A new case of eosinophilic esophagitis

Eosinophilic esophagitis (EE) is a rarely diagnosed condition involving eosinophilic infiltration of the esophageal mucosa The hallmark of this condition is intermittent and often painful dysphagia that may become constant as the disease progresses. It was initially included within the more general condition known as eosinophilic gastroenteritis but it is now considered an independent entity. Attwood et al. called attention to eosinophilic esophagitis as a distinct clinical condition in 1993. Although eosinophilic esophagitis was thought to occur primarily in children, a significant body of evidence suggests that it affects adults as well. We describe a clinical case of a young woman with a long-standing history of dysphagia affected of this rare entity.     

Treatment outcomes for eosinophilic esophagitis in children with esophageal atresia

Eosinophilic esophagitis (EoE) has been reported to be more prevalent in patients with esophageal atresia/tracheoesophageal fistula (EA‐TEF). To date, there is limited data on the management of EoE in this group of patients. The aim of this study is to evaluate the treatment outcomes of EoE in children with EA‐TEF. A retrospective chart review was performed on all EA‐TEF children who were diagnosed with and treated for EoE between January 2000 and September 2013 at the Sydney Children's Hospital. Data collected included details of the patient's treatment, post‐treatment endoscopy, symptoms and nutrition. Twenty patients were included in the study. Median age at diagnosis was 26 months (8–103 months), and median time from diagnosis to last follow‐up was 23 months (2–132 months). Patients were treated with budesonide slurry, swallowed fluticasone, elimination diet alone or in combination. All patients were on proton pump inhibitors at time of diagnosis of EoE which was continued. Six out of seven patients who had furrowing/exudate in endoscopy at diagnosis had complete resolution at a median follow‐up period of 26 months (P = 0.031). Median peak intraepithelial eosinophil count reduced significantly from 30/high‐powered field (HPF) (19–80/HPF) to 8/HPF (0–85/HPF) (median time for improvement = 24 months) (P = 0.015). There was a significant reduction in symptoms of dysphagia and reflux post‐treatment (P < 0.001). Prevalence of strictures significantly decreased (P = 0.016), as did need for dilatations (P = 0.004). In four out of six patients with gastrostomies at baseline, the feeding improved on treatment of EoE and the gastrostomy could be closed. There was also a nonsignificant trend towards improvement in weight and height ‘z scores’ of the patients. Treatment of EoE in children with EA‐TEF was found to significantly reduce intraepithelial eosinophil count, symptoms, strictures and need for dilatations.     

Safety of dilation in adults with eosinophilic esophagitis

Esophageal dilation is an effective therapy for dysphagia in patients with stenosing eosinophilic esophagitis (EoE). Historically, there have been significant concerns of increased perforation rates when dilating EoE patients. More recent studies suggest that improved techniques and increased awareness have decreased complication rates. The aim of this study was to explore the safety of dilation in our population of EoE patients. A retrospective review of all adult EoE patients enrolled in a registry from 2006 to 2010 was performed. All patients who underwent esophageal dilation during this time period were identified and included in the analysis. Our hospital inpatient/outpatient medical records, radiology reports, and endoscopy reports were searched for evidence of any complication following dilation. Perforation, hemorrhage, and hospitalization were identified as a major complication, and chest pain was considered a minor complication. One hundred and ninety‐six patients (41 years [12]; mean age [standard deviation], 80% white, 85% male) were identified. In this cohort, 54 patients (28%) underwent 66 total dilations (seven patients underwent two dilations, one patient underwent three dilations, and one patient underwent four dilations). Three dilation techniques were used (Maloney [24], Savary [29] and through‐the‐scope [13]). There were no major complications encountered. Chest pain was noted in two patients (4%). There were no endoscopic features (rings, furrows, plaques) associated with any complication. Type of dilator, size of dilator, number of prior dilations, and age of patient were also not associated with complications. Endoscopic dilation using a variety of dilators can be safely performed with minimal complications in patients with EoE.     

