all that burns is not GERD Speaker: Ronnie Fass

Report
Eosinophilic Esophagitis:
All That Burns is Not GERD
May 19, 2012
AGA Spring Postgraduate Course
Glenn T. Furuta
Digestive Health Institute
Children’s Hospital Colorado, Aurora, CO
National Jewish Health, Denver, CO
Gastrointestinal Eosinophilic Diseases Program
University of Colorado Denver School of Medicine
Do patients with EoE complain of
heartburn?
Percent and number of
patients in study
29% of 21
Study
Alexander JA et al, 2012
94% of 50
Gonsalves N et al, 2012
39% of 169
Spergel J et al, 2012
54% of 74
Iwanczak B et al, 2011
20% of 149
Assa’ d et al, 2011
YES!
“Practical Solutions for Your Everyday
Clinical Management Problems”
• Diagnostic “criteria”
• Diagnostic clues
• Therapeutic approach
“Practical Solutions for Your Everyday
Clinical Management Problems”
• Diagnostic “criteria”
– Distinguish between GERD and EoE
•
Diagnostic clues
•
Therapeutic approach
Eosinophilic Esophagitis (EoE)
“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 C et al, J Allergy Clin Immunol 2011
How were Consensus
Recommendations developed?
Authorship
Pedi GI
Adult GI
Pathology
Allergy
2007
15
6
5
6
2011
9
14
3
7
New
1
8
1
3
13 new authors
Furuta GT et al, Gastroenterology 2007
Liacouras C et al, J All Clin Immunol 2011
2011 Updated Consensus Report
• EoE is a clinico-pathologic disease
• Clinically characterized by esophageal dysfunction
• Pathologically 1 or more biopsies show eosinophil
predominant inflammation (15+ eos in peak hpf)
• Histopathology is isolated to esophagus
• Other causes need to be excluded
• “PPI responsive esophageal eosinophilia”
• Diagnosis made by clinicians
• Rarely < 15 eos/hpf (if other clinicopathologic
features present)
Liacouras C et al, J Allergy Clin Immunol 2011
“PPI responsive
esophageal eosinophilia”
• Gastroesophageal Reflux Disease
• Eosinophilic Esophagitis
• Something else?
Spechler S et al 2007
Cheng E et al Gut 2012 and DDW 2012
Other changes
• “EE” to “EoE”
• Chronic
• Immune / antigen driven
Liacouras C et al, J Allergy Clin Immunol 2011
Exclude other causes of esophageal
eosinophilia
Liacouras, et al, J Allergy Clin Immunol 2011
“Practical Solutions for Your Everyday
Clinical Management Problems”
• Diagnostic “criteria”
• Diagnostic clues
– Heartburn / “coping mechanisms”
•
Therapeutic approach
Clinical Features- Children
• “GERD” symptoms
• Abdominal pain, vomiting
• Feeding dysfunction
• Coping mechanisms- avoid highly textured
and bulky foods, cut food into small pieces,
lubricating foods, extensive chewing / long
meals
Clinical Features-Adults
• Chest pain-”with alcohol”
• Food impaction-ask 2 questions
– Netherlands- 2 of 59 patients with FBI
• van der Sluis et al DDW 2012
– Australia-6.2% to 23% over a decade
• Mahesh et al DDW 2012
• Dysphagia– 10 year period of 1371 cases
– EoE increased from 1.6 to 11%
• Kidami et al DDW 2012
Straumann A et al, Allergy 2012
Histological features
Liacouras C et al, J Allergy Clin Immunol 2011
“Esophageal epithelial eosinophilia”
• Requires clinical dissection
– Phenotypes
– Quantification
– Detection devices
Lee et al DDW 2012
Gupta et al DDW 2012
Bohm M et al J Clin Gastroenterol 2011
Molina-Infante et al, Clin Gastroenterol Hepatol 2011
Halsey KD et al, Dis Esophagus 2012
Hurrell JM et al, Am J Gastroenterol 2012
Lee J et al, Clin Gastroenterol Hepatol 2012
Sridhara S et al, Clin Gastroenterol Hepatol 2012
Diniz LO et al, Pediatr Radiol 2012
Racial differences in EoE?
“Esophageal epithelial eosinophilia”
• Requires clinical dissection
– Clinical phenotypes
– Quantification
– Detection devices
Molina-Infante et al, Clin Gastroenterol Hepatol 2011
Bohm M et al J Clin Gastroenterol 2011
Halsey KD et al, Dis Esophagus 2012
Hurrell JM et al, Am J Gastroenterol 2012
Lee J et al, Clin Gastroenterol Hepatol 2012
Sridhara S et al, Clin Gastroenterol Hepatol 2012
Diniz LO et al, Pediatr Radiol 2012
PPI responsiveness
“Esophageal epithelial eosinophilia”
• Demands pathophysiological investigation
– Chemotactic factors
miR expression patterns in EoE
– Functional features
– Therapeutic targets
Menard-Katcher C et al DDW 2012
Lu TX et al J Allergy Clin Immunol 2012
Kagalwalla AF et al J Allergy Clin Immunol 2012
Lu TX et al Mucosal Immunol 2012
Mavi P AM J Physiol Gastrointest Liver Physiol 2012
Persad R et al J Pediatr Gastroenterol Nutr 2012
Diagnostic clues / cautions
• Family history of–Esophageal dilations
–Connective tissue diseases
–Recalcitrant GERD
• “Pretreated mucosa”-i.e. use of topical
steroids for other atopic diseases may
diminish esophageal inflammation
• Alimi et al DDW 2012
Diagnostic clues / cautions
• Normal endoscopy in past does not rule
out EoE.
