Tag Archives: inflammatory bowel disease

N2U -Part 3: EoE, IBD, and Cystic Fibrosis

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2015 N2U Syllabus & Presentations

EoE Dietary Pointers (Syllabus pg 83-94): Sally Schwartz, Valeria Cohran

  • Even with SFED, elemental supplements helpful
  • Drink elemental beverages from covered glass with straw (improves palatability)
  • Cross-contamination –big issue
  • Label reading critical

Related posts:

IBD EEN Pointers (Syllabus pg 95-102): Rebecca Pipkorn, Justine Turner

  • Polymeric formulas –most palatable and least expensive. Oral EEN is used costly/not covered
  • EEN particularly helpful with microperforation/flare-up presentation and with infections (eg. TB)
  • EEN induces mucosal healing and improved symptoms

References:

  • Levin et al. Inflamm Bowel Dis. 2014;20:278-285.
  • Johnson et al. Gut 2006;55:356-361.
  • Sigall-Boneh et al. Inflamm Bowel Dis. 2014;20:1353-1360.
  • Wilschanski et al. Gut 1996;38543–548.
  • Critich et al. J Pediatr Gastroenterol Nutr. 2012;54: 298–305. NASPGHAN Guidelines

Conclusions:

  • Enteral therapy offers an alternative to steroids in patients with CD
  • Has potential to improve growth and IBD symptoms
  • Avoids the side effects of steroids
  • Need further research:
  1. – Unclear of the mechanism
  2. – Unclear of the best protocol
  3. – No standard protocol for reintroduction of food

Related posts:

Cystic Fibrosis (Syllabus pg 34-50) Justine Turner

Case in point: 10 yo with CF and poor growth, hx/o DIOS, poor intake, and distention.  Family had refused tube feedings previously.

Key point: Long-term survival is linked to nutritional status

  • Zemel et al. J Pediatr. 2000; 137(3):374-380.
  • Stallings et al. J Am Diet Assoc. 2008; 108(5):832-839.
  • McPhail et al. J Pediatr. 2008; 153(6):752-757.
  • Sharma et al. Thorax 2001; 56:746-750.

Other Caveats:

  • Intervene early
  • Breast milk (often with supplements) is optimal for infants
  • Poor oral intake àcould need periactin and/or supplemental feeds
  • Discussion re: pros/cons of Gtubes (pg 47 in syllabus)
  • Psychology support

Nutrition Goals

  • – Normal growth and optimal nutritional status
  • – Ages 0-2 year: Weight for length >50th percentile
  • – Ages 2-20 year: BMI percentile at or above 50th percentile
  • – BMI for males:23
  • – BMI for females: 22

Nutritional assessment at every visit & review:

  • – Weight, length/height, weight for length, BMI, head circumference in infants
  • – Nutritional education & dietary counseling
  • – Review PERT
  • – Review need for micronutrient supplementation: fat soluble vitamins (A, D, E, K), Ca, Fe, Zn, Na (salt), essential fatty acids

PERT (Pancreatic enzyme replacement therapy):

  • Infants 2000-4000 U lipase with 120 mL breast milk or formula– Mouth care for infants (and breast feeding mother)
  • Children 500-2500 U lipase/kg per meal (≤10000 U/kg/day or ≤ 4000 U/g fat/day); half meal dose with snacks
  • Ideally taken with meals and orally
  • Microspheres preferred formulation
  • Acid blockade (used to optimize enzyme activity)
  • Gold standard to assess adequacy is 72h fecal fat collection

Cystic Fibrosis Related Diabetes

  • Rare before 10 years of age
  • Increases mortality risk 6-fold
  • Weight loss and pulmonary decline begin 2-4 years prior to
  • diagnosis of CFRD

Related posts:

 

Robie House (at Univ Chicago)

Robie House (at Univ Chicago)

 

 

