Eosinophilic esophagitis is characterized by eosinophil-predominant inflammation in the esophagus. Potential etiologies include food and aeroallergen sensitization, genetics involving genes like TSLP, and cytokines/chemokines such as IL-5 and eotaxin-3. The pathogenesis involves activation of epithelial inflammatory pathways producing eotaxin-3, impaired barrier function mediated by loss of desmoglein-1, and increased TGF-β. Clinical features commonly include dysphagia, abdominal pain, failure to thrive, and food impactions. Diagnosis is based on symptoms and histological evidence of ≥15 eosinophils per hpf. Treatment
4. Introduction
• Disorders that selectively affect GI tract
• Eosinophil-rich inflammation in the absence of
known causes for eosinophilia
Rothenberg ME. Middleton's Allergy ; 8th edition. 2014. p. 1095-1106
6. Epidemiology(1)
• EoE is a global health problem now reported
in
- Australia - Japan
- Brazil - Spain
- England - Switzerland
- Italy - Israel
Shitrit AB, Reinus C, Zeides S, et al. Eosinophilic esophagitis. Isr Med Assoc J 2006;8:587.
7. Epidemiology(4)
Noel RJ, Putnam PE, Rothenberg ME. Eosinophilic esophagitis. The New England journal of medicine. 2004;351(9):940-1.
8. Epidemiology(3)
• 0.4% (~4 : 1000) prevalence of EoE in a
random sample of Swedish adults.
• EoE occurred in about 1 : 1000 children in the
Cincinnati metropolitan area over a 10-year
period.
Ronkainen J, Talley NJ, Aro P, et al. Prevalence of eosinophilia and eosinophilic esophagitis in
adults in the community: a random population based study (Kalixanda). Gastroenterology 2006;130:A575
Noel RJ, Putnam PE, Rothenberg ME. Eosinophilic esophagitis. N Engl J Med 2004;351:940-1.
10. Gastrointestinal Eosinophils Under Homeostatic
Healthy States
• Eosinophils are present at low levels in
numerous tissues
• In biopsy and autopsy specimens, organs that
normally demonstrate tissue eosinophils at
substantial levels are
- GI tract - Lymph nodes
- Spleen - Thymus
DeBrosse CW, Case JW, Putnam PE, Collins MH, Rothenberg ME. Quantity and distribution of eosinophils in
the gastrointestinal tract of children. Pediatric and developmental pathology : the official journal of the
Society for Pediatric Pathology and the Paediatric Pathology Society. 2006;9(3):210-8.
11. Gastrointestinal Eosinophils Under Homeostatic
Healthy States
• Eosinophils throughout the GI tract of
conventional healthy mice : normally present
in the lamina propria of the stomach, small
intestine, cecum, and colon.
• Eosinophils are not normally present in Peyer
patches or intraepithelial locations.
• Eosinophils are frequently infiltrate in Peyer
patches regions in EGID.
Mishra A, Hogan SP, Lee JJ, et al. Fundamental signals that regulate eosinophil homing to the gastrointestinal tract. J Clin
Invest 1999;103: 1719-27
Rothenberg ME, Mishra A, Collins MH, et al. Pathogenesis and clinical features of eosinophilic esophagitis. J Allergy Clin
Immunol 2001;108:891-4.
13. DeBrosse CW, Case JW, Putnam PE, Collins MH, Rothenberg ME. Quantity and distribution of eosinophils in
the gastrointestinal tract of children. Pediatric and developmental pathology : the official journal of the
Society for Pediatric Pathology and the Paediatric Pathology Society. 2006;9(3):210-8.
14. Kita H. et al.Middleton's Allergy ; 8th edition. 2014. p. 265-279
PROINFLAMMATORY ROLE OF EOSINOPHILS
16. Kita H. et al.Middleton's Allergy ; 8th edition. 2014. p. 265-279
17. Kita H. et al.Middleton's Allergy ; 8th edition. 2014. p. 265-279
18. Kita H. et al.Middleton's Allergy ; 8th edition. 2014. p. 265-279
MBP, EPX, and ECP have
cytotoxic effects on
epithelium at concentrations
similar to those in biologic
fluids from patients with
eosinophilia
19. Kita H. et al.Middleton's Allergy ; 8th edition. 2014. p. 265-279
MBP triggers
degranulation of mast cells
and basophils.
