Hypereosinophilic syndrome

Jump to: navigation, search

WikiDoc Resources for Hypereosinophilic syndrome

Articles

Most recent articles on Hypereosinophilic syndrome

Most cited articles on Hypereosinophilic syndrome

Review articles on Hypereosinophilic syndrome

Articles on Hypereosinophilic syndrome in N Eng J Med, Lancet, BMJ

Media

Powerpoint slides on Hypereosinophilic syndrome

Images of Hypereosinophilic syndrome

Photos of Hypereosinophilic syndrome

Podcasts & MP3s on Hypereosinophilic syndrome

Videos on Hypereosinophilic syndrome

Evidence Based Medicine

Cochrane Collaboration on Hypereosinophilic syndrome

Bandolier on Hypereosinophilic syndrome

TRIP on Hypereosinophilic syndrome

Clinical Trials

Ongoing Trials on Hypereosinophilic syndrome at Clinical Trials.gov

Trial results on Hypereosinophilic syndrome

Clinical Trials on Hypereosinophilic syndrome at Google

Guidelines / Policies / Govt

US National Guidelines Clearinghouse on Hypereosinophilic syndrome

NICE Guidance on Hypereosinophilic syndrome

NHS PRODIGY Guidance

FDA on Hypereosinophilic syndrome

CDC on Hypereosinophilic syndrome

Books

Books on Hypereosinophilic syndrome

News

Hypereosinophilic syndrome in the news

Be alerted to news on Hypereosinophilic syndrome

News trends on Hypereosinophilic syndrome

Commentary

Blogs on Hypereosinophilic syndrome

Definitions

Definitions of Hypereosinophilic syndrome

Patient Resources / Community

Patient resources on Hypereosinophilic syndrome

Discussion groups on Hypereosinophilic syndrome

Patient Handouts on Hypereosinophilic syndrome

Directions to Hospitals Treating Hypereosinophilic syndrome

Risk calculators and risk factors for Hypereosinophilic syndrome

Healthcare Provider Resources

Symptoms of Hypereosinophilic syndrome

Causes & Risk Factors for Hypereosinophilic syndrome

Diagnostic studies for Hypereosinophilic syndrome

Treatment of Hypereosinophilic syndrome

Continuing Medical Education (CME)

CME Programs on Hypereosinophilic syndrome

International

Hypereosinophilic syndrome en Espanol

Hypereosinophilic syndrome en Francais

Business

Hypereosinophilic syndrome in the Marketplace

Patents on Hypereosinophilic syndrome

Experimental / Informatics

List of terms related to 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; Primary hypereosinophilic syndrome; Secondary hypereosinophilic syndrome; Idiopathic hypereosinophilic syndrome

Overview

Hypereosinophilic syndrome (HES) is a type of myeloproliferative disorder 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] Hypereosinophilic syndrome may be classified into 3 categories: primary, secondary, and idiopathic. Hypereosinophilic syndrome may be caused by either stem cell, myeloid, or eosinophilic neoplasms. Hypereosinophilic syndrome is mainly caused by mutations in the BCR-ABL, PDGFRA, PDGFRβ, and KIT genes.[3] There are some associations with chronic eosinophilic leukemia as it shows similar characteristics and genetic defects.[4] Patients with hypereosinophilic syndrome may be initially asymptomatic. Early clinical features include fatigue, diarrhea, and rash. 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. If left untreated, hypereosinophilic syndrome is progressively fatal. Treatment will depend on the presence of mutations. Treatment of choice for patients with FIP1L1/PDGFRA mutation is imatinib and first line treatment for patients without FIP1L1/PDGFRA mutation is glucocorticoid therapy. The addition of the monoclonal antibody mepolizumab may reduce the dose of glucocorticoids.[5] Once diagnosed and successfully treated, patients with hypereosinophilic syndrome are followed-up periodically every 6 or 12 months depending on the clinical progression. Follow-up testing includes the following tests: complete blood count, biochemical profile (liver enzymes, creatine kinase, renal function, and troponin), electrocardiogram, and tissue biopsies.

Historical Perspective

  • Hypereosinophilic syndrome was first described by Hardy and Anderson 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 3 categories:.[3]
  • Primary hypereosinophilic syndrome
  • Also known as neoplasic hypereosinophilic syndrome
  • Secondary hypereosinophilic syndrome
  • Also known as reactive hypereosinophilic syndrome
  • Idiopathic hypereosinophilic syndrome
  • Other variants of hypereosinophilic syndrome may include myeloproliferative, T lymphocytic, familiar, idiopathic, and organ-restricted hypereosinophilic syndrome variants.

