Mechanisms of asthma and allergic inflammation
Approaches to the treatment of hypereosinophilic syndromes: A workshop summary report

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Hypereosinophilic syndromes are a heterogeneous group of uncommon disorders characterized by the presence of marked peripheral blood eosinophilia, tissue eosinophilia, or both, resulting in a wide variety of clinical manifestations. Although corticosteroids are the first-line therapy for many of these disorders, approaches to the treatment of patients who do not tolerate or are unresponsive to corticosteroids are poorly standardized. A multidisciplinary group of 37 clinicians and scientists participated in a workshop held in May 2005 in Bern, Switzerland to discuss current and future approaches to therapy for 3 eosinophil-mediated disorders: hypereosinophilic syndrome, Churg-Strauss syndrome, and eosinophil-associated gastrointestinal disease. The goal of the workshop was to summarize available data regarding treatment of these disorders to identify the most promising therapies and approaches for further study. There was consensus among all of the participants that the identification of markers of disease progression to assess treatment responses is a research priority for all 3 disorders. Furthermore, the need for newer therapeutic strategies and novel drugs, as well as multicenter trials to assess all treatment modalities, was emphasized.

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Diagnosis

Central to any discussion of therapy for eosinophilic disorders is the differential diagnosis of the eosinophil-associated conditions. In the past, many of these conditions were lumped together as IHES, defined by the following: (1) the presence of eosinophilia (>1500 eosinophils/mm3 for at least 6 months) that remains unexplained despite a comprehensive evaluation for known causes of eosinophilia (including parasitic helminth infections, HIV, drug hypersensitivity, nonhematologic malignancies,

HES treatment outcomes: Indicators of clinical response

Although peripheral blood eosinophilia, the hallmark of HES, is an inexpensive and accessible measure with which to follow the response to treatment, the relationship between the absolute eosinophil count and eosinophil-mediated tissue damage is not consistent. Clearly there are subgroups of patients with eosinophil counts greater than 1500/mm3 who show no evidence of clinical disease, as well as symptomatic patients with HES and normal eosinophil counts on therapy. Although a number of

Treatment outcomes: Indicators of clinical response

Management of CSS involves quelling active inflammation, suppressing the immune response, and managing disease-specific manifestations, such as asthma and sinusitis. Whereas current therapies cannot cure the disease, CSS-targeted therapies seek to minimize tissue and organ damage and prevent relapses. A variety of CSS therapies can dramatically alter the course of CSS: 50% or fewer of those who are untreated die within 3 months of diagnosis, whereas treated subjects have a 6-year survival of

Treatment outcomes: Indicators of clinical response

Patients with EGID require chronic therapy, and disease symptoms and pathology generally return when therapy is discontinued. In the case of EE, in which a high rate of esophageal strictures and remodeling changes in the esophagi of adult patients has been reported, therapy has been advocated to control the inflammation, irrespective of clinical symptoms.13 Whether this holds true for other forms of EGID, such as eosinophilic colitis and eosinophilic gastritis, remains uncertain.

Endoscopic

Transcription factors

The role of transcription factors in regulating or facilitating selective eosinophil development compared with other bone marrow–derived hematopoietic lineages is exceedingly complex. Nevertheless, current data from both mouse and human studies suggest that a handful of transcription factors are critical in eosinophilopoiesis,44 such that the commitment and terminal differentiation of eosinophils from myeloid progenitors requires concomitant expression of C/EBPα, PU.1, and a moderate level of

Conclusion

Despite a number of important advances in our understanding of the causes of HES, CSS, and EGID, the relative lack of large prospective trials addressing different treatment modalities and markers of treatment response continues to impair our ability to formulate a rational approach to therapy for these disorders, particularly in those patients for whom corticosteroids are ineffective or have unacceptable toxicity. To this end, the need for multicenter cooperation cannot be overemphasized. The

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  • Cited by (0)

    The workshop was funded by Office of Rare Diseases Research of the National Institutes of Health, GlaxoSmithKline (GSK), and the American Partnership for Eosinophilic Disorders.

    Disclosure of potential conflict of interest: B. Bochner has consultant arrangements with GlaxoSmithKline. G. Gleich has consultant arrangements with GlaxoSmithKline, Ception Therapeutics, Eosynos, and Novartis Genentech; owns stock in Ception Therapeutics; is founder of Eosynos; has received grants from GlaxoSmithKline and Novartis Genentech; and is on the speakers' bureau for Novartis Genentech. M. Rothenberg has consultant arrangements with GlaxoSmithKline, Ception Therapeutics, and Cambridge Antibody Technology; owns stock in Ception Therapeutics; has received grants from Cambridge Antibody Technology; is on the speakers' bureau for Merck; and is an Honorarium from Tanox. H. Simon has consultant arrangements with GlaxoSmithKline, Greenford, United Kingdom, and has received grants from the Swiss National Science Foundation. M. Wechsler has consultant arrangements with Novartis Genentech; has received grants from Merck; and is on the speakers' bureau for Novartis Genentech and Merck. The rest of the authors have declared that they have no conflict of interest.

    The members of the Hypereosinophilic Syndromes Working Group are shown in the Acknowledgments.

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