Category Archives: Pediatric Gastroenterology Intestinal Disorder

Rifaximin for Crohn’s disease?

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Rifaximin (Xifaxan®) shows promise as a new treatment for Crohn’s disease (Gastroenterology 2012; 142: 473-81).  Rifaximin is an oral medication with minimal systemic absorption; it has a good track record in a number of GI indications, including bacterial gastroenteritis (traveler’s diarrhea), bacterial overgrowth in irritable bowel disease, and hepatic encephalopathy.  There are a few reasons why rifaximin would be considered a good candidate treatment for Crohn’s disease:

  • The pathophysiology of Crohn’s disease involves interaction of adherent bacteria to the intestinal mucosa and with the immune system
  • Other antimicrobials have shown benefit for Crohn’s disease
  • Animal models do not manifest Crohn’s disease when in a bacteria-free environment

In this study of 402 patients with moderate-to-severe Crohn’s disease, a multicenter randomized double-blind trial examined efficacy and safety of rifaximin at doses of 400mg, 800mg, and 1200mg twice daily.  The primary end point was remission based on Crohn’s Disease Activity Index (CDAI).

At the end of the 12-week treatment period, 62% of the 800mg group were in remission compared to 43% of the placebo group.  This difference was maintained 12 weeks afterwards with 45% maintaining remission compared with 43% of patients receiving placebo.  When looking at the other dosing regimens, at 12 weeks, 54% of the 400mg group and 47% of the 1200mg group were in remission based on CDAI.

Clinical response, but not remission, occurred in 56% of placebo patients compared with 63% for 400mg patients, 72% for 800mg patients, and 57% of 1200mg patients.  This trial may have been hampered by patient selection in that the placebo response was high.  This may be due to the fact that ~50% of patients had a low CRP value at baseline.

Safety was good in all patient groups.  However, one rifaximin-treated patient developed C difficile infection.

The fact that a clear dose response was not evident suggests the need for more studies.

Additional Rifaximin References:

  • -NEJM 2011; 364: 22 (pg 81-editorial).  About 10% improvement over placebo in pts with IBS-D.  (see abstract below).  Effects lasted up to 3 months.
  • -JPGN 2009; 49: 400-04. helped symptoms in 61% of IBD pts. n=23 (12 w Crohn). dose 10-30mg/kg/day.
  • -Aliment Pharm Ther 2005; 22: 31-35. Use in SBBO. n=90; 1200mg/day x 7 days. NL glucose breath test in 60% (vs 17% in low dose group); no side effects.
  • -Ann Intern Med 2006; 145: 557-563. double-blind, randomized controlled trial, n=87 for IBS. 400mg tid x 10days. Rx resulted in greater IBS improvement, ~40% improvement vs 20% w placebo during 10 week study
  • -IBD 2006; 12: 335. open-label use of rifaximim (400mg BID) for 30 pts c UC flare on ASA products resulted in clinical remission in 23 of 30.
  • -J Infect 2011; 62: 34-38. Rx may lead to resistant staphylococci.
  • -Hepatology 2010; 52: 1484. Review.

Additional Crohn’s Antibiotic/Probiotic References:

  • -IBD 2009; 15; 17. 40% response to Cipro in treatment of peranal fistulas. n=25. No response to metronidazole.
  • -IBD 2008; 14: 1597, 1585. No proven role for probiotics and IBD except pouchitis (after Abx)
  • -Clin Gastro & Hep 2008; 6: 145. Pouch problems reviewed -excellent review.
  • -IBD 2006; 12: 335. open-label use of rifaximim (400mg BID) for 30 pts c UC flare on ASA products resulted in clinical remission in 23 of 30.
  • -Curr Med Res Opinion 2005; 8: 1165-70. Rx for traveler’s diarrhea.  May be useful for Crohn’s as well.
  • -Gastroenterology 2005; 128: 856. Use of ornidazole prophylaxis reduced recurrence p-op from 37.5% to 8%.
  • -IBD 2004; 10: 318-325. antibiotics & IBD review.
  • -Gastroenterology 2004; 127: 412-21. adherent-invasive E. coli associated with ileal mucosa in 22% of Crohn’s (n=63) ileal mucosa vs. 6% of controls (n=16); higher colonization noted in neo-terminal ileums (36%).

Does necrotizing enterocolitis cause neurologic deficits?

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Quite possibly (J Pediatr 2012; 160: 409-14).

