Hypereosinophilic syndrome, idiopathic
Hypereosinophilic syndrome is a group of rare blood disorders characterized by increased levels of eosinophils (a type of white blood cell that plays a role in the human immune system) persisting for more than six months. The signs and symptoms are due to involvement of several internal organs and there is usually no evidence of parasites, allergy, or other known causes of an elevated eosinophil count. This condition largely occurs in males, typically at middle age. It usually presents with fever, weight loss, fatigue, and rash. An enlarged liver and spleen and liver is often present. The lungs, kidneys, heart, and nervous system can also be affected.
- Abnormality of the nervous system
- Autosomal dominant inheritance
- Endocardial fibrosis
- Myeloproliferative disorder
- Pulmonary infiltrates
- Restrictive cardiomyopathy
- Somatic mutation
- Venous thrombosis
Hypereosinophilic syndrome (HES) is traditionally defined by peripheral blood eosinophilia > 1500/μL persisting ≥ 6 mo. HES was previously considered to be idiopathic but is now known to result from various disorders, some of which have known causes. One limitation of the traditional definition is that it does not include those patients with some of the same abnormalities (eg, genetic defects) that are known causes of HES and who do not fulfill the traditional HES diagnostic criteria for degree or duration of eosinophilia. Another limitation is that some patients with eosinophilia and organ damage that characterize HES require treatment earlier than the 6 mo necessary to confirm the traditional diagnostic criteria.
Information not available.
Numerous techniques are used to diagnose hypereosinophilic syndrome, of which the most important is blood testing. In HES, the eosinophil count is greater than 1.5 × 109/L. On some smears the eosinophils may appear normal in appearance, but morphologic abnormalities, such as a lowering of granule numbers and size, can be observed. Roughly 50% of patients with HES also have anaemia.
Secondly, various imaging and diagnostic technological methods are utilised to detect defects to the heart and other organs, such as valvular dysfunction and arrhythmias by usage of echocardiography. Chest radiographs may indicate pleural effusions and/or fibrosis, and neurological tests such as CT scans can show strokes and increased cerebrospinal fluid pressure.
A proportion of patients have a mutation involving the PDGFRA and FIP1L1 genes on the fourth chromosome, leading to a tyrosine kinase fusion protein. Testing for this mutation is now routine practice, as its presence indicates response to imatinib, a tyrosine kinase inhibitor.
HES is usually a chronic and slowly progressive disease that eventually results in irreversible damage to the heart or other end-organs. Rarely, the disease may be rapidly progressive and fatal. Data from 1975 suggested that a mean survival of 9 months and a 3-year survival rate of only 12% can be expected. Most of the patients on which the data were based presented with advanced cardiac disease. A 1989 report from France noted a 5-year survival rate of 80% and a 10-year survival rate of 42%. This improvement in survival rate probably can be attributed to patient access to earlier diagnosis, treatment, and improved supportive measures.
Some patients with eosinophilia do not require treatment. However, by definition, end-organ involvement is present. Therefore, with rare exception, all patients with HES should receive therapy.
The goal of therapy is to prevent or control organ damage. Because the disease is rarely curable, the focal point is to suppress eosinophil count and ameliorate the factors that cause tissue damage. Remember, however, that certain manifestations of HES, such as cardiac damage, do not correlate directly with the absolute eosinophilia or the duration of the eosinophilia.
- Corticosteroids have been the mainstay of treatment for decades. However, many patients do not respond to corticosteroids and other forms of therapy may be necessary.
- Hydroxyurea and other chemotherapeutic agents. Hydroxyurea interferes with DNA synthesis and inhibits the formation of marrow-derived cells.
- Interferon-alpha. Interferon alpha has induced remission in corticosteroid-resistant patients with HES in small case series.
- Monoclonal antibodies. Anecdotal reports suggest that monoclonal antibodies may be useful in the treatment of HES.
- Tyrosine kinase inhibition.
- Bone marrow transplantation. Bone marrow transplantation should be considered in young patients with refractory disease.
- Other therapies and recommendations. Cyclosporine has been used with success, particularly in combination with corticosteroids. Leukapheresis has no defined role in management of HES, but it has been tried in patients with markedly elevated eosinophil counts in combination with other therapies. Anticoagulants and antiplatelet agents are not indicated for prophylactic use, and their effectiveness is unclear because recurrent thrombotic events nevertheless have occurred in adequately anticoagulated patients with HES.
- Cardiac surgical procedures, including valve replacement, endomyocardectomy or thrombectomy, should be performed when indicated. Splenectomy may be considered in patients with symptomatic splenomegaly.
Refer to Research Publications.