Diagnostic Considerations

Other problems to be considered in the differential diagnosis of hypereosinophilic syndrome include the following:

Allergic diseases
Angiolymphoid hyperplasia with eosinophilia
Collagen vascular diseases
Atopic dermatitisc
Drug reactions
Eosinophilic toxocariasis
Eosinophilic pneumonia
Episodic angioedema with eosinophilia
Hypersensitivity diseases
Malignancy with secondary eosinophilia (eg, Hodgkin lymphoma, acute myeloid leukemia M4 with bone marrow eosinophilia [AML-M4EO])
Parasitic infections

To elicit a history of parasitic infection, the clinician should question the patient regarding travel, immigration, or foreign service at any time in the past. Notably, Strongyloides stercoralis, which is is endemic in tropical and subtropical climates, can propagate itself internally and cause eosinophilia several decades after initial infection.^[28]

The medication history should include prescription drugs, over-the-counter medications, herbal compounds, and nutritional supplement. Clinical suspicion should extend to agents in long-term use, as drug-induced eosinophilia may develop months and even years after initiation of therapy.^[28]

Some types of medications are more likely to cause an eosinophilic drug reaction; these include anticonvulsants, semisynthetic penicillins, and allopurinol. Although drug-induced eosinophilia may develop without other manifestations, such as rashes or fever, certain patterns tend to occur with specific drugs, as follows^[28]:

Hepatitis or DRESS syndrome (drug-induced rash, eosinophilia, and systemic symptoms) – Anticonvulsants
Pneumonitis – Nitrofurantoin, semisynthetic penicillins, nonsteroidal anti-inflammatory drugs
Nephritis – Cephalosporins
Hypersensitivity vasculitis – Allopurinol, phenytoin

