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Hypereosinophilic syndrome

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Hypereosinophilic syndrome

Presented by Yoavanit Srivaro, MD.

Jan9, 2015

Published in: Health & Medicine
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Hypereosinophilic syndrome

  1. 1. Hypereosinophilic Syndrome Yoavanit Srivaro M.D.
  2. 2. Outline • Historical Background • Eosinophil:Morphology,Production, Tissue Distribution • Definition • Pathogenesis • Epidemiology • Classification • Clinical manifestation • Diagnosis • Treatment
  3. 3. Historical Background
  4. 4. Year Event 1846 1st observed by Wharton Jones 1879 1st named by Paul Ehrlich 1968 Term Hypereosinophilic syndrome coined by Hardy and Anderson 1979 Diagnosis critierias for HES established by Chusid and colleagues 1994 1st description of lymphocyte-variant hypereosinophilia 1998 Identification of rearrangement of the FGR1 gene 2001 WHO diagnostic criteria for HES and CEL 2001-2002 Succesful empiric treatment of HES pts with imatinib 2002 Characteriation of the 1st PDGFR alpha rearrangement 2003 Identification of the FIP1L1-PDGFR alpha
  5. 5. Eosinophil • Morphology • Production • Tissue Distribution
  6. 6. Eosinophil: Morphology
  7. 7. Kita H. et al.Middleton's Allergy ; 8th edition. 2014. p. 265-79
  8. 8. Date of download: 12/28/2014 Copyright © 2014 McGraw-Hill Education. All rights reserved. Transmission electron micrograph (×10,000) of an eosinophil showing the characteristic binucleate cell with specific granules containing an electron dense core. The major contents of the cell are listed. (Courtesy of Dr. A. Dewar, National Heart and Lung Institute.) CLC, Charcot Leyden crystal; ECP, eosinophil cationic protein; EDN, eosinophil-derived neurotoxin; EPO, eosinophil peroxidase; GF, growth factor; GM-CSF, granulocyte-monocyte colony-stimulating growth factor; HETE, hydroxyeicosatetraenoic acid; LT, leukotriene; MBP, major basic protein; PAF, platelet-activating factor; PDGF, platelet-derived growth factor; PG, prostaglandin; PSGL, P-selectin glycoprotein ligand; TBX, Legend: From: Chapter 62. Eosinophils and Their Disorders Williams Hematology, 8e, 2010
  9. 9. Kita H. et al.Middleton's Allergy ; 8th edition. 2014. p. 265-79
  10. 10. Eosinophil:Production
  11. 11. Kita H. et al.Middleton's Allergy ; 8th edition. 2014. p. 265-79
  12. 12. Kita H. et al.Middleton's Allergy ; 8th edition. 2014. p. 265-79
  13. 13. Kita H. et al.Middleton's Allergy ; 8th edition. 2014. p. 265-79
  14. 14. Kita H. et al.Middleton's Allergy ; 8th edition. 2014. p. 265-79
  15. 15. Kita H. et al.Middleton's Allergy ; 8th edition. 2014. p. 265-79
  16. 16. Kita H. et al.Middleton's Allergy ; 8th edition. 2014. p. 265-79
  17. 17. Kita H. et al.Middleton's Allergy ; 8th edition. 2014. p. 265-79
  18. 18. Kita H. et al.Middleton's Allergy ; 8th edition. 2014. p. 265-79
  19. 19. Kita H. et al.Middleton's Allergy ; 8th edition. 2014. p. 265-79
  20. 20. Kita H. et al.Middleton's Allergy ; 8th edition. 2014. p. 265-79
  21. 21. Eosinophil:Production • Hematopoietic factors for eosinophil production & differentiation - IL-3 - IL-5 - GM-CSF Kita H. et al.Middleton's Allergy ; 8th edition. 2014. p. 265-79
  22. 22. Kita H. et al.Middleton's Allergy ; 8th edition. 2014. p. 265-79
  23. 23. Kita H. et al.Middleton's Allergy ; 8th edition. 2014. p. 265-79
  24. 24. Kita H. et al.Middleton's Allergy ; 8th edition. 2014. p. 265-79
  25. 25. Kita H. et al.Middleton's Allergy ; 8th edition. 2014. p. 265-79
  26. 26. Kita H. et al.Middleton's Allergy ; 8th edition. 2014. p. 265-79
  27. 27. Kita H. et al.Middleton's Allergy ; 8th edition. 2014. p. 265-79
  28. 28. Kita H. et al.Middleton's Allergy ; 8th edition. 2014. p. 265-79
  29. 29. Ackerman SJ, Bochner BS. Mechanisms of eosinophilia in the pathogenesis of hypereosinophilic disorders. Immunology and allergy clinics of North America. 2007;27(3):357-75.