There have been recent reports that surgery in preterm and even term infants can affect neurodevelopmental outcomes.  This report, which looked at infants born at <30 weeks or birth weight of <1250 g, adds more information in this area.  The surgery group (n=30) had more white matter injury on MRI and lower developmental scores at 2 years than the nonsurgical group (n=178).  Infants requiring bowel surgery had the worst outcomes.  The exact reasons for these outcomes and the significance are unclear, in part due to the small number of infants with bowel surgery.  Potential factors include inflammatory mediators/cytokines, and anesthesia effects.

The article notes that the FDA has issued warnings regarding anesthetic use in neonates and young children.  These agents may cause abnormalities in the developing brain, particularly in the thalamus.

This study has a number of limitations including the lack of preoperative comparative imaging studies.  Nevertheless, despite unresolved issues regarding causality, it is clear that infants who have necrotizing enterocolitis remain at high risk for poor neurodevelopmental outcomes.

Additional references:

  • -Anesth Analg 2007; 104: 509-20.  Anesthetics in neonates and young children.
  • -J Pediatr 2008; 153: 170-5. Adverse neurodevelopmental outcomes in infants with sepsis or NEC.

Gastroesophageal Reflux: I know it when I see it

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      According to Wikipedia, Justice Potter Stewart, in Jacobellis v. Ohio 378 U.S. 184 (1964) stated the following: I shall not today attempt further to define the kinds of material I understand to be embraced within that shorthand description [“hard-core pornography”]; and perhaps I could never succeed in intelligibly doing so. But I know it when I see it, and the motion picture involved in this case is not that. [Emphasis added.]
     To some extent, ‘I know it when I see it’ has been the mantra about identifying gastroesophageal reflux for advocates for pH-impedance (pH-MII).  Enthusiasts have claimed that pH-MII is vastly superior to pH studies alone for many reasons including the ability to detect more GER episodes than conventional pH studies.  Yet, a major flaw has been a paucity of normative data.  To determine whether there is interobserver and intraobserver agreement in the interpretation of pH-MII, seven expert world groups collaborated on a study to analyze ten pediatric 24-hour tracings (J Pediatr 2012; 160: 441-6).
     Five of these studies were considered easy and five were more challenging due to less obvious features like low baselines, retrograde patterns during swallowing, and moving/crying artifacts.   Among 1242 liquid and mixed GER events, 490 (42%) were scored by the majority of observers.  The authors claim that this is “moderate agreement.”  The automated analysis (AA), not surprisingly, had much better agreement than manual analysis.   With AA there was 94% sensitivity rate and 74% specificity. When looking at AA alone, AA missed 6.5% of events scored by observer consensus and  30% of GER episodes recorded with AA were not detected by majority consensus.
     When looking at each pH-MII recording (Figure 2), there was poor agreement on whether the study was pathologic.  Only five of the studies had uniform agreement that the number of episodes (>73 GER episodes) were either pathologic or not. Those with agreement were all negative studies.  The authors conclude, though, that there was “substantial” agreement based on a mean kappa value of 0.70.
     A comparison to a previous pH-MII publication (Scand J Gastro 2011; 46: 271-6) notes that in this previous study, 83% of pH-MII recordings had a concordant symptom association probability despite underdetection of GER episodes with AA; it was recommended to use ‘AA when the symptom association was positive.  If symptom association was negative, they suggested manual analysis.’
    The conclusions from the current study:
  • ‘In theory, AA is favored over manual analysis due to reproducibility’
  • AA does not seem specific enough to ensure correct marking of GER episodes in infants and children yet
  • Consensus to refine AA needs to be reached …to retain confidence …in impedance

If this is the best that worldwide experts can do with this widespread technology, what does that mean for clinicians in practice?

Additional references:

Recent related posts:

