Eosinophilic Esophagitis (EoE)

Joanna Yeh

Peds GI Case Conference

April 2012

Objectives

• Review findings from the First International Gastrointestinal Eosinophilic Research Symposium (FIGERS) from 2007 (EoE consensus recommendations)

• Review literature to find updates on consensus recommendations on EoE since 2007

In 1977, the first report of eosinophilic inflammation of the esophageal

epithelium in an adult with dysphagia and no GERD symptoms was published.

2007 Definition

• Clinicopathological disease characterized by: 1. Symptoms related to esophageal dysfunction

(i.e. dysphagia, GERD type symptoms, feeding intolerance, FTT)

2. Greater than 15 eosinophils per high power field

3. Lack of responsiveness to high dose PPI (2mg/kg/day x 8 weeks) OR normal pH monitoring*

*new description of patients: PPI responsive EoE

DDx of Esophageal Eosinophilia

• Gastroesophageal reflux disease • Eosinophilic esophagitis • Eosinophilic gastroenteritis • Crohn’s disease • Connective tissue disease • Hypereosinophilic syndrome • Achalasia • Vasculitis • GVHD • Infection • Drug hypersensitivity response

Epidemiology

• Males > Females (3:1)

• 16 studies identified 754 pediatric patients with EoE (66% male, mean age was 8.6 years, range was 0.5 to 21.1 years)

• All continents, ?except Africa, predominance in non-Hispanic whites

• Incidence 1:10,000 children per year

• Unclear genetics (eotaxin-3, TSLP)

Clinical Manifestations

• Feeding aversion or intolerance • Vomiting or regurgitation • “GERD refractory to medical or surgical

treatment” • Food impaction or foreign body impaction • Epigastric abdominal pain • Dysphagia or difficulty swallowing • Failure to thrive • (Chest pain) • (Diarrhea)

Endoscopic Features

Concentric rings Trachealization

Feline esophagus

White exudates White specks

Nodules Granularity

Linear furrowing Vertical lines of the esophageal mucosa Linear shearing/”crepe paper mucosa” with passage of endoscope

Schatzki ring

But…

In a study of 381 children with EoE, 30% had a normal appearing esophagus

during endoscopy.

Endoscopy Caveats

• 1 biopsy specimen total (sensitivity 55%) • 3 biopsy specimens total (sensitivity 97%) • 5 biopsy specimens total (sensitivity 100%) • Multiple biopsies obtained along the length of

the esophagus (upper, mid, lower) • Minimum: 2 from distal, 2 from mid • Stomach and duodenum to r/o eosinophilic

gastroenteritis and IBD • Fix with formalin or paraformaldehyde (not

Bouin’s preservative)

Other workup considerations

• Of 223 children, pH probe was performed in 173 patients and 90% of these patients had normal pH probe

• 14 children in the literatures had normal esophageal manometry

• Upper GI for strictures may not correlate with endoscopy

Histopathology

Basal zone hyperplasia Superficial layering of eosinophils

Eosinophlic microabscess

Allergic Component

The majority of patients with EoE (50-80%) is atopic. This is based on the coexistence of atopic dermatitis, allergic rhinitis, and/or asthma and the presence of allergic antigen sensitization

based on skin prick testing or measurement of plasma antigen-specific IgE.

Blood work

• 20-100% of children had elevated peripheral eosinophil counts (usually modest, <2 fold)

• 71-78% of pediatric EoE patients had elevated total IgE levels

• Others: IL5, IL13, IL15, eotaxin-3, basic fibroblast growth factor, antigen-specific T-cell subsets

Treatment

• Systemic corticosteroids

– 1-2 mg/kg/day, max 60 mg

– Useful when urgent sx relief is needed (severe dysphagia, significant weight loss, strictures)

– Clinical sx improve within 7 days, histology improves within 4 weeks

– Discontinuation usually leads to recurrence of symptoms

Treatment

• Topical steroids – 1998 – Swallowed fluticasone propionate (220-440 ug bid) or

beclomethasone x 6-12 weeks – Slurry of oral viscous budesonide (OVB 1-2mg daily) ->

younger children who can’t use inhaler – Esophageal candidiasis – Should not eat or drink for at least 30 min

• Cromolyn doesn’t help • Leukotriene receptor antagonist (i.e. Singulair)

helps symptoms but not histology

Treatment

• Dietary – Use of amino acid based formula is currently the gold

standard (in children, extremely effective in 92-98% of patients), sx resolve within 7-10 days! Histologic resolution in 4-5 weeks.

– 6 most common allergenic foods • Dairy, eggs, wheat, soy, peanuts, fish/shellfish

• SFED = 6 food elimination diet

• 2011 article: milk, wheat, eggs most common!

• Biologics (being studied) – Anti-IL5 antibody, anti-eotaxin-3 antibody

Natural History: A Chronic, Relapsing Disease

• In adults, followed up to 12 years, majority of patients showed evidence of tissue remodeling at endoscopy. Rings, strictures, or small caliber esophagus was found in 86% of patients.

• A study in 381 children, upper GI showed narrowing in 6%, endoscopy showed rings in 12%, 1 required dilation.

• Does not appear to limit life expectancy.

• Not associated with metaplasia (i.e. Barrett’s -> adenocarcinoma).

Summary

• EoE is a clinicopathologic disease isolated to the esophagus

• It represents a chronic, immune/antigen-mediated disease

• With few exceptions, 15 eos/hpf is considered minimum threshold for diagnosis

• Endoscopy with biopsy is the only reliable diagnostic test

• Allergy evaluation is warranted in EoE patients • Disease should remit with dietary exclusion,

topical corticosteroids, or both

References

• Furuta, et al, “Eosinophilic Esophagitis in Children and Adults: A Systemic Review and Consensus Recommendations for Diagnosis and Treatment,” Gastroenterology, 2007.

• Heine, et al, “Emerging management concepts for eosinophilic esophagitis in children,” Journal of Gastroenterology and Hepatology, April 2011.

• Liacouras, et al, “EoE: Updated consensus recommendations for children and adults,” Journal of Allergy and Clinical Immunology, July 2011.