Treatment of Pediatric Eosinophilic Esophagitis: Traditional and Novel Therapies.

PURPOSE OF REVIEW: This review presents and summarizes the existing studies on the treatment goals and options for pediatric eosinophilic esophagitis utilizing rigorous peer-reviewed literature. RECENT FINDINGS: In addition to traditional treatments, emerging biologic therapies continue to evolve the approach to treating pediatric eosinophilic esophagitis. Well defined treatment goals will aid the continued development of new therapies. Further, innovative assessment tools have changed how the clinician is able to assess the effectiveness of therapies with a trend toward less invasive options. The management of pediatric eosinophilic esophagitis continues to evolve with the advent of both novel treatment options and assessment tools. Treatment choices, with benefits and risks involved, should be presented to families upon diagnosis and tailored towards the individual patient and likelihood of adherence and success. Biologic therapy for EoE presents an exciting option for both first line therapy and escalation for those with severe or unresponsive disease.

Development of in-situ Raman diagnosis technique of eosinophil esophagitis.

The spectra of the live tissue with blood flow measured with 785 nm-excitation light showed a very weak signal due to hemoglobin (Hb). It suggested the possibility to detect eosinophil accumulation in the tissue with the 785 nm-excitation light. The excitation wavelength of 633 nm induced strong fluorescence of sapphire glass that is a material of the ball lens of BHRP (Ball lens top hollow optical fiber Raman probe). On the other hand, the previous study suggested that eosinophil including eosinophil peroxidase (EPO) that showed a strong resonance Raman effect with 633 nm-excitation light. The purpose of the present study is to collect basic information and to evaluate the viability of Raman spectroscopic analysis for the detection of eosinophil accumulation in the live esophagus. BHRP with a sapphire ball lens with 500 µm diameter was applied for measurement of live esophagus tissue of a mouse. In this study, Raman spectra of eosinophil were measured with 633 and 785 nm-excitation. The Raman spectra of eosinophil showed a strong contribution of EPO, suggested that a heme chromophore in EPO had pre-resonance enhancement via Q band with the 785 nm-excitation light. Principal component analysis (PCA) is applied for the analysis of Raman spectra of eosinophil, erythrocyte and other granulocytes. Eosinophil was successfully discriminated from other blood cells in the PCA score plots built for the datasets of the spectra measured with 633 and 785 nm-excitation wavelengths. Consequently, our study demonstrates that Raman spectroscopy with 785 nm-excitation had high viability for in situ analysis of eosinophilic esophagitis (EoE).

Computational analysis to define efficacy & molecular mechanisms of 7, 4'- Dihydroxyflavone on eosinophilic esophagitis: Ex-vivo validation in human esophagus biopsies.

Introduction: Eosinophilic Esophagitis (EoE) is a chronic condition characterized by eosinophilic inflammation of the esophagus which leads to esophageal dysfunction with common symptoms including vomiting, feeding difficulty, dysphagia, abdominal pain. Current main treatment options of EoE include dietary elimination and swallowed steroids. Diet elimination approach could lead to identifying the trigger food(s), but it often requires repeated upper endoscopy with general anesthesia and potentially could negatively affect nutrition intake and growth of the child and individuals' quality of life. Although the swallowed steroid treatment of effective, the EoE will universally recur after discontinuation of the treatment. Digestive Tea formula (DTF) has been used by the Traditional Chinese Medicine (TCM) practice to improve GI symptoms in EoE patients, including abdominal pain, GE reflux, and abnormal bowel movement. Previously, a flavonoid small molecule compound 7, 4 dihydroxy flavone (DHF) from Glycyrrhiza uralensis in DTF inhibited eotaxin, Th2 cytokine and IgE production in vitro and in vivo. Method: This study comprehensively evaluates the potential therapeutic and immunological mechanisms underlying DHF improvement of symptoms related to EoE using computational modeling, including target mining, gene ontology enrichment, pathway analyses, protein-protein interaction analyses, in silico molecular docking and dynamic simulation followed by ex-vivo target validation by qRT-PCR using cultured human esophagus biopsy specimen with or without DHF from patients with EoE. Results: Computational analyses defined 29 common targets of DHF on EoE, among which TNF-α, IL-6, IL1ß, MAPK1, MAPK3 and AKT1 were most important. Docking analysis and dynamic simulation revealed that DHF directly binds TNF-α with a free binding energy of -7.7 kcal/mol with greater stability and flexibility. Subsequently, in the human esophagus biopsy culture system, significant reduction in levels of TNF-α, IL-6, IL-8 and IL1-ß was found in the supernatant of biopsy sample cultured with DHF. Furthermore, the gene expression profile showed significant reduction in levels of TNF-α, IL1-ß, IL-6, CCND and MAPK1 in the esophagus biopsy sample cultured with DHF. Discussion: Taken together, the current study provides us an insight into the molecular mechanisms underlying multi-targeted benefits of DHF in the treatment of EoE and paves the way for facilitating more effective EoE therapies.

