History

Obtaining a travel history is critical to assess whether a patient with eosinophilia has been to an area that is endemic for certain infections, including helminthic infections and coccidioidomycosis; the latter, which is the only fungal infection that is frequently associated with eosinophilia, is endemic in the southwestern United States and northern Mexico.^[18]

Obtaining a medication and diet history is crucial to evaluate for allergic reactions associated with eosinophilia. In particular, the temporal relationship of medication changes to the onset of eosinophilia should be assessed. History of discontinued medications should also be obtained, as eosinophilia can persist long after cessation.

Obtaining a history of symptoms associated with lymphoma, especially Hodgkin lymphoma, is important.

Eosinophilic esophagitis should be considered in patients who present with dysphagia and/or food impaction, most commonly involving meat.^[19]

A history that is suggestive of adrenal insufficiency, including the use and tapering of corticosteroids, can provide a clue that the observed eosinophilia is associated with adrenal insufficiency. Hypoadrenalism (ie, Addison disease) is the most common endocrine abnormality associated with eosinophilia.

Findings in the history may indicate specific organ involvement, such as respiratory or cardiovascular symptoms (eg, exertional dyspnea). Other signs and symptoms to ask about are fatigue, fever, muscle pain, rash, visual changes, and weakness.

Physical Examination

A complete physical examination is required, because diseases associated with eosinophilia can involve any part of the body, including the skin, brain, eyes, lymph nodes, lungs, heart, liver, spleen, intestine, bone, and nervous system.

Cholesterol emboli due to atherosclerotic disease, with or without recent vascular catheterization, can present as eosinophilia and end-organ damage to the kidneys, skin, and lower extremities (causing blue/purple toes).

Venous thromboembolism (VTE) is the most common clinical thrombotic complication associated with hypereosinophilia.^[20] An unprovoked thromboembolic event is an indicator of eosinophil-associated tissue damage.^[21]