  30. 30. Eosinophil:Tissue Distribution • Primarily a tissue-dwelling cell • In humans the tissue eosinophil-to-blood ratio is about 100 : 1 • GI tract (but not the esophagus), regulated by eotaxin-1 • Eosinophils also home into the thymus, mammary gland, and uterus, also controlled by eotaxin-1 Kita H. et al.Middleton's Allergy ; 8th edition. 2014. p. 265-79
  31. 31. Eosinophil:Tissue Distribution • Mean bone marrow maturation& storage time is about 4.3 days • Short half-life of 8 to 18 hrs (after enter the blood) • Normal range of blood eosinophils is 0 to 500 cells/microliter • Exhibits diurnal variation in humans Lowest : morning Highest : evening • Tissue life span 2 to 5 days • Cytokines increase eosinophil survival in vitro up to 14 days Kita H. et al.Middleton's Allergy ; 8th edition. 2014. p. 265-79
  32. 32. Definition Eosinophilia Blood eosinophil count exceeding 500 cells/microliter Severity of eosinophilia • Mild eosinophilia 500 to 1,500 cells/microliter • Moderate eosinophilia 1,500 to 5,000 cells/microliter • Severe eosinophilia > 5,000 cells/microliter Roufosse F, Weller PF. Practical approach to the patient with hypereosinophilia. The Journal of allergy and clinical immunology. 2010;126(1):39-44.
  33. 33. Klion AD. et al.Middleton's Allergy ; 8th edition. 2014. p. 1205-23.
  34. 34. Klion AD. et al.Middleton's Allergy ; 8th edition. 2014. p. 1205-23.
  35. 35. Definition Diagnostic criteria for HES established by Chusid and colleagues,1975 1.Peripheral blood eosinophilia (>1,500 cells/microliter) for longer than 6 months 2.Evidence of eosinophil-related target organ damage 3.Exclusion of all other etiologies for eosinophilia Chusid MJ, Dale DC, West BC, Wolff SM. The hypereosinophilic syndrome: analysis of fourteen cases with review of the literature. Medicine. 1975;54(1):1-27.
  36. 36. Definition Contemporary consensus proposal on criteria and classification of eosinophilic disorders and related syndromes 1. Hypereosinophilia-absolute eosinophil count >1,500 cells/microlitr for 1 mo,checked on 2 occasions* 2. Evidence of eosinophil-mediated target organ damage 3. Exclusion of all other potential causes of hypereosinophilia Valent P, et al. Contemporary consensus proposal on criteria and classification of eosinophilic disorders and related syndromes. The Journal of allergy and clinical immunology. 2012;130(3):607-12.e9.
  37. 37. Definition *Tissue hypereosinophilia can be identified in addition to an elevated absolute eosinophil count with tissue hypereosinophilia, defined as: 1. Eosinophils >20% of nucleated cells in bone marrow 2. Extensive tissue infiltration of target organ by histologic analysis 3. Histologic evidence of eosinophil degranulation in a target tissue in the absence of eosinophils in that target tissue Valent P, et al. Contemporary consensus proposal on criteria and classification of eosinophilic disorders and related syndromes. The Journal of allergy and clinical immunology. 2012;130(3):607-12.e9.
