Steroid Treatment for Hypereosinophilic Syndrome

Overview

Background: \- Hypereosinophilic syndrome (HES) is a disorder in which the body has too many eosinophils (a type of white blood cell). Too many eosinophils in HES can cause damage to the heart, nerves, or skin. Certain drugs can help lower eosinophil counts to prevent tissue damage. Corticosteroids, such as prednisone, are used for initial therapy in this disorder. Although most people respond to prednisone, some people develop side effects from it, or do not respond very well to treatment. Better ways of determining the dose to give could help to decide on the best therapy for HES. Objectives: * To determine whether a single-dose of prednisone can be used to predict which people with hypereosinophilia respond to treatment. * To study lack of response to steroid treatment in people with HES. Eligibility: Inclusion criteria: * Individuals with hypereosinophilic syndrome with high eosinophil counts. * Individuals who are willing to have blood drawn before and after getting steroids. Exclusion criteria: * Individuals who are on more than 10mg of prednisone (or similar drug) * Individuals with hypereosinophilic syndrome who are on other medications that could interfere with the study * Women who are pregnant or breast-feeding * Individuals who have a known gene mutation associated with chronic eosinophilic leukemia * Children less than 18 years old who weigh less than 48kg or 106lb Design: * Participants will have a screening visit with a physical exam and medical history. Blood and urine samples will be collected. * Participants will have a single dose of the steroid prednisone by mouth in the morning. Blood samples will be collected 2, 4, 24 hours after this dose. * On the day after the steroid dose, participants will provide another blood sample in the morning. * Participants will start to take prednisone daily when they return home. Blood samples will be collected weekly at the participant s doctor s office. The dose of prednisone will be lowered depending on the weekly eosinophil count. We will try to get each person on the lowest dose of prednisone possible that will control the disorder. Participants who do not respond or have severe side effects will be taken off prednisone. Other treatments will be considered for people who do not respond to steroids. The goal is to evaluate the response to prednisone. Our research will try to figure out why some people do not respond to steroids. Most people will complete the study within 6 to 16 weeks, depending on their response to prednisone.

This study aims to develop a model to determine whether a single, oral, weight-based dose of glucocorticoid (GC) can predict clinical and biologic response to GC s over the long term in subjects with hypereosinophilic syndrome (HES). Subjects with FIP1L1/PDGFRalpha-negative HES, who are symptomatic with eosinophil count \>1500/microL and receiving less than or equal to10 mg prednisone daily, will be enrolled. A single oral dose of prednisone (1 mg/kg rounded to the nearest 5mg) will be administered. Eosinophil count and various laboratory parameters will be assessed at 2 hours, 4 hours and 24 hours following prednisone administration (investigators will be blinded to the results of the eosinophil counts). The subjects will then begin GC therapy at 30 mg prednisone daily followed by a standardized taper. The lowest dose of GC at which symptoms and eosinophilia are controlled will be compared to the change in eosinophil count at 2, 4 and 24 hours post-challenge. Mechanisms and in vitro correlates of GC resistance will also be explored.