Paul J Ufberg DO MBA Maine Medical Center 32215 8 AM Disclosure No conflicts to disclose NASPHAN Slides included in this presentation I like to treat EoE I think MMC should ID: 513614
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Slide1
EoE – Eosinophilic Esophagitis
Paul J. Ufberg DO, MBA
Maine Medical
Center
3/22/15
8 AMSlide2
Disclosure
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 nutritionistsSlide3
Goals of this lecture
Recognize the increasing burden and significance of
EoE
Understand the criteria for diagnosis and basic pathophysiology of the disease
T
reatment options
Discussion of future researchSlide4
Patient
11 year old white male
Chief complaint of abdominal pain
Diffuse
“Always”
Worse for the last 6 month
F
ood (?) are triggersDebilitatingLimiting foodsNausea but no vomitingNo diarrhea
Seen by PCP multiple times
Thought to be:
Infection
Post infection
Reflux/gastritis
Dyspepsia
Functional pain
Valley fever
(AZ)
Celiac disease
Constipation
AllergySlide5
History and Physical Exam
Always a difficult to feed child
Labelled as GER
at 6 months
Never really spit up
W
eight gain at 10
th percentile throughout life
Never “sick” but always “run down”
Deteriorating in school work
Eat and painDon’t eat and miserable
ROS:
Asthma –Home
inhaler never used
Otherwise
unremarkable
Strong
family history
Asthma
Atopy
Exam: unremarkableSlide6
Labs and Studies
Lab workup was unremarkable
CBC
CMP
Inflammatory markers
Celiac panel
Multiple RAST panels – 2 to 3 panels
Radiology unremarkableUGI SBFTCT AbdomenTrial of a PPI and miralax
for 1 month with no improvement Slide7
EGD
Marked changes consistent with
Eoe
60-80
Eoe
/
hpf
in distal esophagus40 Eoe/hpF in proximal esophagusNormal stomach2-3 eosinophils/hpf
in duodenumSlide8
Which are Findings Consistent with
Eoe
???
Liacouras
CA,
Furuta
GT, Hirano I, et al. Eosinophilic esophagitis: updated consensus recommendations for children and adults. J Allergy
Clin
Immunol
2011;128:3–20.Slide9
Esophageal FurrowingSlide10
White PlaquesSlide11
Esophageal RingsSlide12
Esophageal FragilitySlide13
Classification/Grading System for Endoscopically Detected Esophageal Features of EoE -EREFSSlide14
Diagnosis
“Now what?”Slide15
Eosinophilic Esophagitis The BasicsSlide16
Prevalence and SymptomsSlide17
EoE – A Disease in Progress
EoE
first described in the late 1970s
1985 first case series
By 1995
more robust description
Distinct
Triggers mechanisms exploredSeparate disease or part of a spectrum?
Cincinnati Children’s 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
casesSlide18
1995 Distribution of EoESlide19
2013 Distribution of EoESlide20
Symptoms
EE can present at any age
~50 cases/100,000 in patients under 20 years
old
Male predominant 3:1
More common in Non-
H
ispanic whitesAtopy is common Food/environmental allergyAllergic rhinitisEczemaAsthmaSlide21
Figure 1
Clinical Gastroenterology and
Hepatology
2014 12, 589-596.e1DOI: (10.1016/j.cgh.2013.09.008) Slide22
Symptoms
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 randomAdolescents tend to have dysphagia or food impactionDysphagia is also most common in adultsChoking, gagging, “sticking”
Excessive drinking
ImpactionSlide23
Presenting Symptoms
103 Pediatric Patients with
EoE
Symptom
Median Age
No. (%)
Feeding disorder
2.0 (1.2–6.2)
14 (13.6)
Vomiting
8.1 (3.5–12.3)
27 (26.2)
Abdominal pain
12.0 (9.6–15.2)
27 (26.2)
Dysphagia
13.4 (10.0–16.7)
28 (27.2)
Food impaction
16.8 (13.7–19.6)
7 (6.8)
Noel RJ, Putnam PE, Rothenberg ME.
Eosinophilic
esophagitis. N
Engl
J Med 2004;351:940–1.Slide24
Food Impactions
Record review from 1993-2009
Radiology reports of food impaction
UGI
Esophogram
Identified 43 patients with impaction
27/43
(63%) had an EGD23 of 27 had EoE28/43 (63%) - male
Diniz
, L
Causes of Esophageal Food Bolus Impaction in the Pediatric Population
Dig Dis Sci (2012) 57:690–693Slide25
Eoe and Atopic Diseases
CHOP cohort
of 620
patients
2/3 of
Eoe
patients had
atopyAsthma - 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): 101Slide26
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): 101Slide27Slide28Slide29
Long Term Eoe
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 dysphagia11 of 30 needed dilationsAll had persistent Eosinophilia
86% of adults had esophageal structural changes.
