Paul J. Ufberg DO, MBA Maine Medical Center 3/22/15 8 AM
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No conflicts to disclose NASPHAN Slides included in this
presentation I like to treat EoE I think MMC should develop an Eoe
Clinic with multi-specialty teams to include GI, Allergy, social
workers and nutritionists
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Recognize the increasing burden and significance of EoE
Understand the criteria for diagnosis and basic pathophysiology of
the disease Treatment options Discussion of future research
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11 year old white male Chief complaint of abdominal pain
Diffuse Always Worse for the last 6 month Food (?) are triggers
Debilitating Limiting foods Nausea but no vomiting No diarrhea Seen
by PCP multiple times Thought to be: Infection Post infection
Reflux/gastritis Dyspepsia Functional pain Valley fever (AZ) Celiac
disease Constipation Allergy
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Always a difficult to feed child Labelled as GER at 6 months
Never really spit up Weight gain at 10 th percentile throughout
life Never sick but always run down Deteriorating in school work
Eat and pain Dont eat and miserable ROS: Asthma Home inhaler never
used Otherwise unremarkable Strong family history Asthma Atopy
Exam: unremarkable
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Lab workup was unremarkable CBC CMP Inflammatory markers Celiac
panel Multiple RAST panels 2 to 3 panels Radiology unremarkable UGI
SBFT CT Abdomen Trial of a PPI and miralax for 1 month with no
improvement
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Marked changes consistent with Eoe 60-80 Eoe/hpf in distal
esophagus 40 Eoe/hpF in proximal esophagus Normal stomach 2-3
eosinophils/hpf in duodenum
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Liacouras CA, Furuta GT, Hirano I, et al. Eosinophilic
esophagitis: updated consensus recommendations for children and
adults. J Allergy Clin Immunol 2011;128:320.
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Now what?
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EoE first described in the late 1970s 1985 first case series By
1995 more robust description Distinct Triggers mechanisms explored
Separate disease or part of a spectrum? Cincinnati Childrens
retrospective 1991 2003 315 total cases of Eoe in one Ohio County
Only 2.8 % were identified prior to 2000 From 2000-2003 Incidence 1
in 10,000 Prevalence 4.3 in 10,000 CHOP there was a 35- fold
increase in newly diagnosed EE cases 1994 - 2 case 2003 - 72
cases
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EE can present at any age ~50 cases/100,000 in patients under
20 years old Male predominant 3:1 More common in Non-Hispanic
whites Atopy is common Food/environmental allergy Allergic rhinitis
Eczema Asthma
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Figure 1 Clinical Gastroenterology and Hepatology 2014 12,
589-596.e1DOI: (10.1016/j.cgh.2013.09.008)
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Manifestations may vary with age Infants and toddlers may be
poor feeders School aged children may have vomiting and pain Chest
or abdominal pain Frequently appears like GER Vomiting tends to be
random Adolescents tend to have dysphagia or food impaction
Dysphagia is also most common in adults Choking, gagging, sticking
Excessive drinking Impaction
Record review from 1993-2009 Radiology reports of food
impaction UGI Esophogram Identified 43 patients with impaction
27/43 (63%) had an EGD 23 of 27 had EoE 28/43 (63%) - male Diniz, L
Causes of Esophageal Food Bolus Impaction in the Pediatric
Population Dig Dis Sci (2012) 57:690693
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CHOP cohort of 620 patients 2/3 of Eoe patients had atopy
Asthma - 231 (37%) Allergic rhinitis- 243 (39%) Atopic dermatitis -
78 (13%) Prevalences of atopy diseases 3X higher than expected in
the general population 60-70% of Eoe have other atopic diseases
Brown-Whitehorn, T, The link between allergies and eosinophilic
esophagitis: implications for management strategies, Expert Rev
Clin Immunol. 2010 January 1; 6(1): 101
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EE and Atopic disease US prevalence of asthma and atopic
dermatitis in the 1990s and 2000s, expressed as a percentage
Brown-Whitehorn, T, The link between allergies and eosinophilic
esophagitis: implications for management strategies, Expert Rev
Clin Immunol. 2010 January 1; 6(1): 101
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Long term outcome of EoE is still unclear Concern for fibrosis
and subsequent strictures due to remodeling of the esophagus Adult
study of patients with EoE 29 of 30 patients had dysphagia 11 of 30
needed dilations All had persistent Eosinophilia 86% of adults had
esophageal structural changes. 67% had narrowing on radiographic
studies
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Initial guidelines mainly by pediatric specialists Diagnostic
guidelines Clinical symptoms of esophageal dysfunction 15
Eosinophils in 1 high- power field Lack of responsiveness to
high-dose proton pump inhibition (up to 2 mg/kg/day) Normal pH
monitoring of the distal esophagus Rule out other causes of
Eosinophilia Gastroesophageal reflux disease Crohns disease
Connective tissue disease Hypereosinophilic syndrome Infection Drug
hypersensitivity response Furuta GT, et al. Eosinophilic
esophagitis in children and adults: a systematic review and
consensus recommendations for diagnosis and treatment.