20. Kita H. et al.Middleton's Allergy ; 8th edition. 2014. p. 265-279
Eosinophil-mediated
damage is caused by
• Toxic hydrogen
peroxide and halide acids
generated by EPX
• Superoxide generated
by the respiratory burst
oxidase enzyme pathway
in eosinophils
21. Proinflammatory Role of Eosinophils
• Triggering of eosinophils by engagement of
receptors for cytokines, immunoglobulins, and
complement can lead to the generation of a
wide range of inflammatory cytokines
Yousefi S, Gold JA, Andina N, Lee JJ, Kelly AM, Kozlowski E, et al. Catapult-like release of mitochondrial DNA
by eosinophils contributes to antibacterial defense. Nature medicine. 2008;14(9):949-53.
22. Proinflammatory Role of Eosinophils
• TGF-β is linked with epithelial growth, fibrosis,
and tissue remodeling.
• Eosinophils express MHC class II molecules
and relevant costimulatory molecules (CD28,
CD40, CD80 [B7-1], CD86
• Eosinophils secrete cytokines capable of
promoting lymphocyte proliferation ,
activation &Th1 or Th2 polarization (IL-2, -4, -
6, -12, -10).
Rothenberg ME. Middleton's Allergy ; 8th edition. 2014. p. 1095-1106
23. Clinical Evaluation
• Pts with EGID present with a variety of clinical
problems, most often
-Failure to Thrive -Abdominal pain
-Irritability -Gastric dysmotility
-Vomiting -Diarrhea
-Dysphagia -Microcytic anemia
-Hypoproteinemia
Rothenberg ME. Middleton's Allergy ; 8th edition. 2014. p. 1095-1106
26. Clinical Evaluation
Rothenberg ME. Middleton's Allergy ; 8th edition. 2014. p. 1095-1106
•Blood eosinophil
counts are generally
in the normal range
in most pts
• Above-normal
levels can distinguish
pts with active
versus inactive EoE
27. Evaluation for Hypereosinophilic syndrome
Diagnostic criteria for HES established by Chusid and
colleagues,1975
1.Peripheral blood eosinophilia (>1,500 cells/microliter)
for longer than 6 months
2.Evidence of eosinophil-related target organ damage
3.Exclusion of all other etiologies for eosinophilia
Chusid MJ, Dale DC, West BC, Wolff SM. The hypereosinophilic syndrome: analysis of fourteen cases with
review of the literature. Medicine. 1975;54(1):1-27.
28. Evaluation for Hypereosinophilic syndrome
Contemporary consensus proposal on criteria and
classification of eosinophilic disorders and related
syndromes
1. Hypereosinophilia-absolute eosinophil count >1,500
cells/microlitr for 1 mo,checked on 2 occasions*
2. Evidence of eosinophil-mediated target organ
damage
3. Exclusion of all other potential causes of
hypereosinophilia
Valent P, et al. Contemporary consensus proposal on criteria and classification of eosinophilic disorders and
related syndromes. The Journal of allergy and clinical immunology. 2012;130(3):607-12.e9.
29. Evaluation for Hypereosinophilic syndrome
*Tissue hypereosinophilia can be identified in
addition to an elevated absolute eosinophil count
with tissue hypereosinophilia, defined as:
1. Eosinophils >20% of nucleated cells in bone
marrow
2. Extensive tissue infiltration of target organ by
histologic analysis
3. Histologic evidence of eosinophil degranulation
in a target tissue in the absence of eosinophils in
that target tissue
Valent P, et al. Contemporary consensus proposal on criteria and classification of eosinophilic disorders and
related syndromes. The Journal of allergy and clinical immunology. 2012;130(3):607-12.e9.
