Category Archives: Pediatric Gastroenterology Intestinal Disorder

IBS Symptoms in Patients with Celiac Disease

Posted on by

While a gluten-free diet (GFD) is the optimal treatment, adult patients with celiac disease still have a high prevalence of irritable bowel symptoms (IBS) (Clin Gastroenterol Hepatol 2013; 11: 359-65).

The authors examined the prevalence of IBS symptoms by reviewing cross-sectional and case-control studies in adults with celiac disease (≥16 years old).  Initially, the literature search identified 624 studies; the vast majority did not fit the study requirements.  Seven studies (n=3383 participants) reported the prevalence of IBS symptoms in celiac disease.  These studies took place between 2002 to 2011 in five different countries.  IBS was defined using either Rome I, II, or III criteria.  Only one of these studies assessed adherence to a GFD by using negative tissue transglutaminase antibodies on the 2 most recent outpatient visits.

Results: IBS symptoms were present in 38% of all patients with celiac disease.  The pooled odds ratio was higher for celiac disease than controls (OR 5.6, with 95% CI 3.23-9.7).  Nonadherence to a GFD increased the likelihood over those who were adherent by an odds ratio of 2.69

Take-home message: IBS symptoms are present in a high proportion of patients with celiac disease.  While a GFD may improve these symptoms, some individuals will have persistent symptoms.

Related blog entry:

Is functional pain more common in children with … – gutsandgrowth  Previous blog entry examines functional abdominal pain in children and celiac disease.

Additional references:

  • -JPGN 2011; 53: 216. Case report of refractory celiac treated with 6-MP.
  • -Clincal Gastroenterol & Hep 2011; 9: 13. Celaic with persistent symptoms: consider poor adherence**, SBBO*, pancreatic insufficiency*/subclinical pancreatitis, refractory celiac (rare), PLE, giardia, malignancy, lactose intolerance, functional d/o*, microscopic colitis, Crohn’s*, NSAIDs
  • -Gastroenterol 2009; 136: 81, 91, 99, 32. Refractory celiac can be divided into 2 types; 2nd type assoc c abnormal IEL and has poor prognosis. Risk of non-hodgkins lymphoma 3.8-5 .3 fold over gen population in larg Sweish study. n=37869 c NHL, 236,408 controls, 613,961 1st degree relatives. Relatives c 2 fold risk. Absolute NHL risk ~1 in 1421 person-yrs for celiac pt.
  • -Clin Gastroenterol & Hep 2007; 5: 445-450. Causes of nonresponsive celiac.
  • -NEJM 2007; 356: 2548. Nonresponsive due to inhaled gluten in farm setting.
  • -Clin Gastro & Hep 2007; 5: 445. Gluten exposure in 36%, IBS n 22%, lactose intol 8%, refractory CD 10%
  • -Gastroenterol 2011; 141: 1187.  Prevalence of celiac similar in IBS as general population though higher number (7%) with celiac antibodies (esp gliadin).

Impaired Esophageal Function in Neurologically-Impaired Neonates

Posted on by

There are a multitude of gastrointestinal problems that develop in infants who have hypoxic-ischemic encephalopathy (HIE).  One of the most pressing needs is determining how best to feed these infants.  A recent study provides more information on the aberrant esophageal function of these infants (J Pediatr 2013; 162: 976-82).

Design:  provocative esophageal manometry was performed in 34 neonates (27 with HIE and 7 controls).  HIE inclusion criteria included the following:

  1. >36 weeks gestational age
  2. acute perinatal event: abruption, cord prolapse, severe fetal heart rate abnormality
  3. signs of encephalopathy per Sarnat staging at birth

The characteristics of the HIE neonates is further defined and divided into those who were treated with hypothermia and those who received traditional care.  All but one infant had an abnormal brain MRI.

Key results:

  • Peristaltic reflexes, upper esophageal sphincter contractile responses (much greater in HIE patients), lower esophageal sphincter relaxation responses (much lower in HIE patients) and esophageal body coordination and clearance were all noted to be abnormal.
  • Infants treated with hypothermia had greater upper esophageal sphincter contractile responses and improved esophageal clearance (noted by decreased peristaltic durations).

