Hypereosinophilic syndrome is a disease characterized by a persistently elevated eosinophil count (≥ 1500 eosinophils/mm³) in the blood for at least six months without any recognizable cause, with involvement of either the heart, nervous system, or bone marrow.

Hypereosinophilic syndrome can manifest in many different ways from nonspecific symptoms and fatigue to neurological impairment and endomyocardial fibrosis, which may be fatal.

There are three different variants of hypereosinophilic syndrome, myeloproliferative, lymphocytic, and idiopathic.

HES is a diagnosis of exclusion, after clonal eosinophilia (such as FIP1L1-PDGFRA-fusion induced hypereosinophelia and leukemia) and reactive eosinophilia (in response to infection, autoimmune disease, atopy, hypoadrenalism, tropical eosinophilia, or cancer) have been ruled out.

There are some associations with chronic eosinophilic leukemia as it shows similar characteristics and genetic defects. If left untreated, HES is progressive and fatal. It is treated with glucocorticoids such as prednisone.

Signs and symptoms

Depending on eosinophil target-organ infiltration, the clinical presentation of hypereosinophilic syndrome (HES) varies from patient to patient. Individuals with myeloproliferative variant HES may be more likely to experience mucosal ulcerations involving the genitalia or airways, while patients with lymphocytic variant HES typically exhibit prominent skin symptoms such as urticarial plaques, angioedema, and erythroderma. Myeloproliferative variant HES is far more common in men and is typically linked to symptoms more typical of myeloproliferative disorders, including anemia, splenomegaly, hepatomegaly, and fibrotic disease (particularly of the heart).

Patients can develop a range of nonspecific symptoms, including fever, diarrhea, rash, angioedema, weakness, exhaustion, coughing, and dyspnea.

The common and non-specific cutaneous manifestations are either erythematous, itchy papules and nodules that resemble eczema, or urticarial and angioedematous lesions.

Cardiac involvement typically progresses through three phases. Rarely, the early necrotic stage involving the endo-myocardium manifests as acute heart failure. In most cases, however, there are no symptoms. A thrombotic stage ensues after this one, during which thrombi form in the cardiac chambers along the injured endocardium and may separate, resulting in peripheral emboli.

Both the peripheral (polyneuropathy) and central (diffuse encephalopathy) nervous systems may be affected by neurological manifestations. Disorientation, memory loss, and altered behavior and cognitive function are the symptoms of diffuse encephalopathy. Symptoms of peripheral neuropathies can include mixed sensory and motor complaints, symmetric or asymmetric sensory alterations, or pure motor deficits. Stroke or brief ischemic episodes can happen after intracardiac thrombi have been embolised peripherally. In certain patients, procoagulant therapy may result in thrombosis of the intracranial veins (lateral sinus and/or longitudinal vein). This condition is linked to persistent hypereosinophilia.

Eosinophilia in lymphocytic HES is caused by populations of activated T lymphocytes producing more eosinophil hematopoietins, specifically interleukin-5 (IL-5). The extent of end-organ damage varies, and the severity of organ damage is frequently unrelated to the degree or duration of eosinophilia.

Chusid et al. developed empirical diagnostic standards for idiopathic HES in 1975:

  1. More than 1,500/mL of blood eosinophilia for more than six months in a row, along with hypereosinophilic disease signs and symptoms.

Classification

Myeloproliferative HES (M-HES) and lymphocytic HES (L-HES) are the two main categories of HES, along with a few other clearly defined clinical entities.

Steroid-refractory HES has been managed with a variety of cytotoxic treatments.

It has been demonstrated that immunomodulatory drugs, such as interferon-alpha, cyclosporine, and intravenous immunoglobulin, that influence Th2 cytokine production and T cell proliferation can be therapeutically effective in HES.

The U.S. Food and Drug Administration (FDA) has approved imatinib mesylate, a tyrosine kinase inhibitor, as the first treatment for HES.

History

In 1968, the term "hypereosinophilic syndrome" was created to group patients who had several closely related conditions that were all marked by persistently elevated peripheral blood eosinophil levels and organ damage from eosinophilic infiltration.

See also

  • Eosinophilia
  • Chronic eosinophilic leukemia

References

Further reading

  • Cleveland Clinic
  • Mayo Clinic