Features


eoe_sx.png
Eoe_sxs_table.png
Clinical features
  • Presentation
    • Varies with age
      • Pediatric - M:F 3:1, 2/3 have other atopic diseases (food allergy, asthma, AD, AR)
        • Infants and toddlers - often presentEoE_sx_progression.png with feeding difficulties, FTT
        • School-aged children - more likely to present with vomiting or pain
        • Adolescents - food impaction, dysphagia is predominant symptom in adolescents
      • Adult - solid food dysphagia (most common), chest pain, food impaction, upper abdominal pain
    • Symptoms may be concealed by coping mechanisms and difficult to obtain by superficial history
    • Intermittent or daily symptoms
    • Unresponsive to acid blockade, pH probe typically normal


Eoe sxs.png
  • Complications of EoE
    • Food impaction - food retention requiring endoscopic removal in 30-55% of adults with EoE
    • Esophageal stricture - 11-31% of adults with EoE
    • Narrow-caliber esophagus - essentially a stricture involving majority of esophagus, reported to affect up to 10% of adults with EoE
    • Esophageal perforation - may occur spontaneously or due to endoscopic trauma, uncommon

  • Exclusion of other diseases that can cause esophageal eosinophilia:
    • GERD - 5-10% of pediatric patients and 6% of adults with poorly controlled GERD are thought to have EoE
    • PPI-responsive esophageal eosinophilia
      • This may include GERD vs. primary EoE that responds to a PPI (via an unknown mechanism)
    • Eosinophilic gastroenteritis or colitis - may present with abdominal pain, vomiting, diarrhea, FTT, generally sicker than EoE and have >20 eosinophils/hpf in more than one area of the intestine (typically the gastric antrum)
    • Celiac disease
    • Crohn disease
    • Infection (viral, candidal, parasitic)
    • Hypereosinophilic syndrome
    • Achalasia
    • Drug hypersensitivity
    • Vasculitis
    • Pemphigoid vegetans
    • Connective tissue disease
    • GVHD
Histologic features
  • Esophageal biopsy with ≥15 eosinophils/hpf on at least 1 specimen
    • Biopsy performed 8 weeks after PPI to help exclude GERD
    • Normal values: esophagus 0 eos/hpf (1-5 with GER), gastric antrum 10, duodenum 20, colon 10-20

  • Other gross and histologic signs of eosinophilic inflammation:gross histologic signs.png
    • Eosinophil microabscess formation
    • Extracellular eosinophil granules
    • Basal zone hyperplasia
    • Dilated intercellular spaces
    • Mastocytosis and mast cell degranulation
    • Mucosal eosinophilia
    • Superficial layering of eosinophils
    • Epithelial desquamation
    • Rete peg elongation
    • Subepithelial fibrosis/sclerosis–lamina propria fibrosis
    • CD81 lymphocytes and B cells

  • Note that eosinophil-predominant inflammation, often with many more than 15 eosinophils/hpf, associated with abscesses, surface layering, epithelial hyperplasia, etc is highly characteristic but not pathognomonic of EoE
Endoscopic features
  • Longitudinal narrowing (small or narrow-caliber esophagus)
  • White exudates
  • Fixed esophageal rings (corrugated rings or trachealization)
  • Isolated stricture (proximal or distal)
  • Longitudinal shearing (crepe paper esophagus)
  • Linear furrows or vertical lines
  • Transient esophageal rings (feline folds or felinization)
peds_vs_adult_eoe.png



