Banking on New Eosinophilic Esophagitis (EoE) Treatments

In the bank scene of Mary Poppins, Mr. Dawes Sr. tried to instill good financial sense into Michael Banks by taking his tuppence for investment in the Fidelity Fiduciary Bank. His efforts, however, failed, and young Michael clamored to get his money back. As he yelled, “Give me back my money,” patrons in the main lobby of the bank overheard and, thinking the bank wasn’t giving people their money back, started a bank run on Fidelity Fiduciary. Depositors yelled and frantically withdrew all they could until the bank managers refused to release any more funds, causing more panic, uncertainty, and loss of faith in the institution. This was fictional, but it mirrors real-life bank runs such as with the Birkbeck Bank in 1910 and, to a degree, what happens in the throat during eosinophilic esophagitis (EoE).

Eosinophilic esophagitis is an immune-mediated disease that affects at least 150,000 Americans, causing symptoms such as vomiting, difficulty eating, and swallowing difficulties.^[1,2] EoE, at a fundamental level, is when the immune system misidentifies food particles as allergens and starts panicking.^[2,3] Incidence of eosinophilic esophagitis is rising in America, though it remains hard to diagnose, and most people don’t get a proper diagnosis until four to eight years after onset.^[1] Unfortunately, just like an unpaid loan, untreated EoE gets worse over time.

The esophagus is the tube that connects the throat to the stomach. The tube is lined with mucus and a barrier of special cells called epithelial cells, collectively known as the epithelium. Normally, this epithelial barrier, which is several cells thick, is composed almost exclusively of epithelial cells.^[4] People who suffer from EoE have a combination of genetic factors, environmental factors, and a predisposition to extra inflammation in the body - including extra TSLP (see below).^[1] For these people, the barrier is slightly permeable and some food particles get through and cause disruption; they are like Michael Banks yelling for his money back.^[3] The epithelial cells release a chemical called thymic stromal lymphopoietin (TSLP), which is like the patrons in the lobby screaming and panic-withdrawing all of their money immediately.^[3] TSLP is a type of chemical called an “alarmin,” and boy does it earn its name. TSLP activates and recruits immune cells, causes the release of chemical signals that initiate a feedforward loop to amplify its own signal, and even leads to changes in the transcription of DNA into proteins.^[3,5]

Two important effects TSLP has on the esophagus are the training of T Helper cells and the recruitment of eosinophils into the epithelium.^[3] T Helper cells are memory immune cells, and TSLP trains them to recognize food as dangerous, which gives EoE its lasting quality. Eosinophils are the major inflammatory cells present in eosinophilic esophagitis. The epithelium normally has no eosinophils in it, so this change is severe and dramatic.^[4] The inflammation from eosinophils damages the epithelial barrier, the mucous covering it, and can cause fibrosis in and behind the epithelium.^[1]

Treating EoE can be difficult. Since EoE is a response to food, elimination diets - where potentially aggravating foods are removed from the diet - are typically used.^[4] Elimination diets can range from removing only a few problematic foods to almost everything. A skin-prick allergy test has limited predictive value, but may find precisely which foods are most likely to cause an “allergic” response with EoE.^[4] Most people find relief from removing the big six allergens:^[4,1]

• Soy
• Egg
• Milk
• Wheat
• Nuts and peanuts
• Seafood, including fish and shellfish

Finally, an elemental diet is an extreme, kinda gross, but highly effective elimination diet option.^[1] Elemental diets reduce all foods to their most basic, nutritional components, eliminating allergens, flavor, and the need for digestion. If an elimination diet doesn’t provide relief, patients may opt for a medical solution. Topical corticosteroids and proton pump inhibitors (PPIs) are effective first-line medications for some patients.^[1,4] Topical corticosteroids suppress inflammation and immune response, so they may be effective but can lead to increased infections. Proton pump inhibitors lower stomach acid, so they are typically only useful in EoE that is mediated by acid reflux. New biologic medications target specific parts of the inflammation pathway and may have similar anti-inflammatory properties as corticosteroids with fewer side effects. On top of this, clinical trials are underway to investigate the possibility of targeting TSLP and preventing EoE from getting out of control in the first place. With the help of clinical trials, medicine will continue to progress, and you can bank on that.

Creative Director Benton Lowey-Ball, BS, BFA

References:

[1] Muir, A., & Falk, G. W. (2021). Eosinophilic esophagitis: a review. Jama, 326(13), 1310-1318. https://pmc.ncbi.nlm.nih.gov/articles/PMC9045493/

[2] Nurko, S., & Furuta, G. T. (2006). Eosinophilic esophagitis. GI Motility online. https://www.nature.com/gimo/contents/pt1/full/gimo49.html

[3] Rochman, Y., Kotliar, M., Ben-Baruch Morgenstern, N., Barski, A., Wen, T., & Rothenberg, M. E. (2023). TSLP shapes the pathogenic responses of memory CD4+ T cells in eosinophilic esophagitis. Science signaling, 16(802). https://pmc.ncbi.nlm.nih.gov/articles/PMC10602003/

[4] Dellon, E. S., Gonsalves, N., Hirano, I., Furuta, G. T., Liacouras, C. A., & Katzka, D. A. (2013). ACG clinical guideline: evidenced based approach to the diagnosis and management of esophageal eosinophilia and eosinophilic esophagitis (EoE). American Journal of Gastroenterology, 108(5), 679-692. https://journals.lww.com/ajg/fulltext/2013/05000/ACG_Clinical_Guideline__Evidenced_Based_Approach.10.aspx?context=FeaturedArticles&collectionId=2