Natural history of eosinophilic esophagitis: a systematic review of epidemiology and disease course

Abstract

Eosinophilic esophagitis is a chronic immune-mediated esophageal disorder. For its timely diagnosis, clinicians must recognize common symptoms, and understand differences in symptoms across patient groups. The aim of this study is to systematically review the epidemiology and natural history of eosinophilic esophagitis. The MEDLINE, Embase, and Cochrane databases were searched from 1974 to February 2017 for studies describing the epidemiology and natural history of eosinophilic esophagitis. Congress abstracts from 2014 to 2016 were also searched. Search results were screened against predetermined inclusion/exclusion criteria by two independent reviewers, and data extraction was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Of 1376 articles identified, 47 met the inclusion criteria: 20 on epidemiology and 27 on natural history. Incidence and prevalence of eosinophilic esophagitis varied widely across North America and Europe, and increased over time. Incidence increased 131-fold in the Netherlands (1996-2010), 20-fold in Denmark (1997-2006), and 5.1-fold in Calgary, Canada (2004-2008). The most commonly reported symptoms were emesis and abdominal pain in children, and dysphagia and food impaction in adults. Age at diagnosis was 5.9-12.0 years in children, and approximately 30 years in adults. Time between symptom onset and diagnosis was 1.2-3.5 years in children and 3.0-8.0 years in adults. Diagnostic delay was associated with an increased risk of endoscopic features of fibrostenosis. Symptoms of eosinophilic esophagitis differed significantly by age and race. In conclusion, there is an increasing incidence and prevalence of eosinophilic esophagitis. The considerable delay between symptom onset and diagnosis suggests that clinicians do not readily recognize the disease, which may have important clinical ramifications.

Fig. 1

PRISMA diagram of included and excluded studies. An initial systematic review covered the existing literature published until February 1, 2016. An update to the systematic review was carried out covering literature published from January 1, 2016 to February 27, 2017 (the searches were designed to overlap by 1 month to allow for indexing lag within the databases). The identified references from both searches are combined in this PRISMA diagram. PPI-R, proton pump inhibitor-resistant; PRISMA, Preferred Reporting Items for Systematic Reviews and Meta-Analyses.

Fig. 2

(a) Incidence and (b) prevalence of EoE. Representative data are presented for each country as incidence per 100 000/year and prevalence per 100 000. For each country where data are available, rates were taken either from the only study available (even if it relates only to a region) or from the study with the largest sample size. ^†Data relate to a region of this country. ^‡Age- and sex-adjusted values are reported. ^§Study population included children only. ^¶Study population included adults only. ^††For the USA, we represented data from Dellon et al.⁶ instead of Mansoor & Cooper¹³ owing to the use of more standard diagnostic criteria. EoE, eosinophilic esophagitis; NR, not reported; PY, person-years.

Fig. 3

(a) Incidence and (b) prevalence of EoE over time in populations that include both children and adults. Note that populations and methods of estimation were different in the presented studies. EoE, eosinophilic esophagitis.

Fig. 4

Prevalence of dysphagia in adults and children. Sample sizes (n) are shown to the right of each bar. Please note that the denominators of at risk populations from the studies presented in this figure may have different definitions, i.e. some populations may be highly symptomatic or selected. ^†Diagnostic criteria based on esophageal dysfunction or esophageal eosinophilia. ^‡Diagnostic criteria based on eosinophil count per high-power field. ^§Diagnostic criteria based on 2007 guidelines.^¶Diagnostic criteria based on SNOMED-CT diagnosis; no diagnostic codes were reported for any other study. ^††Data refer to dysphagia or food impaction. SNOMED-CT, Systematized Nomenclature of Medicine—Clinical Terms.

Fig. 5

Summary of data related to (a) age at diagnosis and (b) duration of symptoms at diagnosis in children and adults. Error bars show standard deviation (the standard deviation was not reported in all of the studies). Data on mean age at diagnosis were not reported for both children and adults.

Fig. 6

Symptoms by age category. This graph is based on data reported in Moawad et al.