| Hypereosinophilic syndrome |
| Classification and external resources |
An eosinophil, the white blood cell involved in hypereosinophilic syndrome, seen amongst red blood cells. |
| ICD-10 |
D72.1 (ILDS D72.12) |
| ICD-9 |
288.3 |
| ICD-O: |
9964/3 |
| OMIM |
607685 |
| eMedicine |
med/1076 derm/920 |
| MeSH |
D017681 |
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.[1]
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.[2]
There are some associations with chronic eosinophilic leukemia[3] as it shows similar characteristics and genetic defects.[4]
If left untreated, HES is progressively fatal. It is treated with glucocorticoids such as prednisone.[2] The addition of the monoclonal antibody mepolizumab may reduce the dose of glucocorticoids.[5]
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Contents
- 1 Classification
- 2 Signs and symptoms
- 3 Diagnosis
- 4 Treatment
- 5 Epidemiology
- 6 References
- 7 External links
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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.[6][7]
- 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[3]
- Skin lesions[3]
- Thromboembolic disease[3]
- Pulmonary disease[3]
- Neuropathy[3]
- Hepatosplenomegaly[3]
- Reduced ventricular size[3]
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.[4] 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.[4] Roughly 50% of patients with HES also have anaemia.[4]
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.[4] Chest radiographs may indicate pleural effusions and/or fibrosis,[4] and neurological tests such as CT scans can show strokes and increased cerebrospinal fluid pressure.[4]
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.[8]
Treatment
Treatment primarily consists of reducing eosinophil levels and preventing further damage to organs.[4] Corticosteroids, such as Prednisone, are good for reducing eosinophil levels and antineoplastics are useful for slowing eosinophil production.[4] Surgical therapy is rarely utilised, however splenectomy can reduce the pain due to spleen enlargement.[4] If damage to the heart (in particular the valves), then prosthetic valves can replace the current organic ones.[4] Follow-up care is vital for the survival of the patient, as such the patient should be checked for any signs of deterioration regularly.[4] 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.[5] If this becomes successful, it may be possible for corticosteroids to be eradicated and thus reduce the amount of side effects encountered.[5]
Epidemiology
HES is very rare, with only 50 cases being noted and followed up in the United States between 1971 and 1982,[4] corresponding roughly to a prevalence of 1 to 2 per million people. The disease is even more uncommon within the paediatric population.[4]
Patients who lack chronic heart failure and those who respond well to Prednisone or a similar drug have a good prognosis.[4] However, the mortality rate rises in patients with anaemia, chromosomal abnormalities or a very high white blood cell count.[4]
References
- ^ 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.
- ^ a b <New England Journal of Medicine 360:2005 (2009)
- ^ a b c d e f g h Longmore, Murray; Ian Wilkinson, Tom Turmezei, Chee Kay Cheung (2007). Oxford Handbook of Clinicial Medicine. Oxford. p. 316. ISBN 0-19-856837-1.
- ^ a b c d e f g h i j k l m n o p Rothenberg, Marc E. "Treatment of Patients with the Hypereosinophilic Syndrome with Mepolizumab". http://www.emedicine.com/med/topic1076.htm. Retrieved 2008-03-17. Last updated: Updated: Oct 4, 2009 by Venkata Samavedi and Emmanuel C Besa
- ^ a b c Scheinfeld, Noah S. "Hypereosinophilic Syndrome". http://content.nejm.org/cgi/content/full/NEJMoa070812. Retrieved 2008-02-15.
- ^ 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. pp. 606. ISBN 0-7216-0187-1.
- ^ 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". Int J Cardiovasc Imaging 20 (6): 517–22. doi:10.1007/s10554-004-1095-9. PMID 15856635. http://www.kluweronline.com/art.pdf?issn=1569-5794&volume=20&page=517.
- ^ 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. http://content.nejm.org/cgi/content/full/348/13/1201.
External links
- DermNet systemic/hypereosinophilic
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Hematologic disease: Monocyte and granulocyte disease (CFU-GM/CFU-Baso/CFU-Eos), including immunodeficiency (D70-D71, 288)
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Monocytes/
macrophages |
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↑
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Histiocytosis · Chronic granulomatous disease
-cytosis: Monocytosis
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↓
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-penia: Monocytopenia
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| Granulocytes |
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↑
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-cytosis: granulocytosis (Neutrophilia, Eosinophilia/Hypereosinophilic syndrome, Basophilia, Bandemia)
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↓
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-penia: Granulocytopenia/agranulocytosis (Neutropenia/Kostmann syndrome · Eosinopenia · Basopenia)
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| PBD |
chemotaxis/degranulation: Leukocyte adhesion deficiency (LAD1, LAD2) · Chédiak–Higashi syndrome
respiratory burst: (Chronic granulomatous disease, Neutrophil immunodeficiency syndrome, Myeloperoxidase deficiency)
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cell/phys (coag, heme, immu, gran), csfs
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rbmg/mogr/tumr/hist, sysi/epon, btst
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drug (B1/2/3+5+6), btst, trns
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Myeloid hematological malignancy/leukemia histology (ICD-O 9590–9989, C81–C96, 200–208)
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CFU-GM/
and other granulocytes |
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CFU-GM
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Myelocyte
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AML: Acute myeloblastic leukemia (M0, M1, M2), APL/M3
MP (Chronic neutrophilic leukemia)
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Monocyte
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AML (AMoL/M5, Myeloid dendritic cell leukemia)
CML (Philadelphia chromosome, Accelerated phase chronic myelogenous leukemia)
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Myelomonocyte
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AML (M4)
MD-MP (Juvenile myelomonocytic leukemia, Chronic myelomonocytic leukemia)
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Other
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Histiocytosis
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CFU-Baso
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AML (Acute basophilic)
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CFU-Eos
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AML (Acute eosinophilic)
MP (Chronic eosinophilic leukemia/Hypereosinophilic syndrome)
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| MEP |
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CFU-Meg
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AML (AMKL/M7)
MP (Essential thrombocytosis)
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CFU-E
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AML (Erythroleukemia/M6)
MP (Polycythemia vera)
MD (Refractory anemia, Refractory anemia with excess of blasts, Chromosome 5q deletion syndrome, Sideroblastic anemia, Paroxysmal nocturnal hemoglobinuria, Refractory cytopenia with multilineage dysplasia)
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| CFU-Mast |
Mastocytoma (Mast cell leukemia, Mast cell sarcoma, Systemic mastocytosis)
Mastocytosis: Diffuse cutaneous mastocytosis · Erythrodermic mastocytosis · Generalized eruption of cutaneous mastocytosis (adult type) · Generalized eruption of cutaneous mastocytosis (childhood type) · Mast cell sarcoma · Solitary mastocytoma · Systemic mastocytosis · Xanthelasmoidal mastocytosis
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| Multiple/unknown |
AML (Acute panmyelosis with myelofibrosis, Myeloid sarcoma) · MP (Myelofibrosis) · Acute biphenotypic leukaemia
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cell/phys (coag, heme, immu, gran), csfs
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rbmg/mogr/tumr/hist, sysi/epon, btst
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drug (B1/2/3+5+6), btst, trns
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