Eosinophilic diseases: classification, clinical and pathogenetic relationships, and an algorithmic approach to diagnosis

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Abstract

This literature review focuses on current understanding of eosinophil-associated diseases – a heterogeneous group of conditions united by a common feature: an increased number of eosinophils in the blood and/or tissues. This article systematizes current information on the classification, pathogenesis, and diagnosis of eosinophilia, hypereosinophilia (HE), and hypereosinophilic syndrome (HES). It is emphasized that an increased eosinophil count per se is not a diagnosis, but rather a symptom that can be primary (clonal), secondary (reactive), or idiopathic. The clinical manifestations of HE are polymorphic and can affect various organs, necessitating a multidisciplinary approach. The diagnostic algorithm discussed in this review is based on the sequential exclusion of conditions that are common causes of secondary HES, the search for clonality (hematological neoplasms), and a mandatory comprehensive assessment of target organ damage. Accurately determining the type of HES in accordance with current consensus classifications (WHO, ICOG-EO) is the cornerstone for selecting a personalized therapeutic strategy and determining the prognosis.

About the authors

Nadiya F. Frolova

Moscow Clinical Research Center, Hospital No. 52; Russian University of Medicine

Author for correspondence.
Email: nadiya.frolova@yandex.ru
ORCID iD: 0000-0002-6086-5220

Dr.Sci. (Med.), Deputy Chief Physician for Nephrology Care, Head of the Interdistrict Nephrology Center, Moscow Clinical Research Center, Hospital No. 52, Moscow Healthcare Department; Associate Professor, Department of Nephrology, Faculty of Continuous Professional Education, Russian University of Medicine

Russian Federation, Moscow; Moscow

Galina V. Volgina

Russian University of Medicine

Email: volginagv@mail.ru
ORCID iD: 0000-0002-7771-4074

Dr.Sci. (Med.), Professor, Department of Nephrology, Faculty of Continuous Professional Education

Russian Federation, Moscow

Daria S. Fomina

Moscow Clinical Research Center, Hospital No. 52; Sechenov First Moscow State Medical University (Sechenov University)

Email: daria_fomina@mail.ru
ORCID iD: 0000-0002-5083-6637

Dr.Sci. (Med.), Professor, Deputy Director for Research and Clinical Work, Moscow Clinical Research Center, Hospital No. 52, Moscow Healthcare Department; Chief External Expert in Allergology and Immunology of the Moscow Healthcare Department; Professor, Department of Clinical Immunology and Allergology, Sechenov First Moscow State Medical University (Sechenov University)

Russian Federation, Moscow; Moscow

Tatyana S. Kruglova

Moscow Clinical Research Center, Hospital No. 52

Email: surckova.t@yandex.ru
ORCID iD: 0000-0002-4949-9178

Head of the Allergology and Immunology Department

Russian Federation, Moscow

Sergey S. Usatyuk

Moscow Clinical Research Center, Hospital No. 52

Email: usatuk-doc@mail.ru
ORCID iD: 0000-0002-8742-3860

Head of Nephrology Department No. 2

Russian Federation, Moscow

Rustam T. Iskhakov

Moscow Clinical Research Center, Hospital No. 52

Email: stamius@yandex.ru
ORCID iD: 0000-0003-2850-4465

Head of the Intensive Care Department for Nephrological Patients

Russian Federation, Moscow

Zinaida Yu. Mutovina

Moscow Clinical Research Center, Hospital No. 52; Central State Medical Academy of the Administrative Directorate of the President of the Russian Federation

Email: zmutovina@mail.ru
ORCID iD: 0000-0001-5809-6015

Cand.Sci. (Med.), Deputy Chief Physician for Medical Affairs, Moscow Clinical Research Center, Hospital No. 52, Moscow Healthcare Department; Associate Professor at the Department of Therapy, Cardiology, and Functional Diagnostics with a Course in Nephrology, Central State Medical Academy of the Administrative Directorate of the President of the Russian Federation

