Eosinophilic esophagitis: concepts, controversies, and evidence.

Division of Gastroenterology, Hepatology, and Nutrition, University of Cincinnati College of Medicine, Cincinnati Children's Hospital Medical Center, Cincinnati Center for Eosinophilic Disorders, Cincinnati, OH 45229, USA.
Current Gastroenterology Reports 07/2009; 11(3):220-5. DOI: 10.1007/s11894-009-0034-2
Source: PubMed

ABSTRACT Eosinophilic esophagitis has become a prominent chronic esophageal disorder in clinical pediatric and adult gastroenterology. Its manifestations are protean in childhood, but dysphagia predominates the clinical presentation in adults. Adverse immune responsiveness to dietary antigens underlies most cases, as is reflected in clinical and histologic remission with appropriate diet management in the majority, although an understanding of the mechanisms underlying the inflammatory process remains incomplete. Intense investigations to explain the underpinnings of the disorder and to discover effective therapy are ongoing.

  • [Show abstract] [Hide abstract]
    ABSTRACT: Eosinophilic oesophagitis (EO) is an immune/antigen mediated, chronic, relapsing disease characterised by dysphagia, food bolus impaction and a dense oesophageal eosinophilic infiltrate. Characteristic endoscopic features include corrugated rings, linear furrows and white exudates, but none are diagnostic. Despite its increasing prevalence, EO remains underdiagnosed. There is a strong association with other atopic conditions. Symptoms, histology and endoscopic findings can overlap with gastro-oesophageal reflux disease. Currently endoscopy and oesophageal biopsies are the investigation of choice. Oesophageal physiology studies, endoscopic ultrasound, impedance planimetry and serology may have a role in the diagnosis and monitoring of response to therapy. Acid reducing medication is advocated as first line or adjuvant therapy. Dietary therapy is comprised of elimination diets or can be guided by allergen assessment. In adults, topical corticosteroids are the mainstay of therapy. Endoscopic dilatation is safe and effective for the treatment of non-responsive strictures. Other therapeutic options (immunomodulators, biological agents, leukotriene receptor antagonists) are under investigation.
    Postgraduate medical journal 03/2014; 90(1063). DOI:10.1136/postgradmedj-2013-131843 · 1.55 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Eosinophilic oesophagitis (EoE) is an inflammatory disorder of the oesophagus which has become increasingly recognised over recent years, although it remains underdiagnosed in many centres. It is characterised histologically by a significant eosinophilic infiltration of the oesophageal mucosa (>15 eosinophils per high powered field), and clinically with features of oesophageal dysfunction such a dysphagia, food impaction, and proton pump inhibitor (PPI) resistant dyspepsia. Fibrosis and oesophageal remodelling may occur and lead to oesophageal strictures. An allergic predisposition is common in the EoE population, which appears to be primarily food antigen driven in children and aeroallergen driven in adults. Evidence suggests that the pathogenesis of EoE is due to a dysregulated immunological response to an environmental allergen, resulting in a T helper type 2 (Th2) inflammatory disease and remodelling of the oesophagus in genetically susceptible individuals. Allergen elimination and anti-inflammatory therapy with corticosteroids are currently the mainstay of treatment; however, an increasing number of studies are now focused on targeting different stages in the disease pathogenesis. A greater understanding of the underlying mechanisms resulting in EoE will allow us to improve the therapeutic options available.
    Postgraduate medical journal 03/2014; 90(1063). DOI:10.1136/postgradmedj-2012-131403 · 1.55 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Eosinophilic esophagitis (EoE) is a chronic inflammatory disorder associated with allergic hypersensitivity to food. We interrogated >1.5 million genetic variants in EoE cases of European ancestry and subsequently in a multi-site cohort with local and out-of-study control subjects. In addition to replicating association of the 5q22 locus (meta-analysis P = 1.9 × 10(-16)), we identified an association at 2p23 spanning CAPN14 (P = 2.5 × 10(-10)). CAPN14 was specifically expressed in the esophagus, was dynamically upregulated as a function of disease activity and genetic haplotype and after exposure of epithelial cells to interleukin (IL)-13, and was located in an epigenetic hotspot modified by IL-13. Genes neighboring the top 208 EoE-associated sequence variants were enriched for esophageal expression, and multiple loci for allergic sensitization were associated with EoE susceptibility (4.8 × 10(-2) < P < 5.1 × 10(-11)). We propose a model to explain the tissue-specific nature of EoE that involves the interplay of allergic sensitization with an EoE-specific, IL-13-inducible esophageal response involving CAPN14.
    Nature Genetics 07/2014; 46(8). DOI:10.1038/ng.3033 · 29.65 Impact Factor