Hypereosinophilic syndrome


Disorders caused by marked sustained overproduction of eosinophils.

A group of rare chronic disorder is defined by an absolute eosinophil count of at least 1500 cells per cubic millimeter and evidence of eosinophil-related clinical manifestations including intractable, pruritus, pulmonary infiltrates, eosinophilic gastroenteritis , endomyocardial fibrosis, and thromboembolism.

Diagnosis requires sustained eosinophilia for at least 6 months with an absolute eosinophil count ≥ 1.5x 10th to ninth, target organ damage (heart, lung, skin or nervous system involvement) and exclusion of other causes of eosinophilia.

Hypereosinophilia is defined as an absolute eosinophil count greater than 1.5×10 to the ninth in peripheral blood on at least two occasions, separated by at least two weeks.

Eosinophils secrete mediators.

Can lead to cardiomyopathy, gastroenteritis, pneumonitis, cutaneous lesions, sinusitis, neurologic changes, ophthalmologic changes and vasculitis.

Patients with hyper eosinophilia may have tissue infiltration by eosinophils which release mediators that cause inflammation, tissue damage, fibrosis, and thrombosis.

Organs that are typically affected by hypereosinophilia include: heart, lungs, G.I. tract, and skin.

Absence of any molecular or cytogenetic features of clonality.

Bone marrow shows absence of abnormal populations of mast cells, monocytosis, myeloproliferation or dysplasia.

A rare manifestation of malignant disease.

May be a reacive or part of the process as in myeloid leukemia.

Has been associated with radiation, chemotherapy and immunotherapies due to the release of cytokines.

Explanations for hypereisinophilia include helminthic, fungal, HIV infections, allergic disorders, malignancy, and certain medications, including penicillin, cephalosporin, fluoroquinolones, anti-convulsant, and allopurinol.

Hematologic malignancies are the main cause of hypereosinophilias, but eosinophilia can be seen in up to 8.4% of patients with lung cancer.

Hyper eosinophilic syndrome is primary, if caused by stem cell, myeloid, or eosinophil neoplasm, often associated with variants in genes PDGFRA, FDGRB, and FGFRI.

Secondary HES includes lymphoid variants, eosinophilic granulomatosi, and polyangiitis and IgG4  related disease.

Approximately 50% of patients with HES have no identifable etiology.

May be related to fusion gene FIP1L-PDGFRalpha, caused by an interstitial of a part of chromosome 4 deletion.

FIP1L-PDGFRalpha gene activates PDGFRalpha tyrosine kinase, which drives this disease process. 10-20% of such patients possess this gene.

FIP1L-PDGFRalpha positive patients have normal cytogenetic studies and can be diagnosed by reverse transcription polymerase chain reaction fo PDGFRalpha expression, or FISH analysis for CHI2 gene.

The goal of treatment is a reduction in blood and tissue eosinophilia, preventing further organ damage.

Cardiac troponin assessment, EKG, CT scan of the thorax and abdomen, and pulmonary function tests are used to assess the severity of organ damage.

Treatment includes: corticosteroids, interferon-alpha, and cytotoxic drugs.

FIP1L-PDGFRalpha fusion gene positive patients treated with imatinib have a very high complete hematologic response rate (Roche-Lestienne C).

Imatinib, a tyrosine kinase inhibitor is effective in the treatment of primary myeloid forms of the disease including myeloid neoplasms associated with the gene encoding platelet-derived growth factor receptor alpha (PDGFRA).

Benralizumab in patients with PDGFR-negative hypereosinophilic syndrome had a lower absolutely epsinophil counts compared with placebo with responses for 48 weeks in 74% of patients.

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