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REAPPRAISAL OF THE EOSINOPHILIC ESOPHAGITIS ENDOSCOPIC REFERENCE SCORE (EREFS): SUBSCORING INFLAMMATORY AND FIBROTIC FINDINGS IMPROVES THE ASSESSMENT OF DISEASE ACTIVITY

Pierfrancesco Visaggi 1, Irene Solinas 1, Gaia Pellegatta 2, Federico Testi 1, Gaia Cairoli 1, Mauro Mitilini 1, Isabella Dulmin 1, Valeria Poletti 2, Giacomo Marcozzi 2, Massimo Bellini 1, Emanuele Marciano 3, Stefano Siboni 4, Alessandro Repici 2, Edoardo Vincenzo Savarino 5, Nicola de Bortoli 1

Affiliations

1 University of Pisa, Pisa, Italy

2 Humanitas Research Hospital, Rozzano, Italy

3 Azienda Ospedaliero Universitaria Pisana, Pisa, Italy

4 Policlinico San Donato, San Donato Milanese, Italy

5 University of Padua, Padua, Italy

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Abstract

Introduction

The eosinophilic esophagitis (EoE) endoscopic reference score (EREFS) is the validated scoring system for endoscopic findings of EoE. EREFS findings are currently scored cumulatively and correlate modestly with histological disease activity (HDA), symptoms, and adaptive behaviors. However, inflammatory and fibrotic findings may reflect different aspects of EoE, but this has never been evaluated.

Aims & Methods

We investigated the correlation of EREFS inflammatory and fibrotic subscores with HDA, symptoms and adaptive behaviors. In three tertiary referral centres for EoE, consecutive adults (>18 years) undergoing upper endoscopy for suspected or follow up EoE were prospectively enrolled. EREFS was scored as follows: edema 0-1; rings 0-3; exudates 0-2; furrows 0-2; stricture 0-1. The EREFS inflammatory sub-score (EREFS-i) combined the scores of edema, exudates and furrows. The EREFS fibrotic sub-score (EREFS-f) combined the scores of moderate-severe rings (score ≥2) and stricture. Subsequently, at least six esophageal biopsies were collected to assess HDA based on peak eosinophil count/high-power field (PEC/HPF) (active EoE PEC ≥15/HPF; EoE in remission: PEC<15/HPF). Symptoms were assessed using the dysphagia symptoms questionnaire (DSQ). Adaptive behaviors were assessed using the Pisa EoE Adaptation Questionnaire v1.0 (PiEAQ) [reference 1]. Clinical characteristics were recorded. Kruskal-Wallis Rank Sum Test and Pearson’s Chi-squared were used for comparisons. ROC curve analysis was used to calculate the diagnostic accuracy (AUC). Spearman’s test and linear regression models were used to assess relationships between variables. Significance threshold was p<0.05.

Results

121 patients were included. 58% had active EoE, 42% were in histological remission. Baseline clinical data are reported in Table 1. The EREFS total score had modest AUC for predicting HDA (0.68) and did not show significant correlation with DSQ and PiEAQ. In contrast, EREFS-i had AUC of 0.73, with 88.2% sensitivity and 51.4% specificity for predicting HDA, being significantly more accurate compared to the EREFS-f (p<0.001; Figure 1). There was a significant correlation between EREFS-i and PEC/HPF with Spearman’s Rho=0.5 (p<0.001), with linear regression showing that an increase of 1 point of any inflammatory feature corresponded to an increase of 12 eosinophils/HPF (p<0.0001). In contrast, EREFS-f correlated significantly with the use of adaptive behaviors assessed with PiEAQ [Spearman’s Rho of 0.6 (p<0.001); Figure 2], with linear regression showing that an increase of 1 point of any fibrotic feature corresponded to an increase of one adaptive behavior (p=0.001). EREFS, EREFS-i, and EREFS-f had nonsignificant negative correlation with DSQ (p>0.05 for all).

