When we think about the optimal approach to managing patients with eosinophilic esophagitis (EoE), an important question arises: what is the most meaningful endpoint for therapy in EoE — is it histologic remission, endoscopic improvement or symptomatic resolution? While there may be some controversy among investigators regarding which endpoint is most important, most will agree that optimal management of EoE targets each of these three areas. Advances in understanding the natural history of EoE has helped support these endpoints of therapy.
EoE is a chronic immune-mediated, food-antigen-driven disease characterized by histologic inflammation and esophageal dysfunction. Several recent studies have better outlined the natural history of this disorder demonstrating that patients with untreated disease develop increased stricture formation over time and that the risk of stricture formation is often proportional to the duration of their disease. These studies suggest that early in the disease process, inflammatory features (exudates, edema and furrows) predominate and, over time, as inflammation persists, fibrosis develops leading to remodeling changes including rings, strictures and a narrow caliber esophagus. The earlier that we intervene, the higher the likelihood of interrupting the disease process and preventing fibrosis and esophageal remodeling.
Therefore, optimal management of this chronic disease encompasses targeting all treatment endpoints: histologic, endoscopic and symptomatic remission. I believe it is important not only to control inflammation and prevent fibrosis, but also make patients feel better by improving their esophageal dysfunction. For instance, if after treatment, a patient has achieved histologic remission but they still have a narrow caliber esophagus with an esophageal diameter of 12mm, they are likely to have dysphagia and therefore treatment has not been optimized. On the other hand, if a patient feels better after therapy, but endoscopy shows evidence of histologic inflammation, knowing that esophageal inflammation and eosinophil activation contributes to the remodeling and fibrosis, optimal therapy has not yet been achieved. The treatment endpoints that I aim for are the following: histologic remission as defined by 16mm, and improvement of patient’s dysphagia symptoms so that they are eating more naturally without food avoidance or modification. In achieving these targets, we hope to prevent disease complications including stricture formation, food impactions and esophageal perforation.
Optimal management of this chronic disease encompasses targeting all treatment endpoints: histologic, endoscopic and symptomatic remission.
When discussing therapy with patients, I review the pros and cons of all available medical and dietary therapy approaches. If they choose medical therapy, we discuss the various available formulations of swallowed topical corticosteroids, but the decision on which to use tends to be determined in large part by which formulation is covered by the patient’s insurance. If choosing oral viscous budesonide (OVB), I typically start with 1mg swallowed twice daily for at least eight to 12 weeks prior to endoscopy. If the patient has achieved remission based on the above parameters, then at this point, I will taper dosing down to 1mg OVB at bedtime or 1mg OVB alternating with 0.5mg OVB. I would continue on this regimen for maintenance. Prior studies have shown that dosing below 0.5 mg is not enough to maintain histologic remission. If choosing fluticasone 220ug inhaler, based on the severity of the disease, I would recommend starting with two to four puffs swallowed twice daily. Another option is to swallow the fluticasone diskus powder. This method has been described in small case reports and abstracts. Dosing for this approach is 500-1000mg twice daily. With either fluticasone preparation, I would use the higher dose for eight to 12 weeks followed by endoscopy. If remission is achieved, then I would suggest tapering down to one to two doses of the inhaler at night. Typically when using topical corticosteroid formulations, patients are instructed to rinse/gargle their mouth after use and to not eat or drink for 30 minutes after use. There have been some recent case reports of adrenal suppression in children on long-term swallowed topical corticosteroids for EoE. Other rare side effects of chronic inhaler use include osteoporosis. Due to these concerns, I will check some routine safety labs on patients taking maintenance topical corticosteroids. These include yearly cortisol and Adrenocorticotropic hormone (ACTH) blood tests as well as a baseline bone densitometry and a follow up bone densitometry a year later.
If patients choose a dietary approach, there are various options to pursue (elemental diet, allergy testing directed diet, empiric elimination diet), but the most practical and favored approach is the empiric elimination diet. The six-food elimination diet (elimination of milk, wheat, soy, egg, nuts, seafood) has been the longest studied, but newer approaches have also been used with slightly decreased efficacy. These include the four-food elimination diet (milk, wheat, soy, egg), the two-food elimination diet (milk, wheat), or the single-food elimination diet (typically milk). When embarking on a dietary approach, the goal is not to eliminate all the food allergens indefinitely but rather to assess if patients can achieve remission and, if they do, reintroduce foods to identify the trigger foods. Once triggers are identified, patients can eliminate these food(s) as part of their treatment plan and resume a less restricted diet.
The approach I typically use is the six-food elimination diet because it has the greatest effectiveness and requires patients to be on the strictest diet for a shorter duration. We would then reintroduce foods back in the order of least likely culprits to most likely culprits (seafood ->nuts->egg->soy->wheat->milk) to help streamline the reintroduction process and get through it most quickly. I will also discuss the option of a four-food elimination diet and this is a good fit for those patients who may not routinely be taking in nuts or seafood. While there is some recent data on a step-wise approach to dietary elimination (eliminating two foods at a time for six weeks and then continuing to eliminate more foods progressively), we have not had remarkable success on the few patients who have undergone this approach. If patients have a significant history of intolerance to one of the foods (such as milk allergy as a child), this may be a person that would benefit from a single-food elimination diet.
It is important to note that there have been no head-to-head studies comparing dietary elimination with medical therapy so it is difficult to answer the question if either therapy is better. It should therefore be based both on patient preference as well as available local resources. If patients are motivated to try and identify food triggers as a cause for their EoE with a goal of ultimately avoiding the trigger food, then dietary therapy would be a good first choice. If however, a patient’s travel and/or work schedule would make it difficult for them to adhere to a strict diet, we would typically table this approach and pursue medical therapy until a more convenient time. Patients who are not interested in ultimate adjustment of their diet would be counseled to embark on medical therapy. No matter which therapy is chosen, clinical care has focused now on maintenance therapy given the chronicity of the disease. Periodic surveillance endoscopy may be pursued to assure continued remission and this may become easier for patients in the future with development of non-invasive assessments of the esophagus. Despite the fact that EoE is a chronic disease, there are well-established and effective treatments which can achieve histologic, endoscopic and symptomatic remission all with the aim of preventing long-term complications of the disease, ultimately improving the quality of life of our patients.
Dr. Gonsalves has no conflict conflicts to disclose.