ACG Midwest Postgraduate Course Eosinophilic Esophagitis · GERD vs Eosinophilic Esophagitis (EoE):...

Ikuo Hirano, MD, FACG

Ikuo Hirano, MDGastroenterology Division

ACG Midwest Postgraduate Course

Eosinophilic EsophagitisGastroenterology DivisionNorthwestern University Medical School

Management of EoE

• Why should I give my patient with suspected E E i l f PPI h ?EoE a trial of PPI therapy?

• How can I best assess disease activity?• What are the pros and cons of drug and diet

therapies?

ACG Regional Postgraduate Course - St. Louis, MO Copyright 2013 American College of Gastroenterology

1


Case: Patient MH• 18 yo M with 5 year h/o progressive dysphagia

now occurring on a daily basis with monthly, self limited food impactionslimited food impactions

• One ER visit for food impaction• Denies heartburn, refluxate or chest pain• PMH Allergic rhinitis

Case: Patient MH• EGD 3/07: Furrows, edema, exudates, rings.• Path: Marked eosinophilic infiltrate (77 eos/hpf) with

microabscess in both prox and distal esophagus.

• pH study OFF medications: Distal acid exposure 3 7%

What is the patient’s diagnosis?

• pH study OFF medications: Distal acid exposure 3.7%• Allergy evaluation. SPT reactive to sweet potato, peas,

squash, tomato, corn, chicken, rye, wheat, oat, barley. APT negative to same foods. APT equivocal to milk.


2


Case: Patient MH

•EGD 6/08 lansoprazole 30 mg BID. No dysphagia.•Rings. No exudates.Rings. No exudates.•Path: 6 eos/hpf

•EGD 1/12 lansoprazole 30 mg QD. No dysphagia. 7 eos/hpf

Case: Patient MH

•EGD 6/08 lansoprazole 30 mg BID. No dysphagia.•Rings. No exudates.Rings. No exudates.•Path: 6 eos/hpf

•EGD 1/12 lansoprazole 30 mg QD. No dysphagia. 7 eos/hpf

Does this patient have EoE or GERD?


3


GERD vs Eosinophilic Esophagitis (EoE): circa 2005

GERD EoE15

GERD vs Eosinophilic Esophagitis (EoE): circa 2005

GERD EoE15Prospective studies have demonstrated a 33-50% histologic response to PPI therapy

in patients with suspected EoE

Ngo Am J Gastro 2006; Dranove J Pediatric 2009; Sayaj J Pediatr Gastro Nutr 2009; Peterson Dig Dis Sci 2009; Molina-Infante Clin Gastro Hep 2011; Francis Aliment Pharm Ther 2012;

Moawad Am J Gastro 2013; DDW 2013


4


Can GERD cause or contributeto the pathogenesis of EoE?

GERDEoE

Spechler Am J Gastro 2007; 102:1301-1306

?PPI Response = GERD?


5


PPI Response = GERDGERD vs PPI responsive EoE?? “PPI responsive esophageal eosinophilia

(PPIREE)”

Why patients with suspected EoE should be given a course of PPI therapy1. It works. Reduces symptoms and esophageal

eosinophilia in 30-50% of patients2. PPIs are safe3. pH testing is cumbersome and subject to

significant false positive and negative results4. Experimental evidence that GERD may

contribute to allergic inflammation in EoE (Paterson

Am J Physiol 1998; Rhijn Brendenoord DDW 2013)y ; j )

5. PPIs may have anti-inflammatory properties beyond acid suppression (Cheng,Souza Gut 2013; DDW13)

6. Recommended in current guidelines. Current clinical trials exclude PPIREE (Gastro 2007, JACI 2011,

Am J Gastro 2013)


6


Management of EoE

• What do I need to know about PPIREE?• How can I best assess disease activity?• What are the pros and cons of drug and diet

therapies?

EoE Disease Outcomes: More than just counting eosinophilsActivity = Inflammation

Esophagealeosinophilia


7


Are we just scratching the surface?Do the effects of EoE extend beyond the mucosa?

MuscularisPropria

Normal EoE †

Esophageal Subepithelial FibrosisDemonstrated in majority of EoE patients

Normal EoE †Normal EoE †

Straumann et al., Gastroenterology 2003. Aceves J Allergy Clin Immunol 2007 ‡Chehade J Pediatric Gastro NutrLucendo J Allergy Clin Immunol 2011 †


8


EoE Disease Activity: More than just counting eosinophils!

