Transcript
Hypereosinophilic Syndrome
Yoavanit Srivaro M.D.
Outline
• Historical Background
• Eosinophil:Morphology,Production,
Tissue Distribution
• Definition
• Pathogenesis
• Epidemiology
• Classification
• Clinical manifestation
• Diagnosis
• Treatment
Historical Background
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 ptswith imatinib
2002 Characteriation of the 1st PDGFR alpha rearrangement
2003 Identification of the FIP1L1-PDGFR alpha fusion as tx target of imatinib
Eosinophil
• Morphology
• Production
• Tissue Distribution
Eosinophil: Morphology
Kita H. et al.Middleton's Allergy ; 8th edition. 2014. p. 265-79
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, thromboxane; TGF-β, transforming growth factor-β; VEGF, vascular endothelial growth factor.
Legend:
From: Chapter 62. Eosinophils and Their Disorders
Williams Hematology, 8e, 2010
Kita H. et al.Middleton's Allergy ; 8th edition. 2014. p. 265-79
Eosinophil:Production
Kita H. et al.Middleton's Allergy ; 8th edition. 2014. p. 265-79
Kita H. et al.Middleton's Allergy ; 8th edition. 2014. p. 265-79
Kita H. et al.Middleton's Allergy ; 8th edition. 2014. p. 265-79
Kita H. et al.Middleton's Allergy ; 8th edition. 2014. p. 265-79
Kita H. et al.Middleton's Allergy ; 8th edition. 2014. p. 265-79
Kita H. et al.Middleton's Allergy ; 8th edition. 2014. p. 265-79
Kita H. et al.Middleton's Allergy ; 8th edition. 2014. p. 265-79
Kita H. et al.Middleton's Allergy ; 8th edition. 2014. p. 265-79
Kita H. et al.Middleton's Allergy ; 8th edition. 2014. p. 265-79
Kita H. et al.Middleton's Allergy ; 8th edition. 2014. p. 265-79
Eosinophil:Production
• Hematopoietic factors for eosinophilproduction & differentiation
- IL-3
- IL-5
- GM-CSF
Kita H. et al.Middleton's Allergy ; 8th edition. 2014. p. 265-79
Kita H. et al.Middleton's Allergy ; 8th edition. 2014. p. 265-79
Kita H. et al.Middleton's Allergy ; 8th edition. 2014. p. 265-79
Kita H. et al.Middleton's Allergy ; 8th edition. 2014. p. 265-79
Kita H. et al.Middleton's Allergy ; 8th edition. 2014. p. 265-79
Kita H. et al.Middleton's Allergy ; 8th edition. 2014. p. 265-79
Kita H. et al.Middleton's Allergy ; 8th edition. 2014. p. 265-79
Kita H. et al.Middleton's Allergy ; 8th edition. 2014. p. 265-79
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.
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
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
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.
Klion AD. et al.Middleton's Allergy ; 8th edition. 2014. p. 1205-23.
Klion AD. et al.Middleton's Allergy ; 8th edition. 2014. p. 1205-23.
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.
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.
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 degranulationin 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.
HE-related organ damage
Organ dysfunction With
Marked tissue eosinophilinfiltrates
And/OrExtensive 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 orrecurrent 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.
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.
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
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.
Epidemiology
Surveillance, Epidemiology, and End Results (SEER) database
• Prevalence of HES or chronic eosinophilicleukemia 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 hypereosinophilicsyndrome in the United States and an estimate of all hypereosinophilic syndrome incidence. J Allergy Clin
Immunol 2010;126: 179-81.
•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 hypereosinophilicsyndrome in the United States and an estimate of all hypereosinophilic syndrome incidence. J Allergy Clin
Immunol 2010;126: 179-81.
•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 hypereosinophilicsyndrome in the United States and an estimate of all hypereosinophilic syndrome incidence. J Allergy Clin
Immunol 2010;126: 179-81.
Classification
Klion AD. et al.Middleton's Allergy ; 8th edition. 2014. p. 1205-23.
Classification
Klion AD. et al.Middleton's Allergy ; 8th edition. 2014. p. 1205-23.
Classification
Klion AD. et al.Middleton's Allergy ; 8th edition. 2014. p. 1205-23.
Classification
Klion AD. et al.Middleton's Allergy ; 8th edition. 2014. p. 1205-1223.
Classification
Klion AD. et al.Middleton's Allergy ; 8th edition. 2014. p. 1205-23.
Classification
Klion AD. et al.Middleton's Allergy ; 8th edition. 2014. p. 1205-23.
Classification
Klion AD. et al.Middleton's Allergy ; 8th edition. 2014. p. 1205-23.
Classification
Klion AD. et al.Middleton's Allergy ; 8th edition. 2014. p. 1205-23.
