 |
 |
 |
|
 |
 |
 |
|
|
|
|
|
|
Hypereosinophilic Syndrome
Diagnosis
An essential criterion for a diagnosis of HES is marked eosinophilia (total eosinophil count >1500/µL for >6 months). Peripheral blood differential counts typically demonstrate 30% to 70% eosinophils with a white blood cell (WBC) count of 25,000/µL. Bone marrow biopsies show eosinophilia with no dysplasia or blasts. Cytogenetic analysis is usually normal.1 Anemia is present in 50% of patients.2
A second criterion for a diagnosis of HES is that causes of secondary eosinophilia have been ruled out.
Selected Causes of Secondary Eosinophilia
- Allergic disorders
- Asthma and/or atopic disease (rare)
- Allergic bronchopulmonary aspergillosis
- Drug hypersensitivity reactions
- Infectious diseases
- Parasitic
- Fungal
- Human immunodeficiency virus
- Neoplasms
- Leukemia
- Lymphoma
- Adenocarcinoma
- Hypoadrenalism
- Diseases associated with immune dysregulation
- Sarcoid
- Inflammatory bowel disease
- Connective tissue disorders
- Other
- Cholesterol embolization
- Radiation exposure3
The third diagnostic requirement is organ system involvement. The skin, heart, and nervous system are most commonly affected, but any organ can be involved, with severity that ranges from relatively asymptomatic disease to fatal endomyocardial fibrosis.3
Although patients with HES may present with sudden cardiac or neurologic manifestations, more insidious symptoms typically prevail. In a study of 50 patients conducted by the National Institutes of Health, 12% were asymptomatic; signs and symptoms that were present included tiredness (26%), cough (24%), breathlessness (16%), muscle pains or angioedema (14%), rash or fever (12%), and retinal lesion (10%).2,4
Criteria to distinguish myeloproliferative hypereosinophilia from the lymphoproliferative clonal variant were proposed by the World Health Organization (WHO) in 2001.5 The clonal subtype of HES, which is referred to under the WHO classification as chronic eosinophilic leukemia (CEL), is estimated to account for 20% of patients with HES.6
World Health Organization Classification of HES and Chronic Eosinophilic Leukemia6
- Exclude all causes of reactive eosinophilia secondary to:
- Allergy
- Parasitic disease
- Infectious disease
- Pulmonary diseases (hypersensitivity pneumonitis, Loeffler's endocarditis, etc)
- Exclude all neoplastic disorders with secondary, reactive eosinophilia:
- T-cell lymphomas, including mycosis fungoides
- Sézary syndrome
- Hodgkin's lymphoma
- Acute lymphoblastic leukemia/lymphoma
- Mastocytosis
- Exclude other neoplastic disorders in which eosinophils are part of the neoplastic clone:
- Chronic myeloid leukemia (Ph chromosome- or Bcr-Abl-positive)
- Acute myeloid leukemia including those with inv(16), t(16;16) (p13;q22)
- Other myeloproliferative diseases (PV, ET, AMM)
- Myelodysplastic syndromes
- Exclude T-cell population with:
- Aberrant phenotype
- Abnormal cytokinic population
- Diagnose HES in the absence of :
- Demonstratable disease that could cause eosinophilia
- Abnormal T-cell population
- Evidence of clonal myeloid disorder
- Diagnose CEL if :
- Criteria 1 through 4 are met and
- The myeloid demonstrate a clonal cytogenetic abnormality or clonality is shown by other means or
- If blasts are present in the peripheral blood (>2%) or marrow (>5% and <19%)
Ph chromosome=Philadelphia chromosome; PV=polycythemia vera; ET=essential thrombocythemia; AMM=agnogenic myeloid metaplasia; HES=hypereosinophilic syndrome; CEL=chronic eosinophilic leukemia.
References:
- The University of Texas MD Anderson Cancer Center. Hypereosinophilic Syndrome Trials. Background. Available at: http://www.mdanderson.org/diseases/hes/dIndex.cfm?pn=C4A2EAFB-52EC-4AE8-B9B6C3BE88A673CD. Accessed April 21, 2006.
- Weller PF, Bubley GJ. The idiopathic hypereosinophilic syndrome. Blood. 1994;83:2759-2779.
- Klion AD. Recent advances in the diagnosis and treatment of hypereosinophilic syndromes. Hematology (Am Soc Hematol Educ Program). 2005;209-214.
- Fauci AS, Harley JB, Roberts WC, et al. The idiopathic hypereosinophilic syndrome. Clinical, pathophysiologic, and therapeutic considerations. Ann Intern Med. 1982;97:78-92.
- Bain BJ. Eosinophilic leukaemias and the idiopathic hypereosinophilic syndrome. Br J Haematol. 1996;95:2-9.
- Gotlib, J. Molecular classification and pathogenesis of eosinophilic disorders: 2005 update. Acta Haematol. 2005;114:7-25.
|
|
|
|
|
|