Conclusion

We confirmed that, while total EREFS provides a global assessment of endoscopic disease severity, it lacks correlation with histological and clinical disease activity. However, we demonstrated that EREFS-i correlates significantly with PEC and predicts PEC/HPF and that EREFS-f correlates significantly with the use of adaptive behaviors assessed with PiEAQ, which represent known clinical markers of disease activity. Neither EREFS-i nor EREFS-f correlated significantly with DSQ. In conclusion, we showed that, compared to the total EREFS, EREFS sub-scores improve the correlation between endoscopy findings with histology and clinical disease activity markers. Applied to clinical practice, our results represent another step towards precision medicine in the setting of EoE.

Characteristic	N = 121
Sex (M/F)	82/39
Age	40 (31, 50)
EREFS_Score_Total	2.00 (0.00, 3.00)
EREFS_Inflammatory	1.00 (0.00, 2.00)
EREFS_Fibrotic	1.00 (0.00, 2.00)
Dysphagia	73 / 116 (63%)
DSQ	14 (0 – 42)
PiEAQ score	0 (0 – 2)
EREFS total score	2 (0-3)

References

[reference 1] Visaggi P, Del Corso G, Solinas I, Ovidi F, Adamo G, Dulmin I, Baiano Svizzero F, Bellini M, Savarino EV, de Bortoli N. Adaptive Behaviors, Esophageal Anxiety, and Hypervigilance Modify the Association Between Dysphagia Perception and Histological Disease Activity in Eosinophilic Esophagitis. Am J Gastroenterol. 2024 Dec 30. doi: 10.14309/ajg.0000000000003272. Epub ahead of print. PMID: 39787341.

Disclosure

Speaker or consultancy for Apogee Therapeutics, Dr Falk Pharma, Malesci, JB Pharmaceuticals, Sanofi

Conference

UEG Week Berlin 2025

Topics

Oesophagus

Submission format

Abstract

Session

OESOPHAGEAL, GASTRIC AND DUODENAL (Posters)

Citation

United European Gastroenterology Journal 2025; 13 (Supplement 8)

Published

2025

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	AAG overall population (#612)	AAG patients without lesions (#390)	AAG patients with non-NEN polyps (#162)	AAG patients with gNENs (#108)
Sex, female (%)	452 (73.9)	280 (71.6)	280 (71.6)	78 (72.2)
Age (years), median (IQR)	66 (54–74)	61.5 (51-70)	70 (58.7-76.2)	70 (58.7-76.2)
APCA positivity, n (%)	496 (81)	386 (99.1)	125 (77.2)	76 (70.4)
Current smokers, n/n available (%)	48/185 (21.8%)	13/96 (13.5%)	13/96 (13.5%)	13/96 (13.5%)
PPI treatment, n/n available (%)	48/137 (25.9%)	29/98 (29.6%)	7/41 (17.1%)	10/41 (24.4%)
OLGIM, n (%)	II: 245 (40)	II: 144 (37)	II: 63 (39)	II: 60 (56)
OLGA, n (%)	II: 325 (53)	II: 179 (46)	II: 92 (57)	II: 76 (70)
Chromogranin A (ng/mL), median (IQR)	153 (75.5-269.3)	139 (68-221)	139 (68-221)	160 (86.9-251.5)
Gastrin (pg/mL), median (IQR)	667 (336.5-1156.5)	589.0 (281.8–1071.5)	688 (425.8–1200)	874 (362.5-1335)

	S-EoE	F-EoE
Age at diagnosis (n= 3,179) <18 years old	18.5%	30.6%
Inflammatory Score (n= 2,723)	1.62 ± 1.3	1.93 ± 1.32
Fibrosis Score (n=2,723)	1.04 ± 1.04	0.97 ± 1.08
Fibrosis (n=1,701)	58.6 %	62.8 %
EoE-Phenotype (n=3,017)
Inflammatory	75.9 %	79.6 %
Mixed	12.6 %	8.6 %
Stricturing	11.5 %	11.8 %

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