9/2/2015. Functions include:

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1 No conflict of interest. Betsey Kim CRNP, CORLN Division of Otolaryngology The Children s Hospital of Philadelphia Functions include: Movement to inflamed areas Trapping substances Killing cells Antiparasitic and bactericidal activity Participating in allergic reactions Modulating inflammatory responses Eosinophilic esophagitis represents a chronic, immune/antigen-mediated esophageal disease characterized clinically by symptoms related to esophageal dysfunction and histologically by eosinophil-predominant inflammation. Cases significantly increased over last several yrs Approx 1 in 10,000 individuals in early 2000s Current rate = approx 1 in 1,500 to 2,500 individuals EOE new pts > Crohn s disease new pts 1

Heightened awareness Improved recognition True increase in the occurrence/frequency of disease Majority of cases reported from

the 3 rd - 4 th decade of life Children with EOE often have other atopic diseases Dysphagia Food impaction Abdominal pain

food refusal Poor weight gain/ftt Frequent vomiting/spitting up Arching in pain Children Symptoms more suggestive of chronic

2 Heightened awareness Improved recognition True increase in the occurrence/frequency of disease Majority of cases reported from N. America and Europe Male to female ratio is 3:1 Predominance in non-hispanic whites Usually presents in childhood or during the 3 rd - 4 th decade of life Children with EOE often have other atopic diseases Dysphagia Food impaction Abdominal pain Vomiting Chest pain GERD-like symptoms Heartburn Loss of appetite Early satiety Poor weight gain/ftt Infants Feeding issues or food refusal Poor weight gain/ftt Frequent vomiting/spitting up Arching in pain Children Symptoms more suggestive of chronic GERD Heartburn Abdominal pain Vomiting Eat slowly Aversion to certain foods Teenagers/Adults Dysphagia most common complaint Food impaction 2

3 Role of genetics Strong familial association Genes: TSLP and eotaxin 3 Role of atopy Allergic triggers History/Physical exam PPI usage Endoscopy Biopsy/Histopathology Radiography Endoscopic features can SUGGEST EOE but cannot DIAGNOSE EOE 3

Histopathologic features Superficial layering of eosinophils Microabscess formation White plaques Treat symptoms Dysphagia Chronic

4 Esophageal biopsy = GOLD standard in EOE dx Multiple biopsies needed from esophagus and other gastric sites Eosinophil counts obtained from most densely populated high-power field (hpf) EOE dx > 15 eosinophils/hpf EOE EOE is isolated to esophagus Histopathologic features Superficial layering of eosinophils Microabscess formation White plaques Treat symptoms Dysphagia Chronic abdominal pain Vomiting Growth failure Improve tissue histology and chronic inflammation Prevent complications Esophageal strictures/stenosis 4

Specific Food Elimination Effective and recommended 1 st in ALL Dietary Therapy Empiric Elimination children with EOE dx Food allergies main cause of EOE in children EOE Diagnosis Pharmacological

5 Specific Food Elimination Effective and recommended 1 st in ALL Dietary Therapy Empiric Elimination children with EOE dx Food allergies main cause of EOE in children EOE Diagnosis Pharmacological Therapy Elemental Diet Diet & Steroids Can have complete resolution of both clinical and histological abnormalities Steroids 3 dietary regimens 1. Specific food elimination based on allergy testing 2. Empiric diet elimination 3. Elemental diet All dietary therapies show efficacy for EOE tx Most effective & Gold Standard = Elemental Diet Ensures elimination of causative foods Milk Egg Soy Wheat Peanuts Beef Corn Chicken Potato Pork Pharmacological tx may temporarily remove symptoms but disease RETURNS when meds discontinued When trigger foods eliminated from diet, pts enter long-term remission without medication Choice of tx depends on: Disease severity Lifestyle Quality of life Family resources/costs Provider expertise and preferences Combination of dietary and pharmacological tx is frequently used 5

6 No specific medication has yet earned a U.S. FDA indication for EOE tx Categories used include: Proton-pump inhibitors (PPIs) Corticosteroids Leukotriene inhibitors Immunomodulators Biologic agents Effective EOE dx tool (treat 8-12 wks) PPI trial therapy recommended for all EOE pts even if dx seems clear cut Helpful tool in eliminating GERD as cause of EOE Useful for treating GERD symptoms associated with EOE PPI therapy alone is not effective as primary EOE tx Mechanism of Action/Pharmacokinetics: Decreases acid secretion in gastric parietal cells Significantly more effective than H 2 antagonists in reducing gastric acid secretion by up to 99% Onset of action of gastric acid suppression: 1-3 hrs Duration: Can be up to 72 hrs with 50% of max effect at 24 hrs Absorption: Rapid Half-life elimination: About 1 hr Omeprazole (Prilosec) Lansoprazole (Prevacid) Dexlansoprazole (Kapidex) Esomeprazole (Nexium) Pantoprazole (Protonix) Rabeprazole (AcipHex) Ilaprazole (Noltec) OMEPRAZOLE Adult 20 mg 1x/daily for at least 8 wks Pediatric/children 1-16 yrs 5 kg to <10 kg: 5 mg 1x/daily 10 kg to <20 kg: 0 mg 1x/daily >20 kg: 20 mg 1x/daily LANSOPRAZOLE Adults & children >12 yrs 15 mg/daily for at least 8 wks Pediatric/children 1-11 yrs <10 kg: 7.5 mg 1x daily kg: 15 mg 1x or 2x daily 30 kg: 30 mg 1x or 2x daily Common: Headache, nausea, diarrhea, abdominal pain, fatigue & dizziness Infrequent: Rash, itch, flatulence, constipation, anxiety & depression Some studies have shown possibilities for interference with absorption of iron, calcium, magnesium, and Vitamin B12 PPI use may increase risk of Clostridium difficile infections, especially in hospitalized pts Long-term use of PPIs is strongly associated with the development of benign polyps from fundic glands (which is distinct from fundic gland polyposis) Polyps do not cause cancer and resolve when PPIs are discontinued 6

