Implementation of a biopsy protocol to improve detection of esophageal eosinophilia: a Danish registry-based study

Abstract

Background In the North Denmark Region (580 272 inhabitants), only 0–4 cases of possible eosinophilic esophagitis (EoE) were identified annually in 1999–2010, suggesting underdiagnosis. This study aimed to increase the diagnosis of EoE by introducing a regional biopsy protocol for patients with dysphagia.

Methods In 2011, leaders of regional endoscopy units attended a consensus meeting where a biopsy protocol was proposed. The national pathology registry was used to identify patients with esophageal eosinophilic inflammation during 2007–2017.

Results Discussion resulted in consensus on a protocol to take eight biopsy samples in dysphagia patients (four biopsies from 4 cm and 14 cm above the esophagogastric junction–“4–14–4 rule”) regardless of the macroscopic appearance, and to code eosinophilia systematically in the pathology registry. A pictogram showing the 4–14–4 rule was sent to all endoscopy units. The number of patients with esophageal eosinophilia detected per year increased 50-fold after the protocol was implemented in 2011 (median of 1 [interquartile range 0–3] vs. 52 [47–56]; P < 0.001), and the number of biopsy samples per patient doubled (median 4 [4–5] vs. 8 [6–9]; P < 0.04). Of 309 patients diagnosed with esophageal eosinophilia in 2007–2017, 24 % had erosive esophagitis or Barrett’s esophagus, and 74 % had EoE.

Conclusions A consensus-based biopsy protocol and improved coding of eosinophilia in the pathology registry resulted in a 50-fold increase in patients diagnosed with esophageal eosinophilia/year. These patients can now receive treatment. The effort to establish the protocol and change the culture of endoscopists and pathologists was minimal.

