Eosinophilic Esophagitis and Nutritional Consequences Douglas T. Johnston, DO, FACAAI, FAAAAI Assistant Professor of Internal Medicine / Allergy & Immunology Edward Via College of Osteopathic Medicine Carolina Campus Disclosures Speaker bureau: Mylan, Nutricia, Abbott labs Asthma & Allergy Specialists, PA Charlotte, NC Objectives To understand the difference between IgE mediated and non IgE mediated To learn the current definition of eosinophilic esophagitis Review symptoms of eosinophilic gastrointestinal disorders To understand the treatment options of eosinophilic esophagitis Food Allergy In Schools Students with food allergies are protected by Federal law: Rehabilitation Act of 1973, Section 504 Affects about 2 million school-age children In a study of 400 school nurses, 94% reported at least one child with food allergy 44% reported an increase in food-allergic children in their schools over the last 5 years Up to 25% of peanut/tree nut reactions in schools are first-time reactions FAAN Anaphylaxis slide deck 1
Food Allergy In Schools Adverse Food Reactions Most reactions in schools occur from food in the classroom used for projects or celebrations Once a reaction begins, there is no way to know how severe it will become Take all food allergy induced allergic reactions seriously Every school should have a plan for managing food allergies November 13 th 2013: President Obama signed School Access to Emergency Epinephrine Act FAAN Anaphylaxis slide deck Immune Mediated Food Reactions Pathogenesis IgE vs. Non IgE Allergology International. 2013;62:297 307 2
Non IgE Mediated Food Allergy Food protein induced enterocolitis syndrome (FPIES) Food protein induced enteropathy Food protein induced allergic proctocolitis Eosinophilic gastrointestinal diseases (EoE, eosinophilic gastritis, etc.) Food allergy induced atopic dermatitis Food Protein Induced Enterocolitis Syndrome (FPIES) Delayed non IgE mediated reaction to foods, often milk, soy and rice No hives, swelling or respiratory distress Pathogenesis is not entirely clear Involvement of antigen specific T cells Modify intestinal barrier Increase permeability and fluid shifts FPIES Symptoms Profuse repetitive vomiting Severe, can be 15 20 episodes Can be 1 3 hours after ingestion Diarrhea May have blood and/or mucus Typically 2 10 hours after ingestion Dehydration lethargy shock Weight loss and FTT if chronic exposure FPIES Diagnosis No diagnostic tests Skin prick testing to food typically negative Increase in blood neutrophils peaks at 6 hr Diagnosis by history and oral food challenges J Allergy Clin Immunol: In Practice 2013;1:317 22 J Allergy Clin Immunol: In Practice 2013;1:317 22 3
Immune Mediated Food Reactions Venter et al. Clinical and Translational Allergy 2013;3:13 Eosinophilic gastrointestinal disorders Eosinophilic esophagitis (EoE) 530.13 Eosinophilic Gastritis 535.7 Eosinophilic Gastroenteritis 558.41 Less common than EoE May involve stomach, intestine and esophagus Eosinophilic Colitis 558.42 Diarrhea, cramping, bloody stools much like other forms of colitis 2011 Updated Consensus Report EoE is a clinicopathologic disease Clinically characterized by esophageal dysfunction Histologically should have 1 or more biopsies with eosinophil predominant inflammation (15+ eos in most involved HPF) Disease limited to esophagus Must distinguish between EoE and esophageal eosinophila PPI responsive esophageal eosinophilia diagnosis of EoE should be made by a clinician, not a pathologist Liacouras et al, JACI, 2011 4
2011 Updated Consensus Report 6 month effort involving 33 physicians Revised conceptual definition of 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 Clinical Features Male predominance (about 3:1) Multiple reports of familial clustering Strong association with other atopic disorders: asthma, allergic rhinitis, eczema other food allergies Chronic condition Pediatric and Adult EoE likely the same disease Liacouras et al, JACI, 2011 Furuta, GT. Gastroenterology 2007; 133:1342. Symptoms of EoE Clinical Presentation Varies with Age in Children with EoE Symptoms may vary and can differ at different ages Infants and Toddlers: FTT, reflux, irritability, vomiting School age: abdominal pain, vomiting, reflux Feeding Disorder Vomiting Abdominal Pain Dysphagia Food Impaction 13% 26% 26% 27% 7% Fraction of Population Adolescents/Adults: Dysphagia and food impaction, reflux 0 4 8 12 16 20 Age (Years) Noel RJ et al. NEJM 2004 5
Endoscopic Findings in EoE Diagnosis of EoE Normal Ringed Esophagus (Felinization/Trachealization) Furrowing White Plaques Fox et al, Gastrointestinal Endoscopy, 2003 Endoscopic Findings Histologic Findings May suggest but not pathognomonic of EoE Up to 30% of patients with EoE have no definitive endoscopic findings visually Biopsies are essential for diagnosis and monitoring therapy Mucosal Immunology (2011) 4, 139-147 6
Treatment Options Treatment of EoE Systemic steroids Reserved for severe cases; not a good long term option Topical steroids Swallowed MDI (fluticasone) Viscous slurry (budesonide mixed with Splenda or AA powder) Dietary elimination Elemental (amino acid based formulas) Empiric (six food elimination/newer empiric diets) Directed (based on allergy testing) What is Optimal Treatment? Goals 1. Improve symptoms 2. Decrease future risk of disease / normal esophageal biopsy 3. Minimize/eliminate drug side effects (PPIs, Topical corticosteroids) 4. Obtain proper nutrition / weight gain 5. Prevent psychosocial impact of strict elimination diets 6. Treatment is doable Quality of life depends on the balance of above Topical Corticosteroids in Children with EoE RDBPC of 36 children with EoE Fluticasone 880 mcg/day (21 pts) vs placebo (15 pts) 3 months 50% in treatment group had complete resolution of disease with < 1 eos/hpf A highly individualized approach is needed Konioff et al. Gastroenterology. 2006;131:1381-92 7