The Medical Pendulum and Gastroesophageal Reflux

Unexplained chest pain

  • -Journal of Gastroenterology and Hepatology 2010;25:817-22. Has some normative pH-MII data.  ‘Can acid (pH) refluxes predict multichannel intraluminal impedance refluxes? A correlation study.’
  • -JPGN 2010; 50: 25. Reflux detected by Impedance does NOT determine fundoplication outcome. n=34.
  • -JPGN 2010; 52: 129. Review. No normative data. Using SAP>95% to correlate symptoms (better than SI or SSI). Main use is to study intractable pts to establish if nonacid reflux is contributing to symptoms.
  • -J Pediatr 2010; 157: 878 (“death of pH probe”), 949. Use of impedance in children. n=225. (70 were discarded). Notes lack of therapeutic possibilities for non-acid reflux.  Symptom index is + if >50%, SAP if >95%. Symptom index is number of symptoms with reflux episode divided by total number of symptom occurrences. SAP, symptom association probability, is a statistical tool that uses 2-minute windows throughout recording to correlate symptom and reflux event.  pH probe 2nd metal for infant -place 2cm above LES.  pH probe 3rd metal for child -place 3cm above LES
  • -Clin Gastro & Hep 2009; 7: 743. n=39 adults. Non-acid reflux events in patients on therapy correlated with acid reflux parameters when patients studied off therapy. Abnormal impedance parameters: total number of reflux events >63 (avg normal was 28). This study relied on # of reflux events more than SAP or SI. SAP or SI is problematic in patients who lack clinical response to PPIs.
  • -Gastroenterology 2009; 136 (suppl 1): S1896. n=143. #of events (not SI or SAP) is then most conservative estimate as well as the one with the highest likelihood of encompassing other symptom assoication parameters.
  • -J Pediatr 2009; 154: 248. n=50. a high # with normal pH had symptom correlation w GER events. (initial cohort was 80 –30 excluded due to problems with study or insufficient symptoms) SAP is superior for correlating symptoms.
  • -Clin Gastro & Hep 2008; 6: 840. Impedance is best tool -D Castell.; -Clin Gastro & Hep 2008; 6: 880.
  • -Clin Gastro & Hep 2008; 6: 482, 521. ‘Impedance/pH is best tool’. Pts who respond to PPIs likely due so due to its effect on chemostimulation; those who continue with symptoms may do so based on mechanostimulation -related to volumes in esophagus not due to acidity.
  • -J Pediatr 2006; 149: 216. Equal frequency of acid and non-acid reflux in 24 pts with asthma. No correlation identified with resp symptoms.
  • -Clin Gastro & Hep 2006; 4: 167. Impedance does not add to pH probe in UNTREATED patients.
  • -JPGN 2002; 34: 511, 519.
  • -Pediatrics 2006; 118: e299, 793. Impedance data in preterm infants. Asymptomatic and affected infants with similar impedance values and both have reflux to upper esophagus.

A drug that makes a difference: ondansetron

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Ondansetron (Zofran ®) use has become more common and is making a difference (JPGN 2012; 54: 381-86).  This drug has been a terrific advance for so many individuals with disorders that provoke vomiting and nausea.  Not only does it have a high degree of effectiveness, but side effects are also quite uncommon.

The cited study documents ondansetron’s increasing use in Toronto.  This retrospective cohort study of children younger than 18 years with gastroenteritis examined emergency room visits between 2003 and 2008.  20% of 22,125 charts were selected randomly for review (n=3508 patients in final analysis).  During the study period, intravenous rehydration decreased from 27% to 13% and ondansetron use increased from 1% to 18%.  Associated with ondansetron use, mean length of stay decreased from 8.6 to 5.9 hours.  Also, the week following the index visit, there was a reduction in return visits from 18% to 13% as well as decreased need for intravenous rehydration (7% to 4%).

The authors state that analysis elsewhere has indicated that appropriate usage of ondansetron for this indication could result in savings of more than $65 million each year in the U.S.  The main limitation of this study is that other factors could have changed during the study period and resulted in some of these improvements; though, this institution did not have any major changes which could be identified.

Of course, ondansetron is used in many other clinical settings besides the emergency room.  Though the drug is expensive, it is worth the cost.

Additional references:

  • -Arch Pediatr Adolesc Med 2008; 162: 858-65.  Use of antiemetic agents in AGE.
  • -Ann Emerg Med 2008; 52: 22e6-9e6.  Use of oral ondansetron in children with AGE who failed oral rehydration.
  • -NEJM 2006; 354: 1698. Use of zofran did not decrease hospitalization but did decrease need for IV fluids and decreased vomiting.

Pediatric capsule endoscopy experience

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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.

VTE with IBD

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In our children’s hospital, work is underway to systematically screen children for risk factors for venous thromboembolism (VTE) and to establish an algorithm to lower the risk of a VTE with either mechanical or pharmacologic treatments. One of the risk factors has been the presence of inflammatory bowel disease (IBD).  The absolute risk of IBD for VTE is not clear.  However, a recent study relates the risk among a large Danish population of adults and children (Gut 2011; 60: 937-43).

