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Eosinophilic disorders

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Eosinophilic inflammatory responses occur in association with multiple disorders. Although the initial cause and the affected organs vary among the different eosinophilic disorders, there are only 2 major pathways that mediate eosinophilia: (1) cytokine-mediated increased differentiation and survival of eosinophils (extrinsic eosinophilic disorders), and (2) mutation-mediated clonal expansion of eosinophils (intrinsic eosinophilic disorders). Independent from the original trigger, the most common cause of eosinophilia is the increased generation of IL-5–producing T cells. In some cases, tumor cells are the source of eosinophil hematopoietins. The intrinsic eosinophilic disorders are characterized by mutations in pluripotent or multipotent hematopoietic stem cells leading to chronic myeloid leukemias with eosinophils as part of the clone. Here, we propose a new classification of eosinophilic disorders on the basis of these obvious pathogenic differences between the 2 groups of patients. We then discuss many known eosinophilic disorders, which can be further subdivided by differences in T-cell activation mechanisms, origin of the cytokine-producing tumor cell, or potency of the mutated stem cell. Interestingly, many subgroups of patients originally thought to have the idiopathic hypereosinophilic syndrome can be integrated in this classification.

Section snippets

A new classification of eosinophilic disorders

Many earlier classifications of eosinophilic diseases were generated according to the site of eosinophilic infiltration associated with organ damage and dysfunction. This resulted in several disease terms such as eosinophilic dermatitis, gastroenteritis, pneumonia, or fasciitis. Other classifications are based on the numbers of blood eosinophils (eg, hypereosinophilic syndrome). However, research efforts combined with new technologies and therapeutic tools have led to a better understanding of

Eosinophilic disorders resulting from mutations in pluripotent hematopoietic stem cells

Chronic eosinophilic leukemias belong to a special group of chronic myeloid leukemias, in which eosinophil differentiation is dominant, resulting in blood eosinophil counts of greater than 1.5 × 109/L.7 However, other lineages are also affected, because the disease is the result of a mutation in a pluripotent hematopoietic stem cell. Several defined entities have been described. Chromosomal translocations related to breakpoints on chromosome 8p11 result in fibroblast growth factor receptor 1

Allergic diseases

Common diseases are allergic rhinoconjunctivitis,20 bronchial asthma,21 eosinophilic esophagitis,22 and atopic dermatitis.23 Moreover, in most patients with primary eosinophilic gastrointestinal disorders, evidence for IgE-mediated allergic sensitization mechanisms exists.24 Eosinophilic pancreatitis is rare and usually occurs together with eosinophilic gastroenteritis.25 In childhood, food allergy and allergic colitis are common.26 Tissue and blood eosinophilia is a characteristic feature of

Conclusion

In this article, we propose a simple classification scheme of eosinophilic disorders (Fig 1). Eosinophilia might be caused either by mutations in eosinophil precursors or by overexpression of eosinophil hematopoietins. Among the eosinophil hematopoietins, IL-5 appears to be the most prominent. In some cases, IL-3 contributes or is dominant.120 GM-CSF appears to play a less important role but has often been shown to be expressed in in vitro activated eosinophils. The expression of eosinophil

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    (Supported by an unrestricted educational grant from Genentech, Inc. and Novartis Pharmaceuticals Corporation)

    Series editors: Donald Y. M. Leung, MD, PhD, and Dennis K. Ledford, MD

    Work in the laboratory of Dr Hans-Uwe Simon is supported by grants from the Swiss National Science Foundation (grant #310000-107526), the Stanley Thomas Johnson Foundation, Bern, and the OPO-Foundation, Zurich.

    Disclosure of potential conflict of interest: The authors have declared that they have no conflict of interest.

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