Canadian Pediatric Guidelines for Crohn’s Disease

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DR Mack et al. Gastroenterol 2019; 157: 320-48. Full Text: Canadian Association of Gastroenterology Clinical Practice Guideline for the Medical Management of Pediatric Luminal Crohn’s Disease

“When the consensus group met in October 2017, the most recent consensus guidelines for the treatment of CD in pediatric patients were those from” ESPGHAN/ECCO in 2014 with data from June 2013. Thus, the guideline attempts to provide more updated information and recommendations based on incorporating the latest studies.

The authors provide 25 consensus statements.  Here are a few of interest:

  • Recommendation 9: In patients with CD, we suggest exclusive enteral nutrition to induce clinical remission (Recommendation 6 recommends steroids as a treatment for clinical remission; adult Canadian guidelines recommended against using exclusive enteral nutrition)
  • Recommendation 11: In patients with CD in remission, we suggest that if partial enteral nutrition is used it should be combined with other medications to maintain clinical remission.
  • Recommendation 20: When starting infliximab in males, we suggest against using it in combination with a thiopurine.
  • Recommendation 24: In patients with moderate to severe CD who fail to achieve or maintain clinical remission with anti-TNF–based therapy, we suggest ustekinumab to induce and maintain clinical remission.
  • Recommendation 25: In patients with CD, we recommend against cannabis or derivatives to induce or maintain remission.

In addition, the authors provide 13 statements with no recommendations -here are two of them:

  • No consensus J: When starting infliximab in females, the consensus group does not make a recommendation (for or against) regarding combining it with a thiopurine to maintain a durable clinical remission.
  • No consensus L: In patients with CD who have achieved a clinical remission with anti-TNF therapy, the consensus group does not make a recommendation (for or against) regarding assessment for mucosal healing within the first year to determine the need to modify therapy.

Crater Lake, OR

“Intestinal Microbiota Transplant” -New Terminology for Fecal Transplant

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A recent letter to the editor (A Khoruts, LJ Brandt, Am J Gastroenterol 114: 1176) suggests that the terms “Fecal Transplant” or “Fecal Microbiota Transplantation” (FMT) should be abandoned in favor of “intestinal microbiota transplant.”

  • First of all, the authors argue that the word “fecal” is no longer accurate as some transplants occur by swallowing capsules of purified microbiota and the days of “blending raw stool near the bedside are largely over.”
  • Secondly, the term “fecal” is highly problematic.  “We are hard-wired to perceive feces to be disgusting.”
  • Third, the media sensation from the terms FMT or fecal transplant “has not translated into substantial positive consequences, such as funding research…[or] philanthropic fundraising.”

Thus, the authors advocate “Intestinal Microbiota Transplant” or IMT.

My take: (borrowed from authors) It is time to “abandon the scatologic humor that is arguably threatening further development of this promising therapeutic approach.”

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Sunrise at Crater Lake, OR

NY Times: “Our Food is Killing Too Many of Us”

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NY Times: D Mozaffarian, D Glickman Our Food is Killing Too Many of Us

“Improving American nutrition would make the biggest impact on our health care”

An excerpt:

“Instead of debating who should pay for all this, no one is asking the far more simple and imperative question: What is making us so sick, and how can we reverse this so we need less health care? … our food…

Poor diet is the leading cause of mortality in the United States, causing more than half a million deaths per year. Just 10 dietary factors are estimated to cause nearly 1,000 deaths every day from heart disease, stroke and diabetes alone…

Taxes on sugary beverages and junk food can be paired with subsidies on protective foods like fruits, nuts, vegetables, beans, plant oils, whole grains, yogurt and fish….Levels of harmful additives like sodium, added sugar and trans fat can be lowered through voluntary industry targets or regulatory safety standards…

Nutrition standards in schools, which have improved the quality of school meals by 41 percent, should be strengthened; the national Fresh Fruit and Vegetable Program should be extended beyond elementary schools to middle and high schools…

Coordinated federal leadership and funding for research is also essential. This could include, for example, a new National Institute of Nutrition at the National Institutes of Health. Without such an effort, it could take many decades to understand and utilize exciting new areas, including related to food processing, the gut microbiome, allergies and autoimmune disorders, cancer, brain health, treatment of battlefield injuries and effects of nonnutritive sweeteners and personalized nutrition.”

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Crater Lake, OR

 

EoP –Biomarker or Balderdash?

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One of the categories in the game of balderdash is abbreviations.  Someone with extra time on their hands should invent a medical version with obscure acronyms as one of the categories.

An acronym that I recently discovered, EoP, which stands for eosinophil progenitor came to my attention from Dr. Benjamin Enav and Dr. Oral Alpan. they suggested two articles (both letters to the editor) related to EoP as a biomarker for eosinophilic esophagitis:

  • DW Morris et al. J Allergy Clin Immunol 2016;138: 915-8.
  • JT Schwartz et al. J Allergy Clin Immunol 2019; 143: 1221-3.

