Article

Hypereosinophilic syndromes

Institute for Medical Immunology, Université Libre de Bruxelles, Gosselies, Belgium.
Orphanet Journal of Rare Diseases (Impact Factor: 3.96). 09/2007; 2(1, article 37):37. DOI: 10.1186/1750-1172-2-37
Source: PubMed

ABSTRACT Hypereosinophilic syndromes (HES) constitute a rare and heterogeneous group of disorders, defined as persistent and marked blood eosinophilia (> 1.5 x 10(9)/L for more than six consecutive months) associated with evidence of eosinophil-induced organ damage, where other causes of hypereosinophilia such as allergic, parasitic, and malignant disorders have been excluded. Prevalence is unknown. HES occur most frequently in young to middle-aged patients, but may concern any age group. Male predominance (4-9:1 ratio) has been reported in historic series but this is likely to reflect the quasi-exclusive male distribution of a sporadic hematopoietic stem cell mutation found in a recently characterized disease variant. Target-organ damage mediated by eosinophils is highly variable among patients, with involvement of skin, heart, lungs, and central and peripheral nervous systems in more than 50% of cases. Other frequently observed complications include hepato- and/or splenomegaly, eosinophilic gastroenteritis, and coagulation disorders. Recent advances in underlying pathogenesis have established that hypereosinophilia may be due either to primitive involvement of myeloid cells, essentially due to occurrence of an interstitial chromosomal deletion on 4q12 leading to creation of the FIP1L1-PDGFRA fusion gene (F/P+ variant), or to increased interleukin (IL)-5 production by a clonally expanded T cell population (lymphocytic variant), most frequently characterized by a CD3-CD4+ phenotype. Diagnosis of HES relies on observation of persistent and marked hypereosinophilia responsible for target-organ damage, and exclusion of underlying causes of hypereosinophilia, including allergic and parasitic disorders, solid and hematological malignancies, Churg-Strauss disease, and HTLV infection. Once these criteria are fulfilled, further testing for eventual pathogenic classification is warranted using appropriate cytogenetic and functional approaches. Therapeutic management should be adjusted to disease severity and eventual detection of pathogenic variants. For F/P+ patients, imatinib has undisputedly become first line therapy. For others, corticosteroids are generally administered initially, followed by agents such as hydroxycarbamide, interferon-alpha, and imatinib, for corticosteroid-resistant cases, as well as for corticosteroid-sparing purposes. Recent data suggest that mepolizumab, an anti-IL-5 antibody, is an effective corticosteroid-sparing agent for F/P-negative patients. Prognosis has improved significantly since definition of HES, and currently depends on development of irreversible heart failure, as well as eventual malignant transformation of myeloid or lymphoid cells.

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    • "Until recently, the definition of hypereosinophilic syndrome was based on the three criteria described by Chusid et al in 19755: (1) a persistent absolute blood eosinophil count >1.5 × 109/L for more than 6 months (or death before 6 months associated with signs and symptoms of hypereosinophilic disease); (2) a lack of evidence of parasite, allergy or another known cause of eosinophilia; and (3) signs or symptoms of organ involvement, including hepatosplenomegaly, congestive heart failure, gastrointestinal dysfunction, diffuse or focal nervous system abnormalities, pulmonary fibrosis, fever, weight loss or anemia. A detailed description of organ damage induced by eosinophils was reviewed by Roufosse et al.6 A major issue is the lack of robust criteria to define hypereosinophilia–organ damage by radiological or histological examination of the affected tissues.8 "
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