Gastroenterology 2007;133: 134263. 133:1342-63, 2007
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Doubling of papers on Eoe over 4 years Poor use of the
recommendations from 2007 1/3 of physicians were following
guidelines Many doctors not using clinical criteria Time to
consider a revision
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Larger physician panel with more adult and pediatric
representation 33 physicians 6 months Focus on the chronicity of
disease Change of Term EE becoming Eoe Maintain threshold number of
15 eosinophils/hpf In most cases Therapeutic approaches Recognition
of PPI Responsive disease
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What is Eosinophilic Esophagitis (Eoe)? EoE is a chronic immune
or antigen mediated disorder causing esophageal inflammation. It is
associated with esophageal dysfunction resulting from severe
eosinophil-predominant inflammation. Gastric and duodenal mucosa -
normal Esophageal eosinophilia and symptoms do not respond to high
dose Proton Pump Inhibitor (PPI) therapy
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Esophageal biopsy is needed for diagnosis Pathologically 1 or
more biopsy containing 15 eosinophils/hpf is considered threshold
Earlier literature considered 20 Eos/hpf More biopsies the better 1
biopsy -sensitivity 73 % 2 biopsies 84% 3 biopsies 97%
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Peak eosinophil count Eosinophilic granules Layering of
eosinophils Micro abscesses Basal cell hypertrophy Fibrotic changes
These findings may be consistent with EoE without 15 Eos/Hpf
Liacouras CA, Furuta GT, Hirano I, et al. Eosinophilic esophagitis:
updated consensus recommendations for children and adults. J
Allergy Clin Immunol 2011;128:320.
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Considered to be distinct from EoE Possibly a subset of the
disease Progression? Treated with high dose PPI Thought to be
related to: GERD treated with acid suppression Anti-inflammatory
effect from PPI Some combination of multiple factors
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Familial clusters of Eoe and atopy Increased incidents in 1 st
degree relatives 50-90% of patients with Eoe have atopy ~ 75% have
a family history of atopic disease Chromosome loci identified 5q22
Harbors the Thymic stromal lymphopoietin (TSLP) Genetic variant of
TSLP was found on X chromosome Increased atopic disease with 5q22
changes
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Chromosome 2p23 - CAPN14 region 2 fold increase expression in
patients with Eoe specifically in esophagus Up regulated in disease
states Induced by IL-13 Kottyan, Genome-wide association analysis
of eosinophilic esophagitis provides insight into the tissue
specificity of this allergic disease, Nature Genetics,
doi:10.1038/ng.3033; July 2014
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Eoe Vs. GERD Increased Eotaxin-3 and Interleukin-5 (IL-5)
Eotaxin-3 is a chemoattractant for Eosinophils IL-13 likely
stimulants the Eotaxin T-Helper Cells 2 and multiple IL involved
IL-5 and IL-13 has been shown to cause esophageal inflammation in
mouse models Collagen deposition component as well TGF-B is
involved
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Straumann, Pediatric and adult eosinophilic esophagitis:
similarities and differences Allergy Volume 67, Issue 4, pages
477490, April 2012
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Majority of patients with Eoe have food allergy (s) Often not
IgE mediated 5.7-24% have food induced anaphylaxis Average 4-5
foods (categories) Typical allergens Milk # 1 Egg and Soy Wheat,
Corn and Beef Chicken Peanuts, Rice, Potato Oat, Barley, Turkey,
Pea
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Seasonal variation of Eoe Decreased Eoe in the winter Increase
during grass and pollen season In adults increased new diagnosed
Eoe in spring Aeroallergens with age Mold, dust mites and
cockroaches
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What is the goal of therapy? Clinical improvement Improve
symptoms and Quality of life Histologic improvement Prevent
complications/remodeling of esophagus Multiple endoscopies and
medications Endoscopic improvement Prevent complications Multiple
endoscopies and medications All Three?? End points are not clear