Initial 8 wk course of topical corticosteroids is the 1 st line pharmacologic EOE tx Proven effective in improving the clinical & histological EOE features Widely

Budesonide (Pulmicort) Medications can induce remission BUT discontinuation of tx often results in symptom & histological recurrence Asthma medications are SWALLOWED,,

minimize pulmonary delivery Swallowed topical corticosteroids can be a tx option alone or in combination with an elimination diet Fluticasone Propionate 1.

Avoid eating or drinking for 30-60 minutes after using the inhaler Budesonide An oral viscous solution or slurry should be created Aqueous budesonide (Pulmicort

7 Initial 8 wk course of topical corticosteroids is the 1 st line pharmacologic EOE tx Proven effective in improving the clinical & histological EOE features Widely studied Can control but not cure EOE Examples include: 1. Fluticasone propionate (Flovent) 2. Budesonide (Pulmicort) Medications can induce remission BUT discontinuation of tx often results in symptom & histological recurrence Asthma medications are SWALLOWED,, NOT inhaled Coat the esophagus lining and provide topical medication delivery Important to instruct pts in the proper technique Optimize esophageal deposition and minimize pulmonary delivery Swallowed topical corticosteroids can be a tx option alone or in combination with an elimination diet Fluticasone Propionate 1. Do not use a spacer 2. Put the inhaler directly into the mouth, puff at end expiration during a breath hold, and then swallow it 3. Avoid eating or drinking for minutes after using the inhaler Budesonide An oral viscous solution or slurry should be created Aqueous budesonide (Pulmicort Respules) 1 mg/2ml mixed with 5 gm of sucralose (Splenda) Avoid eating or drinking for 30 minutes after swallowing slurry Fluticasone Propionate Adults: mcg/day in a divided dose Children: mcg/day in a divided dose Budesonide Adults: 2 mg/day, typically in a divided dose Children: 1 mg/day 7

8 Candidal esophagitis reported in 5-30% of cases Oral candidiasis reported in only approx 1% of cases Regardless of medication formulation, dose, or whether mouth was rinsed after administration Inhaled (not swallowed) doses of fluticasone higher than 440 mcg/day have been associated with systemic side effects Unknown whether the risk of these side effects is reduced when fluticasone is swallowed and undergoes first pass metabolism in the liver Studies have shown NO evidence of adrenal suppression in up to 2 months of topical corticosteroids tx Long-term safety data not yet available for growth rates or bone density Prednisone may be useful to treat EOE if topical steroids are not effective or in pts who require Rapid Improvement of symptoms Severe dysphagia Dehydration Weight loss Esophageal strictures Not recommended for long-term or chronic management of EOE Prednisone: 1-2 mg/kg/day in divided doses (max 60 mg/day) More common side effects: Aggression, anxiety, agitation, blurred vision, dizziness, fast/irregular heart beat, nervousness, mood changes, irritability, headache and increased hunger Warnings/Precautions: Adrenal suppression Immunosuppression Kaposi s sarcoma Myopathy Ocular effects Psychiatric disturbances Examples include: Montelukast (Singulair) and Cromolyn Sodium (Gastrocom) Data on montelukast are mixed In a case series, Cromolyn sodium was used for 4 wks and failed to demonstrate either symptomatic or histologic improvement These medications are NOT recommended in EOE tx Examples include 6-mercaptopurine and azathioprine Case series reported tx of 3 adult pts with immunomodulators Although pts appeared to respond to these medications, symptoms flared after pts stopped Immunomodulators are NOT recommended in EOE tx due to potential side effects, potential toxicity and lack of data 8

Examples include Mepolizumab and Reslizumab Agents are antibodies against IL-5 Studies showed mixed results with above agents Further studies needed to define role in EOE tx Omelizumab Antibody

9 Examples include Mepolizumab and Reslizumab Agents are antibodies against IL-5 Studies showed mixed results with above agents Further studies needed to define role in EOE tx Omelizumab Antibody against immunoglobulin E & not effective in a case series Biological agents at this time are NOT recommended for EOE tx Biological therapies remain experimental & use is currently undergoing clinical investigation OCT is an oral agent that blocks the effects of prostaglandin D2 and showed decrease in eosinophil count New biological agents including antibodies against IL-13, IL-4, 7 eotaxin 3 are being investigated IL-13 a major regulator of the pathways involved in EOE A recently published study indicated after 12 wk course of IV QAX576 given to adult pts with active EOE, the eosinophil load decreased by 60% New topical corticosteroid formulations Viscous budesonide suspension and dissolving fluticasone tablet 9

Eosinophilic Esophagitis (EoE)

Eosinophilic Esophagitis (EoE) 01.06.2016 EoE: immune-mediated disorder food or environmental antigens => Th2 inflammatory response. Key cytokines: IL-4, IL-5, and IL-13 stimulate the production of eotaxin-3