Tag Archives: Eosinophilic esophagitis

Do We Still Need PPI-REE?

Posted on by

“It is on shaky ground that one defines a disease by a response to therapy rather than by its clinical and mechanistic characteristics.” This is noted in a recent editorial (Clin Gastroenterol Hepatol 2014; 12: 2023-25, study: 2015-22).

The editorial makes this comment because the related study finds that the esophageal tissue from eosinophilic esophagitis (EoE) patients with proton-pump responsive EoE (PPI-REE) was indistinguishable from patients with EoE who do not respond to PPIs.

The study examined 196 consecutive patients and performed immunohistochemistry to examine major basic protein (MP), eotaxin-3, and tryptase.  Key finding: none of these markers were able to distinguish EoE from PPI-REE; however, these 3 assays did identify EoE with 100% accuracy compared with controls.

From the editorial: “We can approach EoE as a disease in which use of PPIs is the first step in treatment, and diet and steroids represent step-up therapy…We may not understand why some patients with EoE respond to PPIs yet others do not.”  It is possible that genetic testing in the future will allow us to distinguish which patients will benefit from PPIs, topical steroids or diets.

Bottomline: Now that it is well-recognized that a substantial portion of EoE patients benefit from PPIs, is it necessary to try to use a separate label for this subset? Probably not.

Related blog posts:

Link to NASPGHAN Lectures and Postgraduate Course

Posted on by

Later this week, our national pediatric GI meeting (North American Society for Pediatric Gastroenterology Hepatology and Nutrition) is starting in Atlanta.  Many in my group are involved and presenting.

The following link (with permission from NASPGHAN) is to the website with links to all of these lectures:

NASPGHAN 2014 Atlanta meeting

For those interested only in the Syllabus for the Postgraduate Course:  NASPGHAN 2014 Postgraduate Course.

Topics include in this 200 page (online) book: primary sclerosing cholangitis, jaundiced infant, acute liver failure, “dreaded” endoscopy wake up calls, endoscopy for biliary tract disease, extraesophageal manifestations of gastroesophageal reflux, constipation, eosinophilic esophagitis, motility disorders, FODMAPs diet, nutrition for neurologically impaired, early onset inflammatory bowel disease, “luminitis” due to non-IBD causes, new IBD treatments, and diet-microbiome.

Should be great!

Also, to plan your meeting -go to NASPGHAN home page and use mobile guidebook: NASPGHAN 2014 has gone mobile using Guidebook!

Sweet Alternative to Splenda for Budesonide

Posted on by

A recent article (JPGN 2014; 59: 317-20) has shown that Neocate Nutra is a good alternative to splenda as a delivery vehicle for budesonide for children with eosinophilic esophagitis.

This retrospective review of 60 children treated with oral viscous budesonide (OVB) who used either splenda (n=46) or with Neocate Nutra (n=14).  With regard to budesonide, in patients less than 10 years, the dose was 1 mg/day and older children received 2 mg/day.  For splenda patients, 10 packets were used to create a slurry whereas with Neocate Nutra powder the amount was 2.5 cm3 per milligram of budesonide.  Followup endoscopy took place at least 10 weeks after the start of treatment.

Key findings:

  • 13 of 14 Neocate Nutra patients achieved a histologic response (peak eosinophils <15/hpf) compared with 30 of 46 Splenda patients.
  • Mean eosinophil count dropped from 62 to 9 for Neocate Nutra patients and from 59.5 to 25.5 for Splenda patients.

Limitations of study: small number, retrospective study.

Take-home message: Neocate Nutra is at least as effective as Splenda as mixture with budesonide.  In addition, many parents may prefer to avoid Splenda.

Related blog posts:

Four Food Group Diet for Adults with Eosinophilic Esophagitis

Posted on by

A recent study published online (here’s a link: EoE 4-food Group Diet) shows that a four food elimination diet was effective in 54% of the adults in this study.  Here’s the abstract:

Background

Eosinophilic esophagitis (EoE) is an esophageal disorder predominantly triggered by food antigens. A six-food group elimination diet (SFGED) achieves remission in more than 70% of adult patients with EoE. After individual food reintroduction, just 1 or 2 food triggers for EoE can be identified in 65% to 85% of the patients, so some dietary restrictions and endoscopies after food challenge may be unnecessary.

Objective

To evaluate the efficacy of a four-food group elimination diet (FFGED) (dairy products, wheat, egg, and legumes) for adult patients with EoE.

Methods

Prospective multicenter study. All patients were reevaluated after 6 weeks on an FFGED. Response to the FFGED was defined by clinical and histologic (<15 eos/hpf) remission. Responders underwent reintroduction of each individual food over 6 weeks followed by endoscopy and esophageal biopsies. Nonresponders were offered a rescue SFGED.

