Introduction

Eosinophilic esophagitis (EoE) is a chronic Th-2 mediated inflammatory disease, closely associated with comorbid allergic disorders, including atopic dermatitis (AD). Studies show that EoE is associated with atopic disease but the prevalence of EoE symptoms in patients with atopic conditions is unknown. To date, a single retrospective study involving 80 atopic patients has shown that the prevalence of dysphagia in atopic patients without a known history of EoE is higher than the control population, while it failed to find a significant association between dysphagia and atopic eczema [1]. Therefore, in our study we evaluated the prevalence of dysphagia in a population of patients severe with atopic dermatitis, candidates to biological therapy, in order to consider the possibility of screening these patients for comorbid EoE.

Aims & Methods

Consecutive patients with moderate to severe AD referred to our tertiary care center from January to October 2023 were prospectively screened. Based on AD severity and phenotypic manifestation and comorbidities, patients were referred to systemic therapy with cyclosporine (CsA), biological drugs (dupilumab, tralokinumab) or JAK inhibitors (upadacitinib, abrocitinib, baricitinib). The presence of dysphagia was evaluated by using the self-administered Eosinophilic Esophagitis Score Activity Index (EEsAI). This score uses seven PRO (patient reported outcome) items that are used to assess characteristics of dysphagia, behavioral adaptations to living with dysphagia and pain while swallowing. The presence of other atopic disorders and esophageal symptoms was also recorded. Questionnaires were collected and analyzed at the gastroenterology department, while the dermatology consultant was blinded from the questionnaire results. Data are presented as mean±SD.

Results

147 patients (85 M, 42.7±23) successfully completed the form. The prevalence of dysphagia in the population was low (7 patients, 4.7%). The prevalence of other atopic conditions was similar in dysphagia and non-dysphagia patients (42 vs 40%). Patients reporting dysphagia were more likely to have heartburn (28.5 vs 7.1%, p=0.043), while other esophageal symptoms did not differ. Based on clinical evaluation by a single experienced dermatology consultant (clinical phenotype of AD, AD severity and comorbidities), patients were assigned to either receive CsA (8 pts, 4 M, 41.7±18y), dupilumab (42 pts, 27 M, 39.6±21y), tralokinumab (21 pts, 11 M, 46.2±12.5y), or Jak inhibitors (76 pts, 43 M, 43±23y). The prevalence of dysphagia was significantly higher in the Dupilumab group as compared to other therapies (19 vs 1.9%, p=0.01), while other esophageal symptoms were comparable between the two groups.

Conclusion

We observed that the overall prevalence of dysphagia is relatively low in severe AD patients. However, we found a higher likelihood of complaining of dysphagia in the subset of patients who were candidate to treatment with Dupilumab. Due to the reported augmented risk for atopic patients to develop EoE, screening AD patients complaining of dysphagia before initiating biologic treatment is pivotal to prevent EoE under-diagnosis and under-treatment. Better characterizing the relationship between AD and EoE and a multidisciplinary approach to atopic patients will facilitate the optimal management to both conditions.

References

1- Eid R, et al. The Prevalence of Dysphagia and Food Impactions is High in Atopic Patients Without a Known History of Eosinophilic Esophagitis (EoE), Journal of Allergy and Clinical Immunology, Volume 149, Issue 2, Supplement, 2022, https://doi.org/10.1016/j.jaci.2021.12.689.

Introduction

Controversy still remains regarding the appropriate tools to investigate symptoms’ severity in Eosinophilic esophagitis (EoE). It is, indeed, recognized that the behavioral adaptation strategies implemented by EoE patients may overshadow the effective burden of dysphagia at presentation. On the other hand, it has also been reported that EoE patients are at higher risk of developing Avoidant restrictive food intake disorder (ARFID) in both pediatric and adult settings, calling for the need of assessing their eating patterns [1]. Given this background, the Eosinophilic Esophagitis Score Activity Index (EEsAI) has been specifically developed to evaluate the severity of dysphagia and eating behaviors in EoE patients [2]. To date, this standardized tool has never been explored in an Italian EoE population.

