1. Allergy Grand Rounds Michael Goldman, M.D. Johns Hopkins Asthma & Allergy Center April 2, 2004

2. This is a 37 y.o. WM who presents with dysphagia of solid foods for three years Chief Complaint

3. HPI Complains of difficulty swallowing solid foods. Steak, chicken, pork, and bread get stuck in the base of throat  emesis, with relief of obstruction No pain on swallowing, no heartburn, no wt. loss No difficulty swallowing liquids Only slight improvement with Nexium. Stopped due to nausea. Referred to GI

4. Work up Normal Exam Normal Exam Barium swallow: narrowing of distal esophagus. Barium swallow: narrowing of distal esophagus. Differential diagnosis: Differential diagnosis: Peptic stricture (from reflux esophagitis), but no history of reflux Peptic stricture (from reflux esophagitis), but no history of reflux Motility disorder (eg achalasia, esophageal spasm) but no mention of abnormal motility or dilated esophagus on barium swallow Motility disorder (eg achalasia, esophageal spasm) but no mention of abnormal motility or dilated esophagus on barium swallow Hypertensive lower esophageal sphincter Hypertensive lower esophageal sphincter Schatzki ring (Lower esophageal mucosal ring) Schatzki ring (Lower esophageal mucosal ring)

5. Achalasia

6. Schatzki Ring

7. Work up Endoscopy: Endoscopy: “Ringed” esophagus “Ringed” esophagus Several “polypoid/nodular” areas, biopsied Several “polypoid/nodular” areas, biopsied Narrowing of the distal esophagus Narrowing of the distal esophagus Not consistent with Schatzki ring Not consistent with Schatzki ring Stricture dilated Stricture dilated

8. Ringed Esophagus

9. Esophageal nodules

10. Whitish exudates

11. Esophageal Stricture with Food Impaction

12. Biopsy Results Esophagus: Esophagus: Moderate chronic inflammation Moderate chronic inflammation Focally parakeratotic (excessive keratin) papillary tissue with increased areas of eosinophils in subepithelium Focally parakeratotic (excessive keratin) papillary tissue with increased areas of eosinophils in subepithelium Read as compatible with squamous papilloma with eosinophilia described in reflux esophagitis. Read as compatible with squamous papilloma with eosinophilia described in reflux esophagitis. No dysplasia No dysplasia

13. Eosinophilic Esophagitis Referred for allergy evaluation

14. Allergy Consultation Dysphagia of solids persists, but no further vomiting episodes since esophageal dilitation. Dysphagia of solids persists, but no further vomiting episodes since esophageal dilitation. No history of food allergy, but on careful questioning reports slight itchy throat to peanuts, eggs, possibly nuts. No history of food allergy, but on careful questioning reports slight itchy throat to peanuts, eggs, possibly nuts. Beer causes facial flushing and mild throat constriction. No reactions to other forms of alcohol. Beer causes facial flushing and mild throat constriction. No reactions to other forms of alcohol.

15. Medical/Social History Allergic rhinitis as a child, treated with immunotherapy. Mild symptoms presently except around pets. Allergic rhinitis as a child, treated with immunotherapy. Mild symptoms presently except around pets. Mild asthma around pets and with exercise in cold air. Uses albuterol prn. No steroids or ER visits since childhood. Mild asthma around pets and with exercise in cold air. Uses albuterol prn. No steroids or ER visits since childhood. Otherwise healthy: no cardiac disease, rashes, arthritis, fevers, chills, diarrhea, travel Otherwise healthy: no cardiac disease, rashes, arthritis, fevers, chills, diarrhea, travel No pets, non smoker, no ETOH abuse. No pets, non smoker, no ETOH abuse.

16. Physical Exam Normal Normal No edema of nasal mucosa No edema of nasal mucosa Clear lungs Clear lungs Cardiac without murmurs Cardiac without murmurs Normal abdominal exam Normal abdominal exam Diagnostic testing performed Diagnostic testing performed What would you test for? What would you test for?

17. Skin Testing-scratch FoodWheal/flareFoodWheal/flare Egg10/45Malt5/12 Peanut7/20Wheat3/5 Fish Mix 6/30Beef0 Hazelnut10/30Chicken0 Almond4/8Milk0 Other nuts 0Soy0 Pork4/12 Shellfish mix 0 Lamb5/15

18. Now What? More skin testing? More skin testing? Confirm with RAST? Confirm with RAST? Food patch testing? Food patch testing? Other blood tests? Other blood tests? Food avoidance? Food avoidance? Epipen? Epipen? Medicines? Medicines?

