EOSINOPHILIC ESOPHAGITISEOSINOPHILIC ESOPHAGITIS

ATILLA ERTAN, MD, FACP, AGAF, MACGATILLA ERTAN, MD, FACP, AGAF, MACG

DisclamerDisclamer

•Grant/Research Support from Grant/Research Support from Centocor, Abbott Labs, Elan-Biogen, Centocor, Abbott Labs, Elan-Biogen, UCB Salix &Sucampo Pharmaceuticals, UCB Salix &Sucampo Pharmaceuticals, Genentech, Axcan & Barrx Inc.Genentech, Axcan & Barrx Inc.

•Scientific Advisory Board Member for Scientific Advisory Board Member for Centocor, UCB Pharmaceuticals Inc, Centocor, UCB Pharmaceuticals Inc, Abbott Laboratories & Prometheus Labs.Abbott Laboratories & Prometheus Labs.

Learning Objectives for EoE

•Recognize & differential diagnosis

•Understand its pathogenesis

• Identify diagnostic criteria

•Recognize management difficulties & different therapeutic approaches

Eosinophilic Esophagitis (EoE)

•12 adults over 2 yr period with >20 IEE

•Dysphagia predominant complaint

•Unremarkable EGD

•pH monitoring normal in 11

Attwood SE et al, Dig Dis Sci 38; 109, 1993

D.W.S.# 1740111-8D.W.S.# 1740111-8

A 37 y/o male with a 5 yrs h/o intermittent food A 37 y/o male with a 5 yrs h/o intermittent food dysphagia & food impactions who had related ER dysphagia & food impactions who had related ER visits. During one of these episodes, he came to visits. During one of these episodes, he came to TMH ER.TMH ER.

MED: NoneMED: None ALL: Penn, shellfishALL: Penn, shellfish PMH/PSH: Hay feverPMH/PSH: Hay fever SH: Married, lawyer, denied T, ETOH & IVDASH: Married, lawyer, denied T, ETOH & IVDA FH: Noncontributory FH: Noncontributory ROS/PE: UnremarkableROS/PE: Unremarkable Emergent EGD & biopsy findingsEmergent EGD & biopsy findings

D.W.S. # 1740111-8D.W.S. # 1740111-8

Food impaction 3-20-2003 Post food impaction 3-20-2003

D.W.S. # 1740111-8D.W.S. # 1740111-8

Linear furrowing, vertical lines & white Linear furrowing, vertical lines & white specksspecks

EOSINOPHILIC ESOPHAGITIS [EoE]EOSINOPHILIC ESOPHAGITIS [EoE]

EoE is a chronic and recurrent inflammatory EoE is a chronic and recurrent inflammatory disease with increase prevalence woldwide and disease with increase prevalence woldwide and characterized by;characterized by;

• Dysphagia, food impaction, GERD & less Dysphagia, food impaction, GERD & less commonly chest pain in predominantly white commonly chest pain in predominantly white males (75-82%)males (75-82%)

• ≥≥15 intraepithelial eosinophils/HPF leads to 15 intraepithelial eosinophils/HPF leads to fibrosis and angiogenesis, with mural thickening, fibrosis and angiogenesis, with mural thickening, loss of elasticity of the esophageal wall and loss of elasticity of the esophageal wall and stricture formation.stricture formation.

• Exclusion of other disorders associated with Exclusion of other disorders associated with similar clinical, histological, or endoscopic similar clinical, histological, or endoscopic featuresfeatures

________________________________________________________________________________________Gastroenterol 133: 1342-63, 2007, Gastroenterol 134: 204-14, 2008 &Gastroenterol 133: 1342-63, 2007, Gastroenterol 134: 204-14, 2008 &Gastroenterol 140: 82-90, 2011. Gastroenterol 140: 82-90, 2011.

PATHOGENESIS OF EoEPATHOGENESIS OF EoE

• EoE is associated with an allergic response to environmental EoE is associated with an allergic response to environmental antigens that lead to cytokine mediators associated esophageal antigens that lead to cytokine mediators associated esophageal eosinophilia. eosinophilia.

• IL-5, IL-13 , IL-15 and other cytokines may play a major role in IL-5, IL-13 , IL-15 and other cytokines may play a major role in eosinophilic recruitment by response to certain food proteins.eosinophilic recruitment by response to certain food proteins.

• There is a clear disarray between circular & longitudinal muscle There is a clear disarray between circular & longitudinal muscle contractions during the peristalsis.contractions during the peristalsis.

• Esophageal distansibility was significantly reduced compared with Esophageal distansibility was significantly reduced compared with controls by using a functional luminal imaging probe [EndoFLIP].controls by using a functional luminal imaging probe [EndoFLIP].

