Pediatric Hypereosinophilic Syndrome

Updated: Aug 02, 2018
  • Author: Bruce M Rothschild, MD; Chief Editor: Harumi Jyonouchi, MD  more...
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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.



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]




Worldwide, hypereosinophilia is rare, especially in children.


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


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


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


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.