Russian Federation, Moscow; Moscow

References

  1. Shomali W., Gotlib J. World Health Organization and international consensus classification of eosinophilic disorders: 2024 update on diagnosis, risk stratification, and management. Am. J. Hematol. 2024;99:946–68. doi: 10.1002/ajh.27287.
  2. Valent P., Klion A.D., Roufosse F. et al. Proposed refined diagnostic criteria and classification of eosinophil disorders and related syndromes. Allergy. 2023;78(1):47–59. doi: 10.1111/all.15544.
  3. Thomsen G.N., Christoffersen M.N., Lindegaard H.M. et al. The multidisciplinary approach to eosinophilia. Front. Oncol. 2023;13:1193730. doi: 10.3389/fonc.2023.1193730.
  4. Marichal T., Mesnil C., Bureau F. Homeostatic Eosinophils: Characteristics and Functions. Front. Med. 2017;4:101. Doi: 10.3389/ fmed.2017.00101.
  5. Weller P.F., Spencer L.A. Functions of tissue-resident eosinophils. Nat. Rev. Immunol. 2017;17(12):746–60. doi: 10.1038/nri.2017.95.
  6. Klion A.D., Ackerman S.J., Bochner B.S. Contributions of Eosinophils to Human Health and Disease. Annu. Rev. Pathol. 2020;15:179–209. doi: 10.1146/annurev-pathmechdis-012419-032756.
  7. Mormile M., Mormile I., Fuschillo S. et al. Eosinophilic Airway Diseases: From Pathophysiological Mechanisms to Clinical Practice. Int. J. Mol. Sci. 2023;24(8):7254. doi: 10.3390/ijms24087254.
  8. Wechsler M.E., Munitz A., Ackerman S.J. et al. Eosinophils in Health and Disease: A State-of-the-Art Review. Mayo Clin. Proc. 2021;96(10):2694–707. doi: 10.1016/j.mayocp.2021.04.025.
  9. Taurisano G., Ruffi M.C., Canalis S., Costanzo G.A.M.L. Hypereosinophilia: clinical and therapeutic approach in 2025. Curr. Opin. Allergy Clin. Immunol. 2025;25(4):258–68. doi: 10.1097/ACI.0000000000001078.
  10. Caminati M., Brussino L., Carlucci M. et al. Managing patients with hypereosinophilic syndrome: a statement from the Italian Society of Allergy. Asthma Clin. Immunol. Cells. 2024;13(14):1180. Doi: 10.3390/ cells13141180.
  11. Valent P., Gleich G.J., Reiter A. et al. Pathogenesis and classification of eosinophil disorders: a review of recent developments in the field. Expert. Rev. Hematol. 2012;5(2):157–76. doi: 10.1586/ehm.11.81.
  12. Wang S.A., Orazi A., Gotlib J. et al. The international consensus classification of eosinophilic disorders and systemic mastocytosis. Am. J. Hematol. 2023;98(8):1286–306. doi: 10.1002/ajh.26966.
  13. Klion A.D. Eosinophilia: a pragmatic approach to diagnosis and treatment. Hematology Am. Soc. Hematol. Educ. Program. 2015;2015(1):92–7. doi: 10.1182/asheducation-2015.1.92.
  14. Simon H.U., Rothenberg M.E., Bochner B.S. et al. Refining the definition of hypereosinophilic syndrome. J. Allergy Clin. Immunol. 2010;126(1):45–9. doi: 10.1016/j.jaci.2010.03.042.
  15. Valent P., Klion A.D., Horny H.P. et al. Contemporary consensus proposal on criteria and classification of eosinophilic disorders and related syndromes. J. Allergy Clin. Immunol. 2012;130(3):607–12. doi: 10.1016/j.jaci.2012.02.019.
  16. Shomali W., Gotlib J. Eosinophils and their disorders. Williams Hematology. Ed. by K. Kaushansky, J.T. Prchal, L.J. Burns, et al. 10th ed. New York: McGraw Hill, 2021.
  17. Tzankov A., Reichard K.K., Hasserjian R.P. et al. Updates on eosinophilic disorders. Virchows Arch. 2023;482:85–97. doi: 10.1007/s00428-022-03402-8.
  18. O’Connell E.M., Nutman T.B. Eosinophilia in Infectious Diseases. Immunol. Allergy Clin. North Am. 2015;35(3):493–522. doi: 10.1016/j.iac.2015.05.003.
