Rita Knotts, MD, on Eosinophilic Esophagitis

Dr Knotts discusses eosinophilic esophagitis (EoE), including the distinguishing characteristics of EoE and gastroesophageal reflux disease and how proton pump inhibitors have transitioned from being used as a diagnostic tool to becoming a treatment for EoE.

 

Rita Knotts, MD, is an assistant professor from NYU-Langone Health Center for Esophageal Health and serves as Section Editor for Gastroenterology Learning Network's Excellence Forum on Esophageal Diseases and Disorders.

 

TRANSCRIPT:

 

Hi, I'm Rita Knotts. I'm an assistant professor at NYU The Center of Esophageal Health. Today, we're going to talk about eosinophilic esophagitis. Eosinophilic esophagitis or EoE is a chronic, local, immune‑mediated esophageal disease. It's characterized mainly by clinical symptoms related to esophageal dysfunction and histologically by an eosinophil‑predominant inflammatory pattern with pathology showing at least 15 eosinophils per high‑power field.

Now, EoE is a distinct entity. It hasn't been around for that long. It was first described in 1993. Earlier guidelines defined it as esophageal dysfunction with the exclusion of other disorders and recommended a therapeutic trial of PPI [proton pump inhibitor for 6 to 8 weeks in an effort to distinguish the distinct entities of GERD and EoE.

Ultimately, this focused mainly on the premise that GERD was the only esophageal disorder that could respond to the acid‑suppressing ability of a PPI and consider GERD and EoE to be mutually exclusive disorders.

Then in 2011 came the introduction of a new disease phenotype, PPI‑responsive esophageal eosinophilia or PPI‑REE. These are patients with EoE features who achieve clinical and histologic remission on PPI therapy and not necessarily associated with GERD.

All iterations of guidelines for EoE have systematically maintained the PPI trial as a diagnostic criterion since PPI‑REE and EoE were considered distinct disorders that had different responses to a PPI trial.

Most recently, since these 2011 guidelines, there's been mounting evidence demonstrating that up to 50% of patients with features of symptomatic EoE have responded to PPI therapy.

This basically calls into question the value of a PPI trial and highlights that PPI‑responsive esophageal eosinophilia and EoE are almost indistinguishable from one another and are different than GERD. In fact, EoE and GERD can actually coexist.

The main change to take note of in these most recent guidelines is the retraction of the term PPI‑responsive esophageal eosinophilia and the consideration of PPI therapy not as a diagnostic criterion for EoE but rather as a therapeutic agent.

Making a diagnosis and managing EoE starts with establishing a diagnosis on endoscopy in patients with suspected EoE. These are patients with esophageal dysfunction and symptoms like regurgitation, vomiting, dysphasia, or heartburn.

Endoscopic findings that you may see include rings, exudates, linear furrows, edema, or strictures. Typically, these are thought of as a part of the EoE endoscopic reference score or the EREF score, which is helpful to report on an endoscopy report because it can also track treatment response.

On histology, we find at least 15 eos on high‑power field, ideally taking 4 biopsies from the proximal and distal esophagus. Remember when you're assessing a patient to consider as they're already on PPI therapy at the time of an endoscopy because this could limit or decrease the yield of your pathologic specimen.

We think EoE progresses from an inflammatory state, which ultimately leads to fibrosis and stenosis. The ultimate goal is to minimize inflammation due to fibrostenotic changes and strictures, which we know have been associated with a longer duration of disease and a delay in diagnosis, particularly in older adults.

When we think of treatment, it's typically thought of as the 3D approach ‑‑ diet, drugs, and dilation ‑‑ with a choice of treatment strategy depending on the disease phenotype, either inflammatory or fibrotic, and patient preference.

Drug therapy can include PPIs, topical steroids ‑‑ it's either budesonide or fluticasone ‑‑ and dietary therapy with an elimination diet. You can also consider dilation.

When we monitor response to chosen therapy, we do this with an upper endoscopy 6 to 8 weeks after treatment has begun. If you're using a PPI, you would typically use omeprazole at 20 to 40 milligrams twice daily or an equivalent, pantoprazole, for PPI for induction. Then it's reasonable to actually consider the minimal effective clinical dose after you reach histologic remission.

With topical steroids, we use fluticasone smaller puffs twice a day. Now, it's important to go through this with the patient because although it comes in an inhaler, it's a swallowed substance. We can also use oral viscous budesonide preparation, which consists of mixing 1 or 2 milligrams of oral viscous budesonide preparation with 5 milligrams of sucralose or something similar.

When you use doses for induction, you can use 2 to 4 milligrams a day in divided doses. Then in maintenance, you can use 1 milligram bid. It's important regardless of which topical steroids that you use that you need to tell people to fast at least 30 to 60 minutes after they take the medication because there's a strong association between esophageal contact time and response to treatment.

Let's talk about dietary therapy. This typically includes a 6‑food elimination diet which excludes milk, meat, eggs, soy, nuts, and fish and seafood. This can produce about a 70% remission rate in adults and children, but it's limited by the large number of endoscopy. It's after each individual reintroduction.

This could be a pretty expensive and arduous process for the patient as every time you reintroduce a new food, you do an endoscopy 6 to 8 weeks later. It's important here to note that milk, meat, and eggs are the most common causative foods found after reintroduction.

Because we know this, it's reasonable to start with a 2‑food elimination diet, eliminating perhaps milk and meat and then stepping it up and reintroducing more foods throughout the process.

A 2‑food elimination diet can actually produce a remission rate of about 40%. This can substantially decrease the number of endoscopies that are needed for each individual reintroduction.

Dilations are really critical in fibrostenotic disease, but they don't affect eosinophil‑induced inflammation, so it should be accompanied by medical therapy in order to diminish esophageal mucosal inflammation.

Now down the pipeline, there are biologic agents that target specific parts of the inflammatory cascade in the esophagus of EoE patients. These include targets like IL‑4, 5, and 13, but they're still underway and they're not the mainstay of therapy yet. Stay tuned. Thank you.