Introduction

Among the constellation of symptoms attributed to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, dysphagia emerged as a rather rare manifestation. This post-COVID-19 dysphagia seems to arise from esophago-gastric junction (EGJ) disorders either triggered or fueled by SARS-CoV-2 infection. New-onset dysphagia is associated with EGJ-outflow obstruction (EGJ-oo) whereas post-COVID-19 aggravation of dysphagia is associated with Achalasia. Available evidence to guide treatment for patients with post-COVID-19 dysphagia are currently lacking.

Aims & Methods

To offer an evidence-based therapeutic approach for patients presenting with post-COVID-19 dysphagia. Patients presenting with post-COVID-19 dysphagia between January 2021-December 2022, underwent esophagogastroduodenoscopy, esophagram, computed tomography and two esophageal high-resolution manometry (HRM) studies 4-8 months apart. The Chicago classification 4.0 was used for HRM diagnosis. SARS-CoV-2 infection was documented through at least one positive reverse transcriptase polymerase chain reaction (RT-PCR) test. Demographics, history of anti-SARS-CoV-2 vaccination, Eckardt scores (ES) were also recorded. A step-up therapeutic approach was applied and evaluated. All patients received proton pump inhibitor (PPI-20mg rabeprazole od) therapy as a first step. If dysphagia and/or vomiting persisted or the patient experienced bolus impaction then pneumatic dilatation (PD) with a rigid 30mm balloon was applied. If dysphagia persisted despite PD then the patient underwent 35mm-PD or per-oral endoscopic myotomy (POEM), based on personal preference and anesthesia eligibility. In the occurrence of type III Achalasia, POEM was offered as second-line treatment. Informed consent was obtained from all patients.

Results

Thirty-two patients (23 females; mean age±SD: 61±8years) were included, eighteen with new-onset dysphagia (median ES:6) and fourteen with aggravation of pre-existing dysphagia (median ES:8 vs 3). All patients with new-onset dysphagia had EGJ-oo whereas those with pre-existing dysphagia exhibited either type II (N=13) or type III (N=1) Achalasia. A female predominance was evident in the EGJ-oo group (female:male ratio of 2.7:1). Achalasia patients exhibited higher median IRP values compared to the EGJ-oo group: 23.1(1.5) vs 17.4(1.7) (P<0.001). In patients with EGJ-oo, dysphagia resolved under PPI treatment over a median(IQR) of 4(2.2) months: IRP 13.4(1.2) vs 17.4(1.7) at baseline (P<0.05). PPI treatment was not effective in the group with pre-existing dysphagia (P=0.8) therefore PD at 30mm was applied in 13 patients and POEM in one patient with type III Achalasia. Interestingly, all patients within the PD-treated Achalasia group required further treatment escalation either PD at 35mm (N=6) or POEM (N=7) for resolution of symptoms. In the 35mm-PD group ES dropped from 8 to 3 (P<0.05) whereas in the POEM-treated group ES dropped from 8 to 1 (P<0.05). POEM was more effective in reducing symptoms compared to 35mm-PD (P=0.003).

Conclusion

Based on HRM, two post-COVID-19 dysphagia phenotypes can be identified each requiring different management. New-onset dysphagia is associated with EGJ-oo and seems to resolve under PPI over time. On the contrary, post-COVID-19 aggravation of dysphagia corresponds to type II or III Achalasia and requires aggressive endoscopic treatment either PD with a larger caliber balloon or POEM, with the latter yielding more favorable results.

References

1. Manolakis A, Trikola A, Chougias D, et al. An elusive manifestation of COVID-19: dysphagia due to esophago-gastric junction disorders. United European Gastroenterology Journal 2022; 10 (Supplement 8)
2. Webler K, Carpenter J, Hamilton V, et al. Dysphagia Characteristics of Patients Post SARS-CoV-2 During Inpatient Rehabilitation. Arch Phys Med Rehabil 2022;103:336-341
3. Lee MY, Oh BM, Seo HG. Prolonged Dysphagia After a COVID-19 Infection in a Patient With Parkinson Disease. Am J Phys Med Rehabil 2021;100:837-839

Disclosure

None

Introduction

Non-invasive biomarkers are needed to improve the management of eosinophilic esophagitis (EoE). We investigated whether eosinophil and lymphocyte counts could be used to diagnose EoE among patients with dysphagia and assess histological, endoscopic, and clinical disease activity in patients with known EoE.