Activity = Inflammation + Tissue Remodeling

EsophagealEosinophilia

Esophageal Fibrostenosis

Methods to detect esophageal remodeling in EoE

• Endoscopy• Upper GI radiologic examination• Endoscopic ultrasonography (EUS)• Functional luminal imaging (FLIP)• Pathology- subepithelial fibrosis

Bi k f fib i d• Biomarkers of fibrogenesis and remodeling (EMT, TGF B, MBP etc)


9


Complications of EoE:Narrow caliber esophagus

Vasilopoulos, Murphy, Auerbach, Massey, Shaker, Stewart, Komorowski, Hogan. Gastro Endosc 2002

Classification and grading of endoscopically detected esophageal features in EoEEoE Endoscopic Reference Score (EREFS)

• Edema (pallor)Edema (pallor)• Rings (“trachealization”)• Exudates (plaques)• Furrows (vertical lines)• Stricture

NORMAL

• Mucosal fragility• Narrow caliber esophagus

Hirano Moy Heckman Thomas Gonsalves Achem. Gut. 2012Research supported by CURED.

EoE


10


Classification and grading of endoscopically detected esophageal features in EoEEoE Endoscopic Reference Score (EREFS)

• Edema (pallor)Edema (pallor)• Rings (“trachealization”)• Exudates (plaques)• Furrows (vertical lines)• Stricture

NORMALInflammatory

Fibrostenotic• Mucosal fragility• Narrow caliber esophagus

Hirano Moy Heckman Thomas Gonsalves Achem. Gut. 2012Research supported by CURED.

EoE

Fibrostenotic

Normal (Grade 0): Distinct vascular markings

Edema (Also referred to as decreased vascular markings, pallor or edema)

EoE Reference Score for Endoscopic Abnormalities (EoE-EREFs)

EoE Endo Atlas NM-IH ver16. Ref: Hirano, Moy Heckman Gut 2012


11


Normal (Grade 0): Distinct vascular markings

Edema (Also referred to as decreased vascular markings, pallor or edema)


Decreased (Grade 1) : Loss of clarity or absence of vascular markings


Mild (Grade 1): Subtle circumferential ridges seen on esophageal distension

Rings (Also referred to as esophageal rings, corrugated esophagus or trachealization)




12





Moderate (Grade 2): Distinct rings that do not occlude passage of diagnostic (8-10 mm) endoscope





Moderate (Grade 2): Distinct rings that do not occlude passage of diagnostic (8-10 mm) endoscope

Severe (Grade 3): Distinct rings that do not permit passage of diagnostic (8-10 mm) endoscope



13


Mild (Grade 1): White lesions involving < 10% of the surface area of the esophagus

Exudates (Also referred to as white exudates, plaques or punctate white spots)



Mild (Grade 1): White lesions involving < 10% of the surface area of the esophagus

Exudates (Also referred to as white exudates, plaques or punctate white spots)


Severe (Grade 2): White lesions involving > 10% of the surface area of the esophagus



14


Furrows (Also referred to as vertical lines or longitudinal furrowing)



Stricture (Estimate luminal diameter)




15


Risk of food impaction correlated with EREFS ring severity score

90

100

n

20

30

40

50

60

70

80%

Foo

d Im

pact

iop<0.05

Nicodeme Clin Gastro Hepatol 2013.

0

10

Ring Score

0 1 2 3

Risk of food impaction correlated with EREFS ring severity score

90

100

n

20

30

40

50

60

70

80

% F

ood

Impa

ctio

p<0.05

EREFS: Allows for uniform characterization Provides information regarding fibrostenosis Complements assessment of therapeutic

0

10

Ring Score

0 1 2 3

Complements assessment of therapeutic outcomes

Nicodeme Clin Gastro Hepatol 2013.


16


Management of EoE

• What is PPIREE and do I need any?• How can we best assess disease activity?• What are the pros and cons of drug and diet

therapies?