19. My recommendations Food avoidance for 1 month: all positive skin tests except wheat (borderline) Food avoidance for 1 month: all positive skin tests except wheat (borderline) Egg, peanut, beer (malt), hazelnut, almond, pork, lamb. Egg, peanut, beer (malt), hazelnut, almond, pork, lamb. Confirm positive tests with cap-Rast. Confirm positive tests with cap-Rast. Check CBC, eosinophil count, total IgE Check CBC, eosinophil count, total IgE No meds prescribed No meds prescribed

20. Blood results FoodkU/LFoodkU/L Egg4.88Malt3.32 Peanut2.56Wheat12.3 Fish (cod, tuna,salmon) <0.35 Hazelnut3.32 Total IgE 627(0-114) Almond3.37 Serum Eos 871 (15-500) Pork4.57WBC6.7K,13%eos Lamb3.43

21. Follow Up Improved but not resolved Improved but not resolved Still with some dysphagia but no choking or vomiting (since dilitation) Still with some dysphagia but no choking or vomiting (since dilitation) Avoiding egg, pork, lamb, fish, malt, peanuts, and nuts Avoiding egg, pork, lamb, fish, malt, peanuts, and nuts Skin tests to individual fish all + except tuna Skin tests to individual fish all + except tuna Skin tests to inhalants +cat, dog, DM, trees, grass. Skin tests to inhalants +cat, dog, DM, trees, grass. No seasonal worsening of dysphagia No seasonal worsening of dysphagia

22. Now What? Recommended wheat avoidance for 2 weeks, symptoms partially improved Recommended wheat avoidance for 2 weeks, symptoms partially improved Pt not interested in neocate trial Pt not interested in neocate trial To start Flovent 220 2 p bid, without spacer, swallowed. To start Flovent 220 2 p bid, without spacer, swallowed. GI follow up in 2 months. GI follow up in 2 months.

23. Adult Eosinophilic Esophagitis Typically seen in young adults (mean age 34) Typically seen in young adults (mean age 34) Dysphagia with bolus impaction is most common symptom Dysphagia with bolus impaction is most common symptom Esophageal strictures common (unlike kids) Esophageal strictures common (unlike kids) Esophageal biopsy necessary for diagnosis Esophageal biopsy necessary for diagnosis Exclude secondary causes: HES, parasitic disease, connective tissue dz (scleroderma), drug reaction Exclude secondary causes: HES, parasitic disease, connective tissue dz (scleroderma), drug reaction

24. Adult Eosinophilic Esophagitis Mean duration to diagnosis 4 years Mean duration to diagnosis 4 years Male : Female = 3 : 1 Male : Female = 3 : 1 50 – 75% atopic 50 – 75% atopic Food sensitization common, but not well studied Food sensitization common, but not well studied

25. Pediatric Eosinophilic Esophagitis Reflux symptoms most common presentation Reflux symptoms most common presentation Vomiting Vomiting Regurgitation Regurgitation Abdominal pain Abdominal pain Dysphagia Dysphagia Food refusal/poor wt. gain Food refusal/poor wt. gain Unresponsive to PPIs for GERD Unresponsive to PPIs for GERD Strictures less common Strictures less common

26. Pediatric Eosinophilic Esophagitis Endoscopy and biopsy needed for diagnosis Endoscopy and biopsy needed for diagnosis Food sensitization very common Food sensitization very common 60-75% skin test positive (egg, milk most common) 60-75% skin test positive (egg, milk most common) 80% in one study positive patch test to foods (wheat most common) 1 80% in one study positive patch test to foods (wheat most common) 1 1 Spergel, JACI 2002, 109:363-368

27. Treatment Food avoidance Food avoidance Effective in children Effective in children Elemental formula reduced eosinophils and symptoms 1 Elemental formula reduced eosinophils and symptoms 1 8/10 resolution, other 2 improved 8/10 resolution, other 2 improved Food avoidance based on all positive skin test and food patch test: 2 Food avoidance based on all positive skin test and food patch test: 2 resolved symptoms in 18/24 kids w/ EE and improved symptoms other 6. Milk, egg most common, but many others implicated. Average of 3.6+/-2.1 foods resolved symptoms in 18/24 kids w/ EE and improved symptoms other 6. Milk, egg most common, but many others implicated. Average of 3.6+/-2.1 foods Mean esophageal eosinophils decreased 55.8/hpf  8.4/hpf Mean esophageal eosinophils decreased 55.8/hpf  8.4/hpf No studies in adults No studies in adults 2 Spergel, JACI 2002, 109:363-368 1 Kelly, Gastroenterology, 1995, 1503-1512

28. Treatment Oral corticosteroids Oral corticosteroids Effective but side effects Effective but side effects Topical Steroids (swallowed “inhaled” steroids) Topical Steroids (swallowed “inhaled” steroids) Swallow FP 220 2pbid Swallow FP 220 2pbid Improvement in both adults and children Improvement in both adults and children Esophageal candidiasis (2/13 kids) 1 Esophageal candidiasis (2/13 kids) 1 1 Teitlebaum, Gastroenterology 2002;122:1216

29. Treatment Esophageal dilitation Esophageal dilitation Relieves obstruction, dysphagia often persists Relieves obstruction, dysphagia often persists PPIs for EE generally ineffective PPIs for EE generally ineffective

30. EE vs. GERD CharacteristicEEGERD AtopyHighNml Food sensitization HighNml Histology >24 eos/hpf 0-7 eos/hpf Peripheral eosinophilia ~50%rare Esophageal pH NormalAbnormal PPI Usually not helpful Helpful SteroidsHelpful Not helpful Food allergen elimination Sometimes helpful Not helpful