IBD Shorts: September 2019

S Olivia et al (including Stanley Cohen from GI Care for Kids) Clin Gastroenterol Hepatol 2019; 17: 2060-7.A Treat to Target Strategy Using Panenteric Capsule Endoscopy in Pediatric Patients with Crohn’s Disease”  In this prospective study with 48 children with Crohn’s disease, pan-enteric capsule endoscopy (PCE) detected inflammation in 34 (71%) at baseline, 22 (46%) at week 24, and 18 (39%) at week 52.  PCE results were used to manage treatment and resulted in change in therapy in 71% at baseline and 23% at week 24.  Furthermore, PCE increased the proportions of patients in deep remission, up to 58% at week 52.

M Wright, et al. J Pediatr 2019; 210: 220-5. This case report of a 4 year-old boy with a perianal abscess and granulomatous colitis identified a NCF4 mutation causing severe neutrophil dysfunction.  He developed osteomyelitis with anti-TNF therapy and did not respond to vedolizumab. He had an excellent outcome following a hematopoietic stem cell transplantation. This study reinforces the potential benefit of investigating VEO-IBD which could allow more targeted therapy. Related blog post:

P Zapater et al. Inflamm Bowel Dis 2019; 25: 1357-66. This study with 112 patients with Crohn’s disease showed that serum interleukin-10 levels were directly related to infliximab and adalimumab levels.  This suggests that serum anti-TNF levels are significantly influenced by immunological activation.

JE Axelrad et al. Clin Gastroenterol Hepatol 2019; 17: 1311-22.  This study, using the Swedish National Patient Register, showed that gastrointestinal infection increased the odds of developing IBD in a nationwide case-control study.  “Of the patients with IBD, 3105 (7%) had a record of previous gastroenteritis compared with 17,685 control subjects (4.1%). IBD cases had higher odds for an antecedent episode of gastrointestinal infection (aOR 1.64), bacterial gastrointestinal infection (aOR 2.02) and viral gastrointestinal infection (aOR 1.55)…a previous episode of gastroenteriitis remained associated with odds for IBD more than 10 years later (aOR 1.26).”  The authors note that they cannot formally exclude misclassification bias, but it appears that enteric infections contribute to the development of IBD in susceptible individuals.

Pediatric capsule endoscopy experience

Capsule endoscopy (CE) in pediatric gastroenterology has become a routine procedure.   The experience of our group is noted in a recent study (JPGN 2012; 54: 409-13).  In this study, our single pediatric center reviewed 284 CE procedures (277 patients) over a five-year period.  The youngest patient to swallow a capsule was 4.6 years old.  Twenty capsules were placed endoscopically, with the youngest & smallest patient being 3 years old (13.5kg).  A patency capsule was used in 23 patients.

Overall, the yield with CE was high. 205 (72%) had positive findings; 154 (54%) had small bowel findings.  The study also compared its data to pediatric and adult meta-analysis.  Similar to other pediatric studies, Crohn disease was the most common indication; in adult studies, CE is used mostly for occult GI bleeding and anemia.  CE procedures did not reach the colon in 65 (21%); 36 of these incomplete procedures had positive findings.

Capsule retention occurred in seven patients (2.4%) which is similar to the meta-analysis studies as well.  Six of the seven had surgery due to capsule retention, though one surgical procedure had been planned and capsule helped identify stricture site.  In addition, one of the seven was retrieved through a tight ileostomy.

Additional references:

  • -Gastroenteology 2010; 139: 1468. Predictions for upcoming advances.
  • -Gastroenterology 2009; 137: 1197. Strongest indication -obscure bleeding.
  • -JPGN 2009; 49: 196. Capsule retention in 5.2% in known IBD. overall 3 of 207 studies (1.4%) To date, >170,000 capsule studies worldwide.
  • -Gastrointest Endosc 2008; 68: 255-66. Authors recommend using CT/colonoscopy as primary investigations & reserving capsule only if negative initial evaluation. 17% of pts had asymptomatic partial small bowel obstruction -contraindicating use of capsule.
  • -Endoscopy 2008; 40: 30-35 & -IBD 2008; 14: 1287. Consider wireless capsule before IPAA in UC.
  • -IBD 2008; 14: 1219. Correlation of capsule & MRI enterolysis. Capsule detected more mucosal lesions.
  • -JPGN 2008; 47: 31. Capsule endoscopy may reclassify pediatric IBD
  • Speed matters.  Additional references listed on this previous blog entry.