The study included 49,799 patients with IBD (14,211 Crohn’s, 35,229 UC) and compared with 477,504 members of the general population.  VTE risk for IBD was increased with HR of 2.0.  The incidence of VTE increased with age; however, the RR was higher in younger patients.  Among those less than 20 years, HR was 6.6 for VTE; HR 6.0 for DVT and 6.4 for PE.  In this age group, “unprovoked” VTE had HR of 4.5.  Unprovoked VTE was defined as event occurring without malignancy, recent surgery, pregnancy or fracture.

Although the relative risk is increased, the authors caution that the absolute risk in younger patients is low.  In those IBD patients less than 20 years, the incidence rate was 8.9 per 10,000 person years.  In contrast, in those IBD patients older than 60, the incidence rate was 54.6 per 10,000 person years.  There did not seem to be a significant difference between Crohn’s disease and ulcerative colitis in absolute or relative risk. The authors conclude that in those IBD patients younger than 20 years without ‘other VTE risk factors or limited mobility, the benefits of prophylaxis may no longer outweigh the risks.”  In older patients (>60 years), even outpatients experiencing flares might benefit from VTE prophylaxis.

Additional references:

  • -NEJM 2012; 366: 860 (letter to editor). Authors emphasize importance of VTE with UC, especially during flares.
  • -Lancet 2010; 375: 657-63. VTE with active IBD and in remission.
  • -Clin Gastroenterol Hepatol 2008; 6: 41-5. Thrombosis with IBD.
  • -Gut 2004; 53: 542-8. IBD -risk factor for VTE?
  • -Gut 2004; 53 (suppl 5): v1-16. IBD guidelines for management.

TNF antagonists and UC

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In my fellowship (15 years ago), the use of thiopurines (eg. azathioprine, 6-mercaptopurine) for ulcerative colitis was debated.  Many physicians urged colectomy rather than using these drugs which could have long-term consequences.  At the time, the risk of thiopurines was less well-understood.  Over time, the use of these agents has become common when mesalamine products were ineffective.  The same issue comes up with TNF antagonists versus colectomy.

A recent study provides more information on the effectiveness of adalimumab for patients with moderate-to-severe UC but does not settle this debate (Gastroenterology 2012; 142: 257-65).  In this study, termed ‘ULTRA-2’ (Ulcerative colitis long-term remission and maintenance with adalimumab 2), the  efficacy of adalimumab for induction & maintenance of remission was studied in 494 patients.  This was a randomized, double-blind, placebo-controlled study; average age was 40 years.

Clinical remission in the adalimumab group were 16.5% at 8 weeks (9.3% placebo).  At 52 weeks, 17.3% in the adalimumab group were in remission (8.5% placebo).  Among patients naive to anti-TNF agents, the response rate was 21.3% at week 8 & 22% at week 52.  Safety overall was similar in both groups; however, in the adalimumab group one patient developed gastric cancer and one developed squamous cell carcinoma.

The authors conclude that adalimumab is safe and more effective than placebo in inducing and maintaining remission among patients with moderate-to-severe UC.

A second study, also published this past month, looks at the use of infliximab for maintenance therapy for UC (Inflamm Bowel Dis 2012; 18: 201-11).  Patients who had achieved benefit from ACT-1 and ACT-2 studies were followed for three years.  Dosage of infliximab could be adjusted.  A total of 229 patients entered the study.  During the study, 70 patients (30.6%) discontinued infliximab due to adverse effects (10.5%), lack of efficacy (4.8%) or other reasons (15.2%); the majority were able to continue infliximab.  The authors indicate that no new safety issues were identified. Yet, there were two deaths among the infliximab group including a 19 year-old nonsmoker who developed lung cancer and a lethal case of histoplasmosis.

Because the improvement compared to placebo is modest with both of these agents, the question about whether to use these medications or proceed to surgery in UC patients is unanswered.

Additional references:

  • -Aliment Pharmacol Ther. 2008 Oct 15;28(8):966-72. Epub 2008 Jul 24.  Long-term outcome of adalimumab therapy for ulcerative colitis with intolerance or lost response to infliximab: a single-centre experience.
  • -Am J Gastroenterol (Oussalah A et al) 2010; 105: 2617-25. Multicenter study of IFX for UC
  • -Gastroenterology 2010; 138: 2282. Severe pediatric UC. 25/33 responded to IFX. colectomy rate 19% at 1 year.
  • -Gastroenterology 2009; 137: 1204 (ed), 1250. lower colectomy rates at 54wks in IFX vs placebo (+concomitant meds): 10% vs. 17%.
  • -Clin Gastro & Hep 2008; 6: 1112. Do NOT use CYA post infliximab and vice versa. n=19. 1 death due to sepsis. Remission rates occur in ~1/3rd but are of short duration.
  • -NEJM 2005; 2462. 69% clinical response @ 8 weeks (vs. 37% placebo) & 45% at week 54 (vs. 20% placebo).
  • -JPGN 2004; 38: 298. 82% short-term response, 63% sustained response; n=16.

