Category Archives: Pediatric Gastroenterology Intestinal Disorder

The Latest on Pediatric Nonceliac Gluten Sensitivity

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 A recent study (R Francavilla et al. Am J Gastroenterol advance online publication, 30 January 2018; doi: 10.1038/ajg.2017.483 ) examined “non-celiac gluten sensitivity” (NCGS) in a multicenter prospective trial from Italy (2013-16). 

This study included 1,114 children with chronic gastrointestinal symptoms and negative for both celiac disease and wheat allergy.  To determine if these children, had  a positive correlation between symptoms and gluten ingestion they were evaluated consecutively through the following phases: run-in, open gluten-free diet (GFD) and DBPC crossover gluten challenge.

Design: If there was a correlation between symptoms and gluten ingestion, then patients were randomized to gluten (10 g/daily) and placebo (rice starch) for 2 weeks each, separated by a washout week. The gluten challenge was considered positive in the presence of a minimum 30% decrease of global visual analogue scale between gluten and placebo.

Key findings:
  • Out of 1,114 children, 96.7% did not exhibit any correlation with gluten ingestion.
  • Among the 36 patients who seemed to show a correlation between gluten ingestion and symptoms, 28 patients entered the DBPC gluten challenge. Of these 28 children, eleven children (39%) tested positive.
  • “No predictive laboratory tests can help in identifying NGCS”

Also, it is worthwhile to quote the authors from their last paragraph: “philosopher Immanuel Kant [said], ‘all our knowledge begins with the senses, proceeds then to understanding, and ends with reason’. NCGS begins in the gut feeling of patients, and we are still in the process of understanding it, hoping that reason is not too far behind.'”

My take: This study shows that very few children (<4%) with chronic gastrointestinal symptoms had correlation with gluten ingestion. Even in this group, NGCS was excluded with a DBPC in >60% of cases.

How Gluten Free is a Gluten-Free Diet?

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A recent analysis (JA Syage et al.The American Journal of Clinical Nutrition, Volume 107, Issue 2, 1 February 2018, Pages 201–207, https://doi.org/10.1093/ajcn/nqx049) (Thanks to Kipp Ellsworth for this reference) of 259 patients with celiac disease (~75% pediatric) showed that a large number with ongoing gluten ingestion based on urine and stool tests of gluten excretion.

Results: The average inadvertent exposure to gluten by CD individuals on a GFD was estimated to be ∼150–400 (mean) and ∼100–150 (median) mg/d using the stool test and ∼300–400 (mean) and ∼150 (median) mg/d using the urine test. The analyses of the latiglutenase data for CD individuals with moderate to severe symptoms indicate that patients ingested significantly >200 mg/d of gluten.

My take (borrowed from authors): These surrogate biomarkers of gluten ingestion indicate that many individuals following a GFD regularly consume sufficient gluten to trigger symptoms and perpetuate intestinal histologic damage.

Free link to full article: Determination of gluten consumption in celiac disease patients on a gluten-free diet

Despite signs like these, a lot of individuals veer off the path.

Fructans, not Gluten, Inducing Symptoms In Patients with Reported Non-Celiac Gluten Sensitivity

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As with yesterday’s post, today’s study (GI Skodje et al. Gastroenterol 2018; 154: 529-39) implicates fructans, not gluten, as a culprit in increasing symptoms in those with self-reported non-celiac gluten sensitivity (NCGS).

These researchers performed a double-blind crossover challenge in 59 individuals who had instituted a gluten-free diet (GFD). The symptoms were assessed with a Gastrointestinal Symptom Rating Scale Irritable Bowel Syndrome (GSRS-IBS) through 3 challenges –gluten, fructan, and placebo.

Key findings:

  • GSRS-IBS mean values for gluten 33.1, for fructan 38.6, and placebo 34.3.  The overall GSRS-IBS value for fructans was significantly higher than for gluten P=.04
  • GSRS-IBS mean values for bloating with gluten 9.3, for fructan 11.6, and placebo 10.1

In a related editorial (K Verbeke, pages471-3), the commentary notes that  alpha-amylase-trypsin inhibitors (ATIs) may be another factor which contributes to symptoms in those with reported NCGS.  ATIs protect plants from pests/parasites by inhibiting their digestive enzymes.  They also resist proteolytic degradation in the human intestine and are known to be potent activators of innate immune cells.

