Category Archives: Pediatric Gastroenterology Intestinal Disorder

Data Supporting Miralax

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A summary of the effectiveness of polyethylene glycol for chronic constipation, fecal disimpaction, and as a bowel preparation are presented in a recent article (JPGN 2013; 57: 134-40).

The article provides information on the biochemistry and mechanism of action along with a good number of references –49.

From the summary:

“PEG is an osmotic laxative used in children in the last few years.  It is more effective than lactulose for the treatment of chronic constipation.  It is equally effective compared with milk of magnesia and mineral oil for the long-term treatment of constipation but has a much better acceptance rate…It is a safe medication without any significant adverse effects.  Because PEG can be mixed in a beverage of the patient’s choice, it has excellent long-term patient acceptance.”

Related blog posts:

High Rates of Anxiety Develop in Kids with RAP

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From NY Times review of a recent Pediatrics study:

Children with chronic stomach pains are at high risk for anxiety disorders in adolescence and young adulthood, a new study has found (goo.gl/I2UvHP ), suggesting that parents may wish to have their children evaluated at some point for anxiety.

Researchers at Vanderbilt University tracked 332 children with recurring stomachaches that could not be traced to a physical cause — so-called functional abdominal pain — comparing them as they reached young adulthood with 147 children who had never had such stomachaches.

About half the teenagers and young adults who had had functional abdominal pain as children developed an anxiety disorder at some point, compared with 20 percent of the control group, the researchers found. The vulnerability to anxiety persisted into adulthood even if the pain had disappeared, although the risk was highest if the pain continued.

Forty percent of the children with functional abdominal pain went on to experience depression, compared with 16 percent of those who had never had these stomachaches.

The study was published on Monday in the journal Pediatrics.

“What this study shows is a strong connection between functional abdominal pain and anxiety persists into adulthood, and it drives home the point that this isn’t by chance,” said Dr. John V. Campo, chairman of the department of psychiatry at Ohio State University, who was not involved in the new study….

Chronic abdominal pain affects 8 percent to 25 percent of school-age children. The problem can lead to school absences and take a toll on families.

“Somebody might say, ‘Of course they have mental issues or they are emotionally distressed — it’s because of the pain,’ ” said Lynn S. Walker, senior author of the study and director of the division of adolescent health at Monroe Carell Jr. Children’s Hospital at Vanderbilt.

“But we found even if the pain went away, these adolescents and young adults still have anxiety,” Dr. Walker said. “So maybe we need to treat their anxiety.”

The state-of-the-art treatment for functional abdominal pain is rehabilitative, focused on getting patients to participate in daily activities despite their stomachaches. “There’s no question that there are triggers for the pain, but the problem is in the perception of the pain and adaptation to the pain,” said Dr. Samuel Nurko, director of a functional abdominal pain center at Children’s Hospital Boston.

Dr. Nurko compared the pain to a light on a dimmer switch, which psychological techniques can help children control. “You don’t take away the pain,” he said. “You ‘dim’ it to be able to cope better.”

The new study underscores the importance of screening children with the condition for anxiety or depression, the authors said. Anxious children tend to be good children who are concerned about doing their best, Dr. Walker said, and parents may be flummoxed by the suggestion that such a child could be grappling with a mental health issue.

Related blog link:

Anxiety and Functional Abdominal Pain | gutsandgrowth  This link has additional links on related material.

Thiopurines associated with reduced risk of colon cancer

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A recent study provides some good news for those using thiopurines (6-mercaptopurine and azathioprine) (Gastroenterol 2013; 145: 166-75).

Using the observational cohort enrolled in the French CESAME study (Cancers et Surrisque Associe aux Maladies Inflammatoires Intestinales En France), the authors followed 19,486 patients with IBD.  60.3% had Crohn’s disease, and 30.1% were receiving thiopurine therapy.  The study period was 2004-2007.  At the start of the study, 2841 patients (14.6%) had long-standing extensive colitis.

