Introduction

Genetic variants associated to a higher risk of developing eosinophilic esophagitis (EoE) and other atopic conditions have been described. However, no study has investigated how these genetic variants influence clinical features of EoE or the atopic concomitances that usually accompanied this disease.

Aims & Methods

This study aims to assess whether single nucleotide polymorphisms (SNPs) in genes related to EoE and atopies associate with disease features and atopic concomitances in a large, representative cohort. Patients diagnosed of EoE according to clinical guidelines were recruited from 4 Spanish referral hospitals and demographical and clinical data were obtained both retrospectively and prospectively. The concomitant atopies analyzed were rhinitis, conjunctivitis, asthma, dermatitis and any food allergy. The recruited cohort was randomly divided into discovery (DC) and validation cohorts (VC) (70% and 30%, respectively). Genotyping was performed using an Open Array platform with 60 SNPs on DNA obtained from peripheral blood. Chi-square or Fisher’s exact test were used for statistical comparisons.

Results

Overall, 647 patients (74.7% male, 32.4±15.2 mean age) were included; 81% of them with an inflammatory phenotype. Rhinitis was the most common atopy (55.8%), while dermatitis was the least frequent (17.5%). Food allergy was documented in 28% of patients.
In relation to EoE characteristics, four SNPs were initially associated with endoscopic findings (measured by EREFS score) and with peak eosinophil counts in esophageal biopsies within the discovery cohort. However, only rs77569859 in the CAPN14 gene remained statistically significant in the validation cohort. TC and CC genotypes of this variant, present in 23.7% of the cohort, were associated with lower EREFS score under a dominant model (3.30±1.60 vs 2.92±1.66, p=0.011 DC/0.002 VC). Additionally, rs76562819, also in CAPN14 gene, showed a trend toward a lower peak eosinophil count per high power field (47.7±24.4 vs 66.6±48.3, p=0.005 DC/0.116VC) under a recessive model (AG and GG genotypes in 11.3% of our patients).
Regarding atopic comorbidities, rs1800925-TT in IL13 (found in 5.7% of our patients) was associated a higher prevalence of conjunctivitis (60% vs 39% in the overall cohort, p=0.020 DC/0.057 VC) and showed a trend toward increased asthma prevalence (54% vs 35%, p=0.056 DC/0.155 VC). A weaker association with asthma was observed for STAT6 rs324015, with an increased prevalence in patients with AG and GG genotypes (41% vs 32%, p=0.079 DC/0.162 VC; present in 34.9 % of the cohort). For dermatitis, a protective effect was seen in patients with the TT genotype of rs2032582 in ABCB1 gene (found in 16.1% of our patients), as the prevalence decreased from 19% to 8% (p=0.033 DC/0.157 VC). No consistent associations were found for rhinitis or food allergy with any SNP across both cohorts.

Conclusion

We have identified significant associations between genetic variants and both clinical features and atopic comorbidities in Spanish patients with EoE, highlighting the potential of genetic profiling to improve clinical characterization and patient management.

Introduction

The global burden of Inflammatory bowel disease (IBD), encompassing ulcerative colitis (UC) and Crohn’s disease (CD), is increasing. Due to its chronic nature, IBD entails long-term healthcare resource use, contributing to substantial economic and environmental costs. Digestive endoscopy, while a cornerstone of disease monitoring, is associated with high energy consumption, greenhouse gas (GHG) emissions, and medical waste. Intestinal ultrasound (IUS) has emerged as a non-invasive, accurate, and potentially more sustainable alternative.

Aims & Methods

The present study aimed to compare the environmental impacts in terms of CO₂ emissions, energy consumption (kWh), and disposable waste of IUS and endoscopy for therapeutic monitoring in IBD. In this single-center, retrospective observational study conducted at IRCCS Humanitas Research Hospital (Rozzano, Milan), all consecutive IUS and lower gastrointestinal endoscopies performed for therapeutic monitoring in IBD patients between January 2022 and December 2025 were included. Procedures for oncologic surveillance in long-standing disease, isolated rectal involvement (<15 cm from the anal verge), or without confirmed IBD were excluded. Clinical and procedural data were collected. Environmental metrics such as CO₂ emissions, energy consumption (kWh), and disposable waste were estimated using validated conversion factors and compared using appropriate statistical tests (Independent-samples t-test or Mann–Whitney U test).