Topical Corticosteroids in Children with EoE 24 children with EoE: 15 given oral viscous budesonide 9 placebo Budesonide 1mg or 2 mg daily (above 5 ft) All received lansoprazole 3 months of treatment repeat biopsy Responders if <6 eos/hpf 87% responded to treatment vs. 0% placebo group Topical Corticosteroids in Children with EoE: Side effects 4 week prospective randomized trial 8 week weaning protocol 80 children (40 oral, 40 topical steroids) 15% esophageal candidiasis was most common side effect in topical steroid group 45% relapse rate by week 24 No long term topical steroid data in children Dohil et al. Gastroenterology. 2010. 129:418-29 Schaefer et al. Clin Gastroenterol Hepatol. 2008;6:165-73. Corticosteroids in EoE Topical Corticosteroids in EoE Key Points You will see patients on fluticasone or budesonide swallow Typically done at home, no food or drink for 30 mins Its doesn t always work Sides effects: look for thrush or think about possible esophageal candidiasis if there is PAIN with swallowing Liacouras et al, JACI, 2011 8
Treatment Options Systemic steroids Reserved for severe cases; not a good long term option Topical steroids Swallowed MDI (fluticasone) Viscous slurry (budesonide mixed with Splenda or AA powder) Dietary elimination Elemental (amino acid based formulas) Empiric (six food elimination/newer empiric diets) Directed (based on allergy testing) Elemental Diet Exclusive feeding of amino acid based formula amino acid based formula Up to 97% response rate Advantages: Most effective of any published therapy Disadvantages: Most life altering May require NG or gastrostomy feeds Cost Markowitz, Am J Gastroenterol 2003 Liacouras, Clin Gast Hepatol 2005 Empiric Dietary Elimination Six food elimination diet Milk, soy, egg, wheat, peanut/tree nuts, shellfish/fish Up to 81% response rate Advantages: Effective No requirement for allergy testing Disadvantages: Difficult May be overly restrictive / may miss potential triggers Nutritional concerns Henderson, JACI 2012 Empiric Elimination Diet in Children 35 children 6 week elimination of milk, soy, egg, wheat, nuts, seafood 74% of children responded symptomatically and histologically (<10 eos/hpf) Peak eosinophils dropped from 80.2 to 13.6 Clin Gastroenterol Hepatol 2006;4(9):1097 102. 9
Directed Dietary Elimination Based on results of both skin prick testing and atopy patch tests Food reintroductions can be done after histologic improvement Up to 77% response With empiric milk elimination Advantages: Effective May be less restrictive than six food elimination Prevents need for corticosteroids Disadvantages: Difficult Testing may lead to over elimination initially Approach to Directed diet Can vary among allergists Often involve a combination of skin prick tests and atopy patch tests Blood allergy tests (sige) not demonstrated to be helpful in studies Milk is almost always eliminated Clinical dietitian involvement is advised Success = No symptoms and normal esophageal biopsies Spergel et al. JACI. 2012 Skin Prick Testing Allergy skin prick testing Elimination diets based on SPT alone are helpful in only a minority of patients Common SPT positives in EoE: milk, egg, soy, wheat, chicken, peanut and beef 9% of patients with EoE have IgE mediated food Rx Most common IgE mediated reactions: Egg, Milk, Peanut Gastroenterology. 2012;142:1451-1459 Ann Allergy Asthma Immunolo. 2005;95:336-43. Spergel et al. JACI. 2012 resources.rhoworld.com http://www.nlm.nih.gov/medlineplus/ency/imagepages/19344.htm 10
Atopy Patch Test (APT) May have utility for diagnosis of non IgE, cellmediated immune responses to foods in EoE 48 hour occlusion / Read at 72 hours Test foods that were negative on SPT Food Allergy Expert Panel guidelines: The EP suggests that SPT, sige tests, and APTs may be considered to help identify foods that are associated with EoE, but these tests alone are not sufficient to make the diagnosis of food allergy. 11
Spergel et al. JACI. 2012 Spergel et al. JACI. 2012 Diet Therapy Key Points Diet therapy is different for everyone Often include elimination of milk, wheat, egg soy Kids may cheat or diet may not work May cause vomiting or abdominal pain in some Many children need supplementation with elemental formula May be at higher risk for bullying Should Children with EoE have Food Allergy Action plans? Most children with EoE do no have anaphylaxis, hives, swelling or respiratory distress after eating the foods they are allergic too. May not need epinephrine or a food allergy action plan If they have immediate reactions to foods, then a food allergy action plan is needed. However, avoidance of foods is just as important Symptoms tend to be more delayed and often do not occur immediately Symptoms may not be life threatening but will effect quality of life 12
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Food Allergy Resources FARE (Food Allergy Research & Education) WWW.FOODALLERGY.ORG NIAID Food Allergy Guidelines http://www.niaid.nih.gov/topics/foodallergy/clinical/pa ges/patients.aspx American Partnership for Eosinophilic diseases APFED www.apfed.org EoE Key Points Symptoms in school age children include abdominal pain, vomiting, weight loss, dysphagia There are multiple treatment options for EoE May not need epinephrine, however about 9% have IgE mediated reactions and will need epinephrine and action plans Allergy testing for culprit foods in EoE is not definitive and diets can change based on follow up endoscopy results Thanks for keeping our kids safe! 14