Eosinophilic esophagitis due to red yeast rice (Monacoline K) in a dietary supplement for hypercholesterolemia.

We present a case of eosinophilic esophagitis (EoE) with positive skin-prick testing for type I allergy to red yeast rice (RYR, Artechol®). RYR is an over-the-counter supplement for hypercholesterolemia, since years famous in Asian countries and now also more and more popular in Western countries. The clinical relevance of IgE-mediated inflammation was proven by a rapid clearance of EoE-symptoms upon discontinuation of RYR. The role of skin-prick testing and allergy testing in general in EoE is controversial, but was of high importance in our patient. It demonstrates that in cases of a clear-cut allergy history, together with positive skin-prick (IgE) testing, a broad elimination diet can thus be avoided.

Eosinophilic Esophagitis: the Potential Role of Biologics in its Treatment.

Eosinophilic esophagitis (EoE) is a chronic, relapsing inflammatory disease of the esophagus, characterized by the presence of significant esophageal mucosal eosinophilic infiltrates. The clinical presentation of EoE in childhood may include failure to thrive and feeding intolerance. The complication of food impaction is often related to the presence of strictures or narrow caliber esophagus. Over the last decade, there has been tremendous progress in the field of eosinophilic disorders, particularly eosinophilic esophagitis. Conventional treatment of eosinophilic esophagitis involves topical swallowed steroids, systemic steroids, elimination diets, and/or esophageal dilation. However, treatment outcomes with the above modalities are not satisfactory for all patients with EoE and alternative treatments are clearly needed. There has been ongoing research targeting the treatment-refractory population of patients with EoE and the population with long-term consequences of the disease and its treatment. With the significant eosinophilic infiltration that characterizes EoE, anti-IL-5 therapies designed to target eosinophilic inflammation have been some of the most studied anti-inflammatory biologic therapies in EoE. In the studies published to date, while various IL-5 inhibitors have decreased the numbers of esophageal eosinophils, they have not depleted them to the levels consistent with histologic remission of EoE. As additional biologics that modulate Th2-mediated immunity are trialed for the treatment of EoE, we stand to learn more about the inflammatory factors mediating this challenging condition. In this review, we discuss the alternative modes of therapy in EoE that have emerged, with a focus on anti-IL-5 therapies and other biologics, their variation of success, and ultimately, the future of treatment in this field.

Eosinophilic esophagitis in children: current knowledge to open new horizons.

Eosinophilic Esophagitis (EoE) is a chronic immune/antigen-mediated condition which is also driven by genetic and environmental factors. It has been deeply investigated over the last years and its incidence is widely increasing in childhood. Although atopic diseases are closely linked with EoE, it does not recognize a classical IgE-mediate immune pathogenesis but it is rather a T helper type 2 inflammatory process. Familial clustering supports genetic predisposition in EoE and recent advances in understanding the genetic basis for EoE may eventually translate into targeted management of the disease. EoE diagnosis is based on clinical symptoms, micro, and macroscopic findings along with exclusion of gastroesophageal reflux disease (GERD) evidence. Management of the disease encompasses both dietary and pharmacological solutions that need to be specifically targeted on patients' history, clinical symptoms, and diagnostic evaluations. New therapies, currently not available in children, may represent the basis for future therapeutic options in the next years.

Eosinophilic Gastrointestinal Disorders.

