ACG Regional Course- Indianapolis
Copyright 2012 ACG
Eosinophilic Esophagitis
Joel Rubenstein, MD, MSc
Veterans Affairs Center for Clinical Management Research
University of Michigan Medical School
EoE Case
16 year
year--old girl with mild chest pain and progressive dysphagia
for solids to the point that she could only tolerate baby food
food.
Biopsies from distal esophagus: > 50 eos
eos/HPF
/HPF
Placed on omeprazole and fluticasone. Mild symptomatic
improvement. Discontinued.
August 2012
1
ACG Regional Course- Indianapolis
Copyright 2012 ACG
Epidemiology in Adults
• Prevalence in populationpopulation-based studies:
– ~ 0.03%
• In pts undergoing EGD for GERD,
dysphagia, food impaction: 0.9
0.9--48%
• More frequent in younger men, atopy
atopy,,
asthma, food allergies.
Sealock R, et al. APT 2010
Definition of EoE
•
•
•
•
Symptoms related to esophageal dysfunction.
15 eosinophils
eosinophils//hpf (peak value).
value
value)).
)
The disease is isolated to the esophagus.
Other causes of esophageal eosinophilia
should be excluded
excluded,, specifically PPI
PPI-responsive
p
esophageal
p g
eosinophilia.
p
Liacouras,, et al. Consensus Guidelines. J Allergy Clin Immunol 2011;128:3Liacouras
2011;128:3-20
August 2012
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GERD and Eos in the Esophagus
• Approximately 16% of patients with
eosinophil-rich esophagitis have
symptomatic improvement by PPI.
• Symptomatic
y p
improvement
p
may
y be
inversely associated with density of eos.
Furuta,, et al. AGA Consensus Recommendations. Gastro 2007.
Furuta
GERD and Eos in the Esophagus
• GERD can cause a mild eosinophilic infiltration.
• GERD might contribute to EoE:
– Increased permeability exposes esophagus to antigens.
• EoE may contribute to GERD:
– Eosinophil secretory products may relax the LES (VIP,
(VIP
platelet activating factor) and alter body motility resulting
in delayed clearance.
– Structural remodeling → shortened esophagus, hiatal
hernia formation.
Spechler S. AJG 2007.
August 2012
3
ACG Regional Course- Indianapolis
Copyright 2012 ACG
EoE Case
16 year-old girl with mild chest pain and progressive dysphagia
for solids to the point that she could only tolerate baby food.
Biopsies from distal esophagus: > 50 eos/HPF
eos/HPF
Placed on omeprazole and fluticasone. Mild symptomatic
improvement. Discontinued.
EoE Case
EGD on omeprazole
l 20
20mg BID
– stricture at GE junction, dilated to 12 mm
– lower esoph 21 eos
eos/HPF,
/HPF, upper esoph 72 eos/HPF
eos/HPF
Now what?
August 2012
4
ACG Regional Course- Indianapolis
Copyright 2012 ACG
Food Elimination in EoE
• Elemental diet
• Skin prick or atopy patch testing
• Empiric elimination
Skin Prick or Atopy Patch Testing
• 146 children with EoE
– 77% had histological resolution after
elimination.
– Most common: egg, milk, soy, wheat, corn
– In other studies, common also included nuts,
peanuts, fish.
Spergel J, et al. Ann Allergy Asthma Immunol. 2005
August 2012
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Empiric Elimination
• Prospective cohort study in adults (n=50) of 6 weeks
elimination of:
– Milk, soy, egg, wheat, nuts/peanuts, fish.
– Sequentially reintroduced foods (n=20).
• Skin prick testing prior.
• 64% histological resolution.
• Dysphagia improved in 94%
• Reintroduction:
– Wheat (60%), milk (50%), soy (10%), nuts (10%), egg (5%)
– SPT accurate in 13%, and negative in 67%
Gonsalves N, et al. Gastro 2012
EoE Case
16 year
year--old girl with mild chest pain and progressive dysphagia for solids to
the point that she could only tolerate baby food.
Biopsies from distal esophagus: > 50 eos
eos/HPF
/HPF
Placed on omeprazole and fluticasone. Mild symptomatic improvement.
Discontinued.
Skin testing negative. Empiric elimination of dairy, wheat, soy,
nuts and fish.
nuts,
fish No change in symptoms.
symptoms Referred for
management.
Atopy patch testing positive for corn. No symptomatic
improvement with elimination.
EGD with corn elimination and PPI: eos
August 2012
6
ACG Regional Course- Indianapolis
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RCTs of Steroids for EoE
Fluticasone vs. placebo in children with EoE
• 21 randomized to F MDI 440mcg BID
without spacer x 3 months.
• 15 to placebo
• ≤ 1 eos
eos/HPF
/HPF at f/u:
– 50% F vs. 9% placebo (p = 0.047)
Konikoff M, et al. Gastro 2006
RCTs of Steroids for EoE
Fluticasone vs. prednisone in children
• 40 to each arm
– Prednisone 1mg/kg BID (max 30 mg BID) x 4 weeks,
then 8 week taper to 0.25mg/kg daily
– Fluticasone 220
220--440 mcg QID x 4 weeks, then 8
week taper to 220220-440 mcg daily.
