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Hypereosinophilic syndrome (HES) constitutes a rare and heterogeneous group of disorders, defined as persistent and marked blood eosinophilia and/or tissue eosinophilia associated with a wide range of clinical manifestations reflecting eosinophil-induced tissue/organ damage.
ORPHA:168956Classification level: Group of disorders
- Prevalence: 1-9 / 100 000
- Inheritance: Not applicable or Unknown
- Age of onset: All ages
- ICD-10: D47.5
- OMIM: -
- UMLS: C1540912
- MeSH: D017681
- GARD: 2804
- MedDRA: 10048643
Prevalence is unknown. It frequently occurs in middle-aged patients, but may concern any age group.
Target-organ damage mediated by eosinophils is highly variable among patients, and consists of dermatological involvement (urticaria, eczema, angioedema, pruriginous papules, nodules, erythroderma) in more than 50% of cases, followed by involvement of lungs (cough, breathlessness and wheezing) and digestive tract (nausea, vomiting, abdominal pain, diarrhea, ascites) in roughly 40%. Cardiac involvement is less frequent, but must be recognized early due to irreversible and life-threatening complications such as acute myocarditis, intraventricular thrombus, endomyocardial fibrosis and valve thickening and/or destruction. Constitutional symptoms of fever, myalgia and fatigue may occur. Other common complications include central or peripheral nervous system involvement, hepato- and/or splenomegaly, and coagulation disorders. Skin involvement is more frequently seen in lymphocytic HES and cardiac damage in FIP1L1-PDGFRA (F/P) fusion gene positive (+) chronic eosinophilic leukemia (CEL; see this term).
Recent advances in underlying pathogenesis have established that what was once thought to be ''idiopathic'' HES may in some cases be due to either primitive involvement of myeloid cells (primary HES), essentially due to occurrence of an interstitial chromosomal deletion on 4q12 leading to creation of the F/P fusion gene (CEL), or to increased interleukin (IL)-5 production by a clonally expanded T cell population (lymphocytic variant HES), most frequently characterized by a CD3-CD4+ phenotype, or due to other reactive causes (secondary HES) such as helminthic infection. However, in roughly 3/4 of cases, pathogenesis remains unknown, now defining idiopathic HES. In those with unexplained persistent asymptomatic hypereosinophilia (HE), the provisional term HE of undetermined significance is given. A small subgroup of patients have HES that shows familial clustering (familial HES), presumably due to an as of yet unknown inherited gene.
Diagnosis of HES relies on the observation of persistent and marked HE (> 1.5 × 109/L) and /or eosinophilic infiltration of tissue(s) responsible for target-organ damage. Once these criteria are fulfilled, further testing for eventual pathogenic classification is warranted using appropriate cytogenetic, phenotypic, and functional approaches. If underlying causes of HE have been excluded, the term idiopathic HES is appropriate.
Differential diagnoses include drug allergies and parasitic infections, solid and hematological malignancies (i.e. chronic myeloid leukemia), eosinophilic granulomatosis with polyangiitis and human T cell lymphotropic virus infection (see these terms).
Management and treatment
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 that is currently available only in the setting of clinical trials or on a compassionate use basis for severe treatment-refractory disease, is an effective corticosteroid-sparing agent for F/P-negative patients.
Prognosis has improved significantly since defining HES, and currently depends on the development of irreversible endomyocardial fibrosis, as well as eventual malignant transformation of myeloid or lymphoid cells.
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