Results

A total of 52 adult patients were included, of whom 12 patients (23%) had previous failure to topical steroid therapy. Twenty-eight of the 52 patients (54%) achieved clinicopathologic remission on the FFGED and 6 of the 19 (31%) nonresponders to the FFGED were successfully rescued with the SFGED. Twenty-two of 28 responders to the FFGED (78%) finished the individual food reintroduction challenge. Milk was identified as an EoE trigger in 11 patients (50%), egg in 8 (36%), wheat in 7 (31%), and legumes in 4 (18%). All patients had just 1 or 2 food triggers, with milk being the only causative food in 27% of the patients.

Conclusions

An FFGED achieved clinicopathologic remission in 54% of adult patients with EoE. An SFGED was effective in almost a third of FFGED nonresponders, resulting in a combined efficacy of 72% of both strategies.

Related blog post:

What is the Role for Allergy Testing in Eosinophilic Esophagitis?

Posted on by

A recent review article (Clin Gastroenterol Hepatol 2014; 12: 1216-23) summarizes the potential role of allergy testing for eosinophilic esophagitis (EoE).

The article summarizes the potential ways to use various allergy testing and reviews the literature on its effectiveness.  The article notes a couple of key points:

  • Overall, using skin prick testing (SPT) and atopy patch testing (APT), allergy testing has not proved more reliable then empirically administering a 6-food elimination diet.  Thus, “the issue remains whether food allergy testing provides a useful tool in EoE.” However, targeted testing-based diets (especially in children) may require elimination of fewer foods.
  • “Serum IgE food-specific IgE panels should not be used for EoE.”  “Testing for foods, especially IgE testing, leads to recognition of food sensitizations that may not be clinically relevant and that on elimination, could result in the loss of tolerance to the food.”
  • Testing for milk allergy is noted have a high false negative rate.
  • IgG based testing is not recommended.  In fact, IgG immunoglobulins are “associated with tolerance rather than allergy.”
  • “Only 8% of children will become tolerant to all foods that cause their EoE.”

Bottomline: While foods commonly triggers EoE, the tests to identify these foods are far from perfect. I find that families are quite uninformed about the frequent lack of correlation between allergy testing and true EoE triggers.

Related blog posts:

Summary of article: GI & Hepatology News August 2014 Role of Allergy Testing in EoE

Elimination Diets for Eosinophilic Esophagitis in Adults

Posted on by

A recent study shows that elimination diets, including a six-food group elimination diet (SFED) can be effective in adults with eosinophilic esophagitis (EoE) (Clin Gastroenterol Hepatol 2014; 12: 1272-79).

This retrospective study identified 31 adults (mean age 36 years) who underwent dietary therapy between 2006-2012.  22 had a targeted elimination diet (TED) and 9 had SFED.

Key findings:

  • Symptoms improved in 71% (68% TED, 78% SFED)
  • Endoscopic appearance improved in 54% (53% TED, 56% SFED)
  • 39% had eosinophil count drop below 15 eos/hpf (32% TED, 56% SFED).  Overall in the entire cohort, mean eosinophil count dropped from 78 eos/hpf at baseline to 43 dos/hpf.
  • Among the nine responders with food reintroduction, the most common foods identified as triggers (using food reintroduction) were milk (4), egg (4), wheat (2), shellfish (1), and legumes (1).

 

Higher Doses of Topical Steroids for Eosinophilic Esophagitis

Posted on by

A recent randomized, double-blind, placebo controlled study (Gastroenterol 2014; 147: 324-33) examined “high-dose” fluticasone propionate (FP) for patients, aged 3-30 years, with eosinophilic esophagitis (EoE).  FP patients received 1760 mcg divided into two doses for three months, then the dose was reduced in half.

Efficacy: Among the 28 FP patients, a complete remission (CR) (≤1 eosinophil/hpf on histology) was evident in 65% compared with 0% CR in 14 placebo patients.  Furthermore, partial response (PR) (multiple definitions of responsiveness -see Figure 2) evident in about 75%.  Reduction in dose to 880 mcg/day resulted in 93% of EoE participants maintaining CR or PR.

Molecular response: The authors also studied the transcriptome prospectively in these patients with the “Eosinophilic esophagitis diagnostic panel” (EDP). “A large portion of the participants receiving FP in phase 1 showed a normalized signature compared with the dysregulated screening and placebo signatures….notably, the 6 FP participants with histologic PR or no remission also had a partial reversal with a signature different from the placebo group…However, there were still a few molecular nonresponders whose signatures failed to normalized upon FP treatment.”

Based on their study findings: the authors recommend assessment at 3 months after initiation of topical steroids because “extending the timeframe for high-dose FP to 6 months does not increase remission status.”

