Hypereosinophilic syndrome
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Maria Fernanda Villarreal, M.D. [2]
Synonyms and keywords: HES; Hypereosinophilic disease;
Overview
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] Hypereosinophilic syndrome 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, hypereosinophilic syndrome 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]
Historical Perspective
- Hypereosinophilic syndrome was first described in 1968.[6]
- In 2003, PDGFRA and FIP1L1 genes mutations were first identified in the pathogenesis of hypereosinophilic syndrome.[7]
Classification
- Hypereosinophilic syndrome may be classified into 2 groups:
- Endomyocardial fibrosis
- Also known as Davies disease
- Loeffler's endocarditis
- Other variants of hypereosinophilic syndrome may include myeloproliferative, T lymphocytic, familiar, idiopathic, and organ-restricted hypereosinophilic syndrome variant.
Pathophysiology
- The pathogenesis of hypereosinophilic syndrome is characterized by [feature1], [feature2], and [feature3].
- Genes associated with the development of hypereosinophilic syndrome,include:
- PDGFRA gene
- PDGFRB gene
- FGFR1 gene
- On gross pathology,there are no are characteristic findings of hypereosinophilic syndrome.
- On microscopic histopathological analysis, hypercellular marrow, and increased eosinophilic precursors are characteristic findings of hypereosinophilic syndrome.
Causes
- Hypereosinophilic syndrome may be caused by either [cause1], [cause2], or [cause3].
- Hypereosinophilic syndrome is caused by a mutation in the BCR-ABL, PDGFRA, PDGFRβ, and KIT gene.[8]
Differentiating Hypereosinophilic Syndrome from Other Diseases
- Hypereosinophilic syndrome must be differentiated from other diseases that cause skin rash, fatigue, and hypereosinophilia, such as:
- Allergic diseases
- Atopic dermatitis
- Drug reactions
- Eosinophilic pneumonia
- Hypersensitivity diseases
- Malignancy with secondary eosinophilia
Epidemiology and Demographics
- Hypereosinophilic syndrome is a very rare disease.
- The prevalence of hypereosinophilic syndrome is approximately 0.36 to 6.3 per 100,000 individuals worldwide.
Age
- Patients of all age groups may develop hypereosinophilic syndrome.
- Hypereosinophilic syndrome is more commonly observed among adults.
Gender
- Males are more likely to be affected from hypereosinophilic syndrome than females, with male to female ratio of 5:1 [9]
Race
- Caucasian individuals are more likely to develop cancer of unknown primary origin.[9]
Risk Factors
- Common risk factors in the development of hypereosinophilic syndrome are previous history of cancer, presence of primary cancer, and history of previous allergic hypersensitivity
Natural History, Complications and Prognosis
- Patients with hypereosinophilic syndrome may be initially asymptomatic.
- Early clinical features include fatigue, diarrhea, and rash.
- If left untreated, the majority of patients with hypereosinophilic syndrome may progress to develop thromboembolism, acute respiratory failure, and death.
- Common complications of hypereosinophilic syndrome include chronic heart failure, myocardial fibrosis, and death.
- Prognosis is generally poor, and the 3 year survival rate of patients with hypereosinophilic syndrome is approximately 12%
- Findings related with poor prognosis in hypereosinophilic syndrome, include: presence of anemia, thrombocytopenia, white blood cell count greater than 100,000 cells/cm3, abnormal marrow and/or basophils, elevated serum levels of vitamin B12, serum tryptase, and abnormal levels of leukocyte alkaline phosphatase.
Diagnosis
Diagnostic Criteria
- The diagnosis of hypereosinophilic syndrome includes the following findings:
- Persistently elevated eosinophil count (≥ 1500 eosinophils/mm³) in the blood
- At least six months without any recognizable cause
- Involvement of either the heart, nervous system, or bone marrow.
Symptoms
- Symptoms of hypereosinophilic syndrome may include the following:
Physical Examination
- Patients with hypereosinophilic syndrome usually have a normal appearance.
- Physical examination may be remarkable for:
-
- Thickening of the skin (lichenification)
- Eczema (flexural areas)
- Dermographism
Laboratory Findings
- Laboratory findings consistent with the diagnosis of hypereosinophilic syndrome include the following:
- Elevated serum IgE immunoglobulin
- Elevated serum vitamin B12
- Elevated serum tryptase
Imaging Findings
- There are no imaging findings associated with hypereosinophilic syndrome.
Other Diagnostic Studies
- Hypereosinophilic syndrome may also be diagnosed using bone marrow biopsy and molecular testing.
- Findings on bone marrow biopsy may include
Treatment
Medical Therapy
- The mainstay of therapy for hypereosinophilic syndrome is glucocorticoids.
- The medical management of hypereosinophilic syndrome is divided into 2 categories:
- Presence of FIP1L1/PDGFRA mutation
- Absence of FIP1L1/PDGFRA mutation
Surgery
- Surgical intervention is not recommended for the management of hypereosinophilic syndrome.
Prevention
- There are no primary preventive measures available for hypereosinophilic syndrome.
- There are no effective measures for the primary prevention of hypereosinophilic syndrome.
- Once diagnosed and successfully treated, patients with hypereosinophilic syndrome are followed-up every 12 months.
- Follow-up testing includes the following tests:
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.
- ↑ 2.0 2.1 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.
- ↑ Longmore, Murray; Ian Wilkinson; Tom Turmezei; Chee Kay Cheung (2007). Oxford Handbook of Clinicial Medicine. Oxford. p. 316. ISBN 0-19-856837-1.
- ↑ 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
- ↑ 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.
- ↑ Hardy WR, Anderson RE (1968). "The hypereosinophilic syndromes". Ann. Intern. Med. 68 (6): 1220–9. PMID 5653621.
- ↑ 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.
- ↑ Gleich GJ, Leiferman KM (2009). "The hypereosinophilic syndromes: current concepts and treatments". Br. J. Haematol. 145 (3): 271–85. doi:10.1111/j.1365-2141.2009.07599.x. PMID 19243381.
- ↑ 9.0 9.1 Hypereosinophilic syndrome: an update. http://www.pneumonologia.gr/articlefiles/20070228_Hypereosinophilic_Syndrome_An_Update.pdf Accessed on April 4, 2016