–Or maybe it does?
• Hauser et al DDW 2012-Belguim
• Le et al DDW 2012-Oklahoma
• Abnormal endoscopy / histology is not
diagnostic of EoE.
“Practical Solutions for Your Everyday
Clinical Management Problems”
• Diagnostic “criteria”
• Diagnostic clues
• Therapeutic approach
– Balance impact of treatment with quality of life
Treatments
• Steroids-topical and systemic
• Diet exclusions
– 6 food elimination
– “Tailored” diet
– Elemental diet
• Dilation
– Medical / nutritional pre-treatment
– Through the scope vs. Bougie
Medical treatments
• Fluticasone
•
•
•
•
•
•
•
Alexander JA et al, Clin Gastroenterol Hepatol 2012
Lucendo AJ et al, J Allergy Clin Immunol 2011
Abu-Sultaneh SM et al, Dig Dis Sci 2011
Peterson KA et al, Dig Dis Sci 2010
Konikoff MR et al, Gastroenterology 2006
Teitelbaum J et al, Gastroenterology 2002
Faubion WA et al, J Pediatr Gastroenterol Nutr 1998
• Budesonide
•
•
•
•
Straumann A et al, Clin Gastroenterol Hepatol 2011
Straumann A et al, Gastroenterology 2010
Dohil R et al, Gastroenterology 2010
Aceves SS et al, Am J Gastroenterol 2007
• Ciclesonide
• Schroeder S et al JACI 2012
• Leukotriene receptor antagonists?
• Lexmond et al DDW 2012
Fluticasone
•
•
•
•
21 FP treated subjects compared to 21 placebo
6 week trial
Histology significantly improved
Symptoms improved (not significantly) in both
groups
• Thrush developed in 26%
Alexander JA et al Clin Gastro Hepatol 2012
Budesonide
• “Oral viscous” budesonide
– Randomized placebo controlled study
– OVB=15, placebo-9
– Significant reduction in symptoms and eosinophilia
Dohil et al Gastroenterology 2010
Ciclesonide
• Converted by epithelial esterases to form the
biologically potent desisobutryl-ciclesonide
(des-CIC)
• Less absorption than other topical steroids
Esterases are expressed by
esophageal epithelia
• 4 children-(4-16 years)
• 8 week treatment
• Clinicopathological response in all
Schroeder S et al J All Clin Immunol 2012
Diet exclusions-adults and children
• “6” food elimination-75%
– Gonsalves N et al, Gastroenterology 2012
– Kagalwalla AF et al, J Pediatr Gastroenterol Nutr 2011
– Kagalwalla AF et al, Clin Gastroenterol Hepatol 2006
• “Tailored” diet-33%-90%
– Molina-Infante et al DDW 2012
– Spergel J et al, Gastrointest Endosc Clin NA 2008
• Elemental diet-95%
– Markowitz JE et al, Am J Gastroenterol 2003
– Kelly K et al, Gastroenterology 1995
Six food elimination diet (SFED)
•
•
•
•
50 adults
6 weeks
Clinicopathological remission with SFED
Eosinophilia returned when diet liberalized
Gonsalves et al, Gastroenterology 2012
Treatments
• Dilation considerations
– Medical / nutritional pre-treatment?
• Kavitt et al DDW 2012
– Through the scope or bougie?
•
•
•
•
•
•
Dhalla et al DDW 2012
Madanick RD et al, Gastrointest Endosc 2011
Jung KW et al, Gastrointest Endosc 2011
Bohm M et al, Dis Esophagus 2010
Dellon ES et al, Gastrointest Endosc 2011
Schoepfer AM et al, Am J Gastroenterol 2010
Biological- Reslizumab-(anti-IL-5 antibody)
• 226 children
(mean age-12 +/1 4)
• 3 doses and placebo
• 12 weeks
• Histological response with
treatment
• Treatment and placebo
symptom response
Spergel JM et al, J Allerg Clin Immunol 2012
Treatment Strategies
• Induce clinical remission-yes
• Induce histological remission– In our experience-yes
– What defines histological remission-?
– Does this prevent complications-?
• Balance benefits of treatment (disease
complications) with treatment complications
and impact of treatment on quality of life.
EoE Complications
• Esophageal stricture
– Weber et al DDW 2012
• Esophageal food / foreign body impaction
• Feeding dysfunction / malnutrition
Treatment complications
• Topical and systemic steroids
• Diet / nutritional exclusions
–Malnutrition
–Diminished quality of life
• Menard-Katcher P et al DDW 2012
• Bajaj et al DDW 2012
• Taft TH et al, Aliment Pharmacol Ther 2011
• Dilation
–Perforation
–Pain
“Practical Solutions for Your Everyday
Clinical Management Problems”
• Rule out other causes of inflammation
• Symptoms may be occult-ask 2 questions
• Treatment choices are increasing and
endpoints are undergoing definition.
Thank you for your attention!

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