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Squamous Epithelium With A Rare Eosinophil



Patient records were reviewed by a pediatric gastroenterologist (V.M.) to ensure that the clinical characteristics of the patients fit the diagnosis of EoE. The slides were reviewed by a pathologist (M.R.) to confirm the presence or absence of EoE. Classic features of EoE consist of numerous intraepithelial eosinophils greater than 15 per high powered field (HPF) (ranging from 35 to over 100 per HPF), superficial eosinophilic microabscesses, basal layer hyperplasia and subepithelial fibrosis. The posttreatment biopsy material consisted of normal appearing squamous mucosa with only rare intraepithelial eosinophils numbering less than 2 per HPF.


Eight 10 µm sections were cut from each block and mounted onto plain glass slides. If the biopsy section contained only epithelium, the sections were scraped from the slides and were ready for total RNA extraction. If biopsy sections contained sub-epithelium, the sections were deparaffinized, stained, dehydrated through graded alcohols using the Paradise FFPE reagent System (Applied Biosystems, Foster City, CA) and subjected to LCM within 2 hours of deparaffinization. About 20,000 epithelial cells were captured on LCM Macro CapSure caps (Applied Biosystems) using the Arcturus XT LCM instrument (Applied Biosystems) and the captured cells in the caps were used to extract total RNA. In either case, only the RNA from the epithelial mucosa was extracted. RecoverAll Total Nucleic Acid Extraction Kits for FFPE tissues (Ambion, Austin, TX) were used for extraction. RNA was further purified and concentrated using the RNEasy Minelute Cleanup Kit (Qiagen, Valencia, CA), and then evaluated by the Agilent Bioanalyzer using an RNA 6000 Nano or Pico LabChip (Agilent Technologies Santa Clara, CA) as described previously [14].




squamous epithelium with a rare eosinophil




Eosinophils are multifunctional granulocytes that contribute to initiation and modulation of inflammation. Their role in asthma and parasitic infections has long been recognized. Growing evidence now reveals a role for eosinophils in autoimmune diseases. In this review, we summarize the function of eosinophils in inflammatory bowel diseases, neuromyelitis optica, bullous pemphigoid, autoimmune myocarditis, primary biliary cirrhosis, eosinophilic granulomatosis with polyangiitis, and other autoimmune diseases. Clinical studies, eosinophil-targeted therapies, and experimental models have contributed to our understanding of the regulation and function of eosinophils in these diseases. By examining the role of eosinophils in autoimmune diseases of different organs, we can identify common pathogenic mechanisms. These include degranulation of cytotoxic granule proteins, induction of antibody-dependent cell-mediated cytotoxicity, release of proteases degrading extracellular matrix, immune modulation through cytokines, antigen presentation, and prothrombotic functions. The association of eosinophilic diseases with autoimmune diseases is also examined, showing a possible increase in autoimmune diseases in patients with eosinophilic esophagitis, hypereosinophilic syndrome, and non-allergic asthma. Finally, we summarize key future research needs.


  • Diagnosis Index entries containing back-references to K20.0: Esophagitis (acute) (alkaline) (chemical) (chronic) (infectional) (necrotic) (peptic) (postoperative) (without bleeding) K20.90ICD-10-CM Diagnosis Code K20.90Esophagitis, unspecified without bleeding2021 - New Code 2022 2023 Billable/Specific Code Applicable ToEsophagitis NOS

eosinophilic K20.0


Objective To determine the accuracy of histopathologic diagnosis in distinguishing eosinophilic esophagitis (EE) from gastroesophageal reflux disease (GERD) in children with upper aerodigestive symptoms.


Abstract: Eosinophilic esophagitis (EoE) is a chronic allergic/immune-mediated esophageal disease. Knowledge related to the clinical presentation, pathogenesis, epidemiology, natural history, treatment, and outcomes of EoE has rapidly evolved over the past 2 decades. This article focuses on the similarly evolving diagnostic framework for EoE. In the initial clinical guidelines, diagnosis of EoE was based on symptoms of esophageal dysfunction; at least 15 eosinophils per high-power field (eos/hpf) on esophageal biopsy; and either a lack of response to high-dose proton pump inhibitor (PPI) therapy, or normal pH monitoring. The first 2 criteria have remained largely unchanged; however, the role of PPIs has been controversial, particularly due to the recognition of PPI-responsive esophageal eosinophilia (PPI-REE), in which patients with suspected EoE experience resolution of symptoms and esophageal eosinophilia with PPI therapy. A quickly expanding evidence base has found that most adult patients with EoE and PPI-REE share similar clinical, endoscopic, histologic, immunologic, and molecular characteristics prior to the use of PPIs. Because of this, the most recent diagnostic guidelines have removed the lack of response to PPIs as a diagnostic criterion; PPIs are now better considered as a treatment for esophageal eosinophilia. EoE should currently be suspected on a clinical basis when there are symptoms of esophageal dysfunction and at least 15 eos/hpf on esophageal biopsies. A history of atopy and endoscopic signs of EoE are strongly supportive of the diagnosis. However, the diagnosis cannot be confirmed until a thorough evaluation of other potential causes of esophageal eosinophilia has been performed.


