Endoscopy with Ileocolonoscopy for Detecting Small-Bowel Lesions in Patients with Seronegative Spondyloarthropathies

• Introduction
• Patients and Methods
• Results
• Findings in the Small Bowel
• Findings in the Upper Gastointestinal Tract
• Findings in the Colon
• Patient Preference
• Discussion
• References

Background and Study Aims: Patients with spondyloarthropathies are often found to have signs of small-bowel inflammation when examined by ileocolonoscopy. Because capsule endoscopy has been found to be superior to other endoscopic and radiological modalities in the detection of small-bowel inflammation, we aimed to compare the diagnostic yield of capsule endoscopy with that of ileocolonoscopy in the detection of small-bowel lesions in patients with spondyloarthropathies.
Patients and Methods: Twenty patients with documented seronegative peripheral arthritis, ankylosing spondylitis, or sacroiliitis, who had not taken nonsteroidal anti-inflammatory drugs (NSAIDs) in the preceding 2 months, participated in the study. The patients underwent capsule endoscopy, followed by ileocolonoscopy within 7 days, with blinded assessment of both examinations. Biopsies were taken when indicated and adverse events were monitored. Patients completed a questionnaire on their satisfaction with the two procedures.
Results: A total of 20 patients (11 men, 9 women; mean age 41 ± 13 years) with seronegative inflammatory spondyloarthropathies but without abdominal complaints completed the study. No adverse effects were reported and all the capsules were excreted. Of these 20 patients, 11 (55 %) had a normal small bowel on both examinations. Significant small-bowel findings (erythema, mucosal breaks, aphthous or linear ulcers, erosions) were detected by capsule endoscopy in six patients (30 %) and by ileocolonoscopy in only one patient. In addition, capsule endoscopy detected significant upper gastrointestinal pathology in 40 % of patients. The patients preferred capsule endoscopy to ileocolonoscopy.
Conclusions: Capsule endoscopy detected more small-bowel lesions than ileocolonoscopy, and provided additional potentially relevant information on upper gastrointestinal pathology in patients with spondyloarthropathies.

Introduction

Seronegative arthritis is characterized by asymmetric peripheral arthritis (usually pauci-articular), sacroiliitis, or spondylitis, and negative serology. This group of arthritides includes reactive arthritis, psoriatic arthritis, and the arthritis associated with inflammatory bowel disease. Over 15 years ago, Mielants and his co-workers showed that a substantial number of these patients have subclinical ileal inflammation [1] [2]. They reported finding macroscopic ileal abnormalities in up to 30 % of these patients, including erythema, edema, ulceration, granulation, and a cobblestone appearance of the ileal mucosa [1]; microscopic abnormalities were found in around 60 % of patients. They suggested that chronic stimulation of the gut by external factors, along with local immunological defense mechanisms, could influence joint destruction [2].

The Given Pillcam SB video capsule endoscope (Given Imaging, Yoqneam, Israel) is a wireless capsule which is easily ingested and which passes from the mouth to the anus via peristalsis. The battery provides 7-8 hours of power, and the capsule takes photographs at a rate of two images per second. The recorded images are downloaded into a computer and can be visualized as a continous video film [3]. The capsule endoscope has been shown to be superior to conventional diagnostic techniques for the investigation of a variety of small-bowel conditions, such as occult gastrointestinal bleeding and suspected Crohn’s disease [4] [5] [6] [7] [8] [9].

The aim of the present prospective study was to compare the diagnostic yield of capsule endoscopy with the diagnostic yield of conventional ileocolonoscopy in patients with seronegative spondyloarthropathies.

Patients and Methods

A total of 21 patients, all 18 years old or over, with documented seronegative peripheral arthritis, ankylosing spondylitis, or sacroiliitis participated in this three-center prospective study. All patients gave written informed consent, and the local ethical committees approved the study. Patients’ age, gender, ethnic origin, gastrointestinal complaints, arthritis history (type and duration), and past and present medications were all recorded, as well as any adverse events associated with either procedure.

