#NASPGHAN19 Postgraduate Course (Part 2)

Here are some selected slides and notes from this year’s NASPGHAN’s postrgraduate course. My notes from these lectures may contain errors of omission or transcription.

Link to the full NASPGHAN PG Syllabus 2019 (Borrowed with permission)

9:00 – 10:20 “Potpourri”

46 Alessio Fasano, MD, MassGeneral Hospital for Children  Celiac disease: Beyond diagnosis

  • Reviewed potential non-biopsy option for diagnosis if anti-TG2 >10 x normal. Pediatricians are not following recommendations –>many children placed on gluten-free diet at lower titer antibody-positivity.
  • Recommends checking Hepatitis B antibody because many children with celiac disease do not seroconvert.
  • TTG levels are good for diagnosis but not as helpful for monitoring after diagnosis.
  • Only 10 out of 1000 are true refractory, about 100 out of 1000 are exquisitely sensitive to gluten

56 Meghana Sathe, MD, UT Southwestern Medical Center The role of the gastroenterologist and hepatologist in Cystic Fibrosis (CF) care today

  • Fecal elastase monitoring useful for determining need for PERT.
  • Discussed CF liver involvement.  Multilobular cirrhosis, 7% of individuals, is most important liver disease in CF.
  • Modulator therapy can elevate liver enzymes and may need to hold if ALT >5 ULN or lower elevation if elevated bilirubin (see Stop Rules -Practical Advice on DILI)
  • DIOS -for partial obstruction, polyethylene glycol and/or gastrogastrin enemas could be used.
  • Consider treatment of SBBO as well which is frequent with CF.

67 Sonia Michail, MD, Children’s Hospital Los Angeles Update on C. difficile

The slide I liked the best was showing a change in microbiome after FMT which is not in syllabus.

82 Ed Hoffenberg, MD, Children’s Hospital Colorado  What the pediatric GI provider needs to know about cannabis

Disclaimer: NASPGHAN/gutsandgrowth assumes no responsibility for any use or operation of any method, product, instruction, concept or idea contained in the material herein or for any injury or damage to persons or property (whether products liability, negligence or otherwise) resulting from such use or operation. The discussion, views, and recommendations as to medical procedures, choice of drugs and drug dosages herein are the sole responsibility of the authors. Because of rapid advances in the medical sciences, the Society cautions that independent verification should be made of diagnosis and drug dosages. The reader is solely responsible for the conduct of any suggested test or procedure. Some of the slides reproduced in this syllabus contain animation in the power point version. This cannot be seen in the printed version.

Transient Exocrine Pancreatic Insufficiency or Misleading Tests?

A recent retrospective study (J Garah et al. JPGN 2019; 68: 574-77) showed that many cases of exocrine pancreatic insufficiency, based on a low fecal elastase (<200), resolved over ~6 months.

Background:

  • 17 of 43 children had adequate data and no other recognized comorbidities which could explain low elastase levels
  • In these 17 children the median age was 3 years
  • Presenting symptoms were failure to thrive, or diarrhea. Children with known etiologies (eg. cystic fibrosis, Shwachman-Diamond, cholestatic liver disease) were excluded.
  • Median elastase at time of diagnosis was 71

Key findings:

  • Median time for normalization of elastase was 6 months. Patients received pancreatic supplements until elastase normalized.
  • 11 of the 17 had values of elastase <100, and an additional two had values of 105.
  • In all 17 children without identifiable underlying diseases, the pancreatic insufficiency was transient.
  • Only two children had fat soluble vitamin deficiency associated with pancreatic insufficiency

The article discusses the use of elastase for diagnosis of pancreatic insufficiency in comparison to more direct/invasive testing which can be difficult to perform.  It is important to recognize that elastase values are often unreliable in the presence of diarrhea or if diluted by urine.  Repeated assays may be needed to have confidence that elastase

My take: This report identifies “transient pancreatic insufficiency” as a frequent explanation for many children and may represent a postinfectious etiology. Thus, if no comorbidity is identified, the prognosis is favorable in most children.

Sculptured Cypress Trees in Retiro Park, Madrid

Fluctuating Elastase Levels in Infants with Cystic Fibrosis

A recent study sheds light on the variability of elastase levels in both pancreatic sufficient (PS) and pancreatic insufficient (PI) infants with cystic fibrosis (CF) (J Pediatr 2013; 162: 808-12).

After eliminating infants who did not have elastase values prior to 3.5 months and after 9 months, the study consisted of 61 formula-fed infants who had been diagnosed with CF.  Diagnosis was established based on either a positive sweat test or having two known CF mutations.

