Category Archives: Pediatric Gastroenterology Intestinal Disorder

Fluctuating Elastase Levels in Infants with Cystic Fibrosis

Posted on by

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

Websites recommended by GI families

Posted on by

Some useful websites that I recommend have been identified by patient’s or their families. They include the following:

As an unrelated aside, a recent commercial might be of interest to anyone who enjoys a little ‘potty humor:’  Kmart’s ‘Ship My Pants’ Commercial [HD] – YouTube

Related blog post:

Oley: Check it out | gutsandgrowth

Paris Classification of Pediatric Crohn’s Disease

Posted on by

A recent study described the phenotypic results of a prospective, web-based registry of new-onset pediatric inflammatory bowel disease (IBD) in 17 European countries and Israel (Inflamm Bowel Dis 2013; 19: 378-85).

The EUROKIDS Registry included 582 pediatric Crohn’s Disease (CD) patients classified according to Paris classification:

  • 16% with L1 involvement of the terminal ileum only
  • 27% with L2 colonic involvement only (more common in younger children)
  • 53% with L3 involvement of the ileum and colon
  • 4% with L4 isolated upper GI disease.  Upper tract disease can be further subdivided into L4A esophagogastric disease and L4B jejunal/proximal ileal disease.
  • *Upper GI disease can coexist with L1, L2 or L3.  In this study, 34 (6%) had esophageal involvement, 102 (18%) had gastric involvement, and 100 (17%) had duodenal involvement.
  • In this study, 165 of the 507 patients did not undergo small bowel imaging. Of those who did, 64% had small bowel follow-through, 38% had MRI, 6% CT, and 5% video capsule.

Other findings:

  • Perianal disease (e.g.. fistula or abscess) noted in 9% at diagnosis.
  • Granulomas were found in 43% of patients who had biopsies from at least 10 segments of the GI tract
  • 82% of CD patients had nonstricturing, nonpenetrating disease (B1), 12% had stricturing disease (B2) and 5% had penetrating disease (B3).  2% had both stricturing and penetrating disease.
  • Extraintestinal manifestations were seen in 20% of the study population.
  • The authors estimated that the diagnostic yield of upper endoscopy  in the workup for pediatric IBD was  7.5% and for intubation of the ileum/ileoscopy 13%.

Study limitations included a selection bias of centers and pediatric gastroenterologists with a special interest in IBD.  Also, in this registry, older adolescents are underrepresented. In about one-third of the centers, patients older than 15 years are seen primarily by adult gastroenterologists.

Don’t Fix What’s Not Broken

Posted on by

A recent study provides information about elective switching from infliximab (IFX) to adalimumab (ADA) in stable Crohn’s disease (CD) (Inflamm Bowel Dis 2013; 19: 761-66).  As a practical matter, patients and families inquire about switching therapy due to potential convenience and flexibility.  Thus far, there is little data to guide clinicians.  As such, the authors explored this question by designing an open-label study which would allow enrollment of any patients who had stable disease for >6 months (Harvey-Bradshaw Index ≤ 8) on IFX therapy.

In total, 29 patients with CD were enrolled with an average age of 39.  Twelve had previous resections.

Key results:

  • 21 patients (72%) were able to remain on ADA at 54 weeks.  8 patients discontinued ADA due to disease activity (n=3), side effects (n=4), or other symptoms (n=1).
  • 4 patients were restarted on IFX therapy; 1 required dose intensification.
  • At 54 weeks, 13 patients indicated a preference for IFX due to efficacy (n=9) or safety profile (n=4).  12 patients indicated a preference for ADA.  4 patients had no preference.

The authors state that a recommendation to avoid elective switching.  In their study, 28% were not able to be maintained on ADA therapy, more patients preferred IFX after experiencing both therapies, and switching back to IFX has been associated (in some) with reduced efficacy.  The main concern with an elective switch is the potential loss of response with very limited therapeutic alternatives.

The authors note that their study showed better results with an elective change than a previous study (the SWITCH trial, n=73).  In the SWITCH trial, “elective switch from IFX to ADA in patients with stable CD led to 47% of patients requiring dose intensification or interruption of treatment” in the ADA arm compared with 16% of patients who continued IFX therapy.  (Adalimumab in Crohn’s Disease Controlled by Infliximab)

The better outcomes in the current trial may have been due to selection of patients with milder disease and the more frequent use of concomitant immunosuppression.  In the current trial, 52% had concomitant immunosuppression (48% thiopurine, 4% methotrexate); in contrast, only 17% received concomitant immunosuppression in the SWITCH trial.  Another important difference was that the patients in the current trial received 160-80 loading doses rather than 80-40 induction.  Also, the trial designs were different.  The current trial enrolled patients without randomization; in contrast, the SWITCH trial randomized some patients to continue IFX and others to change to ADA therapy.

