Identification of Clinical and Laboratory Markers for

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Ulrike von Arnim a Thomas Wex a Friedrich-W. Röhl b Helmut Neumann a. Dörthe Küster c Jochen Weigt a Klaus Mönkemüller a Peter Malfertheiner a.
Original Paper Received: March 28, 2011 Accepted: July 22, 2011 Published online: November 9, 2011

Digestion 2011;84:323–327 DOI: 10.1159/000331142

Identification of Clinical and Laboratory Markers for Predicting Eosinophilic Esophagitis in Adults Ulrike von Arnim a Thomas Wex a Friedrich-W. Röhl b Helmut Neumann a Dörthe Küster c Jochen Weigt a Klaus Mönkemüller a Peter Malfertheiner a a

Department of Gastroenterology, Hepatology and Infectious Diseases, and Institutes of b Biometrics and Medical Informatics, and c Pathology, Otto von Guericke University, Magdeburg, Germany

Key Words Eosinophilic esophagitis  Gastroesophageal reflux disease  Pre-endoscopic marker constellation

Abstract Background: The diagnosis of eosinophilic esophagitis (EoE) and differentiation from gastroesophageal reflux disease (GERD) is potentially challenging and is based upon clinical signs and endoscopic and histological features. In order to alert the endoscopist to consider EoE in patients with esophageal symptoms before performing esophagogastroduodenoscopy, we aimed to identify a set of clinical and laboratory markers for predicting EoE. Methods: The study included 43 patients with either EoE (n = 23) or GERD (n = 20). The diagnosis of EoE was based on International Consensus Criteria. Age, gender, weight loss, history of atopy, dysphagia, history of food impaction, proton pump inhibitor (PPI) refractory heartburn, odynophagia, peripheral eosinophilia, and serum IgE were analyzed. Each symptom or sign was classified as ‘0’ (absent, normal) or ‘1’ (present, elevated), individually analyzed and statistically evaluated among the two groups of patients. Logistic regression analysis was carried out to identify a clinically applicable marker constellation to differentiate EoE from GERD. Results: Univariate analysis identified 6 out of the 10 variables to be significant between both groups. A stepwise procedure of logistic regression led to a model in which 3 out of the initial 10 items were found to be

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relevant for differentiating GERD and EoE. Derived from this model, an optimal differentiation was achieved by using the following simplified equation: peripheral eosinophilia + history of food impaction + PPI refractory heartburn leading to a maximal value of 3 (1 + 1 + 1). Based on a cut-off value of 62, sensitivity and specificity for diagnosing EoE were 91 and 100%, respectively. Conclusion: A defined set of markers including two clinical features and one laboratory parameter is highly predictive of EoE and thus allows physicians to distinguish EoE from GERD even before upper gastrointestinal endoscopy is performed. Copyright © 2011 S. Karger AG, Basel

Introduction

Eosinophilic esophagitis (EoE) is an emerging clinicopathologic condition with a rapidly increasing prevalence [1, 2]. EoE is defined as a chronic, immune/antigen-mediated esophageal disease characterized clinically by symptoms related to esophageal dysfunction and histologically by predominant eosinophilic inflammation of the esophageal mucosa [3] (115 eosinophils per highpower field). Other regions of the upper gastrointestinal tract are usually not affected. Clinically, adults suffering from EoE present with symptoms such as dysphagia for solids [4, 5], retrosternal/ chest pain or ‘refractory’ heartburn and food impaction Ulrike von Arnim, MD Department of Gastroenterology, Hepatology and Infectious Diseases Otto von Guericke University, Magdeburg, Leipziger Strasse 44 DE–39120 Magdeburg (Germany) Tel. +49 391 671 3151, E-Mail ulrike.vonarnim @ med.ovgu.de

Table 1. Demographic data of patients stratified to the clinical diagnosis

Variable

EoE (n = 23)

GERD (n = 20)

p value (Fisher’s test or t test)

Male/female Mean age 8 SD (range), years PPI medication1

16/7 (69.6%) 40.26814.42 (24–69) 20/212

11/9 (55.0%) 56.31816.2 (19–86) 18/193

0.361 0.002 0.585

1

Two weeks prior to diagnosis or anamestic treatment trial. 2 Data not available for 2 patients. 3 Data not available for 1 patient.

[6, 7]. However, other disorders such as gastroesophageal reflux disease (GERD) can present with similar symptoms [3, 7]. The first case of EoE was reported in a patient with vigorous achalasia [9]. Since clinical suspicion of EoE requires histological confirmation, esophageal biopsies are mandatory [3, 8]. The endoscopic features of EoE are variable ranging from subtle mucosal changes to the ‘characteristic’ signs such as longitudinal furrows, white Candida-like speckles, crêpe paper mucosa, small-caliber esophagus, longitudinal shearing, friability, edema and ringed esophagus (i.e. ‘feline esophagus’) [10–13]. However, endoscopic findings are neither specific for EoE nor present in all individuals with EoE [8–14]. In a careful study of endoscopic features of EoE, 42% of patients with EoE did not present the ‘classical’ endoscopic features [14] which underline the need for obtaining a sufficient number of biopsies for histological confirmation of EoE [8–14]. In routine practice a missed histopathological investigation leads to a significant delay in the diagnosis of EoE [15, 16]. The aim of this study was to evaluate various clinical and laboratory values, and to identify a simple, clinically applicable, marker set that could predict the presence of EoE and thus alert the endoscopist performing endoscopy to pay additional attention to esophagus mucosal examination, including the retrieval of sufficient biopsies to rule in or out the diagnosis of EoE. Materials and Methods The study was conducted and carried out in accordance and approval of the local ethical committee of Otto von Guericke University, Magdeburg, Germany. Patients Patients (118 years old) were enrolled at our outpatient department between December 2005 and May 2007, retrospectively (EoE n = 11, GERD n = 8), and from June 2007 and March 2010, prospectively (EoE n = 12, GERD n = 10).

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Digestion 2011;84:323–327

Table 2. Clinical and laboratory parameters stratified to the clin-

ical diagnosis Signs/symptoms

EoE (n = 23)

GERD (n = 20)

Weight loss History of atopy History of food impaction PPI refractory heartburn Dysphagia Odynophagia IgE elevation Peripheral eosinophilia

1 18 20 18 21 3 19 19

3 5 2 4 4 0 2 0

p value 0.324 0.001