Background: Pancreatic elastase is produced by pancreatic acinar cells and is not degraded during intestinal transit.  It can be measured while on pancreatic enzyme replacement therapy (PERT) because it is specific for human elastase rather than porcine elastase.  In addition, samples are stable at room temperature for weeks.

Among this cohort, 28 (46%) were homozygous for the F508del mutation. Infants were part of a large docosahexaenoic acid (DHA) study; as such, they were randomized to receive either standard formula or formula supplemented with DHA.  Monthly stool samples were collected.

Results:

  • Of 29 infants with initial fecal elastase <50 mcg/g, all had a value <200 mcg/g at one year.  However, 3 had a value >200 mcg/g at some time during the first year of life.
  • Of 36 infants with initial elastase <100 mcg/g, 32 had a level <100 mcg/g at 1 year.  Only one infant in this group had a value consistent with PS and this infant had a mutation associated with increased likelihood of PS.
  • Of 12 infants with initial values between 100-200 mcg/g, more variability was noted in their multiple samples.  This group accounted for the majority of infants who were reclassified from PI initially to PS after one year of life.  Among all 48 with values <200 mcg/g, 4 were considered PS at final evaluation.  However, 13 had values >200 mcg/g at some point.
  • 13 infants were considered PS at initial evaluation with a value >200 mcg/g.  At the study conclusion, 3 had values <180 mcg/g.
  • The majority of fluctuation in elastase values occurred during the first 6 months of life.

These results lead to the following conclusions:

  1. Fluctuations in elastase levels during the first year of life indicate that some infants with PS become PI and vice versa.  Retesting at one year of life is important.
  2. The authors recommend that all CF patients with elastase values below 200 mcg/g receive PERT.
  3. One can extrapolate these findings to other populations.  A single normal or abnormal elastase value may not indicate ultimately whether a patient will remain pancreatic insufficient or sufficient. Though, values <50 mcg/g are more likely to indicate persistent PI status.

The authors do provide some speculation regarding these fluctuations.  They note that “a fecal elastase obtained very early in life might not reflect the child’s true functional pancreatic status.  Intestinal mucosal damage can cause secondary pancreatic insufficiency by decreasing signaling of the pancreas from enteroendocrine cells.”

Related blog links:

References:

  • -JPGN 2007; 44: 219.  Use of elastase in CF.  Pancreas secretes elastase; not degraded & does not cross react with porcine elastase, thus allowing measurement even in individuals on enzyme treatment.  Excellent sensitivity/specificity.
  • -J Pediatr 2004; 145: 322 & 285,  A fecal elastase-1   >100mcg/g has a 99% predictive value for excluding pancreatic insufficiency.
  • -JPGN 2003; 36: 314, 392.  Fecal elastase-1 is marker for exocrince pancreatic function & enteropathy.
  • J Peds 2009; 155: supplement. Clinical practice guidelines for infants/children <2 years of age with CF:
  1. -routinely give salt 1/8-1/4tsp/day
  2. -measure elastase & supplement if PI
  3. -Dose: 2000-5000 units lipase per feed –can go as high as 2500 units/kg (max daily 10000 units/kg/day)
  4. -monitor & supplement ADEK
  5. -consider 7% saline Rx & azithromycin in symptomatic

Learning a lot from ChiLDREN (part 1)

Several recent studies highlight the benefits of multisite collaboration to study infrequent pediatric liver problems.  In one of these, it is shown that pancreatic insufficiency (PI) is not a common problem for patients with Alagille syndrome (JPGN 2012; 55: 612-614).

In these studies, the Childhood Liver Disease Research and Education Network (ChiLDREN) collected prospective longitudinal observational date from multiple centers, 16 in this study.

150 subjects who met criteria for Alagille syndrome were enrolled between December 2007 to September 2010.  42 had fecal elastase results available.  Elastase results were characterized as normal if >200 μg/g, indeterminant if 100-200 μg/g, and pancreatic insufficient if <100 μg/g.

  • 40/42 (95%) had normal results
  • 2/40 (5%) were indeterminant

The collaborative study provides a few teaching points:

  1. Fecal elastase is a very reliable tool for detecting exocrine PI with a 99% negative predictive value for ruling out PI.
  2. Previous results suggesting that PI was common in Alagille syndrome were flawed due to the fallibility of previous secretin stimulation testing and due to the occurrence of steatorrhea induced by impaired bile salt secretion

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