  38. 38. HE-related organ damage Organ dysfunction With Marked tissue eosinophil infiltrates And/Or Extensive deposition of eosinophil-derived proteins In the presence or absence of marked tissue eosinophils (1) Fibrosis (lung, heart, digestive tract, skin, and others) (2) Thrombosis with or without thromboembolism (3) Cutaneous (including mucosal) erythema, edema/angioedema, ulceration, pruritus, and eczema (4) Peripheral or central neuropathy with chronic or recurrent neurologic deficit And 1 or more of the following Valent P, et al. Contemporary consensus proposal on criteria and classification of eosinophilic disorders and related syndromes. The Journal of allergy and clinical immunology. 2012;130(3):607-12.e9.
  39. 39. Pathogenesis • 2 Pathogenetically different conditions can trigger eosinophil growth & accumulation 1) Intrinsic defect of eosinophil-committed neoplastic progenitor cells : mutations including those involving PDGFR or FGFR1 2) overproduction of cytokines:IL-3 or IL-5 Valent P, Klion AD, Rosenwasser LJ, Arock M, Bochner BS, Butterfield JH, et al. ICON: Eosinophil Disorders. The World Allergy Organization journal. 2012;5(12):174-81.
  40. 40. Pathogenesis Valent P, Klion AD, Rosenwasser LJ, Arock M, Bochner BS, Butterfield JH, et al. ICON: Eosinophil Disorders. The World Allergy Organization journal. 2012;5(12):174-81. • Degree & pattern of organ involvement are governed by 2 distinct factors. 1) Increased production and/or persistent accumulation of (normal or neoplastic) eosinophils 2) Persistent activation of eosinophils
  41. 41. Pathogenesis • Mediators &substances : from activated eosinophils can cause 1) Tissue remodeling and/or tissue damage. 2) Activate platelets and endothelial cells 3) Alter the production/expression of prothrombotic and antifibrinolytic substances Tissue fibrosis and Thrombosis Valent P, Klion AD, Rosenwasser LJ, Arock M, Bochner BS, Butterfield JH, et al. ICON: Eosinophil Disorders. The World Allergy Organization journal. 2012;5(12):174-81.
  42. 42. Epidemiology Surveillance, Epidemiology, and End Results (SEER) database • Prevalence of HES or chronic eosinophilic leukemia in the United States is between 0.3 and 6.3 cases per 100,000 person-years Crane MM, Chang CM, Kobayashi MG, Weller PF. Incidence of myeloproliferative hypereosinophilic syndrome in the United States and an estimate of all hypereosinophilic syndrome incidence. J Allergy Clin Immunol 2010;126: 179-81.
  43. 43. •SEER 17 area registries •2001-2005 •131 incident cases •78 males & 53 females •Median age at dx : 52.5 years Crane MM, Chang CM, Kobayashi MG, Weller PF. Incidence of myeloproliferative hypereosinophilic syndrome in the United States and an estimate of all hypereosinophilic syndrome incidence. J Allergy Clin Immunol 2010;126: 179-81.
  44. 44. •SEER 17 area registries •2001-2005 •131 incident cases •78males & 53 females •Median age at dx : 52.5 years Crane MM, Chang CM, Kobayashi MG, Weller PF. Incidence of myeloproliferative hypereosinophilic syndrome in the United States and an estimate of all hypereosinophilic syndrome incidence. J Allergy Clin Immunol 2010;126: 179-81.
  45. 45. Classification Klion AD. et al.Middleton's Allergy ; 8th edition. 2014. p. 1205-23
  46. 46. Classification Klion AD. et al.Middleton's Allergy ; 8th edition. 2014. p. 1205-23.
  47. 47. Classification Klion AD. et al.Middleton's Allergy ; 8th edition. 2014. p. 1205-23.
  48. 48. Classification Klion AD. et al.Middleton's Allergy ; 8th edition. 2014. p. 1205-1223.
  49. 49. Classification Klion AD. et al.Middleton's Allergy ; 8th edition. 2014. p. 1205-23.