Aims & Methods

This was a prospective study conducted at four EoE referral centers (Pisa, Padova, Humanitas Research Hospital, Milano Policlinico San Donato). We enrolled consecutive patients undergoing esophagogastroduodenoscopy (EGD) for suspected or known EoE who had performed blood counts within one month before EGD. Histological remission and non-EoE-related dysphagia (NED) were defined according to current guidelines on EoE. Endoscopic characteristics were classified according to the EoE reference score (EREFS). Demographic, clinical and full blood count data were collected. After the EGD, all patients completed the Dysphagia Symptom Questionnaire over 14 days (DSQ). Kruskal-Wallis Rank Sum Test and Pearson’s Chi-squared were used for comparisons. ROC curve analysis was used to assess the diagnostic accuracy. Spearman’s test was used for correlations. Significance threshold was p<0.05.

Results

We included 210 consecutive patients. Of these, 123 had EoE (58.5% active; 41.5% in histological remission) while 87 had non-EoE dysphagia (NED). Characteristics in Table 1. Absolute eosinophil count (AEC) of active EoE was significantly higher than NED (335 vs 90/mm3; p<0.001), and so was eosinophil percentage (4.6% vs 1.1%; p<0.001), and median lymphocyte percentage (30 vs 27%; p<0.001). ROC curve analysis showed that a cut-off of 155 eosinophils/mm3 had an AUC of 0.85, with 71% specificity and 87% sensitivity for the identification of EoE among patients with dysphagia (Figure 1a). Other ROC analyses on the diagnosis of EoE reported in Table 2. With regards to disease monitoring, only eosinophil counts differed significantly between EoE and NED. Median AEC of active EoE was higher than EoE in remission (335 vs 200/mm3; p<0.01), and so was eosinophil percentage (4.6 vs 1.4%; p<0.001) (Table 3). Based on ROC analysis, a cut-off of 325 eosinophils/mm3 had and AUC of 0.70 for the identification of histological remission in EoE, with a specificity of 52.7%% and sensitivity of 82.3% (Figure 1b) (Table 3). There was modest positive correlation between AEC and the EREFS with Spearman’s Rho of 0.4 (p<0.0001), but there was no correlation between AEC and DSQ scores (Rho= -0.01; p=0.9).

Conclusion

Our results show that the AEC in peripheral blood has good accuracy for the diagnosis of EoE in patients with dysphagia and moderate accuracy for monitoring histological disease activity. In addition, AEC was modestly correlated with endoscopic disease activity (EREFS score) but not with symptoms.

Disclosure

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

Introduction

Eosinophilic esophagitis (EoE) is a chronic, condition linked to a type 2 inflammatory response and frequently associated to other atopic conditions. EoE may presents either sporadically, or with aggregation of cases within a same family. Limited information has been provided on the differences in clinical characteristics and disease features between sporadic and familiar EoE, largely due to the lack of large patient cohorts.

Aims & Methods

To find differences in sporadic and familiar cases of EoE which may support distinct clinical management, a cross-sectional analysis of the multicenter EoE CONNECT registry was performed. Demographic and clinical from patients recruited at 42 hospitals in 4 European countries were extracted on March 28th, 2025. Information extracted included 1) age at diagnosis and diagnostic delay; 2) symptoms leading to diagnosis; 3) disease endoscopic and histologic features at diagnosis; and 4) atopic concomitances.