Overall, this study demonstrates prolonged and poorly coordinated peristaltic responses in neonates with HIE.  There are no effective treatments for this type of esophageal dysmotility.  As such, even with current management approaches including gastroesophageal reflux medications and fundoplication, children with HIE remain at risk for aerodigestive malfunction and aspiration.

Related blog links:

Microparticles and Pediatric IBD

Posted on by

Before reading a recent publication (JPGN 2013; 56: 401-07), I was not aware of microparticles; microparticles may play an important role in the development of venous thromboembolism (VTE).  Pediatric patients with inflammatory bowel disease (IBD) have a higher relative risk of VTE compared to their peers than individuals >60 years of age, though the absolute risk is low.  Much of the pathophysiology underlying the increased VTE risk remain uncertain.

Microparticles have been called “platelet dust” and are microvesicles that are released from the plasma membrane of many cells (leukocytes, red blood cells, endothelial cells, and platelets).

This study examined plasma samples from 33 pediatric patients with Crohn disease (CD), 20 pediatric patients with ulcerative colitis (UC), and 60 healthy controls. Subsequently, microparticles’ procoagulant activity was measured.  The CD and UC patients were consecutively enrolled from the outpatient clinic.  Only 3 patients in each IBD group was receiving a biologic therapy (infliximab). The disease activity and extent were compared with measures of procoagulant activity.

Several assays were undertaken to assess microparticles and thrombin generation. Key findings:

  • Increased procoagulant function of microparticles was identified in all CD patients (active and quiescent) and in UC patients with active disease.
  • A positive correlation was found between disease activity scores and procoagulant activity.

The authors note that elevated microparticles “may play a role in inflammation.” Inflammation and coagulation likely influence each other.  The authors note that VTE risk is greatest during flares but is still increased in patients in remission compared with controls.

The authors do not discuss the relationship of mucosal healing to microparticles or VTE. However, given that clinical remission is not defined currently based on mucosal healing, it would be of interest to know the status of these microparticles and the risk of VTE with mucosal healing. Perhaps the “quiescent” CD patients have ongoing disease contributing to their increased risk of VTE and increased procoagulation function of microparticles.

Related blog entry:

VTE with IBD | gutsandgrowth

**According to previous expert consensus guidelines, “routine heparin prophylaxis cannot be justified in children until better evidence is available to suggest that the benefit outweigh the risks”  (Turner D, et al. Am J Gastroenterol 2011; 106: 574-88).

For the pediatric pancreatologists

Posted on by

Pancreatitis is a terrible affliction whether acute, recurrent or chronic.  While pediatric patients often have “mild” problems from acute pancreatitis, even in these cases the pain is usually severe and the treatment, which consists mainly of holding feedings and providing pain relief, does not impress anyone.

A few recent references do provide more data on several aspects of pancreatitis.

The first reference, J Pediatr 2013; 162: 788-92, provides data on the rare problem of acute necrotizing pancreatitis in children.  This retrospective study encompassing 21 years identified seven children.  CT scan showed necrosis of more than 30% and/or more than a 3 cm area in all of these patients.  Etiologies included medications (L-asparaginase, Valproate, Minocycline), diabetes (n=1), and gallstones (n=1).  No patients needed surgery or died.  After discharge, 5 patients had complications which included pseudocysts, diabetes, and pancreatic exocrine insufficiency.

Key points:

  • CT scan (with contrast) is useful in diagnosis and assessment of severity.
  • Initial presentation is similar to cases of acute pancreatitis without necrosis.  Long-term complications are increased.

The second reference: Gastroenterol 2013; 144; issue 6.  The entire issue is devoted to pancreas issues.  Pages 1272-81 review acute pancreatitis, pages 1282-91 review chronic pancreatitis, and pages 1292-1302 review genetic risk factors.

Page 1288 provides a suggested management algorithm for chronic pancreatitis:

Medical therapy recommendations include alcohol/smoking cessation, counsel regarding nutrition/vitamin D/calcium, consider analgesics (start with tramadol), consider adjuncts for pain (e.g.. neuron tin, SSRI, SSNRI, TCAs), assess exocrine and endocrine function (elastase and HgbA1C), use steroids if autoimmune pancreatitis.