  50. 50. Classification Klion AD. et al.Middleton's Allergy ; 8th edition. 2014. p. 1205-23.
  51. 51. Classification Klion AD. et al.Middleton's Allergy ; 8th edition. 2014. p. 1205-23.
  52. 52. Classification Klion AD. et al.Middleton's Allergy ; 8th edition. 2014. p. 1205-23.
  53. 53. Classification Myeloproliferative forms of HES • Mutation in hematopoietic multipotent precursor cells: primary stimulation of the eosinophilia • Mutation-related gain-of-function kinase specifically involved in the pathogenesis (FIP1L1/PDGFR alpha-associated HES) Simon HU, et al. Refining the definition of hypereosinophilic syndrome. The Journal of allergy and clinical immunology. 2010;126(1):45-9.
  54. 54. Encodes Highly conserved protein involved in messenger RNA processing Encodes •Receptor tyrosine kinase •Platelet-derived growth factor receptor alpha Montgomery ND, et al. Diagnostic complexities of eosinophilia. Archives of pathology & laboratory medicine. 2013;137(2):259-69.
  55. 55. •The 4q12 deletion removes negative regulatory motifs encoded to the exon 12 breakpoint •Leading to constitutive activation of this receptor :Receptor tyrosine kinase :Platelet-derived growth factor receptor alpha Montgomery ND, et al. Diagnostic complexities of eosinophilia. Archives of pathology & laboratory medicine. 2013;137(2):259-69.
  56. 56. FIP1L1-PDGFRα enhances eosinophil development by Modifying the expression & activity of lineage-specific transcription factors through Ras/MEK and p38MAPK cascades Fukushima K,et al. FIP1L1-PDGFRalpha imposes eosinophil lineage commitment on hematopoietic stem/progenitor cells. The Journal of biological chemistry. 2009;284(12):7719-32.
  57. 57. Classification Myeloproliferative forms of HES • Clinical Hepatomegaly, Splenomegaly • Laboratory - Circulating myeloid precursors, Increased serum vitamin B12 or Tryptase, Anemia, Thrombocytopenia - Hematologic (myeloid fibrosis, left shift in maturation of myeloidprecursors) - And/or cytogenetic abnormalities suggestive of myeloproliferative disease. Simon HU, et al. Refining the definition of hypereosinophilic syndrome. The Journal of allergy and clinical immunology. 2010;126(1):45-9.
  58. 58. Classification Klion AD. et al.Middleton's Allergy ; 8th edition. 2014. p. 1205-23.
  59. 59. Classification Klion AD. et al.Middleton's Allergy ; 8th edition. 2014. p. 1205-23.
  60. 60. Classification Lymphocytic forms of HES • Lymphocytes generate increased amounts of at least 1 eosinophil hematopoietin - IL-3 and/or IL-5 - Primary cause of secondary polyclonal blood hypereosinophilia Simon HU, et al. Refining the definition of hypereosinophilic syndrome. The Journal of allergy and clinical immunology. 2010;126(1):45-9.
  61. 61. Classification Lymphocytic forms of HES • Aberrant T cells are most often CD3−CD4+ orCD3+CD4−CD8− • Typically present with dermatologic manifestations • Elevated serum IgE & TARC (CCL17) levels • Flow cytometry & T cell receptor rearrangement studies are useful in confirming the dx • Progression to T cell lymphomas occurs in fewer than 3% of these pts Klion AD. et al.Middleton's Allergy ; 8th edition. 2013. p. 1205-23.
  62. 62. Classification Klion AD. et al.Middleton's Allergy ; 8th edition. 2014. p. 1205-23.
  63. 63. Classification Overlap form of HES Organ-restricted eosinophilic disorders • Represent T cell–driven HES • Eosinophilic pneumonia, eosinophilic intrinsic asthma, CSS, Eosinophilic sinus disease, Eosinophilic dermatitis,EGID Simon HU, et al. Refining the definition of hypereosinophilic syndrome. The Journal of allergy and clinical immunology. 2010;126(1):45-9.
