Category Archives: Pediatric Gastroenterology Intestinal Disorder

Varicella and Zoster Infections in Children with Inflammatory Bowel Disease

Posted on by

A recent study (DJ Adams, CM Nylund. J Pediatr 2016; 171: 140-5) looked at a large database (1997-2012) with nearly 9 million admissions.  In this retrospective cohort, there were 4434 admissions related to varicella and 4488 due to herpes zoster.

  • Children with Crohn’s disease had a greater increased risk: Varicella OR 12.75, and Zoster OR 7.9 compared to the general population.
  • Children with ulcerative colitis had increased risk compared to general population but less compared to children with Crohn’s disease: Varicella OR 4.25, and Zoster OR 3.9
  • Overall, the risk of these infections improved among all groups over the 15 year study period

One significant limitation of this study is that children with IBD may have been hospitalized more readily out of concern for their vulnerability.  It is noted that there were no deaths due to these infections in the children with IBD.

My take (from the authors):  the increased risk of Varicella and Zoster “were comparable with that observed in children with HIV, malignancy, and primary immune deficiency.”  Given the difficulty of immunizing children on immunosuppressive treatments, at the very least, immunizing household contacts needs to take place.

Related blog posts:

Fox Theatre on a Tuesday

Fox Theatre (Atlanta) on a Tuesday

Vitamin D and IBD, More Data

Posted on by

Another large study (Kabbani TA, et al. Am J Gastroenterol. 2016;doi:10.1038/ajg.2016.53) links low vitamin D status with worse outcomes in IBD.

An excerpt from summary from HealioGastro: (Low vitamin D linked to higher morbidity, disease severity in IBD)

Binion and colleagues identified 965 IBD patients (61.9% Crohn’s disease; 38.1% ulcerative colitis; 52.3% women; mean age, 44 years) with up to 5 years of follow-up data in University of Pittsburgh Medical Center’s longitudinal IBD natural history registry…

At enrollment, 8.9% of patients were vitamin D deficient and 33.1% had vitamin D insufficiency vs. 4.9% and 23.6%, respectively, at the conclusion of the study period. Among patients who received vitamin D supplements, 67.9% achieved normal levels by the end of the study…

Overall, patients with low vitamin D levels required significantly more steroids, biologics, narcotics, computed tomography scans, emergency department visits, hospital admissions and surgeries compared with those who had normal mean vitamin D levels (P < .05). They also had worse pain, disease activity scores and quality of life (P < .05).

“More importantly, correction of vitamin D deficiency was associated with overall improvement in clinical status,” Binion said.

My take: Vitamin D levels are often low when patients are acutely ill and can improve without supplements in many; this accounts for some of the association with worsened outcomes.  True vitamin D deficiency and insufficiency does have negative physiologic effects and should be treated.

Related blog posts:

Gibbs Gardens

Gibbs Gardens

 

Dreaded Nausea

Posted on by

One symptom that is dreaded by both patients and physicians is nausea.  A helpful review on this topic (K Kovacic, C DiLorenzo. JPGN 2016; 62: 365-71) provides information on functional nausea.  A few points:

Diagnostic:

  • Endoscopy has low yield.  One cited study suggested that in the absence of clinical alarm symptoms, 98% of endoscopies were normal.
  • 4-hour nuclear medicine study ‘may be justified.’

Therapeutic: Numerous drug/alternative therapies are discussed -most with a paucity of data.  These include:

  • Alternatives agents: Ginger, STW5 (iberogast), peppermint oil
  • Antiemetics: Ondansetron, promethazine, prochlorperazine
  • TCAs: amitriptyline, nortriptyline, imipramine, doxepin
  • SSRIs: citalopram, fluoxetine, paroxetine
  • Anxiolytics: buspirone
  • Tetracyclic antidepressant: mirtazapine
  • Antimigraine: cyprohepatadine, propranolol, topiramate, levetiracetam
  • Prokinetics: erythromycin, metoclopropramide, domperidone
  • Others: fludrocortisone, aprepitant, cannabionids
  • Psychology: “early involvement of a psychologist and emphasis on coping strategies and maintaining functioning with continued school attendance is a primary goal.”

The authors note that retrospective data in children suggest that TCAs have a response rate of ~50% (defined as more than a 50% improvement).  In one study, the mean dose of amitriptyline was 50 mg at bedtime.

In a related study, Madani et al (JPGN 2016; 62: 409-13) describe their experience (retrospective review) using cyproheptadine in children with a range of functional gastrointestinal disorders.  The most common indications were functional abdominal pain (36%), functional dyspepsia (23%), combination disorder (17%) and abdominal migraines (12%).  Overall, they included 151 children and they report 110 (72.8%) had complete symptom improvement; the remainder had either partial or no improvement.  In those who responded, the mean initial dose was 0.14 mg/kg/day; the final mean dose was nearly identical. Adverse effects of sleepiness was reported in 13% and weight gain in 10%.

