Specialty hematology ICD-9-CM 288.3 OMIM 607685 | ICD-10 D72.1 (ILDS D72.12) ICD-O 9964/3 DiseasesDB 34939 | |
The hypereosinophilic syndrome (HES) is a disease characterized by a persistently elevated eosinophil count (≥ 1500 eosinophils/mm³) in the blood for at least six months without any recognizable cause, with involvement of either the heart, nervous system, or bone marrow.
Contents
HES is a diagnosis of exclusion, after clonal eosinophilia (such as leukemia) and reactive eosinophilia (in response to infection, autoimmune disease, atopy, hypoadrenalism, tropical eosinophilia, or cancer) have been ruled out.
There are some associations with chronic eosinophilic leukemia as it shows similar characteristics and genetic defects.
If left untreated, HES is progressively fatal. It is treated with glucocorticoids such as prednisone. The addition of the monoclonal antibody mepolizumab may reduce the dose of glucocorticoids.
Classification
In the heart, there are two forms of the hypereosinophilic syndrome, endomyocardial fibrosis and Loeffler's endocarditis.
Signs and symptoms
As HES affects many organs at the same time, symptoms may be numerous. Some possible symptoms a patient may present with include:
Diagnosis
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.
Treatment
Treatment primarily consists of reducing eosinophil levels and preventing further damage to organs. Corticosteroids, such as Prednisone, are good for reducing eosinophil levels and antineoplastics are useful for slowing eosinophil production. Surgical therapy is rarely utilised, however splenectomy can reduce the pain due to spleen enlargement. If damage to the heart (in particular the valves), then prosthetic valves can replace the current organic ones. Follow-up care is vital for the survival of the patient, as such the patient should be checked for any signs of deterioration regularly. After promising results in drug trials (95% efficiency in reducing blood eosinophil count to acceptable levels) it is hoped that in the future hypereosinophilic syndrome, and diseases related to eosinophils such as asthma and eosinophilic granulomatosis with polyangiitis, may be treated with the monoclonal antibody Mepolizumab currently being developed to treat the disease. If this becomes successful, it may be possible for corticosteroids to be eradicated and thus reduce the amount of side effects encountered.
Epidemiology
HES is very rare, with only 50 cases being noted and followed up in the United States between 1971 and 1982, corresponding roughly to a prevalence of 1 to 2 per million people. The disease is even more uncommon within the paediatric population.
Patients who lack chronic heart failure and those who respond well to Prednisone or a similar drug have a good prognosis. However, the mortality rate rises in patients with anaemia, chromosomal abnormalities or a very high white blood cell count.