30. HE-related organ damage
Organ dysfunction
With
Marked tissue eosinophil
infiltrates
And/Or
Extensive deposition of
eosinophil-derived proteins
In the presence or absence
of marked tissue eosinophils
(1) Fibrosis (lung, heart,
digestive tract, skin, and others)
(2) Thrombosis with or without
thromboembolism
(3) Cutaneous (including
mucosal) erythema,
edema/angioedema, ulceration,
pruritus, and eczema
(4) Peripheral or central
neuropathy with chronic or
recurrent neurologic deficit
And 1 or
more of
the
following
Valent P, et al. Contemporary consensus proposal on criteria and classification of eosinophilic disorders and
related syndromes. The Journal of allergy and clinical immunology. 2012;130(3):607-12.e9.
31. Evaluation for Hypereosinophilic syndrome
• Pts with EGID, the diagnosis of HES should
always be considered, especially if they develop
extra-GI manifestations .
• Thus, additional diagnostic testing for HES
should be considered.
Rothenberg ME. Middleton's Allergy ; 8th edition. 2014. p. 1095-1106
32. Evaluation for Hypereosinophilic syndrome
• Pts with marked eosinophilia are at risk for the
development of cardiac disease.
• Routine surveillance of the cardiorespiratory
system is warranted.
Rothenberg ME. Middleton's Allergy ; 8th edition. 2014. p. 1095-1106
35. Definition
• “Eosinophilic esophagitis represents a chronic,
immune/antigen mediated, esophageal
disease characterized clinically by symptoms
related to esophageal dysfunction and
histologically by eosinophil-predominant
inflammation”
Liacouras CA, Furuta GT, Hirano I, Atkins D, Attwood SE, Bonis PA, et al. Eosinophilic esophagitis: updated
consensus recommendations for children and adults. The Journal of allergy and clinical immunology.
2011;128(1):3-20.e6; quiz 1-2.
40. Esophageal eosinophilic inflammation is
mechanistically linked to pulmonary
inflammation, on the basis of the induction of
experimental EoE by repeated delivery of
specific allergens to the lung of mice.
Mishra A, Hogan SP, Brandt EB, et al. An etiological role for aeroallergens and eosinophils in experimental esophagitis. J Clin
Invest 2001; 107:83-90.
41. Fogg MI, Ruchelli E, Spergel JM. Pollen and eosinophilic esophagitis. The Journal of allergy and clinical immunology.
2003;112(4):796-7.
43. Genetics
• 3 Basic approach
1) Mendelian disorder
2) Candidate gene identification
3) Genome wide association study
44.
45.
46. Thymic stromal lymphopoeitin (TSLP)
protein
• GWAS, genotyping 351 patients with EoE and
3104 healthy controls and evaluating 550,000
common variants.
• On chromosome 5q22, a single locus spanning
the TSLP and WD repeat domain 36 (WDR36)
genes showed a significant association with
EoE.
Rothenberg ME, Spergel JM, Sherrill JD, Annaiah K, Martin LJ, Cianferoni A, et al. Common variants at 5q22 associate with
pediatric eosinophilic esophagitis. Nature genetics. 2010;42(4):289-91.
47. Thymic stromal lymphopoeitin (TSLP)
protein
• TSLP has a known role in processes germane
to EoE
1. Polarization of Th2 immunity
2. Induction of eotaxins
Rothenberg ME. Middleton's Allergy ; 8th edition. 2014. p. 1095-1106
49. Blanchard C, Wang N, Stringer KF, et al. Eotaxin-3 and a uniquely conserved gene expression profile in eosinophilic
esophagitis. J Clin Invest 2006;116:536-47.
50.
51.
52.
53. Pathogenesis
• Activation of epithelial inflammatory
pathways (production of eotaxin-3 [encoded
by CCL26]).
Rothenberg ME. Molecular, Genetic, and Cellular Bases for Treating Eosinophilic Esophagitis. Gastroenterology. 2015.
54. Pathogenesis
• Activation of epithelial inflammatory
pathways (production of eotaxin-3 [encoded
by CCL26]).
• Impaired barrier function (mediated by loss of
desmoglein-1).
Rothenberg ME. Molecular, Genetic, and Cellular Bases for Treating Eosinophilic Esophagitis. Gastroenterology. 2015.
