Canadian Pediatric Guidelines for Crohn’s Disease

DR Mack et al. Gastroenterol 2019; 157: 320-48Full 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

Pushing the Boundaries on Dietary Therapy for Crohn’s Disease (CD-TREAT)

A recent study (available online in advance of publication) (V Svolos et al. Gastroenterology https://doi.org/10.1053/j.gastro.2018.12.002) examines the feasibility and science of modifying a diet to mimic exclusive enteral nutrition.

Full text accepted manuscript (from ScienceDirect/Gastroenterology website): Treatment of Active Crohn’s Disease With an Ordinary Food-based Diet That Replicates Exclusive Enteral Nutrition (PDF 135 pages)

Background: The authors note that exclusive enteral nutrition (EEN) is the only established dietary treatment for Crohn’s disease.

This complicated study had three main parts:

  1. Examining the effects of their CD-TREAT diet compared to EEN in 25 healthy adults in a randomized control trial
  2. Animal experiments (rat model) to explore the anti-inflammatory effect of CD-TREAT
  3. Pilot open-label study of 5 children with CD-TREAT diet (8-weeks)

In the first part of this study, the authors modeled a diet based on the components of the formula modulen. This diet continued to exclude gluten, lactose, and alcohol and tried matching other components (macronutrients, vitamins, minerals, fiber).  In place of maltodextrin (the commonest carbohydrate in EEN feeds), the authors substituted foods high in starch and low in fiber.  Also, the authors decreased carbohydrates in CD-TREAT (particularly complex carbohydrates) in favor of protein.  This diet was given to 25 healthy adults.

Key findings:

  • CD-TREAT induced similar effects to EEN on fecal microbiome, composition,metabolome, mean total sulfide, pH, and short-chain fatty acids (SCFA)

In the second part of this study, in the rat model, CD-TREAT and EEN produced similar changes in bacterial load, short-chain fatty acids, microbiome, and in ileitis severity.

In the third part of the study with 5 children, after 8 weeks —Key findings:

  • 4 (80%) had a clinical response
  • 3 (60%) entered a clinical remission with concurrent reductions in calprotectin (mean decrease of 918 +/- 555 mg/kg)

The CD-TREAT diet appears to affect the taxon abundance of many species of the microbiome in a manner similar to EEN therapy.  The authors noted that CD-TREAT also changed the abundance of genera belonging to Actinobacteria, Bacteroides, and Firmicutes.

Unlike EEN, the CD-TREAT diet is subject to more variable individual intakes; it is not identical in all individuals.

My take: The mechanism of action of EEN therapy remains poorly understood.  The CD-TREAT diet, which is far more diverse than EEN, appears to replicate many of the effects of EEN: “the microbial composition, fecal pH, SCFA, total sulfide, fecal bacterial load and fecal metabolome significantly changed in the same direction for both diets.” A larger clinical study is needed to confirm the effectiveness of the CD=TREAT diet.

Related blog posts:

Disclaimer: These blog posts are for educational purposes only. Specific dosing of medications/diets (along with potential adverse effects) should be confirmed by prescribing physician/nutritionist.  This content is not a substitute for medical advice, diagnosis or treatment provided by a qualified healthcare provider. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a condition

Joshua Tree National Park

 

 

Exclusive Enteral Nutrition for Crohn’s Disease -Less Effective in Those with Isolated Colonic Disease

A recent study (Y Xu. Clinical Nutrition 2018; https://doi.org/10.1016/j.clnu.2018.08.022) showed that exclusive enteral nutrition (EEN) is less effective in patient’s with Crohn’s disease with isolated colonic disease.

Abstract Link: Isolated Colonic Crohn’s Disease is Associated with a Reduced Response to Exclusive Enteral Nutrition Compared to Ileal or Ileocolonic Disease

This was a retrospective study of 241 adults: 52 patients in the cCD (isolated colonic disease) group and 189 patients in the non-cCD group.

Key findings:

  • “The rates of clinical remission differed between the two groups (cCD group: 51.9% versus non-cCD group: 68.3%, P = 0.029). Multivariate analyses indicated that isolated colonic involvement was associated with a reduced response to EEN (OR = 2.74; [CI] 95% = [1.2 –6.23], P = 0.016).”
  • “Further analysis showed that even in patients who achieved clinical remission after EEN, inflammatory serum markers declined more slowly in the cCD group than in the non-cCD group, and the time to remission was longer in the cCD group.”

Related blog posts:

IBD Shorts July 2018

DJ Gracie et al. Gastroenterol 2018; 154: 1635-46. This study of 405 adults indicated that IBD triggers anxiety and that anxiety triggers IBD. Specifically: “Baseline CD or UC disease activity were associated with an almost 6-fold increase in risk for a later abnormal anxiety score (hazard ratio [HR], 5.77; 95% CI, 1.89-17.7).  In patients with quiescent IBD at baseline, baseline abnormal anxiety scores were associated with later need for glucocorticosteroid prescription or flare of IBD activity (HR 2.08; 95% CI, 1.31-3.30).”

RL Dalal, B Shen, DA Schwartz. Inflamm Bowel Dis 2018; 24: 989-96.  This review provides updated information on epidemiology, diagnosis, and treatment recommendations for pouchitis.

A Alper et al. JPGN 2018; 66: 934-6. Key finding: Celiac disease is “not increased in children with IBD compared with non-IBD children with gastrointestinal symptoms.”  False-positive tTG serology can occur.

