Αιχμές στην Παθολογία
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1 2 η ΕΠΙΣΤΗΜΟΝΙΚΗ ΗΜΕΡΙΔΑ Αιχμές στην Παθολογία ΔΙΑΓΝΩΣΤΙΚΗ ΠΡΟΣΕΓΓΙΣΗ ΗΩΣΙΝΟΦΙΛΙΑΣ Σταυρούλα Γιαννούλη Λέκτορας Παθολογίας-Αιματολογίας Β Πανεπιστημιακή Παθολογική Κλινική ΓΝΑ Ιπποκράτειο
2 Εosinophil: biology & function IL-5
3 Εosinophil: biology & function IL-5 plays crucial roles in eosinophilic development: - final differentiation and proliferation in the BM - BM release - tissular trafficking and activation - prevention of apoptotic limitation in tissues Kahn et al, Best Prct Res Clin Rheumatol, 2008
4 Eosinophilia Eosinophilia: blood eosinophil count exceeding 0.5 x 10 9 /L. Three levels of severity of eosinophilia - Mild: 0.5 to /L - Moderate: 1.5 to /L - Severe: Greater than /L Levels of blood eosinophilia are an imperfect correlate of the potential for end-organ damage /L is classically considered the level above which organ damage is more likely to occur. Τefferi et al, Mayo Clin Proc, 2010
5 Ηyper-eosinophilic syndrome (HES)..a spectrum of diseases with increased blood eosinophils and tissue damage in common, involving any organ system, especially skin, lung and heart. eosinophilic leukaemia, disseminated eosinophilic collagen disease, eosinophilic collagenosis, Loeffler s endocarditis Definition of HES: Chusid s triad 1) Persistent eosinophilia of 1.5 x 10 9 /L for longer than 6 months 2) Lack of evidence for parasitic, allergic or other Known causes of eosinophilia 3) Presumptive signs and symptoms of organ involvement including hepatosplenomegaly, organic heart murmur, congestive heart failure, nervous system abnormalities, pulmonary fibrosis, fever weight loss and anaemia. Chusid et al, Medicine (Baltimore) 1975
6 HES Organ Involvement
7 Classification of eosinophilia Reactive..stimulation of eosinophil production by eosinopoietic growth factors, mainly IL-5 (EO) Roufosse et al, J Allergy Clin Immunol 2010 P Valent, Blood Reviews, 2009 Gleish & Leiferman, Br J Haematol, 2009
8 Classification of eosinophilia (EO) Reactive..stimulation of eosinophil production by eosinopoietic growth factors, mainly IL-5 Clonal..a primitive BM, clonal expansion of cells belonging to the myeloid lineage with preferential eosinophilic differentiation Roufosse et al, J Allergy Clin Immunol 2010 P Valent, Blood Reviews, 2009 Gleish & Leiferman, Br J Haematol, 2009
9 Classification of eosinophilia (EO) Reactive Clonal Idiopathic..stimulation of eosinophil production by eosinopoietic growth factors, mainly IL-5..a primitive BM, clonal expansion of cells belonging to the myeloid lineage with preferential eosinophilic differentiation..non-reactive, clonal, non non clonal reactive HES Roufosse et al, J Allergy Clin Immunol 2010 P Valent, Blood Reviews, 2009 Gleish & Leiferman, Br J Haematol, 2009
10 Reactive Eosinophilia Allergic Drug hypersensitivity (anticonvulsants, semisynthetic penicillins, allopurinol) Atopic diseases (asthma, eczema, rhinitis) Infectious Disease Helminthic parasitic Protozoal infection Fungal (Coccidiomycosis) Scabies, myiasis ΗIV Other Irradiation Atheroembolsim Malignancy Lymphoma AdenoCA, SCCA, Large cell lung, transitional cell bladder Immunologic Hypoadrenalism Churg-Srauss Sarcoidosis, Inflammatory bowel disease Primary immune deficiencies (Hyper IgE) Graft vs host disease
11 Reactive Eosinophilia Allergic Drug hypersensitivity (anticonvulsants, semisynthetic penicillins, allopurinol) Atopic diseases (asthma, eczema, rhinitis) Infectious Disease Helminthic parasitic Protozoal infection Fungal (Coccidiomycosis) Scabies, myiasis ΗIV Other Irradiation Atheroembolsim Malignancy Lymphoma AdenoCA, SCCA, Large cell lung, transitional cell bladder..drug-induced eosinophilia can develop without other manifestations of adverse drug reactions, but should nevertheless prompt an evaluation of whether organs, including, lungs, kidneys liver and heart are involved Immunologic Hypoadrenalism Sarcoidosis Inflammatory bowel disease Primary immune deficiencies (Hyper IgE, Omenn syndrome) Graft vs host disease -DRESS syndrome: drug induced rash, eosinophilia and systemic symptoms syndrome Roufosse & Weller, J Allergy Clin Immunol conventional allergic diseases (astma, eczema) should be excluded when eosinophilia exceeds 1500/ml Kahn et al, Best Practice Res Clin Rheumatol 2008
12 Reactive EΟ Blood eosinophilia is described in the same range of tumors as tissue eosinophilia: -adrenal, thyroid, pancreas, lung, breast carcinoma, peritoneal mesothelioma, liposarcoma Endomyocardial fibrosis has been reported in association with eosinophilia in lung, renal and pancreatic adenocarcinomas Jaski et al, Cirqulation 1978
13 Reactive EΟ
14 Clonal eosinophilias ΚΙΤ D816V-positive
15 Clonal eosinophilia (4q12) (5q33) (8p11)
16
17 Clonal EO: the myeloproliferative HES Helbig et al, Pol Arch Med 2011
18 Clonal EO: the myeloproliferative HES Helbig et al, Pol Arch Med 2011
19
20 The lymphoproliferative HES
21 The lymphoproliferative HES
22 Mepolizumab: the Anti-IL5 mab
23 Ιdiopathic EO: HES Idiopathic..non clonal, non reactive HES.. The distinction between clonal and idiopathic eosinophilia is arbitrary and evidence suggests that, in some instances, HES actually represents an underlying myeloid neoplasm. Tefferi et al, Mayo Clin Proc 2010
24
25 Chronic eosinophilic leukemia (CEL) vs HES
26 Diagnostic algorithm for clonal or idiopathic eosinophilia. Tefferi A et al. Mayo Clin Proc. 2010;85:
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