  19. Decruyenaere P., Van de Maele B., Hulstaert E. et al. IgE-mediated gastroallergic anisakiasis with eosinophilic oesophagitis: A case report. Acta Clin. Belg. 2022;77(1):396–9. doi: 10.1080/17843286.2020.1822627.
  20. Okumura K., Kubota T., Lefor A.K., et al. Increased number of eosinophils in ascites is associated with intestinal anisakidosis. J. Helminthol. 2019;93(1):126–9. doi: 10.1017/S0022149X17001158.
  21. Molina B., Padoan R., Urban M.L. et al. Dupilumab for Relapsing or Refractory Sinonasal and/or Asthma Manifestations in Eosinophilic Granulomatosis With Polyangiitis: A European Retrospective Study. Ann. Rheum. Dis. 2023;82(12):1587–93. Doi: 10.1136/ ard-2023-224756.
  22. Olaguibel J.M., Sastre J., Rodríguez J.M., Del Pozo V. Eosinophilia Induced by Blocking the IL-4/IL-13 Pathway: Potential Mechanisms and Clinical Outcomes. J. Invest. Allergol. Clin. Immunol. 2022;32(3):165–80. doi: 10.18176/jiaci.0823.
  23. Rauscher C., Freeman A. Drug-induced eosinophilia. Allergy Asthma Proc. 2018;39(3):252–6. doi: 10.2500/aap.2018.39.4120.
  24. Perkins C., Wills-Karp M., Finkelman F.D. IL-4 induces IL-13-independent allergic airway inflammation. J. Allergy Clin. Immunol. 2006;118(2):410–9. doi: 10.1016/j.jaci.2006.06.004.
  25. Cabanas R., Ramirez E., Sendagorta E. et al. Spanish Guidelines for Diagnosis, Management, Treatment, and Prevention of DRESS Syndrome. J. Investig. Allergol. Clin. Immunol. 2020;30(4):229–53. doi: 10.18176/jiaci.0480.
  26. Calle A.M., Aguirre N., Ardila J.C., Cardona Villa R. DRESS syndrome: A literature review and treatment algorithm. W. Allergy Organ. J. 2023;16:100673. doi: 10.1016/j.waojou.2022.100673.
  27. Khoury P., Akuthota P., Kwon N. et al. HES and EGPA: Two Sides of the Same Coin. Mayo Clin. Proc. 2023;98(7):1054–70. Doi: 10.1016/ j.mayocp.2023.02.013.
  28. Strobel M.J., Alves D., Roufosse F. et al. Insights from social media on the patient experience of living with rare eosinophil-driven diseases. J. Patient Exp. 2022;9:23743735221143953. doi: 10.1177/23743735221143953.
  29. Wardlaw A.J., Wharin S., Aung H. et al. The causes of a peripheral blood eosinophilia in a secondary care setting. Clin. Exp. Allergy. 2021;51(7):902–14. doi: 10.1111/cea.13889.
  30. Helbig G., Klion A.D. Hypereosinophilic syndromes – an enigmatic group of disorders with an intriguing clinical spectrum and challenging treatment. Blood Rev. 2021;49:100809. doi: 10.1016/j.blre.2021.100809.
  31. Valent P., Degenfeld-Schonburg L., Sadovnik I. et al. Eosinophils and eosinophil-associated disorders: immunological, clinical, and molecular complexity. Semin. Immunopathol. 2021;43(3):423–38. Doi: 10.1007/ s00281-021-00863-y.
  32. Caminati M., Carpagnano L.F., Alberti C. et al. Idiopathic hypereosinophilic syndromes and rare dysimmune conditions associated with hyper-eosinophilia in practice: An innovative multidisciplinary approach. W. Allergy Organ. J. 2024;17(8):100928. doi: 10.1016/j.waojou.2024.100928.
  33. Klion A.D. Approach to the patient with suspected hypereosinophilic syndrome. Hematology Am. Soc. Hematol. Educ. Program. 2022;2022(1):47–54. doi: 10.1182/hematology.2022000367.
  34. Requena G., van den Bosch J., Akuthota P. et al. Clinical profile and treatment in hypereosinophilic syndrome variants: a pragmatic review. J. Allergy Clin. Immunol. Pract. 2022;10(8):2125–34. Doi: 10.1016/ j.jaip.2022.03.034.
  35. Ogbogu P.U., Bochner B.S., Butterfield J.H. et al. Hypereosinophilic syndrome: a multicenter, retrospective analysis of clinical characteristics and response to therapy. J. Allergy Clin. Immunol. 2009;124(6):1319–25.e3. Doi: 10.1016/ j.jaci.2009.09.022.
