eosinophilic esophagitis- recognition, management, and ... · – occasional heartburn – no...
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Eosinophilic Esophagitis-Recognition, Management,
and Misperceptions
Jaime Liou Wolfe, MD June 20, 2019
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2
Objectives • Recognize the signs and symptoms of
eosinophilic esophagitis (EoE) in different age groups
• Appreciate the change in our understanding of the pathophysiology of EoE
• Understand how EoE is diagnosed • Discuss the treatment options for EoE
• No financial or other disclosures 2
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• 7yo male with difficulty swallowing x 1 year – Occurs when eating – Solids worse than liquids – Occasional heartburn – No choke/gag/cough – “Feels food go down”
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Differential Diagnosis-Dysphagia
• Esophagitis – GERD – Eosinophilic
Esophagitis (EoE) – Infectious
• Anatomic/vascular anomaly
• Traumatic injury • Psychosomatic
• Crohn’s Disease • Motility (i.e.
achalasia) • Mediastinal mass • Neurologic • Connective tissue
disease
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Additional History…
– Washes food down with water – Slow eater – Fine in between episodes – Weight gain slowed – IgE mediated food allergy to peanuts – Father with chronic dysphagia, food impaction
age 20s; “has not gotten it checked”
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What is Eosinophilic Esophagitis (EoE)?
• Chronic inflammation of esophagus – Eosinophil dominant
• Immune-mediated
• Food (?aeroallergen) trigger
So what? 6
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Why EoE Matters • #2 cause esophagitis
• Leading cause of dysphagia and food
impaction in kids and adults
• Complications
• Incidence rising
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Symptoms Vary by Age • Abdominal pain, vomiting, dysphagia
• Infants/Toddlers
- Feeding difficulties (gag/choke/refusal), vomiting • Children
– Vomiting/GER, nausea, abdominal pain, chest pain, poor growth
• Adolescents/adults – Dysphagia, food impaction, chest pain
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Epidemiology • Incidence 1/10,0001
• Prevalence 5-10/10,000
• Young men (3:1)2
• Age 30-50yo • High rate atopy
– 2/3- allergic rhinitis, asthma, eczema – IgE mediated food allergy common (15-40%) – Up to 75% have personal or family history3 1Noel R, et al. N Engl J Med 2004; 351:940-1.
2 Orenstein S, et al. Am J Gastroenterol 2000; 95; 1422-30.
3 Furuta GT, et al. Gastroenterology 2007; 133:1342-63.
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Why the Rise? • Environmental
– Hygiene hypothesis – Dietary changes
(antioxidants, fats, Vitamin D)
– Food processing – Delayed oral exposure to
foods • Early antibiotics • C-section
• Prematurity • Microbiome • Infectious- HSV,
Mycoplasma; H. pylori (inverse)
• Oral/sublingual immunotherapy
• PPI, low Vit D 10
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Evaluation & Diagnosis
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• Physical exam– no diagnostic findings
– Allergic shiners – Rhinitis – Reactive airways – Atopic dermatitis
• Laboratory– no diagnostic tests – Mild peripheral eosinophilia in <50% with EoE1
– Allergy testing (skin prick, IgE) • No direct correlation with non-IgE mediated
disease
1Putnam, PE. Immunol and All Clin N Amer 2009; 29: 1-10.
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• Other questions to ask: – Onset with introduction of solids? – Slow eater? – Drink to wash down food? – Particular food avoidance? – Excessive chewing? – Other atopy-patient, family? – Growth failure?
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Endoscopy
Normal Longitudinal furrowing
Concentric rings, exudate
1Potter J, et al. Gastrointest Endosc 2004; 59:355-61.
-Up to 30% who have histologic EoE have endoscopically normal mucosa1
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• Increased eos/HPF, microabscesses, superficial layering, basal zone hyperplasia
Concentric rings in esophagus
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Diagnostic Criteria Has Changed
• 20071
– ≥ 15 eos/HPF, PLUS – Characteristic symptoms which do not respond to
high dose PPI therapy, OR normal pH monitoring1
• 2011-Proton Pump Inhibitor-responsive Esophageal Eosinophilia (PPI-REE)2
– ≥ 15 eos/HPF, PLUS – Symptoms of esophageal dysfunction, PLUS – Improvement/resolution of symptoms and eosinophilia
after high dose PPI 16
1Furuta GT, et al. Gastroenterology 2007. 2Liacouras CA, et al. J Allergy and Clin Immun. 2011.
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Assumptions
1. GERD and EoE distinct 2. GERD is the only esophageal condition that responds to PPI1
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1Dellon et al. Gastroenterology Vol 155 2018
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New Understanding • AGREE (A Working Group on PPI-REE)1
• GERD and EoE may overlap 1. EoEGERD? (dysmotility) GERD EoE? (impaired mucosal barrier) 2. EoE and PPI-REE similar histologically 3. RNA expression profiles similar 4. Atopy present in EoE and PPI-REE 5. PPI-REE responds to EoE treatment (topical steroids, dietary elimination)
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1Dellon ES, et al. Gastroenterology 2018.
