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!