Among patients with long-standing extensive colitis, the hazard ratio for colrectal high grade dysplasia and cancer was 0.28 for those who received thiopurine therapy compared with those who never received thiopurine therapy.

Thus, this prospective study showed that while colorectal cancer (CRC) was increased in IBD patients with long-standing colitis, this risk was less among the subset who were treated with thiopurines.  Some previous studies have not found a reduction in CRC risk, though they may have been underpowered and biased as these studies came from referral centers.

The authors also cautioned that more than 1/3rd of CRC cases occurred in those without extensive colitis which may necessitate a lower threshold for screening colonoscopy.

Related blog posts:

Magnets: Clear and Present Danger

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As noted in previous blogs (see below for links), ingested magnets represent a significant problem.  Two more studies add data to this issue:

  • JPGN 2013; 57: 14-17.
  • JPGN 2013; 57: 18-22.

The first study relates a retrospective single-hospital experience from 1995-2012 (from Boston).  In total, 112 cases of magnet injuries were identified using an initial computer search followed by manual chart review.  The mean patient age was 6 years.  The incidence rate ratio of 3.44 during the period 2007-2012 indicates a significant uptick in these injuries compared with the prior period. In addition, “office toys” accounted for 18 of 45 injuries during this latter period. Nature of injuries: swallowed magnets accounted for 86% of these injuries with 13 (12%) requiring endoscopic removal and 4 (4%) needing surgical intervention.

The second study analyzed a nationally representative same from the US Consumer Product Safety Commision Database (NEISS) for emergency department (ED) visits involving magnet ingestion in children (< 18 years) from 2002-2011.  NEISS sample includes >100 hospitals and 7 children’s hospitals.  The authors note that searching NEISS is not always straight-forward as specific product codes need to be entered like toy, kitchen gadget, and others.  The findings:

  • 16,386 suspected magnet ingestion related ED visits from 2002-2011
  • 59.4% were boys , 54.7% were younger than 5 years
  • There was a >8-fold increase in visits for these ingestions from 2002 to 2011.
  • Study limitations: NEISS database –likely underestimates problem, and no specific NEISS code for magnets

The authors note that one institution has started screening for magnets prior to MRI after a 5 year-old with unrecognized magnet ingestion developed intestinal perforations after undergoing an MRI for torticollis.

Take-home message: Magnets are, in the words of Tom Clancy, a ‘Clear and Present Danger’ as ingestion of more than one magnet creates a high risk of perforation or fistula.

Related blog posts:

 

 

 

What is Gluten-Free?

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An excerpt from the National Foundation for Celiac Awareness Press Release:

NFCA Press Release about FDA Gluten-Free Labeling Rule

AMBLER, Pa. (August 2, 2013) – The National Foundation for Celiac Awareness (NFCA), a national non-profit organization dedicated to increasing diagnoses and improving quality of life for those with gluten-related disorders, is responding promptly to the U.S. Food & Drug Administration’s (FDA) final rule on gluten-free labeling by announcing new resources for gluten-free consumers to understand the federal regulations.

“For years, gluten-free labels have gone unregulated, putting our gluten-free community in danger,” said Alice Bast, President of NFCA. “We applaud the FDA for finally publishing a standard definition of gluten-free.”NFCA logo

The new regulations state that a food must contain less than 20 parts per million (ppm) of gluten in order to bear a “gluten-free” label. Researchers support less than 20 ppm as a safe threshold for a product to be consumed by individuals with celiac disease and other gluten-related disorders.

“Evidence-based research conclusively supports the 20 ppm level as a safety threshold for gluten-free products,” said Dr. Alessio Fasano, Director of the Center for Celiac Research at MassGeneral Hospital for Children in Boston. “We welcome the new FDA regulations, which will bring us in line with gluten-free labeling regulations for millions of people around the world.”

Related Links:

Thanks to Kayla Lewis for forwarding the press release.

 

TNF Antagonists and Psoriasis

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Using data from the adverse event reporting system (AERS) from the FDA, the authors of a recent report identified a large number of psoriasis rashes which developed among patients receiving tumor necrosis factor α (TNF) antagonists (Inflamm Bowel Dis 2013; 19: 1164-72).

From more than 13 million AERS reports (2004-2011), a total of 5432 reports of psoriasis were noted: 1789 for infliximab, 3475 for adalimumab, and 168 for certolizumab compared with 88 for a control group which consisted of the following medications: propranolol, melamine, and lithium. While the absolute number for certolizumab is lower, the relative risk is similar to infliximab when adjusted for frequency of usage.

The AERS database relies on voluntary reporting and there are numerous reporting biases.  Given that AERS captures only a fraction of all true adverse events, the authors extrapolate that more 15,000 psoriasisiform adverse events occur each.  They note that these reactions typically occur in individuals without a personal or family history of psoriasis.  The onset is variable, but typically occurs 9-11 months after initiating therapy.

Additional references:

  • -IBD 2011; 17: 2512.  n=50.  Skin reactions with adalimumab.  62% of pts develop skin reactions: eczema, acne-like dermatitis, psoriasis-like (6 of 50).  Adalimumab d/c’d in 22%.
  • -JPGN 2010; 52: 230. 6 of 73 pts (8%) developed IFX-induced psoriasis -managed with topical Rx.
  • -Clin Gastro & Hep 2010; 8: xxiv. Image of psoriaform rash assoc with infliximab
  • -Aliment pharmacol Ther 2009; 29: 921-27. Review of psoriaform rash assoc with infliximab. Majority improved when TNF stopped.  Options: Rx w steroids for 3 days around Rx or add MTX.
  • -NEJM 2009; 361: 496. Review of psoriasis.

Unrelated link:

For those of you who do not have teenage sons, perhaps you are not familiar with Jimmy Kimmel’s:  This Week in Unnecessary Censorship – YouTube

What to do with ALTEs?

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While apparent life-threatening events (ALTEs) in infants are quite disturbing, the best management for these events is far from clear. A recent systematic review of ALTEs in infants was undertaken and included studies from 1970-2011 (J Pediatr 2013; 163: 94-9). The authors ultimately identified 37 relevant studies: 18 prospective observational studies and 19 retrospective observational studies.

Results:

  • None of the 37 studies yielded “a high level of evidence for diagnostic or prognostic investigations.”
  • Risk factors for ALTE: prematurity, previous ALTEs, and suspected child maltreatment.
  • Routine screening for gastroesophageal reflux, meningitis, bacteremia, and seizures are “highly unlikely to be helpful in patients who are well-appearing and have no other findings suggestive of a diagnosis.”
  • Testing for GERD “is unnecessary in children with ALTEs.”  “A positive test does not necessarily inform management because causation cannot be established.”  Patients with recurrent ALTEs “may benefit from pH monitoring in combination with symptom recording.

Additional references:

NASPGHAN Consensus guidelines on GERD (2009)

Link: Gastroesophageal Reflux Disease in the Pediatric … – NASPGHAN.o

  • In premature infants, a relationship between GER (i.e. reflux) and pathologic apnea and/or bradycardia has not been established.Despite a lack of convincing evidence, if pathological apnea occurs in the face of pre- existing reflux, then the following two statements are the most common features:
  • Although reflux causes physiologic apnea, it causes pathologic apneic episodes in only a very small number of newborns and infants.
  • When reflux causes pathological apnea, the infant is more likely to be awake and the apnea is more likely to be obstructive in nature.
  • A diagnosis of an acute life-threatening event (ALTE) warrants consideration of causes other than GER (i.e. reflux).Reflux of gastric acid seems to be related to ALTEs (episodes of combinations of apnea, color change, change in muscle tone, choking, and gagging) in < 5 % of infants with ALTE. 
  • -J Pediatr 2009; 155: 516. Bradycardia not improved in preemies treated for GER. n=18. Editorial 464 urges not using GER Rx in neonates –outside clinical trials.
  • -J Pediatr 2009; 154: 374. Apnea associated with reduction in LES tone in premature infants; therefore, GER may be secondary to apnea rather than the reverse. Small study -12 apneic event in 7 infants.
  • -J Pediatr 2008; 152: 365. Compared risk factors with SIDS. One of 153 (0.6%) with ALTE died.
  • -Pediatrics 2005; 116: 1059 & 1217 (editorial). Apnea in preemies is unrelated to GER.
  • -Pediatrics 2004; 113: e128-132. Apnea is unrelated to GER in most preemies; airway problems due to GERD is hard to establish.
  • -J Pediatr 2000; 137: 321 & 298. Poor temporal association between GER & apnea in ALTE patients.
  • -J Pediatr 2001; 138: 355. Metoclopropramide/cisapride do not help apnea in preemies with GER
  • -Pediatrics 2002; 109: 8-11. GER does not cause apnea of prematurity.

Remission in Crohn’s Disease

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A recent article highlights the issue of remission in Crohn’s disease (CD) (Inflamm Bowel Dis 2013; 19: 1645-53).

As noted in previous blog entries (see links below), improvements in remission with ImproveCareNow and with previous drug trials have several limitations due to the current definition of remission.  Currently, even during periods of clinical remission (defined currently mainly by symptoms), laboratory or endoscopic evidence of persistent inflammation can be seen.  Persistent inflammation is likely to lead to progressive bowel damage. With the advent of more effective treatments as well as better biomarkers, a more objective measure of remission is needed.

“Remission is an evolving concept in CD. At its most fundamental level, remission should be a state with little or no risk of disease progression, likely implying the absence of biological evidence of inflammation.”

The authors proposed definitions of remission based on whether the patient has “early” disease or “late” disease.  Early disease “may be defined as disease duration ≤18 months without previous exposure to immunosuppressants or biologics.”

Early disease:

  • Biologic remission (inflammation control): a) mucosal healing on colonoscopy (no ulcers with the exception of a few aphthous ulcers <5 mm in diameter) and/or b) improvements in serum and fecal biomarkers: CRP < 5 mg/L, fecal calprotectin <250 mcg/g
  • Clinical remission in practice (symptom control): complete absence of symptoms; 1-2 formed stools per day without abdominal pain.  In a clinical trial, CDAI <150 points.
  • Outcomes: no disease progression or complications, normal quality of life

Late disease:

  • Biologic remission (inflammation control): a) mucosal healing on colonoscopy (no ulcers with the exception of a few aphthous ulcers <5 mm in diameter) and/or b) improvements in serum and fecal biomarkers: CRP < 5 mg/L, fecal calprotectin <250 mcg/g
  • Clinical remission (symptom control): a: inflammatory symptom improvement (may have residual symptoms due to previous damage or surgery). In clinical trial, CDAI 150-220 points.
  • Outcome: stabilization of noninflammatory symptoms and no progression of structural damage, improved quality of life

The authors goal is to rework remission to include symptom control and histologic/mucosal healing.  This concept is not novel.  Investigators in the adalimumab EXTEND study coined the term “deep remission.” This term referred to patients with both CDAI remission and complete mucosal healing.  Patients who achieved deep remission had improved outcomes, including fewer hospitalizations and fewer surgical resections (Gut 2010; 59: A80).

Bottomline: Improvements in both objective measures of biologic inflammation along with resolution of clinical symptoms are needed to change the long-term outcome for patients with Crohn’s disease.  The definition of remission should reflect this reality.

“When you can measure what you are speaking about and express it in numbers, you know something about it; but when you cannot express it in numbers, your knowledge is of a meagre and unsatisfactory kind” –Lord Kelvin 1883

Related blog entries:

Rethinking top-down treatment?

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Given the effectiveness of biologic therapy and the potential for disease modification, the threshold for “top-down” treatment has been lower at this time as compared with “step-up” treatment.  What about long-term outcomes, does starting soon increase or decrease the likelihood of doing well?  A recent study suggests that “early biologic therapy did not improve disease activity or quality of life” (Inflamm Bowel Dis 2013; 19: 1397-1403).

In this retrospective chart review involving 93 patient’s with Crohn’s disease (between 2004 and 2010), patients whose data was prospectively maintained were categorized into either early biologic therapy or a step-up group. For these patients, the mean age at diagnosis was 28 years.  There were no apparent differences in demographic variables between the groups; however, the early biologic therapy group had higher disease activity and lower quality of life scores at baseline. 20% were current smokers and 61% never smoked.  Disease location was similar in both groups; overall, 35% had ileal disease, 13% colonic disease, 34% ileocolonic, and 7% isolated upper tract disease.

Results:

  • Mean Harvey-Bradshaw index and Short Inflammatory Bowel Disease Questionnaire scores at 3, 6, and 12 months were not different between the groups.
  • Early biologic therapy group had more hospitalizations.
  • No difference in steroid use or surgeries was noted at one year.

Take-home message: This study suggests that differences in outcomes between “top-down” therapy and step-up therapy are more pronounced early in the treatment course but may wane after 1 to 2 years.  However, early biologic therapy “may be a more effective strategy in patients with Crohn’s disease with higher disease activity.”

Relating blog posts:

Injecting steroids for esophageal strictures -does it work?

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A recent report indicates that steroid injections are not effective in patients with cervical anastomotic strictures (Clin Gastroenterol Hepatol 2013; 11: 795-801).

While this double-blind randomized control multicenter study of 60 patients (mean age 63) dealt with a specific subtype of strictures, the implications may be broader.  In this study, all patients had undergone esophectomy with gastric tube reconstruction.  The treatment group had 4 quadrant injections of 0.5 mL (20 mg) of triamcinolone and the control group had saline injections.  After injections, patients had Savary dilation to 16 mm.  Patients were followed for 6 months subsequently.

Results: In the treatment group 45% remained dysphagia-free for 6 months compared with 36% of controls (RR=12.6, p=0.46).  Median number of dilatations was 2 in treatment group compared with 3 in the controls.  One corticosteroid-treated patient developed a probable perforation and was excluded from final analysis. Four patients in the treatment group, and none in controls, developed Candida esophagitis.

No statistically significant decrease in dilatations or symptoms was demonstrated.

In their discussion, the authors review the effects of intraesophageal corticosteroid therapy and previous studies.  “Thus far, RCTs supporting this…are limited and, if available, are only small-sized and not focused on anastomotic strictures.”  According to the discussion, the evidence for steroid injection may be strongest for peptic strictures, primarily based on a small, sham-controlled RCT (Am J Gastroenterol 2005; 100: 2419) which demonstrated lower redilatation rates in this setting.

To prove that steroids would be effective if there was only a 10-20% improvement would take at least 200-750 patients

Take-home message (from authors): the routine use of corticosteroid injections in patients with benign anastomotic strictures cannot be recommended.

Related references:

  • -Refractory strictures (NASPGHAN 2011): =if not >14 mm after 5 sessions.   Complex strictures: >2 cm long, tortuous, or if scope cannot be passed predilatation. Consider Fluoro for complex strictures. Described technique of endoknife if only one-sided stricture which are hard to dilate.
  • -Am J Gastroenterol 2005; 100: 2419.  Double-blind, randomized trial showed benefit of steroid injection for Rx of recalcitrant peptic strictures. Consider triamcinolone along length of stricture; max ~10mg (2-4 mg/injection)
  • -JPGN 2007; 44: 336. n=16 pts. Mitomycin 0.1mg/mL; apply for 2-3min c pledget.
    -JPGN 2006; 42: 437.  Case report of using indwelling balloon for daily dilatation in refractory patients.
  • -Endoscopy. 2006; 38(4):404-7).  Mitomycin C: an alternative conservative treatment for refractory esophageal stricture in children?
  • -JPGN 2005; 41: 35A (pg503).  Use of stents for refractory benign strictures, n=10.
  • -Gastroenterol 1999; 117: 229 & 233. AGA position statement and technical review.

**Dosing regarding triamcinolone or mitomycin C has not been clearly established for esophageal strictures.  Doses listed above are based on my reading of the references but no specific dose is advocated on this posting.