My take: This is yet another study showing that among individuals with NCGS that a GFD is often unnecessary and ineffective.  Fructans are more likely to induce gastrointestinal symptoms; however, their are likely to be several food components which contribute to GI symptoms & sometimes extra-intestinal symptoms.

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Fructans and FODMAPs in Children with Irritable Bowel Syndrome

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A recent randomized control trial (BP Chumpitazi et al. Clin Gastroenterol Hepatol 2018; 16: 219-25) evaluated 23 children in a double-blind placebo (maltodextrin) cross-over design (2014-2016) to determine whether fructans (0.5 g/kg/day with max 19 g divided over 3 meals) worsen symptoms in children with irritable bowel syndrome (IBS). Fructans are a commonly ingested FODMAP carbohydrate (oligosaccharides).  All subjects were 7-18 years (median 12.4 years) and met Rome III IBS criteria.

Key findings:

  • Subjects had more episodes of abdominal pain/day while receiving fructan-containing diet (3.4 ± 2.6) compared with placebo-group (2.4 ± 1.7) (P<.01).
  • The fructan group had more severe bloating (P<.05) and flatulence (P=.01).  This was associated with higher hydrogen production (617 ppm/h compared with 136 pph/h) (P<.001)
  • 18/23 (78%) had more frequent abdominal pain with fructan-containing diet and 12 (52%) had fructan sensitivity which the authors defined as having an increase of ≥30% in abdominal pain frequency following fructan ingestion.

My take: While the number of participants in this study is limited, the implications are clear: in children with irritable bowel, fructans frequently exacerbate symptoms. At this time, though, it is not possible to predict which patients with IBS will benefit.

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Chattahoochee River

Paris Classification Quiz and Explanation

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At one of our ImproveCareNow population management meetings, Dr. Chelly Dykes reviewed the Paris Classification and frequent misconceptions in using this system.  To illustrate this point, I am going to post 6 Quiz Slides and then follow that with the answers and explanation.  These quiz slides were derived from previous ImproveCareNow community meetings.

Answers:

  1. A
  2. B (macroscopic disease counts –erythema alone does not count)
  3. A (macroscopic disease counts)
  4. B (not ileum only unless colonic disease extends beyond cecum)
  5. F (though B acceptable)
  6. F (though B acceptable)

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Briefly noted: Mongersen, Aprepitant, and Anesthetic Outcomes

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BG Feagan et al. Gastroenterol 2018; 154: 61-4.  In this study of GED-0301 (Mongersen), an antisense oligodeoxynucleotide affecting Smad7, was randomly assigned to 63 patients with Crohn’s disease (160 mg/day).  Endoscopic improvement was observed in 37%  at week 12. Clinical remission (CDAI<150) was noted in  32% (4 weeks of Rx), 35%  (8 weeks of Rx) and 48% (12 weeks of Rx). No new safety signals were noted.

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PJ Pasricha et al. Gastroenterol 2018; 154: 65-76.  First of all, I have to say that I like the visual abstracts in many Gastro studies.  In this randomized, double-masked “APRON” study of 126 patients with chronic nausea or gastroparesis receiving Aprepitant, a neurokinin-1 receptor antagonist, or placebo, the key findings were the following:

  • Aprepitant did not reduce symptoms of nausea significantly compared to placebo
  • Apreptiant-treated patients had improvements in secondary outcomes of symptom severity for nausea (1.8 vs 1.0, P=.005 on Gastroparesis Clinical Symptom Index) and overall symptoms (1.3 vs. 0.7, P=.001)

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B Bielawska et al. Gastroenterol 2018; 154: 77-85. Using data (administrative databases) and propensity matching from more than 3 million outpatient colonoscopies (2005-2012), the authors noted that the use of anesthesia assistance (AA) was associated with an increased risk of aspiration pneumonia (OR 1.63) but not perforation (OR 0.99). Though this study is limited by its retrospective design and reliance on administrative data, the authors state “the potential for residual confounding by indication for AA [is] extremely unlikely, especially because AA use in Ontario appears to be driven by institutional policy or business model rather than by patient factors.”

