J. A. Alexander

Epidemiology of Eosinophilic Esophagitis Over Three Decades in Olmsted County, Minnesota

BACKGROUND & AIMS Data on secular trends and outcomes of eosinophilic esophagitis (EE) are scarce. We performed a population-based study to assess the epidemiology and outcomes of EE in Olmsted County, Minnesota, over the last 3 decades. METHODS All cases of EE diagnosed between 1976 and 2005 were identified using the Rochester Epidemiology Project resources. Esophageal biopsies with any evidence of esophagitis and/or eosinophilic infiltration were reviewed by a single pathologist. Clinical course (treatment, response, and recurrence) was defined using information collected from medical records and prospectively via a telephone questionnaire. Incidence rates per 100,000 person years were directly adjusted for age and sex to the US 2000 population structure. RESULTS A total of 78 patients with EE were identified. The incidence of EE increased significantly over the last 3 of the 5-year intervals (from 0.35 [95% confidence interval (CI)], 0-0.87] per 100,000 person-years during 1991-1995 to 9.45 [95% CI, 7.13-11.77] per 100,000 person-years during 2001-2005). The prevalence of EE was 55.0 (95% CI, 42.7-67.2) per 100,000 persons as of January 1, 2006, in Olmsted County, Minnesota. EE was diagnosed more frequently in late summer/fall. The clinical course of patients with EE was characterized by recurrent symptoms (observed in 41% of patients). CONCLUSIONS The prevalence and incidence of EE is higher than previously reported. The incidence of clinically diagnosed EE increased significantly over the last 3 decades, in parallel with endoscopy volume. Seasonal incidence was greatest in late summer and fall. EE also appears to be a recurrent relapsing disease in a substantial proportion of patients.

Prevalence and Predictive Factors of Eosinophilic Esophagitis in Patients Presenting With Dysphagia: A Prospective Study

OBJECTIVES:Eosinophilic esophagitis (EE) is an increasingly recognized cause of dysphagia. We prospectively assessed the prevalence of EE using midesophageal biopsies in patients presenting with no endoscopically evident cause of dysphagia. We also aimed to determine the clinical and endoscopic factors predictive of EE in outpatients undergoing endoscopy for dysphagia.METHODS:Outpatients (18–60 yr of age) undergoing endoscopy for dysphagia at Mayo Clinic, Rochester between June 2005 and June 2006 were enrolled. Patients completed the validated Mayo Dysphagia Questionnaire (MDQ). Biopsies were obtained from the midesophagus if there was no endoscopically evident cause of dysphagia or there were endoscopic findings suggestive of EE. EE was defined as the presence of >20 eosinophils/high-power field. Logistic regression was performed to identify predictors of EE.RESULTS:Of 376 patients enrolled, 238 (63%) completed the MDQ and 222 (59%) had midesophageal biopsies; 33 (15%, 95% CI 6%–12%) had EE by biopsy. Ten of 102 (9.8%) patients who appeared endoscopically normal had EE by biopsy, while 8 of 21 (38%) patients with endoscopic changes suggestive of EE had EE on biopsy. Predictors of EE were younger age, endoscopic features suggestive of EE, absence of use of proton pump inhibitors, and a history of any food impaction for greater than 5 min.CONCLUSIONS:Midesophageal biopsies from normal-appearing mucosa should be obtained in all patients with unexplained solid food dysphagia; this may diagnose EE in about one in 10 cases.

Allergen-Specific In Vitro Cytokine Production in Adult Patients with Eosinophilic Esophagitis

Although the pathogenesis of eosinophilic esophagitis (EE) likely involves hypersensitivity reactions against exogenous allergens, allergen-specific cellular immune responses have not been studied. We investigated allergen-induced cytokine production by peripheral blood mononuclear cells (PBMCs) in adult patients with EE (n=15) and healthy controls (HC; n=9). PBMCs were incubated with nine common food and environmental allergens or a nonspecific mitogen, and the levels of interleukin (IL)-5, IL-10, IL-13, and interferon-γ in the cell-free supernatants were determined. Spontaneous and mitogen-stimulated cytokine production did not differ between EE and HC. House dust mite, ragweed, Aspergillus, milk, and soy induced significantly higher IL-5 production in EE (P < 0.05). House dust mite also augmented IL-13 production in EE (P < 0.05). Furthermore, PBMCs from three EE patients without allergen-specific IgE vigorously produced IL-5 and IL-13 on allergen stimulation. Thus, immune responses in EE are characterized by enhanced production of Th2-like cytokines against both food and environmental allergens.

