Category Archives: Pediatric Gastroenterology Intestinal Disorder

Cyproheptadine for dyspepsia

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A retrospective open-label study has shown that cyproheptadine can be effective for children with dyspeptic symptoms (J Pediatr 2013; 163: 261-7) –thanks to Mike Hart for suggesting this reference.

Methods: In this study, 80 children (65% female) received cyproheptadine for refractory upper gastrointestinal symptoms, including nausea, early satiety, vomiting, retching after fundoplication, and abdominal pain.  The median age was 9.8 years; 48 children were <12 years.  The median dose was 0.19 mg/kg/day and median duration of treatment was 20 weeks.  All patients had undergone upper endoscopy with biopsy.  Gastric emptying studies were undertaken in 52 patients and antroduodenal manometry in 23 patients.

Results:

  • 33 (41%) had a significant response and symptoms resolved in 11 (14%); thus, 55% in total had improvement
  • In those without response, gastrojejunostomy/jejunostomy was placed in 7 patients, and botulinum toxin intrapyloric injection was undertaken in 3 patients
  • Better responses were more common in children <12 years and in females (P=0.04 and 0.03 respectively)
  • Early vomiting after eating and retching after fundoplication responded more favorably than other symptoms
  • Side effects: somnolence (16%), irritable/behavior change (6%), weight gain (5%)

How does cyproheptadine work? While this is not known, the authors speculate that the antiserotonin effects may improve gastric accommodation.

Take-home message: Cyproheptadine may help dyspeptic symptoms, especially in children <12 years and in those with vomiting and retching after fundoplication.  A prospective study would be helpful too.

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EPT for Achalasia

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EPT or esophageal pressure topography (using high-resolution manometry) can help predict outcomes for achalasia (Gastroenterol 2013; 144: 718-25, editorial 681-83).

Background:  Patients with achalasia often present with dysphagia, chest pain, and regurgitation.  These symptoms result from impaired lower esophageal sphincter relaxation and aperistalsis.  While the main treatment has focused on disruption of the sphincter, esophageal body pressures may be important in long-term outcomes.

Three patterns of esophageal body pressures with achalasia:

  • type 1 absence of peristalsis and minimal pressurization
  • type 2 absence of peristalsis with panesophageal pressurization (≥30 mm Hg)
  • type 3 evidence of spasm

According to the cited study which reviewed data from 176 patients in the European achalasia trial (time period: 2003-2008, 18-75 year old), success rates were better with type 2 achalasia (96%, n=114) compared with type 1 (81%, n=44) or type 3 (66%, n=18).

In addition, the EPT findings may influence treatment selection.  Pneumatic dilation (PD) was more successful than Heller myotomy (HM) for type 2 patients (100% vs. 93%, p < 0.05).  However, HM was considered successful more frequently for patients with type 3 achalasia (86% vs. 40% –though not statistically significant due to small numbers).  For type 1, no significant difference was noted between HM and PD at 2 year followup, 81% vs. 85% respectively.

The commentary discusses some of the pertinent issues.   For example, HM may be better than PD among type 1 patients; the exclusion of patients with severe dilatation of esophagus.

Take-home message (from editorial) “The task at hand is to determine whether these distinct categories truly matter in clinical practice…it seems that the subtypes of achalasia do have prognostic value…we …need to determine…whether subtypes can inform treatment options.”

Elevated Celiac Serology Associated with Reduced Infant Birth Weights

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Using a population-based study of 7046 singleton pregnancies (from the Netherlands), the authors of a recent study have shown an inverse relationship between levels of anti-tissue transglutaminase IgA (TTG) antibodies and fetal growth (Gastroenterol 2013; 144: 726-35).

Results:

  • Newborns of positive TTG (>6 U/mL) weighed 159 g less at birth than newborns of mothers who tested negative for TTG.  In addition, newborns with mothers who had intermediate TTG levels ( 0.8 U/mL to 6 U/mL) had growth restriction of 53 g.
  • Among the intermediate TTG group, the results were more pronounced (2-fold greater) in those carrying the HLA risk molecules for celiac disease.
  • These birth weight changes were not associated with maternal nutritional status or deficiencies related to hemoglobin, iron, folate, or vitamin B12 deficiency.
  • Gestational age was not affected by TTG titers.