The authors could not identify any demographics or signs/symptoms that predicted response to high-dose FP. In addition, in this small cohort, no difference in adverse effects compared to placebo were found.

My take on this study is that it raises more questions than it answers.

  • Is the higher induction dose of FP really needed or would 880 mcg/day over a 6 month period result in the same findings?
  • Is FP superior to budesonide which is considered to have less systemic absorption?
  • Should we be using higher doses of budesonide as well?
  • Would patients be better off receiving systemic steroids and transitioning to topical steroids?
  • What are the long-term consequences, good and bad, in using higher steroid doses?

Take-home message: In a carefully designed study with molecular correlation, higher doses of Fluticasone achieved high rates of complete remission in EoE patients.  Except for elemental diets, no dietary therapies have shown to have a higher response rate.

Related blog posts:

Disclaimer: These blog posts are for educational purposes only. Specific dosing of medications/diets (along with potential adverse effects) should be confirmed by prescribing physician/nutritionist.  This content is not a substitute for medical advice, diagnosis or treatment provided by a qualified healthcare provider. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a condition.

 

Putting in Place a Big Piece of the Eosinophilic Esophagitis Puzzle

Posted on by

A recent study (Nature Genetics 2014; doi:10.1038/ng.3033 -thanks to Seth Marcus for this reference) provides novel in-depth molecular and mechanistic information on eosinophilic esophagitis (EoE).  Though the publication and supplemental material span only 8 pages, it is packed with information and highly technical assays and thus takes an effort to work through.

The authors performed a genome-wide association study (GWAS) of SNPs (single nucleotide polymorphisms) from >1.5 million genetic markers.  In total, this study involved samples from 736 EoE patients and 9246 controls. Four prominent markers were identified at 2p23, 5q22, 8p23, adn 15q13; however, the marker at 2p23 was most highly associated with a risk for EoE.  And, 2p23 included the CAPN14 gene (best SNP rs77569859).

Key Results:

  • CAPN14 is “specifically expressed in esophageal epithelium and is dynamically upregulated as a function of disease activity.”  Though CAPN14 is expressed in other tissues, it is primarily in the esophagus and pharynx (Figure 2).
  • CAPN14 encodes calpain 14, a calcium-activated cysteine protease.  CAPN14 showed the greatest upregulation in comparison to all members of the CAPN family.  Calpain proteases mediate protein cleavage for structural proteins, signaling molecules, transcription factors, and inflammatory mediators.  The latter are “germane for allergic responses.”
  • CAPN14 levels are >2-fold increase in individuals with active EoE.
  • CAPN14 gene is modified by IL-13.

Take-home message: (from the authors) This study shows the “potential centrality of CAPN14 in the etiology of EoE….We propose a model that links the interplay of allergic sensitization with an EoE-specific, IL-13-inducible esophageal response involving CAPN14.”

Related blog posts:

 

 

“If all you have is a hammer…”

Posted on by

In my training, one of my mentors would be critical of the mentality “scope first, think second.”  He was concerned that too many gastroenterologists/pediatric gastroenterologists used endoscopy as a tool simply “because if all you have is a hammer, the world looks like a nail.”

A recent publication (Clin Gastroenterol Hepatol 2014; 12: 963-69) on first glance, however, provides ammunition to the “scope first” gastroenterologists and undermines the concept that “functional” GI disorders vastly outnumber “organic” GI disorders.  The key finding was that esophagogastroduodenoscopy (EGD) provided an “accurate” diagnosis in 38%.  This included reflux esophagitis in 21%, eosinophilic esophagitis (EoE) in 5%, eosinophilic gastroenteritis (EGE) in 4%, H pylori in 2%, celiac disease 0.6%, and Crohn’s disease 0.4%. This finding is dramatically higher than previous studies.  In fact, in a recent published study (Understanding Idiopathic Nausea | gutsandgrowth) on idiopathic nausea, a control group of patients with chronic abdominal pain had a normal endoscopy in 100%!

In this prospective study of 290 children (ages 4-18 years with a mean age of 11.9 years), the primary indication for upper endoscopy was chronic abdominal pain.  Of this 290, 216 had at least 1 alarm feature and 125 had at least 2 alarm features.  Alarm features were considered to be the following:

  • Nighttime awakening 33.3%
  • Weight loss 15.6%
  • Family history of IBD 8.4%
  • Vomiting 7.8%
  • Dysphagia 6.9%
  • Nocturnal diarrhea 6.7%
  • Gastrointestinal bleed 5.8%
  • Chronic diarrhea 5.8%
  • Unexplained fever 4.4%
  • Arthralgia 4.0%
  • Growth failure 2.4%
  • Perirectal disease 0.7%
  • Delayed puberty 0.2%

There is little debate that abdominal pain in combination with true alarm symptoms (True red flags in recurrent abdominal pain | gutsandgrowth) merits further evaluation.  The aspect of this report that is worthy of close inspection is the diagnostic yield in the 74 patients without alarm symptoms.  The authors note that 25 (33.7%) had a diagnosis established with EGD including 16 with reflux esophagitis, 4 with EGE, 2 with EoE, 1 with erosive esophagitis, 1 with celiac and 1 with H pylori.  The diagnostic criteria for EGE included ≥10 eosinophils per hpf in the stomach and ≥20 eosinophils per hpf in the duodenum.