Prevalence and endoscopic features of eosinophilic esophagitis in patients with esophageal or upper gastrointestinal symptoms

OBJECTIVE: This study was aimed to evaluate the prevalence of eosinophilic esophagitis (EoE) among patients with esophageal or upper gastrointestinal (UGI) symptoms. METHODS: Patients with esophageal or UGI symptoms including dysphagia food impaction, acid regurgitation, heartburn, chest pain, epigastric pain, nausea and/or vomiting were prospectively collected. The enrolled patients responded to a symptomatic questionnaire and underwent an esophagogastroduodenoscopy and esophageal biopsies. Supportive endoscopic findings of EoE (ring‐like appearance, liner furrows, whitish papules, shearing or friability) were recorded. EoE was diagnosed if patients had chronic UGI or esophageal symptoms, the esophageal biopsy showed ≥15 eosinophils/high‐power field and were unresponsive to 2–3 weeks of proton pump inhibitors. RESULTS: A total of 122 patients were enrolled and supportive endoscopic findings were found in 31 (25.4%) patients [whitish papules: 19 (15.6%), ring‐like appearance: 8 (6.6%), linear furrows: 5 (4.1%)]. One patient had a simultaneous ring‐like appearance and linear furrows. EoE was diagnosed in 8 (6.6%) patients and supportive endoscopic findings and past history of gastroesophageal reflux disease, allergic rhinitis and atopic dermatitis were more common in EoE positive than EoE negative patients. The diagnostic yield of endoscopic findings was 40.0% (2/5) in linear furrows, 25.0% (2/8) in ring‐like appearance and 15.8% (3/19) in whitish papules. CONCLUSION: Prevalence of EoE among patients with esophageal or UGI symptoms was 6.6%. Linear furrows and ring‐like appearance had a relatively high diagnostic value.     

Prevalence of esophageal dysmotility in a cohort of patients with esophageal biopsies consistent with eosinophilic esophagitis

SUMMARY.  Eosinophilic esophagitis (EoE) is increasingly being diagnosed in adults presenting with dysphagia, food impactions, and chest pain. Studies to date provide conflicting data on the association of EoE and esophageal dysmotility. The objective of this study was to evaluate the prevalence of esophageal dysmotility in a cohort of patients with biopsies consistent with EoE at a military treatment facility. This is a prospective evaluation of consecutively identified patients at our institution diagnosed with EoE from March 1, 2005 to June 1, 2007. Thirty-two patients with biopsies consistent with EoE completed a symptom survey and 30 underwent esophageal manometry. The majority of EoE patients (23/30, 77%) had a normal end-expiratory lower esophageal sphincter (LES) pressure (normal range 10–35), whereas six patients had a low-normal LES pressure (6–9 mm Hg) and one patient had a decreased LES pressure (<5 mm Hg). Five patients (15.6%) were diagnosed with a nonspecific esophageal motor disorder (NSEMD). Two patients had high mean esophageal amplitude contractions >180 mm Hg (188 mm Hg, 209 mm Hg). No patient was diagnosed with nutcracker esophagus or diffuse esophageal spasm. Patients with and without NSEMD reported a similar degree of swallowing difficulty, heartburn, belching, chest pain, regurgitation, symptoms at night, and total symptom score. Likewise, eosinophil count on mucosal biopsy was similar between patients with and without a NSEMD. In this cohort, we found the prevalence of an NSEMD to be similar to that of a 10% prevalence found in a gastroesophageal reflux population.     

Frequency of eosinophilic esophagitis in patients with esophageal symptoms: a single‐center Turkish experience

