Eosinophilic esophagitis (EoE) is a chronic, inflammatory allergic disorder of the esophagus caused by the ingestion of food allergens such as wheat, milk, egg or soy. The concept of EoE being an allergic disease, activated by food allergens, is further supported by the fact that a diet in which the aforementioned food allergens are eliminated is effective in children and adults.1,2 However, the exact mechanism by which foods can exacerbate EoE is yet to be defined.
The worldwide incidence of EoE has increased considerably since it was first described as a new disease in 1993.2,3 Although subjects of all ages can be affected, EoE typically presents in males (70%) between 20 and 40 years of age.4 Over the last twenty years, EoE transited from being a very rare disease towards the most common causes of dysphagia (the inability to swallow solid foods) in adolescents and young adults.5 The disease is characterized by symptoms of esophageal dysfunction and vary by age of presentation. Dysphagia and food impactions are typical for adults whereas children typically present with a wide variety of symptoms such as failure to thrive, food refusal, abdominal pain and vomiting.6 This progression from feeding difficulties in young children to dysphagia and bolus impaction in adolescents may be a reflection of the progression of the disease. Especially since it has been proven that prolonged untreated disease with continues inflammation may result in severe narrowing of the esophagus.
The first step in the diagnostic pathway of EoE is to perform a gastroscopy, a procedure where a thin, flexible camera (an endoscope) is used to examine the esophagus and/or stomach. Endoscopic findings that are associated with EoE are narrow rings (strictures) of the esophagus, white exudates, decreased vascularity (edema) or longitudinal furrows, figure 1.
Subsequently if EoE is suspected, esophageal tissue is sampled and examined under a microscope. The study and diagnosis of EoE through the examination of endoscopically removed organs esophageal tissues is called pathology. EoE is diagnosed if the esophageal tissue is infiltrated with multiple eosinophilic granulocytes.
EoE has remained unnoticed for decades, but since its recognition in the early 90s awareness increased substantially, and the worldwide incidence and prevalence in both children and adults has risen extremely rapidly.3 The annual prevalence of EoE in the United States is estimated to be 31 per 100,000 inhabitants which is considerably higher when compared with the annual European incidence rates of 16 per 100,000 inhabitants.3 Nevertheless, with current incidences, EoE can no longer be designated as a rare disease. However, it remains unknown whether the EoE epidemic is caused by a true increase in disease or by the growing number of performed gastroscopic procedures over the last decades. In the Netherlands, all pathology reports are stored in the Dutch national pathology database. This unique nationwide coverage enabled us to accurately estimate the incidence of EoE in the Netherlands over the past two decades and, to determine whether the incidence is influenced by expanding gastroscopy rates.
In total we could identify 2161 patients with EoE of which 1574 (73%) were males and 365 (17%) were children. The mean age at diagnosis for adults was 38 years and for children 10 years. EoE was diagnosed in all age groups but most patients (n=798) were diagnosed between 30 and 50 years of age. The incidence of EoE increased from 0.01 in 1996 to 2.07 per 100,000 inhabitants in 2015, which is an increase of more than 200 times. Incidence is the rate of newly diagnosed cases of the disease. The incidence was higher in males than in females, and higher in adults than in children. In comparison between 1996 and 2016, we observed only a 3.2- fold increase in gastroscopy rates, from 5473 in 1996 to 17702 in 2015. To facilitate a direct comparison with the number of newly diagnosed EoE patient per 100,000 inhabitants, we calculated that the amount of endoscopies with biopsy sampling rose from 30 per 100,000 in 1996 to 105 per 100,000 inhabitants in 2015. The results of this study demonstrated that the incidence of EoE has increased more than 200-fold over the past 20 years and still continues to rise. Whereas, within the same timeframe, we detected only a threefold increase in gastroscopy rates. Therefore we believe that there is a true increase in disease.
However, although the results of our study accurately show that the number of EoE patients in the Netherlands is rising, still many questions remain to be addressed. For instance, why is the incidence of EoE in the United States estimated so high whereas cases from Asia are very scarce (0.01 per 100,000 inhabitants)?7, 8 Presumably genetic and environmental/lifestyle influences play an important role in these geographic incidence differences. The rising incidence could be the result of effects of a “modern lifestyle” for several reasons. First, the increase of EoE coincides simultaneously with the expansion of other allergic diseases such as eczema or asthma over the past decades.9 This sudden increase can be linked to a declined early life exposure to infectious agents / micro-organisms in excessive hygienic environments – the hygiene hypothesis.10 Second, early-life events associated with a modern lifestyle, such as the use of antibiotics and formula feeding in infancy and caesarean delivery have all been positively associated with EoE.11 Finally, dietary changes associated with a western lifestyle including increased sugar and fat intake have been associated with the rise in several allergic diseases and may possibly play also an allergy provoking role in EoE.13,14 Nevertheless, all aforementioned theories are speculative, and more research is warranted to directly correlate these theories to the rising incidence of EoE.
Another topic of debate is whether the gradual increasing incidence of EoE is based on a true expansion of the disease or whether it is a byproduct of the increased recognition of EoE by general practitioners and gastroenterologists. Although we described in our study that the incidence rates outpaced the incidence of endoscopy with biopsy sampling rates, we did not investigate the actual disease awareness among doctors. Despite the fact that significant progress has been made in disease detection, we believe that there is still room for improvement. Healthy organizations should therefore further stimulate awareness, not only among physicians but also among patients, to stimulate better disease recognition and early treatment.
- Lucendo AJ, Molina-Infante J, Arias A, et al. Guidelines on eosinophilic esophagitis: evidence-based statements and recommendations for diagnosis and management in children and adults. United Eur Gastroenterol J. 2017;1:1-24.
- Kelly KJ, Lazenby AJ, Rowe PC, et al. Eosinophilic esophagitis attributed to gastroesophageal reflux: Improvement with an amino acid-based formula. Gastroenterology. 1995;109(5):1503-1512.
- Attwood SEA, Smyrk TC, Demeester T, et al. Esophageal Eosinophilia with Dysphagia A Distinct Clinicopathologic Syndrome. 1993;38(1):109-116.
- Arias Á, Pérez-Martínez I, Tenías JM, et al. Systematic review with meta-analysis: the incidence and prevalence of eosinophilic oesophagitis in children and adults in population-based studies. Aliment Pharmacol Ther. 2016;43(1):3-15.
- Dellon ES, Jensen ET, Martin CF, et al. Epidemiology of eosinophilic esophagitis. Gastroenterol Clin North Am 2014;43:201–18.
- Krishnamurthy C, Hilden K, Peterson K a, et al. Endoscopic findings in patients presenting with dysphagia: analysis of a national endoscopy database. Dysphagia. 2012;27(1):101-105.
- Straumann A, Aceves SS, Blanchard C, et al. Pediatric and adult eosinophilic esophagitis: similarities and differences. Allergy. 2012;67(4):477-490.
- Dellon ES, Erichsen R, Baron JA, et al. The increasing incidence and prevalence of eosinophilic esophagitis outpaces changes in endoscopic and biopsy practice: National population-based estimates from denmark. Aliment Pharmacol Ther. 2015 Apr;41(7):662-70.
- Ngiu CS, Low SF. Meta-analysis and systemic review of prevalence of eosinophilic esophagitis in Asia. J Gastroenterol Hepatol. 2012;27:325.
- Perez Alzate D, Somoza ML, Blanca-Lopez N, et al. Epidemiologyc features in patients with food allergy in an area population from Madrid. Allergy Eur J Allergy Clin Immunol. 2014;69:395.
- Okada H, Kuhn C, Feillet H, et al. The “hygiene hypothesis” for autoimmune and allergic diseases: an update. Clin Exp Immunol. 2010;160(1):1-9.
- Jensen ET, Kappelman MD, Kim HP, et al. Early life exposures as risk factors for pediatric eosinophilic esophagitis. J Pediatr Gastroenterol Nutr. 2013;57(1):67-71.
- Elitsur Y, Alrazzak BA, Demetieva Y. Does helicobacter pylori protects against eosinophilic esophagitis in children? Helicobacter. 2013;18:117.
- Brigham EP, Kolahdooz F, Hansel N, et al. Association between Western diet pattern and adult asthma: a focused review. Ann Allergy, Asthma Immunol. 2015;114(4):273-280.
- Vlieg-Boerstra BJ, de Kroon MJ, Warners MJ et al. Dietary Intake, Inflammation And Mucosal Integrity In Adult Patients With Eosinophilic Esophagitis. J Allergy Clin Immunol. 2017;1.