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Invited Commentaries

Towards Better Diagnosis and Monitoring of Eosinophilic Esophagitis: Are We There Yet?

Baker, Robert D.; Baker, Susan S.

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Journal of Pediatric Gastroenterology and Nutrition: April 2020 - Volume 70 - Issue 4 - p 410
doi: 10.1097/MPG.0000000000002603
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See “Monitoring Eosinophilic Esophagitis Disease Activity With Blood Eosinophil Progenitor Levels” by Henderson et al on page 482.

Currently, endoscopy with esophageal biopsies is the recommended method of diagnosing and monitoring eosinophilic esophagitis (EoE) (1). This is despite the fact that clinicians are uncomfortable with the number of endoscopies required to diagnosis, treat, and monitor patients with EoE. If topical steroids are chosen to treat EoE, diagnosis and monitoring entails 2 to 3 endoscopies initially with surveillance endoscopies every 6 to 12 months. The 6 food elimination protocol, including endoscopies for diagnosis, requires 10 endoscopies over 20 months. Starting in the 1980s, EoE was recognized to be separate from acid reflux-related esophagitis. EoE is now known to be a non-IgE-mediated immune disease characterized by esophageal dysfunction and esophageal biopsies with greater than 15 eosinophils per high powered field (2). As frequently happens in medicine, the picture becomes more complicated before it comes into focus. EoE is not a single, uniform disease, but rather consists of a number of subtypes that respond differently to treatments (3). Younger children often present with vomiting, regurgitation, and feeding difficulties, whereas adolescents have dysphagia, and food impaction (4). There appears to be a stricturing phenotype. Proton pump inhibitor responsive esophageal eosinophilia has been described (5). Although IgE has not been shown to play a role in EoE, IgG4-associated EoE may be yet another phenotype (6). EoE is thought to be a lifelong disease, although the natural history of the disease and its subtypes is poorly understood. The obvious need for a better method of dealing with EoE and its subtypes has generated intense research into less invasive procedures. Nasal endoscopy (7), string test (8), cytosponge test (9), and mucosal impedance (10) have been proposed as improvements over traditional endoscopy. None of these are entirely noninvasive. What is needed is a biomarker, or perhaps a panel of biomarkers. In fact, a number of biomarkers have been proposed and reviewed (11). Few of these biomarkers can distinguish EoE from other atopic diseases.

Elsewhere in this issue of the Journal, Henderson et al present their findings on blood eosinophil progenitor (EoP) levels. Henderson and her colleagues report that EoP levels can differentiate between active and inactive disease in patients who were undergoing diet therapy and that EoP levels correlate with pathologic findings. Further they show that the results were not affected by a history of other atopic diseases and were not affected by concurrent medication including proton pump inhibitors or steroids (dermatologic, inhaled, intranasal). Somewhat unexpectedly, concurrent antihistamine use lowered the EoP cut-off value that detected active EoE.

There are limitations to this study that will need to be addressed before the test can become clinically useful. All patients in this study had a diagnosis of EoE and were undergoing diet therapy and so were a select group. Could EoP levels be used as a diagnostic test? Does it work in other subtypes of EoE? Adults as well as children? What about PPI responsive EoE? Are there other medications in addition to antihistamines that alter results? What about histamine 2 receptor antagonists?

The test requires flow cytometry, which may make it inaccessible in some situations and certainly will make it costly. Of note, in this study, half of the samples had to be excluded as accurate flow cytometry was not possible. The researchers claim that this did not affect the results of the study. It is presumably a readily corrected problem.

Determining EoP levels offers a promising test of EoE and is another step toward better diagnosis and monitoring of EoE.

REFERENCES

1. Chang JW, Yeow RY, Waljee AK, et al. Systematic review and meta-regressions: management of eosinophilic esophagitis requires histologic assessment. Dis Esophagus 2018; 31:
2. Papadopoulou A, Koletzko S, Heuschkel R, et al. Management guidelines of eosinophilic esophagitis in childhood. J Pediatr Gastroenterol Nutr 2014; 58:107–118.
3. Ferguson AE, Fulkerson PC. Eosinophilic esophagitis: time to classify into endotypes? J Allergy Clin Immunol 2018; 142:71–72.
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5. Molina-Infante J, Lucendo AJ. Proton pump inhibitor therapy for eosinophilic esophagitis: a paradigm shift. Am J Gastroenterol 2017; 112:1770–1773.
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7. Philpott H, Nandurkar S, Royce SG, et al. Ultrathin unsedated transnasal gastroscopy in monitoring eosinophilic esophagitis. J Gastroenterol Hepatol 2016; 31:590–594.
8. Furuta GT, Kagalwalla AF, Lee JJ, et al. The oesophageal string test: a novel, minimally invasive method measures mucosal inflammation in eosinophilic oesophagitis. Gut 2013; 62:1395–1405.
9. Katzka DA, Geno DM, Ravi A, et al. Accuracy, safety, and tolerability of tissue collection by Cytosponge vs endoscopy for evaluation of eosinophilic esophagitis. Clin Gastroenterol Hepatol 2015; 13:77.e2–83.e2.
10. Lowry MA, Vaezi MF, Correa H, et al. Mucosal impedance measurements differentiate pediatric patients with active versus inactive eosinophilic esophagitis. J Pediatr Gastroenterol Nutr 2018; 67:198–203.
11. Hines BT, Rank MA, Wright BL, et al. Minimally invasive biomarker studies in eosinophilic esophagitis: a systematic review. Ann Allergy Asthma Immunol 2018; 121:218–228.
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