An Allergy-Immunology View of GI Diseases

Recently, one of our allergy-immunology colleagues, Dr. Kiran Patel, from Emory presented an update on GI Diseases from an allergist viewpoint at one of our GI clinical education meetings. With his permission, many of the slides are noted below.  The slides present a good deal of information, though a lot of nuance and further details were provided by Dr. Patel.

Next few slides discuss typical GI food allergies.  It is not surprising that a lot of allergies manifest with GI symptoms given the amount of immune cells in the intestines and frequent interactions with foods and antigens.

This next slide points out that four of the most common food allergens (cow’s milk, egg, soy, and wheat) are frequently outgrown, whereas with peanuts, tree nuts, fish, and shellfish, it is uncommon to outgrow these allergies..

The next slide discusses potential evaluation.  While the slide states that the positive predictive value of skin prick tests and serum-based IgE tests may be as high as 50%; in fact, when broad panels of allergy tests are ordered, the positive predictive value can be quite low.

Related blog posts:

Dr. Patel did discuss the LEAP study and the LEAP-ON study which overall indicate that early antigen introduction is likely to reduce food allergies. Related blog posts:

 

The next few slides review Food Protein-Induced Enterocolitis Syndrome. Related blog posts:

The next few slides discuss eosinophilic esophagitis (EoE).  Allergy testing has not been very helpful in most patients with EoE. Related blog posts:

The last part of Dr. Patel’s talk focused on GI disease (eg. inflammatory bowel disease presentation) of primary immune deficiencies.  In the bottom slide, the diseases that often present with GI symptoms are boxed.

Disclaimer: These blog posts are for educational purposes only. Specific dosing of medications (along with potential adverse effects) and changes in diet should be confirmed by prescribing physician.  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.

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Is there a link between Eosinophilic Esophagitis and Celiac Disease?

Probably most pediatric gastroenterologists have seen patients who underwent endoscopy for celiac disease and found out that the patient had both celiac disease and esophageal eosinophilia.  Whether the esophageal eosinophilia should be classified as eosinophilic esophagitis (EoE) is based in part on whether one concludes that the EoE is a separate disorder and unrelated to the celiac disease.

One useful retrospective study on this topic (S Hommeida et al. JPGN 2017; 65: 58-63) examines the association between celiac disease and EoE.   Key findings:

  • Among a cohort of 10,201 children seen at the Mayo clinic, 595 were considered to have EoE and 546 had celiac disease.
  • Only 10 patients had both celiac disease and EoE.
  • The risk of EoE was not increased in children with celiac disease compared to those without celiac disease (odds ratio 0.29).  The prevalence of EoE in children with celiac disease was 1.8% whereas the prevalence among all children undergoing endoscopy was 5.8%.
  • 4 of 10 children treated only with GFD clinically improved (no followup histology)

Limitations:

  • The diagnosis of EoE was not clear in this study.  As noted in the associated editorial (pg 1-2), “the use of a high-dose proton pump inhibitor at the time of initial diagnosis is not mentioned.”
  • Overall, the number of patients with both EoE and celiac disease was small.  Thus, a much larger study could be necessary to prove the lack of an association.

My take: This study suggests that there is not an association between EoE and celiac disease. Some patients with both disorders will respond to a gluten free diet, whereas some will require additional treatment directed at EoE.

Related study: T Wallach et al. JPGN 2017; 65: 64-8. This retrospective study showed poor adherence to biopsy guidelines in EoE and celiac disease.  Among 9171 children, 8% were biopsied in accordance with 2007 AGA EoE consensus recommendations and 35% in accordance with  2006 AGA celiac guidelines.  Higher detection rates were observed among patients who had higher adherence to diagnostic guidelines. With both diseases, obtaining sufficient number of biopsies is key; and with celiac disease, obtaining biopsies from duodenal bulb as well as distal duodenum is recommended.

Chattahoochee River, Sandy Springs

Dilatation for Eosinophilic Esophagitis -Pediatric Data

The most recent data in adults has indicated that dilatation for eosinophilic esophagitis (EoE) likely does not have increased risk compare to esophageal dilatation for other causes.  A recent pediatric retrospective study (C Menard-Katcher et al. JPGN 2017; 64: 701-6) reaches a similar conclusion.