Eosinophilic esophagitis (EoE) is a chronic allergic/immune-mediated clinicopathologic condition characterized by symptoms of esophageal dysfunction and eosinophilic infiltration of the esophageal mucosa by at least 15 eosinophils per high-power field (eos/hpf) in the absence of secondary causes.1,2 Clinical presentation varies by age; children present with predominant symptoms of abdominal pain, nausea, vomiting, regurgitation, and failure to thrive, whereas adults and some adolescents present more commonly with solid food dysphagia and food impaction, although heartburn and noncardiac chest pain can also be seen. The dichotomy in clinical presentation is thought to be due to the natural history of the disease with progression from an inflammatory phenotype to a more fibrostenotic phenotype.3-5


The first case of EoE was reported in the literature in 1977; a patient with comorbid asthma and hay fever presented with symptoms of esophageal spasm and was found to have eosinophilic infiltration of the esophageal mucosa.63 Scattered case reports followed throughout the next decade, but EoE was not recognized as a distinct entity until its description was included in several seminal case series published in the early- to mid-1990s.64-66 For the next 10 years or so, there remained substantial diagnostic variability with regard to factors such as biopsy procurement, quantification of eosinophils, threshold of the number of eosinophils to define EoE, and the use of additional testing such as esophageal pH monitoring.67 In order to provide clarification surrounding diagnostic criteria and treatment, the first consensus recommendations for EoE were published in 2007.68


According to these recommendations, a patient would be diagnosed with EoE if he or she met the following criteria: (1) esophageal and/or upper gastrointestinal tract symptoms, (2) a minimum of 15 eos/hpf seen in at least 1 esophageal mucosal biopsy, and (3) either a lack of clinical or histologic response to high-dose PPI therapy, or normal pH monitoring of the distal esophagus. These diagnostic criteria recognized that EoE was isolated to the esophagus and emphasized the importance of excluding other disorders associated with -similar clinical, histologic, or endoscopic features, especially gastroesophageal reflux disease (GERD). At the time, EoE and GERD were considered mutually exclusive diseases, and the purpose of a course of PPI treatment and/or pH monitoring was to rule out inflammation related to GERD as an underlying cause of symptoms and esophageal eosinophilia.69,70 PPI therapy consisted of high-dose administration for 6 to 8 weeks followed by repeat upper endoscopy with biopsies.


In the following years, growing experience and research led to further insight regarding the etiology, pathogenesis, natural history, and treatment of EoE, and updated recommendations were published in 2011.1 Several revisions to the original diagnostic guidelines included the acknowledgement that EoE was a chronic condition driven by an aberrant immune response; the inclusion of select patients with more than 15 eos/hpf on esophageal mucosal biopsies (possibly due to inadequate biopsy specimens, sampling error, chronic disease, or partial treatment response), and a stronger emphasis on the need for excluding other potential causes of esophageal eosinophilia beyond GERD.


Prior to and following the release of the 2011 recommendations, a number of studies were published that confirmed that PPI-REE was seen in both children and adults, and that this condition was common, with PPI response rates ranging from 33% to 74%.72,76-84 A meta-analysis found that approximately 50% of patients with esophageal eosinophilia had a histologic response to a PPI, and that an even higher proportion of patients had a symptomatic response.85 The studies also found that EoE and PPI-REE could not be distinguished by most baseline clinical, endoscopic, or histologic features prior to a trial of PPI therapy.72,84,86,87 In particular, patients with either EoE or PPI-REE presented predominantly with dysphagia, which was often complicated by food impaction, and experienced heartburn at comparable rates. Several studies demonstrated a similar prevalence of endoscopic abnormalities including rings, furrows, white exudates, edema, and friability in the 2 patient populations.84,86,87 Furthermore, the degree of esophageal eosinophilia as well as the histologic findings of eosinophil degranulation and microabscess formation were found to be similar between the 2 groups.72,84,86,87 2ff7e9595c


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