____________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________

J Allergy Clin Immunol 120: 1292-300, 2007J Allergy Clin Immunol 120: 1292-300, 2007Gut 59: 12-20, 2010Gut 59: 12-20, 2010Gastroentrol 138: 275-284, 2010; 139: 182, 2010; 140: 82-90,2011Gastroentrol 138: 275-284, 2010; 139: 182, 2010; 140: 82-90,2011

ENDOSCOPIC FEATURES OF EoEENDOSCOPIC FEATURES OF EoE____________________________________________________________________________• Unremarkable endoscopic mucosa & lumen.Unremarkable endoscopic mucosa & lumen.

• Circular rings, transient or fixed, “feline Circular rings, transient or fixed, “feline esophagus”esophagus”

• Linear furrowing, vertical lines of the mucosaLinear furrowing, vertical lines of the mucosa

• Linear shearing/”crepe paper” mucosa with Linear shearing/”crepe paper” mucosa with passage of endoscope or dilatorpassage of endoscope or dilator

• White exudates/specks, nodules or White exudates/specks, nodules or granularitygranularity

• Stricture/rings: proximal, middle, or distal.Stricture/rings: proximal, middle, or distal.

____________________________________________________________________________

Gastroenterol, 133: 1342, 2007 (modified).Gastroenterol, 133: 1342, 2007 (modified).

* None of the features are specific for EoE. * None of the features are specific for EoE.

J.M.H. # 2096026-6J.M.H. # 2096026-6Linear shearing Linear shearing

A.E. # 2096036-5A.E. # 2096036-5Circular rings, “feline esophagus”Circular rings, “feline esophagus”

I.E. # 3659813-1I.E. # 3659813-1Barrett’s islands & EoE with transient circular ringsBarrett’s islands & EoE with transient circular rings

EGD biopsy for patients with EoE •More than 5-6 biopsies had a sensitivity of

100% even in an unremarkable mucosa.•Due to scaterred histologic distribution,

proximal, mid & distal esophagus should be biopsied.

•Mucosal eosinophilia may show a seasonal variation, possibly related to allergies.

Gastrointest Endosc, 64; 313, 2006 Am J Gastroenterol, 104; 716, 2009 ;

Differential Diagnosis of EoEDifferential Diagnosis of EoE_______________________________________

• Crohn’s disease*

• Connective tissue disorders*

• Hypereosinophilic syndrome

• Infections [herpes & candida]*

• Drug sensitivity response

• Eosinophilic gastroenteritis_______________________________________ *These diseases may have intraepithelial eosinophilia but

less than 15/HPF in one or more biopsy specimens.

EoE & BARRETT’S ESOPHAGUS EoE & BARRETT’S ESOPHAGUS [BE][BE]

• ““BE or BD has not been reported in patients BE or BD has not been reported in patients with EoE” (1,2). with EoE” (1,2).

• ““EoE is not a disease characterized by EoE is not a disease characterized by mucosal ulceration or destruction. Therefore, mucosal ulceration or destruction. Therefore, it seems likely that the pathologic process of it seems likely that the pathologic process of EoE is different from that of GERD and that EoE is different from that of GERD and that adenoca or squamous ca of the esophagus adenoca or squamous ca of the esophagus are not the spectrum of EoE” (2). are not the spectrum of EoE” (2).

Recent studies and our experience showed Recent studies and our experience showed that this relation is not uncommon.that this relation is not uncommon.

1. Am J Gastroenterol, 101: 1900, 2006.1. Am J Gastroenterol, 101: 1900, 2006. 2. Gastroenterology, 133: 1342, 2007. 2. Gastroenterology, 133: 1342, 2007.

A.P.# 01911497-4A.P.# 01911497-4

A 47 y/o male with a 9-10 yrs h/o GERD who had A 47 y/o male with a 9-10 yrs h/o GERD who had recent dysphagia & few episodes of food impaction. recent dysphagia & few episodes of food impaction. He diagnosed as having L.S. Barrett’s with HGD/LGD He diagnosed as having L.S. Barrett’s with HGD/LGD & EoE.& EoE.

MED: Zegerid 40 mg BIDMED: Zegerid 40 mg BID

PMH/PSH & FH: Unremarkable.PMH/PSH & FH: Unremarkable.

SH: Married, IT executive, no tobacco, ETOH or IVDA.SH: Married, IT executive, no tobacco, ETOH or IVDA.

ROS: Gained 40 lbs within last 10 yrs.ROS: Gained 40 lbs within last 10 yrs.