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Bright Angel Trail

Briefly Noted: Pantoprazole dosing for obese children

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V Shakhnovich et al. J Pediatr 2018; 193: 102-8. Using pharmocokinetic data from 41 obese children (6-17 years), the authors conclude that lean body weight dosing of pantoprazole led to pantoprazole pharmocokinetics similar to nonobese peers.  They also note that variability in age-related changes in CYP2C19 activity affected pantoprazole values in children <12 years of age.

Related blog post: #NASPGHAN17 EoE Session -James Franciosis presented data on how CYP2C19*17 allele was important in whether patients responded to PPIs for Eosinophilic Esophagitis.

 

Bright Angel Trail, Grand Canyon

Preterm Infants with Increased Infections Following Acid Suppression Therapy

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A recent study (P Manzoni et al. J Pediatr 2018; 193: 62-7) provide more data on the detrimental effects of gastric acid inhibitors (eg. proton pump inhibitors, histamine-2 receptor antagonists).  This study was a secondary analysis using prospectively collected data from 235 preterm very low birth weight infants. Key findings:

  • “After multivariate analysis, exposure to inhibitors of gastric acidity remained significantly and independently associated with LOS [late-onset sepsis] (OR 1.03); each day of inhibitors of gastric acidity exposure conferred an additional 3.7% odds of developing LOS.”
  • Acid suppression therapy was associated with gram-negative (P<.001) and fungal pathogens (P=.001)
  • The study showed an association between acid blockers and with necrotizing enterocolitis, which was mitigated in those who received bovine lactoferrin

My take (borrowed, in part, from authors): This data “confirm, strengthen, and expand on previous reports describing an association between inhibitors of gastric acidity and infections.”  Thus, the risks of these medications is likely greater than the benefits in the majority of preterm infants.

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Bright Angel Trail

Briefly Noted: Arsenic Levels with GFD, Cellphones, and Enuresis Outcomes

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This post has a couple interesting items:

  1. Arsenic levels were not increased in individuals with celiac disease who were consuming a gluten-free diet
  2. Cellphones: There are good reasons for physicians to avoid giving out their cellphone numbers to patients
  3. Enuresis -most patients respond to bedwetting alarms

RD Watkins et al. Practical Gastroenterology; 2018; 42: 12-6.  In this retrospective review of 39 patients (with available arsenic levels), patients with celiac disease (adult & pediatric) had normal and/or undetectable arsenic levels.  The mean duration on a gluten-free diet was 2.35 years for pediatric patients and 3.31 years for adults.

33 Charts/Bryan Vartabedian: Should Physicians Give Their Cell Phone Numbers to Patients

E Apos et al. J Pediatr 2018; 193: 211-6.  This study showed that enuresis treatment with a bedwetting alarm system was effective in 76% of patients (n=2861) and that mean treatment time to achieve dryness was 62 days. The most frequent age group was 6 years to 10 years of age.

 

View from Bright Angel Trail

Why Does Primary Sclerosing Cholangitis Increase the Risk of Colorectal Cancer in Ulcerative Colitis?

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A recent retrospective study (Clin Gastroenterol Hepatol 2018; 16: 68-74) compared adult patients who had ulcerative colitis (UC) with (n=23) and without primary sclerosing cholangitis (n=120) (PSC). All patients had pancolitis and were in clinical remission.

Key finding:

  • Patients with UC-PSC had more subclinical endoscopic activity (odds ratio (OR) 4.21) and histologic activity (OR 5.13) in the right colon compared with patients without PSC

It is known that the presence of PSC is a risk factor for colorectal cancer (CRC).  A previous meta-analysis (RM Soetiknno et al. Gastrointest Endosc 2002; 56: 48-54) described a OR of CRC of 4.09.

My take: This study shows that UC patients with PSC who are in clinical remission have a greater degree of endoscopic and histologic inflammation in the proximal colon compared to patients without PSC.  This increased inflammation is a likely factor in the increased risk for CRC.

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