Differential Diagnoses

Workup

Curtis C, Ogbogu P. Hypereosinophilic Syndrome. Clin Rev Allergy Immunol. 2016 Apr. 50 (2):240-51. [QxMD MEDLINE Link].
Galli SJ, Goetzl EJ. Eosinophils, basophils, and mast cells. Handin RI, Stossel TP, Lux SE, Stossel TP, eds. Blood: Principles and Practice of Hematology. Baltimore, Md: Lippincott Williams & Wilkins; 1995. 621-40.
Klion AD, Bochner BS, Gleich GJ, et al, and The Hypereosinophilic Syndromes Working Group. Approaches to the treatment of hypereosinophilic syndromes: a workshop summary report. J Allergy Clin Immunol. 2006 Jun. 117(6):1292-302. [QxMD MEDLINE Link].
Chusid MJ, Dale DC, West BC, Wolff SM. The hypereosinophilic syndrome: analysis of fourteen cases with review of the literature. Medicine (Baltimore). 1975 Jan. 54(1):1-27. [QxMD MEDLINE Link].
Simon HU, Rothenberg ME, Bochner BS, Weller PF, Wardlaw AJ, Wechsler ME, et al. Refining the definition of hypereosinophilic syndrome. J Allergy Clin Immunol. 2010 Jul. 126(1):45-9. [QxMD MEDLINE Link].
Klion AD. Eosinophilic myeloproliferative disorders. Hematology Am Soc Hematol Educ Program. 2011. 2011:257-63. [QxMD MEDLINE Link].
Liao W, Long H, Chang CC, Lu Q. The Eosinophil in Health and Disease: from Bench to Bedside and Back. Clin Rev Allergy Immunol. 2015 Sep 26. [QxMD MEDLINE Link].
Valent P, Degenfeld-Schonburg L, Sadovnik I, Horny HP, Arock M, Simon HU, et al. Eosinophils and eosinophil-associated disorders: immunological, clinical, and molecular complexity. Semin Immunopathol. 2021 Jun. 43 (3):423-438. [QxMD MEDLINE Link]. [Full Text].
Shomali W, Gotlib J. World Health Organization-defined eosinophilic disorders: 2022 update on diagnosis, risk stratification, and management. Am J Hematol. 2022 Jan 1. 97 (1):129-148. [QxMD MEDLINE Link]. [Full Text].
Wardlaw AJ. Eosinophils and Related Disorders. Kaushansky K, Lichtman MA, Prchal JT, Levi MM, Press OW, Burns LJ, Caligiuri MA, eds. Williams Hematology. 9th ed. New York, NY: McGraw-Hill Education; 2016. 947-64.
Tefferi A, Patnaik MM, Pardanani A. Eosinophilia: secondary, clonal and idiopathic. Br J Haematol. 2006 Jun. 133(5):468-92. [QxMD MEDLINE Link].
Rothenberg ME. Eosinophilia. N Engl J Med. 1998 May 28. 338(22):1592-600. [QxMD MEDLINE Link].
Gleich GJ, Leiferman KM. The hypereosinophilic syndromes: current concepts and treatments. Br J Haematol. 2009 May. 145(3):271-85. [QxMD MEDLINE Link].
Helbig G, Wieczorkiewicz A, Dziaczkowska-Suszek J, Majewski M, Kyrcz-Krzemien S. T-cell abnormalities are present at high frequencies in patients with hypereosinophilic syndrome. Haematologica. 2009 Sep. 94(9):1236-41. [QxMD MEDLINE Link]. [Full Text].
Cincin AA, Ozben B, Tanrikulu MA, Baskan O, Agirbasli M. Large apical thrombus in a patient with persistent heart failure and hypereosinophilia: Löffler endocarditis. J Gen Intern Med. 2008 Oct. 23(10):1713-8. [QxMD MEDLINE Link].
Yamada Y, Sanchez-Aguilera A, Brandt EB, et al. FIP1L1/PDGFRalpha synergizes with SCF to induce systemic mastocytosis in a murine model of chronic eosinophilic leukemia/hypereosinophilic syndrome. Blood. 2008 Sep 15. 112(6):2500-7. [QxMD MEDLINE Link].
Simon HU, Plötz SG, Dummer R, Blaser K. Abnormal clones of T cells producing interleukin-5 in idiopathic eosinophilia. N Engl J Med. 1999 Oct 7. 341(15):1112-20. [QxMD MEDLINE Link]. [Full Text].
Brugnoni D, Airó P, Rossi G, et al. A case of hypereosinophilic syndrome is associated with the expansion of a CD3-CD4+ T-cell population able to secrete large amounts of interleukin-5. Blood. 1996 Feb 15. 87(4):1416-22. [QxMD MEDLINE Link]. [Full Text].
Hardy WR, Anderson RE. The hypereosinophilic syndromes. Ann Intern Med. 1968 Jun. 68(6):1220-9. [QxMD MEDLINE Link].
O'Connell EM, Nutman TB. Eosinophilia in Infectious Diseases. Immunol Allergy Clin North Am. 2015 Aug. 35 (3):493-522. [QxMD MEDLINE Link].
Lefebvre C, Bletry O, Degoulet P, et al. [Prognostic factors of hypereosinophilic syndrome. Study of 40 cases] [French]. Ann Med Interne (Paris). 1989. 140(4):253-7. [QxMD MEDLINE Link].
Leiva O, Baker O, Jenkins A, Brunner AM, Al-Samkari H, Leaf RK, et al. Association of Thrombosis With Hypereosinophilic Syndrome in Patients With Genetic Alterations. JAMA Netw Open. 2021 Aug 2. 4 (8):e2119812. [QxMD MEDLINE Link]. [Full Text].
Klion A. Hypereosinophilic syndrome: current approach to diagnosis and treatment. Annu Rev Med. 2009. 60:293-306. [QxMD MEDLINE Link].
Fauci AS, Harley JB, Roberts WC, et al. NIH conference. The idiopathic hypereosinophilic syndrome. Clinical, pathophysiologic, and therapeutic considerations. Ann Intern Med. 1982 Jul. 97(1):78-92. [QxMD MEDLINE Link].