More imaging needed?

With new tools at our disposal in diagnosing inflammatory bowel disease, we need to decide how and when to use them.  Potential new modalities include stool inflammatory markers, video capsule endoscopy, CT enterography (CTE), and MR enterography (MRE).  Several studies have shown that the information that these studies yield may change management. The latest of these studies (Inflamm Bowel Dis 2012; 18: 219-25) looked at how the knowledge of CTE effected management and physician confidence with Crohn’s disease.

The authors prospectively assessed 273 patients with established or suspected Crohn’s disease.  In their analysis, 70 patients (48%) of established cases had altered management because of CTE and 69 (54%) of suspected cases.  These changes were considered to be  independent of clinical, serological or histologic findings.  Changes included medication modification in 45 (16.2%), excluding Crohn’s disease in 46 (16.8%), surgery referral in 10 (3.7%), alternate diagnosis established in 9 (3.2%), & canceling surgery in 7 (2.6%).  The authors considered excluding active small disease as an important management plan change; this occurred in 18 patients (6.6%).

The authors state that their current practice is to use MRE for serial imaging rather than CTE, to minimize risks from radiation; though CTE is often the initial imaging.

My take on this article is that information from imaging often increases the certainty about the diagnosis and gives a more complete picture of the severity.  It is likely that more information leads to more aggressive therapy.  At the same time, in pediatric gastroenterology, the trend towards using more effective therapy earlier in the course of the disease has developed even in the absence of extensive imaging (see previous: Only one chance to make first impression).  Whether more imaging in pediatric patients would be worthwhile is not known.

Additional references:

  • -JPGN 2008; 47: 31.  Capsule endoscopy may reclassify pediatric IBD
  • -NEJM 2010; 363: 1, 4. Safety of CT. Can have overdose of radiation and even standard doses could cause complications. Also, a big issue is downstream unnecessary testing due to incidental findings.
  • -Clin Gastro 2008; 6:283. Use of CT enterography.
  • -JPGN 2010; 51: 603.  MRE for suspected IBD.  Useful in Crohn’s disease.
  • -IBD 2004;10: 278-285.  WCE for Crohn’s (review)  Capsule can help differentiate UC from Crohn’s.

Speed matters

Capsule endoscopy is cool.  Like any technology, it has certain advantages and some shortcomings.  Understanding that this technology has limited sensitivity and specificity is an important matter in clinical practice.

The suboptimal sensitivity is apparent in a recent study (Am J Gastroenterology, (10 January 2012) | doi:10.1038/ajg.2011.461).  In this study titled, “Detection of Lesions During Capsule Endoscopy: Physician Performance Is Disappointing,” the authors compare the performance of 17 capsule endoscopists in reading clips from 24 capsule procedures.  18 of these clips were abnormal but only abnormal in <0.1% of frames.  They compared different reading modes, speeds and the experience of the physicians.  By using clips, they were able to truncate the sessions to a similar length as an individual capsule procedure.

Their findings showed detection rates of 69% for angioectasias, 38% for ulcers/erosions, 46% for masses/polyps, and 17% for blood.  For all categories the detection rate was ~45% for SingleView15, QuadView20, and QuadView30; however, SingleView25 had a 25% detection rate.  One surprising finding was how little experience mattered; there was no significant advantage in having more experience.  In fact, the best performer who correctly identified 78% of the abnormalities had read only 45 capsule studies previously; the worst performer with a 17% score had read more than 11,000 previously.