Microbial Signature in Crohn’s

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This recent study (summarized in earlier post today/Dr. Barnard’s talk) provides more information on the microbiome in patients with pediatric Crohn’s.  Here’s a link to full article: Specific transcriptome and microbiome signature in pediatric Crohn’s   Here’s the abstract:

Interactions between the host and gut microbial community likely contribute to Crohn disease (CD) pathogenesis; however, direct evidence for these interactions at the onset of disease is lacking. Here, we characterized the global pattern of ileal gene expression and the ileal microbial community in 359 treatment-naive pediatric patients with CD, patients with ulcerative colitis (UC), and control individuals. We identified core gene expression profiles and microbial communities in the affected CD ilea that are preserved in the unaffected ilea of patients with colon-only CD but not present in those with UC or control individuals; therefore, this signature is specific to CD and independent of clinical inflammation. An abnormal increase of antimicrobial dual oxidase (DUOX2) expression was detected in association with an expansion of Proteobacteria in both UC and CD, while expression of lipoprotein APOA1 gene was downregulated and associated with CD-specific alterations in Firmicutes. The increased DUOX2 and decreased APOA1 gene expression signature favored oxidative stress and Th1 polarization and was maximally altered in patients with more severe mucosal injury. A regression model that included APOA1 gene expression and microbial abundance more accurately predicted month 6 steroid-free remission than a model using clinical factors alone. These CD-specific host and microbe profiles identify the ileum as the primary inductive site for all forms of CD and may direct prognostic and therapeutic approaches.

From Cincinnati Children’s Pediatric Insights (summary of findings):

“The discovery of specific bacterial populations and a core gene signature associated with Crohn’s disease could lead to new diagnostic testing and improved treatment for inflammatory bowel disease (IBD), according to a study led by researchers at Cincinnati Children’s.

‘This study identifies a set of bacteria that are associated with symptoms, and a group of anti-inflammatory genes that are associated with intestinal damage in children with Crohn’s disease,’ says Lee (Ted) Denson, MD, Medical Director of the Inflammatory Bowel Disease Center, senior investigator for the study, published online July 8 in the Journal of Clinical Investigation. Yael Haberman Ziv, MD, was the study’s first author.

Denson’s team studied tissue samples from the ileum, the lowermost portion of the small intestine, in a large number of children with Crohn’s disease. They found specific types of bacteria and a “core” gene expression signature, both of which appear to affect inflammatory changes in the gut. Certain genes in the core signature appeared to be specifically associated with intestinal damage from deep ulcers.”

 

NASPGHAN Awards 2014

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I wanted to congratulate/recognize this year’s awardees at NASPGHAN and to summarize some of the associated presentations.

This blog entry has abbreviated/summarized the presentations. Though not intentional, some important material is likely to have been omitted; in addition, transcription errors are possible as well.

Major Awards:

  1. Harry Shwachman Award: Peter Whitington (Children’s Hospital of Chicago) This award is given for major life long scientific contribution to the field of pediatric gastroenterology.
  2. Distinguished Service Award: Melvin Heyman (UCSF Division Chief and JPGN editor). This award is given for excellence and service in the field of pediatric gastroenterology.
  3. AAP Murray Davidson Award: Jeffrey Hyams (Division Chief Connecticut Children’s)This award is given to an outstanding clinician, scientist and educator.

Fellow Research Award: “Bile Acid Signatures in Children Confer Protection From Clostridium Difficil Infection” ME Tessier et al (Baylor College of Medicine). Conclusions: Stool bile acids profiles are different in children with C difficile infection and could be a predisposing factor.  C diff toxins may alter bile acid profiles via inducing epithelial FGF-19 production.

Young Investigator Award “Analysis of Candidate Genes by Whole Exome Sequencing in Very Early-Onset IBD” J Kelsen (CHOP), et al. VEO-IBD cohort. Excellent presentation! (Related blog post: Just the Beginning: Mutations in Very Early Onset ..)