  64. 64. Classification Klion AD. et al.Middleton's Allergy ; 8th edition. 2013. p. 1205-23.
  65. 65. Classification Undefined forms of HES Episodic angioedema with eosinophilia (Gleich’s syndrome) • 1st described by Gerald Gleich and colleagues in 1984 • This 1st report described four pts (three males, one female) with - Recurrent episodes of angioedema and/or urticaria - 10% to 20% increase in body weight - Fever (three patients) - Hypereosinophilia - Elevated IgM - Leukocyte counts ( reach as high as 108,000 cells/microliter with 88% eosinophils.) • These four pts were followed for a period of 2 to 17 years & none of them developed organ involvement Banerji A,et al. Cytokine-associated angioedema syndromes including episodic angioedema with eosinophilia (Gleich's Syndrome). Immunology and allergy clinics of North America. 2006;26(4):769-81.
  66. 66. Classification Undefined forms of HES Episodic angioedema with eosinophilia (Gleich’s syndrome) • Clinical presentation and diagnosis - Recurrent episodes of # angioedema, urticaria,pruritus ,fever,weight gain # elevated serum IgM, oliguria, leukocytosis with eosinophilia &eosinophil degranulation in the dermis # an elevated IgE Banerji A,et al. Cytokine-associated angioedema syndromes including episodic angioedema with eosinophilia (Gleich's Syndrome). Immunology and allergy clinics of North America. 2006;26(4):769-81.
  67. 67. Classification Undefined forms of HES Episodic angioedema with eosinophilia (Gleich’s syndrome) • Clinical presentation and diagnosis - Episodes usually occur every few weeks to months - Complete resolution of symptoms between episodes - Good prognosis with no visceral organ involvement Banerji A,et al. Cytokine-associated angioedema syndromes including episodic angioedema with eosinophilia (Gleich's Syndrome). Immunology and allergy clinics of North America. 2006;26(4):769-81.
  68. 68. Classification Klion AD. et al.Middleton's Allergy ; 8th edition. 2014. p. 1205-1223.
  69. 69. Classification Klion AD. et al.Middleton's Allergy ; 8th edition. 2014. p. 1205-23.
  70. 70. F.H. Hsieh / Ann Allergy Asthma Immunol 112 (2014) 484e488 Valent P, et al. Contemporary consensus proposal on criteria and classification of eosinophilic disorders and related syndromes. The Journal of allergy and clinical immunology. 2012;130(3):607-12.e9.
  71. 71. Clinical manifestation
  72. 72. Clinical manifestation Ogbogu PU, et al. Hypereosinophilic syndrome: a multicenter, retrospective analysis of clinical characteristics and response to therapy. The Journal of allergy and clinical immunology. 2009;124(6):1319-25.e3.
  73. 73. Cardiac Disease • Acute, necrotic stage • Second stage of heart disease • Later thrombotic & fibrotic stage Klion AD. et al.Middleton's Allergy ; 8th edition. 2014. p. 1205-23.
  74. 74. Cardiac Disease Acute, necrotic stage  Early weeks of illness  Endocardial damage  Myocardial infiltration with eosinophils &lymphocytes  Myocardial necrosis  Eosinophil degranulation & microabscesses  Normal cardiac findings  Prominent subungual and conjunctival splinter hemorrhages.  Elevations of serum troponin Klion AD. et al.Middleton's Allergy ; 8th edition. 2014. p. 1205-23.
  75. 75. Cardiac Disease Second stage of heart disease  Thrombus formation :ventricular endocardium  Progressive scarring :entrapment of chordae tendineae - Mitral valve regurgitation - Tricuspid valve regurgitation  Endomyocardial fibrosis: restrictive cardiomyopathy Klion AD. et al.Middleton's Allergy ; 8th edition. 2014. p. 1205-23.
  76. 76. Cardiac Disease Second stage of heart disease  Thrombus formation :ventricular endocardium  Progressive scarring :entrapment of chordae tendineae - Mitral valve regurgitation - Tricuspid valve regurgitation  Endomyocardial fibrosis: restrictive cardiomyopathy Klion AD. et al.Middleton's Allergy ; 8th edition. 2014. p. 1205-23.
