Epidemiology of Eosinophilic Esophagitis

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1		Jakub Wąsik	--	987	2023-04-11 12:15:05	\|
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This entry is adapted from the peer-reviewed paper 10.3390/jcm12062259

Eosinophilic esophagitis is a Th-2 antigen-mediated disease in which there is an influx of eosinophils to all layers of the esophagus, triggering an inflammatory response. Chronic inflammatory process causes esophageal remodeling, leading to difficulties in swallowing. Food impaction, heartburn, and chest pain are other characteristic (but not pathognomonic) symptoms in adults.

eosinophilic esophagitis esophagus endoscopy GI inflammation

1. Introduction

Eosinophilic esophagitis (EoE) is a chronic inflammatory disease. The first cases of EoE were described in the 1970s ^[1]^[2]. Although half a century will soon have passed since its initial description, we still have many unknowns.

The literature describes an increasing incidence of EoE in recent decades, consisting of approximately five to ten new cases per 100,000 inhabitants annually for both children and adults ^[3]. This consequently contributes to the growing prevalence, which was 15.4 per 100,000 inhabitants before 2007 and has already reached 63.2 per 100,000 inhabitants since 2017 ^[3].

The etiopathogenesis of this disease has not yet been fully elucidated. Regarding risk factors, we still rely on individual reports. The factors that have been extensively studied in recent years are place of residence, race, gender, and age.

The current data show that the immune cells present in the esophagus, which are hyperstimulated by antigens (for example, food antigens), release numerous pro-inflammatory cytokines such as interleukin (IL)-4, IL-5, and IL-13 ^[4]. This drives the entire mechanism of the disease as eosinophils are recruited to stimulate a further inflammatory response ^[5]. As a result of chronic esophagitis, subepithelial fibrous remodeling occurs. If uncontrolled, this may adversely affect the esophagus, leading to motor disorders, dysphagia, and the formation of strictures, which may eventually lead to food bolus impaction ^[6].

The disease may occur at any age. Risk factors for EoE include the being male, Caucasian, and having an atopic disorder such as rhinitis or asthma ^[7]. Currently, EoE is the second-most prevalent cause of chronic esophagitis after gastroesophageal reflux disease (GERD) ^[8]. It is worth mentioning that this disease is now the most common cause of esophageal food bolus impactions in patients presenting to emergency departments ^[9]. EoE is associated with impaired quality of life in many domains, not necessarily due to the disease symptoms ^[10].

2. Epidemiology

It is difficult to provide accurate data on the epidemiology of EoE because the reported data vary. In a 2019 systematic review with a meta-analysis by Navarro et al., which collected data on the prevalence and incidence of EoE in the general population, the prevalence of EoE was 34.2 cases per 100,000 inhabitants ^[11]. In the same study, the overall incidence rate was 4.4 new cases of EoE per 100,000 inhabitants/year ^[11]. EoE occurs three times more often in men than in women, but there are no sex differences concerning the severity of the disease ^[12]^[13]. A study conducted by Schreiner et al. in Swiss patients showed that although the incidence is much higher in men and they had more severe endoscopic changes, their Eosinophilic Esophagitis Activity Index (EEsAI) and EoE-specific quality of life (EoE-QoL-A) were not different from those measured in women ^[14]. In a study in the Dutch population from 1995 to 2019, the mean age at diagnosis in adults was 42.9 ± 15.4 years, which was significantly later in women compared to men (44.5 ± 16.5 years vs. 42.2 ± 14.8 years; p < 0.001) ^[13].

Overall, it can be seen that there is an increasing trend of incidence and prevalence ^[9]^[11]^[15]. In the Netherlands, the incidence rates rose from 0.01 (95% CI: 0.0–0.04) new cases per 100,000 inhabitants in 1995 to 3.16 (95% CI: 2.90–3.44) new cases per 100,000 inhabitants in 2019 ^[13]. Regarding prevalence, the data are very divergent: from 2.3/100,000 in Denmark to 90.7/100,000 in Ohio ^[9]. However, it can be assumed that the frequency of EoE is higher in Western countries than in the East ^[8]^[9]. EoE is most common among Caucasians ^[15]. In a pediatric population, a study conducted by Zdanowicz et al. in northeastern Poland demonstrated that the average annual incidence rate of EoE was 2.83 cases per 100,000 children between 2013 and 2018 ^[16]. In some centers, the frequency may be higher, as demonstrated in a study of Jordanian children between 2015 and 2020 in which 3% of patients were diagnosed with EoE ^[17].

Although there are many descriptions of increasing prevalence and incidence in the literature, to the best of current knowledge there was only one study on mortality in EoE. In a nationwide, population-based matched cohort study in Sweden, there were 1625 patients diagnosed with EoE over 12 years (2005–2017) ^[18]. In the EoE group, there were 4.6 deaths per 1000 person-years, similar to 4.57 deaths per 1000 person-years in population comparators (HR = 0.97, 95% CI = 0.67–1.40). There was also no association with higher mortality from cancer or cardiovascular diseases. Additionally, mortality rates in patients with EoE did not demonstrate a difference between sexes. These results may be reassuring, although more population studies are needed to draw further conclusions.

An interesting issue is the seasonality of the morbidity and severity of symptoms. There was no correlation between the season of the year and the number of newly diagnosed patients in the Dutch study ^[13]. However, according to studies conducted on children in the United States, 45% of the cases were diagnosed in the spring ^[19]. Moreover, in an American study on the seasonal exacerbation of EoE in adults and children, 71% of cases occurred in the fall and summer months ^[20]. In those patients, typical rings (92% vs. 35%; p = 0.001) and strictures (62% vs. 22%; p = 0.002) were detected more often in an upper G.I. endoscopy. Consequently, they were associated with a worse EoE Endoscopic Reference Score (EREFS), a classification system of endoscopy findings in EoE which will be discussed in more detail later in this article (1.7 vs. 3.7; p = 0.01) ^[20].