Results

Endoscopic procedures performed during study period (n=2698) ↓ Exclusion criteria - Endoscopic procedures in trial setting (n=1157) -Endoscopic surveillance in UC (n= 216) -Pouchoscopies & ulcerative proctitis monitoring (n=162) - Operative/ emergency procedures (n=71) ↓ Endoscopic procedures included in the analysis (n=1092) Colonoscopies (n= 710)↵ ↳ Sigmoidoscopies (n=382)

intestinal ultrasounds performed during study period (n=1541) ↓ Exclusion criteria - Indications other than disease monitoring/ patient BMI> 30 Kg/m2 (n= 231) ↓ Intestinal ultrasounds included in the analysis (n=1310) ​

Flowchart 1. Visual representation of the process of selecting procedures to be included in the final analysis. UC: Ulcerative colitis; BMI: Body Mass Index.

During the study period, a total of 1092 endoscopic procedures, comprising 710 colonoscopies and 382 sigmoidoscopies, along with 1310 IUS were performed in 1028 IBD patients (58% UC, 42% CD). Estimated resource use for all endoscopic procedures totaled 1,256 kWh of electricity, 72,080 L of CO₂ emissions, and 585.6 kg of disposable waste, based on procedural averages (~1.5 kWh, 80 L of CO₂, 650 g waste per colonoscopy; ~50% of values for sigmoidoscopies). In contrast, IUS was associated with an estimated 524 kWh of electricity and 196.5 kg of disposable waste (average ~0.4 kWh, almost no CO₂ consumption, 150 g waste per exam). Compared to endoscopy, IUS reduced energy use by 82%, CO₂ emissions by 95%, and waste generation by 66% (P < 0.05 for all comparisons).

Conclusion

While gastrointestinal endoscopy remains indispensable in certain clinical scenarios, its environmental impact is considerable. In contrast, IUS emits almost no equivalent of CO₂, consumes significantly less energy per examination and produces negligible wastes. For therapeutic monitoring in IBD, IUS has demonstrated high diagnostic accuracy with a markedly lower ecological footprint. These findings promote IUS as a sustainable and environmentally friendly alternative for routine IBD monitoring in appropriate scenarios.

Disclosure

A Armuzzi has received consulting and/or advisory board fees from AbbVie, Allergan, Amgen, Arena, Biogen, Bristol-Myers Squibb, Celltrion, Eli-Lilly, Ferring, Galapagos, Gilead, Janssen, MSD, Mylan, Pfizer, Protagonist Therapeutics, Roche, Samsung Bioepis, Sandoz, Takeda, lecture and/or speaker bureau fees from AbbVie, Amgen, Arena, Biogen, Bristol-Myers Squibb, Celltrion, Eli-Lilly, Ferring, Galapagos, Gilead, Janssen, MSD, Mitsubishi Tanabe, Novartis, Pfizer, Roche, Sandoz, Takeda, Tigenix, and research grants from MSD, Pfizer, Takeda and Biogen. A Repici received consulting fee from Medtronic, Fuji and Olympus and has received research grant from Alfa Sigma, Norgine, Boston and Erbe. C Bezzio received speaker’s fees and consulting fees from for Takeda, MSD, Ferring, Abbvie, Galapagos and Janssen. A Dal Buono has received speaker’s fees from Pfizer, MSD, Eli-Lilly, Celltrion, Janssen, and consulting fees from Ferring. R Gabbiadini has received speaker’s fees from Pfizer, MSD, Ferring, Eli-Lilly, Celltrion, Janssen, consulting fees from Pfizer and Abbvie. G. Privitera has received speaker’s fees from Janssen and Alphasigma. B. Masoni and G. Franchellucci declare no conflict of interests.

Introduction

While trans-perineal ultrasound (TPUS) is promising, its accuracy compared to trans-abdominal ultrasound (TAS) and endoscopic ultrasound (EUS) in predicting rectal histoendoscopic activity in ulcerative colitis (UC) is unclear.

Aims & Methods

We aimed to evaluate the reliability of TPUS in predicting rectal histoendoscopic activity in UC using EUS as the reference standard. This prospective study included adult UC patients who underwent TAS and TPUS, followed by EUS. Rectal total wall thickness (TWT) and vascularity (Modified Limberg Score, MLS) were measured on all modalities. Additionally, mucosal thickness (MT) and submucosal thickness (SMT) were assessed on EUS. Receiver operating characteristic (ROC) analysis was performed to determine the area under the curve (AUC) for predicting endoscopic activity (Ulcerative Colitis Endoscopic Index of Severity, UCEIS >1) and histologic activity (Nancy Index >1).

