Background

Hypereosinophilic syndrome varies from an asymptomatic phenomenon to a life-threatening multisystem disease. It is characterized by an eosinophil count of more than 1500/μ L (usually many more) for more than 6 months and multiorgan involvement in the absence of other causes of eosinophilia and in the absence of eosinophil blast cells in the marrow or blood.^[1]Three subtypes are recognized: myeloproliferative, lymphocytic, and idiopathic.^[2]Hypereosinophilic syndrome is very rare in children.

Pathophysiology

Extrinsic hypereosinophilia appears to be caused by eosinophilopoietin cytokines, including interleukin 5 (IL-5), interleukin 3 (IL-3), and granulocyte/monocyte cell–stimulating factor (GM-CSF), resulting in large numbers of circulating eosinophils.

Toxicity of hypereosinophilia is related to fibrosis, especially endomyocardial fibrosis. Fibrosis is caused by mediators contained in eosinophil granules,^[3]including cationic granule proteins (eg, eosinophil-derived neurotoxin, eosinophil peroxidase, major basic protein, eosinophil cationic protein, transforming growth factor alpha and beta), tumor necrosis factor alpha, interleukin 1 beta (IL-1ß), macrophage inflammatory protein, interleukin 6 (IL-6), interleukin 8 (IL-8), IL-5, IL-3, and GM-CSF.

Urokinase-induced plasminogen activation and factor XII-dependent reactions predispose the patient to thrombotic complications.

In platelet-derived growth factor receptor alpha (PDGFRA)-associated hypereosinophilic syndrome, eosinophilia is associated with formation of the FLIP1L1/PDFGRA fusion gene, with increases in tyrosine kinase (TK) activity of PDGFRA.

FIP1L1/PDGFR point mutations often camouflage assays of TK activity, but do not necessarily affect imatinib effectiveness.^[4]

Eosinophilic esophagitis is associated with genetically based loss of esophageal tissue differentiation, with both up and down regulation of proteases and their inhibitors.^[5]

Frequency

Worldwide, hypereosinophilia is rare, especially in children.

Mortality/Morbidity

Death generally results from primary heart damage or secondary endocarditis. Survival is prolonged if the sequelae of organ damage, especially cardiac organ damage, can be controlled. Mean survival is 9 months; the 3-year survival rate is reported to be 12%.

Poor prognostic indicators include the following:

Anemia
Thrombocytopenia
A WBC count higher than 100,000 cells/μ L
Abnormal circulating basophilic cells
Abnormal bone marrow
An elevated vitamin B-12 level
Abnormal leukocyte alkaline phosphatase levels

Race

The prevalence is low, with a racial distribution of cases as follows: 78% whites, 18% blacks, and 4% Asian Americans.

Sex

Hypereosinophilic syndrome has a 55.3% male predominance in the pediatric population.^[6]The male-to-female ratio is 9:1 in adults.

Age

Persons aged 5-80 years can have hypereosinophilic syndrome. Persons aged 41-50 years are most commonly affected. The disease is rare in children.

One report documents a case of eosinophilia (WBC count, 80,000/μ L with 63% eosinophils) in an infant born to a mother with hypereosinophilic syndrome.^[7]The child's eosinophil count returned to normal in 8 months.

Clinical Presentation

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