End points dont always correlate with each other
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PPI therapy Diet changes Focused Empiric Elemental Diet
Steroids Other
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Distinguish Eoe from PPI RE GERD can cause eosinophilia but not
as severe as Eoe GERD and Eoe are not mutually exclusive
Symptomatic patients should be given a trial of PPI High dose PPI
up to 1mg/kg BID 3 months of therapy PPI therapy alone is
insufficient to treat Eoe
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PPI therapy Diet changes Focused Empiric Elemental Diet
Steroids Other
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Milk Most common allergen Consider avoiding
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Strong association with food allergies Remove likely trigger
foods Trial and Error Self directed Clinical experience Allergy
testing Skin prick Patch testing RAST testing inaccurate
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Pros Keep most of the diet intact More specific Effective Cons
Delayed reactions to foods Persistence of reactions Testing can be
difficult to interpret Confounding variables
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Removal of most common food allergens Six food elimination diet
Milk, Soy, Wheat, Egg, Peanuts/Nuts and Fish Studies have
demonstrated a 75% improvement Consider nutritionist to assist with
these changes
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PROS Fairly easy to initiate No testing needed Good results
CONS Hard to maintain May be removing unnecessary foods May not be
removing all triggers Nutritional issues
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Amino acid based formula alone Can be flavored Some beverages
allowed Dum Dum or Smarties - OK Symptomatic improvement in the
first 3-6 weeks 95% response histologically and clinically No
medications needed May be able to reintroduce foods slowly back
into the diet Symptoms may return
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PROS Full nutrition Effective No medications Can get creative
CONS No foods Quality of life issues Bad taste Often requires
alternative feeding option Expensive
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Nutritionist involvement is important Repeat endoscopy timing
Variable Usually need frequent follow ups Reintroduction of foods
can be considered after normal biopsy Patients usually have
multiple (4-5) allergies 25% may be severe and react to most (ALL)
foods Keep in mind the seasons
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PPI therapy Diet changes Focused Empiric Elemental Diet
Steroids Other
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Improve the clinicopathologic features of EoE Effective therapy
as topical therapy Systemic steroids in emergencies When
discontinued symptoms usually recur Multiple options for delivery
Good short term safety Except for fungal infection Variability in
dosing
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Liacouras CA, Furuta GT, Hirano I, et al. Eosinophilic
esophagitis: updated consensus recommendations for children and
adults. J Allergy Clin Immunol 2011;128:320.
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OVB mixing instructions 0.5 mg Pulmicort Respule + 5 g (5
packets) of sucralose (Splenda) = 812 mL slurry OVB 12 mg daily No
solid or liquid food for 30 minutes 10 yr or over received 2
mg/day
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PROS Effective Multiple delivery systems Inhaler Slurry options
or mixing Can be used in an emergency CONS Recurrence with
cessation Not studied for maintenance therapy Concern for long term
steroid effect
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PPI therapy Diet changes Focused Empiric Elemental Diet
Steroids Other
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Cromolyn Sodium mast cell stabilizer no apparent benefit
Limited to a small study Leukotriene receptor agonist - Singulair
no apparent benefit Anti TNF agents showed no benefit IL-5
antagonist Cytokine inhibitor Pending
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Not a first line treatment option Still controversial Does not
address the inflammation Complications not as great as once
believed 404 patients 839 dilations. Chest pain 5% Bleeding