Related posts:

Link: Impressive “water swallowing” NEJM video (thanks to Jose Garza for sharing).  In a person who had undergone an esophagogastric bypass as a child.  Still photo below:

NEJM Chest

Will Asymptomatic Patients with “Potential” Celiac Disease Benefit from a Gluten-free Diet?

Posted on by

A recent study (Volta et al. Clin Gastroenterol Hepatol 2016; 14: 686-93) indicates that those with “potential” celiac disease, who are asymptomatic, are unlikely to benefit from a gluten-free diet.  A useful summary is available on the AGA blog: What Happens to Patients with Markers of Celiac Disease but No Symptoms?

An excerpt:

Celiac disease is an immune-mediated gluten-dependent systemic disorder characterized by serologic and genetic factors and villous atrophy in the small intestine. Although some people test positive for antibodies and carry genetic alleles associated with celiac disease, they have relatively normal or slightly inflamed intestinal mucosa, with no or mild enteropathy. These patients are considered to have potential celiac disease (defined as increased serum levels of antibodies against tissue transglutaminase [tTG] without villous atrophy). They can have gastrointestinal and extra-intestinal symptoms or be completely asymptomatic…

To learn more about progression of potential celiac disease, Umberto Volta et al performed a prospective study to track clinical, serologic, and histologic features of 77 patients. The subjects had normal or slight inflammation of the small intestinal mucosa and were followed for 3 years.

Sixty-one patients had intestinal and extra-intestinal symptoms and 16 were completely asymptomatic at diagnosis…

Gluten withdrawal led to significant clinical improvement in all 61 symptomatic patients.

Of the 16 asymptomatic patients, who were left on the gluten-containing diets, only 1 developed mucosal flattening; levels of anti-endomysial and tTG antibodies fluctuated in 5 of these patients or became undetectable.

My take: In symptomatic patients (but not asymptomatic patients) with potential Celiac disease, a gluten-free diet may be worthwhile.

Related blog posts:

Mina Falls, El Junque

Mina Falls, El Junque

Pacifiers & Reflux in Preterm Infants Plus Swallow Syncope

Posted on by

In a crossover study (J Pediatr 2016; 172: 205-8) with 30 preterm infants (adjusted age 33 weeks at time of study) showed that non-nutritive sucking with a pacifier had no effect on acid and nonacid gastroesophageal reflux based on esophageal pH-impedance.

My take: It is good that sucking a pacifier did not effect reflux.  What would the authors have proposed if it had?

Another curious report: “Syncope with Swallowing” J Pediatr 2016; 172: 209-11.  Case report of a teenager who had syncope with drinking and eating along with atrial septal defect; after repair of ASD, the symptoms persisted and ultimately the patient had a pacemaker placed due to an exaggerated vagoglossopharyngeal reflex leading to high-grade AV block.

Gibbs Gardens

Gibbs Gardens

What happens when anti-TNF therapy is stopped

Posted on by

Another study (NA Kennedy et al. Aliment Pharmacol Ther 2016; 43: 910-23) has examined the issue of outcomes after anti-TNF therapy withdrawal among patients with inflammatory bowel disease.

This study included 166 UK patient cohort (117 with Crohn’s disease [median 31 yrs], 19 with ulcerative colitis [median 40 years]) as part of a retrospective observational study and a meta-analysis incorporating 11 further cohorts totalling 746 patients (624 with Crohn’s dissease, 122 with ulcerative colitis).

Key findings:

  • In the UK cohort, relapse rates were 36% at year and 56% at 2 years for Crohn’s disease
  • In the UK cohort, relapse rates were 42% at year and 47% at 2 years for ulcerative colitis
  • Increased relapse rates were noted for those with a diagnosis prior to age 22 years (hazard ratio (HR) 2.78), calprotectin >50 mcg/g (HR 2.95).
  • In meta-analysis, 1-year relapse rates were 39% for CD and 35% for UC/IBDU patients
  • Retreatment with anti-TNF was successful in 88% for CD and 76% of UC/IBDU patients

To understand this study, it is important to note some of the study criteria.  In the UK cohort, inclusion criteria required the patient to have had at least 12 months of ant-TNF therapy and be in corticosteroid-remission for at least 6 months.  In addition, the relapse rate is likely to be underestimated due to using a definition of relapse that required either commencement of steroids, immunomodulator or anti-TNF therapy.  The meta-anlaysis cohort studies also used clinical relapse rather than endoscopic or other objective markers.

My take: Relapse of clinical symptoms occur in about 40% after withdrawal in highly-selected groups who were doing well prior.  Significantly higher rates of endoscopic relapse are likely.  This study provides strong reasons for not interrupting therapy when it is working.

Related blog posts:

Cures Tshirt

 

How Likely is Reflux in Infants with “Reflux-like” Behaviors?

Posted on by

Another study (Funderburk et al. JPGN 2016; 62: 556-61) has shown that gastroesophageal reflux disease is infrequent in infants with a “strong clinical suspicion for reflux.”  This is a good to know since we also know that pharmacologic therapy for gastroesophageal reflux has not been proven to be effective in infancy either.