DiagnosisEoE_summary_table.png

  • History - focus on eating and swallowing habits
  • Biopsy:
    • Can be patchy disease therefore at least 2-4 specimens from the proximal and distal esophagus should be obtained (more specimens increases sensitivity). Specimens of the gastric antrum and duodenum should also be obtained to exclude other potential causes of esophageal eosinophilia.
    • Biopsy performed 8 weeks after PPI to help exclude GERD
      • Consider adding a nasal steroid to PPI because allergic rhinitis may also cause esophageal eosinophilia (Spergel)
      • GERD typically has 0-5 eos/hpf, but levels up to 60 eos/hpf can occur
    • Some with EoE may have <15 eos/hpf but have strong clinical history and other histologic features indicative of eosinophilic inflammation
    • Other diseases including GERD can have ≥15 eos/hpf; EoE is a clinicopathologic diagnosis, histopathology must be interpreted in the clinical context
    • EoE vs. GERD (Collins)
      • Biopsies from patients on empiric GERD therapy (with or without empiric EoE therapy) that show the characteristic histopathology of EoE fulfill the criteria for a diagnosis of EoE
      • Biopsies from patients on empiric GERD therapy + EoE therapy that do not show eosinophil-predominant inflammation could represent either GERD or EoE. Repeat biopsy after discontinuing EoE therapy may be required
      • Additional helpful data in questionable cases of EoE (but difficult to obtain in non-research center):
        • Extracellular deposits of eosinophil granule contents may be extensive even in biopsies with few intact eosinophils, and may identify EoE in questionable cases
        • The number of mast cells is increased in EoE compared to GERD
        • IgE-positive cells are found in EoE biopsies but few if any are present in GERD
        • Numerous genes upregulated in EoE, with confirmed increased mRNA and protein expression, including eotaxin-3, periostin and TSLP. Down-regulated genes include filaggrin and involucrin that are essential for epithelial barrier integrity.
        • IL-5 gene expression (determined by mRNA) is detected only in EoE
    • EoE vs. eosinophilic gastroenteritis/colitis (Collins): Numerous eosinophils without signs of epithelial invasion or chronic changes is referred to as mucosal eosinophilia, and biopsies that show eosinophil-predominant inflammation associated with infiltration and damage are diagnosed as eosinophilic gastritis or enteritis or colitis. The presence of any acute inflammatory cells raises the possibility of idiopathic IBD.

  • EoE gene expression profiling from biopsy sample - very high specificity/sensitivity in detecting active EoE (vs. GERD and EoE in remission)
  • Barium contrast radiography - can identify anatomic and mucosal abnormalities to support diagnosis and find complications of EoE (e.g. strictures)
  • Esophageal pH monitoring (and pH impedance, where available) - useful to evaluate GERD in patients with esophageal eosinophilia
  • Impedance planimetry - measures esophageal distensibility; lower distensibility may predict future impactions and need for dilation better than eos/hpf

  • Food allergy testing to foods in diet - may identify associated foods. Note that sensitization to foods very common in EoE, and 15-43% may have type-I immediate reaction to food
    • SPT, serum specific IgE
      • SPT usually preferred
      • Some recommend SPT with fresh foods (e.g. milk, egg white, and fresh foods used to prepare atopy patch tests) for best sensitivity
    • Atopy patch testing (APT) - delayed hypersensitivity skin test
    • Combination (SPT+APT) testing in pediatric patients:
      • NPV 88-100% for all foods (except 41% for millk)
      • PPV >74% for the most common foods (milk, egg, and soy), lower PPV as the food became a less commonly known cause of EoE
      • It is up to the physician to determine whether to patch test for foods that are positive on skin testing
    • Most common foods associated with EoE in children: milk, egg, wheat, soy, corn, beef, chicken, peanut, potato, rice
    • In a group of 36 children responsive to an empiric 6 food elimination diet, serial biopsies after food introductions showed that the most common causative allergen was milk (74%), wheat (26%), egg (17%), soy (10%), peanut (6%) , and seafood (0%). A single causative food allergen was identified 72%, 2 foods in 8%, and 3 foods in 8%.
  • Aeroallergen testing - sensitization very common in EoE
    • Diagnoses of EoE increase during allergy seasons which suggesting a possible role for aeroallergens in EoE. In experimental models, dust mite, cockroach and molds induced esophageal eosinophilia.
    • Case reports of patients with AR and exacerbations of EoE correlating with pollen season
  • Blood eosinophil count - eosinophils >300-350/mm3 reported in up to 50% of EoE, may decrease with treatment



Treatment


Medical Therapy

  • Proton pump inhibitors - empiric treatment may help eliminate GERD and PPI-responsive esophageal eosinophilia as a cause of eosinophilia. Also useful for treating EoE with comorbid GERD. Unclear whether beneficial effect is entirely due to acid blockade in some patients.
    • Dose:
      • Adult: depending on patient and chosen PPI, 20-40 mg QD or BID for 8-12 weeks
      • Pediatric: 1 mg/kg/dose BID for 8 to 12 weeks (for maximal dosing use adult recommendations)

