Mortality in Eosinophilic Esophagitis – a nationwide, population-based matched cohort study from 2005 to 2017
Abstract
Background: There is a lack of knowledge about mortality in eosinophilic esophagitis (EoE). Therefore, this study aimed to examine the mortality in EoE.
Methods: A nationwide, population-based matched cohort study was conducted of all EoE patients in Sweden diagnosed between July 2005 and December 2017. Individuals with EoE (n = 1,625) were identified through prospectively recorded histopathology codes from all gastrointestinal pathology reports in Sweden, representing 28 pathology departments (the ESPRESSO study). Each individual with EoE was then matched with up to five reference individuals from the general population (n = 8,003) for age, sex, year of birth, and place of residence. We used the Cox proportional hazard modeling to estimate the adjusted hazard ratio (aHR) and 95% confidence interval (95% CI) while adjusting for other potential confounders. In sensitivity analyses, mortality in EoE patients was compared with mortality in their siblings.
Results: Through December 2017, 34 deaths were confirmed in EoE patients (4.60 per 1,000 person-years) compared with 165 in reference individuals (4.57 per 1,000 person-years). This rate corresponds to an aHR of 0.97 (95% CI = 0.67–1.40). HRs were similar in males (aHR = 1.00 [0.66–1.51]) and females (aHR = 0.92 [0.38–2.18]). We observed no increased risk in mortality due to esophageal or other gastrointestinal cancers in patients with EoE (aHR = 1.02 [0.51–2.02]).
Mortality was similar in EoE patients and their siblings (aHR = 0.91 [0.44–1.85]).
Conclusion: In this nationwide, population-based matched cohort study in Sweden, there was no increased risk of death in patients with EoE compared with their siblings and the general population.
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References
- Spechler SJ. Speculation as to why the frequency of eosinophilic esophagitis is increasing. Curr Gastroenterol Rep 2018;20:26. doi: 10.1007/s11894-018-0633-x
- Navarro P, Arias A, Arias-Gonzalez L, Laserna-Mendieta EJ, Ruiz-Ponce M, Lucendo AJ. 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;49:1116–25. doi: 10.1111/apt.15231
- Dellon ES, Jensen ET, Martin CF, Shaheen NJ, Kappelman MD. Prevalence of eosinophilic esophagitis in the United States. Clin Gastroenterol Hepatol. 2014;12:589–96 e1. doi: 10.1016/j.cgh.2013.09.008
- Mansoor E, Cooper GS. The 2010–2015 prevalence of eosinophilic esophagitis in the USA: A population-based study. Dig Dis Sci. 2016;61:2928–34. doi: 10.1007/s10620-016-4204-4
- Jensen ET, Kappelman MD, Martin CF, Dellon ES. Health-care utilization, costs, and the burden of disease related to eosinophilic esophagitis in the United States. Am J Gastroenterol 2015;110:626–32. doi: 10.1038/ajg.2014.316
- Schoepfer AM, Safroneeva E, Bussmann C, Kuchen T, Portmann S, Simon HU, et al. Delay in diagnosis of eosinophilic esophagitis increases risk for stricture formation in a time-dependent manner. Gastroenterology 2013;145:1230–6 e1-2. doi: 10.1053/j.gastro.2013.08.015
- Eluri S, Runge TM, Cotton CC, Burk CM, Wolf WA, Woosley JT, et al. The extremely narrow-caliber esophagus is a treatment-resistant subphenotype of eosinophilic esophagitis. Gastrointest Endosc 2016;83:1142–8. doi: 10.1016/j.gie.2015.11.019
- Straumann A, Spichtin HP, Grize L, Bucher KA, Beglinger C, Simon HU. Natural history of primary eosinophilic esophagitis: a follow-up of 30 adult patients for up to 11.5 years. Gastroenterology 2003;125:1660–9. doi: 10.1053/j.gastro.2003.09.024
- Lipka S, Keshishian J, Boyce HW, Estores D, Richter JE. The natural history of steroid-naive eosinophilic esophagitis in adults treated with endoscopic dilation and proton pump inhibitor therapy over a mean duration of nearly 14 years. Gastrointest Endosc 2014;80:592–8. doi: 10.1016/j.gie.2014.02.012
- Dellon ES, Gonsalves N, Hirano I, Furuta GT, Liacouras CA, Katzka DA, et al. ACG clinical guideline: evidenced based approach to the diagnosis and management of esophageal eosinophilia and eosinophilic esophagitis (EoE). Am J Gastroenterol 2013;108:679–92; quiz 93. doi: 10.1038/ajg.2013.71
- Dellon ES, Liacouras CA, Molina-Infante J, Furuta GT, Spergel JM, Zevit N, et al. Updated international consensus diagnostic criteria for eeosinophilic esophagitis: Proceedings of the AGREE Conference. Gastroenterology 2018;155:1022–33 e10. doi: 10.1053/j.gastro.2018.07.009
- Ridker PM, Cushman M, Stampfer MJ, Tracy RP, Hennekens CH. Inflammation, aspirin, and the risk of cardiovascular disease in apparently healthy men. N Engl J Med 1997;336:973–9. doi: 10.1056/NEJM199704033361401
- Kundu JK, Surh YJ. Inflammation: gearing the journey to cancer. Mutat Res. 2008;659:15–30. doi: 10.1016/j.mrrev.2008.03.002
- Ludvigsson JF, Lashkariani M. Cohort profile: ESPRESSO (Epidemiology Strengthened by histoPathology Reports in Sweden). Clin Epidemiol. 2019;11:101–14. doi: 10.2147/CLEP.S191914
- Röjler L, Glimberg I, Walker MM, Garber JJ, Ludvigsson JF. Validation of the diagnosis of eosinophilic esophagitis based on histopathology reports in Sweden. Ups J Med Sci. 2021;126.