This retrospective study with 58 infants, including 40 preterm infants, evaluated for GERD with MII-pH studies.  Characteristics of cohort: median gestational age 31 weeks, median birth wt 1683 gm, and median age at study: 70 days. 10 patients were receiving acid suppression therapy.

Indications for testing:

  • Irritability 55%
  • Bradycardia  34%
  • Desaturation 31%
  • Cough 21%
  • Gagging 12%
  • Difficulty feeding 12%
  • Arching 10%
  • Apnea 5%

Key findings:

  • Only 6 infants (~10%) had abnormal MII-pH studies (defined as >95th percentile for reflux episodes/hours or >95th percentile for acid exposure time)
  • None of the symptom indices correlated with symptoms. SI, SSI, or SAP
  • The majority of reflux episodes did not correlate with clinical “reflux” behaviors
  • Small bore (5 Fr) NG tubes were not associated with increased reflux.

In the related commentary by Rachel Rosen (pgs 517-18), she noted that “there is little to no evidence to show that the 3 indices predict any meaningful clinical outcome…including response to fundoplication, or medications.” “The current literature fails to support the use of symptom indices to prove causality when resolution of symptoms with medical or surgical therapies is used as the criterion standard.”

My take: The vast majority of infants with “reflux behaviors” do not have reflux.  Even if they do, current pharmacologic therapies have not been shown to work.  So, there is little  value in reflux testing in most infants.  Finally, given the failure of symptom indices, does the addition of the impedance data to the pH data add any value?

Related blog posts:

Jerusalem Collage -Made from hundreds of postcards. Vik Muniz

Jerusalem Collage -Made from hundreds of pictures/postcards. Look closely -it’s amazing.  by Vik Muniz

Another Rare Cause of Neonatal Diarrhea

Posted on by

A well-described case report (B Harter et al. JPGN 2016; 62: 577-80) provides a description of proprotein convertase 1/3 (PC1/3) deficiency. To date, only 21 cases have been reported.

Clinical features: congenital diarrhea and polyuria; normal endoscopy/histology. This patient required parenteral nutrition until 11 months of age. Her polyuria resolved at 13 months of age. Low serum levels of c-peptide and insulin along with elevated pro-insulin, combined with the polyuria, were suspicious for PC1/3 deficiency. This patient’s diagnosis was established with genetic analysis of the PCSK1 gene.

PC1/3 is responsible for peptide hormone processing in endocrine cells in the gut, and has targets in the hypothalamus and pancreas. Growth hormone deficiency, adrenal insufficiency, diabetes insipidus, and hypogonadism are commonly observed.

Related blog posts:

Gibbs Gardens

Gibbs Gardens

Should Medical Marijuana Get a Free Pass?

Posted on by

In many states, including Georgia, medical marijuana has bypassed the rigorous Food and Drug Administration (FDA) approval process via state laws permitting its usage.  A recent editorial (J Koliani-Pace, CA Siegel. Am J Gastroenterol 2016; 111: 161-62 -thx to Ben Gold for this reference) highlights the dilemma facing physicians with medical marijuana with regard to providing advice/approval for this treatment.

Key points:

  • 12% of people aged 12 years or older report using cannabis in the past year.
  • For gastrointestinal illnesses, there is scant evidence effectiveness.  There is some data indicating that it makes you feel better, but no data proving that there is objective improvement in conditions like Crohn’s disease.
  • Adverse effects require more research.  “Approximately 9% of people who experiment with marijuana will become addicted.”  Other concerns: increased car accidents, altered memory/judgment, hyperemesis syndrome, and respiratory effects.  With increasing availability and increasing THC concentrations, there have been in an increase in emergency department visits related to usage.
  • Lack of quality control: various concentrations of THC and cannabinoids, different administration routes, contaminants.

My take: At least with GI illnesses, more studies are needed to determine whether medical marijuana should be recommended.

Related blog posts:

Gibbs Gardens

Gibbs Gardens

Here’s Why Biologic Therapy for Crohn’s Helps Adolescents Grow

Posted on by

It is well-recognized that Crohn’s disease is associated with delays in the onset and progression of puberty with the potential for stunted growth, impaired bone accrual, and diminished quality of life.

Now, a study (MD DeBoer et al. J Pediatr 2016; 171: 146-52) shows that initiation of anti-tumor necrosis factor α (anti-TNFα) treatment results in a rapid increase in sex hormone and gonadotropin levels.

In 72 adolescents, this observational study followed levels of sex hormones, gonadotropin levels, dual-energy x-ray absorptiometry, along with cytokine/inflammatory markers at initiation of anti-TNFα therapy, at 10 weeks and at 12 months.

Key findings:

  • By week 10 , testosterone z scores in males increased from a median of -0.36 to 0.40 (P<0.05)
  • By week 10 , estradiol z scores in females increased from a median of -0.35 to -0.02 (P<0.01)

My take (from the authors): This study suggests that “systemic inflammation suppresses gonadotropin-stimulated production of sex hormones” and that treatment of this inflammation with anti-TNFα agents allows rapid resumption normal production.

Related blog posts:

Law Quad, Univeristy of Michigan

Law Quad, Univeristy of Michigan