From anaphylaxis to eosinophilic esophagitis: when therapy leads to unintended immune shifts – a case report

From anaphylaxis to eosinophilic esophagitis: when therapy leads to unintended immune shifts – a case report | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Case Report From anaphylaxis to eosinophilic esophagitis: when therapy leads to unintended immune shifts – a case report Urszula Jedynak-Wąsowicz, Liliana Klim, Ewa Cichocka-Jarosz This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9053333/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background Eosinophilic esophagitis (EoE) is a chronic inflammatory disease of the esophagus with symptoms of esophageal dysfunction. It is strongly associated with other atopic conditions in patients and has therefore been recognized as a late manifestation of the atopic march. Sensitization to foods and/or aeroallergens early in life may predispose some individuals to subsequent EoE development. Moreover, the disease was found to emerge as a potential side effect of oral immunotherapy (OIT). However, it remains unclear whether OIT induces or rather “unmasks” a pre-existing but subclinical disorder. Case Presentation We report a boy with IgE-mediated cow’s milk (CM) allergy, confirmed in infancy after anaphylaxis to yogurt, positive skin prick tests, and elevated CM-specific IgE. He tolerated baked milk following a supervised oral food challenge. From early childhood, he developed severe allergic asthma and rhinitis, refractory to standard therapy. Omalizumab (OMA) was initiated at 10 years of age with marked and sustained asthma control. While receiving anti-IgE treatment, at 13 years of age, the patient independently liberalized his diet and tolerated progressively less processed dairy products for 6–8 months without immediate hypersensitivity reactions. He subsequently developed recurrent vomiting and, two months later, experienced anaphylaxis after ingestion of a small amount of ice cream. Despite extensive evaluation during hospitalization, vomiting persisted and was associated with weight loss. Upper endoscopy revealed esophageal inflammation, with histological confirmation of EoE diagnosis. Treatment with proton pump inhibitor therapy, swallowed topical budesonide, and renewed strict CM elimination resulted in rapid clinical improvement, weight gain, reduction of peripheral eosinophilia, and histologic remission. Treatment with OMA was sustained. Conclusions The present case report illustrates that omalizumab can enable functional desensitization to CM in a child with a history of life-threatening reactions, but prolonged unsupervised consumption of CM under anti-IgE therapy may be associated with the onset of EoE. Awareness of this potential complication is crucial for clinicians managing children with severe food allergy and asthma on biological therapy. cow’s milk allergy anaphylaxis eosinophilic esophagitis atopic march anti-IgE therapy Figures Figure 1 Figure 2 Figure 3 Key Message Eosinophilic esophagitis may represent a late manifestation of the atopic march. Anti-IgE therapy effectively controls IgE-mediated disease but does not prevent IgE-independent eosinophilic gastrointestinal inflammation. Apparent food tolerance under biologic therapy does not exclude the risk of eosinophilic esophagitis. New gastrointestinal symptoms in patients with severe atopy warrant timely gastroenterological evaluation. Background Eosinophilic esophagitis (EoE) is a chronic inflammatory disease of the esophagus characterized by symptoms of esophageal dysfunction and a predominant eosinophilic infiltration of the squamous epithelium on histologic examination [1]. It is a complex immunologic disorder, with antigen-driven type 2 inflammation [2]. Clinical manifestations comprise dysphagia, vomiting, nausea, food impactions, chest pain and other symptoms of esophageal dysfunction [3]. Established risk factors for EoE are atopy and allergic conditions, including asthma, allergic rhinitis, atopic dermatitis and food allergy, with high incidence rates in patients suffering from this disorder [3–5]. EoE has also been recognized as a late manifestation of the atopic march, as sensitization to foods and/or aeroallergens early in life may predispose some individuals to subsequent EoE development [6,7]. Finally, EoE has emerged as a side effect of oral immunotherapy (OIT), primarily to food allergens, but also to inhalant allergens in some patients [2,8,9]. Diagnosis of EoE during OIT is an indication for termination of desensitization [8]. However, it remains unclear whether the OIT induces EoE in patients undergoing treatment or rather “unmasks” pre-existing but subclinical disease [10]. Case presentation We describe the case of a boy with cow’s milk (CM) allergy, born at term as a healthy neonate and breastfed until 9 months of age. His mother followed a CM-free diet during breastfeeding due to the child’s atopic dermatitis. At the age of 6 months, the patient experienced an anaphylactic reaction after yogurt ingestion. Cow’s milk allergy was confirmed by positive skin prick tests and elevated CM-specific IgE. A strict CM elimination diet was implemented. Over time, tolerance to baked milk (32 mL) was confirmed by a supervised oral food challenge. From early childhood, at the age of 4 years, the patient developed allergic asthma and allergic rhinitis, requiring regular treatment with inhaled corticosteroids, leukotriene receptor antagonists, antihistamines (2nd gen nsAH1) and intranasal corticosteroids. Despite stepwise escalation of therapy, asthma control progressively worsened, with frequent exacerbations and several hospitalizations. At the age of 10 