Results of ambulatory pH monitoring do not reliably predict response to therapy in patients with eosinophilic oesophagitis

Aliment Pharmacol Ther 2012; 35: #–#

Validation of the Mayo Dysphagia Questionnaire

While multiple instruments characterize upper gastrointestinal symptoms, a validated instrument devoted to the measurement of a spectrum of esophageal dysphagia attributes is not available. Therefore, we constructed and validated the Mayo Dysphagia Questionnaire (MDQ). The 27 items of the MDQ underwent content validity, feasibility, concurrent validity, reproducibility, internal consistency, and construct validity testing. To assess content validity, five esophageal subspecialty gastroenterologists reviewed the items to ensure inclusion of pertinent domains. Feasibility testing was done with eight outpatients who refined problematic items. To assess concurrent validity, 70 patient responses on the MDQ were compared to responses gathered in a structured patient-physician interview. A separate group of 70 outpatients completed the MDQ twice to assess the reproducibility of each item. A total of 148 patients participated in the validation process (78 [53%] men; mean age 62). On average, the MDQ took 6 minutes to complete. A single item (odynophagia) tested poorly with a kappa value of <0.4. Otherwise, the majority of concurrent validity kappa values were in the good to excellent range with a mean of 0.63 (95% CI 0.22-0.89). The majority of reproducibility kappa values were also in the good to excellent range with a median kappa value of 0.76 (interquartile range: 0.67-0.81). Cronbachs alpha values were excellent in the range of 0.86-0.88. Spearman rank correlation coefficients to assess construct validity were also excellent in the range of 0.87-0.98. Thus, the MDQ is a concise instrument that demonstrates overall excellent concurrent validity, reproducibility, internal consistency, and construct validity for the features of esophageal dysphagia.

Oesophageal narrowing is common and frequently under-appreciated at endoscopy in patients with oesophageal eosinophilia.

Estimation of the prevalence of oesophageal narrowing and its clinical relevance in patients with oesophageal eosinophilia is probably underestimated by endoscopy.

Supraesophageal Reflux: Validation of a Symptom Questionnaire

OBJECTIVES: To develop and validate a questionnaire for supraesophageal manifestations of reflux (SER) that will facilitate its study in clinical and research settings. STUDY DESIGN: The Supraesophageal Reflux Questionnaire (SERQ) and previously validated Reflux Symptom Index (RSI) were subjected to multiple types of validity testing, including content validity, concurrent validity, reproducibility, and predictive validity. RESULTS: The concurrent validity and reproducibility of both instruments was good to excellent for most items tested. The predictive validity of the SERQ was superior to the RSI when it included the covariates of history of sinusitis, use of over-the-counter antacid medications, age, gender, and body mass index. CONCLUSIONS: The SERQ will serve as both a useful clinical and research tool by offering not only SER symptom information, like the RSI, but also information about the patients medical history and medication usage that will facilitate use of the SERQ in research protocols. EBM rating: B-2b

An allergic phenotype and the use of steroid inhalers predict eosinophilic oesophagitis in patients with asthma

Patients with eosinophilic oesophagitis (EoE) commonly have asthma and atopy.

Presence of intraepithelial food antigen in patients with active eosinophilic oesophagitis

Although eosinophilic oesophagitis (EoE) is putatively mediated by an abnormal response to food antigen, the oesophagus is considered relatively impermeable to large molecules.

Oesophageal narrowing on barium oesophagram is more common in adult patients with eosinophilic oesophagitis than PPI-responsive oesophageal eosinophilia

To date there have been no clear features that aid in differentiating patients with eosinophilic oesophagitis (EoE) from PPI‐responsive oesophageal eosinophilia (PPI‐REE). However, barium swallow roentgenography is a more sensitive and specific measure to detect subtle fibrostenotic remodeling changes present in EoE. We aim to characterise any clinical, endoscopic, histiological or barium roentgenographic differences between EoE and PPI‐REE.