Eosinophilic esophagitis (EoE) is a chronic, esophageal inflammatory condition characterized by dense eosinophilic infiltration of the esophagus (1–6). Typically, this disorder is diagnosed by the presence of a threshold number of eosinophils as determined by esophageal biopsy and exclusion of other causes of esophageal eosinophilia (4). Evidence suggests this condition is related to an allergic disease process (7,8). Symptoms of pediatric EoE tend to mimic gastroesophageal reflux disease and often include heartburn, chest pain, feeding intolerance, failure to thrive, dysphagia, and food impaction (1,4–6,8–12). Older children and adults present primarily with dysphagia and food impaction (1,4,10–13).
The first report of EoE was published in 1977 (14), and in the mid-1990s, EoE recognition by gastroenterologists and pathologists increased rapidly with a few published reports (3,15). The prevalence is now estimated to be approaching that of Crohn disease and ulcerative colitis (6).
Although the number of EoE diagnoses has increased, controversy remains regarding whether this is a true increase of EoE or simply increased recognition and accurate diagnosing. Straumann and Simon (13) reported an increase from 2 to 23 cases per 100,000 from 1989 to 2004 in Switzerland. Stable demographic and recording conditions support the argument that this is a true increase in EoE. Noel et al (5) reported 315 cases of EoE from 1991 to 2003, with only 2.8% identified before 2000. From 2000 to 2003, the prevalence increased from 9.91 to 42.96 cases per 100,000 children living in the area surrounding the medical center (5). Other studies claim that the identified increase in prevalence is the result of definitive guidelines and increased symptom recognition, which may lead to appropriate testing and diagnosis (2,16). Nevertheless, previous reports were regionally specific, making it unclear whether these trends would be seen in a larger population.
The objective of the present study was to use a national administrative database to identify trends in inpatient diagnoses of esophagitis, with a focus on EoE in the United States. Because there was not a specific EoE diagnostic code before 2008, trends in other related diagnoses and procedures were examined.
We queried the Pediatric Health Information System (PHIS) database for all of the inpatients discharged with specific International Classification of Disease-9th Revision-Clinical Modification (ICD-9-CM) codes related to EoE. PHIS is an administrative database managed by the Child Health Corporation of America that contains clinical and financial data from >40 freestanding children's hospitals in the United States. Between January 1, 1999 and December 31, 2010, there were 29 member hospitals with complete data. These hospitals represented 17 different states in all 4 regions of the United States (Pennsylvania, Michigan, Wisconsin, Ohio, Illinois, Nebraska, Missouri, Virginia, Florida, Tennessee, Alabama, Arkansas, Louisiana, Texas, Colorado, California, and Washington), as well as Washington, DC. For the data we examined, 1 hospital contributed 166 cases; the remainder reported a range of 1 to 45 cases.
A specific code for EoE (530.13) was not established until October 2008; however, before that, EoE was most likely coded as esophagitis, not elsewhere classifiable (NEC) (530.19) (17). Among coding specialists, the code NEC is used to describe a condition indicated by details in the medical record for which a specific code does not exist. We speculated that use of the EoE-specific diagnosis would rise rapidly after the code was instituted, whereas the nonspecific code, esophagitits NEC, would decline. To address the concern of using the less specific esophagitis NEC code as the case definition, we also evaluated the data using a refined definition by combining the esophagitis NEC and EoE diagnosis codes with a billing charge for an endoscopy.
We included all of the inpatients discharged with an ICD-9-CM diagnosis code for any type of esophagitis (530.1X). This includes EoE (530.13) after 2008 and esophagitis NEC (530.19), as previously described. Also included were reflux esophagitis (530.11), acute esophagitis (530.12), and esophagitis, unspecified or not otherwise specified (NOS) (530.10), which would be used when the coding specialist was unable to assign a more specific code because of insufficient information in the medical record (17). To be thorough because of a lack of specificity in the ICD-9-CM code for EoE before 2008, we also included discharge diagnoses of dysphagia (787.2X), foreign body in the esophagus (935.1), and stricture of the esophagus (530.3) to determine whether symptoms and complications of EoE follow similar trends. Percent increases of related diagnoses and billing charges were examined relative to the percent increase in hospital discharges during varying time periods. All of the analyses were conducted using SAS 9.2 (SAS Institute, Cary, NC) and Microsoft Excel 2007.