Methotrexate and liver toxicity

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There are drawbacks with all of the therapies for inflammatory bowel disease; however, usually the inflammatory bowel disease is worse than any of the medications. One of the therapies that  has started to see increased usage in Crohn’s disease is methotrexate (MTX), both as an alternative to thiopurines and as an adjunct to Remicade.  There are a number of side effects; a patient handout is available at the following: http://www.ccdhc.org/diseases/MethotrexateLetter.pdf

One of the concerns with MTX has been liver toxicity, in part because of descriptions in the rheumatology literature with long-term usage.  In Crohn’s disease patients, it appears that the risk is much lower (Inflamm Bowel Dis 2012; 18: 359-67).  This study found 13 trials for their meta-analysis.  A total of 632 participants were included: 373 MTX, 131 thiopurines, 128 placebo.  In the MTX group, elevated hepatic aminotransferases occurred in 1.4 per 100 person-months.  The rate of elevation more than 2-fold the upper limit of normal was 0.9 per 100 person-months.  Thus, of the initial 373 patients, 39 had an abnormal aminotransferase.  26 of these 39 had spontaneous resolution, 3 improved with dose reduction & 10 withdrew from MTX treatment (0.8 per 100 person-months).  Seven of these withdrawals were from one of the earlier studies (Feagan et al. NEJM 1995; 332: 292-97). Besides the low likelihood of needing to stop MTX due to liver toxicity, the other observation was that the liver toxicity was mostly dependent on the dose; therefore, dosage reduction would likely be effective if needed.

In my practice, when considering MTX treatment, I usually recommend the following:

  • Monitoring: Baseline: CXR, CBC, Amylase, Renal, LFTs, urine HCG & then Q2-4 weeks initially, then Q3months
  • Give Folate during therapy.
  • Use zofran if needed for nausea
  • Avoid NSAIDs during treatment due to renal toxicity
  • Contraindicated with pregnancy (MTX=teratogen) -females should see gynecology
  • Families warned in writing that this medication is given once a week; more often can be deadly

Additional references:

  • -IBD 2011; 17: 2521. ~25% remission at 1yr, 16% at 2yrs.. n=93.
  • -JPGN 2011;53: 389. n=64. Supports use of zofran for 1st few months to prevent nausea.
  • -JPGN 2010; 51: 714. Use of MTX after thiopurines. n=27. 48% in remission at 6 months.
  • -JPGN 2009; 48: 526. Use in pediatric CD, n=25. 64% response
  • -JPGN 2009; 48 suppl 2: S111. MTX may be effective for UC.
  • -NEJM 2008; 359: 2790. Similar safety of AZA and MTX in vasculitis patients. AZA may be safer.
  • -IBD 2008; 14: 756. MTX in Crohn’s. n=39. 71% remission (20% steroid-free).
  • -J Clin Pharm & Therapeutics 2007; 32: 327-31.
  • -Am J Health Syst Pharm 2004; 61: 1380-84. review of MTX errors -FDA reported
  • http://www.npsa.nhs.uk/patientsafety/alerrts-and-directives/alerts/oral-methotrexate/
  • -Am J Gastro 2007; 102: 2804-2812. n=60 pediatric patients. ~42% in remission with MTX & ~50% improved. 13% (8) had to stop due to increased LFTs or sepsis.
  • -IBD 2006; 12: 1053. n=61. MTX for AZA nonresponders/breakthroughs: 80% with improvement/ 45% with long-term response; 10% discontinued due to side effects. Steroids stopped in 36.
  • -JPGN 2005; 40: 445. Oral MTX works as well as IM/SC.
  • -JPGN 2003; 37: 392 (194A) 0.4 mg/kg/weekly. 91% response at 2 mo, most still needed remicade
  • -Gastroenterology 2003; 124: suppl 1, A-41 (305) 11/12 responded – able to stop remicade
  • -Feagan et al. NEJM 1995; 332: 292-97.
  • -J Pediatr 1999: 134: 47. Hepatotoxic risk factors. (enzymes & obesity). Consider bx if serial enzymes increased >40% of the time over 1 year
  • -Arthritis Rheum 1997; 40: 2226.

