Hypereosinophilic syndrome

Hypereosinophilic syndrome (HES) is a group of rare disorders characterized by persistent, marked eosinophilia (an elevated eosinophil count of ≥1,500 cells/μL in the blood) lasting for at least six months, with evidence of eosinophil-mediated organ damage, and no identifiable secondary cause such as parasitic infection or allergy. Eosinophils are a type of white blood cell that, when overproduced and activated, can infiltrate and damage multiple organ systems. The heart, lungs, skin, nervous system, and gastrointestinal tract are most commonly affected. Cardiac involvement, including endomyocardial fibrosis and restrictive cardiomyopathy, is a leading cause of morbidity and mortality. Other key symptoms include skin rashes, cough, breathlessness, fatigue, fever, muscle pain, and neurological complications such as peripheral neuropathy or cognitive changes. HES encompasses several subtypes, including myeloproliferative variants (often associated with the FIP1L1-PDGFRA fusion gene), lymphocytic variants (driven by aberrant T-cell populations producing eosinophil-stimulating cytokines like interleukin-5), and idiopathic forms where no underlying cause is identified. The myeloproliferative variant is more common in males and may present with splenomegaly and elevated serum tryptase levels. Treatment depends on the subtype and severity of organ involvement. Corticosteroids remain the first-line therapy for most forms of HES and are effective in many patients. For the myeloproliferative variant harboring the FIP1L1-PDGFRA fusion, the tyrosine kinase inhibitor imatinib is highly effective and often induces complete remission. Additional therapies include hydroxyurea, interferon-alpha, and targeted biologic agents such as mepolizumab (an anti-interleukin-5 monoclonal antibody), which has been approved for certain forms of HES. In refractory cases, other immunosuppressive agents or stem cell transplantation may be considered. Early diagnosis and treatment are critical to prevent irreversible organ damage, particularly to the heart.

Data sourced from FDA regulatory filings and ClinicalTrials.gov. Updated periodically.

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