Transnasal Endoscopy in Unsedated Children to Monitor Eosinophilic Esophagitis

A recent retrospective study (N Nguyen et al. Clin Gastroenterol Hepatol 2019; 17: 2455-2462) describe the feasibility of unsedated transnasal endoscopy (TNE) for monitoring eosinophilic esophagitis (EoE) in children (n=190, subject ages 3-22 years).

TNE was facilitated by distraction with either video google or virtual reality (starting 2016).  NPO time was 2 hours before the TNE.

Key points:

  • Over 294 TNEs were completed from 300 attempts (98% success)
  • Cost of TNE was halved: $4393 compared to $9444 for EGD (does not count pathology costs)
  • Adverse events: 8 (2.7%) with vomiting, 9 (3.1%) spit up, 11 (3.7%) with epistaxis
  • By 2017, TNE accounted for 31.8% of upper endoscopies in 2017

The authors recommend that TNE be offered starting at age 5 years in those without a known stricture.

My take: I am looking forward to less invasive/less costly ways of monitoring treatment response in EoE.  I think TNE can lower costs –though I am a little surprised that the cost of TNE in their institution was still more than $4000.  In our outpatient endoscopy center, costs for an upper endoscopy/biopsy with anesthesia are typically about one-third the cost of an EGD in their study and about three-fourths the cost of a study TNE.

Related study: A Krigel et al. Clin Gastroenterol Hepatol 2019; 17: 2489-96. This study showed increasing use of anesthesia assistance (AA) for colonoscopy in adults from 16.7% in 2006 to 58.1% in 2015. This data was derived from the Premier Perspective database with more than 4.6 million patients who had an outpatient colonoscopy. AA was associated with a median increase in cost of $182 for patients with commercial insurance.

Related blog post: Waiting for the String Test for EoE

 

Eosinophilic Esophagitis and Inflammatory Bowel Disease

A recent study (Limketkai BN, et al. Gut. 2019;doi:10.1136/gutjnl-2018-318074.) shows that the likelihood of eosinophilic esophagitis (EoE) is higher in patients with inflammatory bowel disease (IBD) and that the likelihood of IBD is higher in EoE patients.

Summary from Healio Gastroenterology –Risk for EoE higher in patients with IBD, and vice versa:

  • Researchers conducted a prospective cohort analysis using the Truven MarketScan database from 2009 to 2016 to define the epidemiology and clinical implications of concurrent EoE and IBD diagnoses.
  • Among their cohort comprising 134,013,536 individuals, the incidence of EoE was 23.1 per 100,000 person-years, CD was 51.2 and ulcerative colitis was 55.2.
  • Compared with patients without either diagnosis, the risk for EoE was higher in patients with CD (IRR = 5.4, P < .01; prevalence ratio [PR] = 7.8, P < .01) and UC (IRR = 3.5, P < .01; PR = 5, P < .01). Meanwhile, the risk for IBD was higher among patients with EoE (CD: IRR = 5.7, P < .01; PR = 7.6, P < .01; UC: IRR = 3.4, P < .01; PR = 4.9, P < .01).

Promising Biologic for Eosinophilic Esophagitis

A recent study (I Hirano et al. Gastroenterol 2019; 156: 592-603) showed that RPC4046, a monoclonal antibody against IL13 is a promising agent for eosinophilic esophagitis. This multicenter double-blind study with 99 adults compared RPC4046 at doses of either 180 mg or 360 mg to placebo for 16 weeks.  Endoscopy was performed at baseline and at 16 weeks.  The study population included a high number who were considered steroid-refractory and excluded patients who were responsive to proton pump inhibitors. The study drug was administered initially as an IV load followed by weekly subcutaneous injections.

Key findings:

  • Mean changes in esophageal eosinophil count dropped by 94.8 in patients receiving 180 mg dosing and 99.9 in patients receiving 360 mg dosing.  In contrast, placebo-treated patients had a meager reduction of 4.4.
  • In this phase II study, there were no serious safety issues identified
  • There were no significant changes relative to placebo in dysphagia symptoms using the DSD (dysphagia symptom diary) composite score. Though there was improvement in global PRO measures compared to placebo.

There is an associated editorial (pg 545) explains the need for better therapies.  While both dietary therapies and topical steroids are likely effective in >70%, dietary therapy is plagued by problems with long-term adherence and there may become less effective with longer-term administration.

My take: Particularly for patients with refractory EoE, newer therapies are needed.  Given the chronic nature of EoE, cost of new treatments could be another hurdle.

Related blog posts:

Negligible Effect of Eosinophilic Esophagitis Treatment on Longitudinal Growth

Briefly noted: ET Jensen et al. JPGN 2019; 68: 50-5. This retrospective study with 409 patients with eosinophilic esophagitis (EoE) examined longitudinal growth over 12 months.  “In general, treatment approach was not associated with any significant increase or decrease in expected growth.” In a subset of patients with combined elemental diet and topical steroids (n=13), there was a subtle decrease in linear growth with a change in height z-score of -0.04, CI -0.08 to  -0.01. Interestingly, in these patients with EoE, the baseline height z-scores were lower than expected indicating that a subset may have impaired growth prior to treatment.

Related blog posts:

pictures from Zabriskie Point at sunrise, Death Valley

 

Sex-Based Differences in Incidence of Inflammatory Bowel Disease

Briefly noted: SC Shah, H Khalili et al. Gastroenterol 2018; 155: 1079-89.

