Category Archives: Pediatric Gastroenterology Intestinal Disorder

Wheat Intolerance –Self-Reported in 15%!

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A recent study (MDE Potter et al. Am J Gastroenterol 2018; 113: 1036-44 -thanks to Ben Gold for this reference) examined the frequency of wheat intolerance and chronic gastrointestinal symptoms in a randomly selected population of 3542 in Autstralia via a mail survey.

Key findings:

  • Self-reported wheat sensitivity was 14.9%
  • Prevalence of celiac disease (CD) was 1.2%
  • A doctor-diagnosis of CD was associated with functional dyspepsia with an odds ratio (OR) of 3.35.
  • Self-reported wheat sensitivity was independently associated with irritable bowel syndrome with an OR of 3.55 and almost half (45%) have an underlying functional GI disorder.

In a related editorial (pgs 945-8), Imran Aziz makes several useful points:

  • Gluten-free industry has boomed in U.S. with retail sales going from $0.9 billion in 2006 to ~S24 billion in 2020.
  • While previous studies have shown that gluten can induce symptoms in the absence of CD (Biesiekierski JR et al. Am J Gastroenterol 2011; 106: 508-14), more recent rigorous studies have indicated that “gluten-per-se accounts for 1-in-6 cases with the remaining majority either due to fructans (a type of FODMAP or a nocebo effect.”
  • There are no accurate biomarkers of wheat intolerance
  • Dr. Aziz also cautions against adopting a gluten-free diet without proper counseling.  “The greatest concern is whether these diets are safe in the long-run, given the emerging data suggesting cardiovascular, nutritional, metabolic, and microbial changes.”

My take: This study shows that about 1 in 10 individuals have self-reported wheat intolerance; gluten, though, is the actual culprit in less than 20%.

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Celiac Disease: How Long Is a Gluten Free Diet Needed? (30 Year Data)

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A recent study (L Norsa et al. JPGN 2018; 67: 361-6) examines data from 197 patients with celiac disease (CD) (out of a cohort of 337) who had a diagnosis established before 1985. The authors examined three groups: lifelong strict GFD (n=133), discontinued GFD (n=29), and no GFD (22).  A total of 63 had follow-up endoscopy data available, with 29 in lifelong GFD, 20 in discontinued GFD, and 14 in no GFD.

Key findings:

  • In those with followup endoscopy, in those with lifelong GFD 27 of 29 (93%) had no atrophy (Marsh 0-1-2) on histology, in those with discontinued GFD 12 of 20 (60%) had no atrophy on histology, and in those with no GFD 8 of 14 (57%) had no atrophy on histology.
  • Thus, among the group with long-term poor adherence to gluten-free diet, almost two-thirds showed no recurrence of villous atrophy on duodenal biopsies.
  • In the entire cohort of 197, there were no apparent differences in autoimmune diseases between those receiving lifelong GFD (26%) compared to the other two groups, 17% and 23% respectively.

Limitations:

  • retrospective design.
  • initial diagnosis was more than 30 years ago & there are significant differences in the diagnostic approach currently
  • sample size

My take: This study indicates that some individuals who have been diagnosed with celiac disease may be OK with ongoing gluten consumption. Those who maintained a GFD were much more likely  to have no villous atrophy on duodenal biopsies.

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Eosinophilic Esophagitis -Update

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At a recent morning clinical conference, Dr. Seth Marcus provided a terrific update on eosinophilic esophagitis (EoE).  I am placing some of the slides below and the following is a link to the full lecture: The Evolution of EoE -Seth Marcus

During this part of the presentation, there was a discussion regarding the role of  allergists. Due to the poor predictive value (negative and positive) of allergy testing (skin tests and blood tests), the consensus is that routine allergy evaluation is NOT needed for children with EoE.  However, IgE-mediated food allergies along with other atopic diseases are common in children with EoE and selected patients could benefit from allergy referral.

The slide above reviews the main treatment options: topical corticosteroids, proton pump inhibitor therapy, and elimination diet.  While all of these are reasonable as first-line approaches, many in the group favored proton pump inhibitor (PPI) treatment as initial therapy.  In those with a very good response (<5 eos/hpf at followup), this would allow lower dose PPI as a maintenance option.  Another point of discussion was the fact that PPI responders tend to more favorably metabolize the PPIs to achieve higher therapeutic levels.  It is anticipated that future treatment could be influenced by knowing the individual’s CYP2C19*17 Polymporphisms (#NASPGHAN17 EoE Session)

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The Rise of Eosinophilic GI Diseases –Not Likely Connected to Helicobacter Pylori

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A recent prospective case-control study (J Molina-Infante et al. Am J Gastroenterol 2018; 113: 972-9 -thanks to Ben Gold for this reference) examined the potential connection between Helicobacter pylori and eosinophilic GI diseases.  They examined 808 individuals (404 cases of eosinophilic esophagitis [EoE], 404 controls). Key findings:

  • H pylori prevalence was not different between cases and controls (37% vs. 40%, odds ratio 0.97).  The authors conclude that H pylori which has declined in prevalence globally is not inversely associated with EoE as had been suggested in some previous reports

In an associated editorial, (pg 941-4), the authors note that there has been a dramatic increase in atopic diseases over the past 30 years.  One hypothesis has suggested that these epidemiologic changes are related to a changing microbiome.  This in turn may be related to frequent antibiotic usage.  An example of the proliferation of antibiotics: “20-25% of Swedish adults receive an antibiotic prescription annually.”