Patients who had received nonsteroidal anti-inflammatory drugs (NSAIDs) within the 2-month period prior to enrollment were excluded from the study, as were patients who complained of swallowing difficulties, patients with known or suspected intestinal obstruction, and patients with a cardiac pacemaker or any other implanted electromedical device. Pregnant women and patients with life-threatening conditions were also excluded. The patients were referred by rheumatologists and underwent capsule endoscopy as their initial examination, followed by ileocolonoscopy within 1 week. One patient was excluded for technical reasons (the capsule did not reach the cecum and the patient refused colonoscopy). The physician who interpreted the capsule endoscopy results was blinded to the ileocolonoscopy results and vice versa. Biopsies were taken when indicated (from any macroscopic lesions showing apthae, ulcerations, or polyps). All abnormalities seen in the upper gastrointestinal tract, the small bowel, and the colon were recorded. All patients in whom we found upper gastrointestinal abnormalities were referred to their family physican with a recommendation that they undergo upper gastrointestinal endoscopy.

Patients were examined with the Pillcam SB capsule endoscope after a 10-hour overnight fast. They were connected to the recording device and swallowed the capsule. Patients were required to remain in the clinic for 1 hour in order to verify that capsule transmission was adequate. They were allowed to drink clear liquids 2 hours after capsule ingestion and were free to engage in their normal daily activities. They were allowed to eat a light lunch 4 hours after capsule ingestion and returned for removal of the recorder after 7-8 hours. The duration of the fasting period, ease of ingestion, time of drinking and eating, time of discharge from the clinic, and any symptoms, signs, or discomfort that occurred during the procedure were recorded. The entry times of the capsule into the stomach, the duodenum, the small bowel, and the cecum were recorded, and gastric and small-bowel emptying times were calculated. Capsule endoscopy images were reviewed by three experienced examiners (all with experience of more than 100 capsule endoscopy examinations) and any abnormal findings and their location were recorded. Capsule findings were reported according to Mow et al. [10] as “diagnostic” if there were more than three ulcerations or apthae in the small bowel, “suggestive” if there were three or fewer ulcerations or apthae, and “normal” if there were no abnormal findings.

Three experienced examiners performed the ileocolonoscopies, all of whom had performed more than 1000 colonoscopies. Intubation of the terminal ileum was always attempted for a minimum of 5 minutes. Patients were sedated with midazolam 2.5 mg-5 mg and biatryl 0.1 mg intravenously.

The patients completed a subjective questionnaire that had been designed to compare capsule endoscopy with alternative diagnostic procedures [7]. The questions asked included:

• How would you rate the swallowing of the capsule/introduction of the ileocolonoscope?

• Did you experience pain during the capsule endoscopy/ileocolonoscopy?

• Did you experience discomfort during the capsule endoscopy/ileocolonoscopy?

• Did you experience pain after the capsule endoscopy/ileocolonoscopy?

• Did you experience discomfort after the capsule endoscopy/ileocolonoscopy?

• How would you rate the capsule endoscopy/ileocolonoscopy?

• If you were given the opportunity to choose an examination for diagnosing your problem, would you choose the capsule endoscopy/ileocolonoscopy?

• How would you rate the overall convenience of the test?

  Each question was rated from 0 (worst experience) to 5 (best experience).

  The Z-test was used for the statistical analysis of the results of the procedures, assuming that there was no relationship between the results of the capsule endoscopy and the results of the comparative procedure.

Results

All of the 20 patients who were included completed the study (11 men, 9 women; mean age 41 ± 13 years). Of these, 16 patients (80 %) had seronegative peripheral arthritis, three had sacroiliitis, and one had B27-positive ankylosing spondylitis. The mean duration of the patients’ arthritis was 5.6 ± 5.0 years. None of the patients reported having any abdominal symptoms.

All capsules were excreted and the terminal ileum was seen in all patients. Ileocolonoscopy was successful in all patients and the terminal ileum was intubated in all cases. Unfortunately, the length of ileal intubation was not recorded.

Findings in the Small Bowel

Eleven out of the 20 patients (55 %) had a normal small bowel on both examinations. Capsule endoscopy detected small-bowel pathology in the distal jejunum/proximal ileum region in nine patients (45 %); these lesions included areas of edema, erythema, dilated lymphatics, mucosal breaks, erosions, and linear and aphthous ulcerations (Figure [1] and [2], Table [1]). Of these nine patients, six (30 %) had findings reminiscent of Crohn’s-like disease in the small bowel. According to the criteria described above, these were classified as diagnostic in four patients (20 %) and as suggestive in two patients (10 %). Ileocolonoscopy was positive in only one patient. This patient had abnormal findings in both the proximal and distal ileum on capsule endoscopy (Figure [1]). Routine biopsies were not taken in the ileum and the extent of microscopic involvement was not assessed because this was not the aim of the study. In those few patients with a normal terminal ileum in whom biopsies were taken, the biopsies were normal.