Eosinophilic gastrointestinal disorders (EGID) are a group of disorders characterized by pathologic eosinophilic infiltration of the esophagus, stomach, small intestine, or colon leading to organ dysfunction and clinical symptoms (J Pediatr Gastroenterol Nutr; Spergel et al., 52: 300-306, 2011). These disorders include eosinophilic esophagitis (EoE), eosinophilic gastritis (EG), eosinophilic gastroenteritis (EGE), eosinophilic enteritis (EE), and eosinophilic colitis (EC). Symptoms are dependent not only on the location (organ) as well as extent (layer invasion of the bowel wall). Common symptoms of EoE include dysphagia and food impaction in adults and heartburn, abdominal pain, and vomiting in children. Common symptoms of the other EGIDs include abdominal pain, nausea, vomiting, early satiety, diarrhea, and weight loss. These disorders are considered immune-mediated chronic inflammatory disorders with strong links to food allergen triggers. Treatment strategies focus on either medical or dietary therapy. These options include not only controlling symptoms and bowel inflammation but also on identifying potential food triggers. This chapter will focus on the clinical presentation, pathophysiology, and treatment of these increasingly recognized disorders.

Eosinophilic esophagitis: Pathophysiology, diagnosis, and management.

Eosinophilic esophagitis (EoE) is a multifactorial esophageal inflammation, with a genetic predisposition, which combines a deficient esophageal mucosal barrier, an abnormal immune reaction to environmental allergens mediated by Th2 interleukins, immediate esophageal lesions and dysmotility, with secondary remodeling and fibrosis. Symptoms include reflux, abdominal pain, and food impaction, with a variation according to age. Fibroscopy shows major and minor endoscopic and histologic criteria, with a mucosal count≥15 eosinophils/high power field (Eo/hpf). A new entity has been defined, where gastroesophageal reflux disease (GERD) and EoE share responsibility: the PPIs-sensitive form of EoE (PPI-REE). Children with fibroscopy showing≥15 Eo/hpf need a second endoscopy following 8 weeks of PPI treatment. EoE has a strong association with other atopic disorders. Allergy testing (specific IgE blood test and skin prick tests [SPTs]) identifies patients at risk of anaphylaxis (14.8% of cases). The dietary therapy is based on a 4- to 12-week elimination test followed by endoscopy to check the disappearance of eosinophilic infiltration. The "dietary approaches are the amino acid-based formula, the allergy testing-based targeted diet, and the six-food elimination diet (empirical elimination of milk, wheat, soy, eggs, peanut/nuts, and fish/seafood). A recent first-line trial elimination of milk has been suggested, with wheat as a second elimination, if necessary. Dietary therapy allows remission and catch-up growth in 65% of cases. Swallowed topical steroids (budesonide in viscous gel or fluticasone propionate for nebulization) are an alternative, for which efficacy varies according to clinical and/or histological criteria and with relapses occurring at dosage tapering. Their use may be restricted by side effects, such as oral and/or esophageal candidiasis. The impact on long-term bone health and growth is unknown. Maintenance therapy is not standardized and is team-dependent, combining or not elimination diets and long-term steroids. The long-term risk of EoE is esophageal stenosis (25%) and endoscopic dilation may be repeated. Biotherapies have shown isolated histological improvement without significant clinical efficacy.

Increasing Incidence of Pediatric Eosinophilic Esophagitis in the Southwest of Madrid, Spain.

OBJECTIVES: The incidence of eosinophilic esophagitis is unknown in our area. The aim of our study was to determine the incidence of eosinophilic esophagitis and its possible association with the most frequent absolute annual pollen counts. METHODS: A descriptive retrospective multicenter observational study was designed to calculate the incidence of eosinophilic esophagitis in children aged under 15 years in the southwest region of Madrid, Spain in 2002-2013 (data were provided by the Statistics Institute of Madrid). We collected data on age, sex, clinical presentation, and date of endoscopic diagnosis. Relative risk (RR) was estimated (Stata v.11) using negative binomial regression models to assess the association between incidence and pollen counts (provided by Subiza Clinic). RESULTS: The study population comprised 254 patients (192 male [75.6%], aged 0.5-14.99 years). The clinical presentation was esophageal impaction in 23.6%, dysphagia in 22%, gastroesophageal reflux-like symptoms in 44.9%, and other findings in 9.4%. The annual incidence from 2002 to 2013 per 100 000 children aged <15 years per year was, respectively, 0.81, 1.5, 0.37, 3.17, 3.07, 4.36, 6.87, 7.19, 8.38, 9.05, 9.14, and 9.68. The incidence of eosinophilic esophagitis increased by an average of 19% annually (RR, 1.19; 95%CI, 1.14-1.25; P<.001). In the overall analysis, the relationship between incidence and absolute annual and monthly counts during the pollen seasons of the respective pollen types was analyzed only for Platanus species, which had an RR >1 (1.17 and 1.06, respectively) (P<.05). CONCLUSION: The incidence of diagnosis of pediatric eosinophilic esophagitis increased by an average of 19% annually. No significant association was found between incidence and pollen counts, except for a weak association with Platanus species.

Germination of pollen grains in the oesophagus of individuals with eosinophilic oesophagitis.

BACKGROUND: Eosinophilic oesophagitis (EoE) is characterized by oesophageal dysfunction and, histologically, by eosinophilic inflammation. There is no a clear aetiologic treatment. EoE exacerbations are often seasonal. We hypothesized that the inflammatory response of the oesophageal mucosa in patients with high levels of antibodies to pollen allergens and worsened seasonal EoE might be due to swallowing airborne pollen and the intrusion into the oesophageal mucosa of pollen allergens and pollen tubes, which encounter a pH and humidity resembling the stigma at pollination. OBJECTIVE: The aim of our study was to demonstrate the possible pathogenic role of environmental allergens in EoE through molecular and anatomopathological studies METHODS: One hundred and twenty-nine patients with EoE were tested for environmental and food allergens. Component resolved diagnosis (CRD), histological and botanical analysis was performed. Microscopic examination of oesophageal biopsies of 129 adults patients with EoE, 82 of them with seasonal exacerbation, and 100 controls, with gastroesophageal reflux without eosinophilic infiltrate, were made to verify the presence of callose (polysaccharide abundant in pollen tubes but absent in animal tissues) in the oesophagus. RESULTS: Component resolved diagnosis detected pollen allergens in 87.6% of patients with EoE. The predominant allergens were group 1 grass (55%), Art v 3 (11.3%) and lipid transfer proteins (LTPs) (19.4%) of common Mediterranean foods such as peach, hazelnuts, walnuts and wheat. Callose from pollen tubes was found in 65.6% of biopsies. CONCLUSION: Alteration of the mucosal barrier in EoE might cause the penetration of pollen grains into the oesophageal tissues. In EoE patients, anatomopathological studies searching for intrusion to plant foods and pollen, and specific-guided diet and immunotherapy after plant structures detection in biopsies, might be effective. CLINICAL RELEVANCE: It is possible to see the intrusion into animal tissues (oesophagus mucosa) of plant structures (pollen grains or pollen tubes) using an adecuate histologic botanical analysis. Molecular and anatomopathological studies can help to demonstrate a possible pathogenic role of environmental allergens in EoE.

Management of Gastroesophageal Reflux Disease.

Management of gastroesophageal reflux disease (GERD) commonly starts with an empiric trial of proton pump inhibitor (PPI) therapy and complementary lifestyle measures, for patients without alarm symptoms. Optimization of therapy (improving compliance and timing of PPI doses), or increasing PPI dosage to twice daily in select circumstances, can reduce persistent symptoms. Patients with continued symptoms can be evaluated with endoscopy and tests of esophageal physiology, to better determine their disease phenotype and optimize treatment. Laparoscopic fundoplication, magnetic sphincter augmentation, and endoscopic therapies can benefit patients with well-characterized GERD. Patients with functional diseases that overlap with or mimic GERD can also be treated with neuromodulators (primarily antidepressants), or psychological interventions (psychotherapy, hypnotherapy, cognitive and behavioral therapy). Future approaches to treatment of GERD include potassium-competitive acid blockers, reflux-reducing agents, bile acid binders, injection of inert substances into the esophagogastric junction, and electrical stimulation of the lower esophageal sphincter.

PPI Trial for Eosinophilic Esophagitis: Chaos in the Community.

INTRODUCTION: Despite consensus eosinophilic esophagitis (EoE) statement published in 2011 calling for a 2-month trial of protons pump inhibitor (PPI), the guidelines are not followed by many. We studied the practice patterns in our community and response to a PPI retrial in patients previously diagnosed with "idiopathic EoE." METHODS: All patients presenting to the senior author's practice with suspected EoE from 2011 to 2015. Two cohorts were studied: (1) patients diagnosed in the community as "idiopathic EoE"; (2) treatment naïve patients given a PPI trial at University of South Florida. PPI responsive eosinophilia was defined after 2 months of high dose PPIs after initial diagnosis of mucosal eosinophilia and histologic response of <15 eosinophils per HPF. SPSS v19.0 was used to calculate mean difference and odds ratios (OR) and 95% confidence intervals. RESULTS: In total, 78 patients met inclusion criteria, 46 patients had outside diagnosis of "idiopathic EoE," and 41 patients received a PPI trial at University of South Florida. In total, 34/46 (73.9%) community patients were placed on a PPI, 3/46 (6.5%) were placed on elimination diets, 31/46 (67.4%) steroids, and 21/46 (45.7%) were treated with both steroids/PPIs. Fewer patients received PPI trials in the community 3/46 (6.5%) versus 26/34 (76.5%) at our center [OR, 46.6 (95% CI, 11.3-191.5); P<0.0001]. In total, 12/26 (46.2%) were PPI responders on our retrial despite previously being diagnosed with idiopathic EoE. The group initially diagnosed at our center had a higher PPI response rate 12/15 (80%) versus 12/26 (46.2%) in the community group [OR, 7.58 (1.42, 40.55; P=0.018)]. CONCLUSIONS: The importance of a PPI trial is misunderstood and may be confused with the more traditional PPI trial for gastroesophageal reflux disease. This algorithm is critical and should be done before empiric steroids/diet therapies.

Eosinophilic Esophagitis: An Evidence-Based Approach to Therapy.

In recent years, several randomized controlled trials and meta-analyses have evaluated the efficacy of the various therapeutic options available for treating patients with eosinophilic esophagitis, including dietary modifications, proton pump inhibitors, topical corticosteroids, and endoscopic esophageal dilation. Proton pump inhibitors are currently considered the first-line treatment for eosinophilic esophagitis, achieving histological remission and improvement of symptoms in 50.5% and 60.8% of patients, respectively. The efficacy of topical corticosteroids in eosinophilic esophagitis has been assessed in several trials. Meta-analyses summarizing results indicate that budesonide and fluticasone propionate are significantly superior to placebo, both in decreasing eosinophil densities in the esophageal mucosa and in relieving symptoms. However, owing to differences in drug delivery, viscous budesonide seems to be the best pharmacological therapy for eosinophilic esophagitis. Results for dietary modifications have been mixed depending on the type of diet prescribed. Thus, while exclusive amino acid-based elemental diets are the most effective in inducing histological remission of eosinophilic esophagitis (90.8%), their severe drawbacks limit their implementation in clinical practice. Allergy testing-based food elimination provides a suboptimal remission rate of 45.5%, although this is lower in adults than in children (32.2% vs 47.9%, respectively). In addition, the various available studies are highly heterogeneous. Empirical 6-food elimination diets were shown to be the best diet-based therapy, with a homogeneous remission rate of 72%. Simpler, more convenient empirical schemes have also been evaluated. The aim of this review is to provide an evidence-based overview on the efficacy of the options available for treatment of eosinophilic esophagitis along with a practical management algorithm.

Current Management of Eosinophilic Esophagitis 2015.

Eosinophilic esophagitis (EoE) is a chronic inflammatory condition characterized by esophageal dysfunction and eosinophilic infiltrate (≥15/hpf) in the esophageal epithelium and the absence of other potential causes of eosinophilia. The prevalence is increasing and is the most common cause of solid food dysphagia in children and young adults. This article will review the diagnosis and management of EoE based on consensus conferences, systematic reviews, and meta-analysis and highlights seminal studies in our evolving treatment of this disease. However, all answers are not available and I will remark about the lessons learned in my clinical practice seeing EoE patients over the last 25 years. The complicated etiology of the complaint of dysphagia in EoE patients will be reviewed. The importance of utilizing endoscopy, biopsies, and barium esophagram to help define the 2 phenotypes (inflammatory, fibrostenosis) of EoE will be highlighted. The controversy about PPI-responsive esophageal eosinophilia will be discussed and contrasted with idiopathic EoE. Finally, the 3 treatment options for EoE (drugs, diet, dilation) will be reviewed in detail and a useful clinical management algorithm presented.

An allergist's perspective to the evaluation of Eosinophilic Esophagitis.

Eosinophilic Esophagitis (EoE) is a classic atopic disease as it shares features with other atopic disease on all levels including pathogenesis, genetics, epidemiology, and treatment options. EoE has elements of Th2 pathogenesis with increase levels of Th2 cytokines (IL4, 5, and 13). In addition, it shares atopic genetic risk factors including thymic stromal lymphopoietin (TSLP) loci as a risk factor in genome wide association studies. EoE patients have a higher rate of other atopic disease (asthma, allergic rhinitis and food allergy) compared to the general population indicating their atopic phenotype. Like asthma, atopic dermatitis or food allergy, EoE has increased in the last 20 years. Treatment options include the basic principle of other atopic diseases include using topical steroids or avoidance of the triggers (food or pollen). An allergist provides a critical role as they are experts in the treatment of atopic disease including avoidance strategies.

Endoscopic appearance and location dictate diagnostic yield of biopsies in eosinophilic oesophagitis.

BACKGROUND: Acknowledging that eosinophilic esophagitis (EoE) is a disease with variable involvement throughout the oesophagus, studies have suggested a minimum of five biopsies to diagnose EoE. Although it is accepted that furrows and exudates appear to represent areas of inflammation, no research to date has looked specifically at EoE endoscopic findings to see if eosinophilic infiltrate correlates with specific endoscopic findings. AIM: To evaluate the distribution of eosinophils in EoE and determine whether endoscopic appearances predict the degree of eosinophilia at various locations of the oesophagus. METHODS: We performed a prospective cross sectional study of EoE (treated and untreated) patients to study the distribution of eosinophils according to endoscopic findings. The oesophagus of 10 EoE patients were biopsied up to 32 times in a circumferential manner. The mucosal changes were documented at the site of each biopsy. Histological determination of eosinophil counts and related histopathology of the oesophagus were then correlated with endoscopic findings. Similar biopsy assessments were made in treated (resolved) EoE patients (n = 6) to determine the permanence of specific endoscopic appearances. RESULTS: A total of 16 patients were biopsied (10 EoE, 6 treated EoE). A total of 432 biopsies were obtained in all with 294 biopsies from 10 EoE subjects. Eosinophil density was increased distally in the majority of EoE patients. Biopsies performed in areas of exudates and furrows demonstrated higher eosinophil counts. Lines and normal-appearing oesophagi in EoE subjects were not commonly associated with elevated eosinophil counts (>15 eos/HPF). Rings alone without associated furrows or plaques did not demonstrate elevated eosinophil counts and were seen in resolved EoE (Rx-EoE) as well as in active EoE patients. CONCLUSIONS: Eosinophilic esophagitis remains a variable disease with some patients manifesting extensive disease throughout the oesophagus. Characteristics of furrows and exudates found during endoscopy are associated with higher peak eosinophil counts, requiring fewer biopsies to make a diagnosis. Lines and otherwise normal appearances of the oesophagus suggest a milder mucosal eosinophilia, requiring substantial biopsies to adequately identify fields with diagnostic eosinophil counts.

Value of microarray allergen assay in the management of eosinophilic oesophagitis.

BACKGROUND: Eosinophilic oesophagitis (EoE) is a disorder characterised by oesophageal dysfunction and, histologically, by eosinophilic inflammation. Although treatment, which includes dilatations, oral corticosteroids and restrictive diets, is often effective, choosing the foods to be eliminated from the diet is difficult. OBJECTIVE: Component resolved diagnostic by microarray allergen assay may be useful in detecting allergens that might be involved in the inflammatory process. METHODS: We studied 67 patients with EoE, diagnosed clinically and histologically by endoscopic biopsy. CRD analysis with microarray technology was carried out in the 67 EoE patients, 50 patients with pollen allergy without digestive symptoms, and 50 healthy controls. RESULTS: Allergies were not detected by microarray in only seven of the 67 patients with EoE. Controls with pollen allergy showed sensitisation to different groups of pollen proteins without significant differences. In EoE patients with response to some allergens, the predominant allergens were grasses group 1 and, in particular, nCyn d 1 (Cynodon dactylon) or Bermuda grass pollen in 59.5%, followed by lipid transfer proteins (LTP) of peach (19.40%), hazelnut (17.91%) and Artemisia (19.40%). CONCLUSIONS: In patients with EoE, sensitisation to plant foods and pollen is important. The proteins most frequently involved are nCyn d 1 and lipid transfer proteins, hazelnuts and walnuts. After one year of an array-guided exclusion diet and pollen-specific immunotherapy in the case of high levels of response, patients with EoE showed preliminary significant improvements.