Results

	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 %

Overall, 4,053 patients (75.4 % males, mean age 33.3 ±15.2 years) were analyzed, including 3028 (74.7 %) sporadic (S-EoE), 714 (17.6%) without familiar data and 311 (7.7 %) familiar (F-EoE) cases including 89 families. Among the family forms, n= 76 families showed 2 affected members, n= 11 presented 3 members, and n= 2 with 4 members. In 85/89 families we identified the index case consisting in sons (13), parents (23), siblings (38), or other distant kinships.
The F-EoE forms were diagnosed at younger mean ± SD ages than S-EoE (29.8±15.6 vs. 33.7±15.1; p<0.001) and included a higher proportion of pediatric patients (considered as those below 18 at diagnosis; 30.6% vs. 18.5%; p<0.001)
Symptoms leading to EoE diagnosis were similar across study groups, with slightly higher presences of abdominal pain (as they included more pediatric cases; 7.7% vs. 4.5%; p=0.01) and chocking episodes (7.7% vs. 4.5%; p=0.01) among F-EoE.
Endoscopy presented more severe features according to EREFS among F-EoE (mean ± SD being 2.86 ± 1.66 vs. 2.64 ± 1.68; p=0.054) at the expense of both fibrotic and inflammatory features, despite only the later reach statistical significance (1.93 ± 1.32 vs. 1.62 ± 1.3; p<0.001). Esophageal biopsies exhibited higher mean ± SD peak eosinophil counts in F-EoE cases (57.11 ± 40.7 vs. 52.87 ± 37.97; p=0.04).
F-EoE were more allergic patients, as they presented a higher mean ± SD number of concomitant atopies (1.44 ± 1.25 vs. 1.25 ± 1.22; p=0.009) and all were more common among them, with conjunctivitis and hives reaching statistical significance (p=0.01 and p=0.002 respectively). Overall, a higher proportion of F-EoE had at least one atopy compared to S-EoE (69.4 % vs. 63.8%).

Conclusion

F-EoE seems to present more severely, with earlier onset, more inflammatory load in endoscopy and biopsies and higher concomitant allergic manifestations.

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

Introduction

The LIR!C trial demonstrated that laparoscopic ileocaecal resection (ICR) is a cost-effective alternative to infliximab therapy (IFX) in patients with uncomplicated ileocaecal Crohn’s disease (CD), with comparable quality of life outcomes. The aim of this study was to assess the 10-year follow-up of patients enrolled in the LIR!C trial.

Aims & Methods

This retrospective follow-up study included patients from the original LIR!C trial, a multicentre randomized controlled trial comparing ICR to IFX treatment in patients with ileal CD. Long term follow-up data were collected between February 3 and April 14, 2025. Data extraction was focused on initiation or switch of IBD treatments (corticosteroids, immunomodulators and/or advanced medical therapies) and (re)-resections. The follow-up period ranged from trial enrolment to the last visit with the gastroenterologist or surgeon. Primary outcomes were: (1) proportion of patients in clinical remission without therapy switch (no medical therapy or re-resection in the ICR group, and continuation or the cessation of IFX in case of remission in the IFX group), and (2) therapy-free remission, defined as clinical remission without IBD medication and (re)resections.

Results

Follow-up data were available from 60 ICR patients and 57 IFX patients (87% of 134 patients originally included). The median follow-up time was 12 years (IQR 9-14). The clinical remission rate without therapy switch was 40% in the ICR group compared to 26.3% in the IFX group (p=0.117). Of the 60 ICR patients, 24 (40%) had no additional therapy, 13 (21.7%) received an immunomodulator, 18 (30%) biological therapy and 5 (8.3%) underwent a second resection after biological treatment. In the IFX group, 33 (57.9%) required an ICR of whom 25 (75.8%) had previously received second-line biological treatment. Additionally, 7/57 patients (12.3%) were therapy free, 8 (14%) continued IFX treatment, 6 (10.5%) received other biological treatment, and 3 (5.3%) switched to an immunomodulator. Therapy-free remission was significantly higher in the ICR group when compared to the IFX group (40% vs 12%, p < 0.001).