Aims & Methods

This was a prospective study involving consecutive EoE patients referred to our tertiary center from March 2022. The EEsAI was translated and adapted to an Italian cultural context by replacing “grits” with “porridge”, “dry rice” with “boiled rice” and “omelet and mash” instead of “pudding and jelly”. All patients underwent the EEsAI questionnaire at baseline and after each therapy modification, independently from histological remission. The EEsAI score ranges between 0-100 and consists of two domains: (1) the Visual Dysphagia Question (VDQ) that explores the difficulty in swallowing 8 different food consistencies [meat, mashed potato, boiled rice, hamburger, soft bread, porridge, raw vegetables, fries; range 0-3 for each food] and (2) the Avoidance, Modification and Slowly eating (AMS) score, which measures the behavioral modifications implemented in a 7-day recall period. Data are presented as mean±SD.

Results

40 EoE patients (32M, 31±11 ys) were studied. 26 patients (65% of the population, 23M; 30±12 ys) achieved histological remission: 7 patients (27%; 24±11ys) on proton pump inhibitors, 14 (54%; 31.5±15ys) on topical steroids and 5 patients (19%; 21±11ys) with Interleukin 4 receptor α antibody. The total VDQ questionnaire subscores significantly differ between active and inactive esophagitis (2.6±2.3 vs 1.2±1.4 p=0.01), with a significant difference in the difficulty to swallow boiled rice and hamburger (0.7±1 vs 0.1±0.3; p=0.01 and 0.9±0.9 vs 0.3±0.7; p=0.005, respectively). On the other hand, no difference was observed for all the other food consistencies. Mirroring this, the pre-post treatment total EEsAI scores significantly differ (30±24 vs 16±19 p=0.01). Interestingly, despite the improved severity of dysphagia, no significant differences were observed in Avoidance behavior (0.4±1.1 vs 0.4±0.8), Modification (0.3±1 vs 0.4±1.3), Slow eating (0.8±2 vs 0.6±1.9) and total AMS subscore (2.3±2.3 vs 2±2; all p=NS). Overall, avoidance behaviors were retained in 27% of EoE patients who achieved clinical and histological remission.

Conclusion

EoE patients show a significant improvement in dysphagia severity after histological remission, as measured by the VDQ item. However, this is not paralleled by an improvement in eating behaviors and avoidance strategies. This implies that patients, once established an abnormal eating pattern, avoid to adjust these behaviors, even following resolution of symptoms and histological activity. Properly evaluating eating patterns in EoE patients in clinical practice, through the standardized EEsAI questionnaire is crucial to promptly identify and correct abnormal eating patterns in EoE patients.

References

1. Ketchem CJ, Dellon ES. Avoidant Restrictive Food Intake Disorder in Adults With Eosinophilic Esophagitis. Gastro Hep Adv. 2022;1(1):52-54. doi:10.1016/j.gastha.2021.09.004
2. Schoepfer AM, Straumann A, Panczak R, et al. Development and validation of a symptom-based activity index for adults with eosinophilic esophagitis. Gastroenterology. 2014;147(6):1255-66.e21. doi:10.1053/j.gastro.2014.08.028

Introduction

Eosinophilic esophagitis (EoE) is a Th2-related disease characterized by dysphagia and food impaction. EoE has been associated with several other atopic disorders, supporting the knowledge that it may represent a late manifestation of the so-called “atopic march”. However; in everyday clinical practice, allergic comorbidities are rarely objectivized by means of specialist consultations and often rely on patients’ self-reporting. This bears the risk of not fully recognizing the burden of Th2-related pathology, since EoE patients may outgrow some of the allergic diseases presenting during childhood; or, conversely, they could underestimate the presence and severity of Th2-diseases. To this aim, a multidisciplinary task-force involving multiple specialists was established at our university hospital, in order to systematically investigate newly referred EoE patients.

Aims & Methods

This is a cross-sectional observational study, involving consecutive EoE patients that were referred to our tertiary center from January 2022. We prospectively collected data about patients’ clinical history, specifically recording the presence of Th2-related comorbidities. Each patient underwent an esophagogastroduodenoscopy with differential esophageal biopsies. After reaching a conclusive diagnosis of EoE, patients were referred to dermatology, ear, nose and throat specialist (ENT) for rhinofibroscopy, immunologist (performing prick test, as necessary) and respiratory consultant for spirometry.

Results

40 EoE patients were included (34M, age 31±12 years), with a mean age of onset of 23±16 years. A clinical history of Th2-comorbidities was reported by 90% of the overall population with rhinitis being the most prevalent comorbidity (77.5%), while no patient reported Chronic Rhinosinusitis with Nasal Polyps (CRwNP). Asthma, food allergy and atopic dermatitis (AD) were reported in 15 (37.5%), 14 (35%) and 9 (22.5%) patients, respectively. Following the consultations, the presence of asthma, food allergy and AD did not significantly differ (37.5 vs 30%, 35 vs 45% and 22.5 vs 20%), since only 3 patients reporting a history of asthma did not confirm the diagnosis at spirometry and one patient with a history of AD had dermographic urticaria. On the contrary, following ENT consultation, 6 patients with rhinitis received the diagnosis of CRwNP (0 vs 15%, p=0.01). Overall, nearly 60% of patients had two comorbid Th2 disorders besides EoE and 25% of the whole population of EoE patients had 3 or more.

Conclusion

Our results clearly support the need for a multidisciplinary team approach to investigate the burden of Th2-related pathology in EoE patients. In our hands, the prevalence of Th2-related comorbidities was as high as 97.5% of EoE patients and up to 63% of our population had 2 or more allergic disorders. Furthermore, CRwNP is frequently under-reported and properly diagnosed only following rhinofibroscopy. This is further from being irrelevant when managing EoE patients. Indeed, it may guide the most appropriate choice of therapy by targeting multiple atopic manifestations at the same time, since many Th2-related diseases share common pathophysiological mechanisms and treatment.

Introduction

Eosinophilic esophagitis (EoE) is a chronic, type-2 inflammation-driven esophageal disease causing dysphagia and esophageal dysfunction. Patients with inflammatory bowel disease (IBD) or other type-2 inflammatory disorders may have an increased risk of EoE, but prevalence data are limited. This study examines the prevalence of dysphagia and EoE in patients with type-2 inflammatory diseases or IBD.

Aims & Methods

In this prospective, multicentric, questionnaire-based screening study, patients from the departments of gastroenterology, pulmonology, dermatology, and otolaryngology at the Medical University of Vienna, as well as from the Allergy Center Floridsdorf, were screened for dysphagia using the validated brief esophageal dysphagia questionnaire (BEDQ). The primary endpoint was the prevalence of clinically relevant dysphagia, defined as a BEDQ score ≥10 or a history of bolus impaction in the past year. Endoscopy was offered to symptomatic patients without recent biopsies. Patient characteristics and differences in absolute eosinophil count, eosinophilic cationic protein (ECP), and IgE levels were analyzed using independent-samples T-tests.

Results

A total of 690 patients (45.7% female, mean age 54.5 years) were screened; 54.4% had IBD, 20.2% allergic rhinitis, 16.4% asthma, 8.7% atopic dermatitis, 6.4% chronic rhinosinusitis with nasal polyps (CRSwNP), and 5.2% IgE-mediated food allergy with multiple diagnoses possible. Overall, 5.1% (n=35) exhibited clinically relevant dysphagia. EoE was previously diagnosed in 2.0% (n=14), including four patients with clinically relevant dysphagia. Among the remaining 31 patients, eight had prior endoscopies ruling out EoE, seven underwent endoscopy revealing two new EoE cases, and 16 are still awaiting gastroscopy. No significant differences in IgE, eosinophilic count, or ECP were found between patients with EoE, those with dysphagia, and asymptomatic individuals.

Conclusion

Patients with IBD and type-2 inflammatory diseases exhibit a high prevalence of dysphagia. While EoE is more common than in the general population, most dysphagia remains unexplained. Systematic dysphagia screening in this high-risk population may reduce diagnostic delay.

Clinical Case Summary

We report the case of a 17-year old male referred in December 2020 for intermittent dysphagia and a history of food impaction. An esophago-gastric-duodenoscopy (EGDs) showed a substenosis in mid esophagus, severe rings, diffuse furrowing, edema and exudates (EREFS 6). Eosinophilic esophagitis (EoE) was histologically confirmed. Patient started lansoprazole 15mg bid and swallowed fluticasone from a multi-dose inhaler (880mcg) for 12 weeks. At follow-up, there was a resolution of the substenosis with persistence of all the other EoE features (EREFS 5) and >50 eosinophils/HPF. Galenic oral viscous budesonide (1mg bid) was assigned for 12 weeks with unchanged histological and endoscopic features. He also admitted of not being fully compliant to therapy and refused elimination diets.
In January 2022, a multidisciplinary team approach was pursued and he was sent to immunology, respiratory and ENT consultations conclusive for multiple food allergies; moderate asthma and Chronic Rhinosinusitis with Nasal Polyps. Bronchodilators and anti-H2 were administered with an improvement of respiratory symptoms but persistent dysphagia [Visual Dysphagia Question (VDQ) score 7/10]. In October 2022, based on the multiple Th2 comorbidities, patient was started on Dupilumab 300mg every other week. After 20 weeks, despite achieving histological remission (0 eosinophils/HPF), he still reported dysphagia (VDQ 5) and had an EREFS of 4. In November 2023, Dupilumab posology was modified to 300mg weekly. After 16 weeks, EGDs confirmed absence of eosinophilic infiltration with almost complete resolution of endoscopic (EREFS 1) and clinical (VDQ 2) signs.
Dupilumab at optimized EoE dosing, may have late effects on immune and structural cells beyond the early effects on esophageal eosinophilia. Like in other immune-mediated disorders, a “top-down” approach with biologics could be considered in severe fibro-stenosing EoE patients in order to prevent and even revert esophageal tissue remodeling.

References

Iconography included in the case report:
1- Endoscopic image of patient at diagnosis: At baseline evaluation, endoscopy revealed the presence of a substenosis in mid esophagus accompanied by severe rings, diffuse furrowing, edema and exudates [EoE Endoscopic ReFerence Score (EREFS) 6]
2- Endoscopic image of patient following lansoprazole 15mg bid and topical corticosteroid therapy: there was a resolution of the substenosis with persistence of all the other EoE features (EREFS 5)
3- Endoscopic image of patient after 20 weeks of Dupilumab 300mg every other week: despite the absence of eosinophils at histology, there was persistence of Edema (1), Rings (2) and mild furrowing (1) with a total EREFS score of 4
4- Endoscopic image of patient after 16 weeks of optimized Dupilumab dosing (300mg/week): there was an almost complete resolution of the endoscopic features of EoE with only residual mild furrowing, demonstrating late effects of Dupilumab at optimized EoE dosing on tissue remodeling.

Introduction

Barrett Esophagus (BE) is a pre-cancerous esophageal condition caused by chronic uncontrolled gastro-esophageal reflux disease (GERD). The goal of Proton Pump Inhibitors (PPIs) therapy in BE patients is to effectively achieve symptoms control. However, BE patient tend to be asymptomatic or to under-report acid-related symptoms. Furthermore, previous evidence in Literature showed that optimal control of esophageal acid exposure, as objectively assessed by an on-therapy 24h pH-impedance monitoring (24h MII-pH) is able to decrease COX-2 expression in esophageal biopsy of BE patients [1]. In spite of that, to date, current guidelines [2] suggest the use of a standard dose once daily PPI for chemoprevention in BE patients and do not advise for evaluating the effectiveness of therapy, by means of an on-therapy 24h MII-pH.

Aims & Methods

This is a prospective study involving consecutive BE patients referred to our tertiary center. The diagnosis of non-dysplastic BE was confirmed in all patients through endoscopic and histological assessment by a single experienced endoscopist. After the endoscopy, patients were prescribed therapy with full dose PPIs (either esomeprazole or pantoprazole 40 mg b.i.d.). After one month of PPI therapy, a high-resolution manometry (HRM) and on-therapy 24h MII-pH were performed. GERD refractory patients without BE matched for age, gender and therapy (drug and dose) were used as controls. Data are expressed as mean±SD.

Results

Twenty-five BE patients (16 M, 49±18 years) were enrolled. Fourteen BE patients showed a pathological 24h MII-pH compared to only 4 patients with refractory GERD (56 vs 16%; p=0.001). In both populations, the gastric acid exposure time was sub-optimally controlled by PPI therapy (44±24% vs 50±26% in BE and GERD patients; p=NS). In BE patients, however, total and upright esophageal Acid Exposure Time (AET) were significantly higher and reached pathological values as compared to refractory GERD patients (8.4±11.1% vs 2±3% and 6±6.5% vs 1.7±2.1%, both p<0.01). Total distal and acid refluxes were not significantly different between the two groups (52±30 vs 38±22 and 32±29 vs 21±16, p=NS). Nonetheless, when comparing the duration of the longest reflux episode, BE patients showed significantly longer reflux episodes compared to refractory GERD (33.7±41.4 vs 8.3±12.4 minutes, p=0.02) and more ineffective esophageal swallows at HRM (49±42% vs18±25%; p=0.006).

Conclusion

In our hands, more than half of asymptomatic BE patients show persistently abnormal AET despite PPI therapy. This could be explained by prolonged reflux episodes and a worsened esophageal clearance and motility compared to GERD patients, despite the similar gastric acid exposure time and number of acid refluxes. In BE patients, we found a consistent risk of underestimating the esophageal acid burden by simply relying on patients’ symptoms. Although, further larger studies are needed to validate our results, an on-therapy 24h MII-pH could guide the choice of the most adequate acid-suppressive therapy, by objectively measuring AET values.

References

1- de Bortoli N, Martinucci I, Piaggi P, et al. Randomised clinical trial: twice daily esomeprazole 40 mg vs. pantoprazole 40 mg in Barrett's oesophagus for 1 year. Aliment Pharmacol Ther. 2011;33(9):1019-1027. doi:10.1111/j.1365-2036.2011.04616.x
2- Weusten BLAM, Bisschops R, Dinis-Ribeiro M, et al. Diagnosis and management of Barrett esophagus: European Society of Gastrointestinal Endoscopy (ESGE) Guideline. Endoscopy. 2023;55(12):1124-1146. doi:10.1055/a-2176-2440

Introduction

Endoscopy abnormalities of eosinophilic esophagitis (EoE) are currently graded based on the EoE endoscopic reference score (EREFS) ranging 0 to 9. Research has shown that esophageal biopsies are often omitted in Europe in patients reporting dysphagia when the upper endoscopy (EGD) shows no abnormalities [1]. However, a proportion of patients with eosinophilic esophagitis (EoE) may have normal endoscopy (i.e., EREFS=0), making the diagnosis more difficult and increasing the risk of diagnostic delay.

Aims & Methods

We investigated predictors of a diagnosis of EoE when the EGD is unremarkable (i.e., EREFS=0). Consecutive adult patients (≥18 years) with dysphagia who had EREFS=0 at an EGD with six esophageal biopsies were prospectively enrolled. All patients underwent EGD while off any eosinophil-depleting treatment. EoE with EREFS=0 was diagnosed based on the presence of at least 15 eosinophils/high-power field in at least one of six esophageal biopsies. When all six esophageal biopsies showed <15 eosinophils/high-power field, patients were diagnosed with non-EoE dysphagia (NED). Demographics, diagnostic delay (i.e., interval time between symptoms onset and diagnosis), esophageal symptoms, and atopic comorbidities (i.e., allergic rhinitis, asthma, eczema) were collected for all patients. Pearson's Chi-squared test and Fisher's exact test were used for comparisons. Odds ratios (ORs) were calculated to quantify associations between disease states. Significance threshold was set at p<0.05.

Results

Of 133 included patients, 51 (38%) had NED, while 82 (62%) had EoE with EREFS=0. Patients with EoE were more commonly males (67% vs 35%; p<0.001) and younger (37 vs 46 years; p=0.005) compared to patients with NED. Patients with EoE were diagnosed with a significantly longer diagnostic delay than NED (28 vs 4 months; p<0.001). Heartburn, regurgitation, chest pain and dyspepsia had similar prevalence in the two groups. In contrast, patients with EoE had a significantly higher prevalence of atopic comorbidities compared to NED (83% vs 39%; p<0.001).
The presence of rhinitis, diagnostic delay longer than 12 months, any atopic comorbidity, age younger than 37 years, and male sex were associated with an increased risk of EoE with OR of 47.0, 11.6, 7.4, 3.8, and 3.7, respectively (p<0.01 for all).

Conclusion

EoE remains a possible diagnosis in patients reporting dysphagia even when endoscopy is normal. The presence of rhinitis and longer diagnostic delay, the presence of any atopic comorbidity, and younger age are associated with a diagnosis of EoE and are helpful to raise the suspicion of EoE and prompt endoscopists to collect esophageal biopsies.

References

[1] Tourlamain, G., Garcia-Puig, R., Gutiérrez-Junquera, C., Papadopoulou, A., Roma, E., Kalach, N., Oudshoorn, J., Sokollik, C., Karolewska-Bochenek, K., Oliva, S., Strisciuglio, C., Bauraind, O., Auth, M. K., Thomson, M., Otte, S., Rok, O., Dias, J. A., Tzivinikos, C., Urbonas, V., Kostovski, A., … ESPGHAN EGID Working group (2020). Differences in Management of Eosinophilic Esophagitis in Europe: An Assessment of Current Practice. Journal of pediatric gastroenterology and nutrition, 71(1), 83–90. https://doi.org/10.1097/MPG.0000000000002672