Comparing diets in EoE

There remains a limited number of therapeutic options with EoE.  Dietary therapy can be effective as well as burdensome.  A closer look at dietary treatment effectiveness was recently published (J Allergy Clin Immunol 2012; 129: 1570-8 –thanks to Seth Marcus for alerting me to this article).

Due to eligibility requirements, only 98 patients of an initial 513 met criteria.  The findings from this study may be difficult to generalize because of the following:

  • Highly selected patient population
  • Retrospective study.   Dietary therapy was NOT chosen randomly.
  • Study originates from a specialized center (Cincinnati) which attracts atypical cases of EoE

That being said, the study asks some important questions. What is the remission rate for skin test-directed elimination diet in comparison to six food group elimination diet (SFED) and to an elemental diet?  The SFED actually composed two groups (in my opinion, this is a significant flaw in the study design & has a limiting effect on the conclusions).  The ‘classical’ SFED (42% or 11/26) eliminated the six most common food groups (milk, soy, wheat, egg, nuts, fish/shellfish) whereas a ‘modified’ SFED (58% or 15/26)  combined the classical SFED with foods eliciting positive skin-testing.

Some of the authors terminology:

  • Complete remission: 1 or fewer eosinophils/hpf
  • Partial remission: 2-5 eos/hpf
  • Partial resolution: 6-14 eos/hpf
  • Remission: <15 eos/hpf
  • Non-remission: >15 eos/hpf

Skin prick tests (SPFs) were performed to as many as 62 foods and 11 environmental allergens and graded 0-4.  0 equated to negative control & 4 equated to histamine control -all interpreted at 15 minutes after placement.

Atopy patch tests (APTs) were interpreted at 48 hours with scoring between 0-4.  A score of 2 indicated “erythematous with generalized induration.”  Any score of 2 or higher was considered positive.

Food reintroduction process: “Food reintroductions were initiated only when the peak eosinophil count was less than 15 eosinophils/hpf. If symptoms occurred after reintroduction of a food, patients were instructed to discontinue that food, wait approximately 10 to 14 days, and then reintroduce another food…. A food reintroduction was considered successful if no symptoms were reported and the postpeak eosinophil count was less than 15 eosinophils/hpf.”

Why were so many patients excluded?  The main causes were 181 patients did not meet strict EoE criteria, 122 patients received glucocorticoids, and 52 patients had another eosinophilia-associated condition; less common reasons included patient age >21, being part of a separate drug trial, obvious noncompliance, different diet regimen, and not having 2 consecutive EGDs separated by dietary intervention.

How many endoscopies are needed for dietary therapy?   In this study, the average patient had 8.5 EGDs at Cincinnati.  The greatest number of EGDs took place among patients assigned to an elemental diet (average >11); these patients also had a longer followup period compared to the other two groups: 2.9 years compared with 1.1 for SFED and 2.1 for directed diet.

  • All three diets resulted in improvement in eosinophil count.
  • Overall Remission rates: 96% elemental, 81% SFED, 65% directed diet
  • Complete Remission rates:  59% elemental, 39% SFED, 30% directed diet

One interesting set of data is in Table 4.  This gives the pass rate for various foods with single and multiple food reintroductions.  Milk for example had a pass rate of 35% among the 17 patients who had this as a single food reintroduction.  The values ranged from a low pass rate of 29% for strawberries to a high pass rate of 78% for cocoa and 75% for pork. Soy, eggs, and wheat all hovered near 60% pass rate.

Conclusions by authors:

1. “SFED is no less successful than directed diet and consistent with unreliability of skin testing …Our data…undermine the value of skin test-directed dietary management. ” This is due to the fact that the disease mechanism is not an IgE-mediated disease (skin testing primarily detects IgE-mediated allergens).

2. Elemental diet is superior at inducing histologic remission. However, “multiple studies indicate that adherence is inversely related to the number of foods eliminated.”

Previous related posts:

Guidelines for Eosinophilic Esophagitis

Looking better or feeling better in EoE?

Look of improvement on an EoE diet

Eosinophilic Esophagitis -Six Food Group Diet

MicroRNA signature for eosinophilic esophagitis

The undiscovered country

 

Guidelines for Eosinophilic Esophagitis

For a little while, I’ve meant to complete a post on the EoE guidelines published last fall (J Allergy Clin Immunol 2011; 128: 3-20).  This article, based on the input of 33 physicians with EoE expertise, provides a lot of depth to this unfolding area in pediatric gastroenterology.