Treatment Options for EoE• Endoscopic Therapy• Medical Therapy

T i l t id– Topical steroids– Systemic steroids– Leukotriene antagonists (montelukast)– Mast cell stabilizers (cromolyn sodium)– Immunomodulators (CRTH2 antagonist, azathioprine)– Biologics (anti IL5, anti IL13, anti TNF, anti IgE)

• Dietary Therapy– Empiric elimination diet– Allergy testing directed elimination diet– Elemental diet


17


Topical steroids

• Swallowed - not inhaled– Fluticasone 220ug 2-4 puffs BID– Budesonide 0.5-1 mg BID

• Liquid formulations are mixed with substance (sucralose) to increase viscosity

• Patients instructed to fast for 30 minutes after administration

• Mouth rinse after administration to reduce risk thrush may reduce effectiveness

Randomized, Double-Blind Placebo Controlled Trials Budesonide36 Adults with EoE Placebo or budesonide 1 mg BID x 15 days24 Children with EoE: Placebo or budesonide 0.5-1 mg BID x 3 months

Adult Pediatric

4544

noph

ils p

er h

pf

Before After

84

6662 67

80

70

60

50

40

30

90

80

70

60

50

40

30

90

Adult Pediatric

Placebo

Eos

in

Straumann Gastroenterology 2010; 39:1526-1537 Dohil Gastroenterology 2010; 139:418-429

Budesonide PlaceboBudesonide

4 5

30

20

10

0

30

20

10

0


18


Topical Steroid: Endoscopic Improvement

E1R0E1F1E1R1E2F1

Patient 1 Patient 2 Patient 3E1R2E1F1

Fluticasone

E0R1E0F0 E0R0E0F0 E0R1E0F0

Fluticasone in EoE: What dose?• Konikoff Rothenberg 2006

– 36 Peds; Fluticasone 440 mcg BID x 3 mos vs placebo

– 55% with < 6 eos/hpf • Schaefer Gupta 2008*• Schaefer Gupta 2008

– 80 Peds; RCT fluticasone 220-440 mcg QID vs prednisone x 8 weeks

– 67% with < 6 eos/hpf post fluticasone• Peterson Fang 2009

– 26 Adults; Fluticasone 440 mcg BID vs Esomeprazole x 8 weeks

– 15% with < 5 eos/hpf• Alexander Talley 2012

– 42 Adults; Fluticasone 880 mcg BID x 6 weeks vs placebo42 Adults; Fluticasone 880 mcg BID x 6 weeks vs placebo

– 71% with < 5 eos/hpf• Moawad Wong 2012

– 42 Adults; Fluticasone 440 mcg BID vs esomeprazole x 8 weeks

– 19% with < 7 eos/hpf

*GERD systematically excluded


19


Eosinophilic Esophagitis:Dietary Treatment

• Elemental diet: Amino acid, carbohydrate, lipid, vitamin/mineral based formula (Kelly Sampson Gastroenterology 1995)

• Directed elimination diet: Exclusion of specific food allergens based on the results of allergy testing (skin prick & patch) (Spergel, Liacouras Ann Allergy Asthma Immunol 2005)

• Non-directed elimination diet: Empiric exclusion of common food allergens (Kagalwalla, Li Clin Gastro Hep 2006)

Six Food Elimination Diet (SFED) Prospective Study in Adults (n=50)

6 wk elimination (milk, soy, nuts, eggs, wheat, seafood/shellfish))))

After Diet

Gonsalves, Ritz, Yang, Ditto, Hirano. Gastroenterology 2012

Before Diet


20


Effect of SFED on Esophageal Eosinophilia

100

Proximal Esophagus Distal Esophagus

30

405060708090

PrePostEos/

hpf

01020

100

Effect of SFED on Esophageal EosinophiliaProximal Esophagus Distal Esophagus

30

405060708090

PrePostEos/

hpf ___ ___* P <0.05

01020

Pre PrePost Post

___ ___* *

Median 34 8 48 13


21


100

Effect of SFED on Esophageal EosinophiliaProximal Esophagus Distal Esophagus

30

405060708090

PrePostEos/

hpf ___ ___* P <0.0564% achieved histologic response

defined by < 5 eos/hpf

01020

Pre PrePost Post

___ ___* *

Median 34 8 48 13

16

18

Effect of SFED on Dysphagia Score

Pre

4

6

8

10

12

14 Post____

* P <0.01

*2

4

Pre Post

12MedianScore

____

3.5

*


22


100

Effect of Reintroduction of Foods on Esophageal Eosinophilia


30

405060708090 Pre

Post

Eos/hpf

___ ___

Reintro

01020

Pre Pre

90100



2030

405060708090 Pre

Post

Eos/hpf

___ ___

Reintro

01020

Pre Pre

___ ___

Post Post


23


100



30

405060708090 Pre

Post

Eos/hpf

___ ___

Reintro

___ ___* P <0.01

01020

Pre Pre

___ ___

Post PostReintro Reintro

100



30

405060708090 Pre

Post

Eos/hpf

___ ___

Reintro

___ ___* P <0.01

Food triggers identified by reintroduction:Wheat (60%), milk(50%), soy (10%), egg (5%)

