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Hypereosinophilic syndrome
Specialty	Hematology

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.

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.

• Endomyocardial fibrosis (also known as Davies disease) is seen in tropical areas.
• Loeffler's endocarditis does not have any geographic predisposition.

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:

• Cardiomyopathy
• Skin lesions
• Thromboembolic disease
• Pulmonary disease
• Neuropathy
• Hepatosplenomegaly
• Reduced ventricular size

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 × 10/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 Churg-Strauss syndrome, 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.

References

1. Chusid MJ, Dale DC, West BC, Wolff SM (1975). "The hypereosinophilic syndrome: analysis of fourteen cases with review of the literature". Medicine (Baltimore). 54 (1): 1–27. doi:10.1097/00005792-197501000-00001. PMID 1090795.{{cite journal}}: CS1 maint: multiple names: authors list (link)
2. ^ Fazel R, Dhaliwal G, Saint S, Nallamothu BK (May 2009). "Clinical problem-solving. A red flag". N. Engl. J. Med. 360 (19): 2005–10. doi:10.1056/NEJMcps0802754. PMID 19420370.{{cite journal}}: CS1 maint: multiple names: authors list (link)
3. ^ Longmore, Murray; Ian Wilkinson; Tom Turmezei; Chee Kay Cheung (2007). Oxford Handbook of Clinicial Medicine. Oxford. p. 316. ISBN 0-19-856837-1.
4. ^ Rothenberg, Marc E. "Treatment of Patients with the Hypereosinophilic Syndrome with Mepolizumab". Retrieved 2008-03-17. Last updated: Updated: Oct 4, 2009 by Venkata Samavedi and Emmanuel C Besa
5. ^ Rothenberg ME, Klion AD, Roufosse FE, et al. (March 2008). "Treatment of patients with the hypereosinophilic syndrome with mepolizumab". N. Engl. J. Med. 358 (12): 1215–28. doi:10.1056/NEJMoa070812. PMID 18344568.
6. Cotran, Ramzi S.; Kumar, Vinay; Fausto, Nelson; Nelso Fausto; Robbins, Stanley L.; Abbas, Abul K. (2005). Robbins and Cotran pathologic basis of disease. St. Louis, Mo: Elsevier Saunders. p. 606. ISBN 0-7216-0187-1.{{cite book}}: CS1 maint: multiple names: authors list (link)
7. Smedema JP, Winckels SK, Snoep G, Vainer J, Bekkers SC, Crijns HJ (December 2004). "Tropical endomyocardial fibrosis (Davies' disease): case report demonstrating the role of magnetic resonance imaging" (PDF). Int J Cardiovasc Imaging. 20 (6): 517–22. doi:10.1007/s10554-004-1095-9. PMID 15856635.{{cite journal}}: CS1 maint: multiple names: authors list (link)
8. Cools J, DeAngelo DJ, Gotlib J, et al. (2003). "A tyrosine kinase created by fusion of the PDGFRA and FIP1L1 genes as a therapeutic target of imatinib in idiopathic hypereosinophilic syndrome". N. Engl. J. Med. 348 (13): 1201–14. doi:10.1056/NEJMoa025217. PMID 12660384.

External links

• DermNet systemic/hypereosinophilic

• Hypereosinophilic Syndrome research in UK
• Hypereosinophilic Syndrome on patient.info
• Hypereosinophilic Syndrome on eMedicine
• Hypereosinophilic Syndrome (HES) on American Academy of Allergy, Asthma & Immunology
• Hypereosinophilic syndrome on Mayo Clinic

• Eosinophilic cutaneous conditions
• Myeloid neoplasia
• Monocyte and granulocyte disorders