In a typical capsule study, 40,000-60,000 images are generated.  If there is not a diffuse disease, then the lesion may go undetected.  The findings of these studies, though limited by the small number of interpreting physicians, confirm problems with sensitivity from other studies.  One aspect of this study that deserves emphasis is that speed matters.  As with colonoscopy, additional time reviewing the study does increase the likelihood of identifying abnormalities.  Ultimately, technological innovation may improve the results with capsule endoscopy.  With newer versions of the software,  “suspected blood indicator” (SBI) quickly identified six of the 18 lesions and “QuickView” identified 11 of the 18 lesions.  As with any test, though, if the clinical suspicion is high, having another physician review the study or using an alternative imaging tool may be necessary.

Another problem to keep in mind with capsule endoscopy (or wireless capsule endoscopy -WCE) is that especially in adults there is a significant background abnormality rate that may be clinically unrelated (Clin Gastro & Hepatol 2005; 3: 133-141. n=413. 13.8% with baseline mucosal injury).

Additional references:

  • -IBD 2008; 14: 1219. Correlation of capsule & MRI enteroclysis. Capsule detected more mucosal lesions.
  • -JPGN 2008; 47: 31. Capsule endoscopy may reclassify pediatric IBD.
  • -Dig Liver Dis 2008; 40: 216-223. Study comparing capsule vs EGD in detecting varices.
  • -JPGN 2008; 46:4. Review.
  • -Gastroenterology 2007; 132: 855. Capsule outperforms push enteroscopy.
  • -IBD 2007; 13: 331. Role of WCE in IBD.
  • -Pediatrics 2006; 118: e904. Use of capsule endoscopy for HSP
  • -Clin Gastro & Hep 2005; 3: 959. WCE should be 2nd step in obscure bleed, p egd/col.
  • -Clin Gastro & Hep 2005; 3: 772. WCE outperforms enteroclysis in identifying Crohn’s sm bwl dz.
  • -Gastroenterology 2005; 128: 1172. NSAID injury witnessed in 68% of healthy volunteers p 2 week course; 75% c increased fecal calprotectin.
  • -Clin Gastro & Hepatol 2005; 3: 411. Practical applications & review.
  • -Clin Gastro & Hepatol 2005; 3: 264-70. Study of 30 children; helpful in diagnosing obscure bleeding.
  • -Endoscopy 2005; 37: 960-65. Results of capsule endoscopy trials
  • -Clin Gastro & Hepatol 2005; 3: 133-141. WCE to assess NSAID injury, n=413. 13.8% with baseline mucosal injury. Celebrex with fewer lesions than Naproxen plus omeprazole.
  • -Gortzak Y, Lantsberg L, Odes HS. Video capsule entrapped in a Meckel’s diverticulum. J Clin Gastro 2003; 37: 270-271.
  • -Clin Gastro & Hep 2005; 3: 55. visible lesions c NSAIDs
  • -IBD 2004;10: 278-285. WCE for Crohn’s (review) Capsule can help differentiate UC from Crohn’s.
  • -Clin Gastro & Hepatology 2004; 2:xx. Dx of Peutz-Jeghers w WCE.
  • -Gastro 2004; 126: 643-653. WCE performs well for occult bleeding, especially active bleeding (87% detection rate)
  • -Clinical Gastro & Hepatology 2004; 2: 14-15, 31-40.
  • -Gastroenterology 2003; 124 (suppl 1) A37. abnl small bowel findings common in healthy subjects.
  • -JPGN 2003; 37: 332 (18A), n=58. Crohn’s, polyposis, occult bleeding
  • -Gastroenterology  2003; 124: suppl 1, A-37 (284) 22% of normal pts c abnl wireless findings
  • -Gastroenterology  2002; 123: 999-1005, 1385-88. capsule is superior to radiographs for suspected small bowel dz.
  • -Gastro Endosc 2002; 56: 452-456. Algorithm suggests using this modality if negative upper & lower endoscopy & no acute overt bleeding. If capsule endoscopy is negative & patient is stable, observation appropriate.
  • -Gastro Endosc 2002; 56: 621-24. ASGE guidelines.