55. Pathogenesis
• Activation of epithelial inflammatory
pathways (production of eotaxin-3 [encoded
by CCL26]).
• Impaired barrier function (mediated by loss of
desmoglein-1).
• Increased production and/or activity of
transforming growth factor-b.
Rothenberg ME. Molecular, Genetic, and Cellular Bases for Treating Eosinophilic Esophagitis. Gastroenterology. 2015.
56. Pathogenesis
• Activation of epithelial inflammatory
pathways (production of eotaxin-3 [encoded
by CCL26]).
• Impaired barrier function (mediated by loss of
desmoglein-1).
• Increased production and/or activity of
transforming growth factor-b.
• Induction of allergic inflammation by
eosinophils and mast cells.
Rothenberg ME. Molecular, Genetic, and Cellular Bases for Treating Eosinophilic Esophagitis. Gastroenterology. 2015.
57.
58. Rothenberg ME. Molecular, Genetic, and Cellular Bases for Treating Eosinophilic Esophagitis. Gastroenterology. 2015.
59. Clinical feature(1)
Yan BM, Shaffer EA. Eosinophilic esophagitis: a newly established cause of dysphagia. World journal of gastroenterology :
WJG. 2006;12(15):2328-34.
61. Clinical feature(2)
Noel RJ, Putnam PE, Rothenberg ME. Eosinophilic esophagitis. The New England journal of medicine. 2004;351(9):940-1.
62. Remedios M, Campbell C, Jones DM, Kerlin P. Eosinophilic esophagitis in adults: clinical, endoscopic, histologic findings, and response to
treatment with fluticasone propionate. Gastrointestinal endoscopy. 2006;63(1):3-12.
63. Remedios M, Campbell C, Jones DM, Kerlin P. Eosinophilic esophagitis in adults: clinical, endoscopic, histologic findings, and response to
treatment with fluticasone propionate. Gastrointestinal endoscopy. 2006;63(1):3-12.
Study of 26 adult patients with EoE, all had dysphagia, 11 had
food impaction.
68. Radiographic studies
Figure 2. Radiographic and endoscopic
studies from an 18-year-old female with
history of asthma, eczema, and long-
standing obstructive dysphagia beginning
in early childhood.
A.Barium esophagram showing a small
caliber esophagus
Fox VL, Nurko S, Furuta GT. Eosinophilic esophagitis: it's not just kid's stuff. Gastrointestinal endoscopy. 2002;56(2):260-70.
69. Endoscopic Studies
Fox VL, Nurko S, Furuta GT. Eosinophilic esophagitis: it's not just kid's stuff. Gastrointestinal endoscopy. 2002;56(2):260-70.
70. Endoscopic Studies
Fox VL. Eosinophilic esophagitis: endoscopic findings. Gastrointestinal endoscopy clinics of North America.
2008;18(1):45-57; viii.
71. Endoscopic Studies
Fox VL. Eosinophilic esophagitis: endoscopic findings. Gastrointestinal endoscopy clinics of North America.
2008;18(1):45-57; viii.
72. Endoscopic Studies
Fox VL. Eosinophilic esophagitis: endoscopic findings. Gastrointestinal endoscopy clinics of North America.
2008;18(1):45-57; viii.
73. Endoscopic Studies
A) mucosal edema, concentric ring, linear furrow B) linear furrow, white exudates
C) corrugated appearance, linear shearing
Fox VL. Eosinophilic esophagitis: endoscopic findings. Gastrointestinal endoscopy clinics of North America.
2008;18(1):45-57; viii.
75. Histology
Collins MH. Histopathologic features of eosinophilic esophagitis. Gastrointestinal endoscopy clinics of North
America. 2008;18(1):59-71; viii-ix.
76. Histology
Collins MH. Histopathologic features of eosinophilic esophagitis. Gastrointestinal endoscopy clinics of North
America. 2008;18(1):59-71; viii-ix.
77. Histology
Collins MH. Histopathologic features of eosinophilic esophagitis. Gastrointestinal endoscopy clinics of North
America. 2008;18(1):59-71; viii-ix.