- Ludvigsson JF, Almqvist C, Bonamy AK, Ljung R, Michaelsson K, Neovius M, et al. Registers of the Swedish total population and their use in medical research. Eur J Epidemiol 2016;31:125–36. doi: 10.1007/s10654-016-0117-y
- Brooke HL, Talback M, Hornblad J, Johansson LA, Ludvigsson JF, Druid H, et al. The Swedish cause of death register. Eur J Epidemiol 2017;32:765–73. doi: 10.1007/s10654-017-0316-1
- Ludvigsson JF, Svedberg P, Olen O, Bruze G, Neovius M. The longitudinal integrated database for health insurance and labour market studies (LISA) and its use in medical research. Eur J Epidemiol 2019;34:423–37. doi: 10.1007/s10654-019-00511-8
- Wettermark B, Hammar N, Fored CM, Leimanis A, Otterblad Olausson P, Bergman U, et al. The new Swedish Prescribed Drug Register – opportunities for pharmacoepidemiological research and experience from the first six months. Pharmacoepidemiol Drug Saf. 2007;16:726–35. doi: 10.1002/pds.1294
- Ludvigsson JF, Haberg SE, Knudsen GP, Lafolie P, Zoega H, Sarkkola C, et al. Ethical aspects of registry-based research in the Nordic countries. Clin Epidemiol. 2015;7:491–508. doi: 10.2147/CLEP.S90589
- Dellon ES, Hirano I. Epidemiology and natural history of eosinophilic esophagitis. Gastroenterology. 2018;154:319–32 e3. doi: 10.1053/j.gastro.2017.06.067
- O’Shea KM, Aceves SS, Dellon ES, Gupta SK, Spergel JM, Furuta GT, et al. Pathophysiology of eosinophilic esophagitis. Gastroenterology 2018;154:333–45. doi: 10.1053/j.gastro.2017.06.065
- Straumann A, Conus S, Degen L, Frei C, Bussmann C, Beglinger C, et al. Long-term budesonide maintenance treatment is partially effective for patients with eosinophilic esophagitis. Clin Gastroenterol Hepatol 2011;9:400–9 e1. doi: 10.1016/j.cgh.2011.01.017
- Menard-Katcher P, Marks KL, Liacouras CA, Spergel JM, Yang YX, Falk GW. The natural history of eosinophilic oesophagitis in the transition from childhood to adulthood. Aliment Pharmacol Ther 2013;37:114–21. doi: 10.1111/apt.12119
- Bohm M, Jacobs JW, Jr., Gupta A, Gupta S, Wo JM. Most children with eosinophilic esophagitis have a favorable outcome as young adults. Dis Esophagus 2017;30:1–6. doi: 10.1111/dote.12454
- Capucilli P, Hill DA. Allergic comorbidity in eosinophilic esophagitis: mechanistic relevance and clinical implications. Clin Rev Allergy Immunol 2019;57:111–127. doi: 10.1007/s12016-019-08733-0
- Egeberg A, Skov L, Andersen YMF, Mallbris L, Gislason GH, Silverberg JI, et al. Ten-year mortality is increased after hospitalization for atopic dermatitis compared with the general population, but reduced compared with psoriasis. J Am Acad Dermatol 2017;76:98–105. doi: 10.1016/j.jaad.2016.06.021
- Andersen YM, Egeberg A, Gislason GH, Hansen PR, Skov L, Thyssen JP. Risk of myocardial infarction, ischemic stroke, and cardiovascular death in patients with atopic dermatitis. J Allergy Clin Immunol 2016;138:310–2 e3. doi: 10.1016/j.jaci.2016.01.015
- Ebmeier S, Thayabaran D, Braithwaite I, Benamara C, Weatherall M, Beasley R. Trends in international asthma mortality: analysis of data from the WHO Mortality Database from 46 countries (1993–2012). Lancet 2017;390:935–45. doi: 10.1016/S0140-6736(17)31448-4
- Syed A, Maradey-Romero C, Fass R. The relationship between eosinophilic esophagitis and esophageal cancer. Dis Esophagus 2017;30:1–5. doi: 10.1093/dote/dox050
- Spechler SJ. Barrett esophagus and risk of esophageal cancer: a clinical review. JAMA 2013;310:627–36. doi: 10.1001/jama.2013.226450
- Burke ZD, Tosh D. Barrett’s metaplasia as a paradigm for understanding the development of cancer. Curr Opin Genet Dev 2012;22:494–9. doi: 10.1016/j.gde.2012.08.001
- Molina-Infante J, Prados-Manzano R, Gonzalez-Cordero PL. The role of proton pump inhibitor therapy in the management of eosinophilic esophagitis. Expert Rev Clin Immunol 2016;12:945–52. doi: 10.1080/1744666X.2016.1178574
- Molina-Infante J, Bredenoord AJ, Cheng E, Dellon ES, Furuta GT, Gupta SK, et al. Proton pump inhibitor-responsive oesophageal eosinophilia: an entity challenging current diagnostic criteria for eosinophilic oesophagitis. Gut 2016;65:524–31. doi: 10.1136/gutjnl-2015-310991
- Jensen ET, Kuhl JT, Martin LJ, Langefeld CD, Dellon ES, Rothenberg ME. Early-life environmental exposures interact with genetic susceptibility variants in pediatric patients with eosinophilic esophagitis. J Allergy Clin Immunol 2018;141:632–7 e5. doi: 10.1016/j.jaci.2017.07.010
- Ludvigsson JF, Andersson E, Ekbom A, Feychting M, Kim JL, Reuterwall C, et al. External review and validation of the Swedish national inpatient register. BMC Public Health 2011;11:450. doi: 10.1186/1471-2458-11-450
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