In the discussion, the authors note that other studies have shown that undiagnosed celiac disease increases the risk for intrauterine growth retardation; this risk can be eliminated by treating celiac disease.  The latter is a risk factor for lower neuropsychological performance.  This study was the first that took into effect the different TTG titers and correlated with additional nutritional parameters.

The authors speculate that celiac disease could have direct effects on the placenta.  In addition, other nutritional parameters could play a role such as vitamin D and calcium which were not included in this study.  Another important consideration is that celiac disease can result in increased miscarriages.  As a result, the “true” effect on newborn growth may be underestimated due to a “survivor bias.”

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Fecal Transplants -NY Times Opinion Piece

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The following link (thanks to Kayla Lewis) to a recent NY Times article provides a first hand anecdotal account of fecal microbiota transplant for an adult patient with ulcerative colitis and discusses the use of FMT for Clostridium difficile infections.

http://opinionator.blogs.nytimes.com/2013/07/06/why-i-donated-my-stool/?ref=health

Bottom-line: Expect more questions about this emerging treatment.

Also, a quick way to keep up on NY Times -follow the twitter feed: @nytimesHealth

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Wireless motility capsule -emerging for pediatrics?

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Currently, there are limited options for detecting gastrointestinal motility abnormalities.  The most definitive current evaluation is antroduodenal manometry (ADM) which remains restricted to a few specialized pediatric centers (coming soon to Children’s Center for Digestive Healthcare/Children’s Healthcare of Atlanta –Fall 2013).  And, of course, in many cases of defined motility disorders there are limited available treatments.  This situation has prompted one of my colleagues to state that motility testing is like getting the license plate of the bus that hit you.

A wireless motility capsule has the potential to facilitate motility testing.  A recent study explores it use in 22 patients (8-17 years) referred to a motility center (J Pediatr 2013; 162: 1181-7). The wireless motility capsule, also marketed as the SmartPill, has received FDA approval for use in the diagnosis of gastroparesis and constipation.  It measures intraluminal pressure, temperature, pH, and allows calculation of transit times in different segments of the GI tract.

Methods:

All patients underwent antroduodenal manometry, gastric empyting study (GES), and wireless motility capsule study.  The GES was performed with a 2-hour protocol.  The patient was given a standardized meal of 2 eggs, toast, and jelly with Tc-99m labeled eggs.  A GES was abnormal if >50% of labelled material was in the stomach at 2 hours. Similarly, the wireless motility capsule was ingested immediately prior to a similar standardized meal; this test was performed on a consecutive day with ADM testing.

Results:

  • In the paper, Table II & III lists the values for each test and includes which data was missing.
  • Based on ADM testing: 8 patients had rumination, 10 had normal motility, and 3 had abnormalities (1 with antral hypomotility, 1 with neuropathic dysmotility, 1 with hyperactivity/rumination).
  • Based on wireless capsule, 10 patients had severe gastroparesis.  Of these 10 patients, the ADM was normal in 4 and abnormal in 6.

The authors point out that the wireless motility capsule had excellent sensitivity but only moderate correlation between scintigraphic GES as well as ADM studies.  One possible reason for increased identification of gastric emptying disorders for the capsule include the use of 2-hour rather than 4-hour GES.  In addition, in symptomatic patients, those with normal GES and normal ADM may still have contractility abnormalities  that can be identified with capsule test.

One limitation of the study was the fact that migrating motor complexes (MMCs) was detected in all patients by ADM (as well as by capsule).  As such, there was no opportunity to identify potential false-positive in patients without MMCs.  Similarly, healthy children were not studied and this limits the findings to a highly selected cohort of children referred for motility evaluation.