The trends from 1999 through 2010 for the different ICD-9-CM diagnosis codes are displayed in Figure 1. Between 1999 and 2008, the number of hospitalizations with a diagnosis of esophagitis NEC increased progressively from 204 to 455. During this time period, the discharge diagnosis of esophagitis NEC increased by 123%,whereas total pediatric hospital discharges increased by only 20%. From 2008 to 2010, the total pediatric discharges remained relatively consistent. In 2009, the first full year that the ICD-9-CM code for EoE was used, 245 pediatric patients were discharged with an EoE diagnosis code. This coincided with a decrease in hospital discharges for esophagitis NEC from 455 to 278 (39% decline). Data from 2010 showed a continued increase (34%) in EoE from 2009 to 2010 based on the specific EoE diagnosis code. Comparatively, during this time period (2009–2010), hospital discharges for esophagitis NEC remained relatively constant (<3% increase).
Using the refined case definition, examination of patients having both a billing charge for an endoscopy and a code for esophagitis NEC or EoE revealed an increase of 203% (Fig. 2). Additionally, the growth in endoscopies from 1999 to 2010 was 97%, and the increase in those with a code for esophagitis NEC or EoE was 197%, whereas total hospital discharges increased by only 22% during this period.
Looking at the symptoms and related diagnoses in Figure 1, there was a slight decrease from 2007 to 2009 for esophagitis NOS and a rapid decline in reflux esophagitis. Similar to esophagitis NEC, both of these diagnoses showed little change from 2009 to 2010. Additionally, from 1999 to 2010, dysphagia quadrupled from 1110 to 4567, whereas strictures remained constant (increase of 20%) relative to the hospital discharge increase of 22%.
These data show an increase in pediatric hospitalizations with a diagnosis of EoE between 1999 and 2010, larger than the increase of total hospital discharges, suggesting an increase in the disease process. Furthermore, the continued escalation in 2010 indicates that this is an ongoing increase. Because EoE is most often treated in an outpatient setting, we also believe this increase in inpatients represents an increase in significant cases. Our refined case definition was developed as the best identifier of EoE, because the cases were most likely coded as esophagitis NEC before 2008 and an EoE diagnosis requires an endoscopy, thus capturing true cases of EoE and indicating an increase in diagnosis over time.
In spite of the lack of a specific code for EoE before 2008, we believe that the evidence for an increase in EoE is 3-fold. First, there was a sudden decrease in esophagitis NEC from 2008 to 2009, suggesting that the earlier continuous increase in esophagitis NEC was actually driven by cases of EoE captured by this code before 2008. A plateau in esophagitis NEC was observed from 2009 to 2010, when EoE cases were no longer being coded as esophagitis NEC. Second, the introduction of the specific EoE code also coincides with decreases in esophagitis NOS and reflux esophagitis, suggesting that some EoE cases may have been captured previously with these codes. Third, further support for an increased diagnosis of EoE is provided by the observation of increased dysphagia, a well-recognized symptom of EoE; however, because of the ambiguity of the diagnosis codes, some variability among individuals assigning the code, and the difficulty in diagnosing EoE, some true EoE cases may still be coded as esophagitis NOS or reflux esophagitis. Failure to include these potential “missed” cases would only make our estimate of the escalation of EoE more conservative than the actual increase. Our results are consistent with the local studies, suggesting rapid growth in cases.
The explanation for these increases is unknown. Similar questions have been raised regarding other chronic allergic disorders including asthma and food allergy. EoE is associated with both food and inhalant allergic sensitivities. Timing and dosing of allergen exposures as well as allergen structure and associated particulate inhalation or ingestion can influence allergenicity and the immune response. Changes in these factors may result from present lifestyle trends such as time spent indoors, increased sedentary activities, and diet.