Ogbogu PU, Bochner BS, Butterfield JH, Gleich GJ, Huss-Marp J, Kahn JE, et al. Hypereosinophilic syndrome: a multicenter, retrospective analysis of clinical characteristics and response to therapy. J Allergy Clin Immunol. 2009 Dec. 124 (6):1319-25.e3. [QxMD MEDLINE Link]. [Full Text].
Xie J, Zhang J, Zhang X, Zhang Q, Chung KF, Wang C, et al. Cough in hypereosinophilic syndrome: case report and literature review. BMC Pulm Med. 2020 Apr 15. 20 (1):90. [QxMD MEDLINE Link]. [Full Text].
Schreiber A, LeBlanc M, Thibeault MM, Mathieu S. Generalized Recalcitrant Pruritus as the Presenting Manifestation of Hypereosinophilic Syndrome. J Cutan Med Surg. 2016 Jan 29. [QxMD MEDLINE Link].
Roufosse F, Weller PF. Practical approach to the patient with hypereosinophilia. J Allergy Clin Immunol. 2010 Jul. 126 (1):39-44. [QxMD MEDLINE Link]. [Full Text].
Curtis C, Ogbogu PU. Evaluation and Differential Diagnosis of Persistent Marked Eosinophilia. Immunol Allergy Clin North Am. 2015 Aug. 35 (3):387-402. [QxMD MEDLINE Link].
Wang SA. The Diagnostic Work-Up of Hypereosinophilia. Pathobiology. 2018 Jun 29. 1-14. [QxMD MEDLINE Link]. [Full Text].
Adams JC, Dal-Bianco JP, Kumar G, Callahan MJ. Hypereosinophilic syndrome with characteristic left ventricular thrombus demonstrated by contrast echocardiography. Neth Heart J. 2009 Apr. 17(4):169-70. [QxMD MEDLINE Link]. [Full Text].
Kuchynka P, Palecek T, Masek M, Cerny V, Lambert L, Vitkova I, et al. Current Diagnostic and Therapeutic Aspects of Eosinophilic Myocarditis. Biomed Res Int. 2016. 2016:2829583. [QxMD MEDLINE Link].
Roufosse F. Management of Hypereosinophilic Syndromes. Immunol Allergy Clin North Am. 2015 Aug. 35 (3):561-75. [QxMD MEDLINE Link].
Parrillo JE, Fauci AS, Wolff SM. Therapy of the hypereosinophilic syndrome. Ann Intern Med. 1978 Aug. 89(2):167-72. [QxMD MEDLINE Link].
Roufosse F, Kahn JE, Rothenberg ME, Wardlaw AJ, Klion AD, Kirby SY, et al. Efficacy and safety of mepolizumab in hypereosinophilic syndrome: a Phase III, randomized, placebo-controlled trial. J Allergy Clin Immunol. 2020 Sep 18. [QxMD MEDLINE Link].
FDA Approves First Drug to Treat Group of Rare Blood Disorders in Nearly 14 Years. U.S Food & Drug Administration. Available at https://www.fda.gov/news-events/press-announcements/fda-approves-first-drug-treat-group-rare-blood-disorders-nearly-14-years. September 25, 2020; Accessed: October 15, 2020.
Khoury P, Desmond R, Pabon A, Holland-Thomas N, Ware JM, Arthur DC, et al. Clinical features predict responsiveness to imatinib in platelet derived growth factor receptor alpha-negative hypereosinophilic syndrome. Allergy. 2016 Jan 21. [QxMD MEDLINE Link].
Gotlib J. World Health Organization-defined eosinophilic disorders: 2014 update on diagnosis, risk stratification, and management. Am J Hematol. 2014 Mar. 89(3):325-37. [QxMD MEDLINE Link]. [Full Text].
Helbig G. Imatinib for the treatment of hypereosinophilic syndromes. Expert Rev Clin Immunol. 2018 Feb. 14 (2):163-170. [QxMD MEDLINE Link].
Luciano L, Catalano L, Sarrantonio C, et al. AlphaIFN-induced hematologic and cytogenetic remission in chronic eosinophilic leukemia with t(1;5). Haematologica. 1999 Jul. 84(7):651-3. [QxMD MEDLINE Link]. [Full Text].
Yamada O, Kitahara K, Imamura K, et al. Clinical and cytogenetic remission induced by interferon-alpha in a patient with chronic eosinophilic leukemia associated with a unique t(3;9;5) translocation. Am J Hematol. 1998 Jun. 58(2):137-41. [QxMD MEDLINE Link]. [Full Text].
Malbrain ML, Van den Bergh H, Zachée P. Further evidence for the clonal nature of the idiopathic hypereosinophilic syndrome: complete haematological and cytogenetic remission induced by interferon-alpha in a case with a unique chromosomal abnormality. Br J Haematol. 1996 Jan. 92(1):176-83. [QxMD MEDLINE Link].
Verstovsek S, Tefferi A, Kantarjian H, Manshouri T, Luthra R, Pardanani A, et al. Alemtuzumab therapy for hypereosinophilic syndrome and chronic eosinophilic leukemia. Clin Cancer Res. 2009 Jan 1. 15(1):368-73. [QxMD MEDLINE Link].
Iurlo A, Cattaneo D, Gianelli U. Hypereosinophilic syndromes in the precision medicine era: clinical, molecular aspects and therapeutic approaches (targeted therapies). Expert Rev Hematol. 2019 Dec. 12 (12):1077-1088. [QxMD MEDLINE Link].
Strati P, Cortes J, Faderl S, Kantarjian H, Verstovsek S. Long-term follow-up of patients with hypereosinophilic syndrome treated with Alemtuzumab, an anti-CD52 antibody. Clin Lymphoma Myeloma Leuk. 2013 Jun. 13(3):287-91. [QxMD MEDLINE Link].
Nanagas VC, Kovalszki A. Gastrointestinal Manifestations of Hypereosinophilic Syndromes and Mast Cell Disorders: a Comprehensive Review. Clin Rev Allergy Immunol. 2018 Jul 12. [QxMD MEDLINE Link].

