Thanks for following along with the diagnosis and treatment of eosinophilic esophagitis (EoE)–a condition that during my fellowship training in allergy wasn’t even recognized as a cause of abdominal pain.
Treatment options for EoE are currently:
- Corticosteroids–both oral and inhaled
- Dietary avoidance of known allergic triggers, including but not limited to foods
- Use of PPIs such as Nexium & Protonix
- Treatment principles focus on reducing symptoms and eosinophil counts while, importantly, protecting and preserving quality of life.
- Maintaining diet and nutrition which is harder than it looks! Don’t forget that restoring growth parameters are also essential for adults as well as in children.
As with all diseases, treatment is updated constantly, and new recommendations emerge. As with many inflammatory conditions, steroids work great, but are NOT less filling. Side effects from steroids are many and any time an alternative is successful, you’re better off. Remember, topical steroids are fine, it’s the oral systemic absorption of steroids that contributes to the side effect profile.
Due to the long-term side effects associated with high dose corticosteroids and a tendency for relapse after discontinuation, this therapy is not first-line outside of using short bursts and tapers for severe symptoms needing urgent relief (eg, critical dysphagia, stricture, dehydration and acute weight loss.
Topical corticosteroid are used in EoE through 1 of 2 routes:
- “Gulping” the expressed actuations of an inhaled device; or
- Expressing the contents of a nebulizer respule into a cup, forming a thickened slurry by mixing it with sucralose/maltodextrose (Splenda®), and water.
Use in this manner provides “local” or tailored coating of esophageal tissue, at lower doses (220 μg-1 mg per dose). Faubion and colleagues demonstrated that 880 μg/day of swallowed fluticasone propionate or beclomethasone diproprionate resulted in symptomatic improvement in 4/4 pediatric patients Noel and group at the Cincinnati Children’s Medical Center, noted that non-atopic patients had a better response rate to the topical steroid than the atopic patients. A randomized, controlled trial by Konikoff and colleagues confirmed similar findings independent of pre-treatment eosinophil numbers.
Oral viscous budesonide (OVB) is quickly becoming the preferred therapy to fluticasone. The technique of swallowing a liquid dose may be more effective and efficient than “gulping” a hydrofluroalkane gaseous suspension. Additionally, OVB has comparable efficacy. One study found an 80% decrease in a symptom scoring index and regression of cell counts to less than 7 Eos/HPF; after 3 months of therapy there was decreased fibrosis/remodeling from baseline.
Dosing for fluticasone ranges from 220 to 880 μg per day, and for budesonide, from 0.5 to 2 mg per day; both doses are similar to those used in asthma. With either agent, patients are instructed to not eat or drink for 30 minutes after administration. Complications from topical treatment include oral/esophageal candidiasis. In a 3-year case series studying recurrence, approximately 90% of adults relapsed at a mean of 8 months post discontinuation of 6 weeks of therapy. Just like asthma, when you stop using the controller medication, symptoms will come back. No study of optimal dose or duration of therapy has been performed, but most adult providers recommend a 6-week course while pediatric providers suggest a 12-week course. No long-term safety data exist pertaining to bone or adrenal effects from such small but more readily bioavailable dosing methods used in EoE.
Technically, EoE should not be diagnosed until response to PPI therapy has been determined, according to the 2007 and 2011 consensus guidelines. A certain subset of patients will have PPI-responsive esophageal eosinophilia. Typically, dosing is either 10-40 mg omeprazole or 15-30 mg lansoprazole per dose for 2-3 months. High-dose PPI therapy may distinguish GERD from EoE.
Immunomodulating therapies may offer some promise. The best studied therapy is anti-IL-5. In mice, anti-IL-5 decreases blood and tissue eosinophils, and decreases eotaxin-3 levels. Garret and fellow researchers studied anti-IL-5 in 4 patients with hypereosinophilic syndrome. Symptoms and eosinophilia resolved, and in 1 patient who also had EoE, dysphagia and esophageal eosinophils decreased. Stein and colleagues, in an open-label phase I study of anti-IL-5, noted that blood eosinophilia was reduced but not correlated to decreased levels of IL-5, eotaxin-3, or esophageal eosinophilia. Similarly, there was no significant difference between groups in symptom improvement. Studies of other agents, such as anti-IgE or anti-TNF (infliximab), failed to demonstrate any symptomatic or esophageal histologic improvement. Presently, anti-IL-3 is under investigation in a phase 1 trial, but no data are available pertaining to its safety or efficacy.