If medical therapy ineffective, assessment of pancreatic duct is recommended.  Based on this information, discussion of endoscopic and surgical treatment is outlined as well.

Related blog entries:

High Rates of Helicobacter Pylori Resistance

Posted on by

While the development of antibacterial resistance has broad implications, in gastroenterology patients specific problems have emerged with Helicobacter pylori (H pylori) and this has led to changes in first-line therapy( ).  More data on the treatment resistant H pylori has been published (JPGN 2013; 56: 645-48).

77 consecutive strains of H pylori  from Brazilian children and adolescents were isolated from gastric biopsies and analyzed; this study took place between 2008-2009 and the mean age was 11.1 years.  In 71 strains, there were no previous attempts at eradication.

Results:

  • 40% of strains were resistant to metronidazole
  • 19.5% of strains were resistant to clarithromycin
  • 10.4% of strains were resistant to amoxicillin
  • All strains were susceptible to furazolidone and tetracycline
  • 14/77 (18.2%) patients had multiple resistances

Take-home point: Resistance to antibiotics is altering our approach to H pylori therapy.  Antibiotic susceptibility testing may be needed to improve antibiotic selection and eradication rates.

Related blog links:

Switching from Thiopurines to Methotrexate

Posted on by

Data regarding methotrexate treatment for Crohn’s disease (CD) is limited.  A fairly large retrospective study provides a better idea about its effectiveness over a five-year period (Clin Gastroenterol Hepatol 2013; 11: 667-72).

In total 174 consecutive CD patients (age 35 ±12 y) from 3 hospitals were analyzed.  All of these patients received methotrexate (MTX) after thiopurine therapy. 23% had not responded to an anti-TNF agent.  Most of the patients who had failed thiopurine treatment had an intolerance to thiopurine rather than loss of clinical response.  Data on patient characteristics including smoking status, disease behavior/location, previous treatments, and indication for MTX are detailed in Table 2.  Interestingly, 113 patients were female.  The authors noted that 90% of their patients received MTX parenterally.

Key findings:

  • Patients with sustained clinical benefits from methotrexate monotherapy:  98 (86%) at 6 months, 50 (63%) at 12 months, 27 (47%) at 24 months, and 3 (20%) at 60 months.
  • 45 (26%) discontinue methotrexate due to intolerance, mostly within the first 6 months.  However, adverse effects were generally mild.  Only one patient required hospital admission for an infection (cytomegalovirus).

There are many limitations of this retrospective study.  Nevertheless, a significant portion of patients derived clinical benefit for at least 2 years.

Related blog posts:

Neurological Complications Associated with Inflammatory Bowel Disease

Posted on by

Though I have not seen much in the way of neurological complications in our pediatric inflammatory bowel disease (IBD) population, nevertheless I worry about them.  A recent article provides some insight into the incidence, the pathophysiology and approach to these complications (Inflamm Bowel Dis 2013; 19: 864-72).

Types of neurologic complications: The most common neurologic complication is peripheral neuropathy.  The frequency is quite variable based on data collection method.  In large administrative healthcare data, the prevalence has been reported around 2% whereas in cohort studies the range has been 8-15%. Other complications include meylopathy, cerbrovascular disease, cranial nerve palsy (eg. Melkersson-Rosenthal syndrome), seizures, and demyelinating diseases.

With regard to demyelinating diseases, this has gained additional attention in the setting of biologic agents which have been associated with this complication.  However, the authors note that a pre-biologic treatment study from Olmstead County, observed a prevalence of multiple sclerosis of 1% which was 3.7 times higher than expected.  In addition, similar studies have confirmed this finding.

Potential mechanisms vary greatly depending on the neurologic complication. With regard to cerebrovascular disorders, “venous thromboembolism (VTE) has been shown to occur 3 times more frequently in patients with IBD (the risk increases to 8-10-fold in patients with active colitis) than the general population.”  Hence, VTE prophylaxis is recommended by the authors in hospitalized IBD patients, especially if they are experiencing a disease exacerbation.