78. Histology
Furuta GT, Liacouras CA, Collins MH, Gupta SK, Justinich C, Putnam PE, et al. Eosinophilic esophagitis in children and adults:
a systematic review and consensus recommendations for diagnosis and treatment. Gastroenterology. 2007;133(4):1342-63.
79. Histology
Furuta GT, Liacouras CA, Collins MH, Gupta SK, Justinich C, Putnam PE, et al. Eosinophilic esophagitis in children and adults:
a systematic review and consensus recommendations for diagnosis and treatment. Gastroenterology. 2007;133(4):1342-63.
80. Histology
Collins MH. Histopathologic features of eosinophilic esophagitis. Gastrointestinal endoscopy clinics of North
America. 2008;18(1):59-71; viii-ix.
81. Histology
Collins MH. Histopathologic features of eosinophilic esophagitis. Gastrointestinal endoscopy clinics of North
America. 2008;18(1):59-71; viii-ix.
82. Histology
Collins MH. Histopathologic features of eosinophilic esophagitis. Gastrointestinal endoscopy clinics of North
America. 2008;18(1):59-71; viii-ix.
83. Histology
Collins MH. Histopathologic features of eosinophilic esophagitis. Gastrointestinal endoscopy clinics of North
America. 2008;18(1):59-71; viii-ix.
84. Histology
Collins MH. Histopathologic features of eosinophilic esophagitis. Gastrointestinal endoscopy clinics of North
America. 2008;18(1):59-71; viii-ix.
87. Allergy Evaluation
• Peripheral blood eosinophil count
- There was a significant amount of variability
in the defining level for “peripheral
eosinophilia”
-Range of eosinophils reported as abnormal
ranged from greater than 350 eosinophils
per mm3 to greater than 800 eosinophils per
mm3).
Furuta GT, Liacouras CA, Collins MH, Gupta SK, Justinich C, Putnam PE, et al. Eosinophilic esophagitis in children and adults:
a systematic review and consensus recommendations for diagnosis and treatment. Gastroenterology. 2007;133(4):1342-63.
88. Allergy Evaluation
• Peripheral blood eosinophil count
• One study demonstrated that persistent blood
eosinophilia correlated with persistent
dysphagia.
• In another study, the degree of elevation of
serum eosinophils correlated with the severity
of Eosinophilic esophagitis
Furuta GT, Liacouras CA, Collins MH, Gupta SK, Justinich C, Putnam PE, et al. Eosinophilic esophagitis in children and adults:
a systematic review and consensus recommendations for diagnosis and treatment. Gastroenterology. 2007;133(4):1342-63.
91. 26 Pts with EoE
Identify by BX
SPT+ Milk&Egg
Patch+Wheat
SPT &
Patch test
Avoid
food
Resolution
18 Pts
Partial
improve
6 Pts
Loss F/U
2 Pts
Overall, after intervention, esophageal eosinophil
counts improved from 55.8 to 8.4 eosinophils/HPF
Spergel JM, Beausoleil JL, Mascarenhas M, Liacouras CA. The use of skin prick tests and patch tests to identify causative foods in eosinophilic
92. Treatment
• A trial of specific food allergen and
aeroallergen avoidance
• Systemic or topical glucocorticoids
• Anti–IL-5 monoclonal antibody
• Anti– human IL-13 antibody
• Siglec-F
• PPI
Rothenberg ME. Middleton's Allergy ; 8th edition. 2014. p. 1095-1106
93. Specific food allergen and aeroallergen
avoidance
• Indicated for patients with atopic EoE
• If results are unsatisfactory or avoidance is
difficult for practical reasons
- A diet consisting of an elemental (amino
acid–based) formula
- Avoidance of the most common allergic
foods (cow’s milk, soy, wheat, egg,
peanut/tree nuts, seafood/shellfish)
Rothenberg ME. Middleton's Allergy ; 8th edition. 2014. p. 1095-1106
94. Kagalwalla AF, Sentongo TA, Ritz S, Hess T, Nelson SP, Emerick KM, et al. Effect of six-food elimination diet on clinical and
histologic outcomes in eosinophilic esophagitis. Clinical gastroenterology and hepatology : the official clinical practice
journal of the American Gastroenterological Association. 2006;4(9):1097-102.
