hypereosinophilic syndromes an historical overview christopher spry
DESCRIPTION
‘Development of Diagnostic Criteria and Research Tools for the Study of Idiopathic Hypereosinophilic Syndromes’, 24-25 June 2003. Hypereosinophilic Syndromes An historical overview Christopher Spry. Eosinophils. - PowerPoint PPT PresentationTRANSCRIPT
![Page 1: Hypereosinophilic Syndromes An historical overview Christopher Spry](https://reader035.vdocuments.net/reader035/viewer/2022062408/56813ab6550346895da2b8f0/html5/thumbnails/1.jpg)
![Page 2: Hypereosinophilic Syndromes An historical overview Christopher Spry](https://reader035.vdocuments.net/reader035/viewer/2022062408/56813ab6550346895da2b8f0/html5/thumbnails/2.jpg)
‘Development of Diagnostic Criteria and Research Tools for the Study of Idiopathic Hypereosinophilic Syndromes’, 24-25 June 2003
Hypereosinophilic SyndromesAn historical overview
Christopher Spry
Eosinophils
![Page 3: Hypereosinophilic Syndromes An historical overview Christopher Spry](https://reader035.vdocuments.net/reader035/viewer/2022062408/56813ab6550346895da2b8f0/html5/thumbnails/3.jpg)
“The goddess Eos, … rising now to bring light to immortals and to mortals.” Homer’s Odyssey 5.1
![Page 4: Hypereosinophilic Syndromes An historical overview Christopher Spry](https://reader035.vdocuments.net/reader035/viewer/2022062408/56813ab6550346895da2b8f0/html5/thumbnails/4.jpg)
1871, Eosin Y was first marketed by BASF in Germany
![Page 5: Hypereosinophilic Syndromes An historical overview Christopher Spry](https://reader035.vdocuments.net/reader035/viewer/2022062408/56813ab6550346895da2b8f0/html5/thumbnails/5.jpg)
1879, Paul Ehrlich stained eosinophils, suggested their bone marrow origin & discussed eosinophilic leukemia
1879
![Page 6: Hypereosinophilic Syndromes An historical overview Christopher Spry](https://reader035.vdocuments.net/reader035/viewer/2022062408/56813ab6550346895da2b8f0/html5/thumbnails/6.jpg)
Early cases of ‘eosinophilic leukemia’
1861 & 1876, (Brown 1898) Eosinophilic leukemia diagnosed on unstained blood samples?
1879 onwards, eosinophilic disorders were defined using Ehrlich’s triple stain on blood smears and H & E on tissue sections
1910, water & acetone was introduced to lyse RBC so that accurate wet counts could be made of blood eosinophils
![Page 7: Hypereosinophilic Syndromes An historical overview Christopher Spry](https://reader035.vdocuments.net/reader035/viewer/2022062408/56813ab6550346895da2b8f0/html5/thumbnails/7.jpg)
1919, Shapiro, L.G. illustrated ‘Eosinophilic (polymorphonuclear) leukemia’
![Page 8: Hypereosinophilic Syndromes An historical overview Christopher Spry](https://reader035.vdocuments.net/reader035/viewer/2022062408/56813ab6550346895da2b8f0/html5/thumbnails/8.jpg)
Eosinophil morphology in HES
VacuolesNuclear hyper-segmentationReduced granules
![Page 9: Hypereosinophilic Syndromes An historical overview Christopher Spry](https://reader035.vdocuments.net/reader035/viewer/2022062408/56813ab6550346895da2b8f0/html5/thumbnails/9.jpg)
Eosinophilia and heart disease 1893 Reinbach, & 1936 Löffler
“Left ventricular cavity in endomyocardiopathy with eosinophilia (case 2). Cavity is nearly filled withgranular friable thrombus firmly attached to thickened endocardium.”
![Page 10: Hypereosinophilic Syndromes An historical overview Christopher Spry](https://reader035.vdocuments.net/reader035/viewer/2022062408/56813ab6550346895da2b8f0/html5/thumbnails/10.jpg)
DefinitionsLeukemia or a persistent eosinophilia?