Classification
Myeloproliferative forms of HES
• Mutation in hematopoietic multipotentprecursor cells: primary stimulation of the eosinophilia
• Mutation-related gain-of-function kinasespecifically 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.
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.
•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.
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.
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.
Classification
Klion AD. et al.Middleton's Allergy ; 8th edition. 2014. p. 1205-23.
Classification
Klion AD. et al.Middleton's Allergy ; 8th edition. 2014. p. 1205-23.
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.
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.
Classification
Klion AD. et al.Middleton's Allergy ; 8th edition. 2014. p. 1205-23.
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.
Classification
Klion AD. et al.Middleton's Allergy ; 8th edition. 2013. p. 1205-23.
Classification
Undefined forms of HESEpisodic 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.
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.
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.
Classification
Klion AD. et al.Middleton's Allergy ; 8th edition. 2014. p. 1205-1223.
Classification
Klion AD. et al.Middleton's Allergy ; 8th edition. 2014. p. 1205-23.
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.
Clinical manifestation
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.
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.
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.
Cardiac Disease
Second stage of heart disease
Thrombus formation :ventricular endocardium
Progressive scarring :entrapment of chordaetendineae
- Mitral valve regurgitation
- Tricuspid valve regurgitation
Endomyocardial fibrosis: restrictive cardiomyopathy
Klion AD. et al.Middleton's Allergy ; 8th edition. 2014. p. 1205-23.
Cardiac Disease
Second stage of heart disease
Thrombus formation :ventricular endocardium
Progressive scarring :entrapment of chordaetendineae
- Mitral valve regurgitation
- Tricuspid valve regurgitation
Endomyocardial fibrosis: restrictive cardiomyopathy
Klion AD. et al.Middleton's Allergy ; 8th edition. 2014. p. 1205-23.
Klion AD. et al.Middleton's Allergy ; 8th edition. 2014. p. 1205-23.
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.
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.
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.
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.
Moore PM, Harley JB, Fauci AS. Neurologic dysfunction in the idiopathic hypereosinophilic syndrome. Annals
of internal medicine. 1985;102(1):109-14.
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.
Moore PM, Harley JB, Fauci AS. Neurologic dysfunction in the idiopathic hypereosinophilic syndrome. Annals
of internal medicine. 1985;102(1):109-14.
Moore PM, Harley JB, Fauci AS. Neurologic dysfunction in the idiopathic hypereosinophilic syndrome. Annals
of internal medicine. 1985;102(1):109-14.
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.
Moore PM, Harley JB, Fauci AS. Neurologic dysfunction in the idiopathic hypereosinophilic syndrome. Annals
of internal medicine. 1985;102(1):109-14.
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.
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.
Leiferman KM, Gleich GJ, Peters MS. Dermatologic manifestations of the hypereosinophilic syndromes. Immunology and allergy clinics of North America. 2007;27(3):415-41.
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.
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.
Leiferman KM, Gleich GJ, Peters MS. Dermatologic manifestations of the hypereosinophilic syndromes. Immunology and allergy clinics of North America. 2007;27(3):415-41.
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.
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.
Immunologic abnormalities
Elevated IgE
• Lymphoproliferative or episodic angioedemavariants of HES
• Better prognosis
Klion AD. et al.Middleton's Allergy ; 8th edition. 2014. p. 1205-23.
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
• Myeloproliferativevariant of HES• Require cytotoxictherapy• Less likely to respond to prednisolone
Diagnosis
F.H. Hsieh / Ann Allergy Asthma Immunol 112 (2014) 484e488
Myeloproliferativevariant
F.H. Hsieh / Ann Allergy Asthma Immunol 112 (2014) 484e488
Lymphoproliferativevariant
F.H. Hsieh / Ann Allergy Asthma Immunol 112 (2014) 484e488
Evaluate end organ
involvement
Treatment
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
FIG 2. Response to treatment. The bars represent response rates after 1 month of therapy
Corticosteroid monotherapyinduced complete or partialresponses 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.
FIG 2. Response to treatment. The bars represent response rates after 1 month of therapy
Hydroxyurea monotherapyinduced 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.
FIG 2. Response to treatment. The bars represent response rates after 1 month of therapy
IFN-alpha monotherapyinduced 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.
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.
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.
68 Pts received Imatinib
17 Pts FP -positive 43 Pts
FP -negative
15 Pts
Complete response
2 PtsNon
response
6 +4PtsComplete +Partial
response
33 PtsNon
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.
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?
Summary
• Serious complications of hypereosinophilia
:require urgent tx
1) Myocardial damage
2) Pulmonary involvement with hypoxia
3) Neurological involvement
Summary
• Failure to detect and underlying cause of eosinophilia Diagnostic test to identify of HES variant
Thank You
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