HypereosinophilienSyndrome

HypereosinophilienSyndrome, also known as hypereosinophilic syndrome (HES), is a rare group of disorders defined by persistent eosinophilia and organ damage or dysfunction caused by eosinophil infiltration and mediators, in the absence of an alternative cause.

Diagnostic criteria include persistent eosinophilia of 1.5 × 109/L or higher for at least six months or evidence of organ involvement, with exclusion of secondary causes such as parasitic infections, allergies, autoimmune diseases, and other hematologic neoplasms.

Classification differentiates between primary (clonal or neoplastic eosinophilia with genetic rearrangements such as FIP1L1-PDGFRA), secondary/reactive (infections, medications, autoimmune conditions, malignancies), and idiopathic when no driving cause is found.

Pathophysiology involves eosinophil degranulation releasing cytotoxic proteins that cause tissue injury. Commonly affected systems include the heart (leading to endomyocardial fibrosis and heart failure), skin, lungs, nervous system, and gastrointestinal tract.

Clinical features vary by involved organs. Cardiac involvement is a major source of morbidity and can cause heart failure or thromboembolic events; skin lesions, dyspnea, cough, abdominal pain, and neuropathies may also occur.

Diagnosis requires a comprehensive workup: complete blood count with differential, serologic testing to exclude infections, imaging such as echocardiography or cardiac MRI, and tissue studies. Molecular testing for PDGFRA, PDGFRB, FGFR1 rearrangements, JAK2, and BCR-ABL helps distinguish primary HES from other myeloid neoplasms. Bone marrow examination may be performed.

Treatment typically starts with corticosteroids; targeted therapy with imatinib is effective when a PDGFRA fusion is present. Other options include hydroxyurea, interferon-alpha, and anti-IL-5 therapies (e.g., mepolizumab, benralizumab). Management focuses on controlling eosinophilia and mitigating organ damage, with prognosis depending on organ involvement, especially cardiac disease. Epidemiology indicates a rare condition with variable onset, often in adulthood.