eMedicine Specialties > Hematology > Immune System and Disorders

Hypereosinophilic Syndrome: Differential Diagnoses & Workup

Author: Venkata Samavedi, MBBS, MD, Internist in Houston, TX
Coauthor(s): Ronald A Sacher, MB, BCh, MD, FRCPC, Professor, Internal Medicine and Pathology, Director, Hoxworth Blood Center, University of Cincinnati Academic Health Center; Vincent E Herrin, MD, Associate Professor of Medicine, Divisions of Hematology and Oncology, University of Mississippi School of Medicine; Joe C Files, MD, Director, Division of Hematology, Associate Chairman, Professor, Department of Internal Medicine, University of Mississippi Medical Center; Youwen Zhou, MD, PhD, FRCP(C), Associate Professor, Department of Dermatology and Skin Science, University of British Columbia; 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; Paul Schick, MD, Emeritus Professor, Department of Internal Medicine, Thomas Jefferson University Medical College; Research Professor, Department of Internal Medicine, Drexel University College of Medicine; Adjunct Professor of Medicine, Lankenau Hospital, Wynnewood, PA
Contributor Information and Disclosures

Updated: Oct 4, 2009

Differential Diagnoses

Asthma
Eosinophilic Gastroenteritis
Chronic Myelogenous Leukemia
Eosinophilic Pneumonia
Churg-Strauss Syndrome
Hodgkin Disease
Eosinophilia
Strongyloidiasis
Eosinophilia-Myalgia Syndrome
Eosinophilic Fasciitis

Other Problems to Be Considered

Allergic diseases
Angiolymphoid hyperplasia with eosinophilia
Collagen vascular diseases
Dermatitis, Atopic
Drug reactions
Eosinophilic toxocariasis
Episodic angioedema with eosinophilia
Hypersensitivity diseases
Malignancy with secondary eosinophilia (eg, Hodgkin disease, AML-M4EO)
Parasitic infections

Workup

Laboratory Studies

Laboratory workup for hypereosinophilic syndrome includes the following:

Hematologic studies

  • Eosinophilia is present (>1500 cells/µL).
  • The overall neutrophil count may be normal, but it is often elevated in hypereosinophilic syndrome. Many patients have absolute neutrophilia.
  • Approximately 50% of the patients with hypereosinophilic syndrome are anemic at presentation, often because of anemia of chronic disease.
  • Platelet counts are most often normal, but they may be elevated.
  • Eosinophils in the peripheral blood are mostly mature forms. Immature eosinophilic precursors are rare in the peripheral blood.
  • Morphologic abnormalities that have been described include nuclear hypersegmentation, hypo- and hypergranularity.
  • Cases of hypereosinophilic syndrome with features of MPD show circulating leukocyte precursor anemia and thrombocytopenia or thrombocytosis. Teardrops and nucleated red blood cells may be seen.
  • A National Institute of Health series indicated that the presence of eosinophils with vacuolization and hypogranularity is more commonly associated with cardiac disease.17
  • Leukocytosis in excess of 90,000/µL carries a bad prognosis.

Chemistries

  • Increased serum tryptase level gives a clue to the presence of FIP1L1-PDGFRA mutation. Always rule out C-KIT mutation, which is characteristic of systemic mastocytosis whenever serum tryptase is elevated. This distinction is clinically important because the most common form of C-KIT mutation in systemic mastocytosis, Asp 816 to Val, is not responsive to imatinib treatment.
  • IL-5 is elevated in cases of hypereosinophilic syndrome that are associated with clonal T-cell disease. Interferon alpha should be considered in such cases due to its downregulating effects on IL-5 production by T-helper 2 (TH2) cells.
  • Immunoglobulin E (IgE) levels may be elevated, and hypergammaglobulinemia is common. Increased IgE levels have prognostic significance, as these patients have a lower risk of developing hypereosinophilic syndrome associated cardiovascular disease and respond well to steroid therapy.
  • Serum vitamin B-12 levels may be elevated in the presence of associated myeloproliferative features.

