Do Histological Features of Eosinophilic Esophagitis in Children Correlate With Peripheral Eosinophils?

AIM: Eosinophilic esophagitis (EoE) is a chronic, relapsing inflammatory disease of the esophagus. We investigate whether peripheral eosinophils can be a good indicator of esophageal eosinophilia and whether they correlate with histological findings, such as basilar hyperplasia, spongiosis, microabscesses, number of lymphocytes, and number of neutrophils. METHODS: A retrospective chart review was conducted with EoE patients ages <18 years after obtaining IRB approval. Biopsies obtained from 57 EoE patients were analyzed. Patient demographics, symptoms; complete blood count with differentials obtained at the time of endoscopies or within a month of the procedure, were documented. RESULTS: A significant correlation was observed between peripheral absolute eosinophil count (AEC) and peak esophageal eosinophil count (P value: 0.0009). Subjects with biopsies suggestive of ongoing disease activity or active status had a higher mean of AEC at 577.41 ±â€Š202.60 compared with subjects with inactivity with mean of 305.26 ±â€Š526.67. However, when the subjects were broadly divided with 500 AEC as a cut off (<500 and >500 AEC), it was found that, out of 27 EoE inactive patients, 24 had AEC count less than or equal to 500 and out of 66 EoE active patients, 32 had AEC more than 500. CONCLUSION: Active EoE status meant a higher mean of AEC compared with inactive status; but AEC was not found to be a sensitive tool for detecting active EoE.

Eosinophilic Esophagitis: the Potential Role of Biologics in its Treatment.

Eosinophilic esophagitis (EoE) is a chronic, relapsing inflammatory disease of the esophagus, characterized by the presence of significant esophageal mucosal eosinophilic infiltrates. The clinical presentation of EoE in childhood may include failure to thrive and feeding intolerance. The complication of food impaction is often related to the presence of strictures or narrow caliber esophagus. Over the last decade, there has been tremendous progress in the field of eosinophilic disorders, particularly eosinophilic esophagitis. Conventional treatment of eosinophilic esophagitis involves topical swallowed steroids, systemic steroids, elimination diets, and/or esophageal dilation. However, treatment outcomes with the above modalities are not satisfactory for all patients with EoE and alternative treatments are clearly needed. There has been ongoing research targeting the treatment-refractory population of patients with EoE and the population with long-term consequences of the disease and its treatment. With the significant eosinophilic infiltration that characterizes EoE, anti-IL-5 therapies designed to target eosinophilic inflammation have been some of the most studied anti-inflammatory biologic therapies in EoE. In the studies published to date, while various IL-5 inhibitors have decreased the numbers of esophageal eosinophils, they have not depleted them to the levels consistent with histologic remission of EoE. As additional biologics that modulate Th2-mediated immunity are trialed for the treatment of EoE, we stand to learn more about the inflammatory factors mediating this challenging condition. In this review, we discuss the alternative modes of therapy in EoE that have emerged, with a focus on anti-IL-5 therapies and other biologics, their variation of success, and ultimately, the future of treatment in this field.

Upregulation of non-canonical Wnt ligands and oxidative glucose metabolism in NASH induced by methionine-choline deficient diet.

Wnt ligands regulate metabolic pathways, and dysregulation of Wnt signaling contributes to chronic inflammatory disease. A knowledge gap exists concerning the role of aberrant Wnt signaling in non-alcoholic steatohepatitis (NASH), which exhibits metabolic syndrome and inflammation. Using a mouse model of methionine-choline deficient diet (MCDD)-induced NASH, we investigated the Wnt signaling pathways in relation to hepatic glucose oxidation. Mice fed the MCD diet for 6 weeks developed prominent NASH marked by macrovesicular steatosis, inflammation and lipid peroxidation. qPCR analysis reveals differential hepatic expression of canonical and non-canonical Wnt ligands. While expression of Wnt3a was decreased in NASH vs chow diet control, expression of Wnt5a and Wnt11 were increased 3 fold and 15 fold, respectively. Consistent with activation of non-canonical Wnt signaling, expression of the alternative Wnt receptor ROR2 was increased 5 fold with no change in LRP6 expression. Activities of the metabolic enzymes glucokinase, phosphoglucoisomerase, glyceraldehyde-3-phosphate dehydrogenase, pyruvate kinase, and pyruvate dehydrogenase were all elevated by MCDD. NASH-driven glucose oxidation was accompanied by a 6-fold increase in lactate dehydrogenase (LDH)-B with no change in LDH-A. In addition, glucose-6-phosphate dehydrogenase, the regulatory and NADPH-producing enzyme of the pentose phosphate pathway, was elevated in NASH. These data support a role of accelerated glucose oxidation in the development of NASH, which may be driven by non-canonical Wnt signaling.