Media Gallery

Indurated edematous plaques of hypereosinophilic syndrome on a patient's legs.
Erythroderma in a patient with hypereosinophilic syndrome.

of 2

Author

Venkata Anuradha Samavedi, MBBS, MD Internist in Houston, TX

Disclosure: Nothing to disclose.

Coauthor(s)

Ronald A Sacher, MD, FRCPC, DTM&H Professor Emeritus of Internal Medicine and Hematology/Oncology, Emeritus Director, Hoxworth Blood Center, University of Cincinnati Academic Health Center

Ronald A Sacher, MD, FRCPC, DTM&H is a member of the following medical societies: American Association for the Advancement of Science, American Association of Blood Banks, American Clinical and Climatological Association, American Society for Clinical Pathology, American Society of Hematology, College of American Pathologists, International Society of Blood Transfusion, International Society on Thrombosis and Haemostasis, Royal College of Physicians and Surgeons of Canada

Disclosure: Nothing to disclose.

Vincent E Herrin, MD, FACP Professor of Medicine, Division of Hematology and Medical Oncology, Director, Medicine Residency Program, University of Mississippi School of Medicine

Vincent E Herrin, MD, FACP is a member of the following medical societies: American College of Physicians, American College of Physicians-American Society of Internal Medicine, American Society of Clinical Oncology, Southern Society for Clinical Investigation, American Society of Hematology

Disclosure: Nothing to disclose.

Joe C Files, MD Director, Division of Hematology, Associate Chairman, Professor, Department of Internal Medicine, University of Mississippi Medical Center

Joe C Files, MD is a member of the following medical societies: American Association for the Advancement of Science, American Association for Cancer Education, American College of Physicians, American Federation for Medical Research, American Heart Association, American Medical Association, American Society of Human Genetics, Mississippi State Medical Association, New York Academy of Sciences, Southern Medical Association

Disclosure: Nothing to disclose.

Youwen Zhou, MD, PhD, FRCPC Associate Professor, Department of Dermatology and Skin Science, University of British Columbia Faculty of Medicine; Director, Hyperhidrosis Specialty Clinic, Co-Director, Psoriasis and Phototherapy Centre, Consulting Physician, Department of Dermatology, Vancouver General Hospital; Co-Director, Vitiligo and Pigmentation Clinic, Oncologist Consultant, Skin Tumor Program, BC Cancer Agency

Youwen Zhou, MD, PhD, FRCPC is a member of the following medical societies: American Academy of Dermatology

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.

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

Antoni Ribas, MD Assistant Professor of Medicine, Division of Hematology-Oncology, University of California at Los Angeles Medical Center

Disclosure: Nothing to disclose.

Paul Schick, MD † Emeritus Professor, Department of Internal Medicine, Jefferson Medical College of Thomas Jefferson University; Research Professor, Department of Internal Medicine, Drexel University College of Medicine; Adjunct Professor of Medicine, Lankenau Hospital

Paul Schick, MD is a member of the following medical societies: American College of Physicians, American Society of Hematology

Disclosure: Nothing to disclose.

Hypereosinophilic Syndrome Differential Diagnoses

Diagnostic Considerations

Differential Diagnoses

References

Tables

Contributor Information and Disclosures

What would you like to print?