Differential Diagnoses

Gotlib J. World Health Organization-defined eosinophilic disorders: 2017 update on diagnosis, risk stratification, and management. Am J Hematol. 2017 Nov. 92 (11):1243-1259. [QxMD MEDLINE Link]. [Full Text].
Spry CJF, ed. Eosinophils: A Comprehensive Review and Guide to the Scientific and Medical Literature. Oxford, UK: Oxford University Press; 1988.
Gotlib J. Molecular classification and pathogenesis of eosinophilic disorders: 2005 update. Acta Haematol. 2005. 114(1):7-25. [QxMD MEDLINE Link].
Prieto R, Richter JE. Eosinophilic esophagitis in adults: an update on medical management. Curr Gastroenterol Rep. 2013 Jun. 15(6):324. [QxMD MEDLINE Link].
Feldman RE, Lam AC, Sadow PM, Bleier BS. P-glycoprotein is a marker of tissue eosinophilia and radiographic inflammation in chronic rhinosinusitis without nasal polyps. Int Forum Allergy Rhinol. 2013 May 15. [QxMD MEDLINE Link].
Kasamatsu Y, Kida T, Shigeru M, Tagashira T, Murai N, Takai E, et al. Clinically suspected acute myopericarditis with cardiac tamponade associated with peripheral blood eosinophilia presenting in early pregnancy: a case report. J Med Case Rep. 2013 May 13. 7(1):129. [QxMD MEDLINE Link]. [Full Text].
Tefferi A, Patnaik MM, Pardanani A. Eosinophilia: secondary, clonal and idiopathic. Br J Haematol. 2006 Jun. 133(5):468-92. [QxMD MEDLINE Link].
Criado PR, Criado RF, Avancini Jde M, Santi CG. Drug reaction with Eosinophilia and Systemic Symptoms (DRESS) / Drug-induced Hypersensitivity Syndrome (DIHS): a review of current concepts. An Bras Dermatol. 2012 May-Jun. 87(3):435-49. [QxMD MEDLINE Link].
Watanabe H. Recent Advances in Drug-Induced Hypersensitivity Syndrome/Drug Reaction with Eosinophilia and Systemic Symptoms. J Immunol Res. 2018. 2018:5163129. [QxMD MEDLINE Link]. [Full Text].
Weller PF, Bubley GJ. The idiopathic hypereosinophilic syndrome. Blood. 1994 May 15. 83(10):2759-79. [QxMD MEDLINE Link]. [Full Text].
Bain BJ. Relationship between idiopathic hypereosinophilic syndrome, eosinophilic leukemia, and systemic mastocytosis. Am J Hematol. 2004 Sep. 77(1):82-5. [QxMD MEDLINE Link]. [Full Text].
Gotlib J, Cools J, Malone JM 3rd, et al. The FIP1L1-PDGFRalpha fusion tyrosine kinase in hypereosinophilic syndrome and chronic eosinophilic leukemia: implications for diagnosis, classification, and management. Blood. 2004 Apr 15. 103(8):2879-91. [QxMD MEDLINE Link]. [Full Text].
Tefferi A. Modern diagnosis and treatment of primary eosinophilia. Acta Haematol. 2005. 114(1):52-60. [QxMD MEDLINE Link].
Fletcher S, Bain B. Eosinophilic leukaemia. Br Med Bull. 2007. 81-2:115-27. [QxMD MEDLINE Link]. [Full Text].
Arefi M, Robledo C, Peñarrubia MJ, de Coca AG, Cordero M, Hernández-Rivas JM, et al. Genomic analysis of clonal eosinophils by CGH arrays reveals new genetic regions involved in chronic eosinophilia. Eur J Haematol. 2014 Nov. 93(5):422-8. [QxMD MEDLINE Link].
Shomali W, Gotlib J. World Health Organization-defined eosinophilic disorders: 2019 update on diagnosis, risk stratification, and management. Am J Hematol. 2019 Oct. 94 (10):1149-1167. [QxMD MEDLINE Link]. [Full Text].
Leverone N, Tran S, Barry J, Akuthota P. Diagnoses associated with peripheral blood eosinophilia: A 5-year review. Ann Allergy Asthma Immunol. 2021 Nov. 127 (5):597-598. [QxMD MEDLINE Link]. [Full Text].
Weller PF. Eosinophilia in travelers. Med Clin North Am. 1992 Nov. 76(6):1413-32. [QxMD MEDLINE Link].
Abe Y, Sasaki Y, Yagi M, Mizumoto N, Onozato Y, Umehara M, et al. Endoscopic Diagnosis of Eosinophilic Esophagitis: Basics and Recent Advances. Diagnostics (Basel). 2022 Dec 16. 12 (12):[QxMD MEDLINE Link]. [Full Text].
Di Micco P, Scudiero O, Lombardo B, Lodigiani C. Idiopathic Hypereosinophilia and Venous Thromboembolism: Is There a Pathophysiological or Clinical Link? Description of an Intriguing Clinical Case. J Blood Med. 2020. 11:73-76. [QxMD MEDLINE Link]. [Full Text].
[Guideline] Butt NM, Lambert J, Ali S, Beer PA, Cross NC, Duncombe A, et al. Guideline for the investigation and management of eosinophilia. Br J Haematol. 2017 Feb. 176 (4):553-572. [QxMD MEDLINE Link]. [Full Text].
Boyer DF. Blood and Bone Marrow Evaluation for Eosinophilia. Arch Pathol Lab Med. 2016 Oct. 140 (10):1060-7. [QxMD MEDLINE Link]. [Full Text].
Soter S, Barta I, Antus B. Predicting Sputum Eosinophilia in Exacerbations of COPD Using Exhaled Nitric Oxide. Inflammation. 2013 May 17. [QxMD MEDLINE Link].
[Guideline] Aceves SS, Alexander JA, Baron TH, Bredenoord AJ, Day L, Dellon ES, et al. Endoscopic approach to eosinophilic esophagitis: American Society for Gastrointestinal Endoscopy Consensus Conference. Gastrointest Endosc. 2022 Oct. 96 (4):576-592.e1. [QxMD MEDLINE Link]. [Full Text].
Kirchhof MG, Wong A, Dutz JP. Cyclosporine Treatment of Drug-Induced Hypersensitivity Syndrome. JAMA Dermatol. 2016 Nov 1. 152 (11):1254-1257. [QxMD MEDLINE Link].
Hana CK, Caldera H. Hypereosinophilic Syndrome, Multiorgan Involvement and Response to Imatinib. Cureus. 2020 Jun 7. 12 (6):e8493. [QxMD MEDLINE Link]. [Full Text].
Jain N, Cortes J, Quintas-Cardama A, et al. Imatinib has limited therapeutic activity for hypereosinophilic syndrome patients with unknown or negative PDGFRalpha mutation status. Leuk Res. 2009 Jun. 33(6):837-9. [QxMD MEDLINE Link].
Gotlib J. Tyrosine Kinase Inhibitors and Therapeutic Antibodies in Advanced Eosinophilic Disorders and Systemic Mastocytosis. Curr Hematol Malig Rep. 2015 Sep 24. 79(5):441-7. [QxMD MEDLINE Link].
Fraticelli P, Kafyeke A, Mattioli M, Martino GP, Murri M, Gabrielli A. Idiopathic hypereosinophilic syndrome presenting with severe vasculitis successfully treated with imatinib. World J Clin Cases. 2016 Oct 16. 4 (10):328-332. [QxMD MEDLINE Link]. [Full Text].
Allen JN, Davis WB. Eosinophilic lung diseases. Am J Respir Crit Care Med. 1994 Nov. 150(5 Pt 1):1423-38. [QxMD MEDLINE Link].
Cohen AJ, Steigbigel RT. Eosinophilia in patients infected with human immunodeficiency virus. J Infect Dis. 1996 Sep. 174(3):615-8. [QxMD MEDLINE Link].
Heimall J, Freeman A, Holland SM. Pathogenesis of hyper IgE syndrome. Clin Rev Allergy Immunol. 2009 May 19. epub ahead of print. [QxMD MEDLINE Link].
Nair P, Pizzichini MM, Kjarsgaard M, et al. Mepolizumab for prednisone-dependent asthma with sputum eosinophilia. N Engl J Med. 2009 Mar 5. 360(10):985-93. [QxMD MEDLINE Link].
Nand R, Bryke C, Kroft SH, et al. Myeloproliferative disorder with eosinophilia and ETV6-ABL gene rearrangement: efficacy of second-generation tyrosine kinase inhibitors. Leuk Res. 2009 Aug. 33(8):1144-6. [QxMD MEDLINE Link].
Roufosse F, Goldman M, Cogan E. Hypereosinophilic syndrome: lymphoproliferative and myeloproliferative variants. Semin Respir Crit Care Med. 2006 Apr. 27(2):158-70. [QxMD MEDLINE Link].
Lindsley AW, Schwartz JT, Rothenberg ME. Eosinophil responses during COVID-19 infections and coronavirus vaccination. J Allergy Clin Immunol. 2020 Jul. 146 (1):1-7. [QxMD MEDLINE Link]. [Full Text].
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Media Gallery

