Hypereosinophilic syndromes

Institute for Medical Immunology, Université Libre de Bruxelles, Gosselies, Belgium.
Orphanet Journal of Rare Diseases (Impact Factor: 3.36). 09/2007; 2(1, article 37):37. DOI: 10.1186/1750-1172-2-37
Source: PubMed


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.

Download full-text


Available from: Elie Cogan
  • Source
    • "In cases number 2 and 3, short-term tolerance was satisfying, but long-term follow-up was not feasible. As previously described in humans, treatment discontinuation was followed two months later by recurrence of the disease in case number 1 [2] [20]. The disease rapidly improved within two months of treatment renewal. "
    [Show abstract] [Hide abstract]
    ABSTRACT: A hypereosinophilic syndrome was diagnosed in three cats with refractory dermatitis and marked hypereosinophilia. The cats were treated with imatinib mesylate, a tyrosine-kinase inhibitor at the oral dose of 5 mg per cat. In all three cases, a dramatic improvement was rapidly observed.
    Full-text · Article · Nov 2014
  • Source
    • "In summary, HTLV-1 induces diverse forms of inflammatory disorders [60], [61], which may originate from the functional dysregulation of Tax1bp1. Single-nucleotide polymorphisms (SNPs) in A20 or RNF11, catalytic partners of Tax1bp1, has have linked to many inflammatory diseases [19], [62], [63]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Tax1-binding protein 1 (Tax1bp1) negatively regulates NF-κB by editing the ubiquitylation of target molecules by its catalytic partner A20. Genetically engineered TAX1BP1-deficient (KO) mice develop age-dependent inflammatory constitutions in multiple organs manifested as valvulitis or dermatitis and succumb to premature death. Laser capture dissection and gene expression microarray analysis on the mitral valves of TAX1BP1-KO mice (8 and 16 week old) revealed 588 gene transcription alterations from the wild type. SAA3 (serum amyloid A3), CHI3L1, HP, IL1B and SPP1/OPN were induced 1,180-, 361-, 187-, 122- and 101-fold respectively. WIF1 (Wnt inhibitory factor 1) exhibited 11-fold reduction. Intense Saa3 staining and significant I-κBα reduction were reconfirmed and massive infiltration of inflammatory lymphocytes and edema formation were seen in the area. Antibiotics-induced 'germ free' status or the additional MyD88 deficiency significantly ameliorated TAX1BP1-KO mice's inflammatory lesions. These pathological conditions, as we named 'pseudo-infective endocarditis' were boosted by the commensal microbiota who are usually harmless by their nature. This experimental outcome raises a novel mechanistic linkage between endothelial inflammation caused by the ubiquitin remodeling immune regulators and fatal cardiac dysfunction.
    Full-text · Article · Sep 2013 · PLoS ONE
  • Source
    • "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 "
    [Show abstract] [Hide abstract]
    ABSTRACT: Recent advances in our understanding of the molecular mechanisms underlying hypereosinophilia have led to the development of a 'molecular' classification of myeloproliferative disorders with eosinophilia. The revised 2008 World Health Organization classification of myeloid neoplasms included a new category called "myeloid and lymphoid neoplasms with eosinophilia and abnormalities of PDGFRA, PDGFRB or FGFR1." Despite the molecular heterogeneity of PDGFR (platelet-derived growth factor receptor) rearrangements, tyrosine kinase inhibitors at low dose induce rapid and complete hematological remission in the majority of these patients. Other kinase inhibitors are promising. Further discoveries of new molecular alterations will direct the development of new specific inhibitors. In this review, an update of the classifications of myeloproliferative disorders associated with hypereosinophilia is discussed together with open and controversial questions. Molecular mechanisms and promising results of tyrosine kinase inhibitor treatments are reviewed.
    Preview · Article · Aug 2013 · Hematology Research and Reviews
Show more