67% had narrowing on radiographic studiesSlide30
Natural History – Adult StudySlide31
Esophageal RingsSlide32
Small Caliber EsophagusSlide33Slide34Slide35
Consensus RecommendationsSlide36
2007 Eoe Guidelines - FIGERS
Initial
guidelines mainly
by pediatric
specialists
Diagnostic
g
uidelinesClinical symptoms of esophageal dysfunction15 Eosinophils in 1 high-power fieldLack 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
Crohn’s
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:
1342–63. 133:1342-63, 2007Slide37
2007 to 2011
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 revisionSlide38
2011 Recommendations
Larger physician panel with more adult and pediatric representation
33 physicians
6 months
Focus on the chronicity of disease
Change of Term
EE becoming
EoeMaintain threshold number of 15 eosinophils/hpf
In most cases
Therapeutic approaches
Recognition of PPI Responsive diseaseSlide39
Defining EoE
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) therapySlide40
Defining EoE
Esophageal biopsy is needed for diagnosis
Pathologically
1 or more biopsy containing 15 eosinophils/
hpf
is considered threshold
Earlier literature considered 20 Eos/
hpfMore biopsies the better1 biopsy -sensitivity 73 % 2 biopsies – 84%
3 biopsies – 97%Slide41Slide42
Other Pathologic Findings
Peak
eosinophil count
Eosinophilic granules
Layering
of
eosinophils
Micro abscessesBasal cell hypertrophyFibrotic changesThese 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;128:3–20.Slide43
PPI – Responsive EoE
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 suppressionAnti-inflammatory effect from PPISome combination of multiple factorsSlide44
PPI-REE – EstimatesSlide45
Genetics and PathophysiologySlide46Slide47
Genetics
Familial clusters of
Eoe
and
atopy
Increased incidents in 1
st degree relatives50-90% of patients with Eoe have atopy~ 75% have a family history of atopic diseaseChromosome loci identified 5q22
Harbors the
Thymic
stromal lymphopoietin (TSLP)Genetic variant of TSLP was found on X chromosome
Increased atopic disease with 5q22 changesSlide48
Genetics
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
Ge
n
etics,
doi:10.1038/ng.3033; July 2014Slide49
Immunologic Basis of Eoe
Eoe
Vs. GERD
Increased Eotaxin-3 and Interleukin-5 (IL-5)
Eotaxin-3 is a
chemoattractant
for Eosinophils
IL-13 likely stimulants the EotaxinT-Helper Cells 2 and multiple IL involvedIL-5 and IL-13 has been shown to cause esophageal inflammation in mouse models
Collagen deposition component as well
TGF-B is involvedSlide50
Straumann
,
Pediatric and adult eosinophilic esophagitis: similarities and
differences Allergy
Volume
67, Issue 4,
pages 477–490, April
2012Slide51
Allergens
Majority of patients with
Eoe
have food allergy (s)
Often not
IgE
mediated
5.7-24% have food induced anaphylaxisAverage 4-5 foods (categories)Typical allergensMilk # 1Egg and SoyWheat, Corn and Beef
Chicken
Peanuts, Rice, Potato
Oat, Barley, Turkey, PeaSlide52
Is It Something in the Air?
Seasonal
variation of
Eoe
Decreased
Eoe
in the
winterIncrease during grass and pollen seasonIn adults increased new diagnosed Eoe in springAeroallergens with age
Mold
, dust
mites and cockroaches Slide53Slide54
Treatment OptionsSlide55
Goals of Therapy
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 improvementPrevent complicationsMultiple endoscopies and medications
All Three??
End points are not clear
End points don’t always correlate with each otherSlide56
Treatment Options
PPI therapy
Diet changes
Focused
Empiric
Elemental Diet
Steroids
OtherSlide57
PPI therapy
Distinguish
Eoe
from PPI – RE
GERD can cause eosinophilia but not as severe as
Eoe
GERD and
Eoe are not mutually exclusiveSymptomatic patients should be given a trial of PPI High dose PPI – up to 1mg/kg BID3 months of therapy
PPI therapy alone is insufficient to treat
EoeSlide58Slide59
Treatment Options
PPI therapy
Diet changes
Focused
Empiric
Elemental Diet
Steroids
OtherSlide60
Milk – Does It Do A Body Good?