In this study over a 5-year period, there were 68 dilatations among 40 patients with EoE.

Dilatation was considered complete if a diameter of 15 mm (45 French) was reached or if a deep rent in the mucosa was evident; small (<0.5 cm) shallow rents were “not considered criteria for cessation of dilations.”

Methods:

  • In their institution, areas of narrowing >5 cm in length were typically treated with Maloney dilators and shorter narrowings were managed with balloon dilators (through the scope).
  • For Maloney bougie dilators, often dilations started at 24 French; typically 30 French if scope could traverse narrowing.
  • For balloon, often dilations started at 10 mm.  Fluoroscopy was often used at initial dilation (12 of 19).
  • 17 of 40 required more than one dilation in the study period

Some of the key findings:

  • Approximately 5% of their EoE patients needed dilations.
  • Patients with EoE who needed dilations were older than EoE patients who did not need this: 13.8 vs 8.2 years
  • Postoperative chest pain was most common adverse event, affecting 15% of dilations. In this small series, there were no perforations.
  • At this institution, half of the patients had dilation at their diagnostic endoscopy before starting EoE-specific therapy. However, as noted in their commentary, medical management may obviate the need for dilations.
  • Medical management consisted of “swallowed steroids (62%), dietary therapy (12%) or both (24%).”

My take: Overall, this study indicates that dilations are fairly safe in the EoE population. That being said, in my view, all dilations carry a small but significant risk.

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Musee d’Orsay, Naissance de Venus, Alexandre Cabanel, 1863

 

 

 

 

Is Propofol Safe in Pediatric Patients with Food Allergy and Eosinophilic Esophagitis?

According to a recent study (P Mehta et al. JPGN 2017; 64: 546-49), propofol was safe in pediatric patients with eosinophilic esophagitis (EoE) and food allergy.

This finding was based on a retrospective study of 1365 upper endoscopies (2013-2014).  Though, propofol was used less frequently, “there was no difference in complication rates relative to propofol use.”

Specifically, egg or soy allergy patients had 38 procedures; 114 children had EoE (without known egg or soy allergy) and 27 and EoE and egg or soy allergy.

This study is important because propofol is used frequently in patients with egg and soy allergies despite a contraindication warning on the package insert. Nevertheless, this study does not provide a definitive answer due to the very low rates of allergic reactions to propofol (~1:10,000 to 1:20,000).  In addition, the diagnosis of food allergy in this study relied on review of the medical record.

My take: This study is limited in scope but did not identify any significant safety concerns with propofol in patients who had EoE and/or egg/soy allergies.

Palace of Versailles

A Better Budesonide for Eosinophilic Esophagitis (Part 2)

A recent study (ES Dellon et al Gastroenterol 2017; 152: 776-86) provides more data indicating that a premixed solution of budesonide improves eosinophilic esophagitis (EoE). This study complements a recent report highlighted in a blog post earlier this year:

A Better Budesonide for Eosinophilic Esophagitis

In the present study by Dellon et al, the authors performed a multicenter, randomized, double-blind, placebo-controlled, parallel-group trial of 93 EoE patients (ages 11-40).  All patients had dysphagia and active EoE. The active treatment group received 2 mg twice daily.

Key findings:

  • Dysphagia symptom questionnnaire (DSQ) scores improved more in the active treatment group compared to placebo.  At baseline, the DSQ scores were 29.3 and 29.0 respectively.  After 12 weeks, the the scores were 15.0 and 21.5 respectively.
  • Similarly, the active treatment group peak eosinophil counts improved more.  At baseline, the treatment group had a count (per hpf) of 156 and this dropped to 39; in contrast, the placebo group started at 130 and dropped to 113.
  • The overall histologic response (≤6 eos/hpf) was 39% for the treatment group and 3% for the placebo group.
  • No significant adverse effects could be attributed to budesonide.  There was 1 case of esohageal candidiasis.  “There were no notable differences between the groups in cortisol levels.”