Publication History

Received: 04 March 2020

Accepted: 28 May 2020

Article published online:
05 August 2020

• References

• 1 Dellon ES, Hirano I. Epidemiology and natural history of eosinophilic esophagitis. Gastroenterology 2018; 154: 319-332
• 2 Dellon ES, Erichsen R, Baron JA. et al. The increasing incidence and prevalence of eosinophilic oesophagitis outpaces changes in endoscopic and biopsy practice: national population-based estimates from Denmark. Aliment Pharmacol Ther 2015; 41: 662-670
• 3 Hruz P, Straumann A, Bussmann C. et al. Escalating incidence of eosinophilic esophagitis: a 20-year prospective, population-based study in Olten County, Switzerland. J Allergy Clin Immunol 2011; 128: 1349-1350.e5
• 4 Giriens B, Yan P, Safroneeva E. et al. Escalating incidence of eosinophilic esophagitis in Canton of Vaud, Switzerland, 1993–2013: a population-based study. Allergy 2015; 70: 1633-1639
• 5 van Rhijn BD, Verheij J, Smout AJPM. et al. Rapidly increasing incidence of eosinophilic esophagitis in a large cohort. Neurogastroenterol Motil 2013; 25: 47-52.e5
• 6 Moawad FJ. Eosinophilic esophagitis: incidence and prevalence. Gastrointest Endosc Clin N Am 2018; 28: 15-25
• 7 Gonsalves N, Policarpio-Nicolas M, Zhang Q. et al. Histopathologic variability and endoscopic correlates in adults with eosinophilic esophagitis. Gastrointest Endosc 2006; 64: 313-319
• 8 Hirano I. Clinical relevance of esophageal subepithelial activity in eosinophilic esophagitis. J Gastroenterol 2020; 55: 249-260
• 9 Straumann A, Katzka DA. Diagnosis and treatment of eosinophilic esophagitis. Gastroenterology 2018; 154: 346-359
• 10 Frank L. Epidemiology. The epidemiologist’s dream: Denmark. Science 2003; 301: 163
• 11 Frank L. Epidemiology. When an entire country is a cohort. Science 2000; 287: 2398-2399
• 12 Erichsen R, Lash TL, Hamilton-Dutoit SJ. et al. Existing data sources for clinical epidemiology: the Danish National Pathology Registry and Data Bank. Clin Epidemiol 2010; 2: 51-56
• 13 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 2007; 133: 1342-1363
• 14 Liacouras CA, Furuta GT, Hirano I. et al. Eosinophilic esophagitis: updated consensus recommendations for children and adults. J Allergy Clin Immunol 2011; 128: 2-3
• 15 Sørensen HT, Christensen T, Schlosser HK, Pedersen L. Use of medical databases in clinical epidemiology. 2nd edn. Aarhus: SUN-TRYK, Aarhus Universitet; 2009
• 16 Shaheen NJ, Weinberg DS, Denberg TD. et al. Upper endoscopy for gastroesophageal reflux disease: best practice advice from the clinical guidelines committee of the American College of Physicians. Ann Intern Med 2012; 157: 808-816
• 17 Berg L, Fresvig TG, Bang S. NOMESCO Classification of Surgical Procedures – Nordic Centre for Classifications in Health Care. Copenhagen: Munksgaard Danmark; 2005
• 18 Saffari H, Peterson KA, Fang JC. et al. Patchy eosinophil distributions in an esophagectomy specimen from a patient with eosinophilic esophagitis: implications for endoscopic biopsy. J Allergy Clin Immunol 2012; 130: 798-800
• 19 Hirano I, Moy N, Heckman MG. et al. Endoscopic assessment of the oesophageal features of eosinophilic oesophagitis: validation of a novel classification and grading system. Gut 2013; 62: 489-495
• 20 Internal migrations in Denmark. Statistics Denmark CH; 2019 Accessed: 10 December 2019. https://www.dst.dk/en/Statistik/emner/befolkning-og-valg/flytninger/flytninger-internt-i-danmark
• 21 Dubecz A, Mentrikoski M, Peters JH. Eosinophilic esophagitis with severe GERD. Am J Gastroenterol 2009; 104: 527-529
• 22 Molina-Infante J, Gonzalez-Cordero PL, Ferreira-Nossa HC. et al. Rising incidence and prevalence of adult eosinophilic esophagitis in midwestern Spain (2007–2016). United Eur Gastroenterol J 2018; 6: 29-37
• 23 Attwood SE, Wilson MS. Current hurdles in the management of eosinophilic oesophagitis: the next steps. World J Gastroenterol 2013; 19: 790-796
• 24 Vakil N, van Zanten SV, Kahrilas P. et al. The Montreal definition and classification of gastroesophageal reflux disease: a global evidence-based consensus. Am J Gastroenterol 2006; 101: 1900-1920
• 25 Spechler SJ, Genta RM, Souza RF. Thoughts on the complex relationship between gastroesophageal reflux disease and eosinophilic esophagitis. Am J Gastroenterol 2007; 102: 1301-1306
• 26 Krarup AL, Villadsen GE, Mejlgaard E. et al. Acid hypersensitivity in patients with eosinophilic oesophagitis. Scand J Gastroenterol 2010; 45: 273-281
• 27 Abe Y, Sasaki Y, Yagi M. et al. Diagnosis and treatment of eosinophilic esophagitis in clinical practice. Clin J Gastroenterol 2017; 10: 87-102
• 28 Dellon ES, Liacouras CA, Molina-Infante J. et al. Updated international consensus diagnostic criteria for eosinophilic esophagitis: proceedings of the AGREE Conference. Gastroenterology 2018; 155: 1022-1033.e10
• 29 Syed AAN, Andrews CN, Shaffer E. et al. The rising incidence of eosinophilic oesophagitis is associated with increasing biopsy rates: a population-based study. Aliment Pharmacol Ther 2012; 36: 950-958
• 30 Prasad GA, Alexander JA, Schleck CD. et al. Epidemiology of eosinophilic esophagitis over three decades in Olmsted County, Minnesota. Clin Gastroenterol Hepatol 2009; 7: 1055-1061
• 31 Attwood SE, Smyrk TC, Demeester TR. et al. Esophageal eosinophilia with dysphagia. A distinct clinicopathologic syndrome. Dig Dis Sci 1993; 38: 109-116