  77. 77. Klion AD. et al.Middleton's Allergy ; 8th edition. 2014. p. 1205-23.
  78. 78. Cardiac Disease Later thrombotic & fibrotic stages  Signs & Symptoms - Dyspnea - Chest pain - Signs of LV&RV CHF - Murmurs of atrioventricular valve regurgitation - Cardiomegaly Klion AD. et al.Middleton's Allergy ; 8th edition. 2014. p. 1205-23.
  79. 79. Cardiac Disease Later thrombotic & fibrotic stages  Echocardiography & MRI - Intracardiac thrombi - Endomyocardial fibrosis  Benefit from - Medical tx for CHF - Valve replacement Klion AD. et al.Middleton's Allergy ; 8th edition. 2014. p. 1205-23.
  80. 80. Neurologic Complication • The first type : Embolic strokes • The second type : Encephalopathy : Upper motor neuron signs • The third type : Peripheral neuropathy Klion AD. et al.Middleton's Allergy ; 8th edition. 2014. p. 1205-23.
  81. 81. Neurologic Complication • The first type : Embolic strokes • The second type : Encephalopathy : Upper motor neuron signs • The third type : Peripheral neuropathy Klion AD. et al.Middleton's Allergy ; 8th edition. 2014. p. 1205-23.
  82. 82. Moore PM, Harley JB, Fauci AS. Neurologic dysfunction in the idiopathic hypereosinophilic syndrome. Annals of internal medicine. 1985;102(1):109-14.
  83. 83. Neurologic Complication • The first type : Embolic strokes • The second type : Encephalopathy : Upper motor neuron signs • The third type : Peripheral neuropathy Klion AD. et al.Middleton's Allergy ; 8th edition. 2013. p. 1205-23.
  84. 84. Moore PM, Harley JB, Fauci AS. Neurologic dysfunction in the idiopathic hypereosinophilic syndrome. Annals of internal medicine. 1985;102(1):109-14.
  85. 85. Moore PM, Harley JB, Fauci AS. Neurologic dysfunction in the idiopathic hypereosinophilic syndrome. Annals of internal medicine. 1985;102(1):109-14.
  86. 86. Neurologic Complication • The first type : Embolic strokes • The second type : Encephalopathy : Upper motor neuron signs • The third type : Peripheral neuropathy Klion AD et al.Middleton's Allergy ; 8th edition. 2014. p. 1205-23.
  87. 87. Moore PM, Harley JB, Fauci AS. Neurologic dysfunction in the idiopathic hypereosinophilic syndrome. Annals of internal medicine. 1985;102(1):109-14.
  88. 88. Skin Manifestation • Angioedema & urticaria • Pruritic papules or nodules • Cutaneous microthrombi or digital arteritis • Mucosal ulcers & lymphomatoid papulosis Klion AD. et al.Middleton's Allergy ; 8th edition. 2014. p. 1205-23.
  89. 89. Skin Manifestation • Angioedema & urticaria - Benign courses without cardiac or neurologic complications - Not require corticosteroid therapy, or respond to prednisone alone Klion AD. et al.Middleton's Allergy ; 8th edition. 2014. p. 1205-23.
  90. 90. Leiferman KM, Gleich GJ, Peters MS. Dermatologic manifestations of the hypereosinophilic syndromes. Immunology and allergy clinics of North America. 2007;27(3):415-41.
  91. 91. Skin Manifestation • Pruritic papules or nodules Biopsies • Perivascular infiltration with eosinophils • Mild or moderate perivascular neutrophilic & mononuclear infiltrates without vasculitis Klion AD. et al.Middleton's Allergy ; 8th edition. 2014. p. 1205-23.
  92. 92. Skin Manifestation • Mucosal ulcers & lymphomatoid papulosis - Refractory to therapy - Ulcer:Mouth, nose, pharynx, penis, esophagus, stomach & anus - PDGFRA-positive disease Klion AD. et al.Middleton's Allergy ; 8th edition. 2014. p. 1205-23.
