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Background: Eosinophilic esophagitis (EoE) involves a chronic immune‐mediated response to dietary antigens. Recent work identifies T‐cell clonality in children with EoE, however, it is unknown whether this is true in adults or whether there is a restricted food‐specific T‐cell repertoire. We sought to confirm T‐cell receptor (TCR) clonality in EoE and assess for differences with specific food triggers. Methods: Bulk TCR sequencing was performed on mRNA isolated from esophageal biopsies obtained from adults and children with EoE (n = 15) who had food triggers confirmed by endoscopic evaluation. Non‐EoE adult and pediatric controls (n = 10) were included. Differences in TCR clonality by disease and treatment status were assessed. Shared and similar V‐J‐CDR3s were assessed based on specific food triggers. Results: Active EoE biopsies from children but not adults displayed decreased unique TCRα/β clonotypes and increased relative abundance of TCRs comprising >1% of the total compared to non‐EoE controls and paired inactive EoE samples. Among patients in which baseline, post diet elimination, and food trigger reintroduction samples (n = 6) were obtained, we observed ~1% of TCRs were shared only between pre‐diet elimination and trigger reintroduction. Patients with a shared EoE trigger (milk) had a greater degree of shared and similar TCRs compared to patients with differing triggers (seafood, wheat, egg, soy). Conclusion: We confirmed relative clonality in children but not adults with active EoE and identified potential food‐specific TCRs, particularly for milk‐triggered EoE. Further studies are needed to better identify the broad TCR repertoire relevant to food triggers. [ABSTRACT FROM AUTHOR]

Summary: Eosinophils are a common clinical feature associated with chronic allergic diseases, and elemental diets, systemic steroids, anti‐IL‐5 and anti‐IL‐13 treatment have shown some therapeutic promise. Herein, we present evidence that pre‐ and post‐intraperitoneal administration of tacrolimus (FK506) is very effective in reducing CCR3/Siglec‐F+ eosinophils in Aspergillus‐challenged asthma and EoE, CD2‐IL‐5 induced global eosinophilia, and DOX regulated IL‐13‐induced asthma. We used flow cytometry and anti‐major basic protein (MBP) immunostaining to examine eosinophils in the spleen, bone marrow, BALF, lung, oesophagus and intestine. Additionally, we also performed ELISA and Western blot analyses to show that tacrolimus treatment also reduces the levels of eosinophil‐specific cytokines IL‐4, IL‐5, IL‐13 and TGF‐β, eosinophil‐specific chemokines Eotaxin‐1 and Eotaxin‐2, and progenitors of target RCAN1 mRNA and protein levels. Additionally, the current investigations also show that the TGF‐β‐mediated oesophageal and lung fibrosis is also reduced in Aspergillus‐challenged, CD2‐IL‐5 transgenic and DOX‐responsive IL‐13 mice. Mechanistically, we show that tacrolimus in vitro treatment inhibited bone marrow‐derived eosinophil proliferation and viability by promoting eosinophil apoptosis that may be associated with downregulation of RCAN1. Taken together, we provide in vivo and in vitro evidence that tacrolimus ameliorates eosinophil levels and associated pathogenesis in allergen‐, IL‐5‐ and IL‐13‐induced EoE, EG and asthma pathogenesis. Considering tacrolimus side‐effects and reactivity to several other drugs, we propose the topical use of tacrolimus for paediatric and low‐dose oral for adult patients as a novel therapeutic strategy for the clinical trial to reduce mucosal eosinophilia first in steroid‐refractory or elemental diet non‐responsive adult EoE, EG and asthma patients. [ABSTRACT FROM AUTHOR]

Purpose of Review: This review presents the available data regarding efficacy of nutritional therapy, highlighting clinical decision points and a strategy for reintroduction of foods following an elemental diet for treatment of eosinophilic gastrointestinal disorders. Recent Findings: Elemental and empiric elimination diets are highly effective treatments for eosinophilic gastrointestinal diseases. Standardization in the reintroduction phase, after utilizing the diet for disease remission, is lacking. Summary: Clinicians are confronted with multiple challenges regarding the best practice for food reintroduction and identification of potential dietary triggers including order of foods being challenged and duration between endoscopic procedures. Individualization is required for preference and adherence to optimize quality of life and treatment success for this burdensome and life altering immune driven gastrointestinal disorder. Age specific concerns for children, teenagers, and adults should be assessed using a patient centric approach. [ABSTRACT FROM AUTHOR]

Eosinophilic esophagitis is a relatively recently discovered disease of increasing incidence and prevalence and is a common cause of dysphagia and food bolus impaction. The definition of eosinophilic esophagitis continues to evolve, most recently with the characterization of proton pump inhibitor-responsive esophageal eosinophilia. The number of high-quality prospective, controlled trials guiding therapeutic decisions in eosinophilic esophagitis has increased steadily over the past several years. Treatment options at present focus on dietary therapy, particularly implementation of a 6-food elimination diet, and medical therapy, primarily the use of swallowed, topical corticosteroids. Proton pump inhibitors play an important role in current management. Conservative esophageal dilation is effective at ameliorating dysphagia in symptomatic patients with esophageal strictures. We conducted an evidence-based review of the diagnosis and treatment options in adults with eosinophilic esophagitis. The understanding of eosinophilic esophagitis continues to be refined. Continued validation of appropriate endpoints, however, is essential to establish the efficacy of existing and novel therapeutic approaches. [ABSTRACT FROM AUTHOR]