Eosinophilic esophagitis (EoE) is a chronic, immune/antigen‐mediated esophageal disease characterized with symptoms related to esophageal dysfunction and eosinophil‐predominant inflammation. There has been a dramatic increase in the diagnosis of this disease in recent years. The primary objective of this study was to determine the frequency of EoE in adult patients who were evaluated by gastroenterologists in our clinic with esophageal symptoms. Between November 2010 and May 2011, 311 adult patients who were evaluated in our clinic with esophageal symptoms were enrolled prospectively. All patients underwent endoscopy and had biopsies taken. Gastroesophageal reflux disease was excluded by either proton pump inhibitory treatment or 24‐hour ambulatory pH monitorization. The diagnosis was confirmed by one independent pathologist. Frequency of EoE in patients with esophageal symptoms was 2.6% (n = 8; four men and four women). Mean age at diagnosis was 40.2 ± 8 years. Heartburn was the predominant symptom in patients (75% of the patients), and 87.5% (n = 7) of patients had more than one symptom at diagnosis. Nearly 38% of the patients (n = 3) had a history of allergic disease. Endoscopic findings were as follows: transient/fixed esophageal rings (25%), white exudates (25%), and normal appearance (50%). Median number of circulating eosinophils was 208 (93–659)/mm³. Median number of intraepithelial eosinophils in proximal‐middle 1/3 part and distal 1/3 part of esophagus were 0 (0–50)/hpf and 37 (16–50)/hpf, respectively. In conclusion, EoE is not rare in Turkey, and it should be considered in the differential diagnosis of patients with esophageal symptoms.     

Dysregulation of the Wnt pathway in adult eosinophilic esophagitis

Eosinophilic esophagitis (EoE) is a chronic inflammatory disease characterized pathologically by eosinophil infiltration. In addition to loss of barrier integrity, a dominant T Helper 2‐associated immune response and strong allergic connection, the esophagus tissue undergoes dramatic changes, with frequent presence of mucosal rings, strictures, linear furrows, and trachealization. Although the inflammatory mechanisms behind this disease are being increasingly well understood, the structural features remain unexplained. We examined the expression of key members of the Wnt‐signaling pathway in biopsies from patients with EoE. This pathway has been shown to be critically important in regulating cellular homeostasis, growth, and differentiation and to be dysregulated in several disease conditions. Biopsies from adult EoE patients were collected by endoscopy and mRNA extracted. After cDNA synthesis, the relative gene expression from key upstream (secreted frizzled‐related protein 1) and downstream (c‐myc and Cyclin D1) molecules in the Wnt pathway, as well as several Wnt pathway members (Wnt1, Axin1, low‐density lipoprotein receptor‐related protein 6, glycogen synthase kinase 3 beta, and β‐catenin), were determined. Biopsies from patients with EoE displayed significantly higher expression of secreted frizzed‐related protein 1 than controls, as well as reductions in Cyclin D1 and c‐myc. In contrast, there were no differences in the Wnt pathway molecules. The levels of expression of Cyclin D1 and c‐myc, as well as β‐catenin, in EoE patients showed strong correlations with the frequency of esophageal eosinophils. Our findings suggest that although there are no changes in the overall levels of key Wnt pathway genes in adult EoE, there is evidence for dysregulation of upstream and downstream regulators of Wnt signaling. Importantly, the associations with eosinophilia suggest that these may participate in the pathogenesis of this disease and be markers of disease severity.     

A Japanese case of eosinophilic esophagitis

Eosinophilic esophagitis (EE) is a rarely diagnosed condition involving eosinophilic infiltration of the esophageal mucosa. Here we present a case of EE in a 69-year-old Japanese man, who presented with abdominal pain, appetite loss, and a history of bronchial asthma. Laboratory findings included peripheral eosinophilia and an increased serum immunoglobulin E level. Computed tomography showed diffuse severe thickening of the esophageal wall, and a barium esophagogram revealed a small caliber of the middle and lower portion of the esophagus, without normal peristaltic contractions. Endoscopy of the esophagus showed a pale mucosa, with adherent whitish exudates resembling fungal infection, and prominent ring-like contractions. Histologic examination of a biopsy specimen revealed marked eosinophil infiltration into the esophageal mucosa. Endoscopic ultrasonography (EUS) demonstrated marked circumferential thickening of the esophageal submucosal layer, and an esophageal manometry study showed a high percentage of ineffective esophageal peristalsis and high-amplitude esophageal body contractions. EUS findings showed no change even after oral corticosteroid therapy, although the histological findings were improved. This is thought to be the first documented Japanese case of EE. EE should be considered in the differential diagnosis in cases of esophageal motility disturbance, even if the patients do not complain of dysphagia.     