  93. 93. Leiferman KM, Gleich GJ, Peters MS. Dermatologic manifestations of the hypereosinophilic syndromes. Immunology and allergy clinics of North America. 2007;27(3):415-41.
  94. 94. Respiratory Symptom • Chronic, persistent,nonproductive cough • Asthma • Respiratory symptoms due to CHF • Pulmonary emboli • Eosinophilic lung infiltrates • Pulmonary fibrosis with cardiac fibrosis Klion AD. et al.Middleton's Allergy ; 8th edition. 2014. p. 1205-23.
  95. 95. Gastrointestinal Symptom • Eosinophilic gastritis • Enterocolitis & colitis • Hepatic involvement - Chronic active hepatitis - Focal hepatic lesions - Eosinophilic cholangitis - Budd-Chiari syndrome from hepatic vein obstruction Klion AD. et al.Middleton's Allergy ; 8th edition. 2014. p. 1205-23.
  96. 96. Immunologic abnormalities Elevated IgE • Lymphoproliferative or episodic angioedema variants of HES • Better prognosis Klion AD. et al.Middleton's Allergy ; 8th edition. 2014. p. 1205-23.
  97. 97. Labaratory abnormalities Klion AD. et al.Middleton's Allergy ; 8th edition. 2014. p. 1205-23. •Elevated vitamin B12 levels •Abn LAP scores •Cytogenetic abnormalities •Myelofibrosis, myeloid dysplasia & basophilia • Myeloproliferative variant of HES • Require cytotoxic therapy • Less likely to respond to prednisolone
  98. 98. Diagnosis
  99. 99. F.H. Hsieh / Ann Allergy Asthma Immunol 112 (2014) 484e488 Myeloproliferative variant
  100. 100. F.H. Hsieh / Ann Allergy Asthma Immunol 112 (2014) 484e488 Lymphoproliferative variant
  101. 101. F.H. Hsieh / Ann Allergy Asthma Immunol 112 (2014) 484e488 Evaluate end organ involvement
  102. 102. Treatment
  103. 103. Treatment • Patients with eosinophilia without organ involvement - Benign course - Require no therapy. - Monitoring :serum troponin levels & echocardiographic q 6-months Klion AD. et al.Middleton's Allergy ; 8th edition. 2014. p. 1205-23.
  104. 104. Treatment • F/P-negative eosinophilic patients - A trial course of prednisone (60 mg/day or 1 mg/kg/ day) Klion AD. et al.Middleton's Allergy ; 8th edition. 2014. p. 1205-23.
  105. 105. Treatment • Patients with myeloproliferative variants of HES (documented PDGFRA mutations) - Imatinib 100 to 400 mg/day. - Clinical & hematologic response within 2 to 4 weeks - Newer tyrosine kinase inhibitors: nilotinib, sorafenib, & dasatinib Klion AD. et al.Middleton's Allergy ; 8th edition. 2014. p. 1205-23.
  106. 106. Treatment • Patients with other variants of HES with organ involvement Prednisone (1 mg/kg/day or 60 mg/day in adults) If blood eosinophilia is suppressed Tapered to an alternate-day schedule Klion AD. et al.Middleton's Allergy ; 8th edition. 2014. p. 1205-23.
  107. 107. Treatment • Second line drug for PDGFRA-NEGATIVE HES patients 1. Hydroxyurea 2. Interferon-α 3. Neutralizing anti-IL- 5 monoclonal antibodies Klion AD. et al.Middleton's Allergy ; 8th edition. 2014. p. 1205-23.
  108. 108. Treatment • Patients with aggressive disease that is unresponsive to standard therapies - Bone marrow transplantation Klion AD. et al.Middleton's Allergy ; 8th edition. 2014. p. 1205-23.
  109. 109. Treatment • Marked valvular compromise Cardiac surgery • Endomyocardial thrombosis Thrombectomy • Endomyocardial fibrosis Endomyocardectomy Klion AD. et al.Middleton's Allergy ; 8th edition. 2014. p. 1205-23.