  • Children <5 years/extensive controls.
  • Mutation Findings: IL10RA/IL21R variants, RAG2/PIK3R1 variants
  • Presentation included phenotypic description (clinical and immunity/functional analysis)
  • Gut microbiome development being studied as well
  • Trying to combine microbiome data with genomic data.

William Balistreri Prize “A Prospective Newborn Screening Study for Biliary Atresia” Sanjiv Harpavat (Baylor College of Medicine) et al.   Excellent talk!

Background: 67 infants with biliary atresia (2007-2014) on retrospective review—ALL had elevated conjugated/direct bilirubin levels in first 24-48 hours of life. (Related blog post: Diagnosing biliary atresia earlier | gutsandgrowth)

Repeat testing at 2 weeks can identify those infants that need to be followed closely.  Workup needed for those who remained abnormal at 2 weeks of life.

This algorithm was studied at 4 different hospitals in Houston with 2-12% premature infants)

In newborn period:

  • N=11,636 –121 abnormal on newborn testing (based on hospital’s normative values -usually direct bilirubin >0.4)
  • When repeated at 2 weeks: 102 of these 121 were normal/only 12 continued to test high (2 with BA, 1 A1AT, 1 Rh disease, 8 resolved).  The two patients detected with biliary atresia is in line with the expected frequency of ~1 in 5000.
  • 7 missed retesting. 3 died (congenital heart disease), 2 missed followup, 2 had PCP refuse retesting.
  • Testing results: 100% sensitivity. Good specificity with repeat testing.

Baylor Workup approach to cholestasis:

  • 3-4 day evaluation
  • Day 1: liver panel, A1AT typing, U/S, CXR
  • Days 2-4: liver biopsy/percutaneous cholangiogram, +/- Kasai

Current AAP recommendation (per Ronald Sokol) is for all infants to have fractionated bilirubin.

Take-home message: How can we diagnose every infant on time? Possibly check every infant for direct/conjugated bilirubin in first 48 hours.

Young Clinical Investigator Award: “Poop-MD: A mobile health application accurately identifies acholic stools.” Douglas Mogul

Problem of delayed diagnosis has been improved in some studies with stool color cards. With emergence of smart phones (80% of 18-35 year olds have smart phones), opportunity to identify echoic stools with new technology.

  • PoopMD. Software determines whether stool is bloody, acholic, etc. Can email doctor and place reminder. FREE app.
  • Parents takes the picture of stool and then app analyzes.
  • Pilot study with 45 initial photographs reviewed by panel of 7 pediatricians
  • When at least 6 physicians agreed on stool color as being acholic (n=7), this was tested against app
  • App: 100% sensitivity for acholic stools. 89% specificity.
  • Working on Spanish version and improved interface.

Other awards:

NASPGHAN Foundation Awards

NASPGHAN Foundation Awards

Sponsored Awards

Sponsored Awards

NASPGHAN Postgraduate Course 2014 -Nutriton Module

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Thanks to those who attended yesterday’s talk (10/24/14) at the clinical practice session and to those who provided helpful feedback.

This blog entry has abbreviated/summarized the presentations. Though not intentional, some important material is likely to have been omitted; in addition, transcription errors are possible as well.  If you make it to the bottom of this post, you will find some useful patient resources along with previous related blog entries.

Diet and the Microbiome –Robert Baldassano (CHOP) pg 140 in Syllabus

This was a very effective lecture; it brought together a lot of useful information.

Trying to sort out balance between health and disease and role of dysbiosis (altered microbiome)

  • Things that we ingest such as food (diet), antibiotics, and xenobiotics shape the composition of the gut microbiota and serve as substrates for the gut microbiota to produce metabolites
  • We are not the only organism consuming what we eat

Specific studies:

  • Wu G, et al. Science. 2011 Oct 7;334(6052):105-8  The Bacteroides enterotype was highly associated with animal protein and saturated fats, which equates to frequent meat consumption as in a Western diet. The Prevotella enterotype high values for carbohydrates and simple sugars, indicating association with a carbohydrate-based diet more typical of agrarian societies.
  • De Filippo C, et al. PNAS 2010: 14691-96: African children (compared with European) with more bacterial diversity & richness along with higher levels of short-chain fatty acids
  • Holmes et al. Cell Met 2012; 16: 559. Diet serves as a substrate for the microbiota to produce certain metabolites.

