eosinophilic esophagitis: all that burns is not gerd may 19, 2012 aga spring postgraduate course...
TRANSCRIPT
Eosinophilic Esophagitis:All That Burns is Not GERD
May 19, 2012
AGA Spring Postgraduate Course Glenn T. Furuta
Digestive Health InstituteChildren’s Hospital Colorado, Aurora, CO
National Jewish Health, Denver, COGastrointestinal Eosinophilic Diseases Program
University of Colorado Denver School of Medicine
Do patients with EoE complain of heartburn?
Percent and number of patients in study
Study
29% of 21 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 2007 2011 NewPedi GI 15 9 1
Adult GI 6 14 8Pathology 5 3 1
Allergy 6 7 3
13 new authors
Furuta GT et al, Gastroenterology 2007Liacouras 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 2007Cheng E et al Gut 2012 and DDW 2012
• “EE” to “EoE”
• Chronic
• Immune / antigen driven
Other changes
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 2012Gupta et al DDW 2012Bohm M et al J Clin Gastroenterol 2011Molina-Infante et al, Clin Gastroenterol Hepatol 2011Halsey KD et al, Dis Esophagus 2012Hurrell JM et al, Am J Gastroenterol 2012Lee J et al, Clin Gastroenterol Hepatol 2012Sridhara S et al, Clin Gastroenterol Hepatol 2012Diniz 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 2011Bohm M et al J Clin Gastroenterol 2011Halsey KD et al, Dis Esophagus 2012Hurrell JM et al, Am J Gastroenterol 2012Lee J et al, Clin Gastroenterol Hepatol 2012Sridhara S et al, Clin Gastroenterol Hepatol 2012Diniz LO et al, Pediatr Radiol 2012
PPI responsiveness
“Esophageal epithelial eosinophilia”
• Demands pathophysiological investigation–Chemotactic factors– Functional features–Therapeutic targets
Menard-Katcher C et al DDW 2012Lu TX et al J Allergy Clin Immunol 2012Kagalwalla AF et al J Allergy Clin Immunol 2012Lu TX et al Mucosal Immunol 2012Mavi P AM J Physiol Gastrointest Liver Physiol 2012Persad R et al J Pediatr Gastroenterol Nutr 2012
miR expression patterns in EoE
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
Schroeder S et al J All Clin Immunol 2012
• 4 children-(4-16 years)
• 8 week treatment
• Clinicopathological response in all
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!