years, treatment with omalizumab (450 mg every 2 weeks) was initiated, resulting in marked and sustained improvement in asthma control and a significant reduction in exacerbations. While receiving omalizumab, beginning at the age of 13 years, the patient gradually and independently liberalized his diet. Initial sIgE levels for CM extract and casein were 96.6 kU/L and 22.8 kU/L, respectively. At first, he introduced baked milk and subsequently less processed dairy products, including yogurt, cheese, pizza, and pancakes, all of which were tolerated without immediate allergic symptoms. After approximately 6–8 months of regular dairy consumption, predominantly smoked cheese, the patient developed recurrent daily vomiting, unrelated to physical activity, time of day, or intercurrent infection. Initially, there was no associated weight loss or additional gastrointestinal symptoms. Two months later, at the age of 14 years, the patient experienced an anaphylactic reaction after ingestion of approximately 15 mL of dairy ice cream. Symptoms included vomiting, abdominal cramps, diarrhea, urticaria, dyspnea, and wheezing. Administration of oral antihistamines and inhaled budesonide/formoterol led to complete symptom resolution. The concentration of sIgE levels for CM extract and casein were 13.3 kU/L and 3.2 kU/L, respectively. At that time, the patient’s medications included omalizumab, inhaled budesonide/formoterol, rupatadine, and vitamin D₃ Due to persistent vomiting, the patient was hospitalized. Physical examination on admission was unremarkable. Laboratory investigations showed no signs of systemic inflammation, anemia, or biochemical abnormalities. Peripheral eosinophil count was 700 /µL. Stool tests for Helicobacter pylori , parasites, and occult blood were negative. Abdominal ultrasonography and contrast esophagography revealed no abnormalities. Brain magnetic resonance imaging was also normal. Despite extensive diagnostic evaluation, vomiting persisted throughout hospitalization, resulting in a weight loss of 2.5 kg over 9 days. Owing to depressive symptoms related to his father’s neoplastic disease, fluoxetine therapy was initiated under psychiatric supervision. Upper gastrointestinal endoscopy demonstrated hypertrophic and inflamed esophageal mucosa with linear erosions and thickened folds (Edema/Rings/Exudate/Furrows/Stricture score: 4), as presented in Figs. 1 and 2 . Histopathology revealed up to 27 eosinophils per high-power field, with an overall EoEHSS (Eospinophilic Esophagitis Histologic Scoring System ) score of 8 points. These findings correspond to active eosinophilic esophagitis, characterized by ongoing inflammatory changes and early structural remodeling. Treatment with a high-dose proton pump inhibitor (PPI) and swallowed topical budesonide was initiated, along with renewed strict CM elimination. After 8 weeks of therapy, vomiting had almost completely resolved, asthma control remained stable, and the patient gained 4 kg in body weight. Peripheral blood eosinophil count decreased to 200/µL. Follow-up endoscopy after 3 months demonstrated marked regression of esophageal inflammation, with a maximum of 6 eosinophils per high-power field. The PPI dose was subsequently reduced, swallowed budesonide was discontinued, and a strict CM-free diet was maintained. A summary of our patient’s symptoms and disease chronology is presented in Fig. 3 . Discussion and Conclusions This case illustrates the evolution of allergic disease from an IgE-mediated phenotype in early childhood toward a predominantly non–IgE-mediated, T2-cell–driven inflammatory disorder during adolescence. Despite effective suppression of IgE-dependent pathways with anti-IgE therapy, the patient developed eosinophilic esophagitis (EoE), highlighting distinct immunopathogenic mechanisms underlying food allergy and eosinophilic gastrointestinal disease [3]. Cow’s milk (CM) allergy is a well-recognized risk factor for EoE, and food antigens act as disease triggers primarily through antigen-specific T-cell responses rather than classical IgE-mediated mechanisms [11]. In contrast to IgE-mediated food allergy, EoE pathogenesis is driven by Th2 cytokines such as interleukin-5 and interleukin-13, leading to eosinophil recruitment and esophageal tissue inflammation. These pathways are largely unaffected by anti-IgE therapy [2,3]. Omalizumab effectively neutralizes free IgE and downregulates FcεRI expression on mast cells and basophils, resulting in excellent control of IgE-mediated diseases, including allergic asthma [12,13]. In the United States, it has been approved by the Food and Drug Administration (FDA) for use in patients with severe multiple food allergy to reduce the risk of anaphylaxis, especially after accidental exposure [12,14]. However, it does not directly modulate T-cell–driven inflammation, which likely explains the development of EoE in our patient [15]. Similar cases of EoE occurring during omalizumab treatment have been previously reported in the literature [9,16]. Importantly, the occurrence of EoE should not be interpreted as a treatment failure or a paradoxical effect of anti-IgE therapy, but rather as the unmasking or progression of a coexisting non IgE-mediated disease phenotype. The patient’s tolerance of dairy products for several months without immediate hypersensitivity reactions supports the concept that suppression of IgE-mediated effector pathways may increase the clinical threshold for allergic reactions without inducing true immunological tolerance and therefore does not permit patients to consume the culprit food with impunity [12]. The subsequent onset of chronic gastrointestinal symptoms and histologically