Another study from the United States, conducted in Nevada between 2013 and 2017, showed that in follow-up testing, individuals living in the northern region of the state experienced 1.95 higher odds of an EoE visit when compared to their southern counterparts (OR = 1.95, 95% CI: 1.68, 2.26, p < 0.001) ^[21]. This may be connected to the dry climate of Nevada, which has a longer pollen season and differs significantly from the mild climate of the Netherlands ^[21]. Among children from northeastern Poland, seasonal allergies were observed in 23.08% of children with EoE compared to 8.82% in children without EoE (p = 0.005). The incidences of food allergies in children with or without EoE were similar: 11.1% vs. 2.52%, respectively (p = 0.005) ^[16].

References

Teele, R.; Katz, A.; Goldman, H.; Kettell, R. Radiographic features of eosinophilic gastroenteritis (allergic gastroenteropathy) of childhood. Am. J. Roentgenol. 1979, 132, 575–580.
Dobbins, J.W.; Sheahan, D.G.; Behar, J. Eosinophilic Gastroenteritis with Esophageal Involvement. Gastroenterology 1977, 72, 1312–1316.
Arias, Á.; Lucendo, A.J. Epidemiology and risk factors for eosinophilic esophagitis: Lessons for clinicians. Expert Rev. Gastroenterol. Hepatol. 2020, 14, 1069–1082.
Racca, F.; Pellegatta, G.; Cataldo, G.; Vespa, E.; Carlani, E.; Pelaia, C.; Paoletti, G.; Messina, M.R.; Nappi, E.; Canonica, G.W.; et al. Type 2 Inflammation in Eosinophilic Esophagitis: From Pathophysiology to Therapeutic Targets. Front. Physiol. 2022, 12, 815842.
Khokhar, D.; Marella, S.; Idelman, G.; Chang, J.W.; Chehade, M.; Hogan, S.P. Eosinophilic esophagitis: Immune mechanisms and therapeutic targets. Clin. Exp. Allergy 2022, 52, 1142–1156.
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Dellon, E.S.; Hirano, I. Epidemiology and Natural History of Eosinophilic Esophagitis. Gastroenterology 2018, 154, 319–332.e3.
Chang, J.W.; Haller, E.; Dellon, E.S. Dietary Management of Eosinophilic Esophagitis: Man Versus Food or Food Versus Man? Gastroenterol. Clin. N. Am. 2021, 50, 59–75.
Navarro, P.; Arias, Á.; Arias-González, L.; Laserna-Mendieta, E.J.; Ruiz-Ponce, M.; Lucendo, A.J. Systematic review with meta-analysis: The growing incidence and prevalence of eosinophilic oesophagitis in children and adults in population-based studies. Aliment. Pharmacol. Ther. 2019, 49, 1116–1125.
Lipowska, A.M.; Kavitt, R.T. Demographic Features of Eosinophilic Esophagitis. Gastrointest. Endosc. Clin. N. Am. 2018, 28, 27–33.
de Rooij, W.E.; Barendsen, M.E.; Warners, M.J.; van Rhijn, B.D.; Verheij, J.; Bruggink, A.H.; Bredenoord, A.J. Emerging incidence trends of eosinophilic esophagitis over 25 years: Results of a nationwide register-based pathology cohort. Neurogastroenterol. Motil. 2021, 33, e14072.
Schreiner, P.; Safroneeva, E.; Rossel, J.-B.; Limacher, A.; Saner, C.; Greuter, T.; Schoepfer, A.; Straumann, A.; Biedermann, L. Sex Impacts Disease Activity but Not Symptoms or Quality of Life in Adults with Eosinophilic Esophagitis. Clin. Gastroenterol. Hepatol. 2022, 20, 1729–1738.e1.
Shaheen, N.J.; Mukkada, V.; Eichinger, C.S.; Schofield, H.; Todorova, L.; Falk, G.W. Natural history of eosinophilic esophagitis: A systematic review of epidemiology and disease course. Dis. Esophagus 2018, 31, doy015.
Zdanowicz, K.; Kucharska, M.; Sobaniec-Lotowska, M.E.; Lebensztejn, D.M.; Daniluk, U. Eosinophilic Esophagitis in Children in North-Eastern Poland. J. Clin. Med. 2020, 9, 3869.
Altamimi, E.; Ahmad, B.; Abu-Aqoulah, A.; Rawabdeh, N. Clinico-pathological characteristics of eosinophilic esophagitis in Jordanian children. Gastroenterol. Rev. 2022, 16, 207–212.
Röjler, L.; Garber, J.J.; Roelstraete, B.; Walker, M.M.; Ludvigsson, J.F. Mortality in Eosinophilic Esophagitis—A nationwide, population-based matched cohort study from 2005 to 2017. Upsala J. Med. Sci. 2021, 126, e7688.
Suryawala, K.; Palle, S.; Altaf, M.A. Epidemiology, Clinical Presentation, and Seasonal Variation in the Diagnosis of Children with Eosinophilic Esophagitis in Oklahoma. South. Med. J. 2020, 113, 37–41.
Reed, C.C.; Iglesia, E.G.; Commins, S.P.; Dellon, E.S. Seasonal exacerbation of eosinophilic esophagitis histologic activity in adults and children implicates role of aeroallergens. Ann. Allergy Asthma Immunol. 2019, 122, 296–301.
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Jakub Wąsik

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Update Date: 13 Apr 2023

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1. Introduction

2. Epidemiology

References