The authors note that the diagnostic yield was based on gross endoscopic findings in procedure notes or histologic changes in biopsy reports; “final pathology report on biopsies provided the data source for histologic diagnosis.”

In my opinion there are multiple flaws of this prospective study.

1. There is a very high rate of reflux esophagitis in both the alarm group and the non-alarm group patients with chronic abdominal pain.  Of the entire cohort (n=290), the authors identified reflux esophagitis in 21% and this was “primarily histologic esophagitis.”  Furthermore, the authors state that “the presence or response to PPI therapy was not predictive of esophagitis or GERD.”  So, the obvious problems:

  • Presence of histologic reflux esophagitis varies widely based on the interpreting pathologist.  In a prospective study, more than one pathologist interpreting the histology would be useful.
  • Presence of histologic reflux esophagitis does not exclude the likelihood of coexisting functional disorders (related blog post: Why didn’t patient with documented reflux get better with PPI …).  As a practical matter, “slight” or “focal” esophagitis on histology has questionable real-world relevance in pediatric gastroenterology.
  • The authors acknowledge, “current expert consensus indicates that histology has limited value in evaluating pediatric GERD.”  Yet this diagnostic finding is one of the reasons why the authors claim that EGD is so valuable.

2. In the entire cohort, the authors try to validate their findings by indicating that identification of a diagnosis led to medical therapy that was “effective in approximately 67%” of children with short-term followup. (Only 81% had short-term followup outcomes available).  Yet, there is no control group.  How many children with chronic abdominal pain will improve for a short period without an EGD-based diagnosis?  The answer: a lot of them.

3. Limitations include selection bias toward those with more severe symptoms or alarm symptoms.  In addition, this study included only a small number who were considered to have no alarm symptoms.  Finally, the short-term followup makes conclusions about the response to therapy questionable.

This study will be a useful reference for any pediatric gastroenterologist who wants to justify the need for an endoscopy.  The authors note “the majority of children in our study (93%) met criteria for functional gastrointestinal disorders, and a significant proportion (38%) still had significant histologic findings.  Therefore, we conclude the Rome III criteria alone are not sufficient to identify children who require upper endoscopy, and screening for alarm symptoms has limited utility.”

In my opinion, the reliance on histology as well as selection bias weaken the findings of this study.  If a patient with a histologic diagnosis of reflux (or several other entities) and a presentation of chronic abdominal pain does not improve, the pediatric gastroenterologist should remember that only “a poor carpenter blames his tools.”

Bottomline: EGD remains an important tool in evaluating abdominal pain.  However, I think this study substantially overestimates its utility.

Related blog posts:

 

 

 

 

The Latest on EoE and PPI-REE

Posted on by

A recent study shows similar clinical, endoscopic and histologic findings between eosinophilic esophagitis (EoE) and proton pump inhibitor-responsive esophageal eosinophilia (PPI-REE) (Aliment Pharmacol There 2014; 39: 603-08 -thanks to Seth Marcus for this reference).

The authors used two databases: one from Walter Reed and one from the Swiss EoE database.  All of these patients were >/=18 years.  Response to PPI was defined as achieving less than 15 eos/hpf and a 50% decrease from baseline following at least 6-weeks of PPI treatment.

Demographics: 63 EoE patients, 40 PPI-REE, mean age 40 years (75% male, 89% Caucasian).

Findings:

  • Similar dysphagia 97% vs. 100% (in EoE and  of PPI-REE cohorts)
  • Similar food impaction 43% vs. 35% (in EoE and  of PPI-REE cohorts)
  • Similar heartburn 33% vs. 32% (in EoE and  of PPI-REE cohorts)
  • Similar duration of symptoms: 6.0 years vs 5.8 years (in EoE and  of PPI-REE cohorts)
  • Similar endoscopic findings too: rings 68% in both groups, furrows 70% in both groups, strictures 49% vs 30% (in EoE and  of PPI-REE cohorts)
  • Similar histology: proximal esophagus 39 vs 38 eos/hpf and distal esophagus 50 vs 43 eos/hpf

Take-home message: EoE and PPI-REE are very similar in presentation and indistinguishable without a PPI trial.

Related blog posts: