Among children who underwent EGD for abdominal pain, the prevalence of EoE ranged from 2.1% to 4.9% (29–31), whereas the prevalence of EoE among children with celiac disease ranged from 1.1% to 5.1% (21–25). The prevalence of EoE among children post–liver transplantation were 2.4% and 3.0% (26,27). The only study evaluating the prevalence of EoE among children with UC reported a prevalence of 8.0% (28).
All population-based studies reported a male predominance (range 54%–83%) (8,14,16,19,35–37). The mean/median ages at diagnosis ranged from 6.0 to 10.5 years for population-based studies (8,16). In contrast, the mean age at diagnosis from a single study evaluating the prevalence of EoE among children with esophageal food impaction was 10.1 years (33). Personal history of atopy was found in 14% to 100% (8,16,20,25–27,32,33,35–37) and family history of atopy was present in 7% to 38% of children (8,20,32,35). No publication bias was observed among all subgroups using the Begg test: P = 0.19 (EGD for any indication) and P = 0.88 (EGD with histologic esophageal disease).
We present the first systematic review and meta-analysis of the incidence and prevalence of EoE in children. The population-based incidence rates of EoE in children varied by geographic region, ranging from 1.6 in Denmark (35) to 10 per 100,000 children per year in the United States (8). Likewise, the population-based prevalence varied by geographic region, with the most present reported rates ranging between 0.2 in United Kingdom (15), 8.9 in Australia (14) and 43 per 100,000 children in the United States (8). Similar to our findings, a recent systematic review of the epidemiology of EoE in adults demonstrated a wide variation in population-based prevalence ranging from 20 to 700/100,000 with a pooled prevalence of 30/100,000 individuals (11,12,38). In our systematic review, given that both studies in Australia and the United States were conducted in sole referral centers for the region from which the denominator population was determined, referral bias is less likely to contribute to variations in population-based prevalence; however, the variations may be because of differing distributions of ethnicity, sex, age groups, diagnostic criteria for EoE, and threshold to perform endoscopy and biopsy between study centers. In particular, because EoE is diagnosed endoscopically, detection of disease is largely driven by accessibility to endoscopy services, which may vary widely between regions depending on the presence and number of pediatric gastroenterologists along with wait times to assessment by gastroenterologists and to endoscopy. In addition, detection of EoE is affected by physician awareness and/or willingness to perform an EGD in a patient who presents with symptoms suggestive of EoE and whether a physician routinely obtains esophageal biopsies at the time of EGD regardless of macroscopic appearance of the esophagus.
During the last few decades, both incidence and prevalence increased significantly, with average annual percentage increases of 12% to 17% and 56%, respectively (8,19). The increased incidence of EoE over time in children may be because of a genuine increase in incidence, greater recognition of EoE, or higher use of diagnostic EGDs in children, with the wide variety of symptoms suggestive of EoE. In the study by DeBrosse et al (19), the authors reexamined esophageal biopsy specimens obtained between 1982 and 1999 and found that the proportion of biopsy specimens with ≥15 eosinophils/hpf remained stable in spite of a 40-fold increase in the number of biopsy specimens collected, suggesting that the rise in incidence of EoE is because of enhanced disease recognition rather than higher detection from increased EGD use.
Although EoE accounts for only a minority of children who underwent EGD for any indication (pooled prevalence 3.7%) (7,15–18), the prevalence of EoE among EGDs performed in children with esophageal food impaction and/or dysphagia was high (63%–88%) (32,33). Similarly, the prevalence of EoE in unselected adults undergoing an EGD ranged from 1.0% to 6.5% (39,40). In comparison to children, adults with food bolus impaction or dysphagia had lower prevalence of EoE (12%–48%) (10,41,42). The lower prevalence of EoE in adults with food bolus impaction or dysphagia compared with children may be accounted for by the wider differential diagnosis for food bolus impaction or dysphagia in adults such as esophageal malignancy, peptic stricture, and connective tissue disorders. Because the highest diagnostic yield of endoscopy for EoE occurred among children with dysphagia or food impaction, children with such presenting complaints should be identified at triage and undergo rapid and timely evaluation with EGD to facilitate the diagnosis of EoE. Limited studies have investigated the prevalence of EoE among specific immune-mediated conditions. The pooled prevalence of EoE was 2.3% for children with celiac disease (21–25). Detection bias from frequent biopsy sampling is unlikely to fully explain the elevated prevalence of EoE in celiac disease. A gluten-free diet in patients with celiac disease reduced esophageal eosinophilia in some studies (43,44), whereas others demonstrated persistent esophageal eosinophilia (24,25). Although EoE is thought to be a TH2-mediated atopic disease and celiac disease is a TH1-mediated autoimmune disease, an association between these 2 diseases may be biologically plausible because recent studies suggest the coexistence of TH1- and TH2-mediated diseases is the result of generalized immune dysregulation (22,43,44).
The prevalence of EoE ranged from 2.4% to 3.0% for children post–liver transplantation (26,27). In liver transplant recipients, de novo development of food allergy and gastrointestinal eosinophilic inflammation may be attributed to the potential effect of tacrolimus suppression of TH1 response and promotion of TH2 signal pathways (26,45–47). The prevalence of EoE was 8% among children with UC (28). Like EoE, UC is thought to be TH2 mediated (48).
In our systematic review, EoE primarily was more commonly diagnosed among male children of white ethnicity who had a personal and/or family history of atopy. The male predominance was also seen in adults (12). The median age at diagnosis reported in the studies ranged from 5.4 to 9.6 years. The presenting symptoms of EoE vary by age. Younger children are more likely to present with a wider variety of symptoms compared with older children, who often present with dysphagia or food bolus impaction (6). The predominant symptom of EoE in young adults is dysphagia, similar to that of older children (12). Therefore, the index of suspicion for EoE and rapidity of evaluation with EGD should be guided by the clinical presentation.
In the meta-analyses performed for population-based incidence, children who underwent EGD, and children with histologic esophageal disease, significant heterogeneity was found. Heterogeneity may be explained by differences in geographic region, study period, and intrinsic biases associated with observational studies. Given the small number of studies, stratified or sensitivity analyses were not possible to explore reasons for heterogeneity. To account for heterogeneity, a random effects model was used in all of the meta-analyses. Using the Begg test, we did not find any evidence of publication bias in these subgroups.
The limitations of our systematic review should be considered. First, the quality of the studies was not always optimal. An ideal quality study would be a prospective population-based study with well-described methods of case ascertainment and diagnostic criteria. For optimal accuracy of estimates, this ideal study would take place in a region with a well-defined source population, readily available endoscopy services, and appropriate physician awareness and willingness to conduct EGD and collect esophageal biopsies in patients presenting with symptoms suggestive of EoE. Our systematic review yielded variable methods of case ascertainment and minimal prospective studies. We limited the meta-analyses to subgroups containing ≥5 studies, and studies in which the diagnostic criteria were not reported were excluded from the meta-analyses. Quality characteristics of each study (study design, source of population, and diagnostic criteria for EoE) are shown in Table 1. Second, in the studies identified through the systematic review, the case definition of EoE focused primarily on histologic findings, whereas the present definition of EoE encompasses both clinical and histologic manifestations. Also, the histologic criteria of EoE varied between studies, ranging from 15 to 24 eosinophils/hpf. Acknowledging that the 2011 consensus guidelines recommend a minimum threshold of 15 eosinophils/hpf for the diagnosis of EoE, the incidence and prevalence of EoE in previous studies were likely underestimated (2,3). Third, our search strategy revealed only a small number of studies, all from developed countries. Thus, we cannot comment on the incidence and prevalence of EoE in developing countries. Despite these limitations, we used a comprehensive search strategy and included studies published in all languages and in both abstract and full-article format. Therefore, this review provides a comprehensive summary of the present literature on the epidemiology of EoE in children.
EoE is a chronic disease that has major implications for the consequential burden of disease. Children with EoE will use health care resources in procedures such as EGD, hospital admissions, and clinic visits for diagnosis, monitoring response to therapy, and management of complications (3). In addition, children with EoE often require multidisciplinary services including gastroenterologist, allergist, and dietician.
In conclusion, the incidence rates and prevalence of EoE in children vary by geographic regions in developed countries, with significant increases in these rates with time. Although the prevalence of EoE is low among children who undergo EGD or children with abdominal pain, the prevalence of EoE is high among children who present with food impaction or dysphagia. In younger children with chronic unexplained upper gastrointestinal symptoms unresponsive to present management strategies, the diagnosis of EoE should be considered. To improve our understanding of the worldwide epidemiology of EoE in children, future studies using recently accepted diagnostic criteria for EoE in defined geographic regions should be conducted, especially in developing countries.
1. Matzinger MA, Daneman A. Esophageal involvement in eosinophilic gastroenteritis. Pediatr Radiol
2. Furuta GT, Liacouras CA, Collins MH, et al. Eosinophilic esophagitis in children and adults: a systematic review and consensus recommendations for diagnosis and treatment. Gastroenterology
3. Liacouras CA, Furuta GT, Hirano I, et al. Eosinophilic esophagitis: updated consensus recommendations for children and adults. J Allergy Clin Immunol
4. Mukkada VA, Haas A, Maune NC, et al. Feeding dysfunction in children with eosinophilic gastrointestinal diseases. Pediatrics
5. Aceves SS, Newbury RO, Dohil MA, et al. A symptom scoring tool for identifying pediatric patients with eosinophilic esophagitis and correlating symptoms with inflammation. Ann Allergy Asthma Immunol
6. Liacouras CA, Spergel JM, Ruchelli E, et al. Eosinophilic esophagitis: a 10-year experience in 381 children. Clin Gastroenterol Hepatol
7. Aceves SS, Newbury RO, Dohil R, et al. Distinguishing eosinophilic esophagitis in pediatric patients: clinical, endoscopic, and histologic features of an emerging disorder. J Clin Gastroenterol
8. Noel RJ, Putnam PE, Rothenberg ME. Eosinophilic esophagitis. N Engl J Med
9. Kapel RC, Miller JK, Torres C, et al. Eosinophilic esophagitis: a prevalent disease in the United States that affects all age groups. Gastroenterology
10. Kerlin P, Jones D, Remedios M, et al. Prevalence of eosinophilic esophagitis in adults with food bolus obstruction of the esophagus. J Clin Gastroenterol
11. Straumann A, Simon H-U. Eosinophilic esophagitis: escalating epidemiology? J Allergy Clin Immunol
12. Sealock RJ, Rendon G, El-Serag HB. Systematic review: the epidemiology of eosinophilic oesophagitis in adults. Aliment Pharmacol Ther
13. Stroup DF, Berlin JA, Morton SC, et al. Meta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis Of Observational Studies in Epidemiology (MOOSE) group. JAMA
14. Cherian S, Smith NM, Forbes DA. Rapidly increasing prevalence of eosinophilic oesophagitis in Western Australia. Arch Dis Child
15. Dantuluri S, Ramani P, Basude D, et al. Eosinophilic oesophagitis: are we missing it? J Pediatr Gastroenterol Nutr
16. Rao P, Thomson M, Bromlow H, et al. Clinical, pathological, and epidemiological features of pediatric eosinophilic esophagitis (EE) in the north of England. J Pediatr Gastroenterol Nutr
17. Pulcini JM, Nowicki M, Roy S. Increasing prevalence of eosinophilic esophagitis in the pediatric population of Mississippi. J Allergy Clin Immunol
18. Lee JJ, Baker RD, Khan AR, et al. Childhood esophagitis: then and now. J Pediatr Gastroenterol Nutr
19. DeBrosse CW, Collins MH, Buckmeier Butz BK, et al. Identification, epidemiology, and chronicity of pediatric esophageal eosinophilia, 1982–1999. J Allergy Clin Immunol
20. Lai AL, Girgis S, Liang Y, et al. Diagnostic criteria for eosinophilic esophagitis: a 5-year retrospective review in a pediatric population. J Pediatr Gastroenterol Nutr
21. Francavilla R, Leone G, Fico S, et al. PA16 celiac disease and eosinophilic esophagitis: is there an association? Dig Liver Dis
2009; 41 (suppl 3):S228.
22. Thompson JS, Lebwohl B, Reilly NR, et al. Increased incidence of eosinophilic esophagitis in children and adults with celiac disease. J Clin Gastroenterol
23. Patel C, Singh V. Society for Pediatric Pathology/Paediatric Pathology Society Combined Fall Meeting, Philadelphia, October 2009: underlying diseases and other gastrointestinal abnormalities in patients with celiac disease. Pediatr Dev Pathol
24. Leslie C, Mews C, Charles A, et al. Celiac disease and eosinophilic esophagitis: a true association. J Pediatr Gastroenterol Nutr
25. Ooi CY, Day AS, Jackson R, et al. Eosinophilic esophagitis in children with celiac disease. J Gastroenterol Hepatol
26. Noble C, Francis L, Withers GW, et al. Audit of eosinophilic oesophagitis in children post-liver transplant. Pediatr Transplant
27. Miloh T, Nowak-Wegrzyn A, Wisniewski J, et al.Eosinophilic gastrointestinal disease and de novo food allergies in children post-liver transplantation. Hepatology
2010;52 (Suppl 1):1029A–30.
28. Gersten A, Beneck D, Blanco D, et al. Prevalence of upper gastrointestinal tract inflammation in patients with ulcerative colitis. Lab Invest
29. Thakkar K, Chen L, Tatevian N, et al. Diagnostic yield of oesophagogastroduodenoscopy in children with abdominal pain. Aliment Pharmacol Ther
30. Thakkar KH, El-Serag HB, Messitt TJ, et al. EGD in children with chronic abdominal pain. Gastrointest Endosc
31. Thakkar K, Dorsey F, Gilger MA. Impact of endoscopy on management of chronic abdominal pain in children. Dig Dis Sci
32. Hurtado CW, Furuta GT, Kramer RE. Etiology of esophageal food impactions in children. J Pediatr Gastroenterol Nutr
33. Cheung KM, Oliver MR, Cameron DJS, et al. Esophageal eosinophilia in children with dysphagia. J Pediatr Gastroenterol Nutr
34. Alabraba E, Nightingale P, Gunson B, et al. A re-evaluation of the risk factors for the recurrence of primary sclerosing cholangitis in liver allografts. Liver Transpl
35. Dalby K, Nielsen RG, Kruse-Andersen S, et al. Eosinophilic oesophagitis in infants and children in the region of southern Denmark: a prospective study of prevalence and clinical presentation. J Pediatr Gastroenterol Nutr
36. Gill R, Durst P, Rewalt M, et al. Eosinophilic esophagitis disease in children from West Virginia: a review of the last decade (1995–2004). Am J Gastroenterol
37. Prasad GA, Alexander JA, Schleck CD, et al. Epidemiology of eosinophilic esophagitis over three decades in Olmsted County, Minnesota. Clin Gastroenterol Hepatol
38. Ronkainen J, Talley NJ, Aro P, et al. Prevalence of oesophageal eosinophils and eosinophilic oesophagitis in adults: the population-based Kalixanda study. Gut
39. Veerappan GR, Perry JL, Duncan TJ, et al. Prevalence of eosinophilic esophagitis in an adult population undergoing upper endoscopy: a prospective study. Clin Gastroenterol Hepatol
40. Almansa C, Krishna M, Buchner AM, et al. Seasonal distribution in newly diagnosed cases of eosinophilic esophagitis in adults. Am J Gastroenterol
41. Prasad GA, Talley NJ, Romero Y, et al. Prevalence and predictive factors of eosinophilic esophagitis in patients presenting with dysphagia: a prospective study. Am J Gastroenterol
42. Mackenzie SH, Go M, Chadwick B, et al. Eosinophilic oesophagitis in patients presenting with dysphagia: a prospective analysis. Aliment Pharmacol Ther
43. Simpson CR, Anderson WJA, Helms PJ, et al. Coincidence of immune-mediated diseases driven by Th1 and Th2 subsets suggests a common aetiology. A population-based study using computerized general practice data. Clin Exp Allergy
44. Nilsson L, Kivling A, Jalmelid M, et al. Combinations of common chronic paediatric diseases deviate the immune response in diverging directions. Clin Exp Immunol
45. Romero R, Abramowsky CR, Pillen T, et al. Peripheral eosinophilia and eosinophilic gastroenteritis after pediatric liver transplantation. Pediatr Transplant
46. Granot E, Yakobovich E, Bardenstein R. Tacrolimus immunosuppression — an association with asymptomatic eosinophilia and elevated total and specific IgE levels. Pediatr Transplant
47. Saeed SA, Integlia MJ, Pleskow RG, et al. Tacrolimus-associated eosinophilic gastroenterocolitis in pediatric liver transplant recipients: role of potential food allergies in pathogenesis. Pediatr Transplant
48. Abraham C, Cho JH. Inflammatory bowel disease. N Engl J Med
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Keywords:© 2013 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology,
eosinophilic esophagitis; epidemiology; pediatrics