confirmed EoE suggests that food tolerance under anti-IgE therapy does not preclude the emergence of an eosinophilic gastrointestinal disease. The patient’s history also fits well within the concept of the atopic march. He initially presented with atopic dermatitis in infancy, followed by IgE-mediated food allergy, asthma and allergic rhinitis, and eventually EoE, which is increasingly recognized as a “late” manifestation within the atopic spectrum [6,7]. The diagnostic process in this case also underscores the challenges of recognizing EoE in patients with complex atopic disease. The boy’s vomiting initially occurred without abdominal pain, dysphagia or weight loss and was overshadowed by his history of severe asthma and food allergy. Because there were no objective signs of organic gastrointestinal disease at that time, and in the context of coexisting depressive symptoms, we initially considered functional vomiting secondary to an underlying mood disorder as the most likely explanation. Extensive evaluation for infectious, structural and neurologic causes, which is essential in management of prolonged vomiting in pediatric patients [17], was unrevealing. Only endoscopic assessment with biopsy provided the correct diagnosis. This emphasizes that persistent upper gastrointestinal symptoms in patients with food allergy—especially in the setting of recent changes in diet or immunomodulatory therapy—should prompt consideration of EoE and timely referral for endoscopy, which is considered gold standard for diagnosis and follow-up of EoE [1]. Therapeutically, our patient responded well to a combination of high-dose proton-pump inhibitor, swallowed topical corticosteroid and renewed elimination of CM, with rapid improvement in symptoms, weight gain and marked histologic remission. Asthma control remained good on continued omalizumab. This supports current concepts that EoE and IgE-mediated food allergy, although often co-existing and triggered by the same foods, represent overlapping but distinct immunologic pathways that may require separate but complementary treatment strategies [3]. From a clinical practice perspective, this case raises several important points. First, children with severe IgE-mediated CM allergy who receive biologics such as omalizumab may experience apparent improvement in their food tolerance, but any decision to liberalize the diet should be made under specialist supervision with clear protocols and regular follow-up [12,18]. Unsupervised reintroduction of highly allergenic foods carries a risk not only of breakthrough anaphylaxis once biologic protection wanes, but also of inducing or unmasking EoE. Second, clinicians should actively screen for gastrointestinal symptoms in patients on biologic therapy who increase their exposure to previously eliminated foods. Persistent vomiting, dysphagia, food impaction or unexplained weight loss warrant prompt evaluation for EoE. Finally, our case adds to the growing body of literature suggesting that anti-IgE–facilitated desensitization and EoE are not mutually exclusive, and that suppression of IgE-mediated pathways does not necessarily prevent—and may, in some circumstances, permit the development of a non-IgE-mediated eosinophilic disease. In conclusion, this case illustrates that omalizumab can enable functional desensitization to CM in a child with a history of life-threatening reactions, but prolonged unsupervised consumption of CM under anti-IgE therapy may be associated with the onset of EoE. Awareness of this potential complication is crucial for clinicians managing children with severe food allergy and asthma. Abbreviations EoE eosinophilic esophagitis OIT oral immunotherapy IgE immunoglobulin E CM cow’s milk OMA omalizumab 2 nd gen nsAH1 second generation non-sedating antihistamines EoEHSS Eospinophilic Esophagitis Histologic Scoring System PPI proton pump inhibitor FDA Food and Drug Administration Declarations Ethics approval and consent to participate The authors’ institution does not require ethical approval for publication of a case report. Written informed consent was obtained from the patient’s legal guardian. Consent for publication Written informed consent for publication of clinical details and images was obtained from the patient’s legal guardian. Availability of data and materials All data generated or analyzed during this study are included in this published article. Competing interests The authors declare that they have no competing interests. Funding No external funding was received for this work. Authors' contributions UJW: Conceptualization, data collection, figure preparation, acquisition of images, original draft writing and final draft editing, supervision. LK: Data collection, original draft writing and final draft editing. ECJ: Critical revision and final draft editing. Acknowledgements The authors thank the patient and family for their cooperation, as well as the consulting gastroenterologist Prof. Krzysztof Fyderek (Department of Pediatrics and Gastroenterology, Children’s University Hospital, Krakow, Poland) for his gastroenterological evaluation. 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Elsevier Inc.; 2025;18. https://doi.org/10.1016/j.waojou.2025.101054 Wojas O, Krzych-Fałta E, Żybul P, Żalikowska-Gardocka M, Ilczuk T, Furmańczyk K, et al. The Overlap of Allergic Disorders and Upper Gastrointestinal Symptoms: Beyond Eosinophilic Esophagitis. Nutrients . Multidisciplinary Digital Publishing Institute (MDPI); 2025;17. https://doi.org/10.3390/nu17081355 Hill DA, Grundmeier RW, Ramos M, Spergel JM. Eosinophilic Esophagitis is a Late Manifestation of the Allergic March. J Allergy Clin Immunol Pract. 2018 Sep-Oct;6(5):1528-1533. https://doi.org/10.5281/zenodo.1248931 Hill DA, Spergel JM. Is eosinophilic esophagitis a member of the atopic march? Annals of Allergy, Asthma and Immunology. American College of Allergy, Asthma and Immunology; 2018. p. 113–4. https://doi.org/10.1016/j.anai.2017.10.003 Kuźmiński A, Przybyszewska J, Bartuzi Z. Food allergens and oral immunotherapy as indicators of eosinophilic oesophagitis. Prz Gastroenterol. Termedia Publishing House Ltd.; 2024. p. 362–7. https://doi.org/10.5114/pg.2024.139534 Jin H, Trogen B, Nowak-Wegrzyn A. Eosinophilic esophagitis as a complication of food oral immunotherapy. Curr Opin Allergy Clin Immunol. Lippincott Williams and Wilkins; 2020. p. 616–23. https://doi.org/10.1097/ACI.0000000000000688 Nilsson C, Scurlock AM, Dellon ES, Brostoff JM, Pham T, Ryan R, et al. Clinical Communications Onset of eosinophilic esophagitis during a clinical trial program of oral immunotherapy for peanut allergy. J Allergy Clin Immunol Pract. 2021 Dec;9(12):4496-4501. https://doi.org/10.1016/j.jaip.2021.07.048 Dinardo G, Fiocchi A, Artesani MC, De Angelis P, Rea F, Tambucci R, et al. Eosinophilic Esophagitis and Cow’s Milk: Mechanisms, Challenges, and Treatment Perspectives. Nutrients . Multidisciplinary Digital Publishing Institute (MDPI); 2025. https://doi.org/10.3390/nu17020265 Casale TB, Fiocchi A, Greenhawt M. A practical guide for implementing omalizumab therapy for food allergy. Journal of Allergy and Clinical Immunology. Elsevier Inc.; 2024. p. 1510–7. https://doi.org/10.1016/j.jaci.2024.03.019 Salvati L, Liotta F, Annunziato F, Cosmi L. Therapeutical Targets in Allergic Inflammation. Biomedicines. MDPI; 2022. https://doi.org/10.3390/biomedicines10112874 Mortz CG, Parke L, Rasmussen HM, Kjaer HF, Bindslev-Jensen C. A randomized, double-blind placebo-controlled study on the efficacy of Omalizumab on food allergy threshold in children with severe food allergy. Allergy: European Journal of Allergy and Clinical Immunology. John Wiley and Sons Inc; 2024;79:964–76. https://doi.org/10.1111/all.16046 Gruchalla RS, Sampson HA, Liu AH, Shreffler W, Wallace PK, Togias A, et al. Effects of omalizumab on T lymphocyte function in inner-city children with asthma. Pediatric Allergy and Immunology. Blackwell Publishing Ltd; 2016. p. 328–31. https://doi.org/10.1111/pai.12508 MacGinnitie AJ, Rachid R, Gragg H, Little S V., Lakin P, Cianferoni A, et al. Omalizumab facilitates rapid oral desensitization for peanut allergy. Journal of Allergy and Clinical Immunology. Mosby Inc.; 2017;139:873-881.e8. https://doi.org/10.1016/j.jaci.2016.08.010 Ravindranath A. Chronic vomiting in children: Etiology, diagnosis, and management. Indian Journal of Gastroenterology. Springer; 2020;39:117–22. https://doi.org/10.1007/s12664-020-01035-w Wood RA, Togias A, Sicherer SH, Shreffler WG, Kim EH, Jones SM, et al. Omalizumab for the Treatment of Multiple Food Allergies. New England Journal of Medicine. Massachusetts Medical Society; 2024;390:889–99. https://doi.org/10.1056/nejmoa2312382 Additional Declarations No competing interests reported. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-9053333","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":602068045,"identity":"07aa8dca-e740-4040-9d2f-91419231eea4","order_by":0,"name":"Urszula 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and exudate.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-9053333/v1/23b8a2c07a082fbb1830e6d7.png"},{"id":104782595,"identity":"fd9dd3b0-abf7-4dec-b5af-781348c32116","added_by":"auto","created_at":"2026-03-17 07:57:34","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":599008,"visible":true,"origin":"","legend":"\u003cp\u003eEndoscopic findings in the esophagus: furrows and edema.\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-9053333/v1/3d1f2fe0541e30516e477899.png"},{"id":104782059,"identity":"59dee283-e209-445b-b8c1-307f82b9ff26","added_by":"auto","created_at":"2026-03-17 07:56:47","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":172153,"visible":true,"origin":"","legend":"\u003cp\u003ePatient’s symptoms and disease chronology.\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-9053333/v1/a00b90df46348767a78e6e17.png"},{"id":105727790,"identity":"20a391db-a142-4f4f-b859-348a16726b83","added_by":"auto","created_at":"2026-03-30 11:03:49","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2679204,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9053333/v1/65521f6b-43d7-460c-bb10-52209be739ab.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"From anaphylaxis to eosinophilic esophagitis: when therapy leads to unintended immune shifts – a case report","fulltext":[{"header":"Key Message","content":"\u003cul type=\"disc\"\u003e\n \u003cli\u003eEosinophilic esophagitis may represent a late manifestation of the atopic march.\u003c/li\u003e\n \u003cli\u003eAnti-IgE therapy effectively controls IgE-mediated disease but does not prevent IgE-independent eosinophilic gastrointestinal inflammation.\u003c/li\u003e\n \u003cli\u003eApparent food tolerance under biologic therapy does not exclude the risk of eosinophilic esophagitis.\u003c/li\u003e\n \u003cli\u003eNew gastrointestinal symptoms in patients with severe atopy warrant timely gastroenterological evaluation.\u003c/li\u003e\n\u003c/ul\u003e"},{"header":"Background","content":"\u003cp\u003eEosinophilic esophagitis (EoE) is a chronic inflammatory disease of the esophagus characterized by symptoms of esophageal dysfunction and a predominant eosinophilic infiltration of the squamous epithelium on histologic examination [1]. It is a complex immunologic disorder, with antigen-driven type 2 inflammation [2]. Clinical manifestations comprise dysphagia, vomiting, nausea, food impactions, chest pain and other symptoms of esophageal dysfunction [3]. Established risk factors for EoE are atopy and allergic conditions, including asthma, allergic rhinitis, atopic dermatitis and food allergy, with high incidence rates in patients suffering from this disorder [3\u0026ndash;5]. EoE has also been recognized as a late manifestation of the atopic march, as sensitization to foods and/or aeroallergens early in life may predispose some individuals to subsequent EoE development [6,7]. Finally, EoE has emerged as a side effect of oral immunotherapy (OIT), primarily to food allergens, but also to inhalant allergens in some patients [2,8,9]. Diagnosis of EoE during OIT is an indication for termination of desensitization [8]. However, it remains unclear whether the OIT induces EoE in patients undergoing treatment or rather \u0026ldquo;unmasks\u0026rdquo; pre-existing but subclinical disease [10].\u003c/p\u003e"},{"header":"Case presentation","content":"\u003cp\u003eWe describe the case of a boy with cow’s milk (CM) allergy, born at term as a healthy neonate and breastfed until 9 months of age. His mother followed a CM-free diet during breastfeeding due to the child’s atopic dermatitis. At the age of 6 months, the patient experienced an anaphylactic reaction after yogurt ingestion. Cow’s milk allergy was confirmed by positive skin prick tests and elevated CM-specific IgE. A strict CM elimination diet was implemented. Over time, tolerance to baked milk (32 mL) was confirmed by a supervised oral food challenge.\u003c/p\u003e \u003cp\u003eFrom early childhood, at the age of 4 years, the patient developed allergic asthma and allergic rhinitis, requiring regular treatment with inhaled corticosteroids, leukotriene receptor antagonists, antihistamines (2nd gen nsAH1) and intranasal corticosteroids. Despite stepwise escalation of therapy, asthma control progressively worsened, with frequent exacerbations and several hospitalizations. At the age of 10 years, treatment with omalizumab (450 mg every 2 weeks) was initiated, resulting in marked and sustained improvement in asthma control and a significant reduction in exacerbations.\u003c/p\u003e \u003cp\u003eWhile receiving omalizumab, beginning at the age of 13 years, the patient gradually and independently liberalized his diet. Initial sIgE levels for CM extract and casein were 96.6 kU/L and 22.8 kU/L, respectively. At first, he introduced baked milk and subsequently less processed dairy products, including yogurt, cheese, pizza, and pancakes, all of which were tolerated without immediate allergic symptoms. After approximately 6–8 months of regular dairy consumption, predominantly smoked cheese, the patient developed recurrent daily vomiting, unrelated to physical activity, time of day, or intercurrent infection. Initially, there was no associated weight loss or additional gastrointestinal symptoms.\u003c/p\u003e \u003cp\u003eTwo months later, at the age of 14 years, the patient experienced an anaphylactic reaction after ingestion of approximately 15 mL of dairy ice cream. Symptoms included vomiting, abdominal cramps, diarrhea, urticaria, dyspnea, and wheezing. Administration of oral antihistamines and inhaled budesonide/formoterol led to complete symptom resolution. The concentration of sIgE levels for CM extract and casein were 13.3 kU/L and 3.2 kU/L, respectively. At that time, the patient’s medications included omalizumab, inhaled budesonide/formoterol, rupatadine, and vitamin D₃\u003c/p\u003e \u003cp\u003eDue to persistent vomiting, the patient was hospitalized. Physical examination on admission was unremarkable. Laboratory investigations showed no signs of systemic inflammation, anemia, or biochemical abnormalities. Peripheral eosinophil count was 700 /µL. Stool tests for \u003cem\u003eHelicobacter pylori\u003c/em\u003e, parasites, and occult blood were negative. Abdominal ultrasonography and contrast esophagography revealed no abnormalities. Brain magnetic resonance imaging was also normal. Despite extensive diagnostic evaluation, vomiting persisted throughout hospitalization, resulting in a weight loss of 2.5 kg over 9 days. Owing to depressive symptoms related to his father’s neoplastic disease, fluoxetine therapy was initiated under psychiatric supervision. Upper gastrointestinal endoscopy demonstrated hypertrophic and inflamed esophageal mucosa with linear erosions and thickened folds (Edema/Rings/Exudate/Furrows/Stricture score: 4), as presented in Figs.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e and \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eHistopathology revealed up to 27 eosinophils per high-power field, with an overall EoEHSS (Eospinophilic Esophagitis Histologic Scoring System\u003cb\u003e)\u003c/b\u003e score of 8 points. These findings correspond to active eosinophilic esophagitis, characterized by ongoing inflammatory changes and early structural remodeling.\u003c/p\u003e \u003cp\u003eTreatment with a high-dose proton pump inhibitor (PPI) and swallowed topical budesonide was initiated, along with renewed strict CM elimination. After 8 weeks of therapy, vomiting had almost completely resolved, asthma control remained stable, and the patient gained 4 kg in body weight. Peripheral blood eosinophil count decreased to 200/µL. Follow-up endoscopy after 3 months demonstrated marked regression of esophageal inflammation, with a maximum of 6 eosinophils per high-power field. The PPI dose was subsequently reduced, swallowed budesonide was discontinued, and a strict CM-free diet was maintained. A summary of our patient’s symptoms and disease chronology is presented in Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e "},{"header":"Discussion and Conclusions","content":"\u003cp\u003eThis case illustrates the evolution of allergic disease from an IgE-mediated phenotype in early childhood toward a predominantly non–IgE-mediated, T2-cell–driven inflammatory disorder during adolescence. Despite effective suppression of IgE-dependent pathways with anti-IgE therapy, the patient developed eosinophilic esophagitis (EoE), highlighting distinct immunopathogenic mechanisms underlying food allergy and eosinophilic gastrointestinal disease [3].\u003c/p\u003e\u003cp\u003eCow’s milk (CM) allergy is a well-recognized risk factor for EoE, and food antigens act as disease triggers primarily through antigen-specific T-cell responses rather than classical IgE-mediated mechanisms [11]. In contrast to IgE-mediated food allergy, EoE pathogenesis is driven by Th2 cytokines such as interleukin-5 and interleukin-13, leading to eosinophil recruitment and esophageal tissue inflammation. These pathways are largely unaffected by anti-IgE therapy [2,3].\u003c/p\u003e\u003cp\u003eOmalizumab effectively neutralizes free IgE and downregulates FcεRI expression on mast cells and basophils, resulting in excellent control of IgE-mediated diseases, including allergic asthma [12,13]. In the United States, it has been approved by the Food and Drug Administration (FDA) for use in patients with severe multiple food allergy to reduce the risk of anaphylaxis, especially after accidental exposure [12,14]. However, it does not directly modulate T-cell–driven inflammation, which likely explains the development of EoE in our patient [15]. Similar cases of EoE occurring during omalizumab treatment have been previously reported in the literature [9,16]. Importantly, the occurrence of EoE should not be interpreted as a treatment failure or a paradoxical effect of anti-IgE therapy, but rather as the unmasking or progression of a coexisting non IgE-mediated disease phenotype.\u003c/p\u003e\u003cp\u003eThe patient’s tolerance of dairy products for several months without immediate hypersensitivity reactions supports the concept that suppression of IgE-mediated effector pathways may increase the clinical threshold for allergic reactions without inducing true immunological tolerance and therefore does not permit patients to consume the culprit food with impunity [12]. The subsequent onset of chronic gastrointestinal symptoms and histologically confirmed EoE suggests that food tolerance under anti-IgE therapy does not preclude the emergence of an eosinophilic gastrointestinal disease.\u003c/p\u003e\u003cp\u003eThe patient’s history also fits well within the concept of the atopic march. He initially presented with atopic dermatitis in infancy, followed by IgE-mediated food allergy, asthma and allergic rhinitis, and eventually EoE, which is increasingly recognized as a “late” manifestation within the atopic spectrum [6,7].\u003c/p\u003e\u003cp\u003eThe diagnostic process in this case also underscores the challenges of recognizing EoE in patients with complex atopic disease. The boy’s vomiting initially occurred without abdominal pain, dysphagia or weight loss and was overshadowed by his history of severe asthma and food allergy. Because there were no objective signs of organic gastrointestinal disease at that time, and in the context of coexisting depressive symptoms, we initially considered functional vomiting secondary to an underlying mood disorder as the most likely explanation. Extensive evaluation for infectious, structural and neurologic causes, which is essential in management of prolonged vomiting in pediatric patients [17], was unrevealing. Only endoscopic assessment with biopsy provided the correct diagnosis. This emphasizes that persistent upper gastrointestinal symptoms in patients with food allergy—especially in the setting of recent changes in diet or immunomodulatory therapy—should prompt consideration of EoE and timely referral for endoscopy, which is considered gold standard for diagnosis and follow-up of EoE [1].\u003c/p\u003e\u003cp\u003eTherapeutically, our patient responded well to a combination of high-dose proton-pump inhibitor, swallowed topical corticosteroid and renewed elimination of CM, with rapid improvement in symptoms, weight gain and marked histologic remission. Asthma control remained good on continued omalizumab. This supports current concepts that EoE and IgE-mediated food allergy, although often co-existing and triggered by the same foods, represent overlapping but distinct immunologic pathways that may require separate but complementary treatment strategies [3].\u003c/p\u003e\u003cp\u003eFrom a clinical practice perspective, this case raises several important points. First, children with severe IgE-mediated CM allergy who receive biologics such as omalizumab may experience apparent improvement in their food tolerance, but any decision to liberalize the diet should be made under specialist supervision with clear protocols and regular follow-up [12,18]. Unsupervised reintroduction of highly allergenic foods carries a risk not only of breakthrough anaphylaxis once biologic protection wanes, but also of inducing or unmasking EoE. Second, clinicians should actively screen for gastrointestinal symptoms in patients on biologic therapy who increase their exposure to previously eliminated foods. Persistent vomiting, dysphagia, food impaction or unexplained weight loss warrant prompt evaluation for EoE. Finally, our case adds to the growing body of literature suggesting that anti-IgE–facilitated desensitization and EoE are not mutually exclusive, and that suppression of IgE-mediated pathways does not necessarily prevent—and may, in some circumstances, permit the development of a non-IgE-mediated eosinophilic disease.\u003c/p\u003e\u003cp\u003eIn conclusion, this case illustrates that omalizumab can enable functional desensitization to CM in a child with a history of life-threatening reactions, but prolonged unsupervised consumption of CM under anti-IgE therapy may be associated with the onset of EoE. Awareness of this potential complication is crucial for clinicians managing children with severe food allergy and asthma.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eEoE eosinophilic esophagitis\u003c/p\u003e\n\u003cp\u003eOIT oral immunotherapy\u003c/p\u003e\n\u003cp\u003eIgE immunoglobulin E\u003c/p\u003e\n\u003cp\u003eCM cow’s milk\u003c/p\u003e\n\u003cp\u003eOMA omalizumab\u003c/p\u003e\n\u003cp\u003e2\u003csup\u003end\u003c/sup\u003e gen nsAH1 second generation non-sedating antihistamines\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eEoEHSS Eospinophilic Esophagitis Histologic Scoring System\u003c/p\u003e\n\u003cp\u003ePPI proton pump inhibitor\u003c/p\u003e\n\u003cp\u003eFDA Food and Drug Administration\u0026nbsp;\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors’ institution does not require ethical approval for publication of a case report. Written informed consent was obtained from the patient’s legal guardian.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWritten informed consent for publication of clinical details and images was obtained from the patient’s legal guardian.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll data generated or analyzed during this study are included in this published article.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNo external funding was received for this work.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors' contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eUJW: Conceptualization, data collection, figure preparation, acquisition of images, original draft writing and final draft editing, supervision.\u003c/p\u003e\n\u003cp\u003eLK: Data collection, original draft writing and final draft editing.\u003c/p\u003e\n\u003cp\u003eECJ: Critical revision and final draft editing.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors thank the patient and family for their cooperation, as well as the consulting gastroenterologist Prof. Krzysztof Fyderek (Department of Pediatrics and Gastroenterology, Children’s University Hospital, Krakow, Poland) for his gastroenterological evaluation. \u0026nbsp;\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eAmil-Dias J, Oliva S, Papadopoulou A, Thomson M, Guti\u0026eacute;rrez-Junquera C, Kalach N, et al. Diagnosis and management of eosinophilic esophagitis in children: An update from the European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN). J Pediatr Gastroenterol Nutr. John Wiley and Sons Inc; 2024;79:394\u0026ndash;437. https://doi.org/10.1002/jpn3.12188\u003c/strong\u003e\u003c/li\u003e\n\u003cli\u003eErdle SC, Carr S, Chan ES, Robertson K, Watson W. Eosinophilic esophagitis. Allergy, Asthma and Clinical Immunology. BioMed Central Ltd; 2024. https://doi.org/10.1186/s13223-024-00929-0\u003c/strong\u003e\u003c/li\u003e\n\u003cli\u003eCarr S, Chan ES, Watson W. Eosinophilic esophagitis. Allergy, Asthma and Clinical Immunology. BioMed Central Ltd.; 2018;14. https://doi.org/10.1186/s13223-018-0287-0\u003c/strong\u003e\u003c/li\u003e\n\u003cli\u003eJi R, Cui X, Zhi Y. Eosinophilic esophagitis and allergic susceptibility: A systematic review and meta-analysis. World Allergy Organization Journal. Elsevier Inc.; 2025;18. https://doi.org/10.1016/j.waojou.2025.101054\u003c/strong\u003e\u003c/li\u003e\n\u003cli\u003eWojas O, Krzych-Fałta E, Żybul P, Żalikowska-Gardocka M, Ilczuk T, Furmańczyk K, et al. \u003c/strong\u003eThe Overlap of Allergic Disorders and Upper Gastrointestinal Symptoms: Beyond Eosinophilic Esophagitis. Nutrients . Multidisciplinary Digital Publishing Institute (MDPI); 2025;17. https://doi.org/10.3390/nu17081355\u003c/strong\u003e\u003c/li\u003e\n\u003cli\u003eHill DA, Grundmeier RW, Ramos M, Spergel JM. Eosinophilic Esophagitis is a Late Manifestation of the Allergic March. J Allergy Clin Immunol Pract. 2018 Sep-Oct;6(5):1528-1533. https://doi.org/10.5281/zenodo.1248931\u003c/strong\u003e\u003c/li\u003e\n\u003cli\u003eHill DA, Spergel JM. Is eosinophilic esophagitis a member of the atopic march? Annals of Allergy, Asthma and Immunology. American College of Allergy, Asthma and Immunology; 2018. p. 113\u0026ndash;4. https://doi.org/10.1016/j.anai.2017.10.003\u003c/strong\u003e\u003c/li\u003e\n\u003cli\u003eKuźmiński A, Przybyszewska J, Bartuzi Z. Food allergens and oral immunotherapy as indicators of eosinophilic oesophagitis. Prz Gastroenterol. Termedia Publishing House Ltd.; 2024. p. 362\u0026ndash;7. https://doi.org/10.5114/pg.2024.139534\u003c/strong\u003e\u003c/li\u003e\n\u003cli\u003eJin H, Trogen B, Nowak-Wegrzyn A. Eosinophilic esophagitis as a complication of food oral immunotherapy. Curr Opin Allergy Clin Immunol. Lippincott Williams and Wilkins; 2020. p. 616\u0026ndash;23. https://doi.org/10.1097/ACI.0000000000000688\u003c/strong\u003e\u003c/li\u003e\n\u003cli\u003eNilsson C, Scurlock AM, Dellon ES, Brostoff JM, Pham T, Ryan R, et al. Clinical Communications Onset of eosinophilic esophagitis during a clinical trial program of oral immunotherapy for peanut allergy. J Allergy Clin Immunol Pract. 2021 Dec;9(12):4496-4501. https://doi.org/10.1016/j.jaip.2021.07.048\u003c/strong\u003e\u003c/li\u003e\n\u003cli\u003eDinardo G, Fiocchi A, Artesani MC, De Angelis P, Rea F, Tambucci R, et al. Eosinophilic Esophagitis and Cow\u0026rsquo;s Milk: Mechanisms, Challenges, and Treatment Perspectives. Nutrients . Multidisciplinary Digital Publishing Institute (MDPI); 2025. https://doi.org/10.3390/nu17020265\u003c/strong\u003e\u003c/li\u003e\n\u003cli\u003eCasale TB, Fiocchi A, Greenhawt M. A practical guide for implementing omalizumab therapy for food allergy. Journal of Allergy and Clinical Immunology. Elsevier Inc.; 2024. p. 1510\u0026ndash;7. https://doi.org/10.1016/j.jaci.2024.03.019\u003c/strong\u003e\u003c/li\u003e\n\u003cli\u003eSalvati L, Liotta F, Annunziato F, Cosmi L. Therapeutical Targets in Allergic Inflammation. Biomedicines. MDPI; 2022. https://doi.org/10.3390/biomedicines10112874\u003c/strong\u003e\u003c/li\u003e\n\u003cli\u003eMortz CG, Parke L, Rasmussen HM, Kjaer HF, Bindslev-Jensen C. A randomized, double-blind placebo-controlled study on the efficacy of Omalizumab on food allergy threshold in children with severe food allergy. Allergy: European Journal of Allergy and Clinical Immunology. John Wiley and Sons Inc; 2024;79:964\u0026ndash;76. https://doi.org/10.1111/all.16046\u003c/strong\u003e\u003c/li\u003e\n\u003cli\u003eGruchalla RS, Sampson HA, Liu AH, Shreffler W, Wallace PK, Togias A, et al. Effects of omalizumab on T lymphocyte function in inner-city children with asthma. Pediatric Allergy and Immunology. Blackwell Publishing Ltd; 2016. p. 328\u0026ndash;31. https://doi.org/10.1111/pai.12508\u003c/strong\u003e\u003c/li\u003e\n\u003cli\u003eMacGinnitie AJ, Rachid R, Gragg H, Little S V., Lakin P, Cianferoni A, et al. Omalizumab facilitates rapid oral desensitization for peanut allergy. Journal of Allergy and Clinical Immunology. Mosby Inc.; 2017;139:873-881.e8. https://doi.org/10.1016/j.jaci.2016.08.010\u003c/strong\u003e\u003c/li\u003e\n\u003cli\u003eRavindranath A. Chronic vomiting in children: Etiology, diagnosis, and management. Indian Journal of Gastroenterology. Springer; 2020;39:117\u0026ndash;22. https://doi.org/10.1007/s12664-020-01035-w\u003c/strong\u003e\u003c/li\u003e\n\u003cli\u003eWood RA, Togias A, Sicherer SH, Shreffler WG, Kim EH, Jones SM, et al. Omalizumab for the Treatment of Multiple Food Allergies. New England Journal of Medicine. Massachusetts Medical Society; 2024;390:889\u0026ndash;99. https://doi.org/10.1056/nejmoa2312382\u003c/strong\u003e\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"cow’s milk allergy, anaphylaxis, eosinophilic esophagitis, atopic march, anti-IgE therapy","lastPublishedDoi":"10.21203/rs.3.rs-9053333/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-9053333/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eEosinophilic esophagitis (EoE) is a chronic inflammatory disease of the esophagus with symptoms of esophageal dysfunction. It is strongly associated with other atopic conditions in patients and has therefore been recognized as a late manifestation of the atopic march. Sensitization to foods and/or aeroallergens early in life may predispose some individuals to subsequent EoE development. Moreover, the disease was found to emerge as a potential side effect of oral immunotherapy (OIT). However, it remains unclear whether OIT induces or rather “unmasks” a pre-existing but subclinical disorder.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCase Presentation\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe report a boy with IgE-mediated cow’s milk (CM) allergy, confirmed in infancy after anaphylaxis to yogurt, positive skin prick tests, and elevated CM-specific IgE. He tolerated baked milk following a supervised oral food challenge. From early childhood, he developed severe allergic asthma and rhinitis, refractory to standard therapy. Omalizumab (OMA) was initiated at 10 years of age with marked and sustained asthma control. While receiving anti-IgE treatment, at 13 years of age, the patient independently liberalized his diet and tolerated progressively less processed dairy products for 6–8 months without immediate hypersensitivity reactions. He subsequently developed recurrent vomiting and, two months later, experienced anaphylaxis after ingestion of a small amount of ice cream. Despite extensive evaluation during hospitalization, vomiting persisted and was associated with weight loss. Upper endoscopy revealed esophageal inflammation, with histological confirmation of EoE diagnosis. Treatment with proton pump inhibitor therapy, swallowed topical budesonide, and renewed strict CM elimination resulted in rapid clinical improvement, weight gain, reduction of peripheral eosinophilia, and histologic remission. Treatment with OMA was sustained.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe present case report illustrates that omalizumab can enable functional desensitization to CM in a child with a history of life-threatening reactions, but prolonged unsupervised consumption of CM under anti-IgE therapy may be associated with the onset of EoE. Awareness of this potential complication is crucial for clinicians managing children with severe food allergy and asthma on biological therapy.\u003c/p\u003e","manuscriptTitle":"From anaphylaxis to eosinophilic esophagitis: when therapy leads to unintended immune shifts – a case report","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-03-13 18:49:53","doi":"10.21203/rs.3.rs-9053333/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"95bfdfe3-c71b-484f-93c0-e0f2f224d7d6","owner":[],"postedDate":"March 13th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-03-18T11:41:00+00:00","versionOfRecord":[],"versionCreatedAt":"2026-03-13 18:49:53","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-9053333","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-9053333","identity":"rs-9053333","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}