• Week 4 histological remission:
– 81% prednisone
d i
vs. 50% fluticasone
fl ti
((p < 0
0.05)
05)
• Week 4 symptomatic resolution:
– 100% prednisone vs. 97% fluticasone
– Similar symptomatic recurrence with weaning (45%)
Schaefer E, et al. CGH 2008
August 2012
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RCTs of Steroids for EoE
Budesonide in children
• Budesonide 1 or 2 mg in Splenda qhs
(n=15) or placebo (n=9) x 3 months.
• Histological remission:
– 87% budesonide vs. 0% placebo (p<0.001)
• Sy
Symptoms
po sa
also
so improved
p o ed be
better
e with
budesonide (p=0.03)
Dohil R, et al. Gastro 2010
RCTs of Steroids for EoE
Budesonide in adolescents or adults
• Budesonide 1 mg nebulized BID (n=18) or
saline (n=18) x 15 days.
– Avg. age 33 and 38 years.
– Histological remission: 72% vs. 11% (p <
0.001)
– Dysphagia improved: 72% vs. 22% (p=0.007)
Straumann A, et al. Gastro 2010
August 2012
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ACG Regional Course- Indianapolis
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RCTs of Steroids for EoE
• Oral viscuous budesonide vs. nebulized
• 25 adults randomized to 1mg BID PO or nebulized x 8
weeks.
• No patients with detectable budesonide in serum
• Cortisol stimulation tests normal in all patients
• Histological resolution:
– 64% PO vs. 27% nebulized (p=0.09)
• Max eos count: mean 11 vs. 89, p = 0.02
– Similar good improvement in symptoms with both.
Dellon DDW 2012 #1033
RCTs of Steroids for EoE
• Fluticasone in adults
• 42 adults randomized to F 880ucg BID vs
vs. placebo x 6
weeks.
• Not all patients had GERD excluded. Not all Tx’d with PPI.
• Histological resolution: 62% F vs. 0% placebo (p<0.001)
• No dysphagia in prior 2 weeks:
43% F vs. 29% placebo (p = 0.52)
Alexander, et al. CGH 2012;10:742
August 2012
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Which Steroid?
Age
Tx
Histologic
Resolution
Symptomatic
Resolution
Pediatric
fluticasone MDI
vs. placebo
50% vs. 9%
n/a
Alexander
Adult
fluticasone MDI
vs. placebo
62% vs. 0%
43% vs. 29%
Schaefer
Pediatric
fluticasone MDI
vs. prednisone
50% vs. 81%
97% v. 100%
Konikoff
Maybe budesonide
1mgnebPO BID
or11%
2mg
Straumann
Ped &
budesonide
72% vs.
Adult
vs. placebo
(if payor will allow it)
PO
qhs
Better
with
budesoinde
EoE Case
EGD on omeprazole 20mg BID, empiric food elimination:
elimination:
– stricture at GE junction, dilated to 12 mm
– lower esoph 21 eos
eos/HPF,
/HPF, upper esoph 72 eos/HPF
eos/HPF
Still symptomatic
Add d fluticasone
Added
fl i
440
440mcg BID
August 2012
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ACG Regional Course- Indianapolis
Copyright 2012 ACG
Repeat EGD
No eosinophils on biopsy.
Stricture at GE junction.
Endoscopic Dilation in EoE
• Systematic review and pooled analysis
• 18 studies
t di off dil
dilation
ti
• 468 patients, 671 procedures.
– Majority with visible mucosal tears (of studies
that reported).
– 1 perforation (0.15%)
• EoE patients often report chest pain following
dilation.
Jacobs J & Spechler S. Dig Dis Sci. 2010.
August 2012
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ACG Regional Course- Indianapolis
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Endoscopic Dilation in EoE
•
•
•
•
Retrospective analysis of 293 dilations in 161 patients.
Perforation 1.0%
Mucosal tear 9.0%
Major bleeding 0.3%
– Upper 1/3 vs distal 1/3: OR = 5.62 (2.07, 15.3)
– Middle 1/3 vs. distal 1/3: OR = 4.93 (1.64, 14.8)
14.8)
– Savary vs. TTS: OR= 3.70 (1.18, 5.83)
– Single dilation > 15mm: OR = 4.86
4 86 (1.46,
(1 46 16
16.2)
2)
Jung K, et al. GIE 2011.
Suggested Strategy
Dysphagia / chest pain
Bx while on PPI BID
EoE
Allergy testing
Empiric Elimination
Steroid
Symptoms with eos
August 2012
12
ACG Regional Course- Indianapolis
Copyright 2012 ACG
Suggested Strategy
Dysphagia / chest pain
Bx while on PPI BID
EoE
Allergy testing
Empiric Elimination
Steroid
Dysphagia without eos
Dilate
August 2012
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