While H pylori may be a biomarker associated with poor hygiene/less antimicrobial exposure, it does not appear to be directly related to EoE.  The authors indicate that until we have a better understanding, “in the meantime attention to healthier diets and minimizing antibiotic exposure may optimize public health in terms of atopic disease risk.”

My take: Since our genetics do not change quickly, the dramatic changes in disease frequency of conditions like EoE and Crohn’s disease must be influenced by environmental exposures.  How to lower the risk of these conditions remains uncertain.

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Not a joke –WIFI hotspot at Sunshine Meadows, Banff National Park

“Transparency Hasn’t Stopped Drug Companies From Corrupting Medical Research”

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NY Times Commentary by Marcia Angell: Transparency Hasn’t Stopped Drug Companies From Corrupting Medical Research

Dr. Angell, a former editor of the New England Journal of Medicine examines the recent outrage regarding Dr. José Baselga who resigned from his position as chief medical officer at Memorial Sloan Kettering Cancer Center after “ProPublica and The New York Times revealed that he’d received millions of dollars from drug and device companies … Most of his outside income was not disclosed to the journals in which he published, in violation of their requirements.”  Dr. Baselga has had a huge impact in cancer research; his work led to the discovery of Herceptin, a widely used treatment for breast cancer.

  • She argues that disclosure alone is not sufficient to prevent pharmaceutical companies from corrupting research:
  • “Drug company involvement biases research in ways that are not always obvious, often by suppressing negative results. A review of 74 clinical trials of antidepressants, for example, found that 37 of 38 positive studies — that is, studies that showed that a drug was effective — were published. But 33 of 36 negative studies were either not published or published in a form that conveyed a positive outcome.”
  • “Bias can also be introduced through the design of a clinical trial. For example, the sponsor’s drug may be compared with another drug administered at a dose so low that the sponsor’s drug looks more powerful.”
  • “Disclosure is better than no disclosure, but it does not eliminate the conflict of interest. It’s simply a way of … leaving it to readers to decide whether the research was biased. But most people — even doctors and science reporters — aren’t really equipped to make those judgments, particularly when data are suppressed.”
  • She argues that drug companies should have “no control over the design, interpretation and publication of trial results” and that “doctors should not accept gifts from drug companies, even small ones, and they should pay for their own meetings and continuing education, as is standard in other professions.”

My take (borrowed from author): “we should not let drug companies buy the hearts and minds of researchers. The cost of this is high, and not just in drug prices. It means both doctors and patients believe prescription drugs are better and safer than they really are.”

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Hillel quote at Mercedes Benz Stadium

Anemia in Pediatric Inflammatory Bowel Disease

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A recent retrospective study (G Aljomah et al. JPGN 2018; 67: 351-5) provides some useful information about anemia in the pediatric inflammatory bowel disease (IBD) population. This study included 153 patients, though the diagnostic tests varied considerably; for example, only 42 patients had a serum transferrin receptor (sTR) assay available at followup.

Key points:

  • 67.3% of patients had anemia at diagnosis.  38.5% had anemia of chronic disease (ACD) and the remainder had either iron deficiency anemia (IDA) or IDA in combination with ACD.
  • 20.5% had anemia at followup approximately 1 year after diagnosis. 5.1% with ACD alone and 15.4% had IDA or IDA in combination with ACD.
  • In a subset of patients with more complete data, it was shown that anemia was much more common in patients with Crohn’s disease: 91.2% at diagnosis and 27.3% at followup compared with patients with ulcerative colitis with 40.0% at diagnosis and 7.7% at followup.

The authors used the sTR index (sTR/log ferritin index) to determine if ACD was present.  “This index can differentiate IDA from ACD; however, it cannot separate IDA from the combination of IDA/ACD.  IDA or IDA/ACD were considered to be present if the sTR index was greater than 1.03. An sTR index of <1.03 was taken to be indicative of the presence of ACD.”

Briefly noted: MR Serpico et al. JPGN 2018; 67: 341-5.  This retrospective study  examined the use of allopurinol to optimize thiopurine levels.  32 of 52 patients remained on the combination for 1 year.  In this group, median alanine transaminase decreased to 19 from 77 (P<0.001) and median 6-TG levels increased to 322 from 166 (P<0.001). In addition, steroid-free remission rates improved to 82% (23 of 28).  About 40% of the initial cohort of 52 patients were switched to antitumor necrosis factor therapy.

My take: The initial study shows that anemia is frequent in pediatric IBD, especially at diagnosis (67%).  Even at followup, 20% of patients had ongoing anemia.