Findings in the Upper Gastointestinal Tract

Capsule endoscopy detected upper gastrointestinal pathology in 40 % of patients, indicative of gastritis, duodenitis, esophagitis, or Barrett’s metaplasia. The findings comprised small erosions, erythema, or a cobblestone appearance. In one patient, grade A esophagitis was seen, and one patient was suspected to have Barrett’s esophagus. Because the management of these conditions was not within the scope of our study, these patients were all referred to their family physicians with a recommendation to follow them up endoscopically.

Findings in the Colon

Colonoscopy detected abnormalities in the colon in 20 % of patients. These included one minute hyperplastic polyp and four minute adenomatous polyps (less than 8 mm). No patients had dysplasia. None of these abnormalities was seen on capsule endoscopy because the recording time and the lack of colon cleansing preparation did not permit proper colonic imaging.

Patient Preference

As shown in Table [2], the patients preferred capsule endoscopy to ileocolonoscopy.

Discussion

In this small prospective study, capsule endoscopy appeared to be a safe and effective method for detecting small-bowel pathology in patients with seronegative arthritis, and had a significantly higher diagnostic yield than ileocolonoscopy in such patients. Moreover, the capsule provided additional significant information on upper gastrointestinal tract lesions in the same patients, information that could be useful in patients who often need NSAIDs and who should probably be treated prophylactically. However, the diagnosis of upper gastrointestinal lesions was not the main aim of the study, and so we did not examine all the lesions detected by the capsule by follow-up endoscopy, which should probably be done to ascertain the diagnosis. Furthermore, capsule endoscopy could not be used as a reliable method for excluding upper gastrointestinal pathology for the stratification of patients for prophylactic therapy.

Endoscopy detected macroscopic ileitis in only one of the 20 study patients, a much lower proportion than that found in the historic Belgian series [1] [2]. This may in part be due to our strict exclusion of patients who were on NSAIDs in the 2 months prior to enrollment; there is no mention of NSAID restriction in the Belgian series. Capsule endoscopy detected relevant pathological features in 30 % of the patients, mainly in the jejunum and ileum, above the reach of the ileocolonoscope.

Crucial questions are whether these lesions are truly disease-associated, and whether they reflect prior NSAID usage or a normal spectrum of mucosal changes that can be found in healthy volunteers. Goldstein et al. [11] showed that small-bowel abnormalities occured in around 57/413 healthy volunteers (13.8 %). However, these authors only excluded patients who had been frequent NSAID users (> 3 times/week) within the 2 weeks prior to the procedure. This NSAID-free period may not be long enough. In addition, some of their patients were in fact on low doses of NSAIDs when they were examined. When volunteers who had been lesion-free on the baseline capsule endoscopy examination underwent a second capsule endoscopy examination 2 weeks later, new lesions were seen in a further 7 %, the mean number of lesions being 0.11 per volunteer. It is not clear whether these were missed lesions or newly formed. In another study, Graham et al. [12] found small-bowel lesions in 71 % of chronic NSAID users (> 3 months) when they were examined by capsule endoscopy. In contrast, only 2/20 (10 %) of their control group had minute small-bowel lesions (one had one erosion and one had a red spot). The most recent study by Maiden et al. [13] looked at 40 patients who had been off NSAIDs for 1 month and did not find any erosions, ulcers, or aphthous lesions on baseline capsule endoscopy examination. We therefore feel that our data represent a true pathological entity, as we did not allow NSAID use for a minimum of 2 months prior to enrollment. Furthermore, the frequency of lesions we found was much higher than had been reported from volunteer studies.

The principal dilemma presented by finding subtle abnormalities on capsule endoscopy is that an independent gold standard is missing, because most lesions were outside of the reach of ileocolonoscopy and upper gastrointestinal endoscopy. Invasive methods, such as push-enteroscopy or the even more time-consuming double-balloon enteroscopy [14] [15] [16] [17], would be necessary to prove the existence of these lesions and to provide histological confirmation, but such methods were not employed in the present study and are probably not feasible either. Another unknown is how stable these lesions are. Further studies would be needed to elucidate the clinical relevance of the lesions we detected (all our patients were asymptomatic) and their possible influence on prognosis and management.

In summary, capsule endoscopy is a safe method for diagnosing small-bowel lesions in patients with seronegative arthritis. It is significantly more sensitive than ileocolonoscopy for this purpose and may also provide relevant information about the upper gastrointestinal tract in some of these patients. Larger studies are needed to confirm our results.