There are some limitations to the present study. We used an observational dataset that did not include any biopsy results, which is how EoE is diagnosed. Without this information, we had to rely solely on ICD-9-CM codes and billing charges for classification and this did not allow us to identify misdiagnosed cases of EoE. We have attempted to minimize this problem by including an evaluation of billing charges for endoscopy. Using only ICD-9-CM codes to identify EoE also creates concern because the EoE-specific code only became available in October 2008, which makes it difficult to capture the true EoE trends before this time. Finally, not all of the PHIS hospitals contributed data during the entire study period, which forced us to exclude several hospitals from the analysis. To account for this potential effect, we also evaluated the trends from 2001 to 2010, allowing us to include more hospitals. Although this increased our number of cases, the trends were the same as those we are reporting. Therefore, in spite of the limitations, this considerable and representative database allowed us to compile a large number of EoE cases to determine the trends of EoE.
The long-term effects of EoE remain unknown. Studies that have examined the natural history suggest continued or recurrent symptoms in the majority of patients, with only a small proportion showing resolution (2,18). One concern associated with the chronicity of EoE is esophageal thickening or narrowing that could result in strictures (18,19). Our results do not suggest a significant increase in strictures to date; however, because evidence suggests an increasing prevalence of EoE and because little is known about the long-term effects of this chronic condition, it is important to continue to monitor all of the features of this disease by using all available resources. Large administrative databases are one such resource and can provide useful epidemiologic information, especially with the present availability of an EoE-specific code.
1. Chang F, Anderson S. Clinical and pathological features of eosinophilic oesophagitis: a review. Pathology
2. DeBrosse CW, Collins MH, Buckmeier Butz BK, et al. Identification, epidemiology, and chronicity of pediatric esophageal eosinophilia, 1982–1999. J Allergy Clin Immunol
3. Kelly KJ, Lazenby AJ, Rowe PC, et al. Eosinophilic esophagitis attributed to gastroesophageal reflux: improvement with an amino acid-based formula. Gastroenterology
4. Liacouras CA, Furuta GT, Hirano I, et al. Eosinophilic esophagitis: updated consensus recommendations for children and adults. J Allergy Clin Immunol
5. Noel RJ, Putnam PE, Rothenberg ME. Eosinophilic esophagitis. N Engl J Med
6. Whitney-Miller CL, Katzka D, Furth EE. Eosinophilic esophagitis: a retrospective review of esophageal biopsy specimens from 1992 to 2004 at an adult academic medical center. Am J Clin Pathol
7. Mishra A, Hogan SP, Brandt EB, et al. An etiological role for aeroallergens and eosinophils in experimental esophagitis. J Clin Invest
8. Spergel JM, Beausoleil JL, Mascarenhas M, et al. The use of skin prick tests and patch tests to identify causative foods in eosinophilic esophagitis. J Allergy Clin Immunol
9. 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
10. Cantu P, Penagini R. Eosinophilic oesophagitis: the essentials for daily practice. Scand J Gastroenterol
11. Furuta GT. Eosinophilic esophagitis: an emerging clinicopathologic entity. Curr Allergy Asthma Rep
12. Prasad GA, Alexander JA, Schleck CD, et al. Epidemiology of eosinophilic esophagitis over three decades in Olmsted County, Minnesota. Clin Gastroenterol Hepatol
13. Straumann A, Simon HU. Eosinophilic esophagitis: escalating epidemiology? J Allergy Clin Immunol
14. Dobbins JW, Sheahan DG, Behar J. Eosinophilic gastroenteritis with esophageal involvement. Gastroenterology
15. Attwood SE, Smyrk TC, Demeester TR, et al. Esophageal eosinophilia with dysphagia. A distinct clinicopathologic syndrome. Dig Dis Sci
16. Vanderheyden AD, Petras RE, DeYoung BR, et al. Emerging eosinophilic (allergic) esophagitis: increased incidence or increased recognition? Arch Pathol Lab Med
17. ICD-9-CM Official Guidelines for Coding and Reporting
. Rockville, MD: Centers for Medicare and Medicaid Services and the National Center for Health Statistics. US Department of Health and Human Services; 2009.
18. Spergel JM, Brown-Whitehorn TF, Beausoleil JL, et al. Fourteen years of eosinophilic esophagitis: clinical features and prognosis. J Pediatr Gastroenterol Nutr
19. Straumann A, Spichtin HP, Grize L, et al. Natural history of primary eosinophilic esophagitis: a follow-up of 30 adult patients for up to 11.5 years. Gastroenterology