  36. Radonjic-Hoesli S., Brüggen M.C., Feldmeyer L. et al. Eosinophils in skin diseases. Semin. Immunopathol. 2021;43(3):393–409. Doi: 10.1007/ s00281-021-00868-7.
  37. Balaskas K., Wyss P., Guex-Crosier Y. Ocular involvement in idiopathic hypereosinophilic syndrome: a rare finding. Klin. Monbl. Augenheilkd. 2012;229(4):437–8. doi: 10.1055/s-0031-1299176.
  38. Tamaki H., Chatterjee S., Langford C.A. Eosinophilia in Rheumatologic/Vascular Disorders. Immunol Allergy Clin North Am. 2015;35(3):453–76. doi: 10.1016/j.iac.2015.05.001.
  39. Ihn H. Eosinophilic fasciitis: From pathophysiology to treatment. Allergol. Int. 2019;68(4):437–9. doi: 10.1016/j.alit.2019.03.001.
  40. Bay P., Groh M., Gaillet A., et al. Extracorporeal membrane oxygenation for refractory acute eosinophilic pneumonia. J. Crit. Care. 2024;79:154437. doi: 10.1016/j.jcrc.2023.154437.
  41. Soma S. Pericardial effusion and progressive bilateral effusion as rare presentations of idiopathic hypereosinophilic syndrome. Cureus. 2023;15(8):e44495. doi: 10.7759/cureus.44495.
  42. Dong J.H., Xu S.T., Xu F. et al. Clinical and morphologic spectrum of renal involvement in idiopathic hypereosinophilic syndrome. Clin. Exp. Nephrol. 2021;25(3):270–8. doi: 10.1007/s10157-020-02012-5.
  43. Ono R., Iwahana T., Kato H. et al. Literature reviews of stroke with hypereosinophilic syndrome. Int. J. Cardiol. Heart Vasc. 2021;37:100915. doi: 10.1016/j.ijcha.2021.100915.
  44. Bondue A., Carpentier C., Roufosse F. Hypereosinophilic syndrome: considerations for the cardiologist. Heart. 2022;108(3):164–71. doi: 10.1136/heartjnl-2020-317202.
  45. Réau V., Vallée A., Terrier B. et al. Venous thrombosis and predictors of relapse in eosinophil-related diseases. Sci. Rep. 2021;11(1):6388. doi: 10.1038/s41598-021-85852-9.
  46. Podjasek J.C., Butterfield J.H. Mortality in hypereosinophilic syndrome: 19 years of experience at Mayo Clinic with a review of the literature. Leuk. Res. 2013;37(4):392–5. doi: 10.1016/j.leukres.2012.12.005.
  47. Emmi G., Bettiol A., Gelain E. et al. Evidence-Based Guideline for the Diagnosis and Management of Eosinophilic Granulomatosis With Polyangiitis. Nat. Rev. Rheum. 2023;19(6):378–93. doi: 10.1038/s41584-023-00958-w.
  48. Hellmich B., Sanchez-Alamo B., Schirmer J.H. et al. EULAR Recommendations for the Management of ANCA-Associated Vasculitis: 2022 Update. Ann. Rheum. Dis. 2024;83(1):30–47. doi: 10.1136/ard-2022-223764.
  49. Chung S.A., Langford C.A., Maz M. et al. 2021 American College of Rheumatology/Vasculitis Foundation Guideline for the Management of Antineutrophil Cytoplasmic Antibody-Associated Vasculitis. Arthr. Care Res. 2021;73(8):1088–105. doi: 10.1002/acr.24634.
  50. Wechsler M.E., Akuthota P., Jayne D. et al. Mepolizumab or Placebo for Eosinophilic Granulomatosis With Polyangiitis. N. Engl. J. Med. 2017;376(20):1921–32. doi: 10.1056/NEJMoa1702079.
  51. FDA, FDA Prescriping Information (Nucala) accessed October 5, 2025. https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/ 125526s007lbl.pdf.
  52. Wechsler M., Kovalszki A., Silver J. et al. Pulmonary Function and Asthma Control in Patients With Eosinophilic Granulomatosis With Polyangiitis or Hypereosinophilic Syndrome and Comorbid Asthma Treated With Mepolizumab. Chest. 2024;166(45):28A. Doi: 10.1016/ j.chest.2024.06.048.
  53. Wechsler M.E., Akuthota P., Jayne D. et al. Mepolizumab or Placebo for Eosinophilic Granulomatosis With Polyangiitis. N. Engl. J. Med. 2017;376(20):1921–32. doi: 10.1056/NEJMoa1702079.
