THE IDIOPATHIC HYPEREOSINOPHILIC SYNDROME - CLINICAL PRESENTATION, PATHOGENESIS AND THERAPEUTIC STRATEGIES

The idiopathic hypereosinophilic syndrome (HES) is a heterogenous dise ase entity characterized by persistent unexplained hypereosinophilia g enerally complicated by end-organ damage. Correct diagnosis and manage ment are important in order to prevent long-term complications. Furthe rmore, it appears that HES represents a premalignant state in some pat ients, and close follow-up is necessary to detect early signs of malig nant transformation. Previous studies of patient cohorts have led to t he identification of a subgroup of patients With various clinical and biological features of primitive myeloproliferative disease. Patients in this subgroup have a clinically more aggressive disease in terms of organ damage and eventually develop acute myeloid leukemia. Among the remaining patients, it appears that some present an underlying T-cell disorder characterized by overproduction of Th2-type cytokines in viv o. Indeed, lymphocytes belonging to the Th2 subset are implicated in t he maturation, activation and recruitment of eosinophils, essentially through the production of IL-5. Such patients appear to present a more benign disease at short term; however, they may develop T-cell lympho ma years after initial diagnosis. Therapy of HES includes glucocortico ids, hydroxyurea and more recently, interferon-alpha. Prednisone is ge nerally recommended initially, followed by hydroxyurea in case of trea tment failure. Until now, interferon-alpha has been reserved for refra ctory cases of HES. Our proposal for a new treatment strategy, based o n current understanding of the pathogenesis of different subgroups of HES and on the mechanisms of action of the proposed therapeutic agents , which will be discussed in detail. Moreover, prevention of malignant transformation has become a new subject of concern when considering t he beneficial effects of drugs. (C) 1998 Prous Science. All rights res erved.