95. 60 Pts with EoE
ELED
25 Pts
SFED
35 Pts
6 weeks later Esophageal
Bx Specimen was
obtained
SFED gr. Improve
Esophageal inflammation
26 Pts(74%)
ELED gr improve
Esophageal inflammation
22 Pts (88%)
Kagalwalla AF, Sentongo TA, Ritz S, Hess T, Nelson SP, Emerick KM, et al. Effect of six-food elimination diet on clinical and
histologic outcomes in eosinophilic esophagitis. Clinical gastroenterology and hepatology : the official clinical practice
journal of the American Gastroenterological Association. 2006;4(9):1097-102.
96. Kagalwalla AF, Sentongo TA, Ritz S, Hess T, Nelson SP, Emerick KM, et al. Effect of six-food elimination diet on clinical and
histologic outcomes in eosinophilic esophagitis. Clinical gastroenterology and hepatology : the official clinical practice
journal of the American Gastroenterological Association. 2006;4(9):1097-102.
97. Systemic or topical glucocorticoids
• Systemic glucocorticoids are used for acute
exacerbations
• Topical glucocorticoids are used to provide
long-term control
Rothenberg ME. Middleton's Allergy ; 8th edition. 2014. p. 1095-1106
98. Systemic or topical glucocorticoids
Liacouras CA, Furuta GT, Hirano I, Atkins D, Attwood SE, Bonis PA, et al. Eosinophilic esophagitis: updated
consensus recommendations for children and adults. The Journal of allergy and clinical immunology.
2011;128(1):3-20.e6; quiz 1-2.
99. Konikoff MR, Noel RJ, Blanchard C, Kirby C, Jameson SC, Buckmeier BK, et al. A randomized, double-blind,
placebo-controlled trial of fluticasone propionate for pediatric eosinophilic esophagitis. Gastroenterology.
2006;131(5):1381-91.
100. Konikoff MR, Noel RJ, Blanchard C, Kirby C, Jameson SC, Buckmeier BK, et al. A randomized, double-blind,
placebo-controlled trial of fluticasone propionate for pediatric eosinophilic esophagitis. Gastroenterology.
2006;131(5):1381-91.
101. 36 Pts with EoE
880 g of FP
21 Pts
Placebo
15 Pts
3 mnths later Esophageal
Bx Specimen was
obtained
50% of FP Pts
Improve
9% of Placebo Pts
Improve
Konikoff MR, Noel RJ, Blanchard C, Kirby C, Jameson SC, Buckmeier BK, et al. A randomized, double-blind,
placebo-controlled trial of fluticasone propionate for pediatric eosinophilic esophagitis. Gastroenterology.
2006;131(5):1381-91.
102. Result
• FP decreased esophageal eosinophil levels,
with a more pronounced effect in nonallergic individuals
Konikoff MR, Noel RJ, Blanchard C, Kirby C, Jameson SC, Buckmeier BK, et al. A randomized, double-blind,
placebo-controlled trial of fluticasone propionate for pediatric eosinophilic esophagitis. Gastroenterology.
2006;131(5):1381-91.
Eo/HPF
In Proximal
Esophagus
Eo/HPF
In Distal
Esophagus
P (Value)
FP 65.9 +/- 25.3 84.6+/-19.7 .03
Placebo 1.4+/-1.1 19.6+/- 12.9 .04
103. Anti–IL-5 monoclonal antibody
Spergel JM, Rothenberg ME, Collins MH, Furuta GT, Markowitz JE, Fuchs G, 3rd, et al. Reslizumab in children and
adolescents with eosinophilic esophagitis: results of a double-blind, randomized, placebo-controlled trial. The Journal of
allergy and clinical immunology. 2012;129(2):456-63, 63.e1-3.
105. Spergel JM, Rothenberg ME, Collins MH, Furuta GT, Markowitz JE, Fuchs G, 3rd, et al. Reslizumab in children and
adolescents with eosinophilic esophagitis: results of a double-blind, randomized, placebo-controlled trial. The Journal of
allergy and clinical immunology. 2012;129(2):456-63, 63.e1-3.