References

• 1 Mielants H, Veys E M, Cuvelier C, De Vos M. Ileocolonoscopic findings in seronegative spondyloarthropathies.  Br J Rheumatol. 1988;  27 95-105
  PubMedSearch in Google Scholar
• 2 Mielants H, Veys E M, Goethals K. et al . Destructive lesions of small joints in seronegative spondyloarthropathies: relation to gut inflammation.  Clin Exp Rheumatol. 1990;  8 23-27
  PubMedSearch in Google Scholar
• 3 Eliakim R. Wireless capsule video endoscopy - three years of experience.  World J Gastroenterol. 2004;  10 1238-1239
  PubMedSearch in Google Scholar
• 4 Ell C, Remke S, May A. et al . The first prospective controlled trial comparing wireless capsule endoscopy with push enteroscopy in chronic gastrointestinal bleeding.  Endoscopy. 2002;  34 685-689
  Search in Google Scholar
• 5 Saurin J C, Delvaux M, Gaudin J L. et al . Diagnostic value of endoscopic capsule in patients with obscure digestive bleeding: blinded comparison with video push-enteroscopy.  Endoscopy. 2003;  35 576-584
  Search in Google Scholar
• 6 Cave D R. Wireless video capsule endoscopy.  Clin Perspect Gastroenterol. 2002;  5 203-207
  PubMedSearch in Google Scholar
• 7 Eliakim R, Fischer D, Suissa A. et al . Wireless capsule video endoscopy is a superior diagnostic tool compared to barium follow through and CT in patients with suspected Crohn’s disease.  Eur J Gastroenterol Hepatol. 2003;  15 363-367
  Search in Google Scholar
• 8 Fireman Z, Mahajna E, Broude E. et al . Diagnosing small bowel Crohn’s disease with wireless capsule endoscopy.  Gut. 2003;  52 390-392
  Search in Google Scholar
• 9 Herrerias J M, Caunedo A, Rodriguez-Tellez M. et al . Capsule endoscopy in patients with suspected Crohn’s disease in negative endoscopy.  Endoscopy. 2003;  35 1-5
  Thieme ConnectPubMedSearch in Google Scholar
• 10 Mow W S, Lo S K, Targan S R. et al . Initial experience with wireless capsule enteroscopy in the diagnosis and management of inflammatory bowel disease.  Clin Gastroenterol Hepatol. 2004;  2 31-40
  CrossrefPubMedSearch in Google Scholar
• 11 Goldstein J L, Eissen G M, Lewis B. et al . Video capsule endoscopy to prospectively assess small bowel injury with celecoxib, naproxen plus omeprazole and placebo.  Clin Gastroenterol Hepatol. 2005;  3 133-141
  CrossrefPubMedSearch in Google Scholar
• 12 Graham D Y, Opekun A R, Willingham F F, Qureshi W A. Visible small-intestinal mucosal injury in chronic NSAID users.  Clin Gastroenterol Hepatol. 2005;  3 55-59
  CrossrefPubMedSearch in Google Scholar
• 13 Maiden L, Thjodleifsson B, Theodors A. et al . A quantitative analysis of NSAID-induced small bowel pathology by capsule endoscopy.  Gastroenterology. 2005;  128 1172-1178
  CrossrefPubMedSearch in Google Scholar
• 14 Yamamoto H, Kita H, Sunada K. et al . Clinical outcomes of double-balloon endoscopy.  Gastrointest Endosc. 2004;  60 1032-1034
  CrossrefPubMedSearch in Google Scholar
• 15 Ell C, May A, Nachbar L. et al . Push-and-pull enteroscopy in the small bowel using the double-balloon technique: results of a prospective European multicenter study.  Endoscopy. 2005;  37 613-616
  Thieme ConnectPubMedSearch in Google Scholar
• 16 Heine G DN, Hadithi M, Groenen M JM. et al . Double-balloon enteroscopy: indications, yield, and complications in a series of 275 patients with suspected small-bowel disease.  Endoscopy. 2005;  in press
  PubMedSearch in Google Scholar
• 17 Gay G, Delvaux M, Fassler I. Capsule endoscopy to select indications and route of insertion of push-and-pull enteroscopy.  Endoscopy. 2005;  in press
  PubMedSearch in Google Scholar