Results

A total of 142 UC patients (33.8% female, median age 40 years, BMI 22.5 kg/m²) were included. Disease extent was proctitis (12%), proctosigmoiditis (58%), and extensive colitis (30%). The median SCCAI score was 3 (range: 0-8). Most patients were on 5-ASA (90.8%), azathioprine (31%), and tofacitinib (10.6%).
The median rectal length visualized on TPUS was 3.9 cm (2.4-6.3 cm). Endoscopic remission (UCEIS ≤1) was observed in 49.3% of patients, and histologic remission (NHI ≤1) in 38.7%.
For endoscopic activity, EUS had the highest accuracy, with MT >0.95 mm (AUC: 0.96, sensitivity: 98.6%, specificity: 87%) and MLS >1 (AUC: 0.95, sensitivity: 81.7%, specificity: 94%). TPUS had moderate accuracy(TWT >5.4 mm, AUC: 0.73), while TAS performed poorly (TWT >5.8 mm, AUC: 0.63).
For histologic remission, EUS vascularity (MLS >1) was most predictive (AUC: 0.91, sensitivity: 66.3%, specificity: 98.1%), followed by rectal TWT ≥4 mm (AUC: 0.83) and MT ≥0.95 mm (AUC: 0.86). Among non-EUS techniques, TPUS (TWT ≥6.1 mm, AUC: 0.66) showed moderate accuracy, while TAS was the least predictive (AUC: 0.62).
The Milan Ultrasound Criteria (MUC) demonstrated highest accuracy for endoscopic remission with EUS MUC ≥8 (AUC: 0.94), followed by TPUS (AUC: 0.78) and TAS (AUC: 0.67). For histologic remission, EUS MUC >7 had the highest accuracy (AUC: 0.87), followed by TPUS (MUC ≥9.7, AUC: 0.70) and TAS (AUC: 0.64) (Table 1). BMI-based comparisons showed no significant differences in MUC scores.

Measure	Sensitivity	Specificity	AUC	p-value	95% CI
	Endoscopic Activity
TAS (MUC) (≥8.5)	67.6%	60.9%	0.67	<0.001	0.59-0.76
TPUS (MUC) (≥8)	86%	62.3%	0.78	<0.001	0.70-0.86
EUS (MUC) (≥8)	81.7%	81.2%	0.94	<0.001	0.85-0.95
	Histologic activity
TAS (MUC) (>8.6)	62.8%	66%	0.64	0.005	0.54-0.74
TPUS (MUC) (≥9.7)	59.3%	79.6%	0.70	<0.001	0.61-0.79
EUS (MUC) (>7)	83.7%	81.5%	0.87	<0.001	0.81-0.93

Correlation analysis showed a strong correlation between TPUS and EUS TWT (r=0.371, p<0.001). TPUS and TAS had moderate correlation (r=0.309, p<0.001), while TAS and EUS showed weaker correlation (r=0.264, p=0.002 for average TWT, r=0.234, p=0.005 for lower rectal TWT). MUC scores correlated best between EUS and TPUS (r=0.425, p<0.001).

Conclusion

While EUS remains the most accurate, TPUS shows moderate accuracy for assessing rectal inflammation in UC. However, TPUS is limited to the lower rectum and needs further validation for better reproducibility. Standardized cutoffs and integration into routine UC monitoring could enhance non-invasive assessment, reducing endoscopy reliance and improving patient management.(NCT06717906).

References

1. Sagami S, Kobayashi T, Aihara K, Umeda M, Morikubo H, Matsubayashi M, Kiyohara H, Nakano M, Ohbu M, Hibi T. Transperineal ultrasound predicts endoscopic and histological healing in ulcerative colitis. Aliment Pharmacol Ther. 2020;51(12):1373-1383. [10.1111/apt.15767]
2. Sagami S, Kobayashi T, Aihara K, Umeda M, Odajima K, Morikubo H, Asonuma K, Miyatani Y, Fukuda T, Matsubayashi M, Kiyohara H, Nakano M, Hibi T. Early improvement in bowel wall thickness on transperineal ultrasonography predicts treatment success in active ulcerative colitis. Aliment Pharmacol Ther. 2022;55(10):1320-1329. [10.1111/apt.16817]