Esophageal motor abnormalities in eosinophilic esophagitis identified by high-resolution manometry

Background and Aim: Esophageal motility abnormalities, as measured by conventional manometry (CM), are non‐specific in the majority of patients with eosinophilic esophagitis (EoE). Moreover, the study of CM is limited by poor interobserver agreement. The aims of the present study were: (i) to assess the esophageal patterns in EoE by a topographic analysis of high‐resolution manometry (HRM) data; and (ii) to establish a relationship between motility abnormalities and symptoms of EoE, such as dysphagia and bolus impaction. Methods: All adult patients with EoE diagnosed according to histological criteria, and controls with gastroesophageal reflux disease symptoms and dysphagia, were included. HRM was done in EoE patients and controls. For the analysis of data, the Chicago classification was followed. Results: HRM was performed in 21 patients with EoE, as well as in 21 controls. Of the 21 patients with EoE, 10 (48%) showed pan‐esophageal pressurization, six (28%) showed peristaltic dysfunction, and in five cases (24%), HRM was normal. There was no pan‐esophageal pressurization in controls. Nine of 10 patients with pan‐esophageal pressurization required endoscopic bolus removal (P < 0.05); none had obstructive endoscopy findings. Conclusions: The most frequent esophageal motor abnormality measured by HRM was a pan‐esophageal pressurization. Bolus impaction in patients with EoE was associated with pan‐esophageal pressurization.     

Prospective assessment of the diagnostic utility of esophageal brushings in adults with eosinophilic esophagitis

Patients with eosinophilic esophagitis (EoE) undergo multiple endoscopies with biopsy for both diagnosis and assessment of treatment response, which is inconvenient and costly. Brush cytology has been examined in Barrett's esophagus to reduce the need for repeated endoscopic biopsies. The aim of this pilot study was to evaluate the ability of brush cytology to detect mucosal eosinophilia in patients with EoE. This prospective study included adults with untreated and treated esophageal eosinophilia undergoing endoscopy at a tertiary care center. Patients received paired brushings and biopsies at the proximal and distal esophagus. A blinded pathologist quantified the number of eosinophils and epithelial cells per high‐power field (hpf) on the cytology slides. The ratio of eosinophils/epithelial cells was used to normalize the cytology specimens for density of cells collected. The main outcome measures were sensitivity and specificity of brush cytology, and correlation between cytology and histology. Twenty‐eight patients enrolled. The average age of the cohort was 37.7 ± 10.4 years; 75% of subjects were male. The sensitivity of cytology was 67–69% at the proximal esophagus and 70–72% at the distal esophagus. The specificity was 61–67% proximally and 70–75% distally. Histology was not significantly correlated with the max ratio of eosinophils/epithelial cells per hpf or the absolute number of eosinophils on cytology slides. Cytology using esophageal brushing has limited sensitivity and specificity for the detection of esophageal mucosal eosinophilia. The presence of exudates on endoscopy increased the detection of eosinophilia, which could make cytology useful in pediatric EoE, which often has a more exudative presentation. Diagnostic yield may improve with alternative acquisition techniques or the incorporation of eosinophil degranulation proteins.     

Clinical features of eosinophilic esophagitis: Ten Japanese cases

Aim: We studied eosinophilic esophagitis (EE) to clarify the clinical and endoscopic features of a Japanese case series. Methods: Records of 10 patients diagnosed with EE at our hospital between May 2010 and December 2011 were examined for age, sex, symptoms, allergic disorder, endoscopic findings, and treatment received. Esophageal wall thickness was measured by endoscopic ultrasonography (EUS). Results: Patients were seven males and three females with a mean age of 48 years. Symptoms included dysphagia, heartburn, food impaction, and chest pain. Nine patients had a history of allergic diseases. Increased peripheral eosinophil count was observed in one patient whereas increased immunoglobulin E level was observed in eight patients. Endoscopic findings included longitudinal furrows in all patients, mucosal edema in nine patients, loss of vascular pattern in nine patients, white exudates in six patients, cobblestone‐like appearance in five patients, and concentric rings in three patients. EUS revealed thickening of the esophageal wall in one patient. Histopathological examination revealed eosinophilic infiltration (≥15 eosinophils/high‐powered field) in the esophageal epithelium of all patients. Treatment was required in six patients. Proton pump inhibitor (PPI) therapy was given as the first‐line treatment but was ineffective in four patients and effective in two patients. Steroid therapy was given to three patients unresponsive to PPI therapy and was effective. Conclusions: EE was common among relatively young men and was associated with allergic diseases. Longitudinal furrows were observed as the most characteristic endoscopic finding. Esophageal wall thickening was not commonly observed by EUS.     