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Does PPI Use Increase Pneumonias in Otherwise Healthy Infants?

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A recent study (M-L Blank, et al. JPGN 2018; 67: 335-40) showed that proton pump inhibitors (PPIs) do not appear to increase the risk of pneumonia in otherwise healthy infants.

This study used a cohort of 21,991 patients (2005-2012) in New Zealand and examined the use of a PPI (omeprazole, lansoprazole, or pantoprazole) and its association with lower respiratory tract infections (566 validated cases) and 65 cases of radiography-confirmed community acquired pneumonia (CAP).  For each LRTI and each CAP, there were 10 matched controls.

Key findings:

  • Neither current nor recent use of a PPI was associated with an increased risk of CAP or LRTI resulting in hospitalization or death.
  • The matched odds ratio for CAP with current or past use of PPI was 0.88 and for all LRTI cases the matched odds ratio was 1.13.

My take: This study indicates that PPIs are unlikely to contribute to respiratory infections in otherwise healthy infants.  The larger question is how many of these infants really should be receiving PPIs and what other adverse consequences that may occur.

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Clinical Evaluation Not Sensitive for Aspiration

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A recent retrospective study (in press): abstract link: Presenting Signs and Symptoms do not Predict Aspiration Risk in Children DR Duncan et al. J Pediatr 2018;  https://doi.org/10.1016/j.jpeds.2018.05.030

From Boston Children’s Hospital Notes (9/12/18):

  • More than 80 percent of aspiration was silent
  • Rosen, Duncan and colleagues also found that observed feedings, even by very skilled clinicians, are not sensitive enough to diagnose aspiration in children because of the high rates of silent aspiration. Based on statistical analyses, the degree of agreement between observed feeding and the VFSS was poor for the diagnosis of aspiration.
  • Almost a third of the patients experienced symptoms during or after meals, which may help explain why physicians frequently misdiagnose oropharyngeal dysphagia with aspiration as gastroesophageal reflux disease (GERD).

Full abstract:

Objectives

To determine if any presenting symptoms are associated with aspiration risk, and to evaluate the reliability of clinical feeding evaluation (CFE) in diagnosing aspiration compared with videofluoroscopic swallow study (VFSS).

Study design

We retrospectively reviewed records of children under 2 years of age who had evaluation for oropharyngeal dysphagia by CFE and VFSS at Boston Children’s Hospital and compared presenting symptoms, symptom timing, and CFE and VFSS results. We investigated the relationship between symptom presence and aspiration using the Fisher exact test and stepwise logistic regression with adjustment for comorbidities. CFE and VFSS results were compared using the McNemar test. Intervals from CFE to VFSS were compared using the Student ttest.

Results

A total of 412 subjects with mean (±SD) age 8.9 ± 6.9 months were evaluated. No symptom, including timing relative to meals, predicted aspiration on VFSS. This lack of association between symptoms and VFSS results persisted even in the adjusted multivariate model. The sensitivity of CFE for predicting aspiration by VFSS was 44%. Patients with a reassuring CFE waited 28.2 ± 8.5 days longer for confirmatory VFSS compared with those with a concerning CFE (P < .05).

Conclusions

Presenting symptoms are varied in patients with aspiration and cannot be relied upon to determine which patients have aspiration on VFSS. The CFE does not have the sensitivity to consistently diagnose aspiration so a VFSS should be performed in persistently symptomatic patients.

My take: This study provides more data indicating that clinical evaluations are not reliable in children less than 2 years of age to exclude formal swallow study evaluations and that some symptoms attributed to reflux are in fact due to aspiration.

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Fecal Microbiota Transplantation: How important is the BMI of the stool donor?

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Currently fecal microbiota transplantation (FMT) “best practices” exclude obese stool donors based on a report of germ-free mice gaining weight after FMT from mice with obesity and based on a case report of an individual with 34 pound weight gain after FMT.

A recent report (M Fischer et al. Clin Gastroenterol Hepatol 2018; 16: 1351-3) suggests that the the BMI of the stool donor does not affect recipient weight after a single FMT procedure for C difficile infection.

This analysis included 173 patients with a mean age of 57 years.  One group of 103 were from a randomized control trial; in this group, 66 (64%) received FMT from a normal weight (BMI 18-24.9) donor and 37 (36%) received FMT from an overweight (BMI 25-29.9) donor. Among an additional 70 individuals from an observational cohort, 25 received FMT from normal weight donor, 30 received FMT from overweight donor, and 15 received FMT from an obese donor.

Key finding:

  • There was no significant difference in BMI among the FMT recipients up to 48 weeks after a single FMT.  Based on data from Figure 1, patients who received FMT from normal weight donor had slightly higher mean weight gain at 48 weeks afterwards (not statistically-significant)

The authors caution that a prospective study is required to confirm these findings and in the interim, they recommend exclusion of obese/overweight FMT donors.

My take: There are plenty of willing stool donors –so who knows if this will ever be examined adequately.  This study challenges the idea that FMT from an obese donor will result in recipient obesity, presumably via changes in the microbiome.

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