1912, First patient reported in the USA: ‘myeloid leukemia’
1922, First HES patient reported in the UK: ‘Persistent eosinophilia’
1938, Review of 19 patients with HES: ‘unexplained eosinophilia’
![Page 11: Hypereosinophilic Syndromes An historical overview Christopher Spry](https://reader035.vdocuments.net/reader035/viewer/2022062408/56813ab6550346895da2b8f0/html5/thumbnails/11.jpg)
‘Hypereosinophilic syndromes’
1968, Hardy & Anderson introduced the term ‘hypereosinophilic syndromes’ to cover both malignant and non-malignant diseases of eosinophils
1969, Benvenisti & Ultmann reviewed 48 cases of ‘eosinophilic leukaemia’
![Page 12: Hypereosinophilic Syndromes An historical overview Christopher Spry](https://reader035.vdocuments.net/reader035/viewer/2022062408/56813ab6550346895da2b8f0/html5/thumbnails/12.jpg)
Eosinophilic leukemia is a distinct disease
1957, Bousser: Questionnaire and analysis of patients in France and elsewhere with eosinophilic disorders: two diseases: treat the non-malignant disease with steroids and anticoagulants
Bousser J. (1957) Eosinophilie et leucemie. Sang 28, 553-80
![Page 13: Hypereosinophilic Syndromes An historical overview Christopher Spry](https://reader035.vdocuments.net/reader035/viewer/2022062408/56813ab6550346895da2b8f0/html5/thumbnails/13.jpg)
NIAID program defines HES
1969, Sheldon Wolff set up a group to study vasculitic diseases: distinguished eosinophilic leukemia and HES; none had polyarteritis nodosa; proposed criteria for diagnosing ‘the hypereosinophilic syndrome’ (HES); several had laboratory features of CML without clinical progression to leukemia.
Tony Fauci with Victor Ferrans and others studied over 50 patients with HES, reported in 1982. ‘Idiopathic’ added to ‘HES’.
![Page 14: Hypereosinophilic Syndromes An historical overview Christopher Spry](https://reader035.vdocuments.net/reader035/viewer/2022062408/56813ab6550346895da2b8f0/html5/thumbnails/14.jpg)
1970, 3H-thymidine labelled cells, autoradiographs
Thoracic duct lymph Bone marrow eosinophil metaphase
![Page 15: Hypereosinophilic Syndromes An historical overview Christopher Spry](https://reader035.vdocuments.net/reader035/viewer/2022062408/56813ab6550346895da2b8f0/html5/thumbnails/15.jpg)
T lymphocytes that induce eosinophilia in rats with trichinosis
Thoracic duct lymph
Normal Infected
Large pyroninophilic lymphocytes
![Page 16: Hypereosinophilic Syndromes An historical overview Christopher Spry](https://reader035.vdocuments.net/reader035/viewer/2022062408/56813ab6550346895da2b8f0/html5/thumbnails/16.jpg)
A circulating factor? From T lymphocytes?
1982 Patient and child with eosinophilia 1985-6 Human IL-5 defined. GM-CSF & IL-3
involved too. IL-5-producing T-cell clones found in 16/60
patients with HES
![Page 17: Hypereosinophilic Syndromes An historical overview Christopher Spry](https://reader035.vdocuments.net/reader035/viewer/2022062408/56813ab6550346895da2b8f0/html5/thumbnails/17.jpg)
A chromosomal defect?
1965 Abnormal acrocentric chromosome in two patients: Is this a type of CML? Subsequently, many chromosomal defects described in chromosomes 5,7, 8, 12, 16 and 22
1975 Several features of CML noted, but Phi-negative and no bcr-abl fusion protein tyrosine kinase was found
1994 Clonality detected in some patients 2003 Deletion of chromosome 4 (q12) and
generation of a FIP1L1-PDGFRα tyrosine kinase detected in 9/16 patients
![Page 18: Hypereosinophilic Syndromes An historical overview Christopher Spry](https://reader035.vdocuments.net/reader035/viewer/2022062408/56813ab6550346895da2b8f0/html5/thumbnails/18.jpg)
Idiopathic(?) HES
Roufosse F, Cogan E, Goldman M. The hypereosinophilic syndrome revisited. Annu Rev Med. 2003; 54:169-84.
“.. the term idiopathic should be abandoned in the classification of HES [now that we know there are] myeloproliferative and lymphocytic variants of the HES.
