Hypereosinophilic syndrome: Difference between revisions

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==Overview==
==Overview==


'''Hypereosinophilic syndrome''' (HES) is a type of [[Myeloproliferative disease|myeloproliferative disorder]] characterized by a persistently [[Eosinophilia|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]]. Hypereosinophilic syndrome is a diagnosis of exclusion, after clonal [[eosinophilia]] (such as [[leukemia]]) and reactive [[eosinophilia]] (in response to [[infection]], [[autoimmune disease]], [[atopy]], [[Adrenal insufficiency|hypoadrenalism]], [[Eosinophilia|tropical eosinophilia]], or cancer) have been ruled out. Hypereosinophilic syndrome may be classified into 3 categories: primary, secondary, and idiopathic. Hypereosinophilic syndrome may be caused by either [[stem cell]], [[myeloid]], or [[eosinophilic]] [[Neoplasm|neoplasms]]. Hypereosinophilic syndrome is mainly caused by [[Mutation|mutations]] in the BCR-ABL, PDGFRA, PDGFRβ, and KIT genes. There are some associations with [[chronic eosinophilic leukemia]]  as it shows similar characteristics and [[genetic]] defects. [[Patient|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 analysis|survival]] rate of patients with hypereosinophilic syndrome is approximately 12%. Findings related with poor [[prognosis]] in hypereosinophilic syndrome, include: presence of [[anemia]], thrombocytopenia, [[Blood cell|white blood cell]] count greater than 100,000 cells/cm3, abnormal [[Bone marrow|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 [[Mutation|mutations]]. Treatment of choice for patients with FIP1L1/PDGFRA [[mutation]] is [[imatinib]] and first line treatment for [[Patient|patients]] without FIP1L1/PDGFRA [[mutation]] is [[Glucocorticoid|glucocorticoid therapy]]. The addition of the [[Monoclonal antibodies|monoclonal antibody]] [[mepolizumab]] may reduce the dose of [[glucocorticoids]]. Once diagnosed and successfully treated, [[Patient|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 [[Biopsy|tissue biopsies]].
'''Hypereosinophilic syndrome''' (HES) is a type of [[Myeloproliferative disease|myeloproliferative disorder]] characterized by a persistently [[Eosinophilia|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]]. Hypereosinophilic syndrome is a [[diagnosis]] of exclusion, after [[Clonal colony|clonal]] [[eosinophilia]] (such as [[leukemia]]) and reactive [[eosinophilia]] (in response to [[infection]], [[autoimmune disease]], [[atopy]], [[Adrenal insufficiency|hypoadrenalism]], [[Eosinophilia|tropical eosinophilia]], or cancer) have been ruled out. Hypereosinophilic syndrome may be classified into 3 categories: primary, secondary, and [[idiopathic]]. Hypereosinophilic syndrome may be caused by either [[stem cell]], [[myeloid]], or [[eosinophilic]] [[Neoplasm|neoplasms]]. Hypereosinophilic syndrome is mainly caused by [[Mutation|mutations]] in the BCR-ABL, PDGFRA, PDGFRβ, and KIT genes. There are some associations with [[chronic eosinophilic leukemia]]  as it shows similar characteristics and [[genetic]] defects. [[Patient|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 analysis|survival]] rate of patients with hypereosinophilic syndrome is approximately 12%. Findings related with poor [[prognosis]] in hypereosinophilic syndrome, include: presence of [[anemia]], thrombocytopenia, [[Blood cell|white blood cell]] count greater than 100,000 cells/cm3, abnormal [[Bone marrow|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 [[Mutation|mutations]]. Treatment of choice for [[Patient|patients]] with FIP1L1/PDGFRA [[mutation]] is [[imatinib]] and first line treatment for [[Patient|patients]] without FIP1L1/PDGFRA [[mutation]] is [[Glucocorticoid|glucocorticoid therapy]]. The addition of the [[Monoclonal antibodies|monoclonal antibody]] [[mepolizumab]] may reduce the dose of [[glucocorticoids]]. Once [[Diagnosis|diagnosed]] and successfully treated, [[Patient|patients]] with hypereosinophilic syndrome are followed-up periodically every 6 or 12 months depending on the clinical progression.  Follow-up testing includes the following [[Test|tests]]: [[complete blood count]], [[biochemical]] profile ([[liver enzymes]], [[creatine kinase]], [[renal function]], and [[troponin]]),  [[electrocardiogram]], and [[Biopsy|tissue biopsies]].


