Local Responses to Food Allergens in Eosinophilic Esophagitis: Mechanisms and Clinical Application

Eosinophilic esophagitis (EoE) is an inflammatory disease of the esophagus that
leads to progressive narrowing of the lumen and symptoms of dysphagia and food
impaction. There is a huge increase of EoE prevalence in the last 10 years and
for many patients an acceptable treatment is lacking. Food allergy plays an
important role in eosinophilic esophagitis, but it is unclear which mechanisms
are responsible for this local food-induced immune response in individual
patients. We recently developed an innovative esophageal allergen injection
method, that provides us with the opportunity to investigate the acute immune
response after allergen provocation and may allow identification of local
sensitization in individual patients.

1. To investigate different modes of allergen administration to the esophageal
wall, by testing the effect on visible mucosal changes
2. To investigate which immune cells become activated after allergen
provocation
3. To investigate whether the abnormal response to causative allergens can be
simulated in vitro.
4. To investigate the esophageal motility changes induced by allergen
provocation.

Pathophysiologcial study

EoE patients will undergo two gastroscopies with allergen provocation tests. In
one gastroscopy patients undergo esophageal allergen injections as described in
our pilot study (NL54305.018.15 / METC 2015_195) and in the other gastroscopy
the esophagus is flushed with 50-100 ml of fresh allergens. The order of the
two gastroscopies is randomized. The acute response to allergen provocation
will be registered up to 20 minutes after allergen provocation. Before the
allergen provocation, biopsies from esophageal mucosa are taken for in vitro
allergen provocation and for immune profiling of baseline conditions. After
provocation, biopsies are taken from sites with visible response to allergen
exposure and from sites where no response was seen after exposure to allergens.
Six weeks after the second gastroscopy patients will undergo a High Resolution
Manometry during which allergen provocation is performed by drinking a mixture
of allergens that induced a visible response during the earlier gastroscopies.
In addition, patients undergo a skin prick test and a vena puncture for serum
IgE testing at the start of the study. For the validation of the in vitro
allergen provocation method biopsies are taken from patients that undergo a
gastroscopy for other indications than esophageal complaints. These biopsies
will be used in the in vitro allergen provocation experiments.

The risk of the performed procedures consists of the risk of the gastroscopies
with allergen provocation and the High Resolution Manometry. The risks of
gastroscopies and manometry, such as bleeding and perforation, are very rare
and can be treated expectatively or endoscopically. Anaphylactic reactions to
allergen provocation are very rare in EoE, however any patient with a history
of such reactions will be excluded from participation and these reactions also
were not seen in our pilot study. Nonetheless, medications for management of
acute anaphylactic will be present during and after endoscopy. The study will
evaluate the effect of a local allergen provocation and lead to new insights
into pathophysiology. This could eventually contribute to a new diagnostic
approach and might serve as guidance for dietary therapy in eosinophilic
esophagitis.