Approach to diagnosis of hypereosinophilic syndrome

  • After a thorough workup has excluded causes for secondary eosinophilia, a diagnosis of hypereosinophilic syndrome is suspected in cases of persistent eosinophilia. Any such patients with a documented AEC greater than 1500/µL on at least 2 occasions should be evaluated for hypereosinophilic syndrome, regardless of the presence of symptoms.
  • Complete blood cell (CBC) count and peripheral smear
  • Serum tryptase levels are elevated in FIP1LI-PDGFRA –positive hypereosinophilic syndrome, as well as SM-CEL. Hence, in such cases, workup should include the following:
    • Bone marrow tryptase levels
    • Immunophenotyping of mast cells – Mast cells in systemic mastocytosis coexpress CD117 with CD2 and/or CD25
    • Molecular genetic studies to detect FIP1L1-PDGFRA mutation (which is present in hypereosinophilic syndrome and systemic mastocytosis) and C-KIT mutation (which is present in systemic mastocytosis) are done to determine imatinib sensitivity, as mentioned above.
  • Bone marrow biopsy should be evaluated for the following :
    • Morphologic examinations to look for features of MPDs and to look for dense aggregates of mass cells (greater than 15 cells) in systemic mastocytosis.
    • Special stains should include reticulin stain for myelofibrosis and tryptase staining for mast cells when serum tryptase levels are elevated.
    • Cytogenetics – Most patients with hypereosinophilic syndrome have normal karyotypes. In those who have cytogenetic changes, the changes may vary from aneuploidy to Philadelphia chromosome.
    • Molecular genetic studies should include the following:
      • FIP1L1/PDGFRA should be evaluated in all patients with increased tryptase levels. This mutation is present in both hypereosinophilic syndrome and systemic mastocytosis.
      • C-KIT mutation should also be evaluated in patients with increased tryptase levels.
  • T-cell immunophenotyping
  • T-cell receptor gene rearrangement
  • IL-5 levels
  • Computed tomography (CT) scanning of the chest, abdomen, and pelvis to look for lymphadenopathy and splenomegaly
  • Initial evaluation of suspected hypereosinophilic syndrome should include tests to look for any evidence of end-organ damage
    • Electrocardiography (ECG)
    • Echocardiography (ECHO)
    • Troponin levels: Increased levels indicate presence of cardiomyopathy and predict the onset of cardiogenic shock due to imatinib therapy.
    • Pulmonary function tests
    • Tissue biopsy may be required in symptomatic patients, but it is not always essential.

Imaging Studies

ECHO is helpful in the initial evaluation and monitoring of cardiac disease in patients suspected with hypereosinophilic syndrome.24 Intracardiac thrombi may be detected, as well as the fibrosis that appears not only as areas of increased echogenicity but often as posterior mitral valve leaflet thickening. Because the papillary muscles are often involved in hypereosinophilic syndrome, mitral and tricuspid dysfunction may also be detected by ECHO.

CT scanning of the chest, abdomen, and pelvis is done to look for lymphadenopathy and splenomegaly.

Procedures

  • An endocardial biopsy may be performed via cardiac catheterization if any question about the diagnosis of hypereosinophilic syndrome exists.
  • Perform bone marrow aspiration and biopsy, and submit samples for cytogenetic studies.
    • Occasionally, the findings may suggest an atypical presentation of chronic myelogenous leukemia.
    • Cytogenetic abnormalities or the presence of a myeloproliferative picture in the bone marrow may be indicative of more aggressive disease.
  • If cutaneous involvement is present, skin biopsies may be performed to rule out other diagnoses that have similar skin presentations, such as drug eruptions, cutaneous T-cell lymphoma, Wells syndrome, immunobullous diseases, and vasculitis.

Histologic Findings

Eosinophil infiltrates are present in affected tissues in patients with hypereosinophilic syndrome. Cutaneous histologic features vary with the pattern of presentation. In patients with papular or nodular lesions, perivascular mixed cellular infiltrates (eosinophils and other cell types) are present. However, vasculitis is not present (see Lab Studies).