IBD and diet (Hou JK et al. American Journal of Gastro 2011;106:563-73)

  • High dietary intakes of total fats, PUFAs, omega-6 and meat were associated with an increased risk of CD and UC
  • High fiber and fruit intakes were associated with decreased CD risk
  • High vegetable intake was associated with decreased UC risk.
  • Consumption of meat, particularly red and processed meat increased the likelihood of relapse (Jowett et al Gut 2004)
  • Enteral diet for IBD can improve stool calprotectin within 1-2 weeks.

Take-home messages: Don’t tell your patients with non-stricturing IBD to eat a low fiber diet.  Reduced red meat and reduced oral iron may be helpful.  Vegetarian diet and Mediterranean diets may be helpful.

Related blog posts:

FODMAP: Navigating this Novel Diet –Bruno Chumpitazi, MD, MPH (Texas Children’s Hospital) -page 152 in Syllabus

  • Fermentable Oligosaccharides Disaccharides and Polyols (FODMAPs): Poorly absorbed, osmotically active, rapidly fermented (produce gas)
  • Higher FODMAPs increase breath hydrogen (Murray K et al. Am J Gastroenterol 2014;109:110-9)
  • Higher FODMAPs increase stool/ileostomy output (Barret JS et al. Aliment Pharmacol Ther 2010;31:874-882,Halmos EP J Gastroenterol Hepatol 2013;28(Suppl4):25-28)

Evidence for use of low FODMAPs diet is best in adult irritable bowel syndrome.

  • Shepherd SJ et al. Clin Gastroenterol Hepatol 2008;6:765-71
  • Staudacher HM et al J Nutr 2012;142:1510-18
  • Ong DK et al. J Gastroenterol Hepatol 2010;25:1366-1373
  • Halmos EP et al. Gastroenterology 2014;146:67-75

Limited studies in children.

  • Chumpitazi BP et al. NASPGHAN 2014 abstract n=33 pediatric IBS.  Favorable response noted to low FODMAP diet.

Dietary recommendations were reviewed along with the caveat that obtaining the assistance of a dietician/nutritionist is recommended.

Resources:

Related blog posts:

Nutrition in the Child with Neurological Disabilities –Kathleen Motil (Baylor College of Medicine) pg 162 in Syllabus

  • Nutritional disorders are highly prevalent in children with neurological disabilities: 29-46% are underweight; 8-14% are overweight.
  • Improved nutrition improves behavior, activity level, improves growth, and reduces infections.
  • Cause of nutritional disorders mostly related to inappropriate dietary intake but other factors can play a role
  • Growth/anthropometric measures are key determinant of nutritional assessment
  • Key questions: Is child taking all day to eat? Is child choking with feedings?
  • Critical BMI <12 kg/m-squared
  • Goal for BMI ~25%

Reasons for gastrostomy:

  • Flat growth >6 months/weight below curve
  • Parental request
  • Medication administration
  • Aspiration

Resource:

www.feedingtubeawareness.com  This site contains a terrific PDF download which explains enteral tubes in an easy to understand style along with good graphics. “What You Need to Know Now, A Parent’s Introduction to Tube Feeding is the guide book that every parent wished they had when they were first introduced to feeding tubes.”

Related blog posts:

 

 

 

 

ImproveCareNow Video

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A recent (short ~2:30) ImproveCareNow (ICN) Video explains how ImproveCareNow is a forward-thinking network and how it has the potential to lead to better outcomes for children with inflammatory bowel disease.

If you are part of ICN, this video may help explain to your patients what ICN is all about.

Early Results of FMT for IBD -Any Efficacy?