R. Eliakim, M.D.

Department of Gastroenterology

Rambam Medical Center · Haifa 31096 · Israel·

Fax: +972-4-854-3058

Email: r_eliakim@rambam.health.gov.il

References

• 1 Mielants H, Veys E M, Cuvelier C, De Vos M. Ileocolonoscopic findings in seronegative spondyloarthropathies.  Br J Rheumatol. 1988;  27 95-105
  PubMedSearch in Google Scholar
• 2 Mielants H, Veys E M, Goethals K. et al . Destructive lesions of small joints in seronegative spondyloarthropathies: relation to gut inflammation.  Clin Exp Rheumatol. 1990;  8 23-27
  PubMedSearch in Google Scholar
• 3 Eliakim R. Wireless capsule video endoscopy - three years of experience.  World J Gastroenterol. 2004;  10 1238-1239
  PubMedSearch in Google Scholar
• 4 Ell C, Remke S, May A. et al . The first prospective controlled trial comparing wireless capsule endoscopy with push enteroscopy in chronic gastrointestinal bleeding.  Endoscopy. 2002;  34 685-689
  Search in Google Scholar
• 5 Saurin J C, Delvaux M, Gaudin J L. et al . Diagnostic value of endoscopic capsule in patients with obscure digestive bleeding: blinded comparison with video push-enteroscopy.  Endoscopy. 2003;  35 576-584
  Search in Google Scholar
• 6 Cave D R. Wireless video capsule endoscopy.  Clin Perspect Gastroenterol. 2002;  5 203-207
  PubMedSearch in Google Scholar
• 7 Eliakim R, Fischer D, Suissa A. et al . Wireless capsule video endoscopy is a superior diagnostic tool compared to barium follow through and CT in patients with suspected Crohn’s disease.  Eur J Gastroenterol Hepatol. 2003;  15 363-367
  Search in Google Scholar
• 8 Fireman Z, Mahajna E, Broude E. et al . Diagnosing small bowel Crohn’s disease with wireless capsule endoscopy.  Gut. 2003;  52 390-392
  Search in Google Scholar
• 9 Herrerias J M, Caunedo A, Rodriguez-Tellez M. et al . Capsule endoscopy in patients with suspected Crohn’s disease in negative endoscopy.  Endoscopy. 2003;  35 1-5
  Thieme ConnectPubMedSearch in Google Scholar
• 10 Mow W S, Lo S K, Targan S R. et al . Initial experience with wireless capsule enteroscopy in the diagnosis and management of inflammatory bowel disease.  Clin Gastroenterol Hepatol. 2004;  2 31-40
  CrossrefPubMedSearch in Google Scholar
• 11 Goldstein J L, Eissen G M, Lewis B. et al . Video capsule endoscopy to prospectively assess small bowel injury with celecoxib, naproxen plus omeprazole and placebo.  Clin Gastroenterol Hepatol. 2005;  3 133-141
  CrossrefPubMedSearch in Google Scholar
• 12 Graham D Y, Opekun A R, Willingham F F, Qureshi W A. Visible small-intestinal mucosal injury in chronic NSAID users.  Clin Gastroenterol Hepatol. 2005;  3 55-59
  CrossrefPubMedSearch in Google Scholar
• 13 Maiden L, Thjodleifsson B, Theodors A. et al . A quantitative analysis of NSAID-induced small bowel pathology by capsule endoscopy.  Gastroenterology. 2005;  128 1172-1178
  CrossrefPubMedSearch in Google Scholar
• 14 Yamamoto H, Kita H, Sunada K. et al . Clinical outcomes of double-balloon endoscopy.  Gastrointest Endosc. 2004;  60 1032-1034
  CrossrefPubMedSearch in Google Scholar
• 15 Ell C, May A, Nachbar L. et al . Push-and-pull enteroscopy in the small bowel using the double-balloon technique: results of a prospective European multicenter study.  Endoscopy. 2005;  37 613-616
  Thieme ConnectPubMedSearch in Google Scholar
• 16 Heine G DN, Hadithi M, Groenen M JM. et al . Double-balloon enteroscopy: indications, yield, and complications in a series of 275 patients with suspected small-bowel disease.  Endoscopy. 2005;  in press
  PubMedSearch in Google Scholar
• 17 Gay G, Delvaux M, Fassler I. Capsule endoscopy to select indications and route of insertion of push-and-pull enteroscopy.  Endoscopy. 2005;  in press
  PubMedSearch in Google Scholar

R. Eliakim, M.D.

Department of Gastroenterology

Rambam Medical Center · Haifa 31096 · Israel·

Fax: +972-4-854-3058

Email: r_eliakim@rambam.health.gov.il