Related reference:

  • -Gut 2012; 61: 229-34. SWITCH trial.

Related blog references:

Trouble Sleeping and Gastroesophageal Reflux

Posted on by

Determining whether reflux is causing an infant to have trouble sleeping is quite difficult as a practical matter.  A recent retrospective study adds information to this topic but opens up a can of worms (JPGN 2013; 56: 431-35).

The main problem is that clinical reflux occurs in the majority of infants and that sleeping problems are ubiquitous as well.  This leaves the door open to testing a lot of infants. At the  same time, effective therapeutic options are limited.  So, identifying that reflux is causing trouble sleeping, when feasible, may be akin to getting the license plate of the truck that ran you over.

In this retrospective study (2008-2010) of 24 infants with a median age of 5 months, 18 were receiving acid-suppressing medications prior to evaluation.  Determination that reflux was causally associated with awakenings and arousals was determined with symptom association probabilities (SAP) based on 2-minute measurement intervals with multichannel intraluminal impedance/pH monitoring/simultaneous polysomnography; SAP was considered significant if ≥95%.

Findings: Seven patients had a positive SAP for arousals due to GER (5 exclusively related to non-acid GER).  Nine patients had a positive SAP for awakenings due to GER (4 exclusively related to non-acid GER).

There were several limitations of the study.  Besides the small size, the main limitation of this retrospective study was a selection bias.  Other limitations included a large number of patients with comorbid conditions and the coincident usage of acid-suppressing medications.  19 of 24 patients had one or more significant comorbid conditions: laryngomalacia in 10, prematurity in 5, genetic syndromes in 3, esophageal atresia in 1, and SLE in 1.

Take-home point: This study is in agreement with the general consensus that GER (acid and non-acid) may trigger sleep interruptions in infants. Nevertheless, given the lack of impact on management, only rarely will infants with poor sleep benefit from these investigations.

Related blog entries:

How Histamine-2 Receptor Blockers May Cause Problems for Preemies

Posted on by

Previously, this blog has noted an association between ranitidine usage and necrotizing enterocolitis (NEC) (see below).  Now, another study provides insight into a potential mechanism (JPGN 2013; 56: 397-400).

This study examined the fecal microbiota in 76 premature infants who were enrolled in a case-controlled, cross-sectional study.  25 infants receiving H2-blockers were compared with 51 matched controls.

Results: microbial diversity was lower, relative abundance of Proteobacteria was increased, and Firmicutes was decreased in the stools of infants receiving H2-blockers.

While this study did not specifically examine the effect of H-2 blockers on NEC (no infants in this study had NEC), there are multiple reasons why the findings should be a cause for concern.

  • Gastric acidity acts as a natural defense against bacterial growth and H-2 blockers (as well as proton pump inhibitors) inhibit this defense
  • Previous studies have shown an association between NEC and with diminished microbial diversity/increased Proteobacteria.  Proteobacteria include well-known pathogens like Klebsiella, Shigella, Escherichia coli, and Citrobacter.

Related blog entries:

Budesonide for Ulcerative Colitis

Posted on by

Budesonide (Uceris) has been formulated with the MMX delivery technology and now has been FDA approved for mild to moderate ulcerative colitis in adults.  The potential advantage of budesonide compared with conventional corticosteroids is for targeting anti-inflammatory activity to the colon with less systemic side effects.  The potential downside includes the high cost.  According to one website (see below), the average wholesale cost is just below $1500 per month.  In addition, only a minority of individuals responded to budesonide in published studies:

Induction of Remission in Studies 1 and 2 (reference below)

Treatment Group

Study 1 n/N (%)

Study 2 n/N (%)

UCERIS 9 mg

22/123 (17.9)

19/109 (17.4)

UCERIS 6 mg

16/121 (13.2)

9/109 (8.3)

Reference Arm*

15/124 (12.1)

13/103 (12.6)

Placebo

9/121 (7.4)

4/89 (4.5)

Treatment Difference between UCERIS 9 mg and Placebo (95% CI)†

10.4% (2.2%, 18.7%)

12.9% (4.6%, 21.3%)

Data for budesonide for pediatric patients with ulcerative colitis is not available.

ADHD patients– not at increased risk for Celiac disease

Posted on by

It seems that so many conditions have been linked to Celiac disease; perhaps, Celiac disease is to health problems as Kevin Bacon is to actors (Six Degrees of Kevin Bacon – Wikipedia, the free encyclopedia).  A notable exception may be ADHD (JPGN 2013; 56: 211-14).