My take: Budesonide suspension is useful for EoE but not effective in all patients. A reliable composition from a manufacturer, if not too expensive, would be a big improvement for many kids with EoE. Higher doses of budesonide may be warranted in some cases of EoE.

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Statue outside the Louvre

GI Educational Cartoons For Children

Diana Lerner and the Medical College of Wisconsin have developed additional GI educational videos.  Previously, they had developed cartoon videos explaining endoscopy (prev post: Terrific Educational Videos on Endoscopy).  Now there are several more.  All of these are in English and some in Spanish.

Topics include inflammatory bowel disease, gastroesophageal reflux, eosinophilic esophagitis, and celiac disease.

Here’s the link:  Pediatric Gastroenterology Cartoons For Kids

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Safety of Fluticasone for Eosinophilic Esophagitis (Abstract)

Doerthe A Andreae et al. The American Journal of Gastroenterology 111, 1187-1197 (August 2016) | doi:10.1038/ajg.2016.238

METHODS:

In an open-label, prospective, single-center study, we offered pediatric patients with active EoE fluticasone 2 puffs to swallow twice a day (strengths in μg/puff: 2–4 years: 44, 5–11 years: 110, ≥12 years: 220). Clinical, endoscopic, and histological assessments were performed at baseline and shortly after therapy. If histological remission was seen, fluticasone was continued with clinical follow-ups every 4 months and endoscopic and histological follow-ups yearly. Clinical scores were derived from eight symptoms (abdominal pain, nausea, vomiting, regurgitation, chest pain, dysphagia, food impaction, and early satiety). Endoscopic scores were derived from six features (rings, exudates, furrows, edema, stricture, and shearing). Scores were expressed as ratio (features present/total). In addition to peak eosinophils/high power field (HPF) (primary outcome), histological features (eosinophilic microabscesses, degranulation, superficial layering, basal zone hyperplasia, dilated intercellular spaces, and lamina propria fibrosis) were assessed. Median clinical and endoscopic scores and individual histologic features were compared over 4 time intervals: <4 months, 4–12 months, 13–24 months, and >24 months. Growth and adverse effects were monitored.

RESULTS:

We enrolled 54 patients, 80% male, median age 6.5 years (range 2–17 years), 85% atopic (57% asthma, 68% allergic rhinitis, and 31% atopic dermatitis), and 74% with food allergy. Mean follow-up was 20.4 months, the longest being 68 months (5.7 years). Esophageal eosinophil counts significantly decreased (median peak eosinophils/HPF at baseline 72, <4 months: 0.5, 4–12 months: 1.75, 13–24 months: 10, and >24 months: 12, all P<0.01). All histological features significantly decreased from baseline to all follow-up time points (all P<0.01). Lamina propria fibrosis significantly decreased (% patients with fibrosis at baseline 92, <4 months: 41, 4–12 months: 50, 13–24 months: 45, and >24 months: 39, all P<0.01). Endoscopic features improved (score at baseline 0.37, <4 months: 0.17, 4–12 months: 0.17, 13–24 months: 0, and >24 months: 0.1, all P<0.01, except at >24 months: P<0.05). Symptoms improved (score at baseline 0.22, <4 months: 0, 4–12 months: 0.11, 13–24 months: 0.11, and >24 months: 0.11, all P<0.05 except at >24 months: P=0.05). In a mixed linear regression model that accounts for correlation of repeated observations in the patient in a per-patient analysis, we found that treatment with swallowed fluticasone led to a statistically significant and sustained decrease in peak esophageal eosinophil counts. Asymptomatic esophageal candidiasis was seen in three children but resolved with anti-fungal therapy. Height and weight z-scores followed expected growth curves.

CONCLUSIONS:

We demonstrate that swallowed fluticasone is effective as a long-term maintenance therapy for children with EoE, without growth impediment or serious side effects.

My take: This post, from an abstract, shows a single-center’s experience with fluticasone. This study provides some reassurance regarding safety & efficacy when used as a maintenance medication. However, as noted in links below, higher doses of fluticasone have been associated with adrenal insufficiency.

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