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Never quite right

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After esophageal atresia (EA) repair, problems with reflux and dysphagia effect up to 75-100% of patients.  A new study, JPGN 2013; 56: 609-14, helps provide some understanding why the esophagus is never quite right in these patients.

High resolution esophageal manometry (HREM) was performed in 40 patients with a median age of 8 years at three centers. Data was obtained primarily by chart review; in addition, symptomatology at the time of HRE#M was evaluated through a self-assessment questionnaire completed by the child or his primary caregiver.  35 patients had type C EA which typically accounts for 80-85% of all EA cases. Type C EA refers to a proximal esophageal pouch and a distal tracheoesophageal fistula (TEF).  5 patients had type A. Type A EA is an EA without a distal TEF. At the time of the HREM, 7 (18%) were considered asymptomatic.

Findings:

  • Three different motility patterns were identified: aperistalsis in 15 (38%), pressurization in 6 (15%), and distal contractions in 19 (47%).
  • Aperistalsis occurred primarily in patients with long-gap defects and/or following anastomotic leaks. 8 of 15 patients with aperistalsis had undergone fundoplication.
  • Pressurization (as shown in Figure 1) was when contraction of the entire esophageal body  occurred at once rather than in a progressive manner from proximal to distal esophagus. Distal contraction pattern indicated an absence of proximal esophageal contractions. 4 of 6 patients with pressurization pattern had undergone previous fundoplication.
  • Motility patterns were not predictive of symptoms.  Asymptomatic patients were noted with all three patterns.  However, gastroesophageal symptoms predominated in the aperistalsis group.  Dysphagia was frequent in all three groups.

Study limitations included retrospective data, and small numbers of patients. Furthermore, in patients with long-standing esophageal problems, “asymptomatic” may be related to the patient not knowing what “normal” feels like and may be related to compensatory behaviors.

While HREM explains the pathophysiology in EA patients, given the lack of effective medical treatments for motility disturbances, upper endoscopy is likely to be more useful for clinical management by identifying esophagitis and possibly Barrett’s esophagus.

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Barrett’s Esophagus –refer to cardiology?

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According to a study which examined cause-specific mortality, patients with Barrett’s esophagus may be better off following up with a cardiologist than a gastroenterologist (Gastroenterol 2013; 144: 1375-83).

This study derived data from UK’s Clinical Practice Research Datalink.  8448 patients with Barrett’s esophagus were matched with 155,212 controls based on age, sex and general practice.

Key findings:

  • Patients with BE had increased risk of death from esophageal cancer leading to a 10-year risk of 1.9%.  The absolute mortality rate due to esophageal cancer was 1.44 per 1000 person-years.  Compared to the general population, this was a 4.5 fold relative increase.
  • Ischemic heart disease resulted in 168 patient deaths, nearly 4-fold the number that died of esophageal cancer.
  • Overall, individuals with Barrett’s esophagus had a 21% relative increased risk of all causes of death; the majority were not due to esophageal cancer.  32% were related to circulatory disorders, 24% were due to nonesophageal cancer, and 15% were due to respiratory disease.

While this was a large study, there remain several limitations; most of these are due to reliance on electronic records for the diagnosis of Barrett’s.  Also, some individuals with Barrett’s may have been identified due to other high risk conditions such as cirrhosis (endoscopy for varicose) which could contribute to excess mortality.  In addition, many controls likely had undiagnosed Barrett’s.  Even the attribution of the cause of death can be quite difficult, especially with a database study.

Nevertheless, the population-based setting likely means that the results are likely meaningful to a broad population.

Take-home message: While Barrett’s esophagus increases the risk of death from esophageal cancer, it is possible that strategies which focus on nonesophageal causes of death may be more effective than esophageal surveillance for increasing longevity.

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Mixed-review for Thiopurines

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In this era of biologic agents for inflammatory bowel disease (IBD), the estimation of the risks and the benefits of thiopurines has been changing (Clin Gastroenterol Hepatol 2013; 11: 395-97).

The referenced article is an editorial that reviews new data on thiopurines as well as provide a background for their usage.

Main points:

  • After the SONIC trial, the usage of combination therapy in many IBD patients has regained favor with the main question: “How long to continue combination therapy?”
  • STORI trial evaluated withdrawal of infliximab (IFX) in patients on combined therapy.  More than 40% of patients who were withdrawn from IFX relapsed at 1 year.
  • After >20 years of thiopurine usage, more data is available on both short-term and long-term risks/benefits.  The risk of lymphoma in IBD patients on thiopurines is “4-fold increased…in the 6 evaluated studies.” Nonmelenoma skin cancer risk is increased by a hazard ratio of 5.9 in ongoing users and 3.9 in past thiopurine users.
  • At the same time, more recent studies have lowered the expectation of benefit for thiopurines (AZTEC trial, Cosnes study).

Related references:

  • Cosnes et al. Gastroenterol 2012; 142: s161.
  • Gastroenterol 2012; 142: 63-70.
  • Med Clin North Am 2010; 94: 93-113.

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Frequency of Functional Pain Overlap in Pediatric Crohn’s Disease

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If a patient with Crohn’s disease has pain, it may signal a flare-up of the inflammatory process.  Other causes like secondary infections, strictures, and functional pain need to be considered as well.  Functional pain can be particularly challenging.  A recent study reports on the prevalence of functional pain overlap in this setting (Inflamm Bowel Dis 2013; 19: 826-31).

This study prospectively enrolled 307 patients from two centers; it was a substudy to a cognitive behavioral therapy trial.

Patients in remission were defined by the following:

  • all normal laboratory findings:erythrocyte sedimentation rate <10, albumin >3.5, C-reactive protein <1 mg/dL
  • absence of clinical signs/symptoms of inflammatory bowel disease: 3 or less stools per day, no bloody stools, no nocturnal stools, no strictures, no concurrent steroid therapy
  • no escalation in medical therapy or clinical relapse in previous 6 months

Results: 139 of 307 patients had abdominal pain.  Among those with pain, 18 (13%) patients had functional abdominal pain (FAP). 10 of the 18 had either a colonoscopy or MRI in the previous year.  In these patients, the median PCDAI was 10.

This study noted a higher rate of depression in patients with both FAP and Crohn’s: 56%. This is compared with 29% of Crohn’s patients in remission without pain and 45% of Crohn’s patients with pain due to active disease.

Key points:

  • Pain with or without active disease can lead to an overestimation of disease activity based on PCDAI.
  • Depression is common in patients with pain, regardless of etiology
  • Current diagnostic criteria for FAP are flawed.  In fact, the Rome III criteria for FAP which specify absence of organic disease.
  • Biomarkers and imaging modalities are the best tools to exclude active disease.

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Treating Allergic Reactions to Infliximab

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This week on the GI bulletin board there was a brief discussion about overcoming allergic/anaphylactic reactions to infliximab.  A reference and a thoughtful response by Athos Bousvaros (in italics) follows:

Inflamm Bowel Dis. 2001 Feb;7(1):34-7. Successful desensitization and therapeutic use of infliximab in adult and pediatric Crohn’s disease patients with prior anaphylactic reaction. Puchner TC, Kugathasan S, Kelly KJ, Binion DG.   

 IN summary:

1.  Premed with 4 days of steroids (1mg/kg up to 40mg), and hydrocortisone day of the infusion.

2.  Give two test doses (0.1 mg, 1 mg), each over 10 minutes,

3.  If no problems, run the infusion over 4 hours instead of two.

 

Getting antibodies to infliximab before the challenge may also be helpful.  If high levels of antibodies are present, the patient may be more likely to fail the challenge. WE can “rescue” about half our patients using this protocol, and keep them on infliximab. IMPORTANT that a physician is around during the challenge.

Given the potential for adverse reactions and the importance of not depleting useful treatments, it is definitely worthwhile to read the entire cited reference rather than the aforementioned summary.

Related blog entry:

Overcoming ATIs | gutsandgrowth