In a prospective study from Turkey, a total 362 children between 5 and 15 years who were diagnosed with ADHD at a child psychiatry clinic (2007-2010) were evaluated.  Serum levels of tissue transglutaminase (TTG) IgA and IgG antibodies were obtained; serum IgA levels were determined in those with isolated TTG IgG positivity.  In addition, the authors identified a matched control group of 390 children.

Results:

  • TTG IgA seropositivity was noted in 4 patients with ADHD (1.1%) compared with 3 controls (0.8%).  Only one of the four ADHD patients had histologic evidence of celiac disease (0.27%).
  • There was a higher incidence of TTG IgG in the ADHD group, 3.9% compared with 0.5% in controls. However, serum IgA was normal in all of these patients (indicating that TTG IgA was likely reliable).  Followup TTG IgG testing was negative consistent with false positivity.

Perhaps this result is not surprising to those who have seen a ‘classic’ celiac disease presentation.  In these children who often had physical signs of malnutrition including a bloated abdomen, the effect of a gluten-free diet changed a “perfectly-behaved” (=listless) child into a very active toddler.  So, in these children, a gluten-free diet but not celiac disease triggered hyperactivity.

Related blog posts:

.

Why Social Media is Important for Doctors

Posted on by

The following link is to a NY Times article and below are a few excerpts:

http://well.blogs.nytimes.com/2013/03/21/doctors-and-their-online-reputation/?smid=tw-nytimeshealth&seid=auto

 “While most doctors have come to terms with the fact that their patients routinely go online for information about what ails them, they remain uneasy about a more recent trend: the Internet is quickly becoming the resource of choice for patients to connect with, learn more about and even rate their doctors. And while many have used Facebook, Twitter, LinkedIn or online medical community sites like Sermo to engage with friends and colleagues, few have communicated with patients as, well, doctors. Most abstain for one simple reason: they aren’t sure how to be a doctor online.”
The link discusses a new book by Kevin Pho (KevinMD) and Susan Gay.  “In“Establishing, Managing and Protecting Your Online Reputation: A Social Media Guide for Physicians and Medical Practices,” “Dr. Pho and Ms. Gay offer highly organized key points, useful statistics and exuberant testimonials from doctors who have successfully leapt over the digital divide. There is plenty of practical advice, too, on topics ranging from what to post and when to engage, confer or rebuff, to how to decide what might be unethical or T.M.I. (Answer: ‘Can you say it aloud in a full hospital elevator?”)The book is an excellent and helpful resource. But what elevates it beyond the category of valuable how-to manual is the passionate call to arms that resonates from all those well-enumerated directions and clearly labeled diagrams. Like it or not, the authors warn, the Internet has profoundly changed the patient-doctor relationship, and doctors must embrace its effects on patient care — or risk losing their own influence.'”The article also notes that on the internet many individuals without any scientific background may have equal footing with recognized experts.  Another subject broached in this article is the issue of ranking physicians.”The biggest risk of social media in health care,” they conclude, “is not using it at all.”
Related website resources:

Clostridium difficile in IBD

Posted on by

A useful review of Clostridium difficile infection (CDI) in the inflammatory bowel disease population has been published and makes several useful points (Inflamm Bowel Dis 2013; 19: 194-204). (Thanks to Ben Gold for suggesting this reference.)

Key points:

  • The incidence of CDI in IBD patients is increasing (faster than general population).  The prevalence of CDI in IBD was nearly eight times greater than non-iBD gastrointestinal patients in a recent population-based study (37.3 cases vs. 4.8 cases per 1000 discharges).
  • Though there is some conflicting data, CDI appears to worsen both short- and long-term outcomes in IBD patients.
  • Carriage (asymptomatic) rates in outpatient IBD patients is higher than the general population (8.2% vs. 1%) according to a recent study.
  • Endoscopic appearance of CDI is rarely classic in the setting of IBD.  Only 13% of hospitalized IBD patients with CDI had pseudomembranes (J Crohns Colitis 2010; 4: 194-98).  Thus, endoscopy has little utility in helping to distinguish IBD flare from superimposed infection.
  • Unique IBD risk factors for CDI: colonic disease and steroid use.
  • The review has a thorough discussion of the available testing and recommends testing only patients with unformed stools unless an ileus is present.
  • For recurrent disease, the authors suggest prolonged tapered vancomycin in adults: 125 mg QID for 10-14 days, then 125 mg BID x 1 week, then 125 mg QD x 1 week, then 125 mg QOD for 2-8 weeks.  Alternative approaches could included fidaxomicin, IVIG/antibody therapy, and fecal transplantation.

Related blog posts: