The expanding spectrum of eosinophilic gastrointestinal disorders: summarizing diagnostic challenges, updated consensus diagnostic criteria, molecular drivers and site-specific histopathological changes

Abstract

Aim: Eosinophilic gastrointestinal disorders (EGIDs) are chronic inflammatory conditions defined by eosinophilic infiltration of the gastrointestinal tract in the absence of secondary causes. This study aimed to synthesize current evidence on the clinical spectrum, pathogenesis, diagnostic criteria, and prognostic implications of EGIDs, including eosinophilic esophagitis, gastritis, duodenitis, ileitis, and colitis. Methods: A retrospective, multi-source observational analysis of published clinical datasets on EGIDs was conducted. Systematic searches of PubMed, Scopus, Web of Science, and EMBASE identified eligible studies that included ≥ 10 patients with EGIDs and provided quantitative data on eosinophil counts, clinical features, endoscopic and histopathological findings. Articles reporting secondary causes of eosinophilia were excluded. Data extraction was done and independently verified by two reviewers. Special emphasis was placed on unresolved diagnostic hurdles, pediatric versus adult presentations, and long-term disease implications. Results: A total of eligible datasets highlighted common molecular drivers, including epithelial barrier dysfunction, Th2-skewed immune responses, and genetic susceptibilities (e.g., TSLP, CAPN14). Core symptoms varied by site, with dysphagia predominating in eosinophilic esophagitis, and abdominal pain and diarrhea more frequent in distal EGIDs. Endoscopic findings included rings, furrows, and nodularity, while histology demonstrated patchy eosinophilic infiltration and epithelial damage with site-specific thresholds. Laboratory abnormalities included elevated eosinophil counts, IgE, and biochemical markers of malabsorption. Prognosis was variable, with frequent recurrence and heterogeneity in treatment response. Conclusions: Significant knowledge gaps persist in EGID research and practice. Priority areas include establishing consensus-driven histological thresholds and developing non-invasive biomarkers for disease monitoring. Urgent unresolved questions involve the utility of biomarkers in guiding therapy, monitoring response and systematic evaluation of pediatric versus adult differences. Addressing these gaps will require multidisciplinary collaboration, standardized diagnostic protocols, and longitudinal multicenter studies to improve both clinical care and research consistency.

Keywords

eosinophilic gastroenteritis / eosinophilic esophagitis / gastrointestinal diseases / consensus / biomarkers / histopathology

References

[1] Gleich GJ, Loegering DA. Immunobiology of Eosinophils. Annu Rev Immunol. 1984; 2: 429-59.

[2] Weller PF, Bubley GJ. The Idiopathic Hypereosinophilic Syndrome. Blood. 1994; 83: 2759-79.

[3] Gleich GJ, Adolphson CR. The Eosinophilic Leukocyte: Structure and Function. Adv Immunol. 1986; 39: 177-253.

[4] Kita H. The eosinophil: a cytokine-producing cell? J Allergy Clin Immunol. 1996; 97: 889-92.

[5] Saavedra-Delgado AM, Metcalfe DD. Interactions between food antigens and the immune system in the pathogenesis of gastrointestinal diseases. Ann Allergy. 1985; 55: 694-702.

[6] Furuta GT, Liacouras CA, Collins MH, Gupta SK, Justinich C, Putnam PE, et al. Eosinophilic Esophagitis in Children and Adults: A Systematic Review and Consensus Recommendations for Diagnosis and Treatment. Gastroenterology. 2007; 133: 1342-63.

[7] Rothenberg ME, Mishra A, Brandt EB, Hogan SP. Gastrointestinal eosinophils. Immunol Rev. 2001; 179: 139-55.

[8] Nishitani H, Okabayashi M, Satomi M, Shimoyama T, Dohi Y. Infiltration of peroxidase-producing eosinophils into the lamina propria of patients with ulcerative colitis. J Gastroenterol. 1998; 33: 189-95.

[9] Kelly KJ, Simpson HA, Anderson JA. Eosinophilic gastroenteritis. J Pediatr Gastroenterol Nutr. 2000; 33: 28-35.

[10] Kelly KJ, Lazenby AJ, Rowe PC, Yardley JH, Perman JA, Sampson HA. Eosinophilic Esophagitis Attributed to Gastroesophageal Reflux: Improvement With an Amino Acid-Based Formula. Gastroenterology. 1995; 109: 1503-12.

[11] Sant’Anna AM, Rolland S, Fournet JC, Yazbeck S, Drouin E. Eosinophilic esophagitis in children: symptoms, histology and pH probe results. J Pediatr Gastroenterol Nutr. 2004; 39: 373-7.

[12] Dellon ES, Liacouras CA, Molina-Infante J, Furuta GT, Spergel JM, Zevit N, et al. Updated International Consensus Diagnostic Criteria for Eosinophilic Esophagitis: Proceedings of the AGREE Conference. Gastroenterology. 2018; 155: 1022-33.e10.

[13] Matsushita T, Maruyama R, Ishikawa N, Harada Y, Araki A, Chen D, et al. The Number and Distribution of Eosinophils in the Adult Human Gastrointestinal Tract: A Study and Comparison of Racial and Environmental Factors. Am J Surg Pathol. 2015; 39: 521-7.

[14] Liacouras CA, Furuta GT, Hirano I, Atkins D, Attwood SE, Bonis PA, et al. Eosinophilic esophagitis: updated consensus recommendations for children and adults. J Allergy Clin Immunol. 2011; 128: 3-20.e6; quiz 21.

[15] Molina-Infante J, Bredenoord AJ, Cheng E, Dellon ES, Furuta GT, Gupta SK, et al. Proton pump inhibitor-responsive oesophageal eosinophilia: an entity challenging current diagnostic criteria for eosinophilic oesophagitis. Gut. 2016; 65: 524-31.

[16] Arias A, González-Cervera J, Tenias JM, Lucendo AJ. Efficacy of Dietary Interventions for Inducing Histologic Remission in Patients With Eosinophilic Esophagitis: A Systematic Review and Meta-analysis. Gastroenterology. 2014; 146: 1639-48.

[17] Lucendo AJ, Molina-Infante J, Arias Á, von Arnim U, Bredenoord AJ, Bussmann C, et al. Guidelines on eosinophilic esophagitis: evidence-based statements and recommendations for diagnosis and management in children and adults. United Eur Gastroenterol J. 2017; 5: 335-58.

[18] Cianferoni A, Spergel J. Eosinophilic Esophagitis: A Comprehensive Review. Clin Rev Allergy Immunol. 2016; 50: 159-74.

[19] Hill DA, Spergel JM. The Immunologic Mechanisms of Eosinophilic Esophagitis. Curr Allergy Asthma Rep. 2016; 16: 9.

[20] Dellon ES, Hirano I. Epidemiology and Natural History of Eosinophilic Esophagitis. Gastroenterology. 2018; 154: 319-32 e3.

[21] Schoepfer AM, Safroneeva E, Bussmann C, Kuchen T, Portmann S, Simon H, et al. Delay in Diagnosis of Eosinophilic Esophagitis Increases Risk for Stricture Formation in a Time-Dependent Manner. Gastroenterology. 2013; 145: 1230-6.e1.

[22] Papadopoulou A, Koletzko S, Heuschkel R, Dias JA, Allen KJ, Murch SH, et al. ; ESPGHAN Eosinophilic Esophagitis Working Group and the Gastroenterology Committee. Management guidelines of eosinophilic esophagitis in childhood. J Pediatr Gastroenterol Nutr. 2014; 58: 107-18.

[23] Contreras EM, Gupta SK. Steroids in Pediatric Eosinophilic Esophagitis. Gastroenterol Clin North Am. 2014; 43: 345-56.

[24] Davis BP, Rothenberg ME. Mechanisms of Disease of Eosinophilic Esophagitis. Annu Rev Pathol. 2016; 11: 365-93.

[25] Rothenberg ME. Eosinophilic gastrointestinal disorders (EGID). J Allergy Clin Immunol. 2004; 113: 11-29.

[26] Collins MH, Capocelli K, Yang GY. Eosinophilic Gastrointestinal Disorders Pathology. Front Med (Lausanne). 2018; 4: 261.

[27] Alsohaibani FI, Peedikayil MC, Alzahrani MA, Azzam NA, Almadi MA, Dellon ES, et al. Eosinophilic esophagitis: Current concepts in diagnosis and management. Saudi J Gastroenterol. 2024; 30: 210-27.

[28] Furuta GT, Katzka DA. Eosinophilic Esophagitis. N Engl J Med. 2015; 373: 1640-8.

[29] Dellon ES, Liacouras CA. Advances in clinical management of eosinophilic esophagitis. Gastroenterology. 2014; 147: 1238-54.

[30] Aceves SS. Remodeling and Fibrosis in Chronic Eosinophil Inflammation. Dig Dis. 2014; 32: 15-21.

[31] Collins MH. Histopathology of Eosinophilic Esophagitis. Dig Dis. 2014; 32: 68-73.

[32] Dellon ES, Khoury P, Muir AB, Liacouras CA, Safroneevaet E, Atkins D, et al. A Clinical Severity Index for Eosinophilic Esophagitis: Development, Consensus, and Future Directions. Gastroenterology. 2022; 163: 59-76.

[33] Collins MH, Martin LJ, Alexander ES, Boyd JT, Sheridan R, He H, et al. Newly developed and validated eosinophilic esophagitis histology scoring system and evidence that it outperforms peak eosinophil count for disease diagnosis and monitoring. Dis Esophagus. 2017; 30: 1-8.

[34] Attwood S. Eosinophilic oesophagitis-a common disease, newly recognised. Clin Med (Lond). 2013; 13 Suppl 6: s32-5.

[35] Alhmoud T, Ghazaleh S, Ghanim M, Redfern RE. The Risk of Esophageal Food Impaction in Eosinophilic Esophagitis Patients: The Role of Clinical and Socioeconomic Factors. Clin Exp Gastroenterol. 2022; 15: 153-61.

[36] Klein NC, Hargrove RL, Sleisenger MH, Jeffries GH. Eosinophilic gastroenteritis. Medicine (Baltimore). 1970; 49: 299-319.

[37] Attwood SE. Overview of eosinophilic oesophagitis. Br J Hosp Med (Lond). 2019; 80: 132-8.

[38] Talley NJ, Walker MM, Aro P, Ronkainen J, Storskrubb T, Hindley LA, et al. Non-ulcer Dyspepsia and Duodenal Eosinophilia: An Adult Endoscopic Population-Based Case-Control Study. Clin Gastroenterol Hepatol. 2007; 5: 1175-83.

[39] Uenishi T, Sakata C, Tanaka S, Yamamoto T, Shuto T, Hirohashi K, et al. Eosinophilic Enteritis Presenting as Acute Intestinal Obstruction: A Case Report and Review of the Literature. Dig Surg. 2003; 20: 326-9.

[40] Talley NJ, Shorter RG, Phillips SF, Zinsmeister AR. Eosinophilic gastroenteritis: a clinicopathological study of patients with disease of the mucosa, muscle layer, and subserosal tissues. Gut. 1990; 31: 54-8.

[41] Mungan Z, Attila T, Kapran Y, Tokatli IP, Unal Z. Eosinophilic Jejunitis Presenting as Intractable Abdominal Pain. Case Rep Gastroenterol. 2014; 8: 377-80.

[42] Travers J, Rothenberg ME. Eosinophils in mucosal immune responses. Mucosal Immunol. 2015; 8: 464-75.

[43] Sunkara T, Rawla P, Yarlagadda KS, Gaduputi V. Eosinophilic gastroenteritis: diagnosis and clinical perspectives. Clin Exp Gastroenterol. 2019; 12: 239-53.

[44] Abou Rached A, El Hajj W. Eosinophilic gastroenteritis: Approach to diagnosis and management. World J Gastrointest Pharmacol Ther. 2016; 7: 513-23.

[45] Pineton de Chambrun G, Dufour G, Tassy B, Rivière B, Bouta N, Bismuth M, et al. Diagnosis, Natural History and Treatment of Eosinophilic Enteritis: a Review. Curr Gastroenterol Rep. 2018; 20: 37.

[46] Zhang L, Duan L, Ding S, Lu J, Jin Z, Cui R, et al. Eosinophilic gastroenteritis: Clinical manifestations and morphological characteristics, a retrospective study of 42 patients. Scand J Gastroenterol. 2011; 46: 1074-80.

[47] Barchi A, Vespa E, Passaretti S, Dell’Anna G, Fasulo E, Yacoub MR, et al. The Dual Lens of Endoscopy and Histology in the Diagnosis and Management of Eosinophilic Gastrointestinal Disorders-A Comprehensive Review. Diagnostics (Basel). 2024; 14: 858.

[48] Kweon M, Kiyono H. Eosinophilic gastroenteritis: a problem of the mucosal immune system? Curr Allergy Asthma Rep. 2003; 3: 79-85.

[49] Lamousé-Smith ES, Furuta GT. Eosinophils in the gastrointestinal tract. Curr Gastroenterol Rep. 2006; 8: 390-5.

[50] Hogan SP, Mishra A, Brandt EB, Foster PS, Rothenberg ME. A critical role for eotaxin in experimental oral antigen-induced eosinophilic gastrointestinal allergy. Proc Natl Acad Sci U S A. 2000; 97: 6681-6.

[51] Ong GY, Hsu CC, Changchien CS, Lu SN, Huang SC. Eosinophilic Gastroenteritis Involving the Distal Small Intestine and Proximal Colon. Chang Gung Med J. 2002; 25: 56-61.

[52] Turner KO, Sinkre RA, Neumann WL, Genta RM. Primary Colonic Eosinophilia and Eosinophilic Colitis in Adults. Am J Surg Pathol. 2017; 41: 225-33.

[53] Uppal V, Kreiger P, Kutsch E. Eosinophilic Gastroenteritis and Colitis: a Comprehensive Review. Clin Rev Allergy Immunol. 2016; 50: 175-88.

[54] Alfadda AA, Storr MA, Shaffer EA. Eosinophilic colitis: epidemiology, clinical features, and current management. Therap Adv Gastroenterol. 2011; 4: 301-9.

[55] Anuradha C, Mittal R, Yacob M, Manipadam MT, Kurian S, Eapen A. Eosinophilic disorders of the gastrointestinal tract: imaging features. Diagn Interv Radiol. 2012; 18: 183-8.

[56] Macaigne G. Eosinophilic colitis in adults. Clin Res Hepatol Gastroenterol. 2020; 44: 630-7.

[57] Díaz Del Arco C, Taxonera C, Olivares D, Fernández Aceñero MJ. Eosinophilic colitis: Case series and literature review. Pathol Res Pract. 2018; 214: 100-4.

[58] Alfadda AA, Storr MA, Shaffer EA. Eosinophilic colitis: an update on pathophysiology and treatment. Br Med Bull. 2011; 100: 59-72.

[59] Raghavendran AK, Musunuri B, Rajpurohit S, Pai GC, Shetty S, Shetty A, et al. Eosinophilic Esophagitis in India: A Rare or Underdiagnosed Entity? J Dig Endosc. 2025.