Both of these articles came from researchers at the Cincinnati Children’s Hospital.  In the first, the authors studied 31 children (17 with active eosinophilic esophagitis [EoE], and 14 with inactive EoE).  Key findings:

  • With a cutoff of 15.5 EoPs/mL, there were none of the 17 patients with active EoE below this threshold and 8 of 14 (57%) with inactive EoE were below this threshold.
  • At this cutoff, this pilot study predicted active EoE with a sensitivity of 100%, specificity of 57%, positive predictive value of 74% and negative predictive value of 100%.

The second study, also with 31 children, showed that the peripheral blood EoP levels were significantly increased in patients with active disease and correlated with the
EoEHSS (EoE histologic scoring system) composite ratio.

My take: These studies show that a blood level of EoP is a promising biomarker which could help avoid endoscopy in those with low levels of EoP.

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Liver Shorts August 2019

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JB Talcott et al. JPGN 2019; 69: 145-51.  This small study showed an association with prolonged cholestastic liver disease in children and poorest cognitive outcomes despite successful transplantation.  There were 28 participating children in this study, only 12 with chronic liver disease. Acute liver disease was not associated with deficits in cognitive function.  This study “reinforces the need for timely intervention.”

AA Butt et al. Gastroenterol 2019; 156: 987-96.  This study which used a Veterans database for chronic hepatitis C (HCV) infection (n=242,680) found that treatment with direct-acting antiviral therapy (hazard ratio 0.57) was associated with a significant decrease in risk of cardiovascular disease events.

F DiPaola et al JPGN 2019; 69: 152-59.  This study from the drug induced liver injury (DILI) network (2004-2017) with just 57 cases found that antimicrobials (51%) and antiepileptics (21%) were the leading causes of DILI in children. Related blog: Liver toxicity –Where to Look Online

P Huelin et al. Hepatology 2019; 70: 319-33. This study with 320 consecutive cases of acute kidney injury (AKI) in patients hospitalized for cirrhosis found that urinary neutrophil gelatinase-associated lipocalin (NGAL) (best at day 3) helped differentiate acute tubular necrosis from other types of AKI.

Rapid Progression from Acute Recurrent Pancreatitis to Chronic Pancreatitis

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Briefly noted: QY Lin et al. JPGN 2019; 69: 206-11.  In this INSPPIRE cohort of 442 children, 251 had acute recurrent pancreatitis and 191 had chronic pancreatitis.

Key finding:

  • “Within 6 years after the initial acute pancreatitis attack, cumulative proportion with exocrine pancreatic insufficiency was 18% …diabetes mellitus was 7.7%”

My take: Patients with ARP need routine followup.

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Bridge of the Gods, OR

MZRW for Constipation -Effective in Double-Blind Randomized Control Trial

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A recent study (LLD Zhong et al. Clin Gastroenterol Hepatol 2019; 17: 1303-10) shows that a Chinese remedy MaZiRenWan (MZRW) which is a combination of 6 herbs is an effective agent for constipation based on a double-blind, double-dummy trial of 291 patients with functional constipation. Thanks to Ben Gold for this reference.

MZRW was dosed at 7.5 mg BID and Senna was dosed at 15 mg per day. Mean age of study participants was 45 years.

Key findings:

  • Complete response, defined as an increase of stooling by 1 or more BM per week, was similar between MZRW (68%) and Senna (58%) at week 8.  Both were superior to placebo which had a 33% complete response.
  • At week 16, MZRW had better response than senna or placebo, with complete responses of 47%, 21%, and 18% respectively.
  • No serious adverse effects were reported and there were no significant differences in renal or liver function between the groups.

My take: The authors note that this remedy has been around for 2000 years.  Their data show it appears to be a well-tolerated alternative for the management of constipation in adults.

Mount Batchelor, OR

“When is Celiac Disease Celiac Disease?”

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A recent study (R Auricchio et al. Gastroenterol 2019; 157: 413-20, and editorial PR Green S Guandalini, pg 293-4) provides insight into the topic of “potential celiac disease.”

It is difficult trying to explain the concept of potential celiac disease (CD) to families.  Potential CD refers to the situation of having positive celiac serology but normal duodenal mucosa. In this study, the authors prospectively followed 280 children (age 2-18 yrs) with 2 consecutive abnormal serological tests (anit-TG2, EMA) along with normal duodenal architecture who continued a diet containing gluten.