  110. 110. Ogbogu PU, et al. Hypereosinophilic syndrome: a multicenter, retrospective analysis of clinical characteristics and response to therapy. The Journal of allergy and clinical immunology. 2009;124(6):1319-25.e3.
  111. 111. Result 18 of 161 patients (11%) (FIP1L1-PDGFR alpha) mutation—positive 29 of 168 patients (17%) Aberrant or clonal T-cell population. Ogbogu PU, et al. Hypereosinophilic syndrome: a multicenter, retrospective analysis of clinical characteristics and response to therapy. The Journal of allergy and clinical immunology. 2009;124(6):1319-25.e3.
  112. 112. FIG 2. Response to treatment. The bars represent response rates after 1 month of therapy Ogbogu PU, et al. Hypereosinophilic syndrome: a multicenter, retrospective analysis of clinical characteristics and response to therapy. The Journal of allergy and clinical immunology. 2009;124(6):1319-25.e3.
  113. 113. FIG 2. Response to treatment. The bars represent response rates after 1 month of therapy Corticosteroid monotherapy induced complete or partial responses at 1 month in 85% (120/141) Ogbogu PU, et al. Hypereosinophilic syndrome: a multicenter, retrospective analysis of clinical characteristics and response to therapy. The Journal of allergy and clinical immunology. 2009;124(6):1319-25.e3.
  114. 114. FIG 2. Response to treatment. The bars represent response rates after 1 month of therapy Hydroxyurea monotherapy induced complete responses at 1 month in 33% (6/18) Ogbogu PU, et al. Hypereosinophilic syndrome: a multicenter, retrospective analysis of clinical characteristics and response to therapy. The Journal of allergy and clinical immunology. 2009;124(6):1319-25.e3.
  115. 115. FIG 2. Response to treatment. The bars represent response rates after 1 month of therapy IFN-alpha monotherapy induced complete responses at 1 month in 17% (2/12) Ogbogu PU, et al. Hypereosinophilic syndrome: a multicenter, retrospective analysis of clinical characteristics and response to therapy. The Journal of allergy and clinical immunology. 2009;124(6):1319-25.e3.
  116. 116. FIG 2. Response to treatment. The bars represent response rates after 1 month of therapy Anti IL-5 monotherapy induced complete responses at 1 month in 80% (12/15) Ogbogu PU, et al. Hypereosinophilic syndrome: a multicenter, retrospective analysis of clinical characteristics and response to therapy. The Journal of allergy and clinical immunology. 2009;124(6):1319-25.e3.
  117. 117. FIG 2. Response to treatment. The bars represent response rates after 1 month of therapy Imatinib monotherapy induced complete responses at 1 month in 65% (20/31) Ogbogu PU, et al. Hypereosinophilic syndrome: a multicenter, retrospective analysis of clinical characteristics and response to therapy. The Journal of allergy and clinical immunology. 2009;124(6):1319-25.e3.
  118. 118. 68 Pts received Imatinib 17 Pts FP -positive 43 Pts FP -negative 15 Pts Complete response 2 Pts Non response 6 +4Pts Complete +Partial response 33 Pts Non response Ogbogu PU, et al. Hypereosinophilic syndrome: a multicenter, retrospective analysis of clinical characteristics and response to therapy. The Journal of allergy and clinical immunology. 2009;124(6):1319-25.e3.
  119. 119. Summary • Markedly increased blood eosinophilia >1,500 cells/microliter • Must first & foremost address 2 questions 1) Secondary to common and treatable underlying condition? 2) Itself causing rapidly progressive damage?
  120. 120. Summary • Serious complications of hypereosinophilia :require urgent tx 1) Myocardial damage 2) Pulmonary involvement with hypoxia 3) Neurological involvement
  121. 121. Summary • Failure to detect and underlying cause of eosinophilia Diagnostic test to identify of HES variant
  122. 122. Thank You

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