Hypereosinophilic syndrome

Hypereosinophilic syndrome 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.[2]

Hypereosinophilic syndrome
Other namesHES[1]
SpecialtyHematology
Differential diagnosisClonal eosinophilia, Reactive eosinophilia

HES is a diagnosis of exclusion, after clonal eosinophilia (such as FIP1L1-PDGFRA-fusion induced hypereosinophelia and leukemia) and reactive eosinophilia (in response to infection, autoimmune disease, atopy, hypoadrenalism, tropical eosinophilia, or cancer) have been ruled out.[3][4]

There are some associations with chronic eosinophilic leukemia[5] as it shows similar characteristics and genetic defects.[6] If left untreated, HES is progressive and fatal. It is treated with glucocorticoids such as prednisone.[3] The addition of the monoclonal antibody mepolizumab may reduce the dose of glucocorticoids.[7]

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.[6] 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.[6] Roughly 50% of patients with HES also have anaemia.[6]

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 means of echocardiography.[6] Chest radiographs may indicate pleural effusions and/or fibrosis,[6] and neurological tests such as CT scans can show strokes and increased cerebrospinal fluid pressure.[6]

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 a likely response to imatinib, a tyrosine kinase inhibitor.[8]

Treatment

Treatment primarily consists of reducing eosinophil levels and preventing further damage to organs.[6] Corticosteroids, such as prednisone, are good for reducing eosinophil levels and antineoplastics are useful for slowing eosinophil production.[6] Surgical therapy is rarely utilised, however splenectomy can reduce the pain due to spleen enlargement.[6] If the heart has been damaged (in particular the valves), prosthetic valves can replace the current organic ones.[6] Follow-up care is vital for the survival of the patient; as such, the patient should be checked for any signs of deterioration regularly.[6]

Many cases of hypereosinophilic syndrome may be treated exclusively with monoclonal antibodies such as mepolizumab[7] It may then be typical not to prescribe corticosteroids for this condition, reducing the burden of the side effects associated with corticosteroids.[7]

Epidemiology

The European Medicines Agency (EMA) estimated the prevalence of HES at the time of granting orphan drug designation for HES in 2004 at 1.5 in 100,000 people, corresponding to a current case load of about 8,000 in the EU, 5,000 in the U.S., and 2,000 in Japan.[9]

Patients without chronic heart failure and those who respond well to pharmaceutical treatments have a good prognosis.[6] However, the mortality rate rises in patients with anaemia, chromosome abnormalities or a very high white blood cell count.[6]

History

Hypereosinophilic syndrome was first described as a distinct entity by Hardy and Anderson in 1968.[10]

References
  1. "OMIM Entry - # 607685 - HYPEREOSINOPHILIC SYNDROME, IDIOPATHIC; HES". omim.org. Retrieved 12 May 2019.
  2. 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. S2CID 39212252.
  3. 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.
  4. Reiter A, Gotlib J (2017). "Myeloid neoplasms with eosinophilia". Blood. 129 (6): 704–714. doi:10.1182/blood-2016-10-695973. PMID 28028030.
  5. Longmore, Murray; Ian Wilkinson; Tom Turmezei; Chee Kay Cheung (2007). Oxford Handbook of Clinical Medicine. Oxford. p. 316. ISBN 978-0-19-856837-7.
  6. Rothenberg, Marc E (2008). "Treatment of Patients with the Hypereosinophilic Syndrome with Mepolizumab". The New England Journal of Medicine. 358 (12): 1215–28. doi:10.1056/NEJMoa070812. PMID 18344568. S2CID 6037384. Retrieved 2008-03-17. Last updated: Updated: Oct 4, 2009 by Venkata Samavedi and Emmanuel C Besa
  7. 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. S2CID 6037384.
  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.
  9. European Medicines Agency, Committee for Orphan Medicinal Products. Public summary of opinion on orphan designation: mepolizumab for the treatment of hypereosinophilic syndrome. August 2010.
  10. Hardy, William R.; Anderson, Robert E. (1 June 1968). "The Hypereosinophilic syndromes". Annals of Internal Medicine. 68 (6): 1220–9. doi:10.7326/0003-4819-68-6-1220. eISSN 1539-3704. ISSN 0003-4819. PMID 5653621.
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