In addition to the underlying disease, vitamin deficiencies (eg. Vitamin B12) and medications can trigger neurologic complications.

  • Natalizumab: progress multifocal leukoencephalopathy (PML)
  • Metronidazole: peripheral neuropathy (typically reversible with drug discontinuation)
  • Anti-TNF-α agents (infliximab, adalimumab, certolizumab): demyelination, rarely seizures, and rarely PML
  • Cyclosporine: various neurotoxicity in ~25%

Related blog entries:

Gluten-related Disorders

Posted on by

For those who missed a recent NASPGHAN Foundation webinar, I’ve attached two links (with permission from NASPGHAN foundation):

1. The PDF of the slides –these are very useful:

NASPGHAN GlutenWebinar 6_5_13 Final v34

2. Link to webinar, including CME:

http://limelightdc.com/clientarea/naspghan_gluten_webinar_06_13/landing_page.html

The experts provide a useful review of celiac, wheat allergy, and wheat intolerance.  For celiac screening, the webinar recommends avoiding a panel of serology tests in favor of isolated Tissue Transglutaminase IgA Antibody (possibly with serum IgA level.

Related blog links:

If I have diarrhea after vacation…

Posted on by

I may want to remember this reference: “Enteropathogens and Chronic Illness in Returning Travelers” NEJM 2013; 368: 1817-25.

Some “fun facts:”

  • In 2007, more than 30 million Americans traveled to developing regions. ~8% traveling to these regions needed medical care during or after travel.  Gastrointestinal symptoms were present in more than 25% who sought medical care.
  • According to the GeoSentinel Surveillance Network (42 travel medicine sites), between 1996-2005, 65% of enteric infections were due to parasites, 31% bacteria, and 3% viral. (J Infect 2009; 59: 19-27) (Parasites typically have more long-lasting infections which should be considered in interpreting this data; in addition, some pathogens are more difficult to isolate.)
  • Six pathogens were most prevalent: Giardia, Campylobacter, Entamoeba histolytica, Shigella, Stronglyoides, and Salmonella.

In addition to an enteric pathogen color-coded prevalence map, the article has a useful table identifying areas at high risk, mode of transmission, incubation period, common symptoms, recommended diagnostic tests and treatments.

To minimize the impact of these enteropathogens, physicians can help prepare travelers with appropriate vaccinations, malaria chemoprophylaxis (if needed), and effective anti-bacterial drugs for self-treatment should symptoms develop.

Related blog posts:

Quantifying the Heart Risks of Azithromycin

Posted on by

As noted previously in this blog (New FDA warning for azithromycin (Zithromax) | gutsandgrowth), there have been concerns raised about the risk of cardiovascular death due to the use of azithromycin.  An editorial and new study indicate that this risk is mainly confined to patients at high cardiovascular risk (NEJM 2013; 1665-67 [editorial], 1704-12 [study]).

Background: in 2011, “approximately 40.3 million people in the United States (roughly one eighth of the population) received an outpatient prescription for the macrolide azithromycin.”

In an observational study published last year (NEJM 2012; 366: 1881-90), azithromycin resulted in one death for every 21,000 outpatient prescriptions in comparison to amoxicillin.  Among those with high cardiovascular risk factors, this number was much higher: one in 4100; whereas in those with no risk factors, it was less than one per 100,000.  The risks also corresponded to peak drug levels as the increase in events took place during the 5-day course and an increased risk was not evident subsequently.

The newest study, referenced above. used data from a Danish national health care registry (18-64 year olds). These patients had a lower cardiovascular risk profile.  More than one million prescriptions were studied.  They found no difference in cardiovascular deaths between azithromycin and penicillin.  In a subgroup analysis of patients with a history of cardiovascular disease, the risk ratio was 1.35 though this did not reach statistical significance.

The editorial notes that azithromycin has been shown to reduce deaths in patients treated for community-acquired pneumonia.  However, the two most common indications for treatment remain bronchitis and sinusitis.

Bottom-line: The risks of azithromycin in young and middle-aged persons is exceedingly low or nonexistent.  In individuals with cardiovascular risk factors, azithromycin, other macrolides and fluoroquinolones could trigger a lethal arrhythmia.