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PPIs-More Than Gastric Acid Inhibition
Non-acid related mechanisms – Antioxidant – Blocks secretion of eosinophil trafficking molecule
(eotaxin-3) – Proton pumps in inflammatory cells and non-gastric cells – Patients with normal pH probe can respond to PPI
therapy
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Management
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Goals
Symptom control Histologic normalization Reversal of remodeling Avoidance of complications
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Treatment Options
• 2011 – Elimination Diet – Swallowed Topical Steroid
• 2019
– PPI – Elimination Diet – Swallowed Topical Steroid
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Dietary Therapy
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Classification of Food Allergy
• IgE mediated – Acute (anaphylaxis, oral swelling)
• Cell mediated (Delayed/chronic) – Delayed/chronic (FPIES, food protein
proctitis) • Mixed IgE/cell mediated
– Delayed/chronic (eosinophilic GI disease, eczema)
– Serum IgE and Skin Prick Testing not helpful in EoE!
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Dietary Options
1. Elemental
2. Empiric 6, 4, 2, 1 elimination
3. Directed elimination
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Determining dietary
modification IgE Mediated
• Cow’s Milk • Egg • Peanut • Tree nuts • Fish • Shellfish • Wheat, soy • Sesame
EoE • Cow’s milk
– 40-90% – 50% only trigger1
• Wheat • Egg • Soy
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1Kagalwalla AF et al. Clinc Gastroenterol Hepatol 2017.
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Elimination Diets for EoE
• Elemental – 90% remission1
• 6 Food: Dairy, wheat, soy, egg, nuts, fish/shellfish – 50-75% remission2
• 4 Food: Dairy, gluten, egg, legumes
- 50-65% remission2
• 2 Food: Dairy, gluten – 43% remission3
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1Aria A et al. Gastro 2014. 2Molina Infante J et al. J Allergy Clin Immunol 2018 3Molina-Infante J et al. Expert Rev Gastroenterol Hepatol. 2017
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Dietary Options
• Directed Elimination:
– 12 single arm studies 50% remission1
• Testing techniques varied – Not effective
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1Hirano I et al. AGA Clinical Guidelines 2019.
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Pharmacotherapy
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PPI
• 1-2 mg/kg/day divided BID • Max dose- Lansoprazole 30mg BID,
Omeprazole 40mg BID • 23 observational studies40% histologic
improvement1
– Heterogeneous studies
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1Hirano I et al. AGA Clinical Guidelines 2019.
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• Swallowed topical steroids – Fluticasone – Budesonide slurry – 8 double-blind placebo controlled studies
• 66% remission vs. <15% placebo1
• TRY TO AVOID: Systemic steroids • NOT: Mast cell stabilizers (Cromolyn), leukotriene
antagonists (Montelukast), biologics (Anti-TNFα, Anti-IL5, Anti-IL13)
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1Hirano I et al. AGA Clinical Guidelines 2019
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Swallowed Topical Steroids • Fluticasone
– 1-4yo: 44 mcg, two sprays twice daily – 5-10yo: 110 mcg, two sprays twice daily – ≥11yo: 220 mcg, two sprays twice daily
• Budesonide – < 10yo: 1 mg daily – > 10yo: 2 mg daily
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Limitations in Current Data
• No prospective, double-blind, randomized trial to compare PPI to diet or steroid – Small studies, retrospective – Inconsistent study design
• PPI duration, dose • PPI responder vs. non-responder
– Lack consistent definition re: clinical or histologic response
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Risks/benefits: PPI vs. Diet vs.Topical Steroid • PPI
– Long term safety concerns
• Diet – QOL – Developmental feeding & social skills – Cost – Possible NG/Gtube
• Topical steroid – Local infection – Adrenal suppression – Growth? 34
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Natural History
• Esophageal subepithelial remodeling • Increased angiogenesis • Vascular activation conduits for inflammatory cell trafficking collagen deposition, accumulation of matrix proteins eosinophil accumulation
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EoE Is Chronic, Progressive • 2003- Straumann A et al • 30 adults, 7 year follow-up
– No medical therapy – Dysphagia
• 40% better, 40% stable, 25% worse – Subepithelial fibrosis- worse 86%
• Limitations: – 1/3 s/p dilation – 50% altered eating habits 36
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Do Not Delay Diagnosis
• Symptom as outcome: lack of significant progression
• Dysphagia childrenadult: 30-50% • Patients adapt
• Histology as outcome: significant progression of fibrosis
#1 risk factor fibrostenotic disease = delay in diagnosis
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Challenges • Natural history of EoE still not fully understood
– Variable symptoms– different phenotypes? – Outcomes in asymptomatic patients – Consistent symptom, histologic endpoints
• Distinguishing EoE from GERD
• Non-invasive methods for assessing disease – Less invasive diagnostic modalities – Histologic biomarkers – Genetic markers
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• Treatment – Loss of therapeutic efficacy – Role of rescue therapy for “flares” – Biologic therapy – Need clinical trials comparing therapies
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Take Home
• Symptoms differ by age • Symptoms do not correlate with histology • Food allergy testing not reliable • Need upper endoscopy with biopsies to
diagnose • EoE and PPI-REE same entities
– PPI, dietary elimination, and topical steroids • Avoid delay in diagnosis
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EoE Referrals • Pediatric Specialists of Virginia Fairfax, VA 703.876.2788
– Jaime Wolfe, MD & Darlene Mansoor, MD – Otto Louis-Jacques, MD
• Children’s National Health System Friendship Heights 202.476.3032
– Seema Khan, MD & Hemant Sharma, MD 41