A recent study (JL Yasuda et al. JPGN 2019; 69: 163-70) shows that esophagitis is common with and without proton pump inhibitor (PPI) therapy in children with esophageal atresia (EA).
Background: This study encompassed 310 patients (34% long gap EA) and 576 endoscopies (median age 3.7 years)
- Erosive esophagitis was found in 8.7% of patients.
- 15.2% of patients had esophagitis with >15 eos/hpf; 49% of patients had ≥1 eos/hpf (histologic eosinophilia)
- 87% of endoscopies were preceded by acid suppression therapy; being on acid suppression reduced the odds for abnormal esophageal biopsy (P=0.011).
- Histologic esophagitis was “highly prevalent even with high rates of acid suppressive medications use.”
- For example, among those receiving PPI monotherapy, 150 had normal biopsy and 136 had abnormal biopsy. Among those off all acid suppression, 30 had normal biopsy and 45 had abnormal biopsy.
- For erosive esophagitis, this occurred in 12 on PPI and was not present in 274 on PPI therapy. Among those off all acid suppression, 4 had erosive esophagitis and 70 did not.
- Presence or integrity of fundoplication was not significantly associated with esophagitis.
While this is a large study, the findings have several limitations. This is a single center retrospective study and this center attracts highly complex cases of EA.
My take: In addition to fairly high rates of erosive esophagitis and eosinophilic esophagitis, this study shows a high incidence of microscopic esophagitis, the significance of this is unclear. This study supports the current recommendations of 3 endoscopies in childhood and perhaps more frequent surveillance in those with more complex EA.
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Sign in Hood River, OR
One of the categories in the game of balderdash is abbreviations. Someone with extra time on their hands should invent a medical version with obscure acronyms as one of the categories.
An acronym that I recently discovered, EoP, which stands for eosinophil progenitor came to my attention from Dr. Benjamin Enav and Dr. Oral Alpan. they suggested two articles (both letters to the editor) related to EoP as a biomarker for eosinophilic esophagitis:
- DW Morris et al. J Allergy Clin Immunol 2016;138: 915-8.
- JT Schwartz et al. J Allergy Clin Immunol 2019; 143: 1221-3.
Both of these articles came from researchers at the Cincinnati Children’s Hospital. In the first, the authors studied 31 children (17 with active eosinophilic esophagitis [EoE], and 14 with inactive EoE). Key findings:
- With a cutoff of 15.5 EoPs/mL, there were none of the 17 patients with active EoE below this threshold and 8 of 14 (57%) with inactive EoE were below this threshold.
- At this cutoff, this pilot study predicted active EoE with a sensitivity of 100%, specificity of 57%, positive predictive value of 74% and negative predictive value of 100%.
The second study, also with 31 children, showed that the peripheral blood EoP levels were significantly increased in patients with active disease and correlated with the
EoEHSS (EoE histologic scoring system) composite ratio.
My take: These studies show that a blood level of EoP is a promising biomarker which could help avoid endoscopy in those with low levels of EoP.
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Given seasonal fluctuation in the activity of eosinophilic esophagitis (EoE), aeroallergens have been considered a trigger in some patients.
Briefly noted: A recent study (A Ravi et al. Gastroenterol 2019; 157: 255-6, editorial 17) showed that dust mite antigen was present in esophageal biopsy specimens at a greater level in adult patients with EoE compared to controls. With active EoE, patients had dust mite staining in 1.6% of the field which was significantly greater than patients with inactive EoE (0.7). The control group had a complete absence of epithelial dust mite staining.
The editorial (Seena Aceves) notes that these investigators have also shown gluten accumulation in the EoE esophagus. Whether dust mite antigens or other specific postulated aeroallergens plays a causative role is unclear. This study shows the presence of these antigens in the esophagus but does not show whether this is an epiphenomenon due to increased permeability or whether these antigens activate the local immune system.
A second study (T Patton et al. JPGN 2019; 69: e43-e48) describes the outcome of coexisting celiac disease and eosinophilic esophagitis in 22 children (from a cohort of 350 children with celiac disease. 17 had repeat biopsies. Four of 17 (23.5%) had resolution of EoE with a gluten-free diet. Related blog post: Is there a Link Between Eosinophilic Esophagitis and Celiac Disease?
Sagrada Familia, Barcelona
A recent double-blind, double-dummy study (ES Dellon et al. Gastroenterol 2019; 157: 65-73) found similar efficacy between budesonide and fluticasone for newly-diagnosed eosinophilic esophagitis. They had hypothesized that an oral viscous budesonide would be more effective due to increased esophageal contact time.
Methods: The authors compared an oral viscous budesonide OVB) at 1 mg BID (n=56) to fluticasone (swallowed) MDI dosed at 880 mcg BID (n=55). Patients aged 16-80 years, with mean of 37 years.
- ~95% in both groups with dysphagia
- ~75% with any atopic condition
- ~50% with dilatation required at baseline
- Similar drop in eosinophil count: 73 (OVB) and 77 (MDI) eos/hpf at baseline to 15 and 21 respectively
- Histologic response (<15 eos/hpf) rates of 71% (OVB) and 64% (MDI).