PE: Essentially unremarkable except moderate PE: Essentially unremarkable except moderate obesity.obesity.

LAB: Unremarkable CBC-diff, SMA-6 & other blood LAB: Unremarkable CBC-diff, SMA-6 & other blood tests. tests. Chest/abd CT scanChest/abd CT scan

EUSEUS

Previous history of food impactions:Previous history of food impactions: Case APCase AP

A.P. #01911497-4A.P. #01911497-4L.S. BE with MF/HGD & EoE with transient circular L.S. BE with MF/HGD & EoE with transient circular ringsrings

PathologyPathology

Case APCase AP

Basal zone hyperplasia, increased eosinophils Intraepithelial eosinophils of eosinophils

EUSEUS

A.P. # 019114974 L.S. A.P. # 019114974 L.S. Barrett’s with HGD & EoE , Barrett’s with HGD & EoE , S/P RFA S/P RFA

ALLERGY EVALUATION IN PATIENTS WITH ALLERGY EVALUATION IN PATIENTS WITH EoEEoE• The majority of patients with EoE is atopic The majority of patients with EoE is atopic

based on the coexistence of atophic based on the coexistence of atophic dermatitis, allergic rhinitis, and/or bronchial dermatitis, allergic rhinitis, and/or bronchial asthma with + antigen skin sensitization & asthma with + antigen skin sensitization & abnormal plasma antigen-specific IgE.abnormal plasma antigen-specific IgE.

• 10%-50% of adults had peripheral eosinophilia.10%-50% of adults had peripheral eosinophilia.

• Most patients improve on allergen-free diets.Most patients improve on allergen-free diets.

• Allergist consultation may be recommended.Allergist consultation may be recommended.__________________________________________________________ __________________________________________________________

ClinClin Gastroenterol Hepatol 3:1198-206, 2005.Gastroenterol Hepatol 3:1198-206, 2005. J Pediatr Gastroenterol Nutr 42:22-6, 2006.J Pediatr Gastroenterol Nutr 42:22-6, 2006.

Medical Management # 1Medical Management # 1• Removal of allergenic foods [diary, eggs, Removal of allergenic foods [diary, eggs,

wheat, soy, peanuts, fish/shellfish]- with wheat, soy, peanuts, fish/shellfish]- with unpredictive allergy testing in adults-, unpredictive allergy testing in adults-, may be effective. The elemental diet may may be effective. The elemental diet may be helpful in severe cases (1)be helpful in severe cases (1)

• Endoscopic dilatation is useful in pts with Endoscopic dilatation is useful in pts with fixed strictures/rings. The risk of mucosal fixed strictures/rings. The risk of mucosal tearing and perforation are relatively tearing and perforation are relatively higher (2,3).higher (2,3).

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1. Clin Gastroenterol Hepatol 4: 1097-102, 2006. 1. Clin Gastroenterol Hepatol 4: 1097-102, 2006. 2 & 3. Gastroenterology 127: 364-5, 2004; 133:1342-6, 2 & 3. Gastroenterology 127: 364-5, 2004; 133:1342-6,

2007.2007.

MEDICAL MANAGEMENT # 2MEDICAL MANAGEMENT # 2

• 16 to 50% of pts showed improvement with PPI treatment 16 to 50% of pts showed improvement with PPI treatment (1,2)(1,2)

• Topical [rarely systemic] corticosteroids resolve symptoms. Topical [rarely systemic] corticosteroids resolve symptoms. Fluticasone 440 mcg BID for 6-8 weeks may be effective Fluticasone 440 mcg BID for 6-8 weeks may be effective for an induction therapy (3)for an induction therapy (3)

• A pilot trials with anti-IL-5[Mepolizumab], leukotriene D4 A pilot trials with anti-IL-5[Mepolizumab], leukotriene D4 receptor ab [Montelukast] & Infliximab showed receptor ab [Montelukast] & Infliximab showed improvement in pts with severe EoE. improvement in pts with severe EoE.

• Budesonide suspension (0.25 mg/ml) inhalation BID (4) for Budesonide suspension (0.25 mg/ml) inhalation BID (4) for 50-wks. 50-wks.

______________________________________________________________________________________________________ 1 & 2. J Gastroenterol 101: 1666-70, 2006 & Clin Gastroenterol Hepatol 9: 110-7, 20111 & 2. J Gastroenterol 101: 1666-70, 2006 & Clin Gastroenterol Hepatol 9: 110-7, 20113. Gastrointest Endosc 63:3-12, 2006 Clin Gastroenterol Hepatol 9: 400-9, 20113. Gastrointest Endosc 63:3-12, 2006 Clin Gastroenterol Hepatol 9: 400-9, 2011