Although poorly understood, eosinophilic esophagitis is an inflammatory disease whose prevalence has increased significantly in recent years. According to a recent clinical study, an antibody that blocks this inflammation greatly improves the symptoms associated with this disease.
As the name suggests, eosinophilic esophagitis is inflammation of the esophagus mediated by the presence of excess eosinophils, a class of innate immune system cells commonly involved in allergic reactions. This inflammation can be considered a modern disease as it was first described in 1993.(1) The condition primarily affects children and young adults, the vast majority of whom are male, and is often accompanied by atopic diseases (eczema, asthma, allergic rhinitis ) accompanied ).
In adults, the symptoms of the disease take the form of dysphagia (difficulty swallowing) and food impaction (food gets stuck in the esophagus), while in children the main symptoms are refusal to eat, vomiting and abdominal or chest pain.
Get off in cases
The diagnostic frequency of eosinophilic esophagitis has increased enormously in western countries in recent years and is now similar to that of ulcerative colitis (50-100 cases/100,000 people), and the disease is the leading cause of foodborne illness in children and adults, at least at present 50 years.
The reasons for the rapid increase in the incidence and prevalence of eosinophilic esophagitis, particularly over the past decade, remain unclear. Four main explanations were offered:
1) The hygiene hypothesis : According to this theory, too much hygiene would reduce early exposure to infections and microbes, leading to disruption of the microbiome (dysbiosis) and poor formation of the immune system to recognize antigens. The increase in the prevalence of allergic, autoimmune and inflammatory diseases would be a consequence of this dysbiosis.
2) diet change : Changes in the food production process (treatment of animals with hormones and antibiotics, food additives, ultra-processed foods) also disrupt the microbiome and would favor the development of inflammatory diseases.
3) Helicobacter pylori : The frequency of infection with the intestinal bacterium H. pylori has decreased significantly in recent decades. This eradication is positive for gastric cancer prevention, but this bacterium nonetheless activates certain immune response regulatory T lymphocytes that might protect against esophagitis and other inflammatory or allergic diseases.
4) Esophageal Reflux : The frequency of esophageal reflux has increased significantly in recent years, particularly due to the significant increase in overweight people. Contact of the esophageal mucosa with gastric acid can alter the integrity of the mucosa and allow antigens present in food to enter the cells of the esophagus and trigger an inflammatory response.
A new treatment
Regardless of the mechanism that favors its development, eosinophilic esophagitis remains a disease that significantly affects the quality of life and, over time, can cause fibrosis that leads to narrowing of the esophagus, making it very difficult to eat.
Currently, treatment mainly involves testing whether elimination diets (which exclude major food allergens such as wheat, dairy, fish/seafood, peanuts/tree nuts, egg, and soy) can reduce symptoms. If not, corticosteroids may be swallowed to locally coat the wall of the esophagus and reduce inflammation.
However, these treatments fail in a significant proportion of cases, requiring the development of alternative options to improve the management of the disease.
A major advance in this direction comes from a phase 3 clinical trial in which we tested the effects of dupilumab, an antibody that targets an essential element (signalling of interleukins -4 and -13) of the response when working in multiple inflammatory diseases, including eosinophilic, blocked esophagitis.(2)
The study shows that a weekly dose of the antibody given subcutaneously to adolescents and adults suffering from the disease results in the disappearance of eosinophils from the esophageal tissue in 60% of patients compared to just 5% of patients given placebo received.
The antibody also reduces dysphagia symptoms and improves patients’ quality of life significantly more than placebo, without major side effects.
This new drug could therefore prove to be a welcome addition to the currently underserved treatments for eosinophilic esophagitis.
(1) Attwood SE et al. Esophageal eosinophilia with dysphagia. A pronounced clinicopathological syndrome. dig. To say. Science. 1993; 38:109-16.
(2) Dellon E. et al. Dupilumab in adult and adolescent patients with eosinophilic esophagitis. N.Engl. J.Med. 2022; 387:2317-30.