Pathophysiology

  • The pathogenesis of hypereosinophilic syndrome is characterized by the constitutive activation of tyrosine kinases induced by eosinophils.[8]
  • Other mechanisms of hypereosinophilic syndrome pathogenesis, include: clonal eosinophilic proliferation, and overproduction of eosinophilopoietic cytokines.[8]
  • The overproduction of eosinophilopoietic cytokines (eg. IL-5) will induce epithelial cell and tissue damage.[8]
  • Genes associated with the development of hypereosinophilic syndrome, include:[8]
  • PDGFRA gene
  • PDGFRB gene
  • FGFR1 gene
  • On gross pathology, there are no are characteristic findings of hypereosinophilic syndrome.
  • In some cases, eosinophilia causes infiltration of the myocardium, findings include:
  • Fibrotic thickening of portions of the heart.
  • May involve the mitral or tricuspid valves.
  • The cavity of the ventricles of the heart diminish in size
  • Ventricular mural thrombi may develop.
  • On microscopic histopathological analysis, hypercellular marrow, and increased eosinophilic precursors are characteristic findings of hypereosinophilic syndrome.

Gallery

Microscopic Pathology
Images shown below are courtesy of Professor Peter Anderson DVM PhD and published with permission. © PEIR, University of Alabama at Birmingham, Department of Pathology

Gross Pathology
Images shown below are courtesy of Professor Peter Anderson DVM PhD and published with permission. © PEIR, University of Alabama at Birmingham, Department of Pathology

Causes

  • Hypereosinophilic syndrome may be caused by either stem cell, myeloid, or eosinophilic neoplasms.
  • Hypereosinophilic syndrome is caused by a mutation in the BCR-ABL, PDGFRA, PDGFRβ, and KIT gene.[3]

Differentiating Hypereosinophilic Syndrome from Other Diseases

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:[3]

Symptoms

  • Symptoms of hypereosinophilic syndrome may include the following:[3]

Physical Examination

  • Patients with hypereosinophilic syndrome usually have a normal appearance.
  • Physical examination may be remarkable for:[3]

Laboratory Findings

  • Laboratory findings consistent with the diagnosis of hypereosinophilic syndrome include the following:[9]
  • 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.[3]

Treatment

Medical Therapy

  • The medical management of hypereosinophilic syndrome is divided into 2 categories: presence of FIP1L1/PDGFRA mutation, and absence of FIP1L1/PDGFRA mutation.[9]
  • Treatment of choice for patients with FIP1L1/PDGFRA mutation is imatinib
  • First line treatment for patients without FIP1L1/PDGFRA mutation is glucocorticoid therapy.
  • Initial high-dose prednisone is typically initiated at a dose of 1 mg/kg/day
  • Second line treatment for patients without FIP1L1/PDGFRA mutation include interferon alpha and hydroxyurea.
  • Medical therapies for hypereosinophilic syndrome, include: corticosteroids, cytotoxic agents (eg. hydroxyurea, vincristine), biological response modifers (eg. interferon-alpha), targeted therapy, and mepolizumab.

Surgery

  • Surgical intervention is not recommended for the management of hypereosinophilic syndrome.
  • In some cases, surgical intervention may be required to reduce pain in patients with spleen enlargement due to hypereosinophilic syndrome.

Prevention

  • There are no primary preventive measures available for hypereosinophilic syndrome.[9]
  • There are no effective measures for the primary prevention of hypereosinophilic syndrome.
  • Once diagnosed and successfully treated, patients with hypereosinophilic syndrome are followed-up periodically every 6 or 12 months depending on the clinical progression.
  • Follow-up testing includes the following tests: complete blood count, biochemical profile (liver enzymes, creatine kinase, renal function, and troponin), electrocardiogram, and tissue biopsies.

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. PMID 1090795. doi:10.1097/00005792-197501000-00001. 
  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. PMID 19420370. doi:10.1056/NEJMcps0802754. 
  3. 3.0 3.1 3.2 3.3 3.4 3.5 3.6 3.7 Gleich GJ, Leiferman KM (2009). "The hypereosinophilic syndromes: current concepts and treatments". Br. J. Haematol. 145 (3): 271–85. PMID 19243381. doi:10.1111/j.1365-2141.2009.07599.x. 
  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. PMID 18344568. doi:10.1056/NEJMoa070812. 
  6. Hardy WR, Anderson RE (1968). "The hypereosinophilic syndromes". Ann. Intern. Med. 68 (6): 1220–9. PMID 5653621. 
  7. 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. PMID 12660384. doi:10.1056/NEJMoa025217. 
  8. 8.0 8.1 8.2 8.3 Weller PF (1991). "The immunobiology of eosinophils". N. Engl. J. Med. 324 (16): 1110–8. PMID 2008184. doi:10.1056/NEJM199104183241607. 
  9. 9.0 9.1 9.2 9.3 9.4 Hypereosinophilic syndrome: an update. http://www.pneumonologia.gr/articlefiles/20070228_Hypereosinophilic_Syndrome_An_Update.pdf Accessed on April 4, 2016

Linked-in.jpg