Esophageal dilation: simple and effective treatment for adults with eosinophilic esophagitis and esophageal rings and narrowing

The goal of this article is to present the results of the long‐term treatment with esophageal dilation of a consecutive series of adults with eosinophilic esophagitis (EoE). EoE in adults is a disease of middle aged white males, with recurrent food impactions and dysphagia. The exact treatment of EoE is unknown due to the uncertainty of the pathogenesis. Currently, the long‐term follow‐up of adult EoE patients is limited. Sixteen consecutive adult patients (12 males/4 females between ages 27 and 58 years) with EoE underwent a detailed history and baseline upper gastrointestinal endoscopy (EGD) with multiple esophageal biopsies. Thirteen had esophageal dilation. Fifteen were on proton pump inhibitor (PPI) therapy. After dilation, one patient was treated with a restrictive diet. One patient took prn fluticasone. Most of the patients had allergy testing for food and aeroallergens. Follow‐up evaluation with similar testing was on average 22 months (range: 12–40 months). Six patients were not available for follow‐up. None of the remaining 10 patients had a food impaction; one required further esophageal dilation. Only two patients had intermittent dysphagia. The average dysphagia score decreased from 2.1 to 0.3 (P < 0.002). The average number of eosinophils at follow‐up was not significantly different from baseline (120 eosinophils/HPF proximally and 165 eosinophils/HPF distally (P= 0.75). The gross endoscopy findings were unchanged in all patients except one who normalized. A total of 62% and 75% of patients had positive tests for aeroallergens and food allergens, respectively. Over an average of two years, esophageal dilation provided excellent symptomatic relief among 10 adult EoE patients despite no improvement in the mucosal eosinophilia or gross endoscopic appearance.     

Redefining the role of lymphocytes in gastroesophageal reflux disease and eosinophilic esophagitis

Eosinophilic esophagitis (EoE) and reflux esophagitis (RE) overlap clinically and histologically. RE is characterized by epithelial infiltration with small numbers of neutrophils and eosinophils, EoE by a prominent eosinophilic infiltrate. Lymphocytic esophagitis (LE), a new entity characterized by peripapillary lymphocytosis, questions the role lymphocytes play in esophageal inflammation. We test the hypothesis that lymphocyte infiltration in RE differs from EoE. One blinded pathologist read esophageal biopsies from 39 RE and 39 EoE patients. Both groups demonstrated significant numbers of lymphocytes (RE 22.7 ± 2.2/HPF, EoE 19.8 ± 1.8/HPF). Eosinophils/HPF in RE and EoE were 2.8 ± 0.7 and 74.9 ± 8.2, respectively (P < 0.001). Neutrophils were uncommon in RE (0.26 ± 0.16/HPF) and EoE (0.09 ± 0.04; P = 0.07). Eight of the 39 RE specimens had ≥50 lymphocytes in ≥1 HPF. Two were consistent with LE. There was an inverse correlation between numbers of eosinophils and lymphocytes in EoE (R = ?0.47; P = 0.002), and no correlation between them in RE (R = 0.18; P = 0.36). The patients with EoE who used antireflux medications had fewer lymphocytes (16.3 ± 1.3 vs 22.2 ± 2.3/HPF; P = 0.030) and eosinophils (55.6 ± 5.2 vs 76.0 ± 8.7/HPF; P = 0.042) than those who did not. The pathological role of lymphocytes in RE and EoE may be underestimated. Our observation that 5% of the RE specimens meet histopathological criteria for LE potentially blurs the line between these entities. The observation that eosinophil counts are lower in EoE when antireflux meds are used supports the notion that reflux plays a role in the clinical expression of EoE.     