==Historical Perspective==
==Historical Perspective==
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::*Also known as reactive hypereosinophilic syndrome
::*Also known as reactive hypereosinophilic syndrome
:* '''Idiopathic hypereosinophilic syndrome'''
:* '''Idiopathic hypereosinophilic syndrome'''
*Other variants of hypereosinophilic syndrome may include [[Myeloproliferative disease|myeloproliferative]], [[T lymphocyte|T lymphocytic]], familiar, idiopathic, and [[Organ (anatomy)|organ]]-restricted hypereosinophilic syndrome variants.
*Other variants of hypereosinophilic syndrome may include [[Myeloproliferative disease|myeloproliferative]], [[T lymphocyte|T lymphocytic]], familiar, [[idiopathic]], and [[Organ (anatomy)|organ]]-restricted hypereosinophilic syndrome variants.


==Pathophysiology==
==Pathophysiology==
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==Differentiating Hypereosinophilic Syndrome from Other Diseases==
==Differentiating Hypereosinophilic Syndrome from Other Diseases==
*Hypereosinophilic syndrome must be differentiated from other diseases that cause [[skin rash]], [[fatigue]], and [[hypereosinophilia]], such as:<ref name="pmid19243381">{{cite journal |vauthors=Gleich GJ, Leiferman KM |title=The hypereosinophilic syndromes: current concepts and treatments |journal=Br. J. Haematol. |volume=145 |issue=3 |pages=271–85 |year=2009 |pmid=19243381 |doi=10.1111/j.1365-2141.2009.07599.x |url=}}</ref>
*Hypereosinophilic syndrome must be differentiated from other [[Disease|diseases]] that cause [[skin rash]], [[fatigue]], and [[hypereosinophilia]], such as:<ref name="pmid19243381">{{cite journal |vauthors=Gleich GJ, Leiferman KM |title=The hypereosinophilic syndromes: current concepts and treatments |journal=Br. J. Haematol. |volume=145 |issue=3 |pages=271–85 |year=2009 |pmid=19243381 |doi=10.1111/j.1365-2141.2009.07599.x |url=}}</ref>
:*[[Allergy differential diagnosis|Allergic diseases]]
:*[[Allergy differential diagnosis|Allergic diseases]]
:*[[Atopic dermatitis]]
:*[[Atopic dermatitis]]
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:*[[Eosinophilic pneumonia]]
:*[[Eosinophilic pneumonia]]
:*[[Hypersensitivities|Hypersensitivity diseases]]
:*[[Hypersensitivities|Hypersensitivity diseases]]
:*Malignancy with secondary eosinophilia
:*[[Malignancy]] with secondary [[eosinophilia]]