15% of patients with more than one food trigger

SPT accurately predicted 13% of food triggers

01020

Pre Pre

___ ___

Post PostReintro Reintro

SPT accurately predicted 13% of food triggers.67% of patients with food trigger had negative SPT


24


Endoscopic improvement with SFED

Pre Diet

E1R1E2F2 E1R0E0F1

Patient 1 Patient 2 Patient 3

E1R0E2F1

Post DietE0R1E1F1 E0R0E0F0 E1R0E0F1

ReintroE1R2E1F1 E1R0E0F1 E1R0E2F1

Empiric Elimination Dietary Treatment for EoE in Adults• Prospective Spanish study of 67 adults with EoE • Diet avoidance of wheat milk egg seafood legumesDiet avoidance of wheat, milk, egg, seafood, legumes,

peanuts, soy, rice, corn for 6 weeks (modified SFED)• Disease remission defined as < 15 eos/hpf• 73% response (48 to 3.5 eos/hpf in responders)• Single food trigger in 36%; 2 foods 31%; 3+ foods 33%• Most common triggers: milk (62%), wheat (29%), egg

(26%), legumes (24%)(26%), legumes (24%)• 2 year follow up in 15 pts. Sustained symptom and

histologic response

Lucendo J Allergy Clin Immunol 2013


25


Diet therapy in EoE: PROS• No FDA approved medical therapies for EoE

• Many patients would prefer a dietary alternative rather than chronic steroidsrather than chronic steroids

• Conceptual appeal of removing disease trigger rather than suppress inflammatory consequences

• Elimination diets can be a healthy alternative to conventional Western dietsconventional Western diets

• Goal of diet therapy is the identification of specific food trigger(s), not elimination of all potential food groups

Diet therapy in EoE: PROS• No FDA approved medical therapies for EoE

• Many patients would prefer a dietary alternative rather than chronic steroidsrather than chronic steroids

• Conceptual appeal of removing disease trigger rather than suppress inflammatory consequences

• Elimination diets can be a healthy alternative to conventional Western diets

Provides an important proof of concept regarding the role of dietary allergens in

the pathogenesis of EoEconventional Western diets

• Goal of diet therapy is the identification of specific food trigger(s), not elimination of all potential food groups

the pathogenesis of EoE


26


Suggested Algorithm for ManagementOf Eosinophilic Esophagitis

Suspected EoE

PPI x 8 wksSymptom relief &N l hi t l

EGD with Bx

“PPI Responsive Esophageal Eosinophilia” (EoE vs GERD)

Normal histology

EoE

> 15 Eos/hpf

Topical steroidDietary therapy

EGD with BxPersistent Symptoms and Pathology

Elimination diet↑ Dose topicalSystemic steroidBiologic therapy ?

Esophageal dilation

Persistent dysphagiawith stricture

Consider Maintenance Therapy

Symptom relief &Normal histology

• What do I need to know about PPIREE?PPI therapy is a safe and an effective means of recognizing the potential contribution of acid reflux in suspected EoE.

Management of EoE

p p

• How can do I assess disease activity?Symptoms and histology are important but endoscopic findings complement assessment of esophageal remodeling and provides basis for decision for dilation

• What are the pros and cons of drug and diet therapies?Elimination diets are an effective alternative for motivated children and adults

ACG Clinical Guideline: Evidenced Based Approach to the Diagnosis and Management of Esophageal Eosinophilia and Eosinophilic Esophagitis 2013


27



28

ACG Midwest Postgraduate Course Eosinophilic Esophagitis · GERD vs Eosinophilic Esophagitis (EoE):...

Documents

Transcript of ACG Midwest Postgraduate Course Eosinophilic Esophagitis · GERD vs Eosinophilic Esophagitis (EoE):...