106. Spergel JM, Rothenberg ME, Collins MH, Furuta GT, Markowitz JE, Fuchs G, 3rd, et al. Reslizumab in children and
adolescents with eosinophilic esophagitis: results of a double-blind, randomized, placebo-controlled trial. The Journal of
allergy and clinical immunology. 2012;129(2):456-63, 63.e1-3.
107. Spergel JM, Rothenberg ME, Collins MH, Furuta GT, Markowitz JE, Fuchs G, 3rd, et al. Reslizumab in children and
adolescents with eosinophilic esophagitis: results of a double-blind, randomized, placebo-controlled trial. The Journal of
allergy and clinical immunology. 2012;129(2):456-63, 63.e1-3.
227 Pts with EoE
Reslizumab 1
mg/kg
56 Pts
Reslizumab 3
mg/kg
57 Pts
Reslizumab 2
mg/kg
57 Pts
Placebo
% Reduction Eo
59 %
% Reduction Eo
67 %
% Reduction Eo
64 %
% Reduction Eo
24 %
108. Siglec-F
Rubinstein E, Cho JY, Rosenthal P, Chao J, Miller M, Pham A, et al. Siglec-F inhibition reduces esophageal eosinophilia and
angiogenesis in a mouse model of eosinophilic esophagitis. Journal of pediatric gastroenterology and nutrition.
2011;53(4):409-16.
• New approach is to target the sialic acid–binding
immunoglobulin-like lectin F (Siglec-F)
• An inhibitory receptor expressed on eosinophils
• Siglec-F inhibition was useful in a mouse model of
EoE.
109. Proton Pump Inhihitor
• PPI are useful
1. Eliminate GERD as a cause of esophageal
eosinophilia.
2. GERD is a comorbid disease
3. PPI-responsive esophageal eosinophilia
• Mechanism of PPI
1. Primarily involve acid blockade
2. Other mechanisms
Liacouras CA, Furuta GT, Hirano I, Atkins D, Attwood SE, Bonis PA, et al. Eosinophilic esophagitis: updated
consensus recommendations for children and adults. The Journal of allergy and clinical immunology.
2011;128(1):3-20.e6; quiz 1-2.
110. Proton Pump Inhihitor
• Recommended PPI dose that should be used to
eliminate PPI-responsive esophageal eosinophilia
- Adults
20-40 mg, once or twice daily for 8 to 12 weeks
- Children
1 mg/kg per dose, twice daily for 8 to 12 weeks
Liacouras CA, Furuta GT, Hirano I, Atkins D, Attwood SE, Bonis PA, et al. Eosinophilic esophagitis: updated
consensus recommendations for children and adults. The Journal of allergy and clinical immunology.
2011;128(1):3-20.e6; quiz 1-2.
111. Prognosis
• EoE requires prolonged treatment, similar to
allergic asthma.
• Natural history of EoE has not been fully
delineated.
• Results of a 15-year follow up study of
esophageal eosinophilia indicate that
Vast majority of patients have ongoing
symptoms from childhood into adulthood.
DeBrosse CW, Franciosi JP, King EC, Butz BK, Greenberg AB, Collins MH, et al. Long-term outcomes in pediatric-onset
esophageal eosinophilia. The Journal of allergy and clinical immunology. 2011;128(1):132-8.
112. Prognosis
• If left untreated, chronic EoE will likely develop
into progressive esophageal scarring &
dysfunction -> consideration of esophageal
dilation
• The risk for developing Barrett esophagitis,
especially in pts with coexisting EoE and GERD
• Pts with EoE are at increased risk for developing
other forms of EGID -> routine surveillance of the
entire GI tract by endoscopy
Rothenberg ME. Molecular, Genetic, and Cellular Bases for Treating Eosinophilic Esophagitis. Gastroenterology. 2015.
113. Rothenberg ME. Molecular, Genetic, and Cellular Bases for Treating Eosinophilic Esophagitis. Gastroenterology. 2015.