	ICR group (N=60)	IFX group (N=57)
Total follow-up time (y), median (ICR)	11 (9-14)	13 (9-15)
Prophylactic immunomodulator usage, n (%)	26 (43.3)	35 (61.4)
			P-values
Clinical remission, n (%)	24 (40)	15 (26.3)	0.117
Therapy-free remission, n (%)	24 (40)	7 (12.3)	<0.001
(Re-)resection, n (%)	5 (8.3)	33 (57.9)	<0.001

Conclusion

After 10 years of follow-up, the clinical remission rate without therapy switch was comparable between both groups, highlighting the long-term durability of both treatment approaches. The majority of IFX patients needed ICR within 10 years of follow-up. 40% of the ICR group did not require any additional therapy further supporting ICR as first-line treatment option in ileal CD.

References

Ponsioen, C. Y., de Groof, E. J., Eshuis, E. J., Gardenbroek, T. J., Bossuyt, P. M. M., Hart, A., Warusavitarne, J., Buskens, C. J., van Bodegraven, A. A., Brink, M. A., Consten, E. C. J., van Wagensveld, B. A., Rijk, M. C. M., Crolla, R. M. P. H., Noomen, C. G., Houdijk, A. P. J., Mallant, R. C., Boom, M., Marsman, W. A., Stockmann, H. B., … LIR!C study group (2017). Laparoscopic ileocaecal resection versus infliximab for terminal ileitis in Crohn's disease: a randomised controlled, open-label, multicentre trial. The lancet. Gastroenterology & hepatology, 2(11), 785–792. https://doi.org/10.1016/S2468-1253(17)30248-0

Disclosure

GD'H served as a consultant for AbbVie, Alimentiv, AstraZeneca, Bristol Myers Squibb, Celltrion, Eli Lilly, Exeliom Biosciences, Johnson & Johnson, Pfizer, and Takeda; and has received speakers bureau fees from AbbVie, Eli Lilly, Pfizer, Bristol Myers Squibb, and Takeda.

Introduction

Acute severe ulcerative colitis (ASUC) is a life-threatening complication of ulcerative colitis, requiring hospitalization and potentially surgery. Initial treatment relies on intravenous corticosteroids, but non-responders require rescue therapies such as infliximab or cyclosporine. Janus kinase inhibitors (JAKi), including upadacitinib, and tofacitinib, rapidly modulate immune response and have shown promise in managing ASUC, based on small-scale studies.

Aims & Methods

This single-center retrospective study evaluated the efficacy of JAK inhibitors, upadacitinib and tofacitinib, as a rescue therapy in patients with ASUC not responding to intravenous corticosteroids and/or infliximab who were hospitalized during the period from May 2023 to October 2024. Upadacitinib was administered at a dose of 45 or 60mg/day during hospitalization, with the higher dose reduced to 45mg/day upon discharge. Tofacitinib was administered at 30 mg/day during hospitalization, with the dose reduced to 20mg/day upon discharge. Patient outcome was assessed by partial Mayo score, endoscopic Mayo score (eMayo), and laboratory markers (CRP, hemoglobin, albumin, and fecal calprotectin).

Results

The cohort included 15 patients with ASUC who received JAKi as rescue therapy (8 males, 10 with extensive colitis; 73.3% with prior failure of infliximab): 13 upadacitinib (45mg and 60mg daily in 4 and 9 patients, respectively) and 2 tofacitinib. All patients had failed on intravenous corticosteroids, and one also failed on infliximab as a rescue therapy. All but one patient responded to JAKi and were discharged. One patient with no response underwent a colectomy. Endoscopy was performed at a median time of 8 weeks, with 57 % of patients achieving endoscopic remission (eMayo ≤ 1). During a median follow-up of 26 weeks after initiation of JAKi, 9 patients continued the treatment, 8 on upadacitinib and 1 on tofacitinib. One patient required colectomy, four were switched to another biologic, and one patient (a 76-year-old woman) died of pneumonia one month after starting therapy with JAKi. Within the first 3 months after hospital discharge, no further patients underwent a colectomy.

Conclusion

JAK inhibitors seem to be an effective rescue therapy for ASUC in patients who have already failed infliximab treatment. However, caution is needed in elderly patients.