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As more data emerges on fecal microbiota transplantation (FMT) for inflammatory bowel disease in well-designed trials, it is not clear if FMT will be effective.  A summary of some recent abstracts is available at this link to Gastroenterology and Endoscopy News: Fecal Transplants for IBD Show Mixed Results in Trials

One trial with 53 patients with mild to moderate UC (27 randomized to FMT, 26 to placebo) once weekly for six weeks showed similar results in both groups with 7 FMT patients and 8 placebo recipients experiencing improvement of at least 30% in their Mayo scores.  Dr. Lawrence Brandt said, “It may be that we need to look at the patient’s unique bacterial composition and determine which organisms need to be replaced and formulate FMT accordingly.”

Related blog posts:

Are Biopsies Needed with a Normal-appearing Colonoscopy?

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“Colonoscopy in children routinely includes the practice of obtaining multiple biopsy samples even in the absence of gross mucosal abnormalities.”  This is the beginning of a recent report (JPGN 2014; 58: 773-78) which shows good agreement between endoscopic and histologic findings in a retrospective study of 390 colonoscopies.

Key findings:

  • “A known diagnosis of inflammatory bowel disease was a strong predictor of abnormal histology (OR 6.4 P<0.0001)”
  • 20 of 172 patients with a reportedly normal-appearing colonic mucosa had abnormal histology.  8 had a known diagnosis of IBD, 4 had symptoms/bloodwork highly suspicious for IBD, and another 3 were immunosuppressed.
  • The agreement rate (normal vs. abnormal) between pathologist and endoscopist was 84% with most of the disagreement when the endoscopist reported an abnormal finding whereas the pathologist reported normal histology.  This occurred in 11% of colonoscopies.

The authors “believe our data support the use of a combination of endoscopic appearance and evidence-based risk stratification to…reduce the number of biopsies obtained.”  “The symptom of abdominal pain as a primary indication for performing the procedure was an extremely strong negative predictor of histopathology. ”

Take-home message: If the colon appears normal and there is no prior evidence of IBD/along with reassuring laboratory studies, taking fewer biopsies is appropriate with colonoscopy in children.

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.  Endoscopy decisions should be determined by your physician. 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.

Second-Guessing Aggressive Medical Treatment in Pediatrics

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An excerpt of a review of a recent study (Inflamm Bowel Dis. 2014;20:291-300.) from Healio Gastro, http://bit.ly/1njexRZ.  This study was briefly referenced at the bottom of a previous blog post (UC SUCCESS | gutsandgrowth).

Mortality and malignancy, the most serious complications of pediatric inflammatory bowel disease, were relatively rare and linked most commonly with aggressive treatment rather than the condition itself, according to recent study data.

In a multinational retrospective study, researchers surveyed all pediatric gastroenterologists in 20 European countries and Israel on cancer and/or mortality among their pediatric patients with inflammatory bowel disease (PIBD) from 2006 to 2011.

Among 44 children diagnosed with IBD (median age at diagnosis, 10 years; 26 boys), 18 cases of cancer were identified and/or 31 patients died. Twelve cancer patients had Crohn’s disease, and 19 patients who died had ulcerative colitis (UC). The most common cancers were hematopoietic tumors (n=11). Mortality was attributed to infections (n=14) and other causes, including cancer (n=5), uncontrollable disease activity related to IBD (n=4) and procedural complications (n=3).

“Cancer and mortality in PIBD are rare, but cumulative rates are not insignificant,” the researchers wrote. “…. At least six lymphomas were likely treatment-associated by virtue of their phenotype.”

Researchers said that aggressive therapy with immunosuppressants and biologics has become common among PIBD patients because their disease is often more severe than that found in adults with IBD…

“Nine out of 19 patients with UC died because of an infectious complication. These fatalities may have been prevented by earlier surgical intervention when intensified medical treatment is ineffective.”

Bottomline: Making a colectomy decision is quite difficult when medical therapies may be effective.  Recent guidelines using PUCAI scores may assist physicians in identifying medical failures more quickly.