Milk
Most common allergen
Consider avoidingSlide61
Focused Food Removal
S
trong association with food allergies
Remove likely trigger foods
Trial and Error
Self directed
Clinical experience
Allergy testingSkin prick Patch testingRAST testing – inaccurateSlide62
Focused Food Removal
Pros
Keep most of the diet intact
More specific
Effective
Cons
Delayed reactions to foods
Persistence of reactionsTesting can be difficult to interpret
Confounding variablesSlide63
Empiric Diet Restriction
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 changesSlide64
Empiric Food Diet
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 issuesSlide65
Elemental Diet
Amino acid based formula alone
C
an be flavored
Some beverages allowed
Dum Dum or
Smarties
- OKSymptomatic improvement in the first 3-6 weeks95% response histologically and clinicallyNo medications neededMay be able to reintroduce foods slowly back into the dietSymptoms may return Slide66
Dietary Management Amino Acid–Based FormulaSlide67
Elemental Diet
PROS
Full nutrition
Effective
No medications
Can get creative
CONS
No foods
Quality of life issues
Bad taste
Often requires alternative feeding optionExpensiveSlide68Slide69
Diet - Followup
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) foodsKeep in mind the seasons Slide70Slide71Slide72
Treatment Options
PPI therapy
Diet changes
Focused
Empiric
Elemental Diet
Steroids
OtherSlide73
Corticosteroids
Improve the
clinicopathologic
features of
EoE
Effective therapy as topical therapy
Systemic steroids in emergencies
When discontinued symptoms usually recurMultiple options for deliveryGood short term safetyExcept for fungal infection Variability in dosingSlide74
Steroid Recommendations
Liacouras
CA,
Furuta
GT, Hirano I, et al. Eosinophilic esophagitis: updated consensus recommendations for children and adults. J Allergy
Clin
Immunol
2011;128:3–20.Slide75
Oral Viscous Budesonide (OVB)
OVB mixing instructions
0.5 mg
Pulmicort
Respule
+ 5 g (5 packets) of sucralose (Splenda) = 8–12 mL slurry
OVB 1–2 mg daily No solid or liquid food for 30 minutes
<10
yo
received OVB 1 mg/day > 10 yr or over received 2 mg/daySlide76
Steroids
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 effectSlide77
Treatment Options
PPI therapy
Diet changes
Focused
Empiric
Elemental Diet
Steroids
OtherSlide78
Other Medications
Cromolyn
Sodium – mast cell stabilizer
– no apparent benefit
Limited to a small study
Leukotriene receptor agonist -
Singulair
– no apparent benefitAnti TNF agents showed no benefitIL-5 antagonist – Cytokine inhibitor
PendingSlide79
Surgical - Dilations
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 <0.5% (1 patient)Perforation 0.8 % (3 patients)Slide80
Approach of Treatment
High dose PPI for minimum of 8 weeks
Discuss options for diet
Be honest
Be realistic
Consider ALL options
Include nutritionist and allergist in plan
Make decisions on testing as a teamStress that this is a chronic conditionSlide81Slide82
Back to the PatientSlide83
What About The Patient?
Family considered options
Attempted 6 food elimination diet
Failed
Continued to lose weight
More fatigued
Allergy TestingSlide84
Allergy Testing
Found to be allergic to many (most) foods
Restriction diet
Allowed between 9-12 foods
Symptoms improved
Weight loss persistedSlide85
Next StepSlide86
From Tube to TubeSlide87Slide88
Plan
Majority of calories from
Elecare
Able to eat and function “normally” on 12-15 foods
Food trial of 1-2 foods every month with EGD every 6-8 weeks.
He did gain weightSlide89
Acting and WritingSlide90
Looking ForwardSlide91
Quality of Life in EoE
- Accepted for Publication
Assessment of the impact of treatment on health related quality of life for patients with
Eoe
and their families.
4 centers, 97 patients (
ages 2-18
years)Screened at 0, 2, 6 monthsHRQoL improved during evaluation and treatment, with positive changes strongest for patients with less symptom severity at
baseline
Klinnert
, M;
Health Related Quality of Life Over Time in Children with Eosinophilic Esophagitis (
EoE
) and their
Families JPGN Accepted 6/2/14Slide92
Horizon
Change in the delivery method of steroids
Splenda – a story in serendipity
Antibodies directed specific interleukins
F
ocus on genetics
Change in testing
String and biomarker testingCan we avoid more endoscopies?Eoe multispecialty groupsSlide93
Unresolved IssuesSlide94
Advocacy GroupsSlide95
QuestionsSlide96
Bibliography
http://teamsupern8.com/
Diniz
, L Causes of Esophageal Food Bolus Impaction in the Pediatric Population
Dig Dis Sci (2012)
57:690–693
Management Guidelines of Eosinophilic
Esophagitis in Childhood, Papadopoulou, JPGN Volume 58, Number 1, January
2014 107-118
Furuta
GT, Liacouras CA, Collins MH, et al. Eosinophilic esophagitis in children and adults: a systematic review and consensus recommendations for
diagnosis and treatment. Gastroenterology
2007;133: 1342–63.
Liacouras
CA,
Furuta
GT, Hirano I, et al. Eosinophilic
esophagitis: updated
consensus recommendations for children and adults. J
Allergy
Clin
Immunol
2011;128:3–20
.
Noel RJ, Putnam PE, Rothenberg ME. Eosinophilic
esophagitis. N
Engl
J Med 2004;351:940–1
.
Dellon
, E,
Clinical Gastroenterology and
Hepatology
2014 12, 589-596.e1DOI: (10.1016/j.cgh.2013.09.008)
Klinnert
, M;
Health Related Quality of Life Over Time in Children with Eosinophilic Esophagitis (
EoE
) and their Families JPGN Accepted 6/2/14
Brown-
Whitehorn
, T, The link between allergies and eosinophilic esophagitis: implications for management strategies, Expert Rev
Clin
Immunol
. 2010 January 1; 6(1):
101
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 2014Straumann, Pediatric and adult eosinophilic esophagitis: similarities and differences Allergy Volume 67, Issue 4, pages 477–490, April 2012