![Page 19: Hypereosinophilic Syndromes An historical overview Christopher Spry](https://reader035.vdocuments.net/reader035/viewer/2022062408/56813ab6550346895da2b8f0/html5/thumbnails/19.jpg)
Defining patients who do not have HES
Nail ridges
Pruritic skin lesions
For example:
1981, Spanish toxic oil syndrome; eosinophilia myalgia syndrome
1985, M-4Eo variant of myelomonocytic leukemia
1984, Episodic angioedema associated with eosinophilia
![Page 20: Hypereosinophilic Syndromes An historical overview Christopher Spry](https://reader035.vdocuments.net/reader035/viewer/2022062408/56813ab6550346895da2b8f0/html5/thumbnails/20.jpg)
Major causes of death in HES1. Eosinophilic endomyocardial disease
Fibrosis
Thrombus
Thrombus liquefaction
Hypertrophy
Left ventricle
Thrombosis in the late fibrotic stage
![Page 21: Hypereosinophilic Syndromes An historical overview Christopher Spry](https://reader035.vdocuments.net/reader035/viewer/2022062408/56813ab6550346895da2b8f0/html5/thumbnails/21.jpg)
1981, eosinophilic endomyocardial disease
Left ventricular apex ‘blunted’ Resected tissue
![Page 22: Hypereosinophilic Syndromes An historical overview Christopher Spry](https://reader035.vdocuments.net/reader035/viewer/2022062408/56813ab6550346895da2b8f0/html5/thumbnails/22.jpg)
1987, MBP in the heart in eosinophilic endomyocardial disease
Fluorescent anti-MBP
Endocardium
Adjacent sections
![Page 23: Hypereosinophilic Syndromes An historical overview Christopher Spry](https://reader035.vdocuments.net/reader035/viewer/2022062408/56813ab6550346895da2b8f0/html5/thumbnails/23.jpg)
Eosinophil degranulating onto a heart cell in E-EMF
Electron-dense material
Eosinophil
Heart cell
![Page 24: Hypereosinophilic Syndromes An historical overview Christopher Spry](https://reader035.vdocuments.net/reader035/viewer/2022062408/56813ab6550346895da2b8f0/html5/thumbnails/24.jpg)
Serum ECP levels in HES & EED
Ng/mlHighest levels were in patients with heart disease
![Page 25: Hypereosinophilic Syndromes An historical overview Christopher Spry](https://reader035.vdocuments.net/reader035/viewer/2022062408/56813ab6550346895da2b8f0/html5/thumbnails/25.jpg)
Effects of eosinophil supernatants on isolated rat heart cells and mitochondria
![Page 26: Hypereosinophilic Syndromes An historical overview Christopher Spry](https://reader035.vdocuments.net/reader035/viewer/2022062408/56813ab6550346895da2b8f0/html5/thumbnails/26.jpg)
Major causes of death in HES2. Thrombi & emboli
1982 Retinal vascular occlusions in HES
![Page 27: Hypereosinophilic Syndromes An historical overview Christopher Spry](https://reader035.vdocuments.net/reader035/viewer/2022062408/56813ab6550346895da2b8f0/html5/thumbnails/27.jpg)
Treatment of HES
•1912, Radiotherapy
•1919, Splenectomy and splenic irradiation
•1953, Steroids and ACTH
•1970s, Hydroxyurea
•1970s, Vincristine and other cytotoxic drugs
•1970s, Anticoagulants and anti-platelet drugs
•1974, Leukapheresis and plasma exchange
•1987, Bone marrow transplantation
•1994, Interferon alpha
•2002, Imatinib mesylate (Gleevec)
![Page 28: Hypereosinophilic Syndromes An historical overview Christopher Spry](https://reader035.vdocuments.net/reader035/viewer/2022062408/56813ab6550346895da2b8f0/html5/thumbnails/28.jpg)
<1975 mean survival of 58 patients with HESAbout 12 months from diagnosis
In some cases, the cause of death may have been aggressive chemotherapy attempting to induce ‘remission’.
![Page 29: Hypereosinophilic Syndromes An historical overview Christopher Spry](https://reader035.vdocuments.net/reader035/viewer/2022062408/56813ab6550346895da2b8f0/html5/thumbnails/29.jpg)
1992, onset & death, 30 patients with HES
M/F: 26/4, 6 died. There may be a bimodal age distribution.
![Page 30: Hypereosinophilic Syndromes An historical overview Christopher Spry](https://reader035.vdocuments.net/reader035/viewer/2022062408/56813ab6550346895da2b8f0/html5/thumbnails/30.jpg)
1974-1994, mean survival of 54 patients with HES Over 14 years from diagnosis
Treatment was symptomatic and no attempt was made to induce a ‘remission’.
![Page 31: Hypereosinophilic Syndromes An historical overview Christopher Spry](https://reader035.vdocuments.net/reader035/viewer/2022062408/56813ab6550346895da2b8f0/html5/thumbnails/31.jpg)
Paul Ehrlich, 1854 - 1915
c 1900
![Page 32: Hypereosinophilic Syndromes An historical overview Christopher Spry](https://reader035.vdocuments.net/reader035/viewer/2022062408/56813ab6550346895da2b8f0/html5/thumbnails/32.jpg)
Finally, thanks to all those present and many others!
Particularly:
1968, Paul Beeson & Tony Basten for introducing me to eosinophils
1970, Gerry Gleich for leading the way
1974, John Goodwin for introducing me to my first patient with HES
2003, Amy Klion for the wonderful and unexpected invitation to be here!
Many other eosinophil colleagues and friends, who have often tried and sometimes succeeded in keeping me on the right eosinophilic rails!
![Page 33: Hypereosinophilic Syndromes An historical overview Christopher Spry](https://reader035.vdocuments.net/reader035/viewer/2022062408/56813ab6550346895da2b8f0/html5/thumbnails/33.jpg)