 

Consensus Guidelines on FMT

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Recent links from AGA for FMT (fecal microbiota transplantation) for Clostridium difficile –excellent resource:

Also, summary of recent abstracts from ACG regarding FMT for C difficile, IBS, and IBD: http://t.co/7LFnDYq5V5

Some previous blog posts on this topic:

IBD Update 2014 (part 2)

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5. Inflamm Bowel Dis 2013; 19: 2927-36.  This reference is another article that tries to help discuss the risks and benefits of biologic therapy for pediatric inflammatory bowel disease.  After reviewing the potential risks, the authors provide their “Option Grid” (Page 2932).  The authors state, “in summary, the adult literature supports the concept of the early use of combination therapy…the risks associated with anti-TNF therapy are really not significantly different as compared with thiopurine therapy and perhaps in some cases safer.  Therefore, we should be moving closer to the idea of using anti-TNF therapy early, with or without an immunomodulator.  In the sickest patients, combination therapy probably adds benefit, and then once in remission, consideration can be given for stopping one of the medications, more likely the thiopurine.

6. Gut 2013; 62: 689-94.  Risk of ischemic heart disease in patients with inflammatory bowel disease: a nationwide Danish cohort study.  From 1997 to 2009, the authors compared 28,833 IBD persons to >4.5 million persons without IBD who were matched for age, gender, socioeconomic status, and calendar year.  With a mean follow-up of 13 years, they identified a 59% higher incidence rate of ischemic heart disease in patients with IBD.  Long-term use of immunosuppressive medications, such as azathioprine and anti-tumor necrosis factor-alpha agents, was not associated with an increased risk of ischemic heart disease.

7.   Gastroenterol 2013; 145: 1459-63.  AGA Guideline for Use of Thiopurines, Methotrexate, and Ant-TNF-alpha Biologic Drugs for the Induction and Maintenance of Remission in Inflammatory Crohn’s Disease. This reference was previously noted in blog (with a link) AGA Guidelines for the Use of Thiopurines and Anti … – gutsandgrowt.  The print version does have a nice algorithm (pg 1463).  The accompanying technical review: Gastroenterol 2013; 145: 1464-78.

8. BMJ 2013;347:f6633. Free full-text BMJ article PDF. (Thanks to Mike Hart for this reference) From the abstract:  During 3 421 972 person years of follow-up, we documented 284 cases of Crohn’s disease and 363 cases of ulcerative colitis. The risk of Crohn’s disease was inversely associated with physical activity (P for trend 0.02). Compared with women in the lowest fifth of physical activity, the multivariate adjusted hazard ratio of Crohn’s disease among women in the highest fifth of physical activity was 0.64 (95% confidence interval 0.44 to 0.94). Active women with at least 27 metabolic equivalent task (MET) hours per week of physical activity had a 44% reduction (hazard ratio 0.56, 95% confidence interval 0.37 to 0.84) in risk of developing Crohn’s disease compared with sedentary women with ❤ MET h/wk. Physical activity was not associated with risk of ulcerative colitis (P for trend 0.46). The absolute risk of ulcerative colitis and Crohn’s disease among women in the highest fifth of physical activity was 8 and 6 events per 100 000 person years compared with 11 and 16 events per 100 000 person years among women in the lowest fifth of physical activity, respectively. Age, smoking, body mass index, and cohort did not significantly modify the association between physical activity and risk of ulcerative colitis or Crohn’s disease (all P for interaction >0.35). Conclusion In two large prospective cohorts of US women, physical activity was inversely associated with risk of Crohn’s disease but not of ulcerative colitis.

Comment: While physical activity may directly reduce the risk of Crohn’s disease, it could also be an epiphenomenon of another unmeasured variable (eg. dietary habits) that modifies this risk.

Related blog post:

Understanding IBD Therapy Risks -A Good Link | gutsandgrowth  Provides link to useful 6-minute internet video for families.