- Response to <5 eos/hpf occurred in 61% OVB and 49% MDI; response to <1 eos/hpf was noted in 41% and 35% respectively
- Symptom scores (DSQ) responded similarly as well
- Similar degree of candidiasis 12% for OVB and 16% for MDI
In the associated editorial, the authors speculate that one reason for similar efficacy was the detailed instructions given for patients taking the MDI.
My take: This study supports both topical steroid therapies; practical issues like cost and insurance coverage could be influential in selecting the specific treatment for an individual patient.
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From AGA twitter feed
Full Text Link (courtesy of AGA twitter feed):Efficacy of Budesonide Orodispersible Tablets as Induction Therapy for Eosinophilic Esophagitis in a Randomized Placebo-Controlled Trial AJ Lucendo et al. Gastroenterol 2019; 157: 74-86. https://doi.org/10.1053/j.gastro.2019.03.025
Background & Aims
Swallowed topical-acting corticosteroids are recommended as first-line therapy for eosinophilic esophagitis (EoE). Asthma medications not optimized for esophageal delivery are sometimes effective, although given off-label. We performed a randomized, placebo-controlled trial to assess the effectiveness and tolerability of a budesonide orodispersible tablet (BOT), which allows the drug to be delivered to the esophagus in adults with active EoE.
We performed a double-blind, parallel study of 88 adults with active EoE in Europe. Patients were randomly assigned to groups that received BOT (1 mg twice daily; n = 59) or placebo (n = 29) for 6 weeks. The primary end point was complete remission, based on clinical and histologic factors, including dysphagia and odynophagia severity ≤2 on a scale of 0–10 on each of the 7 days before the end of the double-blind phase and a peak eosinophil count <5 eosinophils/high power field. Patients who did not achieve complete remission at the end of the 6-week double-blind phase were offered 6 weeks of open-label treatment with BOT (1 mg twice daily).
At 6 weeks, 58% of patients given BOT were in complete remission compared with no patients given placebo (P< .0001). The secondary end point of histologic remission was achieved by 93% of patients given BOT vs no patients given placebo (P < .0001). After 12 weeks, 85% of patients had achieved remission. Six-week and 12-week BOT administration were safe and well tolerated; 5% of patients who received BOT developed symptomatic, mild candida, which was easily treated with an oral antifungal agent.
In a randomized trial of adults with active EoE, we found that budesonide oral tablets were significantly more effective than placebo in inducing clinical and histologic remission. Eudra-CT number 2014-001485-99; ClinicalTrials.gov ID NCT02434029.
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A recent study (K Radicic, RF Stokes. Clin Gastroenterol Hepatol 2019; 1408-9) indicated that taking biopsies from three esophageal areas (proximal, mid, and distal) improved the likelihood of identifying eosinophilic esophagitis (EoE).
- In their study, among 96 patients with EoE, 55.2% were positive (>15 eos/hpf) in only 1 of the 3 levels.
- 17 patients (17.7%) were positive in the mid-esophagus alone, and 6 patients (6.3%) were positive in the proximal esophagus alone.
The authors state that a 2-level biopsy protocol missed the diagnosis of EoE in roughly 1 of 5 patients.
My take: This study is provocative. However, the reasons why 3 levels improved their yield could be related to other factors rather than location.
- Prior studies have shown higher yield when taking 5 or 6 biopsies rather than fewer biopsies; thus, the location of biopsies may not be as important as the number of specimens
- Prior studies have shown that having another pathologist review the slides can increase the yield by ~20%; this indicates that careful review of specimens by itself is helpful. Perhaps, more specimen containers will increase the time that a pathologist reviews the biopsies.
My view is that if adequate numbers of biopsies are taken from several locations, a single jar for all the specimens should suffice (& reduce costs) –though a formal study could be beneficial to confirm this.
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From NASPGHAN 2014 EoE Slide Set
A recent retrospective study (J Robson et al. Clin Gastroenterol Hepatol 2019; 17: 107-14) utilized a pathology database encompassing the vast majority of Utah pediatric cases to determine the incidence and prevalence of eosinophilic esophagitis (EoE) from 2011 to 2016.
The authors determined cases of EoE by looking for symptomatic children with isolated esophageal eosinophilia (more that 14 eos/hpf) in the absence of other comorbid conditions.
- 1060 children met the criteria for a new diagnosis of EoE
- Average annual incidence of EoE was 24 per 100,000 children; this is nearly double the previously reported rate 12.8 per 100,000 from Hamilton County, Ohio in 2003.
- Prevalence of EoE was 118 per 100,000 children
The authors speculate on several factors that produced this increased incidence rate –all related to EoE risk factors:
- Predominant non-Hispanic White population
- High rates of atopy
- Increased capture rate of their database
- Also, the authors did NOT exclude PPI-responsive esophageal eosinophilia (which is a subtype of EoE and not a different disease
The authors note that “there is reason to believe that this [high incidence rate] is a conservative estimate:”
- ~2% of pathology reports had 10-14 eos/hpf. Further review of these cases would likely have identified some which have exceeded the >14 threshold
- Some pediatric EoE cases are diagnosed by adult gastroenterologists who did not use the pathology databases
My take: This study shows high rates of EoE but comes as no surprise. And, there are likely a large number of individuals with mild EoE which has not been diagnosed. In my experience, families and physicians often overlook altered eating habits as related solely to behavior. Useful questions to uncover dysphagia include the following: how long does it take your child to eat? does your child have to drink a lot of liquids when eating? does food get stuck frequently?
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