  54. Wechsler M.E., Silver J., Wolff G. et al. Long-Term Safety and Efficacy of Mepolizumab in Eosinophilic Granulomatosis With Polyangiitis. Arthr. Rheumatol. 2025;77(8):1052–62. doi: 10.1002/art.43146.
  55. Pongdee T., Deb A., Silver J. et al. Mepolizumab Reduces Systemic Corticosteroid (SCS)-Related Toxicities Compared to Chronic SCS Use in Patients With EGPA. J. Allergy Clin. Immunol. 2025;155(2):AB455. doi: 10.1016/j.jaci.2024.12.1055.
  56. Bettiol A., Urban M.L., Dagna L. et al. Mepolizumab for Eosinophilic Granulomatosis With Polyangiitis: A European Multicenter Observational Study. Arthr. Rheumatol. 2022;74(2):295–306.
  57. Ishii T., Kunishige H., Kobayashi T. et al. Real-World Safety and Effectiveness of Mepolizumab for Patients With Eosinophilic Granulomatosis With Polyangiitis in Japan: Long-Term Observation of the MARS Study. Mod. Rheumatol. 2024;34(5):978–87. doi: 10.1093/mr/roae100. PMID: 39508562.
  58. Kitamura N., Hamaguchi M., Nishihara M. et al. The Effects of Mepolizumab on Peripheral Circulation and Neurological Symptoms in Eosinophilic Granulomatosis With Polyangiitis (EGPA) Patients. Allergol. Intern. 2021;70(1):148–9. doi: 10.1016/j.alit.2020.08.005.
  59. Yamane T., Hashiramoto A. Mepolizumab Exerts Crucial Effects on Glucocorticoid Discontinuation in Patients With Eosinophilic Granulomatosis With Polyangiitis: A Retrospective Study of 27 Cases at a Single Center in Japan. Arthr. Res. Ther. 2023;25(1):110.6. doi: 10.1186/s13075-023-03097-5.
  60. Rios-Garces R., Prieto-Gonzalez S., Hernandez-Rodriguez J. et al. Response to Mepolizumab According to Disease Manifestations in Patients With Eosinophilic Granulomatosis With Polyangiitis. Eur. J. Int. Med. 2022;95:61–6. doi: 10.1016/j.ejim.2021.08.021.
  61. Wechsler M.E., Nair P., Terrier B. et al. Benralizumab Versus Mepolizumab for Eosinophilic Granulomatosis With Polyangiitis. N. Engl. J. Med. 2024;390(10):911–21. doi: 10.1056/NEJMoa2311155.
  62. Wechsler M.E., Agmon-Levin N., Jayne D.R.W. et al. Discontinuation of Oral Glucocorticoids and Achievement of Remission in Patients With Eosinophilic Granulomatosis With Polyangiitis Treated With Benralizumab or Mepolizumab. ACR Open Rheumatol. 2025;7(9):e70096. doi: 10.1002/acr2.70096.
  63. Biddle K., Jade J., Wilson-Morkeh H. et al. The 2025 British Society for Rheumatology Management Recommendations for ANCA-Associated Vasculitis. Rheumatol. (Oxford, England). 2025;64(8):4470–94. doi: 10.1093/rheumatology/keaf474.
  64. Manka L.A., Guntur V.P., Denson J.L. et al. Efficacy and Safety of Reslizumab in the Treatment of Eosinophilic Granulomatosis With Polyangiitis. Ann. Allergy Asthma Immunol. 2021;126(6):696–701.e691. Doi: 10.1016/ j.anai.2021.01.035.
  65. ClinicalTrials.gov. NCT05263934: Efficacy and Safety of Depemokimab Compared With Mepolizumab in Adults With Relapsing or Refractory Eosinophilic Granulomatosis With Polyangiitis (EGPA) (OCEAN), accessed December 16, 2025. https://clinicaltrials.gov/study/ NCT05263934.
  66. Menzies-Gow A., Corren J., Bourdin A. et al. Tezepelumab in Adults and Adolescents With Severe, Uncontrolled Asthma. N. Engl. J. Med. 2021;384(19):1800–9. Doi: 10.1056/ NEJMoa2034975.
  67. Lipworth B.J., Han J.K., Desrosiers M. et al. Tezepelumab in Adults With Severe Chronic Rhinosinusitis With Nasal Polyps. N. Engl. J. Med. 2025;392(12):1178–88. doi: 10.1056/NEJMoa2414482.

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