What Happens When Topical Steroids Are Stopped in Eosinophilic Esophagitis

A recent retrospective study (T Greuter et al. Clin Gastroenterol Hepatol 2019; 17: 419-28) shows that patients with eosinophilic esophagitis who continued to take swallowed topical corticosteroids (STC) did much better than patients who did not.

Using the Swiss EoE database, the authors analyzed 229 patients with a mean age of 39 years at diagnosis.  Median followup was 5 years.  The authors initiated STC, almost all received fluticasone, at 1 mg BID for 2-4 weeks followed by maintenance treatment indefinitely.

Key findings:

  • There was frequent discontinuation of STC by patients, such that patients were actually taking STC at only 41% of visits.
  • Higher proportions of patients taking STCs were doing well compared to those not taking STCs:
    • clinical remission was 31% compared to 4.5% respectively (P<.001),
    • endoscopic remission was 49% compared to 18% respectively (P<.001)
    • histologic remission was 45% vs 10% respectively (P<.001)
    • complete remission was 16% vs 1% respectively (P<.001)
  • No dysplasia or mucosal atrophy was detected.  Esophageal candidiasis was observed in 2.7% of visits in patients taking STC

My take: This study shows that patients who maintained STC therapy had better esophageal outcomes than patients who stopped their treatment.  What is not known is the optimal long-term dose.

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Increased Risk of Eosinophilic Esophagitis in Esophageal Atresia Patients

Briefly noted: U Krishnan et al. Analysis of eosinophilic esophagitis in children with repaired congenital esophageal atresia. JACI 2018. Published online Oct 24, 2018.

This retrospective, single-center study examined 4 eosinophilic esophagitis (EoE) study cohorts and identified EoE in 20 of 110 patients (18%) who had surgically-repaired esophageal atresia.

This association has been seen previously: . 2014 Dec 21; 20(47): 18038–18043.  This case study stated ” We are suggesting that EoE is a frequent concomitant problem in patients with history of congenital esophageal deformities, and for this reason any of these patients with refractory reflux symptoms or dysphagia (with or without anastomotic stricture) may benefit from an endoscopic evaluation with biopsies to rule out EoE.”

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Association and Causation: Early Life Risk Factors for Eosinophilic Esophagitis

A recent case-control study (CP Witmer et al. JPGN 2018; 610-5) using the Military Health System Database examined 1410 cases of eosinophilic esophagitis (EoE) and matched them with 2820 controls; the study period was 2008-2015.

  • The authors found that early exposure to proton pump inhibitors (PPIs), histamine-2 receptors (H2RAs), and antibiotics were all associated with an increased risk of developing EoE with adjusted odds ratios of 2.73, 1.64, and 1.31.
  • In addition, among atopic problems, milk protein allergy had an adjusted odds ratio of 2.37 and eczema 1.97. –for developing EoE.

My take: This study does not determine whether the use of PPIs, H2RAs or antibiotics are involved in causation of EoE or whether patients with EoE simply receive these medications more frequently.  Nevertheless, the findings reinforce the idea that these medications should be used less frequently in infants.

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The Rise of Eosinophilic GI Diseases –Not Likely Connected to Helicobacter Pylori

A recent prospective case-control study (J Molina-Infante et al. Am J Gastroenterol 2018; 113: 972-9 -thanks to Ben Gold for this reference) examined the potential connection between Helicobacter pylori and eosinophilic GI diseases.  They examined 808 individuals (404 cases of eosinophilic esophagitis [EoE], 404 controls). Key findings:

  • H pylori prevalence was not different between cases and controls (37% vs. 40%, odds ratio 0.97).  The authors conclude that H pylori which has declined in prevalence globally is not inversely associated with EoE as had been suggested in some previous reports

In an associated editorial, (pg 941-4), the authors note that there has been a dramatic increase in atopic diseases over the past 30 years.  One hypothesis has suggested that these epidemiologic changes are related to a changing microbiome.  This in turn may be related to frequent antibiotic usage.  An example of the proliferation of antibiotics: “20-25% of Swedish adults receive an antibiotic prescription annually.”