Key findings:

  • 42 (15%) developed villous atrophy at median followup of 60 months
  • 89 (32%) became serologically-negative for CD
  • Cumulative incidence of progression to villous atrophy was 43% at 12 years.
  • The strongest predictive factor for villous atrophy was age: 7% of children less than 3 years developed flat mucosa, compared with 51% for age 3-10 and 55% for those older than 10 years

Advice on potential CD from editorial –titled “When is Celiac Disease Celiac Disease?”

  • Review the biopsies: were there adequate biopsy specimens? ≥4 from descending duodenum and ≥1 from duodenal bulb
  • Have a second specialist pathologist review specimens
  • If a patient with potential CD is symptomatic, institute a gluten-free diet and then follow for clinical and serologic response
  • If asymptomatic, “a wait and see approach is appropriate with interval biopsies every 2 years, if the elevated antibodies persist”

The editorial also note that none of the patients in this cohort would have been mislabeled with a diagnosis of CD using the non-biopsy approach as none of them had tTG antibodies >10 times the upper level of normal.

My take: This useful study should help with counseling parents about the likelihood of developing celiac disease in those with the “potential” label.  Younger children (<3 yrs), compared to older children, are less likely to convert from potential celiac disease to actual celiac disease..

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Crater Lake, OR

How Long Should Be PPIs Be Used in Patients with Esophageal Atresia?

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A recent study (FR Grunder et al. JPGN 2019; 69: 45-51) examines the use of proton pump inhibitor use after surgical repair of esophageal atresia; this involved a longitudinal cohort (n=73) with prospectively collected data over 11 years.

Background: While PPIs have been used for long-term treatment due to the high frequency of reflux and concerns regarding anastomotic strictures, the authors note that data on long-term outcomes/natural history and benefits/risks of this approach are lacking.

Key findings:

  • 48% of patients had PPIs discontinued at followup.
  • Among the 43 with PPI discontinuation, 40 had endoscopy results available.  Histologic abnormalities were noted in 8 (19%) which was lower than in the group receiving ongoing PPI use (n=19, 63%).. These 8 patients had PPI restarted.
  • Among patients unable to discontinue PPI therapy, there was a higher rate of prior anti-reflux surgical procedure, 27% compared to 5% who had anti-reflux procedure among group who were able to discontinue PPI therapy.
  • Patients more likely to remain on PPIs more frequently had a prior anastomotic leak and/or moderate to severe tracheomalacia.
  • The authors state that among patients receiving PPIs, there was more frequent recurrent pneumonia as well as more frequent use of inhaled beta-adrenergic agonists and steroids. However, this was not shown to be a causal association.  It is unclear whether these patients had more severe esophageal dysfunction or whether PPI use contributed to this outcome.

In their discussion, the authors note that PPIs have not been shown to reduce the rate of anastomotic strictures.  They argue that “PPI could be used more selectively in the following: in children with long-gap EA or anastomotic tension or anastomotic leak; after a first dilatation for anastomotic stricture rather than systematically, given the lack of preventive effect of PPI; and in children whose esophagoscopy demonstrates peptic esophagitis, eosinophilic esophagitis, or gastric metaplasia.”

My take: The authors are probably right that a large fraction of EA patients may not need long-term PPI use.  Selecting which patients will benefit will remain a challenge. Published guidelines recommend monitoring for GERD complications in EA, especially after stopping PPIs.

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University of Virginia

 

Sunshine and Inflammatory Bowel Disease

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A recent provocative study (EA Holmes et al. JPGN 2019; 69: 182-88) describes an inverse association between sunshine exposure and the development of pediatric inflammatory bowel disease (IBD).  Among a cohort of 99 children with IBD and 396 controls, the authors used questionnaires to estimate past sun exposure along with other variables.

Key finding:

  • “For each 10 min increment in leisure-time sun exposure in summer or winter there was a linear 6% reduction in the odds of having IBD (P=0.002)”

There was no corresponding data with regard to vitamin D status.

My take:  Being active and going outside are likely good for one’s health and there have been other studies suggesting more sun exposure could reduce the rate of Crohn’s disease. Does Sun Exposure Lower the Risk of Crohn Disease? | gutsandgrowth  Despite this, in my view, this study’s findings have limited value.

  1. There may be many confounders that separate children with more sun exposure from those with less exposure, including diets, exercise, camping, exposure to animals and soil, and many other variables. In addition, there may have been problems with recall bias.
  2. The role of vitamin D was not studied. In previous studies, the importance of vitamin D in its effect on the IBD/immune system have yielded inconsistent results.
  3. In those with IBD, suggesting that more sun exposure may have prevented IBD would not be helpful; this is due to the flimsy evidence and this information could be interpreted  as blaming the family.
  4. Correlation does not prove causation.  For example, a far-fetched association of correlation that is not likely to have a causal association: Rates of Drowning by Falling in Pools and Nicholas Cage Films (National Geographic: Nicholas Cage Movies vs. Drownings)

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View from Wahkeenah Falls Trail, OR