Daniel Addoquaye
Eosinophilic Esophagitis or as it is more commonly known as EoE, is a chronic condition that affects the esophagus and causes inflammation due to a buildup of eosinophils, a type of white blood cell, in the lining of the esophagus. Patients with EoE often report symptoms such as food impaction, chest pain, abdominal pain, vomiting, and in children, stunted growth or poor weight gain. EoE can occur at any age, however a majority of cases are in adolescents and adults under fifty. There is a male predominance, with men being affected three to four times as many times as females. Additionally, EoE is also more frequently reported in White populations compared with other races/ethnicities and there is a strong association with atopic diseases. The prevalence is currently estimated at 0.5–1 in 1000, and EoE is now the most common cause of food impaction. The incidence of EoE is approximately 1/10,000 new cases per year, and the rise in incidence is outdoing increases in recognition and endoscopy volume. Scientists are currently developing new epidemiologic techniques to estimate the incidence and prevalence of EoE. These efforts provide insights into trends in the number of cases and the overall impact of EoE as a health concern.
Researchers have identified two rare gene variants associated with inherited forms of EoE. The roles played by variants of the genes desmoplakin (DSP) and periplakin (PPL) were published in Nature Communications on November 23, 2021. The study, led by Tetsuo Shoda and Marc Rothenberg, revealed that the proteins generated by these genes are localized within desmosomes in the epithelial layer of the esophagus. Desmosomes play a crucial role in cell adhesion. The variants of DSP and PPL weaken the epithelial barrier, making the tissue more susceptible to damage from inflammation-causing eosinophils, which contribute to symptoms such as abdominal pain and food impaction. The researchers utilized whole-genome sequencing and identified these variants in five members of a family with multiple generations affected by EoE. Additionally, they tested another 61 families with familial EoE and found 13 families with either the DSP or PPL variants. This is extremely conclusive evidence, especially for a rare disease like EoE. The team's findings suggest that these gene variants could open up new avenues of research for potential treatments.
There are also numerous hypotheses relating to other potential causes. One hypothesis is the “Allergen and Hygiene Hypothesis”, which suggests that our cleaner and more sterile environment in developed countries exposes our immune systems to fewer types of antigens, making it harder for tolerance to develop. This then leads to a rise in EoE and other allergic diseases. Another hypothesis is the “Helicobacter Pylori Hypothesis” which states that the decline in the prevalence of Helicobacter pylori in the US may have a role in the increasing incidence of EoE. Studies have shown an inverse relationship between H. pylori and EoE, suggesting that the removal of H. pylori from the environment could be a direct cause. With another hypothesis being the “Proton Pump Inhibitor Hypothesis”. This hypothesis states that the increase in the use of proton pump inhibitor (PPI) medications has been suggested as a potential factor in the rising incidence of EoE. PPIs can increase upper GI tract permeability, leading to new antigen exposure routes, and have been associated with the development of food-specific IgE antibodies. However, it is important to note that many individuals diagnosed with EoE have no previous history of PPI use and PPIs have shown anti-inflammatory and anti-eosinophil effects in both laboratory and clinical settings. This hypothesis is therefore very unlikely to be true.
Those living with EoE manage symptoms through lifestyle changes such partaking in elimination diets. These diets' goal is to improve symptoms of EoE by eliminating foods such as dairy, wheat, egg, and soy. Dupixent (dupilumab) is the only medical therapy to date that has been approved by the Food and Drug Administration (FDA) to treat eosinophilic esophagitis specifically, instead of its symptoms. Dupixent reduces the inflammation associated with the disease and improves patients’ ability to swallow food. EoE is chronic and does not spontaneously go away. The endoscopic signs and esophageal eosinophilia persist in the absence of treatment. When treatment is stopped, symptoms, endoscopic signs, and esophageal eosinophilia recur in the vast majority of patients. In fact, untreated, recent data finds that EoE can progress from an inflammatory-predominant phenotype in children to a fibrosis-predominant phenotype in adults. This helps explain the differences in symptoms between these age groups. In children, eosinophilic inflammation is characterized by white plaques, decreased vascularity, mucosal edema, and linear furrows. Adults experience subepithelial collagen deposition leading to esophageal rings, narrowing, strictures, and dysphagia as the primary symptoms. EoE is largely a newly discovered and rare disease. Future research on long term effects, causes, and genes responsible for this disease are needed in order to develop new and safe treatments.
References:
American Academy of Allergy, Asthma & Immunology (AAAAI). (n.d.). Eosinophilic Esophagitis. Retrieved from https://www.aaaai.org/conditions-treatments/related-conditions/eosinophilic-esophagitis
Sleiman, P. M. A., Wang, M. L., Cianferoni, A., Aceves, S., Gonsalves, N., Nadeau, K., ... & Hakonarson, H. (2021). GWAS identifies four novel eosinophilic esophagitis loci. Nature Communications, 12(1), 1-10. https://doi.org/10.1038/s41467-021-26939-9
Cincinnati Children's. (n.d.). Two Genes Associated with Familial EoE. Retrieved from https://scienceblog.cincinnatichildrens.org/two-genes-associated-with-familial-eoe/
Johns Hopkins Medicine. (n.d.). Eosinophilic Esophagitis. Retrieved from https://www.hopkinsmedicine.org/health/conditions-and-diseases/eosinophilic-esophagitis
Aceves, S. S. (2014). Eosinophilic esophagitis: Immunopathogenesis, esophageal remodeling, and fibrosis. Gastroenterology Clinics, 43(2), 297-311. https://doi.org/10.1016/j.gtc.2014.02.004
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