More on Hypereosinophilic Syndrome

Overview: Hypereosinophilic Syndrome
Differential Diagnoses & Workup: Hypereosinophilic Syndrome
Treatment & Medication: Hypereosinophilic Syndrome
Follow-up: Hypereosinophilic Syndrome
Multimedia: Hypereosinophilic Syndrome
References
Further Reading
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References

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Keywords

hypereosinophilic syndrome, HES, idiopathic hypereosinophilic syndrome, Loeffler endocarditis, Loeffler's endocarditis, chronic eosinophilic leukemia, CEL, eosinophilia, systemic mastocytosis –associated eosinophilia, SM-CEL, FIP1L1-PDGFRA mutation, C-KIT mutation, tyrosine kinase inhibitors

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Contributor Information and Disclosures

Author

Venkata Samavedi, MBBS, MD, Internist in Houston, TX
Disclosure: Nothing to disclose.

Coauthor(s)

Ronald A Sacher, MB, BCh, MD, FRCPC, Professor, Internal Medicine and Pathology, Director, Hoxworth Blood Center, University of Cincinnati Academic Health Center
Ronald A Sacher, MB, BCh, MD, FRCPC is a member of the following medical societies: American Society of Hematology
Disclosure: Glaxo Smith Kline Honoraria Speaking and teaching; Talecris Honoraria Board membership

Vincent E Herrin, MD, Associate Professor of Medicine, Divisions of Hematology and Oncology, University of Mississippi School of Medicine
Vincent E Herrin, MD is a member of the following medical societies: American College of Physicians-American Society of Internal Medicine and 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 Cancer Education, American Association for the Advancement of Science, 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, and Southern Medical Association
Disclosure: Nothing to disclose.

Youwen Zhou, MD, PhD, FRCP(C), Associate Professor, Department of Dermatology and Skin Science, University of British Columbia; 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, FRCP(C) is a member of the following medical societies: American Academy of Dermatology
Disclosure: Nothing to disclose.

Paul Schick, MD, Emeritus Professor, Department of Internal Medicine, Thomas Jefferson University Medical College; Research Professor, Department of Internal Medicine, Drexel University College of Medicine; Adjunct Professor of Medicine, Lankenau Hospital, Wynnewood, PA
Paul Schick, MD is a member of the following medical societies: American College of Physicians, American Heart Association, American Society of Hematology, International Society on Thrombosis and Haemostasis, and New York Academy of Sciences
Disclosure: Nothing to disclose.

Medical Editor

Antoni Ribas, MD, Department of Medicine, Division of Hematology-Oncology, Assistant Professor of Medicine, University of California at Los Angeles Medical Center
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

Troy H Guthrie, Jr, MD, Director of Cancer Institute, Baptist Medical Center
Troy H Guthrie, Jr, MD is a member of the following medical societies: American Federation for Medical Research, American Medical Association, American Society of Hematology, Florida Medical Association, Medical Association of Georgia, and Southern Medical Association
Disclosure: Nothing to disclose.

CME Editor

Rajalaxmi McKenna, MD, FACP, Southwest Medical Consultants, SC, Department of Medicine, Good Samaritan Hospital, Advocate Health Systems
Rajalaxmi McKenna, MD, FACP is a member of the following medical societies: American Society of Clinical Oncology, American Society of Hematology, and International Society on Thrombosis and Haemostasis
Disclosure: Nothing to disclose.

Chief Editor

Emmanuel C Besa, MD, Professor, Department of Medicine, Division of Hematologic Malignancies, Kimmel Cancer Center, Thomas Jefferson University
Emmanuel C Besa, MD is a member of the following medical societies: American Association for Cancer Education, American College of Clinical Pharmacology, American Federation for Medical Research, American Society of Hematology, and New York Academy of Sciences
Disclosure: Nothing to disclose.

 
 
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