This study evaluated pooled data with 207,600 incident cases of IBD from a population of 478 million. Key findings:

  • Female patients had lower a lower risk of Crohn’s disease during childhood until 10-14 years of age, but then a risk afterwards
  • For ulcerative colitis, there was a divergence in risk after 45 years of age, when men had a significantly higher incidence.

My take: the differences indicate that genetic factors (men with a Y chromosome and only one chromosome X) along with sex hormones play a role in the pathogenesis of IBD.

Graphs depict Female/Male Incidence Rate Ratio

AGREE proceedings: Briefly noted: ES Dellon, CA Liacouras, J Molina-Infante, GT Furuta et al. Gastroenterology 2018; 155: 1022-33.  This report provides updated recommendations from AGREE conference –which have been widely cited previously on this blog and elsewhere.  One of the remarkable features on this report is the fact that there are 64 authors (by my count) –thus reading the affiliations and the conflict of interest disclosures alone would take some time.

For a good review on this topic:

Time to Diagnosis in Eosinophilic Esophagitis

According to a recent retrospective study (CC Reed et al. Clin Gastroenterol Hepatol 2018; 16: 1667-9) the time to diagnosis of eosinophilic esophagitis (EoE) has NOT improved  between 2000 and 2014.  In this single tertiary-care center study with 677 cases, the predicted length of symptoms prior to diagnosis was the following:

  • 2000-2006: 6.1 years
  • 2007-2011: 7.2 years
  • 2011-2014: 7.2 years

While in the pediatric cohort the trend was the same, the length of symptoms preceding diagnosis was shorter: 2.8 years, 3.5 years and 3.7 years respectively for the above-mentioned time periods.

My take: In GI circles, EoE is quickly considered for a variety of clinical presentations.  This study suggests that

  • #1 for families and primary care doctors that many are unaware of this entity
  • #2 the symptoms of EoE are often insidious

Related blog posts:

Updated Consensus Guidelines for Eosinophilic Esophagitis

Full text: ES Dellon, CA Liacouras,  J Molina-Infante, GT Furuta et al. Gastroenterol 2018; 155: 1022-33.

This article provides a thorough review of EoE -including clinical features, differential diagnosis, diagnostic criteria, and treatments.

Key point: “The evidence suggests that PPIs are better classified as a treatment for esophageal eosinophilia that may be due to EoE than as a diagnostic criterion, and we have developed updated consensus criteria for EoE that reflect this change.”

Related blog posts:

Eosinophilic Esophagitis -Update

At a recent morning clinical conference, Dr. Seth Marcus provided a terrific update on eosinophilic esophagitis (EoE).  I am placing some of the slides below and the following is a link to the full lecture: The Evolution of EoE -Seth Marcus

During this part of the presentation, there was a discussion regarding the role of  allergists. Due to the poor predictive value (negative and positive) of allergy testing (skin tests and blood tests), the consensus is that routine allergy evaluation is NOT needed for children with EoE.  However, IgE-mediated food allergies along with other atopic diseases are common in children with EoE and selected patients could benefit from allergy referral.

The slide above reviews the main treatment options: topical corticosteroids, proton pump inhibitor therapy, and elimination diet.  While all of these are reasonable as first-line approaches, many in the group favored proton pump inhibitor (PPI) treatment as initial therapy.  In those with a very good response (<5 eos/hpf at followup), this would allow lower dose PPI as a maintenance option.  Another point of discussion was the fact that PPI responders tend to more favorably metabolize the PPIs to achieve higher therapeutic levels.  It is anticipated that future treatment could be influenced by knowing the individual’s CYP2C19*17 Polymporphisms (#NASPGHAN17 EoE Session)

Related blog posts:

Reslizumab (recombinant anti-IL-5) for Eosinophilic Esophagitis

Reslizumab, a monoclonal recombinant antibody to interleukin-5 did not receive FDA approval for eosinophilic esophagitis.  However, a recent report (J Markowitz et al. Journal of Pediatric Gastroenterology and Nutrition: June 2018 – Volume 66 – Issue 6 – p 893–897)  describes the outcomes of patients who entered the randomized control trial and continued to receive subsequently via open label extension (OLE, n=6) or through compassionate use (CU, n=4. This study provides data over 9 years of treatment.

Key findings:

  • Median eosinophil count dropped from 35 to 3
  • No serious adverse events were noted
  • Clinical features improved.  For example, dysphagia dropped from 42% to 0% and vomiting dropped from 67% to 17%

My take: Though this is a small study, it shows that in selected patients disruption of the inflammatory pathways can result in significant clinical improvement.

Pics from Ameila Island and thereabouts -Not sure whose dog  (not ours)

Impedance Measurements with Eosinophilic Esophagitis

Briefly noted: MA Lowry et al. JPGN 2018; 67: 198-203.  This study showed that active eosinophilic esophagitis (EoE) was associated with much lower impedance values that inactive EoE, NERD, and controls.  At 2, 5 and 10 cm above the squamo-columnar junction, median values of impedance with active EoE were 1069, 1368, and 1707 respectively.  In comparison, inactive EoE had median values were 3663, 3657, and 4494, respectively.  My take: Since impedance was also performed during endoscopy with sedation, this does not represent a significant advance in current management.

Sunrise at Amelia Island