Diagnosis of EoE. The authors caution that this diagnosis is not a histologic diagnosis as a number of entities can cause esophageal eosinophilia; at the same time, a minimum number of eosinophils, 15/hpf, is a necessary diagnostic threshold.  A small number of patients may have EoE with fewer than 15/hpf, including PPI-responsive EoE, inadequate biopsy sampling, seasonal variation, or partial treatment (eg. patient on corticosteroids).

How many biopsies?  In one cited study in the article, 2, 3, and 6 biopsies had sensitivity of 84%, 97%, and 100% respectively.  Endoscopic biopsies remain the only reliable diagnostic test.

Why are there a subset of PPI-responsive EoE patients?  Potential explanations include improvement in immune-activation after healing of esophageal mucosa, inherent anti-inflammatory property of PPIs, or due to pitfalls in current diagnostic testing.  Due to recognition of this disorder, pH testing may be needed in many patients with suspected EoE.  Even still, the authors note that “PPI responsiveness or diagnostic testing (pH monitoring) might not adequately distinguish GERD and EoE.”

How useful are genotypic features?  Clinical  use of genotypes is not feasible at this time.  However, it is anticipated that esophageal gene expression will emerge as one way to differentiate EoE from other conditions and to determine optimal treatments.

What type of allergy evaluation? The majority of EoE patients have concurrent atopic diseases, including rhinitis, asthma, and eczema.  Thorough evaluation by an allergist (or immunologist) is recommended.  Specific recommendations: skin prick testing (SPT), serum IgE for immediate-type food allergy.  Atopy patch testing (APT) has high negative predictive values, >90%, except for milk which is ~50%.  APT needs to “be standardized and validated.”

Biomarkers? “Insufficient evidence to support any peripheral marker” including cytokines, and IgE (total).

Treatment –PPI: PPIs are useful to distinguish GERD as well as PPI-responsive EoE from EoE requiring other treatments.  They also help with symptomatic treatment in some patients who have secondary GERD.  Recommended dose in children 1 mg/kg/dose BID.

Treatment –Dietary: Three dietary regimens have potential effectiveness: 1) selective food diet based on allergy testing, 2) dietary restriction of the most likely food antigens (eg. six food group diet elimination) and 3) strict amino acid based diet.  Tolerance of foods that have been shown previously to provoke EoE is unlikely to develop in the majority of EoE patients.

Treatment –Corticosteroids: Corticosteroids are effective but when discontinued EoE almost always recurs.  Systemic corticosteroids can be particularly useful when severe dysphagia is present.  With severe endoscopic findings, a course of corticosteroids may help reduce the need for dilatation or lessen the risk.  Long-term use of systemic steroids is not recommended.  Topical steroids should be considered in all patients with EoE.  Recommended doses are given.

  • For fluticasone:  88-440 μg 2-4 times per day (max 880 μg BID)
  • For budesonide: 1mg daily (<10 y) and 2 mg daily (≥10 y)
Treatment –Dilation:  Dilation can provide relief of dysphagia.  In most cases, medical or dietary therapy should be attempted prior to use of dilation.  Goal of 15-18 mm.  Practical advice (not validated in studies): Limit dilation progression per session to 3 mm or less after resistance has been encountered.
Treatment –Alternatives:  Cromolyn, leukotriene receptor antagonists, or immunosuppressive agents (eg azathioprine, 6-mercaptopurine) are “not recommended.”
Complications: Perforations (spontaneous & procedure-related), food impactions, strictures, and narrow caliber esophagus.  There has not been evidence of an increased esophageal cancer risk in EoE patients to date.
Unresolved issues: Despite the extensive consensus on many of these issues, the conclusions inform the reader of how far we need to go.  Some of the unresolved questions include such basic problems:
  • “Importance of treating asymptomatic patients”
  • “Natural history of EoE and rates and predictive indexes of complications”
  • “Accuracy of skin prick and patch testing”
  • “Optimal end points of treatment”

Previous related blog posts:

The undiscovered country

Eosinophilic Esophagitis -Six Food Group Diet

Practical information on EoE for families:

http://www.ccdhc.org/diseases/EoE.html