==Epidemiology and Demographics==
==Epidemiology and Demographics==
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== Treatment ==
== Treatment ==
=== Medical Therapy ===
=== Medical Therapy ===
*The medical management of hypereosinophilic syndrome is divided into 2 categories: presence of FIP1L1/PDGFRA [[mutation]], and absence of FIP1L1/PDGFRA [[mutation]].<ref name="lupdate">Hypereosinophilic syndrome: an update.  http://www.pneumonologia.gr/articlefiles/20070228_Hypereosinophilic_Syndrome_An_Update.pdf Accessed on  April 4, 2016</ref>
*The [[Medical management company|medical management]] of hypereosinophilic syndrome is divided into 2 categories: presence of FIP1L1/PDGFRA [[mutation]], and absence of FIP1L1/PDGFRA [[mutation]].<ref name="lupdate">Hypereosinophilic syndrome: an update.  http://www.pneumonologia.gr/articlefiles/20070228_Hypereosinophilic_Syndrome_An_Update.pdf Accessed on  April 4, 2016</ref>
::*Treatment of choice for patients with FIP1L1/PDGFRA [[mutation]] is [[imatinib]]
::*Treatment of choice for [[Patient|patients]] with FIP1L1/PDGFRA [[mutation]] is [[imatinib]]
::*First line treatment for patients without FIP1L1/PDGFRA [[mutation]] is [[Glucocorticoids|glucocorticoid therapy]].  
::*[[First-line treatment|First line treatment]] for [[Patient|patients]] without FIP1L1/PDGFRA [[mutation]] is [[Glucocorticoids|glucocorticoid therapy]].  
::*Initial high-dose [[prednisone]] is typically initiated at a dose of 1 mg/kg/day  
::*Initial high-dose [[prednisone]] is typically initiated at a dose of 1 mg/kg/day  
::*Second line treatment for [[Patient|patients]] without FIP1L1/PDGFRA [[mutation]] include [[interferon alpha]] and [[hydroxyurea]].
::*Second line treatment for [[Patient|patients]] without FIP1L1/PDGFRA [[mutation]] include [[interferon alpha]] and [[hydroxyurea]].
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=== Surgery ===
=== Surgery ===
* Surgical intervention is not recommended for the management of hypereosinophilic syndrome.
* [[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.
* In some cases, [[Surgery|surgical intervention]] may be required to reduce [[pain]] in [[Patient|patients]] with [[spleen]] enlargement due to hypereosinophilic syndrome.


=== Prevention ===
=== Prevention ===
*There are no primary preventive measures available for hypereosinophilic syndrome.<ref name="lupdate">Hypereosinophilic syndrome: an update.  http://www.pneumonologia.gr/articlefiles/20070228_Hypereosinophilic_Syndrome_An_Update.pdf Accessed on  April 4, 2016</ref>
*There are no [[Primary prevention|primary preventive]] measures available for hypereosinophilic syndrome.<ref name="lupdate">Hypereosinophilic syndrome: an update.  http://www.pneumonologia.gr/articlefiles/20070228_Hypereosinophilic_Syndrome_An_Update.pdf Accessed on  April 4, 2016</ref>
*There are no effective measures for the primary prevention of 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 periodically every 6 or 12 months depending on the clinical progression.   
*Once [[Diagnosis|diagnosed]] and successfully treated, [[Patient|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.
*Follow-up testing includes the following [[Test|tests]]: [[complete blood count]], [[Biochemistry|biochemical profile]] ([[Liver function tests|liver enzymes]], [[creatine kinase]], [[renal function]], and [[troponin]]), [[electrocardiogram]], and [[Biopsy|tissue biopsies]].


==References==
==References==

Latest revision as of 13:51, 11 April 2019

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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. 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. 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. There are some associations with chronic eosinophilic leukemia as it shows similar characteristics and genetic defects. 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. 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.[1]
  • In 2003, PDGFRA and FIP1L1 gene mutations were first identified in the pathogenesis of hypereosinophilic syndrome.[2]

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

Pathophysiology

  • PDGFRA gene
  • PDGFRB gene
  • FGFR1 gene

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

Race

  • Caucasian individuals are more likely to develop cancer of unknown primary origin.[6]

Risk Factors

Natural History, Complications and Prognosis

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

Laboratory Findings

Imaging Findings

  • There are no imaging findings associated with hypereosinophilic syndrome.

Other Diagnostic Studies

Treatment

Medical Therapy

Surgery

Prevention

References

  1. Hardy WR, Anderson RE (1968). "The hypereosinophilic syndromes". Ann. Intern. Med. 68 (6): 1220–9. PMID 5653621.
  2. 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.
  3. 3.0 3.1 3.2 3.3 3.4 3.5 3.6 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.
  4. 4.0 4.1 4.2 4.3 Weller PF (1991). "The immunobiology of eosinophils". N. Engl. J. Med. 324 (16): 1110–8. doi:10.1056/NEJM199104183241607. PMID 2008184.
  5. 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.
  6. 6.0 6.1 6.2 6.3 6.4 Hypereosinophilic syndrome: an update. http://www.pneumonologia.gr/articlefiles/20070228_Hypereosinophilic_Syndrome_An_Update.pdf Accessed on April 4, 2016