Indurated edematous plaques of hypereosinophilic syndrome on a patient's legs.
Erythroderma in a patient with hypereosinophilic syndrome.
Granuloma with a central core of eosinophilic debris surrounded by a peripheral palisade of epithelioid histiocytes and eosinophils from a patient with Churg-Strauss syndrome (allergic granulomatosis).
Magnified view of papules and nodules with central necrosis in a patient with Churg-Strauss syndrome (allergic granulomatosis).
High-power photomicrograph of fascia shows heavy inflammatory infiltration with numerous eosinophils, lymphocytes, and occasional plasma cells in a patient with eosinophilic fasciitis.
Lower back part of the legs in a patient with eosinophilic fasciitis shows hypopigmentation, induration, biopsy site, and asymmetric involvement.
Egg of Schistosoma hematobium, with its typical terminal spine.

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Author

Michaelann Liss, DO Consulting Staff, Department of Hematology/Oncology, The Vancouver Clinic/South West Washington Medical Center

Michaelann Liss, DO is a member of the following medical societies: American College of Physicians, American Medical Association, American Osteopathic Association, American Society of Hematology, Pennsylvania Medical Society, American Physical Therapy Association

Disclosure: Nothing to disclose.

Coauthor(s)

Erik L Zeger, MD Consulting Staff, Main Line Oncology Hematology Associates

Erik L Zeger, MD is a member of the following medical societies: Alpha Omega Alpha, American Association for Cancer Research, American Society of Hematology

Disclosure: Nothing to disclose.

Palaniandy Kogulan, MBBS, MD Assistant Director of Internal Medicine, Synergy Medical Education Alliance; Assistant Professor of Medicine, Michigan State University College of Human Medicine

Palaniandy Kogulan, MBBS, MD is a member of the following medical societies: American College of Physicians, Infectious Diseases Society of America, Michigan State Medical Society

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Marcel E Conrad, MD Distinguished Professor of Medicine (Retired), University of South Alabama College of Medicine

Marcel E Conrad, MD is a member of the following medical societies: Alpha Omega Alpha, American Association for the Advancement of Science, American Association of Blood Banks, American Chemical Society, American College of Physicians, American Physiological Society, American Society for Clinical Investigation, American Society of Hematology, Association of American Physicians, The Society of Federal Health Professionals (AMSUS), International Society of Hematology, Society for Experimental Biology and Medicine, SWOG

Disclosure: Partner received none from No financial interests for none.

Chief Editor

Emmanuel C Besa, MD Professor Emeritus, Department of Medicine, Division of Hematologic Malignancies and Hematopoietic Stem Cell Transplantation, Kimmel Cancer Center, Jefferson Medical College of Thomas Jefferson University

Emmanuel C Besa, MD is a member of the following medical societies: American Association for Cancer Education, American Society of Clinical Oncology, American College of Clinical Pharmacology, American Federation for Medical Research, American Society of Hematology, New York Academy of Sciences

Disclosure: Nothing to disclose.

Additional Contributors

Pradyumna D Phatak, MBBS, MD Chair, Division of Hematology and Medical Oncology, Rochester General Hospital; Clinical Professor of Oncology, Roswell Park Cancer Institute

Pradyumna D Phatak, MBBS, MD is a member of the following medical societies: American Society of Hematology

Disclosure: Received honoraria from Novartis for speaking and teaching.

Acknowledgements

Daniel R Lucey, MD, MPH Chief, Fellowship Program Director, Department of Internal Medicine, Division of Infectious Diseases, Washington Hospital Center; Professor, Department of Internal Medicine, Uniformed Services University of the Health Sciences

Daniel R Lucey, MD, MPH is a member of the following medical societies: Alpha Omega Alpha and American College of Physicians

Disclosure: Nothing to disclose.