While H pylori may be a biomarker associated with poor hygiene/less antimicrobial exposure, it does not appear to be directly related to EoE.  The authors indicate that until we have a better understanding, “in the meantime attention to healthier diets and minimizing antibiotic exposure may optimize public health in terms of atopic disease risk.”

My take: Since our genetics do not change quickly, the dramatic changes in disease frequency of conditions like EoE and Crohn’s disease must be influenced by environmental exposures.  How to lower the risk of these conditions remains uncertain.

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Budesonide Looks Better for Eosinophilic Esophagitis

A recent retrospective study (JM Fable et al. JPGN 2018; 66: 26-32) found that patients with eosinophilic esophagitis (EoE) who were treated with oral viscous budesonide (OVB) had more favorable outcomes than those treated with fluticasone propionate (FP).  This single center study included 68 pediatric patients (mean age 10.6 years) with 20 receiving FP and 48 OVB.

Dosing in study:

  • FP 110 mcg/actuation 2 puffs twice a day if 1-10 years, and 220 mcg/actuation 2 puffs twice a day if >10 years
  • OVB: 0.5 mg twice a day if 1-10 years, and 1 mg twice a day if >10 years
  • The authors noted that Duocal (which contains cornstarch and coconut oil) was a suitable alternative to Splenda.  They note that Neocate Nutra is effective too (limited by cost/coverage) as is pasteurized honey and maple syrup.

Key findings:

  • Histologic response (<15 eos/hpf) was noted in 75% (36/48) of OVB group and 40% (8/20) of FP group
  • Mean post-treatment peak eos/hpf was 12 ± 16 in OVB group and 20 ± 29 in the FP group (P=0.002)
  • Histologic remission (<5 eos/hpf) was noted in 54% OVB group and 35% FP group
  • In OVB-treated patients, those without asthma were more likely to achieve a histologic response (P=0.031)

Since this is a retrospective study, there are several potential limitations, including possible selection bias.  In addition, higher doses of topical agents have been shown to have higher response rates.

My take: Budesonide is probably better than fluticasone for EoE and its high first-pass metabolism indicates that it is probably safer as well.

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Cytosponge for Eosinophilic Esophagitis

A recent prospective study (DA Katzka et al. Am J Gastroenterol 2017; 112: 1538-44 -thanks to Ben Gold for this reference) provided more information regarding the potential utility of the cytosponge for eosinophilic esophagitis (EoE); the cytosponge has been studied for Barrett’s esophagus.

Background: 86 adult patients were recruited; 6 could not swallow sponge.  In the remainder, 105 procedures were performed comparing the cytosponge to standard endoscopic biopsies. The cytosponge technique can be completed in ~5 minutes without sedation. “All that is required is centrifuging the cytosponge specimen in its preservative to create a pellet followed by routine paraffin embedding and processing.”

Key findings:

  • Cytosponge was considered to have adequate specimen in 102 of 105 cases, compared with 104 of 105 with endoscopic sampling
  • Using a cutoff of <15 eos/hpf for inactive disease, the authors found that the cytosponge had a sensitivity of 75% and a specificity of 86%.
  • Six patients had active EoE on cytosponge with negative endoscopic biopsies.
  • 14 patients with active EoE with endoscopic biopsies had <15 eos/hpf with cytosponge
  • No complications were noted with cytosponge.

The sensitivity of 75% is likely due to inadequate contact between cytosponge and esophageal wall which could be related to technique, especially in those with a normal caliber esophagus.

My take: The cytosponge appears to identify active EoE in the majority of adult patients.  In those with abnormal cytosponge, the likelihood of active EoE would be very high; as such, it could be a useful biomarker.  It is still probable that many with normal cytosponge result would need endoscopy due to suboptimal sensitivity.

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