  • Corticosteroids - improve the clinicopathologic features of EoE in most EoE_steroid_doses.png
    patients but disease almost always recurs when discontinued, and optimal treatment duration and long term safety is unknown for swallowing steroid medications intended for asthma
    • Topical - should be considered in all patients with EoE (children and adults) for both initial and maintenance therapy. Thrush common (up to 10% of adults, 20% of children)
      • Viscous suspension of budesonide = pulmicort respule 0.5 mg + 5 packets of splenda, or 2 x 0.5 mg respules + 10 packets splenda or applesauce
      • There are no established protocols for maintenance dosing of fluticasone, however decreasing budesonide dose can lead to relapse
      • No eating or drinking 30-60 minutes after swallowing
      • Ciclesonide 80-160 mcg 2 puffs swallowed BID reported to be effective with lower systemic bioavailability
    • Systemic - reserved for emergency cases (e.g. severe dysphagia, hospitalization, and weight loss), can induce remission at 1-2 mg/Kg with relapse after discontinuation
  • Mepolizumab (Bosatria) - anti-IL-5 antibody, small studies demonstrated a significant decrease in esophageal eosinophilia and improvement in esophageal remodeling but clinical response was variable. Currently not recommended for EoE but more studies are pending.
  • Other allergic diseases (asthma, AD, rhinits, etc.) should be treated maximally
  • Esophageal dilation - used for strictures caused by EoE, can provide immediate and long-lasting relief of dysphagia in patients with high-grade esophageal strictures, but there is a small risk of perforation, and monotherapy of EoE with frequent dilatation does not address the underlying cause.


Dietary Therapy

  • Elimination of food protein antigens causing EoE effective in children, leads to near-complete resolution of both clinical and histologic abnormalities. May be effective in motivated and adherent adults as well. Tolerance to foods causing EoE unlikely to develop therefore diet may need to be continued indefinitely.
  • Dietary regimens:
    • Strict elemental amino acid–based formula diet (almost always effective if adherent)
    • Elimination diets
      • Elimination diet based on empirically eliminating the most common food allergens (e.g. "6 food" elimination diet: milk, soy, peanut, egg, wheat, seafood)
        • In a group of 36 children responsive to an empiric 6 food elimination diet, serial biopsies after food introductions showed that the most common causative allergen was milk (74%), wheat (26%), egg (17%), soy (10%), peanut (6%) , and seafood (0%). A single causative food allergen was identified 72%, 2 foods in 8%, and 3 foods in 8%.
      • Elimination diet based on allergy testing (i.e., eliminate all foods positive on SPT and APT)
        • Milk should also be avoided, even if milk SPT and/or APT are negative, as these tests seem to have a poor NPV for milk, and milk is reported to be the most common cause of EoE
          • Limited data suggests that a subset of patients with cow's milk-mediated EoE may tolerate baked cow's milk, but SPT/sIgE/APT are not useful for predicting which patients will tolerate it
        • If no foods identified by testing, proceed to elemental amino-acid based diet or 6 food elimination diet
      • Holbreich: for adults, a 2 food (cow's milk, wheat/gluten) or 4 food (cow's milk, wheat/gluten, soy, egg) may be easier to adhere to and may be effective
  • Consultation with a registered dietitian is strongly encouraged to ensure that proper calories, vitamins, and micronutrients are maintained
Dietary EoE tx.png

Disease Monitoring
  • Definition of remission or successful treatment is not agreed upon and varies between <2-15 eos/hpf and resolution of symptoms
  • Optimal biopsy interval is unclear
    • Consider repeat biopsy 8-12 weeks after elimination diet; if normal, then an eliminated food was causative, if remained abnormal, proceed to elemental diet x 8-12 weeks with follow-up biopsy
    • Reassuring to see a marked drop in eosinophils even if level remains >15 eos/hpf
    • Note that there may be discordance between symptoms and histologic changes, therefore symptom response alone is an insufficient marker of disease remission
  • No known association with malignancy directly from the presence of EoE

Food Reintroduction

Summary EoE Management Algorithm
Summary EoE algo.png


References