AK Shaikhkhalil et al. JPGN 2018; 66: 909-14. The authors showed that using a quality-improvement effort, there was increase utilization of enteral exclusive therapy (EEN).  Baseline 5.was <5% and by completion of intervention, utilization increased to approximately 50%. The interventions to achieve this are specified in this article, including talking points.  EEN is described as “nutrition therapy.” Patients are offered oral EEN and if not adequate by 3-4 days, nasogastric feedings are initiated (~15%).  Interestingly, of those to complete EEN therapy, 97% did not need NG placement.

Pictures from Ameilia Island:

Amelia Island

Position Paper: Nutrition in Pediatric Inflammatory Bowel Disease

E Miele et al. JPGN 2018; 66: 687-708.

Full text linkNutrition in Pediatric Inflammatory Bowel Disease: A Position Paper on Behalf of the Porto Inflammatory Bowel Disease Group of the European Society of Pediatric Gastroenterology, Hepatology and Nutrition

This position paper from ESPGHAN makes a total of 53  recommendations and 47 practice points.  There are too many to summarize in this blog post, but I will highlight a few.

Vitamins/Minerals:

  • Due to insufficient data, we do not recommend routine measurement or supplementation of zinc and selenium in children with IBD (EL 2).
  • We recommend monitoring vitamin D levels in all children with IBD (EL 2).
  • We recommend monitoring folic acid annually (EL 2).
  • We do not recommend routine measurement or supplementation of vitamin B1, B2, B3, B6, B7 and vitamin C in children with IBD (EL 2).
  • We recommend folic acid supplementation (either 1 mg daily or 5 mg weekly) in children with IBD receiving MTX therapy (EL 2).
  • We recommend that either serum cobalamin levels or methylmalonic acid level in blood or urine should be measured in children with active ileal CD, children with ileal resection of >20 cm and UC children ileal pouch surgery at least annually (EL 4)

Enteral Nutrition:

  • EEN has the same efficacy as oral steroids in the induction of remission of children with active luminal CD (EL 1). EEN is recommended for a period of at least 8 weeks (EL 1).
  • The use of standard polymeric formula, with a moderate fat content, is recommended unless other conditions are present (eg, cow’s milk protein allergy) (EL 1).
  • Due to the highly demanding adherence, EEN should not be considered as an option for long-term maintenance therapy.
  • EEN is not efficacious in the induction and maintenance of remission of pediatric UC (EL 4).
  • PEN is a treatment option to maintain remission in selected patients with mild disease and low risk of relapse (EL 4).
  • A specific carbohydrate diet (SCD) for induction or maintenance of remission in pediatric IBD patients should not be recommended (EL 4). More evidence on the benefit of SCD from RCTs is needed before such a dietary restriction can be recommended to pediatric IBD patients

My take: This position paper provides a lot of useful information and makes some recommendations that are practical.  The use of diets for maintenance therapy does not receive a favorable view.

Related blog posts:

Disclaimer: These blog posts are for educational purposes only. Specific dosing of medications/diets (along with potential adverse effects) should be confirmed by prescribing physician/nutritionist.  This content is not a substitute for medical advice, diagnosis or treatment provided by a qualified healthcare provider. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a condition.

“Eternal Nutrition” Therapy

NASPGHAN twitter feed (with links to enteral therapy podcasts) was probably a typo &/or autocorrect issue:

“Podcast series must! Eternal Nutrition as Primary Therapy for Crohn’s disease.

Related blog posts:

Why Does Enteral Nutrition Work for Crohn’s Disease? Is it due to the Microbiome?

A recent study (K Gerasimidis et al. Am J Gastroenterol advance online publication 3 November 2015; doi: 10.1038/ajg.2015.357. Full Text: Extensive Modulation of the Fecal Metagenome in Children With Crohn’s Disease During Exclusive Enteral Nutrition) finds that treatment with Exclusive Enteral Nutrition further reduces microbiome diversity compared to healthy controls. This was an unexpected finding as the authors state: “we would expect EEN treatment to normalize the perceived ‘dysbiotic’ microbiota toward a healthier state.”

Reference from KT Park’s twitter feed. Here’s the abstract:

OBJECTIVES:

Exploring associations between the gut microbiota and colonic inflammation and assessing sequential changes during exclusive enteral nutrition (EEN) may offer clues into the microbial origins of Crohn’s disease (CD).

METHODS:

Fecal samples (n=117) were collected from 23 CD and 21 healthy children. From CD children fecal samples were collected before, during EEN, and when patients returned to their habitual diets. Microbiota composition and functional capacity were characterized using sequencing of the 16S rRNA gene and shotgun metagenomics.

RESULTS:

Microbial diversity was lower in CD than controls before EEN (P=0.006); differences were observed in 36 genera, 141 operational taxonomic units (OTUs), and 44 oligotypes. During EEN, the microbial diversity of CD children further decreased, and the community structure became even more dissimilar than that of controls. Every 10 days on EEN, 0.6 genus diversity equivalents were lost; 34 genera decreased and one increased during EEN. Fecal calprotectin correlated with 35 OTUs, 14 of which accounted for 78% of its variation. OTUs that correlated positively or negatively with calprotectin decreased during EEN. The microbiota of CD patients had a broader functional capacity than healthy controls, but diversity decreased with EEN. Genes involved in membrane transport, sulfur reduction, and nutrient biosynthesis differed between patients and controls. The abundance of genes involved in biotin (P=0.005) and thiamine biosynthesis decreased (P=0.017), whereas those involved in spermidine/putrescine biosynthesis (P=0.031), or the shikimate pathway (P=0.058), increased during EEN.

CONCLUSIONS:

Disease improvement following treatment with EEN is associated with extensive modulation of the gut microbiome.

My take: We really don’t know why EEN works and we have a lot to learn about a ‘healthy’ microbiome.

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