More imaging needed?

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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.

Food as medicine

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Two recent articles add some useful information regarding enteral therapy for Crohn’s disease (Inflamm Bowel Dis 2012; 18: 246-53 & JPGN 2012; 54: 298-305).

The first article enrolled 34 children with newly-diagnosed Crohn’s disease.  Patients were divided into elemental and polymeric formula groups and followed in a prospective, double-blind randomized controlled trial for two years.  Measures of improvement included the PCDAI as well as fecal calprotectin and fatty acids.  Both groups of patients responded clinically.  93% (14/15) of the elemental formula group achieved remission based on PCDAI scores (<11) and 79% (15/19) of the polymeric formula group.  The initial treatment was use of formula (along with only clears) either by NG or oral for 6 weeks.  All patients had NG placed at time of endoscopy and if sufficient oral intake was demonstrated (for 2 days), NG was removed.  All subjects had small bowel and colonic disease.  Although calprotectin levels decreased, they remained very elevated.  In the EF group, the median calprotectin dropped from 2023 μ/g to 1113 μ/g, though only one patient had a level below 400; similarly in the PF group the calprotectin dropped from 1929 μ/g to 1134 μ/g, and only two patients had a level below 400.  Some to the reasons why changes in diet may be useful have been alluded to in a previous post: Eat your veggies…if you don’t want to get sick.

The second reference is a clinical guideline on the use of exclusive enteral nutrition EEN).  The introduction notes that 65% of European pediatric gastroenterologists use EEN compared to 4% for North American pediatric gastroenterologists.  In pediatric trials, EEN and corticosteroids were considered ‘equally effective’ in a pediatric meta-analysis which included five randomized controlled trials (n=147).  However, a Cochrane review favored corticosteroid treatment over EEN in a meta-analysis that included adult and pediatric patients (n=192 EEN, n=160 corticosteroids).  According to the authors, small studies have demonstrated other potential advantages of EEN including higher rates of mucosal healing and better linear growth.  With regard to mucosal healing, the initial cited study casts with ongoing elevated calprotectin indicates that this does not occur in the majority of children with EEN therapy.  Other caveats:

  • Disease location: some evidence favors small bowel disease rather than colonic disease
  • Formula composition: does not seem to matter whether elemental or polymeric
  • Duration of therapy: majority treat for 6-8 weeks of EEN.  The authors recommend at least 8 weeks
  • Time for response: Inflammatory markers improve in a little as a week, remission typically 2-4 weeks
  • Concomitant medications: many places initiate immunomodulator treatment; others cycle EEN
  • Start with goal 120% of ‘maintenance’ nutrient needs.  On 1st day, authors recommend starting at 1/2 goal volume and gradually increase over 1-2 days
  • Partial enteral nutrition (PEN) (eg. overnight feedings & normal daytime diet) has been helpful in improving growth and may improve remission rates.
Why not EEN or PEN? Potential barriers include cost, difficulty changing diet, fear of tube feedings, and more acceptable alternatives.  At the same time, some of these barriers could be overcome.  Quality of life measures have improved in children receiving enteral nutrition.

The use of more top-down therapy may affect all of the above considerations (Only one chance to make first impression).

Additional references:

  • -Cochrane Database Syst Rev 2007; CD000542.  Enteral nutritional therapy vs corticosteroids to induce remission in Crohn’s disease.
  • -Gastroenterology 2011; 141: 742. AGA guidelines on use of enteral nutrition in wide variety of conditions.
  • -Gastroenterology 2008; 135 : 1005. omega-3 fatty acids ineffective in Crohn’s dz for maintaining remission.
  • -Pediatr Res 2007; 61: 356-60.  Enteral nutrition effect on protein turnover in adolescents with Crohn’s disease.
  • -J Pediatr 2000; 136: 285-91. Nutritional Rx w polymeric diet is effective w/in 8 weeks in 32/37.
  • -Scand J Gastro 2001; 36: 383-8. Elemental & polymeric diets successful in maintaining remission in ~43% of adults with complete steroid withdrawal
  • -JPEN 1992; 16: 499. improved wt,ht, decreased prednisone, decreased CDAI
  • -JPGN 2000; 31 (supp 2) A291. Polymeric vs elemental diet.
  • -JPGN 2002; 35: 339-40. Lactase deficiency – same prevalence in IBD as in RAP.
  • -JPGN 2000; 31: 3 & 8. EN about as effective as steroids for primary Rx.