Monday, September 23, 2013

Eosinophilic esophagitis: Updated consensus recommendations

A task force made up of 33 experts from multiple disciplines present updated recommendations for the diagnosis and management of eosinophilic esophagitis (EoE) in this month’s issue (J Allergy Clin Immunol 2011;128:3-20). Liacouras and colleagues performed an exhaustive literature review to inform new clinical recommendations (CR) for 5 categories: diagnostics, genetics, allergy evaluation, therapies, and complications. They also offer recommendations for future critical research areas. Importantly, they provide a concept definition to assist clinicians with framing the clinical presentation of EoE. Liacouras et al. state this concept definition: “Eosinophilic esophagitis represents a chronic, immune/ antigen-mediated esophageal disease characterized clinically by symptoms related to esophageal dysfunction and histologically by eosinophil-predominant inflammation.”


Overview of diagnostic recommendations: The task force makes recommendations in the diagnostic areas of history and physical exam, endoscopy, histology, pH monitoring, and laboratory findings. Among these are a thorough H & P, with emphasis on eating and swallowing symptoms, proximal and distal endoscopic biopsies, and gastric pH and pH impedance testing. Additionally, Liacouras et al. recommend that any and all histological findings be reported until EoE-specific findings are identified. The authors note that very few laboratory tests have been demonstrated to be informative, with the exception of peripheral esosinophil count and skin prick testing.


Overview of genetic studies and recommendation: Noting that the previous consensus report, published in 2007 (Gastroenterology 2007;133:1342–1363), presented a single genotype study, Liacouras et al. provides a substantial review of recent genetic research. Two important genetic findings are the description of an EoE transcriptome with increased expression of eotaxin-3 and IL-13, and the report of a single susceptibility locus, 5q22, for EoE that contains genes encoding thymic stromal lymphopoetin (TSLP), a critical cytokine in TH2 cell commitment. An X-linked variant of TSLP and a common deletion mutation in the filaggrin gene family have also been identified.


Overview of allergic evaluation: Atopic conditions including food allergy, asthma and eczema are known to associate with EoE and the task force emphasizes allergist/immunologist consultation for management of comorbid allergic symptoms. Skin prick testing is necessary to identify reactive allergens and eliminate or mitigate them. Liacouras et al. recommend assessment of allergen-specific IgE to document sensitivity prior to initiating desensitization/tolerance protocols.


Overview of therapeutic options: Liacouras et al. review and recommend a multifocal treatment strategy that includes proton-pump inhibitors (PPI), dietary restrictions, and topical corticosteroids. Oral steroids are recommended only for severe symptom presentations. They also state that alternative therapies, such as cromolyn sodium, LTR antagonists and immunosuppressive drugs, are not recommended based on lack of efficacy data.


Overview of complications: Liacouras et al. point out the common complications, namely, emergent food impaction, esophageal stricture, and non-interventional (“spontaneous”) esophageal perforation. They go on to discuss esophageal dilation for mitigation, but advise that it is best applied as an “add-on” intervention to the recommended clinical management.


Liacouras et al. provide recommendations for the focus of future studies for each of the 5 areas they cover and conclude that the most pressing need is for research to distinguish EoE from gastric esophageal reflux disease (GERD), with several other priorities, such as translational analysis to describe EoE phenotypes, and idenfication of EoE biomarkers and unique histological findings.


We asked lead author Chris Liacouras, from the Children’s Hospital of Philadelphia, to tell us more about our current understanding of EoE and where the research will go from here:


JACI: How has our understanding of EoE changed since the 2007 consensus recommendations were published?


Liacouras: We have been been extremely fortunate that the number of physicians and scientists interested in EoE has grown tremendously since the original Consensus Report in 2007 as noted by the number of additional authors included in the 2011 Updated Guidelines. The most important component of the Updated recommendations continues to be the understanding of the definition which attempts to explain that EoE is an antigen/immune medicated disease process different from acid induced or PPI-responsive esophageal eosinophilia. Additionally, the other most significant advances since 2007 have been made in genetics and with the identification of specific esophageal biochemical tissue markers.


JACI: In your opinion, what is the next priority area in EoE research after the need to distinguish it clinically and pathologically from GERD?


Liacouras: Currently, EoE has become one of the interesting and confusing disorders for both gastroenterologists and allergists. Apart from the need for physicians to identify and accurately diagnose patients with EoE, there are many areas of ongoing research that need to be explored. Clinically, it is essential that we continue to pursue the natural history, non-invasive testing, best treatment options and which patients are likely to develop complications. In addition, scientifically, we need to identify the etiology, pathophysiology, and development of esophageal fibrosis in patients with EoE. We also need to continue to explore the genetics of the disease.


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