Gender is a determinative factor in the initial clinical presentation of eosinophilic esophagitis

Eosinophilic esophagitis (EoE) is a chronic, immune‐mediated disease resulting in symptoms of esophageal dysmotility. Abnormalities include dysphagia, food impaction and reflux. Although men appear to comprise a majority of the EoE population, few studies have directly assessed gender‐associated clinical differences. The aim of this study is to identify the effect of gender on the initial clinical presentation of adult‐onset EoE patients. We reviewed our electronic medical record database from January 2008 to December 2011 for adults diagnosed with EoE per the 2011 updated consensus guidelines. Patient demographics, presenting symptoms, endoscopy findings and complications were recorded. Proportions were compared using chi‐squared analysis, and means were compared using the Student's t‐test. A total of 162 patients met the inclusion criteria and 71 (44%) were women. Women were more likely to report chest pain (P = 0.03) and heartburn (P = 0.06), whereas men more commonly reported dysphagia (P = 0.04) and a history of food impaction (P = 0.05). Endoscopic findings were similar between groups. No patients suffered esophageal perforations. These data suggest that men report more fibrostenotic symptoms and women report more inflammatory symptoms at the time of diagnosis. There was no difference in endoscopic findings between genders. This is one of the only reviews comparing differences in clinical presentation, endoscopic findings and complications between gender for EoE. The current recommended guidelines state that any patient with symptoms of esophageal dysfunction should be biopsied for EoE. Our findings support biopsying patients with typical and atypical symptoms of dysmotility including heartburn and chest pain.     

Administrative coding is specific,but not sensitive,for identifying eosinophilic esophagitis

The use of administrative databases to conduct population‐based studies of eosinophilic esophagitis (EoE) in the United States is limited because it is unknown whether the International Classification of Diseases, Ninth Revision (ICD‐9) code for EoE, 530.13, accurately identifies those who truly have the disease. The aim of this retrospective study was to validate the ICD‐9 code for identifying cases of EoE in administrative data. Confirmed cases of EoE as per consensus guidelines (symptoms of esophageal dysfunction and ≥ 15 eosinophils per high‐power field on biopsy after 8 weeks of twice daily proton pump inhibitor therapy) were identified in the University of North Carolina (UNC) EoE Clinicopathologic Database from 2008 to 2010; 2008 was the first year in which the 530.13 code was approved. Using the Carolina Data Warehouse, the administrative database for patients seen in the UNC system, all diagnostic and procedure codes were obtained for these cases. Then, with the EoE cases as the reference standard, we re‐queried the Carolina Data Warehouse over the same time frame for all patients seen in the system (n = 308 372) and calculated the sensitivity and specificity of the ICD‐9 code 530.13 as a case definition of EoE. To attempt to refine the case definition, we added procedural codes in an iterative fashion to optimize sensitivity and specificity, and restricted our analysis to privately insured patients. We also conducted a sensitivity analysis with 2011 data to identify trends in the operating parameters of the code. We identified 226 cases of EoE at UNC to serve as the reference standard. The ICD‐9 code 530.13 yielded a sensitivity of 37% (83/226; 95% confidence interval: 31–43%) and specificity of 99% (308 111/308 146; 95% confidence interval: 98–100%). These operating parameters were not substantially altered if the case definition required a procedure code for endoscopy or if cases were limited to those with commercial insurance. However, in 2011, the sensitivity of the code had increased to 61%, while the specificity remained at 99%. The ICD‐9 code for EoE, 530.13, had excellent specificity for identifying cases of EoE in administrative data, although this high specificity was achieved at an academic center. Additionally, the sensitivity of the code appears to be increasing over time, and the threshold at which it will stabilize is not known. While use of this administrative code will still miss a number of cases, those identified in this manner are highly likely to have the disease.