Dilation relieves critical esophageal narrowing and related symptoms, but will not alter the underlying pathophysiology. Its benefit is maximized for dysphagia and impaction from ring/stricture or other critical narrowing. Several studies have demonstrated the efficacy of dilation, though it is balanced by risks including perforation, deep mucosal tears, pain, linear renting, and bacteremia. Relief is also likely to be transient, because 75%-50% of patients who receive this therapy have recurrence at 2-20 months and need additional dilation.
A 6-week trial of 10 patients conducted by Kellyand colleagues in 1995 demonstrated the role of an exclusively elemental diet. At the conclusion of the study, 8/10 had complete histologic and symptomatic resolution and the other 2 subjects showed drastic improvement, demonstrating an elemental diet as a potential treatment. As with steroid therapy, however, upon discontinuation, all patients relapsed. A larger study of elemental diet therapy in 51 patients was conducted by Markowitz and colleagues. The researchers noted symptomatic response by 8 days and normalization in biopsy by 1 month in 49 of the patients studied. Liacouras and colleagues followed 389 patients with EoE over 10 years, 160 whom were treated with elemental diet and noted a 97% response rate to the diet and biopsy counts that were comparatively lower than 75 patients on swallowed fluticasone. Though exceptionally effective, elemental therapy is limited in that a patient’s only source of nutrition is a very specific hypoallergenic formula. This may not be appropriate for adolescents or adults. Some cases require placement of gastrostomy tube to assist with feeding.
An alternative approach is a tailored/guided diet that avoids only an individual’s known food sensitizations based on skin prick and/or patch testing. Spergel and colleagues described 120 patients placed on a guided elimination diet based on allergen testing. After 6-8 weeks, 112 had near complete tissue resolution, though 39 relapsed upon reintroducing eliminated foods. In this cohort, 77% had at least 1 positive prick skin test, and 85% had 1 positive atopy patch test. Prick skin tests were most commonly positive to milk, egg, soy, and peanut. The foods that were most commonly positive to atopy patch test were corn, soy, wheat, and milk. Most patients were sensitized to multiple foods, and dietary nonresponders had more sensitizations than responders. Positive predictive value and negative predictive value for 13 commonly positive foods in EoE were published in a previous post.
Follow-up of patients with EoE should be frequent, at least 4 times per year, with consideration for repeat endoscopy at those intervals as well. Repeat endoscopy is the only way to monitor disease progress, because symptoms do not always correlate with disease progression. One pediatric study found that an initial cell count of 6 or greater was predictive of a repeat positive biopsy.
At each follow-up visit, diet should be reviewed, diet/medication compliance assessed, and consideration given for additional food testing if symptoms or histology are not improving. As noted previously, there are no studies that have evaluated adequate or optimal duration of treatment for either dietary avoidance or topical steroid duration. Very little formal guidance is available to determine key long term predictors of disease resolution, the optimal interval for repeat biopsy, and the effect of these factors on the development of long term sequelae.
Complications from EoE include:
- Schatzki ring
- Esophageal trachealization and stretching,
- Esophageal furrowing and narrowing, microabscesses, webbing,
- Food impaction, persistent/progressive dysphagia, and lamina propria fibrosis.
Esophageal remodeling in EoE occurs as a result of subepithelial fibrosis and is reported in 15%-40% of affected adults. Predictors that influence the likelihood of developing fibrosis are presently unknown. To date, there is no identified association with progression to malignancy directly from the presence of EoE. Some have observed a potential link between celiac disease and EoE, which may share some common gene upregulations with EoE, but this association is not well understood.
The natural history of food allergy/sensitization within EoE has not been well-described. Lastly, while preliminary work and observation indicates that quality of life can be affected significantly, little formal study of EoE quality of life exists. This particular area of research is very important to continue to define, as the quality of life issues that affected families face are distinct from those of the general food allergy community.